Transactions of The Royal Society of Tropical Medicine and Hygiene
◐ Oxford University Press (OUP)
Preprints posted in the last 30 days, ranked by how well they match Transactions of The Royal Society of Tropical Medicine and Hygiene's content profile, based on 18 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.
Wekunda, P. W.; Ogunbode, O.; Okunromade, O.
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Introduction: Nigeria continues to report one of the highest burdens of diphtheria globally, with Kano State accounting for a disproportionate share of cases and deaths. Understanding epidemiological patterns and mortality determinants is essential for guiding targeted interventions. Objectives: To describe the distribution of diphtheria cases in Kano State by socio-demographic and clinical characteristics, Local Government Area, and month of reporting, and identify independent predictors of mortality. Methods: We conducted a retrospective cohort study of 21,369 patients with clinically compatible and laboratory-confirmed diphtheria using secondary data from medical records (2022-2025). Descriptive statistics summarized patient characteristics and disease distribution. Associations with mortality were assessed using chi-square or Fishers exact tests. Multivariable logistic regression identified predictors of mortality, reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Of 21,369 patients, 13,557 (63%) were female, with a median age of 11 years (IQR: 7-13.6). Children aged 5-9 years accounted for 29% of cases. Prior contact with a case was reported in 2,633 (12%) patients, while 168 (1%) were laboratory-confirmed. Overall, 13,468 (63%) patients were unvaccinated and 5,381 (25%) fully vaccinated; Diphtheria antitoxin DAT was administered to 2,035 (10%). Cases occurred in all local government areas (LGAs), with four accounting for 60% of cases. Transmission occurred year-round, peaking in March 2024 and August 2023 and 2025. Overall, 1,131 deaths occurred (CFR: 5.3%). Compared with patients aged [≥]20 years, younger age groups had higher odds of mortality: 0-4 years (aOR = 26.74, 95% CI: 17.64-42.72), 5-9 years (aOR = 19.77, 95% CI: 13.17-31.33), 10-14 years (aOR = 8.21, 95% CI: 5.41-13.13), and 15-19 years (aOR = 2.46, 95% CI: 1.45-4.26). Prior contact with a case was associated with lower odds of mortality (aOR = 0.42, 95% CI: 0.30-0.55), whereas laboratory confirmation (aOR = 2.33, 95% CI: 1.48-3.56) and DAT receipt (aOR = 2.55, 95% CI: 2.19-2.96) were associated with higher odds. Prior vaccination was associated with lower odds of mortality among fully vaccinated (aOR = 0.52, 95% CI: 0.44-0.61) and partially vaccinated patients (aOR = 0.61, 95% CI: 0.47-0.80). Conclusions and recommendations: During the study period, diphtheria was more common among younger children, females, and the unvaccinated. Although concentrated in a few LGAs, transmission was widespread and varied seasonally. Mortality was associated with younger age, laboratory-confirmed infection, and use of diphtheria antitoxin, whereas vaccination and prior contact were protective. Reducing the burden requires sustained efforts to strengthen routine immunization, implement targeted vaccination campaigns, ensure early detection and prompt treatment, and improve contact tracing and case management.
Nelson, E.; Carcamo, P. M.; Ribeiro dos Santos, G.; Sylvestre Ribeiro, G.; Rodrigues da Costa, T.; Ilaria Dorigatti, I.; Salje, H.; Moreira, L. A.; Cummings, D. A. T.; Ko, A. I.
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Wolbachia-based interventions were less effective in achieving introgression in Rio de Janeiro than other settings. Reduced introgression occurred in locations where dengue was historically high, raising concerns of inequity. We examined factors affecting Wolbachia introgression in Rio through trajectory modeling, spatiotemporal Bayesian models, and Ae. aegypti abundance estimation. During the intervention (2017-2020), Wolbachia introgression was 26% (median; IQR,14-44%), with four distinct trajectories. Despite receiving more releases, densely populated areas with low socioeconomic status had lower introgression. In spatiotemporally explicit multivariable regressions, higher Ae. aegypti abundance, temperature, population density and lower socioeconomic status were associated with reduced introgression. Improved characterization of Ae. aegypti abundance and other structural/environmental predictors of introgression could be used to calibrate release doses to ensure equitable benefits from Wolbachia interventions.
Chandradeva, N.; Glover, A. C.; Whittaker, C.; Brewer, T.; Challenger, J. D.; Slater, H. C.; Sherrard-Smith, E.; Churcher, T. S.
