PLOS Neglected Tropical Diseases

Background: Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by parasites from the Leishmania donovani complex. VL is endemic in 54 countries, with East Africa (EA) accounting for [~]70% of the global burden. Therefore, there is a pressing need to prioritize VL research in EA. Transcriptomics analysis in rodent models and patients following treatment have shown that immune homeostasis is not restored by the end of treatment. However, comprehensive proteomic studies in VL remain scarce, and the few available studies were conducted outside EA. Methodology/Principal Findings: As a part of ImmStat@cure consortium, we used the Olink Reveal proximity extension assay to profile circulating proteins in VL patients from Ethiopia, Kenya and Sudan. By comparing patients at admission and 17 days after treatment with SSG-PM, we have identified a systemic Th1-cytotoxic inflammatory profile at admission, characterized by high abundance of IFN{gamma}, IL-1B, IL-6, and the granzymes A and B. Chemokines with high abundance included CXCL8/10/11, CCL3, CCL4, CCL8, CXCL8 and CCL20, consistent with the recruitment of monocytes, macrophages, T cells, and NK cells. There were also evidence of immune regulation/exhaustion, with high levels of PD1, PD-L2, IDO1 and KYNU. Although the immune profiles were similar at admission, country specific differences were observed after treatment. Kenyan patients exhibited a sustained inflammatory profile and signatures of myeloid recruitment, characterized by high levels of IL-1B, IL-6 , IL-12A, CXCL8, CCL2, CCL3, CCL4, CCL7 and CEBPB. Sudanese patients showed signatures associated with lymphocyte activation and immune regulation. Conclusions/Significance: These results highlight the complexity of the immune changes associated with VL, identifying both core conserved profiles at admission and country-specific profiles after treatment. The data provided here will provide a valuable resource for future comparative studies across more diverse different geographic regions, for linkage studies that assess the impact of parasite genotype on immune / metabolic response and for use during the evaluation of new therapies against VL.

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.

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.

Background Schistosomiasis is a parasitic disease caused by flatworms known as schistosomes. The infection cycle starts when people shed eggs through the stool or the urine. Larva infects freshwater snails to later infect humans through the skin during water based activities. Schistosomiasis is commonly associated with rural areas. In this study, we wanted to see if the schistosomiasis distribution is different in rural and urban areas, along with potential risk factors associated with schistosomiasis distribution. Methodology Fresh urine samples were collected from 1,699 school-aged children (5 - 15 years old) in urban and rural sites in the Kimpese health district. Prevalence of haematobium and mansoni schistosomiasis was determined using, respectively, the urine sedimentation and the Point-of-Care Circulating Cathodic Antigen test with a quantitative estimate of infection intensity obtained with an RDT-Reader. Collected risk factors were tested for association with schistosomiasis infection and its intensity. Results The overall prevalence of schistosomiasis found in urban and rural areas was 75% and 82% respectively, with higher prevalence of S. mansoni in rural schools, and higher S. haematobium prevalence in urban schools. The difference in total prevalence between schools in urban and rural areas was significant, X2 (1, N = 1699) = 13.03, p = .0003. S. mansoni intensity of infection was also higher in rural children (mean = 162 mV) compared to those in urban areas (mean = 76 mV) (p < 2e-16). Male gender, washing dishes in the river, and swimming were associated with schistosomiasis in urban areas. Age, Springs, and rivers were significant factors in rural sites. Age, river, and washing dishes in the river were factors associated with the intensity of infection. Conclusion Our results showed very high prevalence in both rural and urban areas, which implies that control programs should consider them with the same interest and also revise control strategies.

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.

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.

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.

Background: Visceral leishmaniasis (VL) is caused by Leishmania donovani and differentiates under the influence of biotope-specific gut bacteria in the Leishmania donovani-transmitting sand fly vector, Phlebotomus argentipes, which coexists with the Leishmania donovani-non-transmitting Sergentomyia species in the Indian subcontinent. Hypothesis: Sergentomyia are primarily herpetophilic. Interestingly, we identified a specific population of anthropophilic Sergentomyia babu babu, a proven naturally non-competent vector for transmitting Leishmania donovani, with high abundance and human-bite incidences in VL-non-endemic regions, compared with VL-endemic regions of India. Thus, the possibility of egesting gut bacteria to humans from VL-non-transmitting Sergentomyia and inducing downstream immune cascades remains undeniable. Innovation: We characterized gut bacteria from anthropophilic Sergentomyia babu babu in both VL-endemic and VL-non-endemic regions of India and found that a heat-inactivated formulation of Heyndrickxia sporothermodurans [NCBI Sequence Read Archive (SRA): PRJNA1403236], isolated from anthropophilic Sergentomyia babu babu from a VL-non-endemic region, prevented and cured L. donovani infection by inducing IL-23~Th17. More importantly, it also prevented the initial parasite establishment by inducing phagocytosis, ROS, and TNF- in circulatory Ly6G-CD11b+Ly6Chi monocytes. To the best of our knowledge, this is the first report confirming that the gut bacteria of VL-non-transmitting sand flies are critical and need to be investigated in depth for developing therapeutics and/or prophylactics against visceral leishmaniasis (VL), and suggests that possible bite-transfer of gut bacteria from disease-non-transmitting vectors to hosts may restrict disease pathogenicity. Further clinical trials are needed to warrant (Indian patent: 202511041013, April 28, 2025).

