Nosocomial outbreak of the pandemic Influenza A (H1N1) 2009 in critical hematologic patients during seasonal influenza 2010-2011: detection of oseltamivir resistant variant viruses

Abstract

BackgroundThe pandemic influenza A (H1N1) 2009 (H1N1pdm09) virus infection caused illness and death among people worldwide, particularly in hematologic/oncologic patients because influenza infected individuals can shed virus for prolonged periods, thus increasing the chances for the development of drug-resistant strains such as oseltamivir-resistant (OST-r) variant.MethodsThe aim of our study was to retrospectively evaluate the clinical importance of OST-r variant in circulating strains of the pandemic H1N1pdm09 virus. By means of RT-PCR and Sanger sequencing we analysed the presence of OST-r variant in 76 H1N1pdm09 laboratory-confirmed cases, hospitalized at the hematologic/oncologic ward at Spedali Civili of Brescia –Italy.ResultsOut of 76 hospitalized hematologic/oncologic patients, 23 patients (30.2%) were infected by H1N1pdm09 virus. Further investigation revealed that 3 patients were positive for the OST-r variant carrying the H275Y mutation. All the 23 infected patients were immuno-compromised, and were under treatment or had been treated previously with oseltamivir. Three patients died (13%) after admission to intensive care unit and only one of them developed H275Y mutation.ConclusionsOur retrospective observational study shows that pandemic influenza A (H1N1) 2009 virus can cause significant morbidity and even mortality in hematologic/oncologic patients and confirms the high rate of nosocomial transmission of pandemic H1N1pdm09 virus in these critical subjects. Indeed, the reduction in host defences in these hospitalized patients favoured the prolonged use of antiviral therapy and permitted the development of OST-r strain. Strategies as diagnostic vigilance, early isolation of patients and seasonal influenza A(H1N1) vaccination may prevent transmission of influenza in high risk individuals.

Dengue Virus Evolution under a Host-Targeted Antiviral

“…As such, the antiviral activity can often be overcome by a single mutation. For example, individual SNPs are responsible for resistance of HCV to daclatasvir and of influenza A virus to oseltamivir (14,15). In contrast to the published reports on directly acting antivirals, it is possible that the virus in this study did not undergo enough replication cycles to allow a resistant mutant to develop.…”

“…The important role of minor subspecies in accelerated resistance has been shown in various viruses, including HIV (13) and hepatitis C virus (HCV) (12). In the case of HCV and influenza virus, drug-resistant strains arise due to single-nucleotide polymorphisms (SNPs) (14,15), which are easily acquired due to the error rate of the RNA polymerase.…”

Viral Respiratory Infections in Patients with Cancer

“…Three of them developed acute respiratory distress syndrome and required intubation and mechanical ventilation, and eventually died because of fatal influenza pneumonia. Three patients were infected by OST-r variant (54). Redelman-Sidi et al investigated this infection in cancer patients and hematopoietic stem cell transplant recipients.…”

Point-Counterpoint: Can Newly Developed, Rapid Immunochromatographic Antigen Detection Tests Be Reliably Used for the Laboratory Diagnosis of Influenza Virus Infections?

“…Outbreaks are especially dangerous for immunocompromised patients, for whom there is a risk of prolonged shedding and development of oseltamivir resistance. An outbreak in a hematologic/ oncologic unit resulted in 23/76 patients (32%) developing nosocomial influenza, three patients being identified with oseltamivir-resistant virus, and 3 patients expiring (27). An outbreak investigation in the Netherlands found nosocomial transmission of oseltamivir-resistant virus, leading to three cases of pneumonia and two mortalities (28).…”

“…In light of the recent FDA proposal to increase the classification of RIDTs from class I to class II devices subject to special control and performance standards (27), it will be of interest to learn how many different RIDTs remain commercially available in the next few years. If adopted, this new rule would (i) identify the minimum acceptable performance criteria, (ii) identify the appropriate comparator for establishing the performance of new assays, and (iii) call for mandatory annual analytical reactivity testing of contemporary influenza strains, including testing of newly emerging strains that pose a danger of public health emergency.…”