Kathryn Hedegaard

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.

Prevalences of HTLV-1 infection and associated risk determinants in an urban population in Guinea-Bissau, West Africa.

Objective: To assess the prevalence and modes of transmission of HTLV‐1 infection in an adult population in Bissau, and to evaluate possible interactions between the pattern of spread of HTLV‐1 and HIV‐1/HIV‐2. Design and Methods: Univariate and multivariate analyses were used to evaluate gender‐ and age‐specific HTLV‐1 prevalences as well as associated risk determinants in an adult population based on a serosurvey comprising 2127 individuals from 304 randomly selected houses in Bissau. Results: Using stringent Western blot criteria, the overall seroprevalence of HTLV‐1 was 3.6%, 2.2% among men and 4.7% among women, respectively. One individual was seropositive to HTLV‐2. The prevalence of HTLV‐1, which increased with age in both genders, however more markedly among women, was >4 times higher (9.4%) among older individuals (>44 years of age) than among younger individuals (2.4%). Blood transfusion and HIV‐2 seropositivity were independently associated with HTLV‐1 seropositivity in men. Among women, both HIV‐2 seropositivity and HIV‐1 seropositivity were significant risk determinants. Having had sexual partners was associated with a fivefold increased risk among women but did not reach significance. Conclusion: The adult population of Guinea‐Bissau has a higher prevalence of HTLV‐1 than reported from most other countries in West Africa. The gender‐ and age‐specific pattern of spread of HTLV‐1 closely resembles that observed for HIV‐2, another retrovirus prevalent to the region. The close correlation between HTLV‐1 and HIV‐2 most likely reflects the shared risk factors related to sexual behavior. The implication of the high percentage of double infections in this population needs to be determined.

Maternal mortality: only 42 days?

Objective A maternal death is defined by WHO as ‘the death of a woman while pregnant or within 42 days of termination of pregnancy…’. The origin of the 42 days is no longer clear. In developing countries, the burden imposed by pregnancy and birth on a womans body may extend beyond 42 days as pregnancy‐related anaemia can persist for longer and vaginal haemorrhaging and risk of infections are not necessarily over after six weeks. We therefore examined duration of excess mortality after delivery in rural Guinea‐Bissau.

Factors associated with maternal mortality in rural Guinea‐Bissau. A longitudinal population‐based study

Objective To assess demographic and obstetric risk factors for pregnancy‐related death in a multiethnic rural population in a developing country.

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.

Treatment of Plasmodium falciparum malaria with quinine in children in Guinea-Bissau: one daily dose is sufficient.

We have earlier obtained good results in falciparum malaria by treating children with low doses of quinine for 7 days in Guinea-Bissau. In order to further simplify treatment, we compared outcome in 100 children with falciparum malaria treated in 1999/2000 for 7 days with 15 mg quinine salt/kg/dose twice daily (group I), 100 children treated with 7.5 mg quinine salt/kg/dose twice daily (group II), and 100 children treated with one single daily dose of 15 mg/kg. One day 28, parasites had reappeared in 12%, 15%, and 9%, respectively. These results are similar to what has been found after previous successful treatment regimens. Apart from a higher incidence of vomiting during the first 24 h of treatment in the groups treated with 15 mg/kg/dose no significant differences in symptoms or side-effects were found between the groups. In patients suffering from uncomplicated malaria, treatment with quinine can be simplified to one single dose of 15 mg/kg bodyweight whenever logistics make 2 daily doses less feasible.

Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country

OBJECTIVE To compare detection of respiratory syncytial virus (RSV) for diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in different clinical settings in a community study in Guinea‐Bissau.

Persisting high hospital and community childhood mortality in an urban setting in Guinea‐Bissau

Aim: To describe paediatric hospitalization in a West African capital in relation to overall childhood mortality in the community and to evaluate the potential impact of improved management at the hospital.

No benefits from combining chloroquine with artesunate for three days for treatment of Plasmodium falciparum in Guinea-Bissau

The use of a combination of chloroquine and artesunate has been suggested for treatment of malaria in Africa. We used concomitant as well as sequential medication with these 2 drugs in relation to each drug separately for children infected with Plasmodium falciparum in Guinea-Bissau from March 2000 to November 2001. By block-randomization, 474 children with symptomatic malaria were divided into 4 groups and given either a total of 8 mg artesunate per kg bodyweight for 3 d, a total of 25 mg chloroquine base per kg bodyweight for 3 d, both drugs concomitantly for 3 d, or both drugs in sequence. All children were followed weekly for 5 weeks. On day 28, parasites had been detected in 40% of the children who were treated with artesunate only compared with 21% treated with chloroquine, 20% treated with artesunate in combination with chloroquine, and 16% treated with artesunate and chloroquine in sequence; on day 35 the corresponding percentages were 48%, 29%, 27%, and 24%, respectively. The outcome of the combination of chloroquine and artesunate in the doses studied was similar to the outcome of chloroquine monotherapy regardless of whether the 2 drugs are given concomitantly (relative risk [RR] = 0.93, 95% CI 0.56-1.53, P = 0.76) or in sequence (RR = 0.78, 95% CI 0.47-1.28, P = 0.32). Thus, neither an antagonistic, an additive, or a synergistic effect of the 2 drugs was indicated.

Can mothers be trusted to give malaria treatment to their children at home

Children with symptomatic malaria in Bissau were randomly assigned to treatment with chloroquine 25 mg base/kg given supervised at a health centre or unsupervised by the mothers at home. On day 7, a blood sample for drug analyses was drawn and the children were then followed once weekly for 5 weeks. The data were analysed on an intention to treat basis. No differences were seen in the outcome of treatment nor in the blood drug concentrations on day 7 between the two groups. Mothers in Bissau can be trusted to give adequate anti-malarial medication to their children at home.