Background: Severe rotavirus diarrhea in children is a major cause of morbidity globally and mortality in developing countries. It is estimated to be responsible for >453,000 deaths in children <5 years of age globally and 232,000 in the African region. The aim of the current study was to determine the prevalence of rotavirus gastroenteritis among hospitalized children <5 years of age in Enugu and to support awareness and advocacy efforts for the introduction of rotavirus vaccines in Nigeria.
Methods: World Health Organization-standardized case forms were used to collect data from eligible children with non-bloody diarrhea from October 2010 to September 2012. Data collected included socio-demographic and clinical information. Stool samples were obtained from recruited children and tested for rotavirus antigen using the Oxoid Prospect ELISA Kit (Basingstoke, United Kingdom).
Results: Of the 615 diarrhea stool samples collected, 344 (56%) were positive for human rotavirus. Of the 344 positive samples, 329 (96%) were children <2 years of age, while 247 (77%) were <1 year of age. Peak rotavirus season occurred during the cold dry months of December to April during which 95% of all cases occurred.
Conclusions: This study found a relatively high incidence of severe rotavirus-associated diarrhea disease in Nigeria and infants were the most affected. It highlights the urgent need for introduction of rotavirus vaccine into the national immunization program and the need to adequately equip health facilities to enable them administer intravenous fluids to severe diarrhea patients to reduce morbidity and mortality.
From the *Institute of Child Health, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State, Nigeria; †World Health Organization Regional Office for Africa (WHO/AFRO), Brazzaville, Republic of Congo; ‡Nuguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana; §Department of Paediatrics; ¶Department of Microbiology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State; ‖Department of Pediatrics; ††Department of Microbiology, Enugu State University Teaching Hospital, Nigeria; **Mother of Christ Specialist Hospital; ‡‡World Health Organization Country Office for Nigeria (WCO); §§National Primary Health Care Development Agency, Federal Ministry of Health, Abuja; and ¶¶Depatment of Community Medicine, College of Medicine, University of Nigeria, Enugu Campus, Nigeria.
Accepted for publication, August 7, 2013.
Funding was provided by WHO thorough the WHO Regional Office for Africa. The authors have no other funding or conflicts of interest to disclose.
Address for correspondence: Beckie N. Tagbo, MB BS, FWACP, PhD, Institute of Child Health, University of Nigeria Teaching Hospital (Old Site), UNTH Road, 400001 Enugu, Nigeria. E-mail: firstname.lastname@example.org.
Diarrhea is responsible for 15% of the 10.5 million deaths among children <5 years of age in the developing world.1 Rotavirus infection has been reported as the single most important cause of severe dehydrating diarrhea in children. Rotavirus is a ubiquitous organism that causes human disease independent of socio-economic status.2 Its incidence is not likely to be affected by improvement in hygiene and environmental health. Recent global reported estimates3,4 attributed 111 million cases and 453,000 mortalities in children <5 years of age to rotavirus annually (with 232,000 deaths occurring in the sub-Saharan Africa). In Nigeria, a high incidence of childhood diarrhea is estimated to account for over 160,000 of all deaths in children <5 years of age annually and of this number approximately 20–30% are associated with rotavirus infections.4–8 The actual burden of rotavirus diarrhea among children <5 years of age is probably underestimated in our environment, as testing for specific etiologic agents like rotavirus and other viruses is not routinely performed. Rotavirus vaccines represent an important preventive approach to reducing rotavirus infection and offer the best hope for control of these ubiquitous infections.9 World Health Organization (WHO)/ Regional Office for Africa, in collaboration with Federal Ministry of Health and Institute of Child Health and University of Nigeria Teaching Hospital (UNTH) in anticipation of the possible introduction of rotavirus vaccine in Nigeria tentatively by 2015, undertook the current study to assess the epidemiology of rotavirus infections among hospitalized children <5 years of age with acute watery diarrhea in Enugu, South East Nigeria.