Tsetse flies are strictly found is sub-Saharan Africa where they are responsible for the transmission and maintenance of African trypanosomiases in humans (HAT) and animals (AAT). Vector control has been recognized as an essential tool to fight against these diseases. Nevertheless, it requires the best possible knowledge of the biology of the targeted population. Population genetics tools can prove very useful to obtain such information but require the use of polymorphic and reliable genetic markers. In this paper we present the development of microsatellite markers using a new high-throughput sequencing based technology (SSRseq). We applied it on two species of tsetse flies from three HAT foci and obtained more accurate results as compared to microsatellite loci developed with classic methods. We could indeed use 9 to 14 SSRseq loci without the several problems generally met with classic microsatellites, as all were located in autosomes, without short allele dominance or stuttering and very few null alleles. SSRseq loci appeared much more polymorphic in tsetse flies as compared to other species (fungi, trees, bees, or fishes), which suggested much higher effective population sizes, much higher mutation rates of the genome or both, suggesting high capacities for evolutionary adaptation. With the 9-14 loci kept, we confirmed the propensity of these flies to move almost freely in the whole zones investigated, and also highlighted the possible evolutionary response of one of the unkept loci regarding vector control devices used in these HAT foci, which will require further studies. We suggest for further population structure studies to use only loci with less than 1% missing data, which proved being a good and fast selection strategy to get the most reliable results.

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.

Chagas disease, caused by the parasite Trypanosoma cruzi, remains a major health concern, with effective immune control relying heavily on CD8+ T cells. However, the metabolic factors that regulate CD8+ T cell function during infection are not well understood. Acute T. cruzi infection induced metabolic remodeling in parasite-specific and effector CD8+ T cells, characterized by increased reliance on glycolysis, altered mitochondrial homeostasis, oxidative stress, and increased CD38 expression. Nicotinamide riboside (NR), an NAD+ precursor, improved mitochondrial function, reduced mitochondrial reactive oxygen species (mROS) and CD38 expression, decreased apoptosis, and enhanced CD8+ T cell effector responses in vitro and in infected mice. In vivo, NR treatment increased intracellular NAD+ levels in CD8+ T cells and improved parasite control during acute infection, reducing parasitemia and skeletal muscle parasite burden. Furthermore, transient NR supplementation was associated with persistent metabolic and functional changes in memory CD8+ T cells during chronic infection. These findings identify NAD+ metabolism as a modulator of CD8+ T cell metabolic fitness during T. cruzi infection and support its further investigation as a host-directed strategy to enhance parasite control.

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 [&le;]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.

Background: Preventive chemotherapy via single-dose benzimidazoles remains the core strategy for soil-transmitted helminth (STH) control. However, single-dose regimens often yield sub-optimal clearance against species such as Trichuris trichiura and hookworm. This systematic review and meta-analysis evaluated the comparative efficacy of repeated-dose versus standard single-dose albendazole or mebendazole regimens in paediatric populations. Methods: Registered prospectively on PROSPERO (CRD420261491616), a comprehensive search of PubMed, Embase, Cochrane Library, and Google Scholar identified clinical trials comparing repeated-dose against single-dose albendazole or mebendazole in paediatric STH infections. Primary outcomes were cure rate (CR) and egg reduction rate (ERR). Random-effects models synthesized pooled odds ratios (OR) and mean differences (MD). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Five randomized clinical trials (N = 1,718 participants) met the inclusion criteria. Overall, repeated dosing demonstrated significant superiority in cure rate (pooled OR = 4.47, 95% CI: 1.58-12.67; I{superscript 2} = 92%) and egg reduction rate (pooled MD = 0.17, 95% CI: 0.01-0.32; I{superscript 2} = 87%). Discussion: Repeated-dose benzimidazole regimens offer superior overall therapeutic efficacy compared to standard single-dose administration in children. However, this therapeutic advantage is drug-specific: multi-dose albendazole consistently enhances parasite clearance across trial settings, whereas multi-dose mebendazole exhibits variable performance and lacks conclusive superiority over single dosing. Conclusion: Transitioning to targeted, multi-dose albendazole protocols--rather than mebendazole--may serve as an effective public health intervention to eliminate residual parasite reservoirs in high-transmission endemic regions.

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).

Introduction: Acute gastroenteritis (AGE) is a global public health problem and a major cause of mortality in low- and lower-middle-income countries. Human bocavirus (HBoV) is among the viral agents associated with this condition. Therefore, investigating the presence of HBoV in cases of AGE in Salvador, Bahia, as well as its prevalence and circulating strains, is important. Objective: To investigate the occurrence of HBoV infection during an AGE outbreak in Salvador. Methods: A total of 178 samples were analyzed for HBoV using nested polymerase chain reaction (nested PCR), and the amplification products were visualized by agarose gel electrophoresis. HBoV was detected in 5.7% of the samples analyzed. Conclusion: This study contributes to the understanding of HBoV epidemiology as a secondary agent associated with acute gastroenteritis during a norovirus outbreak in Salvador. Continued investigation and identification of the etiological agents involved in outbreaks are essential for evaluating the causes of AGE. These findings also highlight the need for broader diagnostic approaches and the importance of phylogenetic analysis for monitoring and controlling viral infections.

