Peter James Dodd

Background: Diabetes is a growing public health challenge globally, with a disproportionate burden occurring in low- and middle-income countries (LMICs). In Kenya, limited evidence exists on type 2 diabetes mellitus (T2DM) screening coverage, undiagnosed diabetes, and progression through the diabetes care cascade. This study assessed the prevalence and determinants of T2DM testing, quantified undiagnosed T2DM, and examined the T2DM care cascade in Kenya. Methods: We analysed data from the 2015 Kenya WHO STEPwise survey, a nationally representative cross-sectional survey of adults aged 18–69 years. The analysis included 4,167 participants after excluding individuals with missing fasting plasma glucose (FPG) measurements and those below the age of 18 and above 69 years. Diabetes testing was defined as self-reported prior blood glucose measurement by a health worker among individuals without known diabetes. Diabetes was defined as FPG ≥7 mmol/L, previous diagnosis, or current diabetes treatment. Weighted prevalence estimates with 95% confidence intervals (CI) were calculated. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with diabetes screening while accounting for the complex survey design. Results: Overall, 11.9% (95% CI: 9.7–14.5) of participants reported ever being tested for diabetes. The weighted prevalence of diabetes was 2.66% (95% CI: 2.06–3.42), while 53.4% (95% CI: 39.0–67.4) of diabetes cases were previously undiagnosed. Testing prevalence was highest among older adults, individuals with tertiary education, obese participants, and those with hypertension, but lowest among younger adults, individuals with no formal education, and residents of the North Eastern region. Among individuals with diabetes, 46.9% were aware of their diagnosis, 40.8% of those aware were on treatment, and only 26.4% of those on treatment had achieved glycaemic control. In multivariable analysis, older age (60–69 years: aOR=6.29, 95% CI: 3.66–10.79), tertiary education (aOR=2.65, 95% CI: 1.33–5.27), poorest wealth quintile (aOR=8.42, 95% CI: 4.11–17.24), obesity (aOR=2.13, 95% CI: 1.41–3.21), and hypertension (aOR=1.64, 95% CI: 1.21–2.23) were significantly associated with increased odds of diabetes testing. Conclusion: Diabetes testing coverage in Kenya remains low, with more than half of diabetes cases remaining undiagnosed and substantial losses occurring across the diabetes care cascade. These findings highlight critical gaps in early diagnosis, linkage to care, treatment uptake, and glycaemic control. Strengthening integrated diabetes screening and care services, particularly for underserved and high-risk populations, is essential to improve early detection and continuity of care in Kenya.

Background: Tuberculosis preventive treatment (TPT) with levofloxacin reduces tuberculosis disease incidence in multidrug-resistant or rifampicin-resistant (MDR/RR)-tuberculosis household contacts. However, with age, disease progression risk falls and the frequency of adverse events (AE) rises. Methods: To inform decision-makers, we evaluated the cost-effectiveness of expanding the use of MDR/RR-TPT by age, with and without tests of tuberculosis infection. We modelled MDR/RR-household contact management (HHCM) in 189 countries, incorporating age-dependent risks of disease progression, death and AEs. Incremental cost-effectiveness ratios were calculated as USD/disability-adjusted life year (DALY) averted, and as a fraction of per capita gross domestic product (GDP). Findings: Compared to baseline of MDR/RR-HHCM with TPT for those M. tuberculosis infection were dominated by those without testing. Globally, full use of MDR/RR-HHCM with TPT for all would avert 11,900 (10,400 to 13,800) episodes of tuberculosis, 9,960 (9,100 to 10,900) deaths, and 289,000 (262,000 to 321,000) DALYs, but would result in 71,000 (68,000 to 74,000) SAEs and cost $359 million (294 to 449). Interpretation: Expanding MDR/RR-TPT use to older ages without testing appears cost-effective in most settings, but may require substantial resources and result in large numbers of AEs. Funding: Unitaid

