Zika virus epidemic (2015-2016)

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Saved Wikipedia (June 29, 2021) - "2015–2016 Zika virus epidemic"

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In early 2015, a widespread epidemic of Zika fever, caused by the Zika virus in Brazil, spread to other parts of South and North America. It also affected several islands in the Pacific, and Southeast Asia.[2] In January 2016, the World Health Organization (WHO) said the virus was likely to spread throughout most of the Americas by the end of the year.[3] In November 2016, WHO announced the end of the Zika epidemic.[4]

In February 2016, WHO declared the outbreak a Public Health Emergency of International Concern as evidence grew that Zika can cause birth defects as well as neurological problems.[5][6] The virus can be transmitted from an infected pregnant woman to her fetus, then can cause microcephaly and other severe brain anomalies in the infant.[7][8][9] Zika infections in adults can result in Guillain–Barré syndrome.[9] Prior to this outbreak, Zika was considered a mild infection, as most Zika virus infections are asymptomatic, making it difficult to determine precise estimates of the number of cases.[10] In approximately one in five cases, Zika virus infections result in Zika fever, a minor illness that causes symptoms such as fever and a rash.[11][12]

The virus is spread mainly by the Aedes aegypti mosquito, which is commonly found throughout the tropical and subtropical Americas. It can also be spread by the Aedes albopictus ("Asian tiger") mosquito, which is distributed as far north as the Great Lakes region in North America.[13] People infected with Zika can transmit the virus to their sexual partners.[14]

A number of countries were issued travel warnings, and the outbreak was expected to reduce tourism significantly.[6][15] Several countries took the unusual step of advising their citizens to delay pregnancy until more was known about the virus and its impact on fetal development.[16] Furthermore, the outbreak raised concerns regarding the safety of athletes and spectators at the 2016 Summer Olympics and Paralympics in Rio de Janeiro.[17][18][19]

Epidemiology

As early as August 2014, physicians in Natal, in northeastern Brazil began to investigate an outbreak of illness characterized by a flat pinkish rash, bloodshot eyes, fever, joint pain and headaches. While the symptoms resembled dengue fever, testing ruled out this and several other potential causes. By March 2015, the illness had spread to Salvador, Bahia[75] and had appeared in three different states.[76] Then, in May 2015, researchers from the Federal University of Bahia and the Evandro Chagas Institute determined, using the RT-PCR technique, that the illness was an outbreak of Zika virus.[77][78] Although, the first confirmed Zika virus infection in Brazil were diagnosed in a returning traveller in March 2015.[79]

The Uganda Virus Research Institute conducts research near the Zika Forest from which the virus takes its name.

The Zika virus was first isolated in 1947, in a rhesus monkey in a forest near Entebbe, Uganda.[80] Although serologic evidence indicated additional human exposure during subsequent decades in parts of Africa and Asia,[81] before the 2007 Yap Islands Zika virus outbreak, only 14 cases of human Zika virus disease had been documented.[80]

Researchers generally believe the virus was brought to Brazil by an infected traveler who had been exposed to the virus in French Polynesia, who was then bitten by a mosquito that then infected others.[82][83][84] Phylogenetic analysis of the first Brazilian infections have strongly indicated that the circulating virus is the Asian, rather than African, strain of the virus, and was genetically similar to the virus found in the outbreak in French Polynesia.[83][84] It appears Zika's route – from Africa and Asia to Oceania and then the Americas – may mirror that of chikungunya and dengue, both of which are now endemic in a large portion of the Americas.[85]

The specific event that brought the virus to Brazil was uncertain until March 2016. Brazilian researchers had suggested that the Zika virus arrived during the 2014 FIFA World Cup tournament.[82] French researchers speculated the virus arrived shortly afterwards, in August 2014, when canoeing teams from French Polynesia, New Caledonia, Easter Island, and the Cook Islands, which had been or were experiencing Zika outbreaks, attended the Va'a World Sprint Championships in Rio de Janeiro.[76][83] However, the outbreak in French Polynesia is known to have peaked and declined precipitously by February 2014, lending doubt to the suggestion the virus arrived later that year in Brazil with spectators and competitors.[86] In March 2016, a study published in Science, which developed a "molecular clock" based on the count of virus mutations in a relatively small sample, suggested Zika virus arrived in the Americas (most likely in Brazil) from French Polynesia between May and December 2013, well before the World Cup and Va'a Championships.[86] In the Science article, Faria and colleagues managed to trace the origins of the virus strain that is circulating in Brazil and found that this strain has little genetic variability when compared to the strain of French Polynesia; after relating the number of travellers arriving in Brazil from French Polynesia with the cases reported and the events happening in that year, the team was able to deduce that the virus arrived in Brazil in 2013 during the Confederation Cup, when Tahiti's team played against other teams in a few Brazilian cities, which attracted many tourists from both places.[87] Zika virus usually has very mild, or no symptoms, so it took almost a year for Brazil to confirm the first case of the disease. By then the outbreak was already widespread. Factors associated with the rapid spread of Zika virus in Brazil include the non-immune population, high population density, tropical climate and inadequate control of Aedes mosquitoes in the country.[88] The Zika virus epidemic also revealed structural problems of the health system, in particular in public health services and basic sanitation in Brazil.[89]

The above average warm temperatures of 2015–2016 caused by a strong El Nino created an environment conducive to the spread of the Zika Virus in Brazil[2010]. The 2015 -16 El Nino increased ocean and ground surface temperatures to above average [2010]. January 2016 brought about nine consecutive months with temperatures 1.04 °C above the global average.[90] It is important to note, however, that while South America had areas experiencing 2.0 °C above average temperatures (for 1981–2010), areas including Argentina, Southern Brazil and Uruguay experienced temperatures 0.5 °C below average.[90]

Precipitation is another crucial factor to consider as Eastern Brazil and other areas in southern South America experienced high amounts of precipitation in early 2016.[90] The environmental conditions of increased rainfall and higher average temperatures in the South American region, lead to both a longer mosquito season and a higher mosquito density[91] which created an environment in which the Zika carrying Aedes aegypti and Aedes albopictus mosquitoes can thrive. Looking forward, climate models suggest that regions favorable to the Aedes mosquitoes will grow, widening the range of Zika and other mosquito-carried diseases.[92] The potential for epidemics will spread inland and into other regions of the world, not just in tropical environments.[93]

Confirmed cases have been reported in 40 countries or territories in South America, North America, and the Caribbean,[94] as well as 16 in the western Pacific and one in Africa since the beginning of 2015 (see table).

Many countries with no cases of mosquito transmission have reported travel-related Zika cases: people who moved or came home from a Zika-affected region before they showed symptoms (see table).

Transmission

See also: Zika virus § Transmission

Zika is a mosquito-borne disease. The resurgence of Aedes aegypti's worldwide distribution over the past 2–3 decades makes it one of the most widely distributed mosquito species.[95] In 2015, Aedes albopictus was present in tropical, subtropical, and temperate regions of the Americas, reaching as far north as the Great Lakes of North America and, internationally, living alongside Aedes aegypti in some tropical and subtropical regions.[13]

The Aedes aegypti mosquito usually bites in the morning and afternoon hours, and can be identified by the white stripes on its legs.[96] The mosquito species (Aedes aegypti, mainly, and Aedes albopictus) that can spread Zika virus can also spread dengue, chikungunya, and yellow fever.[97]

Zika can also be sexually transmitted between partners of both genders.[98] Sexual transmission of Zika has been documented in nine countries—Argentina, Canada, Chile, France, Italy, New Zealand, Peru, Portugal, and the United States—during this outbreak.[99]

Zika is transmitted from pregnant women to the fetus ("vertical transmission"), and causes microcephaly and other severe brain anomalies in infants born of women infected with the virus.[7][9][100]

A baby with microcephaly (left) compared to a baby with a typical head size

Zika infections in adults can cause Guillain–Barré syndrome.[9]

Diagnosis

Main article: Zika fever

Symptoms of Zika virus[101]

Symptoms are similar to other flaviviruses such as dengue fever or the alphavirus that causes chikungunya,[102] but are milder in form and usually last two to seven days.[6] It is estimated that 80% of cases are asymptomatic.[103] The main clinical symptoms in symptomatic patients are low-grade fever, conjunctivitis, transient joint pain (mainly in the smaller joints of the hands and feet) and maculopapular rash that often starts on the face and then spreads throughout the body.[102]

It is difficult to diagnose Zika virus infection based on clinical signs and symptoms alone due to overlaps with other arboviruses that are endemic to similar areas.[104] The methods currently available to test for Zika antibodies cross-react with dengue antibodies. An IgM-positive result in a dengue or Zika ELISA test can only be considered indicative of a recent flavivirus infection. Plaque-reduction neutralization tests (PRINT) can be performed and may be specific.[105] The Zika virus can be identified by RT-PCR in acutely ill patients.[6]

RT-PCR testing of serum and tissue samples can be used to detect the presence of the Zika virus. However, the RT-PCR test with serum is only helpful while the virus is still in the blood which is generally within the first week of the illness. After this period other methods should be used to determine if the virus is still present in the body. A test for IgM antibodies has seen to be effective over longer periods of time, as these antibodies can be present starting 4 days after the beginning of the illness and up to 12 weeks after that. However, it is suggested that a PRINT test be performed following a test for IgM antibodies to help eliminate false positives resulting from other flaviviruses. The PRINT test looks for viral-specific neutralizing antibodies. However, this test can still produce false positive results, for Zika, in individuals who have received immunization for or had previously been exposed to other flaviviruses.[106]

Containment and control

The Americas

Several countries, including Colombia, Ecuador, El Salvador, and Jamaica, advised women to postpone getting pregnant until more was known about the risks.[16][107] Plans were announced by the authorities in Rio de Janeiro, Brazil, to try to prevent the spread of the Zika virus during the 2016 Summer Olympics in Rio.[108] The health ministry of Peru installed more than 20,000 ovitraps during the 2015 dengue outbreak. The same ovitraps will be used to monitor a potential Zika outbreak in tropical regions of Peru.[109]

On January 15, 2016, because of the "growing evidence of a link between Zika and microcephaly" the Centers for Disease Prevention and Control (CDC) issued a travel warning advising pregnant women to consider postponing travel to Brazil as well as the following countries and territories where Zika fever had been reported: Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, Venezuela, and the Commonwealth of Puerto Rico.[110] On January 20, the Ministry of Health of Chile published a health notice.[111] On January 22, eight more countries and territories were added to the list of those affected: Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa.[112]

On February 1, Costa Rica and Nicaragua were added to the list, bringing the number of countries and territories affected to 28.[113] The agency issued additional guidelines and suggested that women thinking about becoming pregnant consult with their physicians before traveling.[114] Canada issued a similar travel advisory.[108][115] Questions have been raised about the readability and effectiveness of the press releases issued by the WHO/PAHO, CDC, and the ministries of health of affected countries with the average readability of a press release by the WHO measured at 17.1 on the Flesch Kincaid grade level readability test.[116]

On February 5, after the laboratory confirmation of a Zika virus infection in the U.S. in a non-traveler, which was linked to sexual contact with an infected partner, the CDC issued interim guidelines for prevention of sexual transmission of Zika virus for the United States.[103] These guidelines recommend that men who reside in or have traveled to an area of active Zika virus transmission who have a pregnant partner should abstain from sexual activity or consistently and correctly use condoms during sex for the duration of the pregnancy.[103] The guidelines recommend that pregnant women discuss any possible Zika exposure with their male partners.[103] The guidelines recommend that non-pregnant women and their partners consider taking similar measures.[103]

On February 8, CDC elevated its response efforts to a Level 1 activation, the highest response level at the agency. The CDC then issued a statement on February 23 further encouraging adherence to this guidance after 14 reports of possible sexual transmission of the virus were under investigation.[117][118] A bill, Zika Authorization Plan Act of 2016 (H.R. 4562), was introduced in the second session of the United States 114th Congress by Representative Curt Clawson (R-FL) on February 12, 2016,[119][120] aimed at reducing the spread of the virus.[121]

Paraguay reported its first case of Zika in a pregnant woman on March 11.[122] On March 18, CDC cautioned men who have been infected with Zika from attempting to conceive children due to probability of virus transfer from man to woman during sexual activity which in turn can affect the fetus, under this caution, men are advised not to try conception until six months after the infection.[123]

Colombia reported its first cases of microcephaly associated to the Zika virus on April 14, 2016.[124] The CDC authorized emergency use of a Zika Virus RNA Qualitative test on April 28 to detect Zika virus in the blood of patients who have symptoms of Zika virus infection and live in or have traveled to an area with ongoing Zika virus transmission. This is the first commercial test to detect Zika virus authorized by the United States Food and Drug Administration for emergency use.[125]

On May 6, Major League Baseball announced that a series of games between the Miami Marlins and Pittsburgh Pirates scheduled to be played at the end of the month in San Juan, Puerto Rico would be relocated to Marlins Park in Miami, Florida after a number of players on each team voiced concerns regarding the threat of Zika exposure.[126] By mid-August at least 37 people had contracted the virus in neighborhoods near the city of Miami, Florida, though officials estimated that the actual number of infections was much higher due to under-reporting of mild illness.[127] It was determined in June that travelers to Dominican Republic lead New York City in positive Zika tests.[128]

The first-affected area in the continental United States, the Wynwood neighborhood of Miami, was declared Zika-free in September, 2016.[129] After the virus stopped circulating in South Beach, all of Florida was declared Zika-free in December, 2016.[130] One case of local transmission was reported in Texas up until September, 2017.[131] As of 2018, Zika remains endemic in Puerto Rico,[132] but the number of cases was reduced from about 8,000 reported per month at the peak in August 2016 to about 10 reported per month in April 2017.[133]

Asia

Following the spread of Zika infection into Southeast Asia in June 2016, Singapore, Thailand and Vietnam become the most heavily affected.[45][134] Singapore has planned to release an army of mosquitoes that contain the Wolbachia bacteria to fight the Aedes aegypti mosquito population.[135] The Association of Southeast Asian Nations (ASEAN) members have increased information sharing and joint research on the virus.[136][137] On September 30, Thailand confirmed that two babies has born with microcephaly.[138] Prior to the case, Thailand has allowed abortion for pregnant women that have been affected by birth defects.[139] Malaysia is still undecided on the issue,[140] with doctors there letting the mother make the decision whether or not to abort.[141] Rentokil, a Malaysian pest company, has designed an Integrated Mosquito Management (IMM) program to curb the spread of Aedes mosquito.[142] On October 17, Zika was declared as endemic in Vietnam by the country Health Ministry due to the number of local cases.[143] Vietnam confirmed that one baby has born with microcephaly on October 31.[144] Following the rise of local Zika infection cases in the Philippines, the virus have also been declared as endemic by the country Health Department.[145] The government of the republic hosting the “One Philippines against Zika” national summit on October 28 with church in the country has joint fight to curb the spread of the virus by issuing a pastoral guidance to help raise awareness about the mosquito-borne disease among local communities.[146][147][148] Taiwan has also seen an increase of infection, most of the cases are believed to be imported from other countries.[149] On October 27, Myanmar reported its first imported case on a pregnant foreign woman.[36]

International

Governments or health agencies such as those of Australia,[150] Canada,[151] China,[152] Hong Kong,[153] Indonesia,[154] Ireland,[107] Japan,[155] Malaysia,[156] New Zealand,[157] Philippines,[158] Singapore,[159] South Korea,[160] Taiwan,[161] the United Kingdom,[162] United States[163] as well the European Union[108] issued travel warnings. The warnings are predicted to have an effect on the tourism industry in affected countries.[164][165][166]

To prevent the transmission of the Zika virus, WHO recommends using insect repellent, wearing long-sleeved clothes to cover the body, and using screens and mosquito nets to exclude flying insects from dwellings or sleeping areas. It is also vital to eliminate any standing water near homes to minimize breeding areas for mosquitoes. Authorities can treat larger water containers with recommended larvicides.[96][167] Furthermore, the Centers for Disease Control and Prevention (CDC) recommends that containers holding water near homes either be sealed or scrubbed once per week, because mosquito eggs can stick to them.[97]

On February 1, 2016, WHO declared the cluster of microcephaly cases and other neurological disorders a Public Health Emergency of International Concern,[5] which may reduce the number of visitors to the Rio Olympics in 2016.[168] The designation has been applied in the past to the [Western African Ebola virus epidemic (2013 - 2016)], the outbreak of polio in Syria in 2013, and the 2009 flu pandemic.[169] South Korea held an emergency meeting in response to the WHO declaration on February 2, 2016.[160] A second meeting of the WHO-convened emergency committee, held on March 8, 2016, reaffirmed the situation's status as a Public Health Emergency of International Concern. The committee reported that evidence was increasing for a causal relationship between Zika virus and microcephaly and other neurological conditions, and called for continued research, aggressive mosquito control, and improved surveillance and communication of risks to the public. The report stated that pregnant women should be advised not to travel to affected areas, and should use safe sex practices if their partners lived in or travelled to affected areas throughout their pregnancy.[170] On March 9, 2016, WHO announced that research should prioritise prevention and diagnosis, not treatment, and in particular non-live vaccines suitable for pregnant women and those of childbearing age, novel mosquito control measures, and diagnostic tests that can detect dengue and chikungunya as well as Zika.[171]

Responses

See also: Mosquito control

The Brazilian Army has sent more than 200,000 troops to go "house to house" in the campaign against Zika-carrying mosquitoes.

In January 2016, it was announced that, in response to the Zika virus outbreak, Brazil's National Biosafety Committee approved the releases of more genetically modified Aedes aegypti mosquitoes throughout their country.[172] Previously, in July 2015, Oxitec had published results of a test in the Juazeiro region of Brazil, of so-called "self-limiting" mosquitoes, to fight dengue, chikungunya, and Zika viruses. They concluded that mosquito populations were reduced by over 90% in the test region.[172][173][174] Male genetically modified mosquitoes mate with females in the wild and transmit a self-limiting gene that causes the resulting offspring to die before reaching adulthood and thus diminishes the local mosquito population.[172][174] In January 2016 the technique was being used to try to combat the Zika virus in the town of Piracicaba, São Paulo.[175]

On February 1, 2016, the WHO declared the current Zika virus outbreak an international public health emergency,[5][176] and the Brazilian President released a decree that increased local and federal pest control agents' access to private property required by mobilization actions for the prevention and elimination of Aedes mosquito outbreaks in the country.[177]

Some experts have proposed combatting the spread of the Zika virus by breeding and releasing mosquitoes that have either been genetically modified to prevent them from transmitting pathogens or that have been infected with the Wolbachia bacterium, thought to inhibit the spread of viruses.[178][179] Another proposed technique consists of using radiation to sterilize male larvae so that when they mate, they produce no progeny.[180] Male mosquitoes do not bite or spread disease.[181]

In February, the Brazilian federal government mobilized 60% of the country's Armed Forces, or about 220,000 soldiers, to warn and educate the populations of 350 municipalities on how to reduce mosquito breeding grounds.[182]

A joint statement on the sharing of data and results on the Zika outbreak in the Americas and future public health emergencies was issued on February 10, 2016, by a group of more than 30 global health bodies.[183] The statement reinforces a similar consensus statement issued by WHO in September 2015.[184] The statement calls for free access to all data as rapidly and widely as possible.[185]

In February 2016, Google announced that they were donating $1 million via UNICEF to fight the spread of the Zika virus and offering professional personnel to help to determine where it will hit next.[186]

Prevention and treatment

While there are no known cures for Zika, there have been recent developments in Zika vaccination. Three vaccine designs are showing high confidence levels of protection against the Zika virus. Scientists have conducted tests on the rhesus monkey, and human trials began in late 2016.[187]

This preventative treatment is promising, but it will take years before it is available for widespread usage.[188]

British experts are clear that any of the vaccines would take considerable time to develop. Dr Ed Wright, a senior lecturer and virologist at the University of Westminster, said: "All of the vaccines currently under development are many years away from being licensed and available for widespread public use." Jonathan Ball, professor of molecular virology at the University of Nottingham, said: "We knew that these vaccines worked in mice and now the researchers have shown that they also protect non-human primates from Zika virus infection." "The next step will be to see if these vaccines are safe and the scientists hope to start early trials in humans to address this."[189]

Kineta, a Seattle-based biotech company, is actively working on treatments and has received an undisclosed amount of funding from National Institute of Allergy and Infectious Disease, one of the National Institutes of Health, to carry on the research. Kineta CEO Dr Shawn Iadonato said in a statement. "We are eager to expand testing of our broad spectrum antivirals in Zika virus as they have shown compelling efficacy across other flaviviruses such as Dengue and West Nile and have the potential for long-term development."[190]

As of July 26, 2016, [Inovio Pharmaceuticals, Incorporated] dosed the first subject in its multi-center phase I trial to evaluate Inovio's Zika DNA vaccine (GLS-5700). In addition to the previously announced US FDA approval for the conduct of the study, Health Canada's Health Products and Food Branch has also approved this study, which will be conducted at clinical sites in Miami, Philadelphia, and Quebec City. The phase I, open-label, dose-ranging study of 40 healthy adult volunteers is evaluating the safety, tolerability and immunogenicity of GLS-5700 administered with the CELLECTRA®-3P device, Inovio's proprietary intradermal DNA delivery device. In preclinical testing, this synthetic vaccine induced robust antibody and T cell responses – the immune responses necessary to fight viral infections – in small and large animal models.[191]

Direct Relief, an emergency response organization, established a Zika Fund and fulfilled requests for supplies in 14 affected countries.[192]

Challenges to US response

In May 2017, the Government Accountability Office published a report, "Emerging Infectious Diseases: Actions Needed to Address the Challenges of Responding to Zika Virus Disease Outbreak", to correspond with an associated House subcommittee hearing. The GAO said that even though scientific breakthroughs have increased in recent years, the United States remains unprepared to handle a Zika virus outbreak.[193]

Timothy Persons, head scientist at the GAO, listed areas of limited research that damage the United States’ ability to effectively respond to a Zika outbreak, including an accurate record of the number of cases in the United States, components associated with transmission from mothers to children (especially regarding pregnancy), risk of transmission through bodily fluid as related to the potential for sexual transmission of the virus, impact of prior exposure to Zika and other arboviruses, and both short-term and long-term outcomes. Recent outbreaks have been connected to an alarming a spike in microcephaly, a birth defect that inhibits the proper development of a baby's brain, and Guillain-Barré syndrome, which causes paralysis.[193]

Other challenges include the lack of a safe and effective vaccine, a complicated diagnostic process, and faltering support for research funding in the federal government. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), said "There aren’t any federally licensed vaccines or specific therapeutics currently available to prevent or treat Zika." Zika is often difficult to distinguish from other illnesses that are spread by mosquitoes, like dengue, West Nile, and chikungunya, among others. President Trump's budget proposal for 2018 proposed stripping $800 billion from Medicaid over ten years. Democratic Representative Frank Pallone of New Jersey said that this decision "endangers our ability to manage public health emergencies like Zika."[193]

