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Abstract Background HIV infection among children, particularly those under 24 months of age, is often rapidly progressive; as a result guidelines recommend earlier access to combination antiretroviral therapy (cART) for HIV infected children. Losses to follow-up (LTFU) and death in the interval between diagnosis and initiation of ART profoundly limit this strategy. This study explores correlates of LTFU and death prior to ART initiation among children. Methods The study is based on 337 HIV-infected children enrolled into care at an urban centre in The Gambia, including those alive and in care when antiretroviral therapy became available and those who enrolled later. Children were followed until they started ART, died, transferred to another facility, or were LTFU. Cox proportional hazards regression models were used to determine the hazard of death or LTFU according to the baseline characteristics of the children. Results Overall, 223 children were assessed as eligible for ART based on their clinical and/or immunological status among whom 73 (32.7%) started treatment, 15 (6.7%) requested transfer to another health facility, 105 (47.1%) and 30 (13.5%) were lost to follow-up and died respectively without starting ART. The median survival following eligibility for children who died without starting treatment was 2.8 months (IQR: 0.9 - 5.8) with over half (60%) of all deaths occurring at home. ART-eligible children less than 2 years of age and those in WHO stage 3 or 4 were significantly more likely to be LTFU when compared with their respective comparison groups. The overall pre-treatment mortality rate was 25.7 per 100 child-years of follow-up (95% CI 19.9 - 36.8) and the loss to programme rate was 115.7 per 100 child-years of follow-up (95% CI 98.8 - 137). In the multivariable Cox proportional hazard model, significant independent predictors of loss to programme were being less than 2 years of age and WHO stage 3 or 4. The Adjusted Hazard Ratio (AHR) for loss to programme was 2.06 (95% CI 1.12 – 3.83) for being aged less than 2 years relative to being 5 years of age or older and 1.92 (95% CI 1.05 - 3.53) for being in WHO stage 3 or 4 relative to WHO stage 1 or 2. Conclusions Earlier enrolment into HIV care is key to achieving better outcomes for HIV infected children in developing countries. Developing strategies to ensure early diagnosis, elimination of obstacles to prompt initiation of therapy and instituting measures to reduce losses to follow-up, will improve the overall outcomes of HIV-infected children.

Abstract Background There is little data on responses to combination antiretroviral therapy (cART) among HIV-infected children in the West African region. We describe treatment outcomes among HIV-1 and HIV-2 infected children initiating cART in a research clinic in The Gambia, West Africa. Methods All treatment naive HIV-infected children who initiated cART according to the WHO ART guidelines for children between October 2004 and December 2009 were included in the analysis. Kaplan-Meir estimates and sign-rank test were used to investigate the responses to treatment. Results 65 HIV-1 and five HIV-2 infected children aged 10 copies/ml (4.4 – 6.0) respectively. The median age at treatment initiation of the five HIV-2 infected children was 12 years (range: 4.6 – 14.0) while their median baseline CD4+ T cell count and HIV-2 viral load were 140 cells/mm3 (Range: 40 – 570 cells/mm3) and 4.5 log10copies/mL (Range: 3.1 - 4.9 log10copies/mL) respectively. Among HIV-1 infected children P = 0.0004), 21% (15 – 22; P = 0.005) and 15% (15 – 25; P = 0.0422) respectively, while the median (IQR) increase in absolute CD4 T cell count from baseline to 12, 24 and 36 months for those ≥5 years at ART initiation were 470 cells/mm3 (270 – 650; P = 0.0005), 230 cells/mm3 (30 – 610; P = 0.0196) and 615 cells/mm3 (250 – 1060; P = 0.0180) respectively. The proportions of children achieving undetectable HIV-1 viral load at 6-, 12-, 24- and 36 months of treatment were 24/38 (63.2%), 20/36 (55.6%), 8/22 (36.4%) and 7/12 (58.3%) respectively. The probability of survival among HIV-1 infected children after 12 months on ART was 89.9% (95% CI 78.8 – 95.3). CD4 T cell recovery was sub-optimal in all the HIV-2 infected children and none achieved virologic suppression. Two of the HIV-2 infected children died within 6 months of starting treatment while the remaining three were lost to follow-up. Conclusions The beneficial effects of cART among HIV-1 infected children in our setting are sustained in the first 24 months of treatment with a significant improvement in survival experience up to 36 months; however the outcome was poor in the few HIV-2 infected children initiated on cART.

Abstract Background High early mortality rate among HIV infected patients following initiation of antiretroviral therapy (ART) in resource limited settings may indicate high pre-treatment mortality among ART-eligible patients. There is dearth of data on pre-treatment mortality in ART programmes in sub-Sahara Africa. This study aims to determine pre-treatment mortality rate and predictors of pre-treatment mortality among ART-eligible adult patients in a West Africa clinic-based cohort. Methods All HIV-infected patients aged 15 years or older eligible for ART between June 2004 and September 2009 were included in the analysis. Assessment for eligibility was based on the Gambia ART guideline. Survival following ART-eligibility was determined by Kaplan-Meier estimates and predictors of pre-treatment mortality determined by Cox proportional hazard models. Result Overall, 790 patients were assessed as eligible for ART based on their clinical and/or immunological status among whom 510 (64.6%) started treatment, 26 (3.3%) requested transfer to another health facility, 136 (17.2%) and 118 (14.9%) were lost to follow-up and died respectively without starting ART. ART-eligible patients who died or were lost to follow-up were more likely to be male or to have a CD4 T-cell count < 100 cells/μL, while patients in WHO clinical stage 3 or 4 were more likely to die without starting treatment. The overall pre-treatment mortality rate was 21.9 deaths per 100 person-years (95% CI 18.3 - 26.2) and the rate for the composite end point of death or loss to follow-up was 47.1 per 100 person-years (95% CI 41.6 - 53.2). Independent predictors of pre-treatment mortality were CD4 T-cell count Conclusion Approximately one third of ART-eligible patients did not start ART and pre-treatment mortality rate was found high among HIV infected patients in our cohort. CD4 T-cell count

Abstract Background Nigeria's national standard has recently moved to artemisinin combination treatments for malaria. As clinicians in the private sector are responsible for attending a large proportion of the population ill with malaria, this study compared prescribing in the private and public sector in one State in Nigeria prior to promoting ACTs. Objective To assess prescribing for uncomplicated malaria in government and private health facilities in Cross River State. Method Audit of 665 patient records at six private and seven government health facilities in 2003. Results Clinicians in the private sector were less likely to record history or physical examination than those in public facilities, but otherwise practice and prescribing were similar. Overall, 45% of patients had a diagnostic blood slides; 77% were prescribed monotherapy, either chloroquine (30.2%), sulphadoxine-pyrimethamine (22.7%) or artemisinin derivatives alone (15.8%). Some 20.8% were prescribed combination therapy; the commonest was chloroquine with sulphadoxine-pyrimethamine. A few patients (3.5%) were prescribed sulphadoxine-pyrimethamine-mefloquine in the private sector, and only 3.0% patients were prescribed artemisinin combination treatments. Conclusion Malaria treatments were varied, but there were not large differences between the public and private sector. Very few are following current WHO guidelines. Monotherapy with artemisinin derivatives is relatively common.

