Infection, Genetics and Evolution

In the past decade, dengue fever has emerged as a major public health on Reunion Island in the Southwest Indian Ocean. During the 2018-2022 outbreak, an unusual increase in ocular complications was reported in some patients. To investigate a potential viral cause, we analysed 447 blood samples from hospitalized patients with and without ophthalmic symptoms. Genetic sequencing revealed the co-circulation of two strains of dengue virus serotype 1, both genetically linked to strains previously identified in Asia. Notably, all patients with ophthalmic symptoms were infected with viruses from a single cluster within genotype I, which harbored several unique mutations. These findings suggest that the rare ocular complications observed during this outbreak may be associated with specific viral cluster. Further laboratory studies are required to confirm this potential link.

IntroductionDengue has been prevalent in a regular fashion in Bangladesh and Chattogram for the last 6-7 years and is showing some serotype twisting. So, the objectives of the present study were to explore the burden of dengue serotypes in Chattogram. MethodsIn this study, 223 Dengue RT-PCR positive patients were evaluated for serotyping. Gender and age group, along with cycle threshold (CT) values, were also collected. Data after collection were compiled, analyzed, and plotted in Microsoft Excel and GraphPad Prism 10.4. Ethical clearance was taken to conduct the study. ResultsAmong 223 patients analyzed, males and females were found near equal (113 and 110). Middle-aged patients were more than the extremes of age. The mean {+/-} SD of age was 33.55 {+/-} 13.67 years. Regarding serotype distributions, isolated Den 1, Den 2 and Den 3 were found 1.3%, 73.1% and 6.7%, respectively. Concurrent infections with multiple serotypes were observed in several patients, most notably the Den 2 and Den 3 combination, which accounted for 14.3% (n=32) of the cases. Other co-infections were less frequent: the Den 1 and Den 2 pairing appeared in 3.6% (n=8) of the cohort, while triple-serotype infections (Den 1, 2, and 3) and Den 3/Den 4 pairings were rare, each occurring in only 0.4% of patients. Statistical analysis of CT values revealed no significant sex-based differences for Den 2 and Den 3. However, significant variations in CT values were observed when comparing Den 1 against both Den 2 and Den 3 (p < 0.05). In contrast, the difference between Den 2 and Den 3 Ct values remained statistically insignificant. ConclusionIn the year 2025, Dengue serotypes 2 and 3 were found to be the most prevalent, both in isolated or in combinations and Den 1 and Den 4 were found minimum. Exposure to multiple serotypes and twisting from one serotype to another might influence the dengue outcome in future, which needs further exploration.

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a serious condition induced by Dengue virus which becomes fatal if not detected early and treated appropriately. So objectives of the present study are to observe the different patterns of presentations, clinical features and outcome of HLH induced by Dengue. MethodsIn this observational study, 14 patients admitted and diagnosed HLH as per diagnostic criteria, were included after informed written consent. Study conducted in a period of six months from 01/07/2025 to 31/12/2025. All patients were followed up till discharge. After collection, all data were analyzed by Microsoft Excel 2010. Ethical clearance was taken from Ethical Review Board of the Medical College. ResultsAmong 14 cases, male were more affected then the female (78.6% VS 21.4%) and majority were in between 20 to 50 years age groups. Clinical data showed, all 14 cases had fever for >7 days, joint pain 3(21.4%), headache 11(78.6%), skin rashes 10(71.4%), retro-orbital pain 2(14.3%), vomiting 11(78.6%),bleeding 10(71.4%), cough 4(28.6%), loose motion 9(64.3%), abdominal pain 7(50.0%), anorexia 2(14.3%), Melaena 2(14.3%), jaundice 4(28.6%) and spleenomegaly 9(64.3%). One(7.1%) case had history of Hypertension. Laboratory data showed different level of Bi or Pancytopenia, high ferritin, high TG, low fibrinogen, raised liver enzymes and low sodium. Dengue RT PCR and serology results showed 8(42.9%) cases were both IG M and Ig G dengue antibody positive, 6 cases were RT PCR positive, 2 cases were IgM and another 4 cases were IgG positive. Outcome of patients revealed, among all 14 cases12(85.8%) patients improved uneventfully and 2 were shifted to ICU where one improved and one died. ConclusionDengue is prevailing for long time and different complications are evolving and HLH is a relatively newer incident among the dengue patients. Infection by different serotypes at different time or multiple dengue serotype infection may be related with HLH and it might be a future subject to explore and to evaluate.

