Abstract
BackgroundHuman infections with highly pathogenic avian influenza (HPAI) A (H5N1) viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions.MethodsWe included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar), including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality.FindingsWe identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6–29 years) and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.76–0.86).InterpretationA model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection.
Highlights
Since 1997, human and poultry outbreaks of highly pathogenic avian influenza (HPAI) A (H5N1) have had devastating health, economic, and social impact in 15 countries in Asia, Africa, and the Middle East [1,2,3,4,5,6]
We investigated factors associated with increased mortality following HPAI H5N1 virus infection to guide public health messages, resource distribution, and triage of infected individuals
We conducted a systematic search of all available literature describing human cases of HPAI H5N1 virus infection and developed a prognostic decision tree
Summary
Since 1997, human and poultry outbreaks of highly pathogenic avian influenza (HPAI) A (H5N1) have had devastating health, economic, and social impact in 15 countries in Asia, Africa, and the Middle East [1,2,3,4,5,6]. Human cases of HPAI H5N1 virus infection with high mortality continue to be detected sporadically in several countries [8]. Human infections with HPAI H5N1 virus are associated with high mortality, but it is still largely unknown which demographic and clinical factors place an individual at higher risk of death. Human infections with highly pathogenic avian influenza (HPAI) A (H5N1) viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions
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