PLoS Neglected Tropical Diseases最新文献

Background: The 20-minute whole blood clotting test (20WBCT) is widely used in patients with viper envenomation in resource-limited settings. The unclotted result guides the need for antivenom administration. Confusion has arisen on how to interpret "partially clotted" for the test due to a paucity of data. This study's primary aim was to evaluate the association between fibrinogen concentrations (FC) and states of clotting from the 20WBCT in green pit viper (GPV) envenomation.

Methods: Patients aged ≥18 years who presented to our hospital with GPV bites were enrolled between September 2022 and November 2023. All 20WBCT were done by laboratory technicians and the results were video recorded. Corresponding blood samples were quantified for FC. Two investigators, blinded to clinical/laboratory data, interpreted clotting results from recordings. A third investigator resolved conflicts.

Results: Thirty-nine patients contributed 188 blood samples. 20WBCT results were categorized as completely clotted, partially clotted (subdivided into mostly or minimally clotted), or unclotted, with median FC of 259.1, 223.5, 226.1, and 48.7 mg/dL, respectively. FC in the unclotted group were significantly lower than those in the other groups (completely: p = 0.001; mostly: p < 0.001; minimally: p = 0.002), with no differences among the completely clotted and two subgroups of the partially clotted. The unclotted 20WBCT had 28.6% sensitivity and 99.4% specificity for detecting FC < 100 mg/dL. Further analysis found that a FC < 70 mg/dL best predicted the unclotted result (the area under the receiver operating characteristic curve was 0.99 (0.99-1.0) and the accuracy was 98.9%).

Conclusions: Compared with the partially clotted samples (either mostly or minimally clotted), FC were significantly lower in the unclotted, but similar to the completely clotted samples. The partially clotted samples should be interpreted as completely clotted.

Objective: This study aimed to investigate the spatiotemporal heterogeneity of human brucellosis and quantify the exposure-lag-response relationships of key socioeconomic and livestock production drivers in Ningxia, China, from 2007 to 2022. The goal was to generate evidence for developing targeted, integrated interventions in this high-burden pastoral region.

Methods: We conducted a retrospective ecological study integrating human brucellosis surveillance data with county-level socioeconomic and livestock production statistics. A multi-analytic framework was employed: Joinpoint regression analyzed long-term trends; spatiotemporal scan statistics identified high-risk clusters; GeoDetector quantified the explanatory power of potential drivers on spatial heterogeneity; and Distributed Lag Nonlinear Models (DLNMs) were constructed to assess the nonlinear and lagged effects of significant drivers on monthly incidence.

Results: The human brucellosis incidence rate in Ningxia increased 167-fold, from 0.52 to 86.83 per 100,000 population between 2007 and 2022. Spatiotemporal analysis revealed a persistent high-risk cluster (Relative Risk, RR = 4.22, P < 0.001) in 11 eastern counties. GeoDetector identified livestock-related factors as primary spatial drivers, with sheep inventory (q = 0.96) and cattle inventory (q = 0.92) showing the highest explanatory power. DLNM results indicated a significant 3-year lagged risk associated with low cattle stocking levels (RR = 2.75), while sheep stocking exhibited a complex, non-linear U-shaped lag effect. In contrast, higher regional Gross Domestic Product (GDP) was associated with an immediate lower risk (RR = 0.81).

Conclusion: The brucellosis epidemic in Ningxia is characterized by intense spatial clustering and is associated with distinct, lagged effects of livestock production structures coupled with immediate economic influences. The findings underscore that livestock production metrics can serve as effective proxies for risk mapping even in the absence of direct animal infection data. Our study highlights the necessity for a dual-strategy intervention: implementing risk-based veterinary public health measures in high-incidence clusters while leveraging economic development to strengthen long-term prevention and control capacities.

