BACKGROUND:The decline in global child mortality is an important public health achievement, yet child mortality remains disproportionally high in many low-income countries like Guinea-Bissau. The persisting high mortality rates necessitate targeted research to identify vulnerable subgroups of children and formulate effective interventions. OBJECTIVE:This study aimed to discover subgroups of children at an elevated risk of mortality in the urban setting of Bissau, Guinea-Bissau, West Africa. By identifying these groups, we intend to provide a foundation for developing targeted health interventions and inform public health policy. METHODS:We used data from the health and demographic surveillance site, Bandim Health Project, covering 2003 to 2019. We identified baseline variables recorded before children reached the age of 6 weeks. The focus was on determining factors consistently linked with increased mortality up to the age of 3 years. Our multifaceted methodological approach incorporated spatial analysis for visualizing geographical variations in mortality risk, causally adjusted regression analysis to single out specific risk factors, and machine learning techniques for identifying clusters of multifactorial risk factors. To ensure robustness and validity, we divided the data set temporally, assessing the persistence of identified subgroups over different periods. The reassessment of mortality risk used the targeted maximum likelihood estimation (TMLE) method to achieve more robust causal modeling. RESULTS:We analyzed data from 21,005 children. The mortality risk (6 weeks to 3 years of age) was 5.2% (95% CI 4.8%-5.6%) for children born between 2003 and 2011, and 2.9% (95% CI 2.5%-3.3%) for children born between 2012 and 2016. Our findings revealed 3 distinct high-risk subgroups with notably higher mortality rates, children residing in a specific urban area (adjusted mortality risk difference of 3.4%, 95% CI 0.3%-6.5%), children born to mothers with no prenatal consultations (adjusted mortality risk difference of 5.8%, 95% CI 2.6%-8.9%), and children from polygamous families born during the dry season (adjusted mortality risk difference of 1.7%, 95% CI 0.4%-2.9%). These subgroups, though small, showed a consistent pattern of higher mortality risk over time. Common social and economic factors were linked to a larger share of the total child deaths. CONCLUSIONS:The study's results underscore the need for targeted interventions to address the specific risks faced by these identified high-risk subgroups. These interventions should be designed to work to complement broader public health strategies, creating a comprehensive approach to reducing child mortality. We suggest future research that focuses on developing, testing, and comparing targeted intervention strategies unraveling the proposed hypotheses found in this study. The ultimate aim is to optimize health outcomes for all children in high-mortality settings, leveraging a strategic mix of targeted and general health interventions to address the varied needs of different child subgroups.

Objectives: Between 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. Methods: We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. Results: The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0. Conclusion: In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.

Background Health Care Workers (HCW) faced a high risk of exposure to SARS-CoV-2. In the present study, we described the presence and duration of anti-S and anti-N IgG antibodies against SARS-CoV-2 among HCW to evaluate the immunity response induced by either SARS-CoV-2 infection or COVID-19 vaccination. Methods Case-cohort study of 465 HCW from hospitals from the islands of Santiago and São Vicente, conducted in 2021, of which 217 were cases (SARS-CoV-2 infection) and 248 controls (no SARS-CoV-2 infection). Study participants were followed-up until 6 months after recruitment for longitudinal analysis of antibody dynamics, independently of SARS-CoV-2 vaccination status. ELISA test for anti-N and anti-S1 SARS-CoV-2 IgG antibodies were performed on serum samples using collected at baseline (T0) and at 6 months (T6). Among vaccinated participants, these two time points corresponded to a mean time from vaccination of 115 (SD: 60 days) and 350 days (SD: 74 days) respectively. Results Of the 396/465 (85%) tested for anti-SARS-CoV-2 antibodies at T0, 36% (n=66/185) of cases and 12% of controls (n=26/211) were positive for anti-N. Among the vaccinated at T0 165/166 (96%) cases and 200/205 (97%) controls were positive for anti-S1. The anti-S1 among the case and control group remained high at T6, with 177/179 (99%) cases and 197/198 (99%) controls of HCW tested at 6 months being positive. Among 250 (67%) vaccinated, who were anti-N negative at T0-,115(32%) remain negative at T6. Conclusion These findings showed that only 31% of cases had anti-N. The results also showed positive results for IgG anti-N in HCW without previous SARS-CoV-2 infection, which could be considered asymptomatic cases. Most vaccinated participants had Anti-S after vaccination and they remained high during the 6 months of follow-up. Nonetheless, at least (65/354) had a new infection (32 cases, 33 controls). Funding: EDCTP (RIA2020EF-3049)