Controversies

Some efforts to contain the spread of Zika virus have been controversial. Oxitec, the company behind the "self-limiting" mosquitoes, which pass on a fatal gene to their offspring, released in Brazil, has faced criticism from environmental groups, who fear that releasing a new mosquito strain into the wild will damage the ecosystem. In the short term, the concern is that a drop in the mosquito population could affect the populations of other species. Supporters claim that the environmental impact of the "self-limiting" mosquitoes will be minimal, since only one species of mosquito is being targeted and the genetically-modified mosquitoes are still safe for predators to eat. Oxitec Product Development Manager Derric Nimmo likened the process to "going in with a scalpel and taking away Aedes aegypti, leaving everything untouched."[194] Since Aedes aegypti is an imported invasive species in Brazil, some experts expect that its eradication will have little impact on the environment. However, other environmentalists emphasize that the long-term consequences of eliminating an entire species cannot be predicted.[195]

Government recommendations that women delay pregnancy have also proven to be controversial. Human and reproductive rights groups have deemed the recommendations irresponsible and difficult to follow, since women alone are tasked with avoiding pregnancy despite having little control to do so.[196] A 2012 study suggests that 56% of pregnancies in Latin America and the Caribbean are unplanned (compared to an average unplanned pregnancy rate of 40% worldwide).[197] Access to contraceptives might be limited in regions where the Roman Catholic Church is predominant, such as in El Salvador.[198] Anti-abortion laws in much of the region leave women with no recourse once they become pregnant. Aside from three countries where abortion is widely available (French Guiana, Guyana, and Uruguay) and three countries where abortion is allowed in cases of fetal malformation (Colombia, Mexico, and Panama), most of the region only permits abortion in the cases of rape, incest, or danger to the mother's health. In El Salvador, abortion is illegal under all circumstances.[196]

On February 5, 2016, the UN High Commissioner for Human Rights urged Latin American governments to consider repealing their policies regarding contraception and abortion, emphasizing that "upholding human rights is essential to an effective public health response."[199] On February 16, 2016, the Vatican condemned the UN for its call to action, deeming it "an illegitimate response" to the Zika crisis and emphasizing that "a diagnosis of microcephaly in a child should not warrant a death sentence."[200]

On February 18, 2016, after a trip to Latin America, Pope Francis stated that "avoiding pregnancy is not an absolute evil" in cases such as the Zika virus outbreak. His comments sparked speculation that the use of contraception may be morally permissible in the prevention of the Zika virus.[201]

Scientific communication and concerns

The 2015–2016 Zika virus outbreak became an important topic on many social media sites, especially on Twitter. An analysis of Twitter posts on February 2, 2016 showed that 50 tweets per minute were posted about Zika, many of which contained the hashtags #salud, which means health in Spanish as well as #who, which served as a reference to the World Health Organization.[202]

The epidemic also caused a rise in tweets from college students upset that their spring break trips and study abroad plans had been changed or cancelled due to the virus’ spread.[202]

Many studies have been conducted on the connections and impact of social media mentions of Zika. One analysis found that the primary topics discussed on Twitter before the peak of the outbreak regarding Zika included Zika's impact, reactions to Zika, pregnancy and microcephaly, transmission routes of Zika, and case reports.[203] During the summer of 2016 when Zika was spreading at a much faster rate, this social media analysis determined that the major topics on Twitter regarding Zika had become concerns about the spread of Zika, criticism of Congress, news about Zika, and scientific information about Zika.[203] The same study also found that tweets from reputable institutions and people holding scientific credentials demonstrated the ability of Twitter as a source to spread information quickly on the internet.[203] Another study found that the Centers for Disease Control and Prevention as well as the general public showed similar concerns about Zika. The CDC's posts on Twitter during the outbreak focused on symptoms and education for Zika.[204] However, the public had more of a tendency to focus concern on the consequences of Zika on women and infants, such as microcephaly.[204]

While there was concern for children on social media, this concern was lacking in countries largely impacted by Zika virus, such as Brazil. In Brazil, struggling mothers of infants with microcephaly caused by Zika have used support systems on social media on the cellphone chat app called Whatsapp or on Facebook pages that can help connect mothers in need of supplies and money to donors.[205]

The heavy traditional news and social media coverage of the virus spreading did cause concern over lack of reliability. Research has found that between May and June 2016, four out of five social media posts about Zika provided accurate information, but inaccurate posts were much more popular. This led many researchers to worry about the quality of information being spread and shared on social media.[206] Google Trends showed that Zika did not become a trending topic for the media until January 2016.[207] A study done found that 81 percent of the most popular posts on Facebook about Zika did contain truthful information, but posts spreading false information were far more popular.[206] Initial media reports on Zika in the United States focused on reassuring viewers and readers that Zika was not a threat in the United States.[207] Studies have found that real-time social media updates are desirable methods for communication during the emergence of infectious diseases. However, misinformation is common and data control in the cyber world has become a growing necessity.[204]

Many people criticized the lack of governmental response from the U.S. Government in the wake of the crisis.[208] The United States was criticized for a lack of preparedness in terms of an ability to contain a virus outbreak in the United States. The Obama Administration requested an emergency supplemental appropriation of $1.86 billion for both domestic and international response to the crisis.[209] In response to this request, Congress redirected $589 million from funds previously dedicated to Ebola instead of allocating new funds.[209] Another criticism regarding Zika funding had to do with the fact that Congress members still took vacation in July 2016 before allocating any of the funds requested in February 2016.[210]

In August 2016, the Centers for Disease Control and Prevention reported that they had spent $194 million of the initial $222 million allocation to fight Zika virus.[211] Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases said that the NIAID was running out of funds, which would substantially slow down the development of vaccines.[212] Although the government faced criticism for not responding strongly enough to the Zika outbreak, the government eventually provided funding of $1.1 billion for Zika in October 2016. It took congress nearly seven months to agree to this allocation, which left many prevention and education projects without funding for a substantial amount of time.[213] Senate Democrats urged Republicans to approve the full amount of funding more quickly rather than waiting for major transmission of Zika virus to begin in the United States.[214]

In 2017, public health experts are still concerned about the failure of the Zika response in the United States.[215] Many officials failed to provide information about Zika's sexual transmission. New York City subway systems had posters about mosquitos while all local cases reported had been picked up elsewhere or transmitted sexually.[215] Many experts believe that the United States lacked severely in providing the public with information to prevent sexual transmission of the virus.[215]

EVIDENCE TIMELINE - 2014

2014 (12 June to 13 July) - World Cup (FIFA) in Brazil

2014 : Ebola outbreak, West Africa ; DTRA funds vaccine from NewLink in September 2014

EVIDENCE TIMELINE - 2015

2015 : Tally of use of word "Zika" in USA/Canada newspapers (via newspapers.com, as of June 29 2021)

2015 (Jan 08) - Moderna Launches New Venture "Valera LLC" for Infectious Diseases (from press release)

2015 (May 11) - First use of word "zika" as in "zika virus" in any USA newspaper on newspaer.com

2015 (May 31) - Zika in island nation of Jamaica (no fatal cases noted)

2015 (May) - Starting in May 2015, "Brazilian officials began to sound alarms that it was to blame for an otherwise mysterious outbreak of babies born with microcephaly [...]. Around the same time, heartbreaking photographs of children born with the condition shot around the globe."

This was reported in a NYTimes article in November 2016 :  Article source : [HN01NN][GDrive]   /

"But about 18 months ago [18 MONTHS before Nov 19 would be May 2015], , Brazilian officials began to sound alarms that it was to blame for an otherwise mysterious outbreak of babies born with microcephaly, or unusually small heads and malformed brains. Around the same time, heartbreaking photographs of children born with the condition shot around the globe."

2015 (July) - Barney Graham of Vaccine Research Center at the N.I.H., learns at a meeting of the threat developing, from a Brazilian doctor who "pulled him aside at the meeting in Bethesda, Md."

This was reported in a NYTimes article in November 2016 :   NYTimes article source : [HN01NN][GDrive]  ...

"   [Dr. Barney Scott Graham (born 1953)], deputy director of the Vaccine Research Center at the N.I.H, was at a meeting in July 2015 when he learned of the threat. A Brazilian doctor pulled him aside at the meeting in Bethesda, Md., which had been called to discuss chikungunya, another tropical disease.

“I know we’re here about chikungunya,” Dr. Graham said the doctor told him. “But I really want to tell you about Zika virus.”

Within months, the link seemed increasingly clear, and public health officials predicted that the virus would probably infect millions of people. In December, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases at the N.I.H., called a meeting with the top members of his vaccine staff.  "

2015 (Sep 29) - The News Journal (Delaware) - START FEARING ZIKA !!!!!!! ... "That little rash you have? Let's hope it's not Zika Fever"

Full newspaper page : [HN01PM][GDrive]

Mentioned : 

2015 (Nov 5-9) ... Confidential Disclosure agreement signed between NIAID, Vaccine Research Institute, and Moderna

Amendment One was signed as of October 28, 2016

NOTE - This was SUPERCEDED by a "COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT" signed between Moderna, VRC, NIAID in August 2016

See [HX0018][GDrive]

2015 (Nov 22) - The Spokesman-Review :  Mention of "zika virus" in "EARTHWEEK" article. 

Full newspaper page : [HN022P][GDrive]  / Image of clip of this article :  [HN022Q][GDrive]

2015 (Nov 29) - WSJ: "Brazil Links Dengue-Like Virus to Birth Defects ; Nine states with Zika infections see surge in babies born with small head"

Associated Press   /    Nov. 29, 2015 6:18 pm ET  /  Source (saved as PDF) : [HN022O][GDrive

NOTE - This is the earliest article in the year 2015 on WSJ.com that has any use of the word "Zika"

RIO DE JANEIRO—The dengue-like Zika virus has been linked for the first time to cases of babies being born with small heads, or microcephaly, Brazil’s government said.

Scientists studying a surge of such cases in northeastern Brazil found the presence of the virus in the blood of a baby born with birth defects in Ceara state, the government said. The girl died.

The link to Zika “is an unprecedented situation in the global scientific community,” the Health Ministry said in a statement released Saturday.

Researchers with the U.S. Centers for Disease Control and Prevention will soon travel to Brazil at the government’s request to study the link between the rare neurological condition and the virus.

Brazilian health officials believe pregnant women are more vulnerable to developing fetuses with microcephaly if they are infected with Zika in their first trimester. This year, the ministry has reported 739 cases of babies born with microcephaly in nine states that have been hit by Zika infections, while last year the same region reported only 45.

“Research on the subject should continue to clarify issues such as how it is transmitted, what it does to the body, how the fetus gets infected and the time of greatest vulnerability for pregnant women,” the ministry’s statement said.

Microcephaly “usually reflects an underlying reduction in the size of the brain,” according to the CDC. The disorder can affect motor skills and cause mental retardation.

The same mosquito that carries the dengue virus, Aedes aegypti, is also responsible for spreading Zika, a disease that until now was known as a mild version of dengue with symptoms such as fever, rash and joint pain.

Outbreaks of Zika have occurred in Africa, Southeast Asia and the Pacific Islands. The virus isn’t found in the U.S., but cases of Zika have been reported in returning travelers, according to the CDC.

In its statement, Brazil’s Health Ministry reported two other deaths associated with the Zika virus not involving microcephaly. The victims were an adult male who suffered from lupus and a 16-year-old girl.

2015 (Dec) - Fauci calls a staff meeting regarding Zika outbreak ... (per a 2016 NYTimes article)

NYTimes article source : [HN01NN][GDrive]   /

Within months [of Dr. Barney Scott Graham (born 1953) and others at the VRC / NIAID knowing of the Zika breakout] , the link seemed increasingly clear, and public health officials predicted that the virus would probably infect millions of people. In December, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases at the N.I.H., called a meeting with the top members of his vaccine staff.

Similar meetings were occurring elsewhere in the vaccine world — at small companies like [Inovio Pharmaceuticals, Incorporated] and [NewLink Genetics Corporation], in the offices of big manufacturers like GlaxoSmithKline and Sanofi, and at the Walter Reed Army Institute of Research, which is a few miles from the N.I.H. campus in Bethesda, where Dr. Fauci’s team works.

“I said, all hands on deck,” Dr. Fauci recalled. “We have a serious problem here. We’ve got to really move.”

2015 (Dec 18) - The Poughkeepskie Journal - "Outbreak of dengue fever largest in 60 years"

Full newspaper page : [HN022X][GDrive]  /  Clip above : [HN022Y][GDrive]

2015 (Dec 22) - WSJ: "Spreading Virus Adds to Brazil’s Woes ;Some health officials link outbreak of mosquito-borne pathogen to rising instances of infant deaths from rare disease"

 Up to 3,000 babies feared impacted

By Reed Johnson, and Betsy McKay   /   Dec. 22, 2015 7:31 pm ET  /  Source : [HN022N][GDrive

SÃO PAULO—Brazil is in the grips of yet another crisis: a fast-spreading virus some health officials are linking to thousands of cases of infant brain damage and 40 related deaths this year.

Health authorities have declared a national emergency as they battle the Zika virus, a mosquito-borne pathogen that has been detected across much of South America’s largest country.

Symptoms include fever, rashes, headaches, joint aches and vomiting, lasting from a few days to about a week. The virus is rarely lethal, and it is usually treated with bed rest and liquids.

Health officials believe the virus this year alone is responsible in Brazil for an explosion of cases of microcephaly, an extremely rare condition in which babies are born with shrunken skulls because their brains aren’t growing properly. But they say microcephaly hasn’t been linked to Zika virus outbreaks before.

On Tuesday, Brazil’s Health Ministry released figures showing that as of Saturday, the number of suspected Zika-related microcephaly cases had climbed to 2,782, a surge of nearly 16% from the previous week. The number of confirmed deaths shot up to 40 from 29 over the period. By comparison, Brazil had 147 cases of microcephaly for all of 2014.

“This is probably the largest outbreak of Zika ever recorded,” said Ann Powers, acting chief of the arboviral diseases branch at the Atlanta-based Centers for Disease Control and Prevention. “There’s a lot of concern about what it means, what the implications are, and what we can potentially do for containment and control.”

There are multiple potential causes of microcephaly in gestating babies, including genetic abnormalities, exposure to toxins and maternal alcohol abuse. Dr. Powers said there is a “suggestive” link between microcephaly and Zika, but said the connection couldn’t be confirmed until additional studies have been performed.

No vaccine exists to combat the Zika virus. Alarmed health and government officials are mobilizing communities nationwide to battle mosquitoes and have enlisted the help of international health agencies, including the World Health Organization and the CDC.

Brazilian government officials are dispatching army troops and other crews to drain water-logged areas and search out and eradicate larvae-filled water supplies. The state of São Paulo, Brazil’s most populous, has assembled a medical task force to coordinate diagnosis and treatment efforts.

With its introduction into Brazil and other countries in the Americas, including Colombia, El Salvador and Mexico, Zika is following a pattern similar to other mosquito-borne viruses that are riding speedily to new parts of the world.

The virus is carried by the Aedes aegypti and Aedes albopictus species, the same mosquitoes that transmit dengue and a similar disease, chikungunya. Those mosquitoes populate the southern U.S., Caribbean, Central and South America, Dr. Powers said.

The size of the Brazilian outbreak may be the reason health authorities are finding unusual neurological symptoms and disorders for the first time, she said.

Another reason may be a mutation in the virus, she said, adding that scientists are studying genetic sequences to look at whether changes have occurred that could lead to these disorders.

Still, chikingunya isn’t circulating widely on its own in the U.S. and any Zika outbreaks in the U.S. would be limited, Dr. Powers said, because the mosquitoes that carry it aren’t present year-round.

“This is a very good example of how something found in the past in one location can really turn out to be a problem in another,” she said.

Chikungunya, an infection that causes fever and severe, lasting joint pain, has long circulated in Africa, Asia and parts of Europe, but didn’t reach the Americas until 2013, when public health authorities found evidence of transmission in the Caribbean.

Since then, chikungunya has swept through the Americas.

“It does seem to be following a pattern similar to chikungunya,” Dr. Powers said of Zika.

With the Southern Hemisphere’s summer vacation season now under way and the nation gearing up for an influx of tourists for the 2016 Olympic Games in Rio de Janeiro, some Brazilian officials say they fear the infection rate could surge in coming months.

The Zika virus first surfaced in Africa in the late 1940s, and has hopscotched to Southeast Asia, the Western Pacific and more recently to Latin America. Exactly how it reached Brazil, why it is spreading so fast and how it became such a threat to developing fetuses isn’t yet understood. Brazilian health officials don’t know the exact number of adults infected with the Zika virus because the vast majority of them don’t receive hospital treatment.

What is clear is that Brazil’s mosquito population has surged over the past few years, paradoxically, as a result of a record drought that has hit the nation’s northeast and southeast. As water supplies dried up, anxious residents began storing emergency water supplies in swimming pools, plastic jugs and other containers, creating a huge stock of mosquito-breeding areas.

The Brazilian government’s infectious-disease officials are well-regarded throughout the region. But with the country mired in its worst economic crisis since the Great Depression and the nation’s capital transfixed by a massive corruption scandal and impeachment proceeding against President Dilma Rousseff, some worry that the nation isn’t mobilizing fast enough to battle the quick-moving epidemic.

Osmar Terra, a medical doctor, former state health secretary and current federal legislator from the southern state of Rio Grande do Sul, said he believes Brazil could have as many as 100,000 cases of infection in 2016 if emergency measures aren’t taken soon.

“This is an unprecedented human tragedy,” said Dr. Terra, who based his projections on his handling of the outbreak of the H1N1 virus in 2009. “We need a crisis cabinet” to deal with the situation.

Dr. Terra favors using drones to detect pools and hidden water supplies, allowing authorities to enter private homes without permission to search for stored water, and even urging women to delay pregnancy.

Other health professionals are giving some of the same advice. Experts say the Zika virus can be passed through a pregnant woman’s placenta to her fetus, with the greatest danger occurring during the first trimester.

Thomaz Gollop, a professor of genetic medicine at the University of São Paulo, is recommending his female patients under the age of 35 to wait a few more months this year before getting pregnant.

“Having a child is a lifelong commitment,” Dr. Gollop said.

Microcephaly cases with suspected links to the Zika virus have been reported in 19 of Brazil’s 26 states as well as the federal district of Brasília, the nation’s capital. But its effects are being felt most keenly in poor, northeastern states including Pernambuco, Paraíba, Ceará and Bahia.

Jussara Araujo, health secretary of Itapetim, in Pernambuco, said in a phone interview that the town had recorded 11 suspected cases of Zika-related microcephaly since October. But because the municipality of 13,800 lacks adequate medical infrastructure, pregnant mothers suspected of being infected had to be taken to the state capital of Recife, about 220 miles away.

“We are very saddened,” Ms. Araujo said. “We have no experts to handle it.”

One of those expectant mothers is Jackeline Palmeira de Araujo, a 26-year-old farmer who is 39 weeks’ pregnant. She said she is avoiding stagnant water, covering up with extra clothing and getting regular ultrasounds to check on her gestating daughter.  So far, everything is normal. But, “I am very scared,” Ms. Palmeira de Araujo said.

EVIDENCE TIMELINE - 2016

2016 (Jan 02) - The Citizens Voice (Wilkes Barre, PA) - "Brazil fears birth defects linked to mosquito-borne virus"

Full newspaper page : [HN022R][GDrive]  /  Clip above :  : [HN022S][GDrive]

2016 (Jan 17)

https://www.newspapers.com/image/188560068/?terms=zika&match=1

2016-01-17-the-anniston-star-pg-6a-clip-hawaii-baby-brain-damage.jpg

Mentioned : Dr. Scott C. Weaver (born 1957)  

2016 (Jan 27) - Journal of American Medical Association : "Viewpoint : The Emerging Zika Pandemic ; Enhancing Preparedness"

Source PDF : [HP00CF][GDrive][DOI:10.1001/jama.2016.0904]

Authors :  [Lawrence Oglethorpe Gostin (born 1949)] and [Dr. Daniel Richard Lucey (born 1955)]

The Zika virus (ZIKV), a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis, originated in the Zika forest in Uganda and was discovered in a rhesus monkey in 1947. The disease now has “explosive” pandemic potential, with outbreaks in Africa, Southeast Asia, the Pacific Islands, and the Americas.1 Since Brazil reported Zika virus in May 2015, infections have occurred in at least 20 countries in the Americas.2 Puerto Rico reported the first locally transmitted infection in December 2015, but Zika is likely to spread to the United States. The Aedes species mosquito (an aggressive daytime biter) that transmits Zika virus (as well as dengue, chikungunya, and yellow fever) occurs worldwide, posing a high risk for global transmission. Modeling anticipates significant international spread by travelers from Brazil to the rest of the Americas, Europe, and Asia.3 What steps are required now to shore up preparedness in the Americas and worldwide?

Pg 1 or 2 : [HP00CG][GDrive]

World Health Organization Leadership :

2016 (Jan 28) - NPR : "WHO Warns Of Zika Virus's 'Alarming' And 'Explosive' Spread"

Source : [HM001T][GDrive] 

In her first major address on the Zika outbreak, the head of the World Health Organization, Dr. Margaret Chan, said the mosquito-borne virus has gone from being "a mild threat to one of alarming proportions." Chan spoke Thursday in Geneva.

The apparent link between Zika and severe birth defects in children in Brazil still hasn't been definitively proven but Chan says the threat is so high that she's calling for an emergency committee to advise her on "the appropriate level of international concern and for recommended measures that should be undertaken in affected countries and elsewhere." There's no vaccine or treatment for Zika. Chan says eliminating mosquito breeding grounds is one of the most important defenses against the disease.

"We really need to concentrate on mosquito control," Chan said in a briefing to the Executive Committee of the WHO.

The Zika virus was first detected in the Americas in May 2015 in Brazil. It has since spread in Chan's words "explosively" to 22 countries and territories in the hemisphere. There have also been a handful of cases in the mainland United States, but all of those have been in people who recently returned from Zika-affected areas.

"Arrival of the virus in some places," Chan says, "has been associated with a steep increase in the birth of babies with abnormally small heads and in cases of Guillain-Barre syndrome [a neurological condition]."

Another top official at the briefing, Dr. Marcos Espinal, the director of Communicable Diseases and Health Analysis at the WHO's Pan American Health Organization, noted that those neurological conditions have so far only been found in Brazil. Espinal said this raises the possibility that other factors in addition to Zika may be causing the severe health problems. Some researchers have wondered whether someone who gets infected with Zika and dengue at the same time, for instance, may suffer worse effects.