BackgroundChildren who are HIV-exposed uninfected (HEU) show greater morbidity and mortality than HIV-unexposed children (HUU). In this study we investigate sex differences in growth, infection rates and antibody response among HEU and HUU infants. MethodsThe study enrolled 107 pregnant women with HIV and 103 pregnant women without HIV with follow-up of their infants from birth to 12 months of age. Study measures assessed included growth parameters, the prevalence of children with overt disease symptoms as reported by the mother, PCR-based assessment of infections (cytomegalovirus (CMV), respiratory syncytial virus (RSV), rhinovirus, influenza A & B, rotavirus and malaria) as well as antibody profile to CMV, RSV and enterovirus infections. ResultsCompared to male HUU, male HEU infants had lower Height-for-age-z-scores ({beta} -0.75; P=0.047) in mixed-effect model accounting for age. Additionally, they showed transiently lower Weight-for-age-z-scores at 3 months (1.07 vs 0.05, P=0.04), with higher risk of rhinorrhea (RR=2.29, P=0.02) and lower enterovirus titers at birth (P=0.0066). Female HEU showed transiently higher stunting at 6 months (0% vs 21%; P=0.01) and lower CMV viremia at 6 months, with elevated CMV antibody titers at 3 months (P=0.04) compared to female HUU. With prevalence ranging from 25%-61%, CMV and Rhinovirus infections were dominant in all groups. HEU and HUU exhibited similar antibody decay and acquisition patterns for CMV, RSV, and Enterovirus across both sexes. ConclusionHEU infants show transient sex-based differences in growth, infection and immune profiles raising the relevance for considering sex as a key parameter to assess infant health.

Influenza A(H3N2) subclade K virus was detected in Canada early in the 2025/26 influenza season, bearing an antigenic transition in the hemagglutinin (HA) glycoprotein. Analysis of 396 HA sequences from Canada showed antigenic divergence from 2025/26 influenza vaccine strains, consistent with partial mismatch. Phylodynamic analysis revealed sustained pre-vaccine transmission without clear post-vaccine expansion. Phylogenetic and phylogeographic analyses indicated interprovincial mixing within a highly connected metapopulation, highlighting the value of genomic surveillance for real-time epidemiologic inference and public health decision-making.

The measles outbreak in Jalisco, Mexico (January-February 2026) experienced vigorous sustained transmission with an exponential growth rate = 0.10 (95% CI: 0.10-0.11) per day, doubling time = 6.3 days (95% CI: 6.3-6.9), yielding the effective reproduction number at 3.34 (95% CI: 3.16-3.54), with elevated incidence among infants and young adults.

The emergence of vaccine covered serotypes causing invasive pneumococcal disease (IPD) is a serious concern worldwide. We investigated the unexpected rise of serotype 4 causing IPD primarily in non-vaccinated young adults after the COVID-19 pandemic that further spread to adults [&ge;] 65 years in recent years. For this purpose, we conducted a retrospective study of serotype 4 IPD cases (n=827) reported in Spain between 2009 and 2024. Whole-genome sequencing was performed to assess clonal lineages and phylogenetic relationships. Clinical and epidemiological data were compared between serotype 4 and all other serotypes causing IPD. Epidemiological and genomic analysis confirmed that the rise started as an abrupt cluster of IPD cases in Seville (Andalusia) in the year 2022 due to the ST15063 within GPSC12 lineage. This outbreak initially caused pneumonia episodes that required hospitalization in young individuals associated with high rates of tobacco smoking, alcohol, and inhaled drugs such as cannabis and cocaine, followed by a general distribution pattern throughout the country in the following years, affecting the elderly population. Experimental studies to evaluate potential underlying mechanisms confirmed that ST15063 serotype 4 strains displayed enhanced infection rates of human lung cells that significantly increased in the presence of cigarette smoke exposure and by influenza H3N2 virus coinfection, but not with H1N1. These findings highlight the need for targeted vaccination strategies not only against pneumococcus but also against respiratory viruses such as influenza, RSV and COVID-19 and demonstrate the importance of molecular surveillance to establish effective interventions in high-risk populations.

