SEARCH

SEARCH BY CITATION

Keywords:

  • rotavirus;
  • incidence;
  • vaccine;
  • epidemiology;
  • Guatemala
  • Rotavirus;
  • incidence;
  • vaccin;
  • épidémiologie;
  • Guatemala
  • Rotavirus;
  • incidencia;
  • Vacuna;
  • epidemiología;
  • Guatemala

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objectives  To assess the burden of rotavirus disease in Guatemala, in view of the recent introduction of a national rotavirus vaccination programme.

Methods  We examined data from an active, facility-based surveillance system in Santa Rosa, Guatemala, from October 2007 through September 2009 among children <5 years of age presenting to the hospital or ambulatory clinics with diarrhoea (≥3 loose stools in 24 h during the last 7 days). Demographic and epidemiological data were collected, and specimens were tested for rotavirus via enzyme immunoassay. Genotyping was performed via reverse transcriptase polymerase chain reaction.

Results  We enrolled 347 hospitalized patients <5 years of age with diarrhoea and 1215 from ambulatory clinics. Specimens from 275 (79%) hospitalized children and 662 (54%) from ambulatory visits were tested for rotavirus. Rotavirus accounted for 32% of hospitalizations and 9% of ambulatory visits for diarrhoea, resulting in adjusted annual rates of 36 hospitalizations and 372 ambulatory visits per 10 000 children. Ninety-one per cent of hospitalizations and 81% of ambulatory visits for rotavirus diarrhoea occurred in children <2 years. G1P8 represented 71% and 95% of rotavirus genotypes for 2007–2008 and 2008–2009 rotavirus seasons, respectively.

Conclusions  Rotavirus is a major cause of diarrhoea in children <5 years of age in Santa Rosa, Guatemala, highlighting the potential health benefits of vaccination and the need for continued surveillance to assess impact and effectiveness of the rotavirus vaccination programme in Guatemala.

Objectifs:  Evaluer la charge des maladies à rotavirus au Guatemala, au vu de l’introduction récente d’un programme national de vaccination contre le rotavirus.

Méthodes:  Nous avons examiné les données d’un système de surveillance actif basé sur les établissements de santéà Santa Rosa, au Guatemala, d’octobre 2007 à septembre 2009 chez les enfants <5 ans présentés à l’hôpital ou dans des cliniques ambulatoires et souffrant de diarrhée (≥3 selles liquides en 24 heures au cours des sept derniers jours). Les données démographiques et épidémiologiques ont été recueillies et des spécimens ont été testés pour le rotavirus par dosage immunoenzymatique. Le génotypage à l’aide de la réaction en chaine de la polymérase et de la transcriptase inverse a été effectué.

Résultats:  Nous avons recruté 347 patients <5 ans hospitalisés souffrant de diarrhée et 1215 dans les cliniques de soins ambulatoires. Des spécimens de 275 (79%) enfants hospitalisés et 662 (54%) en visites ambulatoires ont été testés pour le rotavirus. Le rotavirus représentait 32% des hospitalisations et 9% des visites ambulatoires pour la diarrhée, résultant en des taux annuels ajustés de 36 hospitalisations et 372 visites ambulatoires par 10.000 enfants. 91% des hospitalisations et 81% des visites ambulatoires pour les diarrhées à rotavirus survenaient chez des enfants <2 ans. G1P8 représentait 71% et 95% des génotypes de rotavirus pour les saisons à rotavirus de 2007–2008 et 2008–2009, respectivement.

Conclusions:  Le rotavirus est une cause majeure de diarrhée chez les enfants <5 ans à Santa Rosa, au Guatemala, soulignant les avantages potentiels de la vaccination pour la santé et la nécessité d’une surveillance continue pour évaluer l’impact et l’efficacité du programme de vaccination contre le rotavirus au Guatemala.

Objetivos:  Evaluar la carga de la enfermedad por rotavirus en Guatemala, en vista de la reciente introducción de un programa nacional de vacunación para rotavirus.

Métodos:  Hemos analizado datos provenientes de un sistema de vigilancia activo en instalaciones de Santa Rosa, Guatemala, entre Octubre del 2007 y Septiembre 2009, de niños <5 años de edad que se presentaban en el hospital o ambulatorios con diarrea (≥3 heces blandas en 24 horas durante los últimos siete días). Se recolectaron datos demográficos y epidemiológicos, y a los especímenes se les realizaron pruebas para rotavirus mediante inmunoensayo enzimático. Se realizó el genotipaje mediante PCR.

