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Abstract Background Despite twinning being common in Africa, few prospective twin studies have been conducted. We studied twinning rate, perinatal mortality and the clinical characteristics of newborn twins in urban Guinea-Bissau. Methods The study was conducted at the Bandim Health Project (BHP), a health and demographic surveillance site in Bissau, the capital of Guinea-Bissau. The cohort included all newborn twins delivered at the National Hospital Simão Mendes and in the BHP study area during the period September 2009 to August 2011 as well as singleton controls from the BHP study area. Data regarding obstetric history and pregnancy were collected at the hospital. Live children were examined clinically. For a subset of twin pairs zygosity was established by using genetic markers. Results Out of the 5262 births from mothers included in the BHP study area, 94 were twin births, i.e. a community twinning rate of 18/1000. The monozygotic rate was 3.4/1000. Perinatal mortality among twins vs. singletons was 218/1000 vs. 80/1000 (RR = 2.71, 95% CI: 1.93-3.80). Among the 13783 hospital births 388 were twin births (28/1000). The hospital perinatal twin mortality was 237/1000. Birth weight Conclusions Twins had a very high perinatal mortality, three-fold higher than singletons. A birth weight

Abstract Background Little is known about the prevalence of pulmonary tuberculosis (TB) in low income countries. We conducted a cross sectional survey for pulmonary TB and TB symptoms in Bissau, Guinea-Bissau, in an urban cohort with known HIV prevalence. TB surveillance in the area is routinely based on passive case finding. Methods Two cohorts were selected based on a previous HIV survey, but only 52.5% of those enrolled in the adult cohort had participated in the HIV survey. One cohort included all adults living in 384 randomly selected houses; in this cohort 8% (135/1687) were HIV infected. The other included individuals 50 years or older from all other houses in the study area; of these 11% (62/571) were HIV infected. Symptom screening was done through household visits using a standardised questionnaire. TB suspects were investigated with sputum smear microscopy and X-ray. Results In the adult cohort, we found 4 cases among 2989 individuals screened, giving a total TB prevalence of 134/100,000 (95% CI 36-342/100,000). In the >50 years cohort, we found 4 cases among 571 individuals screened, giving a total prevalence of 701/100,000 (191-1784/100.000). Two of the eight detected TB cases were unknown by the TB program. Of the total TB cases five were HIV uninfected while three had unknown HIV status. The prevalence of TB symptoms was 2.1% (63/2989) and 10.3% (59/571) in the two cohorts respectively. Conclusions In conclusion we found a moderately high prevalence of pulmonary TB and TB symptoms in the general population, higher among elderly individuals. By active case finding unknown cases were detected. Better awareness of TB and its symptoms needs to be promoted in low income settings.

Abstract Background IFN-γ responses to M. tuberculosis antigens are used as in-vitro diagnostic tests for tuberculosis infection. The tests are highly specific but sensitivity may be impaired due to immuno-suppression. The objective of this small exploratory study was to compare three novel biomarkers for in-vitro diagnosis of tuberculosis – MCP-1, MCP-3 and IL-1RA – with the current established biomarker IFN-γ and the newly described IP-10 and MCP-2. Methods Whole blood from 8 patents with active tuberculosis and from 7 healthy controls was stimulated with M. tuberculosis specific antigens and mitogen in the Quantiferon In Tube test tubes. Levels of biomarkers were measured using Luminex and ELISA (IFN-γ). Results We found all five new biomarkers were expressed in significantly higher concentrations compared to IFN-γ. IP-10 and MCP-3 levels in the un-stimulated samples were higher in patients compared with controls. Conclusion All biomarkers had diagnostic potential as they could differentiate between the patients and the controls. IP-10 and MCP-2 seemed most promising as they were expressed in high levels with antigen stimulation and were low in the un-stimulated samples. Further studies are needed to explore the potential of these highly expressed novel biomarkers individually and in combination.

Background: Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D., Methods: Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers., Results: In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25-75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356-568), 11.8% (10.1-13.4) and 0.50 µg/L (0.30-0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period., Conclusion: The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change., (© 2024. The Author(s).)

