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Tropical Medicine & International Health

Wiley

Preprints posted in the last 7 days, ranked by how well they match Tropical Medicine & International Health's content profile, based on 14 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Evaluating Mean Platelet Volume in relation to Disease Severity in Paediatric Sickle Cell Anaemia: A Cross-Sectional Study in Kwara State, North-Central Nigeria

Oladimeji, F. D.; Adewoyin, A. D.; Oyeleke, K. O.

2026-09-02 hematology 10.64898/2026.08.28.26361349 medRxiv
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Background: Sickle cell anaemia (SCA) is characterised by chronic haemolysis, inflammation, platelet activation, and recurrent vaso-occlusive complications. Mean platelet volume (MPV) is a readily available platelet index, but evidence regarding its relationship with disease severity in paediatric SCA remains limited and inconsistent, particularly in African populations. Objective: To evaluate the relationship between MPV and disease severity among children with SCA in Kwara State, North-Central Nigeria. Methods: This hospital-based cross-sectional study included 51 clinically stable children with confirmed SCA consecutively recruited from the paediatric haematology clinic of Children Emergency Specialist Hospital, Ilorin. Complete blood count, including MPV, was performed using a Rayto RT-7600 automated haematology analyser. Disease severity was assessed using a composite clinical and laboratory scoring system based on a previously described method. Pearson's correlation, Spearman's rank correlation, simple linear regression, and the Kruskal-Wallis test were used as appropriate. Statistical significance was set at p < 0.05. Results: Of 51 participants, 14 (27.5%) had mild, 33 (64.7%) moderate, and 4 (7.8%) severe disease. Mean MPV was 9.34 +/- 0.76 fL (range, 8.0-11.2). Pearson's correlation showed a weak positive, non-significant linear relationship with severity score (r = 0.231, p = 0.103), whereas Spearman's analysis showed a weak positive monotonic association (rho = 0.286, p = 0.042). Regression explained 5.3% of severity-score variation (R2 = 0.053, p = 0.103). MPV did not differ significantly across severity categories (H = 2.163, p = 0.339). MPV correlated inversely with haemoglobin (r = -0.556, p < 0.001) and positively with platelet count (r = 0.307, p = 0.029). Conclusion: MPV showed a weak relationship with disease severity but inconsistent statistical evidence across analyses. The limited explained variance and absence of significant differences between severity categories do not support MPV as a standalone severity marker. Larger longitudinal studies are warranted. Keywords: Sickle cell anaemia; Mean platelet volume; Disease severity; Platelet indices; Paediatric haematology; Cross-sectional study; Nigeria.

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Rural-urban disparities and associated factors of SARS-CoV-2 infection in Zambia: A convergent mixed-methods study using the Proximate Determinant Framework.

Wantakisha, E. W. R.; Nyirenda, S.; Narayani, M.

2026-08-31 epidemiology 10.64898/2026.08.25.26361355 medRxiv
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Background Rural-urban disparities in SARS-CoV-2 infection epidemiology remain poorly quantified and understood in Zambia despite differences in healthcare access, services and preventive interventions. This study examined the geographical distribution and associated factors of SARS-CoV-2 cases across selected rural and urban districts of Zambia. Methods A convergent mixed-methods study comprised of quantitative survey and qualitative interviews was conducted in; Ndola (Urban), Kafue (Peri-urban) and Lufwanyama (Rural). The proximate determinant framework guided variable selection and interpretation. Quantitative combined (Hospital-surveillance data with community survey), while qualitative included In-depth interviews. Participants were sampled using multistage sampling technique. Quantitative data were analysed using STATA version 17, while qualitative data were analysed thematically. Findings were integrated through triangulation. Results A total of 528 participants were included, with a median age 31 years (15-71). Overall SARS-CoV-2 positivity was 12.6%, varying across rural (16.5%), peri-urban (14.9%), and urban (9.9%) settings, though residence was not associated with infection (P<0.132). Participants aged [&ge;]49 years had significantly higher odds of infection (aOR=8.78; 95% CI:1.15-66.99), whereas secondary education (aOR=0.37; 95% CI:0.16-0.86) and hospital-based testing (aOR=0.37; 95% CI:0.15-0.92) were associated with lower odds of infection. Vaccine uptake was highest in urban areas but was not independently associated with infection. Qualitative findings revealed marked rural-urban differences in perceived susceptibility, testing access, vaccine decision-making, and adherence to preventive measures, explaining several quantitative observations. Conclusion SARS-CoV-2 infection across rural and urban settings in Zambia was influenced by demographic, behavioral, and health-system factors rather than geographic residence alone. These findings highlight the need for context-specific prevention strategies, equitable access to testing, strengthened community surveillance, and targeted risk communication to improve preparedness and response for future respiratory disease outbreaks.

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Diagnostic performance, implementation fidelity, and costs of the World Health Organization three-test HIV testing strategy in Malawi: a national retrospective evaluation

Chimpandule, T.; Tweya, H.; Goeke, L.; Masina, T.; Macheso, S.; Low, N.; Jahn, A.; Imai-Eaton, J. W. W.

