Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use. METHODS AND FINDINGS: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507. INTERPRETATION: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947.

STRIKE-HBV: establishing an HBV screening programme in Kilifi, Kenya-challenges, successes and lessons learnt.

OBJECTIVES: Chronic hepatitis B infection affects 65 million people in the WHO African Region, but only 4.2% of these are diagnosed and 0.2% on treatment. Here, we present a short report describing establishment of a hepatitis B virus (HBV) programme in Kenya. We share experiences, successes and challenges to support development of future programmes. METHODS: From March 2023, we began the 'STRIKE-HBV' Study to identify people living with HBV (PLWHB) in Kilifi, Kenya. We employed local staff and provided education and training. Individuals were identified through three routes: (1) we offered free-of-charge HBV testing for all non-pregnant adults attending Kilifi Country Hospital (KCH) outpatient department; (2) we invited PLWHB to reattend for review; and (3) we invited close contacts of PLWHB for screening and vaccination if HBV was negative. All those seropositive for HBV were offered a comprehensive liver health assessment. RESULTS: We have established a framework for HBV screening, assessment and linkage to care in Kilifi. Between March 2023 and March 2024, we collected data for 80 PLWHB, comprising (1) screening of 1862 people of whom 30 were seropositive, (2) enrolment of 38 people known to be living with HBV and (3) testing of 97 close contacts of PLWHB, of whom 12 were positive. Among a limited subset with elastography data, we identified 9 of 59 as having significant fibrosis, and a further 6 people had laboratory aspartate transaminase (AST) to platelet ratio index (APRI) scores in keeping with fibrosis. We encountered challenges including procurement delays for hepatitis B surface antigen testing kits and HBV vaccinations, and issues accessing liver elastography. CONCLUSIONS: HBV screening was well received by the Kilifi population, has identified people at risk of liver disease progression and is improving linkage to care and vaccination at KCH. Future HBV programmes in WHO Africa can build on this experience as we work to develop accessible, affordable and acceptable care pathways.

Evaluating the effectiveness of the National Health Insurance Fund in providing financial protection to households with hypertension and diabetes patients in Kenya.

BACKGROUND: Non-communicable diseases (NCDs) can impose a substantial financial burden to households in the absence of an effective financial risk protection mechanism. The national health insurance fund (NHIF) has included NCD services in its national scheme. We evaluated the effectiveness of NHIF in providing financial risk protection to households with persons living with hypertension and/or diabetes in Kenya. METHODS: We carried out a prospective cohort study, following 888 households with at least one individual living with hypertension and/or diabetes for 12 months. The exposure arm comprised households that are enrolled in the NHIF national scheme, while the control arm comprised households that were not enrolled in the NHIF. Study participants were drawn from two counties in Kenya. We used the incidence of catastrophic health expenditure (CHE) as the outcome of interest. We used coarsened exact matching and a conditional logistic regression model to analyse the odds of CHE among households enrolled in the NHIF compared with unenrolled households. Socioeconomic inequality in CHE was examined using concentration curves and indices. RESULTS: We found strong evidence that NHIF-enrolled households spent a lower share (12.4%) of their household budget on healthcare compared with unenrolled households (23.2%) (p = 0.004). While households that were enrolled in NHIF were less likely to incur CHE, we did not find strong evidence that they are better protected from CHE compared with households without NHIF (OR = 0.67; p = 0.47). The concentration index (CI) for CHE showed a pro-poor distribution (CI: -0.190, p < 0.001). Almost half (46.9%) of households reported active NHIF enrolment at baseline but this reduced to 10.9% after one year, indicating an NHIF attrition rate of 76.7%. The depth of NHIF cover (i.e., the share of out-of-pocket healthcare costs paid by NHIF) among households with active NHIF was 29.6%. CONCLUSION: We did not find strong evidence that the NHIF national scheme is effective in providing financial risk protection to households with individuals living with hypertension and/diabetes in Kenya. This could partly be explained by the low depth of cover of the NHIF national scheme, and the high attrition rate. To enhance NHIF effectiveness, there is a need to revise the NHIF benefit package to include essential hypertension and/diabetes services, review existing provider payment mechanisms to explicitly reimburse these services, and extend the existing insurance subsidy programme to include individuals in the informal labour market.

