Volume 14, Issue 7 , Pages e592-e595, July 2010
Rotavirus disease burden, Nicaragua 2001–2005: defining the potential impact of a rotavirus vaccination program☆
Article Outline
- Summary
- 1. Introduction
- 2. Methods
- 3. Results
- 4. Discussion
- Conflict of interest
- Funding
- Ethical approval
- References
- Copyright
Summary
Background
In October 2006, a rotavirus vaccine was introduced in Nicaragua for routine immunization of all children. We document the baseline diarrheal disease burden in Nicaragua prior to the vaccine program to facilitate future studies to measure vaccine impact.
Methods
We analyzed national data for 2001–2005 on total acute gastroenteritis healthcare visits, hospitalizations, and mortality in Nicaraguan children aged <5 years.
Results
Prior to vaccine introduction, by age 5 years, one in four Nicaraguan children required an outpatient consultation, one in 34 were hospitalized, and one in 2487 died from rotavirus-associated diarrhea, representing approximately 41 122 outpatient visits, 4460 hospitalizations, and 60 deaths per year that are preventable through vaccination. Almost half of the total acute gastroenteritis burden was in children <1 year of age. Two distinct seasonal peaks were noted in acute gastroenteritis hospitalizations and deaths.
Conclusions
Existing data sources on all-cause acute gastroenteritis could be useful for establishing diarrhea disease burden and monitoring trends after vaccine introduction. Blunting of winter season peaks in rates of diarrhea, particularly among children aged <1–2 years, would be a useful indicator of impact from rotavirus vaccination.
Keywords: Rotavirus, Diarrhea, Viral gastroenteritis, Vaccine, Disease burden
1. Introduction
Rotavirus, the most common cause of severe gastroenteritis in children aged <5 years worldwide, accounts for an estimated 2.4 million hospital admissions and 527 000 deaths each year.1, 2 The tremendous global burden of rotavirus has prompted the prioritization of vaccine development and introduction by several international agencies, including the World Health Organization (WHO) and the Global Alliance for Vaccines and Immunizations (GAVI).3 Two new rotavirus vaccines with good efficacy against severe rotavirus disease – RotaTeq® (Merck Vaccines, Whitehouse Station, NJ, USA) and Rotarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium) – have recently been licensed for use in many countries.4, 5 Low and middle income countries in the Latin American region have been among the first to add new rotavirus vaccines to the routine childhood immunization schedule. As such, monitoring the trends of diarrheal disease before and after vaccine introduction in these regions will be crucial to assess impact and gather the necessary data for decision-makers to use in evaluating and sustaining a vaccination program.
In October 2006, a rotavirus vaccine (RotaTeq) was added to the national vaccination schedule in Nicaragua, after a large nationwide outbreak of rotavirus diarrhea in 2005 led to an unexpected increase in diarrhea mortality, hospitalizations, and outpatient visits and garnered substantial attention from decision-makers and public health authorities in Nicaragua.6, 7 In response to the recent rotavirus vaccine introductions in many countries worldwide, the WHO has published a generic protocol outlining approaches to monitoring the impact of rotavirus vaccination on disease burden.8 Vaccine introduction in Nicaragua provided us an early opportunity to field-test one aspect of this protocol – assessing vaccine impact by monitoring trends in diarrhea disease burden. As a first step in preparing to monitor trends of acute gastroenteritis in Nicaragua, we examined national data for acute gastroenteritis hospitalizations and outpatient visits among children aged <5 years to establish baseline incidence of disease prior to vaccine introduction, against which acute gastroenteritis trends can be compared as the vaccine program matures.