Surveillance is essential in the fight against antimicrobial resistance (AMR), to monitor the extent of resistance, inform prevention, control measures, and evaluate intervention progress. Traditional surveillance methods based on phenotypic antimicrobial susceptibility data offer important but limited insights into resistance mechanisms, transmission networks, and spread patterns of resistant bacterial strains. Fortunately, genomic technologies are increasingly accessible and can overcome these limitations. Genomics has the potential to advance traditional bacteriology in routine diagnosis and surveillance, it often relies on the initial isolation of bacterial strains from clinical specimens using conventional culture methods. Culture-based phenotypic characteristics are essential for making inferences about newly recognized genomic patterns. The Africa CDC Pathogen Genomics Initiative (Africa PGI) aims to enhance disease surveillance and public health partnerships through integrated, cross-continent laboratory networks equipped with the tools, human resource capacity and data infrastructure to fully leverage critical genomic sequencing technologies. For genomic surveillance of AMR, it is essential to optimize routine clinical microbiology laboratory services that are weak in many African countries. In this review, we outline shortcomings in clinical microbiology laboratories across Africa that compromise pathogen genomic epidemiology. We emphasize the necessity of investing in bacteriology and enhancing leadership capacity to fully capitalize on the advantages offered by genomic antimicrobial resistance (AMR) surveillance., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Achieving the ambitious goals of the Immunisation Agenda 2030 (IA2030) requires a deeper understanding of factors influencing under-vaccination, including timely vaccination. This study investigates the demand- and supply-side determinants influencing the timely uptake of key childhood vaccines scheduled throughout the first year of life in The Gambia., Methods: We used two nationally-representative datasets: the 2019-20 Gambian Demographic and Health Survey and the 2019 national immunisation facility mapping. Using Bayesian multi-level binary logistic regression models, we identified key factors significantly associated with timely vaccination for five key vaccines: birth dose of hepatitis-B (HepB0), first, second, and third doses of the pentavalent vaccine (Penta1, Penta2, Penta3), and first-dose of measles-containing vaccine (MCV1) in children aged 12-35 months. We report the adjusted Odds Ratios (aORs) and 95 % Credible Intervals (95 % CIs) in each case., Results: We found that demand-side factors, such as ethnicity, household wealth status, maternal education, maternal parity, and the duration of the household's residency in its current location, were the most common drivers of timely childhood vaccination. However, supply-side factors such as travel time to the nearest immunisation clinic, availability of cold-storage and staffing numbers in the nearest immunisation clinic were also significant determinants. Furthermore, the determinants varied across specific vaccines and the timing of doses. For example, delivery in a health facility (aOR = 1.58, 95 %CI: 1.02-2.53), living less than 30 min (aOR = 2.11, 95 %CI: 1.2-8.84) and living between 30 and 60 min (aOR = 3.68, 95 %CI: 1.1-14.99) from a fixed-immunisation clinic was associated with timely HepB0, a time-sensitive vaccine that must be administered within 24 h of birth. On the other hand, children who received Penta1 and Penta2 on time were three- to five-fold more likely to receive subsequent doses on time (Penta2 and Penta3, respectively). Finally, proximity to an immunisation facility with functional vaccine cold-storage was a significant supply-side determinant of timely MCV1 (aOR = 1.4, 95 %CI: 1.09-1.99)., Conclusions: These findings provide valuable insights for programme managers and policymakers. By prioritising interventions and allocating scarce resources based on these identified determinants, they can maximize their impact and ensure children in The Gambia receive timely vaccinations throughout their first year of life, contributing to IA2030 goals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Oghenebrume Wariri reports financial support was provided by European and Developing Countries Clinical Trials Partnership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Competing Interests: Competing interests: BG, CF, KP, NES, FF, SM-C, UO, JC, EM, EP, KI, DS, DG, RK, BEN, BB, CK-C, TW, LL and SL-M have no competing interests related to this manuscript to disclose. STJ has received grants from sub-Saharan Africa ConsorTium for the Advancement of Innovative Research and Care in Sepsis (STAIRS), funded by German Federal Ministry of Education and Research (BMBF), and African Research Collaboration on Sepsis (ARCS), funded by UK National Institute for Health and Care Research. STJ is co-founder and Board Member of Walimu, a Ugandan NGO, a Board and Executive Committee Member of the Global Sepsis Alliance and Secretary General and Board and Executive Committee Member of the African Sepsis Alliance. NK is President of the Global Sepsis Alliance. AS has a patent planned for machine learning tool for research support. YBN is staff member of the World Health Organization. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

Background: Effective surface cleaning in hospitals is crucial to prevent the transmission of pathogens. However, hospitals in low- and middle-income countries face cleaning challenges due to limited resources and inadequate training., Methods: We assessed the effectiveness of a modified TEACH CLEAN programme for trainers in reducing surface microbiological contamination in the newborn unit of a tertiary referral hospital in The Gambia. We utilised a quasi-experimental design and compared data against those from the labour ward. Direct observations of cleaning practices and key informant interviews were also conducted to clarify the programme's impact., Results: Between July and September 2021 (pre-intervention) and October and December 2021 (post-intervention), weekly surface sampling was performed in the newborn unit and labour ward. The training package was delivered in October 2021, after which their surface microbiological contamination deteriorated in both clinical settings. While some cleaning standards improved, critical aspects such as using fresh cleaning cloths and the one-swipe method did not. Interviews with senior departmental and hospital management staff revealed ongoing challenges in the health system that hindered the ability to improve cleaning practices, including COVID-19, understaffing, disruptions to water supply and shortages of cleaning materials., Conclusions: Keeping a hospital clean is fundamental to good care, but training hospital cleaning staff in this low-income country neonatal unit failed to reduce surface contamination levels. Further qualitative investigation revealed multiple external factors that challenged any possible impact of the cleaning programme. Further work is needed to address barriers to hospital cleaning in low-income hospitals., (© 2024. The Author(s).)

