Progress in the Introduction of Rotavirus Vaccine — Latin America and the Caribbean, 2006–2010

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Rotavirus disease is the leading cause of childhood morbidity and mortality related to diarrhea in Latin America and the Caribbean (LAC), where an estimated 8,000 deaths related to rotavirus diarrhea occur annually among children aged <5 years (1). After two safe and effective rotavirus vaccines became available, the World Health Organization (WHO) in 2007 recommended inclusion of rotavirus vaccine in the immunization programs of Europe and the Americas, and in 2009 expanded the recommendation to all infants aged <32 weeks worldwide (2). This report describes progress in the introduction of rotavirus vaccine in LAC, where it was first introduced in 2006 in Brazil, El Salvador, Mexico, Nicaragua, Panama, and Venezuela; by January 2011, it was included in the national immunization schedules of 14 countries in LAC. Estimated national rotavirus vaccine coverage (2 doses of the monovalent vaccine or 3 doses of the pentavalent vaccine) among children aged <1 year in 2010 ranged from 49% to 98% (median: 89%) in the 11 LAC countries with vaccine introduction before 2010. Of the 14 countries that had introduced rotavirus vaccine into their national immunization programs, 13 participate in a hospital-based rotavirus surveillance network. Data from some countries in this network and from other monitoring efforts in LAC countries (3–6) have shown declines in hospitalizations and deaths related to severe diarrhea after rotavirus vaccine introduction. The rapid introduction of rotavirus vaccine in LAC demonstrates the benefits of the early commitment of national decision makers to introduce these vaccines in low-income and middle-income countries at the same time as in high-income countries.
WHO recommends two rotavirus vaccines: a 2-dose monovalent vaccine (Rotarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and a 3-dose pentavalent vaccine (RotaTeq, Merck & Co. Inc., West Point, Pennsylvania). WHO recommends that the first dose of either vaccine be administered at age 6–15 weeks. The maximum age for administering the last dose of either vaccine should be 32 weeks, with an interval of at least 4 weeks between doses. This report summarizes 2010 WHO and United Nations Children's Fund (UNICEF) estimates of national vaccination coverage with the complete rotavirus series (2 doses of the monovalent vaccine or 3 doses of the pentavalent vaccine) and with the complete 3-dose series of diphtheria-tetanus-pertussis vaccine (DTP3) among children aged <1 year for the 14 countries with a rotavirus vaccine program. These estimates were derived through a country-by-country review of the best available data, including reports from Pan American Health Organization (PAHO) member states on the annual standardized Joint Reporting Form, and were supplemented by special coverage surveys and other published and unpublished data (7). As with national coverage reporting for other vaccines, age of administration for each dose was not reported. Countries were grouped on the basis of child and adult mortality rates, according to WHO mortality strata.*
Before rotavirus vaccine introduction in LAC, PAHO implemented a surveillance network for hospitalizations of children with rotavirus using standardized case definitions and laboratory methods. Any child aged <5 years hospitalized for treatment of acute diarrhea at a sentinel hospital conducting surveillance was eligible for enrollment, which required having stool specimens collected and tested for rotavirus using enzyme immunoassays. A child who tested positive for rotavirus was defined as having rotavirus diarrhea. Of the 14 countries that had introduced rotavirus vaccine into their national immunization programs (Table 1), surveillance data on the prevalence of rotavirus infection among children hospitalized with diarrhea were available from six of 14 countries during January–December 2006, before the introduction of vaccine, and from 12 of 14 countries during January–December 2010, after the introduction of vaccine. This report summarizes the surveillance data from the six countries in 2006 and from the 12 countries in 2010. This report also highlights data from El Salvador and Venezuela, where rotavirus surveillance was in place from 2006 to 2010 and vaccine was introduced in 2006, thus providing an opportunity for approximately four birth cohorts to be vaccinated before 2010.
As of June 1, 2011, rotavirus vaccine had been introduced into the national childhood immunization programs of 14 (44%) of 32 countries in LAC. Five of the 14 countries had high child mortality (WHO stratum D), and nine had low child mortality (WHO stratum B). In 2010, coverage with rotavirus vaccines among children aged <1 year in the 11 LAC countries that had introduced rotavirus vaccine before 2010 ranged from 49% to 98% (median: 89%), representing approximately 7 million infants (66% of the 10.6 million surviving infants in the 2010 birth cohort in LAC) (Table 1). DTP3 coverage ranged from 78% to 99% in these countries (Table 1).
In 2010, among 14,354 children aged <5 years who were hospitalized for diarrhea and tested for rotavirus, 4,266 (30%) had laboratory-confirmed rotavirus disease (Table 2). In El Salvador, where vaccine coverage was 92% during 2010, rotavirus prevalence was 43% (1,025 rotavirus-positive stool specimens out of 2,370 stool specimens from children aged <5 years hospitalized with diarrhea) in 2006 and 24% in 2010 (524 of 2,191). In Venezuela, where rotavirus vaccine coverage was 49% during 2010, rotavirus prevalence was similar at 32% (258 of 808) in 2006 and 31% (76 of 242) in 2010.