Background The Hump-nosed pit viper is a recognized but neglected medically significant species causing morbidity and mortality, with non-availability of a specific antivenom. There are many gaps in our understanding of its envenomation, including burden, clinical syndrome, complications and management. Methodology The study is a retrospective sub analysis of the Prospective VENOMS registry and hospital records of Hump Nosed Pit Viper envenomation from a single tertiary care center in coastal Karnataka from May 2018 to March 2024. Epidemiology, syndrome, complications and treatment strategies have been described. A linear mixed model analysis was conducted to study the effect of different therapeutic interventions in combating venom induced consumptive coagulopathy (VICC) Principal Findings Of 46 cases, 24 patients had VICC. The most common complications were AKI (21.7%), TMA (10.9%) and stroke (4.4%). Anaphylaxis to ASV (23.9%) was the most common therapeutic complication. Therapeutic interventions included ASV, administration of blood products and therapeutic plasma exchange along with supportive care. The linear mixed model revealed that administration of blood products (p=<0.001) had the strongest influence on the INR value, however, often resulting in a transient decline in INR value. ASV (p=0.052) caused only marginally significant change in INR. The role of TPE could not be statistically inferred, however, individual cases with severe VICC improved without complications, therefore it required further study but can be considered in critical cases. Conclusions/Significance This study describes the syndrome of hump-nosed pit viper envenomation, while highlighting the urgent need for a species-specific antivenom, recommends treatment strategies that can be used in the interim. Additionally, geo-spatial mapping draws attention to hotspots and the hypothesis that HNPV in coastal Karnataka have regionally distinct toxicity trends.

BackgroundCambodia has made great progress in reducing malaria transmission and is targeting elimination. While this progress is particularly marked for Plasmodium falciparum, the situation is different for Plasmodium vivax. It is generally assumed that symptomatic patients are effectively diagnosed using rapid diagnostic tests (RDTs), regardless of transmission intensity. MethodsIn 2023 we conducted a cross-sectional survey among 986 treatment-seeking patients in 6 provinces of Cambodia with varying reported malaria cases. Malaria RDT (Pf/Pv), microscopy and qPCR diagnostics of Plasmodium infections and species determination were performed. ResultsUsing qPCR, Plasmodium infections were diagnosed in 156 patients (15.8%, 95% CI: 13.7-18.2%) from all 6 provinces. Positivity rate was markedly different between health centers (HCs) and ranged between 57.2% and 0.5%. Parasitemia of infected patients was different between HCs and was lower in HCs with the lowest positivity rate compared to those with higher rates. The majority of Plasmodium infections (75%) were caused by P. vivax, however all human malaria species were identified as well as the simian parasite P. knowlesi. Overall sensitivity of RDTs to detect Plasmodium infections was 39.7% (95% CI: 28.9-51.6%) and specificity was 100% (95% CI: 99.5-100%). The proportion of RDT true positives was significantly different between HCs, and a tendency for higher false negative rates in low transmission areas compared to higher ones was observed. ConclusionWhile our results confirm that P. falciparum parasites are nearly eliminated from Cambodia, we show that current practice for diagnosis of Plasmodium infections among febrile patients is challenged, especially in very low transmission settings.

BackgroundHIV exposed infants (HEIs) are at a higher risk of infant mortality compared to their counterparts who are not HIV exposed. Early Infant Diagnosis (EID) is the critical first step in reducing HIV-related infant mortality through prompt identification of HIV-infected infants and subsequent initiation of antiretroviral therapy. However, there is limited information on Uptake of EID and factors associated with its timely completion among HIV exposed infants. Therefore, this study aimed at determining the uptake of EID and factors associated with its timely completion among HIV exposed infants at Lira Regional Referral Hospital (LRRH). MethodsThe study was a retrospective cohort of 252 HEIs born in the period of 1st January 2021 to 31st December 2021 chosen through consecutive sampling. Data abstraction tools were used to collect data on uptake of 1st, 2nd, 3rd DNA-PCR and final rapid test from mother-baby pair files and EID register. The main outcome was Uptake of EID and classified as timely and untimely according to the PMTCT guideline. Data was analyzed using descriptive statistics and generalized estimating equations (GEE) with poisson family, log link and unstructured correlation structure. ResultsThe timely uptake of EID among HIV exposed infants at 4-6 weeks, 9 months, 6 weeks after cessation of breastfeeding and 18 months were 80.1% (95% CI:74.5-84.7), 84.2% (95% CI:79.0-88.3), 3.7% (95% CI:2.0-7.0) and 78.8% (95% CI:73.2-83.6) respectively. Having cotrimoxazole given was associated with timely completion of EID [aRR=2.974, 95% CI (1.45-6.10)] ConclusionUptake of EID among HEIs was sub-optimal, below the Ministry of Healths 90% target. Timely cotrimoxazole administration was associated with EID completion,