Background: Reversing the rising burden of non-communicable diseases (NCDs) in Kenya requires implementing and scaling up prevention and control interventions. Health economics can help to inform priority-setting processes by comparing the costs and outcomes of alternative interventions. However, there is limited research on the role of health economic evidence in NCD priority setting in Kenya. This study explored the perspectives of Kenyan stakeholders regarding the use of, and barriers affecting the uptake of health economic evidence in NCD priority setting in Kenya. Methods: We conducted sixteen comprehensive interviews with Kenyan stakeholders engaged in NCD policy, management and research. The study participants comprised officials from the Ministry of Health at national and county levels, representatives from civil society organisations, the private sector, health economists, and researchers. We applied an inductive thematic approach in coding and data analysis. Results: The study found a limited and inconsistent uptake of health economic evidence for informing NCD decision making, which was described as fragmented, ad hoc, and peripheral. Investment cases and cost analyses were the most applied forms of economic evidence. Key barriers to increased uptake included the low prioritisation of health economic evidence within decision-making processes, misalignment between health economic research outputs and policy priorities, and limited capacity to conduct and interpret economic analyses. The scarcity of locally relevant, high-quality economic data also emerged as a major impediment to the reliability and credibility of health economic evidence. Conclusion: Despite growing recognition of its value, health economic evidence remains inconsistently integrated into NCD decision-making in Kenya. Addressing gaps in prioritisation, capacity, data availability, and alignment between research and policy needs may strengthen the systematic and sustained use of health economic evidence to support effective NCD policy and resource allocation. Analysts should involve the relevant stakeholders while designing and generating health economic evidence to improve uptake. Clinical trial number: Not applicable.

Background: The World Health Organization (WHO) recommends 4-month treatment for children with non-severe pulmonary tuberculosis, outlining eligibility criteria for settings with and without chest X-ray (CXR). We evaluated the diagnostic accuracy of the WHO eligibility criteria in settings without CXR (WHO-criteria) and developed clinical scores to support disease classification. Methods: Using data from an individual participant dataset (IPD; Decide TB) of children with confirmed/unconfirmed tuberculosis from four diagnostic studies (RaPaed-TB, Umoya, TB-Speed HIV, TB-Speed Decentralisation), we assessed the diagnostic accuracy of the WHO-criteria (with/without bacteriological testing) using expert CXR interpretation as a reference. We developed two multivariable logistic regression models with (Score 1) and without (Score 2) bacteriological testing, converted coefficients into integer scores with a threshold of >10 corresponding to a sensitivity ≥70%. Results: Of 2,383 children in the Decide TB IPD, 633 (26.6%) met the eligibility criteria for a 4-month regimen, of whom 116 (18.3%) had radiologically severe disease. With and without bacteriological testing, the WHO-criteria had sensitivities of 30.1% (95%CI: 20.3%-40.2%) and 21.7% (95%CI: 10.4%-34.5%), and specificities of 83.4% (95%CI: 80.2%-86.4%) and 81.9% (95%CI: 78.8%-84.9%), respectively. Score 1 and Score 2 had sensitivities of 41.1% (95%CI: 32.4%-49.5%) and 30.9% (95%CI: 22.6%-40.4%), and specificities of 77.3% (95%CI: 73.6%-80.8%) and 83.0% (95%CI: 79.5%-86.3%), respectively. Using WHO-criteria, 91/116 (78.4%) and 105/116 (90.5%) of children were at risk of undertreatment, compared to 68/116 (58.6%) and 80/116 (68.9%) when using developed scores. Conclusions: Developed scores demonstrated better sensitivity than WHO-criteria, however, performance remained suboptimal. Implementing shorter antituberculosis regimens without CXR remains challenging in children.