2026-09-01 hiv aids 10.64898/2026.08.30.26361753 medRxiv
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Background: In 2019, WHO recommended three consecutive reactive serological test results for HIV diagnosis to reduce false-positive diagnoses. Malawi changed from a two-test to a three-test strategy in 2022 as HIV test positivity declined. We assessed diagnostic performance, implementation fidelity, and costs. Methods: We analysed national HIV testing data from Nov 1, 2022, to Oct 31, 2025. Using observed three-test classifications as the reference standard, we reconstructed classifications under the two-test strategy. We estimated positive predictive value (PPV), implementation fidelity, potential false-positive diagnoses prevented, incremental costs, and time to offset testing costs through avoided antiretroviral therapy expenditure. Results: Among 9,885,599 encounters eligible for implementation-fidelity analysis, 99.98% followed a valid three-test pathway. The diagnostic-performance analysis included 9,862,908 encounters, of which 171,351 (1.7%) were classified HIV-positive and 9,138 (0.09%) were inconclusive. Under the two-test strategy, 1,209 inconclusive encounters with a T1+/T2+/T3- sequence would have been classified as HIV-positive. Retesting and reference-laboratory data indicated that 82.5% of these would subsequently be classified as HIV-negative, corresponding to 997 false-positive diagnoses prevented (10.3 per 100 000 three-test non-positive encounters; 95% CI 9.7-10.9). Retesting within 1-2 weeks was associated with the highest odds of potential false-positive classification (adjusted OR 39.37, 95% CrI 30.63-50.61). The incremental cost was US$471 per false-positive diagnosis averted and was offset within 7.30 years. Conclusions: Malawi's transition to a three-test HIV testing strategy prevented false-positive diagnoses and unnecessary antiretroviral therapy at modest cost, supporting broader adoption of WHO guidance in similar settings. Funding: Gates Foundation.

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A target trial emulation study to estimate the causal effect of intravenous iron use during pregnancy and its effect on haematological and birth outcomes in Pakistan

Yazdani, N. S.; Oakley, E.; Khan, A.; Qazi, M. F.; Khakwani, S.; Sheikh, A.; Mazhar, A.; Iqbal, U. M.; Marquis, J.; Liaqat, B.; Kumari, K.; Caniglia, E. C.; Hotwani, A.; Nisar, I.; Jehan, F.; Smith, E. R.; Hoodbhoy, Z.

2026-09-03 epidemiology 10.64898/2026.08.29.26361700 medRxiv
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Background: Despite several trials on the hematological outcomes of intravenous (IV) iron in pregnancy, only few have examined its effect on birth outcomes. We estimated the causal effect of IV-iron on moderate or severe anaemia and birth outcomes. Methods: Women presenting to routine antenatal care in Pakistan with haemoglobin <10 g/dL were eligible for treatment. We used target trial emulation (TTE) methodology to estimate the effect of IV-iron treatment within 14 days of anaemia identification, compared to no treatment, on anaemia status at follow-up. A modified TTE analysis examined birth outcomes at delivery for singleton pregnancies, including birthweight, size-for-gestational-age, and mortality. We conducted a separate TTE for each of five gestational-age periods and pooled the results of each TTE. Results: We screened 3115 pregnancies of which 1715 were eligible for IV-iron; 1043 participants were treated during pregnancy. Those who received IV-iron had half the risk of moderate or severe anaemia in pregnancy compared with no treatment (pooled relative risk (RR) 0.40; 95% confidence interval (CI): 0.27, 0.59). The pooled effect of IV-iron on stillbirth suggested an 83% risk reduction (95% CI 55-94%), and trends were similar for perinatal and neonatal mortality. Conclusion: IV-iron treatment improved haematological status in pregnant women and was associated with a large reduction in stillbirth. Given limited data from randomised trials regarding fetal death and treatment earlier in pregnancy, this study contributes important information to the potential benefit of IV-iron in contexts where anaemia and its sequelae are a major public health problem.

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Development and Validation of a Point-of-Care Triage Scorecard to Enhance Tuberculosis Case Detection During Active Community Screening in Yogyakarta, Indonesia

Catrianiningsih, D.; Felisia, F.; Abdalla, A. S.; Puspitasari, S.; Dwihardiani, B.; Mulia, H. N.; Hidayat, A.; Triasih, R.

