Edward McSweegan - Retired NIH & Global Virus Network

2017 international meeting of the Global Virus Network

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The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 40 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. The 2017 meeting was held from September 25-27 in Melbourne, Australia, and was hosted by the Peter Doherty Institute for Infection and Immunity and the Institut Pasteur. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including the recent Zika epidemic, infections by human papillomavirus, influenza, HIV, hepatitis C, HTLV-1, and chikungunya viruses, and new and emerging viruses in the Australasia region. Plans for the 2018 meeting also are noted.

A pilot study to expand treatment of chronic hepatitis C in resource-limited settings

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The past five years have seen a revolution in the treatment of chronic hepatitis C, as short duration oral regimens of direct-acting antiviral drugs (DAAs), with nearly 100% cure rates for all genotypes, have replaced longer courses of ribavirin and injected interferon. Although initially very expensive, these DAAs are now becoming available in generic equivalents in countries with large numbers of chronically infected people, such as India. However, a number of obstacles may hinder the delivery of these drugs in resource-limited settings, including lack of access to diagnostic testing and the restriction of treatment to a small number of medical specialists. New approaches are therefore needed to make DAAs available to the estimated 71 million infected people, many of whom disproportionately live in low- or middle-income countries. A recent pilot study (ASCEND) of hepatitis C management in a low-income population in Washington, D.C., demonstrated that trained nurse practitioners, primary care physicians and hepatologists were equally successful in diagnosing and treating patients, indicating that such an approach might be successful in resource-limited regions of the world. Members of the Global Virus Network have received funding to carry out a similar training project in a region of India with a high prevalence of hepatitis C. This paper reviews the challenges of delivering DAA therapy in low- and middle-income countries, describes plans for performing and evaluating the effectiveness of a training program in India, and discusses future needs for the eventual elimination of hepatitis C.

Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

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In response to the outbreak of Zika virus (ZIKV) infection in the Western Hemisphere and the recognition of a causal association with fetal malformations, the Global Virus Network (GVN) assembled an international taskforce of virologists to promote basic research, recommend public health measures and encourage the rapid development of vaccines, antiviral therapies and new diagnostic tests. In this article, taskforce members and other experts review what has been learned about ZIKV disease in humans, its modes of transmission and the cause and nature of associated congenital manifestations. After describing the make-up of the taskforce, we summarize the emergence of Zika in the Americas, Africa and Asia, its spread by mosquitoes, and current control measures. We then review the spectrum of primary Zika virus disease in adults and children, sites of persistent infection and sexual transmission, then examine what has been learned about maternal-fetal transmission and the congenital Zika syndrome, including knowledge obtained from studies in laboratory animals. Subsequent sections focus on vaccine development, antiviral therapeutics and new diagnostic tests. After reviewing current understanding of the mechanisms of emergence of Zika virus, we consider the likely future of the pandemic.

2016 International Meeting of the Global Virus Network

6 Recommendations
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Mar 2017
Ramesh Akkina
Heinz Ellerbrok
William Hall
[...]
Anders Vahlne

The Global Virus Network (GVN) was established in 2011 in order to strengthen research and responses to current viral causes of human disease and to prepare against new viral pandemic threats. There are now 38 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. GVN scientists meet annually to learn about each other's current research, address collaborative priorities and plan future programs. The 2016 meeting was held from October 23–25 in Hokkaido, Japan, in partnership with the Japanese Society for Virology, the National Institute of Infectious Diseases of Japan and the Research Center for Zoonosis Control of Hokkaido University. This report highlights the accomplishments of GVN researchers in many priority areas of medical virology, including the current Zika epidemic, infections by human papillomavirus, influenza, Ebola, Lassa, dengue, HIV, hepatitis C, and chikungunya viruses, and the development of improved diagnostics and new vaccines.