Chan and WHO were sharply criticized for moving too slowly to address the 2014 Ebola outbreak in West Africa. Some public health experts say the world's health agency has not been moving fast enough on Zika. Georgetown professors [Lawrence Oglethorpe Gostin (born 1949)] and [Dr. Daniel Richard Lucey (born 1955)], writing this week in JAMA, said, "WHO headquarters has thus far not been proactive, given potentially serious ramifications."

Chan's emergency committee is meeting on Monday to determine what measures should be taken both in the affected countries and elsewhere to address the outbreak.

Dr. Espinal said the virus is expected to spread to other parts of the world where dengue — which is spread by the same mosquito — is also present.

He added that he expects this outbreak to grow from the current estimate of 1 million cases to 3 to 4 million cases before it's brought under control.

Because symptoms are typically mild, the severity of the threat has not been established. But as Chan said in the briefing in Geneva: "Questions abound. We need to get some answers quickly."

2016 (Jan 29)

https://www.newspapers.com/image/269314043/?terms=zika&match=1

2016-01-29-the-orlando-sentinel-pg-a6-clip-zika.jpg

2016 (Jan 29) - NYTimes : "Vaccine for Zika Virus May Be Years Away, Disease Experts Warn"

By Katie Thomas  /   Jan. 29, 2016   /  Source : [HN01V1][GDrive]   

As public health officials warn that the Zika virus is swiftly spreading across the Americas, the search is on to develop a vaccine to halt the disease, which could infect as many as four million people by the end of the year and has been linked to severe birth defects.

But even as a host of companies have announced plans to develop a vaccine, disease experts say it could be years — maybe as long as a decade — before an effective product makes its way to the public. Not only are scientists still learning about the virus, which until recently was viewed as relatively benign, but any vaccine must go through rigorous testing to ensure that it is safe and effective.

“It’s very important for people to be realistic,” said Dr. Jesse Goodman, a professor of medicine and infectious disease at Georgetown University, who between 2003 and 2009 was the director of the center at the Food and Drug Administration that approves vaccines. “It is a complex process, and for Zika, it hasn’t been on the map until this exploded in Brazil.”

Researchers are not only exploring ways to develop a vaccine but are also hoping to create a rapid test that would detect the presence of the virus’s antibodies.

But for both the vaccine and test research, experts say most drug companies have been reluctant to invest in drugs or treatments for diseases in the developing world unless they see a financial reward.

Brazil has been grappling with the virus since the first case appeared in May 2015, and it has since spread to more than 20 other countries in the region, according to the World Health Organization, which on Thursday rang an alarm about the disease. Public health officials are particularly worried that Zika leads to a condition known as microcephaly, in which infants are born with abnormally small heads and damaged brains. Although researchers have not conclusively identified Zika as the cause, the number of babies born in Brazil with microcephaly has risen sharply along with the spread of the virus. Zika was first identified in 1947 in Uganda, but it rose to international attention in 2007, when an outbreak was identified in the Pacific islands.

Two major vaccine makers, the British company GlaxoSmithKline and Sanofi Pasteur, a French manufacturer, said this week that they were looking into the feasibility of developing a Zika vaccine by building on previous successes with other diseases.

GlaxoSmithKline developed a vaccine for Ebola, which showed success in early clinical trials and is still being tested. Last year, Sanofi received approvals for the world’s first vaccine for dengue, which is closely related to Zika. However, Sanofi sounded a note of caution this week, even as it said it would look into a Zika vaccine. “There are too many unknowns about Zika to reliably judge the ability to research and develop a vaccine effectively at this time,” it said in a statement.

A handful of smaller companies have also said they are working on Zika vaccines, some on more aggressive timelines. One team, a collaboration between [Inovio Pharmaceuticals, Incorporated], the South Korean company [GeneOne Life Science, Inc.] and academic researchers in Canada and the United States, has said its product could be ready for emergency use by this fall. Two other companies, Hawaii Biotech and the [Protein Sciences Corporation], also announced plans for a Zika vaccine.

Meanwhile, public health officials said government researchers were working on at least two approaches to a vaccine and hoped to begin testing one of them in early clinical trials by the end of this year. That approach is a DNA vaccine method, which creates virus-like particles when it is placed into cells. The method was tried in a vaccine for West Nile, a related virus, and was found to be safe in early trials, but never progressed because the National Institutes of Health couldn’t find a company willing to develop it further, said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases at the N.I.H.

Researchers will try the same approach with Zika by inserting a Zika gene into the same platform, in place of the West Nile gene. “I do not anticipate that we will have any problem partnering with pharmaceutical companies now,” he told reporters Thursday, referring to Zika.

Dr. Fauci added, however, “While these approaches are promising, it is important to understand that we will not have a widely available, safe and effective Zika vaccine this year and probably not even in the next few years.”

In a telephone interview Friday, Dr. Fauci said several factors could affect how long it would take for a vaccine to be approved, including how rampantly the disease spreads. A fast-moving disease, for example, would more quickly permit researchers to see if the vaccine is working.

Dr. Fauci said researchers were also eager to develop a rapid test to assess whether a person had been infected with Zika, to help pregnant women, in particular, find out if they have had the disease. A majority of people who are infected with Zika do not show any symptoms, and existing tests only seek out the active virus, which lasts in the body only for a short time. An easier-to-use test that looks for antibodies specific to Zika would be more useful, Dr. Fauci said, and he said academic researchers and some companies were exploring this avenue.

But even if the vaccine shows early success, drug companies — which have the capacity to manufacture large quantities of the product — must take an interest, he said, noting that earlier efforts to develop vaccines for West Nile and chikungunya, a related disease, have failed for lack of interest on the part of drug makers.

“It wasn’t perceived as a big economic boon for them to do that,” he said Friday.

Public health advocates have long criticized pharmaceutical companies for failing to invest in remedies for diseases that primarily afflict people in developing countries or ones that do not have a reliable market.

“What the private sector is most interested in are developing treatments for diseases that are known, common and predictable,” said [Lawrence Oglethorpe Gostin (born 1949)], a Georgetown law professor who co-wrote an article this week in the medical journal JAMA calling on officials to aggressively combat Zika. He has called for more public-private partnerships to give pharmaceutical companies better incentives to develop treatments for neglected diseases.

“Most of these diseases are unpredictable,” he said. “They’re sporadic, often they flare up in poor countries, and then they go away.”

Others said the Zika outbreak should be a lesson to public health officials not to ignore low-profile diseases. “We need to have better tools for these diseases,” said Dr. Carolina Batista, the Latin America medical manager for the Drugs for Neglected Diseases initiative, who is based in Brazil. “We should not wait for the crisis to come and then start.”  

2016 (Jan 29) - NYTimes : "Opinion : How Scared Should You Be About Zika?", written by  Michael T. Osterholm

Written by [Dr. Michael Thomas Osterholm (born 1953)]   /   PDF source : [HN024W][GDrive] 

See Zika virus epidemic (2015-2016)    /   

Image :  [HN024X][GDrive]

Every time there is a major infectious disease outbreak that scares us — Ebola in West Africa in 2014, Middle East Respiratory Syndrome (MERS) on the Arabian Peninsula in 2012 and in South Korea in 2015, and now the Zika virus in South and Central America and the Caribbean — government leaders, the public and the news media demand explanations, guidance and predictions, and often express indignation that not enough was done to prevent it. Today everyone is asking about Zika: How did this crisis happen, and what do we need to do to make it go away? We immediately forget about the outbreak that came before it, and don’t plan for the ones we know are on the horizon. Almost no one wants to talk about Ebola or MERS now, or what we have or haven’t done to try to prevent an ugly recurrence.

When it comes to diseases, we have a very short attention span, and we tend to be reactive, rather than proactive. Instead of devoting ourselves to a comprehensive plan to combat microbial threats, we scramble to respond to the latest one in the headlines. There are lessons from previous infectious disease outbreaks that could and should have left us much better prepared than we are.

First, the mosquito that transmits this disease, the species Aedes aegypti, has never been more numerous or lived in more locations. Think of Aedes aegypti as the Norway rat of mosquitoes; it has evolved to live in close quarters with humans, and the trash that humans create. This is quite different from most other species of mosquitoes, like the ones that transmit West Nile virus, which tend to lay their eggs in marshes, rice fields, ditches, the edges of streams and small, temporary rain pools.

The world has changed dramatically in the past 40 years with regard to increasing the habitat for Aedes aegypti breeding. An explosion of plastic and rubber solid waste now litters virtually all parts of the globe, particularly in the developing world. Non-biodegradable containers, used tires and discarded plastic bags and wrappers — whether in the backyard, a roadside ditch or an abandoned lot — make ideal habitats for these mosquitoes to lay their eggs. All they need is a little rainfall.

This species is currently present in 12 states in the United States, mostly in the Southeast. But its close cousin, Aedes albopictus, known as the Asian tiger mosquito, came to the United States in the 1980s and is now in some 30 states, including the entire Eastern Seaboard up to New York City. For now, fortunately, this species does not appear to be a significant factor in the transmission of Zika to humans. What we in North America have to worry about is whether the Asian tiger mosquito can become a more effective transmitter of the virus to humans. If that happened, we would face a very serious risk of an outbreak here.

One of the solutions to this problem is called “vector control.” It involves both eliminating the places where these mosquitoes breed, or chemically treating those sites, and spraying chemical insecticides to kill adult mosquitoes, or at least keep them away from where humans live, work and play. We must clean up the garbage to have any hope of reducing Zika infections in humans.

From the 1950s through the 1970s, there was a major initiative to eradicate Aedes aegypti from the Americas by public health organizations, nonprofits and national governments. It almost succeeded. In part, that was because eliminating these mosquitoes’ breeding sites was much simpler before the spread of plastic and rubber waste. But governments and nonprofit agencies decided too early that the job had been done, and dismantled these programs to save money. Now the mosquito is back.

This is not new science or new policy. Now we’ve got an outbreak on our hands, and although the symptoms of Zika itself are absent to mild for most, for some there can be devastating consequences to infection. An increasing number of infected women have given birth to babies with microcephaly, which causes small heads and brain damage. We’re learning that Zika can lead to Guillain-Barré syndrome, a dangerous autoimmune disorder that can cause paralysis. Some believe we need more scientific data to confirm these more severe manifestations. I don’t agree; I believe the evidence is already compelling.

We shouldn’t have needed thousands of babies born with severe birth defects or people of all ages developing life-threatening autoimmune paralysis to remind us that mosquitoes pose a serious health threat. Dengue viruses, which are also transmitted by these two mosquito species, caused 2.3 million cases of dengue fever and far more serious dengue hemorrhagic fever in 2013 in the same countries in the Americas that have been, or will be, affected by Zika. These included more than 37,000 severe illnesses and 1,300 deaths. And yet these numbers hardly raised an eyebrow in the United States. If we had paid more attention then, we might be more prepared now.

Zika is here to stay in the Western Hemisphere; it will be part of life for many years to come. Even if we make vector control efforts a major initiative, it will only reduce, but not eliminate, the risk of Zika. What we need next, urgently, is a vaccine.

Some critics are suggesting that such vaccine research for Zika should have been done years ago, but this isn’t entirely fair. It was only in the past two years that there was any indication this virus could cause serious human disease. Now we have to catch up. But it’s going to be complicated. If Guillain-Barré syndrome is indeed caused by the patient’s immune response to the virus, as happens with other infectious diseases, could the vaccine itself put us at risk? This will take careful research to determine. And it will take time.

The point is, we should have anticipated that the large increase in mosquitoes would create a major health crisis. Just as we should have anticipated that a deadly hemorrhagic disease caused by the Ebola virus would emerge one day from the remote forests and threaten the vast slums of the rapidly growing megacities of Africa. We should now anticipate that the MERS virus will result in more deadly outbreaks outside of the Arabian Peninsula, as it did in Seoul, South Korea. We should anticipate that viruses such as Venezuelan equine encephalitis may spread from their jungle homes and be even more deadly than Zika.

Even more than these viruses, we should be afraid of a planet-wide catastrophe caused by influenza. The best way to avert a pandemic is to develop a game-changing universal influenza vaccine. All these crises are largely predictable and we can do much in advance to lessen the effects and diminish the spread. And believe me, the cost of acting now will be infinitely less than the cost of not acting in the long run.

2016 (Feb) - Atheric Pharmaceutical, LLC created by Dr. Robert Malone

Website ..  March 2016 : https://web.archive.org/web/20160323154754/http://www.atheric.com/  

June 12 2016 : https://web.archive.org/web/20160612035610/http://www.atheric.com/ 

Oct 19 https://web.archive.org/web/20161019000059/http://www.atheric.com/ 

.... reference to NIH work ... https://web.archive.org/web/20160909014847/https://directorsblog.nih.gov/2016/09/06/treating-zika-infection-repurposed-drugs-show-promise/ 

2016 (Feb 03) - NYTimes : "Fighting the Zika Virus / By NYTimes The Editorial Board"

Source : [HN01NH][GDrive

[Dr. David Lowell Heymann (born 1946)], chairman of the World Health Organization’s Zika emergency committee, and Dr. Margaret Chan, the W.H.O.’s director general.   Credit...  Salvatore Di Nolfi/Keystone, via Associated Press [HN01NI][GDrive]

The World Health Organization and its director general, Dr. Margaret Chan, were right to declare the Zika virus an international public health emergency, even if its suspected link to severe birth defects has not been proved. The mosquito-borne disease is a serious threat: It is usually so mild as to be undetectable in adults, yet as it has exploded across South and Central America it has been followed by a surge in babies born with underdeveloped heads, a condition called microcephaly.

The emergency designation will galvanize coordinated international monitoring and action of the sort that was tragically missing in the first months of the Ebola pandemic. The W.H.O.’s decision, however, could reduce travel to affected countries, which would be an economic burden. Brazil, where Zika made its first major appearance in the Western Hemisphere last May, is especially fearful that visitors will stay away from the Olympic Games in August. It cannot let that prevent it from being completely transparent about this serious threat and the steps it is taking to protect people.

In Latin America, where many nations outlaw abortion, some governments have advised that pregnancies be delayed, which can create only greater anxiety for women who have sadly limited control over such decisions.

All of this adds urgency to the work of medical researchers investigating any possible link between microcephaly and Zika infection, for which there is no cure. And it puts a heavy responsibility on the W.H.O. and institutions like the Centers for Disease Control and Prevention and the Pan American Health Organization to give clear and realistic guidance on how to avoid infection. The C.D.C. has issued a list of countries pregnant women should try to avoid visiting and has advised travelers on how to protect against mosquito bites.

Fighting Zika will not be easy. Like Ebola, it is nurtured by heat, humidity and poverty, conditions that can be intensified by globalization and global warming. Unlike Ebola, Zika is primarily spread by a mosquito, the Aedes aegypti, which is rampant in hot climates. The risk of a major outbreak in the United States is low because of effective mosquito-control programs and air-conditioning.

A vaccine or an effective treatment is still a long way off. Immediate responses, like increasing access to birth control and abortion, face stiff legal and cultural resistance in the affected region. That leaves mosquito control as the most effective weapon available now. One method being tried in Brazil is to release Aedes mosquitoes that are genetically modified to produce self-destroying offspring.

These and other measures should gain momentum now that Zika has been declared an emergency. That is essential not only to protect women and their babies, but also for improving the global response to other obscure germs waiting their turn in some hot, humid place.

2016 (Feb 08) - C-SPAN: White House briefing, Zika (Fauci Schuchat)

Live link :  https://www.c-span.org/video/?404432-1/white-house-briefing-zika-virus   /  Saved 1080p video : [HM007C][GDrive

Notes (Housatonic ITS Research notes) :
  • accidentally said "ebola" once when talking about "zika"
  • Already understood concept of "molecular fingerprint" that suggests virus came to south America across the pacific ocean
  • No other causes offered about microcephaly ... no level of uncertainty suggested ...
  • Did not communicate that the rates are already decreasing ...
  • Already talking about a vaccine
  • Said south america noticed rates "going up in the fall" ...  Which is consistent with data... 

2016 (Feb 10) US Congressional briefing, "Global Zika Virus Outbreak" (Fauci Frieden)

Live Link :  https://www.c-span.org/video/?404389-1/hearing-global-zika-virus-outbreak    /  Saved 1080p video : [HM0077][GDrive

Note behind Fauci - Dr. James Carroll Hill (born 1941)   

NOTE  - On Feb 12 2016,   ... this was happening at same time as Zika fear ...  (file erroneously called 2016-02-16-cspan-org-hearing-biological-threat-preparedness-img-1 )

2016 (Feb 13) - C-SPAN, Washington Journal : National and International Response to Zika Virus (with Alexandra Phelan)

https://www.c-span.org/video/?404169-4/washington-journal-alexandra-phelan-zika-virus

see Alexandra Louise Phelan (born 1986)  

FEBRUARY 13, 2016

Alexandra Phelan talked about federal and international public health efforts to contain the Zika virus outbreak. A video clip was shown of testimony by Centers for Disease Control Director Dr. Tom Frieden February 10, 2016

2016 (Feb 16) - The Minnesota Daily - "Osterholm, officials prep 'playbook' for Zika virus; School leaders have constructed strategies to address a range of global infectious diseases."

Saved source : [HN024Y][GDrive]   /  by  Hannah Weikel  /  Published February 16, 2016

Mentioned : Dr. Michael Thomas Osterholm (born 1953)   /   Zika virus epidemic (2015-2016)

Image :  [HN024Z][GDrive]

In a small, first-floor office on the University of Minnesota campus, Jill DeBoer plans for worst-case scenarios.  DeBoer, the director of the Academic Health Center’s Office of Emergency Response, has bookshelves holding binders filled with detailed response plans — “playbooks” — for every disease that has been a threat to students since the team organized in 2004. 

DeBoer said similar groups formed nationwide after the anthrax attacks following 9/11, but those groups have shifted in recent years to prepare for more than bioterrorism — be it a case of meningitis on campus, a bridge collapse or something that hasn’t yet been seen. 

The AHC-OER is now forming a Zika virus playbook, DeBoer said. The team has sent information and travel warnings to all University students studying in affected countries. 

“The first partner we call is the GPS Alliance because often these infectious disease issues start off in other countries, and so with H1N1, with Ebola, with Zika, that’s our first call,” DeBoer said.

There’s a specially tailored response team for every scenario, she said. The size of the team varies with the scope of the threat, ranging from a handful of people to more than 50. Each team member has two backups.

DeBoer said the AHC-OER works with the Minnesota Department of Health — which has its own emergency team — and monitors the spread of diseases around the world.    “We have to be prepared for anything,” she said. “I feel our response system should be able to coordinate and respond to almost anything.”

School of Public Health and Medical School professor [Dr. Michael Thomas Osterholm (born 1953)], who is also the director of the University’s Center for Infectious Disease Research and Policy, addressed global infectious disease preparedness in a lecture last week. 

“The next pandemic is going to happen,” he said at the talk. “It could happen tomorrow; it could be happening today.”

[Dr. Michael Thomas Osterholm (born 1953)] said no group is ready for the next pandemic because global systems are disjointed and broken.   “There are so many holes in this ship,” he said at the lecture. “Even if we bail it out as much as we can with all our strength, we might still be sinking.”

[Dr. Michael Thomas Osterholm (born 1953)] said influenza is the biggest threat, and when — not if — an outbreak happens in Minnesota, there won’t be enough vaccines to go around, he said.  “Today, many of our key drug producers are offshore. If we have a pandemic that interrupts travel and trade, that will be a challenge,” he said. “I don’t care how prepared you are at a state level, if you have a vaccine or not makes all the difference.”

University biochemistry junior Melanie Raphael attended the lecture and said she was worried that people know too little about the importance of vaccines.

She said college students lack awareness of diseases that threaten other parts of the world.  “It took me a while to even hear about [the Zika virus],” Raphael said. “Here in college, we are kind of isolated from the rest of the world.” 

Infectious diseases can come to the U.S. from other parts of the world through travel, like what’s happened with the Zika virus, said MDH infectious disease epidemiologist Richard Danila.     “We are always on the lookout for the next big event, whether that’s an influenza virus or a pandemic like Zika,” he said.

When a new disease makes headlines, it’s hard for scientists to prevent misinformation in the media, Danila said. 

MDH strategically shares information with Minnesotans to control panic due to bad information, said Cheryl Petersen-Kroeber, deputy director of MDH Emergency Preparedness and Response.   “Epidemiologists base their decisions on the science they have at the time,” Petersen-Kroeber said. “Sometimes it’s hard because the science is always changing.”

2016 (February 22 issue) - Chemical & Engineering News : "Gearing Up To Fight Zika : Researchers scramble to develop tools and treatments to combat the mosquito-borne virus"

Bethany Halford / C&EN Boston  /  C&EN, 2016, 94 (8), pp 33–36February 22, 2016  / Source (this was paid content) - [HP00AH][GDrive]

Mentioned :  Dr. Thomas Patrick Monath (born 1940)   /  Sina A Bavari (born 1959)   /  NewLink Genetics Corporation  /  Zika virus epidemic (2015-2016)   /   Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960)  /  

When the Pan American Health Organization put out an alert last May about the first confirmed cases of Zika virus infection in Brazil, the news barely registered. After all, compared with other mosquito-borne viruses, such as potentially life-threatening dengue and yellow fever, Zika seemed pretty harmless. Only 20% of people infected with Zika even become ill, and their symptoms tend to be mild—fever, rash, joint pain, and conjunctivitis.

But in January, nine months after the organization raised the alarm, doctors in Brazil reported a disturbing trend that coincided with Zika’s spread across the country. Since October 2015, more than 4,000 babies in Brazil had been born with abnormally small heads and brains—a rare condition known as microcephaly. Although further analysis lowered that figure by 462 cases, the sharp rise nonetheless has experts worried that Zika could be to blame. For comparison, Brazil reported just 147 cases of microcephaly in 2014.

Zika is also being blamed for an uptick in cases of Guillain-Barré syndrome, a potentially life-threatening disorder in which the body’s immune system attacks the central nervous system and causes paralysis. As with microcephaly, the evidence connecting Zika and Guillain-Barré is still circumstantial. Nevertheless, the link is strong enough for the World Health Organization to declare the Zika outbreak a public health emergency of international concern.

Margaret Chan, WHO’s director-general, said earlier this month that the virus is “spreading explosively” through the Americas, with cases of active virus transmission in at least 26 countries and territories in the Americas. Panic over the virus has prompted health officials in some countries to take the drastic measure of advising women to delay pregnancy for months or longer. In El Salvador, Deputy Health Minister Eduardo Espinoza asked women to avoid becoming pregnant until 2018.

With Zika making headlines for the past month, scientists have been scrambling to get a handle on the virus. Industry, government, and academic scientists have all announced efforts to develop and test treatments and vaccines. But the path ahead for these researchers is long and full of pitfalls. Even though Zika has been around for almost 70 years, surprisingly little is known about the virus and its basic biology. A PubMed search for “Zika virus” turns up mostly case studies.