Strengthening in-country sequencing capacity generated 28 Lassa virus genomes from human clinical cases, expanding our knowledge of Lassa fever in Guinea. Phylogeographic analysis revealed cross-border exchange between Liberia and the NZerekore region, and a Sierra Leone introduction into the Gueckedou area. Enhanced genomic surveillance is crucial to guide future public health actions.

IntroductionSequence-based typing (SBT) has been the standard molecular typing method for understanding Legionella pneumophila genetic relationships. However, genome-scale typing approaches, namely core-genome (cg) or whole-genome (wg) multilocus sequence typing (MLST), provide higher discriminatory power. To advance these capabilities, the Legionella International Typing (LIT) workgroup was established to develop, evaluate, and disseminate a novel cgMLST schema with enhanced wgMLST resolution for L. pneumophila investigations. MethodsWe created and populated the LIT cg/wgMLST schema with chewBBACA software using more than 9000 genome assemblies representative of the species diversity. We applied a multi-step refinement workflow, considering loci prevalence, diversity and presence/absence profile across the species tree, to select the final cg/wgMLST loci, and compared the performance of the LIT cgMLST schema with the previously used 1521-loci schema and assessed its congruence with SBT. ResultsThe LIT schema includes 2009 loci present in 98% of the dataset, forming the static cgMLST schema for routine genomic surveillance, plus 2698 accessory loci for an in-depth wgMLST analysis of clusters of interest. The LIT cgMLST schema maintains moderate agreement with SBT and presents high clustering congruence with the 1521-loci schema, while providing increased resolution. Analysis of epidemiologically related isolates using the LIT cgMLST schema for initial cluster delineation, followed by cluster-specific dynamic wgMLST analysis extending the cgMLST with accessory loci shared among isolates within each cluster, demonstrated increased confidence for outbreak investigation and source identification. ConclusionsThe LIT schema is expected to contribute to harmonizing genomic surveillance of Legionnaires disease at both local and global levels. The schema and associated resources for local implementation are available on Zenodo (https://doi.org/10.5281/zenodo.17871973).

IntroductionBuruli ulcer (BU) is a neglected tropical disease primarily affecting skin and sometimes bone. Standard therapy consists of rifampicin (RIF, once daily) plus clarithromycin (CLA, twice daily) over 8 weeks. Adding amoxicillin-clavulanate (AMX/CLV) may shorten treatment, but predicting treatment success before clinical trial implementation is challenging. AimsTo assess the probability of bacterial eradication following treatment with novel investigational BU regimens over different intervals using a mechanism-based modelling and simulation approach. MethodsIn vitro time-kill assays with RIF, CLA, and AMX/CLV alone and in combination were performed with a range of clinical isolates of Mycobacterium ulcerans. Bactericidal activity was characterized using a bacterial growth dynamics model, including an Emax function to describe the drug effect. Subsequently, clinical trial simulations were performed to evaluate drug disposition and skin penetration in a cohort of virtual subjects, taking into account interindividual variability in pharmacokinetics and pharmacodynamics (n=70/arm). Several regimens, including standard therapy and AMX/CLV-containing combinations with higher RIF doses were assessed. The probability of eradication at 4-8 weeks was assessed across strains with different susceptibility and assuming varying bacterial load at start of treatment. ResultsBeta-lactam containing combinations resulted in higher potency and maximum killing rates relative to the currently recommended regimens. Consequently, regimens containing AMX/CLV with higher RIF doses (20 mg/kg q.d. or 10 mg/kg b.i.d.) outperformed standard therapy, achieving 100% eradication within 4 weeks for baseline loads up to 1,000 CFU/mL across most isolates, except one from China. At higher loads (10,000 CFU/mL), 6 weeks were required. ConclusionsThe use of mechanism-based modelling and clinical trial simulations provides a robust translational framework for the evaluation of novel therapies for neglected diseases, such as BU. Irrespective of differences in bacterial susceptibility, adding AMX/CLV or using RIF-AMX/CLV dual therapy may reduce BU treatment from 8 to 4 weeks.