Exposure to extreme heat in pregnancy increases the risk of stillbirth. Progress in reducing stillbirth rates has stalled, and populations are increasingly exposed to high temperatures and climate events that may further undermine health strategies. This narrative review summarises the current clinical and epidemiological evidence of the impact of maternal heat exposure on stillbirth risk. Out of 20 studies, 19 found an association between heat and stillbirth risk. Recent studies based in low- to middle-income countries and tropical settings add to the existing literature to demonstrate that all populations are at risk. Additionally, both short-term heat exposure and whole-pregnancy heat exposure increase the risk of stillbirth. A definitive threshold of effect has not been identified, as most studies define exposure as above the 90th centile of the usual temperature for that population. Therefore, the association between heat and stillbirth has been found with exposures from as low as >12.64°C up to >46.4°C. The pathophysiological pathways by which maternal heat exposure may lead to stillbirth, based on human and animal studies, include both placental and embryonic or fetal impacts. Although evidence gaps remain and further research is needed to characterise these mechanistic pathways in more detail, preliminary evidence suggests epigenetic changes, alteration in imprinted genes, congenital abnormalities, reduction in placental blood flow, size and function all play a part. Finally, we explore this topic from a public health perspective; we discuss and evaluate the current public health guidance on minimising the risk of extreme heat in the community. There is limited pregnancy-specific guidance within heatwave planning, and no evidence-based interventions have been established to prevent poor pregnancy outcomes. We highlight priority research questions to move forward in the field and specifically note the urgent need for evidence-based interventions that are sustainable., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Neonatal sepsis is traditionally classified as early-onset sepsis (EOS) and late-onset sepsis (LOS) disease categories. This paradigm was based on observed epidemiological data from high income settings. However, increasing availability of microbiology results from diverse settings challenges these assumptions, necessitating re-examination of neonatal sepsis classifications., Objectives: To review the literature describing the aetiology of EOS and LOS in hospitalized neonates with stratification of pathogen spectrum by low- (LIC), middle- (MIC) and high-income (HIC) country settings, to critically re-examine the continued appropriateness of the 'EOS vs. LOS' sepsis paradigm in all settings., Sources: PubMed was searched for peer-reviewed English full-text articles published from inception up until 8 August 2022., Content: Studies often report on either EOS or LOS, rather than both. We identified only 49 original articles reporting on pathogen distribution of both EOS and LOS in the same hospital setting. Clear differences in sepsis aetiology were shown between LIC, MIC and HIC settings, with increasing importance of Klebsiella pneumoniae and decreasing importance of Group B Streptococcus in the first 72 hours of life in LIC and MIC., Implications: The concept of 'EOS vs. LOS' may be less useful for predicting the pathogen spectrum of neonatal sepsis in LIC and MIC, but the paradigm has shaped reporting of neonatal sepsis, and our understanding. Future neonatal sepsis reporting should utilize strengthening the reporting of observational studies in epidemiology for newborn infection (STROBE-NI) reporting guidelines and clearly describe timing of infection by day, and variation in pathogen spectrum across the neonatal period. Data identified in this review challenge the generalizability of the prevailing EOS/LOS paradigm in LIC and MIC., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: The COVID-19 pandemic caused widespread morbidity and mortality and resulted in the biggest setback in routine vaccinations in three decades. Data on the impact of the pandemic on immunisation in Africa are limited, in part, due to low-quality routine or administrative data. This study examined coverage and timeliness of routine childhood immunisation during the pandemic in The Gambia, a country with an immunisation system considered robust., Methods: We obtained prospective birth cohort data of 57 286 children in over 300 communities in two health and demographic surveillance system sites, including data from the pre-pandemic period (January 2015-February 2020) and the three waves of the pandemic period (March 2020-December 2021). We determined monthly coverage and timeliness (early and delayed) of the birth dose of hepatitis B vaccine (HepB0) and the first dose of pentavalent vaccine (Penta1) during the different waves of the pandemic relative to the pre-pandemic period. We implemented a binomial interrupted time-series regression model., Result: We observed no significant change in the coverage of HepB0 and Penta1 vaccinations from the pre-pandemic period up until the periods before the peaks of the first and second waves of the pandemic in 2020. However, there was an increase in HepB0 coverage before as well as after the peak of the third wave in 2021 compared with the pre-pandemic period (pre-third wave peak OR = 1.83, 95% CI 1.06 to 3.14; post-third wave period OR=2.20, 95% CI 1.23 to 3.92). There was some evidence that vaccination timeliness changed during specific periods of the pandemic. Early Penta1 vaccination decreased by 70% (OR=0.30, 95% CI 0.12 to 0.78) in the period before the second wave, and delayed HepB0 vaccination decreased by 47% (OR=0.53, 95% CI 0.29 to 0.97) after the peak of the third wave in 2021., Conclusion: Despite the challenges of the COVID-19 pandemic, The Gambia's routine vaccination programme has defied the setbacks witnessed in other settings and remained resilient, with coverage increasing and timeliness improving during the second and third waves. These findings highlight the importance of having adequate surveillance systems to monitor the impact of large shocks to vaccination coverage and timeliness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Beate Kampmann’s research institute, the MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK, has received funding for maternal immunization studies. BK is the Director for the IMPRINT (Immunizing pregnant women and Infants) network and receives funding from MRC/UKRI. The remaining authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: Timeliness of routine vaccination shapes childhood infection risk and thus is an important public health metric. Estimates of indicators of the timeliness of vaccination are usually produced at the national or regional level, which may conceal epidemiologically relevant local heterogeneities and makeitdifficultto identify pockets of vulnerabilities that could benefit from targeted interventions. Here, we demonstrate the utility of geospatial modelling techniques in generating high-resolution maps of the prevalence of delayed childhood vaccination in The Gambia. To guide local immunisation policy and prioritize key interventions, we also identified the districts with a combination of high estimated prevalence and a significant population of affected infants., Methods: We used the birth dose of the hepatitis-B vaccine (HepB0), third-dose of the pentavalent vaccine (PENTA3), and the first dose of measles-containing vaccine (MCV1) as examples to map delayed vaccination nationally at a resolution of 1 × 1-km 2 pixel. We utilized cluster-level childhood vaccination data from The Gambia 2019-20 Demographic and Health Survey. We adopted a fully Bayesian geostatistical model incorporating publicly available geospatial covariates to aid predictive accuracy. The model was implemented using the integrated nested Laplace approximation-stochastic partial differential equation (INLA-SPDE) approach., Results: We found significant subnational heterogeneity in delayed HepB0, PENTA3 and MCV1 vaccinations. Specificdistricts in the central and eastern regions of The Gambia consistentlyexhibited the highest prevalence of delayed vaccination, while the coastal districts showed alower prevalence forallthree vaccines. We also found that districts in the eastern, central, as well as in coastal parts of The Gambia had a combination of high estimated prevalence of delayed HepB0, PENTA3 and MCV1 and a significant population of affected infants., Conclusions: Our approach provides decision-makers with a valuable tool to better understand local patterns of untimely childhood vaccination and identify districts where strengthening vaccine delivery systems could have the greatest impact., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The Gambia's routine childhood vaccination programme is highly successful, however, many vaccinations are delayed, with potential implications for disease outbreaks. We adopted a multi-dimensional approach to determine the timeliness of vaccination (i.e., timely, early, delayed, and untimely interval vaccination). We utilised data for 3,248 children from The Gambia 2019-2020 Demographic and Health Survey. Nine tracer vaccines administered at birth and at two, three, four, and nine months of life were included. Timeliness was defined according to the recommended national vaccination windows and reported as both categorical and continuous variables. Routine coverage was high (above 90%), but also a high rate of untimely vaccination. First-dose pentavalent vaccine (PENTA1) and oral polio vaccine (OPV1) had the highest timely coverage that ranged from 71.8% (95% CI = 68.7-74.8%) to 74.4% (95% CI = 71.7-77.1%). Delayed vaccination was the commonest dimension of untimely vaccination and ranged from 17.5% (95% CI = 14.5-20.4%) to 91.1% (95% CI = 88.9-93.4%), with median delays ranging from 11 days (IQR = 5, 19.5 days) to 28 days (IQR = 11, 57 days) across all vaccines. The birth-dose of Hepatitis B vaccine had the highest delay and this was more common in the 24-35 months age group (91.1% [95% CI = 88.9-93.4%], median delays = 17 days [IQR = 10, 28 days]) compared to the 12-23 months age-group (84.9% [95% CI = 81.9-87.9%], median delays = 16 days [IQR = 9, 26 days]). Early vaccination was the least common and ranged from 4.9% (95% CI = 3.2-6.7%) to 10.7% (95% CI = 8.3-13.1%) for all vaccines. The Gambia's childhood immunization system requires urgent implementation of effective strategies to reduce untimely vaccination in order to optimize its quality, even though it already has impressive coverage rates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wariri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E . coli ( n = 315) S. aureus ( n = 232), and K. pneumoniae ( n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia.

