resistance, page-36

H1N1 Tamiflu Resistance Crosses Tipping Point
Recombinomics Commentary 03:07
December 4, 2009


Within the past two weeks, the number of documented cases of oseltamivir resistance in H1N1 viruses has risen from 57 to 96. Around one third of these cases occurred in patients whose immune systems were severely suppressed by haematological malignancy, aggressive chemotherapy for cancer, or post-transplant treatment. The clusters in the two hospital wards should be viewed in the context of these overall trends. Although all incidents of oseltamivir resistance merit investigation, no evidence suggests that events to date constitute a public health threat.

The above comments from the WHO update on transmission of H1N1 with H274Y in hospitals in Wales and North Carolina, claims no evidence suggests that the sharp spike in cases, or the clear human to human transmission, is a public health threat, but the evidence in the report alone clearly identifies a threat. Moreover, the numbers in the report appear to represent only a subset of associated evidence, which raises concerns that a tipping point has been reached and readily detectable H274Y will be reported in the upcoming weeks, signaling the early stages of fixing H274Y in pandemic H1N1, as happened in seasonal H1N1.

The rapid appearance of H274Y in patients receiving Tamiflu suggested that H274Y was transmitting as a minor species and was largely undetected in untreated cases. However, there was concern that the H274Y level would rise, leading to readily detected transmission. The reports of transmission in clusters of immuno-suppressed patients indicate the concern has been realized, and transmission resembles the early stages of fixing of H274Y in H1N1 seasonal flu.

In addition to the clusters in Wales and North Carolina, smaller clusters have been reported and recent sequences show that H274Y in earlier sub-clades is appearing more frequently, which represents fit sub-clades.

The sub-claded linked first examples of H274Y in a patient not receiving Tamiflu has now also been reported in an H274Y case in Tennessee, while recent cases in Georgia and Spain represent another sub-clade with multiple examples of H274Y. The lack of linkage in these examples suggests that the level of H274Y is much wider than reported, which may be linked to limited testing of milder cases.

Thus, the explosion of cases with H274Y is expected to continue to rise and create more problems in the management of patients. H274Y will eliminate Tamiflu and Peramivir and limit anti-virals to Relenza, which will further strain the health care system.