Seroprevalence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers in Kenya.

BACKGROUND: Few studies have assessed the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) in Africa. We report findings from a survey among HCWs in 3 counties in Kenya. METHODS: We recruited 684 HCWs from Kilifi (rural), Busia (rural), and Nairobi (urban) counties. The serosurvey was conducted between 30 July and 4 December 2020. We tested for immunoglobulin G antibodies to SARS-CoV-2 spike protein, using enzyme-linked immunosorbent assay. Assay sensitivity and specificity were 92.7 (95% CI, 87.9-96.1) and 99.0% (95% CI, 98.1-99.5), respectively. We adjusted prevalence estimates, using bayesian modeling to account for assay performance. RESULTS: The crude overall seroprevalence was 19.7% (135 of 684). After adjustment for assay performance, seroprevalence was 20.8% (95% credible interval, 17.5%-24.4%). Seroprevalence varied significantly (P < .001) by site: 43.8% (95% credible interval, 35.8%-52.2%) in Nairobi, 12.6% (8.8%-17.1%) in Busia and 11.5% (7.2%-17.6%) in Kilifi. In a multivariable model controlling for age, sex, and site, professional cadre was not associated with differences in seroprevalence. CONCLUSION: These initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.

Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study.

BACKGROUND: Ten-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2-11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12-59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County. METHODS: This study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999-Dec 31, 2010) and postvaccine (Jan 1, 2012-Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016. FINDINGS: Surveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03-0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17-0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5-14 years [adjusted IRR 0·26, 95% CI 0·11-0·59], and ≥15 years [0·19, 0·07-0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19-0·35) and non-PCV10-type carriage increased (1·71, 1·47-1·99). INTERPRETATION: Introduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa. FUNDING: Gavi, The Vaccine Alliance and The Wellcome Trust of Great Britain.

Pharmacotherapy for hypertension in Sub-Saharan Africa: a systematic review and network meta-analysis.

BACKGROUND: The highest burden of hypertension is found in Sub-Saharan Africa (SSA) with a threefold greater mortality from stroke and other associated diseases. Ethnicity is known to influence the response to antihypertensives, especially in black populations living in North America and Europe. We sought to outline the impact of all commonly used pharmacological agents on both blood pressure reduction and cardiovascular morbidity and mortality in SSA. METHODS: We used similar criteria to previous large meta-analyses of blood pressure agents but restricted results to populations in SSA. Quality of evidence was assessed using a risk of bias tool. Network meta-analysis with random effects was used to compare the effects across interventions and meta-regression to explore participant heterogeneity. RESULTS: Thirty-two studies of 2860 participants were identified. Most were small studies from single, urban centres. Compared with placebo, any pharmacotherapy lowered SBP/DBP by 8.51/8.04 mmHg, and calcium channel blockers (CCBs) were the most efficacious first-line agent with 18.46/11.6 mmHg reduction. Fewer studies assessing combination therapy were available, but there was a trend towards superiority for CCBs plus ACE inhibitors or diuretics compared to other combinations. No studies examined the effect of antihypertensive therapy on morbidity or mortality outcomes. CONCLUSION: Evidence broadly supports current guidelines and provides a clear rationale for promoting CCBs as first-line agents and early initiation of combination therapy. However, there is a clear requirement for more evidence to provide a nuanced understanding of stroke and other cardiovascular disease prevention amongst diverse populations on the continent. TRIAL REGISTRATION: PROSPERO, CRD42019122490. This review was registered in January 2019.

Patient costs of diabetes mellitus care in public health care facilities in Kenya.

