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.

BK virus (BKV) and JC virus (JCV) are present within the renal system of most adults. Reactivation may be linked to immunodeficiency, since many of the extant virus strains have been isolated from urine or kidney tissue of patients who were receiving immunosuppressive therapy or who had disorders of the immune system. To more critically evaluate the relationship between immunodeficiency and viruria, urine samples from individuals infected with human immunodeficiency virus (HIV) with various degrees of immunodeficiency were screened for the presence of viral DNA. JCV viruria occurred in 24%-27% of immunocompetent control subjects and was not increased with immunodeficiency. By contrast, there were both qualitative and quantitative changes in BKV viruria in immunodeficient subjects. The incidence of BKV viruria was increased, and some immunodeficient subjects shed BKV at levels up to 3000 times greater than levels shed by any of the nonimmunodeficient controls. DNA sequence rearrangements in the viral regulatory region did not appear to be required for shedding of virus, although they were present in approximately 20% of samples.

Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects.

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

DNA sequences for the VP1 gene which codes for the major capsid protein of BK virus (BKV) and may be responsible for antigenic variability were determined for seven BKV isolates. The observed sequence differences and those previously reported correlate with the typing of isolates into four groups by haemagglutination inhibition. Amino acid coding alterations were found to be clustered within residues 61 to 83. Each antigenic group was found to have a characteristic amino acid sequence between residues 61 and 83. Several clones originating from a single isolate, although differing slightly in restriction enzyme digestion patterns, were found to be identical in this region. The VP1 sequences of three of the four groups were analysed by hydropathy plots and two hydrophilic areas of high antigenicity were identified. One of these corresponds to residues 61 to 83 and it is postulated that this region is the epitope responsible for serotypic differences between BK isolates.

BK virus antigenic variants: sequence analysis within the capsid VP1 epitope.

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.

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

A polyoma virus isolated from the urine of a renal transplant patient has been grown on primary human foetal fibroblasts and its pattern of replication studied by thin section electron microscopy. Virus replication is characterized by the appearance of spherical, crystalline arrays in the nucleoplasm which differ from the nuclear virus crystals found in cells infected by the human polyoma virus prototypes JC and BK. A serological study has substantiated differences between the prototypes and the MG isolate. The affinity of MG and other polyoma viruses for the cell membrane suggests a possible basis for the demyelinating effect seen in cases of polyoma-associated progressive multifocal leucoencephalopathy.

Development of a new human polyoma virus strain (MG).

Light and electron microscopic studies on foetal human fibroblast and glial cells infected with B. K. virus show a cytopathogenic effect similar to but not identical with that caused by polyoma and SV 40 viruses in murine and monkey cells, respectively. The first cytopathogenic effects appear at approximately 14 days and are complete at about 30 to 40 days. Light microscopy of unstained monolayers demonstrates roughening of the cell surface, liberation of exudate, cytoplasmic vacuolization and rounding of cells. Stained preparations show the same features and a series of nuclear changes consisting of light eosinophilic patches in the nucleoplasm, chromatin clumping and the development of a typical inclusion body. The nucleolus is not involved.

The cytopathology and development of a human polyoma virus (B.K.).

The stimulation of human lymphocytes in culture by urine-derived BK polyoma virus, as measured by the incorporation of3H-thymidine, is reported.

Lymphocyte stimulation by urine-derived human polyoma virus (BK).

/pdf/enterotoxinogenic-bacteria-in-africa-33n9aqnco2.pdf

G. Lecatsas

Papers

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

Development of a new human polyoma virus strain (MG).

The cytopathology and development of a human polyoma virus (B.K.).

Lymphocyte stimulation by urine-derived human polyoma virus (BK).

Enterotoxinogenic bacteria in Africa.