Rotavirus vaccination in Central American children

Abstract

Rotavirus is the leading cause of acute diarrhea in children younger than five years of age around the world. Severe dehydration and mortality rates are higher in developing countries, especially those from Latin America, Africa, and Asia. The vaccine has been introduced in the national immunization programs of more than half of Latin American countries, and impact data from some of these nations has been already published. The two rotavirus vaccines, the 2-dose monovalent (RV-1) and the 3-dose pentavalent (RV-5) vaccine, have been available in the market to all Central American countries. Rotavirus vaccine has been universally introduced in the expanded immunization national programs of Guatemala, Honduras, El Salvador, Nicaragua and Panama, but not in Belize and Costa Rica. This review summarizes what has been published about the epidemiology and impact of universal rotavirus vaccination in Central America.

Keywords::

• Central America
• children
• developing countries
• Latin America
• rotavirus
• vaccination
• vaccine introduction
• vaccine preventable diseases

Rotavirus is the leading cause of acute vaccine-preventable diarrhea in children around the world who are younger than 5 years of age. Severe dehydration and mortality rates are higher in developing countries, especially in Latin America, Africa and Asia. In Latin America and the Caribbean, rotavirus is responsible for around 15,000 deaths, 75,000 hospital admissions and 2,000,000 outpatient visits every year. Therefore, vaccination is a key point among the global efforts to achieve Millennium Development Goal 4 and reduce childhood mortality by two-third by 2015.

To date, the rotavirus vaccine has been introduced in the national immunization programs of more than half of the Latin American countries, and impact data from some of these nations have been already published or reported. Among the most populated countries in Latin America, Brazil and Mexico have seen the most dramatic beneficial impact of universal rotavirus vaccination in terms of decreasing hospital admission rates, outpatient visits, severely dehydrated cases, and in particular, deaths [1].

Rotavirus surveillance networks in Central American and other Latin American countries were crucial for determining the disease burden. Cost-effectiveness studies in these nations and the involvement of Latin American countries in clinical trials evaluating the safety, efficacy and immunogenicity of the currently available rotavirus vaccines were key factors in Latin America to introduce the vaccine at a faster rate compared with other pediatric vaccines [1–7]. Historically, at least one to two decades or even more has been the gap delay between developed and developing countries in introducing universal vaccines in the extended immunization programs. However, the story of rotavirus seemed different for Latin America.

The two rotavirus vaccines, the two-dose monovalent vaccine (RV1, Rotarix ^® , GSK) and the three-dose pentavalent vaccine (RV5, RotaTeq ^® , Merck), are available in the private market of all Central American countries. The vaccine has been universally introduced in the expanded immunization national programs of Guatemala, Honduras, El Salvador, Nicaragua and Panama, but not in Belize and Costa Rica. The first countries to introduce universal rotavirus vaccination were El Salvador (RV1), Nicaragua (RV5) and Panama (RV1) in 2006, followed by Honduras (RV1) in 2009 and Guatemala (RV1) in 2010. The Ministry of Health of each country, the national immunization or advisory committees, the Pan-American Health Organization Revolving Fund and the collaboration of public–private partnerships such as Global Alliance for Vaccines and Immunization rotavirus funding occurred in Nicaragua and Honduras [8], all have contributed to rotavirus vaccine introduction. In this editorial, we focus only on what has been published regarding the epidemiology and impact of universal rotavirus vaccination in Central America in those countries where it has been introduced.

In El Salvador, rotavirus was associated with a large outbreak of diarrhea throughout the country in December 2000 and continued until late February 2001 [9]. The outbreak was associated with an increase in the number of hospitalizations and deaths due to acute gastroenteritis, particularly among children younger than 5 years of age. Estimates of disease burden revealed that rotavirus was responsible for 23,080 consultations in El Salvador in 2001 and that 1 in 7 children would require a consultation by the age of 5. It was estimated that 295 children in the country died due to rotavirus infection by the age of 5. This risk of death from rotavirus for a child <5 years (1 in 531) was comparable at that point with that of a Vietnamese child and near one-half of the risk estimated at a global level (1 in 293).

Before the introduction of the two-dose RV1 vaccine schedule in 2006, rotavirus accounted for around 35% of diarrhea admissions in El Salvador. Following universal vaccination with this vaccine, the impact and decrease in hospital outpatient visits and hospital admissions have been reported [10,11]. From January 2006 to June 2009, laboratory-confirmed rotavirus case hospitalizations decreased by 84% from 2006 to 2008 and a 69% reduction was seen by 2009. The impact was especially important in infants younger than 1 and 2 years of age. Investigators found that vaccination provided 76% protection against rotavirus admissions among children younger than 2 years of age. Also, hospital admissions for all-cause diarrhea among children younger than 5 years of age decreased by 40% from 2006 to 2008 and a 51% reduction was seen by 2009. This illustrates the well-known herd immunity effect of rotavirus vaccines, as few children aged more than 2 years of age were vaccinated during the study period [11].