OBJECTIVE: To estimate the direct and indirect costs of diabetes mellitus care at five public health facilities in Kenya. METHODS: We conducted a cross-sectional study in two counties where diabetes patients aged 18 years and above were interviewed. Data on care-seeking costs were obtained from 163 patients seeking diabetes care at five public facilities using the cost-of-illness approach. Medicines and user charges were classified as direct health care costs while expenses on transport, food, and accommodation were classified as direct non-health care costs. Productivity losses due to diabetes were classified as indirect costs. We computed annual direct and indirect costs borne by these patients. RESULTS: More than half (57.7%) of sampled patients had hypertension comorbidity. Overall, the mean annual direct patient cost was KES 53 907 (95% CI, 43 625.4-64 188.6) (US$ 528.5 [95% CI, 427.7-629.3]). Medicines accounted for 52.4%, transport 22.6%, user charges 17.5%, and food 7.5% of total direct costs. Overall mean annual indirect cost was KES 23 174 (95% CI, 20 910-25 438.8) (US$ 227.2 [95% CI, 205-249.4]). Patients reporting hypertension comorbidity incurred higher costs compared with diabetes-only patients. The incidence of catastrophic costs was 63.1% (95% CI, 55.7-70.7) and increased to 75.4% (95% CI, 68.3-82.1) when transport costs were included. CONCLUSION: There are substantial direct and indirect costs borne by diabetic patients in seeking care from public facilities in Kenya. High incidence of catastrophic costs suggests diabetes services are unaffordable to majority of diabetic patients and illustrate the urgent need to improve financial risk protection to ensure access to care.

[Optimizing observer performance of clinic blood Pressure measurement: a position statement from the Lancet Commission on Hypertension GroupOtimização do desempenho do observador na medição clínica da pressão arterial: posicionamento do Grupo da Lancet Commission on Hypertension]. / Optimización del desempeño del observador al medir la presión arterial en el consultorio: declaración de posición de la Comisión Lancet de Hipertensión.

High blood pressure (BP) is a highly prevalent modifiable cause of cardiovascular disease, stroke, and death. Accurate BP measurement is critical, given that a 5-mmHg measurement error may lead to incorrect hypertension status classification in 84 million individuals worldwide. This position statement summarizes procedures for optimizing observer performance in clinic BP measurement, with special attention given to low-tomiddle- income settings, where resource limitations, heavy workloads, time constraints, and lack of electrical power make measurement more challenging. Many measurement errors can be minimized by appropriate patient preparation and standardized techniques. Validated semi-automated/automated upper arm cuff devices should be used instead of auscultation to simplify measurement and prevent observer error. Task sharing, creating a dedicated measurement workstation, and using semi-automated or solar-charged devices may help. Ensuring observer training, and periodic re-training, is critical. Low-cost, easily accessible certification programs should be considered to facilitate best BP measurement practice.

A hipertensão é uma causa altamente prevalente de doença cardiovascular, acidente vascular cerebral e morte. A medição precisa da pressão arterial (PA) é um aspecto crítico, uma vez que erros de mensuração da ordem de 5 mmHg podem levar a uma classificação incorreta do status de hipertensão em 84 milhões de pessoas em todo o mundo. O presente posicionamento resume os procedimentos para otimizar o desempenho do observador (o indivíduo responsável pela mensuração da PA) na mensuração clínica da PA, com atenção especial para contextos de baixa a média renda, onde recursos limitados, cargas de trabalho pesadas, restrições de tempo e falta de energia elétrica tornam mais desafiadora a tarefa de medir a PA. Muitos erros de mensuração podem ser minimizados pela preparação adequada do paciente e pelo uso de técnicas padronizadas. Para simplificar a mensuração e evitar erros do observador, devem-se utilizar dispositivos semiautomatizados ou automatizados validados, com manguito para braço, ao invés de auscultação. O compartilhamento de tarefas, a criação de uma estação de trabalho dedicada à mensuração e o uso de dispositivos semiautomatizados ou com carga solar podem ajudar. É essencial que seja assegurado o treinamento e retreinamento periódico do observador. Programas de certificação de baixo custo e de fácil acesso devem ser considerados para facilitar a adoção das melhores práticas na mensuração da PA.