2. Methods
Nicaragua is a low income country in Central America with a gross national income of 980 US dollars per capita and an annual birth cohort of approximately 150 000 and an infant mortality rate of 21.5 per 1000 live births.9 In Nicaragua, 21.0% of the population lives without access to an improved water source and 10.0% of the children aged <5 years are considered underweight for age.9 A majority (85.0%) of the population utilize healthcare facilities operated by the Ministry of Health, which includes 1059 healthcare facilities, including 32 hospitals providing inpatient services to the population, and 172 health centers and 855 health posts that provide primary care services. On a weekly basis, each of the public health centers and hospitals organized into local health units, report to the Ministry the number of outpatient visits, hospitalizations, and deaths due to diarrhea. At the Ministry, the data are compiled in an electronic database. To estimate the national burden of diarrheal disease leading to outpatient visits, hospitalization, and death in children <5 years old, we reviewed the Ministry of Health's computerized records on total countrywide reports of acute gastroenteritis from January 2001 to December 2005. Limited data exist in Nicaragua on the proportion of severe diarrhea cases attributable to rotavirus disease. Therefore, we utilized surveillance data from neighboring Honduras10, 11 and El Salvador12, 13 and a review of rotavirus disease burden in Latin America14 to estimate the proportion of all-cause acute gastroenteritis among children <5 years of age attributable to rotavirus. In the review of studies from Latin America,14 some studies included children <3 and others <5 years of age, however, the authors did not find a difference in detection rates between the two age groups. In El Salvador and Honduras, active surveillance indicates rotavirus detection rates of approximately 43% (range in Latin America:14 16–52%) in the hospital setting, approximately 30% (range 18–42%) in the outpatient setting, and approximately 70% in any setting during the rotavirus season (typically weeks 1–20). To estimate the annual rotavirus disease burden, we multiplied the annual number of acute gastroenteritis visits among children aged <5 years by setting with these rotavirus detection rates of 43% (hospitalized children) and 30% (outpatient visits). Subsequently, we calculated the cumulative risk that a child would experience these events (outpatient visit, hospitalization, or death) before reaching the age of 5 years. Cumulative risks were expressed as the inverse of the annual birth cohort (n ≈ 150 000) divided by the respective median number of events among children <5 years of age from 2001 through 2005. Finally, to illustrate temporal and seasonal trends in diarrheal visits, we plotted the 2001–2005 weekly mean of total gastroenteritis for children <5 years of age. Data for the year 2006 were not available because of a nationwide healthcare worker strike during the first six months of the year.
3. Results
Among children <5 years old, the Ministry computerized records for public health facilities identified an annual median of 137 074 non-hospital consultations (range 129 418–147 878), 10 373 hospitalizations (range 8623–13 083), and 140 in-hospital deaths (range 78–178) for diarrhea (Figure 1). Thus, prior to rotavirus vaccine introduction in Nicaragua, by age 5 every child required an outpatient consultation, one in 14 were hospitalized, and one in 1069 died as a result of diarrhea.
Figure 1.
Cumulative risk of diarrheal- and rotavirus-associated events for all children aged <5 years—Nicaragua, 2001–2005a.
In neighboring countries, active surveillance indicates rotavirus detection rates of approximately 43% in the hospitalized setting and approximately 30% in the outpatient setting.6, 10, 11, 13, 14 Assuming similar rotavirus detection rates in Nicaragua and assuming the fraction of diarrhea deaths attributable to rotavirus is similar to that for hospitalizations, we estimate rotavirus-associated diarrhea in children <5 years old to annually result in 41 122 outpatient visits (range 38 825–44 363), 4460 hospitalizations (range 3708–5626), and 60 deaths (range 34–77). Cumulative risks were approximately 1:4 for consultation, 1:34 for hospitalization, and 1:2487 for death by the fifth birthday (Figure 1).
Examination of total acute gastroenteritis non-hospital consultations and hospitalizations over the five year study period showed two distinct seasonal peaks, one during the winter–spring months of February through May and a larger peak during the summer (June through September) months (Figure 2). Almost half of the total gastroenteritis burden was among children <1 year of age. In 2005, the winter–spring peak was substantially greater than in each of the previous four years, with an increase in number of events of 10% for <1-year-olds and 12% for 1–5-year-olds.
Figure 2.
Total acute gastroenteritis events in children aged ≤11 months and 12–59 months old, by week—Nicaragua 2001–2005.
Trends of in-hospital mortality from acute gastroenteritis among children <5 years of age also had a similar bi-annual seasonality (Figure 3). Because rotavirus is suspected to be responsible for a majority of the severe diarrhea events during weeks 1–20 in Central America,13, 15 the peak in diarrhea mortality during these weeks is also likely to be associated with rotavirus.