The transmission dynamics of Trypanosoma cruzi in natural environments exhibit considerable variation at the micro-locality scale. However, the specific biotic and abiotic factors driving this heterogeneity remain largely unidentified. The Atlantic Forest of the state of Espírito Santo (ES) presents a unique transmission network of T. cruzi, in which Triatoma vitticeps represents the absolute majority among existing triatomines, with high infection rates and diversity of genotypes, frequently invading homes. No infection was found in peridomestic mammals. This study aimed to elucidate the spatial and environmental distribution patterns of T. vitticeps and its infection by T. cruzi DTUs throughout Espírito Santo, quantifying the influence of abiotic variables on both vector occurrence and infection dynamics. Species Distribution Modeling (SDM) of T. cruzi genotypes in T. vitticeps collected in the Atlantic Forest of Espírito Santo was performed using the ModleR package, in the R programming language, with climate and landscape variables (~1km²) selected by Spearman's correlation [-0.7 ≤ ρ ≤ 0.7]. True Skill Statistic (≥ 0.7) was used to evaluate model performance. Decision tree to classify T. vitticeps infection by T. cruzi was created using machine learning algorithms in WEKA 3.8.6 software. The SDMs of T. vitticeps and its infection demonstrated: i. Central and South mesoregions presented better environmental conditions for their occurrence; ii. association with mountainous regions with high altitudes, humid and superhumid, with vegetation density and vigor and high values of topographic diversity; iii. Schoener similarity suggests Z3 is mixed, dominated by TcIV and TcIII in Central-South, with TcIII influence Northwest and North Coast; iv. Infection was explained by wind speed, mammal richness, and temperature, with the decision tree identifying 84% of positives and 29% of negatives. T. vitticeps may originate in high-altitude regions and disperse via wind to lowlands, promoting domiciliary invasion and supporting previously hypothesized long-distance transmission of T. cruzi.

Background: We aimed to establish an external quality assessment (EQA) programme for the yaws eradication campaign that would meet the needs of reference and district-level laboratories in low- and middle-income countries.

Methodology/principal findings: We designed proficiency testing items (PTIs) using a plasmid containing gene target sequences for Treponema pallidum (TP) and Haemophilus ducreyi (HD). The storage stability of the plasmids under different environmental conditions was then tested. A proficiency testing panel of seven swabs loaded with different concentrations of plasmids in different combinations, as well as human HEK293 cells to simulate the sample background, was prepared and sent to participating reference (RL) and district (DL) laboratories in Ghana, Côte d'Ivoire and Cameroon followed by three rounds of blinded proficiency testing. We tested quantitative real-time PCR (qPCR) performance of reference laboratories and loop-mediated isothermal amplification (LAMP) performance of district laboratories and retested 20% of human field samples at the PTI provider's laboratory to further assess qPCR quality.

Findings: PTIs proved to be stable in dry conditions with no significant loss of copy number. Participating laboratories achieved qPCR results with a concordance of 95.0-100.0% (97.7% ± 5.2% (mean±standard deviation ((SD)) with the provider and a concordance of 76.0-100.0% (TP: 90.3 ± 13.7% and HD: 78.5 ± 7.5% (mean±SD)) for LAMP results, with inconsistencies, particularly in the detection of low HD plasmid DNA levels combined with high TP plasmid copies. Retesting of field samples resulted in 100% correct TP and HD sample identification by the African reference laboratories.

Conclusions/significance: We have developed a functional plasmid-based EQA programme specifically designed to meet the needs of resource-poor settings in the tropics. The programme is suitable as a blueprint for other disease programmes.

Background: Cutaneous leishmaniasis (CL) is a vector-borne, neglected tropical disease of the skin. It is a public health problem in Ethiopia, associated with reduced health-related quality of life (HRQoL). The Cutaneous Leishmaniasis Impact Questionnaire (CLIQ), a CL-specific measurement, was developed and validated in Brazil. This study aimed to translate, culturally adapt, and validate the CLIQ in Amharic.

Methods: Translation, cultural adaptation, and pilot-testing of an Amharic version of the CLIQ were performed, involving a group of experts and affected individuals. The translated Amharic version of the CLIQ was administered to adults with confirmed active CL between February and September 2023. The Amharic version of the CLIQ was evaluated using Cronbach's α, inter-rater reliability, and assessments of face, content, construct, and criterion validity.