The burden of severe Covid-19 has been relatively low in sib-Saharan Africa compared to Europe and the Americas. However, SARS-CoV-2 sero-prevalence data has demonstrated that there has been more widespread transmission than can be deduced from reported cases. This could be attributed to under reporting due to low testing capacity or high numbers of asymptomatic SARS-CoV-2 infection in communities. Recent data indicates that prior SARS-CoV-2 exposure is protective against reinfection and that vaccination of previously SARS-CoV-2 infected individuals induces robust cross-reactive antibody responses. Considering these data, calls for a need for a re-think of the COVID-19 vaccination strategy in sub-Saharan African settings with high SARSCoV-2 population exposure but limited available vaccine doses. A potential recommendation would be to prioritize rapid and widespread vaccination of the first dose, while waiting for more vaccines to become available., Competing Interests: Potential conflicts of interest. B. K. participates in a DSMB for a COVID-19 vaccine and has advised the COVAX group on use of COVID vaccines in pregnant women. She also directs the vaccine center at LSHTM and the IMPRINT network. She also holds several grants for vaccine research studies outside of COVID-19 vaccines. E. U. claims participation in a PaTs COVID drug trial and held a position on the National Immunisation Technical Advisory Group, The Gambia. I. A. received an African Research Leader Fellowship grant (MR/S005293/1) and NIHR-MPRU at UCL grant (2268427 LSHTM) and has also participated in the WHO Programme Advisory Group, Malaria Vaccine Implementation Programme, the WHO Technical Advisory Group, Respiratory Syncytial Virus, and WHO Africa Region, Regional Immunisation Technical Advisory Group. O. T. I. is currently an employee of Sanofi Pasteur. All views expressed are those of the author and do not reflect those of her employer. All other authors report no potential conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Empiric studies exploring the timeliness of routine vaccination in low-and middle-income countries (LMICs) have gained momentum in the last decade. Nevertheless, there is emerging evidence suggesting that these studies have key measurement and methodological gaps that limit their comparability and utility. Hence, there is a need to identify, and document these gaps which could inform the design, conduct, and reporting of future research on the timeliness of vaccination. We synthesised the literature to determine the methodological and measurement gaps in the assessment of vaccination timeliness in LMICs. We searched five electronic databases for peer-reviewed articles in English and French that evaluated vaccination timeliness in LMICs, and were published between 01 January 1978, and 01 July 2021. Two reviewers independently screened titles and abstracts and reviewed full texts of relevant articles, following the guidance framework for scoping reviews by the Joanna Briggs Institute. From the 4263 titles identified, we included 224 articles from 103 countries. China (40), India (27), and Kenya (23) had the highest number of publications respectively. Of the three domains of timeliness, the most studied domain was 'delayed vaccination' [99.5% (223/224)], followed by 'early vaccination' [21.9% (49/224)], and 'untimely interval vaccination' [9% (20/224)]. Definitions for early (seven different definitions), untimely interval (four different definitions), and delayed vaccination (19 different definitions) varied across the studies. Most studies [72.3% (166/224)] operationalised vaccination timeliness as a categorical variable, compared to only 9.8% (22/224) of studies that operationalised timeliness as continuous variables. A large proportion of studies [47.8% (107/224)] excluded the data of children with no written vaccination records irrespective of caregivers' recall of their vaccination status. Our findings show that studies on vaccination timeliness in LMICs has measurement and methodological gaps. We recommend the development and implement of guidelines for measuring and reporting vaccination timeliness to bridge these gaps., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2022 Wariri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Declaration of interests None to declare.

