Elsevier

The Lancet

Volume 374, Issue 9693, 12–18 September 2009, Pages 903-911
The Lancet

Articles
Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates

https://doi.org/10.1016/S0140-6736(09)61203-4Get rights and content

Summary

Background

Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities.

Methods

We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years.

Findings

We calculated that Hib caused about 8·13 million serious illnesses worldwide in 2000 (uncertainty range 7·33–13·2 million). We estimated that Hib caused 371 000 deaths (247 000–527 000) in children aged 1–59 months, of which 8100 (5600–10 000) were in HIV-positive and 363 000 (242 000–517 000) in HIV-negative children.

Interpretation

Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality.

Funding

Gavi Alliance and the Vaccine Fund.

Introduction

Haemophilus influenzae type b (Hib) is a common cause of serious diseases in children worldwide. Its most frequent manifestations are pneumonia and meningitis, but it can also cause infections of the epiglottis, soft tissues, bones, joints, and other sites.

Highly effective and safe protein–polysaccharide conjugate Hib vaccines have been available for almost 20 years. They have almost completely eliminated Hib disease in both developed and developing countries in which they are routinely used.1, 2, 3, 4, 5, 6, 7 These vaccines also reduce asymptomatic nasopharyngeal carriage and substantially protect unvaccinated people even at moderate vaccine coverage (40–50%).8, 9, 10, 11 After licensure, Hib vaccines have been quickly introduced in North America and western Europe, but slowly in developing countries12 because of high cost, concerns about programme sustainability, limited vaccine supply, and uncertainty about Hib disease burden.13, 14, 15

Hib pneumonia is difficult to identify, and surveillance studies underestimate the burden of other diseases caused by Hib.15, 16, 17, 18 WHO has developed a rapid Hib disease assessment method that accounts for limitations of meningitis surveillance. The method also estimates the burden of Hib pneumonia on the basis of two clinical trials of Hib vaccine, which suggest that, for every case of Hib meningitis, there are five cases of radiographic Hib pneumonia.19, 20, 21, 22 Vaccine trials to measure non-laboratory-confirmed Hib disease burden have provided important insights into the limitations of conventional surveillance studies and the burden of Hib disease.

WHO estimated that Hib causes about 3 million cases of serious disease and 386 000 child deaths every year.23 The Bellagio Child Survival Study Group suggested that Hib vaccine could prevent 403 000 childhood deaths every year.24 We undertook this new analysis of the global burden of Hib disease for two reasons. The completion of two additional vaccine trials25, 26 has helped to clarify the burden of Hib disease in Asian countries (where conventional methods showed low incidence of Hib meningitis) and provided data for the proportion of pneumonia preventable by Hib vaccines in Asia.15 We developed methods for country-specific and regional estimates of Hib disease burden that are systematic and well documented. Our effort was done together with a project to estimate the global burden of Streptococcus pneumoniae disease in children.27

Section snippets

Methods

Methods are described in detail in the accompanying webappendix pp 3–9, but a concise description is provided here. We did a literature review and developed methods for estimating Hib disease burden from three serious clinical syndromes: meningitis, pneumonia, and non-pneumonia, non-meningitis invasive disease (disease in which Hib was isolated from a normally sterile body fluid).

We did a literature review of studies published between 1980 and 2005. We used broad search criteria to identify

Results

We identified 15 099 studies by our literature search.35 205 studies contributed data to Hib primary endpoints. For Hib meningitis, 110 studies provided incidence data, of which 59 met quality criteria; 116 provided age distribution data, and 50 reported data for case-fatality ratio. Data availability substantially varied in different regions (table 1). Of the 59 Hib meningitis incidence studies meeting quality criteria, only five were from the WHO eastern Mediterranean and three from southeast

Discussion

We estimate that, in 2000, Hib caused 8·13 million serious illnesses (UR 7·33–13·2 million) and 371 000 deaths (247 000–527 000) in children younger than 5 years. Of the deaths, 8100 (5600–10 000) occurred in HIV-infected children. Hib disease accounted for 5·6% (3·9–7·7%) of the estimated 6·6 million post-neonatal child deaths and 16% of the estimated 1·8 million pneumonia deaths in HIV-negative children.28, 40 These Hib-attributable deaths in children are almost entirely vaccine preventable.

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