Risk Factors for Severe Outcomes following 2009 Influenza A (H1N1) Infection: A Global Pooled Analysis

Maria D Van Kerkhove,Walter Haas,Anthony W Mounts,Rhonda Owen,Silke Buda,Kensuke Nakajima,Richard Pebody,Marianne A B Van Der Sande,Patricia Santa-Olalla,Louise Pelletier,Christl A Donnelly,Yoshihiro Takayama,Jeffrey Cutter,Wanna Hanshaoworakul,Kumnuan Ungchusak,Juno Thomas,Artemis Koukounari,Tokuaki Shobayashi,Vivek Shinde,Isabelle Bonmarin,Tomi Sunagawa,Vernon J Lee,Julie Vachon,Seema Jain,Kiyosu Taniguichi,Luis O Carlino,Darren Hunt,Feng Zijian,Yu Hongjie,Giovanna Jaramillo-Gutierrez,Arnaud Orelle,Gérard Krause ,Beverley J Paterson ,Cornelia C H Wielders ,E V Palacios ,Shuk-Kwan Chuang ,Albert Ka-Wing Au ,Claudia González ,Jean‐Michel Heraud ,Katelijn Vandemaele ,María José Sierra-Moros

doi:10.1371/journal.pmed.1001053

Abstract

Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions--Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, The Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom--to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5-14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50-64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors' Summary.

Highlights

In late April 2009, a novel strain of influenza A H1N1 was identified in Mexico and the United States
Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes
Data were collected on approximately 70,000 patients requiring hospitalization, 9,700 patients admitted to intensive care unit (ICU), and 2,500 fatalities from 19 countries and administrative regions across the Americas, Asia, Europe, and Africa

Summary

Introduction

In late April 2009, a novel strain of influenza A H1N1 was identified in Mexico and the United States. Risk factors for severe disease following seasonal influenza infection have been well documented in many countries, and include chronic medical conditions such as pulmonary, cardiovascular, renal, hepatic, neuromuscular, hematologic, and metabolic disorders, some cognitive conditions, and immunodeficiency [5,6,7]. Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Risk factors for severe disease following seasonal influenza infection have been well documented in many countries (for example, pregnancy; chronic medical conditions such as pulmonary, cardiovascular, renal, hepatic, neuromuscular, hematologic, and metabolic disorders; some cognitive conditions; and immunodeficiency), risk factors for severe disease following infection early in the 2009 H1N1 pandemic were largely unknown. To assess the frequency and distribution of known and new potential risk factors for severe H1N1 infection, this study was conducted to collect data (from 1 April 2009 to 1 January 2010) from surveillance programs of the Ministries of Health or National Public Health Institutes in 19 countries_Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong (special administrative region), Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom

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