Rotavirus Surveillance --- Worldwide, 2001--2008

Rotavirus infection is the leading cause of severe acute diarrhea among young children worldwide (1,2). An estimated 527,000 children aged <5 years die from rotavirus diarrhea each year, with >85% of these deaths occurring in low-income countries of Africa and Asia (3). Two licensed rotavirus vaccines have shown efficacy of 85%--98% against severe rotavirus diarrhea in trials conducted in the Americas and Europe (4,5), and they have been introduced into routine immunization programs in 11 countries in these regions and in Australia. Additional trials of these vaccines are ongoing to assess efficacy in low-income countries of Asia and Africa, where vaccine performance might be affected by factors such as concurrent enteric infections, greater prevalence of malnutrition, and a greater prevalence of unusual rotavirus strains. Results of these additional trials are expected within the next 1--2 years. To collect epidemiologic and burden-of-disease data that could form the basis of vaccination policy worldwide, beginning in 2001, the World Health Organization (WHO), in collaboration with partners, established networks of hospital-based sentinel surveillance sites for detection of rotavirus diarrhea and characterization of rotavirus strains. This report presents an analysis of results from the WHO surveillance networks for 2001--2008, which indicated that approximately 40% of diarrhea hospitalizations among children aged <5 years worldwide were attributed to rotavirus infection. The most common rotavirus strains found were G1, G2, G3, G4, and G9, and the distribution of strains varied markedly across regions. These data demonstrate the substantial burden of rotavirus diarrhea worldwide and highlight the potential health impact of vaccination.

Since 2001, regional networks of sentinel hospital-based sites have been established in 35 countries located in each of the six WHO regions worldwide.* These sites have conducted rotavirus surveillance using standard guidelines described in a WHO generic protocol (6). The period of surveillance differed among the sites depending on when regional networks were established. All data presented in this report were obtained during August 2001--July 2008.

At each site, all children aged <5 years hospitalized with diarrhea (i.e., three or more loose stools in a 24-hour period) were enrolled. Approximately 5 cc of bulk stool were collected from each patient with diarrhea and placed in a screw-top container, preferably within 48 hours of hospital admission. Specimens were stored in a freezer at -4°F (-20°C) until rotavirus testing was performed, generally in a hospital laboratory within the country. A confirmed case of rotavirus diarrhea was defined as diarrhea in a patient who had rotavirus antigen detected by a commercial enzyme immunoassay (EIA) (most frequently used assay was IDEIA^™ Rotavirus [Oxoid Ltd (Ely), Cambridge, United Kingdom]) in a fecal specimen. G and P genotypes of strains were characterized in a sample of rotavirus-positive specimens by reverse transcription--polymerase chain reaction (RT-PCR) (7), generally in a regional reference laboratory.

To avoid bias from seasonal patterns of rotavirus disease, only data for complete years at each site were analyzed. The percentages of children hospitalized with diarrhea who tested positive for rotavirus and the distribution of strains among rotavirus-positive specimens in each WHO region were examined. Median detection rates and the range of detection rates for all countries within each region and for all countries overall were calculated. Data for the South-East Asian and Western Pacific regions were combined for this report because countries in these two regions were part of a single surveillance network.

A total of 62,584 (range: 3,374--26,065 per WHO region) hospitalized patients aged <5 years with acute diarrhea were tested for rotavirus during the study period at all sites combined (Table 1). The overall median detection rate of rotavirus among all countries was 40%. The median rotavirus detection rate was lowest in the Region of the Americas (34%) and highest in the South-East Asian and the Western Pacific regions (45%).

Of the 4,936 rotavirus-positive specimens from all regions for which strains were characterized, 325 were from the African Region, 388 specimens were from the Region of the Americas, 323 were from the European Region, 1,290 were from the Eastern Mediterranean Region, and 2,610 were from the South-East Asian and the Western Pacific regions (Table 2). The most common strains in all regions except the Eastern Mediterranean and African regions were G1P[8], G9P[8], and G2P[4], accounting for approximately two thirds of strains in these regions. In the Eastern Mediterranean and African regions, specimens characterized in the category "other" accounted for 50% and 46% of strains, respectively; this category included specimens in which either the G or P type (or both) of the infecting strain could not be characterized.

Reported by: Dept of Immunization, Vaccines, and Biologicals, World Health Organization, Geneva, Switzerland. World Health Organization Regional Offices in Brazzaville, Republic of the Congo (African Region), District of Columbia, United States (Region of the Americas), Cairo, Egypt (Eastern Mediterranean Region), Copenhagen, Denmark (European Region), New Delhi, India (South-East Asian Region), and Manila, Philippines (Western Pacific Region). Rotavirus Vaccine Program, PATH, Seattle, Washington. Global Immunization Div; Div of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC.

Editorial Note:

The hospital-based surveillance findings in this report indicate that, during 2001--2008, rotavirus accounted for approximately 40% of hospitalizations for diarrhea among children aged <5 years worldwide. This percentage is greater than those percentages reported in two literature reviews (one reviewing studies published during 1986--1999 and one reviewing studies conducted during 1990--2004), which indicated a median rotavirus detection rate of 22% and 29%, respectively, for diarrhea hospitalizations among children aged <5 years (2,3). The higher rotavirus detection rates in the surveillance networks described in this report might reflect more standardized approaches for selection of patients (e.g., enrolling inpatients only and excluding those with milder disease) and/or improved collection and testing of specimens (e.g., obtaining whole stool specimens and avoiding rectal swabs, which might yield a falsely low rotavirus detection rate) than were used in the studies included in these reviews. Alternatively, the higher detection rates described in this report might reflect changing trends in the etiology of severe childhood diarrhea over the past 2--3 decades, reflecting either an absolute increase in the incidence of rotavirus diarrhea or a relatively greater decrease in the incidence of diarrhea from other causes. One review of more recent studies published during 2000--2004 reported a median detection rate of 39% (1), which is comparable to the overall rate observed in the surveillance data presented in this report. Similarly, surveillance data collected using a consistent approach (i.e., systematic sampling of patients seeking care for diarrhea) at Dhaka Hospital in Bangladesh during 1993--2004 also indicate that the percentage of childhood diarrhea hospitalizations attributed to rotavirus increased from 22% during 1993--1995 to 42% during 2002--2004 (8).