Introduction: the need to correctly measure and follow body composition as a simple disease prevention metric is important, especially where the healthcare infrastructures are poor. The variety of inexpensive devices available for this purpose is large. However, it is imperative to validate them in relation to the gold standard method, dual-energy absorptiometry X-ray (DEXA). In low-income countries, DEXA measurements aren't available. Thus, easy-to-use, and accurate devices are indispensable. In Guinea-Bissau, two relatively inexpensive, bioelectrical impedance scales, simple to use, are available. However, their accuracy has not been assessed in this setting. The study compares the level of agreement in measurements between, the Tanita® BC-545 and the Omron Karada Scan BF511, in adult volunteers., Methods: volunteers grouped for athletic and sports modalities at stadiums and sports facilities in Bissau were included. All anthropometric measurements were done in both devices. For statistical analysis, we created Bland-Altman plots to assess their level of agreement., Results: the study included 274 participants, mean age 27.4 years, 214 (78%) males. For body fat, the median between the Omron and Tanita measures was 2.6 and the interquartile was 5.2. The Omron measured median body mass index, -0.3 kg/m 2 and 0.8 kg/m 2 of interquartile below that of the Tanita. For visceral fat, the Omron measured 1% of median and an interquartile of 2% above that of the Tanita. For skeletal muscle, the Omron median measured 11.3% and 11.4 % of interquartile below that of the Tanita. The intra-class correlation coefficient (ICC) for body fat (BF), body mass index (BMI) and skeletal muscle (SM) was 0.99 and for VF it was 1.00 on both devices., Conclusion: the results indicate a good level of agreement between the two devices. In resource-limited settings, the Omron is likely a reasonable substitute for more expensive body composition devices., Competing Interests: The authors declare no competing interests., (Copyright: Lilica Sanca et al.)

Background: The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic., Methods: A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes., Results: There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98-1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07-5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI, .09-.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI, .96-1.24)., Conclusions: In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes., Clinical Trials Registration: NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90)., Competing Interests: Potential conflicts of interests . T. B. reports grants or contracts from Novo Nordisk, Simonsen, Lundbeck, Kai, Erik and Susanna Olesen's Charitable Found, GSK, Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Pentabase, Roche, Novartis, Kancera AB, Janssen, and Astra Zeneca; consulting fees from GSK and Pfizer; honoraria for lectures from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie, and Astra Zeneca; and donation of trial medication from Eli Lilly. P. E. K. reports participation on Data Safety Monitoring Board or Advisory Board on trials “Specific and non-specific effects of measles and BCG vaccines for mother and child (MATVAC)”, “Evaluating the effectiveness of different BCG strains in Guinea-Bissau: A randomized trial of the impact on neonatal hospital admissions”, and “BCG vaccine to reduce unplanned absenteeism due to COVID-19 illness of health care workers in Guinea-Bissau and Mozambique. A multi-center single-blinded randomized controlled trial (BCG-COVID-RCT)”, and “A randomized trial of providing BCG vaccination immediately to neonates admitted to the intensive care unit in Guinea-Bissau: Effect on mortality”. C. W. reports honoraria for a lecture from Novartis; and participation on the Advisory Board on COVID-19 Treatments, Danish government. I. S. J. reports honoraria from Pfizer for being chairman for the European Congress of Clinical Microbiology and Infectious Diseases 2023 COVID-19 symposium. M. G. N. reports to be scientific founder and have stock in TTxD and Lemba. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Maternal priming with the Bacille Calmette-Guérin (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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The 'thrifty phenotype' hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data were available on 7-34 year-old twins ( n = 209, 97 males) and singletons ( n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p = 0.055), weight (WAZ -0.73, p = 0.024) and BMI (BAZ -0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.

Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height., Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age., Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood., Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity., (© 2022. The Author(s).)

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 C-OPV 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: n MatAb =51/3,132; n noMatAb =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., Funding: ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation., Competing Interests: OB received a scholarship from the Lundbeck Foundation. All other authors declare no competing interests., (© 2022 The Authors.)