Background Children under the age of five are generally more susceptible to respiratory viral infections, but during the pandemic there have been many reports that children have a low risk of severe SARS-CoV-2 infection. It has been questioned to what extend children have been infected with SARS-CoV-2. We therefore conducted a survey to determine the prevalence among children under 5 years of age in Guinea-Bissau and investigate potential risk factor related to COVID-19 infection. Methods This is a cross-sectional study, carried out in children under 5 years of age in the study area of the Bandim Health Project, a health and demographic surveillance system located in Guinea-Bissau, between April and July 2022. SARS-Cov-2 antibodies were investigated using rapid diagnostic tests (OnSite Rapid Test, CTK Biotech, USA) to determine the prevalence. Risk ratios (RR) were calculated with 95% confidence intervals using binomial regression. Results The study included 831 children. The overall prevalence of SARS-Cov-2 antibodies was 51% (423/831). The prevalence was lowest among the youngest children aged 6–11 months. Older children had significant higher RRs, ranging from 1.47 (12 -23 months) to 1.80 (48–59 months). Other risk factors included whether the child had attended school/kindergarten: RR=1.33 (1.15–1.54); whether child had been ill during the pandemic: RR=1.22 (1.03–1.44); whether someone had died in the house, RR=1.40 (1.15–1.70) and children whose guardian (usually the mother) had attended school for more than five years, RR=1.49 (1.26–1.75). Conclusion Confirmed cases of SARS-CoV-2 in Guinea-Bissau only represent about 0.5% of the population. However, this study indicates extensive circulation of SARS-CoV-2 since more than half of children under five year of age tested positive for SARS-CoV-2. Age of the child, deaths occurred in the house and education level of the guardian were all associated with previous SARS-CoV-2 infection.

Mortality rates by 6 weeks of age tended to be reduced among neonates born to mothers who had a BCG vaccine scar, compared with those born to mothers with no BCG scar. Background Maternal priming with the Bacille Calmette-Guerin (BCG) vaccine has been associated with reduced offspring mortality rates. We investigated this association in a cohort of frail neonates. Methods We performed an observational study within a randomized BCG trial conducted at the neonatal intensive care unit (NICU) in Guinea-Bissau from 2015 to 2017. At NICU admission and after informed consent, the maternal scar status was evaluated by visual inspection before neonates were randomized 1:1 to receive BCG + oral polio vaccine immediately or at hospital discharge. Stratified by maternal scar status, we assessed overall in-hospital and postdischarge mortality rates through 42 days of age in Cox proportional hazards models providing adjusted mortality rate ratios (aMRRs). Results Overall, 62% of mothers (903 of 1451) had a BCG vaccine scar. During NICU admission, the mortality risk was 1.7% (15 of 903) for neonates born to mothers with a scar versus 3.3% (18 of 548) for those born to mothers with no scar; the aMRR for maternal scar versus no scar was 0.53 (95% CI, .26-1.05), 0.39 (95% CI, .13-1.05) for unvaccinated and 0.70 (95% CI, .26-1.87) for vaccinated neonates. Conclusions This small study indicates that maternal BCG vaccine might be associated with reduced all-cause NICU mortality rate. If confirmed elsewhere, this finding would have substantial ramifications for global health.

Background Early 2-dose measles vaccine (MV) at 4 and 9 months of age vs. the WHO strategy of MV at 9 months of age reduced all-cause child mortality in a previous trial. We aimed to test two hypotheses: 1) a 2-dose strategy reduces child mortality between 4 and 60 months of age by 30%; 2) receiving early MV at 4 months in the presence versus absence of maternal measles antibodies (MatAb) reduces child mortality by 35%. Methods Single-centre open-label community-based randomised controlled trial in Guinea-Bissau, with 2:1 block-randomisation by sex to a 2-dose (4 + 9 months) vs. 1-dose (9 months) MV strategy. Healthy children were eligible 4 weeks after the 3rd diphtheria-tetanus-pertussis-containing vaccine. Before randomisation a blood sample was collected to determine MatAb level. The primary outcome was all-cause mortality. Hazard ratios (HR) were derived from Cox regression in the per protocol population. We tested for interactions with national campaigns with oral polio vaccine (C-OPV). Trial registration: NCT01486355. Findings Between August 2011-April 17th 2015, 6,636 children were enroled, 6,598[n(2-dose)=4,397; n(1-dose)=2,201] were included in the analysis of the primary outcome, The HR(2-dose/1-dose) between 4 and 60 months was 1.38 (95%CI: 0.92- 2.06) [deaths: n(2-dose)=90; n(1-dose)=33]. Before the 9-month MV and the HR(1-dose/no dose) was 0.94 (0.45-1.96) [deaths: n(2-dose)=21; n(1-dose)=11]. The HR(2-dose/1-dose) was 0.81 (0.29-2.22) for children, who received no C-OPV [deaths/children: n(2-dose)=10/2,801; n(1-dose)=6/1,365], and 4.73 (1.44-15.6) for children, who received COPV before and after enrolment (p for interaction=0.027) [deaths/children: n(2-dose)=27/1,602; n(1-dose)=3/837]. In the 2-dose group receiving early MV at 4 months, mortality was 50% (20-68%) lower for those vaccinated in the presence of MatAb vs. the absence of MatAb [deaths/children: nMatAb=51/3,132; nnoMatAb=31/1,028]. Interpretation The main result contrasts with previous findings but may, though based on a small number of events, be explained by frequent OPV campaigns that reduced the mortality rate, but apparently interacted negatively with early MV. The beneficial non-specific effects of MV in the presence of MatAb should be investigated further. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.

