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Journal articleShah A, 2026,
International epidemiology of antimicrobial resistance in people living with chronic lung infection
, Thorax, ISSN: 0040-6376Background: Antimicrobial resistance (AMR) is a global threat for people with chronic lung infection, however international AMR epidemiology in bronchiectasis and Cystic Fibrosis (CF) is poorly characterised. In this study we retrospectively analyse international longitudinal AMR epidemiology in bronchiectasis and CF.Methods: Microbiology data was analysed from 110323 respiratory samples in 19143 individuals with bronchiectasis or CF across 11 cities, 8 countries, 3 continents between 2011-2024. Longitudinal AMR prevalence, multi-drug and extensive-drug resistance (MDR,XDR) and multiple antibiotic resistance (MAR) index was analysed by disease and country. Pilot analysis of concurrent/disjoint resistance in antimicrobial pairs and triplets in regional datasets was performed to inform combination or cyclical antimicrobial choice.Findings: Geographic AMR differences were noted across pathogens in bronchiectasis and CF with increased Pseudomonas aeruginosa resistance in central/southern Europe and increased Klebsiella pneumoniae resistance in Hong Kong. MDR burden was high in emergent pathogens Escherichia coli (CF:MDR-32.6%;XDR-12.4%; Bronchiectasis:MDR-39.2%;XDR-4.9%) and K.pneumoniae (CF:MDR-22.7%;XDR-15.6%; A longitudinal rise in P.aeruginosa AMR was seen in bronchiectasis across 4 centres for antipseudomonal aminoglycosides (p=<0.001;OR/yr:1.44;(95%CI:1.24-1.67)), fluoroquinolones (p=0.002;OR/yr:1.13;(95%CI:1.05-1.23)), cephalosporins (p=0.005;OR/yr:1.17;(95%CI:1.051.30)), penicillins with beta-lactamase inhibitor (p=0.02;OR/yr:1.18;(95%CI:1.03-1.35)) and carbapenems (p=0.048;OR/yr:1.11;(95%CI:1.00-1.23)). Rising longitudinal K.pneumoniae AMR was seen for cephalosporins (p=0.01;OR/yr:1.32;(95%CI:1.06-1.65)) and carbapenems (p=0.04;OR/yr:1.64;(95%CI:1.03-2.62)). Significant increased AMR by MAR index was seen in residual culture-positive CF individuals on triple CFTR modulator therapy (p<0.001). Strong concurrent resistance was noted in bronchiectasis across
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Journal articleTshiakuisha CN, Glover AC, Watsenga F, et al., 2026,
The spread of pyrethroid-resistant mosquitoes and their predicted malaria burden across the Democratic Republic of the Congo
, Current Research in Parasitology & Vector-Borne Diseases, Vol: 10, ISSN: 2667-114XMalaria control in the Democratic Republic of the Congo (DRC) is increasingly challenged by pyrethroid resistance in mosquito populations, although its epidemiological consequences remain uncertain. Entomological data from discriminating-dose bioassays conducted on wild mosquitoes were collated to characterise temporal changes in pyrethroid resistance since 2009. These estimates were incorporated into a mechanistic malaria transmission model to quantify how resistance may have reduced the effectiveness of insecticide-treated nets (ITNs) and affected malaria burden. Model projections were compared with malaria prevalence estimates from the 2013–2014 and 2023–2024 Demographic and Health Surveys, which were used as external comparisons rather than for model fitting. Counterfactual scenarios were generated in which mosquitoes remained fully susceptible to pyrethroids throughout the study period. The model estimated that pyrethroid resistance increased substantially over time and reduced the protection provided by pyrethroid-only ITNs. Nationally, approximately 8.6% of malaria clinical cases, corresponding to 33.6 million additional cases, and approximately 76,000 additional deaths between 2009 and 2024 were attributable to pyrethroid resistance in the modelled counterfactual comparison. The introduction of pyrethroid-PBO ITNs from 2019 partially restored the protection lost to pyrethroid resistance. These findings highlight the potential epidemiological consequences of pyrethroid resistance while also emphasising the uncertainty arising from sparse resistance surveillance and limited epidemiological observations. Improved entomological surveillance and continued deployment of more effective vector-control tools will be important for malaria control in the DRC.
