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Micro-elimination of Hepatitis C virus (HCV) infection in the General Population Cohort in rural Uganda: Long-term follow-up to assess feasibility and outcomes of a screening and treatment intervention.
Get PDFBACKGROUND: The availability of highly effective curative direct acting antiviral (DAA) therapy for hepatitis C virus (HCV) is a cornerstone of elimination strategies. We report on long-term follow-up as part of a programme that delivered HCV screening and treatment in a population cohort in Uganda. METHODS: Screening for HCV, HIV and HBV was offered to > 7000 participants in the Kyamulibwa General Population Cohort (GPC) in Kalungu District in rural South-West Uganda in 2011. In 2017, DAA treatment was offered to those individuals who had previously tested HCV RNA positive who could still be traced, with fixed dose combination ledipasvir + sofosbuvir (LED/SOF) for 12 weeks, and post-treatment follow-up at 24 weeks. Clinical review and elastography was repeated in 2023, and verbal autopsy data reviewed. RESULTS: 13 individuals tested HCV RNA positive, of whom five had been born in Uganda and eight originated from Rwanda. The median age at HCV diagnosis was 61 (range 48-90) and 10/13 (77 %) were male. Six years later, five had died, one had left the area, and seven individuals were traced, all of whom accepted treatment, with confirmed cure (sustained virologic response (SVR)). After a further six year interval, four of those treated were followed up. Among those who had died, a high prevalence of liver disease was suggested by verbal autopsies. CONCLUSION: Among individuals offered DAA treatment, acceptance and cure rate were high. In this setting, HCV infection likely contributed to mortality, and affected older adults and migrants, suggesting these groups might be priorities for future micro-elimination programmes
Major Causes of Perinatal and Paediatric Mortality in Sub-Saharan Africa and South Asia: Adjustment for Selection Bias in the CHAMPS Network.
Get PDFBACKGROUND: Studies of child mortality that employ minimally invasive tissue sampling (MITS) produce highly accurate cause of death data; however, selection bias may render these as non-representative of their underlying populations. OBJECTIVES: Estimate cause-specific mortality fractions and rates for the five most frequent causes-underlying and others in the chain of events leading to death-among stillbirths, neonatal, infant and child deaths-in Sub-Saharan Africa and South Asia, adjusted for any identified selection biases. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network collects standardised, population-based, longitudinal data on causes of death among stillbirths and under-five children in 12 catchments in seven countries in Sub-Saharan Africa and South Asia. Cause-specific mortality fractions and rates were calculated for the five most frequent causes among stillbirths, neonatal, infant and child deaths, and for the five most frequent maternal conditions among perinatal deaths; all estimates were subsequently adjusted for selection bias. Selection probabilities were estimated from membership in subgroups defined by factors hypothesised to affect selection. RESULTS: In 2017-2020, of 10,122 deaths ascertained, 5847 (57.8%) were enrolled in CHAMPS and 2654 (26.2%) additionally consented to MITS. Estimates were calculated for 265 and 65 site/age-specific causes of death and maternal conditions, respectively; five (1.9%) and four (6.2%) required adjustment, respectively, but they did not meaningfully change. Estimates were calculated for 34 site-specific causes of death among all stillbirths and under-five deaths combined; 28 (82.4%) required adjustment (all included age at death), and change-in-estimates demonstrated considerable variability. CONCLUSIONS: Selection bias is not a concern in the CHAMPS Network. Deaths where MITS were performed accurately represent the distribution of causes of death in their respective target populations, specifically when stratified by age or adjusted accordingly. Future studies of child mortality that employ MITS should consider adjusting for age at death for their measures of frequency
Estimates of epidemiological parameters for H5N1 influenza in humans: a rapid review.