Background: Health care-associated infections (HCAI) in neonatal units in low- and middle-income countries (LMIC) are a major cause of mortality. This scoping review aimed to synthesise published literature on infection prevention and care bundles addressing neonatal HCAI in LMICs and to construct a Classification Framework for their components (elements)., Methods: Five electronic databases were searched between January 2001 and July 2020. A mixed-methods approach was applied: qualitative content analysis was used to build a classification framework to categorise bundle elements and the contents of the classification groups were then described quantitatively., Findings: 3619 records were screened, with 44 eligible studies identified. The bundle element Classification Framework created involved: (1) Primary prevention, (2) Detection , (3) Case management , and Implementation (3 + I ) . The 44 studies included 56 care bundles with 295 elements that were then classified. Primary prevention elements (128, 43%) predominated of which 71 (55%) focused on central line catheters and mechanical ventilators. Only 12 elements (4%) were related to detection . A further 75 (25%) elements addressed case management and 66 (88%) of these aimed at outbreak control., Interpretation: The 3 + I Classification Framework was a feasible approach to reporting and synthesising research for infection-relevant bundled interventions in neonatal units. A shift towards the use in infection prevention and care bundles of primary prevention elements focused on the neonate and on commonly used hospital devices in LMIC (e.g., self-inflating bags, suctioning equipment) would be valuable to reduce HCAI transmission. Detection elements were a major gap., Funding: This work was made possible in part by the John D. and Catherine T. MacArthur Foundation, the Bill & Melinda Gates Foundation, ELMA Philanthropies, The Children's Investment Fund Foundation UK, The Lemelson Foundation, and the Ting Tsung and Wei Fong Chao Foundation under agreements to William Marsh Rice University. The project leading to these results has also received the support of a fellowship from the "la Caixa" Foundation (ID 100010434). The fellowship code is LCF/BQ/EU19/11710040. EJAF is an Academic Clinical Fellow whose salary is funded by the UK National Institute for Health Research (NIHR). NES receives a Research Training Program Scholarship (Australian Commonwealth Government)., Competing Interests: We declare no competing interests., (© 2021 The Authors.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.

The literature on the timeliness of childhood vaccination (i.e. vaccination at the earliest appropriate age) in low-and middle-income countries has important measurement and methodological issues that may limit their usefulness and cross comparison. We aim to conduct a comprehensive scoping review to map the existing literature with a key focus on how the literature on vaccination timeliness has evolved, how it has been defined or measured, and what determinants have been explored in the period spanning the last four decades. This scoping review protocol was developed based on the guidance for scoping reviews from the Joanna Briggs Institute. We will include English and French language peer-reviewed publications and grey literature on the timeliness of routine childhood vaccination in low-and middle-income countries published between January 1978 through to 2021. A three-step search strategy that involves an initial search of two databases to refine the keywords, a full search of all included electronic databases, and screening of references of previous studies for relevant articles missing from our full search will be employed. The search will be conducted in five electronic databases: MEDLINE, EMBASE, Global Health, CINAHL and Web of Science. Google search will also be conducted to identify relevant grey literature on vaccination timeliness. All retrieved titles from the search will be imported into Endnote X9.3.3 (Clarivate Analytics) and deduplicated. Two reviewers will screen the titles, abstracts and full texts of publications for eligibility using Rayyan-the web based application for screening articles for systematic reviews. Using a tailored data extraction template, we will extract relevant information from eligible studies. The study team will analyse the extracted data using descriptive statistical methods and thematic analysis. The results will be presented using tables, while charts and maps will be used to aid the visualisation of the key findings and themes. The proposed review will generate evidence on key methodological gaps in the literature on timeliness of childhood vaccination. Such evidence would shape the direction of future research, and assist immunisation programme managers and country-level stakeholders to address the needs of their national immunisation system., Competing Interests: The authors have declared that no competing interests exist.

Health systems in sub-Saharan Africa have remained overstretched from dealing with endemic diseases, which limit their capacity to absorb additional stress from new and emerging infectious diseases. Against this backdrop, the rapidly evolving COVID-19 pandemic presented an additional challenge of insufficient hospital beds and human resource for health needed to deliver hospital-based COVID-19 care. Emerging evidence from high-income countries suggests that a 'virtual ward' (VW) system can provide adequate home-based care for selected patients with COVID-19, thereby reducing the need for admissions and mitigate additional stress on hospital beds. We established a VW at the Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine, a biomedical research institution located in The Gambia, a low-income west African country, to care for members of staff and their families infected with COVID-19. In this practice paper, we share our experience focusing on the key components of the system, how it was set up and successfully operated to support patients with COVID-19 in non-hospital settings. We describe the composition of the multidisciplinary team operating the VW, how we developed clinical standard operating procedures, how clinical oversight is provided and the use of teleconsultation and data capture systems to successfully drive the process. We demonstrate that using a VW to provide an additional level of support for patients with COVID-19 at home is feasible in a low-income country in sub-Saharan Africa. We believe that other low-income or resource-constrained settings can adopt and contextualise the processes described in this practice paper to provide additional support for patients with COVID-19 in non-hospital settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Globally, about 3-quarters of births now occur in healthcare facilities, with the proportion being 50% for sub-Saharan Africa, where healthcare-associated infections among newborns are typically 3-20 times higher than in facilities in high-income countries. As this upward trend in institutional deliveries continues, the demand for specialized neonatal care also rises, with dedicated units often only available in tertiary referral hospitals in the case of low- and middle-income countries. Preventing nosocomial infections among vulnerable newborns requires effective and feasible control strategies and interventions. The role of cleaning and cleaners in reducing risks and maintaining a clean safe environment has until very recently been neglected at policy, program, practice, and research levels. There is now an opportunity to reposition cleaning within global and national initiatives related to Water, Sanitation and Hygiene, Infection Prevention and Control, and Antimicrobial Resistance. The evidence base should also be strengthened on cost-effective bundles of cleaning interventions, particularly in the context of low-resource settings. Here increasing overcrowding and shortages of staff and supplies present major threats to neonatal survival and well-being and heighten the case for optimizing the use of low-cost, back-to-basics interventions like cleaning., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Gambia Demographic and Health Survey 2013 data showed that up to 63% of deliveries in the country occur in health facilities. Despite such a high rate, there are few facility-based studies on delivery outcomes in the country. This analysis ancillary to a randomized control trial describes occurrence of poor pregnancy outcomes in a cohort of women and their infants delivering in a government health facility in urban Gambia. Methods: Using clinical information obtained during the trial, we calculated rates of poor pregnancy outcomes including stillbirths, hospitalization and neonatal deaths. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) in the risk factors analysis. Results: Between April 2013 and 2014, 829 mothers delivered 843 babies, including 13 stillbirths [15.4 (7.1-23.8)] per 1,000 births. Among 830 live born infants, 7.6% ( n = 63) required hospitalization during the 8-week follow-up period. Most of these hospitalizations (74.6%) occurred during the early neonatal period (<7 days of life). Severe clinical infections (i.e., sepsis, meningitis and pneumonia) ( n = 27) were the most common diagnoses, followed by birth asphyxia ( n = 13), major congenital malformations ( n = 10), jaundice ( n = 6) and low birth weight ( n = 5). There were sixteen neonatal deaths, most of which also occurred during the early neonatal period. Overall, neonatal mortality rate (NMR) and perinatal mortality rate (PMR) were 19.3 (CI: 9.9-28.7) per 1,000 live births and 26.1 (CI: 15.3-36.9) per 1,000 total births, respectively. Severe clinical infections and birth asphyxia accounted for 37 and 31% of neonatal deaths, respectively. The risk of hospitalization was higher among neonates with severe congenital malformations, low birth weight, twin deliveries, and those born by cesarean section. Risk of mortality was higher among neonates with severe congenital malformations and twin deliveries. Conclusion: Neonatal hospitalization and deaths in our cohort were high. Although vertical interventions may reduce specific causes of morbidity and mortality, data indicate the need for a holistic approach to significantly improve the rates of poor pregnancy outcomes. Critically, a focus on decreasing the high rate of stillbirths is warranted. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01800942., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Camara, Oluwalana, Miyahara, Lush, Kampmann, Manneh, Okomo, D'Alessandro and Roca.)

