PLoS Neglected Tropical Diseases最新文献

Rift Valley fever (RVF) is a concern in East and Central Africa, particularly following periods of heavy rainfall and flooding. However no human outbreaks have been reported in the Democratic Republic of the Congo (DRC). To assess whether this reflects a true absence of virus circulation, we estimated RVF seroprevalence in Goma (eastern DRC) and examined context-specific risk factors, comparing the findings with data from outbreak-prone countries. A two-year longitudinal study, across six health facilities in DRC, Kenya and Uganda, enrolled febrile subjects aged ≥10 years. Human serum samples were analyzed for RVF virus and anti-RVF antibodies. Demographic, behavioral, occupational and environmental factors were evaluated. 4,806 participants were enrolled: 1,370 (28.5%) DRC, 1,468 (30.6%) Kenya and 1,968 (40.9%) Uganda. 253 participants (5.3%) tested positive for RVF by serological and/or molecular assays: 19 (1.4%) DRC, 29 (2.0%) Kenya and 205 (10.4%) Uganda (p < 0.001). Only in Uganda, subjects tested positive for RVF virus by PCR (10 subjects, 0.5%). Occupations and activities involving contact with livestock, predominated in Kenya and Uganda, whereas handling of raw meat was most common in DRC. No specific occupations or activities were significantly associated with RVF exposure in DRC while several significant factors were identified for Kenya and Uganda. Multivariate analysis across all three countries showed that being from Uganda, male, over 20 years of age, employed as butcher or crop farmer and engaging in animal-related activities, were independently associated with RVF positivity, as was contact with sheep. Despite a prevailing sense that RVF transmission does not occur in DRC, we found a seroprevalence of 1.4%, comparable to Kenya where RVF is well documented. Further research targeting high-risk human and animal populations in DRC is warranted. A One Health approach will contribute to defining the ecology of local transmission of RVF in DRC.

Despite the availability of a highly effective vaccine, yellow fever virus (YFV) is still endemic in 47 countries globally. Although disease due to YFV was first recorded in 1635, factors contributing to its spread remain poorly understood today. Using archival data from the nineteenth century, we digitalised and mapped the 1857 yellow fever (YF) epidemic in Lisbon, Portugal, to understand how transmission dynamics and spatial and environmental characteristics led to disparities in health outcomes between sociodemographic groups. We modelled the basic and effective reproduction number (R0 and Rt) and found that transmission dynamics throughout this pre-vaccination era epidemic are consistent with prevailing estimates (R0 ≃ 5). Transmission peaked at the end of October 1857 when YF was declared an epidemic, then declined until January 1858. YFV killed 4.2% of the population with infection attack rates ranging between 10.3-13.5%. Out of the 34 parishes in urban Lisbon, our hotspot analysis identified 15 statistically significant high-risk parishes near the coastline. Our maps, combined with a digital terrain model, show that the highest number of deaths occurred within connected streets confined in low-elevation built-up areas with homes. We discuss the potential role of wind and temperature in aiding mosquito dispersal across Lisbon, which were believed as the main historical environmental drivers of YF. More people died at home than in hospitals, and although working-aged men accounted for most fatalities, the highest probability of death was found among women working at home. Our study highlights the role of human-environment interactions in shaping a historical YF epidemic in a pre-vaccination urban setting and enhances our understanding of modern-day transmission dynamics.

Human leukocyte antigen-G (HLA-G) is an immunomodulatory molecule known to play a crucial role in immune tolerance and regulation. In the context of human African trypanosomiasis (HAT), higher soluble HLA-G levels were detected in the plasma of confirmed cases, representing a serological marker of T. b. gambiense infection. As trypanosomes also invade extravascular tissues, especially the skin, this study explored the potential role of HLA-G in the dermal immune response during T. b. gambiense infection. Blood and skin samples from 50 seronegative individuals, 45 seropositive suspects and 36 confirmed HAT cases, collected between 2018 and 2022 in endemic foci of Guinea and Côte d'Ivoire, were analyzed. Plasmatic and dermal levels of HLA-G proteins were quantified by ELISA and immuno-histochemistry, respectively, and compared to the trypanosome detection results in the same samples. The implication of soluble HLA-G plasma level as a biomarker of T. b. gambiense infection was confirmed. In the dermis, HLA-G isoforms were expressed either with a granular distribution or with in diffuse halos. Granular patterns of dermal HLA-G were directly associated with the presence of trypanosomes in the dermis. The presence of diffuse halos was correlated to higher sHLA-G levels in the plasma. In total, this study provides the first evidence of the involvement of HLA-G in the extravascular immune response against parasites, especially in the skin. It shows that HLA-G distribution in the extravascular compartment also represents a biomarker of trypanosome infection.

