H1N1pdm Influenza Infection in Hospitalized Cancer Patients: Clinical Evolution and Viral Analysis

Abstract

BackgroundThe novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil.MethodsWe performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir.ResultsA total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3–69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range = 11–63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples.ConclusionsProlonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation.

Clinical presentations and outcomes of influenza infection among hematology/oncology patients from a single cancer center: pandemic and post-pandemic seasons

“…this rate is high compared with the mortality from pandemic influenza in the general population, which was reported to be  0.5% [2]. In contrast, mortality rates in hematology/oncology patients with pH1N1 infection were reported at a wide range of estimates (0-22%) in different studies [5,22,[24][25][26][27][28]. In our study, almost all patients who died had pneumonia with progressive respiratory failure.…”

Sequence analysis of the 2009 pandemic influenza A H1N1 virus haemagglutinin gene from 2009-2010 Brazilian clinical samples

“…2). These results are in agreement with the findings reported by Souza et al (2010), suggesting continuous viral evolution.…”

Bioluminescence-Based Neuraminidase Inhibition Assay for Monitoring Influenza Virus Drug Susceptibility in Clinical Specimens

“…All four respective H275Y isolates propagated from the above clinical specimens revealed highly reduced inhibition by oseltamivir and normal inhibition by zanamivir. The elevated zanamivir IC 50 suggests the presence of an exogenous source of NA (e.g., bacteria) in clinical sample 11, similarly to previous reports (30). To avoid such false positives that may arise from bacterial contamination, a second generation of the QFlu substrate (mentioned above) with a modified chemical structure (21) specific to influenza NA has recently been developed.…”

“…As discussed above, the presence of exogenous NA could interfere with the test outcome, which is especially relevant for clinical specimens (30). In terms of IC 50 reproducibility when testing virus isolates, protocol B produced the most desirable outcome, as opposed to the one-step reaction under manufacturer recommendations (protocol A).…”