Sex differences in measles fatality and Edmonston-Zagreb measles vaccine.
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Child↗
Biomedical subjects
P Aaby
Publications and source records attributed to P Aaby.
Prolonged breast feeding, diarrhoeal disease, and survival of children in Guinea-Bissau.
OBJECTIVE: To analyse the impact of breast feeding on diarrhoeal disease and survival in children above 1 year of age in Guinea-Bissau, west Africa. DESIGN: A community study of an open cohort followed up weekly by interviews over 15 months. Data on feeding practices, anthropometry, and survival were recorded for three years. SETTING: 301 randomly selected houses in a semiurban area in the capital, Bissau. SUBJECTS: 849 children aged less than 3 years. MAIN OUTCOME MEASURES: Incidence and duration of diarrhoea, weight for age, and death of a child. RESULTS: The incidence of diarrhoea was higher in weaned children than in partially breast fed children, both in 1 year olds (relative risk 1.41; 95% confidence interval 1.23 to 1.62) and in 2 year olds (1.67; 1.29 to 2.15). The mean duration of an episode of diarrhoea was 5.3 days in breast fed children compared with 6.3 days in weaned children (P = 0.001). Independent of the age of weaning, a similar increase was found in an analysis comparing, for each child, the rate and duration of diarrhoea one month before and one month after weaning. Children with low weight for age were breast fed longer than the better nourished children (P = 0.02). Children aged 12-35 months who were not breast fed had a 3.5 times higher mortality (1.4 to 8.3) than breast fed children. CONCLUSIONS: The beneficial effects of breast feeding are not restricted to infancy. Though children who are partially breast fed after infancy may have a lower state of nutrition than the weaned ones, the benefit in terms of lower morbidity may be more important for child survival in places with a high morbidity from diarrhoea and with high mortality.
Age Factors↗
Risk factors for Cryptosporidium diarrhea in early childhood: a case-control study from Guinea-Bissau, West Africa.
Cryptosporidium is increasingly recognized as an important agent of diarrhea in normal and immunocompromised humans. In young children in developing countries the parasite is a cause of persistent diarrhea with an associated excess mortality. To elucidate possible determinants of cryptosporidiosis, an open cohort of young children from a semiurban area of the capital of Guinea-Bissau was followed for 2 years. Data about possible risk factors were recorded each month, and a nested case-control study of 125 children with Cryptosporidium diarrhea and an equal number of matched controls was conducted. The following risk factors were identified by conditional multiple logistic regression: keeping of pigs (odds ratio (OR) = 2.5, 95% confidence interval (CI) 1.4-4.7) and dogs (OR = 2.1, 95% CI 1.0-4.2) in the household, storage of cooked food for later consumption (OR = 1.8, 95% CI 1.0-3.3), and child's sex (OR for boys = 1.9, 95% CI 1.0-3.4). Breast feeding was protective (OR = 0.3, 95% CI 0.1-1.1). The findings provide clues for interventions against this major cause of childhood diarrhea and give suggestions for further studies.
Animals↗
Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in Guinea-Bissau: five-year follow-up.
A trial of protective efficacy which compared medium-titre Edmonston-Zagreb (EZ) measles vaccine (10(4.6) p.f.u.) from the age of 4 months with the standard Schwarz (SW) measles vaccine given from the age of 9 months was started in an urban community in Guinea-Bissau in 1985. Because trials of high-titre measles vaccine have found increased mortality among female recipients, we examined whether EZ medium-titre vaccine was associated with any long-term impact on mortality, suppression of T-cells, or growth. The mortality rate ratio over 5 years of follow-up was 1.12 for EZ children compared with children in the standard group (P = 0.63). Seventy-five percent of the children still residing in the area at 5 years of age took part in an immunological and anthropometric examination. There was no difference in T-cell subsets between the two groups. There was no difference in mid-upper-arm circumference, but EZ children were significantly shorter than the children in the standard group. In conclusion, medium-titre EZ was not associated with reduced survival or persistent immunosuppression.
Age Factors↗
The etiology of early childhood diarrhea: a community study from Guinea-Bissau.
A potential enteropathogen was found in 50% of 1219 diarrheal episodes and 48% of 511 asymptomatic controls in a 1-year community study of childhood diarrhea. Rotavirus (3% of episodes), Cryptosporidium species (6%), and enteropathogenic Escherichia coli (EPEC) with EPEC adherence factor (4%) were more prevalent in cases than controls. Giardia lamblia (19%) was the most prevalent organism but was not associated with diarrhea. Enterotoxigenic E. coli (12%), Strongyloides stercoralis (5%), Shigella species (2%), Entamoeba histolytica trophozoites (2%), and Vibrio cholerae (1%) were found at nonsignificantly higher rates. Salmonella and Campylobacter species were more prevalent among control infants. Cryptosporidium species and sequential infections from other pathogens caused persistent diarrhea.
