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Towards triple elimination of HIV, syphilis and HBV mother-to-child transmission: Protocol of a simplified and integrated strategy in Burkina Faso and The Gambia: Protocol for the phase 1 of the TRI-MOM project.
Get PDFINTRODUCTION: Mother-to-child transmission (MTCT) of HIV, syphilis, and hepatitis B virus (HBV) commonly observed in the WHO African region is associated with excess morbidity and mortality. Despite some progress, the coverage of interventions to prevent MTCT of these infections remains insufficient, particularly for syphilis and HBV. To fulfil these gaps and achieve the triple elimination of MTCT of these infections by 2030, the World Health Organization (WHO) advocates for integration of prevention of MTCT (PMTCT) activities for HBV with HIV and syphilis antenatal services. In partnership with the local governments, the TRI-MOM project, conducted in 2 phases, aims to evaluate a simplified (based on inexpensive rapid diagnostic tests), integrated (in maternal and child health services) and coordinated (between the various programs and health care workers) strategy for the triple elimination of HIV, syphilis and HBV MTCT in Burkina Faso and The Gambia.
METHODS AND ANALYSIS: The strategy will be implemented in 5 rural and urban health facilities in each country and will include four activities: i) training sessions for healthcare workers working in maternal and child health services, ii) screening of pregnant women of the three infections using rapid diagnostic tests at the first antenatal visit, iii) clinical assessment and treatment of women tested positive for any of the 3 infections, and iv) raising awareness on HIV, Syphilis and HBV PMTCT among pregnant women and empowering those screened positive. 17,000 pregnant women are expected to be screened. The strategy will be evaluated through an interdisciplinary, mixed-methods approach comprising three studies: i) a quantitative and qualitative cross-sectional study conducted both before and after the implementation of the strategy to assess its impact on triple screening coverage in pregnant women; ii) a an intervention study with longitudinal follow-up of pregnant women positive for any of the three infections to assess the coverage of PMTCT measures; and iii) a cost and cost-effectiveness analysis of the project compared to the reference situation in each country, which will rely on a micro costing study to estimate the incremental cost of the strategy per mother/child couple compared with the reference situation in each country, and compare it to the number of avoided infections.
ETHICS AND DISSEMINATION: The study protocol has been approved by the competent authorities of the countries participating to the research (the LSHTM/MRCUG Scientific Coordinating Committee, the Gambia Government/MRC Joint Ethics Committee, the LSHTM ethics committee, the Burkinabe National Ethical Committee for Research in Health and the French Commission on Information Technology and Liberties). Results on the feasibility and acceptability of the triple elimination strategy will be disseminated using different media including policy briefs, posters and articles.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05951751
Nonlinear relationships between urban morphology, socioeconomic conditions, and infectious disease risk: evidence from COVID-19 in Tokyo
Get PDFUrban infectious disease outbreaks pose critical challenges to public health in rapidly urbanizing cities. The COVID-19 pandemic provided a natural experiment to examine how area-level environmental and socioeconomic contexts are associated with infection risk over time. This study analyzed seven pandemic stages in Tokyo, Japan (2020–2022), across 53 municipalities using random forest-based interpretable machine learning models with SHapley Additive exPlanations and partial dependence plots diagnostics. Feature selection and nonlinear modeling identified key drivers among 49 candidate variables. The results revealed significant spatial clustering of COVID-19 infection rates, with persistent hotspots in central wards like Shinjuku, Minato, and Shibuya, while suburban regions of Western Tokyo maintained lower infection rates. Key built environment factors exhibited stage-specific, nonlinear, and threshold-like associations with infection rates, including road density (25 km km
−2
), FAR (0.25–0.3), and population density (400 and 600 people/km
2
). These associations were predominantly positive beyond the identified thresholds, indicating elevated infection risk under higher density and connectivity conditions. Socio-demographic factors also showed temporal specificity: the percentage of foreigners displayed a threshold around 1.5%, and construction worker density emerged as a relevant correlate during the Omicron-dominated phase. Overall, the relative importance and marginal patterns of these associations varied across intervention stages, highlighting temporal instability in area-level risk correlates. Importantly, these findings are associational rather than causal, reflecting contextual exposure conditions at the municipal scale. From an environmental epidemiology perspective, the results suggest that stage-sensitive and spatially explicit interpretation of area-level indicators may enhance infectious disease surveillance, compared with approaches assuming temporally invariant or linear effects
Multistakeholder perspectives on geographical accessibility to emergency obstetric care in Benin City, Nigeria