Ticks are the second most important vector of infectious diseases, after mosquitoes, and can transmit several diseases of concern for both human and veterinary health. This study molecularly barcoded ticks collected from goats in Pakistan and screened for associated pathogens. From July 2023 to June 2024, examination of 253 goats (Capra hircus) in the 7th district of Khyber Pakhtunkhwa found 170 goats infested with 1,305 ticks, equating to a mean abundance of 5.15 ticks per goat. A phenol-chloroform technique was used to extract DNA and subsequently amplify the presence of pathogen DNA targeting 16S, 18S gltA, and ompA genes. Tick DNA was also amplified for the molecular confirmation of species using 12S rDNA partial sequence. All collected ticks were identified morphologically and molecularly as Haemaphysalis Punctata (519), Hyalomma anatolicum (380), Hae. sulcata (269), and Hy. excavatum (137), including 361 females, 323 males, 286 larvae and 198 nymphs. This study detected several tick-borne pathogens including Colpodella spp., Ehrlichia spp. and Rickettsia hoogstraalii, as well as detecting the bacteria Providencia rettgeri. Rickettsia hoogstraalii was found in Haemaphysalis punctata collected from Karak District. In contrast, Hy. excavatum from Banuu district were found to carry P. rettgeri. Hyalomma excavatum infesting goats in Buner, Chitral, and Hy. anatolicum form Kohistan, District tested positive only for Colpodella spp. whereas a single species of uncultured Ehrlichia spp. was found in Hae. sulcata collected from Mansehra, and Lakki Marawat district. This research's novel report of human pathogenic microbes detected in ticks has implications for livestock and human health, as well as the role ticks potentially play in zoonotic disease transmission in Pakistan.

Giardia lamblia (syn. intestinalis, duodenalis) is the causative agent of Giardiasis, a diarrheal disease of global medical importance, especially problematic in young children living in unhygienic, resource-constrained settings. Diagnostics of potential Giardia infections are generally done through classic light-microscopy stool examination. This is often insufficient, and ELISA-based fluorescence detection using costly proprietary reagents is employed. These reagents are often not affordable in contexts where they are needed the most, and this limits their use to resource-rich settings where Giardiasis is rarely problematic. To address these issues in medical equity while designing novel strategies to investigate the Giardia cyst wall, we report on the development and characterisation of alpaca derived single-domain antibodies, known as nanoantibodies, elicited against G. lamblia enriched cyst-wall preparations. We evaluated the effectiveness and binding capacity of twelve unique E. coli-produced recombinant nanoantibody sequences for Giardia cyst wall detection and provide proof of concept for the effectiveness and versatility of these protein domains.

