Background: Rotavirus is the most common cause of severe gastroenteritis and dehydration in young children in both industrialized and developing countries. The anticipated introduction of rotavirus vaccine into Togo’s national immunization program highlights the need for baseline data on the burden of this disease.
Methods: We conducted sentinel surveillance for rotavirus gastroenteritis among children <5 years of age in Sylvanus Olympio Teaching Hospital of Lome (Togo) from February 2008 through January 2012, based on the World Health Organization’s generic protocol. Rotavirus was detected in stool specimens by enzyme linked immunosorbent assay. The strain characterization by genotyping was performed at Noguchi Memorial Institute for Medical Research in Accra (Ghana) and at Medunsa campus in Pretoria (South Africa).
Results: 803 children with acute gastroenteritis were enrolled and of which 390 (48%) were positive for rotavirus. The difference of age among children with rotavirus and nonrotavirus gastroenteritis was significant (P < 0.010) with rotavirus cases younger than nonrotavirus cases. From December to February, significantly (P < 0.002) more cases of rotavirus gastroenteritis were enrolled compared with other months of the year. Vomiting (P = 0.04) was more common in children with rotavirus than nonrotavirus gastroenteritis. The most common G-P combinations were G3P (23%), G1P (12%), G1P[6/8] (8%), G2P (7%), G12P (7%) and G3/12P (6%).
Conclusions: The prevalence of rotavirus is high among children with acute gastroenteritis in Togo. Continued and extended rotavirus surveillance will be important to monitor changes in the epidemiology of rotavirus disease and the impact of vaccination after introduction.
From the *Department of Paediatrics, Sylvanus Olympio Teaching Hospital of Lome, Togo, Africa; ‡Laboratory Department, Sylvanus Olympio Teaching Hospital of Lome, Togo; †MRC Diarrheal Pathogens Research Unit, University of Limpopo (Medunsa campus), Pretoria, South Africa; §Focal point of EPI in WHO/Togo; ¶Noguchi Memorial Institute for Medical Research, University of Legon, Accra, Ghana; and ‖World Health Organization, Regional Office for Africa, Brazzaville, Congo.
Accepted for publication June 19, 2013.
The authors have no conflicts of interest to disclose.
Address for correspondence: Enyonam Tsolenyanu, PhD, Department of Pediatrics, National Coordinator for Rotavirus Gastroenteritis Surveillance, BP 80796 Lome, Togo. E-mail: firstname.lastname@example.org.
Gastroenteritis is very common in children <5 years. Complications and deaths from this disease are still frequent.1,2 Diarrhea is the cause of 11% of the deaths among children <5 years of age worldwide.1 Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children.3–10 The number of rotavirus gastroenteritis episodes in the world is estimated as 25 million annually. The deaths from rotavirus disease are estimated at 453,000 children with 145,000–300,000 of these deaths occurring in sub-Saharan Africa.11–14 Improved sanitation has little effect on rotavirus infection.12,15 Many African countries do not have data on the epidemiology of rotavirus.9,13,16,17 Vaccines against rotavirus are available and have been shown to be effective.4,5,18 In sub-Saharan Africa, genotypes of circulating rotavirus strains differ from 1 country to another.13,16,19,20 In anticipation of the introduction of rotavirus vaccine into the routine immunization schedule in Togo, this study highlights the importance of epidemiological data on this disease and knowledge of circulating strains before vaccine introduction.
PATIENTS AND METHOD
We started sentinel surveillance for rotavirus gastroenteritis in February 2008 at the Sylvanus Olympio Teaching Hospital of Lome, which is the main referral hospital of Togo. We implemented the generic protocol of the World Health Organization on hospital surveillance for rotavirus gastroenteritis.17 Children <5 years of age hospitalized with acute gastroenteritis, who had disease symptoms ≤ 7 days duration before admission and whose stools contained no blood, were enrolled in the surveillance program. Children with gastroenteritis beginning during the hospitalization were excluded. From each enrolled child, approximately 5 mL of stool was collected in a sterile container. The sample was collected within 48 hours of hospitalization.