Abstract Background The world is set on the eradication of measles. Continuation of the measles vaccine (MV) after eradication could still reduce morbidity because the MV has so-called beneficial nonspecific effects. We evaluated the effect of a “booster” dose of the MV on overall severe morbidity. Methods We conducted a randomized controlled trial among children aged 17.5 to 48 months in Guinea-Bissau, where the MV is recommended only at 9 months of age. At the time of this interim analysis, 3164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or to no vaccine. Severe morbidity (a composite outcome of nonaccidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns. Results There were no measles cases during the trial period. There were 43 nonaccidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR, 0.72; 95% confidence interval [CI], .38–1.38). At 12 months of follow-up, the number needed to treat to prevent 1 severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR, 0.91; 95% CI, .46–1.81). Conclusions MV2 may reduce nonmeasles severe morbidity by 28% (−38% to 62%), although this did not achieve statistical significance in this study. If significant in higher powered studies, this has major implications for child health, even after measles eradication. Clinical Trials Registration NCT02943681.

The recommendation to provide inactivated influenza vaccine (IIV) to pregnant women is based on observed protection against influenza-related morbidity in mother and infant. Non-live vaccines may have non-specific effects (NSEs), increasing the risk of non-targeted infections in females. We reviewed the evidence from available randomised controlled trials (RCTs) of IIV to pregnant women, to assess whether IIV may have NSEs. Four RCTs, all conducted in low- and middle-income settings, were identified. We extracted information on all-cause and infectious mortality and adverse events in women and their infants. We conducted meta-analyses providing risk ratios (RR). The meta-analysis for maternal all-cause mortality provided a RR of 1.48 (95% CI = 0.52–4.16). The estimates for miscarriage/stillbirth and infant all-cause mortality up to 6 months of age were 1.06 (0.78–1.44) and 1.11 (0.87–1.41), respectively. IIV was associated with a higher risk of non-influenza infectious adverse events, with meta-estimates of 2.01 (1.15–3.50) in women and 1.36 (1.12–1.67) in infants up to 6 months of age. Thus, following a pattern seen for other non-live vaccines, IIV was associated with a higher risk of non-influenza infectious adverse events. To ensure that scarce resources are used well, and no harm is inflicted, further RCTs are warranted.

Background: Live attenuated vaccines have been observed to have particularly beneficial effects for child survival when given in the presence of maternally transferred immunity (priming). We aimed to test this finding and furthermore explore the role of paternal priming. Methods: In an exploratory, retrospective cohort study in 2017, parental Bacillus Calmette-Guerin (BCG) scars were assessed for infants from the Bandim Health Project (BHP) who had participated in a 2008-2013 trial of neonatal BCG vaccination. Parental scar effects on mortality were estimated from birth to 42 days, the age of the scheduled diphtheria-tetanus-pertussis (DTP) vaccination, in Cox proportional hazard models adjusted with Inverse Probability of Treatment Weighting. Findings: For 66% (510/772) of main trial infants that were still registered in the BHP area, at least one parent was located. BCG scar prevalence was 77% (353/461) among mothers and 63% (137/219) among fathers. In the first six weeks of life, maternal scars were associated with a mortality reduction of 60% (95%CI, 4% to 83%) and paternal scars with 49% (-68% to 84%). The maternal scar association was most beneficial among infants that had received BCG vaccination at birth (73% (-1% to 93%)). Although priming was less evident for paternal scars, having two parents with scars reduced mortality by 89% (13% to 99%) compared with either one or none of the parents having a scar. Interpretation: Parental BCG scars were associated with strongly increased early-life survival. These findings underline the importance of future studies into the subject of inherited non-specific immunity and parental priming. (C) 2021 The Authors. Published by Elsevier Ltd.