Figure 3.
Total acute gastroenteritis-associated deaths in children aged <5 years during 2001–2005, by weeks of year.
4. Discussion
Our data indicate that Nicaragua, given its high diarrhea disease burden, represents a vital opportunity to improve childhood health through a new vaccine program that has the potential to substantially decrease the morbidity, mortality, and healthcare costs associated with rotavirus disease. Prior to vaccine introduction, we estimate that each year 41 122 outpatient visits, 4460 hospitalizations, and 60 deaths from rotavirus occurred among children aged <5 years in Nicaragua. In other words, assuming that these episodes are independent infections among separate children, by age 5, approximately 28% of children born in Nicaragua would have visited a Ministry clinic for treatment of an episode of rotavirus diarrhea, one in 34 would be hospitalized, and one in 2487 would have died from rotavirus disease. The fact that half of the burden of gastroenteritis is in children <1 year of age, with high vaccine coverage and under assumptions of similar vaccine efficacy as in the clinical trial, the impact from vaccination would be notable in children <1–2 years of age after the first 2–3 years of vaccine introduction.
By examination of existing Ministry data, our findings indicate that it will be possible to discern the impact of vaccination, although careful analysis and interpretation will be required. The overall annual reduction in diarrhea-associated medical outcomes is expected to only be about 20.0–30.0% after the vaccine program matures and such a decline could be masked by annual secular variation in natural disease trends. However, examination of disease trends during the winter–spring months when rotavirus is most prevalent and overall reductions in all-cause gastroenteritis are likely to be greater, could allow for more specific assessment of the impact of vaccine in reducing rotavirus events. Furthermore, the impact of vaccination should be most visible on diarrhea events in children <1 year and <2 years of age during the first 1–3 years of a vaccine program, and would only extend to older children after the program matures in the next 4–5 years. Nicaragua and other countries currently adopting the rotavirus vaccine could monitor trends in these specific seasonal- and age-groups to determine the real-world impact of a new vaccine program.
Based on a global review of the scientific literature, an estimated one in five children require an outpatient visit for rotavirus disease and one in 65 require hospitalization by age 5 years.2 Our disease burden estimates for Nicaragua are higher than the global estimate of rates for rotavirus-associated outpatient visits and hospitalizations. Differences in healthcare-seeking behavior or access might in part explain this finding. While the estimate for in-hospital diarrhea death from our data is substantially lower than the WHO estimate of 1020 deaths,1 in-hospital deaths frequently underestimate total deaths from rotavirus in a community.10, 11, 13 For example, in Honduras, only approximately 15% of all diarrhea deaths are reported through hospital discharge records. By dividing the number of in-hospital deaths in Nicaragua by 0.15 we estimate approximately 400 deaths from rotavirus diarrhea. Furthermore, the WHO estimate reflects mortality patterns in the early 1990
s, and diarrhea mortality has declined considerably in many Latin American countries over the past two decades, which could also in part explain some of the discrepancy between the two estimates.
Several caveats must be considered when interpreting our findings. First, estimates of rotavirus-specific disease burden in Nicaragua were not available. The estimates of rotavirus-specific disease burden and mortality used in this analysis are extrapolations from previous studies and surveillance data from neighboring countries.10, 11, 13, 14 However, our reference rate of 43% for hospitalizations attributable to rotavirus is consistent with detection rates of 42% seen in Nicaragua during an outbreak investigation in February 2005.6 Although our data do not include private hospitals and clinics, more than 85% of the Nicaraguan population uses public facilities that report to the Ministry of Health. The estimates of children requiring outpatient visits also may be overestimates given the likelihood that children may have two or more visits for the same infection. In addition, inaccuracies in reporting may occur that would have led us to under- or overestimate disease burden.
