Searching for Sharp Drops in the Incidence of Pandemic A/H1N1 Influenza by Single Year of Age

BACKGROUND During the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52-53 years old in 2009, but the precise range of ages affected has not been delineated. METHODS AND FINDINGS To test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951-1959 (hospitalized) and 1953-1960 (not hospitalized). CONCLUSIONS The reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957.The project described was supported by the National Institute Of General Medical Sciences [Award Number U54GM088558], http://www.nigms.nih. gov/. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of General Medical Sciences or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Searching for Sharp Drops in the Incidence of Pandemic A/H1N1 Influenza by Single Year of Age

Background: During the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52–53 years old in 2009, but the precise range of ages affected has not been delineated. Methods and Findings: To test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951–1959 (hospitalized) and 1953–1960 (not hospitalized). Conclusions: The reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957

Recognizing true H5N1 infections in humans during confirmed outbreaks.

INTRODUCTION: The goal of this study was to evaluate whether any characteristics that are evident at presentation for urgent medical attention could be used to differentiate cases of H5N1 in the absence of viral testing. METHODOLOGY: Information about exposure to poultry, clinical signs and symptoms, treatments, and outcomes was abstracted from existing data in the global avian influenza registry (www.avianfluregistry.org) using standardized data collection tools for documented and possible cases of H5N1 infection who presented for medical attention between 2005-2011 during known H5N1 outbreaks in Azerbaijan, Indonesia, Pakistan and Turkey. RESULTS: Demography, exposure to poultry, and presenting symptoms were compared, with only the common symptoms of fever and headache presenting significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to  infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases. Overall, oseltamivir treatment showed a survival benefit, with the greatest benefit shown in H5N1 cases who were treated within two days of symptom onset (51% reduction in case fatality). CONCLUSION: Since prompt treatment with antivirals conferred a strong survival benefit for H5N1 cases, presumptive antiviral treatment should be considered for all possible cases presenting during an outbreak of H5N1 as a potentially life-saving measure

A Comparison of Clinical and Epidemiological Characteristics of Fatal Human Infections with H5N1 and Human Influenza Viruses in Thailand, 2004–2006

BACKGROUND: The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004-2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases. METHODS AND FINDINGS: NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality. Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001). CONCLUSIONS: In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment

Searching for sharp drops in the incidence of pandemic A/H1N1 Influenza by single year of age

Fil: Hartman Jacobs, Jessica. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.Fil: Archer, Brett Nicholas. National Health Laboratory Service. National Institute for Communicable Diseases; Sudáfrica.Fil: Baker, Michael G. University of Otago. Department of Public Health; Nueva Zelanda.Fil: Cowling, Benjamin J. The University of Hong Kong. School of Public Health; China.Fil: Heffernan, Richard T. Wisconsin Department of Health Services. Division of Public Health; Estados Unidos.Fil. Mercer, Geoff. Australian National University. National Centre for Epidemiology and Population Health; Australia.Fil: Uez, Osvaldo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Epidemiología; Argentina.Fil: Hanshaoworakul, Wanna. Ministry of Public Health. Department of Disease Control; Tailandia.Fil: Viboud, Cécile. National Institutes of Health. Division of International Epidemiology and Population Studies; Estados Unidos.Fil: Schwartz, Joel. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.Fil: Tchetgen Tchetgen, Eric. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.Fil: Lipsitch, Marc. Harvard School of Public Health. Department of Epidemiology; Estados Unidos.BackgroundDuring the 2009 H1N1 pandemic (pH1N1), morbidity and mortality sparing was observed among the elderly population; it was hypothesized that this age group benefited from immunity to pH1N1 due to cross-reactive antibodies generated from prior infection with antigenically similar influenza viruses. Evidence from serologic studies and genetic similarities between pH1N1 and historical influenza viruses suggest that the incidence of pH1N1 cases should drop markedly in age cohorts born prior to the disappearance of H1N1 in 1957, namely those at least 52–53 years old in 2009, but the precise range of ages affected has not been delineated.Methods and FindingsTo test for any age-associated discontinuities in pH1N1 incidence, we aggregated laboratory-confirmed pH1N1 case data from 8 jurisdictions in 7 countries, stratified by single year of age, sex (when available), and hospitalization status. Using single year of age population denominators, we generated smoothed curves of the weighted risk ratio of pH1N1 incidence, and looked for sharp drops at varying age bandwidths, defined as a significantly negative second derivative. Analyses stratified by hospitalization status and sex were used to test alternative explanations for observed discontinuities. We found that the risk of laboratory-confirmed infection with pH1N1 declines with age, but that there was a statistically significant leveling off or increase in risk from about 45 to 50 years of age, after which a sharp drop in risk occurs until the late fifties. This trend was more pronounced in hospitalized cases and in women and was independent of the choice in smoothing parameters. The age range at which the decline in risk accelerates corresponds to the cohort born between 1951–1959 (hospitalized) and 1953–1960 (not hospitalized).ConclusionsThe reduced incidence of pH1N1 disease in older individuals shows a detailed age-specific pattern consistent with protection conferred by exposure to influenza A/H1N1 viruses circulating before 1957

Human Disease from Influenza A (H5N1), Thailand, 2004

Direct contact with sick poultry, young age, pneumonia and lymphopenia, and acute respiratory distress syndrome should prompt specific laboratory testing for H5 influenza

Age and gender distribution of sampled cases compared to all cases reported to NAIS in 28 provinces.

<p>Age and gender distribution of sampled cases compared to all cases reported to NAIS in 28 provinces.</p