Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963-1·68) deaths globally, declining from 3·69 million (3·04-4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0-92·9) per 100 000 population to 16·4 (12·6-21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811-1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000-882 000) and 501 000 (373 000-648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0-21·5]), followed by norovirus (10·2% [2·4-17·0]) and Shigella spp (9·3% [5·4-15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5-48·5) for rotavirus, 24·0% (15·1-36·7) for Shigella spp, and 23·4% (13·7-34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290-49 000) and 18 800 (4650-44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. Gates Foundation.
Mosquito-borne diseases continue to pose major public health challenges, necessitating the development of environmentally safe biological control agents. Although several bacterial larvicides are currently used, novel gut-associated bacteria with high specificity and low non-target toxicity remain under-explored. This study (This is the first report demonstrating mosquito larvicidal activity of Alcaligenes faecalis against Culex quinquefasciatus larvae.) reports, for the first time, the mosquito larvicidal potential of Alcaligenes faecalis against Culex quinquefasciatus larvae. A bacterial (This is the first report demonstrating mosquito larvicidal activity of Alcaligenes faecalisagainst Culex quinquefasciatus larvae.) isolate, obtained from the midgut of naturally dead and moribund Cx. quinquefasciatus larvae, was identified as Alcaligenes faecalis strain BUMCn01 (GenBank accession: PX526002) based on morphological, biochemical, physiological, and 16S rRNA gene analyses. Larvicidal bioassays using A. faecalis strain BUMCn01 formulation were performed against all four larval instars. Bacterial localization and aggregation in the larval midgut following exposure to A. faecalis strain BUMCn01 were examined by scanning electron microscopy. Field efficacy was evaluated in sewage drains of different depths. Laboratory evaluations of the A. faecalis strain BUMCn01 formulation was also conducted on non-target aquatic organisms (Chironomus circumdatus larvae, Daphnia spp., Poecilia reticulata, and tadpoles of Bufo spp.). Furthermore, bacterial proteins were isolated and assessed for larvicidal efficacy against 3rd instar larvae, to identify the bacterial component responsible for the bioactivity. The isolate was identified as Alcaligenes faecalis strain BUMCn01 using a polyphasic approach including morphological, biochemical, physiological and 16S rRNA gene sequence analysis (GenBank accession: PX526002).The Alcaligenes faecalis BUMCn01 formulation resulted in clear dose-response relationship. 100% mortality was recorded in 1st instar larvae after 24 h and in 2nd and 3rd instars Cx. quinquefasciatus larvae after 48-72 h at 2.0 mg/mL. 24 h LC₅₀ values ranged from 395 µg/mL to 490 µg/mL across all larval instars, with 1st instar larvae being the most susceptible. Scanning electron microscopy revealed bacterial proliferation and dense aggregation witin the treated larval midgut, comparison with control indicating oral ingestion and possible gut mediated toxicity. Field trials demonstrated complete larval elimination within 7-9 days at an application rate of 100 ml/m2, with moderate residual activity. In non-target aquatic organisms, the A. faecalis BUMCn01 formulation exhibited no mortality in tadpoles of Bufo spp. and only mild effects on C. circumdatus, Daphnia spp. and guppy (P. reticulata). The isolated proteins were found to possess potent larvicidal activity (24 h LC50 of 491 µg/mL) against 3rd instar larvae. This study provides the first evidence that (The isolate was identified as Alcaligenes faecalis strain BUMCn01 using a polyphasic approach including morphological, biochemical, physiological, and 16S rRNA gene sequence analysis (GenBank accession: PX526002).) Alcaligenes faecalis strain BUMCn01 exhibits significant larvicidal activity against Culex quinquefasciatus. Bacterial proteins appear to be the primary toxic agent. The Alcaligenes faecalis BUMCn01 formulation showed significant efficacy in laboratory and field trials with minimal non-target toxicity, supporting its potential use as a microbial larvicide in integrated mosquito management.
