Conducting clinical research in a resource-constrained setting: lessons from a longitudinal cohort study in The Gambia.

Clinical research conducted to Good Clinical Practice (GCP) standards is increasingly being undertaken in resource-constrained low-income and middle-income countries (LMICs) settings. This presents unique challenges that differ from those faced in high-income country (HIC) contexts, due to a dearth of infrastructure and unique socio-cultural contexts. Field experiences by research teams working in these LMIC contexts are thus critical to advancing knowledge on successful research conduct in these settings. The Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine has operated in The Gambia, a resource-constrained LMIC for over 70 years and has developed numerous research support platforms and systems. The unit was the lead clinical collaborator in a recently completed Expanded Program on Immunization Consortium (EPIC) study, involving a multicountry collaboration across five countries including the USA, Canada, Belgium, Papua New Guinea and The Gambia. The EPIC study recruited and completed follow-up of 720 newborn infants over 2 years. In this paper, we provide in-depth field experience covering challenges faced by the Gambian EPIC team in the conduct of this study. We also detail some reflections on these challenges. Our findings are relevant to the international research community as they highlight practical day-to-day challenges in conducting GCP standard clinical research in resource-constrained LMIC contexts. They also provide insights on how study processes can be adapted early during research planning to mitigate challenges

COVID-19 reinfections in The Gambia by phylogenetically distinct SARS-CoV-2 variants-first two confirmed events in west Africa.

At the beginning of the COVID-19 pandemic, in early 2020, the scientific community hypothesised that SARS-CoV-2 transmission would eventually be hindered by herd immunity, conferred by natural infection, vaccination, or both.1 However, essential questions about whether infection with SARS-CoV-2 confers protection against reinfection and the length of time the protection lasts after either infection or vaccination remain open. These answers are crucial for the development of appropriate health control measures worldwide and become more important as new viral variants spread

Estimating Need for Glasses and Hearing Aids in The Gambia: Results from a National Survey and Comparison of Clinical Impairment and Self-Report Assessment Approaches.

Few estimates are available of the need for assistive devices (ADs) in African settings. This study aimed to estimate population-level need for glasses and hearing aids in The Gambia based on (1) clinical impairment assessment, and (2) self-reported AD awareness, and explore the relationship between the two methods. The Gambia 2019 National Eye Health Survey is a nationally representative population-based sample of 9188 adults aged 35+ years. Participants underwent standardised clinical vision assessments including the need for glasses (distance and near). Approximately 25% of the sample underwent clinical assessment of hearing and hearing aid need. Data were also collected on self-reported awareness, need and access barriers to vision and hearing ADs. Overall, 5.6% of the study population needed distance glasses (95% CI 5.0-6.3), 45.9% (95% CI 44.2-47.5) needed near glasses and 25.5% (95% CI 22.2-29.2) needed hearing aids. Coverage for each AD was very low (<4%). The agreement between self-report and clinical impairment assessment for AD need was poor. In conclusion, there is high prevalence and very low coverage for distance glasses, near glasses and hearing aids in The Gambia. Self-report measures alone will not provide an accurate estimate of AD need

Prevention and treatment for COVID-19 associated severe pneumonia in the Gambia (PaTS-COVID-19), a single-blinded randomized clinical trial: study protocol

Background: The coronavirus disease (COVID-19) pandemic resulted in an unprecedent global response for the development of COVID-19 vaccines. However, as viral mutations continue to occur, potentially decreasing the efficacy of currently available vaccines, and inequity of vaccine access continues, identifying safe and effective drugs to minimise severity of COVID-19 disease remains a priority. Methods: We designed an adaptive individually randomised single blinded non identical placebo-controlled trial to evaluate the safety and efficacy of repurposing licenced treatments for COVID-19 patients in an African setting. The trial has two cohorts: Cohort 1 recruits mild and moderate COVID-19 cases and their household contacts. Cases are actively followed up for 14 days, with a final visit at day 28. There are two co-primary endpoints: clinical progression to severe-pneumonia and persistence of the virus at day 14. The primary endpoint for household contacts is infection during a 14-day follow-up period. Cohort 2 recruits hospitalized patients with severe COVID-19 associated pneumonia followed up actively until discharge or death, and passively until day 90, with a final visit. The primary endpoint is clinical progression or death. Conclusions: This randomised trial will contribute African-specific data to the global response to COVID-19. Besides the efficacy of drugs on clinical progression, the trial will provide information on the dynamics of intra-household transmission. Trial registration: This study is registered with Clinical Trials.gov with registration number NCT04703608 and with Pan African clinical trials registry with registration number PACTR202101544570971

Respiratory syncytial virus infection among children younger than 2 years admitted to a paediatric intensive care unit with extended severe acute respiratory infection in ten Gavi-eligible countries: the RSV GOLD—ICU Network study