Background: While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens., Methods: Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children <18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression., Results: Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics., Conclusions: Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Access to quality emergency obstetric and newborn care (EmONC); having a skilled attendant at birth (SBA); adequate antenatal care; and efficient referral systems are considered the most effective interventions in preventing stillbirths. We determined the influence of travel time from mother's area of residence to a tertiary health facility where women sought care on the likelihood of delivering a stillbirth. We carried out a prospective matched case-control study between 1st January 2019 and 31st December 2019 at the Federal Teaching Hospital Gombe (FTHG), Nigeria. All women who experienced a stillbirth after hospital admission during the study period were included as cases while controls were consecutive age-matched (ratio 1:1) women who experienced a live birth. We modelled travel time to health facilities. To determine how travel time to the nearest health facility and the FTHG were predictive of the likelihood of stillbirths, we fitted a conditional logistic regression model. A total of 318 women, including 159 who had stillborn babies (cases) and 159 age-matched women who had live births (controls) were included. We did not observe any significant difference in the mean travel time to the nearest government health facility for women who had experienced a stillbirth compared to those who had a live birth [9.3 mins (SD 7.3, 11.2) vs 6.9 mins (SD 5.1, 8.7) respectively, p = 0.077]. However, women who experienced a stillbirth had twice the mean travel time of women who had a live birth (26.3 vs 14.5 mins) when measured from their area of residence to the FTHG where deliveries occurred. Women who lived farther than 60 minutes were 12 times more likely of having a stillborn [OR = 12 (1.8, 24.3), p = 0.011] compared to those who lived within 15 minutes travel time to the FTHG. We have shown for the first time, the influence of travel time to a major tertiary referral health facility on the occurrence of stillbirths in an urban city in, northeast Nigeria., Competing Interests: The authors have declared that no competing interests exist.

In this Perspective, David Mabey and colleagues discuss a recent PLOS Medicine article on azithromycin as an intervention for reducing child mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: Sick newborns admitted to neonatal units in low-resource settings are at an increased risk of developing hospital-acquired infections due to poor clinical care practices. Clusters of infection, due to the same species, with a consistent antibiotic resistance profile, and in the same ward over a short period of time might be indicative of an outbreak. We used whole-genome sequencing (WGS) to define the transmission pathways and characterise two distinct outbreaks of neonatal bacteraemia in a west African neonatal unit., Methods: We studied two outbreaks of Burkholderia cepacia and multidrug-resistant extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae in a neonatal unit that provides non-intensive care on the neonatal ward in the Edward Francis Small Teaching Hospital, Banjul, The Gambia. We used WGS to validate and expand findings from the outbreak investigation. We retrospectively sequenced all clinical isolates associated with each outbreak, including isolates obtained from swabs of ward surfaces, environmental fluid cultures, intravenous fluids, and antibiotics administered to newborns. We also sequenced historical B cepacia isolates associated with neonatal sepsis in the same ward., Results: Between March 1 and Dec 31, 2016, 321 blood cultures were done, of which 178 (55%) were positive with a clinically significant isolate. 49 episodes of neonatal B cepacia bacteraemia and 45 episodes of bacteraemia due to ESBL-producing K pneumoniae were reported. WGS revealed the suspected K pneumoniae outbreak to be contemporaneous outbreaks of K pneumoniae (ST39) and previously unreported Klebsiella quasipneumoniae subspecies similipneumoniae (ST1535). Genomic analysis showed near-identical strain clusters for each of the three outbreak pathogens, consistent with transmission within the neonatal ward from extrinsically contaminated in-use intravenous fluids and antibiotics. Time-dated phylogeny, including retrospective analysis of archived bacterial strains, suggest B cepacia has been endemic in the neonatal ward over several years, with the Klebsiella species a more recent introduction., Interpretation: Our study highlights the emerging threat of previously unreported strains of multidrug-resistant Klebsiella species in this neonatal unit. Genome-based surveillance studies can improve identification of circulating pathogen strains, characterisation of antimicrobial resistance, and help understand probable infection acquisition routes during outbreaks in newborn units in low-resource settings. Our data provide evidence for the need to regularly monitor endemic transmission of bacteria within the hospital setting, identify the introduction of resistant strains from the community, and improve clinical practices to reduce or prevent the spread of infection and resistance., Funding: Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Lack of a unified and comparable classification system to unravel the underlying causes of stillbirth hampers the development and implementation of targeted interventions to reduce the unacceptably high stillbirth rates (SBR) in sub-Saharan Africa. Our aim was to track the SBR and the predominant maternal and fetal causes of stillbirths using the WHO ICD-PM Classification system., Methods: This was a retrospective observational study in a major referral centre in northeast Nigeria between 2010 and 2018. Specialist Obstetricians and Gynaecologists assigned causes of stillbirths after an extensive audit of available stillbirths' records. Cause of death was assigned via consensus using the ICD-PM classification system., Results: There were 21,462 births between 1 January 2010 and 31 December 2018 in our study setting; of these, 1177 culminated in stillbirths with a total hospital SBR of 55 per 1000 births (95% CI: 52, 58). There were two peaks of stillbirths in 2012 [62 per 1000 births (95% CI: 53, 71)], and 2015 [65 per 1000 births (95% CI, 55, 76)]. Antepartum and intrapartum stillbirths were almost equally prevalent (48% vs 52%). Maternal medical and surgical conditions (M4) were the commonest (69.3%) cause of antepartum stillbirths while complications of placenta, cord and membranes (M3) accounted for the majority (45.8%) of intrapartum stillbirths and the trends were similar between 2010 and 2018. Antepartum and intrapartum fetal causes of stillbirths were mainly due to prematurity which is a disorder of fetal growth (A5 and I6)., Conclusions: Most causes of stillbirths in our setting are due to preventable causes and the trends have remained unabated between 2010 and 2018. Progress toward global SBR targets are off-track, requiring more interventions to halt and reduce the high SBR.