Resultados:  Se incluyeron 347 pacientes <5 años hospitalizados con diarrea y 1215 de clínicas ambulatorias. Los especímenes de 275 (79%) niños hospitalizados y 662 (54%) de visitas ambulatorias se examinaron para rotavirus. El rotavirus era responsable de un 32% de las hospitalizaciones y un 9% de las visitas a ambulatorios por diarrea, resultando en tasas anuales ajustadas de 36 hospitalizaciones y 372 visitas ambulatorias por 10,000 niños. Un 91% de las hospitalizaciones y un 81% de las visitas ambulatorias por diarrea por rotavirus sucedió en niños <2 años. G1P8 representó un 71% y 95% de los genotipos de rotavirus durante los periodos de 2007–2008 y 2008–2009, respectivamente.

Conclusiones:  El rotavirus es la principal causa de diarrea en niños <5 años en Santa Rosa, Guatemala, enfatizando los beneficios potenciales en la salud de la vacunación y la necesidad de una vigilancia continuada para evaluar el impacto y la efectividad del programa de vacunación para rotavirus en Guatemala.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Rotavirus is the leading cause of severe childhood diarrhoea worldwide, resulting in nearly 500 000 deaths in children <5 years of age (Parashar et al. 2003). Developing countries are disproportionately affected by higher morbidity and mortality, accounting for >80% of rotavirus-related deaths (Parashar et al. 2003). Rotavirus is estimated to cause approximately 40% of all diarrhoea hospitalizations and deaths and a quarter of ambulatory visits for diarrhoea in Latin America and the Caribbean, resulting in approximately 10 million episodes of diarrhoea annually, two million seeking care in a clinic, 75 000 hospitalizations and 15 000 deaths (de Oliveira et al. 2008; Rheingans et al. 2007).

Diarrhoea is the 2nd most common cause of morbidity and death in Guatemalan children under 5 years of age (Allebeck 2008). In February 2010, a rotavirus vaccination programme was introduced in Guatemala. Baseline data about rotavirus disease burden are important for the assessment of the potential value of rotavirus vaccines and to better characterize post-implementation vaccine impact. To provide such information, we examined data from an active, facility-based surveillance system for diarrhoea in the department of Santa Rosa, Guatemala.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Site

Guatemala is a low-middle-income country with gross national income per capita of 2680 US$ and an annual birth cohort of approximately 450 000 (WHO 2010). In June 2007, we began a facility-based surveillance for diarrhoea in the Department of Santa Rosa, Guatemala. Santa Rosa has a population of 308 522 and is one of 22 departments in Guatemala. Indigenous populations represent approximately 3% of the total population of Santa Rosa, as compared with 40% nationally. It is located 80 km south-east of Guatemala City and divided into 14 municipalities. Temperature in Santa Rosa varies little throughout the year with no more than 3 °C separating the highest average daily temperature from the lowest in a given year. The amount of rainfall, however, does exhibit substantial variation with an average of 200 cm per month most of the year, but with negligible rainfall between December and March, the dry season (Instituto Nacional de Sismologia 2010).

In Santa Rosa, there are four levels of government-supported healthcare: the Regional Hospital of Cuilapa, 14 health centres in each municipality and staffed by a physician and several nurses, 56 health posts each staffed by a nurse and convergence centres, which provide healthcare through several contracted non-governmental organizations. Other sources of healthcare in Santa Rosa are private clinics, two small private hospitals, pharmacies and traditional healers. A 2006 healthcare utilization survey estimated that 35% of children <5 years of age with diarrhoea in Santa Rosa were taken to a governmental facility for care (Arvelo et al. 2009).

Surveillance

Diarrhoea surveillance was conducted at the Regional Hospital of Cuilapa, a 176-bed referral hospital, and at all of the ambulatory governmental healthcare facilities in the municipality of Nueva Santa Rosa, which includes one health centre and five health posts. Surveillance nurses identified patients presenting with signs or symptoms suggestive of diarrhoea by reviewing ward registers for diarrhoea-related admission diagnoses or by determining the chief complaints of patients waiting to be admitted from the emergency department or treated at the health centre and health posts.