Get PDFIntroduction In many Nigerian cities, travel to emergency obstetric care (EmOC) remains challenging, and the so-called urban advantage is shrinking. Benin City, Nigeria, has four major referral hospitals providing EmOC, yet maternal mortality remains very high. While facility-based deliveries are common, many women still face significant delays in reaching timely, appropriate care. This study explored women’s and stakeholders’ perspectives on EmOC geographical accessibility in this rapidly urbanising city. Methods This descriptive qualitative study was conducted in four referral hospitals in Benin City, Nigeria. In-depth interviews were conducted with 44 purposively recruited women who had experienced obstetric emergencies, alongside 11 key stakeholders, including health service planners and policymakers. Women were recruited from hospital settings and communities in three local government areas identified as having the poorest geographical access to EmOC. Thematic analysis followed Braun and Clarke’s six-step approach. Results Four themes emerged from our study: 1) travel challenges force some women to use unsafe transport and seek informal care in emergencies, 2) bypassing non-preferred facilities prolonged travel to obstetric care, 3) systemic inefficiencies further complicates EmOC geographical access, and 4) multi-sectoral action needed to improve EmOC geographical access. Women described unsafe roads, lack of transport, and security concerns, particularly at night, leading to delays or resorting to traditional birth attendants. Referral inefficiencies, workforce shortages, and inadequate facility readiness compounded these delays. Participants proposed infrastructure upgrades, birth preparedness, improved insurance coverage, and stronger referral coordination to reduce in-transit delays and ensure equitable access. Discussion Timely access to EmOC in urban settings is undermined by the intersection of spatial inequities, system dysfunction, and unreliable service availability. Addressing these challenges requires integrated infrastructure planning, strengthened referral coordination, and investment in health workforce retention. Without effective implementation of existing policies and targeted support for high-burden areas, maternal health inequities will persist even in urban contexts
HIV-1 drug resistance among pregnant and breastfeeding mothers and its association with paediatric HIV infections in the Dolutegravir era in Uganda.
Get PDFOBJECTIVES: To determine the prevalence and patterns of HIV drug resistance mutations among pregnant and breastfeeding women in Uganda following the rollout of dolutegravir, characterize circulating HIV-1 subtypes and their association with resistance, and identify factors associated with vertical HIV transmission.
MATERIALS AND METHODS: This study involved 46 pregnant and 154 breastfeeding mothers in Uganda with viral loads (VLs) >1000 copies/mL. Residual plasma underwent genotypic resistance testing on the Illumina MiSeq platform, and HIVDRMs and subtypes were interpreted using the Stanford HIVdb algorithm. Participant characteristics were summarized descriptively, and associations between subtypes, HIVDRMs, and vertical transmission were assessed using chi-square tests, t-tests, and logistic regression.
RESULTS: Among 200 participants, 53.0% (95% CI: 46.0-59.9) had resistance to at least one antiretroviral therapy (ART) class. HIVDRM prevalence was 41.5% (CI: 34.8-48.5) for NNRTIs, 20.5% (CI: 15.4-26.7) for NRTIs, 4.0% (CI: 2.0-7.8) for PIs and 3.5% (CI: 1.7-7.2) for INSTIs. Notably, 13.5% had accessory mutations, including T97A, which can contribute to DTG resistance. HIV-1 subtypes A (57.0%) and D (30.5%) were most common, with few subtype C (6.5%) and recombinant forms (6.0%). Subtype D and routine/repeat VL monitoring following intensive adherence counselling were associated with HIVDRMs (P = 0.01 and P = 0.04 respectively). Seven infants tested HIV-1 positive, with poor maternal adherence and repeat VL significantly associated with seropositivity (P = 0.004 and P = 0.027, respectively).
CONCLUSION: This high HIVDRM burden highlights the urgent need for routine resistance testing, subtype-specific treatment strategies and improved ART adherence support to reduce mother-to-child-transmission, particularly in women with subtype D infections
Effectiveness of Puppetry-Based Sexual Health Promotion and Education Interventions: A Scoping Review
No full textDespite the widespread implementation of puppets as an art-based intervention for health promotion and behavioral change, no prior synthesis of the literature on the effectiveness of puppetry on sexual health outcomes exists. The purpose of this study was to describe the methods, efficacy, and evidence base for puppetry as a channel for sexual health education interventions across global settings and demographics. A scoping review was conducted using the PICOS framework and PRISMA-ScR guidelines, examining studies across 16 databases up to and including March 1, 2025. Twenty-seven studies (N = 27) met the inclusion criteria. In summary, puppetry interventions spanned diverse global settings, sexual health domains, and populations, with a notable recent rise in implementation. Findings indicate puppetry can improve sexual health behaviors and related antecedents. However, the evidence base remains limited. Recommendations for interventions include involving familiar facilitators for intervention delivery, continuous reinforcement of educational material, and participatory methods to enhance program inclusivity, relevance, and continuity. Comprehensive evaluations that include rigorous study design, robust intervention descriptions, and theoretical foundations to guide study design and analysis will improve future research to further demonstrate how puppetry improves sexual health outcomes and cultures of respect, equity, and sustained behavior change
Using inverse probability of censoring weighting to estimate hypothetical estimands in clinical trials: Should we implement stabilisation, and if so how?