Population-Based Estimate of Melioidosis, Kenya.

Melioidosis is thought to be endemic, although underdiagnosed, in Africa. We identified 5 autochthonous cases of Burkholderia pseudomallei infection in a case series in Kenya. Incidence of B. pseudomallei bacteremia in Kenya's Kilifi County is low, at 1.5 cases per million person-years, but this result might be an underestimate.

Patient costs of hypertension care in public health care facilities in Kenya.

BACKGROUND: Hypertension in low- and middle-income countries, including Kenya, is of economic importance due to its increasing prevalence and its potential to present an economic burden to households. In this study, we examined the patient costs associated with obtaining care for hypertension in public health care facilities in Kenya. METHODS: We conducted a cross-sectional study among adult respondents above 18 years of age, with at least 6 months of treatment in two counties. A total of 212 patients seeking hypertension care at five public facilities were interviewed, and information on care seeking and the associated costs was obtained. We computed both annual direct and indirect costs borne by these patients. RESULTS: Overall, the mean annual direct cost to patients was US$ 304.8 (95% CI, 235.7-374.0). Medicines (mean annual cost, US$ 168.9; 95% CI, 132.5-205.4), transport (mean annual cost, US$ 126.7; 95% CI, 77.6-175.9), and user charges (mean annual cost, US$ 57.7; 95% CI, 43.7-71.6) were the highest direct cost categories. Overall mean annual indirect cost was US$ 171.7 (95% CI, 152.8-190.5). The incidence of catastrophic health care costs was 43.3% (95% CI, 36.8-50.2) and increased to 59.0% (95% CI, 52.2-65.4) when transport costs were included. CONCLUSIONS: Hypertensive patients incur substantial direct and indirect costs. High rates of catastrophic costs illustrate the urgency of improving financial risk protection for these patients and strengthening primary care to ensure affordability of hypertension care.

Blood Pressure and Arterial Stiffness in Kenyan Adolescents With the Sickle Cell Trait.

The potential association between sickle cell trait (SCT) and increased arterial stiffness/blood pressure (BP) has not been evaluated in detail despite its association with stroke, sudden death, and renal disease. We performed 24-hour ambulatory BP monitoring and arterial stiffness measurements in adolescents raised in a malaria-free environment in Kenya. Between December 2015 and June 2016, 938 randomly selected adolescents (ages 11-17 years) who had been continuous residents of Nairobi from birth were invited to participate in the study. Standard clinic BP measurement was performed, followed by 24-hour ambulatory BP monitoring and arterial stiffness measurement using an Arteriograph24 (TensioMed Ltd., Budapest, Hungary) device. SCT status was determined using DNA genotyping in contemporaneously collected blood samples. Of the 938 adolescents invited to participate, 609 (65%) provided complete data for analysis. SCT was present in 103 (15%). Mean 24-hour systolic and diastolic BPs were 116 (standard deviation (SD), 11.5) mm Hg and 64 (SD, 7) mm Hg, respectively, in children with SCT and 117 (SD, 11.4) mm Hg and 64 (SD, 6.8) mm Hg, respectively, in non-SCT children. Mean pulse wave velocity (PWV) was 7.1 (SD, 0.8) m/second and 7.0 (SD, 0.8) m/second in SCT and non-SCT children, respectively. We observed no differences in PWV or in any clinic or ambulatory BP-derived measures between adolescents with and without SCT. These data suggest that SCT does not independently influence BP or PWV.

The Malaria-High Blood Pressure Hypothesis.

