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Journal articleCidade JP, Taccone FS, Reyes LF, et al., 2026,
Immune dysregulation through longitudinal lymphocyte trajectories and their clinical determinants in hospitalized COVID-19 patients
, Intensive Care Medicine Experimental, Vol: 14Objective: Immune dysregulation plays a pivotal role in the pathophysiology of sepsis and COVID-19, with lymphopenia emerging as a consistent marker of severity and poor prognosis. However, most existing studies have assessed lymphocyte counts at isolated time points, limiting insights into their temporal behavior and prognostic value. The dynamics of lymphocyte recovery or persistence of lymphopenia remain largely unexplored in large populations, as well as the impact of adjunctive therapies such as corticosteroids. We hypothesized that the persistence or recovery of lymphopenia may be key to understanding disease progression and predicting outcomes. Using the multinational ISARIC cohort, we investigated longitudinal lymphocyte trajectories in hospitalized patients and the clinical determinants associated with their evolution over time. Methods: We conducted a multinational prospective observational cohort study using data from the ISARIC-WHO Clinical Characterization Protocol. Patients with confirmed SARS-CoV-2 infection and at least four lymphocyte measurements during the first 28 days of hospitalization were included. We analyzed lymphocyte trajectories, Cox regression survival analyses and multivariable linear regression modelling. We also applied multistate models and joint modeling to assess the association between lymphocyte trajectories and 28-day mortality, incorporating corticosteroid use as a time-varying covariate. Results: Of 945,317 screened patients, 231,933 hospitalized adults with confirmed COVID-19 and sufficient lymphocyte data were included, with 56.6% classified as lymphopenic. Lymphopenia was independently associated with higher rates of ICU admission, organ support, and in-hospital mortality (OR = 1.52, 95% CI 1.48–1.55), and lower absolute lymphocyte counts were strongly linked to worse survival in adjusted Cox models (HR = 1.33 per 1 × 10⁹ cells/L decrease, 95% CI 1.28–1.38). Multistate modeling revealed that lymphope
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Journal articleNgwili N, Kachepa U, Korir M, et al., 2026,
Spatial and temporal risk mapping of human and porcine Taenia solium infections in Malawi: a systematic review and geostatistical approach
, One Health Outlook, Vol: 8, ISSN: 2524-4655Background Taenia solium, colloquially called the pork tapeworm, is a zoonotic parasite with a human definitive host and a porcine intermediate host. Humans can become an aberrant intermediate host due to accidental ingestion of parasite eggs from the environment or through autoinfection, resulting in human cysticercosis (HCC), neurocysticercosis (NCC) if the central nervous system is infected. Pigs become infected with the larval stage, porcine cysticercosis (PCC), through the ingestion of parasite eggs shed by humans through defecation. Malawi has been classified as endemic for T. solium by the WHO based on the presence of key risk factors; however, the subnational distribution is not known. To ensure the appropriate resources are mobilized to support targeted future T. solium control measures in Malawi, there is a need to understand the variation in T. solium endemicity status across the country.Methods The current study uses a systematic literature review (SLR) using a pre-registered protocol; (PROSPERO CRD42023411044) to collate all available evidence on T. solium in Malawi. A geospatial risk mapping approach was conducted based on data from Malawi demographic health surveys (MDHS), and pig density data from the Food and Agriculture Organization (FAO) database to create geospatial risk maps of endemic subnational areas for 2000, 2004, 2010, and 2016. To create a single composite risk factor map for the four years from the MDHS, each parameter was plotted as a binary variable with the high or low risk categories and overlaid into a single composite risk factor classification. Additional data from hospital records on NCC and meat inspection records across several Agricultural Development Divisions (ADDs) were also collected.
