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Journal articleJohnson LF, Kubjane M, Imai-Eaton JW, et al., 2026,
Towards ending tuberculosis in South Africa: an uncertainty analysis of the programmes and factors most critical to future declines.
, Glob Health Action, Vol: 19BACKGROUND: The WHO End Tuberculosis (TB) strategy targets 80% and 90% reductions in TB incidence and mortality, respectively, between 2015 and 2030. OBJECTIVE: To assess which policy-changeable and external factors are most critical to reducing future TB in South Africa. METHODS: We adapted an existing mathematical model of TB and HIV in South Africa. Prior distributions were specified to represent uncertainty ranges for 27 model parameters that are highly uncertain and potentially important in driving future TB dynamics. Latin Hypercube Sampling was used to sample 1000 parameter combinations from these distributions, and the model was projected to 2040 for each. Partial rank correlation coefficients (PRCCs) were calculated to assess correlation between each parameter and average adult TB incidence and mortality rates over 2025-2040. RESULTS: Adult TB incidence and mortality rates in South Africa were projected to decline by 46% (95% uncertainty interval [UI]: 17-69%) and 54% (95% UI: 21-84%) respectively by 2030, relative to 2015. The parameters most strongly associated with future TB incidence were the increase in microbiological testing in symptomatic individuals due to near-point-of-care/tongue swab (NPOC/TS) testing (PRCC = -0.67), reductions in social contact rates post-COVID (PRCC = -0.61), the probability of sputum testing in symptomatic individuals in the absence of NPOC/TS testing (PRCC = -0.39), and the efficacy of TB preventive therapy (PRCC = -0.35). TB mortality predictors were similar. CONCLUSIONS: Increasing testing among people with TB symptoms, including through new NPOC/TS technologies, is likely to have the largest impact on progress towards End TB goals in South Africa, though attainment by 2030 is unlikely.
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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 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 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 articleFraser K, Cibrelus L, Horton J, et al., 2026,
Yellow fever outbreak potential in Djibouti, Somalia and Yemen: a mathematical modelling study
, BMC Global and Public Health, Vol: 4, ISSN: 2731-913XBackgroundThe importation of arbovirus diseases into new countries is a global concern. This risk is exacerbated by human movement and climate change effects. In the World Health Organization (WHO) Eastern Mediterranean regional office, three countries - Djibouti, Somalia, and Yemen - are currently classified as potential or moderate risk for yellow fever (YF) outbreaks.MethodsHere we present a quantitative assessment of the risk of introduction and propagation of yellow fever virus (YFV) transmission in Djibouti, Somalia and Yemen. This modelling has two components: i) projecting the risk of importation of infectious individuals into the countries of interest using a radiation model of human movement and ii) estimating the risk of onward transmission given importation using a dynamic compartmental model of yellow fever virus transmission. Both components are multiplicatively combined to give an overall relative outbreak risk combining both risk of importation and risk of an outbreak given importation.ResultsWe show that areas such as the western coast of Yemen, regions of Somalia bordering Ethiopia and Kenya, and Djibouti City have potential for YF outbreaks (where the estimated probability of an outbreak given an imported infectious case is over 50%). This is due to environmental suitability for transmission based on factors such as temperature and projected human mobility between endemic and at-risk regions.ConclusionsCountries bordering existing YF endemic regions are potentially vulnerable to both introduction of YF cases and subsequent outbreak spread. This promotes the awareness of YF importation potential when conducting clinical surveillance in at-risk countries.
