Amabelia Rodrigues

Changes in prevalence and incidence of HIV-1, HIV-2 and dual infections in urban areas of Bissau, Guinea-Bissau: is HIV-2 disappearing?

Objectives:To assess the changes in HIV prevalence and incidence between 1996 and 2006 in urban areas of Bissau. Design:A cross-sectional survey of 384 randomly selected houses within a community-based follow-up study of HIV-1 and HIV-2. Methods:A total of 3242 individuals aged at least 15 years were eligible for inclusion. Participants were interviewed about behavioral and socio-economic factors and had a blood sample drawn. A total of 2548 individuals were tested for antibodies to HIV-1 and HIV-2, of whom 649 had taken part in a similar survey in 1996. Results:With 0.5% HIV dual reactions included, the overall HIV-1 prevalence was 4.6% (118 out of 2548) and the HIV-2 prevalence was 4.4% (112 out of 2548). The prevalence of HIV-1 increased more for women than men especially in the 25–34-year age group. HIV-2 prevalence decreased below 45 years of age but not for individuals more than 45 years old. The incidence rate between 1996 and 2006 was 0.5 per 100 person-years for HIV-1 and 0.24 per 100 person-years for HIV-2. Compared with a previous period from 1987 to 1996, the incidence of HIV-2 is declining whereas no significant increase in the incidence of HIV-1 was observed. Conclusions:The present study shows an increasing prevalence of HIV-1 and a decreasing prevalence of HIV-2 in Guinea-Bissau. HIV is generally a bigger problem for women. Despite the general decline in prevalence, HIV-2 may continue as an infection in older people, especially women.

Testing the hypothesis that diphtheria–tetanus–pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries

Background Measles vaccines (MV) have sex-differential effects on mortality not explained by protection against measles infection. Objective The authors examined whether whole-cell diphtheria–tetanus–pertussis (DTP) vaccine has sex-differential and non-specific effects. Data sources and eligibility Following previous reviews and a new search, the effect of DTP on mortality up to the next vaccination was assessed in all studies where DTP was given after BCG or DTP was given after MV and there was prospective follow-up after ascertainment of vaccination status. Setting High-mortality countries in Africa and Asia. Methods The initial observation of negative effect of DTP generated six hypotheses, which were examined in all available studies and two randomised trials reducing the time of exposure to DTP. Main outcome Consistency between studies. Results In the first study, DTP had negative effects on survival in contrast to the beneficial effects of BCG and MV. This pattern was repeated in the six other studies available. Second, the two ‘natural experiments’ found significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated children. Third, the female–male mortality ratio was increased after DTP in all nine studies; in contrast, the ratio was decreased after BCG and MV in all studies. Fourth, the increased female mortality associated with high-titre measles vaccine was found only among children who had received DTP after high-titre measles vaccine. Fifth, in six randomised trials of early MV, female but not male mortality was increased if DTP was likely to be given after MV. Sixth, the mortality rate declined markedly for girls but not for boys when DTP-vaccinated children received MV. The authors reduced exposure to DTP as most recent vaccination by administering a live vaccine (MV and BCG) shortly after DTP. Both trials reduced child mortality. Conclusions These observations are incompatible with DTP merely protecting against the targeted diseases. With herd immunity to whooping cough, DTP is associated with higher mortality for girls. Randomised studies of DTP are warranted to measure the true impact on survival.

Increased female-male mortality ratio associated with inactivated polio and diphtheria-tetanus-pertussis vaccines: Observations from vaccination trials in Guinea-Bissau.