This review focuses on leishmaniasis caused by Leishmania (L.) infantum in Tunisia, a vector-borne parasitic disease transmitted through the bite of infected female sandflies. Leishmaniasis manifests as a spectrum of clinical forms, ranging from benign cutaneous lesions, to a severe and potentially fatal visceral form. In Tunisia, L. infantum is the etiological agent of visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). While CL typically manifests as a single, small facial lesion, atypical forms are sometimes observed. VL primarily affects children under the age of five and immunocompromised individuals, although an increasing number of cases have been reported in immunocompetent adults in recent years. Although neglected, leishmaniasis is an emerging and growing public health concern in Tunisia, particularly due to the increasing incidence of VL among adults and potential spread of both CL and VL to previously non-endemic areas. This expansion is demonstrated by the fact that L. infantum has a geographical distribution mainly in the humid, sub-humid and semi-arid regions of the north, but gradually spreading towards the central and southern parts of the country. This literature review was conducted through a systematic search of PubMed, Scopus, and Google Scholar for studies published between 1904 and 2024, focusing on the clinical, epidemiological, molecular, and ecological aspects of L. infantum in Tunisia. In addition to its clinical variability, L. infantum presents a biochemical variability with three isoenzymatic variants (zymodemes) identified in Tunisia: MON-1 (predominantly associated with VL), MON-24 (predominantly associated with CL), and MON-80 (implicated in both forms). Our review found that VL remains highly endemic in northern Tunisia but has expanded southward in recent decades, while cutaneous cases due to L. infantum are increasingly recognized. Isoenzymatic and molecular studies confirm the predominance of the MON-1 zymodeme, with sporadic detection of MON-24 and MON-80. Domestic dogs remain the main reservoir, and Phlebotomus (P.) perniciosus is the principal vector for VL, though other Phlebotomus species have been implicated in CL transmission. These findings highlight the importance of integrating molecular tools alongside classical isoenzyme methods for a better understanding of parasite dynamics and epidemiological monitoring. The transmission cycle of L. infantum is not fully elucidated, but domestic dogs and P. perniciosus are considered the primary reservoir and vector for VL, respectively, while, other potential mammalian hosts and sandflies vectors were suspected for CL. Comparative data from Algeria, Morocco, Libya, and southern Europe suggest both common patterns and local specificities in L. infantum transmission, underscoring the importance of regional collaboration. The epidemiological and clinical complexity of L. infantum, together with its expanding geographic distribution in Tunisia, underscores the need for further integrated research to clarify transmission cycles and implement effective prevention and control strategies.
Cutaneous leishmaniasis (CL) is a debilitating neglected tropical disease characterized by lesions that can range from self-healing to permanent disfiguration. A predominant Th1 response, which stimulates IFN-γ production, is crucial for parasite control during self-healing CL. While IFN-γ primarily activates macrophages to produce nitric oxide via inducible nitric oxide synthase (iNOS), leading to parasite control, it also activates other downstream pathways involved in cell autonomous immunity. One such pathway is the activation of guanylate-binding proteins (Gbps), a class of interferon-inducible GTPases. However, the role of Gbps during CL has been minimally explored. Utilizing RNA-Seq, we found that Leishmania major infection leads to the upregulation of several Gbps in C57BL/6 mice. In vitro studies using GbpChr3 knockout (KO) and C57BL/6 control mice reveal that bone marrow-derived macrophages from KO mice exhibit higher parasite burdens following IFN-γ treatment, independent of Gbp localization to the parasite. Single-cell RNA-Seq identifies macrophages as the primary expressers of Gbps during L. major infection in vivo. In vivo, GbpChr3 KO mice display increased disease severity and parasite load. GbpChr3 KO macrophages and monocytes show elevated ARG-1 and reduced iNOS expression, indicating a shift toward a parasite-permissive environment that supports parasite growth. These findings highlight a critical role for Gbps in immune-mediated control of CL.IMPORTANCELeishmania parasites cause cutaneous lesions that are often resistant to drug treatment, and no vaccine is currently available, highlighting the need to better understand host mechanisms that control infection. In this manuscript, we explore the role of guanylate-binding proteins (Gbps) in host macrophages during Leishmania major infection. We demonstrate that Gbps are critical for host defense both in vitro and in vivo. Notably, this protection is independent of Gbp localization to the parasite, revealing a novel aspect of Gbp biology. Instead, we find that differences in parasite burden and disease severity in Gbp-deficient mice are linked to altered activation of tissue macrophages and monocytes. Our findings suggest that Gbps coordinate inducible nitric oxide synthase expression in macrophages, the primary cells that house and control Leishmania parasites, and play a unique immunoregulatory role during infection.
