PLoS Neglected Tropical Diseases[JOURNAL]
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200 papers
Correction: Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes: Relationship with Gene Expression in Patients with Scrub Typhus.
PLOS Neglected Tropical Diseases Editors
PLoS Negl Trop Dis · 2026 May · PMID 42081439 · Full text
[This corrects the article DOI: 10.1371/journal.pntd.0001028.].
[This corrects the article DOI: 10.1371/journal.pntd.0001028.].
"I called people to carry me to the latrine": Podoconiosis patients' access to water, sanitation, and hygiene in Butaro, Rwanda.
Ngowi NSN, Ufitinema P, Qambayot MA … +1 more , Schurer JM
PLoS Negl Trop Dis · 2026 Apr · PMID 42060689 · Full text
Podoconiosis is a preventable Neglected Tropical Disease (NTD) that results in significant lower limb swelling and chronic disability. Its management can be done at home by regularly washing feet with clean water and soa...
Podoconiosis is a preventable Neglected Tropical Disease (NTD) that results in significant lower limb swelling and chronic disability. Its management can be done at home by regularly washing feet with clean water and soap and using protective footwear. This study aimed to explore podoconiosis patients' experiences with access to water, sanitation, and hygiene (WASH) and to identify barriers and facilitators of home-based management (HBM). In this qualitative phenomenological study, participants were recruited following a screening conducted in Butaro Sector (Rwanda) to identify individuals with lower limb lymphedema. Randomly selected individuals underwent a clinical assessment, and only those confirmed to have podoconiosis were invited for an interview. In-depth interviews, supplemented by observation and photographs, were conducted. Transcripts were inductively coded using Dedoose (version 9.0.80) and analyzed through thematic analysis. Overall, 26 interviews were conducted across all five cells of Butaro Sector. Poverty and physical discomfort were major barriers in accessing WASH and HBM essentials, with many relying on family or neighbors for support. Shame, laughter, and discrimination from community members further hindered access to WASH. However, some participants found a financial solution in selling animal and household waste. Moreover, participants demonstrated little or no knowledge about podoconiosis which influenced their treatment choices. Many attributed the disease to witchcraft, blood infection, or God's will. Common care choices included traditional healers, self-care, or health centers. These findings demonstrate the need to integrate community education into podoconiosis management programs to address misconceptions and stigma while promoting income-generating activities to ensure consistent access to HBM essentials.
Maternal anemia in helminth-infected pregnant women: Dose-response with hookworm intensity and other risk factors in a Ugandan cross-sectional study.
Akena G, Ishimwe MPS, Nteziyaremye T … +3 more , Okello M, Kazigo AK, Hakizimana T
PLoS Negl Trop Dis · 2026 Apr · PMID 42060615 · Full text
BACKGROUND: Anemia remains a significant global public health challenge, affecting approximately 25% of the world's population and disproportionately impacting pregnant women, with an estimated 40% prevalence worldwide....
BACKGROUND: Anemia remains a significant global public health challenge, affecting approximately 25% of the world's population and disproportionately impacting pregnant women, with an estimated 40% prevalence worldwide. Intestinal helminth infections exacerbate this burden, with anemia prevalence reported as high as 55.6% among infected pregnant women compared to 16.4% in those uninfected. This study aimed to determine the burden of anemia and its determinants among pregnant women with helminthiasis attending antenatal care at tertiary Hospitals in western Uganda. Methods: A hospital-based cross-sectional study was conducted from 1st November 2022-1st March 2023, enrolling 420 pregnant women diagnosed with helminthiasis attending antenatal clinics. Data were collected via interviewer-administered questionnaires and laboratory records. Descriptive statistics and multivariable logistic regression analyses were performed using IBM SPSS version 23 to identify factors independently associated with anemia. Results: The prevalence of anemia was 26.2% (95% CI: 22.2-30.6), with 39.1% (95% CI: 30.5-48.4) mild, 35.5% (95% CI: 27.1-44.7) moderate, and 25.5% (95% CI: 18.2-34.3) severe cases. Multivariate analysis showed that moderate and heavy hookworm intensities increased anemia risk nearly two-fold (aOR = 1.90, 95% CI: 1.16-3.54; p = 0.028) and 2.4-fold (aOR = 2.40, 95% CI: 1.06-5.41; p = 0.041), respectively. Protective factors included being a student (aOR = 0.17, 95% CI: 0.05-0.63; p = 0.008), deworming ≥3 months prior (aOR = 0.11, 95% CI: 0.01-0.88; p = 0.038), using borehole water (aOR = 0.60, 95% CI: 0.36-1.00; p = 0.048), and gestational age 14-27 weeks (aOR = 0.57, 95% CI: 0.35-0.92; p = 0.020). Conclusions: Maternal anemia showed a clear dose-response with hookworm intensity, with risk increasing from moderate to heavy infection. Delayed deworming and unsafe water increased odds, whereas being a student and second-trimester gestation were protective. Timely anthelminthic treatment, improved water access, and strengthened antenatal care are critical in endemic settings.