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Journal articleAhmed S, Mangal TD, Hallett TB, et al., 2026,
When is elimination of an infectious disease cost- effective? An analytical framework to guide elimination priorities
, Cost Effectiveness and Resource Allocation, Vol: 24, ISSN: 1478-7547BackgroundElimination targets for infectious diseases are increasingly common in global health, yet the economic rationale for pursuing elimination is often assumed rather than rigorously assessed. Existing evaluations frequently emphasise future cost savings or broader economic benefits while overlooking health opportunity costs—the health that could have been gained had resources been allocated elsewhere. This study aimed to develop an analytical framework to investigate when disease elimination generates positive net health benefit (NHB) and to illustrate how key factors interact to shape this assessment.MethodsWe constructed a generalisable analytical framework incorporating ten factors related to intervention and disease costs, intrinsic disease/intervention characteristics, and stakeholder viewpoints and evaluation parameters. The framework was applied to create an exemplar model that showed how these factors jointly influence the NHB of achieving elimination. This was evaluated across wide parameter ranges informed by the literature, using different cost-effectiveness thresholds, discount rates, and time horizons. ResultsThe framework revealed distinct regions of parameter space in which elimination yield positive NHB. The cost effectiveness threshold, discount rates, disease burden, and intervention impact were strong determinants of NHB. In particular, lower thresholds, higher discount rates, and shorter time horizons reduced the likelihood that elimination would generate positive NHB. The framework also showed that elimination may be cost effective in some settings but not in others, even for the same disease, due to differences in costs, burden, and opportunity costs.ConclusionsDisease elimination is not always a good investment; its value depends on the interplay between disease characteristics, programme costs, and the health opportunity costs of resource use. The proposed framework provides a transparent, health opportunity cost-based structure f
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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 articleAng HJ, McCormack C, Donnelly C, et al., 2026,
Association of dengue severity with the serotype of infection: a systematic review and meta-analysis
, EClinicalMedicine, ISSN: 2589-5370Background Dengue is a mosquito-borne infection caused by one of four dengue virus serotypes (DENV1-4) that circulates endemically across the tropics and subtropics. To date, there is contrasting evidence on the relationship between the serotype of infection and disease severity. Methods We conducted a systematic review (PROSPERO, CRD42023443101) and meta-analysis to examine the association between the serotype of symptomatic infections with severe disease while accounting for both prior exposure status and geographic region, with 18 severity defined by (i) the 1997 World Health Organization (WHO) guidelines, (ii) the 2009 WHO guidelines or (iii) hospitalisation. We searched the Global Health, Embase Classic + Embase, and Medline databases using Ovid for studies published up to 20 January 2025 and extracted case counts with matched serotype and severity information. We fitted generalised linear mixed models to estimate the proportions of severe cases, running independent analyses per severity definition, and stratifying by prior exposure-serotype combinations (e.g. primary DENV2) and geographic region (Asia versus Americas). Heterogeneity was assessed using the 𝜏 26 and 𝐼 metrics and risk of bias was assessed by adapting an established tool for risk of bias in prevalence studies. 28 Findings Our search yielded 4621 unique records, with 71 studies included for the meta-analysis. We found that, on average, DENV3 in Asia resulted in the highest proportion of DHF/DSS (21·00% [95% CrI: 13·02 to 30·44%]) and hospitalised (22·00% [95% CrI: 0·88 to 75·31%]) cases among symptomatic primary infections, while also causing the highest proportion
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Journal articleMangal T, Mohan S, Molaro M, et al., 2026,
System-wide investments generate health and enhance HIV, TB and malaria control in Malawi
, Nature Communications, ISSN: 2041-1723Global health initiatives have expanded access to HIV, tuberculosis, and malaria services in low-income countries, yet these programmes often operate within fragile health systems where shortages of healthcare workers and essential medicines limit their effectiveness and sustainability. Evaluating investments in health system capacity remains challenging because their benefits are difficult to attribute. Here, using a dynamic microsimulation model of Malawi’s health system, we show that health system strengthening investments alone could avert 11.4% of disability-adjusted life years between 2025 and 2035, delivering a return of $26.1 per dollar invested. Combining system strengthening with HIV, tuberculosis, and malaria programme expansion produces three times greater health impact than disease-focused investment alone, delivering a return of $11.7 per dollar invested compared with $5.4 for disease-focused expansion alone. These findings support a shift toward integrated global health financing strategies that combine health system strengthening with disease-targeted programmes.
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Journal articleSimmons OS, Vicco A, Martínez-Vega RA, et al., 2026,
Overall and serotype-specific dengue virus transmission intensity in Mexico, 2016–2023: a modelling study of case-notification data
, PLoS Medicine, Vol: 23, ISSN: 1549-1277BackgroundMexico, and the Americas region more widely, have experienced increased dengue incidence in recent years, and there are concerns that the changing climate may enhance dengue virus (DENV) transmission in the future. Whilst previous studies have characterised spatial heterogeneities in the long-term average risk of DENV infection in Mexico, the extent to which DENV transmission changes year-to-year has not been investigated. Furthermore, the extent to which DENV’s four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) may differ in their transmissibility remains poorly characterised, both in Mexico and globally.Methods and findingsIn this study, we characterised the spatial and temporal variations in DENV transmission intensity, as defined by the force of infection, across 27 states in Mexico. We analysed annual dengue case data reported to the National Epidemiological Surveillance System (SINAVE) in Mexico between 2016 and 2023, which comprised 833,629 probable or confirmed cases, using established catalytic models and a new, serotype-specific extension of these models that characterises differences in the transmission intensity of the different serotypes. We found evidence of large spatial, temporal, and serotype-specific heterogeneities in transmission intensity across Mexico. Serotype-specific force of infection estimates suggest that DENV-1 and DENV-2 have historically circulated at high levels across Mexico, with DENV-4 showing a low transmission intensity throughout the study period. We found evidence of increasing DENV-3 transmission intensity across some states in recent years, coinciding with large outbreaks. The extent to which the serotype-specific transmission intensity estimates generated in this study are affected by potential heterogeneities in case reporting across states and through time remains to be validated in future studies.ConclusionsThis work quantifies serotype-specific differences in DENV transmission intensity using routinely co
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