Effective malaria vector control in endemic areas requires understanding the distribution and composition of Anopheles species, as shifts in malaria vector species and composition can influence the efficacy of control interventions and transmission patterns. The current study explored the temporal and spatial distribution of Anopheles species and their infection with Plasmodium in different transmission settings in Tanga region and Unguja, Zanzibar, United Republic of Tanzania. From September 2021 to December 2023, monthly entomological surveys were conducted in 11 villages in Tanga and four Shehias in Unguja. Anopheles mosquitoes were sampled every month in each of 11 villages in Tanga and four Shehias in Unguja, 10 households were consented to participate in each village or Shehia. Mosquitoes were collected indoors and outdoors using CDC light traps, Furvela tent traps, Indoor and Outdoor prokopack. Species identification was performed using PCR, and Plasmodium infections were detected using TaqMan real-time PCR assay. A total of 4771 Anopheles mosquitoes collected (3,766 and 905 in Tanga and Unguja respectively), PCR amplification failed in 100 samples. Among successfully identified specimens, An. gambiae s.s. (43.8%) and An. merus (37.1%) were predominant. In Unguja, An. arabiensis (55.7%) and An. merus (41.9%) were most common. Seasonal variations were observed, with An. gambiae s.s. and An. funestus s.s. peaking in the short rainy season, An. arabiensis peaking in both dry and long rainy seasons, and An. merus peaked during both the wet and dry seasons, suggesting relatively stable occurrence throughout the year. Plasmodium infection rates for An. gambiae s.s., An. funestus s.s., An. arabiensis, and An. merus were 3.0% in Tanga and 1.2% in Unguja but only found in An. arabiensis. In Tanga, An. gambiae s.s., An. merus, and An. funestus s.s. were more abundant in upland and lowland areas than in the highlands, with urbanization limiting An. merus occurrence. In Unguja, An. arabiensis and An. merus were less common in semi-urban areas but showed a sharp increase during the wet season. The study indicates a shift in An. gambiae s.l. sibling species composition has taken place in the study areas compared to previous reports. In the past, An. merus was not considered an important vector in Tanzania. However, in this study An. merus was observed as the second most abundant species across coastal and inland areas of Tanga and Unguja during both wet and dry season. Combined with its observed infection with P. falciparum, the findings suggest An. merus may contribute to perennial transmission of malaria in the region. This presents a new challenge to malaria vector surveillance and control including the need for a year-round multi-strategic approach.
Current interventions targeting malaria control in sub-Saharan Africa (SSA) are focused on Plasmodium falciparum, the most prevalent species infecting humans. Despite renewed efforts for malaria elimination in SSA, little attention has been paid to the neglected parasites P. malariae, P. ovale spp., and P. vivax and the impact of interventions like long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS) with non-pyrethroid insecticides, and/or seasonal malaria chemoprevention (SMC) on these minor Plasmodium spp. To address this research gap, the aim of this observational study was to assess the impact of two sequential interventions, IRS and SMC combined with LLINs, on the Plasmodium spp. reservoir, with particular emphasis on the non-falciparum minor species, in Bongo District, an area characterized by high seasonal transmission in the Northern Sahelian belt of Ghana. Using an interrupted time-series study design, five age-stratified surveys, each of ~2,000 participants, were undertaken at the end of the wet seasons between 2012 and 2022. Across this 10-year study period, infections with P. malariae and P. ovale spp. were detected using a species-specific PCR targeting the 18S rRNA gene, while P. vivax was not detected. In 2015, following IRS, the prevalence of the minor Plasmodium spp. declined in all ages from baseline in 2012, with participants being significantly less likely to be infected with P. malariae (13.7% vs 1.4%) and P. ovale spp. (5.7% vs 0.4%). Despite this decline, in 2017, 32 months after IRS was discontinued and SMC was introduced, the prevalence of P. malariae (2.9%) and P. ovale spp. (4.0%) rebounded, with approximately a 2- and 10-fold increase, respectively. This rebound in the minor species was observed in all age groups, except for the younger children (< 5 years) targeted by SMC. Finally, when we examined this population in 2020 and 2022 after continued deployment of SMC, the prevalence of P. malariae continued to increase (7.4% and 5.8%), while the prevalence of P. ovale spp. declined (2.6% and 1.3%). Results show that both IRS and SMC were effective not only against P. falciparum but also reduced the prevalence of P. malariae and P. ovale spp. in Bongo District. Going forward, molecular diagnostics will be critical to identify changes in the submicroscopic reservoir of the minor Plasmodium spp. found in adolescents and adults and to achieve malaria elimination in this region of Ghana.