Background: The 2-fold increase in female mortality after high-titer measles vaccine may have occurred because many children received diphtheria-tetanus-pertussis (DTP) vaccine or inactivated polio vaccine (IPV) after high-titer measles vaccine. Objective: We examined whether DTP vaccine and IPV were associated with increased female mortality when they were the most recent vaccine administered to children who had not received measles vaccine. Setting and Design: IPV was used as a control vaccine in 4 randomized trials of early measles vaccination (MV) with enrollment at 4–6 months of age conducted in Guinea-Bissau. Many children had not received all 3 DTP vaccinations before enrollment, and therefore received DTP after IPV or MV. We examined whether DTP vaccination status at enrollment affected the female-male mortality ratio. Population: 9544 children enrolled in 4 trials. Main outcome measure: The female-male mortality ratio in different vaccine groups. Results: Females had a higher mortality rate than males among children randomized to receive IPV (mortality rate ratio [MR] 1.52, 95% CI 1.02–2.28), but females had a similar mortality rate to males among children randomized to receive MV (MR 1.01, 0.69–1.46) and among children in the IPV group after they had received MV at 9 months of age or later (MR 0.88, 0.68–1.14). Children who had not received a third dose of DTP before enrollment (and were likely to receive DTP after MV or IPV) tended to have a higher mortality than children who had received all 3 doses of DTP (MR 1.30, 0.97–1.73). This effect was seen only among girls (MR 1.61, 1.08–2.40) and not among boys (MR 1.02, 0.67–1.54). Girls had a lower mortality when MV was the most recent vaccine received rather than DTP or IPV (MR 0.49, 0.28–0.87). Conclusions: Randomization to IPV was associated with higher female than male mortality. However, the increased female mortality might result from additional doses of DTP received after enrollment and before measles vaccination.

Randomised study of effect of different doses of vitamin A on childhood morbidity and mortality

Abstract Objectives To determine whether the dose of vitamin A currently recommended by the World Health Organization or half this dose gives better protection against childhood morbidity and mortality. Design Randomised study. Setting A combined oral polio vaccine and vitamin A supplementation campaign in Guinea-Bissau, Africa. Participants 4983 children aged 6 months to 5 years. Interventions One of two doses of vitamin A (recommended and half); oral polio vaccine. Main outcome measures Mortality and morbidity at six and nine months. Results Mortality was lower in the children who took half the recommended dose of vitamin A compared with the full dose at both six months (mortality rate ratio 0.69, 95% confidence interval 0.36 to 1.35) and nine months (0.62, 0.36 to 1.06) of follow-up. There was a significant interaction between sex and dose, the lower dose being associated with significantly reduced mortality in girls (0.19, 0.06 to 0.66) but not in boys (1.98, 0.74 to 5.29). The lower dose of vitamin A was consistently associated with lower hospital case fatality in girls (0.19, 0.02 to 1.45). Paradoxically, in children aged 6-18 months, the low dose was associated with slightly higher morbidity. Conclusions Half the dose of vitamin A currently recommended by WHO may provide equally good or better protection against mortality but not against morbidity.

Tuberculin Reaction, BCG Scar, and Lower Female Mortality.

Background: Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific. Methods: Skin tests and BCG scarring were monitored at ages 2 months (n = 2332) and 6 months (n = 1817) in children born from March 2000 to July 2002. A tuberculosis (TB) surveillance system allowed us to exclude from the analysis children with likely TB exposure. The children were followed for survival until 18 months of age. Results: Among children with a tuberculin skin test at 2 and 6 months of age, the mortality rate ratio for skin test reactors (>1 mm) versus nonreactors (0–1 mm) was 0.54 (95% confidence interval = 0.30–0.99). Comparing children with and without a BCG scar, the ratio was 0.55 (0.31–0.96). The effect of a skin test reaction or a BCG scar seemed stronger among girls; for those with positive reaction, the mortality ratio was 0.31 (0.11–0.88) among girls and 0.84 (0.39–1.82) among boys; and for BCG scar, the results were 0.41 (0.21–0.82) and 0.88 (0.34–2.30), respectively. Conclusions: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.

Asymmetric introgression between the M and S forms of the malaria vector, Anopheles gambiae, maintains divergence despite extensive hybridization.