Panama was one of the first countries in Central America to introduce the rotavirus vaccine in its national immunization program using a two-dose schedule. The coverage rate increased over the last years and the impact in terms of decreased hospital admissions and mortality rates associated with acute diarrhea has been dramatic [12,13]. Prior to the two-dose regimen of RV1 vaccine introduction in March 2006, an estimated 15% of infants younger than 6 months of age and 85% of infants younger than 12 months of age had had at least one episode of rotavirus infection. Retrieving information from five representative surveillance hospitals in the country, including the national tertiary referral children’s hospital, investigators recently compared data prior to and post vaccine introduction. In 2008, 2 years after vaccine introduction, a 30% decrease in terms of all-cause acute gastroenteritis-related hospitalizations and a 47% decrease in mortality were seen in Panamanian children. The observed decrease in mortality was 45% in children younger than 1 year of age and 54% in children aged 1–4 years. Also, the number of hospital admissions decreased significantly by 28% in children younger than 12 months of age and by 31% in those aged 1–4 years. Current surveillance is ongoing and has demonstrated so far that these reductions have been also demonstrated for rotavirus-specific hospitalizations and deaths.

Nicaragua was the first Global Alliance for Vaccines and Immunization eligible country to incorporate rotavirus vaccine into its national extended immunization program in October 2006, using the pentavalent vaccine (RV5). A 1-year study, April 2008 to March 2009, was conducted in León to determine the prevalence of rotavirus in the primary care setting following RV5 introduction [14]. This is the second largest city in Nicaragua, with an estimated population of 192,000. Of 387 children with diarrhea and a total number of 410 episodes, only 3.5% were due to rotavirus during this period. This was lower when compared with previous rates of 14–35%, demonstrating the impact of RV5 vaccine introduction. In another case-control study, active surveillance for laboratory-confirmed rotavirus cases from July 2007 to June 2010 was performed at four hospitals [15]. Around 1200 children with rotavirus diarrhea were enrolled, of whom 86% were older than 6 months of age. Of these, 91% required hospital admission and 735 had severe rotavirus diarrhea. Vaccination was associated with a significantly lower risk of rotavirus hospitalization among children younger than 1 year of age (odds ratio: 0.36; 95% CI: 0.22–0.57) compared with children aged >1 year (odds ratio: 0.70; 95% CI: 0.47–1.05). Effectiveness of the vaccine was twofold greater among the 6–11 months group compared with the >12 months group. Thus, the investigators demonstrated a good vaccine efficacy against rotavirus hospitalizations (≈64%) and severe rotavirus disease (≈70%) among infants younger than 12 months of age, and a nationwide decrease in hospital admissions due to diarrhea during the rotavirus seasons of 2007 through 2010.

In Guatemala, diarrhea has been historically one of the most common causes of morbidity and death in children younger than 5 years of age. Therefore, the rotavirus vaccine was a priority for this country and RV1 was introduced in 2010 in a two-dose regimen. Prior to its introduction, in a study in which children <5 years of age presenting to ambulatory clinics or hospitals with acute diarrhea from October 2007 through September 2009 were enrolled [16], rotavirus was identified in a third of patients whose stools were tested. Among rotavirus hospitalizations, 90% occurred in children younger than 2 years of age and 28% among those aged <6 months. Although post-introduction surveillance has been maintained in this country and preliminary results have shown a decrease both in morbidity and mortality rates, the impact of vaccine introduction has not been published.

In Honduras, estimates prior to universal rotavirus vaccine introduction revealed that for the 2000–2004 period, rotavirus was responsible every year for approximately 66,600 consultations, 1880 hospital admissions and 70 in-hospital deaths among children younger than 5 years of age [17]. The risks of consultation and death were higher in children from Honduras than other countries from the region. Since vaccine introduction, a decrease in rotavirus-associated diarrhea and deaths has been documented in this country [7]; however, paucity of published information exists since then.

Although rotavirus is the leading cause of acute viral diarrhea in children from Belize and Costa Rica and produce significant morbidity, recent published information from these countries is scarce [4,18]. The successful history of the other Central American and Latin American countries, as well as other nations around the world, should motivate Costa Rica and other countries from the region to introduce universal vaccination against rotavirus in their national immunization programs.

In conclusion, a significant reduction in all-cause diarrhea, rotavirus-specific diarrhea and attributed mortality has been observed in Central American countries following universal rotavirus vaccination over the past 7 years. Some of the current challenges include maintaining adequate and continuous surveillance data on all-cause and rotavirus diarrhea, rates of intestinal intussusception and the distribution of circulating genotypes in those countries that have already introduced the vaccine [4,18–21]. It is time now for Latin American countries to move ahead and study the epidemiology and impact of norovirus in children, the current leading cause of acute viral diarrhea in countries where rotavirus vaccine has been introduced.

Financial & competing interests disclosure

None of the authors are employees of a pharmaceutical company. R Ulloa-Gutierrez has served as an invited speaker for Sanofi Pasteur, GSK, Wyeth, Pfizer and Merck; on Advisory Boards of Sanofi Pasteur, GSK and Wyeth; and as chairman and co-chairman of Sanofi Pasteur and GSK; meeting expenses from GSK, Sanofi Pasteur, Wyeth, Pfizer and Merck; and a research study funded by GSK. ML Avila-Aguero has served as an invited speaker for Sanofi Pasteur, GSK, Novartis and Pfizer and on Advisory Boards of Sanofi Pasteur and GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.