The substantial health burden of rotavirus diarrhea in the world underscores the need for effective interventions (e.g., vaccines) for the control of this disease as part of a comprehensive approach for prevention and control of diarrhea. For optimum results, rotavirus vaccines need to provide good protection against the range of rotavirus strains in circulation. Although the two licensed rotavirus vaccines differ in strain composition (i.e., one is monovalent, and one is pentavalent), both appear to provide protection against a variety of strains, including some strains not included in either of the licensed vaccines (4,5). The findings in this report support other observations that strains with G types 1--4 and 9 generally are the most prevalent (9), although the Eastern Mediterranean and African regions showed a high prevalence of other strains. As rotavirus vaccines are implemented in immunization programs worldwide, the sentinel hospital-based rotavirus surveillance networks described in this report will provide valuable baseline information to assess the future impact of vaccination. These sites also will provide platforms for conducting specialized epidemiologic studies of vaccine performance (e.g., vaccine effectiveness evaluations) and for detecting possible changes in the epidemiology of rotavirus disease (including possible changes in strains) in the postvaccination era. In countries of Latin America where vaccines have been licensed and recommended by WHO, existing surveillance networks currently are being used to conduct such evaluations of vaccine impact and effectiveness.

The findings in this report are subject to at least two limitations. First, although the countries participating in the various regional networks conducted surveillance using a standard generic WHO protocol, methods were adapted according to local needs (e.g., obtaining information on use of oral rehydration therapy or antibiotics before hospitalization) and availability of resources. These variations might have affected the comparability of data across sites, but key factors such as criteria for enrollment of cases, procedures for obtaining fecal specimens, and methods of rotavirus detection and strain characterization were well standardized. Formal assurance and standardization systems are being implemented to ensure further improvement in the quality and comparability of data across various countries and networks. Second, although surveillance generally was conducted in large pediatric hospitals that cared for a substantial number of patients with acute gastroenteritis, these sites might not be representative of the total population of the country.

Data generated from global rotavirus surveillance networks highlight the burden of rotavirus hospitalizations, including those in low-income countries that are eligible for financial support for vaccine purchase through the GAVI Alliance (formerly known as the Global Alliance for Vaccines and Immunizations). Fourteen low-income countries in regions where vaccine efficacy is proven (i.e., Latin America and Europe) are currently eligible for GAVI Alliance support for rotavirus vaccine purchase. If ongoing trials in Africa and Asia show good vaccine efficacy, this support likely will be extended to the remaining 58 countries eligible for GAVI Alliance funding in other regions. The availability and use of rotavirus vaccines globally should have a substantial impact on hospitalizations and mortality associated with childhood diarrhea and thereby will contribute to achievement of the United Nations' Millennium Development Goals for reduction of childhood mortality.^†

References

1. Parashar UD, Gibson CJ, Bresee JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerg Infect Dis 2006;12:304--6.
2. Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis 2003;9:565--72.
3. Parashar UD, Burton A, Lanata C, et al. World Health Organization estimates of the global mortality from rotavirus in children in the year 2004. J Infect Dis 2009 (in press).
4. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006;354:11--22.
5. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006;354:23--33.
6. World Health Organization. Generic protocol for (i) hospital-based surveillance to estimate the burden of rotavirus among children and (ii) a community-based survey on utilization of health care services for gastroenteritis in children. Geneva, Switzerland: World Health Organization; 2002. Available at https://www.who.int/vaccines-documents/docspdf02/www698.pdf.
7. Gentsch JR, Glass RI, Woods P, et al. Identification of group A rotavirus gene 4 types by polymerase chain reaction. J Clin Microbiol 1992;30:1365--73.
8. Tanaka F, Faruque AS, Luby SP, et al. Deaths from rotavirus disease in Bangladeshi children: evidence from hospital-based surveillance. Pediatr Infect Dis J 2007;26:1014--8.
9. Gentsch JR, Laird AR, Bielfelt B, et al. Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs. J Infect Dis 2005;192:S146--59.

* The following countries were included in the regional surveillance networks: Ghana, Kenya, Uganda, and Zambia in the African Region; Guyana, Nicaragua, Suriname, St. Vincent and Grenadine, Chile, Venezuela, Paraguay, Bolivia, El Salvador, Honduras, and Guatemala in the Region of the Americas; Georgia, Tajikistan, and Ukraine in the European Region; Egypt, Iran, Jordan, Libya, Morocco, Oman, Pakistan, Sudan, and Yemen in the Eastern Mediterranean Region; and China, Hong Kong, Malaysia, Myanmar, South Korea, Taiwan, Thailand, and Vietnam in the South-East Asian and Western Pacific regions.

^† Available at http://www.unicef.org/mdg/mortalitymultimedia/index.html.

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Date last reviewed: 11/20/2008