SUBJECTS AND METHODS
This cross-sectional descriptive study was conducted as part of the WHO supported rotavirus sentinel surveillance in Enugu, South East, Nigeria, the capital city of Enugu State, Nigeria. Enugu State of Nigeria has an estimated population of 3.3 million according to the 2006 national census data.10 Many inhabitants of the state are Nigerians of Igbo ethnic nationality. The main occupations of the inhabitants are public service, trading and agriculture. The 3 accredited tertiary health Institutions providing specialist child care services among other medical services were selected as surveillance sites. The Institute of Child Health, UNTH, Enugu served as the main site. Enugu State University of Science and Technology Teaching Hospital, Park Lane and Mother of Christ Specialist Hospital both in Enugu were subsites. Surveillance was conducted over a 24-month period (from October 2010 to September 2012).
Ethical clearance was sought and obtained from the Ethics and Research Committee of UNTH, Enugu. Informed consent was obtained from the caregivers of the selected children before enrollment in the study.
WHO-standardized case report forms were used to collect data from eligible <5 hospitalized children with gastroenteritis. Data collected included socio-demographic characteristics (age, gender, place of domicile, source of drinking water, sewage disposal method) and clinical information comprising history of vomiting, diarrhea or fever, rotavirus vaccination status, medications taken before presentation and assessment of degree of dehydration on admission and outcome.
Eligibility criteria for the study were hospitalized children from 0 to 59 months (< 5 years) of age with gastroenteritis of ≤7 days’ duration. Children <5 years of age who presented with bloody diarrhea or whose symptoms have lasted for >7 days or acquired the gastroenteritis in the course of hospitalization for treatment of other diseases (hospital-acquired gastroenteritis) were excluded from the study.
A spoonful of diarrheal stool (size of a small grape) sample was collected in a well-labeled universal container after completion of the case record form. The specimens were stored in their containers in refrigerators at 2–8°C temperature until analysis within the hospital or until transfer for analysis/storage at the main site laboratory.
The stool samples obtained from enrolled children were tested for rotavirus antigen using the Oxoid Prospect ELISA Kit. All positive samples and a proportion (10%) of negative samples were sent to the WHO regional reference laboratories in either Ghana or South Africa for quality control.
Data generated from the study were analyzed using the WHO New Vaccines Surveillance Module and Graph Pad Prism Version 5.
A total of 617 <5 children with gastroenteritis were eligible for the study out of which 615 were enrolled into the study. Of these, 344 (56%) had human rotavirus detected by ELISA in their diarrheal stools. The percentage rotavirus positivity in the 3 hospitals was 54% for UNTH, 64% for Enugu State University of Science and Technology Teaching Hospital and 56% for Mother of Christ Specialist Hospital. The variation was not statistically significant (P = 0.59).
Among the 615 children studied, 374 (61%) were males while 241 (39%) were females, respectively, giving a male to female ratio of 1.6:1 for all diarrhea cases. Similarly, of the 344 rotavirus-positive cases, 59% were males while 41% were females resulting in a male to female ratio of 1.4:1. Of the 344 positive samples, 329 (96%) were children <2 years of age, while 264 (77%) were infants (Fig. 1A). Further disaggregation of infants showed that 73% were 6–11 months of age (Fig. 1B) and cumulative age distribution showed a sharp rise in rotavirus infection during the first 12 months of life (Fig. 1C).
The peak rotavirus season coincided with the peak diarrheal season during the cold dry period from December to April in which 95% of all cases occurred (Fig. 2).
Although the number of diarrhea cases was high during 5 months of the year (December to April), rotavirus percentage positivity in diarrhea stools remained high for 6–7 months of the year (October/November to April/May; Fig. 2).
Of the 344 rotavirus-associated diarrhea cases, 237 (69%) required intravenous fluids while 173 (64%) of 271 ELISA rotavirus-negative cases required intravenous fluids (Table 1). The difference was not statistically significant (P = 0.20). Vomiting was significantly present in a higher proportion of rotavirus-positive children (89%) than in rotavirus-negative children (77%; P < 0.0001). Only 1 case of shock was observed among rotavirus-positive children and none in the rotavirus-negative children.
Overall, 0.6% mortality was recorded in subjects with rotavirus gastroenteritis. Quality control showed 100% for positive samples at WHO reference laboratories in Ghana and South Africa.