A Global Perspective on the Emerging Threat of Zika and Dengue Co-infection.
Saha A, Anjum M, Labiba SJ … +3 more , Jaman M, Al Sayed A, Rahat RJ
PLoS Negl Trop Dis · 2026 Apr · PMID 42054339 · Full text
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Abundance of the vector Aedes aegypti in urban and rural areas in Managua, Nicaragua.
Suazo-Laguna H, Mojica-DÍaz J, Lopez MM … +4 more , Balmaseda A, Harris E, Coloma J, Juarez JG
PLoS Negl Trop Dis · 2026 Apr · PMID 42048403 · Full text
BACKGROUND: Ae. aegypti is the primary vector of dengue, chikungunya, Zika, and yellow fever viruses, traditionally associated with urban environments. However, its presence and abundance in rural settings remain underst...
BACKGROUND: Ae. aegypti is the primary vector of dengue, chikungunya, Zika, and yellow fever viruses, traditionally associated with urban environments. However, its presence and abundance in rural settings remain understudied. This study compares Ae. aegypti populations between rural and urban communities in Managua, Nicaragua, across different seasons over multiple years. METHODS: Entomological surveys were conducted in 500 randomly selected houses (250 rural, 250 urban) during the rainy and dry seasons of 2022 and 2023. Immature mosquitoes were collected from water-holding containers, and adult mosquitoes were sampled using aspirators. Stegomyia, pupal, and adult indices were calculated. Generalized linear mixed models (GLMM) and generalized additive mixed models (GAMM) were used to evaluate factors associated with pupal productivity and adult female abundance. RESULTS: Rural communities consistently exhibited higher immature and adult Ae. aegypti abundance than urban communities across most entomological indices. Rural households accounted for 74% of collected pupae and had 3.34 times higher pupal counts compared with urban households (95% CI: 2.17-5.15, p < 0.001). Barrels were the most productive container type in both settings, with uncovered barrels increasing pupal counts by 73% (IRR = 1.73, 95% CI: 1.63-1.82, p < 0.001). Total adult female abundance was significantly higher in rural communities compared to urban ones (IRR = 1.39, 95% CI = 1.13 - 1.72, p < 0.001). Rural households also exhibited 67% higher female rates per person than urban households (IRR = 1.67, 95% CI: 1.33-2.09). Nonlinear modeling revealed threshold-like dynamics between pupal counts and adult female abundance, with sharp increases in adult density once pupal abundance exceeded 50 pupae. CONCLUSION: We consistently observed that rural communities in Managua sustain significantly higher Ae. aegypti populations than urban ones. The identification of pupal thresholds linked to adult abundance highlights the importance of preventing containers from reaching high productivity levels. Overall, these findings challenge the perception of Ae. aegypti as predominantly urban and underscore the need for integrated rural-urban surveillance and context-specific vector control strategies.
Evaluation of long-term consequences among snakebite survivors in rural Kenya including validation of a functional limitations assessment tool.
Ngari C, Cattell-Ravdal S, Wasonga SA … +12 more , de Oliviera RC, Ngage TO, Dolinaj L, Asila LA, Steinhorst J, Mwethera PG, Kitwan L, Amuasi JH, Lalloo DG, Aglanu LM, Oluoch GO, Stienstra Y
PLoS Negl Trop Dis · 2026 Apr · PMID 42048402 · Full text
BACKGROUND: Snakebite envenoming, a neglected tropical disease, causes functional limitations and disability, yet the burden and optimal assessment methods remain unclear. We describe the frequency and severity of disabi...
BACKGROUND: Snakebite envenoming, a neglected tropical disease, causes functional limitations and disability, yet the burden and optimal assessment methods remain unclear. We describe the frequency and severity of disability and functional limitation among snakebite survivors in Kenya and validate a tool to evaluate interventions and guide rehabilitation. METHODS: Snakebite survivors whose incident occurred at least six months prior to the day of survey and healthy community controls in Kitui County, Kenya, were sampled and assessed using the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Scale (BUFLS). The BUFLS was tested for construct validity based on five a priori hypotheses and discriminant validity. RESULTS: In total, 140 snakebite survivors and 57 community controls were included. Of the 140 survivors, 87 (62.1%) were categorised as having more severe envenoming (SBE) based on reporting multiple clinical symptoms, while 53 (37.9%) were categorised as snakebite only (SB) having reported localised redness or no symptoms at all. Among survivors with more severe envenoming, 49% reported mild disabilities, compared to 32% in the snakebite survivors who presented with less severe symptoms of envenoming. The highest levels of disabilities were observed in the domains of mobility, participation, and life activities. In the control group, 12% reported mild disabilities, reflecting real-world background disability common in rural sub-Saharan African communities. The BUFLS met the predefined construct validity criteria and displayed good discrimination between snakebite survivors and controls. The activities mainly affected were those requiring gross motor skills within the BUFLS domains of food preparation, personal care, work and mobility. CONCLUSION: Snakebite survivors exhibit high rates of long-term disability and gross motor skill functional limitations, which must be considered when designing and evaluating public health interventions improving management and rehabilitation. The BUFLS provides a valid tool for assessing functional limitations in regions where cytotoxic envenoming predominates.
