Understanding the child mortality decline in Guinea-Bissau: the role of population-level nutritional status measured by mid-upper arm circumference.

BACKGROUND: Malnutrition is considered an important contributing factor to child mortality, and the mid-upper arm circumference (MUAC) is regarded as one of the better anthropometric predictors of child mortality. We explored whether the decline in child mortality over recent decades could be explained by changes in children's MUAC. METHODS: This prospective study analysed individual-level data from 47 731 children from the capital of Guinea-Bissau followed from 3 months until 36 months of age over 2003 to 2016. We used standardization to compare the mortality rate as if only the MUAC distribution had changed between an early period (2003-05) and a late period (2014-16). We adjusted the analyses for age, sex, socioeconomic-related possessions and maternal education. RESULTS: A total of 949 deaths were included in the analysis. The adjusted mortality rate was 18.9 [95% confidence interval (CI) 14.3-23.3] deaths per 1000 person-years (pyrs) in the early period and declined to 4.4 (95% CI 2.9-6.0) deaths per 1000 pyrs in the late period, a 77% (95% CI 71-83%) reduction in the mortality rate. At all calendar years, the MUAC distribution in the population was close to the WHO reference population. MUAC below -1 z-score was associated with increased child mortality. The change in MUAC distribution from the early period to the late period (in the early period mortality standardization) corresponded to 1.5 (95% CI 1.0-2.2) fewer deaths per 1000 pyrs, equivalent to 11% (95% CI 7-14%) of the observed change in child mortality. CONCLUSIONS: From 2003 to 2016, child mortality in urban Guinea-Bissau declined considerably but, though a low MUAC was associated with increased mortality, changes in the MUAC distribution in the population explained little of the decline. Understanding the driving factors of child mortality decline can help scope tomorrow's interventions.

Thymus size at 6 months of age and subsequent child mortality.

OBJECTIVE: To examine determinants of thymus size at age 6 months and investigate whether thymus size at this age is a determinant of subsequent mortality. STUDY DESIGN: Thymus size was measured by transsternal sonography in 923 6-month-old children participating in a measles vaccination trial in Guinea-Bissau. RESULTS: Thymus size was strongly associated with anthropometric measurements. Boys had larger thymuses than girls, controlling for anthropometry. Crying during sonography made the thymus appear smaller. Children who were not vaccinated with Bacille Calmette-Guérin (BCG) or were vaccinated with BCG in the preceding 4 weeks before inclusion into the study had larger thymuses. Children who had malaria or had been treated with chloroquine or Quinimax in the previous week before inclusion had smaller thymuses. Controlled for background factors associated with thymus size and mortality, small thymus size remained a strong and independent risk factor for mortality (hazard ratio = 0.31; 95% confidence interval = 0.18 to 0.52). CONCLUSIONS: Small thymus size at age 6 months is a strong risk factor for mortality. To prevent unnecessary deaths, it is important to identify preventable factors predisposing to small thymus size.

Prophylactic antibiotics to prevent pneumonia and other complications after measles: community based randomised double blind placebo controlled trial in Guinea-Bissau.

OBJECTIVE: To investigate whether prophylactic antibiotics can prevent complications of measles. DESIGN: Community based, randomised, double blind, placebo controlled trial. SETTING: Bandim Health Project study area in Bissau, Guinea-Bissau, west Africa. PARTICIPANTS: 84 patients with measles during a measles epidemic in Bissau in 1998 (fewer than originally planned owing to interruption by war). INTERVENTIONS: Sulfamethoxazole-trimethoprim (co-trimoxazole) or placebo for seven days. MAIN OUTCOME MEASURES: Pneumonia and admission to hospital. Also weight change during the first month of infection, diarrhoea, severe fever, oral thrush, stomatitis, conjunctivitis, and otitis media. RESULTS: The median age of the patients with measles was 5.4 (range 0.49-24.8) years. One of 46 participants who received co-trimoxazole developed pneumonia, in contrast to six of 38 participants who received placebo (odds ratio 0.08 (95% confidence interval 0 to 0.56), adjusted for age group). The number needed to treat was 7 (4 to 48). All three participants admitted to hospital had received placebo (P=0.09). The weight gain during the first month after inclusion was 15 (2-29) g/day in the placebo group and 32 (23-42) g/day in the co-trimoxazole group (P=0.04, adjusted for age group, weight for age at inclusion, measles vaccination status, and duration of disease). Significantly less conjunctivitis occurred among recipients of co-trimoxazole than placebo, as well as a non-significant tendency to less diarrhoea, severe fever, oral thrush, and stomatitis. Complications of otitis media were the same in the two groups. CONCLUSIONS: The group that received prophylactic antibiotics had less pneumonia and conjunctivitis and had significantly higher weight gains in the month after inclusion. The results indicate that prophylactic antibiotics may have an important role in the management of measles infection in low income countries. TRIAL REGISTRATION: Clinical trials NCT00168532.