Controlled human infection models can play an important role in vaccine development, particularly for neglected tropical diseases such as helminth infections. Currently, controlled infection models have been established for schistosomiasis and hookworm. This review highlights the developments in the controlled human schistosomiasis infection model (CHI-S) and the controlled human hookworm infection model (CHHI) and their contributions to vaccine development. In general, both models are considered safe and well-tolerated. Measures to decrease risk of potential adverse events were taken when developing the models. For both models, production of challenge agents follows the principles of Good Manufacturing Practice. Both models have proven to reliably detect infection and can be used to assess efficacy of immunization strategies. While hookworms and schistosomes are both helminths, the controlled human infection (CHI)-studies have also highlighted differences between these pathogens. Notably, schistosomiasis seems to induce more, dose-dependent, systemic symptoms, whereas in hookworm models skin symptoms are much more prominent. Infection levels for schistosomiasis are therefore limited and lower than those usually seen in endemic populations, whereas for hookworm it is possible to reach levels comparable to mild-moderate intensity infection in the field. Host responses to short-term infection were also different: short-term schistosome infection induced immune-tolerance, whereas short-term infection with hookworm larvae seems to induce a more pro-inflammatory response compared to that seen in the adult worms. Most studies have been performed in naïve non-endemic populations, however, currently the models are being expanded to endemic areas. This has raised new questions around the impact of non-native strains of parasites or vectors to the endemic parasite strains and the environment. Studies in endemic areas, however, will significantly contribute towards understanding the immunology of these helminth infections in pre-exposed individuals. In general, the success of these established models is encouraging to the further development of controlled human helminth infection models.
Several issues that affect prevention and treatment of heartworm infections require more intensive research. The incidence of heartworm infection in the USA is increasing, but the factors that underlie this trend remain incompletely understood. The contributions of climate change, vector range expansion, client compliance and resistance to macrocyclic lactones (ML) are likely interrelated and require investigation. Molecular-level research has not yet identified the causative mechanisms underlying ML resistance (MLR), but surveys of genomic markers associated with the trait reveal worrying trends in the presence and frequency of these resistance alleles. Research is needed to confirm the phenotypic relevance of these markers and to identify the gene(s) responsible for it. Developing highly inbred strains of MLR heartworms may be necessary but would require multigenerational studies of targeted breeding of selected parasites in dogs. A second issue of concern for veterinarians is the increasing extra-label use of emodepside products for the treatment of multiple anthelmintic drug resistant (MADR) canine hookworms (Ancylostoma caninum), which are already common throughout the USA. Emodepside is not approved for use in dogs in the USA, but a cat topical product containing the drug is, and is being used orally in hookworm-infected dogs. Emodepside has activity against larval and adult stages of many filarial parasites and the safety of this drug in heartworm-infected dogs has not been reported. It is perhaps unlikely that such studies will be undertaken, given the lack of economic motivation. Nonetheless, a review of the relevant literature leads to the conclusion that the status of heartworm infection in a dog bearing an apparently MADR hookworm infection be determined before starting treatment with emodepside, with caution exercised should it ensue.