BackgroundDengue virus (DENV) appears to manipulate several cellular metabolic pathways to permit its replication and immune evasion in the host. Here, we employed high-resolution mass spectrometry (HR-MS) to investigate the serum metabolomic landscape of clinical DENV infection. MethodsSerum specimens from primary dengue (n=11), secondary dengue (n=9) samples, and healthy controls (n=10) were used for untargeted and targeted metabolomic quantification on a Waters Xevo G2-XS QTof Mass Spectrometer. The binding potential of selected ligands against DENV NS1, NS3, and NS5 was evaluated. Crystal structures were retrieved from Protein Data Bank and prepared using the Schrodingers protein preparation wizard. Based on findings from untargeted metabolomics, we validated certain bioactive lipid metabolites using commercial enzyme immunoassays. ResultsSerum metabolomic profiling revealed multiple distinct patterns for primary and secondary dengue versus controls. A consistent peak was observed at 2.06 mins across all samples. Certain bioactive lipid metabolites, such as, lysophospholipids, phosphatidylcholines, phosphatidylserines, and phosphatidylinositols, were detected alongside carnitine fragments, ceramides, diacylglycerols (DAGs), and bile acid conjugates in dengue. Molecular docking showed that DAG consistently exhibited strong binding to all the DENV proteins. Notably, LPC 22:6 showed a selectively strong affinity for NS5. Enzyme validation showed that in the secondary dengue cohort, LPC was significantly elevated than primary and healthy controls (p<0.05). ConclusionsOur investigations of the metabolomic landscaping, unveiled certain characteristic anabolic shift revealing metabolic vulnerabilities in clinical DENV infection, warranting investigations for use as potential biomarkers of inflammation in disease diagnosis and prognosis. Author summaryDengue is a mosquito-borne tropical viral infection that can range in severity from asymptomatic to life-threatening manifestations. Dengue virus (DENV) hijacks cellular machinery to sustain its survival in the host. Using high-resolution mass spectrometry (HR-MS), we studied the serum metabolomic imprints of dengue infection. The binding ability of selected metabolomic ligands against DENV NS1, NS3, and NS5 was studied. We found several distinct retention patterns for the dengue cases, with a consistent peak at 2.06 min across all samples. Further, several bioactive lipid metabolites were detected in the dengue infected cohort. Our molecular docking studies showed that diacylglycerol, a lipid metabolite exhibited strong binding with all the DENV proteins. We concluded that certain unique lipid metabolomic imprints exist in clinical DENV infection. The identified metabolomic signatures reveal significant potential for metabolomics to elucidate host-virus interactions, contributing to the advancement of antiviral and symptomatic treatments, along with prognostic or diagnostic biomarkers of dengue disease.

BackgroundElimination of Plasmodium vivax is challenging due to its dormant liver stages (hypnozoites), which can reactivate weeks or months after the primary infection, causing relapses and ongoing transmission of the parasite. Despite these challenges, P. vivax clinical case numbers have declined over the past decade in Cambodia. We used parasite genotyping to assess whether the decline in case numbers was reflected in parasite diversity and relatedness as a proxy to transmission. MethodsGenotyping was conducted on 182 symptomatic P. vivax isolates collected in eastern Cambodia in 2014, 2015, 2019 and 2023. A panel of 93 microhaplotype markers (vivaxGEN panel) was genotyped using Illumina sequencing. Population genetic measures were applied to determine infection diversity and relatedness (identity-by-descent (IBD)) each year. ResultsThe genetic results correlated well with clinical case numbers for the study years. The percentage of polyclonal infections was 5% in 2023 compared to 22-48% in earlier years (p<0.05) suggesting substantial reduction in superinfection and aligning with accelerated primaquine use in 2021. The cases in 2023 also had the highest percentage of infections with IBD >0.95 with one or more other infections (81.4% versus 8.9-10.8% in 2014-2019) indicative of inbreeding following population bottlenecking. In 2019, there was a spike in polyclonal infections (48%) and population diversity following local interruption of critical malaria control services. ConclusionsOur findings illustrate the potential of microhaplotype genotyping to inform on P. vivax transmission to assess intervention efficacy. In eastern Cambodia, the data provides evidence to support of widespread use of radical cure for patients with P. vivax malaria.

