Demographic and Clinical Predictors of Mortality from Highly Pathogenic Avian Influenza A (H5N1) Virus Infection: CART Analysis of International Cases

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. We included all cases of human HPAI H5N...

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Published inPloS one Vol. 9; no. 3; p. e91630
Main Authors Patel, Rita B., Mathur, Maya B., Gould, Michael, Uyeki, Timothy M., Bhattacharya, Jay, Xiao, Yang, Khazeni, Nayer
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 25.03.2014
Public Library of Science (PLoS)
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Summary: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. We 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. We 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). A 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.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: NK. Performed the experiments: MM RP. Analyzed the data: MM. Wrote the manuscript: PR MM. Compiled and organized data: RP. Served as reviewers for the systematic search: RP MM. Provided critical edits to analysis and interpretation of data: MG. Advised on article inclusion, background, analysis and interpretation of data, and contributed to revising the manuscript: TMU. Provided advice on design of work: JB. Provided professional translation for acquisition of Chinese data: YX. Conceptualized the project, defined research questions, collaborated on substantial portions of manuscript writing, and served as an arbitrator for the systemic search: NK.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0091630