Background: Shiga toxin-producing Escherichia coli O157:H7 (STEC-O157: H7) infection is related to major outbreaks and serious diseases such as hemolytic uremic syndrome (HUS). In March 2019, a gastroenteritis outbreak occurred in the day care center of Vila Velha-Brazil, and a death occurred by HUS. Epidemiological investigation was conducted to identify the agent involved and source of infection. Methods and materials: A descriptive study. Cases were: children or employees who presented diarrhea or vomiting from March 1st to April 5th, 2019. A semi-structured questionnaire was applied. The rate attack of cases per class was calculated. Stool samples were collected from the cases and from water reservoir, kitchen tap reducer, water toy, water and food. Laboratory techniques used: culture, Polymerase chain reaction (PCR), and pulsed field electrophoresis- PFGE. Results: There were 24 cases of diarrhea, of these two (79,0%) were children, five (20,9%) employees. The cases reduced by 92% after the suspension of day care activities in March 26th. The 2-year-old class had the highest attack rate (40,0%) and there were no case in the 4-year-old class. Bloody diarrhea was reported in five (21,0%), abdominal pain nine (38,0%), vomiting eight (33,0%), and three (12,0%) evolved to HUS, with one death (33% lethality by SHU). STEC-O157: H7 was detected in two children who had bloody diarrhea (one with HUS) and in the water tap reducer. The PFGE analysis identified that, the genetic homology between case strains was 90% and the genetic similarity between the cases and the water tap reducer was 64,0%. Conclusion: A gastroenteritis outbreak occurred in the day care center involving the EHEC O157: H7 strain. It is suggested that E. coli was introduced into the day care center by an infected person, spreading the outbreak, maintained by person-to-person transmission, stop the school activities and professionals guide about the characteristics of the disease helped in minimizing the severity of cases. It was recommended to guide teachers/staff about how to prevent fecal-oral transmission diseases, and to monitor water quality in the day care center.

BackgroundThe World Health Organisation estimates a global deficit of approximately 4.3 million health workers, particularly doctors, nurses and midwives. Guinea-Bissau is among the 36 countries that suffer from a critical need for human resources (less than 23 health professionals per 10.000 inhabitants). The present research investigates the impact of clinical trials on health worker’s capacity and training.MethodsThis is a qualitative study. I interviewed health professionals who assisted in clinical trials during the past five years and obtained assistance to attend health-related courses. The interviews collected data about the professional’s technical capacity, clinical practices, work conditions, their qualification for their work and socio-economic variables. Additionally, documents about clinical trials conducted in Guinea-Bissau through North-South cooperation, were analysed.ResultsInterviews were held with 35 health professionals (21 female, 14 male) who participated in clinical trials with the Bandim Health Project (Guinea-Bissau) as research assistants and who received subsidies to realise undergraduate or graduate degrees. Among those interviewed, 28 (80%) received support to realise an undergraduate degree in nursing, 4 (11%) a laboratory course, and 3 (9%) a postgraduate course. Twenty-four (24; 69%) stated that they experienced significant improvements in their working conditions within the institutions where they worked after their clinical trials; 7 (20%) declared that they have progressed in their career after being placed in a health center or a hospital; 29 (83%) stated that the participation in clinical trials significantly strengthened their technical capacity and had a positive impact on their careers.ConclusionI observed a positive impact of the involvement in clinical research on the development of health professionals’ capacity. However, the quantity of clinical research in Guinea-Bissau is insufficient to train all health practitioners in this area.

BackgroundStudying the causes of hospitalisation is useful to understand the profile of illness and identify the most effective interventions. Guinea-Bissau was projected to reduce the under-5 mortality rate from 200 to 80/1000 live births (2005–2015); and the causes of the deaths were attributed: neonatal, pneumonia, malaria and diarrhea. In 2014 the mortality rate was 55/1000 live births in Guinea-Bissau, and malaria, diarrhea and respiratory infection were the main causes of illness. The present study aims to describe the main causes of hospitalisation and death in children under 5 years in the paediatric clinic of the ‘Simão Mendes’ National Hospital.MethodDescriptive and retrospective study, with search of data from health care records. STATA and Microsoft Excel programmes were used for data analysis and cleaning. Cases defined as: children under 5 years of age, diagnosed from 2015 to 2017.ResultsIn 17,250 cases of hospitalisation, the overall lethality rate for 2015–2017 was calculated at 7.5%. There was an increase in the lethality rate (10.8%) in 2017. Among the main causes of hospitalisation were gastrointestinal infection (26.9%), malaria (23%), respiratory infection (17.6%) and septicaemia (16.1%). Septicaemia is the disease with the highest lethality rate during these three years (18%), the case fatality rate due to gastrointestinal infection in 2017 (7.7%) was double compared with 2015 and 2016; 19% of deaths occured for those who lived far from hospital (>40 km).Conclusion2017 had fewer hospitalisation cases and is the year with the highest lethality rate. Gastrointestinal infection and malaria were the main causes of hospitalisation. The rate of lethality from diarrhoea and septicaemia has increased significantly and with worse outcome in those living far from Bissau.