RATIONALE: Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. OBJECTIVE: In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. METHODS AND RESULTS: We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. CONCLUSIONS: Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease.

Invasive Salmonellosis in Kilifi, Kenya.

BACKGROUND: Invasive salmonelloses are a major cause of morbidity and mortality in Africa, but the incidence and case fatality of each disease vary markedly by region. We aimed to describe the incidence, clinical characteristics, and antimicrobial susceptibility patterns of invasive salmonelloses among children and adults in Kilifi, Kenya. METHODS: We analyzed integrated clinical and laboratory records for patients presenting to the Kilifi County Hospital between 1998 and 2014. We calculated incidence, and summarized clinical features and multidrug resistance. RESULTS: Nontyphoidal Salmonella (NTS) accounted for 10.8% and 5.8% of bacteremia cases in children and adults, respectively, while Salmonella Typhi accounted for 0.5% and 2.1%, respectively. Among 351 NTS isolates serotyped, 160 (45.6%) were Salmonella Enteritidis and 152 (43.3%) were Salmonella Typhimurium. The incidence of NTS in children aged <5 years was 36.6 per 100 000 person-years, being highest in infants aged <7 days (174/100 000 person-years). The overall incidence of NTS in children varied markedly by location and declined significantly during the study period; the pattern of dominance of the NTS serotypes also shifted from Salmonella Enteritidis to Salmonella Typhimurium. Risk factors for invasive NTS disease were human immunodeficiency virus infection, malaria, and malnutrition; the case fatality ratio was 22.1% (71/321) in children aged <5 years and 36.7% (11/30) in adults. Multidrug resistance was present in 23.9% (84/351) of NTS isolates and 46.2% (12/26) of Salmonella Typhi isolates. CONCLUSIONS: In Kilifi, the incidence of invasive NTS was high, especially among newborn infants, but typhoid fever was uncommon. NTS remains an important cause of bacteremia in children <5 years of age.

Burden, causes, and outcomes of people with epilepsy admitted to a rural hospital in Kenya.

OBJECTIVE: People with epilepsy (PWE) develop complications and comorbidities often requiring admission to hospital, which adds to the burden on the health system, particularly in low-income countries. We determined the incidence, disability-adjusted life years (DALYs), risk factors, and causes of admissions in PWE. We also examined the predictors of prolonged hospital stay and death using data from linked clinical and demographic surveillance system. METHODS: We studied children and adults admitted to a Kenyan rural hospital, between January 2003 and December 2011, with a diagnosis of epilepsy. Poisson regression was used to compute incidence and rate ratios, logistic regression to determine associated factors, and the DALY package of the R-statistical software to calculate years lived with disability (YLD) and years of life lost (YLL). RESULTS: The overall incidence of admissions was 45.6/100,000 person-years of observation (PYO) (95% confidence interval [95% CI] 43.0-48.7) and decreased with age (p < 0.001). The overall DALYs were 3.1/1,000 (95% CI, 1.8-4.7) PYO and comprised 55% of YLD. Factors associated with hospitalization were use of antiepileptic drugs (AEDs) (odds ratio [OR] 5.36, 95% CI 2.64-10.90), previous admission (OR 11.65, 95% CI 2.65-51.17), acute encephalopathy (OR 2.12, 95% CI 1.07-4.22), and adverse perinatal events (OR 2.87, 95% CI 1.06-7.74). Important causes of admission were epilepsy-related complications: convulsive status epilepticus (CSE) (38%), and postictal coma (12%). Age was independently associated with prolonged hospital stay (OR 1.02, 95% CI 1.00-1.04) and mortality (OR, 1.07, 95% CI 1.04-1.10). SIGNIFICANCE: Epilepsy is associated with significant number of admissions to hospital, considerable duration of admission, and mortality. Improved supply of AEDs in the community, early initiation of treatment, and adherence would reduce hospitalization of PWE and thus the burden of epilepsy on the health system.