Clonorchis sinensis, a common food-borne liver fluke in East Asia, is a Group 1 carcinogen strongly linked to cholangiocarcinoma. In recent years, molecular biology and multi-omics studies have revealed that this parasite drives chronic inflammation of the bile duct epithelium, epigenetic abnormalities, and the formation of precancerous lesions. Concurrently, circulating miRNAs, DNA methylation patterns, differential protein expression, metabolite profiles, and parasite-specific antigens have been proposed as potential early molecular biomarkers, which offers new avenues for the non-invasive detection of precancerous conditions. However, current research mainly remains at the laboratory stage and studies have small-scale cohorts, lacking multi-center, large-sample prospective validation and standardized detection protocols, which limits their clinical applicability. Furthermore, traditional imaging and histological methods exhibit limited sensitivity for early identification. This review aims to systematically summarize the molecular carcinogenic mechanisms associated with C. sinensis infection, recent advances in molecular biomarker research, and strategies for identifying precancerous lesions. It will particularly focus on discussing the major obstacles in clinical translation and future directions, with the goal of providing insights for early screening and prevention strategies. Clonorchis sinensis et cholangiocarcinome : mécanismes moléculaires et avancées sur les biomarqueurs. Clonorchis sinensis, une douve du foie fréquemment transmise par voie alimentaire en Asie de l’Est, est un cancérogène du groupe 1 fortement associé au cholangiocarcinome. Ces dernières années, des études de biologie moléculaire et multi-omiques ont révélé que ce parasite induit une inflammation chronique de l’épithélium des voies biliaires, des anomalies épigénétiques et la formation de lésions précancéreuses. Parallèlement, les microARN circulants, les profils de méthylation de l’ADN, l’expression différentielle des protéines, les profils métaboliques et les antigènes spécifiques du parasite ont été proposés comme biomarqueurs moléculaires précoces potentiels, ouvrant ainsi de nouvelles perspectives pour la détection non invasive des états précancéreux. Cependant, les recherches actuelles restent principalement au stade du laboratoire et portent sur de petites cohortes, sans validation prospective multicentrique à grande échelle ni protocoles de détection standardisés, ce qui limite leur applicabilité clinique. De plus, les méthodes d’imagerie et histologiques traditionnelles présentent une sensibilité limitée pour le diagnostic précoce. Cette revue vise à synthétiser de manière systématique les mécanismes moléculaires de la carcinogenèse associés à l’infection par C. sinensis, les avancées récentes en matière de recherche sur les biomarqueurs moléculaires et les stratégies d’identification des lésions précancéreuses. Elle s’attache plus particulièrement à examiner les principaux obstacles à la transposition clinique et les perspectives d’avenir, afin d’éclairer les stratégies de dépistage précoce et de prévention.
Dirofilaria repens is the leading cause of subcutaneous (dogs) and subcutaneous/ocular dirofilariosis (humans) in the Old World. Despite its rapid geographical spread, driven by climate change, the emergence of new invasive vectors (Aedes albopictus) and growing interest in its study due to the emergence of new cases in areas previously free of the parasite, amongst other factors, scientific research into this pathogen remains limited. This study provides the first longitudinal bibliometric analysis of global research on D. repens (1955-2025). Data from Web of Science and Scopus were processed using PRISMA and RAMIBS protocols, resulting in a normalized corpus of 624 documents analyzed via science mapping techniques. The field exhibits a sustained annual growth rate of 3.79%, transitioning into an exponential expansion phase in 2011. While Italy retains historical leadership, spatial analysis confirms a research displacement towards Central and Eastern Europe (Germany, Poland). Thematic evolution reveals a structural shift from isolated clinical case reports to a multidisciplinary ecosystem dominated by molecular epidemiology, vector competence, and surveillance. Dirofilaria repens has gone from being a minor and neglected issue to having a significant number of reports and studies subject to interest in addressing the disease that results from its infection in different hosts. However, the intellectual structure exposes an operational fragmentation between clinical medicine and medical entomology. Future research must overcome national silos and integrate reservoir management with vector control, transforming the current reactive approach into a predictive preventive system aligned with the One Health framework.