Background Patient-level data on life-threatening respiratory syncytial virus (RSV) infection in children in low-income and lower-middle-income countries (LMICs) are scarce, and this scarcity might limit demand for RSV interventions in LMICs who rely on support from Gavi, the Vaccine Alliance. We aimed to describe the characteristics of RSV-positive children younger than 2 years who were admitted to paediatric intensive care units (PICUs) with extended severe acute respiratory infection (eSARI) in Gavi-eligible countries. Methods The RSV GOLD—ICU Network study is a 2-year prospective, multicountry, observational study of children younger than 2 years admitted to a PICU with eSARI. The study was conducted at 12 referral hospitals in Bolivia, Cameroon, The Gambia, Ghana, Haiti, Mozambique, Nepal, Nigeria, Sudan, and Tanzania. For comparison with a high-income country, patients were also included from two referral hospitals in the Netherlands. Children were eligible for inclusion if they were aged between 4 days and 2 years, admitted to a PICU, and met the WHO eSARI definition. RSV infection was confirmed within 72 h of PICU admission via a molecular point-of-care test at LMIC study sites and via a PCR test at the Dutch study sites. Clinical data were extracted from admission charts of patients; underlying conditions that were identified at admission were classified as comorbidities. Socioeconomic and demographic data were collected via a written, structured, parental questionnaire. Findings Between April 28, 2021, and Sept 30, 2023, we included 2118 children who were admitted to a PICU with eSARI in the ten participating countries. 614 (29·0%; range 23·0–38·2) of 2118 children tested positive for RSV and 608 were included in descriptive analyses as six medical files were lost at one study site and data could not be retrieved. Among all 608 children infected with RSV, 379 (62%) were male and 229 (38%) were female. Median age at testing was 3·0 months (IQR 1·3–7·7). 30 (5%) of 608 children died from RSV infection. RSV fatality occurred at seven of ten participating LMIC study sites and was highest in Tanzania (seven [27%] of 26 children). Median age at testing of children who died with RSV infection was 1·8 months (IQR 1·1–4·2).Interpretation To our knowledge, this is the first prospective, multicountry study reporting data from children admitted to a PICU with life-threatening RSV infection in Gavi-eligible countries. As there is no access to intensive care for most children in LMICs, RSV prevention is urgently needed

SARS-CoV-2 seroprevalence in pregnant women in Kilifi, Kenya from March 2020 to March 2022

BackgroundSeroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya.MethodsWe obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG).ResultsA total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0–0.06] in March 2020 to a high of 89.4% [95% CI 83.36–93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% [95% CI 57.06–62.34] tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 37.4% [95% CI 34.83–40.04] tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence.ConclusionAnti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Agricultural water management problems and alternative solutions for Konya-Cumra province

Bu çalışma, Konya ili Çumra ilçesindeki çiftçilerin tarımsal sulamada karşılaştıkları sorunları belirlemek ve bunlara sürdürülebilir pratik çözümler sunmak amacıyla yapılmıştır. Çalışmada veriler arazi incelemesi ve yaklaşık 50 çiftçi ile yüz yüze anketlerden elde edilmiştir. Söz konusu anketlerden çiftçilerin eğitim seviyeleri, çiftçilik deneyimi, sulama suyu kaynağı, su yönetimindeki mevcut durum, arazi büyüklüğü, mevcut bitki deseni ve sulama maliyetleri gibi konularda veriler toplanmıştır. Sonuç olarak, çiftçilerin yaklaşık%46'sı ilkokul, %30'u orta okul, % 20'si lise ve % 4'ününde üniversite mezunu olduğu; çoğunluğunun 20 yıldan daha fazla tarım deneyimine sahip olduğu; sulama suyu kaynağı alarak yerüstü ve çoğunlukla yeraltı sularını kullandıkları; sulanan alanın kontrolsüz büyümesi sonucunda sulama suyu zamanında almadıkları bazı köylerde toplulaştırma hizmeti olduğunu ve arazilerin genellikle 10-19 ha arasında olduğu; sulama suyu maliyetlerini oldukça yüksek buldukları; bitki deseni olarak çoğunluğun tahıl, mısır, şeker pancarı ve kuru fasulye olduğu; çiftçilerin%96'sının sulamasuyu maliyetini yüksek buldukları tespit edilmiştir. Sonuç olarak, mevcut su kaynaklarının miktarı göz önüne alındığında, bitki deseninin mevcut su kaynağına göre yeniden şekillendirilmesi yani sulama suyu ihtiyacı düşük olan ve bölgeye oldukça uygun tahıl türü bitkilere devlet desteğinin artırılması önerilebilir.This study was conducted to analyze the water management problems faced by farmers and suggesting the practical solutions for those problems in the Konya province of Çumra, Turkey. Data were obtained from both field visits and about 50 farmers by using the face-to-face questionnaires. In those questionnaires, education level of farmers with their farming experience, water resources used in irrigation, current status of agricultural water management, land size, crop patterns, and irrigation cost were researched. The following results were obtained; about 46% of the farmershave primary school education, 30 % of them secondary school education, 20 % high school and 4% university education; most of the farmers have more than 20 years of farming experience; both surface and groundwater resources were used for irrigation; irrigated lands were increased without any control so irrigation intervals were very long in some cases, only few villages have land consolidation services and land size was about 10-19 ha. In general; cereals, sugar beet, maize and dry bean were common field crops, most farmers, 96%, indicated that irrigation costswere very high. In accordance with these results, crop pattern should be reorganized. Government should subsidize crops having low irrigation water requirement such as cereals

Statistical analysis of censored data

This thesis deal with the statistical analysis of censored data by means of simulation studies on the weibull, log-Normal, and gamma distributions. The simulations are carry out by 10,000 repetitions at different parameter settings, sample sizes (n) and censoring schemes. For to all distributions, the obtained results exhibit the accuracy of parameters for larger sample sizes (n), as well as the reliability of parameters to different combinations of the parameters values. The results support the idea that sample size is a key factor in the enhancement of the accuracy of the parameter estimates in the cases of censored data, detailed simulation results are provided including tables and figures illustrating the estimator’s behaviour under different conditions. These findings offer valuable insights for statistical inference involving censored data in various practical applications