Managing hypertension in rural Gambia and Kenya: Protocol for a qualitative study exploring the experiences of patients, health care workers, and decision-makers.

Background: Hypertension is the single leading risk factor for premature death in Sub-Saharan Africa (SSA). Prevalence is high, but awareness, treatment, and control are low. Community-centred interventions show promise for effective hypertension management, but embedding such interventions sustainably requires a good understanding of the wider context within which they are being introduced. This study aims to conduct a systematic health system assessment exploring the micro (patients/carers), meso (health care workers and facilities), and macro (broader system) contexts in rural Gambia and Kenya. Methods: This study will utilise various qualitative approaches. We will conduct (i) focus group discussions with people living with hypertensive to map a 'typical' patient journey through health systems, and (ii) in-depth interviews with patients and family carers, health care workers, decision-makers, and NCD partners to explore their experiences of managing hypertension and assess the capacity and readiness of the health systems to strengthen hypertension management. We will also review national guidelines and policy documents to map the organisation of services and guidance on hypertension management. We will use thematic analysis to analyse data, guided by the cumulative complexity model, and theories of organisational readiness and dissemination of innovations. Expected findings: This study will describe the current context for the management of hypertension from the perspective of those involved in seeking (patients), delivering (health care workers) and overseeing (decision-makers) health services in rural Gambia and Kenya. It will juxtapose what should be happening according to health system guidance and what is happening in practice, drawing on the experiences of study participants. It will outline the various barriers to and facilitators of hypertension management, as perceived by patients, providers, and decision-makers, and the conditions that would need to be in place for effective and sustainable implementation of a community-centred intervention to improve the management of hypertension in rural settings.

Evaluating the implementation of the Primary Health Integrated Care Project for Chronic Conditions: a cohort study from Kenya.

Introduction: In Kenya, non-communicable diseases (NCDs) are estimated to account for almost one-third of all deaths and this is likely to rise by over 50% in the next 10 years. The Primary Health Integrated Care for Chronic Conditions (PIC4C) project aims to strengthen primary care by integrating comprehensive NCD care into existing HIV primary care platform. This paper evaluates the association of PIC4C implementation on clinical outcomes. Methods: Outcomes included proportion of new patients, systolic blood pressure (SBP), fasting plasma glucose (FPG), diastolic blood pressure, hypertension control, random plasma glucose, diabetes control, viral load and HIV viral suppression. We used interrupted time series and binomial regression with random effects for facility-level data and generalised mixed-effects regression for visit-level data to examine the association between PIC4C and outcomes between January 2017 and December 2021. We conducted sensitivity analysis with restrictions on sites and the number of visits. Results: Data from 66 641 visits of 13 046 patients with hypertension, 24 005 visits of 7267 patients with diabetes and 84 855 visits of 21 186 people with HIV were analysed. We found evidence of association between PIC4C and increase in proportion of new patients per month with hypertension (adjusted OR (aOR) 1.57, 95% CI 1.39 to 1.78) and diabetes (aOR 1.31, 95% CI 1.19 to 1.45), small increase in SBP (adjusted beta (aB) 1.7, 95% CI 0.8 to 2.7) and FPG (aB 0.6, 95% CI 0.0 to 1.1). There was no strong evidence of association between PIC4C and viral suppression (aOR 1.20, 95% CI 0.98 to 1.47). In sensitivity analysis, there was no strong evidence of association between PIC4C and SBP (aB 1.74, 95% CI -0.70 to 4.17) or FPG (aB 0.52, 95% CI -0.64 to 1.67). Conclusions: PIC4C implementation was associated with increase in proportion of new patients attending clinics and a slight increase in SBP and FPG. The immediate post-PIC4C implementation period coincided with the COVID-19 pandemic, which is likely to explain some of our findings.

A systematic review of Hepatitis B virus (HBV) prevalence and genotypes in Kenya: Data to inform clinical care and health policy.