Objectives: Bacille Calmette-Guérin (BCG) vaccination lowers the risk of severe infection; we tested whether effects are modulated by maternal BCG in a large cohort of BCG-vaccinated newborns from Guinea-Bissau., Methods: Maternal BCG scar status were inspected at enrolment in a BCG trial conducted from 2014 to 17 in Bissau, Guinea-Bissau. We tested associations with background factors for potential confounding; maternal age affected effect estimates >5% and accordingly, all analyses were adjusted for maternal age. Hospitalization data was collected prospectively and assessed in Cox-models providing adjusted Incidence Rate Ratios (aIRRs). In-hospital risk of death (case-fatality) risk was assessed using binomial regression providing adjusted Risk Ratios (aRRs)., Results: 60% (6,309/10,598) of mothers had a scar. The maternal-scar/no-scar admission aIRR was 0.96 (0.81-1.14) from 0 to 6 weeks and 1.12 (0.97-1.28) for 6 weeks-3 years. The 6-week in-hospital case-fatality infection aRR was 0.59 (0.34-1.05); 0.40 (0.17-0.91) for males and 0.86 (0.38-1.94) for females. Protection was especially evident against sepsis, the overall 6-week aRR=0.49 (0.26-0.91); no effect was observed for non-infectious deaths or after 6 weeks of age. Effects were similar across BCG strains and multivariate models adjusted for socioeconomic status did not affect estimates., Conclusion: Among BCG-vaccinated newborns, there was a trend for fewer in-hospital deaths from infection associated with maternal BCG priming, especially for males. Providing BCG to adults without a vaccination scar might enhance their offspring's capacity to handle severe infections. Brief 40-word summary: Within a trial comparing BCG strains for their overall effects on morbidity and mortality in Guinea-Bissau, vertical priming with BCG (represented by the maternal BCG scar) was associated with beneficial sex-differential effects on offspring survival., Competing Interests: Declaration of Competing Interest At the time the data collection was conducted, several of the authors were affiliated with the Statens Serum Institute (SSI) in Copenhagen which administered, but did not finance, their grants. SSI was a producer of BCG. However, SSI did not fund the vaccines, the study, or the researchers and neither the SSI or funders had any influence on the study design, data collection, analysis, interpretation or writing of the report, nor the decision to submit the paper for publication. None of the authors have any commercial, financial, or personal interests, relationships or other associations that might pose a conflict of interest in relation to this study. Data sharing agreement. Deidentified participant data with a data dictionary can be shared after approval of a data-sharing proposal sent to Professor Christine Stabell Benn (cbenn@health.sdu.dk)., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Randomized controlled trials (RCTs) indicate that bacille Calmette-Guérin (BCG) vaccination provides broad beneficial "nonspecific" protection against infections. We investigated the effect on in-hospital mortality of providing BCG immediately upon admission to a neonatal intensive care unit (NICU), rather than BCG-at-discharge. The pretrial NICU mortality was 13% and we hypothesized that BCG would reduce mortality by 40%., Methods: Parallel-group, open-label RCT was initiated in 2013 in Guinea-Bissau. Neonatal intensive care unit-admitted neonates were randomized 1:1 to BCG + oral polio vaccine (OPV) immediately (intervention) versus BCG + OPV at hospital discharge (control; usual practice). The trial was discontinued due to decreasing in-hospital mortality and major NICU restructuring. We assessed overall and disease-specific mortality by randomization allocation in cox proportional hazards models providing mortality rate ratios (MRRs)., Results: We recruited 3353 neonates, and the overall mortality was 3.1% (52 of 1676) for BCG-vaccinated neonates versus 3.3% (55 of 1677) for controls (MRR = 0.94; 0.64-1.36). For noninfectious causes of death, the MRR was 1.20 (0.70-2.07), and there tended to be fewer deaths from infections in the BCG group (N = 14) than among controls (N = 21) (MRR = 0.65; 0.33-1.28)., Conclusions: Providing BCG + OPV to frail neonates was safe and might protect against fatal infection in the immediate newborn period. Deaths due to prematurity and perinatal complications were unaffected by BCG., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent., Methods: A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010-2014) and a fever study in Ghana (2007-2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes-genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site., Results: Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR; Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S . Enteritidis and S . Typhimurium in Ghana; an ST313 isolate carrying bla CTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged <5 years in several West African countries., Conclusions: We identified the circulation of multiple MDR iNTS serovar STs in the sampled sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The burden of diabetes mellitus in Sub-Saharan Africa is growing rapidly, and yet the prevalence and patient characteristics are still largely unknown., Objectives: We analyzed clinical and demographic characteristics of Type 2 diabetes (T2DM) patients attending a diabetes clinic in Guinea-Bissau from February 2008 to April 2014, and estimated the prevalence and risk factors of unknown-impaired fasting plasma glucose (FPG) and diabetes, as well as excess mortality associated with T2DM., Methods: We characterized T2DM patients attending the national diabetes clinic in Bissau. Diabetes was diagnosed based on FPG. We matched T2DM patients 1:1 with non-diabetes community controls on age and sex to determine relevant risk factors for T2DM using logistic regression. Furthermore, we matched patients 1:6 with community controls to assess long-term survival (until February 2019) in a Cox regression using calendar time as the underlying timescale. Verbal autopsies determined the cause of death among T2DM patients and controls., Results: The mean age among T2DM was 50.6 (SD 11.1), and the mean FPG at first consultation was high (13.2 mmol/L (SD 5.1)). Ethnicity, family history of diabetes, hypertension, and anthropometrics differed among T2DM patients, community controls with impaired FPG, and healthy controls. Family history of diabetes (OR = 5.65, 95% CI: 3.10-10.3) and elevated waist circumference (2.33, 1.26-4.29) were significant risk factors for T2DM. 20.4% (59/289) of community controls had abnormal FPG. T2DM patients had an excess mortality hazard ratio of 3.53 (95%CI: 1.92-6.52). Deaths caused by bacterial infections, including foot ulcers, were more common among T2DM patients, compared with community controls (54% (7/13) vs. 19% (5/27) (P = 0.02))., Conclusion: Several risk factors including were associated with T2DM in Guinea-Bissau. We found a high prevalence of elevated FPG among randomly selected community controls. In combination with higher mortality among T2DM patients, an urgent need for better treatment options and increased awareness.