Results: The translated and culturally modified Amharic version of the CLIQ was administered to 250 adults with CL. Of these, 158 (63.2%) participants had localized CL, and 114 (45.6%) were categorized as having moderately severe CL at enrolment. The Amharic version of the CLIQ had acceptable internal consistency (α = 0.913) and very good stability (ICC: 0.935 (95% C.I.: 0.908, 0.957)). It exhibited acceptable content validity with a modified kappa coefficient of 0.33 to 1.0. Confirmatory Factor Analysis revealed a two-cluster tool with factor loading of 0.33-0.83 for cluster 1 and 0.19 to 0.7 for cluster 2. A statistically significant difference was observed in median scores of severities (P < 0.001) and clinical phenotypes (P = 0.009). There was a significant reduction in CLIQ scores at Day 90 compared to Day 1 (P < 0.05). The clinically important difference of the CLIQ was calculated to be 12.

Conclusion: The Amharic version of the CLIQ is a reliable and valid instrument to measure the HRQoL associated with CL in adults in Ethiopia and can be used as a patient-reported outcome measure in the assessment of CL and its treatment.

Toxoplasma gondii (T. gondii) is an opportunistic protozoan parasite capable of infecting nearly all warm-blooded animals, including humans. Infection with T. gondii often triggers potent inflammatory responses that can lead to severe and potentially life-threatening tissue damage. Based on the mechanistic relationship between the gut microbiota and the host immune system, this study explores the metabolic regulatory network orchestrated by the gut microbiota during T. gondii infection. Using intraperitoneal infection models with both a wild-type ME49 strain and an attenuated ME49Δα-amy strain, we report for the first time a pivotal role for N-acetyl-D-glucosamine (GlcNAc) in modulating parasite-induced inflammation. Integrated analysis of 16S rRNA sequencing and metabolomic profiling revealed that GlcNAc, a gut microbiota-associated metabolite, was significantly enriched in mice infected with the ME49Δα-amy strain. Exogenous administration of GlcNAc to T. gondii-infected mice resulted in the marked downregulation of key pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-12, and a significant upregulation of the anti-inflammatory cytokines IL-10 and TGF-β. Moreover, GlcNAc treatment substantially reduced parasite burden and alleviated infection-associated weight loss. These findings not only elucidate the immunomodulatory function of microbiota-related metabolites in the context of zoonotic parasitic infections but also provide a novel theoretical foundation for the development of microbiota-targeted therapeutic strategies against toxoplasmosis. Collectively, our work offers important insights that may inform public health interventions aimed at controlling and preventing zoonotic parasitic diseases.

Objective: To investigate the clinical distinctions between scrub typhus meningitis and brucellar meningitis in children, and to identify potential biomarkers with early differential diagnostic value to support clinical decision-making.

Methods: A retrospective analysis was conducted on 13 pediatric patients diagnosed with brucellar meningitis admitted to Kunming Children's Hospital over the past decade. Thirteen cases of scrub typhus meningitis were selected as controls using an age- and sex-matching strategy. The clinical manifestations, laboratory findings, and cerebrospinal fluid (CSF) characteristics were compared between the two groups. Receiver operating characteristic (ROC) curve was employed to assess the diagnostic performance and clinical utility of key biomarkers.

Results: The pre-admission fever and duration of fever were significantly shorter in the scrub typhus meningitis group. Laboratory evaluation revealed that serum ferritin, procalcitonin (PCT), C-reactive protein (CRP), and creatinine (Cr) levels were markedly higher in the scrub typhus group compared with the brucellosis group. No statistically significant differences were observed in CSF biochemical parameters. ROC analysis demonstrated that ferritin (AUC = 0.870) and PCT (AUC = 0.846) exhibited the greatest diagnostic accuracy, followed by CRP (AUC = 0.814) and Cr (AUC = 0.799). All patients achieved complete clinical recovery following standardized treatment, with no recurrences or fatalities.

Conclusions: Although scrub typhus meningitis and brucellar meningitis share considerable clinical overlap in children, serum ferritin and PCT levels may represent potential diagnostic signals for early differential diagnosis, warranting validation in larger prospective cohorts. High Ferritin levels or PCT levels may provide preliminary clues toward scrub typhus meningitis. Early recognition and targeted antimicrobial therapy are associated with favorable prognostic outcomes.