Get PDFInverse probability of censoring weighting is an approach used to estimate the hypothetical treatment effect that would have been observed in a clinical trial if certain intercurrent events had not occurred. Despite the unbiased estimates obtained by inverse probability of censoring weighting when its key assumptions are satisfied, large standard errors and wide confidence intervals can be potential concerns. Inverse probability of censoring weighting with unstabilised weights can be simply implemented by calculating the reciprocal of the probability of being uncensored by the intercurrent events. To improve precision, stabilisation can be realised by replacing the numerator in the unstabilised weights with functions of the time and baseline covariates. Here, we aim to investigate whether stabilised weight is a preferred choice and if so how we should specify the numerator. In a simulation study, we assessed the performance of inverse probability of censoring weighting implementations with unstabilised weights and with different forms of stabilisation when the outcome analysis model was correctly specified or mis-specified. Scenarios were designed to vary the prevalence of the intercurrent event in one or both randomised arms, the existence of a deterministic intercurrent event, the indirect effect through baseline covariates and overall treatment effect, the existence and the pattern of time-varying effect and sample size. Results show that compared with unstabilised weights, stabilisation improves the efficiency of the inverse probability of censoring weighting estimator in most cases and the improvement is obvious when we stabilise for the baseline covariates. However, stabilisation risks increasing the bias when the outcome analysis model is mis-specified
Screening for Trypanosoma cruzi infection (Chagas disease) in the Latin American population living with HIV in London.
Get PDFBACKGROUND: There are an estimated 2482 people born in Latin American countries receiving care for HIV in the United Kingdom. Although national guidance recommends screening for Trypanosoma cruzi infection (Chagas disease) in this population, there is no formal screening programme. The aim of this study was to investigate the sero-epidemiology of T. cruzi in Latin American people living with HIV in London, with a view to informing screening strategies. METHODS: This was a cross-sectional study, using serological screening for T. cruzi and questionnaires. Adults receiving HIV care in three London hospital outpatient clinics and who were born in one of the 21 Chagas-endemic countries of South America, Central America or Mexico were identified by searching electronic medical records for country of birth codes. Eligible participants were invited to undergo T. cruzi screening (a single recombinant immunoglobulin G (IgG)-enzyme-linked immunosorbent assay (ELISA)) during routine HIV outpatient appointments. Positive screening tests were confirmed with an immunofluorescence antibody test, with discordant results resolved by an adjudicating immunoblot. RESULTS: A total of 351 participants were recruited between June 2023 and March 2025, including 181 (52%) who were born in Brazil, 73 (21%) in Colombia, 19 (5%) in Ecuador, 16 (5%) in Argentina, 15 (4%) in Venezuela and 12 (3%) in Bolivia. Uptake of serological screening was high (97% when offered face to face). Four participants (1%) had a positive screening test, of whom one had confirmed T. cruzi infection (seroprevalence 0.3%, 95% CI 0.01-1.6%), and three were deemed false positive screening tests. CONCLUSIONS: We report a low seroprevalence of T. cruzi infection in Latin American migrants in London living with HIV. Since the clinical consequences of untreated T. cruzi infection can be fatal, screening uptake is high, and individuals in non-endemic countries generally only need to be screened once, we recommend testing all Latin American people with HIV, especially women of reproductive age, those from high-prevalence countries and those with poor immune-virological control
The Malaria Vaccine Implementation Programme study area in Ghana: results of a household survey prior to the introduction of the RTS,S/AS01 vaccine.