In conclusion, our study demonstrates the significant health burden of rotavirus among Nicaraguan children. Our findings suggest that monitoring trends in non-hospital consultations and hospitalizations for all-cause diarrhea using routinely collected data could allow assessment of the impact of vaccination, although careful analyses and interpretation of data is required. Rotavirus-specific surveillance and vaccine effectiveness studies will provide a more accurate assessment of the public health benefits of vaccination. Indeed, early post-licensure data from the USA indicate that the declines in rotavirus disease after vaccine introductions appear to be substantially greater than expected.16, 17 In a recently conducted study from Nicaragua, we demonstrated that rotavirus vaccination prevented ∼50% of the rotavirus hospitalizations at four sentinel hospitals.7 Countries considering rotavirus vaccine introduction will greatly benefit from establishing active surveillance programs for monitoring rotavirus diarrhea at sentinel hospitals according to the WHO generic protocol on rotavirus surveillance, preferably 2–3 years prior to introduction.18
Conflict of interest
None of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence or bias our work.
Funding
This work was performed under a collaborative arrangement with PATH and was funded in part by the GAVI Alliance. The GAVI Alliance was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Ethical approval
The current study was deemed to be public health practice and exempt from the human subjects review at the involved institutions. The study did not involve gathering patient identifying information.
References
- World Health Organization (WHO). Global and national estimates of deaths under age five attributable to rotavirus infection: 2004. Geneva: WHO; 2006. Available at: http://www.who.int/immunization_monitoring/burden/rotavirus_estimates/en/ (accessed November 2009).
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- Rotavirus vaccines: current prospects and future challenges. Lancet. 2006;368:323–332
- Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006;354:11–22
- Safety and efficacy of a pentavalent human–bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006;354:23–33
- Outbreak of rotavirus gastroenteritis with high mortality, Nicaragua, 2005. Rev Panam Salud Publica. 2008;23:277–284
- Association between pentavalent rotavirus vaccine and severe rotavirus diarrhea among children in Nicaragua. JAMA. 2009;301:2243–2251
- World Health Organization (WHO). Generic protocol for monitoring impact of rotavirus vaccination on rotavirus disease burden and viral strains. WHO/IVB/0816. Geneva: WHO; 2009, p. 1–73.
- United Nations Department of Economic and Social Affairs. World population prospects: the 2008 revision. United Nations; 2009. Available at: http://esa.un.org/unpp/index.asp (accessed November 2009).
- . Rotavirus en las diarreas infantiles de Honduras. Med Clín (Honduras). 1992;1:14–20
- Burden of diarrhea among children in Honduras, 2000-2004: estimates of the role of rotavirus. Rev Panam Salud Publica. 2006;20:377–384
- Pan American Health Organization. Vigilancia de diarreas por rotavirus, 2005-2007. Available at: http://www.paho.org/Spanish/AD/FCH/IM/Rotavirus_TablasVigilanciaMarzo2008.pdf (accessed November 2009).
- Rotavirus in El Salvador: an outbreak, surveillance and estimates of disease burden, 2000–2002. Pediatr Infect Dis J. 2004;23:S156–S160
- . The epidemiology of rotavirus diarrhea in Latin America. Anticipating rotavirus vaccines. Rev Panam Salud Publica. 2004;16:371–377
- Diarrhea morbidity and mortality in Mexican children: impact of rotavirus disease. Pediatr Infect Dis J. 2004;23:S149–S155
- Delayed onset and diminished magnitude of rotavirus activity—United States, November 2007–May 2008. MMWR Morb Mortal Wkly Rep 2008; 57:697–700.
- Decline and change in seasonality of US rotavirus activity after the introduction of rotavirus vaccine. Pediatrics. 2009;124:465–471
- World Health Organization. Vaccine Assessment and Monitoring Team. Generic protocols for (i) hospital-based surveillance to estimate the burden of rotavirus gastroenteritis in children and (ii) a community-based survey on utilization of health care services for gastroenteritis in children. Field test ed. Geneva: Vaccines and Biologicals, World Health Organization; 2002.
☆ The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention (CDC).
PII: S1201-9712(09)00349-X
doi:10.1016/j.ijid.2009.08.014
Published by Elsevier Inc.
Volume 14, Issue 7 , Pages e592-e595, July 2010