For surveillance purposes, a case of diarrhoea was defined as ≥3 loose stools in a 24-h period with onset during the last 7 days in a person of any age that is a resident of the department of Santa Rosa and is hospitalized at the Regional Hospital of Cuilapa or presents to the health centre or posts in Nueva Santa Rosa and is a resident of that municipality. Clinical and epidemiologic data were collected using standardized patient interviews and for hospitalized patients, chart reviews were also completed. Data were collected using hand-held personal digital assistants.

Laboratory tests

Whole stool samples were requested from all enrolled patients. Collected specimens were kept at 4 °C and transported within 24 h to the laboratory at the Regional Hospital of Cuilapa and tested via qualitative enzyme immunoassay (EIA) for the detection of rotavirus (Group A) with the IDEIA Rotavirus test (Dako Ltd., Ely, UK). A sample of positive and negative specimens was tested at the Universidad del Valle de Guatemala to assure quality control. All specimens testing positive for rotavirus were sent to the rotavirus reference laboratory at the Centers for Disease Control and Prevention (CDC) in Atlanta for genotyping using reverse transcriptase polymerase chain reaction (RT-PCR) (Gentsch et al. 1992; Gouvea et al. 1990).

Data analysis

We examined data on all enrolled patients <5 years of age meeting the case definition for diarrhoea. We analysed hospital and ambulatory encounters for all causes of diarrhoea, including those with rotavirus testing and confirmed rotavirus disease, by month of year and age group from 1 October 2007 through 30 September 2009. Emergency department visits were not included in this analysis. Population-based rates for diarrhoea-associated healthcare utilization were calculated using denominators for the catchment area of the healthcare facilities extrapolated from the most recent census in Guatemala in 2002. The calculated rates were adjusted upward by 65% in both hospital and ambulatory settings to account for the finding that only 35% of the Santa Rosa community in the <5 age group utilize the facilities from which the surveillance data originate (Arvelo et al. 2009). Rotavirus disease rates were derived by the application of the per cent of rotavirus-positive test results to the adjusted rates of diarrhoea-associated healthcare utilization. To assess the potential relationship of seasonality with climatic factors, we compared average daily temperature and accumulated rainfall from 1990 to 2008 by month with the adjusted rates of rotavirus-specific health encounters during the study period.

Not all enrolled children provided stool samples for rotavirus testing. Therefore, we compared tested children to non-tested children with regard to age and seasonality to assess for bias in our data and adjusted our per cent of rotavirus positivity where necessary. We then evaluated the distribution of rotavirus and non-rotavirus disease among rotavirus-tested children by sex and age groups of <1, 1 to <2, and 2–4 years in hospital and ambulatory settings. We also examined genotype data by month and healthcare setting. Analyses were completed using Statistical Analysis System version 9.2 (SAS Institute, Cary, NC, USA) and Microsoft Excel 2007.

Ethics

Parents or guardians of children who met the case definition were requested to provide written, informed consent for the participation of their children. The protocol received approval from the ethics committee of the Universidad del Valle de Guatemala (Guatemala City, Guatemala) and the institutional review board of the CDC (Atlanta, GA, USA) and from the Guatemalan Ministry of Public Health and Welfare.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

A total of 347 hospitalizations and 1215 ambulatory visits for diarrhoea were recorded among children <5 years of age between 1 October 2007 and 30 September 2009 in Santa Rosa, Guatemala. This yielded an adjusted annual rate of diarrhoeal hospitalizations of 111 per 10 000 children <5 years of age and a diarrhoea rate for ambulatory visits of 4133 per 10 000 children <5 years of age. Five in-hospital deaths were also captured during the study period.

Rotavirus testing was performed in 79% of hospitalizations (275 of 347) and 54% of ambulatory visits (662 of 1215). When compared to non-tested children, no significant differences in seasonality for rotavirus-tested children were observed. However, significant differences in testing patterns by age group were apparent (Table 1). Among hospitalized children, rotavirus was identified in 31% of tested stool specimens (86 of 275) resulting in an estimated annual hospitalization rate of 34 hospitalizations per 10 000 children (Table 2). Rotavirus testing was positive in a smaller proportion of ambulatory visits, with 9% of tested specimens positive for rotavirus (57 of 662) resulting in a rotavirus ambulatory visit rate of 372 per 10 000 children. The per cent positivity remained essentially unchanged in both the hospital and the ambulatory settings after adjusting for age group. Overall mean duration of illness prior to hospitalization or healthcare visit was 3 days (range: 1–7 days) among patients positive for rotavirus. In terms of clinical symptoms of patients with rotavirus, 111 (79%) reported irritability, 99 (70%) had increased thirst, 93 (66%) presented with associated vomiting, and 39 (28%) had abdominal pain or cramps. Of the recorded deaths among all patients with diarrhoea, four were tested for rotavirus and one was positive.