Background: Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) have demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects., Methods: This was a parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2851 randomized, 2840 analyzed) vs BCG-Russia (2845 randomized, 2837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and purified protein derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3191 neonates randomized, 3184 analyzed) with BCG-Russia (3170 randomized, 3160 analyzed). Mortality and morbidity data were collected by telephone, at home visits, and at the National Hospital and assessed in Cox models providing 6-week mortality rate ratios (MRRs) and hospitalization incidence rate ratios (IRRs)., Results: By age 6 weeks, there were 140 and 130 admissions among neonates vaccinated with BCG-Denmark and BCG-Russia, respectively (IRR, 1.08 [95% confidence interval {CI}, .84-1.37]). For BCG-Japan, there were 185 admissions vs 161 admissions for BCG-Russia (IRR, 1.15 [95% CI, .93-1.43]). The 6-week mortality did not differ: BCG-Denmark/BCG-Russia (MRR, 1.15 [95% CI, .74-1.80]); BCG-Japan/BCG-Russia (MRR, 0.71 [95% CI, .43-1.19]). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia., Conclusions: BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study., Clinical Trials Registration: NCT02447536., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: Receiving Bacille Calmette-Guérin (BCG)-Denmark vaccine at birth has been associated with ~40% reductions in all-cause neonatal mortality. We evaluated determinants of BCG skin reaction characteristics by age 2 months and tested the association with subsequent mortality., Methods: Prospective observational study amalgamating five trials providing BCG-at-birth that were conducted between 2002 and 2018 in Guinea-Bissau. The reaction status and size were evaluated at home-visits by 2 months of age among 6012 neonates; mortality from 2 to 12 months was assessed at subsequent visits. Reaction determinants were evaluated by binomial regression providing risk ratios (RRs). In Cox-models providing adjusted mortality rate ratios (aMRRs), we assessed the association between (1) having a 2-month reaction (yes/no) and (2) reaction size tertiles and subsequent all-cause mortality risk. A subgroup had their BCG reaction evaluated and were bled at age 4 weeks; their samples underwent in vitro analysis for specific and non-specific cytokine responses., Results: The BCG strain was the main determinant for developing a 2-month reaction and the reaction size: the BCG-Russia/BCG-Denmark RR for large-reaction was 0.38 (0.30-0.47) and the BCG-Russia/BCG-Japan RR was 0.61 (0.51-0.72). 5804 infants (96.5%) were reactors by age 2 months; 208 (3.5%) were non-reactors. The 2-12 months mortality risk was 4.8% (10/208) for non-reactors, 2.9% (64/2213) for small reactors, 1.8% (30/1710) for medium reactors and 0.8% (15/1881) for large reactors. The reactor/non-reactor aMRR was 0.49 (0.26-0.95) and there was a linear trend of decreasing mortality with increasing reaction size (p for trend <0.001). BCG reactors had higher 4-week specific and non-specific cytokine responses, responses that were highest among those with large reactions., Conclusion: Among BCG-vaccinated infants, having a BCG skin reaction by age 2 months was associated with markedly better survival, as was the reaction size. Our findings thus support that BCG has substantial effects on all-cause mortality. Emphasising at-birth vaccination with immunogenic BCG strains and revaccinating non-reactors and small reactors could have major public health benefits., Trial Registration Numbers: NCT00146302, NCT00168610, NCT00625482, NCT01989026 and NCT02447536., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The human immunodeficiency virus (HIV) remains a leading cause of maternal morbidity and mortality in Sub-Saharan Africa. Prevention of mother-to-child transmission (PMTCT) has proven an effective strategy to end paediatric infections and ensure HIV-infected mothers access treatment. Based on cross-sectional data collected from June 2008 to May 2013, we assessed changes in HIV prevalence, risk factors for HIV, provision of PMTCT antiretroviral treatment (ART), and the association between HIV infection, birth outcomes and maternal characteristics at the Simão Mendes National Hospital, Guinea-Bissau's largest maternity ward. Among 24,107 women, the HIV prevalence was 3.3% for HIV-1, 0.8% for HIV-2 and 0.9% for HIV-1/2. A significant decline in HIV-1, HIV-2, and HIV-1/2 prevalence was observed over time. HIV infection was associated with age and ethnicity. A total of 85% of HIV-infected women received ART as part of PMTCT, yet overall treatment coverage during labour and delivery declined significantly for both mothers and infants. Twenty-two percent of infants did not receive treatment, and 67% of HIV-2-infected mothers and 77% of their infants received ineffective non-nucleoside reverse transcriptase inhibitors for PMTCT. Maternal HIV was associated with low birth weight but not stillbirth. Inadequate continuity of care and ART coverage present challenges to optimal PMTCT in Guinea-Bissau.