What we do know is that Zika is a flavivirus, a member of the same family as dengue, yellow fever, and West Nile virus. Zika is primarily transmitted via bites from infected mosquitoes, but in recent weeks doctors have reported that the virus can be sexually transmitted as well.

It was first identified in a monkey in Uganda’s Zika forest in 1947, but only a handful of human Zika cases were reported until a 2007 outbreak in Micronesia’s Yap Island. An outbreak in French Polynesia followed six years later. Last November officials in that country reexamined the cases of microcephaly that followed the outbreak. Before the outbreak, about one case of microcephaly was reported each year. In 2014–15, officials found 17 cases of fetuses and infants with “central nervous system malformations,” which includes microcephaly.

As the case connecting Zika to serious health effects builds, the world would love a vaccine or treatment for the virus. But because so few have studied Zika, drug developers currently have few tools to work with. For example, there’s no commercially available, U.S. Food & Drug Administration-approved test to screen for Zika virus.

Tracking Zika in people is hard because it’s difficult to determine that they’re infected with Zika and not a related flavivirus or that they’re not infected with more than one virus, says Priscilla L. Yang, a flavivirus expert at Harvard Medical School. Simultaneous infection with Zika and another virus could cause health effects that haven’t been seen before.

Scientists can use polymerase-chain-reaction-based methods to distinguish Zika from other flaviviruses. But those tests are accurate only during the short window patients still have the virus in their system—about seven days after infection. By the time a patient has symptoms that warrant a visit to the doctor, the virus is no longer circulating in their bloodstream, Yang notes.

Another option is to look for antibodies against the virus. But Zika and dengue are closely enough related that antibodies to Zika also recognize dengue and vice versa. Making a definitive diagnosis based on antibodies is possible but becomes time-consuming and laborious, Yang says.

For scientists who have compounds that might be effective against Zika, actually testing them has been tough. “We have small molecules that seem to be broadly acting against dengue and West Nile virus,” Yang says. “We want to test them, but getting access to the live virus has been hard.” She’s heard that certain labs known to have the Zika virus have been bombarded with hundreds of requests from researchers.

Even if someone manages to access the live virus and can find a compound that kills it in cells, the researcher will hit another roadblock: To date, no one has published practical animal models of Zika virus to screen potential therapies against. Yang points to a paper from the 1970s in which scientists did an intracranial injection of Zika virus in newborn mice, but she notes that is a poor model because many small molecules can’t slip past the blood-brain barrier.

“We’re basically starting from scratch on this one, unfortunately,” says [Sina A Bavari (born 1959)], chief scientific officer (CSO) at the U.S. Army Medical Research Institute of Infectious Diseases. Bavari and colleagues are currently working with pharma companies to see if they have any compounds that inhibit Zika replication in cells.

They’re primarily interested in compounds that have passed the hurdles of Phase I or Phase II clinical trials but are sitting idle for business reasons. That’s because it can take upward of a year and a half just to get a new compound ready for Phase I. “My worry is that by the time we get something out the door, this outbreak will have already burned out,” Bavari says.

Scientists are also grappling with this question: If only 80% of people infected with Zika have symptoms, who would get the treatment? The most vulnerable patients are pregnant women, but Bavari points out, there’s a high bar when it comes to approving a medication that can be given to them. “They don’t even want to drink caffeine,” he says.

Other scientists are working to develop a vaccine against the Zika virus. Earlier this month President Barack Obama said he would ask Congress for $1.8 billion to combat Zika at home and abroad. Of those funds, $200 million would be used for vaccine development. The U.S. National Institute of Allergy & Infectious Diseases, Sanofi Pasteur, and [NewLink Genetics Corporation] are among the heavy hitters in the vaccine field who’ve said they’ll step up to the plate.

Even so, it could take three to five years before a vaccine is ready, experts say. [Dr. Thomas Patrick Monath (born 1940)], CSO of [NewLink Genetics Corporation]'s infectious disease division, led that firm’s efforts to develop an Ebola vaccine and was CSO at Acambis, where he worked on vaccines for dengue and yellow fever. Monath tells C&EN he thinks a large field trial of 10,000 to 20,000 people across multiple sites will be necessary to determine efficacy once a Zika vaccine is developed. “Only after those trials would you contemplate doing studies in pregnant women,” he says.

Monath also says because so many people who are infected with Zika never show any symptoms, it is more difficult to determine whether the vaccine has actually prevented infections. Still, he thinks a large enough trial should be conclusive.

But some scientists say the emphasis on vaccines is misplaced. “We just don’t know enough about Zika virus right now to run around and vaccinate people,” Bavari says. “Understanding the immunopathology and immunology behind it would be really prudent before starting a full vaccination program.”

Harvard’s Yang says developing a vaccine for every emerging virus is impractical. “Vaccines are, for the most part, specific. You have one virus, and you have one vaccine for it,” she explains. “I don’t think we’ll ever have the luxury of enough resources to get a vaccine against every single possible emerging virus or enough time to do it in a reactive way.”

One area that’s not getting as much attention, she says, is development of broadly acting antivirals that could keep a virus in check while the immune system fights it off. Classical antivirals go after a single viral enzyme, but viruses are quick to develop resistance to them. “If people could identify targets that have the potential to be effective against multiple viral pathogens, it could be game-changing,” Yang says.

[Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960)], a Vanderbilt University professor who works on antivirals, agrees. “There are so many viruses out there. We need to be working on a much more broad-spectrum approach to infectious disease,” he says. “If we can develop more tools to combat broad categories of viruses, I think we would be much better off than we are today.”  [ Note - [Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960) passed July 25, 2017 ]

In the meantime, scientists agree that the research community needs to be more organized if it’s going to have a real shot at combating Zika. Yang thinks the first steps should be figuring out how to get the necessary reagents to the labs that need them and agreeing on standards so they can compare results and learn from each other’s work. “If you actually want to have some sort of impact, we all need to work together,” she says. In an encouraging sign, earlier this month, major scientific institutions and top research journals agreed to share data relevant to Zika virus.

Bavari agrees scientists need to be better at organizing their efforts, but he has doubts about the direction the community is taking. “The outbreak is moving so quickly that I am worried people will jump and we won’t do the correct research,” he says. 

Recalcitrant Mosquito Blamed For Zika’s Spread

With a treatment or vaccine for Zika potentially years away, countries are relying on mosquito control to curb the virus’s spread. Aedes aegypti mosquitoes, which inhabit tropical and subtropical regions, have been named as the culprit in transmitting the virus.

But getting rid of Aedes aegypti is extremely difficult because the mosquitoes don’t seem to be affected by most spraying regimens, says Joseph M. Conlon, an entomologist and technical adviser to the American Mosquito Control Association. According to Conlon, Aedes aegypti feed during the day, but pesticides must be sprayed at dawn or dusk. Also, mosquitoes like to come indoors to feed. So, unless pesticides are sprayed inside homes, chances are good they’re not getting to the insects.

These mosquitoes are very small, and you can’t feel the bites. “Oftentimes you don’t even know you’ve been bitten,” Conlon says.

To get rid of the biting bugs, it’s critical to eliminate any standing water. “I’ve seen Aedes aegypti breeding in discarded soda bottle caps,” Conlon says. “They’re survivors.”

Despite Aedes aegypti’s survival skills, the mosquitoes actually have a fairly limited flight range of about 150 meters. That has made some scientists suspect that because Zika has spread so quickly, the more common Culex mosquito may be transmitting the virus as well. The theory is currently being investigated.

“If that is true, that brings this to a whole different level,” Conlon says. Culex mosquitoes have a much larger range, he notes, but they can usually be controlled through common mosquito abatement programs. ◾

2016 (feb 24) - CSPAN  :  Zika Virus Response

https://www.c-span.org/video/?405208-1/hearing-global-zika-virus-outbreak

FWitnesses testified at a hearing on the federal response to the Zika virus and efforts to prevent further transmission. The panelists included Florida’s health secretary, representatives from the Centers for Disease Control, the National Institute of Allergy and Infectious Diseases, and the U.S. Olympic Committee. close 

2016-02-24-cspan-org-hearing-global-zika-virus-outbreak.pdf

2016-02-24-cspan-org-hearing-global-zika-virus-outbreak-img-1.pdf

2016 (Feb 25) - NYTimes video :  "U.S. President Obama on Vaccine for Zika"

President Obama said there is a “promising pathway” for developing a vaccine against Zika, adding that the virus is not, apparently, a very complicated one.

Video : [HN01NJ][GDrive]  

[HN01NK][GDrive]

2016 (March 02) - PLOS Neglected and Tropical Diseases : "Zika Virus: Medical Countermeasure Development Challenges"

Full saved PDF : [HP00C5][GDrive]   /    DOI:10.1371/journal.pntd.0004530 

[Dr. Robert Wallace Malone (born 1959)] 1,2*, Jane Homan 3, [Dr. Michael Vincent Callahan (born 1962)] 4, [Dr. Jill Glasspool-Malone (born 1960)] 1,2, Lambodhar Damodaran 5, Adriano De Bernardi Schneider 5, Rebecca Zimler 6,  James Talton 7, Ronald R. Cobb 7, Ivan Ruzic 8, Julie Smith-Gagen 9, Daniel Janies 5‡,   [Dr. James Miller Wilson V (born 1969)] 10‡, Zika Response Working Group

  1. 1 RW Malone MD LLC, Scottsville, Virginia, United States of America,  (* RWMaloneMD@gmail.com )
  2. 2 Class of 2016, Harvard Medical School Global Clinical Scholars Research Training Program, Boston, Massachusetts, United States of America,
  3. 3 ioGenetics, Madison, Wisconsin, United States of America,
  4. 4 Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America,
  5. 5 Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina, United States of America,
  6. 6 University of Florida, Department of Entomology and Nematology, Florida Medical Entomology Laboratory, Vero Beach, Florida, United States of America,
  7. 7 Nanotherapeutics, NANO-ADM Advanced Development and Manufacturing Center, Alachua, Florida, United States of America,
  8. 8 Analytical Outcomes, Washington Crossing, Pennsylvania, United States of America,
  9. 9 School of Community Health Sciences, University of Nevada, Reno, Nevada, United States of America,
  10. 10 Nevada  Center for Infectious Disease Forecasting, University of Nevada, Reno, Nevada, United States of America

Introduction

Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment.

[...]

2016 (Mar 11) - CDC Weekly MMR : "Increase in Reported Prevalence of Microcephaly in Infants Born to Women Living in Areas with Confirmed Zika Virus Transmission During the First Trimester of Pregnancy — Brazil, 2015"

Weekly / March 11, 2016 / 65(9);242–247  ;   On March 8, 2016, this report was posted online as an MMWR Early Release.  /   Saved PDF : [HG00GW][GDrive

Wanderson Kleber de Oliveira, MSc1; Juan Cortez-Escalante, MD2; Wanessa Tenório Gonçalves Holanda De Oliveira, MSc1; Greice Madeleine Ikeda do Carmo, MSc1; Cláudio Maierovitch Pessanha Henriques, MD1; Giovanini Evelim Coelho, PhD1; Giovanny Vinícius Araújo de França, PhD1 

Summary

Table 1 :  [HG00GX][GDriveTABLE. Average annual number of full-term infants reported with microcephaly* during 2000–2014 compared with 2015, prevalence of microcephaly in 2015, and number of states reporting confirmed transmission of Zika virus,† by region — 19 states, Brazil, 2015 
Figure 1 : [HG00GY][GDriveFIGURE 1. Locations of nine states with reported cases of microcephaly in 2015 exceeding 3 standard deviations and three states exceeding 20 standard deviations above the mean number of cases reported annually during 2000–2014 — Brazil, January 1, 2015–January 7, 2016 
Figure 2 : [HG00GZ][GDriveFIGURE 2. Number of reported cases of microcephaly* in full-term newborns following laboratory-confirmed Zika virus transmission§ — Pernambuco, Paraíba, and Bahia states, Brazil, 2015

2016 (Mar 26) - Austin-American Statesman - "Zika Virus - Genetic sleuths uncover Zika's viral secret"

Full newspaper page : [HN022T][GDrive]   /  Newspaper clip : [HN022U][GDrive]    /   Interesting quote :

2016 (April 09) - Peter Hotez issues dire warning of microcephaly ; Dr. Jill Glasspool Malone issues a "Look what Atheric did" comment!

http://outbreaknewstoday.com/zika-hotez-gives-dire-warning-microcephaly-on-the-gulf-coast-would-be-public-health-equivalent-of-katrina-37872/

2016-04-09-outbreaknewstoday-com-zika-hotez-gives-dire-warning-microcephaly-on-the-gulf-coast-would-be-public-health-equivalent-of-katrina.pdf

2016-04-09-outbreaknewstoday-com-zika-hotez-gives-dire-warning-microcephaly-on-the-gulf-coast-would-be-public-health-equivalent-of-katrina-img-1.jpg


Jill Glasspool Malone

APRIL 10, 2016 AT 7:29 AM

I hope Dr. Hotez, a man I greatly admire, will take a peak at what our company has developed. We have been working 24/7 for months -and have clinical trials planned and developed for anti-virals against Zika virus. Our company is rapidly working and has one part of the solution. Re-purposed, currently marketed anti-malarial drugs are the most suitable drug candidates for immediate clinical testing for use in protecting against the Zika Virus infection, including Zika Virus fetal syndrome and GBS. Provisional patents filed with the USPTO. These compounds are autophagy inhibitors, and in vitro testing has demonstrated efficacy. The lead candidates are approved by the FDA for use during pregnancy, and cross the placenta enabling clinically significant pharmacodistribution to both mother and fetus. What Atheric Pharmaceutical has accomplished so far:

Research and Meta-analysis of drug compounds, review paper published in PLoS NTD. Patents filed, with due diligence performed for field of use.

In-vitro screening of compounds ongoing, with lead drugs candidates identified within range for prophylactic and therapeutic indicators, using High Content Imaging ZIKV/Vero infection/foreskin fibroblast assays. FDA involvement, with pre-IND meeting initiated. Two different clinical Trials in development, with clinical site selection ongoing in two countries. Our results so far are being written up and will be published as soon as we can find time to write them up.

2016 (April 11) - USA Today : "'Scarier than we initially thought': CDC sounds warning on Zika virus"

Gregory Korte, USA TODAY /  With Dr Anthony Stephen Fauci (born 1940)  ; Dr. Anne Schuchat (born 1960) 

Source : [HM001V][GDrive]  

Dr. Anne Schuchat, principal deputy director of the Centers for Disease Control and Prevention, and Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, speak about the Zika virus during a press briefing in the Brady Press Briefing Room at the White House on April 11, 2016.[HM001W][GDrive]

WASHINGTON — Public health officials used their strongest language to date in warning about a Zika outbreak in the United States, as the Obama administration lobbied Congress for $1.9 billion to combat the mosquito-borne virus.

"Most of what we've learned is not reassuring," said [Dr. Anne Schuchat (born 1960)], the principal deputy director of the Centers for Disease Control and Prevention. "Everything we look at with this virus seems to be a bit scarier than we initially thought.

As summer approaches, officials are warning that mosquito eradication efforts, lab tests and vaccine research may not be able to catch up. There are 346 cases of Zika confirmed in the continental United States — all in people who had recently traveled to Zika-prone countries, according to the most recent CDC report. Of those, 32 were in pregnant women, and seven were sexually transmitted.

But in Puerto Rico, the Virgin Islands and American Samoa, the virus is now being transmitted locally. Of the 354 cases in the territories, only three are travel-related, and 37 involved pregnant women.

Schuchat said the virus has been linked to a broader array of birth defects throughout a longer period of pregnancy, including premature birth and blindness in addition to the smaller brain size caused by microcephaly. The potential geographic range of the mosquitoes transmitting the virus also reaches farther northward, with the Aedes aegypti species present in all or part of 30 states, not just 12. And it can be spread sexually, causing the CDC to update its guidance to couples.

And researchers still don't know how many babies of women infected with Zika will end up with birth defects, or what drugs and vaccines may be effective.

"This is a very unusual virus that we can't pretend to know everything about it that we need to know," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "I'm not an alarmist and most of you who know me know that I am not, but the more we learn about the neurological aspects, the more we look around and say this is very serious."

That assessment, delivered to reporters at the White House on Monday, comes the week after the White House informed Congress it was moving more than $510 million previously earmarked to combat Ebola in Africa with Zika prevention efforts closer to home.

"What I've done is take money from other areas of non-Zika research to start. We couldn't just stop and wait for the money," Fauci said. "When the president asked for $1.9 billion, we needed $1.9 billion."

As Congress stalls funding, White House will move Ebola funds to Zika

White House press secretary Josh Earnest said the newest warning "hopefully serves as motivation for members of Congress to pay attention to this important topic."

But congressional Republicans accused the White House of trying to "politicize" Zika. "We’re glad the administration has agreed to our request to use existing Ebola funds to address the Zika epidemic," said Doug Andres, a spokesman for House Speaker Paul Ryan, R-Wis. "If additional Zika resources are needed those funds could and should be addressed through the regular appropriations process."

But Democrats said the potential human toll of the virus can't wait on the budget cycle.

“Down the road we'll find a vaccine. Down the road we will be able to manage this problem," said Sen. Bill Nelson, D-Fla., on the floor of the Senate Monday. "But in the meantime there's a great deal of trauma (and) some extraordinary heartbreak to some families.”

Zika has been known to exist since 1947, but was long considered to be a minor disease that causes only mild illness.

Late last year, Zika became linked to a dramatic increase in Brazil of microcephaly, a birth defect in which babies are born with abnormally small heads. If Zika’s role in causing birth defects is confirmed, it would be the first mosquito-borne illness to cause microcephaly, and the first infectious cause of microcephaly to be identified in more than 50 years, according to the CDC.

Doctors have known for years that Zika virus is associated with Guillain-Barre syndrome, in which the body attacks its own nerves, causing paralysis.

But a study released Monday also links Zika to a second autoimmune disorder called acute disseminated encephalomyelitis. It resembles multiple sclerosis and involves a swelling of the brain and spinal cord. New studies also show that the Zika virus appears to hone in on brain cells and kill them.

The Centers for Disease Control announced Monday it was providing $3.9 million in emergency Zika funding to Puerto Rico. saying the number of cases there is doubling every week and could reach into the hundreds of thousands. The money will go to increased laboratory capacity.

"We are quite concerned about Puerto Rico, where the virus is spreading throughout the island," Schuchat said. "We think there could be hundreds of thousands of cases of Zika virus in Puerto Rico and perhaps hundreds of affected babies."

2016 (April 13) via MedicalXpress.com : "CDC: Zika definitely causes severe birth defects"

by By Mike Stobbe   /  Source : [HW009M][GDrive

Mentioned : Zika virus epidemic (2015-2016)   /   Dr. Thomas Hill Shepard (born 1923)   /   Dr. Thomas Randall Frieden (born 1960)  /  

Confirming the worst fears of many pregnant women in the United States and Latin America, U.S. health officials said Wednesday there is no longer any doubt the Zika virus causes babies to be born with abnormally small heads and other severe brain defects.

Since last year, doctors in Brazil have been linking Zika infections in pregnant women to a rise in newborns with microcephaly, or an unusually small skull. Most outside experts were cautious about drawing such a connection. But now the U.S. Centers for Disease Control and Prevention says enough evidence is in.

"There is no longer any doubt that Zika causes microcephaly," CDC Director [Dr. Thomas Randall Frieden (born 1960)] said. The CDC said it is also clear that Zika causes other serious defects, including damaging calcium buildups in the developing brain.

Among the evidence that clinched the case: Signs of the Zika virus, which is spread primarily through mosquito bites and can also be transmitted through sex, have been found in the brain tissue, spinal fluid and amniotic fluid of microcephaly babies.

The CDC and other health agencies have been operating for months on the assumption that Zika causes brain defects, and they have been warning pregnant women to use mosquito repellent, cover up, avoid travel to Zika-stricken regions and either abstain from sex or rely on condoms. Those guidelines will not change.

But the new finding should help officials make a more convincing case to the public for taking precautions. Some experts hope it will change public thinking about Zika the way the 1964 surgeon general's report convinced many Americans that smoking causes lung cancer.

"We've been very careful over the last few months to say, 'It's linked to, it's associated with.' We've been careful to say it's not the cause of," said the CDC's Dr. Sonja A. Rasmussen. "I think our messages will now be more direct."

The World Health Organization has made similar statements recently. A WHO official applauded the CDC report.

"We feel it's time to move from precautionary language to more forceful language to get people to take action," said Dr. Bruce Aylward, who is leading WHO's Zika response.

The CDC announced its conclusion in a report published online by the New England Journal of Medicine.

Zika has been sweeping through Latin America and the Caribbean in recent months, and the fear is that it will only get worse there and in the U.S. with the onset of mosquito season this spring and summer.

Public health authorities have mounted aggressive mosquito-eradication efforts, including extensive spraying and campaigns to eliminate the sources of standing water in which mosquitoes breed. Those can include flower pots, swimming pool covers, discarded tires and pet water bowls.

The virus causes only a mild and brief illness, at worst, in most people. But in the last year, infections in pregnant women have been strongly linked to fetal deaths and devastating birth defects, mostly in Brazil, where the Health Ministry said Tuesday that 1,113 cases of microcephaly have been confirmed since October.

So far, there have been no documented Zika infections in the U.S. caught from mosquitoes. Nearly 350 illnesses in the 50 states were reported as of last week, all linked to travel to Zika outbreak regions. Thirty-two of the victims were pregnant.

The CDC report comes at a time when health officials have been begging Congress to approve an emergency $1.9 billion in supplemental funding to fight Zika internationally and prepare for its spread in the U.S. Earlier Wednesday, top House Republicans said they will probably grant a portion of that, but probably not until September.

As the microcephaly cases rose in Latin America, a number of theories circulated through the public. Some claimed the cause was a vaccine given to pregnant women. Some suspected a mosquito-killing larvicide, and others wondered whether genetically modified mosquitoes were to blame.

Investigators gradually cast those theories aside and found more and more circumstantial evidence implicating Zika. CDC officials relied on a checklist developed by a retired University of Washington professor, [Dr. Thomas Hill Shepard (born 1923)], who listed seven criteria for establishing if something can be called a cause of birth defects.

Among other things, researchers found that the spike in microcephaly in Brazil involved women who were infected with Zika during the first or second trimester of pregnancy. They also discovered more direct evidence in the form of the virus or its genetic traces.

"In the case of Zika, if you get live virus from spinal fluid from microcephalic kids, that's pretty damn good evidence," [Dr. Thomas Hill Shepard (born 1923)] said in an interview.

Researchers still don't have some of the evidence they would like. For example, there are no published studies demonstrating Zika causes such birth defects in animals. There is also a scarcity of high-quality studies that have systematically examined large numbers of women and babies in a Zika outbreak area.

"The purist will say that all the evidence isn't in yet, and they're right," the WHO's Aylward said, "but this is public health and we need to act."

