[Source: PLoS ONE, full page: (LINK). Abstract, edited.]

Open Access / Peer-Reviewed / Research Article

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

Rita B. Patel, Maya B. Mathur, Michael Gould, Timothy M. Uyeki, Jay Bhattacharya, Yang Xiao, Nayer Khazeni

Published: March 25, 2014 / DOI: 10.1371/journal.pone.0091630



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.

Citation: Patel RB, Mathur MB, Gould M, Uyeki TM, Bhattacharya J, et al. (2014) Demographic and Clinical Predictors of Mortality from Highly Pathogenic Avian Influenza A (H5N1) Virus Infection: CART Analysis of International Cases. PLoS ONE 9(3): e91630. doi:10.1371/journal.pone.0091630

Editor: Gerardo Chowell, Arizona State University, United States of America

Received: November 9, 2013; Accepted: February 11, 2014; Published: March 25, 2014

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Funding: This research was supported by the Agency for Healthcare Research and Quality (1 K08 HS019816, Dr. Khazeni). See http://www.ahrq.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.