Get PDFBACKGROUND: The ongoing H5N1 panzootic in mammals has amplified zoonotic pathways to facilitate human infection. Characterising key epidemiological parameters for H5N1 is critical should it become widespread. AIM: To identify and estimate critical epidemiological parameters for H5N1 from past and current outbreaks, and to compare their characteristics with human influenza subtypes and the 2003 Netherlands H7N7 outbreak. METHODS: We searched PubMed, Embase, and Cochrane Library for systematic reviews reporting parameter estimates from primary data or meta-analyses. To address gaps, we searched PubMed and Google Scholar for studies of any design providing relevant estimates. We estimated the basic reproduction number for the recent outbreak in the United States (US) and the 2003 Netherlands H7N7 outbreak. In addition, we estimated the serial interval for H5N1 using data from previous household clusters in Indonesia. We also applied a branching process model to simulate transmission chain size and duration to assess if simulated transmission patterns align with observed dynamics. RESULTS: From 46 articles, we identified H5N1's epidemiological profile as having lower transmissibility (R0 < 0.2) but higher severity compared to other human subtypes. Evidence suggests H5N1 has a longer incubation (∼ 4 days vs. ∼ 2 days) and serial intervals (∼ 6 days vs. ∼ 3 days) than human subtypes, impacting transmission dynamics. The epidemiology of the US H5 outbreak is similar to the 2003 Netherlands H7N7 outbreak. Key gaps remain regarding latent and infectious periods. CONCLUSIONS: We characterised critical epidemiological parameters for H5N1 infection. The current US outbreak shows lower pathogenicity, but similar transmissibility compared to prior outbreaks. Longer incubation and serial intervals may enhance contact tracing feasibility. These estimates offer a baseline for monitoring changes in H5N1 epidemiology. CLINICAL TRIAL: Not applicable
Severe infection incidence among young infants in Dhaka, Bangladesh: an observational cohort study.
Get PDFINTRODUCTION: Heterogeneity in definitions of severe infection, sepsis and serious bacterial infection (SBI) in infants limits the comparability of randomised controlled trials (RCTs) of infection prevention interventions. To inform the design of infection prevention RCTs for infants in low-resource settings, we estimated the incidence of severe infection and death among Bangladeshi infants aged 0-60 days using variations in case definitions. METHODS: Among 1939 infants born generally healthy in Dhaka, Bangladesh, severe infection was identified through up to 12 scheduled community health worker home visits from 0 to 60 days of age or through caregiver self-referral. The primary severe infection case definition combined physician documentation of standardised clinical signs and/or diagnosis of sepsis/SBI, plus either a positive blood culture or parenteral antibiotic treatment for ≥5 days. Incidence rates were estimated for the primary severe infection definition, the WHO definition of possible SBI, blood culture-confirmed infection and five alternative definitions including non-injury death. RESULTS: Severe infection incidence per 1000 infant-days was 1.2 (95% CI 0.97 to 1.4) using the primary definition, 0.84 (0.69 to 1.0) using the WHO definition of possible SBI, 0.026 (0.0085 to 0.081) using blood culture-confirmed infection and 0.061 (0.029 to 0.13) for death. One-third of cases met criteria for the primary severe infection definition through physician diagnosis of sepsis/SBI rather than the standardised clinical signs, and 85% of cases were identified following caregiver self-referral despite frequent scheduled visits. CONCLUSIONS: Severe infection incidence in infants varied considerably by case definition. Using a clinical sign-based definition may miss a substantial proportion of cases identified by physician diagnosis of sepsis/SBI. A consensus definition of severe infection in infants that balances permissiveness and stringency and can be operationalised in low-resource countries would improve the comparability of RCTs. If health facilities are accessible and caregivers readily seek care for infant illness, frequently scheduled home assessments may not be necessary
‘You can sleep hungry just to buy the medicine’: Applying a patient-centred model of cumulative complexity to explore how patients manage the lifelong workload of hypertension care in Kenya
Get PDFThis research applies the Cumulative Complexity model to examine patient experiences of hypertension management following prescription of anti-hypertensive medication in the public health system in Kenya. Set in Kiambu County, central Kenya, it draws on abductive analysis of interviews with patients (n = 24), caregivers (n = 7) and non-participant observation in four purposively selected public facilities conducted between November 2022 and April 2023. Patients undertook three kinds of ‘work’ to reduce their blood pressure: processing work to accept hypertension diagnosis and its chronic dimension; practical work managing care and medications, and work of managing emotions. Four inter-related domains of patient capacity influenced patients' ability to do this work: individual financial resources; physical functioning; social support and religious faith. Variations in treatment cost and medicine availability increased patient workload. When workload overwhelmed capacity treatment adherence was interrupted. Interruptions in treatment resulted in negative feedback loops further reducing patient capacity. Recognising temporal variability in workload and capacity is key to understand treatment adherence in resource constrained settings. Consideration of adaptive counter-agency can strengthen treatment burden models. We encourage policy makers to prioritise addressing treatment burdens to support treatment adherence and sustained hypertension control
Addiction Lives: Isidore Obot.
No full textIsidore Obot was born in 1948 as the sixth of seven children in a small village in Akwa Ibom State, Nigeria. In the period leading up to Nigerian independence there was a growing emphasis on educating young people to prepare them for post independence challenges.