Screening transplant donors for HTLV-1 and -2. Robert C. Gallo, Luc Willems, Hideki Hasegawa and the Global Virus Network’s Task Force on HTLV-1. Blood 2016 128:3029-3031. doi: https://doi.org/10.1182/blood-2016-09-739433

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Dec 2016
E. McSweegan

The Global Virus Network: Challenging chikungunya

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The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World." Copyright © 2015. Published by Elsevier B.V.

Unorthodox Alternative Therapies Marketed to Treat Lyme Disease

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Background: Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Methods: Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. Results: More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Conclusions: Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful.

A quarter-century of Indo-U.S. vaccine research collaboration: Working through informal channels 25 years ago, officials built a bilateral vaccine program that continues to support solid research in this field

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Jan 2012
E. McSweegan

Antiscience and ethical concerns associated with advocacy of Lyme disease

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Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health.

Scientific evidence and best patient care practices should guide the ethics of Lyme disease activism

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Johnson and Stricker published an opinion piece in the Journal of Medical Ethics presenting their perspective on the 2008 agreement between the Infectious Diseases Society of America (IDSA) and the Connecticut Attorney General with regard to the 2006 IDSA treatment guideline for Lyme disease. Their writings indicate that these authors hold unconventional views of a relatively common tick-transmitted bacterial infection caused by the spirochete Borrelia burgdorferi. Therefore, it should come as no surprise that their opinions would clash with the IDSA's evidence-based guidelines for the diagnosis and treatment of Lyme disease. Their allegations of conflict of interest against the IDSA resemble those made against the National Institutes of Health, the Food and Drug Administration and the Centers for Disease Control and Prevention in 2000, which were found to be baseless. It is the responsibility of all physicians and medical scientists to stand up to antiscientific, baseless and unethical attacks on those who support an evidence-based approach to caring for patients.

Lyme Disease and the Politics of Public Advocacy

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Jan 2009
E. McSweegan

Anti-tumor necrosis factor-alpha treatment for Lyme borreliosis

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Jan 2008
E. McSweegan

A Critical Appraisal of “Chronic Lyme Disease”

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"Chronic Lyme disease" is often used to explain persistent pain, fatigue, and neurocognitive symptoms in patients without any evidence of previous acute Lyme disease. Once this diagnosis is given, prolonged treatment with multiple antimicrobial agents may follow. This review examines the scientific evidence for chronic borrelia infection and explains the approach to clinical evaluation and management in patients with a diagnosis of chronic Lyme disease.

Correspondence - The Lyme vaccine: a cautionary tale

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Feb 2007
E. McSweegan

Lyme vaccine demonized by advocacy groups

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Apr 2006
E. McSweegan

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Plague

Mar 2005
E. McSweegan

The 14th-century plague that decimated the medieval world left indelible marks on the European psyche, culture, and genome (in the form of the CCR5-Δ32 deletion allele, which today confers some resistance to HIV). Centuries later, the memories of that infectious apocalypse were still so compelling that the Travelers Insurance Co included the plague in their 1964 New York World’s Fair exhibit “The Triumph of Man.” The exhibit’s 13 historical audiovisual dioramas depicted humanity’s ascent from the African plains to outer space. The eighth exhibit, entitled “The Black Death,” was a reminder of just how rocky and uncertain was that ascent.

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Online punching bags [4]

Mar 2005
E. McSweegan

Bullets and Bacilli: The Spanish-American War and Military Medicine

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Jul 2004
E. McSweegan

Biodefence funds have tight strings attached

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Feb 2004
E. McSweegan

Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and how science impacts upon all aspects of society and life.