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Journal articleMcCain K, Topazian HM, Challenger JD, et al., 2026,
Public health impact of catch-up vaccination or additional booster doses with pre-erythrocytic malaria vaccine R21/Matrix-M: a modelling study
, BMC Medicine, Vol: 24, ISSN: 1741-7015Background The malaria vaccine R21/Matrix-M is recommended for young children in malaria-endemic regions. However, the small vaccine-eligible population and waning vaccine efficacy mean that routine vaccination is unlikely to prevent severe cases in older children who experience significant malaria burden. As R21/Matrix-M vaccination expands, targeting older age groups may be warranted, depending on funding. Methods Using a stochastic, individual-based P. falciparum malaria transmission model, we estimate the impact of 1) one-off catch-up campaigns with R21/Matrix-M to previously unvaccinated age groups between age 6 months and 14 years, and/or 2) extra boosters at 2, 5 and/or 10 years after the primary series in low, moderate, and high transmission settings. We assume that vaccine immunogenicity in older children is equivalent to that of the standard target age group, though clinical trials have shown lower immunogenicity in older children.ResultsCatch-up campaigns in moderate-to-high transmission settings targeting younger children averted the most uncomplicated cases per 1000 additional doses (358 (95% Credible Interval (CI) 113-570) in children aged 6 months-2 years at 45% PfPR2-10), compared with targeting older children. In low transmission settings, the impact was similar across age groups, with a slightly higher impact when targeting school-aged children (373 (95% CrI 240-518) in children aged 5-9 years at 5% PfPR2-10). Across extra booster strategies, an extra booster 10 years post-primary series averted the most severe cases per 1000 additional doses at low transmission (12 (95% CrI 6-18) at 5% PfPR2-10), but the least at high transmission (-4 (95% CrI -11-3) at 45% PfPR2-10). Expanding the vaccine-eligible population in areas of moderate-to-high transmission often had higher incremental efficiency than routine age-based vaccination at low transmission. Sensitivity analyses assuming lower immunogenicity in older children modestly reduced the per-dose impac
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Journal articleTopazian HM, Morgan CE, Goel V, 2026,
Spatial and temporal associations between animal ownership and malaria prevalence in Africa using cross-sectional national Demographic and Health Surveys.
, One Health, Vol: 23, ISSN: 2352-7714Use of zooprophylaxis as a malaria control strategy has been recommended historically, but a complex relationship exists between animal ownership and malaria infection, with mixed associations described in the literature. We sought to characterize this relationship spatially and temporally in malaria-endemic regions of Africa. We used data from 392,843 individuals from 66 Demographic and Health surveys from countries within Africa to investigate the association between household animal ownership and Plasmodium infection. We used Bayesian models with Integrated Nested Laplace Approximation to incorporate spatially varying coefficient processes, allowing the association of interest to vary over space, time, and within strata of vector species occurrence, land cover, and number of animals owned by households. Spatially varying intercept models showed that ownership of cattle, chickens/poultry, goats, horses/donkeys/mules, pigs, and sheep was broadly associated with malaria infection, with odds ratios ranging from 1.55 to 1.67. However, spatially varying slope models revealed considerable heterogeneity, with odds ratio estimates for all animal types demonstrating both protective and harmful effects varying from 0.33 to 3.33 both subnationally and across time. We found no evidence that modification by vector species, number of animals owned, and land cover fully explained the variation in estimates. Unobserved localized cultural, behavioral, or ecological factors likely modify the association between animal ownership and malaria prevalence. Further exploring the nature of this relationship over space and time will be important to understanding how context-specific One Health dynamics between humans, animals and the environment affect malaria prevention and control efforts.
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Journal articleLopes BC, Dutra JVR, Moreira FRR, et al., 2026,
Wastewater surveillance of dengue and chikungunya during the worst arbovirus epidemic in Brazil.
, Water Res, Vol: 300This study evaluated wastewater-based epidemiology (WBE) for monitoring dengue virus (DENGV) and chikungunya virus (CKV) during Brazil's most severe arbovirus epidemic, focusing on the city of Belo Horizonte, Minas Gerais. From March 2022 to August 2024, 24-hour composite raw sewage samples were collected weekly from two major wastewater treatment plants, encompassing over 80% of the city's population. Viral RNA was quantified via RT-qPCR and positive samples underwent genome sequencing for genotype characterization. DENGV and CKV RNA were detected in over 90% of samples across both wastewater treatment plants (WWTPs), demonstrating sustained and widespread viral circulation throughout epidemic and inter-epidemic periods. Although CHIKV concentrations varied significantly across years, DENGV concentrations remained statistically stable, and no significant correlations were observed between wastewater viral loads and reported clinical cases. A considerable proportion of samples presented concentrations below the limit of quantification, indicating that while WBE is highly sensitive for qualitative detection of arboviruses, quantitative interpretation remains methodologically constrained. Sequencing confirmed the presence of DENGV-1 sorotype I and CKV genotype V, clustering with contemporaneous Brazilian strains and reflecting regional transmission dynamics. Wastewater-based modelling further suggested that reported clinical cases may substantially underestimate true infection burden, although quantitative estimates were highly sensitive to assumptions regarding viral shedding variability. These findings demonstrate that WBE provides a sensitive, non- invasive, population level approach for tracking arboviral circulation and viral diversity during large-scale outbreaks and could complement public health surveillance frameworks, especially in regions with limited diagnostic capacity or high levels of underreporting, to enhance epidemic response and control strategies.
