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.

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.

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.

SARS-CoV-2 seroprevalence and implications for population immunity: Evidence from two Health and Demographic Surveillance System sites in Kenya, February-December 2022.

BACKGROUND: We sought to estimate SARS-CoV-2 antibody seroprevalence within representative samples of the Kenyan population during the third year of the COVID-19 pandemic and the second year of COVID-19 vaccine use. METHODS: We conducted cross-sectional serosurveys among randomly selected, age-stratified samples of Health and Demographic Surveillance System (HDSS) residents in Kilifi and Nairobi. Anti-spike (anti-S) immunoglobulin G (IgG) serostatus was measured using a validated in-house ELISA and antibody concentrations estimated with reference to the WHO International Standard for anti-SARS-CoV-2 immunoglobulin. RESULTS: HDSS residents were sampled in February-June 2022 (Kilifi HDSS N = 852; Nairobi Urban HDSS N = 851) and in August-December 2022 (N = 850 for both sites). Population-weighted coverage for ≥1 doses of COVID-19 vaccine were 11.1% (9.1-13.2%) among Kilifi HDSS residents by November 2022 and 34.2% (30.7-37.6%) among Nairobi Urban HDSS residents by December 2022. Population-weighted anti-S IgG seroprevalence among Kilifi HDSS residents increased from 69.1% (65.8-72.3%) by May 2022 to 77.4% (74.4-80.2%) by November 2022. Within the Nairobi Urban HDSS, seroprevalence by June 2022 was 88.5% (86.1-90.6%), comparable with seroprevalence by December 2022 (92.2%; 90.2-93.9%). For both surveys, seroprevalence was significantly lower among Kilifi HDSS residents than among Nairobi Urban HDSS residents, as were antibody concentrations (p < 0.001). CONCLUSION: More than 70% of Kilifi residents and 90% of Nairobi residents were seropositive for anti-S IgG by the end of 2022. There is a potential immunity gap in rural Kenya; implementation of interventions to improve COVID-19 vaccine uptake among sub-groups at increased risk of severe COVID-19 in rural settings is recommended.

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.

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.

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.

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.

Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine in adults in Kenya: a phase 1/2 single-blind, randomised controlled trial.

Background: There are limited data on the immunogenicity of coronavirus disease 2019 (COVID-19) vaccines in African populations. Here we report the immunogenicity and safety of the ChAdOx1 nCoV-19 (AZD1222) vaccine from a phase 1/2 single-blind, randomised, controlled trial among adults in Kenya conducted as part of the early studies assessing vaccine performance in different geographical settings to inform Emergency Use Authorisation. Methods: We recruited and randomly assigned (1:1) 400 healthy adults aged ≥18 years in Kenya to receive ChAdOx1 nCoV-19 or control rabies vaccine, each as a two-dose schedule with a 3-month interval. The co-primary outcomes were safety, and immunogenicity assessed using total IgG enzyme-linked immunosorbent assay (ELISA) against SARS-CoV-2 spike protein 28 days after the second vaccination. Results: Between 28 th October 2020 and 19 th August 2021, 400 participants were enrolled and assigned to receive ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Local and systemic adverse events were self-limiting and mild or moderate in nature. Three serious adverse events were reported but these were deemed unrelated to vaccination. The geometric mean anti-spike IgG titres 28 days after second dose vaccination were higher in the ChAdOx1 group (2773 ELISA units [EU], 95% CI 2447, 3142) than in the rabies vaccine group (61 EU, 95% CI 45, 81) and persisted over the 12 months follow-up. We did not identify any symptomatic infections or hospital admissions with respiratory illness and so vaccine efficacy against clinically apparent infection could not be measured. Vaccine efficacy against asymptomatic SARS-CoV-2 infection was 38.4% (95% CI -26.8%, 70.1%; p=0.188). Conclusions: The safety, immunogenicity and efficacy against asymptomatic infection of ChAdOx1 nCoV-19 among Kenyan adults was similar to that observed elsewhere in the world, but efficacy against symptomatic infection or severe disease could not be measured in this cohort. Pan-African Clinical Trials Registration: PACTR202005681895696 (11/05/2020).