The hope is that the public will start paying closer attention. [...]

https://www.c-span.org/video/?408153-1/hearing-us-biodefense

APRIL 14, 2016

Biological Threats

Several federal agency leaders testified on the state of the nation’s defense against biological threats. Dr. Stephen Redd said the Zika virus was a new threat and supplemental appropriation was needed to effectively address the problem. Other threats identified included avian influenza, and bioterrorism. close 

Richard Hatchett M.D.

Acting Director

Department of Health and Human Services->Biomedical Advanced Research and Development Authority

2016 (April 29) - Orange Country Register :  San Juan Capistrano lab gets FDA OK to deploy Zika test -  A private laboratory in San Juan Capistrano has developed the first federally approved commercial test for the Zika virus."

PDF saved as : [HN02EX][GDrive]  

The test was approved under an emergency authorization from the Food and Drug Administration and will be made widely available to physicians as early as next week, according to Quest Diagnostics, which created it.

The Zika blood test, which must be administered within seven days of the onset of symptoms, is expected to hasten diagnosis. Currently, doctors have to coordinate with public health officials to have an analysis run at government labs, which has created a backlog. It can take two to three weeks for results, according to OC Health Care Agency.

“What this means is it broadens access by patients and physicians to quality testing in the United States as well as Puerto Rico,” said Wendy H. Bost, director of corporate communications for Quest.

The New Jersey-based testing giant employs 44,000 people, including 650 medical doctors and experts. The company reported $1.86 billion in revenue in the first quarter.

Most health insurance plans should cover the cost of the blood test. The patient list price is $500, while uninsured patients will pay $120, according to Bost.

The vast majority of people infected with Zika, which is most commonly spread by tropical mosquitoes, don’t get very sick. But it can be dangerous for the fetus of an infected pregnant woman.

The virus can cause birth defects, including microcephaly, which can cause abnormally small heads and brains. It’s also “very likely” the virus is causing paralysis in some adults, according to the Centers for Disease Control and Prevention.

Orange County has reported infestations of the tropical mosquitoes, but health officials have warned a Zika outbreak here is unlikely. The virus has spread rapidly across the Western Hemisphere, starting with an outbreak in May in Brazil. This week Brazilian officials reported the number of children born with microcephaly remained stable at 4,908.

Puerto Rico on Friday reported the first U.S. Zika-related death in a 70-year-old man who died in February. Authorities said the man recovered from the first Zika symptoms, then suffered internal bleeding from a related autoimmune condition. Colombia reported three similar deaths.

The first case of Zika in Orange County was reported in March when a Costa Mesa man in his 40s picked up the virus while traveling in Central America, then returned home. He did not become seriously ill and recovered by the time testing confirmed he had Zika.

“Not that many months ago, Zika was seen as a far-off tropical disease,” said Dr. Matthew Zahn, the top epidemiologist with the Health Care Agency. “Now it’s closer to home.”

The authorization from the FDA allows for testing at dozens of Quest labs, but so far the San Juan Capistrano location should meet demand when the test becomes available next week

2016 (May 10)  - NYTimes : "A Race to Unravel the Secrets of the Zika Virus"

Source : [HN01VU][GDrive

BALTIMORE — Leave it to the youngest person in the lab to think of the Big Idea.

Xuyu Qian, 23, a third-year graduate student at Johns Hopkins, was chatting in late January with Hongjun Song, a neurologist.

Dr. Song was wondering how to test their three-dimensional model of a brain — well, not a brain, exactly, but an “organoid,” essentially a tiny ball of brain cells, grown from stem cells and mimicking early brain development.

“We need a disease,” Dr. Song said.

Mr. Qian tossed out something he’d seen in the headlines: “Why don’t we check out this Zika virus?”

Within a few weeks — a nanosecond compared with typical scientific research time — that suggestion led to one of the most significant findings in efforts to answer a central question: How does the Zika virus cause brain damage, including the abnormally small heads in babies born to infected mothers?

The answer could spur discoveries to prevent such devastating neurological problems. And time is of the essence. One year after the virus was first confirmed in Latin America, with the raging crisis likely to reach the United States this summer, no treatment or vaccine exists.

“We can’t wait,” said Dr. Song, at the university’s Institute for Cell Engineering, where he and his wife and research partner, Dr. Guo-Li Ming, provided a pipette-and-petri-dish-level tour. “To translate our work for the clinic, to the public, normally it takes years. This is a case where we can make a difference right away.”

The laboratory’s initial breakthrough, published in March with researchers at two other universities, showed that the Zika virus attacked and killed so-called neural progenitor cells, which form early in fetal development and generate neurons in the brain.

In April, the team and other collaborators published a study in the journal Cell showing that this assault by Zika resulted in undersize brain organoids: Damaged progenitor cells created fewer neurons, leading to less brain volume.

That may explain the smaller brains and heads, a condition called microcephaly, of some babies exposed to Zika during pregnancy.

"Guo-Li Ming, professor of neurology and neuroscience, and Hongjun Song, professor of neurology at the Johns Hopkins Hospital in Baltimore, Md, are investigating how the Zika virus causes brain damage"Credit...  Gabriella Demczuk for The New York Times [HN01VV][GDrive

“I think they’ve nailed it,” said Dr. Eric Rubin, a professor of immunology and infectious diseases at Harvard. “That is totally consistent with the pathology that has been seen in the kids that died or the aborted fetuses. ”

The experiments here suggest other worrisome aspects of Zika infection: that even low doses of the virus for short periods can cause damage and that it is most dangerous in the first trimester of pregnancy but can also be harmful in the second.

“The really sad news is not only can the virus infect neural progenitor cells, but it turns them into a factory,” Dr. Song said.

“The cells produce more virus and they actually can spread it,” said Dr. Ming, adding that infected cells appear to create a “bystander effect,” releasing chemicals as they die that damage or kill neighboring uninfected progenitor cells.

And the organoid results contain a frightening hint of why Zika is also associated with adult neurological disorders, including Guillain-Barré syndrome, a temporary paralysis. Dr. Song said they found that Zika infection is “even worse” in glial cells, which support and insulate neurons and are present throughout life, not just in fetal development.

But there is much more to learn, and the collaboration catalyzed by a remark from a junior scientist now includes nine labs at six sites across the country.

Among them is a specialized lab at the National Center for Advancing Translational Sciences (Ncats), which is testing drugs on neural progenitor cells, hoping to find compounds that can stop the virus. Rapidly testing thousands of compounds in varying doses, the lab has already zeroed in on a promising candidate. If the drug succeeds in further testing, it could allow scientists to skip much of the safety evaluation necessary for creating new drugs or vaccines.

Many other researchers are also rushing to understand how Zika wreaks its damage. Teams in Brazil and at the University of California, San Diego have also found that the virus attacked neural progenitor cells and shrank brain organoids. The San Diego team reported that Zika overactivated a molecule that normally protects against viruses, and the excess activity seems to switch on genes that galvanize progenitor cell destruction.

A Rush of Research

In Rio de Janeiro, Stevens Rehen, a neuroscientist at D’Or Institute for Research and Education, said the Brazilian team was also testing drugs, seeking one that blocked the Zika virus. But they can test only those approved in Brazil; importing drugs from elsewhere involves weeks of red tape. “The idea is to be fast,” Dr. Rehen said.

At the University of Pittsburgh, Carolyn Coyne, a microbiologist, and Dr. Yoel Sadovsky, an obstetrician and microbiologist, are investigating how the virus enters the placenta. They determined that Zika does not infect trophoblasts, placental cells that protect against most viruses.

But there could be other routes: Does the virus sneak in through breaks in the lining? Does it hide in “Trojan horse” cells? Does it piggyback on antibodies from related infections, like dengue?

“Going through the placenta is not the only way to infect a fetus,” Dr. Sadovsky said.

Separately, scientists at other institutions, including Vanderbilt; the University of California, San Francisco; and Washington University in St. Louis, are examining questions like how the immune system recognizes the virus.

“We don’t know enough,” said Sara Cherry, a microbiologist at the University of Pennsylvania, who is also testing drugs already approved for other diseases, investigating their effects on cells from the placenta and blood-brain barrier.

“We don’t understand necessarily why Zika infection of the brain leads to particular cell deaths. Also, there may be different populations that are more or less sensitive to the virus.”

Indeed, Dr. Rubin, of Harvard, said, “It wouldn’t be surprising if the virus had to get to a specific kind of cell in the placenta, or that cell had to be in a specific phase in its growth cycle to get infected.”

Meanwhile, Dr. Ming and Dr. Song continue to explore. They are investigating which snippet of Zika’s genetic material is its lethal weapon, and are comparing Zika-infected brain organoids to tissue from a fetus aborted by a pregnant woman with Zika.

Experiments from all these labs will provide clues, Dr. Rubin said. But they will not tell the whole story. “In a person, it’s way more complicated,” he said.

Dr. Song and Dr. Ming, both 46, met as high school classmates in Wuhan, China. Now at the Institute for Cell Engineering, their offices are both on the seventh floor “She has the better view,” Dr. Song said.

“No, it’s the same,” assured Dr. Ming.

Longtime collaborators, “we do argue, but eventually we will come to an agreement,” she said. In their labs, students, like their two teenage children, “know when to go to me and when to go to her,” Dr. Song said.

Their son Max, 17, is an adjunct lab member of sorts, and his artwork mapping the Zika virus’s international journey graces the cover of the journal that published his parents’ first Zika study, Cell Stem Cell.

By February, the couple was puzzling over how to study the Zika virus when they had no samples of it; even if they could get some, their lab did not have university approval to work with Zika.

Then Dr. Song received an email from his friend Hengli Tang, a virologist at Florida State University. Since meeting as graduate students, they had vacationed and celebrated holidays together, but never worked together.

Dr. Tang studied H.I.V. and hepatitis C, and recently had equipped his lab to study dengue, a cousin of the Zika virus that is carried by the same type of mosquito. So when the Zika epidemic erupted in South America, it seemed a natural focus.

As a virus guy, Dr. Tang is comfortable with frightening pathogens. At gatherings with other researchers, he laughed, “We always start with, like: ‘What virus are you? I’m herpes.’”

But the brain was terra incognita, and Dr. Tang figured he needed a brain guy to support his Zika research grant application. “Who do I know in neuro?” he asked himself.

He emailed Dr. Song. Seconds later, the phone rang.

“He said, ‘I didn’t read the email, I just saw Zika and called,’” Dr. Tang recalled. “He was all excited and said, ‘We were just discussing where to find Zika, because we have the perfect system to study Zika.’”

The next day, neural cells were winging their way to Dr. Tang’s lab in Florida, packed in vials in ice, the first of many rapid-fire FedEx exchanges. (At one point, FedEx temporarily interrupted the breakneck pace by delaying a shipment, questioning whether the unit of measurement, milliliters, was correct, Dr. Tang said.) The Johns Hopkins researchers sent four kinds of cells: two types of stem cells, which can be turned into other human cell types; neurons; and neural progenitor cells.

A Scramble for Samples

Dr. Song and Dr. Ming were betting the Zika virus targeted neural progenitor cells; they had long studied microcephaly cases unrelated to the Zika virus and knew progenitor cells were damaged in those cases.

They sent cells derived from two people, one healthy and one with schizophrenia, because those were the cells they had, and they wondered if schizophrenia would yield different results. It didn’t.

It takes years to learn to handle these finicky cells. Dr. Tang had no such experience, so a Johns Hopkins postdoctoral student, Zhexing Wen, immediately flew to Florida to help. Later, Xuyu Qian did, too.

To obtain samples of the Zika virus, Dr. Tang had to scramble. His usual supplier, a nonprofit tissue bank, was back-ordered till July, but finally a commercial source sold him a paltry two milliliters of Zika for $300 each. That was not nearly enough to test on the Johns Hopkins cells. So Dr. Tang had to propagate the virus, eventually producing 800 milliliters.

To do so, he wanted to mimic the journey the virus takes from animals to humans. First, he grew it in monkey cells, then in mosquito cells.

The first strain was from Africa, where Zika was identified in 1947. While quite similar to the Brazilian strain, Asian strains are closer, so he eventually obtained a Cambodian strain and another strain from the current epidemic in Puerto Rico. In the lab’s experiments, different strains have yielded similar results.

Because the students in his lab are young women, Dr. Tang opted for safe-handling precautions beyond those normally required for Zika.

He was not expecting much from the first experiments adding Zika to the four types of cells. “To be honest, this was supposed to be a pilot study,” he said. “We had no idea whether, first of all, the virus would even infect these cells.”

But within a week, the results were striking. The virus attacked neural progenitor cells much more aggressively than the neurons or stem cells.

“I was overwhelmed,” Dr. Song said.

Suddenly they had a likely answer to “one of the very first questions people want to know,” Dr. Tang said.

The results suggested that the Zika virus was most dangerous in the first trimester, when most progenitor cells form. In those cells, the infection increased activity of an enzyme, caspase-3, which signals and also contributes to the death of cells, Dr. Ming said.

Dr. Rehen, the Brazilian neuroscientist working on similar research, described caspase-3 as a sort of smoking gun.

“If you see someone dead in the street, the person could be killed by a knife or by a car,” he said. “If you see caspase is involved, you can see that the weapon was a knife. The killer uses the knife; the killer is the Zika.”

In healthy humans, this and other enzymes contribute to “programmed cell death,” necessary so cells do not divide or grow endlessly, like cancerous cells. But kill too many cells or at the wrong time, and development goes awry, drastically.

Quickly, the Johns Hopkins researchers found their cellphones buzzing as other scientists saw ways to build on their results.

“There’s so many emails I can’t keep track,” Dr. Song said. “It’s, ‘I’m missing this piece, can you send me that?’ or ‘I don’t understand this part.’”

But the first experiments lacked a crucial element, they knew. They were done on cells in plates, in 2-D. How would Zika work in 3-D, in a more complex, more brainlike experiment?

Enter the brain organoids, spheres at most the size of a BB, containing stem cells differentiated into most types of brain cells. As they grow, they mimic fetal brain development; a 100-day-old organoid resembles the late second trimester of pregnancy, Dr. Ming said.

They shipped organoids to Dr. Tang in Florida, a task made easier because three high school students, including Max, had spent summer internships designing miniature spinning bioreactors, used to incubate organoids. Constructed with 3-D printed parts, they were smaller than standard bioreactors and cheaper to use because they needed less cell-growing material.

Meanwhile, after the March finding, the Ncats lab in Rockville, Md., sprang into action. Wei Zheng, who runs the lab, part of the Therapeutics for Rare and Neglected Diseases program, said the fact that Zika increased the caspase-3 enzyme gave him a way to test drugs on cells infected with Zika.

First, search for drugs that block the spike in caspase-3. Then, weed out those drugs that are toxic to the cells themselves. Finally, see if any remaining drugs prevented the Zika virus from killing cells.

Dr. Zheng noted that Zika took about three days to kill its progenitor cell victims, and did not kill all of them. If it did, he said, “you wouldn’t see a baby” at all.

It is possible, though, Dr. Ming said, when Zika strikes very early in pregnancy, it destroys so many cells that miscarriage results.

A Possible Testing Gold Mine

Ncats has perhaps the world’s largest collection of drugs and compounds, some half a million. During a recent visit, an employee who goes by the name Pepper showed how samples are fetched from glass-walled carousels by giant yellow robotic arms in a meticulously programmed ballet resembling an albatross love dance.

Many of the compounds are untested in people. But one collection contains about 2,800 drugs approved in the United States or other countries. Another library holds about 2,000 compounds that have been through some human safety testing.

Those libraries are potential gold mines. If safety-tested compounds block Zika in laboratory cells, they can be tested in people faster than new drugs or vaccines.

“We want to focus on the drugs that are immediately useful in people with the disease,” said Dr. Christopher Austin, the director of Ncats, noting that similar drug-testing was done with Ebola, yielding some compounds that are in clinical trials now.

The Johns Hopkins researchers needed time to grow more neural progenitor cells, but Dr. Zheng started anyway, first on brain tumor cells he infected with Zika. Three compounds seemed effective - a caspase inhibitor, a Russian antidepressant, and a common vitamin - so he whisked them to other researchers to try.

After receiving progenitor cells, he started again. He found 173 drugs blocked caspase-3 increase, about three dozen did so without harming cells, and one — just one — prevented the Zika virus from killing cells. That drug, which he declined to identify, is not approved but has undergone safety testing and is in a clinical trial with cancer patients, he said.

He sent the drug to Johns Hopkins, where early testing is yielding similar results. But even if results are replicated in mice and humans, hurdles remain, including determining if it is safe for pregnant women and deciding who to treat, since many women infected with Zika have had healthy babies

Also, a drug that can “save the cells after they’re infected” is not the real prize, Dr. Song said. “The best drug would actually prevent the cells from being infected in the first place.”

2016 (May 16) - The Vaccine Reaction : "Birth of the Zika Industry"

by Marco Cáceres  /   Published May 16, 2016 

https://thevaccinereaction.org/2016/05/birth-of-the-zika-industry/

2016-05-16-thevaccinereaction-org-birth-of-the-zika-industry.pdf

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[...]  Now, think of Zika. Before this year, very few people had ever even heard of the Zika virus. Now, practically everyone in the world knows about Zika and believes that the primary cause of babies being born with shrunken heads (microcephaly) and brain damage in Brazil is that their mothers were bitten by the Zika-carrying mosquito while they were pregnant.

Why does everyone believe that? Because public health officials at the U.S. Centers for the Disease Control and Prevention (CDC) and National Institutes of Health (NIH) say so.1 Forget that these federal health agencies have provided no solid scientific evidence of a causal relationship. That’s beside the point. It’s the CDC and NIH.

We are being asked to overlook the fact that the theory that Zika causes microcephaly has all sorts of gaping holes in it and2 that there are at least three reports or studies by organizations in Latin America, which have raised serious questions about the Zika-microcephaly link. These independent sources either have proposed another cause of the microcephaly cases in Brazil or have failed to determine a causal link between Zika and brain disorders.3 4 5

Because the CDC and NIH have proclaimed it so, the Zika virus has been accepted to be one of the greatest threats to humanity in a long time. Last year, Zika was an obscure and relatively harmless virus known to produce no symptoms in the vast majority of those who contracted it or only very mild symptoms in a minority of those infected. CDC officials said so.

Most people infected with Zika virus won’t even know they have the disease because they won’t have symptoms. The most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis (red eyes). Other common symptoms include muscle pain and headache.2

The illness is usually mild with symptoms lasting for several days to a week. People usually don’t get sick enough to go to the hospital, and they very rarely die of Zika. For this reason, many people might not realize they have been infected.6

In a few short months, however, Zika has suddenly been transformed into a cause  célèbre—the source of tremendous fear and angst for the public. So, naturally, Zika has now become an industry, and it will later become a market. The key product in this nascent industry will be vaccines.

But first come the players—the companies that will develop, produce, market and sell the vaccines. Then, come the financiers—that, in addition to pharmaceutical companies themselves, include governments, private investors and international organizations that will front the money for the development work in the hope of either earning spectacular profits or a miraculous solution to a perceived a health crisis.

There are no shortage of players. Why? Because Zika is a new industry, and new industries represent commercial opportunities. Money. The U.S. government has offered to jumpstart the industry by proposing $1.9 billion for Zika research.7

The World Health Organization (WHO) has set up a UN Zika Response Multi-Partner Trust Fund (MPTF) to ” finance critical unfunded priorities in the response to the Zika outbreak.”8 The WHO announced on February 17, 2016 that it would seek $56 million from its member countries to help combat Zika. Included in those funds would be money to “fast-track” the development of vaccines.9 

Even wealthy philanthropists like Microsoft co-founder Paul Allen are doing their part to spur on this new industry. On February 19, 2016, Mr. Allen announced two grants worth more than $2 million, aimed at fighting Zika. Of the total, $1.5 million will go to the American Red Cross in support of efforts to “control the mosquitoes that transmit the virus and educate the public in Brazil and other Latin American countries.” The remaining $550,000 will go to Chembio Diagnostics Systems, Inc. of Medford, NY to “develop a suite of rapid tests to quickly diagnose Zika and differentiate it from diseases with similar symptoms.”10 

It is a given that wherever there is plenty of money up for grabs, the politicians will get involved to try and funnel some of it to their constituencies. For example, U.S. Senator Charles Schumer of New York has been pushing hard for Congress to approve the $1.9 billion request for Zika research. Sen. Schumer is hoping some of those funds will go to SUNY Upstate Medical University in Syracuse, NY.

Referring to the $1.9 billion request, Sen. Schumer said:

We need to get this done as soon as possible so that institutions like SUNY Upstate can use their expertise to help stem the spread of Zika. … If you care about this country, if you care about the safety of pregnant mothers, if you care about stemming this horrible disease, pass this emergency bill that will let institutions like SUNY Upstate help us understand, treat and prevent Zika.11 

The race is on to develop vaccines against Zika. It seems that almost daily the media is highlighting a new company or institution that is entering the race. Thus far, there are at least 18 competitors around the world.12 For example, there is Brazil’s own renowned Butantan Institute in São Paulo and NIH in Bethesda, MD.12 There is  Bharat Biotech International Pvt. Ltd. of Hyderabad, India; Sanofi SA of Paris, France; Inovio Pharmaceuticals, Inc. of Plymouth Meeting, PA; NewLink Genetics Corp. of Ames, IA; and Scripps Research Institute of  La Jolla, CA.13

There is Johnson & Johnson, Inc. of New Brunswick, NJ; Merck & Co. of Kenilworth, NJ; Pfizer, Inc. of New York City, NY; and possibly Takeda Pharmaceutical Company Ltd. of Osaka, Japan.14 There’s Protein Sciences Corp.15 of Meriden, CT and GeneOne Life Science, Inc. of Seoul, South Korea and possibly GlaxoSmithKline plc of London, UK.16 And just last month, Immunovaccine Inc. of Halifax, Nova Scotia, Canada and defense engineering firm Leidos, Inc. of Reston, VA announced a collaborative agreement on Zika vaccine research.17 There are others, and there will likely be many more in the years to come.

It seems everybody wants in on the action. It is exciting to be one of the early pioneers in a brand new industry with lots of growth potential, particularly when it has such strong government support and when the prospects for mandated use of the vaccines are so promising… for the industry, that is. There is already talk about Zika being with us forever and becoming one of those things against which we will routinely vaccinate.

Once Zika virus arrives in the United States, it will be here to stay. Leading experts now predict that the mosquito-borne disease will become a constant low-level threat that Americans will need to be vaccinated against routinely—as we do now for rubella, a virus that, like Zika, causes birth defects.18

What is important to understand is that once you create a profitable industry, there is seldom any turning back. It’s here to stay, until it is no longer profitable.