Introduction: Of 1.2 million children and young adolescents (<15 years) developing tuberculosis (TB) yearly, more than 50% are undiagnosed and unreported to national TB programmes (NTPs) and the World Health Organization (WHO). This is mainly due to poor performance of microbiological tests, limited clinical skills and structural barriers for childhood TB diagnosis at decentralised levels of care. Treatment decision algorithms (TDAs) could improve child TB outcomes but require external validation. We aim to evaluate a comprehensive TDA-based approach for childhood TB screening, diagnosis and treatment decision-making at district hospital (DH) and primary health centre (PHC) levels in Mozambique and Zambia. Methods and analysis: Decide TB is a pragmatic, hybrid effectiveness-implementation type 2 cluster-randomised trial with a stepped wedge design. The comprehensive TDA-based approach (intervention) will be implemented under programmatic conditions in four districts in each country (each comprising one DH and six PHCs), randomly selected to switch sequentially from the standard of care to the intervention. Evaluations will assess epidemiological, clinical, economic, social sciences, implementation and health policy endpoints. Aggregated and individual data from children with presumptive TB will be extracted from facility registers and individual data will be collected using an electronic medical record (EMR), both data sources will be entered in national Demographic Health Information System 2 databases. Questionnaires and individual/group interviews (among healthcare workers (HCWs), parents/caregivers and key informants), supervision and mentoring reports and quantitative cost tools will be used. Ethics and dissemination: Ethics approval was obtained from national ethics committees in Mozambique (Instituto Nacional de Saúde review board and National Committee for Bioethics in Health) and Zambia (University of Zambia ethical review board and National Health Research Authority); this includes a waiver for analysing data collected by NTPs (no identifiable information reported, intervention with minimal risk) without individual consent from children’s parents/caregivers. Informed consent will be obtained from HCWs, parents/caregivers and key informants. Results will be openly shared with the scientific community, WHO and national and international stakeholders for translation into policy and practice. Procedures for requesting further use of Decide TB data will be publicly available. Trial registration number: NCT06593080 ; PACTR202407866544155.

Current efforts to reduce global tuberculosis incidence have proved insufficient, highlighting that urgent action is needed to address underlying modifiable risk factors such as undernutrition. We aimed to estimate the global impact of eliminating undernutrition on tuberculosis incidence among adults, accounting for varying nutritional status by country, sex, and age, in addition to incorporating the continuous, non-linear relationship between BMI and tuberculosis risk. For this modelling study, we used a continuous risk framework to consider the population-level implications of BMI distributions for tuberculosis incidence in adults aged 15 years or older in 2023. We generated BMI distributions for each country, sex, and age group, and applied a bilinear model for the logarithmic relative risk of tuberculosis incidence at different BMI values. We assessed the impact of eliminating moderate-to-severe undernutrition (BMI 2) or all undernutrition (BMI 2) on tuberculosis incidence by constructing counterfactual BMI distributions that redistributed those with low BMI to high BMI, proportional to the remaining density. We estimated that eliminating moderate-to-severe undernutrition could avert 1·4 million (95% uncertainty interval 1·1-1·7) tuberculosis episodes globally, representing 14·6% (12·6-16·6) of global adult incidence in 2023, while eliminating all undernutrition could avert 2·3 million (1·8-2·7) episodes, representing a reduction in global tuberculosis incidence of 23·7% (20·9-26·5). The largest proportional reductions in tuberculosis incidence could be achieved by eliminating undernutrition in the WHO African, South-East Asia, and Eastern Mediterranean regions; in females; and in adolescents or older adults. Almost a quarter of global tuberculosis incidence in adults could be averted by eliminating undernutrition, approximately two-and-a-half times higher than current estimates. These findings highlight the urgent need to scale up population-level nutritional interventions, which could have myriad social and health benefits beyond tuberculosis, alongside research to establish optimal implementation strategies and impacts. None.