Nigeria has made significant progress toward the elimination of onchocerciasis through mass drug administration (MDA) of ivermectin, with ten states recently declared eligible to stop treatment following WHO-recommended epidemiological and entomological assessments. However, reliable spatial prevalence estimates remain necessary to guide elimination strategies, particularly in areas with limited surveillance. We applied model-based geostatistical analysis using Monte Carlo Maximum Likelihood Estimation to assess the spatio-temporal distribution of onchocerciasis prevalence across Nigeria from 1989 to 2024. Climatic, hydrographic, socio-economic, and topographic variables were incorporated to predict prevalence in unsampled locations. Predicted prevalence declined substantially over time. During 1997-2000, 64.9% (24/37) of states had mean predicted prevalence between 10-30%, and 5.4% (2/37) exceeded 30%. By 2017-2020, 70.3% (26/37) of states were classified within the 0-2% category, increasing to 86.5% (32/37) in 2021-2024. Nevertheless, resurgence was observed in selected areas; for example, Taraba State showed an absolute increase of 44.1 percentage points between 2013-2016 and 2021-2024 (p = 0.013). High-prevalence clusters persisted along international and interstate borders, particularly in southern Nigeria. Model performance was strong (correlation between observed and predicted prevalence: 0.80-0.86; RMSE < 0.08). The estimated spatial correlation range increased from 31.93 km (95% CI: 31.92-31.94 km) in 1997-2000 to 180.20 km (95% CI: 180.20-180.20 km) in 2021-2024. Mean annual temperature, rainfall in the driest quarter, elevation, and river flow accumulation were significant predictors of prevalence. These findings underscore the need for complementary approaches such as predictive modelling to strengthen the field surveys in planning and surveillance of the disease. To sustain the progress toward onchocerciasis elimination in Nigeria, there is a need for adaptive, climate-informed strategies, intensified surveillance in high-risk areas, and enhanced coordination, particularly in cross-border and hard-to-reach communities.

Background: Snakebite prevention is often neglected despite snake envenoming being a major problem in the rural tropics. We aimed to describe the epidemiology of snakebites in rural Sri Lanka to identify potential focused preventative strategies.

Methods: The Anuradhapura Snakebite Cohort prospectively recruits snakebites admitted to the Teaching Hospital, Anuradhapura, in Sri Lanka. Epidemiological data on all snakebites from August 2013 to October 2014 and May 2017 to January 2023 were extracted.

Results: There were 4708 snakebites, and 2202 were authenticated by specimen identification or serum analysis using enzyme-linked immunosorbent assay [H. hypnale, 988 (44·6%), D. russelii, 737 (33·3%), B. caeruleus, 101 (4·6%), N. naja, 62 (2·8%)]. Median age was 42y (IQR:29-54y), and 3027 were male (64·6%). There were 1659 (37·5%) snakebites in domestic gardens, 1153 (26·0%) on farmland, and 870 (19·6%) indoors. 3642/4620 (78·8%) were lower-limb bites, mainly the foot (3273; 70·9%). 1435/4671 (30·7%) occurred between 6 and 9 pm. Increased numbers of bites were reported from September to February. Of 988 H. hypnale bites, 781 (82·1%) occurred outdoors, 493 (51·8%) on the foot, and 252 (26·2%) on the hand. 704 (73·0%) H. hypnale bites occurred at home, and on the hand while cleaning the surrounding environment and collecting firewood. Of 721 D. russelii bites, 643 (89·2%) occurred on the foot, 310 (43·0%) on farmland and 286 (39·7%) outdoors. Of the 101 B. caeruleus bites, 75 (74·3%) occurred at night, and sixty (60·6%) while victims slept. Of 62 N. naja bites, 53 (85·5%) occurred during the day and 37 (59·7%) outdoors.

Conclusion: We identified epidemiological findings that indicate possible avenues for prevention. Protective footwear would prevent outdoor bites, including 83% D. russelii bites and 52% H. hypnale bites. Long-handled tools would prevent H. hypnale bites to the hands, and safer sleeping environments would prevent B. caeruleus bites.