Competing Interests: Competing interests: None declared.

Background: Aetiological data for neonatal infections are essential to inform policies and programme strategies, but such data are scarce from sub-Saharan Africa. We therefore completed a systematic review and meta-analysis of available data from the African continent since 1980, with a focus on regional differences in aetiology and antimicrobial resistance (AMR) in the past decade (2008-18)., Methods: We included data for microbiologically confirmed invasive bacterial infection including meningitis and AMR among neonates in sub-Saharan Africa and assessed the quality of scientific reporting according to Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI) checklist. We calculated pooled proportions for reported bacterial isolates and AMR., Findings: We included 151 studies comprising data from 84 534 neonates from 26 countries, almost all of which were hospital-based. Of the 82 studies published between 2008 and 2018, insufficient details were reported regarding most STROBE-NI items. Regarding culture positive bacteraemia or sepsis, Staphylococcus aureus, Klebsiella spp, and Escherichia coli accounted for 25% (95% CI 21-29), 21% (16-27), and 10% (8-10) respectively. For meningitis, the predominant identified causes were group B streptococcus 25% (16-33), Streptococcus pneumoniae 17% (9-6), and S aureus 12% (3-25). Resistance to WHO recommended β-lactams was reported in 614 (68%) of 904 cases and resistance to aminoglycosides in 317 (27%) of 1176 cases., Interpretation: Hospital-acquired neonatal infections and AMR are a major burden in Africa. More population-based neonatal infection studies and improved routine surveillance are needed to improve clinical care, plan health systems approaches, and address AMR. Future studies should be reported according to standardised reporting guidelines, such as STROBE-NI, to aid comparability and reduce research waste., Funding: Uduak Okomo was supported by a Medical Research Council PhD Studentship., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Invasive bacterial diseases cause significant disease and death in sub-Saharan Africa. Several are vaccine preventable, although the impact of new vaccines and vaccine policies on disease patterns in these communities is poorly understood owing to limited surveillance data., Methods: We conducted a hospital-based surveillance of invasive bacterial diseases in The Gambia where blood and cerebrospinal fluid (CSF) samples of hospitalized participants were processed. Three surveillance periods were defined in relation to the introduction of pneumococcal conjugate vaccines (PCVs), before (2005- 2009), during (2010-2011) and after (2012-2015) PCV introduction. We determined the prevalences of commonly isolated bacteria and compared them between the different surveillance periods., Results: A total of 14 715 blood and 1103 CSF samples were collected over 11 years; overall, 1045 clinically significant organisms were isolated from 957 patients (972 organisms [6.6%] from blood and 73 [6.6%] from CSF). The most common blood culture isolates were Streptococcus pneumoniae (24.9%), Staphylococcus aureus (22.0%), Escherichia coli (10.9%), and nontyphoidal Salmonella (10.0%). Between the pre-PCV and post-PCV eras, the prevalence of S. pneumoniae bacteremia dropped across all age groups (from 32.4% to 16.5%; odds ratio, 0.41; 95% confidence interval, .29-.58) while S. aureus increased in prevalence, becoming the most prevalent bacteria (from 16.9% to 27.2%; 1.75; 1.26-2.44). Overall, S. pneumoniae (53.4%), Neisseria meningitidis (13.7%), and Haemophilus influenzae (12.3%) were the predominant isolates from CSF. Antimicrobial resistance to common antibiotics was low., Conclusions: Our findings demonstrate that surveillance data on the predominant pathogens associated with invasive disease is necessary to inform vaccine priorities and appropriate management of patients., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Staphylococcus aureus is a major human pathogen. Panton-Valentine leukocidin (PVL) is a virulence factor produced by some strains that causes leukocyte lysis and tissue necrosis. PVL-associated S. aureus (PVL-SA) predominantly causes skin and soft-tissue infections (SSTIs) but can also cause invasive infections such as necrotizing pneumonia. It is carried by both community-associated methicillin susceptible S. aureus (CA-MSSA) and methicillin resistant S. aureus (CA-MRSA). This study aims to determine the prevalence of PVL-SA among patients seen at an urban Gambian hospital and associated antibiotic resistance. Methods: Archived clinical S. aureus (70 invasive bacteraemia and 223 non-invasive SSTIs) from 293 patients were retrieved as well as relevant data from clinical records where available. Antibiotic susceptibility was assessed using disc diffusion according to Clinical Laboratory Standards Institute (CLSI) guidelines. Genomic DNA was extracted and the presence of lukF and lukS PVL genes was detected by conventional gel-based PCR. Result: PVL-SA strains accounted for 61.4% (180/293) of S. aureus isolates. PVL prevalence was high in both Gambian bacteraemia and SSTIs S. aureus strains. Antimicrobial resistance was low and included chloramphenicol (4.8%), cefoxitin (2.4%), ciprofloxacin (3.8%), erythromycin (8.9%), gentamicin (5.5%) penicillin (92.5%), tetracycline (41.0%), and sulfamethoxazole-trimethoprim (24.2%). There was no association of PVL with antimicrobial resistance. Conclusion: PVL expression is high among clinical S. aureus strains among Gambian patients. Reporting of PVL-SA clinical infections is necessary to enable the monitoring of the clinical impact of these strains in the population and guide prevention of the spread of virulent PVL-positive CA-MRSA strains. SUMMARY   Staphylococcus aureus ( S. aureus ) is a major human pathogen with several virulence factors. We performed a retrospective analysis to investigate the prevalence of one such virulence factor (PVL) amongst clinical S. aureus samples. We found a high prevalence in our setting but antimicrobial resistance including methicillin resistance was low.

