TORONTO — Seven healthy people on a train from Ho Chi Minh City to Hanoi in Vietnam caught Tamiflu-resistant H1N1 flu, researchers reported Wednesday in a prominent medical journal.
The transmission event, which occurred in July, is one of the largest clusters of cases of resistant H1N1 seen so far and the first time so many linked cases have been seen in previously healthy people who had not been on the drug.
Surveillance since the summer has only turned up three additional drug resistant viruses, the authors note in their letter to the New England Journal of Medicine. But they say they cannot rule out the possibility of ongoing transmission of resistant pandemic H1N1.
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.
This, however, is a case where healthy people, who weren't taking the drug and who had no known contacts with sick people in the week before they fell ill, were infected with resistant viruses — "which is an apparent transmission of the resistant virus in a more normal community setting," Penn said.
"This is different and it does raise the levels of concern. But it also I think reinforces the message that we do need to be constantly monitoring for this. And reporting it as quickly as it's observed."
The scientists, from Vietnam's National Institute of Hygiene and Epidemiology and Oxford University's clinical research unit in Vietnam, reported that the event first hit the radar in early September when routine screening of H1N1 viruses turned up three with the mutation known to confer resistance to Tamiflu.
The ensuing public health investigation uncovered a tale of a 42-hour train trip in which 10 students who didn't know each other prior to the journey socialized on the train.
Six of the 10 became sick a day or two after arriving at their destination. Two didn't develop symptoms and public health officials were not able to trace two others.
Interestingly, a seventh person who travelled in a different carriage on the same train and who doesn't appear to have been in contact with the students also contracted Tamiflu resistant H1N1 during the trip.
"Ongoing transmission from the cluster was not detected, but the tracing of all contacts was not possible, so ongoing transmission (of resistant virus) cannot be ruled out," the authors wrote, adding that careful use of flu antivirals should be stressed to minimize that risk.
Penn said to date there have been over 100 cases of Tamiflu-resistant H1N1 viruses spotted. About a third have been seen in immunocompromised patients. Of the remaining two-thirds, nearly all have been in people who took the drug to treat or prevent illness, or who had close contact with people who took the drug for one of those purposes.
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.
The authors reported they were able to grow viruses from samples from three of the cases.
Penn said the WHO will want to know if the viruses have been checked for other mutations that might account for the seemingly easy spread of resistant viruses. "I think we'll be in touch with the authors."
It used to be thought that flu viruses that developed resistance to Tamiflu would be so weakened by the mutation that confers resistance that they would not be able to spread from person to person. But that belief was shattered in the winter of 2008 when Norway reported a startling rate of Tamiflu resistance in seasonal H1N1 viruses.
Over the next year, the resistant seasonal H1N1 viruses virtually crowded out the Tamiflu-susceptible versions of the virus — a precedent public health authorities don't want to see repeated with the pandemic virus.
"But we are expecting and we've said this, that as the pandemic spreads through this Northern Hemisphere winter and as the medicines continue to be used around the world, the number of sporadic cases is going to rise, as it has been at a steady by small rate," Penn said.
"And then the risk of this sort of event occurring is going to increase with more virus around and those infections being treated."
Makes you wonder what happened on the train.
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