The aim of this systematic review and meta-analysis is to evaluate available prevalence and viral sequencing data representing chronic hepatitis B (CHB) infection in Kenya. More than 20% of the global disease burden from CHB is in Africa, however there is minimal high quality seroprevalence data from individual countries and little viral sequencing data available to represent the continent. We undertook a systematic review of the prevalence and genetic data available for hepatitis B virus (HBV) in Kenya using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 checklist. We identified 23 studies reporting HBV prevalence and 8 studies that included HBV genetic data published in English between January 2000 and December 2021. We assessed study quality using the Joanna Briggs Institute critical appraisal checklist. Due to study heterogeneity, we divided the studies to represent low, moderate, high and very high-risk for HBV infection, identifying 8, 7, 5 and 3 studies in these groups, respectively. We calculated pooled HBV prevalence within each group and evaluated available sequencing data. Pooled HBV prevalence was 3.4% (95% CI 2.7-4.2%), 6.1% (95% CI 5.1-7.4%), 6.2% (95% CI 4.64-8.2) and 29.2% (95% CI 12.2-55.1), respectively. Study quality was overall low; only three studies detailed sample size calculation and 17/23 studies were cross sectional. Eight studies included genetic information on HBV, with two undertaking whole genome sequencing. Genotype A accounted for 92% of infections. Other genotypes included genotype D (6%), D/E recombinants (1%) or mixed populations (1%). Drug resistance mutations were reported by two studies. There is an urgent need for more high quality seroprevalence and genetic data to represent HBV in Kenya to underpin improved HBV screening, treatment and prevention in order to support progress towards elimination targets.

Examining the responsiveness of the National Health Insurance Fund to people living with hypertension and diabetes in Kenya: a qualitative study.

OBJECTIVES: To assess the responsiveness of the National Health Insurance Fund (NHIF) Supa Cover benefit package to the needs of individuals with diabetes and hypertension in Kenya. DESIGN, SETTING AND PARTICIPANTS: We carried out a qualitative study and collected data using key informant interviews (n=39) and focus group discussions (n=4) in two purposively selected counties in Western Kenya. Study participants were drawn from NHIF officials, county government officials, health facility managers, healthcare workers and individuals with hypertension and diabetes who were enrolled in NHIF. We analysed data using a thematic approach. RESULTS: Study participants reported that the NHIF Supa Cover benefit package expanded access to services for people living with hypertension and diabetes. However, the NHIF members and healthcare workers had inadequate awareness of the NHIF service entitlements. The NHIF benefit package inadequately covered the range of services needed by people living with hypertension and diabetes and the benefits package did not prioritise preventive and promotive services. Sometimes patients were discriminated against by healthcare providers who preferred cash-paying patients, and some NHIF-empanelled health facilities had inadequate structural inputs essential for quality of care. Study participants felt that the NHIF premium for the general scheme was unaffordable, and NHIF members faced additional out-of-pocket costs because of additional payments for services not available or covered. CONCLUSION: Whereas NHIF has reduced financial barriers for hypertension and diabetes patients, to enhance its responsiveness to patient needs, NHIF should implement mechanisms to increase benefit package awareness among members and providers. In addition, preventive and promotive services should be included in NHIF's benefits package and mechanisms to monitor and hold contracted providers accountable should be strengthened.

Recurrent spontaneous Escherichia coli meningitis in an adult: a case report.

