Community Transmission of Tamiflu Resistant Pandemic H1N1 in Israel

community transmission of ph1n1 tamiflu resistance in israel

h274y is a genetic marker indicating that a flu virus is resistant to our major antiviral tx drug, tamiflu. tamiflu is one of the very few still useful antiviral drugs that we have available. it is credited with saving many lives during our current flu pandemic. so, what if we lose this drug?

why is it important to look at this possibe outcome? what we are seeing is increasing numbers of novel swine flu cases in which tamiflu resistance has occured in widely separated locales. it is ominous in that some of these patients were never even treated with tamiflu. so how did this happen, and what is the future impact? dr. niman reminds us that pandemic h1n1 is following the same pattern as seasonal h1n1 in which tamiflu resistance occurred within a relatively short time frame world wide. this is going to be a hugh problem at some point. what really concerns me is that many of the resistant cases have occurred in locations where the much more virulent bird flu virus is endemic. if a host is co-infected with tamiflu resistant swine flu as well as bird flu, that would be very bad indeed as tamiflu is really important in keeping bird flu in check in places like indonesia where the populations of whole villages have been treated to stop the chain of transmission.

in november 2009, a healthy 2-year-old boy was admitted to the pediatric intensive care unit at the western galilee hospital in nahariya, israel, after he had been hit by a car. one day before the accident, he had exhibited fever and cough (for which he had been treated with acetaminoiphen). his 4-year-old brother had recovered recently from an influenza-like illness without antiviral treatment.

the above comments are from the upcoming paper entitled “community-acquired oseltamivir-resistant pandemic (h1n1) 2009 in child, israel”. the child was subsequently treated with oseltamivir, but the sample collected prior to the start of treatment was h274y positive. since the brother was the likely index case in the familial cluster, and had not been treated, he likely also had been infected with ph1n1 containing h274y.

the h274y detected in the younger brother was in a mixture with wild type, and detected with a sensitive assay directed at h274y. since the confirmation was reported after the start of tamiflu treatment and the patient’s condition improved, detection of h274y did not change the antiviral treatment. thus, although the detection of h274y was not related to treatment, the only matching category for this patient in who and cdc reports would be detection of h274y in a patient treated with tamiflu.

the train passengers in vietnam, who were treated with tamiflu after sample collection, represented a similar situation. h274y was detected through routine screening of the samples months after the patients recovered. it appears that these patients, who had h274y prior to treatment, would also be categorized as h274y in patients treated with tamiflu.

the authors of the above paper, as well as the paper on the train passengers, noted the low number of patients who were h274y positive and not linked to treatment. however, this low number appears to be based on a classification system that is factually correct, but misleading to most, including physicians and researchers in the field. the situations in israel and vietnam are common, since testing for h274y is not done in real time, and even when in-house testing is in place, patients are still started on tamiflu prior to receipt of test results. thus, patients with h274y and no treatment are largely limited to patients that are tested but not treated, which is rare because most hospitalized patients are treated and most non-hospitalized patients, like the index case in this cluster, are not tested.

the vast majority of 2010 ph1n1 sequences in japan now have h274y and isolates cluster in phylogenetic analysis, indicating h274y is widely transmitted in japan.