Archive for December 3, 2009

Switching Gears for an Influenza Pandemic: Validation of a Duplex Reverse Transcriptase PCR Assay for Simultaneous Detection and Confirmatory Identification of Pandemic (H1N1) 2009 Influenza Virus

Journal of Clinical Microbiology  1 Dec 2009  V.47  N.12  p.3805-3813

Jason J. LeBlanc,1* Yan Li,3 Nathalie Bastien,3 Kevin R. Forward,1,2 Ross J. Davidson,1,2 and Todd F. Hatchette1,2

Department of Pathology and Laboratory Medicine, Queen Elizabeth II Health Science Center, Halifax, Nova Scotia, Canada,1 Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada,2 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada3

Rapid methods for the detection and confirmatory identification of pandemic influenza A virus (also known as pandemic [H1N1] 2009) are of utmost importance. In this study, a conventional reverse transcriptase PCR (RT-PCR) assay for the detection of influenza A virus and the hemagglutinin of swine lineage H1 (swH1) was designed, optimized, and validated. Nucleic acids were extracted from 198 consecutive nasopharyngeal, nasal, or throat swab specimens collected early in the outbreak (127 negative specimens, 66 specimens with pandemic [H1N1] 2009 influenza virus, 3 specimens with seasonal [H1N1] influenza A virus, and 2 specimens with seasonal [H3N2] influenza A virus). The performance characteristics of the duplex RT-PCR assay were assessed and compared to those of various detection methods: a monoplex RT-PCR assay at the National Microbiology Laboratory, a real-time RT-PCR assay using a Centers for Disease Control and Prevention protocol, an in-house multiplex RT-PCR assay (targeting influenza A virus, influenza B virus, and respiratory syncytial virus), and a rapid antigen test (the Binax Now Influenza A & B assay). The sensitivity of the duplex RT-PCR assay for influenza A virus detection was 97.2%, whereas the sensitivities were 74.6%, 71.8%, 47.8%, and 12.7% for the other four assays, respectively. The duplex RT-PCR assay was also able to identify swH1 in 94% of the cases, thereby reducing the number of specimens forwarded to reference laboratories for confirmatory identification. Only a limited number of specimens that contained influenza A virus had amounts of virus that fell below the limit of detection of the assay with the swH1 primers. Overall, the duplex RT-PCR assay is a reliable method for the simultaneous detection and confirmatory identification of pandemic (H1N1) 2009 influenza virus and would be particularly attractive to laboratories without real-time RT-PCR capabilities.

abstract

http://jcm.asm.org/cgi/content/abstract/47/12/3805

PDF

http://jcm.asm.org/cgi/reprint/47/12/3805

December 3, 2009 at 11:57 pm Leave a comment

The Emotional Epidemiology of H1N1 Influenza Vaccination

N Engl J of Medicine  Nov 26, 2009  V.361  N.22

Perspective

Danielle Ofri, M.D., Ph.D.

Last spring, when 2009 H1N1 influenza first came to our attention, my patients were in a panic. Our clinic was flooded with calls and walk-in patients, all with the same question: “When will there be a vaccine?”

It was all so new then, and we didn’t have an answer. That lack of answer seemed to fuel anxiety to a fever pitch. A substantial cohort of my patients continued calling, almost on a weekly basis, to ask about the vaccine.

These, of course, were the same patients who routinely refused the seasonal flu vaccine. Each year we’d go through the same drill: I’d offer them the flu shot. I’d explain the clinical reasoning behind this recommendation. I’d strongly encourage vaccination…

abstract

http://content.nejm.org/cgi/content/full/NEJMp0911047?query=TOC

PDF

http://content.nejm.org/cgi/reprint/NEJMp0911047v1.pdf

December 3, 2009 at 11:53 pm Leave a comment

Australia’s Winter with the 2009 Pandemic Influenza A (H1N1) Virus

N Engl J of Medicine  Nov 26, 2009  V.361  N.22

Perspective

James F. Bishop, M.D., Mary P. Murnane, B.A., and Rhonda Owen, B.Sc.