Reported by

Lucia Helena de Oliveira, MSc, Jennifer Sanwogou, MPH, Cuauhtemoc Ruiz-Matus, MD, Gina Tambini, MD, Pan American Health Organization. Susan A. Wang, MD, Mary Agocs, MD, World Health Organization. Umesh Parashar, MBBS, Manish Patel, MD, National Center for Immunizations and Respiratory Diseases; Rishi Desai, MD, EIS Officer, CDC. Corresponding contributor: Manish Patel, mpatel@cdc.gov , 404-639-2343.

Editorial Note

Since 2006, countries in LAC have made substantial progress in implementing rotavirus vaccination. All low-income LAC countries eligible for vaccine financing through the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization), except Haiti, have introduced rotavirus vaccine. In total, an estimated 7 million infants (or 66% of all infants) in LAC were fully vaccinated against rotavirus during 2010, providing an opportunity to reduce the burden of rotavirus hospitalizations and deaths in this region. Coverage with rotavirus vaccine in some of these countries was lower than DTP3 coverage, with a coverage gap between the two vaccines exceeding 15 percentage points in Brazil, Colombia, Peru, and Venezuela. Factors that might explain this coverage gap might include differences in timeliness of routine vaccination in countries, differences in how countries implement WHO's recommendation to initiate rotavirus vaccination at age 6–15 weeks and to complete the full 2-dose or 3-dose series by age 32 weeks, vaccine shortages, or logistical challenges resulting from the relatively large rotavirus vaccine cold chain volume and the need for additional vaccine carriers to deliver rotavirus vaccines (8). Evaluating the reasons for the coverage gap between DTP3 and rotavirus vaccine and addressing them will be important to gain the full benefit of rotavirus vaccine. Possible strategies for narrowing this gap in vaccine coverage could include improvements in the timeliness of vaccination and in the tracking of infants who miss vaccination, and assessment of the benefits and risks of the WHO age restriction policy (9).
Although rotavirus vaccines were studied extensively before licensure, insight into the important aspects of the vaccine's performance often is better determined after a vaccine has been used widely, particularly in settings with established prevaccine disease surveillance. El Salvador and Venezuela established sentinel surveillance by 2006 and maintained the surveillance for several years after introducing rotavirus vaccine into their national immunization programs. This allows assessment of trends in rotavirus positivity before and after vaccine introduction in these countries. A substantial decrease in the percentage of rotavirus diarrhea cases in 2010 compared with 2006 was observed in El Salvador, where national rotavirus vaccine coverage was 92%, and was not observed in Venezuela, where coverage was 49%. All sentinel surveillance data should be interpreted cautiously because changes in surveillance and clinical practices over time can influence the results. Therefore, the actual impact of rotavirus vaccine introduction on rotavirus disease is best interpreted by a combination of data from sentinel surveillance and special studies. A study in El Salvador documented that vaccine introduction in 2006 resulted in substantial declines in 2008 and 2009 in rotavirus hospitalizations at sentinel hospitals and in health-care visits for childhood diarrhea, compared with prevaccine rates in 2005 and 2006 (3). Furthermore, vaccination has prevented approximately 140,000 diarrhea-related hospitalizations and 1,300 diarrhea-related deaths annually among children aged <5 years in Brazil and Mexico, two large countries that introduced the vaccine early but were not part of the PAHO surveillance network when vaccine was introduced (4,10). These findings underscore the value of conducting sentinel surveillance for several years before and after vaccine introduction and highlight that rotavirus vaccine is an important tool for improving children's survival.
Recent data from Mexico and Brazil indicate that rotavirus vaccines might be associated with a low-level increased risk for intussusception, a form of intestinal obstruction in infants (10). However, recognizing that the benefits far outweigh the risks, regulatory agencies and immunization advisory committees have favored continuing rotavirus vaccination (10). This experience has highlighted the need that ministries of health have for reliable data on the health impact and safety of rotavirus vaccine. Surveillance systems are crucial for collecting such data, and systems such as the PAHO network can be used to conduct timely assessments of rotavirus vaccine impact and safety assessments. For example, case-control studies in El Salvador (5) and Nicaragua (6), where PAHO initiated surveillance in 2006 and 2007, respectively, have offered convincing evidence of successes in vaccine programs. In addition, these studies have generated questions for future research by demonstrating that vaccine effectiveness is lower in high child-mortality settings compared with low child-mortality settings (5,6).
The findings in this report are subject to at least three limitations. First, the administrative methods used to determine vaccine coverage might be inaccurate as a result of imprecise data on the size of the target population and the number of doses administered. Second, because of potential changes in the catchment population and because prevalence of rotavirus can be affected by incidence of acute diarrhea caused by nonrotavirus pathogens, hospital-based surveillance systems are less robust in quantifying the impact of vaccine than population-based systems. Finally, the absence of surveillance data from before the vaccines were introduced could pose a challenge for some countries in interpreting postvaccination trends in rotavirus disease; this challenge could be overcome by using these sites to conduct case-control studies to monitor effectiveness.
In total, approximately 7 million infants in LAC were vaccinated against rotavirus in 2010. Although coverage with rotavirus vaccine already exceeds 70% in most countries, coverage is lower than DTP3 coverage in some countries, and this discrepancy warrants attention. The existing rotavirus surveillance network in LAC provides an opportunity to collect valuable data on the benefits of vaccination for decision-makers, health-care providers, and parents. The rapid introduction of rotavirus vaccine in low-income and middle-income countries in the region demonstrates that challenges to introducing new vaccines can be overcome; this is particularly encouraging for countries in Asia and Africa, where most rotavirus deaths occur. The vaccine will be introduced into countries in Asia and Africa during the next 3–5 years; already, a total of 16 countries, 12 of which are in Africa, have secured funding from the GAVI Alliance for introducing rotavirus vaccine in 2012 and 2013. Given the successful experience with rotavirus vaccines both in developing and developed regions of LAC, the global use of rotavirus vaccines should have a substantial impact on diarrheal morbidity and mortality, thus accelerating progress towards reaching the fourth Millennium Development Goal of reducing mortality among children.