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Implementing vector control interventions against infectious diseases is operationally challenging, with delivery and population uptake taking considerable time within a community. Studies have suggested that the slow mass drug administration (MDA) of the endectocide, ivermectin, may have contributed to the lower epidemiological impact against malaria observed in recent cluster-randomised controlled trials, although evidence supporting this hypothesis is lacking. It is unclear whether interventions which have short but highly effective durations of entomological impact are more impactful than tools which kill the same number of mosquitoes but over a longer period. Transmission dynamics mathematical models can be used to explore the trade-offs between product profiles and investigate how different implementation periods could influence disease control. First, we use a simple vector-borne disease compartmental model to explore the epidemiological impact of killing the same number of mosquitoes over 10, 30 or 90 days. We find that for different mosquito-killing periods, the total number of cases averted is similar, although the observable impact may depend on when efficacy is assessed. Secondly, we adapted an existing malaria transmission model and simulated the fast and slow deployment of an effective endectocide MDA campaign in different seasonal settings. In perennial and seasonal settings and for a given coverage, slow MDA deployment averts more clinical cases of malaria than a fast synchronised distribution (completed in a single day, although the difference was modest). The benefits of the intervention depend on how well-timed a deployment is relative to the peak of the transmission season, with the efficacy of an ivermectin-like endectocide MDA being up to approximately 42% lower if started late. The work indicates that the time taken to complete MDA campaigns is unlikely to drive major differences in the effectiveness of short-lived endectocides and showcases how transmission dynamics models can be used to support epidemiological trial interpretation.
Fletcher, C.; Mila, C.; Moirano, G.; Araujo, E.; Lührsen, D.; Codeco, C.; Codeco Coelho, F.; Lowe, R.
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Brazil has one of the highest dengue burdens globally, with transmission influenced by climate events. Yet, the effects of compound climate extremes on dengue risk and prediction have not been quantified to date. Using a Bayesian spatiotemporal model of monthly dengue cases across 435 health regions from 2010 to 2025, we estimated relative risk associated with interacting long-lag and short-lag drought indicators and temperature anomalies across nine Koppen-Geiger climatic zones, adjusting for absolute temperature and El Nino-Southern Oscillation. Long-lag dry, mid-lag warm and short-lag wet conditions were associated with the highest relative risk in five climatic zones, with temperature anomalies modifying hydrometeorological dynamics more strongly in temperate than tropical areas. Climate covariates improved the prediction of case counts and outbreaks compared to baseline models at lead times of 1, 3, 6 and 12 months, and for the upcoming season 5 months ahead. Improvements were greatest in the Northeast, Southeast, and Midwest. Recent dengue incidence provided the greatest improvement at the 1-month lead, whereas combining incidence with climate information performed best at 3- and 6-month leads. We extended our framework to weekly state-level predictions of the season ahead to align with national public health planning. We proposed a multi-staged dengue forecasting approach to enhance early warning and response across Brazil.
Kussa, Y.; Lema, S.
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BackgroundIn Ethiopia as other Sub-Sharan African countries malaria in pregnancy is a major public health threat particularly in the rural communities. Immunosuppression during pregnancy increases the risk of placental malaria; this, in turn, leads to anemia, low birth weight, preterm delivery, and stillbirth, causing severe complications that pose a life-threatening risk to both the mother and fetus. Hence, this study is aimed to assess the prevalence of malaria, and associated factors among pregnant women attending antenatal clinics in Damot Gale district, South Ethiopia. MethodAn institutional-based cross sectional study was conducted from March 1 to May 30, 2024. A multistage sampling technique and pre-tested semi-structured questionnaires were used for data collection. Using standard parasitological methods, blood samples collected from 389 participants were analyzed through microscopic examination of Giemsa-stained thick and thin blood films. Logistic regression was used to assess factors associated with malaria. Adjusted odds ratio with 95% confidence interval was calculated and P-value < 0.05 was considered statistically significant. ResultsIn this study the prevalence of malaria among pregnant women was 10.5% (95% CI: 7.7-13.6%). Among the malaria-positive pregnant women (9%) were P. falciparum infected, followed by P. vivax (1.3) and mixed infections (0.2%). In the multivariate analysis, multigravdae (AOR = 0.358; 95% CI: 0.14-0.92), utilization of LLINs (AOR = 0.286; 95% CI: 0.119-0.687) and use of IRS (AOR = 0.068; 95% CI: 0.027-0.172) were significantly associated with malaria among pregnant women. ConclusionMalaria is still a public health problem among pregnant women in Damote-gale district. The present study indicated that adequate distribution and proper utilization of bed nets In addition seasonal proper spray of IRS might be helpful to prevent and control malaria.
Simons, D.
