Rapid progress towards the development of rotavirus vaccines has prompted a reassessment of the disease burden of rotavirus diarrhoea in developing countries and the possible impact of these vaccines in reducing diarrhoeal morbidity and mortality among infants and young children. We examined the epidemiology and disease burden of rotavirus diarrhoea among hospitalized and clinic patients in African countries through a review of 43 published studies of the etiology of diarrhoea. The studies were carried out from 1975 through 1992, and only those in which a sample of more than 100 patients with diarrhoea were specifically screened for rotavirus by using an established diagnostic test were included. Rotavirus was detected in a median of 24% of children hospitalized for diarrhoea and in 23% who were treated as outpatients; 38% of the hospitalized patients with rotavirus were < 6 months and 81% were < 1 year of age. Rotavirus was detected year-round in nearly every country and generally exhibited distinct seasonal peaks during the dry months. In 5 countries where rotavirus strains had been G-typed, 74% of strains were of one of the four common serotypes (G1 to G4), G1 was the predominant serotype, and 26% were non-typeable. This cumulative experience from 15 African countries suggests that rotavirus is the most important cause of severe diarrhoea in African children and that most strains in circulation today belong to common G types that are included in reassortant vaccines. Wherever large numbers of cases of rotavirus diarrhoea occur early in infancy, immunization at birth may protect the children before their first symptomatic infection.

Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization.

Recent studies have shown that in developed countries rotaviruses are the single most important etiologic agents of acute gastroenteritis that requires hospitalization of infants and young children. Although deaths from gastroenteritis are, in general, infrequent in the developed countries, an effective rotavirus vaccine would clearly be of benefit to reduce the heavy toll of morbidity from gastroenteritis due to rotavirus. In the developing countries the impact of diarrheal diseases is staggering. It was recently estimated that in Asia, Africa, and Latin-America during a one-year period there would be 3.5 billion cases of diarrhea and 5-10 million deaths associated with diarrhea; in addition, diarrhea was ranked first in freqency in the categories of disease and mortality. In the developing countries rotaviruses are known to cause diarrhea, but their relative role in this high mortality rate is not yet known. epidemiologic data indicate that development of an effective rotavirus vaccine would reduce morbidity, and they suggest that a vaccine would also reduce a portion of the mortality from diarrheal disease. The prospects and approaches for the development of an effective rotavirus vaccine are presented. The recent successful propagation of rotavirus type 2 in cell culture represents an important step in this regard. In addition, the antigenic relation between human and animal strains offers another possible approach. The need for a live attenuated vaccine is indicated by the prime role played by local intestinal immunity in resistance to rotavirus disease.

Approaches to Immunization of Infants and Young Children Against Gastroenteritis Due to Rotaviruses

quent in the developed countries, an effective rotavirus vaccine would clearly be of benefit to reduce the heavy toll of morbidity from gastroenteritis due to rotavirus. In the developing countries the impact of diarrheal diseases is staggering. It was recently estimated that in Asia, Africa, and Latin America during a one-year period there would be 3.5 billion cases of diarrhea and 5-10 million deaths associated with diarrhea; in addition, diarrhea was ranked first in frequency in the categories of disease and mortality. In the developing countries rotaviruses are known to cause diarrhea, but their relative role in this high mortality rate is not yet known. Epidemiologic data indicate that development of an effective rotavirus vaccine would reduce morbidity, and they suggest that a vaccine would also reduce a portion of the mortality from diarrheal disease. The prospects and approaches for the development of an effective rotavirus vaccine are presented. The recent successful propagation of rotavirus type 2 in cell culture represents an important step in this regard. In addition, the antigenic relation between human and animal strains offers another possible approach. The need for a live attenuated vaccine is indicated by the prime role played by local intestinal immunity in resistance to rotavirus disease.

Approaches to Immunization of Infants and Young Children Against

Anticipating rotavirus vaccines: epidemiology and surveillance of rotavirus in South Africa.

Ever since Escherich (1885) first isolated the organism now known as Escherichia coli from the stools of infants, medical microbiologists have been faced with the problem of distinguishing between those strains capable of causing diarrhoea and those that are harmless gut commensals. Epidemiological investigations were greatly facilitated by the description by Kauffmann (1947) of a serotyping scheme for E. coli, and Taylor (1961) later reported that 17 0 serogroups of E. coli had been implicated as possible causes of epidemic infantile enteritis. These infantile enteropathogenic E. coli (EPEC), having been discovered by epidemiological studies using serotyping, belonged by definition to a restricted range of serogroups. More recently it was shown that other E. coli strains may produce enterotoxins, and these enterotoxigenic E. coli (ETEC) usually belong to particular serogroups which are different from those associated with EPEC. E. coli strains belonging to a third range of serogroups may cause an illness resembling shigella dysentery, and these may be regarded as entero-invasive E. coli (EIEC). E. coli strains that cause diarrhoea may therefore be considered as three groups, as follows.

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Escherichia coli diarrhoea.

A microbiological investigation of Black infants suffering from severe acute summer gastroenteritis revealed enteropathogenic agents in 30 out of 37 patients (81%). Enterotoxigenic bacteria were isolated from 15 patients (41%). A total of 16 enterotoxigenic strains were isolated, comprising 9 enterotoxigenic Escherichia coli strains secreting labile and stable toxin on their own and in combination, and labile-toxin secreting strains of Klebsiella pneumoniae (4), Enterobacter cloacae (2) and Proteus vulgaris (1). In the case of the latter three species, however, 6 out of the 7 strains were isolated from patients who were excreting other enteric pathogens, whereas only 2 out of 9 enterotoxigenic E. coli patients had concomitant infections with other pathogens. No invasive bacteria were isolated except for 2 shigella strains. Salmonella and shigella strains were found in four patients. No correlation was found between the enteropathogenicity of E. coli and its serotype. Rotavirus was observed by negative staining electron microscopy in only two patients (6%) but using a reverse complement fixation test rotavirus antigen was detected in the stool of 17 out of 35 patients (49%). The low EM detection rate may well be due to the patients being admitted for treatment late in the course of their illness when the degree of viral shedding has decreased below EM detectability. No significant difference in clinical presentation was noted between the various aetiological agents. Only one patient was being solely breast-fed compared to 16% of control non-diarrhoeic infants. Evidence of malnutrition was noted in over half of our patients.

Barry D. Schoub

Papers

A microbiological investigation of acute summer gastroenteritis in Black South African infants