Table 1.   Rotavirus testing by health setting, age group and season – Santa Rosa, Guatemala, October 2007—September 2009*
 HospitalAmbulatory
Tested n = 275 (%)Non-tested n = 28 (%)P-valueTested n = 662 (%)Non-tested n = 497 (%)P-value
  1. *Rotavirus testing status could not be determined for 44 hospitalized and 56 ambulatory patients.

Age group
 <1 year153 (56)10 (36)0.0440207 (31)158 (32)0.8499
 1 year99 (36)13 (46)0.2761217 (33)199 (40)0.0108
 2–4 years23 (8)5 (21)0.0984238 (36)140 (28)0.0052
Season
 Dry122 (44)13 (46)0.8341170 (26)122 (25)0.6603
 Rainy153 (56)15 (54)0.8341492 (74)375 (75)0.6603
Table 2.   Diarrhoea, rotavirus testing and rotavirus disease among children by age group and type of health setting Santa Rosa, Guatemala, October 2007–September 2009
Age group (years)All diarrhoea NRotavirus tested N (% of all diarrhoea)Rotavirus positive N (% of tested)
Hospital
 <5347275 (79)86 (31)
 <1176153 (87)41 (27)
 113499 (74)37 (37)
 2–43723 (62)8 (35)
Ambulatory clinics
 <51215662 (54)57 (9)
 <1366207 (57)25 (12)
 1435217 (50)24 (11)
 2–4414238 (57)11 (5)

Diarrhoea hospitalizations among children <5 years in Santa Rosa exhibited a seasonal pattern that mirrored that of rotavirus hospitalizations, with 46% (158 of 347) of all diarrhoea hospitalizations occurring in January and February (Figure 1). The proportion of tested specimens from hospitalized patients positive for rotavirus increased from 31% annually to 59% (72 of 122) during these two months. In the ambulatory setting, peaks of diarrhoeal disease were also observed in January and February, with 24% (292 of 1215) of all ambulatory visits for diarrhoea occurring during these months, and the proportion of tested specimens positive for rotavirus increasing to 31% (52 of 170) from 9% annually. The seasonal peak of rotavirus activity coincided with the driest months of the year (Figure 2). As temperature varied little, no correlation was identified with rotavirus activity.

image

Figure 1.  Healthcare utilization rates for diarrhoea and rotavirus disease among children <5 years – Santa Rosa, Guatemala, 2007–2009.

Download figure to PowerPoint

image

Figure 2.  Average monthly rainfall and hospitalization rates for rotavirus disease among children <5 years – Santa Rosa, Guatemala, 2007–2009.

Download figure to PowerPoint

The mean age of children was 13 months for rotavirus hospitalizations and 15 months for rotavirus ambulatory visits. Among rotavirus hospitalizations, 90% were among children <2 years of age and 28% among those <6 months of age. The age distribution was similar in the ambulatory setting, with children <2 years of age accounting for 81% of those testing positive for rotavirus, and children <6 months of age comprising 37%. Males comprised 65% of hospitalized and 56% ambulatory patients with rotavirus.

Of 143 rotavirus-positive specimens from hospital and ambulatory settings, 74% (n = 106) also had genotyping data available. The most commonly identified genotype during both study periods was G1P[8] representing 71% and 95% of isolated genotypes for the 2007–2008 and 2008–2009 rotavirus seasons, respectively (Table 3). In the 2007–2008 period, a less common genotype, G12P[6], was found in 19% of isolated genotypes.

Table 3.   Rotavirus genotypes identified among children with rotavirus diarrhoea <5 years of age – Santa Rosa, Guatemala, 2007–2009*
GenotypeOctober 2007–September 2008October 2008–September 2009
N (%)N (%)
  1. *106 (74%) of 143 rotavirus EIA-positive samples also had genotype data.