Introduction: Integrated care is increasingly adopted to address the needs of patients with multimorbidity, but cost-effective configuration of integrated healthcare pathways remains unclear. This study reviewed decision analytic models (DAMs) used in economic evaluations of integrated care interventions for cardiometabolic multimorbidity. Methods: A systematic search of eight electronic databases was conducted to identify peer-reviewed articles published in English until November 2024. Studies using DAMs to evaluate integrated care interventions for patients at risk or having cardiometabolic multimorbidity were included. Data on DAMs characteristics, integrated care models evaluated, and diseases were summarised. The quality of reporting was assessed using Philips (2006) checklist. Results: Sixteen studies met inclusion criteria. Most studies (81%) were cost utility analyses, focused on hypertension and/or diabetes concordant multimorbidity (69%). High-income countries accounted for 69% of the studies. Markov models were used the most (63%), with only three studies employing individual patient simulation (microsimulation) models. Few studies were explicit about data validation and reporting uncertainty. Conclusion: Economic evaluations of integrated care cardiometabolic multimorbidity should adopt microsimulation to better capture patient-level interactions and health outcomes. Better reporting of validation and uncertainty is needed. There is limited application of DAM-based economic evaluations of integrated care in low- and middle-income countries.

Background Post–licensure vaccine effectiveness and impact studies provide evidence on how vaccines perform under routine programme conditions in the real world. In sub–Saharan Africa (SSA), vaccine introductions frequently coincide with concurrent public health and social measures that may influence disease risk and transmission. Failure to account for these concurrent interventions may affect the interpretation of vaccine effects. Methods We conducted a systematic review of post–licensure vaccine effectiveness and impact studies conducted in children under five years of age in SSA. Electronic databases were searched for peer–reviewed studies published between January 2000 and December 2019. Eligible studies used observational designs to estimate vaccine effectiveness or population–level impact. Two reviewers independently screened studies, extracted data, and assessed methodological quality using Joanna Briggs Institute tools. We examined study designs, vaccines evaluated, outcomes assessed, and whether public health and social measures (PHSMs) were measured or adjusted for. A narrative synthesis was undertaken. In addition, we conducted a meta–analysis for rotavirus and pneumococcal conjugate vaccines where we explored the heterogeneity in individual–level effectiveness estimates where designs and outcomes were comparable. Results Sixty–four studies met the inclusion criteria, covering eight vaccine–preventable diseases. Rotavirus vaccines were most frequently evaluated, followed by pneumococcal conjugate vaccines. Case-control and ecological designs were most common, while cohort and time–series analyses were less frequently used. None of the included studies collected, reported, or adjusted for PHSMs such as nutrition, WASH, or access to healthcare. The implications of this omission varied by pathogen. Rotavirus vaccine effectiveness estimates from comparable individual–level designs were consistent across settings, with no evidence of between–study heterogeneity. Pneumococcal vaccine effectiveness estimates showed substantial heterogeneity, which appeared to reflect differences in outcome definitions, host risk profiles, and study context. Estimates for other vaccines were generally protective in direction, although the magnitude and precision varied across studies. Conclusions Post–licensure vaccine effectiveness and impact studies in SSA rarely account for concurrent PHSMs. The consequences of this omission are not uniform across vaccines. For some pathogens, effectiveness estimates appear robust to unmeasured contextual change, while for others they are highly sensitive to outcome choice and setting. Future evaluations should prioritise systematic measurement of key PHSMs and consider study designs that better account for time–varying context. Strengthening routine data systems to capture these factors is essential for generating interpretable evidence to inform immunisation policy.

