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.

Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection.

The WHO African region bears a disproportionate burden of morbidity and mortality related to chronic hepatitis B virus (HBV) infection and accounts for an estimated 70% of new HBV infections worldwide. We investigated the extent to which HBV clinical trials represented populations in this region by searching the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for interventional clinical trials published in English between database inception and May 29, 2023, using the search term "Hepatitis B". We identified 1804 unique clinical trials, of which 18 (1·0%) recorded involvement of the WHO African region. There is no evidence that the number of HBV clinical trials in this region has improved over time. The diversity of new interventions and industry sponsorship in the WHO African region were low, with trials of HBV comparing poorly with those of other endemic infectious diseases (eg, malaria, HIV, and SARS-CoV-2). HBV research and clinical trial investigations have neglected the WHO African region, leading to profound health inequities. HBV clinical trials are urgently needed to evaluate the efficacy of newly discovered therapeutics and to ensure that interventions can be equitably distributed and deployed as they become available.

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.

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).