Low birth weight infants and Calmette-Guérin bacillus vaccination at birth: community study from Guinea-Bissau.

BACKGROUND: In developing countries, low birth weight (LBW) children are often not vaccinated with Calmette-Guérin bacillus (BCG) at birth. Recent studies have suggested that BCG may have a nonspecific beneficial effect on infant mortality. We evaluated the consequences of not vaccinating LBW children at birth in Guinea-Bissau. METHODS: Between 1989 and 1999, 7138 children born at the central hospital had a birth weight registered. We assessed BCG coverage until 3 years of age. Data on tuberculin skin test (TST) for 297 children and BCG scar for 1319 children in the study population were reanalyzed for differences between normal birth weight (NBW) children and LBW children. We assessed the effect of early BCG vaccination on mortality to 12 months of age. RESULTS: Among LBW children there were 1.5- to 3-fold more unvaccinated individuals than among NBW children up to 4 months of age. There was no overall difference between LBW and NBW children in TST or BCG scarring; LBW children vaccinated early may have had slightly reduced reactions to tuberculin. Among 845 LBW children, 182 had received BCG within the first week of life. Controlling for background factors and censoring at first diphtheria-tetanuspertussis vaccination, measles vaccination or at 6 months of age (whichever came first), the mortality rate ratio for BCG-vaccinated versus -unvaccinated LBW children was 0.17 (95% confidence interval, 0.06-0.49), with an even stronger effect for LBW children vaccinated in the first week of life (mortality rate ratio, 0.07; 95% confidence interval, 0.01-0.62). CONCLUSIONS: The policy of not vaccinating with BCG at birth had a negative impact on vaccination coverage for LBW children. Early BCG vaccination had no large negative impact on TST and BCG scarring. Mortality was lower for BCG-vaccinated than for unvaccinated LBW children controlling for available background factors. BCG vaccination of LBW children may have a beneficial effect on survival that cannot be explained by protection against tuberculosis. Future studies should examine possible adverse effects from equalizing BCG policy for LBW and NBW children.

BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG?

Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.

Níveis de anticorpos contra o sarampo entre as mulheres em idade fértil na população da Guiné-Bissau expostas a sarampo natural e a imunização contra o sarampo / Levels of antibodies against the measles enter the women in fertile age in the population of the Guiné-Bissau displayed the natural measles and the immunization against the measles

O objetivo do trabalho é determinar o estado imunitário e os níveis de anticorpos contra sarampo em mulheres de 14 a 25 anos de idade residentes em Bissau, entre os anos de 1997 e 1998, correlacionado com antecedentes vacinais e a infecção natural do sarampo. Metodologia: Estudo transversal de soroprevalência de sarampo realizado em uma coorte de mulheres nascidas no bairro Bandim-I no período de 1976 a 1982. Foram coletadas informações sobre exposição ao sarampo e amostras de sangue para determinação do título de anticorpos contra a doença pelo teste de Inibição da Hemaglutinação (HAI). Resultados: Das 2240 mulheres nascidas no período de interesse, foram encontradas 783, das quais 420 tiveram o nível de anticorpo determinado. A maioria das mulheres estudadas estavam com 15 a 16 anos de idade. Foi duas vezes maior a chance de estar protegida contra a doença naquelas mulheres que adoeceram de sarampo em relação às que não adoeceram, controlando o efeito das outras variáveis (p=0,051). Identificou-se um ligeiro aumento da prevalência de soroproteção contra o sarampo em mulheres que receberam duas doses de vacina e uma diminuição na prevalência da soroproteção nas mulheres que haviam tido filhos, embora sem comprovação estatística.