NEWS SCAN: Resistant H1N1, Tamiflu's pandemic benefits, Canada's flu vaccine sources, dengue predictions

Sep 29, 2010

Another multidrug-resistant H1N1 case reported
Resistance to three antiviral drugs was detected in 2009 H1N1 influenza virus collected from a 5-year-old boy in the Netherlands who died earlier this year from a combination of leukemia and multiple infections, according to a letter published online by the New England Journal of Medicine (NEJM). The boy was hospitalized in November with flu-like symptoms while being prepared for stem-cell transplantation. After the 2009 H1N1 virus was detected, he was treated with oseltamivir (Tamiflu) and broad-spectrum antibiotics. He underwent the transplantation on Nov 23, but an increased viral load was detected on Dec 2, and the H275Y mutation in viral neuraminidase, which confers resistance to oseltamivir but not zanamivir (Relenza), was found. He was then treated with intravenous zanamivir and subsequently recovered clinically. But on Jan 11 he was hospitalized again with signs of a lower respiratory tract infection, and tested positive for influenza, cytomegalovirus, and rhinovirus. He was treated again with IV zanamivir, but he ultimately died. Retrospective sequencing of H1N1 virus isolates revealed the I223R mutation in neuraminidase, which has been linked to oseltamivir resistance in H3N2 flu viruses. Further testing of the virus showed varying degrees of resistance to oseltamivir, zanamivir, and the experimental antiviral peramivir. The authors write that the boy's inadequate immune response and possibly suboptimal drug levels may have contributed to emergence of the I223R mutation. The case is similar to one reported last week, in which a 14-year-old girl died of a resistant H1N1 infection and other illnesses, with the virus showing resistance to the same three drugs.
Sep 29 NEJM letter
Sep 23 CIDRAP News report of case in 14-year-old girl

Chinese study fleshes out Tamiflu benefits during pandemic
A Chinese study of patients who were hospitalized and closely monitored during the early months of the pandemic outbreak suggests that oseltamivir (Tamiflu) protected patients against radiographically confirmed pneumonia and shortened the duration of fever and viral RNA shedding. The researchers, who published their findings in the British Medical Journal (BMJ), performed a retrospective review of 1,295 Chinese patients who had lab-confirmed 2009 H1N1 infections from May 2009 to Jul 31, 2009. During that time China's health ministry required all suspected pandemic flu patients to be hospitalized and treated with antivirals, and it recommended taking additional respiratory samples to gauge viral clearance to help with hospital discharge timing. The researchers determined that 76% were treated with oseltamivir within a median of 3 days of becoming symptomatic. Of 920 patients who had chest x-rays, only 12% had pneumonia findings. Another key finding was that viral shedding among the patients started from 1 day before symptom onset to 8 days after onset for 91% of patients, which they said is longer than the 5-day shedding seen for adults with seasonal flu. The investigators urged caution when interpreting their results, pointing out that not all patients had chest radiographs. They wrote that while their findings show benefits for oseltamivir treatment, more study is needed to help fine-tune clinical recommendations and public health response.
Sep 28 BMJ abstract
Sep 28 EurekAlert press release

Canada seeks backup source of pandemic flu vaccine
The Canadian government is looking for a backup source of pandemic influenza vaccine in case its main supplier can't deliver, the Canadian Press (CP) reported. The government is seeking a 10-year contract with a domestic company to provide pandemic vaccine and part of the seasonal vaccine supply. In addition, it has asked for proposals from other companies for a 3-year contract to provide seasonal vaccine and serve as a secondary supplier of pandemic vaccine, if necessary. If two contracts are awarded, the step will be a departure from Canada's long-standing policy of having just one source of pandemic vaccine. The report said the move may be in part a response to criticism that arose at the peak of the H1N1 pandemic, when it appeared for a while that Canada wasn't getting enough vaccine to meet the demand. Sanofi Pasteur has submitted a bid to provide the backup supply of pandemic vaccine, a company spokeswoman told the CP. In 2001 Canada became the first country to make a deal for pandemic vaccine, when it signed a contract with GlaxoSmithKline, which has the only flu vaccine production facility in the country, the story noted. That contract will expire in 2011.
Sep 27 CP story

Predictions market group launches dengue project
In a follow-up of its pandemic flu prediction markets, Iowa Electronic Health Markets, based at the University of Iowa, recently launched a dengue forecast project. The group's prediction markets average participant predictions to produce a consensus forecast on a range of topics, from political races to flu activity, according to a posting yesterday from Philip Polgreen, MD, MPH, a faculty member with the program, on ProMed-mail, the Internet-based reporting system of the International Society for Infectious Diseases. The markets are designed to synthesize experts' experience from the field and observations from past outbreaks. Participants use virtual money to make trades. In the electronic market's latest project, participants are asked to predict the total number of US dengue cases in 2010, the percentage increase in clinical cases in the Americas this year, and the number of US states that will report locally acquired dengue cases in 2010.
Sep 28 ProMed-mail post

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