Thursday, December 10, 2009

On Wednesday, December 9th, The New England Journal of Medicine published an article on a community cluster of oseltamivir-resistant 2009 H1N1 influenza in Vietnam. The article summarizes community level transmission of the resistant virus among students riding a train from Ho Chi Minh City to Hanoi.

Excerpts from the NEJM article - LQ Mai et al.:

“Oseltamivir-resistant infection with the 2009 pandemic influenza A (H1N1) virus has so far been described only rarely… Only 3 of the 32 patients with oseltamivir-resistant infection reported on as of this writing were not receiving oseltamivir when the resistant viruses were detected, and ongoing community transmission has not yet been shown. However, the emergence of oseltamivir-resistant 2009 H1N1 influenza remains a grave concern, since widespread oseltamivir resistance has been observed in seasonal H1N1. This resistance was unrelated to selective drug pressure, and the H275Y substitution did not appear to reduce transmissibility or severity. We report on a cluster of seven cases of oseltamivir-resistant 2009 H1N1 infection in Vietnam.

In July 2009, during a 42-hour journey, 10 students socialized together in the same train carriage. None of the students knew each other before the journey, none had contact with a person with suspected influenza in the week before the trip, none were symptomatic during the journey, and none were previously or currently receiving oseltamivir. Fever developed in four of the students within 12 hours after arrival and in two more students within 48 hours after arrival.
Nasal swabs, throat swabs, or both from all seven persons were positive for 2009 H1N1 RNA when tested with reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, and viruses were successfully cultured from specimens obtained from three of the persons. The H275Y substitution was detected retrospectively in diagnostic specimens obtained from all seven subjects before any oseltamivir treatment.

All patients recovered uneventfully, although one patient, with the highest 50% inhibitory concentration, continued to test positive on RT-PCR until day 9, despite receiving oseltamivir from the day of the onset of illness.

In this cluster, infection developed in at least 6 of the 10 people who were probably exposed to the index patient; this shows that resistant 2009 H1N1 viruses are transmissible and can replicate and cause illness in healthy people in the absence of selective drug pressure. Ongoing transmission from the cluster was not detected, but the tracing of all contacts was not possible, so ongoing transmission cannot be ruled out. However, only three other resistant cases have been detected in Vietnam as of this writing, and all were due to selection of resistant viruses during treatment rather than person-to-person transmission.

The loss of oseltamivir as a treatment option for severe 2009 H1N1 infection could have profound consequences.”

Recommendations to minimize risk included the following:

  • The use of oseltamivir should be restricted to prophylaxis and treatment in high-risk persons or the treatment of people with severe or deteriorating illness.
  • Antiviral stockpiles should be diversified.
  • Optimal dosages and combination therapies should be urgently studied.
  • Close monitoring and reporting of resistance to neuraminidase inhibitors.

This transmission episode is notable, as it is one of the largest clusters of oseltamivir-resistant 2009 H1N1 cases recorded thus far, with the highest number of epidemiologically-linked cases occurring among previously health people who were not taking the antiviral.

Helen Branswell from The Canadian Press reported on WHO’s reaction to the publication of the community cluster.


“…The event is a warning that resistant viruses can spread among healthy people and more such events may be in store, an antiviral expert with the World Health Organization said.

‘What this looks to be is ... the sort of situation we have been alert for, because it's something that we certainly don't want to see happening but need to know about if it does,’ Charles Penn said in an interview from Geneva.

Penn said this event is different from two recent clusters, in which severely immunocompromised patients in hospitals in Wales and North Carolina developed and probably transmitted among themselves Tamiflu-resistant H1N1 virus. It's known that resistance develops easily in such patients.

Prior to this report, he said, there have only been four cases spotted in people who hadn't taken the drug and didn't have traceable exposure to someone who had.

‘And then the risk of this sort of event occurring is going to increase with more virus around and those infections being treated.’ "

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