Objectives: The aim of this study was to characterize an unusual case of spontaneous, community-acquired Escherichia coli meningitis in an adult presenting to a general hospital in Kenya, where initial clinical recovery was followed by reinfection with an MDR, hospital-acquired strain. Patient and methods: An adult presented to a hospital in Kenya with meningitis symptoms. E. coli was cultured from CSF. Treatment with ceftriaxone was successful; however, the patient relapsed a few days later. E. coli was cultured from CSF and blood during the reinfection episode, though the patient died during admission. We sequenced the isolates using Illumina MiSeq and performed antimicrobial susceptibility testing, fitness and virulence assays on the bacteria. Results: The E. coli isolates from the two episodes were found to be distinct: the initial strain was ST88, serotype O8 H17 while the subsequent episode was caused by an ST167, serotype O101 H5 MDR strain. The ST88 strain was susceptible to all drugs except ampicillin and amoxicillin/clavulanate while the ST167 strain was MDR, including to all ß-lactam drugs due to the presence of the carbapenemase gene bla NDM-5. The hospital-acquired ST167 strain was also resistant to newer drugs such as cefiderocol and eravacycline, which are currently not available locally, and had overall lower fitness and virulence in vitro compared with the initial infecting strain. Conclusions: Though less fit and virulent in vitro, the MDR strain was fatal, suggesting that host factors, rather than bacterial virulence, may have been of greater importance in this patient's outcome.

Determining the optimal diagnostic and risk stratification approaches for people with hypertension in two rural populations in Kenya and The Gambia: a study protocol for IHCoR-Africa Work Package 2.

Background: Sub-Saharan Africa (SSA) has one of the highest prevalences of hypertension worldwide. The impact of hypertension is of particular concern in rural SSA, where access to clinics and hospitals is limited. Improvements in the management of people with hypertension in rural SSA could be achieved by sharing diagnosis and care tasks between the clinic and the community. To develop such a community-centred programme we need optimal approaches to identify and risk stratify patients with elevated blood pressure. The aim of the study is to improve the evidence base for diagnosis and risk estimation for a community-centred hypertension programme in two rural settings in SSA. Methods: We will conduct a cross-sectional study of 1250 adult participants in Kilifi, Kenya and Kiang West, The Gambia. The study has five objectives which will determine the: (1) accuracy of three blood pressure (BP) measurement methods performed by community health workers in identifying people with hypertension in rural SSA, compared to the reference standard method; (2) relationship between systolic BP and cardiovascular risk factors; (3) prevalence of hypertension-mediated organ damage (HMOD); (4) accuracy of innovative point-of-care (POC) technologies to identify patients with HMOD; and (5) cost-effectiveness of different combinations of BP and HMOD measurements for directing hypertension treatment initiation. Expected findings: This study will determine the accuracy of three methods for community BP measurement and POC technologies for HMOD assessment. Using the optimal methods in this setting it will estimate the prevalence of hypertension and provide the best estimate to date of HMOD prevalence in SSA populations. The cost-effectiveness of decision-making approaches for initiating treatment of hypertension will be modelled. These results will inform the development of a community-centred programme to improve care for hypertensive patients living in rural SSA. Existing community engagement networks will be used to disseminated within the research setting.

Many people live with high blood pressure in sub-Saharan Africa. In this region, the proportion of people with high blood pressure is one of the highest in the world. However, few people with high blood pressure are treated and this can lead to serious medical issues and even death. This is particularly true in rural areas where treatment and understanding of blood pressure is lower than in cities. There are many reasons why high blood pressure is a major health problem in rural sub-Saharan Africa, such as a lack of clear symptoms; less access to healthcare; and limited time to travel to clinics for care. One option for improving the management of blood pressure is to use a community-centred approach, where care is brought into the community making it easier to access. To bring care into the community, we need to find out what is the best way for community health workers to identify who needs to be treated. Standard techniques may not be useful in a rural community and could require too many resources to make them practical. This study aims to determine what is the best way to identify high blood pressure and related health complications in a community setting. The study will take place across two sites: one in Kilifi, Kenya and the other in Kiang West, The Gambia. We will enrol 1250 participants, with 625 in each country. The people living in these areas have been involved in the design of this study through community engagement and have helped identify the need for improving how blood pressure is treated in a rural areas. Throughout this study, we will continue to meet with the communities. Once the study is completed, we will use our strong links with the communities, healthcare providers and policymakers to share the results.