Background: Chronic infection of Toxoplasma gondii (T. gondii) induces the anxiety-like behavior in hosts, which is closely linked to neuroinflammatory processes. Cis-aconite decarboxylase 1 (Acod1) is an enzyme that is responsible for itaconate production in Krebs Cycle. Emerging evidence highlights the Acod1/itaconate axis as a key regulatory node in macrophage immune-metabolic reprogramming. However, its role in infection-induced neurobehavioral alterations remains unclear. Here, we investigated the role of Acod1/itaconate axis in the anxiety induced by T. gondii chronic infection in mice.

Methods: To assess anxiety-like behaviors, we performed open field test and elevated plus maze test. Transcriptomic alterations and neuroinflammatory responses in the mouse amygdala were profiled via RNA sequencing, immunofluorescence staining, quantitative PCR (qPCR), and western blot. The functional role of the Acod1/itaconate axis was further investigated using Acod1-/- mice. Additionally, the therapeutic potential of dimethyl itaconate (DI), a cell-permeable itaconate derivative, was evaluated in chronically T. gondii-infected mice. The levels of indoleamine 2,3-dioxygenase (IDO), and serotonin (5-hydroxytryptamine, 5-HT) in serum were measured by enzyme-linked immunosorbent assay. Finally, DI's anti-inflammatory mechanism was identified in the microglial cell line BV-2 cells.

Results: Chronic T. gondii infection induced anxiety-like behaviors in mice and triggered the activation of Acod1/itaconate axis in the amygdala. Transcriptomic and histological analyses revealed upregulation of neuroinflammation-related genes, along with microglia activation. Genetic knockout of Acod1 induced the anxiety-like phenotypes, which were rescued by DI administration. Notably, DI treatment conferred both prophylactic and therapeutic benefits, effectively mitigating anxiety induced by infection. Mechanistically, DI suppressed T. gondii-induced M1 polarization in microglia to mitigate neuroinflammation via activating Nrf2 signaling. These events further reduced indoleamine IDO expression, leading to increased 5-HT levels and subsequent amelioration of anxiety-like behavior.

Conclusions: Our findings demonstrate that the Acod1/itaconate axis plays an important role in regulating anxiety-like behavior by modulating neuroinflammation during chronic T. gondii infection. These results reveal a promising immune-metabolic drug target for treating T. gondii-associated neuropsychiatric conditions.

This viewpoint draws lessons from the elimination of visceral leishmaniasis (VL) as a public health problem in the Southeast Asia region (SEAR) to inform efforts in East Africa (EA), now the global epicenter of Leishmania donovani transmission. VL is fatal and there is no licensed vaccine. Success in India relied on robust surveillance, rapid diagnosis, single-dose treatment, vector control, and multi-partner coordination. EA faces additional challenges than SEAR with multiple sand fly vectors, sensitive diagnostics and longer treatment regimens, high population mobility, and gaps in ecological and epidemiological knowledge. We highlight how strategies from South Asia could be adapted while acknowledging EA's unique ecological and health system complexities. These insights aim to guide sustainable VL control towards elimination of VL as a public health concern in the region.

This study investigated the diversity of trypanosomatids infecting small mammals in a fragmented forest landscape in southeastern Brazil, to gain insight into their role in transmission cycles and to assess potential public health risks. Eighteen small mammals were captured; seventeen were included in laboratory analyses: Didelphis albiventris (n = 4), Marmosops incanus (n = 4), and Nectomys squamipes (n = 9) were captured in the Mata da Tapera Municipal Natural Park, Minas Gerais State. To detect infection and assess host infectiousness, we used xenodiagnoses (Rhodnius neglectus and Lutzomyia longipalpis), 18S rRNA nested PCR, molecular typing, and parasitological culture. Leishmania infantum was identified in three individuals (two N. squamipes and one D. albiventris), L. braziliensis in one M. incanus, Trypanosoma cruzi DTU TcI in two D. albiventris, and T. lainsoni was detected in one D. albiventris and one N. squamipes. This integrated diagnostic strategy illustrates the value of combining parasitological, molecular, and experimental approaches for zoonotic surveillance at the wildlife-urban interface. Our findings document the occurrence of zoonotic trypanosomatids in a human-modified landscape and highlight potential transmission risks to humans and domestic animals, particularly in an area with active ecotourism, emphasizing the need for targeted surveillance within a One Health framework.