Child↗
Long term impact of high titer Edmonston-Zagreb measles vaccine on T lymphocyte subsets.
Several trials of high titer measles vaccine (> 10(4.7) plaque-forming unit) have found female recipients of Edmonston-Zagreb (EZ) vaccine to have lower survival than female recipients of standard measles vaccine. Two trials with medium and high titer EZ vaccine from the age of 4 months were conducted in Guinea-Bissau. To test for possible long term impact on the immune system, an investigation of T cell subsets was conducted among all children still residing in the community at 3 to 5 years of age. No differences were found between recipients of medium titer vaccine and controls. In the second trial, however, recipients of high titer had lower CD4:CD8 ratios than controls and had significantly higher CD8 percentages and lower CD4:CD8 ratios than recipients of medium titer EZ. When analyzed by sex, differences were found only among the girls. However, these differences were small and seemed unlikely to explain the reduced survival which has been associated with high titer EZ measles vaccination. In the 2 years after the investigation of T cell subsets, there was no increased mortality for recipients of EZ vaccine. Hence it is unlikely that high titer vaccine has an persistent adverse effect on survival after 3 years of age.
CD4-CD8 Ratio↗
Severe cryptosporidiosis in children with normal T-cell subsets.
Though Cryptosporidium spp. is considered to cause only a self-limiting illness in immunocompetent children, data from Guinea Bissau suggest that cryptosporidiosis may be a significant cause of deaths in developing countries. An impaired cellular immune function could explain the severe course of cryptosporidiosis in these children. We therefore investigated in a community study whether pre-infectious CD4/CD8 status had an impact on incidence and severity of cryptosporidiosis. Of 168 children below two years of age 21 experienced Cryptosporidium-infection within 156 days after blood sampling, but no tendencies of pre-infectious impaired cellular immune function was found in the cases compared with controls, nor did nine children who acquired persistent diarrhoea or three who died have impaired CD4/CD8 status.
CD4-Positive T-Lymphocytes↗
Sex-specific differences in mortality after high-titre measles immunization in rural Senegal.
Administration of high-titre measles vaccine (Edmonston-Zagreb (EZ) at > 10(5) plaque-forming units (PFU) per dose) before the age of 9 months has been recommended in areas with high measles mortality before the routine age of immunization after 9 months. The study compares the long-term survival after high-titre measles immunization at 5 months of age with that following routine immunization with standard-titre vaccine at 10 months of age. At 5 months of age the high-titre group received Edmonston-Zagreb (EZ-HT, 5 months) or Schwarz (SW-HT, 5 months) at titres > 10(5) PFU per dose, while the standard-titre group received placebo at 5 months of age and < 10(4) PFU per dose of Schwarz vaccine at 10 months (SW-std, 10 months). All the children were followed up to at least 36 months of age. The mortality ratio (MR) for infants in the EZ-HT, 5 months and SW-HT, 5 months groups was 1.32 (P = 0.089) and 1.45 (P = 0.092), respectively, which did not differ significantly from that of recipients of the SW-std, 10 months. The higher MR among recipients of the high-titre vaccines was due to the significantly lower survival among females compared with the females who received SW-std vaccine (EZ-HT, 5 months MR = 1.76, P = 0.013; SW-HT, 5 months MR = 2.14, P = 0.017). For children aged 5-10 months the high-titre measles vaccine did not increase mortality relative to unvaccinated children who had received placebo.
Bias↗
Reduced childhood mortality after standard measles vaccination at 4-8 months compared with 9-11 months of age.
OBJECTIVE: To evaluate the impact on mortality of standard Schwarz measles immunisation before 9 months of age. DESIGN: Children vaccinated in 1980-3 at 4-5, 6-8, and 9-11 months of age were followed to migration, death, or the age of 5 years. SETTING: One urban district and nine villages in two rural areas of Guinea-Bissau. SUBJECT: 307 children vaccinated at 4-8 months and 256 at 9-11 months. MAIN OUTCOME MEASURES: Mortality from 9 months to 5 years of age for children immunised at 4-5, 6-8, and 9-11 months. RESULTS: Mortality was significantly lower in children vaccinated at 6-8 months than at 9-11 months (mortality ratio = 0.63, (95% confidence interval 0.41 to 0.97), p = 0.047). As vaccination was provided in semiannual or annual campaigns it is unlikely that age at vaccination reflected a selection bias. The trend was the same in all three study areas. Improved survival after early immunisation was not related to better protection against measles infection. With a Cox multivariate regression model to adjust for age, sex, season at risk, season at birth, measles infection, and region, children vaccinated at 4-8 months had a mortality ratio of 0.61 (0.40 to 0.92, p = 0.020) compared with children vaccinated at 9-11 months. Reimmunised children tended to have lower mortality than children who received only one vaccine (0.59 (0.28 to 1.27, p = 0.176)). CONCLUSION: Standard measles vaccination before 9 months is not associated with higher childhood mortality than is the currently recommended strategy of immunising from 9 months, and it may reduce mortality. This has implications for measles immunisation strategy in developing countries.