Background: Use of oral cholera vaccine (OCV) is globally recommended as a public health response to cholera outbreaks, alongside water, sanitation and hygiene (WASH) interventions. Estimating vaccine effectiveness during emergencies in low- and middle-income countries is challenging because vaccination campaigns are often implemented over short time frames, while individual-level data are frequently incomplete due to constraints in infrastructure, resources and data systems. There is a need for pragmatic approaches that can generate timely, policy-relevant evidence using routinely collected data. Methods: We analysed routine surveillance data from a large 2022–2023 cholera outbreak in Blantyre District, Malawi. The EpiEstim framework was used to generate estimates of the time-varying reproduction number (Rₜ) from line-listed case data. We modelled changes in 𝑅 _???? as a function of cumulative OCV coverage using a log-linear framework and propagated uncertainty through posterior sampling. Lagged WASH exposure variables were incorporated in the model to generate adjusted vaccine effectiveness estimates and to explore potential interaction effects. Sensitivity analyses assessed robustness to alternative lag structures. Findings: The Blantyre outbreak was characterised by an initial period of low-level transmission followed by a sharp increase in cases from late November 2022, after which transmission declined steadily through April 2023. This decline coincided with the implementation of a reactive OCV campaign. The majority of the cases were among middle-aged men living in urban Blantyre. The unadjusted vaccine-associated reduction in transmission was estimated at 53.52% (95% credible interval (CrI):42.5–64.1%). After adjusting for a 7-day rolling average WASH activity, total vaccine effectiveness increased to 62.1% (95% CrI: 49.3–74.9%). Sensitivity analyses using alternative lag structures for WASH exposure produced comparable adjusted estimates. Interpretation: Implementation of OCV contributed to a substantial reduction in cholera transmission during the outbreak. This study demonstrates a feasible approach for estimating vaccine-attributable impact whilst accounting for public health and social measures, such as WASH interventions. The methods described will be useful in outbreaks where classical observational designs are not possible, providing actionable evidence to policy makers for outbreak response in resource-limited settings. Funding: MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership (UKRI), National Institute for Health and Care Research (NIHR) Global Health Research Group on Gastrointestinal Infections and Wellcome through the core grant to the Malawi-Liverpool-Wellcome Research Programme. Research in context: Evidence before this study: Before undertaking this analysis, our team and collaborators generated detailed epidemiological and genomic evidence describing the 2022–2023 cholera outbreak in Blantyre, Malawi. Our previous fine-scale spatial work demonstrated marked heterogeneity in cholera burden across urban Blantyre. We found that transmission concentrated in densely populated informal settlements and areas with poor water and sanitation infrastructure. Our genomic analysis of outbreak isolates showed that the epidemic was driven by a recently introduced seventh-pandemic El Tor Vibrio cholerae sub-lineage AFR15 linked to regional and international transmission events, with epidemic expansion occurring during late 2022. These studies characterised where transmission occurred and the evolutionary origin of the outbreak strain. The population-level effect of reactive oral cholera vaccination (OCV) or concurrent and improved water, sanitation and hygiene (WASH) interventions on transmission dynamics during the outbreak was not quantified. In linked work, we conducted a systematic review of post-licensure vaccine impact and effectiveness studies from sub-Saharan Africa (CRD42023436851) to assess the principal study designs and the extent to which they adjusted for concurrent public health and social measures (PHSMs), such as WASH interventions. We searched PubMed, EMBASE, MEDLINE, CINAHL, and Google Scholar for vaccine impact or effectiveness studies conducted in children under five years and screened reference lists of included studies. Across all eligible studies, none measured or adjusted for concurrent PHSMs. Added value of this study: Using surveillance, vaccination, and WASH data collected from Blantyre district by the Malawi Ministry of Health, we estimated the vaccine-associated reduction in transmission during a large reactive OCV campaign. By linking time-varying R ₜ estimates to cumulative vaccine coverage within a posterior sampling framework, we provide field-relevant effectiveness estimates from a setting where traditional individual-level designs were not feasible. We further evaluated whether concurrent WASH activity materially altered vaccine effect estimates. Implications of all the available evidence: Taken together with prior spatial and genomic analyses of the same outbreak, our findings provide a more complete picture of cholera control in Malawi. The earlier work clarified transmission geography and pathogen introduction. The present analysis quantifies the population-level impact of reactive vaccination under real-world programme conditions. This integrated evidence base supports ministries of health in interpreting vaccine performance during rapidly evolving outbreaks and in strengthening the routine data systems required for timely evaluation of interventions.