BackgroundChikungunya virus (CHIKV) is an Aedes transmitted arbovirus. Demographic changes coupled with the expanding footprint of the mosquito from climate change have the potential to shift the global burden from the virus. MethodsHere we use projections of human demography and Aedes mosquitoes distribution to estimate baseline and future burden from CHIKV under different climate change scenarios in 178 countries. We then estimate the potential of vaccines to mitigate the growing burden. FindingsWe found that under RCP2.6 (an optimistic climate change scenario), the global population at risk from CHIKV will increase by 30.2% to 5.4 billion individuals. We estimated a 35% increase in annual infections, 49% increase in cases and a 128% increase in deaths. A similar impact was found under the more pessimistic RCP8.5 climate change scenario. In Europe and the Americas, the growing presence of Aedes will drive the growing case burden, with increases in human population size being key elsewhere. Ageing populations will result in major increases in the number of CHIKV-related deaths in all continents outside Africa. Vaccinating 50% of individuals aged 12y+ with a vaccine providing 70% protection against disease and 40% protection against infection would avert 29% of cases and 31% of deaths. InterpretationThese findings highlight how climate change will expand the footprint of CHIKV circulation, while demographic changes will lead to substantially increased case burden in affected countries. Vaccines will be critical to minimising this changing global burden. FundingCEPI

Antibiotic resistance genes (ARGs) circulating among clinically relevant bacteria pose serious challenges to public health. Given the ancient and environmental bacterial origins of ARGs, a better understanding of the carriers of ARGs beyond the clinically most relevant species is urgently needed for more farsighted resistance monitoring and intervention measures. While the risks of emerging ARGs from environmental sources have been recognized, the identification bottlenecks stem from the limitations of shotgun metagenomic sequencing and bioinformatic methods. Here, we used long-read metagenomic sequencing and bacteria-specific methylation profiles to re-establish the links between established (well-described) or latent (absent in databases) ARGs and their bacterial and genetic contexts in wastewater. The base modification data produced by PacBio SMRT sequencing was analyzed by an in-house pipeline utilizing position weight matrices and UMAP visualizations. The approach was validated by a synthetic community with known bacterial composition. Our analysis revealed several previously unreported ARGs and their hosts with varying risk levels defined by their potential as emerging public health threats. For instance, Arcobacter, as one of the prevalent taxa in influent wastewater, was shown to carry a latent beta-lactamase gene with high predicted mobility potential. Of the other emerging beta-lactamases, we provided a real-life example of ongoing pdif module-mediated genetic reshuffling of the blaMCA gene occurring at least within Acinetobacter hosts in our samples. Additionally, we identified Simplicispira, Phycisphaerae, and environmental groups of the Bacteroidales order as the carriers of established, clinically important ARGs. These findings support the intermediate host roles of strictly environmental bacteria for the further dissemination of mobilized ARGs, highlighting the importance of exploring the uncultivated, or non-pathogenic, carriers of ARGs for the early detection of newly arising ARGs and mobility mechanisms.