Where do those data go? Reuse of screening results from clinical trials to estimate population prevalence of HBV infection in adults in Kilifi, Kenya.

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6-4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4-6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity.

Seroprevalence, correlates and kinetics of SARS-CoV-2 nucleocapsid IgG antibody in healthcare workers and nonclinical staff at a tertiary hospital: A prevaccine census study.

BACKGROUND: Healthcare workers and nonclinical staff in medical facilities are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS-CoV-2 infection since most infected HCWs and other staff may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions. METHODS: This was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay. RESULTS: One thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted value (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The staff categories with higher prevalence included pharmacy (25.6%), outreach (24%), hospital- based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result after adjusting for age, sex and comorbidities included prior COVID-19 like symptoms, odds ratio (OR) 2.0 [95% confidence interval (CI) 1.3-3.0, p = 0.001], a prior positive SARS-CoV-2 PCR result OR 12.0 (CI: 7.7-18.7, p<0.001) and working in a clinical COVID-19 designated area, OR 1.9 (CI 1.1-3.3, p = 0.021). The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later; OR 0.7 (CI: 0.48-0.95, p = 0.025). CONCLUSIONS: The prevalence of anti- SARS-CoV-2 nucleocapsid IgG among HCWs and nonclinical staff was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.

Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in three Kenyan referral hospitals: Repeated cross-sectional surveys 2020-21.

INTRODUCTION: The high proportion of SARS-CoV-2 infections that have remained undetected presents a challenge to tracking the progress of the pandemic and estimating the extent of population immunity. METHODS: We used residual blood samples from women attending antenatal care services at three hospitals in Kenya between August 2020 and October 2021and a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. We fitted a two-component mixture model as an alternative to the threshold analysis to estimate of the proportion of individuals with past SARS-CoV-2 infection. RESULTS: We estimated seroprevalence in 2,981 women; 706 in Nairobi, 567 in Busia and 1,708 in Kilifi. By October 2021, 13% of participants were vaccinated (at least one dose) in Nairobi, 2% in Busia. Adjusted seroprevalence rose in all sites; from 50% (95%CI 42-58) in August 2020, to 85% (95%CI 78-92) in October 2021 in Nairobi; from 31% (95%CI 25-37) in May 2021 to 71% (95%CI 64-77) in October 2021 in Busia; and from 1% (95% CI 0-3) in September 2020 to 63% (95% CI 56-69) in October 2021 in Kilifi. Mixture modelling, suggests adjusted cross-sectional prevalence estimates are underestimates; seroprevalence in October 2021 could be 74% in Busia and 72% in Kilifi. CONCLUSIONS: There has been substantial, unobserved transmission of SARS-CoV-2 in Nairobi, Busia and Kilifi Counties. Due to the length of time since the beginning of the pandemic, repeated cross-sectional surveys are now difficult to interpret without the use of models to account for antibody waning.

Scaling up the primary health integrated care project for chronic conditions in Kenya: study protocol for an implementation research project.

INTRODUCTION: Amid the rising number of people with non-communicable diseases (NCDs), Kenya has invested in strengthening primary care and in efforts to expand existing service delivery platforms to integrate NCD care. One such approach is the AMPATH (Academic Model Providing Access to Healthcare) model in western Kenya, which provides the platform for the Primary Health Integrated Care Project for Chronic Conditions (PIC4C), launched in 2018 to further strengthen primary care services for the prevention and control of hypertension, diabetes, breast and cervical cancer. This study seeks to understand how well PIC4C delivers on its intended aims and to inform and support scale up of the PIC4C model for integrated care for people with NCDs in Kenya. METHODS AND ANALYSIS: The study is guided by a conceptual framework on implementing, sustaining and spreading innovation in health service delivery. We use a multimethod design combining qualitative and quantitative approaches, involving: (1) in-depth interviews with health workers and decision-makers to explore experiences of delivering PIC4C; (2) a cross-sectional survey of patients with diabetes or hypertension and in-depth interviews to understand how well PIC4C meets patients' needs; (3) a cohort study with an interrupted time series analysis to evaluate the degree to which PIC4C leads to health benefits such as improved management of hypertension or diabetes; and (4) a cohort study of households to examine the extent to which the national hospital insurance chronic care package provides financial risk protection to people with hypertension or diabetes within PIC4C. ETHICS AND DISSEMINATION: The study has received approvals from Moi University Institutional Research and Ethics Committee (FAN:0003586) and the London School of Hygiene & Tropical Medicine (17940). Workshops with key stakeholders at local, county, national and international levels will ensure early and wide dissemination of our findings to inform scale up of this model of care. We will also publish findings in peer-reviewed journals.