Stool samples were immediately sent to the laboratory of Sylvanus Olympio Teaching Hospital (sentinel site laboratory), where they were stored at −20°C until tested. An enzyme linked immunosorbent assay (ELISA; IDEIA Rotavirus OXOID) was used for diagnosis of rotavirus infection according to the manufacturer’s specifications. Batch testing was conducted monthly. All ELISA-positive samples and 10% of negative samples were stored at −20° C until transfer to reference laboratories, at Noguchi Memorial Institute for Medical Research in Accra (Ghana) and at MRC Diarrheal Pathogens Research Unit, Medunsa campus in Pretoria (South Africa). Quality control was performed at the reference laboratory by ELISA test. Positive ELISA stool samples were subjected to polyacrylamide gel electrophoresis for quality control and to determine the electropherotype profile of ribonucleic acid. Reverse-transcription polymerase chain reaction was used to determine the genotypes of VP4 (P) and VP7 (G).
Statistical analysis was performed by Epi info. χ2 test was used to compare some variables. A value P < 0.05 was significant.
During the 48-month surveillance period (February 2008 to January 2012), 803 children were enrolled in the surveillance with stool sample collected on all. A total of 390 stool samples tested positive for rotavirus by ELISA. The rotavirus gastroenteritis rate was 48% over the study period, but the rate varied slightly from year to year (Fig. 1). Children <2 years of age accounted for 87% of all cases of gastroenteritis and 92% of confirmed cases of rotavirus gastroenteritis. The rotavirus gastroenteritis rate was on average 51% in this age group. Children under the age of 4 months accounted for 11% of ELISA-positive cases (Fig. 2). The sex ratio for all acute gastroenteritis cases was 1.2. However, the prevalence of rotavirus gastroenteritis was 49% in girls and 48% in boys. Over half (52%) of all confirmed cases for rotavirus gastroenteritis occurred in December, January and February. During these 3 months, the prevalence of rotavirus gastroenteritis averaged 58% (Fig 3).
Clinical symptoms were more severe in rotavirus gastroenteritis than nonrotavirus gastroenteritis cases (Table 1). The number of episodes of diarrhea was >10 times per 24 hours in 12% of cases for rotavirus gastroenteritis and 8% for nonrotavirus gastroenteritis (P = 0.2). Vomiting was more common in children with rotavirus than in those without rotavirus (78% vs. 56%, P = 0.04). Fever was observed in 85% of children with rotavirus gastroenteritis and 80% of children without rotavirus (P > 0.05). Dehydration was observed in 52% of children with rotavirus gastroenteritis including 19% of children with severe dehydration. Among children with nonrotavirus gastroenteritis, 38% were dehydrated including 10% who were severely dehydrated.
For rotavirus and nonrotavirus gastroenteritis, rehydration of children was made orally in 20% of cases, intravenously in 43% of cases and both channels combined in 37% of cases. Sixteen children with gastroenteritis died including 5 with rotavirus gastroenteritis (31%). All deaths due to rotavirus occurred in children <12 months of age. In >84% of cases, the duration of rotavirus gastroenteritis ranged from 3 to 8 days. The median duration of rotavirus gastroenteritis was 6 days. No child had been vaccinated against rotavirus before admission.
The strain was a long electropherotype in 49% of cases and short electropherotype in 51% of cases. The strains G2 and G3 were associated to the short electropherotype. The most common VP7 genotype varied from year to year. P genotype was the most common for VP4 (Fig 4). A wide variety of genotype combinations circulated each year. During the surveillance period, G3P was the most common combination (23%), followed by G1P (12%), G1P[6/8] (8%), G2P (7%), G12P (7%), G3/12P (6%), G2P (5%) and G1P (2%). G-P combinations for which there were 3 or fewer specimens accounted for a combined 30% of all specimens (Fig. 4).