Age Factors↗
Divergent mortality for male and female recipients of low-titer and high-titer measles vaccines in rural Senegal.
The female/male mortality ratio among unimmunized children and children vaccinated with standard or high-titer measles vaccines was examined for all children born in the period 1985-1991 in a rural area of Senegal. The female/male mortality ratio from 9 months to 5 years of age for unvaccinated children was 0.94 (95% confidence interval (CI) 0.75-1.19), significantly different from the ratio of 0.64 (95% CI 0.48-0.85) for recipients of the Schwarz standard measles vaccine (p = 0.040). In the 4-year period, where high-titer measles vaccines were used in the study area, the female/male mortality ratio was 1.33 (95% CI 1.00-1.78) for recipients of high-titer Edmonston-Zagreb or Schwarz vaccines compared with 0.67 (95% CI 0.42-1.07) for recipients of the Schwarz standard vaccine (p = 0.013). Hence, the Schwarz standard and high-titer measles vaccines have divergent sex-specific effects on mortality throughout childhood. Further studies of the underlying mechanisms are needed.
Cause of Death↗
[Higher mortality due to measles in Senegal for children with siblings of the opposite sex].
The impact on case fatality of contracting measles infection from a sibling of the opposite sex was examined using data collected over a 20 year period in 31 isolated villages in Eastern Senegal. The interval between outbreaks of measles in a village was usually greater than ten years. During outbreaks, 766 children lived in families with two maternal siblings under ten years of age; 107 (14.0%) died of measles. The risk of dying of measles decreased with age, increased with the age difference between siblings and decreased with the size of the village. Adjusting for these factors, children in families with a boy and girl were found to have higher mortality than children in families with two boys or two girls (odds ratio (OR) = 1.81 (1.17-2.82)). The increase in risk was the same for boys and girls in male-female families. Cross-sex transmission of measles may be an important determinant of severity of infection.
Child↗
Cryptosporidiosis in infancy and childhood mortality in Guinea Bissau, west Africa.
OBJECTIVE: To investigate the epidemiology of and mortality from cryptosporidiosis in young children in Guinea Bissau, West Africa. DESIGN: Three year community study of an open cohort followed up weekly. SETTING: 301 randomly selected houses in a semi-urban area in the capital, Bissau. SUBJECTS: 1315 children aged less than 4 years. MAIN OUTCOME MEASURES: Cryptosporidium infection detected by examination of stools during episode of diarrhoea and death of a child. RESULTS: Cryptosporidium spp were found in 239 (7.4%) out of 3215 episodes of diarrhoea. The parasite was most common in younger children (median age 12 months) and at the beginning of the rainy seasons. The prevalence of cryptosporidiosis was 15% (77/513) in cases of persistent diarrhoea compared with 6.1% (148/2428) in diarrhoea lasting less than two weeks (p < 0.0001). Cryptosporidiosis was associated with excess mortality in children who had the infection in infancy, and this excess mortality persisted into the second year of life (relative mortality 2.9 (95% confidence interval 1.7 to 4.9)). The excess mortality could not be explained by malnutrition, or by socioeconomic factors, hygienic conditions, or breast feeding. CONCLUSIONS: Cryptosporidiosis is an important cause of death in otherwise healthy children in developing countries.
Child, Preschool↗
Long-term survival after Edmonston-Zagreb measles vaccination in Guinea-Bissau: increased female mortality rate.