When the World Health Organization declared a “public health emergency of international concern” on April 25, 2009, after the emergence in Mexico of pandemic influenza A (H1N1) virus, Australia activated its well-rehearsed plan for response to pandemic influenza.1 The Australian Health Management Plan for Pandemic Influenza is a strategic outline, based on evidence and international best practices, of actions and interventions that the health care community should consider taking during a pandemic. It describes the planning assumptions, the phases of a response, and the key actions that minimize a pandemic’s effects on the population and the health care community. Over the subsequent 6 weeks, the implementation of border-control measures — including requirements that travelers entering Australia declare whether they have symptoms of influenza or have been in contact with someone with severe respiratory illness and that contacts of persons with known influenza be traced — gave the health care community time to learn more about the natural history of the new influenza strain…

abstract

http://content.nejm.org/cgi/content/full/NEJMp0910445?query=TOC

PDF

http://content.nejm.org/cgi/reprint/NEJMp0910445v1.pdf

December 3, 2009 at 11:51 pm Leave a comment

Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand

N Engl J Medicine  Dec.3, 2009  V.361  N.23  p.2209-2220

Supachai Rerks-Ngarm, M.D., Punnee Pitisuttithum, M.D., D.T.M.H., Sorachai Nitayaphan, M.D., Ph.D., Jaranit Kaewkungwal, Ph.D., Joseph Chiu, M.D., Robert Paris, M.D., Nakorn Premsri, M.D., Chawetsan Namwat, M.D., Mark de Souza, Ph.D., Elizabeth Adams, M.D., Michael Benenson, M.D., Sanjay Gurunathan, M.D., Jim Tartaglia, Ph.D., John G. McNeil, M.D., Donald P. Francis, M.D., D.Sc., Donald Stablein, Ph.D., Deborah L. Birx, M.D., Supamit Chunsuttiwat, M.D., Chirasak Khamboonruang, M.D., Prasert Thongcharoen, M.D., Ph.D., Merlin L. Robb, M.D., Nelson L. Michael, M.D., Ph.D., Prayura Kunasol, M.D., Jerome H. Kim, M.D., for the MOPH–TAVEG Investigators

Background The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control.

Methods In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years.

Results In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], –4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, –13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed.

Conclusions This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research.

abstract

http://content.nejm.org/cgi/content/full/361/23/2209?query=TOC

PDF

http://content.nejm.org/cgi/reprint/361/23/2209.pdf

December 3, 2009 at 11:50 pm Leave a comment

Abacavir–Lamivudine versus Tenofovir–Emtricitabine for Initial HIV-1 Therapy

N Engl J Medicine  Dec.3, 2009  V.361  N.23  p.2230-2240

Paul E. Sax, M.D., Camlin Tierney, Ph.D., Ann C. Collier, M.D., Margaret A. Fischl, M.D., Katie Mollan, M.S., Lynne Peeples, M.S., Catherine Godfrey, M.D., Nasreen C. Jahed, M.P.H., Laurie Myers, M.S., David Katzenstein, M.D., Awny Farajallah, M.D., James F. Rooney, M.D., Belinda Ha, Ph.D., William C. Woodward, M.D., Susan L. Koletar, M.D., Victoria A. Johnson, M.D., P. Jan Geiseler, M.D., Eric S. Daar, M.D., for the AIDS Clinical Trials Group Study A5202 Team

Background The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.

Methods In a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir–lamivudine or tenofovir disoproxil fumarate (DF)–emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or 200 copies per milliliter at or after 24 weeks).

Results A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir–lamivudine group than in the tenofovir DF–emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir–lamivudine group versus 26 (7%) in the tenofovir DF–emtricitabine group. The time to the first adverse event was also shorter in the abacavir–lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.

Conclusions In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir–lamivudine than in those assigned to tenofovir DF–emtricitabine.

abstract

http://content.nejm.org/cgi/content/short/361/23/2230?query=TOC

PDF

http://content.nejm.org/cgi/reprint/361/23/2230.pdf

December 3, 2009 at 1:11 am Leave a comment

The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza

N Engl J Medicine  Dec.3, 2009  V.361  N.23  p.2204-2207

Perspective

Debra Birnkrant, M.D., and Edward Cox, M.D., M.P.H.

On October 23, 2009, Food and Drug Administration (FDA) Commissioner Margaret Hamburg issued an Emergency Use Authorization (EUA) for peramivir for intravenous injection (BioCryst Pharmaceuticals). Peramivir is an unapproved investigational neuraminidase inhibitor that may be effective in treating certain hospitalized adult and pediatric patients with suspected or confirmed cases of 2009 H1N1 influenza. The EUA allows health care providers to use peramivir, subject to specified conditions. This is the first EUA that has been issued for an unapproved drug….

abstract

http://content.nejm.org/cgi/content/full/361/23/2204?query=TOC

PDF

http://content.nejm.org/cgi/reprint/361/23/2204.pdf

December 3, 2009 at 1:08 am Leave a comment


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