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Background. Nigeria's reported Lassa fever case fatality ratio (CFR) rose from 18.9% at week 23 of 2025 to 25.0% in 2026, prompting concerns over failing clinical care. Because surveillance artefacts can also alter CFRs, candidate mechanisms that published data can resolve were identified and evaluated. Methods. This ecological study extracted weekly state-level counts from 474 Nigeria Centre for Disease Control and Prevention situation reports (2017-2026). Per a pre-specified plan, years were compared at phase-matched points, year-on-year CFR changes were decomposed into within-state and between-state components, and tipping-point ascertainment shifts calculated. Weekly incident and cumulative published totals were compared post hoc. Findings. Of 11 candidate mechanisms, 2 could be evaluated fully and 5 in part. On weekly incident counts, 2026 did not differ from 2025 at the phase-matched midpoint (+0.3 percentage points, 95% CI -5.0 to 7.6); within-state (-1.1, 95% CI -4.7 to 3.0) and between-state (+0.5, -2.0 to 2.9) components spanned zero. Conversely, the published cumulative CFR was 5.4 to 6.2 percentage points higher because 70 deaths were added retrospectively by week 36 outside weekly reports. Reconciling cumulative figures would require 279 missed survivors (6% of suspected cases not confirmed). Interpretation. The 2026 CFR rise came from deaths added to cumulative totals outside the weekly counts, and published data cannot attribute it to care. Endemic zoonotic CFRs cannot serve as clinical outcome measures unless testing volumes, deaths added late, and post-mortem sampling are published alongside case counts. Funding. US NSF-NIH-NIFA EEID; UK BBSRC; Birgitta Sintring Fellowship (Uppsala University).
Mafirakureva, N.; McQuaid, C. F.; Harker, M.; Garcia-Prats, A.; Hesseling, A. C.; Seddon, J. A.; Dodd, P.
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Background. Tuberculosis preventive treatment (TPT) with levofloxacin reduces tuberculosis disease incidence in multidrug-resistant or rifampicin-resistant (MDR/RR)-tuberculosis household contacts. However, with age, disease progression risk falls and the frequency of adverse events (AE) rises. Methods. To inform decision-makers, we evaluated the cost-effectiveness of expanding the use of MDR/RR-TPT by age, with and without tests of tuberculosis infection. We modelled MDR/RR-household contact management (HHCM) in 189 countries, incorporating age-dependent risks of disease progression, death and AEs. Incremental cost-effectiveness ratios were calculated as USD/disability-adjusted life year (DALY) averted, and as a fraction of per capita gross domestic product (GDP). Findings. Compared to baseline of MDR/RR-HHCM with TPT for those <15 years, adding TPT up to 45 years was cost-effective at a threshold of 30% GDP in 160/189 modelled countries including 17 of the 30 highest incidence countries. Of these 160 countries, the intervention was cost-saving in 46. Strategies targeting TPT to those testing positive for M. tuberculosis infection were dominated by those without testing. Globally, full use of MDR/RR-HHCM with TPT for all would avert 11,900 (10,400 to 13,800) episodes of tuberculosis, 9,960 (9,100 to 10,900) deaths, and 289,000 (262,000 to 321,000) DALYs, but would result in 71,000 (68,000 to 74,000) SAEs and cost $359 million (294 to 449). Interpretation. Expanding MDR/RR-TPT use to older ages without testing appears cost-effective in most settings, but may require substantial resources and result in large numbers of AEs. Funding. Unitaid
Ngmembong, C. N.; Captain-Esoah, M.; Lareef, S.; Angyiereyiri, E. D.; Donkor, M. N.; Dassah, S. D.; Azameti, M. K.; Motey, G. A.; Adetunde, L. A.; Abalori, T. A.; Frempong, K. K.; Kubio, C.; Asoala, V.; Boakye, D. A.; Dadzie, S. K.; Antwi, F. O.; Adjei, M. R.; Grobusch, M. P.; Bakajika, D.; Lule, F. J.; Juma, E.; Braka, F.; Achu, D.
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Objectives To assess microfilaraemia, chronic lymphatic filariasis (LF)-related morbidity, and community knowledge and self-reported preventive behaviours in a rural community in northern Ghana following prolonged mass drug administration (MDA). Design Community-based cross-sectional study. Setting Birifor community, Lawra Municipality, Upper West Region, northern Ghana, from October 2024 to January 2025. Participants A total of 261 community members aged 10 years and above were selected using random sampling and participated in the study. Outcome measures Outcome measures included microfilaraemia detected by night blood microscopy, chronic LF-related morbidity identified through clinical examination, and community knowledge and self-reported preventive behaviours assessed using a structured questionnaire. Results No microfilariae were detected (0/261; 0%). Chronic lymphoedema was identified in five individuals (1.9%), all aged over 40 years. Awareness of LF was high (95.8%), yet only 39.5% of participants demonstrated good community knowledge and self-reported preventive behaviours. Misconceptions regarding transmission, particularly beliefs that LF is hereditary or caused by spiritual factors, were common. MDA participation was high (93.1%). All five individuals with chronic lymphoedema reported loss of income, and three (60%) reported additional household income loss due to caregiving responsibilities. Conclusions No microfilaraemia was detected, suggesting very low transmission in the study area, although residual infection cannot be excluded. Chronic LF-related morbidity and gaps in community knowledge persist despite high MDA participation. Sustained surveillance using more sensitive diagnostic approaches, together with morbidity management and disability prevention, community education and support for affected households, will be important to sustain LF elimination efforts.
de Klerk, J. N.; Pilgrim, J.; Baylis, M.; Blagrove, M.; Medlock, J. M.; Vaux, A. G. C.; Bruce, R. C.; Folly, A. J.; Sedda, L.