2026-08-31 infectious diseases 10.64898/2026.08.27.26361569 medRxiv
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In primary healthcare centers lacking advanced imaging, community-based active tuberculosis (TB) case finding often relies on basic symptom screening. This approach often misses cases and leads to the inefficient allocation of rapid molecular testing (RMT). We aimed to develop and internally validate a simple clinical triage scorecard to improve TB detection and guide RMT use in resource-constrained settings. We conducted a retrospective cross-sectional study of 15,137 adults ([&ge;]18 years) evaluated within the Zero TB Yogyakarta program (2020-2025). Participants with complete clinical assessments and confirmatory GeneXpert results were included. Using multivariable logistic regression, we identified independent clinical predictors, which were subsequently transformed into an integer-based point scorecard. Model performance was evaluated via discrimination and calibration, utilizing bootstrap resampling (1,000 iterations) for internal validation. Among the 15,137 participants, 251 (1.7%) were GeneXpert-positive. The final multivariable model identified eight independent predictors: age, male sex, body mass index, prolonged cough, hemoptysis, unexplained weight loss, TB contact history, and diabetes mellitus. The model demonstrated strong predictive accuracy, with an optimism-adjusted AUROC of 0.836 and good calibration. When translated to the integer scorecard and compared directly to standard national symptom screening, the scorecard performed (AUROC 0.81 vs. 0.73; p<0.001). At a high sensitivity cut off score of [&ge;] 0, the tool achieved 93.63% sensitivity and 41.33% specificity. This point-of-care clinical scorecard provides higher diagnostic accuracy than standard symptom screening algorithms. By offering flexible operational thresholds, it empowers local health programs to dynamically balance the urgency of case detection with available diagnostic capacity, optimizing GeneXpert allocation where advanced radiological imaging is unavailable.

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Location-allocation modeling identifies strategic health facilities to expand access to snakebite antivenom in the Brazilian Amazon

Garcia Campos, M. A.; Rocha, T. A. H.; Perez de Souza, J. V.; Murase, L. S.; Murta, F.; Sartim, M. A.; Sachett, J.; Seabra de Farias, A.; Azevedo Machado, V.; Wen, F. H.; Staton, C. A.; Monteiro, W. M.; Gerardo, C. J.; Nickenig Vissoci, J. R.

2026-08-31 public and global health 10.64898/2026.08.28.26360696 medRxiv
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Background: Snakebite envenoming is a major cause of preventable death and disability in the Brazilian Amazon, where long distances, sparse roads, and dependence on river transport delay access to antivenom. We developed location-allocation models to identify community health centers that could strategically expand access to antivenom in Amazonas State, Brazil. Methodology/Principal Findings: We conducted an ecological geospatial study using a 2025 WorldPop population surface, locations of existing and candidate health facilities, and a multimodal road-and-river transportation network derived from OpenStreetMap and HydroSHEDS. Population demand was represented by 7,065 populated centroids, including 1,586 within Indigenous territories. We applied a maximize-coverage algorithm with a six-hour travel-time threshold. Two models were developed: one for Amazonas excluding Manaus and one for populations living in Indigenous territories. Both models began with 77 facilities already providing antivenom and progressively added candidate community health centers until coverage gains plateaued. The plateau occurred at 110 facilities, corresponding to 33 additional centers. In the model excluding Manaus, this configuration covered 1,118,831 people, or 75.11% of the target population; 87.61% of those covered could reach care within three hours. In Indigenous territories, coverage increased from 50.55% to 69.50%, reaching 50,434 people, of whom 81.39% were within three hours of care. Validation used 3,595 snakebite notifications from the 30 highest-burden municipalities in the Brazilian Notifiable Diseases Information System during 2023-2025. The median proportion reaching care within six hours was 40.81% in observed data and 72.17% in model estimates. Conclusions/Significance: Strategically equipping 33 additional existing community health centers could substantially expand timely access to antivenom, particularly in rural and Indigenous areas. Location-allocation modeling that incorporates river transportation can support evidence-based decentralization of time-sensitive health services in geographically complex settings.

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Spatiotemporal Mapping of Point-of-Care Diagnostic Accessibility: A Data-Driven Pipeline for Point-of-Care Distribution Analysis in Western Uganda

Bergman, D.; Nyehangane, D.; Besancon, L.; Podkorytova, M.; Tsoumari, V.; Staikoglou, D.; Kimuli, A. N.; Richard, M. R.; Ogwok, P.; Nankoma, C.; Alfven, T.; Mwanga-Amumpaire, J.; Gaudenzi, G.

2026-09-01 public and global health 10.64898/2026.08.28.26361594 medRxiv
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All primary healthcare centers owned by the Ugandan government in the Western Region of Uganda were submitted to a questionnaire concerning current availability of POCT from the Essential diagnostic List 2 part 1a and 1b, and the African laboratory inventory done by African Society of Laboratory Medicine and AfricaCDC. The data from the questionnaire was then linked to open source geodata provided by TomTom, and population data to calculate and visualize the accessibility of captured POCT. Findings: Availability of POCT Malaria is almost 100%, HIV 68-90%, and >30% for a majority of the POCT in the EDL-2 panel. 90% of the population in Western Region live within 1 hour by car from most of the essential POCT. Figures in the complementary web-based application visualize the accessibility of POCT for Western Uganda. Diagnostic deserts are visualized. Interpretation: Access to POCT at primary health care facilities in western Uganda has expanded substantially over the past decades. The geo-mapping tool presented here could inform policy decisions on strengthening diagnostic capacity at the national, regional, and provincial level. Funding: Swedish Research Council and Infravis All supplementary materials and a preprint of this submission are available on our OSF repository https://osf.io/j7puk/.

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A mechanistic statistical model of dengue dynamics in an endemic region

Luna-Martinez, N.; Cruz-Rodriguez, E. X.; Bernal-Castro, E. A.