2016 (May 31) - Youtube, This Week in Virology : "Zika Virus! - This Week in Virology Live from the American Society for Microbiology"

Streamed live on May 31, 2016 , Youtube channel  American Society for Microbiology  :  https://www.youtube.com/watch?v=PvOD0f0WaFk  /  Saved MP4 : [HV00KJ][GDrive]   / Housatonic Bitchute version : https://www.bitchute.com/video/sD08RsuX1B74/ 

A special live episode of the popular science podcast This Week in Virology at the headquarters of the American Society for Microbiology. Podcast host Vincent Racaniello will hold a conversation with four leading experts on flaviviruses to discuss what we know about the emerging pathogen Zika virus and the state of ongoing research.

Guests

2016  (June 26)

https://www.newspapers.com/image/345652118/

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https://www.newspapers.com/image/345652180/?terms=zika%20rna&match=1

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2016 (July 08) - mRNA vaccine for Zika ? 

https://www.newspapers.com/image/227710923/?terms=zika%20mrna&match=1

2016-07-08-the-philadelphia-inquirer-pg-a15

https://drive.google.com/file/d/1MToSBLtmk0fcatR9iN5zvHE-UTWnx6MS/view?usp=sharing

https://www.newspapers.com/image/227710965 

2016-07-08-the-philadelphia-inquirer-pg-a17

https://drive.google.com/file/d/1MTCkQtyGZz1qiLoUD9pc1s6TGc0jj8N0/view?usp=sharing

2016-07-08-the-philadelphia-inquirer-pg-a17-clip-zika-vax

https://drive.google.com/file/d/1MTh4eQgRVuVJvxuefnpcjNb5bghAuVB2/view?usp=sharing

2016 (Aug) - PLOS Neglected and Tropical Diseases : "Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome"

Also see : [Zika virus epidemic (2015-2016)]

PMID: 27560129  /   PMCID: PMC4999274  /    DOI: 10.1371/journal.pntd.0004877   /    Saved PDF : [HP00C8][GDrive]

Abstract

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain-Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of "TORCH" viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: Drs. Robert Malone and Jill Glasspool-Malone are principal stockholders of Atheric Pharmaceutical, LLC. Robert Malone is the managing partner of Atheric Pharmaceutical. Dr. Michael Callahan is the Chief Medical Officer of the Zika Foundation.

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2016 (Aug 04) - Trump breaks silence on Zika, believes it is "under control"

https://abcnews.go.com/Politics/trump-breaks-silence-zika-remains-silent-federal-funds/story?id=41116537

2016 (Aug 23) - USA's Texas A&M University - "Students innovate against Zika in 48 hours"

August 23, 2016 By Melanie Balinas  /  Saved PDF of source : [HE007V][GDrive]  

Mentioned :  Dr. Michael Vincent Callahan (born 1962)    /  Zika virus epidemic (2015-2016)     

When 80 motivated and innovative students from five universities work together, novel ideas will emerge. The first [U] Invent produced 12 solutions to combat the spread of the Zika virus through educational and conceptual solutions. More than $4,000 in award funds and an opportunity for two students from a winning team to meet with the Centers for Disease Control and Prevention (CDC) was presented to the students.

Innovate Against Zika is the first [U] Invent program implementing the highly successful Aggies Invent model which gives students 48 hours to collaborate in teams solving identified design challenges related to a specific topic. The students have complete access to the Engineering Innovation Center (EIC) and topic experts throughout the innovation competition. 

“It was great having other universities participate in the first [U] Invent,” said Rodney Boehm, associate professor of practice.  “All of the students blended into tight teams and it allowed us to show how we innovate at Texas A&M University.”

The Texas A&M University College of Engineering and The Zika Foundation partnered to host Innovate Against Zika with the goal of applying new discoveries about the Zika mosquito using trans-discipline expertise to halt the spread of the Zika virus through the rapid development and implementation of low-cost, sustainable solutions. Student teams chose from one of three tracks for their needs statement: vector (mosquito) control, immune households or community resiliency and sustainability.

“This weekend opened my eyes to the ability for people to pull themselves together for a common cause,” said Garrett Harmon. “It’s really motivating to me to think more about my education and what I’m doing now so I can have a great effect of people in the future.”

Innovate Against Zika was stacked with 20 of the brightest researchers in the fields of public health, entomology, chemistry, architecture, engineering and biotechnology to guide and advise the students throughout the weekend. Some of the mentors and presenters included Dr. R. Ulrich Bernier, the acting national program leader and research chemist with the USDA’s Agricultural Research Service, whose efforts are focused on surveillance and control of the vector(s) responsible for pathogen transmission; [Dr. Michael Vincent Callahan (born 1962)], a physician scientist board certified in internal medicine, infectious disease, tropical medicine (DTM&H) and mass casualty care and a clinical and research faculty member at Massachusetts General Hospital/Harvard Medical School; and Josue Young, a researcher in the Medical Entomology Department at the Gorgas Memorial Institute in Panama City, Panama.

“Control of Zika is a problem-rich issue,” said [Dr. Michael Vincent Callahan (born 1962)]. “We therefore are compelled to bring this challenge to a solution-rich setting where new answers can be identified. This is the first time engineers, architects and urban planners have been given complete access to Zika-mosquito experts. We believe this event has identified new solutions to this growing global problem.”

The first-place team, awarded $1,000, was SWATeam. The team developed an app that engages young people in games to find mosquito areas, provides education and allows the community to learn more about Zika. The team consisted of two Texas A&M students — Kendra Mack, from biomedical sciences and Ankita Brahmaroutu from the college of medicine — and five University of Texas students —Jason He, electrical engineering; Annabel Wang, Ishani Chakravarty, and Justin Zhong, chemical engineering; and Zhra Biabani, economics.

The Bucket List team took second place and was awarded  $750. This team developed a Zika protection kit that is contained in a mosquito trap to form a multi-dimensional solution. The members of this team included Kedar Balakrishna, Diego Garcia, Austin Lu, Liana Polikaitis and Ashley Tucker, biomedical engineering; Jessica Lee, biomedical science; and Megan Rodriguez, nuclear engineering.

The third-place team, awarded $500, developed an education program in a pictogram that would be attached to rain barrels currently being distributed by non-governmental organizations worldwide. The Persistent Pictogram team consisted of three Texas A&M students, Mo Adesanmi, chemical engineering, Clare Elizondo, biomedical science and Jane Frederick, biomedical engineering; two Wichita State University students, Hannah Hund, biomedical engineering and LaRissa Lawrie, strategic communications; and Stephanie Strong, chemistry and biology from East Carolina University.

[...]  The CDC showed its interest in Innovate Against Zika by offering to bring two members from the winning team to Atlanta to present the team’s innovation to the Zika response team, speak with its technology transfer experts and tour its insectary.   [...]

2016 (August 27) - The Lancet 

ARTICLES| VOLUME 388, ISSUE 10047, P891-897,AUGUST 27, 2016

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2816%2930902-3/fulltext 

PDF [405 KB]

Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation

Giovanny VA France, PhD

Prof Lavinia Schuler-Faccini, PhD

Wanderson K Oliveira, MSc

Claudio M P Henriques, MD

Eduardo H Carmo, PhD

Vaneide D Pedi, MSc

Open AccessPublished:June 29, 2016DOI:https://doi.org/10.1016/S0140-6736(16)30902-3

2016 (Aug 31) - Zika Virus Response Efforts, Georgetown panel (Fauci Gostin)

Live link : https://www.c-span.org/video/?414561-1/dr-anthony-fauci-discusses-zika-virus  /  Saved 1080p video : [HM007H][GDrive]

PEOPLE IN THIS VIDEO

2016 (Sep 03)

https://www.newspapers.com/image/266357141/?terms=zika%20gene%20therapy&match=1

2016-09-03-the-honolulu-advertiser-pg-b6-clip-new-therapies

2016 (Sep 07) - "Moderna gains BARDA Zika vax funding; closes $474M funding round"

https://www.cipherbio.com/data-viz/organization/Moderna/news/Moderna%2Bgains%2BBARDA%2BZika%2Bvax%2Bfunding%3B%2Bcloses%2B$474M%2Bfunding%2Bround

2016-09-07-cipherbio-com-data-moderna-barda-round-info.pdf

Moderna is edging toward a total $2 billion in funding after just 5 years of life after announcing a major new funding round--which coincides with a potential $125 million BARDA grant to help fund its mRNA Zika vaccine research. First, to its latest funding round that officially closed today with $474 million in the kitty. Specific names were not given, but the Cambridge, MA-based biotech and 2013 Fierce 15 company said that this latest equity financing included “strong support from existing institutional investors” as well as “world-class strategic pharmaceutical partners … and new institutional investors from the United States, Europe and Asia.” Moderna did not reveal in its PR or to FierceBiotech who these investors are. It also remained schtum on its highly anticipated IPO plans. “Our focus over the coming year will be to continue advancing our pipeline into the clinic,” the company said. [...]  “We currently have two Phase I clinical studies underway and anticipate moving additional programs into the clinic by the end of this year. We continue to evaluate the public markets and will look to go public at a time that makes sense for the company.” “Moderna is, yet again in its short 5 years, accelerating its expansion and entering a new growth phase,” said Stéphane Bancel, CEO of the biotech. “We are pivoting toward a new chapter in our company’s history, and we feel privileged to deploy our substantial capital resources to advance our mission to deliver on the promise of mRNA therapeutics as an entire new class of medicines.” The cash will be used to push on with its development work and bring preclinical candidates into the lab, as well as building a new GMP manufacturing facility--all the while committing $100 million a year as a consistent investment pot for its mRNA technology platform. Moderna currently has around $1.4 billion in cash on its balance sheet and the potential for over $230 million of extra funds from grants funnelled through a number of charitable and government bodies, including the Bill & Melinda Gates Foundation and BARDA--the U.S. government’s emergency health department. And it is BARDA that today has also given $8 million upfront to Moderna--with the potential for a total $125 million if development goes well--for early-stage work on its Zika messenger RNA (mRNA) vaccine. The vax is currently preclinical with the work being undertaken by Valera, Moderna’s infectious disease-focused venture, but the biotech is planning to submit an IND with the FDA by year’s end that will allow it to start human testing. Under the funding deal, the initial $8 million will support a Phase I study, toxicology studies, vaccine formulation and manufacturing, with an extra $117 million earmarked to support Phase II and Phase III, as well as large-scale manufacturing. The company told FierceBiotech that based on the funding from BARDA, it shouldn’t need to add too much of its own cash to the development program: “We anticipate the award will fund the bulk of our development and manufacturing for the vaccine,” the biotech said. It said that much of the work will be done internally, but it will call on its existing collaboration with CRO Charles River Laboratories to “support GLP toxicology studies and a collaboration with PPD to support Phase I and Phase II studies.” “We believe our mRNA vaccine technology offers potential advantages in efficacy, speed of development, and production scalability and reliability, which may position Moderna as a leader in preparing for and responding to infectious disease threats, such as Zika, that place millions of people at risk around the world,” Bancel said of its BARDA funding. “We feel a tremendous sense of responsibility to advance our Zika mRNA vaccine as quickly as possible, and we are thankful to BARDA for its commitment to support and help expedite our development efforts. We plan to initiate a Phase I study within the next several months.” Moderna already has several early-stage mRNA infectious disease vaccine studies ongoing in the U.S. and Europe, having dosed around 250 healthy human volunteers to date. The company says it plans to publish its first set of clinical data from its first Phase I next year. BARDA is not however putting all of its eggs in one basket, having last week announced it was also paying out $19.8 million upfront and more than $300 in total to Japanese pharma Takeda for its Zika vaccine work as the transmission of the virus continues its spread across the Americas, Africa and Asia. The deal is a similar one for both companies, although Takeda is in line for a larger funding pot, with its work also preclinical with plans for a Phase I before 2017. Sanofi ($SNY), GlaxoSmithKline ($GSK), India’s Bharat Biotech and Inovio Pharmaceuticals ($INO) are also all working on versions of their own vaccine for the virus that is believed to cause microcephaly in newborns. These players have taken several different approaches to the vaccine, with Inovio using a DNA vaccine while Takeda is looking at an inactivated Zika virus rather than the more common attenuated-virus approach. Moderna will use its mRNA approach, saying in a statement that it will deliver mRNA to the body’s cells, which, in turn, produce antigenic proteins as if the body was infected by a virus. “These antigenic proteins are identified and remembered by the immune system. When a person is exposed to the pathogen in the future, the body is able to recognize it as foreign and mounts an immune response, including production of antibodies that can help to destroy the pathogen.” Moderna says that, to its knowledge, “we are the only company developing a Zika vaccine that uses mRNA to drive cellular protein expression directly.” It has split its development programs down into a series of ventures focused on cancer, infectious diseases, rare diseases, and personalized cancer vaccines. The biotech already has a number of major backers and deals with Big Pharma, including AstraZeneca ($AZN), Alexion ($ALXN), Merck ($MRK) and Vertex ($VRTX).

2016 (Sep 08) - The Boston Globe : "Moderna gets grant to develop Zika (mRNA) vaccine"

Mentioned - Stéphane J. Bancel (born 1972)   

Full newspaper page : [HN022J][GDrive]  

Clip above : [HN022K][GDrive]

2016 (Sep 08) - C-SPAN : Democratic News Conference on Legislative Action  (VP Joe Biden)

Vice President Biden joined congressional Democrats on the East Front steps of the U.S. Capitol urging Republicans to take action on Zika funding, the Merrick Garland Supreme Court nomination, and gun violence prevention. In addition, Vice President Biden expressed his deep concerns about the dysfunction in Washington. House and Senate Minority Leaders Nancy Pelosi (D-CA) and Harry Reid (D-NV) also criticized Republicans for legislative inaction. close 

https://www.c-span.org/video/?414954-1/vice-president-biden-congressional-democrats-call-legislative-action

2016 (Sep 18) - The Empowering Neurologist EP. 27 : "Zika Virus Research - with Dr. Michael Callahan"

Source : [HW008M][GDrive]   / See Dr. Michael Vincent Callahan (born 1962)  

Dr. Michael Callahan is CEO and co-founder of the Zika Foundation. He is a highly respected “physician scientist”,  who is board-certified in internal medicine, infectious disease, tropical medicine and mass casualty care, and is on both the clinical and research faculty at Massachusetts General Hospital/Harvard Medical School.

Dr. Callahan has clinical appointments globally, including in Thailand, Indonesia, Panama, and Nigeria. From 2005-2012, Dr. Callahan established Prophecy, the first rapid deployment clinical research capability for catastrophic infectious diseases outbreaks, such as Ebola.

Dr. Callahan has served as special advisor on infectious disease to two presidents, the Secretaries of Defense and of Health and Human Services, and  the Office of the Commissioner of the FDA. Dr. Callahan has been deployed to 7 mass casualty disease outbreaks, including Ebola, Marburg, H5N1 and H7N9 bird flu, and MERS. He used his experience with dengue to launch the Zika Foundation, where he is accelerating sustainable and low-cost interventions to protect women and men from Aedes mosquitos, which transmit dengue, chikungunya and the Zika virus.  His mission is to ensure that the 64 million pregnancies that occur every year in the tropical Americas are kept safe from Zika, and to prevent the epidemic of paralytic Guillain-Barre Syndrome that may well occur in southern nations over the next five years.

The interview that you're about to see challenges our basic understanding of the Zika virus. Dr. Callahan reveals, for example, that new research clearly demonstrates that Zika virus can have long-term neurological effects in adults. He discusses how the aerial spraying efforts, so common in South Florida, are actually ineffective and inappropriate for targeting the specific mosquito that transmits the virus.

However, Dr. Callahan does provide us with some very important, and actionable, tools for reducing our risk of contracting Zika, both in terms of what we can do to reduce the prevalence of the Aedes mosquito and also how we can protect ourselves day-to-day.

It's clear that we have to rewrite the book as it pertains to our understanding of mosquitoes, specifically as it relates to the Aedes mosquito that serves as the carrier of the Zika virus. Unlike what we’re used to, this mosquito lives indoors, and, according to Dr. Callahan, is actually able to watch our eyes to determine when is the best time to inflict its bite.

Dr. Callahan explores the effectiveness of various insect repellents and even touches upon his research dealing with genetically modified male mosquitoes in an attempt to limit the reproduction of the mosquito that carries this threatening virus.

Original on Youtube : https://www.youtube.com/watch?v=h1h7CcAjUpk   /  Housatonic copy on Bitchute : https://www.bitchute.com/video/k1D9E6b3PCfL/ Saved version :   [HV00KF][GDrive

2016 (Sep 27) - "Zika Symposium at 2016 International Congress of Entomology"

https://www.youtube.com/watch?v=yb_qpFGd2js 

Zika Symposium at 2016 International Congress of Entomology

1,075 viewsSep 27, 2016

Entomological Society of America

At the 2016 International Congress of Entomology in Orlando, Florida in September 2016, international scientists shared the latest research about the Zika virus and Aedes aegypti mosquitoes. Speakers included Dr. Stephen Higgs from Kansas State University, Dr. Brian Foy from Colorado State University, Dr. Constancia Ayres from Fiocruz in Brazil, Dr. Anthony James from the University of California, Irvine, and Dr. Fiona Hunter from Brock University.

2016 (Oct 28) ... Amendment One to Confidential Disclosure agreement signed between NIAID, Vaccine Research Institute, and Moderna

Original disclosure signed Nov 5-9, 2015

This amendment adds Zika ... 

See [HX0018][GDrive]

2016 (Nov 01) - NYTimes : "Colombia Is Hit Hard by Zika, but Not by Microcephaly"

By Donald G. McNeil Jr. and Julia Symmes Cobb  /  Oct. 31, 2016  /   [HN01VQ][GDrive]  

ZZuleima at home with her baby, Milagros, who was born with microcephaly, and one of her older daughters."Credit...  Katie Orlinsky for The New York Times[HN01VR][GDrive]

BARRANQUILLA, Colombia — This tropical city on the Caribbean coast may hold the answer to one of the deeper mysteries of the Zika epidemic: Why has the world’s second-largest outbreak, after Brazil’s, produced so few birth defects?

In Brazil, more than 2,000 babies have been born with microcephaly, abnormally small heads and brain damage caused by the Zika virus. In Colombia, officials had predicted there might be as many as 700 such babies by the end of this year. There have been merely 47.

The gap has been seen all over the Americas. According to the World Health Organization, the United States has 28 cases — almost all linked to women infected elsewhere. Guatemala has 15, and Martinique has 12.

Had the rest of the Americas been as affected as northeastern Brazil, a tidal wave of microcephaly would be washing over the region. Most experts say that will not happen, but they are at a loss as to why.

Discovering what stopped microcephaly in Colombia may help other countries tamp down the epidemic’s worst effects.

There are some obvious differences between Colombia’s epidemic and Brazil’s. The population here is less than a quarter that of Brazil, and almost half of its residents live at higher altitudes, where mosquitoes are rarer.

And Zika circulated silently for much longer in Brazil. The virus arrived there by early 2014, and not in Colombia until late 2015. Having just fought a severe chikungunya epidemic in 2014, Colombia was more ready than Brazil to send forth the anti-mosquito battalions.

But all that does not seem sufficient to explain the disparity. Increasingly, there is evidence for two other possibilities.

Pregnant women here, alerted to the tragedy unfolding in Brazil, may have sought abortions in greater numbers, officials say. Others seem to have heeded the government’s controversial advice to delay pregnancy altogether.

Dr. Miguel Parra-Saavedra, the director of maternal-fetal medicine at the Cedifetal Clinic in Barranquilla and one of the country’s leading high-risk pregnancy specialists, is among the experts who suspect many pregnant women in Colombia, alarmed by news reports, sought ultrasounds and aborted deformed fetuses.

Some of his own patients have done so.

Dr. Parra-Saavedra heads a study of Zika-related birth defects in cooperation with the Centers for Disease Control and Prevention. In the course of the research thus far, he has diagnosed 13 cases of fetal microcephaly.

Four of the mothers terminated their pregnancies immediately, he said. Another four, and possibly a fifth, sought abortions but were turned down by their health insurance companies.

Only four patients, Dr. Parra-Saavedra said, deliberately chose to have their babies.

Among those who tried to have an abortion was Zuleima, a 37-year-old mother of two healthy daughters.

When she and her husband Jaime, 47, an unemployed mine-machinery operator, learned that their unborn daughter was microcephalic, they requested what is here called “pregnancy interruption.”

Abortion is legal in Colombia to protect a mother’s health, and the health ministry considers a severely deformed baby a threat to maternal mental well-being.

But Zuleima — who asked that the couple’s surnames not be used because some relatives opposed abortion — was already 31 weeks pregnant.

While the abortion law does not specify which week is too late, her insurer balked, she said, saying it needed time to decide whether to pay for the procedure.

“There were papers and papers to fill out, and the company didn’t say no and didn’t say yes,” she recalled. “They said, ‘We’ll call you later.’”

“They never did — and then it was too late. I had to have the baby.”

She spoke as she nursed her newborn daughter, Milagros. Standing behind her, Dr. William O. Contreras, a neurosurgeon, said in English that Milagros had no frontal lobes and that the connection between her two brain hemispheres was abnormally small.

“When this happens,” he said, “there is no intelligence, no coordination, no attention, no initiative, no calculation — and no memories at all.”

Dr. Fernando Ruiz, Colombia’s vice minister for public health, also says that it is “very possible” that abortions lowered the microcephaly rate here.

“Colombia has some of the most progressive laws and regulations in South America,” he said in an interview. With gynecologists alert to the threat, he said, many women had ultrasounds early enough to made decisions.

Even a very small increase in the abortion rate could account for a sharp reduction in microcephaly.

Just 320 legal abortions were officially reported in Colombia in 2011, according to the Guttmacher Institute, a New York-based research organization supporting abortion rights. Yet the institute estimates that there actually were 400,400 abortions each year in Colombia.

In this country, most abortions are not performed in clinics by vacuum aspiration, but are induced by misoprostol, a drug that causes strong contractions, said Dr. Guido Parra Anaya, the director of the Procrear assisted fertility clinic in Barranquilla.

Any doctor can prescribe the drug, and none are legally obligated to report it.

Misoprostol also is commonly given out by illegal providers here, according to the Guttmacher Institute. Frequently, women are told to take the pills and go to a hospital when heavy bleeding starts, as if they had had a miscarriage. Colombian hospitals treat an estimated 93,000 women a year for postabortion complications.

In July, Dr. Martha Lucia Ospina, the director of Colombia’s National Institutes of Health, reported that fetal deaths reported as miscarriages on death certificates had increased by 8 percent. The numbers have begun returning to normal only recently.

In Brazil, by contrast, abortion is permitted only in cases of rape or incest or to save the mother’s life, and illegal abortions are hard to get because the police, under pressure from evangelical Christians in Brazil’s Congress, began cracking down on clandestine clinics a decade ago.

Also, because the microcephaly surge in Brazil appeared with no warning, even women who might have risked illegal abortions had no time to receive ultrasounds.