Lyme disease: a potential polymicrobial infection

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Nov 2003
E. McSweegan

Lack of trained security staff delays US visas

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Jun 2003
E. McSweegan

Long-term effects of antiterrorism legislation

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Feb 2003
E. McSweegan

Raccoons, parasites have bioterrorism potential

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Nov 2002
E. McSweegan

Screening Foreign Scholars

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Sep 2002
E. McSweegan

Scourge: The Once and Future Threat of Smallpox

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Mar 2002
E. McSweegan

Portugal: A case history in S&T cooperation (vol 291, pg 2549, 2001)

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Aug 2001
E. McSweegan

Lyme disease (LD) is a potential health concern for school-age children

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Jul 2001
E. McSweegan

Portugal: A Case History in S&T Cooperation

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Apr 2001
E. McSweegan

In 1989, formal United States-Portugal cooperation in science and technology (S&T) was almost nonexistent. Within Europe, only the former German Democratic Republic had less scientific contact with U.S. S&T agencies. A dozen years later, it would seem that not much has changed. A recent search of

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Pox warning

Feb 2001
E. McSweegan

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Address to the AAAS

Dec 1999
E. McSweegan

Earlier this year Science asked readers to imagine what life would be like in the year 2050. Here, we present the final December installment of these fictional essays.

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Hot times for hot labs

Nov 1999
E. McSweegan

A Tool for Assessing Impacts on Health

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Feb 1999
E. McSweegan

Submitting Biologics Applications to the Center for Biologics Evaluation and Research Electronically

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The Food and Drug Administration (FDA) has gained significant experience with computer-assisted licensing applications, and has concluded that continued reliance on customized formats is a burden for the FDA and industry. As a result, the FDA is working to standardize the content and format of electronically submitted applications, and to establish procedures for electronic applications that will: create minimal additional work for industry and reviewers, establish consistency across the FDA's centers, and expedite the review process. The FDA is proposing to move to a paperless regulatory process by the year 2002. Toward that goal, the FDA's Center for Biologics Evaluation and Research (CBER) has released new guidance for the electronic submission of biologic and product license applications; case report forms, tabulations, and statistical data; and lot release protocols. A pilot program for Investigational New Drug applications also has been initiated.

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Scientist-Diplomats

Oct 1998
E. McSweegan

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Prion diseases

Mar 1998
E. McSweegan

Infectious Diseases and Mental Illness: Is There a Link

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Mar 1998
E. McSweegan

Dissecting complex carbohydrates with “virtual” tools

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Nov 1997
E. McSweegan

TNF antibodies get new lease

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Feb 1997
E. McSweegan

Bioluminescence and Chronic Disease

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Nov 1996
E. McSweegan

The Infectious Diseases Impact Statement: A Mechanism for Addressing Emerging Diseases

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Jun 1996
E. McSweegan

The use of an Infectious Diseases Impact Statement (IDIS) is proposed for predictive assessments of local changes in infectious diseases arising from human-engineered activities. IDIS is intended to be analogous to an Environmental Impact Statement. The drafting of an IDIS for specific activities, particularly in developing nations, would provide a formal mechanism for examining potential changes in local health conditions, including infected and susceptible populations, diseases likely to fluctuate in response to development, existing control measures, and vectors likely to be affected by human activities. The resulting survey data could provide a rational basis and direction for development, surveillance, and prevention measures. An IDIS process that balances environmental alterations, local human health, and economic growth could substantially alter the nature of international development efforts and infectious disease outbreaks.

Emerging bacterial zoonotic and vector-borne diseases. Ecological and epidemiological factors

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Among the etiologic agents of emerging infectious diseases are several bacterial organisms that naturally reside in animal and arthropod hosts. The most compelling emerging bacterial zoonotic and vector-borne diseases in the United States are Lyme disease; a Southern erythema migrans-like illness; human monocytic ehrlichiosis; human granulocytic ehrlichiosis; a novel cat flea-associated typhus group rickettsiosis; bartonelloses of immunocompetent and immunocompromised persons, particularly with AIDS; and sylvatic plague. Some of these antimicrobial-treatable infections are life threatening. During the acute stage of illness when antimicrobial agents are most effective, the flulike clinical signs and symptoms and available laboratory tests frequently do not point to a particular diagnosis. Epidemiological factors determined by the ecology of the bacteria are often the most useful diagnostic clues. The recognition of these evolving problems emphasizes the need for development of better laboratory diagnostic methods, for surveillance for and tracking of disease, and for continued research into factors contributing to transmission of the organisms. The continual appearance of previously unidentified bacterial infections requires prospective national strategies for timely recognition of the syndrome, identification of the agent, establishment of criteria and methods for diagnosis, optimization of the treatment regimen, and determination of successful approaches to prevention and control.

Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in HospitalsA Challenge to Hospital Leadership

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Objective. —To provide hospital leaders with strategic goals or actions likely to have a significant impact on antimicrobial resistance, outline outcome and process measures for evaluating progress toward each goal, describe potential barriers to success, and suggest countermeasures and novel improvement strategies.

Bacterial endotoxins and pathogenesis of Gram-negative infections: Current status and future direction

1 Recommendation
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100 years after the discovery of a bacterial 'endotoxin', 50 years after the introduction of antibiotics and 25 years after the routine use of intensive care units to support septic shock patients, Gram-negative infections continue to account for significant morbidity and mortality. In the coming decade, basic research on the structure/function of LPS, the cytokine cascade, and receptor-mediated intracellular signalling responses to LPS and cytokines will provide a greater understanding of the molecular, cellular and systemic responses to endotoxin and infection. New therapeutic agents now emerging from research, and better designed clinical trials to assess those agents will contribute to the next significant decline in sepsis- and shock-related morbidity and mortality. This article summarizes the findings of a workshop convened at the National Institutes of Health (NIH) to examine current research on endotoxin and Gram-negative septic shock.

Current Status of Bacterial Endotoxins

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Intestinal mucus gel and secretory antibody are barriers to Campylobacter jejuni adherence to INT 407 cells

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An in vitro mucus assay was developed to study the role of mucus gel and secretory immunoglobulin A (sIgA) in preventing attachment of Campylobacter jejuni to INT 407 cells. An overlay of rabbit small intestinal mucus was found to impede the attachment of C. jejuni to a monolayer of INT 407 cells. Mucus from rabbits previously colonized with C. jejuni was found to completely inhibit bacterial adherence to the underlying cells. Anti-Campylobacter sIgA was readily detected in mucus samples from previously exposed rabbits and was responsible for eliminating bacterial adherence to the INT 407 cells. This was shown by loss of inhibition after mucus absorption with Campylobacter cells. sIgA-containing mucus caused aggregation of the C. jejuni cells within the mucus layer of the assay system. Nonimmune mucus and sIgA alone were unable to cause bacterial aggregation, suggesting a cooperative role for mucus and sIgA. Antibodies responsible for adhesion inhibition were cross-reactive among several Campylobacter strains and were not directed solely against flagellar antigens.

Identification and characterization of two Campylobacter jejuni adhesins

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Campylobacter jejuni is able to colonize the human intestinal mucosa and cause disease. For this reason, it was important to investigate mechanisms by which C. jejuni adheres to epithelial cells and intestinal mucus gel. All strains of C. jejuni used were able to adhere to INT 407 epithelial cells and mucus, but high adherence to one substrate did not necessarily indicate comparable adherence to the other. The adherence of C. jejuni to cells was inhibited partially by treating the bacterial cells with proteases or glutaraldehyde or by adding a certain carbohydrate (fucose or mannose) to the medium. The flagellum of C. jejuni was identified as a potential adhesin by comparing adherence of flagellated and aflagellated variants. Shearing of the bacterial cells to remove the flagella reduced bacterial adhesion, whereas immobilization of the flagellum with KCN increased adhesion. Purified flagella showed specific, fucose-resistant binding to epithelial cells but not to intestinal mucus. The presence of a second, nonproteinaceous adhesin was suggested because no single treatment of the bacteria completely inhibited adhesion. Lipopolysaccharide (LPS) was identified as another C. jejuni adhesin. [3H]LPS specifically bound to epithelial cells, and this phenomenon was inhibited by periodate oxidation of the LPS or glutaraldehyde fixation of the epithelial cells. LPS, unlike flagella, was fucose sensitive and inhibited binding of whole bacterial cells to INT 407 cells. LPS was also able to bind to intestinal mucus gel. These data indicate that both flagella and LPS are important in adhesion to the mucosal surface.