2026-09-03 epidemiology 10.64898/2026.09.01.26361961 medRxiv
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Background Dengue is a major public health challenge, and predictive models are crucial for early warning systems. However, many current modeling practices rely exclusively on climatic factors or employ complex algorithms that lack the interpretability needed for informed public health decision-making. To address these shortcomings, we developed and validated a multidimensional, interpretable statistical model to predict monthly dengue incidence. Methodology/Principal Findings We used a Generalized Linear Mixed Model (GLMM) with a Negative Binomial distribution to analyze 14 years (2010-2023) of spatiotemporal data from 37 municipalities in Huila, Colombia, an endemic region. The model integrates non-linear and lagged effects of climatic, demographic, and socioeconomic factors. The final model underwent rigorous external validation on an independent test set (2021-2023). Our model demonstrated high predictive discrimination (R2 = 0.743, Spearman's {rho} = 0.657), accurately capturing the timing of epidemic outbreaks. Key findings include the identification of an optimal thermal window for transmission at 27-28{degrees}C, a threshold effect for precipitation above 800 mm, and a saturation dynamic in outbreak autocorrelation. Conclusions/Significance This mechanistically-informed statistical approach provides a robust and transparent tool for epidemiological surveillance, successfully balancing high predictive performance with the explanatory power needed for effective, data-driven public health interventions.

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Preferences for receiving study results among pregnant women participating in a phase III clinical trial in Papua New Guinea.

Mengi, A.; Bagita-Vangana, M.; Tesine, P.; Laman, M.; Bolnga, J. W.; Ome-Kaius, M.; Kulimbao, J.; Mase, J.; Mal, L. S.; Mnjala, H.; Lee, G.; Cassidy-Seyoum, S. A.; Thriemer, K.; Unger, H. W.

2026-08-31 medical ethics 10.64898/2026.08.27.26361571 medRxiv
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Disseminating study results to participants is an ethical responsibility for researchers but remains uncommon in low- and middle-income countries, and participants preferences for receiving study results are poorly understood. This study examined study result dissemination preferences among pregnant women in a phase III malaria prevention trial in Papua New Guinea (PNG). Participants completed an interviewer-administered questionnaire (survey) assessing their interest in and motivation for receiving trial results and preferences for dissemination methods and content. Associations between participants characteristics and dissemination preferences were explored using multivariable logistic regression analysis. Of 1172 trial participants, 96.0% (1125/1172) completed the survey, and of these 99.6% (1121/1125) wanted to learn about the trial results. The main motivation factors driving participants interest were an acknowledgment of their contribution to research (51.7%; n=579) and a better understanding of the study (45.0%; n=505). Most participants (78.9%; n=884) wanted to learn about the trial findings through written summary and a group meeting with other participants at the nearest clinic (31.1%, n=349). Multivariable regression analysis indicated that participants from rural/peri-urban clinics were more likely to choose non-electronic media dissemination approaches such as a group meeting as compared to urban-dwelling participants. Frequently selected items (>50% of participants) for content included information regarding good results of the study, purpose of the study, medical treatment advances, results specific to me, and how study was conducted. There was heterogenicity in the preference for dissemination content: compared to urban clinics rural clinics are less likely to want to learn about how and why study was conducted and medical and scientific advances. Overall, the majority wanted to learn about trial results, highlighting the importance of integrating dissemination into research activities in PNG. Variation in preferences for mode and content of dissemination between study clinics suggests that dissemination activities could be tailored to local context and preferences.

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Access to malaria diagnosis and treatment in Zambia in the context of scaling-up community case management: results from repeated national cross-sectional surveys

Mao, Z.; Bennett, A.; Silumbe, K.; Miller, J. M.; Millar, J.; Slater, H.; Yukich, J. O.; Ashton, R. A.; Kyomuhangi, I.; Andrada, A.; Karabo, R.; Eisele, T.

2026-08-31 public and global health 10.64898/2026.08.25.26361362 medRxiv
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Background: Community case management has been scaled up nationally in Zambia over the last decade. However, there is limited evidence on how this nationwide implementation has affected febrile patients' access to malaria diagnosis and treatment in Zambia. Methodology: This study analyzed four rounds of Malaria Indicator Survey (MIS) data (2012-2021) to evaluate: 1) proportion of all-ages individuals with fever who sought treatment from a formal provider, 2) proportion of individuals going to CHWs over time, among those who sought treatment at a formal provider, 3) time duration between fever onset and treatment seeking at a formal provider, and 4) proportion of children <5 with malaria that received Artemether-Lumefantrine (AL) treatment. Mixed-effect logit models were employed to examine determinants of treatment-seeking behavior and factors affecting AL receipt among children <5 with malaria cases. Results: The proportion of febrile patients seeking treatment remained below 60% throughout 2012-2021, and AL receipt among children with malaria cases consistently stayed below 50%. The mean interval between fever onset and initial treatment-seeking encounter decreased from 2.42 days in 2012 to 1.71 days in 2021. Among formal care seekers, CHW utilization increased from 1.5% in 2012 to 10.0% in 2018 before declining to 3.2% in 2021. Longer walking time to the nearest health facility was associated with lower odds of treatment seeking, whereas CHW density was not associated with treatment seeking or AL receipt. Children who did not went to formal providers had lower odds of AL receipt than those who sought treatment from CHWs. Conclusion: Despite nationwide CCM scale-up over the last decade, significant barriers persist in malaria patients' access to diagnosis and treatment in Zambia. Our results indicate that while CCM coverage should be maintained and further expanded, additional complementary interventions are also needed to overcome remaining access barriers.

