An expert review of environmental heat exposure and stillbirth in the face of climate change: Clinical implications and priority issues.

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.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Africa: Current Considerations and Future Projections.

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.

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

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.

Priorities in reducing child mortality: Azithromycin and other interventions.

In this Perspective, David Mabey and colleagues discuss a recent PLOS Medicine article on azithromycin as an intervention for reducing child mortality.

Applying the WHO ICD-PM classification system to stillbirths in a major referral Centre in Northeast Nigeria: a retrospective analysis from 2010-2018.

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.

Community-acquired Invasive Bacterial Disease in Urban Gambia, 2005-2015: A Hospital-based Surveillance.

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.

Vaccines for preventing invasive salmonella infections in people with sickle cell disease.

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.

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.

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.

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

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.

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.

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 and www.ClinicalTrials.gov (05 January 2010).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 24 September 2014. 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.

Vaccines for preventing invasive salmonella infections in people with sickle cell disease.

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.Date of most recent searches: 05 May 2015. 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.

Early-versus late-onset sepsis in neonates - time to shift the paradigm?

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.

Assessing the impact of a cleaning programme on environmental hygiene in labour and neonatal wards: an exploratory study in The Gambia.

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.

Timeliness of routine childhood vaccination among 12-35 months old children in The Gambia: Analysis of national immunisation survey data, 2019-2020.

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.

Mapping the timeliness of routine childhood vaccination in The Gambia: A spatial modelling study.

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-km2 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.

Maternal colonization and early-onset neonatal bacterial sepsis in the Gambia, West Africa: a genomic analysis of vertical transmission.

OBJECTIVES: To define bacterial aetiology of neonatal sepsis and estimate the prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs. METHODS: We carried out a cross-sectional study of newborns with clinical sepsis admitted to three hospitals in the Gambia neonatal wards. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically-matched paired neonatal blood cultures and maternal genital tract bacterial isolates. RESULTS: We enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0-6 after birth) of which 26% (36/137) were because of a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis because of Staphylococcus aureus (n = 5), Klebsiella pneumonia (n = 2), and Enterococcus faecalis (n = 1), phenotypically matched their maternal genital tract isolates. Pairwise single-nucleotide variants comparisons showed differences of 12 to 52 single-nucleotide variants only between maternal and newborn S. aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36). CONCLUSIONS: We found a low prevalence of vertical transmission of maternal genital tract colonization in maternal-newborn pairs for early-onset neonatal sepsis in the West African context. Identifying infection acquisition pathways among newborns is essential to prioritize preventive interventions, which could be targeted at the mother or infection control in the hospital environment, depending on the major pathways of transmission.

Using an Antibiogram Profile to Improve Infection Control and Rational Antimicrobial Therapy in an Urban Hospital in The Gambia, Strategies and Lessons for Low- and Middle-Income Countries.

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.

Impact of the COVID-19 pandemic on the coverage and timeliness of routine childhood vaccinations in the Gambia, 2015-2021.

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.

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.

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. 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 and www.ClinicalTrials.gov (05 January 2010).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 09 February 2012. 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 initial search. Of these, 15 were not suitable for inclusion in this review and one study is awaiting further assessment. 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.