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In England and Wales, Usutu virus (USUV) was detected in 2020 and is now established. West Nile virus (WNV) has so far only been detected in a single location, in two Aedes vexans mosquito pools sampled during 2023 surveillance. Given the growing threat to the UK from Culex-borne viruses there is a need to undertake risk assessments to contribute to preparedness and surveillance strategy for both viruses across human and animal health sectors. Here, we present the first application of a mechanistic R0-based model, incorporating temperature dependence and combining data on vector species distribution with projected future climate scenarios, to assess transmission suitability for WNV and USUV across England and Wales. Under current climate conditions, the two viruses showed comparable spatial patterns, with risk concentrated most heavily in the southeast along the Thames estuary and extending into Kent, Essex and Surrey, as well as around Cambridgeshire and adjacent counties, and across Yorkshire, Nottinghamshire and Lincolnshire. This pattern broadly corresponded with the cumulative distribution of Culex mosquito abundance established in our earlier work (Culex pipiens pipiens, Culex pipiens molestus and Culex torrentium). Both viruses were projected to show increasing transmission suitability risk over time, with substantially steeper increases under Representative Common Pathway (RCP) 8.5 then RCP 4.5. Equine WNV cases were predicted to be most likely in southeast England, in particular around Newmarket, driven by the region's dense horse population. Among the human population, London was identified as the highest-risk area, with Liverpool and Manchester also showing elevated risk levels, driven by a combination of high human and mosquito distributions. When human population distributions were age-adjusted to account for the proportion of over 60 years-olds, there was elevated risk in coastal regions, particularly in the east (Norfolk and Suffolk) and southeast (Kent) of England. The geographic distribution of positive mosquito and bird USUV cases recorded in 2023 and 2024 broadly overlapped with areas predicted to have higher USUV suitability, providing validation for the model's spatial outputs. By characterising relative spatial transmission suitability risk, this work adds to a growing understanding of where arbovirus emergence and spread are most likely across England and Wales, and can support decisions around resource allocation, targeted surveillance efforts, and public health readiness. The results also underscore the importance of incorporating climate change and vector ecology into future modelling work, given their likely influence on how arbovirus risk evolves over time.
Trivedi, S. G.; Singh, S. K.; Pramanik, S. K.
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BackgroundFebrile neutropenia requires rapid empirical antibiotic therapy, with regimen selection shaped by local prescribing practice and pathogen patterns. We described starting treatment, later drug changes, microbiological findings, and inpatient outcomes. MethodsThis ambispective cohort comprised 96 episodes from 90 patients admitted to a tertiary-level teaching hospital. Treatment and outcome analyses used each episode as the unit of observation. Recorded variables included the starting antibiotics, later regimen modification, microbiology, hospitalization length, invasive fungal infection (IFI) as captured in study records, and disposition. Comparisons based on escalation status were exploratory. ResultCefoperazone-sulbactam appeared in 62/96 initial regimens (64.6%), amikacin in 42 (43.8%), teicoplanin in 28 (29.2%), and meropenem in 14 (14.6%). Eighteen episodes (18.8%) required a change that broadened or substituted antibacterial therapy. Among 31 microbiologically documented infections, 22 (71.0%) yielded Gram-negative organisms and 9 (29.0%) were polymicrobial. Median length of admission was 18.5 days in the escalation group and 9 days in the remainder (p<0.001). Mortality was 27.8% (5/18) with escalation and 5.1% (4/78) without it (p=0.011), with nine inhospital deaths overall (9.4%). ConclusionAntibacterial management differed within this cohort, with treatment escalation required in 18 of 96 episodes. Gram-negative organisms comprised most microbiologically confirmed infections. Escalation marked a clinically complex course with prolonged hospitalization and greater observed mortality; the observational design does not establish comparative efficacy or causation.
Bakhoum, M. T.; Fall, A. G.; Segard, A.; Seck, M. T.; Thiall, A. S.; Gimonneau, G.; Ravel, S.; DE MEEUS, T.