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Electronic health data exploring cardiorespiratory responses of transfusions in preterm infants: An international multicenter cohort study

Honore, A.; Rech, T.; Scrivens, A.; Binotto, I.; Zandvoort, C. S.; van der Staaij, H.; Peck, M.; Zivanovic, S.; Stanworth, S. J.; Hartley, C.; Dame, C.; Deschmann, E.; the Neonatal Transfusion Network,

2026-09-03 pediatrics 10.64898/2026.09.01.26361418 medRxiv
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Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

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Policy implementation gap: a qualitative evaluation of the implementation of Ghana's national cancer control strategy

Jawhara, B.; Baatiema, L.

2026-08-31 health policy 10.64898/2026.08.28.26361597 medRxiv
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Background: Cancer is a growing public health challenge in Ghana, with 27,385 new cases and 17,944 deaths recorded in 2022. Ghana developed a National Cancer Control Strategy (NCCS) in 2011 to guide prevention, early detection, treatment, and palliative care. The strategy expired in 2016 and has not been formally evaluated or renewed, leaving cancer control efforts without a guiding policy framework for nearly a decade. This study examined how the strategy was implemented, what barriers were encountered and what stakeholders recommend for a strengthened national cancer response. Methods: We conducted a qualitative descriptive study using semi-structured key informant interviews. Fifteen participants were recruited through purposive sampling, supplemented by snowball referrals, representing three groups: Ministry of Health policymakers, frontline healthcare providers and representatives of cancer-focused non-governmental organisations. Data were collected between June and September 2025 and analysed using Braun and Clarke's six-phase thematic analysis framework, guided deductively by the WHO Health Systems Building Blocks framework Results: Three themes emerged: NCCS interventions and systems implemented, capturing progress in cancer awareness, HPV vaccination and pilot screening programmes alongside persistent geographic and financial inequities in access; barriers to implementation, including inadequate financing, infrastructure and workforce shortages, the absence of a national cancer registry and governance failures, among them the finding that no frontline healthcare provider interviewed had any awareness of the NCCS; and recommended implementation strategies, including co-production of a renewed strategy, establishment of a dedicated National Cancer Control Programme, expanded health insurance coverage and decentralisation of oncology services. Conclusion: The NCCS was not operationally embedded in the health system. The evidence points to failures in policy dissemination as a constraint that precedes resource constraints. Addressing Ghana's rising cancer burden requires renewed political commitment, co-produced governance structures and accountability mechanisms. These findings have relevance for other low- and middle-income country settings facing similar challenges.

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The use of computerised testing to assess cognitive performance in people with HIV in South Africa

Edmond, E. C.; Dreyer, A. J.; Winston, A.; Khoo, S. H.; Joska, J.; Nightingale, S.

2026-08-31 hiv aids 10.64898/2026.08.27.26361083 medRxiv
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Background Computerised cognitive testing may address the global challenge in identifying cognitive changes in people living with HIV scalably and affordably. We assessed a computerised battery (CB) of cognitive tests, in a prospective cohort (CONNECT) of people with HIV in a low-income peri-urban area of Cape Town, South Africa during a national programmatic switch from efavirenz- to dolutegravir-based antiretroviral therapy (ART). Methods We recruited 170 people with HIV and 91 people without HIV (controls) (140[82%] and 41[45%] followed up). The CB and gold-standard pen&paper cognitive testing (P&P) were performed at both timepoints. Technology familiarity/use questionnaire data were also collected. We compared performance in detecting lower group-level cognitive performance associated with efavirenz treatment. Furthermore, the CB was compared to P&P in classifying individuals with low cognitive performance, correlation of global test scores and domain-level scores between batteries, and practice effects between timepoints. Exploratory principal component analysis was also performed. Results People with HIV on efavirenz at baseline had lower performance on the computerised battery than controls, {Delta}T=2.6, p=0.0047. This difference was lost after switching to dolutegravir-based ART at follow-up. CB and P&P global T were moderately correlated (R2=0.203, p<0.001), and the CB performed moderately in classification of low cognitive performance against the gold standard (AUC 0.70, sensitivity 0.52, specificity 0.76, PPV 0.40, and NPV 0.84). Selecting the first three principal components improved both classification of low cognitive performance (AUC 0.77) and correlation strength with P&P global T (R2=0.3, p<0.001). The CB did not show practice effects. Most participants owned a mobile phone (95%, 85.9% of these smartphones). Performance was better in smartphone owners ({Delta}T=1.8) and computer owners (23%, {Delta}T=1.8). Conclusions Delivering computerised cognitive testing was feasible in this low-income southern African setting. The CB showed reasonable construct validity (detecting known lower cognitive performance associated with efavirenz-ART) and may detect broad cognitive characteristics such as processing speed and accuracy. However, correlation of CB results with gold standard P&P testing was low-moderate and may limit its applicability as a diagnostic tool. This might be improved by including a wider range of cognitive domains tested in the CB, or data driven analysis. Brief CBs may fulfil an initial screening role, followed by more detailed clinical assessment.