In an urban area of Guinea-Bissau, 384 children were enrolled in a randomized trial comparing morbidity and mortality rates after receiving high-titer Edmonston-Zagreb (EZ) measles vaccine administered from 4 months of age, with a control group receiving inactivated poliomyelitis vaccine at 4 months of age and the standard Schwarz vaccine from 9 months of age. Children were followed to the age of at least 3 years. The mortality ratio of the EZ vaccinees compared with control subjects was 1.79 (range, 1.06 to 3.02; p = 0.027) if children were excluded at the time of migration; if deaths after migration were included, the mortality ratio was 1.53 (range, 0.94 to 2.49; p = 0.087). Girls in the EZ group had significantly higher mortality rates than girls in the control group (mortality ratio = 1.95; range, 1.07 to 3.56; p = 0.027); there was no difference for the boys (mortality ratio = 0.98; range, 0.41 to 2.30). Adjustment for background factors in a Cox regression model did not modify these estimates. Furthermore, female recipients of EZ vaccine had more days with diarrhea (relative risk = 1.35; range, 1.17 to 1.56; p = 0.00003) and were more likely than control subjects to visit a health center in the month after vaccination (relative risk = 1.86; range, 1.05 to 3.31; p = 0.027); those who consulted were more likely to die subsequently (mortality ratio = 2.31; range, 0.99 to 5.41; p = 0.054). These observations were unplanned and require confirmation in larger studies.
Cause of Death↗
Excess mortality after early exposure to measles.
The impact of exposure to measles before 6 months of age has been investigated by comparing survival to 5 years of age for exposed children and controls in an urban (Bandim) and a rural (Quinhamel) area of Guinea-Bissau. In Bandim, cumulative mortality from time of exposure to age 5 years was 34.4% among exposed children and 9.3% among controls. In a matched pair analysis, exposed children had a mortality ratio (MR) of 3.80 (95% confidence interval [CI]: 1.42-10.18) compared with controls. In an unpaired analysis using Cox' regression model to standardize for background variables (sex, measles infection, age at exposure, exposure from own household, measles vaccination), there was little change in the MR (3.84, CI: 1.55-9.48). Even after 2 years of age, the exposed children tended to have higher mortality (MR = 7.96, CI: 0.98-64.74). In the rural area, the MR between exposed children and controls was 11.39 (CI: 1.42-91.51). Limited serological data suggest that at least some of the exposed had subclinical measles. In the urban area, where two studies of early exposure have been carried out, excess mortality among exposed children corresponds to 40% and 52%, respectively, of the acute measles mortality. Since these deaths would not be associated with measles in a study of protection against death after vaccination, measles immunization may have a much greater effect on childhood mortality than has previously been assumed.
Age Factors↗
Child mortality impact of a measles outbreak in a partially vaccinated rural African community.
In spite of a measles vaccination coverage of 58%, 33% of 60 infant and child deaths were attributed to measles in a rural area of Kenya in 1988. Among 252 measles cases, there were 20 acute and 5 late deaths which may have been caused by the measles. Median age at infection was 44 months, with 16% of cases below 1 year of age. The highest age-specific attack rates (43% and 41%) were in unvaccinated children 6-11 months and 1-2-year-olds. The overall case fatality rate for children below 5 years was 12.6%, for unvaccinated children below 5, 16.2% and among children below 9 months, 24%. Children in homes with several cases had a higher case fatality ratio than had isolated cases, although not significantly so (RR 1.93, 95% CI 0.71-5.24). The median age of the children who died was 12 months. Overall vaccine efficacy was 62% for children 1-4 years. Our findings suggest that the measles vaccination coverage must be raised considerably in order to reduce mortality rates, and that alternative ways to project infants are needed.
Child↗
HIV-2 infection in Bissau, West Africa, 1987-1989: incidence, prevalences, and routes of transmission.
In a community study, the HIV-1 and HIV-2 antibody status of the inhabitants of 100 randomly chosen houses in Bissau, West Africa, were followed from 1987 to 1989. There was no HIV-1 infection alone, while the HIV-2 seroprevalence in adults was 8.9% (58 of 652) in 1987 and 10.1% (61 of 603) in 1989. HIV-2 seroprevalence in 15- to 39-year-olds was 6.1% in 1987 and 11.3% in newcomers in 1989 [the Mantel-Haentzel weighted relative risk (RRMH) = 1.86; 95% confidence interval (CI): 1.07-3.24]. Three hundred thirty adults who were HIV-2 seronegative in 1987 were reexamined in 1989; seven had seroconverted. Follow-up time was 700 person years, giving an incidence of HIV-2 infection of 1 per 100 person years. With a history of sexually transmitted disease (STD), the RR of seroconverting was 9.95 (2.31-42.80). Blood transfusions received since 1987 did not result in seroconversions. No case of vertical transmission of HIV-2 was seen. There was an excess mortality in those who were HIV-2 seropositive; however, it was statistically significant only for children (RR = 22.27; 95% CI: 6.92-71.70; p < 0.0001), not for adults (RR = 2.16; 95% CI: 0.81-5.76; p = 0.23), when considering death from disease only.
Adolescent↗
Case-fatality rates in severe measles outbreak in rural Germany in 1861.
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Adolescent↗
Measles mortality in same-sex and mixed-sex siblings in Kenya.
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Adolescent↗