Get PDFBACKGROUND: In 2019, the RTS,S/AS01E malaria vaccine (RTS,S) was introduced into Ghana's routine health system as part of the Malaria Vaccine Implementation Programme (MVIP). Household surveys were conducted prior to vaccine introduction and approximately 18 and 30 months post-introduction. We present a description of the area in Ghana based on the baseline household survey including malaria prevalence, malnutrition, wealth, insecticide-treated net (ITN) coverage, other health interventions (deworming, Vitamin A supplementation (VAS)), coverage of Expanded Programme on Immunization (EPI) vaccines, and health-seeking behaviour for febrile children. METHODS: The baseline household survey was conducted between 25 February and 18 March 2019 in a representative sample of 6778 households across 66 districts (33 in each of the implementing and comparator areas) in Ghana. Caregivers of children aged 5-48 months were interviewed. For each child, vaccination details were transcribed from the maternal and child health record book, and we measured the mid-upper arm circumference and obtained a malaria Rapid Diagnostic Test (RDT). Survey-weighted coverage estimates were obtained using standard survey methods. Survey Poisson regression was used to estimate prevalence ratios. RESULTS: Overall, 7768 children were included in the study, and 21% (95% CI 18-23) tested positive for malaria parasitemia by RDT. About 87%, 95%CI (85-89) of all households owned at least one ITN, and 62%, 95%CI (59-64) of children aged 5-48 months slept under an insecticide-treated net (ITN) the night before the survey. Additionally, 22%, 95%CI (21-24) of children reported having fever in the two weeks preceding the survey; among those with reported fever, 72%, 95%CI (69-74) sought advice or treatment, 40%, 95%CI (37-44) were tested for malaria, and 42%, 95%CI (39-46) of those with fever took an antimalarial drug. Additionally, 17%, 95%CI (16-19) had a mid-upper arm circumference (MUAC) ≤ 13.5 cm, and 1%, 95%CI (0-1) had a (MUAC) ≤ 11.5 cm. The uptake of vitamin A VAS in the 6 months prior to the survey was 36%, based on routine delivery through EPI, and deworming coverage was 29%. Coverage of EPI vaccines was > 90%. Indicators in comparison and implementation areas were comparable. CONCLUSIONS: The pilot implementation and evaluation of the RTS,S malaria vaccine in Ghana was conducted in an area with substantial malaria transmission and illness, modest health-seeking behaviour and ITN use, and good EPI vaccine coverage. This study has established the baseline comparability between implementation and comparator areas, which serves as the foundation for future feasibility assessments
Crystal structure of Schistosoma mansoni cathepsin D1 in complex with a nanobody reveals the conformation of the propeptide-bound state.
Get PDFSchistosoma mansoni cathepsin D1 (SmCD1) has been shown to be an essential enzyme for helminth metabolism due to its role in haemoglobin degradation: a key amino-acid source for the developing parasite. Therefore, the enzyme is a potential target for the development of antischistosomal inhibitors. SmCD1 has significant sequence identity to cathepsin D-like proteases found in other schistosome species and homology to mammalian aspartic proteases. Here, we report the first crystal structures of a helminth cathepsin D, SmCD1, and have identified a single-domain antibody (nanobody) that specifically binds to SmCD1 with nanomolar affinity but does not recognize human cathepsin D. We have mapped the epitope of the nanobody by determining the crystal structure of the enzyme-nanobody complex, revealing the conformation of SmCD1 in the propeptide-bound state
Treatment adherence with an oral nine-month regimen for rifampicin-resistant tuberculosis in South Africa.
No full textBACKGROUND: Adherence to antituberculosis therapy is an important determinant of treatment outcome in rifampicin-resistant tuberculosis (RR-TB). Understanding adherence to contemporary treatment regimens in routine care is needed to support implementation in TB programs. We aimed to characterize temporal adherence patterns among people receiving oral treatment for RR-TB. METHODS: We conducted a prospective observational cohort study at a referral TB hospital in South Africa. People ≥15 years with pulmonary RR-TB starting an oral 9-12-month regimen were included. Treatment adherence was measured using a digital pillbox during ambulatory care and with directly observed therapy during hospital care. The primary outcome was proportion of adherence days through nine months. Latent class group-based trajectory modelling was used to identify temporal adherence patterns. RESULTS: 209/248 (84.3%) participants had assessable adherence data from the digital pillbox or directly observed therapy. Overall median adherence was 82% (IQR 63-98) with combined measures, and 72% (IQR 51-92) with digital pillbox only. Four distinct adherence patterns were identified. Adherence was 93-100% in the first month. Two groups, representing 136 (65.1%) individuals, had small reductions in adherence over time, separated by higher and lower early adherence. In the other two groups, there was a 50% reduction in adherence by months three (48/209, 23.0%) and six (25/209, 12.0%), respectively. Lower adherence over time was associated with having exclusive ambulatory care, treatment with the shorter regimen only, and age <40 years. CONCLUSIONS: Treatment adherence declined over time in distinct temporal patterns. Group characteristics could identify individuals who may benefit from enhanced treatment support