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Female contraceptive cover duration for miltefosine-containing regimens for the treatment of women with leishmaniasis

Chu, W.-Y.; Alves, F.; Dorlo, T. P. C.

2026-09-02 infectious diseases 10.64898/2026.08.31.26360682 medRxiv
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Introduction Miltefosine is the only approved oral antileishmanial agent, but its use in women of childbearing potential (WOCBP) is restricted due to preclinical teratogenicity. Current labeling recommends contraception during treatment and for at least five months thereafter, based solely on its long terminal elimination half-life. This study re-evaluated the required contraceptive duration using an exposure margin-based approach. Methods Virtual populations were generated from anthropometric data of 382 Indian, 4,462 Eastern African, and 4,019 Brazilian WOCBP with leishmaniasis. Published population pharmacokinetic models were used to simulate miltefosine exposure following 14-42-day regimens for visceral leishmaniasis (VL), post-kala-azar dermal leishmaniasis (PKDL), and cutaneous leishmaniasis (CL). A developmental safety exposure threshold was derived from the rat no-observed-adverse-effect level (0.6 mg/kg/day for 10 days) and adjusted using a 10-fold safety margin. Contraceptive durations resulting in median residual post-contraception exposure (AUCEOC-{infty}) below this threshold were considered supportive of contraceptive discontinuation. Results The developmental safety exposure threshold was estimated at 2.5 mg{middle dot}day/L. Despite pharmacokinetic differences across geographical regions and disease manifestations, required minimum contraceptive durations were consistent: three months from treatment initiation for the 14-day regimen, four months for 21- and 28-day regimens, and five months for the 42-day regimen. For the 14-day regimen, a single dose of a long-acting injectable contraceptive administered at treatment initiation would provide sufficient coverage. Conclusion An exposure margin-based approach supports shorter contraceptive durations than current recommendations. For the 14-day VL regimen, three months of contraception may provide a practical alternative to current labeling.

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Case Fatality of Leptospirosis in the Dominican Republic, 2012-2026: A 14-Year National Surveillance Analysis

Sanchez, J. J.; Alcantara, L. V.; De Luna, D.; Aleuy, O. A.; Bellon, M. B.; Cruz Raposo, J. L.; Dye, T. D. V.

2026-09-03 epidemiology 10.64898/2026.09.01.26361950 medRxiv
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Background: Case fatality reflects the quality and timeliness of clinical care for leptospirosis, yet no study has examined it at a national level in the Dominican Republic (DR), where leptospirosis is endemic. We describe the case fatality rate (CFR) of leptospirosis in the DR between 2012 and 2026 and identify associations with mortality. Methods: We conducted an analytical cross-sectional study, using national surveillance records merged with a discharge-condition extract via a composite key. We calculated CFR with Wilson 95% confidence intervals among 5,412 valid cases (suspected, probable, or confirmed) reported from January 2012 through June 2026. We compared proportions with Pearson's chi-square test, assessed annual trend with ordinary least squares linear regression, and fitted multivariable logistic regression models to account for confounding. Results: Overall CFR was 8.5% (460/5,412), with no significant annual trend (p=0.372). CFR was higher in men than women (p < 0.001) and increased significantly with age (p < 0.001). Male gender (OR: 1.79; 95%CI: 1.18-2.73) and pre-existing comorbidity (OR: 1.76; 95% CI: 1.21- 2.57) were independent predictors of death. Clinical complications were the strongest predictor in the adjusted model (OR: 3.16; 95%CI: 2.17-4.61), attenuating the gender effect. CFR varied widely by province (2.43-22.22%) and correlated negatively with incidence at the province level (p = 0.066). Conclusions: Leptospirosis case fatality is concentrated among men, people with comorbidity, and those who develop clinical complications. These national, long-term findings can help prioritize clinical and surveillance resources as extreme weather events are expected to intensify across the Caribbean.

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Assessing the association between contraceptive agency and preference-aligned fertility management among Ugandan women: A 12-month prospective cohort study

Birabwa, C.; Wasswa, R.; Amongin, D.; Rakesh, G.; Beth, P.; Sneha, C.; Gomez, R.; Atuyambe, L.; Liu, J.; Waiswa, P.; Holt, K.