BackgroundTalaromycosis, caused by the fungus Talaromyces marneffei, is a leading cause of HIV-associated death in Southeast Asia. Current culture-based diagnosis only identifies late-stage infection, limiting understanding of disease burden and disease spectrum. We evaluated the clinical performance of anti-Mp1p IgM and IgG enzyme immunoassays (EIA) for talaromycosis diagnosis. MethodsThis diagnostic study included 423 adults with advanced HIV disease and culture-confirmed talaromycosis as cases, and 206 non-talaromycosis individuals with and without HIV who have never traveled to Asia as controls. Anti-Mp1p IgM and IgG antibodies were measured using conventional double-sandwich EIA. Diagnostic performance was assessed using the healthy control group and the HIV control group separately. Assay cut-offs were based on both the Youden index generated from the receiver operating characteristic curves, and separately using a pre-defined specificity of 95%. ResultsAt the pre-defined 95% specificity, IgM had low to moderate accuracy of 62.3% and 87.9%, and a low sensitivity of 8.3% and 21.3%, when evaluated with healthy and HIV controls, respectively. IgG had similarly low accuracy of 52.2% and 78.4%, and a low sensitivity of 21.5% and 30.5%, when evaluated using healthy and HIV controls, respectively. Both IgM and IgG assays performed better in HIV controls than healthy controls. ConclusionsThe anti-Mp1p IgM and IgG EIAs show low utility for the diagnosis of acute talaromycosis. However, at the high specificity cut-off of 95%, the assays have utility in the detection of T. marneffei exposure at both individual and population levels, and. provides a foundation for future sero-epidemiological studies. IMPORTANCETalaromycosis, caused by the dimorphic fungus Talaromycosis marneffei endemic in Southeast Asia, southern China, and northeastern India, is an invasive fungal infection that causes over 25,000 cases and 6,000 deaths annually but remains neglected in the global health community. Current diagnosis requiring culture-based testing is too slow, often resulting in patient death before treatment can begin. This study presents the first large-scale clinical evaluation of antibody tests for talaromycosis. While the antibody tests showed limited sensitivity for diagnosing acute disease, the high specificity makes them useful in determining prior exposure to T. marneffei, providing a new tool for public health investigation of disease prevalence at a population level, and for clinicians to identify individuals at risk for disease reactivation who may benefit from prevention strategies. The research provides important groundwork for improving disease control efforts in regions where this neglected infection is endemic.

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, and South Africa. 476 (12%) "resisters" remained free of Mtb infection despite substantial exposure to highly infectious TB patients. GWAS identified a novel chromosome 13 locus (rs1295104126) associated with resistance across the multi-ancestry meta-analysis. Comparing Mtb-infection to all uninfected contacts, irrespective of exposure, yielded a different locus on chromosome 6 (rs28752534), near the HLA-II region. These findings demonstrate a common genetic basis for resistance to Mtb infection across multi-ancestral cohorts with potential to elucidate novel mechanisms of protection from Mtb infection.

BackgroundEvidence emerging from Sub-Saharan Africa indicates that people living with HIV (PLHIV) on long-term antiretroviral therapy (ART) especially when the viral load is undetectable, may falsely test negative for HIV on rapid diagnostic tests. This study assessed the prevalence and factors associated with false negative rapid diagnostic HIV tests among Patients on antiretroviral therapy, with undetectable viral load levels at Kisenyi Health Center IV, Kampala, Uganda. MethodsBetween October 2023 and February 2024, a cross-sectional study was conducted among 1,248 PLHIV on ART with undetectable viral loads at Kisenyi Health Center IV. Participants were recruited consecutively, and HIV re-testing was conducted in accordance with the national serial rapid testing algorithm. The algorithm includes a screening test (Determine HIV-1/2), a confirmatory test (Stat-Pak(R)), and a tie-breaker test (SD Bioline(R)). Enzyme-linked immunosorbent assay (ELISA) was used as the final confirmatory method. Data on socio-demographics and clinical characteristics was collected using an electronic data abstraction tool. Logistic regression analysis was done to assess for factors associated with false negative results, using STATA version 14.0. ResultsThe median age of the participants was 34.0 (interquartile range 29.0-42.5 years). The prevalence of false-negative rapid test results was 3.2% (40/1248; CI:2.20-4.2). CD4 (aOR 1.001, CI:1.001-1.003) and duration on ART (aOR 0.884, CI:0.801-0.978) were significantly associated with false-negative HIV results. ConclusionFalse-negative results were observed in approximately 3 in every 100 PLHIV on ART with an undetectable viral load. Serial rapid testing alone may be suboptimal for detecting HIV infection in this population. Further confirmatory testing in individuals who test negative on rapid testing is recommended.