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Journal articleFitch J, Ariadi MD, Kwun MJ, et al., 2026,
Artificial intelligence-guided phenotypic drug repurposing against Streptococcus pneumoniae
, Advanced Science, ISSN: 2198-3844The prevalence of antimicrobial resistance (AMR) within the common bacterial pathogen Streptococcus pneumoniae makes it a priority for the development of new antibiotics. While artificial intelligence (AI) has recently boosted phenotype-based repurposing of drugs for other human pathogens, this remains to be investigated for S. pneumoniae. Thus, we leveraged ensembles of transformer, graph, and tree models, each trained on a set of 1849 actives along with 34 503 inactives, to prospectively examine 6747 drugs. Of 11 selected candidate antibiotics, nine were found to strongly reduce in vitro growth of S. pneumoniae R6, with IC50 values of ≤ 0.4 µg/mL. The most potent drugs, thiostrepton and ceftiofur, had IC50 values of 0.0001 µg/mL (60.1 pM) and 0.0004 µg/mL (764 pM), respectively. Thiostrepton remained highly potent even against multidrug-resistant strains, suggesting it could be effectively deployed to treat common non-invasive S. pneumoniae infection as part of antibiotic stewardship efforts.
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Journal articleMichalow J, Cori A, Kimani J, et al., 2026,
Optimal deployment of gonorrhoea point-of-care tests: modelling the potential impact of diagnostic confirmation testing and screening strategies across five priority populations in Kenya
, The Journal of Infectious Diseases, Vol: 234, Pages: e714-e723, ISSN: 0022-1899BackgroundGonorrhea treatment in sub-Saharan Africa relies on syndromic management, which has poor diagnostic performance and misses asymptomatic infections. Point-of-care tests (POCTs) could address these limitations, but anticipated supply constraints necessitate strategic allocation to maximize impact.MethodsWe developed a deterministic compartmental model of gonorrhea transmission in Kenya to evaluate allocating POCTs for diagnostic confirmation of symptomatic care attendees versus screening of routine healthcare service attendees across five priority populations: female sex workers (FSW), their male clients (CFSW), pregnant women, adolescent girls and young women, or total population men. We modeled constrained and unrestricted POCT availability during 2025–2030, and estimated infections averted relative to baseline syndromic management. Quality-adjusted life years (QALYs) gained were quantified using probability tree models.ResultsAt baseline, incidence was highest among FSW (11.9 [UI: 5.7–18.6] per 100 per year) and CFSW (13.1 [6.9–24.8]), while most QALY losses (80.6% [76.1%–83.8%]) were among pregnant women and their infants. With constrained POCTs (sufficient to test 0.1% of adults annually), diagnostic confirmation averted the most transmission when among symptomatic FSW (2.1% [0.6%–5.6%] of infections) or CFSW (2.2% [0.8%–5.3%]), and the most morbidity when among symptomatic pregnant women (3.5% [1.8%–7.2%] of QALY losses). Screening averted <1% of infections or QALY losses across populations. With unrestricted POCTs, screening had larger absolute impacts but lower per-test efficiency than diagnostic confirmation.ConclusionsOur modeling supports prioritizing diagnostic confirmation over screening, consistent with WHO guidance to strengthen etiologic diagnosis within syndromic care. Diagnostic testing among symptomatic pregnant women had the largest impact on mitigating gonorrhea-related morbidity.