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In sub-Saharan Africa, human and animal health is threatened by African trypanosomoses. These diseases are caused by trypanosomes that are transmitted primarily by tsetse flies. Vector control remains one of the most effective strategies for reducing disease transmission, but requires a minimum level of knowledge of the population biology, ecology and dispersal patterns of the targeted vectors. In this respect, population genetic approaches using appropriate polymorphic genetic markers can provide valuable tools to inform and optimize control strategies. Senegal is currently engaged in a national tsetse control programme and has been identified as a study country within a European Union-funded research initiative, COMBAT (controlling and progressively minimizing the burden of animal trypanosomosis). Baseline entomological studies are currently underway in the Sine Saloum (Southern Senegal). This preliminary study aimed to characterize the population genetic structure and connectivity of tsetse fly species present in Southern Senegal, Glossina palpalis gambiensis and G. morsitans submorsitans, in order to assess their population sizes (geographically and demographically), population densities and dispersal capacities. The two species exhibited markedly contrasting population structures. The first, G. p. gambiensis, displayed an isolation by distance with rather dense subpopulations exchanging immigrants at short distances (1.6 km/generation) and continuously from Sine-Saloum to Casamance, in line with the apparent continuity of the mangrove network found along this coast. In contrast, G. m. submorsitans presented a relatively dense population over a 75 km wide area, fragmented into sparsely distributed, very dense and interconnected pockets. These findings indicate that G. p. gambiensis likely constitutes a large metapopulation comprising 3266 effective individuals on average (and up to 7765), whereas G. m. submorsitans appeared as a single and large population, scattered in small pockets that could be readily replenished by immigrants from distant areas in case of control. These results suggest that elimination is not a realistic option for any of these two populations. Alternatively, localized integrated pest management is likely to be the most effective approach for controlling the negative effects of these biting flies on domestic animals, by reducing trypanosome transmission. However, further entomological investigations and the use of more informative genetic markers are needed to obtain a more precise understanding of the epidemiological processes involved.
Holmes, A. L.; de Glanville, W. A.; Katiti, W. A.; Mendes, A. J. F.; Bodenham, R. F.; Lukambagire, A.; Mmbaga, B. T.; Rubach, M. P.; Crump, J. A.; Cleaveland, S.; Viana, M.; Halliday, J. E. B.
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Brucellosis is a globally distributed and widely under-appreciated zoonotic bacterial disease that causes infertility and abortion in livestock and febrile illness in humans, sometimes with debilitating sequelae. Brucellosis incidence estimates typically focus on acute presentations and range from 50 to 100 per 100,000 people per year for endemic settings, showing marked variation within and between countries. Estimating brucellosis incidence in low-resource settings is complicated by lack of access to and utilisation of health care and high-quality diagnostic testing for many people in rural communities. To estimate brucellosis incidence in a pastoralist population in northern Tanzania, we developed a Bayesian model that integrates multiple data sources including diagnostic test results from a hospital-based prevalence study performed in 2016-2017, test sensitivity and specificity, and data from a community-based healthcare utilisation survey in 2019-2020. We show that this population experienced a high incidence of brucellosis with wide uncertainty, with estimates of 387.6 (95% HPDI: 103.3 - 903.5) illnesses per 100,000 people per year for the total population, 199.7 (95% HPDI: 16.2 - 584.6) for individuals aged >15 years, and 632.4 (95% HPDI: 180.1 - 1379.4) for children aged [≤]15 years. These incidence estimates were among the highest in the world to date. The wide density intervals for these incidence estimates reflect uncertainty in the underlying parameter values used. Sensitivity analyses show that healthcare utilisation influenced incidence estimates the most. This result indicates that accounting for low levels of healthcare utilisation is essential to avoid under-estimating disease incidence. Our findings illustrate that brucellosis is a frequent cause of illness in this population. Increased access to treatment, prevention, and accurate diagnostic testing would greatly improve understanding of brucellosis epidemiology and the health of many people living in similar at-risk communities.
Dinkel, K. A.; Ruisch, A.; Mathur, I.; Bowe, R. T.; Windus, P.; Nonvignon, J.; Walker, D. G.; Torkelson, A. A.
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BackgroundNipah virus (NiV) is a zoonotic pathogen in the Henipavirus genus that causes severe, often fatal disease in humans. The World Health Organization and the Coalition for Epidemic Preparedness Innovations (CEPI) have designated NiV as a priority pathogen with pandemic potential. While CEPI is funding research on medical countermeasures, including vaccines and monoclonal antibodies (mAbs), there remains limited understanding of how at-risk countries will use them. This study aims to address this gap through targeted interviews and demand forecasting for 10 countries: Australia, Bangladesh, Cambodia, India, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. Methodology/Principal FindingsInterviews with country and global stakeholders gathered data on regional sentiment, financing, and affordability. Profiles were developed to summarize each countrys perceived outbreak risk and their likely use of countermeasures. Demand was estimated by integrating these perspectives into models of likely country-level responses to three NiV outbreak scenarios: Expected, Amplified, and Extended. In the Expected scenario, countries focused on reactive use with global annual demand ranging from approximately 800 to 5,000 doses for vaccine-only, mAb-only, and combination interventions. Ring strategies were preferred given outbreak size and infrequency. Demand was highest for vaccine-only and combination interventions, with lower demand for mAbs-only due to affordability concerns and less familiarity in Bangladesh and India. In Amplified and Extended scenarios, countries expanded their responses to include preventive campaigns for healthcare workers and rural populations. These campaigns would require approximately 410,000 and 6,300,000 doses, respectively, if introduced in all 10 countries. Conclusions/SignificanceThis study has revealed existing sentiments regarding Nipah disease and interventions and modeled demand across three outbreak scenarios. Given global annual demand based on current epidemiology, Nipah countermeasure markets are unlikely to be commercially viable solely on routine country-financed demand. Instead, market health will require external financing and stockpile mechanisms to maintain demand between sporadic outbreaks. Author SummaryNipah virus (NiV), which causes severe and often fatal disease in humans, is recognized by the Coalition for Epidemic Preparedness Innovations (CEPI) as a priority pathogen with pandemic potential. In response, CEPI has supported the development of vaccines and monoclonal antibodies (mAb). However, limited evidence exists on how at-risk countries will deploy these medical countermeasures. We interviewed key decision-makers across 10 at-risk countries, along with global experts on NiV, to better understand disease prioritization, financing and affordability considerations, and countermeasure preferences. Interview findings informed the development of a demand forecast in response to Nipah outbreaks of varying intensity. At expected outbreak levels, countries focused their response on reactive strategies given outbreak size and infrequency. As outbreaks grew in size, countries considered expanding their response to include preventive campaigns targeting healthcare workers and at-risk, rural populations. This study provides new insights into country-level perspectives on NiV and medical countermeasures and quantifies expected demand across three outbreak scenarios and 10 countries. Our findings can provide a foundation for the strategic development of an international Nipah countermeasure stockpile, designed to address episodic NiV outbreaks and enhance pandemic preparedness.