He attended primary school and then a residential seminary school run by Catholic priests from Ireland. His final year (1967) coincided with the beginning of the Nigerian civil war when schools were closed in affected areas, but he was able to complete his secondary school education later in another school. Like many of his mates Isidore took his studies very seriously and developed interest in reading on a wide range of subjects.
His sister and her husband had left for the United States on a study abroad scholarship programme and he joined them in the US, studying at Loyola College in Baltimore from 1973. His family expected him to study medicine, but he chose psychology instead, a subject which no one in his village knew anything about. He completed a bachelor’s degree within four years, did a Master’s in the same department and then moved to Howard University in Washington where he did his doctorate. He later completed a Master of Public Health degree at Harvard University and has held several training and post-graduate fellowships.
In those graduate programmes he encountered direct references to addiction, and he began to focus greater attention on substance abuse as a behavioural health issue (however, his interest in the field of addiction had initiated in high school in Nigeria when he read about behaviour in foreign magazines, in particular Time and Readers’ Digest). He also developed a strong interest in survey research. As a research fellow working with Jim Anthony at the Johns Hopkins School of Public Health, he was drawn to analysis of data from secondary sources like the US National Household Survey.
Isidore returned to Nigeria in late 1982 for a compulsory year of national service, went back to the US for postdoctoral training and then took up a position at the University of Jos, in Nigeria, in 1985. Among the courses he taught was the psychology of substance abuse, the only course on addiction in the university.
He and his colleagues wanted to do research, but little funding was available. Personal funds were the only means of supporting research. In the late 1980s he gained a small grant from the university to conduct a population survey of alcohol and other drug use in the central (middle belt) region of the country. This resulted in the publication of a monograph, and he also contributed data from the survey to a WHO publication edited by Robin Room.
Addiction was not regarded as a serious problem in Nigeria before independence and professionals who saw the problem coming called for a response based on law enforcement, where the main problem was cannabis and the way to limit use was to limit supply. The late 1980s to early 1990s was a period of growing interest in all aspects of the drug scene in Nigeria. From what was primarily a trafficking country, citizens became users in large numbers and addiction became a disorder of public health concern.
The earliest published studies were by Professor Lambo and colleagues working in psychiatric facilities. In the late 1980s Dr Ona Pela founded the Nigerian Institute on Substance Abuse. Obot expanded addiction research to include social and behavioral aspects. In 1990 he founded a research society: the Centre for Research and Information on Substance Abuse (CRISA). The Centre is known in particular for two activities: the first is the Biennial International Conference on Drugs, Alcohol and Society in Africa, launched in Nigeria in 1991; the second is the publication of the African Journal of Drug and Alcohol Studies, launched in 2000, of which he is editor in chief. Both the conference series and the journal have benefitted from many external grants.
Working in the addiction field has not been easy as addiction is a highly stigmatized area in Africa. CRISA has conducted surveys with funding from the Nigerian government and has also received small grants to conduct research on alcohol, train practitioners, organize conferences and provide services for people who use drugs.
Obot was influenced by the work of Thomas Adeoye Lambo, Professor of Psychiatry at the University of Ibadan, who later became deputy director of WHO in Geneva.
In terms of where the field is heading, the Nigerian government has adopted harm reduction as a policy. The national survey, funded by the European Union and carried out by CRISA in 2017, opened many eyes to the extent of the problem and is about to be repeated in 2025. Obot considers that there is a need for stand-alone and degree-awarding programmes in substance use within social and sciences to give addiction independence as a core discipline in higher education
Genetic dynamics of the Duffy antigen receptor for chemokines gene and Plasmodium vivax circulation within sub-Saharan Africa.
Get PDFINTRODUCTION: Duffy antigen receptor for chemokines (DARC) is a transmembrane receptor (glycoprotein) expressed on human red blood cells. Sub-Saharan Africa (sSA) individuals, who suffer the most of the global malaria burden, predominantly carry a Duffy negative phenotype. Expression of this gene (found among Duffy-positive individuals) is known to be essential for P. vivax invasion of RBCs. While P. falciparum is the predominant Plasmodium in sSA, the upward trend in P. vivax infection is a major threat to the malaria eradication programme in the region. Since Duffy null individuals (homozygous negative) lack DARC expression, we investigated the DARC gene dynamics in relation to the emerging presence of P. vivax infections in a previously predominant P. falciparum endemic region. METHODS: A total of 223 DARC genes were retrieved from the NCBI database across various countries, Nigeria, Cameroon, Ethiopia, Madagascar and South Africa and were used for population dynamic analysis using different population genetic metrics. FINDINGS: Among these sSA countries, South Africa showed the most haplotype and nucleotide diversity compared to other parts of sSA. Various selection pressures were observed in Western Africa and the Central African Republic. Population structure analysis revealed DARC population clustering of Cameroon, Nigeria and Ethiopia (despite Ethiopia's geographic distance), suggestive of shared ancestry and minimal DARC locus divergence. Conversely, South Africa and Madagascar showed a distinct genetic lineage reflecting differences in evolutionary pressures. CONCLUSION: Our analysis suggests minimal genetic diversity within sSA with evidence of selection potentially attributed to the recent emergence of P. vivax infections. However, greater diversity was observed in South Africa. Evidence of selection of this gene and detection of P. vivax among Duffy-null individuals in the other regions is truly a public health concern
The economic burden of COVID-19 premature mortality in Kuwait.
