Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008

The surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using an NA inhibition assay. The 50% inhibitory concentration values (IC50S) of 4,570 viruses collected globally from October 2004 to March 2008 were determined. Based on mean IC50S, A(H3N2) viruses (0.44 nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses (outliers), a threshold of a mean IC50 value + 3 standard deviations was defined for type/subtype and drug. Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility. Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some outliers contained previously reported mutations (e.g., I222T in the B viruses), while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2) viruses) were novel. The R371K B virus outlier exhibited high levels of resistance to both inhibitors (>100 nM). A substantial variance at residue D151 was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance of newly identified NA mutations is unknown. A rise in the incidence of oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was detected in the United States and in other countries in the ongoing 2007 to 2008 season. As of March 2008, the frequency of resistance among A(H1N1) viruses in the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors

Reducing the Burden of Influenza-Associated Complications with Antiviral Therapy

INTRODUCTION: Influenza imposes an annual burden on individuals, society, and healthcare systems. This burden is increased by the development of complications that are often more severe than the primary infection. Here, we examine the main complications associated with influenza and review the effectiveness of antiviral therapy in reducing the incidence of such events. MATERIAL AND METHODS: The content of this review is taken from the study of the authors' extensive collection of reference materials, examination of the bibliographical content of relevant papers, and the results of Medline searches. RESULTS: The most commonly encountered complications in adults are sinusitis, pharyngitis, bronchitis, and, particularly in the elderly, bacterial pneumonia. Such complications may exacerbate pulmonary complaints. Children are particularly prone to post-influenza croup and otitis media. Complications involving the central nervous system, heart, or skeletal muscle also occur in influenza patients. Influenza-associated complications impose sizeable healthcare costs in terms of outpatient contacts, hospitalizations, and antibiotic use. Vaccination is the primary prevention strategy for influenza and its complications, but has limitations. Neuraminidase inhibitors have demonstrated efficacy in reducing the incidence of influenza-associated complications in populations with different ages and risks. CONCLUSIONS: Influenza complications place a large burden on healthcare providers and society. Neuraminidase inhibitors can reduce the incidence of such complications, particularly in high-risk groups