The annual rotavirus detection rate of 48% among children <5 years of age hospitalized with rotavirus gastroenteritis in Togo is relatively high compared with other countries in Africa where prevalence rates varying between 20% and 63% have been seen.9,16,19–25 In developed countries, in Europe particularly, studies have shown that the prevalence varied between 41% and 46%.2,6,7,10,26,27 The high prevalence of rotavirus gastroenteritis globally suggests that, unlike for other causes of gastroenteritis, improved sanitary conditions will probably not be enough to fight against rotavirus infection.12,15
Similar to previous studies, our study found that severe rotavirus gastroenteritis usually occurred before the age of 2 years and mainly before the age of 12 months. The difference observed in the distribution of cases of rotavirus and nonrotavirus gastroenteritis by age was significant with rotavirus cases being younger than nonrotavirus cases. After this period of life, children may acquire a natural immunity that will prevent severe manifestations of reinfection.28,29 Low detection rates in newborns and small infants <4 months may result from protection by maternal antibodies.15,24,29 We did not observe significant difference between girls and boys for rotavirus gastroenteritis. Other studies have found that girls were more susceptible to rotavirus gastroenteritis than boys.10,15
There was a significant seasonal peak of rotavirus gastroenteritis between December and February. In Togo, this time of year is the hot, dry season. Samples taken in the same department from 39 children during an outbreak of acute gastroenteritis between January and February 2007 found that 74% of cases were positive for rotavirus by ELISA.16 Other studies have identified peaks of rotavirus gastroenteritis during the same period of the year in other tropical countries.15,20,22–25
The clinical picture was much more severe for rotavirus compared with nonrotavirus gastroenteritis as has been observed in previous studies. Case management was often at odds with the severity of dehydration. Severe dehydration, the only indication of parenteral rehydration, was observed at the admission in 14% of rotavirus and nonrotavirus gastroenteritis cases combined. However, the oral rehydration therapy was used only in 20% cases. The World Health Organization recommends an oral rehydration solution and zinc for treatment of gastroenteritis. This strategy achieves excellent results and significantly reduces mortality from this disease.30,31
Of the 16 deaths due to gastroenteritis that occurred during the study period, 5 (31%) were due to rotavirus. All but 1 of the children with rotavirus gastroenteritis who died were dehydrated before admission. Two children had severe dehydration and 2 others had evident signs of dehydration. Rehydration was made intravenously for the 2 children with severe dehydration and for 1 of the children with evident signs of dehydration. One child with no signs of dehydration and 1 child with evident signs of dehydration were rehydrated orally alone. These deaths did not occur on admission, but rather between the third and fifth days of hospitalization suggesting that dehydration may have been exacerbated at the hospital. These deaths highlight the need to ongoing training for the staff, particularly in terms of management of gastroenteritis. Rehydration was recommended in these children, but the quantity of liquid was likely not appropriate for the degree of dehydration. In addition, monitoring was not conducted to readjust the quantity of liquid based on the degree of hydration of the child.30,31
The long electropherotype profile was represented almost equally with the short profile among children <5 years of age hospitalized with rotavirus gastroenteritis. In the literature, the short profile has been suggested to be responsible for severe forms of gastroenteritis,32 while the long profile is also predominant in milder gastroenteritis at the community level.14
In Togo, circulating rotavirus strains varied considerably over time as has been previously observed in literature. This genotypic variation over time justifies the need for continued surveillance to better observe the genotypic variability by year, particularly in the post rotavirus vaccination area.16 In 2008, G1 and G2 genotypes were detected in >60% of all specimens. In 2009, the proportion decreased (33%), and then in 2010 few G1 and G2 genotypes were detected. While the proportion of genotypes G1 and G2 decreased, the G3 genotype which was poorly represented in 2008 (7%), increased to become a majority (43%) in 2010. This genotype G3, like the G12 genotype that emerged in 2009, was uncommon6,13,16,33 or nonexistence16,21,27,34 in other countries. Nontypeable genotypes were represented each year with a proportion ranging from 9% to 16%.
Diversity for P types was lower than G types. P was represented in large numbers each year: 40% in 2008, 57% in 2009 and 66% in 2010. Genotype combinations were very diverse from year to year. Genotypic diversity has also been observed in other countries but to a lesser degree.33,35 Overall between 2008 and 2010, G3P showed a relative predominance in Togo but the prevalence of this combination was 25%. In contrast to Togo, where no one genotype dominates, up to 80% of cases of rotavirus gastroenteritis in the literature4,6,16,21,26 are due to G1P. In Togo, this G1P was found only in 12% of cases. Other sub-Saharan African countries have also observed genotypic diversity and unusual genotypes as in our study.13,16,19,20,23,24 Current rotavirus vaccines were shown to provide broad heterotypic protection against a wide variety of circulating strains in clinical trials.4,18,36–38 Given the yearly changes in circulating genotypes and the enormous diversity observed, evaluating the performance and impact of rotavirus vaccines and monitoring circulating strains pre- and postrotavirus vaccine introduction would be important in countries like Togo with great strain diversity.