No full textBACKGROUND: COVID-19 has caused substantial mortality worldwide, with significant economic consequences. In countries with segmented labour markets, such as Kuwait—where most citizens work in the public sector and most non-Kuwaitis occupy high-exposure essential jobs—the economic impact of premature mortality could be considerably high and these losses may differ across population groups. No prior study in the Gulf region has quantified these losses using established valuation methods.
METHODS: We conducted a retrospective analysis of all confirmed COVID-19 deaths in Kuwait between 2020 and 2022. Years of Potential Life Lost (YPLL) was calculated to measure the epidemiological burden of premature mortality. The economic cost of premature mortality was estimated from a societal perspective using three approaches: the Value of Statistical Life (VSL), the Human Capital Approach (HCA), and the Friction Cost Approach (FCA). Consumption, wage, and employment parameters were drawn from national 2021 surveys, and all estimates were expressed in 2021 international dollars (PPP using VSL, 548 million PPP using FCA. Kuwaitis accounted for a larger share of VSL and HCA losses, whereas non-Kuwaitis bore the greatest share of YPLL and HCA losses in working ages. Sensitivity analyses showed that VSL results were most affected by discount rate and risk aversion, HCA by age-at-death and wage assumptions, and FCA by vacancy multipliers and friction periods; however, the relative ranking of the methods remained consistent.
CONCLUSIONS: Premature COVID-19 deaths in Kuwait generated a significant economic burden, falling most heavily on non-Kuwaiti working-age men. The findings highlight the need for improved occupational protections, stronger support for migrant workers, and targeted preparedness strategies in countries with similar dual labour-market systems.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-25940-x
Degrees of uncertainty: conformal deep learning for non-invasive core body temperature prediction in extreme environments.
Get PDFAccurate estimation of core body temperature (CBT) is essential for physiological monitoring, yet current non-invasive methods lack statistically calibrated uncertainty estimates required for safety-critical use. Here we introduce a conformal deep learning framework for real-time, non-invasive CBT prediction with calibrated uncertainty, demonstrated in high-risk heat-stress environments. Developed from over 140,000 physiological measurements across six operational domains, the model achieves a test error of 0.29 °C, outperforming the widely used ECTemp™ algorithm with a 12-fold improvement in calibrated probabilistic accuracy and statistically valid prediction intervals. Designed for integration with wearable devices, the system uses accessible physiological, demographic, and environmental inputs to support practical, confidence-informed monitoring. A customizable alert engine enables proactive safety interventions based on user-defined thresholds and model confidence. By combining deep learning with conformal prediction, this approach establishes a generalizable foundation for trustworthy, non-invasive physiological monitoring, demonstrated here for CBT under heat stress but applicable to broader safety-critical settings
A quest for questions: The JUSTRA as a matrix for navigating just food system transformations in an era of uncertainty
Get PDFA just food system transformation is imperative to meet this century's goals of environmental sustainability, economic fairness, and equitable social well-being. While considerations of justice are beginning to inform food system transformation debates, there remains a lack of conceptual and practical integration of these two historically separate disciplinary perspectives. This perspective therefore proposes the just transformation matrix (JUSTRA), which integrates justice and transformation concerns using an interrogative approach. Interrogatives probe the historical, present, and future intersections of justice with specific food system elements. If used conscientiously, the JUSTRA can assist a wide spectrum of food system actors in strategizing, implementing, and monitoring just food system transformations. It can also help stakeholders to more thoughtfully engage with power imbalances both among users and in the broader food system more broadly—if used “in bona fides.” Thus, while further testing is necessary to fully realize the potential of the JUSTRA, the matrix can become a powerful tool in multi-stakeholder dialogues to navigate unpredictable, diverse, and power-laden complexities of just food system transformations