References

1. Tate JE, Burton AH, Boschi-Pinto C, et al. 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. Lancet Infect Dis 2011; October 24 [Epub ahead of print].
2. World Health Organization. Rotavirus vaccines: an update. Wkly Epidemiol Rec 2009;84:533–40.
3. Yen C, Armero Guardado JA, Alberto P, et al. Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador. Pediatr Infect Dis J 2011;30(1 Suppl):S6–10.
4. do Carmo GM, Yen C, Cortes J, et al. Decline in diarrhea mortality and admissions after routine childhood rotavirus immunization in Brazil: a time-series analysis. PLoS Med 2011;8:e1001024.
5. de Palma O, Cruz L, Ramos H, et al. Effectiveness of rotavirus vaccination against childhood diarrhoea in El Salvador: case-control study. BMJ 2010;340:c2825.
6. Patel M, Pedreira C, De Oliveira LH, et al. Association between pentavalent rotavirus vaccine and severe rotavirus diarrhea among children in Nicaragua. JAMA 2009;301:2243–51.
7. World Health Organization. WHO-UNICEF estimates of Rota_last coverage [Data as of July 20, 2011]. Geneva, Switzerland: World Health Organization; 2-11. Available at http://apps.who.int/immunization_monitoring/en/globalsummary/timeseries/tswucoveragerota_last.htm. Accessed November 23, 2011.
8. de Oliveira LH, Danovaro-Holliday MC, Sanwogou NJ, Ruiz-Matus C, Tambini G, Andrus JK. Progress in the introduction of the rotavirus vaccine in Latin America and the Caribbean: four years of accumulated experience. Pediatr Infect Dis J 2011;30(1 Suppl):S61–6.
9. Patel MM, Clark AD, Glass RI, et al. Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: benefits of mortality reduction versus risk of fatal intussusception. Vaccine 2009;27:2916–22.
10. Patel MM, Lopez-Collada VR, Bulhoes MM, et al. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. N Engl J Med 2011;364:2283–92.

* Countries are assigned to WHO mortality strata based on both child and adult mortality (additional information available at http://www.who.int/whr/2003/en/member_states_182-184_en.pdf ). Rotavirus vaccine efficacy in different countries has been found to correlate with WHO mortality strata with higher efficacy in countries in low mortality strata, such as stratum B, and lower efficacy in countries in high mortality strata, such as stratum D (2).

Progress in the Introduction of Rotavirus Vaccine — Latin America and the Caribbean, 2006–2010December 2, 2011 / 60(47);1611-1614