In Colombia, women now normally have three ultrasounds during a pregnancy. The increased screening has made for hard choices.

Microcephaly can also be caused by other viruses or genetic mutations, but the Zika virus causes unprecedented levels of brain damage.

“In my 22 years as an ultrasound physician, I have never seen microcephaly like this,” Dr. Parra-Saavedra said. “The heads are much smaller, to a severe degree.”

Although pockets of dead cells that foreshadow microcephaly may appear earlier, fetal heads do not become unmistakably small until early in the third trimester.

Health insurers, financially struggling here, are reluctant to approve late abortions because they must pay for neonatal intensive care if the child is born alive.

"Kiara Munoz, 18, and her son Juan Diego in Barranquilla, Colombia. Juan Diego was born with microcephaly."Credit..   Katie Orlinsky for The New York Times[HN01VS][GDrive]

For mothers, the diagnosis is understandably difficult. By the third trimester, fetuses on ultrasounds look much like newborn babies, not like embryos.

The first scans of Kiara Munoz’s son, Juan Diego, were normal. By the time his microcephaly was evident, she was in her seventh month and could see his face clearly.

“The gynecologist said I could terminate, and I cried,” said Ms. Munoz, who is 18 but looks 15. “It was very hard because the baby was so big. My husband and I decided to keep him. I am hoping for a miracle.”

Colombia’s Zika epidemic peaked in February and was declared over in late July. Many women who became pregnant during that time are still due to give birth, so more microcephaly cases may appear.

But they will still be far fewer than originally predicted.

Dr. Ruiz said that based on Brazil’s experience, he had expected to see 700 cases of Zika-related microcephaly this year. Now, he expects 100 to 250 at most.

In December, Dr. Ruiz asked women in Colombia to delay pregnancies, and he says he believes many did so, although he cannot prove it yet.

A drop in the birthrate would indicate that many women heeded the advice, but the national health statistics office takes 18 months to tally up each year’s birthrate.

In some Latin American countries, suggestions from health ministers that women delay pregnancy met harsh resistance — both from the Roman Catholic Church and from women’s groups complaining that there was too little access to contraception.

El Salvador faced a backlash when it asked women to stop having children for two years. But Colombia’s health ministry asked women to delay for only six to eight months while officials watched how the epidemic unfolded. Some women found that sensible.

As her husband, Gustavo, a police officer, and her young son Sebastian watched, Madis Dominquez, 27, explained how she happened to be getting a four-month ultrasound in September.

She originally planned to become pregnant last December, she said, “but they said, ‘Please wait six months.’ So I waited till May, when they said it looked safe again.”

How many women followed her example will not be known for some time.

The epidemic appears to be winding down in much of Latin America as the hottest, rainiest months end and as more people, having been bitten, develop immunity.

Some experts thought it might have been premature to declare the epidemic over in Colombia, because the virus had infected less than 1 percent of the population. In French Polynesia, it infected more than 60 percent before cases disappeared.

A study done by scientists at London’s Imperial College estimated that across Latin America, where the geography is far more diverse than on Pacific islands, it may be two to three years before widespread immunity stops the epidemic.

In places like Puerto Rico, where the virus arrived relatively late, microcephaly cases are expected to keep increasing. The first live birth of a child with Zika-related microcephaly was reported last month.

Donald G. McNeil Jr. reported from Barranquilla, and Julia Symmes Cobb from Bogotá, Colombia.

2016 (Nov 7) - TRUMP WINS PRESIDENCY IN MAJOR UPSET

2016 (Nov 18) - NYTimes : "Zika Is No Longer a Global Emergency, W.H.O. Says"

Source : [HN01NL][GDrive]  /  By Donald G. McNeil Jr.

Nine photos taken in September 2016 of infants who were born with microcephaly in Pernambuco state, Brazil. W.H.O. declared an end to the global health emergency for the virus on Friday.     Credit...   Felipe Dana/Associated Press[HN01NM][GDrive]

The World Health Organization declared an end to its global health emergency over the spread of the Zika virus on Friday, prompting dismay from some public health experts confronting the epidemic.

An agency advisory committee said it ended the emergency — formally known as a Public Health Emergency of International Concern — because Zika is now shown to be a dangerous mosquito-borne disease, like malaria or yellow fever, and should be viewed as an ongoing threat met as other diseases are, sometimes with W.H.O. help.

Committee members repeatedly emphasized that they did not consider the Zika crisis over.

“We are not downgrading the importance of Zika,” said Dr. Peter Salama, executive director of the W.H.O.’s health emergencies program. “We are sending the message that Zika is here to stay and the W.H.O. response is here to stay.”

Like all mosquito-borne diseases, Zika is seasonal and may repeatedly return to countries with the Aedes aegypti mosquitoes that carry it, Dr. Salama added.

Individual countries facing serious new Zika outbreaks could still declare local emergencies, said [Dr. David Lowell Heymann (born 1946)], chair of the advisory committee.

But other experts worried that the W.H.O.’s declaration might slow the international response to an epidemic that is still spreading, and lull people at risk into thinking they were safe.

Dr. Anthony S. Fauci, director of the National Institute for Allergy and Infectious Diseases, which is funding efforts to find a Zika vaccine, suggested that it was premature to lift the state of emergency since summer is just beginning in the Southern hemisphere.

“Are we going to see a resurgence in Brazil, Colombia and elsewhere?” he asked. “If they pull back on the emergency, they’d better be able to reinstate it. Why not wait a couple of months to see what happens?”

His agency would not slow down its vaccine efforts, he said.

Since the W.H.O. first declared a state of emergency on Feb. 1, the Zika virus has spread to almost every country in the Western Hemisphere except Canada. Thousands of babies suffer deformities caused by the infection, and more are expected.

Recent outbreaks and related birth defects have also been detected in Southeast Asia, although scientists believe the Zika virus has circulated there for decades.

The most severe deformity is microcephaly, a tiny head with a severely underdeveloped brain; but fetuses have also been killed by the virus, and infected infants have been born blind, deaf, with clubbed feet and permanent limb rigidity.

Scientists also fear that many infected babies who appear normal now may suffer from intellectual deficits or mental illnesses later in their lives.

The Centers for Disease Control and Prevention expressed no opinion about the W.H.O.’s decision, but noted that it “did not change the urgent need to continue our work.”

The agency also reiterated the warning it issued in January that pregnant women should avoid traveling to areas where the virus was being transmitted.

Other experts, like Dr. Fauci, were more critical. The W.H.O. decision is “unwise,” said [Lawrence Oglethorpe Gostin (born 1949], director of Georgetown University’s O’Neill Institute for National and Global Health Law.

Although the virus is not killing or deforming as many babies as originally expected, “the international response has been lethargic,” Dr. Gostin said.

“W.H.O.’s action to call off the global emergency has provided reason for governments and donors to pull back even more,” he said.

Even if the outbreak no longer meets the technical definition of an emergency under 2005 international health regulations, there is an important psychological component to declaring an emergency.

Headlines suggesting the crisis is over may lead people to take fewer precautions against sexual and mosquito-borne transmission, experts said.

“We are still not out of the woods,” said [Dr. Scott C. Weaver (born 1957)], a virologist at the University of Texas Medical Branch in Galveston who was among the first to warn that the virus threatened the Americas.

The disaster in northeast Brazil, where more than 2,000 babies have been born with microcephaly, will probably not be repeated, [Dr. Scott C. Weaver (born 1957)] said. And he “would not be surprised if the disease had run its course in Central America and the Caribbean.”

But, he added, “I think the worst is yet to come in southern Brazil — places like São Paulo. And some places in the Amazon haven’t seen the virus at all yet.”

When a large portion of a population has been infected with a virus and has recovered, rising “herd immunity” usually ends the transmission of a virus for several years, until enough susceptible victims are born.

Dr. Albert I. Ko, a Yale epidemiologist who has worked in northeast Brazil for years, said he understood the W.H.O.’s rationale but felt the agency had acted too soon. The full extent of the damage in Latin America is unknown, he said, because many infected babies are yet to be born.

Also, Asian governments are just beginning to realize that they face a crisis, he added, and may now take fewer countermeasures.

When the W.H.O. declared an emergency in February, it was intended in part to get scientists to explore the Zika-microcephaly connection and to make countries cooperate in fighting the epidemic.

At the time, it was unknown whether Brazil’s surge in microcephalic babies was caused by the Zika virus, which had been discovered in 1947 and was considered a mild disease.

Later, W.H.O. officials declared themselves satisfied that Zika was the main cause of the microcephaly outbreak.

In a later meeting, officials decided that the risk was not sufficient to justify canceling the Olympic Games in Rio de Janeiro, but was high enough that pregnant women should avoid traveling to the area.

2016 (Nov 16) - AMENDMENT TWO to Moderna, NIAID, VRC agreement

"(a) Section 3. The Confidential Information of NIAID to be disclosed under the Agreement is hereby amended to include information relating to the human parainfluenza virus ("hPIV") and related vaccines and assays."

See [HX0018][GDrive]

2016 (Nov 19) - NYTimes : "The Race for a Zika Vaccine"

Source : [HN01NN][GDrive]   /   By Katie Thomas  /   Nov. 19, 2016  /   NewLink Genetics Corporation  /  Dr. Thomas Patrick Monath (born 1940)  /   Inovio Pharmaceuticals, Incorporated  /   Zika virus epidemic (2015-2016)   /  Dr. Barney Scott Graham (born 1953)  /  

MADISON, Wis. — The Zika virus thrives in tropical climates. But it is also growing in this cold-weather city — up a flight of stairs, past a flier for lunchtime yoga and behind a locked door. That is where scientists working in a lab for Takeda, the Japanese drug company, inspect and test vials of the virus.

They are engaged in an all-out race to halt Zika, a disease that has set off worldwide alarm because of its links to severe birth defects. Day and night, these researchers are trying to crack the code to the virus.

“We’re slaves to the cells,” Jeremy Fuchs, a senior researcher at the lab, said.

And they are far from alone. Perhaps never before have so many companies and government organizations worked so quickly to develop a vaccine from scratch. Vaccines usually take a decade or more to develop. But researchers say a Zika vaccine could be available as early as 2018, in what would be a remarkable two-year turnaround.

More than a dozen companies are on the hunt, in addition to government stalwarts like the National Institutes of Health. To get ahead, some teams are employing innovative technologies that rely on splicing DNA, a method that has the potential to revolutionize the development of vaccines but that has never before been approved for use in humans.

The prestige of solving the puzzle and the chance to save lives are possible rewards. For the companies, another motive is the potential for significant profit. Unlike many recent viral outbreaks, which have been confined to poor areas, Zika has spread to countries like Brazil and the United States, with millions of wealthy people and governments that can afford public vaccination campaigns.

“It’s highly unusual,” said [Dr. Thomas Patrick Monath (born 1940)], the chief scientific officer and chief operating officer of [NewLink Genetics Corporation], one of the companies developing a vaccine. “It reflects the big opportunity and public health need, and also the fact that we have more, different technologies available today.”

But meeting the ambitious timeline is far from guaranteed. To keep the fast pace, some clinical trial organizers are trying to start their tests in South America over the next few months, when Zika infection rates are expected to be at their height there.

The timing is crucial. An outbreak of Zika provides an ideal testing ground for a vaccine, so the preventive medication can be evaluated in a population exposed to the virus. Researchers will know in short order whether the vaccines being tested are effective.

If they miss the window, a vaccine could be delayed for a year or more — a result that could lead to millions more people becoming infected with the virus.

“It’s a race against nature,” said Michel De Wilde, a vaccine research consultant and former executive at Sanofi, a French vaccine manufacturer.

The virus, spread by mosquitoes and sexual intercourse, has now been reported in more than 70 countries. This summer, it landed in the United States, spreading quickly in Puerto Rico and turning up in Miami. Government officials have advised pregnant women to avoid parts of Miami where the virus is active. In a sign that Zika will be a continuing threat, on Friday the World Health Organization lifted its nine-month emergency declaration and said it would shift to a longer-term effort to combat the virus.

By September, after acrimonious debate and a long delay in Congress, President Obama approved a $1.1 billion spending package to fight the virus. About $400 million of the money will go toward developing a vaccine and diagnostic tests.

The escalation of attention has been remarkable. Identified nearly seven decades ago, Zika was once considered mostly harmless, because about 80 percent of people who are infected show no symptoms.

But about 18 months ago, Brazilian officials began to sound alarms that it was to blame for an otherwise mysterious outbreak of babies born with microcephaly, or unusually small heads and malformed brains. Around the same time, heartbreaking photographs of children born with the condition shot around the globe.

[Dr. Barney Scott Graham (born 1953)], deputy director of the Vaccine Research Center at the N.I.H, was at a meeting in July 2015 when he learned of the threat. A Brazilian doctor pulled him aside at the meeting in Bethesda, Md., which had been called to discuss chikungunya, another tropical disease.

“I know we’re here about chikungunya,” Dr. Graham said the doctor told him. “But I really want to tell you about Zika virus.”

Within months, the link seemed increasingly clear, and public health officials predicted that the virus would probably infect millions of people. In December, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases at the N.I.H., called a meeting with the top members of his vaccine staff.

Similar meetings were occurring elsewhere in the vaccine world — at small companies like [Inovio Pharmaceuticals, Incorporated] and [NewLink Genetics Corporation], in the offices of big manufacturers like GlaxoSmithKline and Sanofi, and at the Walter Reed Army Institute of Research, which is a few miles from the N.I.H. campus in Bethesda, where Dr. Fauci’s team works.

“I said, all hands on deck,” Dr. Fauci recalled. “We have a serious problem here. We’ve got to really move.”

High Stakes and Confidence

No single person directs an operation as widespread as the race for the Zika vaccine. But Dr. Fauci certainly sits near the center of it and comes with a singular perspective.

An immunologist, Dr. Fauci, 75, has led the National Institute of Allergy and Infectious Diseases for more than three decades, playing a role in nearly every major disease outbreak since the 1980s.

And to hear him tell it, the Zika virus does not stand much of a chance.

“Without being presumptuous, most of us in the field feel that we will get a vaccine for Zika,” Dr. Fauci said recently, his staccato Brooklyn accent underscoring his confidence. “So it’s really a question of what’s the best one, how quickly can you get it, is it safe, and is it scalable?”

But he also knows the stakes.

“For a pregnant woman,” he said, “it’s absolutely devastating in its potential impact.”

His team, and the others chasing a Zika vaccine, started with a couple of big advantages. For one, the economic incentives are clear. The first company to develop an effective vaccine will win a toehold in a market that could ultimately reap billions in profit. And because governments are paying for some of the early development, the financial risk is limited.

Also, the disease belongs to a family of viruses known as flaviviruses, which scientists have been battling for more than a century. Vaccines already exist for some of these viruses, such as yellow fever, Japanese encephalitis and dengue.

Another good sign: Adults infected with Zika seem to fight off the illness on their own, meaning the human body, if given the right tools, already has the resources to defeat it.

The vaccine hunters had several options. The tried-and-true method is what is known as a killed vaccine, in which a dead virus is injected into the body. The body then builds its defense against the virus in a way that also protects against the live version. This is how many vaccines work, including those for polio and the flu.

Several teams, including those at Takeda and one at Walter Reed, chose that path. Walter Reed’s candidate entered early clinical trials in this month. Sanofi has signed on to bring that product to market.

The advantage of the killed vaccines is that they are reliable. Several vaccine specialists said they were confident a Zika vaccine using this method would succeed. The downside is that developing one takes time, sometimes decades.

Other teams, including Dr. Fauci’s scientists at the N.I.H., decided on a newer approach. It involves manufacturing a harmless piece of the virus’s DNA, the molecule that acts like an instruction manual for the body. Once injected, the DNA tells human cells to make Zika proteins. Those proteins then assemble themselves into harmless viruslike particles that trick the body into developing antibodies that can fight the disease if it arrives.

It is a startlingly simple and fast approach. Dr. Fauci’s team created a prototype that it could begin testing in mice within weeks.

“You can jump in right away,” he said.

However, DNA vaccines are largely unproved in humans. While the technology has been approved for animals, none of the vaccines have been approved for humans. A vaccine developed by the N.I.H. to prevent West Nile, another virus related to Zika, succeeded in early trials but never completed trials and was not brought to market because researchers could not find a drug company that was interested.

Part of the reason DNA vaccines are tricky, researchers say, is because the vaccine’s DNA must reach the nucleus of a person’s cells before it can begin instructing them to make Zika proteins. When the vaccine is injected into the body, not all of it reaches the nucleus, lowering its effectiveness.

To solve this problem, some companies are trying a similar method that uses RNA, a molecule in the body that is more flexible than DNA. Among the things it can do is carry out, on its own, the instructions contained in DNA. The vaccine would not need to reach a cell’s nucleus to trigger the immune response.

GlaxoSmithKline and Moderna Therapeutics, using government grants, are working on RNA vaccines for Zika that are still in their early stages.

Testing in Zika Zones

If one or more Zika vaccines are successful, it is unclear who would ultimately get them. The medication could be used only during outbreaks, or it could become routine in some parts of the world.

Early trials of the DNA-based vaccine developed by the N.I.H. are underway, and studies have begun in Puerto Rico of a similar vaccine being developed by [Inovio Pharmaceuticals, Incorporated].

The next step will be to test the vaccines in a larger pool of people who live where Zika is present. That stage must be intricately set so that the trials occur at just the right moment, at the height of summer in Latin America, which starts in December.

Not a day can be wasted. The N.I.H.’s trial coordinators are setting up trial sites at more than 20 locations in Central and South America. Once the trials begin, the coordinators will monitor local Zika cases, moving resources to sites of outbreaks and away from places where the virus is quiet.

Researchers say they are taking a lesson from the Ebola outbreak of 2014, which also spurred a race for a vaccine. In that case, the outbreak was brought under control before many of the trials could take place.

“All of us felt like we kind of really missed the boat with Ebola,” said Col. Nelson Michael, who is leading the Zika vaccine effort at Walter Reed. “We brought troops too slowly into the fight.”

In a clinic at the University of Maryland School of Medicine in Baltimore in September, several volunteers waited hours in a hallway to be among the first to receive the experimental DNA vaccine being developed by the N.I.H.

Some read college textbooks, others browsed Facebook.

Jen Wenzel, a volunteer and a postdoctoral fellow in neuroscience, said she signed up out of curiosity — and to make extra money. Volunteers are paid as much as $1,600 if they complete the study.

When it was her turn, Ms. Wenzel winced and looked away from the needle about to deliver the vaccine. “Take a deep breath,” said a nurse, who then quickly jabbed the needle into Ms. Wenzel’s arm, making her gasp in surprise.

And with that, Ms. Wenzel became the 29th person at the University of Maryland, and one of only dozens worldwide, to have received a potential Zika vaccine. Over the next two years, she will return to the clinic for follow-up tests to see how well it works.

Of course the researchers chasing a vaccine — and the many millions of people concerned about catching the virus — hope to have an answer long before then.

2016 (Nov 21) 

Zika: Researchers create powerful tool for vaccine, antiviral development

Researchers have created a powerful tool for studying the Zika virus that should be useful for vaccine and antiviral drug development. The tool creates versions of the virus that are stripped of genes that make them infectious, making them safer to work with.

https://www.medicalnewstoday.com/articles/314237 

2016 (Nov 28) - MILLIONS THREATENED

https://www.newspapers.com/image/286309399/?terms=zika%20rna&match=1

2016-11-28-the-monitor-mcallen-texas-pg-7a-clip-zika.jpg

2016 (Dec 06) - Boston Globe : "A Zika Vaccine is being developed at Warp Speed - Will there be a market for it?"

https://www.newspapers.com/image/444622080/?terms=zika%20gene%20therapy&match=1

2016-12-06-the-boston-globe-pg-c4-c5-clip-zika-vax.jpg

2016 (Dec 13) - 21st century cures act

https://en.wikipedia.org/wiki/21st_Century_Cures_Act

PDF : https://www.govinfo.gov/content/pkg/PLAW-114publ255/pdf/PLAW-114publ255.pdf 


Research and drug development[edit]

Division A, titled “21st Century Cures,” contains provisions related to National Institutes of Health funding and administration, reducing opioid abuse, medical research, and drug development.[6]



FDA drug approval process[edit]

The 21st Century Cures Act modified the FDA Drug Approval process. It was intended to expedite the process by which new drugs and devices are approved by easing the requirements put on drug companies looking for FDA approval on new products or new indications on existing drugs. For instance, under certain conditions, the act allows companies to provide "data summaries" and "real world evidence" such as observational studies, insurance claims data, patient input, and anecdotal data rather than full clinical trial results.[8][10][11]

Targeted drugs for rare diseases[edit]

The 21st Century Cures Act facilitates the development and approval of genetically targeted and variant protein targeted drugs for treatment of rare diseases.[12]

Informed consent[edit]

In section 3024, the 21st Century Cures Act allows researchers to waive the requirement for "informed consent" in cases where clinical testing of drugs or devices "poses no more than minimal risk" and "includes appropriate safeguards to protect the rights, safety, and welfare of the human subject."[12]

One example is a high-tech bandage that monitors blood flow. Standard procedure requires researchers to obtain the patient's permission before testing any new device on them. However, in this example, researchers might want to test the bandage on unconscious patients. In such circumstances, researchers may waive an informed consent requirement since the patient is still getting the standard, medically accepted care of blood pressure and heart rate monitoring. Researchers would still need to obey standard research protocols including institutional review boards to approve their research design and ethics.[8]

Human research subject protections[edit]

The 21st Century Cures Act calls on the Secretary of Health and Human Services to harmonize differences between the HHS Human Subject Regulations and FDA Human Subject Regulations. In so doing, the Secretary may change rules applying to vulnerable populations in order "to reduce regulatory duplication and unnecessary delays" and "modernize such provisions in the context of multisite and cooperative research projects."

