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1.  Loss to follow-up occurs at all stages in the diagnostic and follow-up period among HIV-infected patients in Guinea-Bissau: a 7-year retrospective cohort study 
BMJ Open  2013;3(10):e003499.
Objectives
To describe loss to follow-up (LTFU) at all stages of the HIV programme.
Design
A retrospective cohort study.
Setting
The HIV clinic at Hospital National Simão Mendes in Bissau, Guinea-Bissau.
Participants
A total of 4080 HIV-infected patients.
Outcome measures
Baseline characteristics, percentages and incidence rates of LTFU as well as LTFU risk factors at four different stages: immediately after HIV diagnosis (stage 1), after the first CD4 cell count and before a follow-up consultation (stage 2), after a follow-up consultation for patients not eligible for antiretroviral treatment (ART; stage 3) and LTFU among patients on ART (stage 4).
Results
Almost one-third of the patients were lost to the programme before the first consultation where ART initiation is decided; during the 7-year observation period, more than half of the patients had been lost to follow-up (overall incidence rate=51.1 patients lost per 100 person-years). Age below 30 years at inclusion was a risk factor for LTFU at all stages of the HIV programme. The biggest risk factors were body mass index <18.5 kg/m2 (stage 1), male gender (stage 2), HIV-2 infection (stage 3) and CD4 cell count <200 cells/μL (stage 4).
Conclusions
In this study, LTFU constituted a major problem, and this may apply to other similar ART facilities. More than half of the patients were lost to follow-up shortly after enrolment, possibly implying a high mortality. Thus, retention should be given a high priority.
doi:10.1136/bmjopen-2013-003499
PMCID: PMC3808780  PMID: 24163204
2.  Impact of isoniazid preventive therapy on mortality among children less than 5 years old following exposure to tuberculosis at home in Guinea-Bissau: a prospective cohort study 
BMJ Open  2013;3(3):e001545.
Objective
In a cohort of children less than 5 years old exposed to adult intrathoracic tuberculosis (TB) in 1996–1998, we found 66% increased mortality compared with community controls. In 2005, we implemented isoniazid preventive therapy (IPT) for children exposed to TB at home, and the present study evaluates the effect of this intervention on mortality.
Setting
This prospective cohort study was conducted in six suburban areas included in the demographic surveillance system of the Bandim Health Project in Bissau, the capital city of Guinea-Bissau.
Participants
All children less than 5 years of age and living in the same house as an adult with intrathoracic TB registered for treatment in the study area between 2005 and 2007 were evaluated for inclusion in the IPT programme.
Main outcome measures (end points)
The all-cause mortality rate ratio (MRR) between exposed children on IPT, exposed without IPT and unexposed community control children.
Results
A total of 1396 children were identified as living in the same houses as 416 adult TB cases; of those, 691 were enrolled in the IPT programme. Compared with community controls, the IPT children had an MRR of 0.30 (95%CI 0.1 to 1.2). The MRR comparing exposed children with and without IPT was 0.21 (0.0 to 1.1). The relative mortality in IPT children compared with community controls in 2005–2008 differed significantly from the relative mortality of exposed untreated children compared with the community controls in 1996–1998 (test of interaction, p=0.01).
Conclusions
In 2005–2008, exposed children on IPT had 70% lower mortality than the community control children, though not significantly. Relative to the community control children, the mortality among TB-exposed children on IPT in 2005–2008 was significantly lower than the mortality among TB-exposed children not on IPT in 1996–1998.
doi:10.1136/bmjopen-2012-001545
PMCID: PMC3612806  PMID: 23535699
3.  Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau: an observational cohort study 
BMJ Open  2012;2(6):e001509.
Objective
The WHO aims for 90% coverage of the Expanded Program on Immunization (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of diphtheria−tetanus−pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10 and 14 weeks and measles vaccine (MV) at 9 months when this study was conducted. The WHO assesses coverage by 12 months of age. The sequence of vaccines may have an effect on child mortality, but is not considered in official statistics or assessments of programme performance. We assessed vaccination coverage and frequency of out-of-sequence vaccinations by 12 and 24 months of age.
Design
Observational cohort study.
Setting and participants
The Bandim Health Project's (BHP) rural Health and Demographic Surveillance site covers 258 randomly selected villages in all regions of Guinea-Bissau. Villages are visited biannually and vaccination cards inspected to ascertain vaccination status. Between 2003 and 2009 vaccination status by 12 months of age was assessed for 5806 children aged 12–23 months; vaccination status by 24 months of age was assessed for 3792 children aged 24–35 months.
Outcome measures
Coverage of EPI vaccinations and frequency of out-of-sequence vaccinations.
Results
Half of 12-month-old children and 65% of 24-month-old children had completed all EPI vaccinations. Many children received vaccines out of sequence: by 12 months of age 54% of BCG-vaccinated children had received DTP with or before BCG and 28% of measles-vaccinated children had received DTP with or after MV. By 24 months of age the proportion of out-of-sequence vaccinations was 58% and 35%, respectively, for BCG and MV.
Conclusions
In rural Guinea-Bissau vaccination coverage by 12 months of age was low, but continued to increase beyond 12 months of age. More than half of all children received vaccinations out of sequence. This highlights the need to improve vaccination services.
doi:10.1136/bmjopen-2012-001509
PMCID: PMC3532986  PMID: 23166127
4.  Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study 
BMJ Open  2012;2(6):e001587.
Background
Decisions about when to start an antiretroviral therapy (ART) are normally based on CD4 cell counts and viral load (VL). However, these measurements require equipment beyond the capacity of most laboratories in low-income and middle-income settings. Thus, there is an urgent need to identify and test simple markers to guide the optimal time for starting and for monitoring the effect of ART in developing countries.