G1P[8]30 (71)61 (95)
G1P[6,8]1 (2)
G4P[6]1 (2)1 (2)
G9P[8]2 (3)
G12P[6]8 (19)
G1,12P[6,8]2 (5)

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Our data show that rotavirus is a major cause of severe diarrhoea resulting in substantial morbidity in the youngest of children in Santa Rosa, Guatemala. Over the 2-year study period, one-third of diarrhoea-associated hospitalizations in children <5 years of age were attributable to rotavirus. We estimated an annual adjusted rotavirus hospitalization rate of 36 per 10 000 children and an adjusted rotavirus ambulatory visit rate of 372 per 10 000 children. In other words, nearly one of every 50 children born in Santa Rosa, Guatemala, will be hospitalized and one in every five will be seen in an ambulatory clinic because of rotavirus disease by the age of 5 years. This tremendous health burden highlights the potential health benefits of introducing rotavirus vaccines in Guatemala.

The rate of healthcare utilization for rotavirus disease we found in Santa Rosa is similar to that found for other Latin American countries, and also remarkably consistent with global estimates derived by other studies (Gomez et al. 1998; Guardado et al. 2004; Parashar et al. 2003). The proportion of diarrhoeal hospitalizations attributable to rotavirus is also consistent with other studies completed in the Americas and with estimates for other low-middle-income countries (Kane et al. 2004; Parashar et al. 2006). Of note, Guatemala-specific data from the Rotavirus Surveillance Network in the Americas found 52% of specimens to test positive for rotavirus in 2006 (de Oliveira et al. 2008). This figure is higher than our estimate of 31% and may be a reflection of year-to-year variations commonly observed with rotavirus disease, regional differences in the burden of rotavirus disease within Guatemala, or differences in the severity of patients enrolled in the two surveillance systems, as the detection rate of rotavirus is known to increase with increasing severity of illness. Further studies and analysis of ongoing surveillance data will help improve the precision of rotavirus burden estimates for Guatemala.

The incidence of rotavirus disease spiked in Santa Rosa during January and February, typically the driest months of the year, and during these months rotavirus caused nearly 60% of diarrhoea hospitalizations. This seasonal pattern reported in these manuscript is striking, as the traditional belief is that rotavirus disease exhibits seasonality in temperate climates but less so in tropical settings (Cook et al. 1990). Indeed, while minimal annual variation in temperature was observed, the seasonality of rotavirus in Guatemala coincided with the months with less rainfall. Other studies have also found that rotavirus incidence increased during drier months of the year (Levy et al. 2009). With increasing amount of data now becoming available from international rotavirus surveillance networks, a careful review of seasonal patterns in relation to temperature and rainfall is desirable to better determine characteristics of rotavirus seasonality.

The principal rotavirus genotype isolated in Santa Rosa during the study period was G1P[8], a component of both currently available vaccines. However, each study year demonstrated a slightly different pattern of circulating strains, including unusual strains such as G12P[6], which has both G and P antigens that are heterologous to the strain included in the monovalent rotavirus vaccine (G1P8) which is currently being used widely in Latin America. While both rotavirus vaccines appear to provide good protection against a range of circulating strains, the pattern of strains should be monitored following vaccine introduction and specific evaluations of strain-specific vaccine effectiveness should be considered if unusual strains are detected through ongoing surveillance.

There are some limitations to these findings. While the surveillance platform is facility-based, adjustments for population estimates needed to be made to account for the low proportion of the catchment population that seeks medical care in the government facilities that provide the data for the surveillance system. However, we are reassured that our estimates of disease are consistent with other estimates from Latin America. A second limitation is that Santa Rosa does not reflect the same ethnic diversity found in other parts of Guatemala with only 3% of its inhabitants being indigenous and thereby limiting the ability to generalize these findings to the rest of the country. In February 2009, a similar surveillance effort in a highland area of Guatemala with a large indigenous population was started to address this limitation. Finally, not all participants submitted a stool sample for rotavirus testing, particularly in the ambulatory setting, and not all samples that tested positive underwent genotyping, which may have limited our results.