2026-08-31 sexual and reproductive health 10.64898/2026.08.27.26361582 medRxiv
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Background There has been a proliferation of new person-centered and human rights-based contraception measures in recent years, though their application in research remains limited. Improved measures offer an opportunity to examine how contraceptive decision-making agency relates to individuals ability to act in line with their contraceptive preferences. We sought to assess the association between contraceptive agency and subsequent Preference-aligned Fertility Management (PFM) over 12 months in a cohort of women in rural Uganda. Methods We analyzed data from a prospective cohort study conducted in five largely rural Ugandan districts from 2022 to 2024. Data were collected at baseline, 6 and 12 months from a convenience sample of women who were new users of contraception or not using contraception. We used mixed-effects logistic regression models to examine the association between baseline Agency in Contraceptive Decisions Scale overall and subscale scores and future PFM Index scores at 6 and 12 months, assessing whether associations varied over time using interaction terms for follow-up time point. We used interactions between agency scores and follow-up visit to assess whether associations differed between the 6- and 12-month visits. We assessed effect modification by age group and baseline contraceptive method category using three-way interaction terms and predicted probabilities. Results The analytic sample comprised 2,227 women. The percentage of women practicing PFM increased from 85.7% at baseline to 93.3% at 12 months. A one-unit increase in Agency in Contraceptive Decisions Scale score was associated with higher odds of subsequent PFM (aOR: 1.68, 95% CI: 1.10-2.54). Subscales 3 (knowledge aligned with preferences) and 4 (control over use or non-use) of the Agency in Contraceptive Decisions Scale were significantly associated with future PFM (aOR: 1.31, 95% CI: 1.04-1.66 and aOR: 1.27, 95% CI: 1.06-1.51, respectively). The association between overall contraceptive agency and PFM did not differ between the 6- and 12-month visits. Three-way interaction tests suggested that the associations between the overall Agency in Contraceptive Decisions Scale score and the PFM outcomes varied jointly by age group and baseline contraceptive method category: overall PFM Index (p<0.001), PFM1 (p=0.011), and PFM2 (p<0.001). Conclusion Our findings suggest that higher levels of contraceptive agency may help women act in line with their contraceptive preferences. Increasing womens knowledge and control over contraceptive use may be particularly essential for preferred contraceptive use. The findings also suggest that the association between contraceptive agency and PFM may vary by womens age group and the method of choice, though further exploration is necessary to examine this influence.

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Vaginal Steaming Practices Among Women At Mulago Sti Clinic, Uganda: Prevalence, Lactobacilli Proportion Differences, And Associated Factors.

Kakai, D.; Twinamasiko, N.; Kigozi, E.; Namutale, R.; Mutesi, B. A.; Bagaya, J.; Akinyi, L.; Kajumbula, H.; Nakubulwa, S.

2026-09-01 obstetrics and gynecology 10.64898/2026.08.28.26361407 medRxiv
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Abstract Background: Vaginal steaming has gained popularity among women for reasons known best to them. However, the effects of vaginal steaming on vaginal lactobacilli levels remain poorly understood and understudied. This study investigated the prevalence, assessed differences in the presence of bacterial vaginosis (BV) among women who practiced vaginal steaming and those who do not and determined the factors associated with vaginal steaming among women attending Mulago Sexually Transmitted Infections (STI) clinic in Uganda. Methods: This study utilized a cross-sectional design to enroll 181 women aged 18 to 49 years who were systematically sampled at Mulago STI clinic. Interviews were conducted to obtain the demographic characteristics of the participants. Vaginal swabbing and Gram staining were done to attain lactobacilli counts by microscopy which were categorized using the Nugent score. Data were analyzed using Stata. The potential confounding effects of other variables on the relation between vaginal steaming and the presence of bacterial vaginosis as well as factors associated with vaginal steaming were assessed using modified Poisson regression. Results: Prevalence of vaginal steaming was 40.3%, (95% confidence interval (CI) 33.0% - 48.0%). There were 41.1% women who practiced vaginal steaming occasionally, 53.4% who used hot water having herbs and 78.1% who practiced vaginal steaming for medical reasons. There was no difference in the presence of bacterial vaginosis when women who practiced vaginal steaming were compared to those who did not (p-value = 0.286). Factors that were significantly associated with vaginal steaming included having experienced vaginal issues (aPR = 0.07, 95% CI 0.01 - 0.12, p value = < 0.001) and contraceptive use (aPR= 0.52, 95% CI 0.37 - 0.72, p value = 0.001). Conclusions: About 2 in every 5 women at Mulago STI clinic reported to have indulged in vaginal steaming. There was no difference in the presence of bacterial vaginosis when women who practiced vaginal steaming were compared to those who did not. Having experienced vaginal issues and contraceptive use were significantly associated with vaginal steaming among women at Mulago STI clinic, Uganda. The Ministry of Health of Uganda should establish targeted screening and treatment for bacterial vaginosis alongside other sexually transmitted infections.

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Predictors of Time to Start of Trophic Feeding in Preterm Neonates Admitted to Neonatal Intensive Care Unit of Adama Hospital Medical College, Ethiopia: A Retrospective Cohort Study

Misha, B.; Dassie, G. A.; Mohammad, I.

2026-08-31 epidemiology 10.64898/2026.08.26.26361481 medRxiv
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Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

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Factors associated with the use of Long Acting Reversible Contraceptives among adolescents at first level hospitals in Lusaka, Zambia.