Correction: Socioeconomic drivers of human Brucellosis in Ningxia, China: A one health and spatiotemporal analysis for targeted intervention.
Zhang P, Ma X, Pan T … +4 more , Dang J, Pan D, Chen M, Liang P
PLoS Negl Trop Dis · 2026 Apr · PMID 42048326 · Full text
[This corrects the article DOI: 10.1371/journal.pntd.0014124.].
[This corrects the article DOI: 10.1371/journal.pntd.0014124.].
Correction: One health at the last mile: Multi-scale predictors of Schistosoma japonicum infection in southwest china across two decades of control.
PLOS Neglected Tropical Diseases Staff
PLoS Negl Trop Dis · 2026 Apr · PMID 42048317 · Full text
[This corrects the article DOI: 10.1371/journal.pntd.0013573.].
[This corrects the article DOI: 10.1371/journal.pntd.0013573.].
Functional single nucleotide polymorphisms in CACNA2D3 and other autophagy-related genes are associated with leprosy among Brazilians.
Espasandin I, Cardoso CC, Leal-Calvo T … +9 more , Mendes MA, Latini ACP, de Castro SHM, Leturiondo AL, Bezerra OCL, Pinheiro RO, Sales AM, Moraes MO, Kehdy FSG
PLoS Negl Trop Dis · 2026 Apr · PMID 42044188 · Full text
BACKGROUND: Autophagy is a crucial host defense mechanism against intracellular pathogens, including Mycobacterium leprae. Genetic variants in autophagy-related genes have been associated with susceptibility to leprosy,...
BACKGROUND: Autophagy is a crucial host defense mechanism against intracellular pathogens, including Mycobacterium leprae. Genetic variants in autophagy-related genes have been associated with susceptibility to leprosy, but their functional relevance remains incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigate the association of single nucleotide polymorphisms (SNPs) in three genes involved in autophagy, CACNA2D3, LRRK2 and IRGM. A total of 3,480 individuals from three Brazilian populations were included in a case-control design. We confirmed that the SNP rs1449325 in CACNA2D3 was associated with leprosy per se protection in the overdominant model (ORoverdTC = 0.70; p = 0.00443) in Rio de Janeiro, which was then replicated in samples from Manaus and Rondonópolis. Curiously, CC genotype of rs1449325 was associated with leprosy per se risk in the recessive model in Rio de Janeiro (ORrecCC = 1.51; p = 0.00476), Manaus (ORrecCC = 3.06; p = 1.44E-07) and Rondonópolis (ORrecCC = 1.50; p = 0.0240). Data from public eQTLs databases and gene expression analysis from whole blood samples suggested increasing CACNA2D3 expression levels with TT < CT < CC genotypes. In the literature, CACNA2D3 mRNA levels are positively correlated with calcium influx levels. Taken together, the genetic and expression data support the hypothesis that either low or high levels of calcium leads to M. leprae susceptibility. Associations of SNPs in LRRK2 and IRGM genes were also observed in the Rio de janeiro population, although not confirmed in replication cohorts. However, a protective effect of the LRRK2 haplotype C/G/G/T/G (rs7308720/rs7133914/rs10878434/rs3761863/rs7962370), apparently driven by rs3761863 T allele, was observed in Rio de Janeiro (ORhap = 0.44; p = 0.0121). This allele was associated with lower levels of LRRK2 mRNA expression in skin biopsy samples from leprosy patients, as well as in tibial nerve and fibroblast samples of healthy individuals from public databases. CONCLUSIONS/SIGNIFICANCE: Our results highlight a dual role of calcium signaling and autophagy gene regulation in leprosy susceptibility. Variants in CACNA2D3 and LRRK2 modulate host response to M. leprae infection and represent potential targets for improved therapeutic and preventive approaches.
Improved and customized dengue serodiagnostics through combined NS1/IgM testing and novel dual-cut-off IgG ELISA.
Saschenbrecker S, Muigg N, Klemens O … +1 more , Klemens JM
PLoS Negl Trop Dis · 2026 Apr · PMID 42044185 · Full text
BACKGROUND: Accurate diagnostics of dengue virus (DENV) infection are essential for patient management, outbreak control, and vaccine implementation. Serological testing plays a key role, especially when molecular assays...