Kasamatsu, A.; Ohama, Y.; Tomo, Y.; Imai, K.; Nakayama, S.-i.; Omori, R.; Yamagishi, T.; Yasuda, M.; Akeda, Y.
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Background: Treponema pallidum quantitative polymerase chain reaction (qPCR) positivity and cycle threshold (Ct) by rapid plasma reagin (RPR), disease stage, and other characteristics are poorly characterized in routine-care specimens, leaving it unclear when qPCR of such specimens is informative for diagnosis. Methods: This Japanese multicenter cross-sectional study explored qPCR positivity and Ct by these characteristics. Nonblood specimens collected during routine care underwent qPCR at a central laboratory for this study. Bayesian logistic and normal regressions modeled positivity and mean Ct of TP0574 and polA with stage-specific continuous automated RPR terms, patient characteristics, collection site, and facility random intercepts. Estimates were standardized over the analyzed specimens. Population-group predictions were instead averaged within each group. Results: Among 154 nonblood specimens from 145 patients (71.7% non-MSM men and women) at 14 facilities, 109 (70.8%) were qPCR positive. At RPR 1, adjusted positivity was 72.2% (95% credible interval, 60.9%--82.9%) in primary and 43.8% (16.7%--69.9%) in secondary syphilis. Positivity showed a modest downward trend with RPR in primary but increased in secondary syphilis, reflecting a stage-by-RPR interaction (secondary-to-primary ratio of odds ratios, 1.78; 1.25--2.65). Predicted positivity showed an upward trend with RPR values among MSM; adjusted positivity was relatively high for genital/urethral/urinary and anal/perianal/rectal specimens. Adjusted mean Ct increased with RPR in primary and followed an inverted-U pattern in secondary syphilis. Conclusions: In primary syphilis, nonblood qPCR positivity was high even at low RPR. When serologic findings remain inconclusive in this stage, qPCR is highly recommended for securing an early diagnosis.
Siddiq, A. I.; Arthur-Gyimah, T.; Aitee, G. D.-G.; Oku, J. N. A. J.; Vondee, E.; Asumang, G. O.
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Background: Anaemia in women of reproductive age is a persistent contributor to maternal morbidity and adverse birth outcomes in sub-Saharan Africa. Ghanaian surveys have repeatedly placed national anaemia prevalence in the World Health Organization's severe public health problem range, yet the geographical distribution of this burden, and the socioeconomic factors that may account for it after geographical adjustment, remain insufficiently elucidated. Methods: This cross-sectional study analysed the women's and geospatial files of the 2022 Ghana Demographic and Health Survey. Anaemia was defined as altitude- and smoking-adjusted haemoglobin below World Health Organization thresholds among 7,557 women aged 15-49 years with a valid measurement. Survey-weighted multivariable logistic regression, accounting for clustering, stratification, and sampling weights, was used to elucidate socioeconomic and demographic correlates. Cluster-level prevalence was tested for spatial clustering with global Moran's I and local Getis-Ord Gi* statistics (k-nearest neighbour weights, k = 8). Results: Weighted anaemia prevalence was estimated at 41.1% (mild: 22.6%, moderate: 17.3%, and severe: 1.1%). Pregnant women appeared to have higher adjusted odds of anaemia than non-pregnant women (adjusted odds ratio [AOR] 1.71, 95% CI 1.38-2.12), as did women in the Northern (AOR 1.54, 95% CI 1.16-2.06) and Savannah (AOR 1.35, 95% CI 1.04-1.76) regions relative to Greater Accra, while the Ahafo region showed lower odds (AOR 0.64, 95% CI 0.43-0.94). Associations with rural residence, education, and wealth that were significant in crude analysis appeared substantially attenuated after adjustment. Moran's I suggested significant positive spatial autocorrelation (I = 0.156, p = 0.001); Getis-Ord Gi* identified 109 hotspot and 117 cold spot clusters among 618 clusters, with hotspots concentrated in the north and cold spots in the mid-southern forest belt. Conclusion: Two in five women of reproductive age in Ghana were estimated to have been anaemic in 2022. Risk appeared to be shaped more by region and pregnancy status than by household wealth or education once geography was accounted for. Anaemia-control programming may benefit from prioritising the identified northern hotspot areas alongside routine antenatal supplementation.
