Articles
2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis

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Summary

Background

WHO recommends routine use of rotavirus vaccines in all countries, particularly in those with high mortality attributable to diarrhoeal diseases. To establish the burden of life-threatening rotavirus disease before the introduction of a rotavirus vaccine, we aimed to update the estimated number of deaths worldwide in children younger than 5 years due to diarrhoea attributable to rotavirus infection.

Methods

We used PubMed to identify studies of at least 100 children younger than 5 years who had been admitted to hospital with diarrhoea. Additionally, we required the studies to have a data collection midpoint of the year 2000 or later, to be done in full-year increments, and to assesses diarrhoea attributable to rotavirus with EIAs or polyacrylamide gel electrophoresis. We also included data from countries that participated in the WHO-coordinated Global Rotavirus Surveillance Network (consisting of participating member states during 2009) and that met study criteria. For countries that have introduced a rotavirus vaccine into their national immunisation programmes, we excluded data subsequent to the introduction. We classified studies into one of five groups on the basis of region and the level of child mortality in the country in which the study was done. For each group, to obtain estimates of rotavirus-associated mortality, we multiplied the random-effect mean rotavirus detection rate by the 2008 diarrhoea-related mortality figures for countries in that group. We derived the worldwide mortality estimate by summing our regional estimates.

Findings

Worldwide in 2008, diarrhoea attributable to rotavirus infection resulted in 453 000 deaths (95% CI 420 000–494 000) in children younger than 5 years—37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than 5 years. Five countries accounted for more than half of all deaths attributable to rotavirus infection: Democratic Republic of the Congo, Ethiopia, India, Nigeria, and Pakistan; India alone accounted for 22% of deaths (98 621 deaths).

Interpretation

Introduction of effective and available rotavirus vaccines could substantially affect worldwide deaths attributable to diarrhoea. Our new estimates can be used to advocate for rotavirus vaccine introduction and to monitor the effect of vaccination on mortality once introduced.

Funding

None.

Introduction

Rotavirus infection is the leading cause of severe diarrhoea in young children worldwide.1 Since 2006, two effective rotavirus vaccines, RotaTeq (Merck and Co, PA, USA) and Rotarix (GSK Biologicals, Rixensart, Belgium), have been licensed, and they are recommended for use in all countries by WHO, particularly in those countries with high diarrhoea-related mortality in children younger than 5 years.2, 3, 4, 5, 6 Substantial declines in morbidity and mortality attributable to rotavirus and all-cause diarrhoea have been recorded in high-income and middle-income countries that have introduced rotavirus vaccines so far.7, 8, 9, 10, 11, 12, 13 Before rotavirus vaccines become more widely used in immunisation programmes, particularly in low-income countries where most deaths attributable to rotavirus infection happen, documenting the baseline number of deaths attributable to rotavirus infection is important. These baseline estimates will help countries assess the potential value of vaccination and measure the effect of vaccines on mortality attributable to rotavirus infection.

By applying the proportion of severe cases of diarrhoea caused by rotavirus infection in children admitted to hospital to the estimated all-cause child deaths attributable to diarrhoea, WHO estimated 527 000 deaths in 2004 (range 475 000–580 000) in children younger than 5 years due to diarrhoea attributable to rotavirus infection.14 New all-cause child mortality estimates released recently by the Child Health Epidemiology Reference Group of WHO and UNICEF15 documented an overall decline in the mortality of children younger than 5 years with a change in the number of deaths due to diarrhoea from 1·8 million deaths in 2003 to 1·3 million in 2008.15, 16 WHO estimated that there were 1·24 million deaths due to diarrhoea in children younger than 5 years in 2008. In view of these new figures for overall diarrhoea-related deaths, rotavirus-related mortality estimates need updating.

Although overall child diarrhoea-related mortality has declined over the past few years, this decline might not be uniform for all causes that contributed to these deaths. In particular, improvements in sanitation and hygiene have a large effect on diarrhoea caused by bacteria and parasites, which are mainly transmitted through contaminated food and water, and less of an effect on rotavirus diarrhoea, which is transmitted largely through person-to-person contact.17, 18, 19, 20, 21 Thus, the decrease in overall diarrhoea-related mortality might be disproportionately due to decreases in bacterial and parasitic causes of diarrhoea. Indeed, a previous study22 showed that although diarrhoea-related mortality has declined over the past three decades the proportion of severe diarrhoea attributable to rotavirus has increased. Since this previous study several reports of rotavirus disease burden have been published and the WHO-coordinated Global Rotavirus Surveillance Network has provided additional data on rotavirus disease burden in countries where data was not previously available.

Our objective is to update the rotavirus-related mortality estimate for children younger than 5 years on the basis of a review of recent published work and data from the WHO-coordinated rotavirus surveillance network.23

Section snippets

Search strategy and selection criteria

To estimate the number of deaths attributable to rotavirus infection in 2008, we used the same methods as used in the previous rotavirus mortality estimate14 and we followed the PRISMA guidelines. We searched PubMed, with the keyword “rotavirus” as our primary search term, to identify studies published between January, 2001, and January, 2011. We did not limit our search by language.

We limited our analysis to studies that met each of our criteria: a data collection midpoint in the year 2000 or

Results

Specimens from 151 172 children younger than 5 years in 65 countries were tested as part of 131 studies that met our inclusion criteria (figure 1, table 2). Rotavirus detection rates ranged from 12% to 68% with a median of 39%. The highest mean detection rate (49%, 95% CI 34–64) was in group A, the countries with the lowest levels of child mortality, and the lowest mean detection rate (33%, 28–38) were in groups D and E in Africa (figure 2).

We estimated that worldwide, each year,

Discussion

We estimated that, in 2008, rotavirus caused the deaths of 453 000 children younger than 5 years—ie, one of every 260 children born each year will die from diarrhoea caused by rotavirus infection by their fifth birthday. Although the proportion of rotavirus detected in children admitted to hospital with diarrhoea was highest in developed countries, most rotavirus-related deaths were in developing countries in Africa and Asia. India alone accounted for a fifth of these deaths (in part due to the

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    The WHO-coordinated Global Rotavirus Surveillance Network is composed of participating ministries of health, sentinel hospital sites, and the rotavirus laboratory network

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