Paradigm Shift Intervention Monitoring
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Commentary
Widespread
H1N1pdm09 Tamiflu
Resistance in the United States
Recombinomics
Commentary 23:45
May 23, 2012
The recently released H1N1pdm09 NA sequences from Mexico confirm widespread transmitting oseltamivir (Tamiflu), H274Y, resistance in Mexico in 2012. Although most of the eight sequences were partial, all covered position 274, and all had Y at that position. Earlier sequences from Mexico City had H274Y and were closely related to each other and recent sequences from the United States (Texas, California, Illinois). The recent sequences from Mexico had associated characterization sheets which included location, as well as collection date for the 8 sequences, which were collected between Jan 2 and Feb 28, 2012. The earliest case was from Puebla, just south of Mexico City, but subsequent sequences were from cases located throughout the country, from Veracruz on the eastern coast, and central Mexico, as well as Hidalgo City, near the Texas border.
Similar sequences were also found in Texas, as demonstrated by the sequences released by the CDC and described above. Most of these isolates were from cases who had no exposure to oseltamivir, and at least one of the three samples from patients with exposure were collected a day after the start of treatment, raising concerns that a subset of the sequences that had H at position 274, also had Y at that position at concentrations below 50% of the signal (samples with H274Y at a level below 50% are reported as wild type).
Phylogenetic analysis of the full (1410 BP) NA sequences raised concerns that samples with H274Y were markedly higher than the sixteen cases described above by the CDC or the 10 sequences released by Biologia Molecular y Validacion de Tecnicas in Mexico. Nine of the NA sequences (from 7 patients) matched at all 1410 positions (listed below as H274Y consensus match) and were collected in 2012 (Mexico City / Veracruz City in Mexico and Texas / Illinois in the United States). Related sequences (Mexico City / San Luis Potosi City in Mexico and Texas / California in the United States) are listed below as H274Y consensus related.
However, in addition to the full sequences with H274Y, are NA sequences that match at all 1409 of the consensus positions other than C823T, which codes for H274Y. These isolates (274H consensus match) were seen in late 2011 / early 2012 isolates in Mexico, but are also present throughout the United States, as well as one sequence from France (Paris), raising concerns that H274Y is widespread in North America.
Additional related sequence (274H consensus related) are also widespread. Most 2011 sequences are from Mexico, but sequences are widespread in the United States (California and Pennsylvania) and the earliest sequences was from an isolate in France (Grenoble). 2012 sequences are also widespread outside of the United States (Mexico and Guatemala) as well as throughout the United States (with Texas representing the sate with the most isolates).
The listed sequences suggest the H274Y was initially in Mexico and Texas in a sub-clade that could efficient spread and become dominant. The number of related 2012 cases in the United States raises concerns that the spread of H274Y in H1N1pdm09 in early 2012 will mimic the worldwide fixing of H274Y in seasonal influenza A in the 2008/2009.season in the northern hemisphere.
H274Y consensus match
Mexico
EPI366289 A/Mexico/1818/2012
EPI366295 A/Mexico/2440/2012
CY120057 A/Mexico/InDRE5726/2012
United States
EPI370412 A/Illinois/01/2012
EPI370409 A/Illinois/01/2012
EPI366331 A/Texas/23/2012
EPI366333 A/Texas/23/2012
EPI366336 A/Texas/24/2012
EPI368650 A/Texas/29/2012
H274Y consensus related
Mexico
EPI366286 A/Mexico/1474/2012
EPI355256 A/Mexico/InDRE1474/2012
CY120059 A/Mexico/InDRE6023/2012
United States
EPI370385 A/California/21/2012
EPI368642 A/Texas/26/2012
EPI368654 A/Texas/30/2012
EPI370394 A/Texas/31/2012
EPI370388 A/Texas/33/2012
EPI370391 A/Texas/34/2012
EPI370418 A/Texas/35/2012
274H consensus match
Mexico
EPI353407 A/Mexico/52/2011
EPI357941 A/Mexico/52/2011
EPI353404 A/Mexico/3720/2011
EPI359689 A/Mexico/254/2012
EPI353442 A/Mexico/254/2012
EPI366298 A/Mexico/689/2012
United States
EPI353384 A/Alabama/01/2012
EPI353390 A/Colorado/01/2012
EPI370424 A/Colorado/12/2012
EPI368427 A/Georgia/08/2012
EPI368681 A/Idaho/07/2012
EPI362960 A/Kansas/04/2012
EPI353398 A/Maine/01/2012
EPI357958 A/Maryland/03/2012
EPI356258 A/Missouri/03/2012
EPI357955 A/New Mexico/01/2012
EPI353425 A/Texas/05/2012
EPI357964 A/Utah/08/2012
EPI370427 A/Utah/11/2012
EPI358140 A/Utah/09/2012
EPI362987 A/Washington/15/2012
EPI368663 A/Washington/19/2012
EPI357952 A/Wisconsin/02/2012
EPI357932 A/Wisconsin/06/2012
EPI357489 A/Paris/196/2012
274H consensus related
2011
EPI352302 A/Grenoble/1772/2011
EPI353410 A/Mexico/56/2011
EPI366292 A/Mexico/239/2011
EPI353436 A/Mexico/3723/2011
EPI369844 A/Mexico/InDRE3740/2011
EPI353387 A/California/52/2011
EPI349357 A/Pennsylvania/16/2011
2012
EPI362990 A/Guatemala/18/2012
EPI353401 A/Mexico/210/2012
EPI359689 A/Mexico/254/2012
EPI357938 A/Mexico/430/2012
United States
EPI370422 A/Alabama/06/2012
EPI370430 A/Alaska/01/2012
EPI356264 A/California/12/2012
EPI362963 A/California/19/2012
EPI356273 A/Delaware/01/2012
EPI368456 A/Florida/06/2012
EPI357929 A/Georgia/03/2012
EPI368685 A/Georgia/06/2012
EPI356261 A/Idaho/03/2012
EPI362975 A/Idaho/05/2012
EPI368438 A/Kansas/07/2012
EPI362954 A/Kentucky/03/2012
EPI370434 A/Louisiana/01/2012
EPI368443 A/Maine/03/2012
EPI362984 A/Michigan/01/2012
EPI358143 A/Missouri/04/2012
EPI357935 A/Nebraska/06/2012
EPI357944 A/Nevada/06/2012
EPI368679 A/Nevada/11/2012
EPI362981 A/New York/03/2012
EPI356270 A/North Carolina/04/2012
EPI358134 A/North Carolina/06/2012
EPI368436 A/North Carolina/09/2012
EPI362966 A/North Dakota/01/2012
EPI362993 A/North Dakota/02/2012
EPI362972 A/Oklahoma/01/2012
EPI368673 A/Rhode Island/04/2012
EPI368429 A/South Carolina/08/2012
EPI358147 A/Tennessee/02/2012
EPI368688 A/Tennessee/05/2012
EPI352601 A/Texas/02/2012
EPI353422 A/Texas/04/2012
EPI366328 A/Texas/07/2012
EPI356282 A/Texas/18/2012
EPI357973 A/Texas/21/2012
EPI362978 A/Texas/22/2012
EPI370406 A/Texas/27/2012
EPI356279 A/Utah/06/2012
EPI370432 A/Virginia/07/2012
EPI368676 A/Wyoming/06/2012
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