Background: Salmonella infections are a common bacterial cause of invasive disease in people with sickle cell disease especially children, and are associated with high morbidity and mortality rates. Although available in some centres, people with sickle cell anaemia are not routinely immunized with salmonella vaccines. This is an update of a previously published Cochrane Review., Objectives: To determine whether routine administration of salmonella vaccines to people with sickle cell disease reduces the morbidity and mortality associated with infection., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted a search of the LILACS database and the World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch) and ClinicalTrials.gov (www.clinicaltrials.gov).Date of most recent searches: 17 October 2018., Selection Criteria: We planned to select all randomized controlled trials that compared the use of either the inactivated vaccine or an oral attenuated vaccine with a placebo among people with sickle cell disease. Equally, studies that compared the efficacy of one vaccine type over another were to be selected for the review., Data Collection and Analysis: No trials of salmonella vaccines in people with sickle cell disease were found., Main Results: There is an absence of randomized controlled trial evidence relating to the scope of this review., Authors' Conclusions: It is expected that salmonella vaccines may be useful in people with sickle cell disease, especially in resource-poor settings where the majority of those who suffer from the condition are found. Unfortunately, there are no randomized controlled trials on the efficacy and safety of the different types of salmonella vaccines in people with sickle cell disease. We conclude that there is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of the different types of salmonella vaccines as a means of improving survival and decreasing mortality from salmonella infections in people with sickle cell disease. However, we believe that there are unlikely to be any trials published in this area, therefore, this review will no longer be regularly updated.

Background: Treating vaso-occlusive painful crises in people with sickle cell disease is complex and requires multiple interventions. Extra fluids are routinely given as adjunct treatment, regardless of the individual's state of hydration with the aim of slowing or stopping the sickling process and thereby alleviating pain. This is an update of a previously published Cochrane Review., Objectives: To determine the optimal route, quantity and type of fluid replacement for people with sickle cell disease with acute painful crises., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted searches of Embase (November 2007), LILACS, www.ClinicalTrials.gov (05 January 2010), and the WHO ICTRP (30 June 2017).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 16 February 2017., Selection Criteria: Randomised and quasi-randomised controlled trials that compared the administration of supplemental fluids adjunctive to analgesics by any route in people with any type of sickle cell disease during an acute painful episode, under medical supervision (inpatient, day care or community)., Data Collection and Analysis: No relevant trials have yet been identified., Main Results: Sixteen trials were identified by the searches, all of which were not eligible for inclusion in the review., Authors' Conclusions: Treating vaso-occlusive crises is complex and requires multiple interventions. Extra fluids, generally oral or intravenous, are routinely administered during acute painful episodes to people with sickle cell disease regardless of the individual's state of hydration. Reports of their use during these acute painful episodes do not state the efficacy of any single route, type or quantity of fluid compared to another. However, there are no randomised controlled trials that have assessed the safety and efficacy of different routes, types or quantities of fluid. This systematic review identifies the need for a multicentre randomised controlled trial assessing the efficacy and possible adverse effects of different routes, types and quantities of fluid administered to people with sickle cell disease during acute painful episodes.

Background: Female sexual dysfunction is the persistent or recurring decrease in sexual desire or arousal, the difficulty or inability to achieve an orgasm, and/or the feeling of pain during sexual intercourse. Impaired sexual function can occur with all types of female genital mutilation (FGM) owing to the structural changes, pain, or traumatic memories associated with the procedure., Objectives: To conduct a systematic review of randomized and nonrandomized studies into the effects of sexual counseling with or without genital lubricants on the sexual function of women living with FGM., Search Strategy: Cochrane Central Register of Controlled Trials, MEDLINE, African Index Medicus, SCOPUS, LILACS, CINAHL, ClinicalTrials.gov, Pan African Clinical Trials Registry, and other databases were searched to August 2015. The reference lists of retrieved studies were checked for reports of additional studies, and lead authors contacted for additional data., Selection Criteria: Studies of girls and women living with any type of FGM who received counselling interventions for sexual dysfunction were included., Data Collection and Analysis: No relevant studies that addressed the objective of the review were identified., Conclusions: Despite a comprehensive search, the authors could not find evidence of the effects of sexual counseling on the sexual function of women living with FGM. Studies assessing this intervention are needed., Prospero Registration: CRD42015024593., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Counselling is a routine practice done before deinfibulation in women with type III female genital mutilation (FGM). However, cultural and social pressures, in addition to maladaptation to the changes in the body post deinfibulation, cause some women to choose to be reinfibulated after being deinfibulated., Objective: To conduct a systematic review of the impact of counselling prior to deinfibulation on patient satisfaction, marital satisfaction, and rate of requests for reinfibulation among women living with type III FGM. The secondary aim was to assess the impact of male partner involvement in counselling on patient satisfaction, marital satisfaction, and rate of requests for reinfibulation., Search Strategy: Major databases including Cochrane Central Register of Controlled Trials, Medline, SCOPUS, and ClinicalTrials.gov were searched until August 2015., Selection Criteria: Studies comparing women with type III FGM who received counselling before deinfibulation versus no counselling were included., Data Collection and Analysis: Two team members independently screened and collected data., Results: No eligible studies were identified., Conclusion: There is no evidence to conclude that counselling before deinfibulation influences patients' satisfaction with overall quality of care or rates of request for reinfibulation., Prospero Registration: CRD42015024675., (© 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Introduction: Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to one third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease., Methods and Outcomes: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2015 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview)., Results: At this update, searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations., Conclusions: In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antibiotic prophylaxis in children aged under 5 years, antibiotic prophylaxis in children aged 5 years or older, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines.

Background: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%)., Methods and Findings: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner., Conclusions: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children., Trial Registration: Pan African Clinical Trials Registry PACTR201102000277177.