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.

Importance: Coccidioidomycosis, also known as Valley fever, is a serious fungal disease caused by inhaling Coccidioides spores aerosolized from the soil. Despite rising public health concern, the distribution and incidence of coccidioidomycosis in the US remain poorly characterized as not all states are required to report cases, and case under-ascertainment is presumed to be high, particularly outside of the endemic region. Objective: To estimate monthly, county-level coccidioidomycosis incidence across the US while accounting for widespread under-ascertainment. Design, Setting, and Participants: We integrated multisource data, including human cases diagnosed in electronic health records, serological testing of dogs, and ecological and sociodemographic predictors, in a machine learning model estimating monthly, county-level coccidioidomycosis incidence. The model was trained on surveillance data from Arizona and California from 2013 to 2023, then applied to predict incidence in states across the contiguous US over the same time period. Main Outcomes and Measures: Incidence of coccidioidomycosis at the monthly county level. Results: The model predicted coccidioidomycosis incidence from 2013 to 2023 for 3,108 counties from all states in the contiguous US. The model identified 60 counties in non-reporting states where predicted incidence was [&ge;]2 cases per 100,000 population (considered moderate to high incidence). In states with mandatory reporting outside of Arizona and California, the model predicted county-level incidence rates that were 28% higher (95% bootstrap interval, 0.1%-69.8%) than those captured in national surveillance, equating to a total of 608 potentially missed cases per year (95% bootstrap interval, 340-964). Conclusions and Relevance: In this cross-sectional study, the model quantified case under-ascertainment for coccidioidomycosis relative to Arizona and California, and highlighted the potential for alternative data sources to fill in gaps in mandatory reporting. Estimating incidence while accounting for under-ascertainment and non-reporting may help efforts to improve public and physician awareness and to detect emergence in new regions.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging, tick-borne zoonosis caused by severe fever with thrombocytopenia syndrome virus (SFTSV) and is associated with high case-fatality rates in humans and cats. No vaccines or antiviral drugs are currently available for the prevention or treatment of feline SFTS. Because cats with SFTS often develop blood viral RNA loads exceeding those in severe human cases, we hypothesized that some naturally recovered cats develop strong neutralizing antibody responses and may serve as a potential source of antibody-rich serum for passive immunotherapy. We compared 80% plaque-reduction neutralization test (PRNT80) titers in convalescent sera from six human SFTS survivors and 14 cats that had recovered from naturally acquired SFTS, then evaluated the therapeutic efficacy of convalescent cat serum in SFTSV-infected, interferon receptor-deficient AG129 mice. Some SFTS-recovered cats showed high PRNT80 titers. Passive administration of high-titer convalescent cat serum early after infection protected SFTSV-infected mice. A single dose given at 2 or 3 days post-infection completely protected mice, whereas treatment at 4 days post-infection resulted in 40% survival. Administration on two consecutive days was associated with lower late-phase viremia in surviving mice. Sera from three independent SFTS-recovered cats improved survival, with greater effects observed for sera with higher neutralizing antibody titers. These findings indicate that some cats recovering from SFTS can develop high neutralizing antibody titers and their sera can exert therapeutic effects in an SFTSV-infected mouse model. These findings support further evaluation of passive immunotherapy as a treatment strategy for feline SFTS.

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.

Aedes albopictus (Skuse), the Asian tiger mosquito, is a highly competent arboviral vector whose range has expanded substantially across the United States over the past four decades. Despite predictive models placing Nebraska within the species' climatically suitable range, its establishment status in the state has remained poorly characterized. Here, we report results from a nine-year mosquito surveillance program (2017-2025) conducted across 44 Nebraska counties in collaboration with the Nebraska Department of Health and Human Services. Ae. albopictus was detected in five counties, with sustained, annually increasing populations documented in Richardson, Douglas, and Lancaster counties. Richardson County recorded continuous detections during 2017-2025, with proportional representation rising to 60.50% of collected mosquitoes by 2025. In Douglas and Lancaster counties, temporal advancement of first seasonal detection in 2024 and 2025 provide evidence consistent with successful overwintering rather than annual reintroduction. A cumulative degree-day model predicted adult emergence in mid-May across all county-year combinations, consistently preceding trap deployment by two to seven weeks and revealing a systematic early-season surveillance gap. Generalized linear mixed-effects models indicated that trap-level detection persistence, rather than urban location, was the primary predictor of yearly Ae. albopictus positivity, suggesting that current invasion dynamics are driven by focal source populations. These findings provide strong evidence for the establishment of Ae. albopictus in eastern Nebraska and highlight the need for earlier seasonal surveillance and standardized criteria to define establishment in northward-expanding vector populations.