BACKGROUND: Accurate diagnostics of dengue virus (DENV) infection are essential for patient management, outbreak control, and vaccine implementation. Serological testing plays a key role, especially when molecular assays are unavailable or viremia subsides; yet, cross-reactivity with other flaviviruses remains a challenge. This study examined the diagnostic accuracy of four Euroimmun ELISAs, including a newly developed dual-cut-off IgG ELISA. METHODS: The Dengue Virus NS1 ELISA, Anti-Dengue Virus Type 1-4 ELISA (IgM), Anti-Dengue Virus Type 1-4 ELISA (IgG; native antigen/gE-based), and the novel Anti-Dengue Virus NS1 ELISA 2.0 (IgG; recombinant NS1-based, with an alternative higher cut-off for flavivirus-endemic regions) were analyzed. Sensitivity was determined using sera from 22 Vietnamese patients with RT-PCR-confirmed DENV infection, collected during acute (t1, 1-6 dpo), early convalescent (t2, 4-9 dpo), and late convalescent (t3, 13-19 dpo) phases. Specificity was assessed with samples from 500 healthy German blood donors (HBD) and 40 patients each with West Nile virus (WNV) or Zika virus (ZIKV) infection. RESULTS: Sensitivities were 90.5%/70.0%/0% (t1/t2/t3) for NS1, 33.3%/85.0%/77.3% for IgM, 66.7%/100%/100% for IgG, and 33.3%/65.0%/100% vs. 19.1%/50.0%/100% for IgG 2.0 (standard vs. alternative cut-off). Combined NS1/IgM testing achieved 100% sensitivity in single acute-phase samples. Combined IgM and IgG 2.0 testing confirmed recent infection by IgM/IgG seroconversion or ≥4-fold IgG increase in 100% of paired samples. Overall specificity was 85.7% (HBD/WNV/ZIKV: 95.0%/50.0%/5.0%) for IgG, compared to 95.7% (98.2%/95.0%/65.0%) and 99.5% (99.8%/97.5%/97.5%) for IgG 2.0 using standard and alternative cut-offs, respectively. CONCLUSIONS: Euroimmun ELISAs support customized, highly accurate and versatile diagnostic strategies applicable to various dengue testing contexts. Combining NS1 and IgM ELISAs may offer a practical alternative to molecular assays during acute infection. The native antigen/gE-based IgG ELISA enables early sensitive IgG detection, although with limited specificity. With minimal cross-reactivity, the NS1-based dual-cut-off ELISA 2.0 (IgG) reliably captures DENV-specific IgG dynamics and enhances differentiation from other flaviviruses, which could provide an advantage in the use for convalescent-phase diagnostics, epidemiological surveillance, and pre-vaccination screening.
Standardized LDH-to-lymphocyte ratio improves early mortality prediction in severe fever with thrombocytopenia syndrome: A 15-day competing-risk bedside model.
Ma R, Wang J, Jiang Z … +6 more , Ding S, Zhang R, Xu Y, Wang R, Lin L, Chen Z
PLoS Negl Trop Dis · 2026 Apr · PMID 42044165 · Full text
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease associated with a high mortality risk. Early triage is critical, but risk prediction can be biased because many patients are ad...
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease associated with a high mortality risk. Early triage is critical, but risk prediction can be biased because many patients are admitted several days after symptom onset and some leave hospital early. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective single-center cohort study of 459 consecutively hospitalized patients with laboratory-confirmed SFTS. The primary analysis included 392 patients with ascertained in-hospital vital status. Of these, 387 patients with complete admission predictor data formed the derivation cohort for a prespecified 15-day prediction horizon after symptom onset, selected to capture the clinically relevant early high-risk phase of SFTS. Symptom onset was treated as time zero, hospital admission as delayed entry (left truncation), and discharge alive within 15 days as a competing event. We compared the admission-based standardized lactate dehydrogenase-to-lymphocyte ratio (sLLR) with other ratio biomarkers for prediction of 15-day in-hospital death. We then developed a prespecified five-predictor bedside model including age, neurological manifestations, prothrombin time, platelet count, and sLLR. Individualized 15-day death risk was estimated as CIF@15 from cause-specific Cox models. Model performance was assessed by discrimination, calibration, clinical utility, and prediction error, with bootstrap internal validation. Among 387 patients in the derivation cohort, 67 died within 15 days. Admission sLLR showed the best discrimination for 15-day mortality (area under the curve [AUC] 0.797, 95% confidence interval [CI] 0.738-0.855). Using an ROC-derived threshold (sLLR ≥ 2.79), the 15-day cumulative incidence of in-hospital death was 48.2% versus 10.3% in the lower-sLLR group (P < 0.001). The five-predictor model improved discrimination (AUC 0.867, 95% CI 0.824-0.910) compared with the corresponding model without sLLR (P = 0.009), showed good calibration, provided higher net benefit across clinically relevant thresholds, and achieved low prediction error (Brier score at day 15: 0.097). sLLR added prognostic information beyond standard admission variables. A simple five-factor model may provide a practical tool for real-world early risk stratification of hospitalized patients with SFTS, helping clinicians identify those at increased risk of death within 15 days after symptom onset, although external validation in independent multicenter cohorts is still needed.