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Journal articleArkell P, de Neri Machado F, Vicco A, et al., 2026,
Sero-catalytic and spatial modeling of dengue virus force of infection in Timor-Leste
, Nature Communications, ISSN: 2041-1723Dengue virus (DENV) infection causes significant morbidity and mortality across tropical and sub-tropical regions, including in Timor-Leste. In this study we present the results of a national, population-representative serological survey, used to determine the drivers of observed variations in DENV force-of-infection (FOI, i.e. the average annual per-capita risk of infection for a susceptible person) at high spatial resolution. Households were randomly selected from census data and occupants aged above one year were tested using the Panbio Indirect dengue IgG enzyme-linked immunosorbent assay between October 2021 and February 2023. Sero-catalytic models accounting for household effect were applied to estimate the DENV FOI in enumeration areas (EAs, roughly equivalent to neighbourhoods/villages). Spatial models were applied to the local FOI estimates to assess their associations with climate and environmental factors, and to predict the FOI across the rest of Timor-Leste. A total of 4780 individuals from 1755 households across 102 EAs participated. DENV seroprevalence and FOI estimates were highly spatially heterogeneous across Timor-Leste, ranging from 0.010 (95% Credible Interval (CrI): 0.005, 0.018) in EA 10104032 in Fatubossa, municipality Aileu, to 0.519 (0.295, 0.816) in EA 40403012 in Goulolo, municipality Bobonaro. Relative humidity was negatively associated with DENV FOI. The spatial models predicted highest DENV FOI along the Northern and Eastern coasts, with hotspots of transmission in Dili and Baucau cities. Findings will strengthen surveillance and guide the implementation of additional DENV control strategies such as Wolbachia-carrying mosquitoes (currently being deployed in some parts of Timor-Leste), or vaccination.
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Journal articleOkell L, Courlet P, Venezia F, et al., 2026,
Modelling the potential effect of cabamiquine-pyronaridine for chemoprevention against Plasmodium falciparum malaria
, Antimicrobial Agents and Chemotherapy, ISSN: 0066-4804Preventive treatment (chemoprevention) is a key intervention for reducing the burden of Plasmodium falciparum malaria in children. The impact of the current widely-used drug combination, sulphadoxine–pyrimethamine-amodiaquine (SP-AQ), is challenged by emerging drug resistance and adherence to multi-day dosing. Cabamiquine is a novel antimalarial with activity against liver and blood stage malaria parasites, administered as a single dose and under development in combination with pyronaridine. We used mathematical modelling to translate early phase 1 clinical results into estimates of its potential impact as malaria chemoprevention. Pharmacokinetic–pharmacodynamic (PKPD) models of cabamiquine and pyronaridine were combined, assuming Bliss independence, to estimate time-varying protection against infection. PKPD results were incorporated into an established individual-based malaria transmission model to evaluate the impact of seasonal malaria chemoprevention (SMC) across settings with differing transmission and seasonality. Cabamiquine–pyronaridine was predicted to provide protection of >95% for approximately four weeks, slightly outperforming SP-AQ even in children who fully adhere to SP-AQ treatment. Six weeks after treatment, cabamiquine-pyronaridine protection dropped for the regimens containing <200mg cabamiquine, but the combination could still outperform SP-AQ at doses ≥200mg. When deployed as SMC, longer duration of protection may enable fewer, more widely spaced treatment cycles while maintaining impact, improving projected cost-effectiveness. Cabamiquine–pyronaridine shows strong potential as a next-generation single-dose chemoprevention regimen, supporting continued clinical development and evaluation.
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Journal articleDrake KO, Franceschi VB, Nascimento FF, et al., 2026,
Untangling the effects of within-host and between-host natural selection in viruses with applications to evolution of HIV-1 co-receptor usage.
, J R Soc Interface, Vol: 23The fitness of a pathogen can be characterized at multiple levels corresponding to different life cycle stages. Typically, epidemiological studies for measuring pathogen fitness compute a single selection coefficient for pathogen variants that encompasses the entire lifecycle. However, evolution towards greater fitness within hosts can potentially compromise transmissibility. To address this, we develop a population-genetic model and software for the inference of multi-level selection coefficients. Our approach builds on population-genetic models previously applied to macro-evolution, whereby speciation and extinction rates are state-dependent. We relate this state dependence to within- and between-host selection. Evolution of beneficial phenotypes within hosts may occur rapidly (higher 'speciation'), but reduce rates of dispersal between hosts (higher 'extinction'). This new coalescent-based method improves on existing multi-state speciation and extinction models by accounting for highly nonlinear population dynamics and variable sampling through time, making it suitable for epidemiology. We characterize the accuracy of this method using birth-death and coalescent simulations before analysing a real dataset of HIV-1 genetic sequences. We quantified the multi-level relative fitness underlying HIV-1 'co-receptor switching'. In accordance with previous observations, we estimate that the relative transmissibility of X4-tropic virus is 9%, while within-host switching to X4-tropism is approximately 7-fold higher than switching to R5-tropism, indicating a strong within-host and between-host trade-off of co-receptor usage.
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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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