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Journal articleRamani A, Dixon-Zegeye M, Basanez M-G, 2026,
Identifying implementation units that would benefit from alternative treatment strategies to accelerate the elimination of onchocerciasis transmission in Africa
, Frontiers in Tropical Diseases, ISSN: 2673-7515Background: The World Health Organization proposes that elimination of onchocerciasis transmission (EOT) be verified in 12 endemic countries by 2030. In sub-Saharan Africa (SSA), where most cases occur, Niger is the only country that has been verified to date. Despite decades of ivermectin mass drug administration (MDA), infection persists in West and Central Africa. Alternative treatment strategies (ATS) are necessary to accelerate progress towards EOT by 2030 and beyond. Methods: We used the EPIONCHO-IBM transmission model to project the number of years, from 2026, to reduce microfilarial (mf) prevalence below 1% across 1,634 implementation units (IUs) in 19 SSA countries. We fitted the model to geostatistically-derived mf prevalence in 1975, 2000 and 2018, and projected mf prevalence through to 2025. We classified IUs according to their baseline endemicity, intervention history programmatic performance, and current (2025) MDA frequency (annual or biannual). For those IUs that would not reach < 1% mf prevalence by 2030 if current strategies were continued, we simulated ATS (increasing treatment frequency, improving coverage, and adopting moxidectin MDA) from 2026 to 2040. Results: Of the 1,486 IUs currently under annual ivermectin MDA, 45% would require ATS. In those low-moderate endemicity IUs, biannual ivermectin would have a comparable impact to that of switching to annual moxidectin; in those with high endemicity, adopting biannual moxidectin would be more impactful. Of the 148 IUs currently receiving biannual ivermectin, 24% would benefit from ATS, switching to biannual moxidectin being the best option. Conclusion: This work brings into sharper focus which IU profiles are most likely to require ATS across SSA. In highly-endemic IUs with long intervention histories, biannual moxidectin MDA may be required under our modelling assumptions, with substantial uncertainty surrounding the permanent sterilising effect, of the two drugs under comparison, upon adu
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Journal articleShe B, Mohan S, Murray-Waston RE, et al., 2026,
Health impacts of expanding the health workforce across cadres under an incremental budget in Malawi
, BMJ Global Health, ISSN: 2059-7908Like many others, Malawi’s health care system faces significant health workforce shortages largely due to budget constraints that limit training, recruitment and retention of staff. A crucial question is how to best allocate a limited incremental budget to expand different health care workers (HCW) cadres so that the potential health gains are maximised, which is more important now than ever considering recent withdrawal and reduction in donor funding. This research aims to provide a practical answer to this question. We designed a range of budget allocation scenarios for HCW expansion across cadres and used the “all diseases – whole healthcare system” Thanzi La Onse (TLO) model to estimate the resulting population health outcomes. We find that, indeed, how to allocate the incremental budget among cadres is an important determinant of the potential health impact. Concentrating all of the budget on expanding a single cadre – such as Clinical, Pharmacy, or Nursing and Midwifery - is not the most effective use of the resources, even when that cadre currently faces the greatest staffing shortages. Similarly, allocating the budget in a manner that mirrors the current distribution of spending and results in a uniform expansion across cadres does not generate the greatest possible gains. Instead, an allocation that uplifts staffing for multiple cadres, accounting for the additional time and costs required to meet the future healthcare needs, yields the greatest benefits. We conclude that, in the context of complex interplay between demography, epidemiology, treatment scope and effectiveness, and health resource constraints, human resources for health (HRH) bottlenecks in achieving health gains are multifactorial and a needs-based, balanced mix of cadres and skills is required for future HRH expansion. As such, health system models such as the TLO that capture this interplay can make potential contributions to strengthening HRH planning.