Spatial representativeness matters for Climate-Driven Dengue Forecasting.
Khamthong K, Phramrung K
PLoS Negl Trop Dis · 2026 Apr · PMID 42044157 · Full text
Accurate forecasting of dengue incidence requires statistical models that explicitly accommodate overdispersion, temporal dependence, and delayed environmental forcing. We develop a Bayesian negative binomial dynamic reg...
Accurate forecasting of dengue incidence requires statistical models that explicitly accommodate overdispersion, temporal dependence, and delayed environmental forcing. We develop a Bayesian negative binomial dynamic regression model to generate monthly forecasts of dengue hemorrhagic fever (DHF) incidence in Kanchanaburi Province, Thailand. Transmission persistence is captured through lagged dengue incidence, while delayed climatic effects are represented using locally observed maximum temperature and relative humidity. Model adequacy and predictive performance are assessed using posterior predictive checks and leave-one-out cross-validation (LOO-CV). The negative binomial specification consistently outperforms Poisson-based alternatives under substantial overdispersion. Importantly, forecasting performance is not determined solely by the strength of marginal climate-dengue associations. Instead, it depends critically on the spatial representativeness of climatic inputs relative to the population at risk. Models informed by climatically representative observations yield more stable and robust out-of-sample forecasts, even when marginal associations are comparatively weaker. These findings underscore the distinction between explanatory association and predictive utility in climate-driven infectious disease models and provide practical guidance for the development of climate-informed dengue early warning systems in endemic settings.
The typhoid Mary legacy: Genomic epidemiology uncovers contemporary carriage dynamics across two decades of enteric fever surveillance in England and Wales.
Nisbet AM, Mohamed I, Verlander NQ … +6 more , Powell D, Waters EV, Nelson A, Kirkbride H, Langridge GC, Chattaway MA
PLoS Negl Trop Dis · 2026 Apr · PMID 42044148 · Full text
Modern knowledge regarding 'healthy bacterial carriers' traces back to the legacy of typhoid Mary, who unknowingly infected >50 people with enteric fever. Yet, the intricacies of typhoidal Salmonella carriage, inclusive...
Modern knowledge regarding 'healthy bacterial carriers' traces back to the legacy of typhoid Mary, who unknowingly infected >50 people with enteric fever. Yet, the intricacies of typhoidal Salmonella carriage, inclusive of Salmonella Typhi and Paratyphi A/B, remain largely unknown. Using data collected by the United Kingdom Health Security Agency's Salmonella reference laboratory and enhanced surveillance, we examined cases of enteric fever in England and Wales between 2004-2023, to track disease trends and identify carriers. In total, 8,297 cases of enteric fever were reported during the study period, including concerning rises post-pandemic that are not linked to emerging bacterial strains. 92% of cases reported travel, mainly to Southern Asia, and disease was most prevalent in more deprived communities. Around 2.7% of cases failed to clear after three weeks, constituting carriage, but only 0.1% persisted over a year. Odds of carriage were significantly increased in patients aged 81-90 (447%, p < 0.001) and in non-travel associated cases (64%, p = 0.025) while odds were significantly decreased in patients aged 21-30 (35%, p = 0.046) and in S. Paratyphi A infections (35%, p = 0.01). Isolates linked to carriage failed to cluster under specific lineages or genotypic clades, aside from a small S. Paratyphi B population potentially circulating locally in England. This study highlights increased prevalence of acute enteric fever infection in more deprived communities, and elevated risk of TS carriage in elderly patients and those without recent foreign travel. Our findings suggest host immune function likely plays a greater role in carriage risk than bacterial genotype. Given the lack of genetic signature for carriage, future research must focus on host factors influencing persistence, and repeat sampling post-antibiotic treatment should be implemented to identify 'modern day typhoid Marys' and reduce disease transmission.
A repetitive nucleotide insertion in the rplV gene is associated with in vitro resistance to azithromycin in Rickettsia typhi.
Phuklia W, Chowongkomon K, Padith K … +9 more , Phommasone K, Mayxay M, Richards AL, Batty EM, Robinson MT, Newton PN, White NJ, Day NPJ, Ashley EA
PLoS Negl Trop Dis · 2026 Apr · PMID 42044123 · Full text
BACKGROUND: Murine typhus, caused by Rickettsia typhi, is a treatable febrile illness in Laos, where azithromycin treatment failure has been reported. Antibiotic susceptibility testing for Rickettsia spp. is challenging...