Section 3023 provides for joint or shared review of research, review by institutional review boards other than that of the sponsor of research, and use of other means "to avoid duplication of effort."[12]

Medical research[edit]

The act allocates $4.8 billion to the National Institutes of Health for precision medicine and biomedical research.[1][8][10] Of this, $1.5 billion is earmarked for research on brain disease.[1] Another $1.8 billion is dedicated to cancer research in what is called the "Beau Biden Cancer Moonshot" initiative, named in honor of Vice President Joe Biden's son, who died of brain cancer in 2015.[1][8][13][14]

Strategic Petroleum Reserve sales[edit]

The act requires sale of 25 million barrels of crude oil (10,000,000 in 2017, 9,000,000 in 2018, and 6,000,000 in 2019) from the Strategic Petroleum Reserve.[15][16] Revenue from these sales will provide part of the NIH funding provided in the law.[17]

Electronic health records information blocking[edit]

The Act defined interoperability and prohibited[18] information blocking.[19] Information blocking is defined as a practice that interferes with or prevents access to electronic health information, that is, information about a patient's medical history or treatment.[12][20]

Under section 4004, information blocking can expose entities to fines of up to $1 million per violation.[12]

Medical software[edit]

Medical software is regulated as a medical device by the FDA in the Federal Food, Drug, and Cosmetic Act.[21] Section 3060 of the 21st Century Cures Act was created as an amendment to section 520 of the FD&C Act, which addressed how medical devices are defined.[22][23] It outlined software functions that would be exempt from FDA regulation, such as those used for administrative purposes, encouraging a healthy lifestyle, electronic health records, clinical laboratory test results and related information, and clinical decision tools.[6][24]


2016 (Dec 16) - Wall Street Journal : "America’s Next Defense Against Zika and Other Foreign Invaders"

By Betsy McKay and Peter Loftus  /  PDF of saved source : [HN022L][GDrive

Mentioned :  ADViSYS Inc.  /  

PHILADELPHIA— Dr. Keith Hamilton took his turn in the patient chair and braced for the sting of an experimental Zika vaccine.

The injection was the easy part. Next, a nurse jabbed three tiny needles in his upper arm with a device that delivered two electrical jolts strong enough to flex muscle. He said it felt like a needle piercing his arm, again and again.

Dr. Hamilton, an infectious-diseases doctor, was on a break from his rounds to volunteer in a landmark trial of a next-generation vaccine at the University of Pennsylvania’s medical school.

The Zika epidemic is accelerating work on this and other experimental DNA vaccines, which could turn out to be America’s best defense against infectious-disease outbreaks that now spread around the world with alarming speed, fueled by rising populations and global travel. These vaccines, made with synthetic DNA, can be developed and manufactured quickly.

Researchers in the U.S. and Canada have injected dozens of volunteers in the past few months with two competing DNA vaccines intended to provide immunity to the Zika virus. The mosquito-borne virus has caused hundreds of birth defects, including brain damage, and fetal deaths, mostly in Brazil.

Image : [HN022M][GDrive]
  • Defensive Measures :Conventional vaccines made from viral and bacterial invaders trigger the creation of antibodies. Experimental DNA vaccines instruct the body to make proteins that resemble the invaders and set off the body's defenses.
  • MADE IN THE FACTORY:  Inactivated vaccine
      • A virus or bacterium, or a piece, is cultivated – often in an egg – and then killed or inactivated with a chemical, to create an injectable vaccine.
      • The vaccine is injected into a patient. When the body detects a new virus, the immune system generates antibodies to attack and kill the virus.
  • MADE IN THE BODY:  DNA vaccine
      • Synthetic DNA is created that resembles genetic material from a virus or bacterium. It is then used to make a DNA vaccine.
      • The vaccine is injected into a patient. Sometimes, an electrical charge is then delivered at the site of the vaccine injection, to help the DNA penetrate cells.
      • The synthetic DNA penetrates cell membranes and instructs the cells to make proteins that resemble the virus, triggering the immune system to produce antibodies.

Inovio Pharmaceuticals Inc., which makes the vaccine in the trial here, is in a race to market its vaccine and accompanying “electroporation device,” a tool the size of an electric toothbrush that uses a jolt of electricity to help usher the firm’s DNA vaccine into human cells.

One of the National Institutes of Health is pursuing its own DNA vaccine for Zika in a trial that began this summer.

While there are significant hurdles, some researchers believe DNA vaccines could provide faster, more effective ways to combat Zika, as well as Ebola, Middle East respiratory syndrome and other deadly viruses and bacteria that have sickened millions.

Scientists can develop DNA vaccines in weeks and begin human trials within months. DNA vaccines also may provide longer-lasting immunity compared with conventional vaccines and, in some cases, even cure the malady they are intended to protect against.

Conventional vaccines take years to develop and test. They often cost more than pharmaceutical companies are likely to recoup from sales in the mostly poor tropical countries where the diseases originate. The economics discourage many firms from producing them for new, emerging diseases.

Yet the stakes are high, concluded a report this year from health experts convened by the U.S. National Academy of Medicine: “A pandemic could kill as many people as a devastating war.”

Preparedness against most of the emerging infectious diseases that threaten the world is hobbled by a lack of vaccines and drugs, experts say.

More than 41 million people have died around the world over the past decade from AIDS, malaria, tuberculosis, Ebola and other tropical diseases, according to a tally by the Institute for Health Metrics and Evaluation at the University of Washington.

The World Health Organization declared last month ​that Zika was no longer a global public health emergency, but public-health leaders said it would remain a long-term crisis until a vaccine is developed to prevent its spread.

Zika has infected more than 170,000 people in the Americas, according to the Pan American Health Organization, with hundreds of thousands more suspected cases. Brazil is girding for a resurgence of the virus as summer arrives in the southern hemisphere.

DNA vaccines are made with so-called platform technologies, building blocks that shave years off development time. Ideally, they could deliver protection while an epidemic was still spreading instead of years later. Ebola, which struck West Africa in 2014, still has no licensed vaccine.

Traditional vaccines are developed by growing batches of viruses and bacteria, a slow, labor-intensive process. DNA vaccines are made by inserting a gene related to a particular virus or bacterium into pieces of synthetic DNA called DNA plasmids, an all-purpose platform.

Last fall, as it became apparent that Zika was taking a toll, researchers at the National Institute of Allergy and Infectious Diseases, or NIAID, retrieved an experimental DNA vaccine the agency had developed about a decade ago for West Nile virus. The vaccine had shown promise in human tests, but no company agreed to finish development and produce it.

The health agency retooled the shelved West Nile vaccine by substituting a gene for Zika in the platform DNA, providing “a big head start on Zika,” said Anthony Fauci, the NIAID director. “That’s where the field of vaccinology is going—having a series of readily interchangeable platforms.”

NIAID took less than four months from the time it settled on a vaccine design to begin a human trial, said Barney Graham, deputy director of the agency’s Vaccine Research Center. The trial to assess its safety, and see if it generates an immune response, began in August. Initial results are expected by years-end. A second DNA vaccine is also being tested.

The DNA vaccines by Inovio and NIAID were the first two administered to human volunteers among nearly 30 Zika vaccines in development, according to the World Health Organization.

Even if Inovio’s and NIAID’s vaccines work in human trials, they aren’t likely to be on the market for a couple of years, the approximate time needed to satisfy regulatory requirements for effectiveness and safety.

From a business perspective, the market may be small if public-health authorities determine that a Zika vaccine need only be stockpiled for emergencies rather than administered routinely to the general population.

Companies pursuing Zika vaccines are hoping public demand for widespread immunization will create a commercial market similar to the vaccine for rubella, another disease that causes birth defects. Any Zika vaccine wouldn’t likely be aimed at pregnant women because of potential risks, but instead administered more broadly to young people.

Hundreds of millions of people are at risk, said Thomas Monath, chief operations officer of the infectious-disease division at [NewLink Genetics Corporation] , which is developing two Zika vaccines.

Zika, he said, “is the biggest opportunity for a new vaccine that’s come along in my career, and I’ve been in vaccines for 40 years.”

Electric shocks

Scientists have been working on DNA vaccines for a quarter-century, including ones for the flu and severe acute respiratory syndrome, known as SARS, an infectious virus that sprang from China in 2002 and killed 774 people out of more than 8,000 infected on several continents. None of the DNA vaccines have made it to market for human use. The main problem has been that human cells don’t easily absorb them.

Inovio’s electroporation device is intended to be a solution. After the vaccine shot, the device delivers a mild electrical current to the same spot on the arm, temporarily opening cell membranes to allow the DNA inside. “That’s the fire that cooks the meal.” said J. Joseph Kim, Inovio’s chief executive.

In late summer 2015, Dr. Kim read about the spread of Zika in South America and began work on a DNA vaccine to fight the virus. It only took about two weeks to design the DNA sequences on a computer and make a small batch of the vaccine. By December 2015, it was being tested on mice.

In June, the Food and Drug Administration approved a human study, based on animal tests that showed the vaccine triggered immunity to the Zika virus.

Inovio and GeneOne Life Science Inc., which are codeveloping the vaccine with academic collaborators at the University of Pennsylvania and the nearby Wistar Institute, a medical-research center, began their trial in July, around the same time as NIAID.

Dr. Hamilton, one of about 40 people who have volunteered to receive the experimental vaccine, said electroporation “felt more like putting a needle in multiple times rather than an electrical shock.”

Helping science was worth the discomfort, he said: “This is a small piece in a larger puzzle to come up with an effective vaccine for the people who need it the most.”

The Inovio trial is expected to be completed this month. Researchers are monitoring the volunteers for any side effects, as well as taking blood tests to see if the vaccine induces the expected immune response.

Inovio, based in Plymouth Meeting, Pa., also began a 10-month trial this summer with 160 participants in Puerto Rico, where Zika spread rapidly.

Dr. Kim, the company’s 47-year-old chief executive, got his Ph.D. in biochemical engineering at the University of Pennsylvania, where he met David Weiner, a biologist and now a director at Inovio.

After working in vaccine manufacturing and research at Merck & Co., Dr. Kim co-founded a company called Viral Genomix in 2000. The company later acquired a San Diego-based company called Inovio and took its name.

Inovio explored experimental DNA vaccines for HIV, among other technologies. At the time, the vaccines showed promise in animal studies, but failed in humans when given via standard vaccine injections.

Drs. Kim and Weiner turned to electroporation—first tried in the 1980s to boost the effectiveness of chemotherapy. In 2006, they tested an electroporation device, developed by a Texas company called [ADViSYS Inc.], to immunize monkeys against a form of HIV.

One evening, close to midnight, Dr. Kim’s home phone rang. It was Dr. Weiner calling to say the HIV vaccine, assisted by the electroporation device, had kick-started an immune response in the monkeys.

“That really triggered the path we’re on now,” Dr. Kim said. His company acquired [ADViSYS Inc.] in 2007.

The company reported positive results for its DNA vaccine against Ebola; 64 of 69 subjects mounted a strong antibody response after three doses. Inovio’s vaccine for Middle East respiratory syndrome—a virus that can cause fatal respiratory illness—was developed with GeneOne in partnership with the Walter Reed Army Institute of Research. It is in an early clinical trial.

Inovio has had to delay a new trial of its vaccine against human papillomavirus vaccine until next year after the FDA in October asked the company for more information about the stability and sterility of the disposable parts in its electroporation device, which is used to both inject vaccine and deliver an electrical jolt. Its device in the Zika trial delivers only the shock.

Not everyone has embraced DNA vaccines. Merck & Co. explored a DNA vaccine for HIV several years ago, but dropped it after a study in 2007 found it didn’t work.

Merck is now exploring synthetic RNA-based vaccines, a spokeswoman said. In theory, the approach is easier because RNA needs only to get into a cell’s cytoplasm—the material between its outer surface and the core nucleus. DNA vaccines must penetrate the nucleus to work, said W. Ripley Ballou, head of Glaxo’s U.S. vaccine research center in Rockville, Md.

GlaxoSmithKline also is exploring an RNA-based vaccine for Zika, in collaboration with NIAID. It is being tested in animals and could move to human studies next year, Dr. Ballou said.

Using the method for different vaccines is a relatively simple process, he said, “once you figure out how to do it.”

Health frontier

NIAID has pioneered DNA vaccines over the past several years for HIV, Ebola and other diseases.

Dr. Graham at the agency’s Vaccine Research Center began thinking about a Zika vaccine after learning about the spread of the virus from a Brazilian researcher who approached him at a conference in July 2015.

NIAID researchers started work on the vaccine in November and accelerated their efforts after the World Health Organization declared in February that the complications of Zika posed a global public health emergency. By June, the agency had an experimental vaccine for the human trial.

NIAID’s Zika vaccine doesn’t use an electroporation device and it may not be necessary, according to Julie Ledgerwood,  chief of the clinical trials program for the Vaccine Research Center.

Data from NIAID’s trials of the DNA Zika vaccine in monkeys, and evidence from its progenitor West Nile vaccine in humans, “makes us think this vaccine is highly immunogenic and it should work well even delivered by traditional needle,” Dr. Ledgerwood said.

A few studies conducted by other scientists have found little difference in the immune response generated by experimental DNA vaccines for HIV and the H5N1 flu that were given with and without electroporation.

NIAID has used electroporation in animal tests. “In our opinion, the device development probably still has a way to go,” Dr. Graham said. “But the technology itself, I think, is promising.”

Whether with or without an electrical shock, a successful DNA vaccine would accelerate the exploration of new technologies against Zika and other outbreaks, said Kayvon Modjarrad, associate director for emerging infectious disease threats at the Walter Reed Army Institute of Research

Dr. Modjarrad is the principal investigator of the DNA vaccine trial for Middle East respiratory syndrome that uses electroporation.

“The way we make vaccines now and what’s on the horizon,” he said, “is very, very different from the way we’ve been making vaccines for the past 100 years.”

2016 (Dec 21) - mosquitos GMO

https://www.newspapers.com/image/513986921/?terms=zika%20gene%20therapy&match=1

2016-12-21-the-journal-times-racine-wisconsin-pg-b5-clip-gmo-mosquitos.jpg

2016 (Dec 31) - year in review - Zika is referred to as "AN INTERNATIONAL SCOURGE"

https://www.newspapers.com/image/278136154/?terms=zika%20rna&match=1

2017 (March 30) - NPR : "Why Didn't Zika Cause A Surge In Microcephaly In 2016?"

March 30, 20172:21 PM ET  /  Saved PDF : [HM0071][GDrive

Back in 2015, Brazil reported a horrific a surge in birth defects. Thousands of babies were born with brain damage and abnormally small heads, a condition called microcephaly.

Scientists quickly concluded the Zika virus was the culprit. So when Zika returned last year during Brazil's summer months of December, January and February — when mosquitoes are most active — health officials expected another surge in microcephaly cases. But that never happened.

"We apparently saw a lot of cases Zika virus in 2016. But there was no microcephaly," says Christopher Dye of the World Health Organization.

The difference between 2015 and 2016 "is spectacular," he says.

Health officials were predicting more than 1,000 cases of microcephaly in the northeast of Brazil last year. But there were fewer than 100, Dye and his colleagues report [see https://www.nejm.org/doi/full/10.1056/NEJMc1608612 ] Wednesday in the New England Journal of Medicine.

"This is a huge, huge discrepancy," Dye says. "So what could possibly be the explanation for that?"

Scientists aren't sure, Dye says. But he and his colleagues suggest a few possibilities in their study.

First off, Dye says, health officials could have vastly overestimated the number of Zika cases in Brazil.

Zika can be misdiagnosed as another mosquito-borne virus, called chikungunya. Both viruses cause a fever, a rash and joint pain. "So chikungunya can easily be mistaken for Zika," Dye says. But chikungunya doesn't cause microcephaly.

So perhaps Brazil actually didn't have that many Zika cases in 2016. And in turn, there weren't a lot of babies born with microcephaly.

Now for this theory to hold true, we're talking about thousands of Zika cases being mistaken for a totally different virus that's not even closely related to Zika. Could this really happen?

"Yes, I do think it's a possibility," Dye says. "This is this is our best view of what happened in 2016."

But Albert Ko at Yale School of Public Health doesn't quite buy it.

"Misdiagnosis is a reasonable hypothesis. But it's not clear that this explanation accounts for the whole story," says Ko, an epidemiologist, who is studying mothers and babies born with Zika in the northeast part of Brazil.

Ko think's there's another possible explanation: Zika might not be working alone. When a pregnant woman contracts Zika, that might not be enough to cause microcephaly in all cases.

Since the surge in Brazil's microcephaly cases in 2015, many scientists began to wonder whether a second virus could be involved. Maybe another infection combines with Zika to make the disease worse and increase the risk of birth defects.

Dye agrees that this phenomenon could be contributing to the overestimation of microcephaly cases.

In particular, scientists have their eyes on another mosquito-borne virus, which is common in Brazil, called dengue. In 2015, the country recorded more than 1.5 million cases of dengue, including many in the northeast, where many of the birth defects occurred.

"Everything is probably speculation at this point," Ko says. "But many groups are concerned about the exposure to dengue in Brazil."

Here's why. Dengue is a complex virus. There are actually five different versions. Prior exposure to one version of dengue can actually make your illness worse when you're exposed to a second version.

And what's closely related to dengue? Zika.

"So another hypothesis is that prior exposure to dengue may actually enhance or promote the risk of birth defects from Zika," Ko says.

Right now, there is no evidence that a dengue infection exacerbates the symptoms of Zika — or increases its risk to pregnant women.

But several studies suggest it could happen. For starters, the presence of dengue antibodies helps the Zika virus infect cells in a petri dish.

And now, scientists are reporting that dengue antibodies make a Zika infection more deadly in mice.

Typically mice don't get Zika. But a team at Mount Sinai School of Medicine in New York engineered the animals to be susceptible to a Zika infection by crippling their immune systems.

The engineered mice get a fever and show signs of neurological problems when they're infected with Zika. Fewer than 10 percent of them die from the infection.

But when the mice received dengue antibodies before the Zika infection, the outcome was quite different. More than 80 percent of the mice died after eight days, immunologist Jean Lim and her colleagues report Thursday in the journal Science.

So now the big question is: Does a similar phenomenon occur in people? Ko is working on epidemiological studies in northeast Brazil, right now, to see whether that is the case. If the dengue theory turns out to be true, it could mean the global threat of Zika for pregnant women is less dire than scientists originally thought.

2017 (July 13) 

Volume 170, Issue 2, 13 July 2017, Pages 273-283.e12

Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

https://www.sciencedirect.com/science/article/pii/S0092867417307596


2017 (August 26) - The Lancet : 

ARTICLES| VOLUME 390, ISSUE 10097, P861-870, AUGUST 26, 2017

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2817%2931368-5/fulltext

PDF : https://www.thelancet.com/action/showPdf?pii=S0140-6736%2817%2931368-5 

2017-08-26-the-lancet-infection-related-microcephaly-after-2015-and-2016-zika-virus-outbreaks-in-brazil.pdf

Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis

Dr Wanderson Kleber de Oliveira, PhD 

Giovanny Vinícius Araújo de França, PhD

Eduardo Hage Carmo, MD

Bruce Bartholow Duncan, MD

Ricardo de Souza Kuchenbecker, MD

Maria Inês Schmidt, MD

Published:June 21, 2017DOI:https://doi.org/10.1016/S0140-6736(17)31368-5

2017-08-26-the-lancet-infection-related-microcephaly-after-2015-and-2016-zika-virus-outbreaks-in-brazil-fig-2a.jpg

2017-08-26-the-lancet-infection-related-microcephaly-after-2015-and-2016-zika-virus-outbreaks-in-brazil-fig-2b.jpg


The findings in this report are subject to at least four limitations. First, this is an ecologic analysis, with only limited laboratory evidence of Zika virus infection for the pregnancy outcomes described. Second, data were obtained from an ad hoc surveillance system established by MoH after the first cases possibly linked to maternal Zika virus disease were identified. The enhanced awareness regarding this event might have resulted in an increased ascertainment and reporting of cases, including identification of false positives. Third, microcephaly was probably underascertained in Brazil before this event, so the increases might not be as large as suggested by these findings; however, they are substantial increases compared with cases of microcephaly reported during 2000–2014, and in some states, such as Paraíba and Pernambuco, exceed the rate of 5.1 per 10,000 births in Brazil during 1995–2008, estimated by the Latin American Collaborative Study of Congenital Malformations (8). Finally, this study was limited to analysis of the temporal and geospatial association between the increased prevalence of microcephaly in Brazil and earlier Zika virus transmission, and other possible causes of microcephaly were not evaluated in this analysis. 

2017-08-26-the-lancet-infection-related-microcephaly-after-2015-and-2016-zika-virus-outbreaks-in-brazil-table-1.jpg

Table: 1950 confirmed cases of infection-related microcephaly by diagnostic method and occurrence after the first epidemic wave of Zika virus infection

in regions of Brazil; January, 2015–November, 2016


Figure 2: Monthly incidence of possible Zika virus infection and monthly frequency of confirmed infection-related microcephaly in Brazil, 2015–16, compared with the historical mean risk of microcephaly in Brazil States included per region: Distrito Federal, Goiás, Mato Grosso, and Mato Grosso do Sul (centre-west); Alagoas, Bahia, Ceará, Maranhão, Paraíba, Pernambuco, Piauí, Rio Grande do Norte, and Sergipe (northeast); Acre, Amapá, Amazonas, Pará, Rondônia, Roraima, and Tocantins (north); Espírito Santo, Minas Gerais, Rio de Janeiro, and São Paulo (southeast); and Paraná, Rio Grande do Sul, and Santa Catarina (south). The vertical dotted line shows the start of 2016.
Figure 2: Monthly incidence of possible Zika virus infection and monthly frequency of confirmed infection-related microcephaly in Brazil, 2015–16, compared with the historical mean risk of microcephaly in Brazil States included per region: Distrito Federal, Goiás, Mato Grosso, and Mato Grosso do Sul (centre-west); Alagoas, Bahia, Ceará, Maranhão, Paraíba, Pernambuco, Piauí, Rio Grande do Norte, and Sergipe (northeast); Acre, Amapá, Amazonas, Pará, Rondônia, Roraima, and Tocantins (north); Espírito Santo, Minas Gerais, Rio de Janeiro, and São Paulo (southeast); and Paraná, Rio Grande do Sul, and Santa Catarina (south). The vertical dotted line shows the start of 2016.

2017-08-26-the-lancet-infection-related-microcephaly-after-2015-and-2016-zika-virus-outbreaks-in-brazil-fig-3

Figure 3: Kernel density estimates of the distribution of possible Zika virus infections in pregnant women in Brazil in 2015 (A) and 2016* (B)

*Cases are up to Nov, 12, 2016.

2017-08-26-the-lancet-infection-related-microcephaly-after-2015-and-2016-zika-virus-outbreaks-in-brazil-fig-4

Figure 4: Kernel density estimates of the distribution of confirmed infection-related microcephaly in Brazil Cases in Brazil after the first wave of Zika virus outbreaks (September, 2015–April, 2016; A), and after the second wave up to data closure (May, 2016–Nov 11, 2016; B). 

2018 (April 20) - NYTimes : ""

https://www.nytimes.com/2018/04/20/health/zika-study-ethics.html?searchResultPosition=4

WASHINGTON — Members of a government ethics panel have renewed their criticisms of a controversial study in which volunteers are to be deliberately infected with the Zika virus.

In an article published this month in the journal Science, panel members called for the establishment of ethics committees to review the design of such human-challenge studies, which are sometimes used to test vaccines.

“There is no way to turn back time,” said Ms. Seema Shah, a bioethicist at the University of Washington who chaired the panel and is a co-author of the new paper.

“When you’re asking someone to take a risk that won’t benefit them but may benefit others in the future, you need to know two things — that proper protections are in place, and that it’s really going to move the needle.”