In conclusion, this study illustrates the substantial burden of rotavirus disease among young children in Guatemala and provides baseline data to compare with future disease trends following implementation of rotavirus vaccination. Continued investigations are needed to assess disease burden among indigenous populations and within the private healthcare system. Additional investigation into costs of rotavirus disease to allow assessment of cost-effectiveness of rotavirus vaccination is also necessary. The Guatemalan Ministry of Public Health and Welfare implemented a rotavirus vaccine programme in February 2010, and this active surveillance platform will provide a useful tool to evaluate vaccine impact and effectiveness following introduction of rotavirus vaccine.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

We would like to thank the Guatemala National Epidemiology Centre, the Health Area of Santa Rosa and the Regional Hospital of Cuilapa for their cooperation. We are grateful to Gerard Lopez, Fredy Muñoz and their team of programmers for the development of the Questionnaire Mobile program for data entry on PDAs. The authors would like to thank the following individuals for administrative and scientific support: Isabella Danel, Celia Cordón-Rosales, Stacy Kopka, Jon Gentsch, Aleida Roldan, and Jennifer Gray. We are very thankful for the active participation of the residents of Santa Rosa. This publication was supported in part by the U.S Centres for Disease Control and Prevention (CDC). Its findings and conclusions are those of the authors and do not necessarily represent the views of CDC.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
  • Allebeck P (2008) Pan American Health Organization (PAHO), Health in the Americas, 2007. European Journal of Public Health 18, 348.
  • Arvelo W, Padilla N, Henao O et al. (2009) Healthcare utilization and treatment practices for diarrheal diseases in rural Guatemala – 2006. Emerging Infectious Disease Conference, Atlanta, GA.
  • Cook SM, Glass RI, Lebaron CW & Ho MS (1990) Global seasonality of rotavirus infections. Bulletin of the World Health Organization 68, 171177.
  • de Oliveira LH, Danovaro-Holliday MC, Matus CR & Andrus JK (2008) Rotavirus vaccine introduction in the Americas: progress and lessons learned. Expert Review of Vaccines 7, 345353.
  • Gentsch JR, Glass RI, Woods P et al. (1992) Identification of group A rotavirus gene 4 types by polymerase chain reaction. Journal of Clinical Microbiology 30, 13651373.
  • Gomez JA, Nates S, De Castagnaro NR, Espul C, Borsa A & Glass RI (1998) Anticipating rotavirus vaccines: review of epidemiologic studies of rotavirus diarrhea in Argentina. Revista Panamericana de Salud Publica 3, 6978.
  • Gouvea V, Glass RI, Woods P et al. (1990) Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens. Journal of Clinical Microbiology 28, 276282.
  • Guardado JA, Clara WA, Turcios RM et al. (2004) Rotavirus in El Salvador: an outbreak, surveillance and estimates of disease burden, 2000–2002. Pediatric Infectious Disease Journal 23, S156S160.
  • Instituto Nacional de Sismologia V, Meteorologia e hidrologia (2010) http://www.insivumeh.gob.gt/meteorologia/ESTACIONES/SANTA%20ROSA/LOS%20ESCLAVOS%20PARAMETROS.htm (accessed 27 April 2010).
  • Kane EM, Turcios RM, Arvay ML, Garcia S, Bresee JS & Glass RI (2004) The epidemiology of rotavirus diarrhea in Latin America. Anticipating rotavirus vaccines. Revista Panamericana de Salud Publica 16, 371377.
  • Levy K, Hubbard AE & Eisenberg JN (2009) Seasonality of rotavirus disease in the tropics: a systematic review and meta-analysis. International Journal of Epidemiology 38, 14871496.
  • Parashar UD, Hummelman EG, Bresee JS, Miller MA & Glass RI (2003) Global illness and deaths caused by rotavirus disease in children. Emerging Infectious Diseases 9, 565572.
  • Parashar UD, Gibson CJ, Bresse JS & Glass RI (2006) Rotavirus and severe childhood diarrhea. Emerging Infectious Diseases 12, 304306.
  • Rheingans RD, Constenla D, Antil L, Innis BL & Breuer T (2007) Economic and health burden of rotavirus gastroenteritis for the 2003 birth cohort in eight Latin American and Caribbean countries. Revista Panamericana de Salud Publica 21, 192204.
  • WHO (2010) Immunization profile – Guatemala. http://www.who.int/immunization_monitoring/en/globalsummary/countryprofileresult.cfm?C=gtm (accessed 21 May 2010).