Echinococcus multilocularis (E. m) infection causes alveolar echinococcosis (AE), a serious zoonotic disease characterized by invasive larval growth in the liver. The parasite establishes a chronic infection, suggesting effective modulation of host immunity. Here, we investigated the role of the CCR8/CCL1 chemokine axis in shaping the hepatic immune microenvironment during E.m infection. In infected wild-type (WT) mice, chronic infection specifically activated the hepatic CCR8/CCL1 axis, which was associated with a marked accumulation of FOXP3+ regulatory T cells (Tregs). Notably, although CCR8+ T cells expanded numerically, their production of effector (IFN-γ, TNF-α, and perforin) was significantly impaired. In contrast, infected CCR8-knockout (KO) mice developed smaller hepatic lesions, exhibited a reduction in liver weight, and had significantly lower serum ALT levels. Mechanistically, CCR8 deficiency enhanced the effector functions of CD4+ and CD8+ T cells, skewing the immune response towards a Th1 phenotype, and partially reversed the immunosuppressive milieu. Our findings establish that the CCR8/CCL1 axis drives the formation of an immunosuppressive niche in the liver by recruiting both Tregs and functionally suppressed CCR8+ T cells, thereby facilitating parasite immune evasion. This study not only elucidates a pivotal mechanism of immune escape in AE but also identifies CCR8 as a promising novel immunotherapeutic target for this neglected tropical disease.

Background: West Nile Virus (WNV) is a zoonotic arbovirus maintained in a transmission cycle between Culex mosquitoes and birds, occasionally spilling over into humans. The impact of avian biodiversity on WNV circulation remains debated, with studies reporting both negative and positive correlations (dilution and amplification effects respectively) across different settings. In Europe, this relationship remains largely unexplored, particularly in regions with high WNV transmission, such as Emilia-Romagna in Northern Italy.

Methods: We explored the association between avian biodiversity and WNV circulation in Culex mosquitoes in Emilia-Romagna using 11 years (2013-2023) of entomological surveillance data paired with two avian data sources. We calculated avian biodiversity indices (Shannon's, Simpson's, and Chao2) from observation records from the Farmland Bird Index project and applied linear regression models to assess their relationship with WNV detection frequency. Moreover, we used Bayesian spatiotemporal regression models and gridded weekly avian abundance estimates from the eBird project to analyse the associations between avian species richness indices and WNV transmission risk quantified by vector index (VI) at 68 geolocated mosquito traps across the region.

Results: We observed consistent negative associations between WNV detection frequency in the Culex population and avian biodiversity indices, supporting the dilution effect hypothesis (DEH). We found that non-passerine species richness was negatively associated with VI while passerine species richness showed a positive association after adjusting for covariates and spatial random effects. These findings suggest that passerines may amplify WNV transmission, whereas the presence of non-passerine species is associated with reductions in WNV circulation.

Significance: This study provides the first empirical evidence supporting the DEH for WNV in Europe. These findings have important implications for biodiversity conservation and integrated public health surveillance activities across Europe.

Based on plague disaster and climate data from China between 1912 and 1949, this study comprehensively employed the Mann-Whitney U test, mutation test, and optimal parameter geographic detector to investigate the relationship between plague epidemic characteristics and climate change across different geographic regions. Findings reveal significant spatiotemporal divergence in plague epidemics between northern and southern China: Southern plague exhibits a clearly defined "high-amplitude stable decline" trend, while northern plague shows a slow downward trajectory amid intense fluctuations, lacking a significant linear trend. Moreover, all three plague hotspots highly overlap with natural reservoirs. This divergence stems from fundamentally different climate-driven mechanisms in the north and south, with interactive detection indicating that synergistic effects between dual factors generally outweigh single-factor impacts. Northern plague is jointly controlled by precipitation fluctuations and thermal variations, primarily driven by the interaction between annual precipitation and trends in annual mean high temperatures (q-value: 31.46%); In contrast, southern plague is more sensitive to warming transitions in the climate system, primarily governed by the synergistic effects of annual temperature difference variations and trends in low temperatures, precipitation, and mean temperature (q-values: 38.44%, 34.92%, and 34.77%). Spatio-temporal coupling analysis further reveals that climate abruptions act as temporal triggers for epidemic shifts: Northern plague exhibits delayed peaks 1-2 years after precipitation abruptions, while Southern plague frequency declines during high-temperature abruptions. Spatially, high-value zones of Northern annual high-temperature trends form ecological barriers segmenting adjacent hotspots, whereas Southern low-value zones of annual temperature difference trends correspond to plague hotspots. By elucidating historical variations in plague sensitivity to climate fluctuations, this study provides crucial historical evidence and reference for contemporary plague surveillance and public health risk assessment under climate change.