No child had received rotavirus vaccine before admission. Rotavirus gastroenteritis surveillance confirms important public health problem caused by rotavirus infection with its high prevalence in children <2 years of age. These findings will probably be used by policy makers for the integration of the rotavirus vaccine in Expanded Program on Immunization in Togo.
Our study has several limitations. First, surveillance was only conducted at a single hospital that serves as a national referral center. Despite the annual consistency of rotavirus detection in this study, these data may not be representative of rotavirus disease in rural areas or other urban areas. Second, we did not test for other pathogens so we do not know the causes of diarrhea in children with nonrotavirus gastroenteritis. However, regardless of the other causes, rotavirus gastroenteritis was more severe than nonrotavirus gastroenteritis. Third, genotyping was not performed on specimens collected in 2011. However, given the diversity of circulating rotavirus strains in 2008–2010, the 2011 specimens will also likely reflect this diversity.
Rotavirus gastroenteritis is a serious public health problem because of its high prevalence in Togo. Children <2 years are mainly affected by the disease and mortality, because rotavirus among children <1 year of age was high. Given that improvement of sanitary conditions has had little effect on rotavirus infection, vaccination is the only weapon to have a significant impact on rotavirus gastroenteritis. Continued monitoring of rotavirus disease trends and circulating strains pre- and postrotavirus vaccine introduction is important to determine the impact of vaccine in Togo.
The authors would like to thank GAVI, World Health Organization and Ministry of health in Togo.
1. Liu L, Johnson HL, Cousens S, et al.Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379:2151–2161
2. Fourquet F, Desenclos JC, Maurage C, et al. [Acute gastro-enteritis in children in France: estimates of disease burden through national hospital discharge data]. Arch Pediatr. 2003;10:861–868
3. Banerjee I, Ramani S, Primrose B, et al. Comparative study of the epidemiology of rotavirus in children from a community-based birth cohort and a hospital in South India. J Clin Microbiol. 2006;44:2468–2474
4. O’Ryan M. Rotarix (RIX4414): an oral human rotavirus vaccine. Expert Rev Vaccines. 2007;6:11–19
5. Block SL, Vesikari T, Goveia MG, et al.Pentavalent Rotavirus Vaccine Dose Confirmation Efficacy Study Group. Efficacy, immunogenicity, and safety of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine at the end of shelf life. Pediatrics. 2007;119:11–18
6. Forster J, Guarino A, Parez N, et al.Rotavirus Study Group. Hospital-based surveillance to estimate the burden of rotavirus gastroenteritis among European children younger than 5 years of age. Pediatrics. 2009;123:e393–e400
7. Van Damme P, Giaquinto C, Huet F, et al. Multicenter prospective study of the burden of rotavirus acute gastroenteritis in Europe, 2004–2005: the REVEAL study. J Infect Dis. 2007;195(Suppl 1):S4–16
8. Van Damme P, Giaquinto C, Maxwell M, et al. Distribution of rotavirus genotypes in Europe, 2004–2005: the REVEAL Study. J Infect Dis. 2007;195(suppl 1):S17–S25
9. de Villiers FP, Sawyerr TN, de Villiers GK. The incidence and clinical presentation of infantile rotavirus diarrhoea in Sierra Leone. S Afr Med J. 2009;99:249–252
10. Fau C, Billaud G, Pinchinat S, et al. [Epidemiology and burden of rotavirus diarrhea in day care centers in Lyon, France]. Arch Pediatr. 2008;15:1183–1192
11. Tate EJ, Burton HA, 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 programs: a systematic review and meta-analysis. Lancet. 2012;12:136–41
12. Parashar UD, Burton A, Lanata C, et al. Global Mortality Associated with Rotavirus Disease among Children in 2004. J Infect Dis. 2009;200(suppl 1):S9–S15
13. Sanchez-Padilla E, Grais RF, Guerin PJ, et al. Burden of disease and circulating serotypes of rotavirus infection in sub-Saharan Africa: systematic review and meta-analysis. Lancet Infect Dis. 2009;9:567–576
14. Aminu M, Esona MD, Geyer A, et al. Epidemiology of rotavirus and astrovirus infections in children in northwestern Nigeria. Ann Afr Med. 2008;7:168–174