Identification and characterization of mouse small intestine mucosal receptors for Escherichia coli K-12(K88ab)

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Adhesion of 3H-labeled Escherichia coli K-12(K88ab) to CD-1 mouse small intestine mucus and brush border preparations, immobilized on polystyrene, was studied. E. coli K12(K88ab) was shown to adhere readily to either crude mucus or brush border preparations, but not to bovine serum albumin. In contrast, the nearly isogenic E. coli K-12 strain, i.e., lacking the K88ab plasmid, did not bind well to either mucus, brush borders, or bovine serum albumin. The adhesion of E. coli K-12(K88ab) to both mucus and brush borders required pilus expression (i.e., growth at temperatures greater than 18 degrees C) and was inhibited by pretreatment of either mucus or brush borders with trypsin, pronase, or sodium metaperiodate and by the presence of D-galactosamine. Crude mucus was fractionated by gel filtration, and the proteins in receptor-containing fractions were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Separated proteins were Western blotted to nitrocellulose. Adhesion of 35SO4-labeled E. coli K-12(K88ab) and 35SO4-labeled E. coli K-12 to Western blots followed by autoradiography revealed two E. coli K-12(K88ab)-specific mucus receptor proteins (57 and 64 kilodaltons). Brush borders contained the same two receptor proteins present in mucus and an additional 91-kilodalton receptor protein.

Identification andCharacterization ofMouseSmallIntestine Mucosal Receptors forEscherichia coli K-12(K88ab)

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Adhesion of enterotoxigenic Escherichia coli to immobolized intestinal mucosal preparations: a model for adhesion to mucosal surface components

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The ability of enterotoxigenic strains of E. coli to adhere to immobilized mucosal components prepared from the large and small intestines of mice was examined in vitro. Various strains of E. coli were labeled with (3H)-acetate and incubated in tissue culture plates containing immobilized mucosal components or bovine serum albumin. E. coli strains which were positive for K88 or K99 antigen, and one E. coli strain isolated from a human urinary tract infection, were shown to adhere readily to large and small intestinal mucosal preparations, but not to bovine serum albumin. E. coli K-12 and a variety of enterotoxigenic strains isolated from humans, including a CFA/1 positive strain, demonstrated little or no ability to adhere to any of the preparations. E. coli adhesion to the mucosal preparations was shown to be mannose-resistant for all E. coli strains tested, but was inhibited by growth of the organisms at 18°C. Adhesion of each of the K88 or K99 positive strains was inhibited by homologous antiserum, but not by heterologous antiserum or normal rabbit serum. The data indicate that the mucosal preparations employed contain receptors for specific bacterial adhesins, and suggest that the use of such preparations may provide an alternative to the use of whole cells both as a source of receptor and as a means of investigating the adhesive properties of E. coli.

Interaction of the lectin limulin with capsular polysaccharides from Neisseria meningitidis and Escherichia coli

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The lectin limulin from the serum of the horseshoe crab binds to -acetylneuraminic acid and 2-keto-3-deoxyoctonate residues. These interactions were examined using capsular polysaccharides from strains of and . Our findings indicate that limulin has greatest reactivity with homopolymers of -acetylneuraminic acid as compared with heteropolymers of either sugar. Polysaccharides with α(2→9) ketosidic linkages were most efficient in precipitating this lectin. Finally, -acetylated homopolymers of -acetylneuraminic acid were more reactive than their -acetyl-negative counterparts.

In vitro adhesion of enterotoxigenic Escherichia coli to soluble components of intestinal mucus gel /

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E. McSweegan

Typescript. Binder's title: ETEC adhesion to intestinal mucus gel. Thesis (Ph. D.)--University of Rhode Island, 1984. Includes bibliographical references (leaves 95-102).