Ofori, D. K.; Acheampong, A.; Kudzordzi, P.-C.; Nyarko, P.; Nseide, C. W.; Boateng, E. A.; Tanko, Y. S.; Caffrey, C. R.; Otabil, K. B.
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Urogenital schistosomiasis, caused by Schistosoma haematobium, remains a major public health challenge among school-aged children in rural Ghana. Although urogenital indicators are well-established, systemic hepatic biomarker alterations in post-mass drug administration pediatric settings remain poorly characterized. This cross-sectional study evaluated point-of-care urinalysis profiles alongside a panel of serum hepatic and renal biomarkers in 174 children (aged 3 to 16 years) from the Sene West District, Ghana. Active infection (urine microscopy egg detection) was identified in 84 participants (48.3%, median egg count = 4.50 eggs/10 mL, IQR: 1.00 - 9.25). Active infection was strongly associated with microhematuria (57.1% vs. 11.1%, p < 0.001), proteinuria (42.9% vs. 22.2%, p = 0.004), and leukocyturia (27.4% vs. 4.4%, p < 0.001). Children with active infection also demonstrated a higher frequency of composite categorical hepatic biomarker alterations (60.7% vs. 37.8%, p = 0.002), whereas categorical renal alterations showed no significant difference (p = 0.332). Controlling for age and sex, multivariable logistic regression confirmed active infection as a significant independent predictor of composite hepatic biomarker alterations (aOR = 2.54, 95% CI: 1.37 - 4.69, p = 0.003), but not renal alterations (aOR = 1.40, p = 0.359). Continuous medians for individual serum biomarkers showed no significant differences between groups. Combining composite hepatic biomarker thresholds with routine dipstick screening improves the detection of subclinical morbidity in pediatric field settings.
Oyibo, W.; Blair, A. M.; Oladipo, O.; Ogbulafor, N.; Urude, R. O.; Onwuachusi, G.; Anabike, C.; Ntadom, G.; Okoronkwo, C.; Uhomoibhi, P.; Eze, N.; Oresanya, O.; Mahmoud, A.; Okoro, O.; Aduagba, B.; Ijezie, S.; Okoh, F.; Kawu, I.; Ozor, L.; Maikore, I.; Maxwell, K.; Ezeiru, S.; Nwokolo, E.; Amajoh, C.; Audu, M.; Mokuolu, O.; Biyama, Z.; Adeyoju, T.; Obike, N.; Ilelaboye, J.; Lawson, A.; Conway, D. J.
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Introduction: The continuing high and inequitable global malaria burden requires improved methods to understand trends and target control. Current methods often involve infection prevalence surveys, but additional parasitological measures could increase precision in estimating infection burdens of communities. Methods: Focusing on the country with most malaria globally, examinations of slides from 10,651 children under five sampled in the 2021 national Malaria Indicator Survey in Nigeria were performed to measure asexual parasite densities in infected children and discriminate sexual stages and species. Variation in these indices among the six different geopolitical zones and 37 individual states including the Federal Capital Territory were compared with the variation indicated by infection prevalence alone. Results: Among the six major geopolitical zones, only one had significantly higher asexual parasite prevalence than others, but parasite densities within infected children revealed more significant variation among the different zones. Comparing results for 2021 with previous data from 2018, one zone showed lower asexual parasite prevalence and two had lower sexual parasite prevalence, but three had higher asexual parasite densities in infected children. Variation in parasite densities among individual states also highlighted significant geographical and temporal differences, extending the detection of heterogeneity within each geopolitical zone. Overall trends were driven by the predominant parasite species Plasmodium falciparum as prevalence and density of the other species were much lower. Conclusions: Findings indicate that understanding complex patterns of geographical and temporal variation is enhanced by including asexual parasite density measurement, providing opportunities for more precise targeting of malaria control within high burden countries.
Abraham, P.; Fransisca, L.; Adella, J.; Rahmalia, A.; Jimanto, V.; Angeline, S.; Putri, A.; Mannion, K.; Sakalidis, V.; Sutanto, I.; Pasaribu, A. P.; Poespoprodjo, J. R.; Simpson, J. A.; Price, R. N.; Devine, A.