15. Rodrigues A, de Carvalho M, Monteiro S, et al. Hospital surveillance of rotavirus infection and nosocomial transmission of rotavirus disease among children in Guinea-Bissau. Pediatr Infect Dis J. 2007;26:233–237
16. Mwenda JM, Ntoto KM, Abebe A, et al. Burden and epidemiology of rotavirus diarrhea in selected African countries: preliminary results from the African Rotavirus Surveillance Network. J Infect Dis. 2010;202(Suppl):S5–S11
17. World Health Organization. Generic Protocol 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 Version. 2002 Geneva World Health Organization Available at: www.who.int/vaccines-documents/
18. Armah GE, Sow SO, Breiman RF, et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;376:606–614
19. Enweronu-Laryea CC, Sagoe KW, Glover-Addy H, et al. Prevalence of severe acute rotavirus gastroenteritis and intussusceptions in Ghanaian children under 5 years of age. J Infect Dev Ctries. 2012;6:148–155
20. Fischer TK, Aaby P, Mølbak K, et al. Rotavirus disease in Guinea-Bissau, West Africa: a review of longitudinal community and hospital studies. J Infect Dis. 2010;202(suppl):S239–S242
21. Benhafid M, Youbi M, Klena JD, et al. Epidemiology of rotavirus gastroenteritis among children <5 years of age in Morocco during 1 year of sentinel hospital surveillance, June 2006–May 2007. J Infect Dis. 2009;200(suppl 1):S70–S75
22. Mpabalwani M, Oshitani H, Kasolo F, et al. Rotavirus gastro-enteritis in hospitalized children with acute diarrhoea in Zambia. Ann Trop Paediatr. 1995;15:39–43
23. Akoua-Koffi C, Akran V, Peenze I, et al. [Epidemiological and virological aspects rotavirus diarrhoea in Abidjan, Côte d’Ivoire (1997–2000)]. Bull Soc Pathol Exot. 2007;100:246–249
24. Cunliffe NA, Kilgore PE, Bresee JS, et al. Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization. Bull World Health Organ. 1998;76:525–537
25. Bonkoungou IJ, Sanou I, Bon F, et al. Epidemiology of rotavirus infection among young children with acute diarrhoea in Burkina Faso. BMC Pediatr. 2010;10:94
26. Payne DC, Staat MA, Edwards KM, et al. Active, population-based surveillance for severe rotavirus gastroenteritis in children in the United States. Pediatrics. 2008;122:1235–1243
27. Giaquinto C, Callegaro S, Andreola B, et al. Prospective study of the burden of acute gastroenteritis and rotavirus gastroenteritis in children less than 5 years of age, in Padova, Italy. Infection. 2008;36:351–357
28. Velázquez FR, Matson DO, Calva JJ, et al. Rotavirus infections in infants as protection against subsequent infections. N Engl J Med. 1996;335:1022–1028
29. Fischer TK, Valentiner-Branth P, Steinsland H, et al. Protective immunity after natural rotavirus infection: a community cohort study of newborn children in Guinea-Bissau, west Africa. J Infect Dis. 2002;186:593–597
30. USAID, UNICEF, WHO. Diarrhoea Treatment Guidelines Including New Recommendations for the Use of ORS and Zinc Supplementation for Clinic-based Healthcare Workers. 2005 Arlington The MOST project
31. Fischer Walker CL, Fontaine O, Young MW, et al. Zinc and low osmolarity oral rehydration salts for diarrhoea: a renewed call to action. Bull World Health Organ. 2009;87:780–786
32. Cascio A, Vizzi E, Alaimo C, et al. Rotavirus gastroenteritis in Italian children: can severity of symptoms be related to the infecting virus? Clin Infect Dis. 2001;32:1126–1132
33. Ramachandran M, Das BK, Vij A, et al. Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol. 1996;34:436–439
34. Kim JS, Kang JO, Cho SC, et al. Epidemiological profile of rotavirus in the Republic of Korea: results from prospective surveillance in the Jeongeub District, 1 July 2002 through 30 June 2004. J Infect Dis. 2005;192(suppl 1):S49–S56
35. Ramachandran M, Das BK, Vij A, et al. Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol. 1996;34:436–439
36. Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, et al.Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006;354:11–22
37. Salinas B, Pérez Schael I, Linhares AC, et al. Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants. Pediatr Infect Dis J. 2005;24:807–816
38. 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(Suppl 1):S146–S159
rotavirus; epidemiology; Togo; sub-Saharan Africa