Ikabongo, I.; Macha, S.; Vwalika, B.; Kaonga, P.; Masumo, M. m.; Halwiindi, H.; Kunka, E.; Hazemba, A. N.

2026-08-31 sexual and reproductive health 10.64898/2026.08.26.26361478 medRxiv
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Background: Unintended adolescent pregnancies remain a public health challenge in Zambia, where LARC use is low despite their effectiveness. Barriers such as stigma, misconceptions, and limited access persist. Previous studies conducted in Lusaka district did not explore the challenges faced by adolescents in trying to access and use LARCs. Understanding these challenges is crucial for developing targeted interventions to promote safe and effective contraception practices. This study examined factors influencing adolescent knowledge, willingness, and uptake of LARCs in public health facilities in Lusaka. Methods: A cross-sectional study was conducted between November 2024 and March 2025 among adolescent girls aged 15-19 years in five first-level hospitals in Lusaka, Zambia, using structured questionnaires to obtain quantitative data1. LARC use was measured as a binary outcome, with multiple regression identifying associated factors. Results: There were 400 participants in total, of whom 48% (181/376) had ever used a LARC. In the adjusted model, age was significantly associated with LARC use (AOR = 1.27, 95% CI: 1.11-1.77; p < 0.001). Adolescents who were willing to delay pregnancy had markedly higher odds of using LARCs (AOR = 7.46, 95% CI: 1.42-39.06; p = 0.017). Knowledge of LARCs remained a strong independent predictor, more than doubling the likelihood of uptake (AOR = 2.69, 95% CI: 1.12-6.46; p = 0.027). Having children was also significantly associated with higher LARC use (AOR = 2.62, 95% CI: 1.11-6.23; p = 0.029), while participants with unknown HIV status had lower odds of LARC use (AOR = 0.31, 95% CI: 0.10-0.97; p = 0.044). In addition, adolescents residing in Chipata had substantially higher odds of LARC uptake compared to those in Kanyama (AOR = 317.93, 95% CI: 35.01-2887.2; p < 0.001). Conclusions: The findings indicate that age, knowledge of LARCs, reproductive experience (having children), and willingness to delay pregnancy were significantly associated with higher odds of LARC uptake, and almost half of the participants had already used a LARC method. Although higher education showed an upward trend, it was not statistically significant in the adjusted model. Limited awareness and variability in service delivery across clinics highlight the need for strengthened counseling and reliable access to LARCs. As this study focused only on adolescents already attending Family Planning Clinics, further research is needed to assess LARC availability, accessibility, and quality of counseling across different settings in Zambia.

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Types, Subtypes and Positivity Rates of Seasonal Influenza in Uganda, 2019-2023

Nankya, M. A.; Owor, N.; Kayiwa, J. T.; Lutwama, J. J.; Gidudu, S.; Bahizi, G.; Ario, A. R.

2026-09-01 infectious diseases 10.64898/2026.08.29.26361662 medRxiv
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Background: Seasonal influenza, commonly known as flu, is an acute respiratory, highly contagious illness caused by influenza viruses. A clear understanding of influenza seasonality is crucial for guiding prevention and treatment strategies, including decisions on vaccination timing to prevent outbreaks. While well documented in temperate regions, data on influenza epidemiology in tropical areas, particularly sub-Saharan Africa, remain limited. We described the types, subtypes and positivity rate of seasonal influenza in Uganda during 2019-2023. Methods: We abstracted data from the National Influenza database on positive seasonal influenza cases confirmed by Polymerase Chain Reaction. The cases were disaggregated by age group, sex, region, month and year of reporting. Using Microsoft excel, we calculated the influenza positivity rate and disaggregated it by strain, sex, age, region and time. Test positivity rate was computed as the number of positive cases as a percentage of the total samples tested. Results: Among 17,957 individuals tested, the overall positivity rate for seasonal influenza was 5% (936 cases). Positivity was higher among males compared to females (7% vs. 4%), with children aged 5-9 years having the highest positivity rate (16%), while individuals aged 50-54 years had the lowest (1%). The median positivity rate was 4%, with a range of 1-16%. Regionally, the central region reported a positivity rate of 5%, with rates across all regions ranging from 5% to 8%. Over time, there was a gradual decline in positivity rates, decreasing from 16.5% in 2019 to 5.3% in 2023. Seasonal influenza exhibited bimodal peaks, with the primary peak occurring between March and May and a secondary peak from October to December. Influenza A was the predominant strain, accounting for 70% of seasonal influenza cases (669/936). Among the Influenza A subtypes, H3N2 was most common, representing 63% of cases (425/669). Conclusions: The declining seasonal influenza positivity rates from 2019 to 2023 and the predominance of Influenza A and H3N2 highlight the need for sustained surveillance in Uganda. Given Influenza A's high genetic variability and potential for novel strain emergence, monitoring circulating strains, informing vaccine development, and implementing targeted interventions for high-risk groups and regions are critical to controlling and preventing outbreaks.