BACKGROUND: Murine typhus, caused by Rickettsia typhi, is a treatable febrile illness in Laos, where azithromycin treatment failure has been reported. Antibiotic susceptibility testing for Rickettsia spp. is challenging due to absence of resistant strains. We aimed to induce an azithromycin-resistant in R. typhi and investigate its genetic basis. METHODOLOGY: R. typhi Wilmington was cultured in azithromycin-containing media (R. typhiAZM), starting at a concentration of 0.0019 mg/L and gradually increased to 0.0625 mg/L. Resistant populations were selected up to 0.125 mg/L. MICs were determined using plaque assay and qPCR, and DNA sequencing was performed for rplD (L4), rplV (L22), and 23S rRNA domain V. Protein modeling of azithromycin-binding sites was conducted, and strain stability was assessed over 24 passages without azithromycin (R. typhi AZM (-)). RESULTS: MICs for wild type (R. typhiWT) and R. typhiAZM were 2 mg/L versus >16 mg/L (plaque assay) and 0.25 mg/L versus 8 mg/L (qPCR). A 15-nucleotides insertion (5'-AAAGGAAGAGCAACT-3') was found in the rplV of R. typhiAZM, but not other isolates. Protein modeling suggested the insertion extends the L22 loop, potentially affecting azithromycin binding site within the ribosomal exit tunnel. R. typhiAZM reverted to wild type MIC and genotype by 24 passages without azithromycin. R. typhiAZM exhibited an 8 -fold higher MIC than R. typhiWT. CONCLUSION: Repetitive insertion in rplV was associated with azithromycin resistance and may interfere with drug binding. R. typhiAZM was unstable without selective pressure. This approach may help generate resistant strains for assay validation. The role of rplV mutations in azithromycin susceptibility warrants further investigation.
Clinical epidemiology of snakebite envenoming in hospitals 11 provinces of Yangtze River Basin and southern regions of China: A retrospective hospital-based analysis.
Yan S, Fu W, Yan Z … +13 more , Hu Y, Song X, Wang J, Hao W, He L, Chen Y, Diané M, Souaré IS, Guo W, Bin W, Ma Y, Han X, Lv C
PLoS Negl Trop Dis · 2026 Apr · PMID 42044109 · Full text
BACKGROUND: As the largest developing country, China works towards reducing mortality and disability from snakebite envenoming (SBE) by 50% before 2030, as epidemiological evidences are essential. METHODS: A cross-sectio...
BACKGROUND: As the largest developing country, China works towards reducing mortality and disability from snakebite envenoming (SBE) by 50% before 2030, as epidemiological evidences are essential. METHODS: A cross-sectional survey was conducted in 11 provinces in China using a multistage stratified cluster random sampling, and hospitalized snakebite victims with complete case histories from January 1, 2017, to December 31, 2021, were included. RESULTS: A total of 40,817 snakebite victims were enrolled in this study. The most common snake species were Agkistrodon halys (16.04%) and Trimeresurus stejnegeri (11.40%). However, 56.36% of the snake species remained unidentified. Furthermore, our results revealed that 60.36% of snakebite victims were males, 63.71% were older than 50 years, 59.70% were peasants, 11.14% experienced moderate envenomation on admission, and 0.64% had severe envenomation on admission. Ultimately, only 6.82% of the victims achieved complete healing, whereas 82.44% of snakebite victims demonstrated improvement in their condition upon discharge. Only 69.57% of snakebite victims received antivenom treatments. Furthermore, age, occupation, hospitalization duration, snake specie, site of bite, location, activity, envenomation on admission, clinical manifestation, and treatment significantly affected the discharge outcomes of snakebite victims. CONCLUSIONS: This study is the first large-sample investigation focusing on the epidemiological characteristics of SBE in China, addressing research gaps and filling the void in the relevant the World Health Organization data. The findings call for authorities and managers to strengthen partnerships, coordination, and resources, reduce SBE incidents, and ensure that victims receive fair, safe, and effective treatments.
Subarachnoid neurocysticercosis in a rural area of the Bolivian Chaco: A population-based survey through the use of a novel urine antigen assay.
Barbiero A, Micieli M, Castillo Y … +21 more , Espinoza Guerrero C, Di Maggio T, Petrini V, Spinicci M, Aguzzoli C, Ribelli B, Macchioni F, Gabrielli S, Menacho S, Strohmeyer M, Roselli M, Poma V, Cuellar R, Crespo E, Monasterio J, Cosmi F, Camargo WM, O'Neal S, Garcia HH, Nicoletti A, Bartoloni A
PLoS Negl Trop Dis · 2026 Apr · PMID 42044104 · Full text
Neurocysticercosis (NCC) is a major public health concern in low-middle-income countries. Subarachnoid NCC (SANCC), a less frequent form of NCC, is characterized by severe clinical evolution, high mortality and impactful...