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The radical cure of Plasmodium vivax requires treatment of the dormant liver stages with either primaquine or tafenoquine but is constrained by the risk of severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. A revised case-management package, New Primaquine Treatment (NPT), was designed to support safe radical cure in Indonesia, and included G6PD screening, targeting high dose primaquine and early clinical review. A decision-tree model was constructed using individual-level data from a study, that treated patients with 7mg/kg primaquine according to their G6PD activity: primaquine administered over 7 days (G6PD normal individuals), 14 days (individuals with intermediate G6PD deficiency), or 8 weeks (if severely G6PD deficient). The model incorporated costs, adverse events, and P. vivax recurrence over a six-month time horizon. A business-as-usual comparator was created using historical P. vivax recurrence data for Indonesia overall and the three provinces separately. The primary outcome was disability-adjusted life-years (DALYs) averted. Costs were analyzed from health system and societal perspectives, and incremental cost-effectiveness ratios (ICERs) were compared with Indonesias Health Technology Assessment recommended willingness-to-pay thresholds of 1 and 3 gross domestic product per capita (US$4,925 and $14,475). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. Overall NPT averted 0.0011 DALYs per patient with an incremental cost of US$7.40 per patient from a health system perspective. This resulted in an ICER of US$6,636 per DALY averted, which was not cost-effective at the $4,925 threshold. Cost-effectiveness varied across settings: from US$5,098 per DALY averted in Papua to US$20,051 per DALY averted in southern Sumatra and US$80,825 per DALY averted in northern Sumatra. The ICER reduced when the societal perspective was included, with NPT cost-effective in Indonesia overall ($2,261/DALY averted) and in Papua ($675/DALY averted). The risk of P. vivax recurrence and intervention costs were the most influential parameters on the ICER. Overall, NPT was between the 1-3x GDP per capita cost-effectiveness thresholds in Indonesia; however, cost-effectiveness varied significantly across settings, indicating that NPT may not be an optimal use of resources in areas with low incidence.
van Wyk, S.; Gwasupika, J.; Mapahla, L.; Asua, V.; Harrison, L. E.; Kamya, M. R.; Nankabirwa, J. I.; Barnes, K. I.
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Artemisinin partial resistance (ART R) associated Plasmodium falciparum Kelch13 mutations is expanding across Africa. However, their population level consequences remain poorly understood, particularly in settings of moderate to high malaria transmission. We investigated associations between Kelch13 and partner drug mutation prevalence and monthly confirmed malaria incidence across 16 Ugandan districts from 2017 to 2022, using integrated molecular, epidemiological, climatic, malaria control, and antimalarial resistance data and negative binomial regression. Combined prevalence of WHO validated and candidate Kelch13 mutations increased over the study period. Each 10 percentage point increase in Kelch13 prevalence was associated with a 13.1% higher incidence after multivariable adjustment (aIRR 1.131, 95% CI 1.090 to 1.174). Furthermore, each 10% increase in pfcrt K76T was associated with a 24% increase in malaria transmission. As expected, ITN distribution >80%, IRS coverage >90%, and higher altitude were associated with lower incidence, whereas temperatures of 25 to 30C, relative humidity of 60 to 80%, and higher precipitation were associated with higher incidence. The persistence of the Kelch13 and pfcrt K76T association after adjustment suggests that expanding ART R associated parasite populations are independently associated with malaria incidence. The relationship may be bidirectional. These findings support interpreting ART R within its ecological and intervention context and integrating molecular, epidemiological, and malaria control surveillance to safeguard antimalarial efficacy.
Hounsell, R.; Silal, S. P.; Norman, J.; Monyake, R.; Immaculate, A.; Besigye, A.; Biroma, G.; Magoola, J.; Kishore, N.; Pallas, S. E.; Ward, K.
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Routine infant vaccination has helped reduce cases and deaths from diphtheria, tetanus, and pertussis globally. However, these diseases continue to pose serious health risks as protective immunity wanes over time. Three booster doses of diphtheria-tetanus-pertussis-containing vaccine (DTPCV) administered from 12-months to 15-years of age increase duration of protection beyond childhood. Growing demands on government health spending underscore the importance of understanding the health and economic impact of vaccines prior to introduction. Using an integrated multi-disease epidemiological-economic model, we estimated the health impact (cases averted, deaths averted, and changes to population immunity) and budget impact of introducing DTPCV booster doses in Uganda. Compared to no DTPCV boosters, introducing all three booster doses is projected to result in 2.2 times the proportion of the population protected against symptomatic diphtheria and 2.8 times against tetanus infection among Ugandans under 15 years of age by 2039. Compared to introduction of the early childhood booster (EC) at 18 months of age, introducing all three DTPCV boosters simultaneously is projected to avert 3.2 times the number of tetanus cases over fifteen years at 2.4 times the incremental cost. The projected government vaccination cost per planned dose was USD 0.58 for simultaneous introduction of all three boosters compared with USD 0.68 for the EC booster alone. The average annual incremental cost of all three DTPCV booster doses is USD 2.79 million. Under modelled assumptions, simultaneous introduction of all three DTPCV booster doses in Uganda provides the greatest health gains, with a lower government vaccination cost per planned dose than introduction of the EC booster alone, but may still pose affordability challenges for Ugandas government.