Influenza A(H1N1) virus resistance to oseltamivir
2008 Southern hemisphere influenza season
The table and text include data from the world
13 January 2009
The 2008 southern hemisphere season saw low to moderate levels of influenza activity in general. In Australia, influenza activity was moderate and peaked in August-September with A(H3N2) and B viruses predominating. New Zealand reported regional activity mainly due to influenza A (H3N2). In South Africa, influenza activity began in May and increased in June–July and A(H1N1) viruses predominated. In South America, activity was moderate in Argentina where B viruses were predominant, while Chile and Brazil reported low activity due to influenza A and B.
A total of 1344 influenza A(H1N1) viruses, which had been obtained from samples collected during the second and third quarters of 2008 (week 14 to week 40), were tested for oseltamivir resistance and 588 (44%) were found to be resistant (see table 1 below). Resistance was assessed by neuraminidase inhibition assay or the presence of a H275Y mutation in the neuraminidase* , or both. Forty-four countries and territories reported test results, the majority of countries being from the African, American and Asian WHO Regions (see map below). The number of viruses tested varied considerably by country/territory, ranging from 1–583, leading to difficulties in the interpretation of comparative data for some countries/territories or Regions.
Map: Prevalence of oseltamivir-resistant H1N1 viruses, April to September 2008
Table 1. Influenza A(H1N1) virus resistance to oseltamivir, the second and the third quarters 2008 (1 April 2008 - 30 September 2008) as of 15 January 2009
Data from the African Region indicated that 89% of the 292 A(H1N1) viruses tested were resistant. South Africa and Senegal both reported 100% oseltamivir resistance for 225 and 10 isolates analysed, respectively, while Ghana reported an increasing prevalence of oseltamivir-resistant A(H1N1) viruses from May to July, 59% overall. Oseltamivir use in influenza-infected patients is generally uncommon in these countries, and no link between oseltamivir exposure and resistance at the individual patient level was noted.
One of two H1N1 viruses tested from one country (Jordan) in the Eastern Mediterranean Region had the H275Y resistance mutation. Thailand and India were the only countries that submitted data from the South-East Asia Region and none of the 13 A(H1N1) isolates tested from that region were found to be resistant. In the Western Pacific Region, China, Hong Kong Special Administrative Region reported a prevalence of 17% oseltamivir resistance in 583 A(H1N1) samples tested, while Japan reported one positive sample out of seven tested. Australia reported 71 resistant viruses out of 76, a prevalence of 93%. Other countries in the region also reported high proportions of resistant viruses, Vietnam 21/31, the Philippines 10/11, New Caledonia 7/7, Singapore 3/6 and New Zealand 2/2 viruses, while Malaysia did not detect any resistant viruses. The WHO Collaborating Centre in Melbourne reported that until June, almost all Asia-Oceania viruses were sensitive but from July, most viruses had become resistant. In the Americas, Uruguay, Costa Rica, El Salvador, Argentina, the United States of America, Brazil and Chile reported prevalence rates of 82%, 74%, 66% ,50%, 30%, 22% and 13% respectively. Of the 275 viruses tested from countries in Central and South America, 98 were found to be resistant (36%).
Analysis of NA sequences of some of these viruses have shown that, although the resistant mutants do not share a single origin, the variant predominant in Europe during the first quarter of 2008 has become predominant in other regions.
Preliminary summary reports from countries, areas or territories
* The mutation in N1 neuraminidase of human influenza virus which confers high-level resistant to oseltamivir is a single amino acid substitution of the relevant histidine (H) to tyrosine (Y) at position 275. Most of the early work on structure and inhibitor design is based on two other subtypes (N2 and N9) and the corresponding amino acid in these subtypes is at position 274. Consequently, some scientists use 'N2 numbering' (H274Y) and some use the actual 'N1 numbering' (H275Y).