Death from sepsis in the neonatal period remains a serious threat for millions. Within 3 days of administration, bacille Calmette-Guérin (BCG) vaccination can reduce mortality from neonatal sepsis in human newborns, but the underlying mechanism for this rapid protection is unknown. We found that BCG was also protective in a mouse model of neonatal polymicrobial sepsis, where it induced granulocyte colony-stimulating factor (G-CSF) within hours of administration. This was necessary and sufficient to drive emergency granulopoiesis (EG), resulting in a marked increase in neutrophils. This increase in neutrophils was directly and quantitatively responsible for protection from sepsis. Rapid induction of EG after BCG administration also occurred in three independent cohorts of human neonates., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Sub-Saharan Africa has the highest natural twinning rate in the world. Unfortunately, due to lack of adequate care during pregnancy, labor and postnatally, twin mortality in Sub-Saharan Africa also remains very high. Thus, it has been estimated that one in five twins dies during the childhood years. In spite of this, surprisingly few twin studies have been conducted in the region, making additional epidemiological data much needed. In 2009, we established one of the first twin registries in Sub-Saharan Africa at the Bandim Health Project in Guinea-Bissau. The registry had two main objectives. First, we wanted to describe the twinning rate and mortality patterns among newborn twins, including mortality risk factors and hospitalization patterns. Such studies can help the local clinicians improve twin health by identifying the most vulnerable children. Second, and in light of the rapidly increasing diabetes rates in Africa, we wanted to use the registry to particularly focus on metabolic disorders. Twins are often born with low birth weight, which according to the 'thrifty phenotype hypothesis' could predispose them to metabolic disorders later in life. Yet, no such 'fetal programming' data have previously been available from African twins despite the fact that nutritional patterns and influences from other factors (e.g., infections) could be markedly different here compared to high-income settings. In this article, we summarize the findings and current status of the Guinea-Bissau twin registry.

Background: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa., Methods: Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for β-lactamase were performed on all pathogens., Results: Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity., Conclusions: Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.