Emerging Viral Infections, Hypertension, and Cardiovascular Disease in Sub-Saharan Africa: A Narrative Review.

BACKGROUND: Sub-Saharan Africa (SSA) has the highest age-adjusted burden of hypertension and cardiovascular disease (CVD). SSA also experiences many viral infections due to unique environmental and societal factors. The purpose of this narrative review is to examine evidence around how hypertension, CVD, and emerging viral infections interact in SSA. METHODS: In September 2021, we conducted a search in MEDLINE, Embase, and Scopus, limited to English language studies published since 1990, and found a total of 1169 articles. Forty-seven original studies were included, with 32 on COVID-19 and 15 on other emerging viruses. RESULTS: Seven articles, including those with the largest sample size and most robust study design, found an association between preexisting hypertension or CVD and COVID-19 severity or death. Ten smaller studies found no association, and 17 did not calculate statistics to compare groups. Two studies assessed the impact of COVID-19 on incident CVD, with one finding an increase in stroke admissions. For other emerging viruses, 3 studies did not find an association between preexisting hypertension or CVD on West Nile and Lassa fever mortality. Twelve studies examined other emerging viral infections and incident CVD, with 4 finding no association and 8 not calculating statistics. CONCLUSIONS: Growing evidence from COVID-19 suggests viruses, hypertension, and CVD interact on multiple levels in SSA, but research gaps remain especially for other emerging viral infections. SSA can and must play a leading role in the study and control of emerging viral infections, with expansion of research and public health infrastructure to address these interactions.

SARS-CoV-2 seroprevalence in three Kenyan health and demographic surveillance sites, December 2020-May 2021.

BACKGROUND: Most of the studies that have informed the public health response to the COVID-19 pandemic in Kenya have relied on samples that are not representative of the general population. We conducted population-based serosurveys at three Health and Demographic Surveillance Systems (HDSSs) to determine the cumulative incidence of infection with SARS-CoV-2. METHODS: We selected random age-stratified population-based samples at HDSSs in Kisumu, Nairobi and Kilifi, in Kenya. Blood samples were collected from participants between 01 Dec 2020 and 27 May 2021. No participant had received a COVID-19 vaccine. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Locally-validated assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. We adjusted prevalence estimates using classical methods and Bayesian modelling to account for the sampling scheme and assay performance. RESULTS: We recruited 2,559 individuals from the three HDSS sites, median age (IQR) 27 (10-78) years and 52% were female. Seroprevalence at all three sites rose steadily during the study period. In Kisumu, Nairobi and Kilifi, seroprevalences (95% CI) at the beginning of the study were 36.0% (28.2-44.4%), 32.4% (23.1-42.4%), and 14.5% (9.1-21%), and respectively; at the end they were 42.0% (34.7-50.0%), 50.2% (39.7-61.1%), and 24.7% (17.5-32.6%), respectively. Seroprevalence was substantially lower among children (<16 years) than among adults at all three sites (p≤0.001). CONCLUSION: By May 2021 in three broadly representative populations of unvaccinated individuals in Kenya, seroprevalence of anti-SARS-CoV-2 IgG was 25-50%. There was wide variation in cumulative incidence by location and age.

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.

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immunoglobulin G Antibody Seroprevalence Among Truck Drivers and Assistants in Kenya.

In October 2020, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G seroprevalence among truck drivers and their assistants (TDA) in Kenya was 42.3%, higher than among healthcare workers and blood donors. Truck drivers and their assistants transport essential supplies during the coronavirus disease 2019 pandemic, placing them at increased risk of being infected and of transmitting SARS-CoV-2 over a wide geographical area.