Neurocysticercosis (NCC) is a major public health concern in low-middle-income countries. Subarachnoid NCC (SANCC), a less frequent form of NCC, is characterized by severe clinical evolution, high mortality and impactful neurological sequelae in survivors. However, due to a long pre-clinical period, early diagnosis and treatment of SANCC would likely improve the clinical course and reduce the occurrence of complications. To date, data on the prevalence of SANCC in endemic settings are scant, and there are no commercially available tests for SANCC screening in at-risk populations. Between October 2023 and May 2024, we conducted a population-based cross-sectional study aimed at implementing a non-invasive screening for SANCC in a low-resource area of the Plurinational State of Bolivia, using a home-made Ag-ELISA urine assay based on the monoclonal antibody set TsW5-TsW8. Questionnaires were also administered to the study population to assess the presence of behaviors and risk factors for active transmission of Taenia solium in the area. The study involved 1,232 subjects aged ≥10 years, 1,130 of whom delivered a urine sample. Among them, a median age of 27.4 years was observed, with 38.1% of subjects being males. Overall, 7 subjects with positive urine antigen test, confirmed on two different samples, were identified and underwent magnetic resonance imaging. The diagnosis of SANCC was radiologically confirmed in 4/7 subjects, for a prevalence of SANCC in the enrolled population of 3.54/1,000. The antigen assay showed a positive predictive value for SANCC of 57.1%. Risk factors for active transmission of T. solium, such as lack of access to adequate sanitation and the widespread practice of domestic pig breeding and sacrifice, were frequent. While further studies are needed to better define the diagnostic performance of the employed urine assay, this study confirms the presence of SANCC in the study area, consistent with evidence from similar endemic settings.
Look what you make my tissues do: The role of metalloproteinases and their inhibitors in Bothrops snakebites.
Ferreira Neves JC, Magalhães-Gama F, Ibiapina HNS … +10 more , Seixas KB, Barbosa ÊS, Malheiro A, Sachett JAG, Campi-Azevedo AC, Martins-Filho OA, Teixeira-Carvalho A, Sartim MA, Monteiro W, Costa AG
PLoS Negl Trop Dis · 2026 Apr · PMID 42030365 · Full text
BACKGROUND: Bothrops envenomation induces extensive local tissue destruction and a robust inflammatory response, largely driven by the host's endogenous molecular pathways. Among these, Matrix Metalloproteinases (MMPs),...
BACKGROUND: Bothrops envenomation induces extensive local tissue destruction and a robust inflammatory response, largely driven by the host's endogenous molecular pathways. Among these, Matrix Metalloproteinases (MMPs), zinc-dependent endopeptidases responsible for extracellular matrix (ECM) degradation, play a central role. The clinical severity of envenomation is therefore strongly influenced by the balance between MMPs and their specific inhibitors, the TIMPs. This study investigated the contribution of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 and TIMP-1, TIMP-2, TIMP-3, and TIMP-4 to the inflammatory response following Bothrops snakebites. METHODS AND FINDINGS: In this study, we prospectively enrolled 30 patients, classified them as Mild or Severe, and quantified circulating MMPs and TIMPs concentrations before and after antivenom administration using a multiplex Luminex platform. Early inflammatory markers and initial MMPs activation (MMP-2, MMP-7, MMP-9, MMP-10) did not differ significantly between groups. However, post-antivenom molecular trajectories diverged sharply. Mild cases exhibited effective enzymatic regulation, restoring the MMPs/TIMPs profile toward a state that favored ECM turnover and tissue repair. In contrast, Severe cases showed persistent dysregulation, with a sustained imbalance that hindered ECM reorganization and perpetuated damaging inflammatory pathways. CONCLUSION: These findings suggest that the regulation of MMP/TIMP balance following antivenom therapy may be associated with clinical evolution. Further studies are required to determine whether these molecular patterns can be validated as prognostic markers or therapeutic targets.
Global dispersal of Burkholderia pseudomallei and the evolving endemicity of melioidosis in the United States of America.
Currie BJ, Kaestli M, Meumann EM
PLoS Negl Trop Dis · 2026 Apr · PMID 42030350 · Full text
Melioidosis is a clinical disease in humans and animals following infection with the soil and water bacterium Burkholderia pseudomallei. The global footprint of melioidosis has been rapidly expanding, but it remains uncl...
Melioidosis is a clinical disease in humans and animals following infection with the soil and water bacterium Burkholderia pseudomallei. The global footprint of melioidosis has been rapidly expanding, but it remains unclear how much this represents unmasking of longstanding but previously unrecognised presence of B. pseudomallei and how much is from recent dispersal of B. pseudomallei. What is now clear is that the predicted establishment of B. pseudomallei in the southern United States has eventuated, with melioidosis endemic in Mississippi and likely to be endemic in Georgia and Texas. It is now time to move beyond concern of B. pseudomallei as a biothreat agent and to pivot towards addressing the gaps in public health responses to the enigmatic disease that it causes.
A functional crosstalk between circulating follicular helper 2 T cells and memory B cells drives anti-Plasmodium vivax antibodies.