Objectives
(1) To evaluate anthropometric measurements and measurement of plasma-soluble form of the urokinase plasminogen activator receptor (suPAR) levels as potential risk factors for early mortality among HIV-infected patients; (2) to assess whether these markers could help identify patients to whom ART should be prioritised and (3) to determine if these markers may add information to CD4 cell count when VL is not available.
Design
An observational study.
Setting
The largest ART centre in Bissau, Guinea-Bissau.
Participants
1083 ART-naïve HIV-infected patients.
Outcome measures
Associations between baseline anthropometric measurements, CD4 cell counts, plasma suPAR levels and survival were examined using Cox proportional hazards models.
Results
Low body mass index (BMI≤18.5 kg/m2), low mid-upper-arm-circumference (MUAC≤250 mm), low CD4 cell count (≤350 cells/μl) and high suPAR plasma levels (>5.3 ng/ml) were independent predictors of death. Furthermore, mortality among patients with low CD4 cell count, low MUAC or low BMI was concentrated in the highest suPAR quartile.
Conclusions
Irrespective of ART initiation and baseline CD4 count, MUAC and suPAR plasma levels were independent predictors of early mortality in this urban cohort. These markers could be useful in identifying patients at the highest risk of short-term mortality and may aid triage for ART when CD4 cell count is not available or when there is shortness of antiretroviral drugs.
doi:10.1136/bmjopen-2012-001587
PMCID: PMC3532999  PMID: 23151393
Public Health
5.  Testing the hypothesis that diphtheria–tetanus–pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries 
BMJ Open  2012;2(3):e000707.
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.
Article summary
Article focus
MV has sex-differential non-specific effects for child survival. We examined whether DTP vaccine has negative effects for survival, particularly for girls.
We tested six hypotheses suggesting that DTP may have negative health consequences if found to be true.
Furthermore, we conducted two randomised trials reducing the time of exposure to DTP as most recent vaccination by providing a live vaccine shortly after DTP.
Key messages
All available studies suggest that the effect of DTP on child survival is opposite of the effects of BCG and MV. In the two natural experiments, DTP-vaccinated children had significantly higher mortality than DTP-unvaccinated children.
Among DTP-vaccinated children, girls have higher mortality than boys in all studies, whereas the tendency is the opposite for BCG- and measles-vaccinated children. DTP administered after MV in randomised trials of MV is associated with increased female but not male mortality.
Reducing time of exposure to DTP as the most recent vaccination with BCG or MV reduce child mortality.
Strengths and limitations of this study
Since the healthiest children are vaccinated first, one would expect DTP to be associated with a benefit. However, all the data suggest consistently that DTP is associated with a negative effect for girls.
A randomised trial of the effect of DTP on overall survival could not be conducted. There is a need to conduct such studies now.
doi:10.1136/bmjopen-2011-000707
PMCID: PMC3364456  PMID: 22619263
6.  Does the effect of vitamin A supplements depend on vaccination status? An observational study from Guinea-Bissau 
BMJ Open  2012;2(1):e000448.
Objective
Vitamin A supplementation (VAS) is estimated to reduce all-cause mortality by 24%. Previous studies indicate that the effect of VAS may vary with vaccination status. The authors evaluated the effect of VAS provided in campaigns on child survival overall and by sex and vaccination status at the time of supplementation.
Design
Observational cohort study.
Setting and participants
The study was conducted in the urban study area of the Bandim Health Project in Guinea-Bissau. The authors documented participation or non-participation in two national vitamin A campaigns in December 2007 and July 2008 for children between 6 and 35 months of age. Vaccination status was ascertained by inspection of vaccination cards. All children were followed prospectively.
Outcome measures
Mortality rates for supplemented and non-supplemented children were compared in Cox models providing mortality rate ratios (MRRs).
Results
The authors obtained information from 93% of 5567 children in 2007 and 90% of 5799 children in 2008. The VAS coverage was 58% in 2007 and 68% in 2008. Mortality in the supplemented group was 1.5% (44 deaths/2873 person-years) and 1.6% (20 deaths/1260 person-years) in the non-supplemented group (adjusted MRR=0.78 (0.46; 1.34)). The effect was similar in boys and girls. Vaccination cards were seen for 86% in 2007 and 84% in 2008. The effect of VAS in children who had measles vaccine as their last vaccine (2814 children, adjusted MRR=0.34 (0.14; 0.85)) differed from the effect in children who had diphtheria–tetanus–pertussis vaccine as their last vaccine (3680 children, adjusted MRR=1.29 (0.52; 3.22), p=0.04 for interaction).
Conclusion
The effect of VAS differed by most recent vaccination, being beneficial after measles vaccine but not after diphtheria–tetanus–pertussis vaccine.
Article summary
Article focus
Vitamin A supplementation (VAS) is estimated to reduce all-cause mortality by 24%.
The effect of VAS may vary with vaccination status, being beneficial with or after measles vaccine (MV) but not after diphtheria–tetanus–pertussis (DTP) vaccine.
Key messages
The effect of VAS is heterogeneous.
The effect of VAS varied with vaccination status: supplemented children had lower mortality than non-supplemented children when MV was the most recent vaccine but not when DTP was the most recent vaccine.
The effect of VAS tended to differ by season of supplementation.
Strengths and limitations of this study
Information was collected on the individual level, and the children were followed prospectively.
Due to the observational nature of the study, the comparison of supplemented and non-supplemented children should be interpreted with caution.
However, a selection bias is unlikely to have worked in different directions for children who had DTP and MV as the most recent vaccine.
doi:10.1136/bmjopen-2011-000448
PMCID: PMC3278485  PMID: 22240648

Results 1-6 (6)