Did drug-resistant swine flu spread between teens?

indigo girl · Sep 11, 2009

additional spread of tamiflu resistance in the united states

h274y is a genetic marker that some influenzas carry signifiying resistance to the antiviral drug, tamiflu.

three state public health laboratories perform antiviral resistance testing and report their results to cdc. an additional two oseltamivir resistant 2009 influenza a (h1n1) viruses have been identified by these laboratories, bringing the total number to nine.
the above comments from the latest cdc update (week 34) describe two more cases of oseltamivir resistance in states that do their own antiviral resistance (ca, ny, wi). wi's week 34 report had no resistance in swine h1n1 and ny has not updated its site since the end of seasonal flu reporting in april, so it is likely that the two new cases are from california. california has already reported resistance in an h1n1 hospitalized case in northern california, and the cdc has not identified a tamiflu linkage, raising concerns that the h1n1 in this case is evolutionarily fit. moreover, the first evolutionarily fit pandemic h1n1 identified in hong kong was from a traveler from san francisco, increasing concerns that evolutionarily fit h1n1 with h274y is circulating in northern california. the latest two cases are also likely form california, and although the week 34 report indicated these new cases had a tamiflu linkage, the relationship between the collection date of the h274y positive samples and the start of tamiflu treatment remains unclear.
these nine cases in the us are in addition to three cases in japan, three in hong kong and at least one each from denmark, canada, thailand, china, and singapore. thus, 20 cases have been made public, including at least two were evolutionarily fit.
roche has recently issued a press release on reports of 13 tamiflu resistant cases and noted that these cases were rare and expected because of prior tamiflu resistant cases, including a rate of 4% in children. however, the cases in children were many years ago in japan, where sub-optimal doses of tamiflu were used to treat symptomatic children. most of these children were infected with h3n2 and most resistance markers were not h274y, these cases represented an usual set of circumstances which have not produced any recent cases. indeed, there have been been no recent h3n2 cases resistant to tamiflu, and all recent h1n1 cases (seasonal as well as pandemic) have involved just one change, h274y. moreover, the seasonal cases were almost exclusively in patients who had not been treated with tamiflu.
the latest report from hong kong describes another case in a patient that had not received tamiflu, and was presumably from a brother (32m), who was positive for tamiflu sensitive h1n1 three days earlier. the short time between the start of tamiflu treatment and the appearance of resistance was similar to data from singapore. the rapid appearance of h274y in patients being treated with tamiflu is similar to the rapid appearance of resistance in patients on prophylactic tamiflu, strongly supporting the silent spread of a sub-population with h274y,
thus, the detected h274y is not due to de novo spontaneous appearances, but were linked to widespread pandemic h1n1 with h274y.

http://www.recombinomics.com/news/09100901/h274y_us_additional.html

indigo girl · Sep 11, 2009

camper to camper transmission of tamiflu resistant h1n1

http://www.recombinomics.com/news/09100902/h274y_camper_h2h.html

on july 8, she experienced cough and headache without fever, and on july 9 she experienced chills, worsening headache, and loose stools. despite these symptoms, her oseltamivir dose was not increased to a therapeutic treatment dose. on july 10, the last day of the first camp session, she traveled away from camp with three family members while ill, returning on july 12, afebrile and with a cough, to attend the second session. on july 12, a rapid influenza detection test was positive for influenza a.
a second previously healthy adolescent girl, who resided in the same cabin as patient a, began oseltamivir chemoprophylaxis at a dose of 75 mg daily on july 7 after exposure to patient c. on july 10, patient b left camp for a home visit during the break between camp sessions. the next day, while at home, she experienced onset of fever (101.9ºf [38.8ºc]), sore throat, and cough. she continued to engage in normal activities while ill, including visiting a shopping mall and movie theater. she returned to camp for the second session on july 12 with fever, headache, cough, malaise, and myalgias. on july 12, a rapid influenza detection test was positive for influenza a.
on august 14, cdc testing of viral rna detected h275y and i223v mutations
the above comments are from tomorrow's mmwr and describe two summer campers who were infected with oseltamivir (tamiflu resistant) pandemic h1n1 while on prophylactic tamiflu. since the campers shared the same cabin, and developed symptoms four days apart, it is likely that one camper infected the other. the scenario is also supported by the detection of the same rare marker, i223v, which has not been reported in other human or swine pandemic h1n1 isolates, but is present in two avian h1n 1isoaltes (see list here).
the report of this human to human transmission follows a similar report in hong kong, reported yesterday. in that case a younger (32m) brother was treated with tamiflu, and his older brother (38m) developed symptoms and was positive for tamiflu resistant pandemic h1n1 even though he had no tamiflu exposure. other family members were also infected, and like the younger brother, were tamiflu sensitive, suggesting the index case was infected with a mixture and the brother was infected by the h274y positive version, while other family members were infected with wild type h1n1.
these resistant sequences are most easily detected in patients taking prophylactic tamiflu, because they are being monitored and symptoms while on tamiflu raises suspicions of resistance. the hong kong case was discovered because of an aggressive surveillance program, which detected h274y in an earlier traveler from san francisco , who also had no tamiflu exposure increasing concerns of transmission by evolutionarily fit h1n1 with h274y.
these repeated outbreaks of h274y on multiple genetic backgrounds of pandemic h1n1 raise concerns that the fixing of h274y in seasonal flu, which was driven by recombination and genetic hitchhiking, will be repeated in pandemic h1n1 in the near future.