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Journal articleBotwright S, Munira SL, Megiddo I, et al., 2026,
Uncertainty in economic evaluation: a pragmatic guide for health technology assessment (HTA) agencies in resource-constrained settings
, PharmacoEconomics, ISSN: 1170-7690Understanding the financial and health consequences if economic evaluation assumptions prove incorrect is essential for managing the risk associated with benefit package decisions, particularly in resource-constrained and overburdened healthcare systems. Yet these are also the settings that face the greatest challenges in conducting comprehensive uncertainty analysis, owing to a range of factors including limited skilled staff, data constraints, and short timelines to generate evidence in time to influence policy. This paper takes a pragmatic approach to support health technology assessment agencies in these settings to generate policy-relevant uncertainty analysis, drawing on good practice literature and the authors’ collective experience conducting economic evaluation for policy across resource-constrained settings. For each step of the economic evaluation process, we outline the main sources of uncertainty, principles for deciding which uncertainty analysis to prioritise, and approaches to overcome some of the common challenges faced when dealing with constrained timelines, data, and skilled staff. The overarching goal is to support better-informed decisions, by targeting uncertainty analysis to factors that actually affect decisions and by effectively communicating this decision-relevant uncertainty to policymakers.
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Journal articleJudge C, Iani FCM, Finch E, et al., 2026,
Drivers of sylvatic yellow fever transmission in southeast Brazil: a joint epidemiological and phylodynamic inference.
, Lancet Planet HealthBACKGROUND: Yellow fever virus (YFV) has caused substantial human disease in Brazil, driven by spillover from outbreaks in nearby non-human primates (NHPs). As disease surveillance in NHPs is challenging, the impact of environmental conditions on YFV outbreaks in NHPs remains poorly understood. In this study, we aimed to use joint inference modelling to overcome these obstacles by integrating diverse data streams and to estimate YFV transmission dynamics in NHPs to enhance understanding of yellow fever disease ecology. METHODS: We applied a multistage analysis using epidemiological, phylogenetic, demographic, and meteorological data in conjunction with mechanistic and statistical modelling. We used EpiFusion joint inference models to infer YFV infection dynamics in NHPs from 2015 to 2019, and statistical generalised additive models to test hypothesised associations between NHP infections and environmental variables and human cases. FINDINGS: The effective reproduction number (Rt) of YFV in NHPs was approximately 1·0, indicating that small changes in transmissibility can enable explosive sylvatic outbreaks. We also found the possibility of large, entirely unobserved outbreaks in NHPs. El Niño sea surface temperature anomalies at medium-term and long-term lags were important predictors of YFV infection dynamics in NHPs. Finally, we found that the risk of YFV spillover to humans, measured in terms of the effect of NHP infections on human cases, was correlated with the number of NHP infections, with a 7-day to 21-day lag. INTERPRETATION: YFV might be establishing recurrent transmission in NHP populations in southeast Brazil, indicating that more comprehensive and consistent surveillance is needed. Identifying key environmental drivers and their lags with human YFV cases can be used to develop early warning systems to guide reactive vaccination and public health campaigns to prevent future outbreaks. FUNDING: None.
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Journal articleKim Y, Mills C, Donnelly CA, 2026,
Cross-border travel patterns affect magnitude estimates for the Ebola Bundibugyo epidemic
, Nature Health<jats:title>Abstract</jats:title> <jats:p>A geographic spread approach is often used to estimate the true burden of infectious disease cases in a source population by leveraging statistical signals generated by cases exported and reported elsewhere. Here we estimated an upper bound on the likely burden of Bundibugyo virus disease cases in the Democratic Republic of Congo early in the unfolding 2026 epidemic based on the number of cases imported and confirmed in Uganda. We expanded a geographic spread approach to account for its specific epidemiological contexts: most cross-border movements between the Democratic Republic of Congo and Uganda are short-duration trips, and, at the time of this analysis, all cases imported and confirmed in Uganda were individuals who travelled specifically to seek healthcare. Incorporating these factors substantially affected burden estimates, highlighting both the potential severity of the epidemic in its early phase and the critical need to consider local epidemiological contexts when applying geographic spread approaches to reduce and be aware of potential biases in estimates for early epidemic responses.</jats:p>
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