This report of rotavirus ELISA percentage positivity of 56% in the current study is 1 of the highest reported in the WHO/ Regional Office for Africa region in recent times, hence underscoring the urgent need for the prevention and prompt management of cases in Nigeria. The prevalence observed in the current study is much higher than the WHO global network surveillance of rotavirus diarrhea prevalence of 39–52% in the African region.11 It is also higher than the 45.4%, 34.9%, 33.8% and 31.5% reported in the Ugandan,11 Italian12 and Saudi Arabian13 and Latin American14 studies, respectively. Also, our observed prevalence is higher compared with other previous rates reported elsewhere in Nigeria.5–7,15 Similarly, the recorded prevalence in the current study is relatively higher compared with the 30.8% reported among asymptomatic children within Benin City, South–South and Nigeria.8
Higher percentage positivity of rotavirus was recorded in male children compared with their female counterparts. This finding is consistent with similar studies in hospitalized children with rotavirus-induced gastroenteritis in Jos, Nigeria,16 Jordan17 and Bahrain18 in the Middle East. The reason for this male preponderance observed globally is unclear. Additionally, however, it may be partly socio-cultural giving the fact that male children are preferred because the general belief in the study population is that the boys will take after their parents. This belief results in male children receiving more care and attention from parents and so are more likely to be brought to hospital than their female counterparts. It has also been reported that boys are 2 times more likely to be hospitalized than girls,19 hence explaining the slight male preponderance.
In the current study, most of the affected children were <2 years of age, with infants accounting for >3 quarters of the cases. Similar findings have been reported by Junaid et al16 in Jos, North East Nigeria as in other studies. This may be partly due to the fact that in underdeveloped settings the early peak of rotavirus diarrhea in life may result from early exposure to contaminated sources, undetectable antibodies in early infancy as well as overcrowding. Additionally, almost all children experience at least 1 rotavirus infection by 3 years of age.2 The occurrence of rotavirus infection, especially in infants, underscores the need for the introduction of rotavirus vaccination in early childhood.
Rotavirus positivity was highly seasonal with a peak during the dry, cool months similar to findings by other authors.16,20,21 Seasonal rotavirus outbreaks are known to occur in the coldest time of the year. However, percentage rotavirus positivity remained relatively high during most of the year (8 months), although it dropped to 0 during the other 4 months of the year.
Dehydration and requirement for intravenous fluids were common and contributed to high morbidity in the current study. Similar clinical scenario has been reported in previous studies.17,22,23 More children with diarrhea who tested positive to rotavirus had vomiting, compared with their counterparts that were rotavirus negative. Frequently associated vomiting in severe rotavirus diarrhea renders oral rehydration therapy ineffective, thus necessitating the need for a higher level of specialized care in a secondary or tertiary health facility. However, access to such facilities is usually low in developing countries resulting in higher mortality, though similar morbidity compared with developed countries.
The observed low mortality in this study is probably due to the low number of participants, availability and access to tertiary health care services at the study sites. This highlights the limitation of the current study. Being a hospital-based study that involved only hospitalized children, it is not likely to be representative of the situation in the communities where health facilities and specialized care are not readily accessible. We, therefore, recommend a population based study to further evaluate the level and pattern of disease burden in the country.
In conclusion, Nigeria is a country with wide ethnic diversity and this is the first evidence-based study in Enugu and Nigeria to determine the burden of rotavirus disease. There is relatively very high burden of severe rotavirus-associated diarrheal disease in the population studied. The disease burden is highest among infants during the dry cooler months of the year. These findings highlight the urgent need for introduction of rotavirus vaccine into the national routine immunization program as well as other preventive and improved case management measures.
F.C. Akpali, N. Nwankwo, D. Ezenwaka, P. Nwachukwu, A. Okonkwo and P.O. Oha assisted with secretarial documentation, data collection, specimen transportation and data entry. The authors also thank study participants for their willingness to participate.
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Rotavirus; diarrhea; 5 years; children; epidemiology; Nigeria; ELISA