Salsabila ZZ, Kochayoo P, Khunsri T … +6 more , Tianpothong P, Leepiyasakulchai C, Thawornpan P, Hafalla JCR, Adams JH, Chootong P
PLoS Negl Trop Dis · 2026 Apr · PMID 42030338 · Full text
BACKGROUND: The induction of long-term humoral immune responses depends upon the interaction between T follicular helper (Tfh) and B cells in germinal centers, leading to development of memory B cells (MBCs) and class-sw...
BACKGROUND: The induction of long-term humoral immune responses depends upon the interaction between T follicular helper (Tfh) and B cells in germinal centers, leading to development of memory B cells (MBCs) and class-switched antibodies. Expansion and activation of circulating Tfh2 (cTfh2) cells were detected in both vivax and falciparum malaria subjects. However, how these cells help B cells generate anti-malarial immunity is still unclear. Here, we assessed the breadth and competency of antibody responses from P. vivax subjects and related them to the frequency and activation status of cTfh2 subset. We also demonstrated the ability of P. vivax antigen to trigger cTfh2 cell activation and the function of cTfh2 cells to help MBCs secrete antibodies. METHODOLOGY/PRINCIPAL FINDINGS: Of 40 subjects with acute P. vivax malaria, 23 were seropositive for anti-PvDBPII antibodies (High and Low responders). Three High Responders (HRs) produced inhibitory antibodies against PvDBPII-human erythrocyte binding. An expansion of cTfh2 cells was detected in seropositive subjects. While their frequency did not differ significantly between High and Low Responders (LRs), the expression of co-stimulatory molecule ICOS in cTfh2 cells was higher in HRs. Activation of cTfh2 cells was specifically stimulated by PvDBPII antigen. In cTfh2-MBC co-cultures, proliferation and activation of cTfh2 cells were detected after receiving signal from MBCs. These activated cTfh2 cells then promoted MBC differentiation into antibody secreting cells (ASCs) which secreted anti-PvDBPII IgG. A decrease in cTfh2 cell activation was observed upon the addition of IFN-γ to the co-cultures. Importantly, cTfh2 cells played a role in producing anti-malarial specific antibodies. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that activation of cTfh2 cells, marked by the upregulation of ICOS molecules, was notably observed in subjects who produced high titers of anti-PvDBPII antibodies in response to P. vivax infection. This was also seen in a few subjects who produced high levels of antibody with inhibitory function. The PvDBPII antigen specifically stimulated cTfh2 cell proliferation and activation. Additionally, interactions between cTfh2 cells and MBCs promoted both cTfh2 activation and anti-PvDBPII antibody secretion.
Post-chikungunya chronic arthralgia in Burkina Faso: Frequency and associated factors.
Kaboré F, Savadogo WJE, Bayala YLT … +6 more , Sompougdou C, Sougué C, Ouedraogo A, Zongo YE, Zabsonré/Tiendrébeogo WJS, Ouédraogo DD
PLoS Negl Trop Dis · 2026 Apr · PMID 42030337 · Full text
INTRODUCTION: Chikungunya is an arboviral disease characterized by acute osteoarticular manifestations with a risk of progression to chronicity. African data on post-chikungunya chronic arthralgia are scarce. This study...
INTRODUCTION: Chikungunya is an arboviral disease characterized by acute osteoarticular manifestations with a risk of progression to chronicity. African data on post-chikungunya chronic arthralgia are scarce. This study aimed to identify factors associated with post-chikungunya chronic arthralgia in Burkina Faso. PATIENTS AND METHODS: This was a descriptive and analytical cross-sectional study with ambispective data collection, conducted from April 22 to December 28, 2024, at the Medical Center of Pouytenga. All patients aged 16 years and older with RT-PCR- confirmed chikungunya virus infection were included. The evaluation comprised an initial clinical phase and telephone follow-up at 6 months of evolution. RESULTS: We enrolled 174 patients, of whom 111 met the inclusion criteria. The mean age was 31.18 years ± 11.27 years with a female predominance of 66.67% (n = 74). Initial osteoarticular manifestations affected 92.79% of patients (n = 103), predominantly inflammatory arthralgia in 92.23% (n = 95) and symmetric polyarticular involvement in 73.79% (n = 76). At 6 months of evolution, 28.16% (n = 29) of patients had post-chikungunya chronic arthralgia, with persistence in the ankles in 65.52% of cases (n = 19). Multivariate analysis identified two significantly associated risk factors for chronic arthralgia were age greater than 31 years (OR = 6.22; 95% CI [2.35-16.47]; p < 0.001) and dengue coinfection (OR = 18.67; 95% CI [1.74-199.70]; p = 0.016]; p = 0.024). CONCLUSION: Our study found that 28.16% of patients develop post-chikungunya chronic arthralgia at 6 months post infection. Age above 31 years was demonstrated to be a significant predictor of disease chronicity, while the potential role of dengue co-infection, observed in only 4 patients with wide confidence intervals, requires further investigation.
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