The suggestion that genetic divergence can arise and/or be maintained in the face of gene flow has been contentious since first proposed. This controversy and a rarity of good examples have limited our understanding of this process. Partially reproductively isolated taxa have been highlighted as offering unique opportunities for identifying the mechanisms underlying divergence with gene flow. The African malaria vector, Anopheles gambiae s.s., is widely regarded as consisting of two sympatric forms, thought by many to represent incipient species, the M and S molecular forms. However, there has been much debate about the extent of reproductive isolation between M and S, with one view positing that divergence may have arisen and is being maintained in the presence of gene flow, and the other proposing a more advanced speciation process with little realized gene flow because of low hybrid fitness. These hypotheses have been difficult to address because hybrids are typically rare (<1%). Here, we assess samples from an area of high hybridization and demonstrate that hybrids are fit and responsible for extensive introgression. Nonetheless, we show that strong divergent selection at a subset of loci combined with highly asymmetric introgression has enabled M and S to remain genetically differentiated despite extensive gene flow. We propose that the extent of reproductive isolation between M and S varies across West Africa resulting in a ‘geographic mosaic of reproductive isolation’; a finding which adds further complexity to our understanding of divergence in this taxon and which has considerable implications for transgenic control strategies.

Changing pattern of malaria in Bissau, Guinea Bissau.

Objectiveu2002 To describe the epidemiology of malaria in Guinea‐Bissau, in view of the fact that more funds are available now for malaria control in the country.

Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial

Background Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. Methods 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Results Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Conclusion Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.

Fecal carriage of ESBL-producing E. coli and K. pneumoniae in children in Guinea-Bissau: a hospital-based cross-sectional study.

Background In recent years, the world has seen a surge in extended-spectrum β-lactamase (ESBL)-producing bacteria. However, data on the dissemination of ESBL-producing Enterobacteriaceae in the community from systematically enrolled study subjects in Africa remains limited. To determine the prevalence, phenotypic resistance patterns and genetic characteristics of ESBL-producing E. coli and K. pneumoniae in fecal carriage and to analyze associated risk factors in children attending a pediatric emergency department in Guinea-Bissau. Methodology/Principal Findings From June to September 2010, children <5 years of age with fever or tachycardia attending a pediatric emergency ward during the day was screened for ESBL carriage in feces. Socio-demographic and health seeking behavior data was collected. Antibiotic susceptibility was tested with VITEK2 and EUCAST disk diffusion method, molecular characterization of ESBL-encoding genes was performed with multiplex PCR and clonal relatedness was established by automated rep-PCR. Of 408 enrolled children 133 (32.6%) were ESBL carriers. In total, 83 E. coli and 91 K. pneumoniae ESBL-producing isolates were obtained. Nearly all isolates were multidrug-resistant. Co-resistance to ciprofloxacin, trimethoprim-sulfamethoxazole and aminoglycosides was common. Of the isolates, 38.5% were co-resistant to these classes plus extended-spectrum cephalosporins, which infers resistance to all easily available antibiotic agents for treatment of gram-negative sepsis in Guinea-Bissau. The predominant resistance-encoding gene subgroup was bla CTX-M-1 and epidemiologic typing showed that the bacterial ESBL population was highly diverse both for E. coli and K. pneumoniae. Bed sharing with another child <5 years of age was a risk factor for ESBL carriage, indicating crowding as a potential risk factor for transmission of ESBL-producing bacteria. Conclusions/Significance Prevalence of ESBL-producing bacteria in this population was high and clonally diverse. This is alarming considering the limited diagnostic and treatment possibilities in Guinea-Bissau and other resource-poor countries.

Reduced in-hospital mortality after improved management of children under 5 years admitted to hospital with malaria : randomised trial

Objective To test whether strict implementation of a standardised protocol for the management of malaria and provision of a financial incentive for health workers reduced mortality. Design Randomised controlled intervention trial. Setting Paediatric ward at the national hospital in Guinea-Bissau. All children admitted to hospital with severe malaria received free drug kits. Participants 951 children aged 3 months to 5 years admitted to hospital with a diagnosis of malaria randomised to normal or intervention wards. Interventions Before the start of the study, all personnel were trained in the use of the standardised guidelines for the management of malaria, including strict follow-up procedures. Nurses and doctors were randomised to work on intervention or control wards. Personnel in the intervention ward received a small financial incentive (