Ticks transmit a wide range of protozoan, bacterial, and viral pathogens to humans and animals globally. However, data on ticks infesting domestic ruminants and the pathogens they carry are scarce in Malawi. In this study, we examined ticks collected from domestic ruminants and screened them for selected veterinary and medically important protozoan and bacterial pathogens. A total of 964 ticks were collected from 202 cattle, 63 goats, and 16 sheep across eleven districts in Malawi. Ticks were morphologically identified to species level using taxonomical keys, with molecular confirmation by PCR amplification and sequencing of the 12S ribosomal RNA (12S rDNA) and cytochrome c oxidase subunit I (COI) genes. Tick DNA was further screened for tick-borne pathogens using species-specific PCR assays. Identified tick species included Rhipicephalus microplus (30.5%), Rhipicephalus appendiculatus (23.3%), Rhipicephalus decoloratus (13.2%), Rhipicephalus evertsi (9.8%), Hyalomma rufipes (7.5%), Amblyomma variegatum (6.3%), Rhipicephalus sanguineus sensu lato (tropical lineage) (3.6%), Hyalomma truncatum (2.8%), Rhipicephalus simus (2.0%), Rhipicephalus pravus (0.6%), and Rhipicephalus annulatus (0.4%). Overall, 37.0% of ticks carried at least one tick-borne pathogen, with Theileria parva being the most prevalent (34.7%), followed by Anaplasma marginale (17.4%), Babesia bigemina (14.9%), Anaplasma ovis (11.2%), Ehrlichia ruminantium (9.2%), Theileria mutans (8.4%), Babesia bovis (2.2%), and Anaplasma bovis (2.0%). This study provides the first molecular identification of ticks infesting domestic ruminants in Malawi and documents associated tick-borne pathogens. Notably, Rhipicephalus appendiculatus was identified for the first time in southern Malawi, refining current understanding of East Coast fever epidemiology and highlighting the need for updated surveillance approaches. Identification des agents pathogènes transmis par les tiques chez les ruminants domestiques au Malawi et émergence de la tique Rhipicephalus appendiculatus dans la région sud : implications pour la lutte contre la fièvre de la côte est. Les tiques transmettent un large éventail d'agents pathogènes protozoaires, bactériens et viraux aux humains et aux animaux à l'échelle mondiale. Cependant, les données sur les tiques infestant les ruminants domestiques et les agents pathogènes qu'elles transportent sont rares au Malawi. Cette étude a examiné des tiques prélevées sur des ruminants domestiques et a recherché certains agents pathogènes protozoaires et bactériens d'importance vétérinaire et médicale. Au total, 964 tiques ont été collectées sur 202 bovins, 63 chèvres et 16 moutons dans onze districts du Malawi. Les tiques ont été identifiées morphologiquement jusqu'à l'espèce à l'aide de clés taxonomiques, avec confirmation moléculaire par amplification PCR et séquençage des gènes de l'ARN ribosomique 12S (ADNr 12S) et de la sous-unité I de la cytochrome c oxydase (COI). L’ADN des tiques a ensuite été analysé à la recherche d’agents pathogènes transmis par les tiques à l’aide de tests PCR spécifiques à l’espèce. Les espèces de tiques identifiées comprenaient Rhipicephalus microplus (30,5 %), Rhipicephalus appendiculatus (23,3 %), Rhipicephalus decoloratus (13,2 %), Rhipicephalus evertsi (9,8 %), Hyalomma rufipes (7,5 %), Amblyomma variegatum (6,3 %), Rhipicephalus sanguineus sensu lato (lignée tropicale) (3,6 %), Hyalomma truncatum (2,8 %), Rhipicephalus simus (2,0 %), Rhipicephalus pravus (0,6 %) et Rhipicephalus annulatus (0,4 %). Au total, 37 % des tiques étaient porteuses d'au moins un agent pathogène transmis par les tiques, Theileria parva étant le plus fréquent (34,7 %), suivi d'Anaplasma marginale (17,4 %), Babesia bigemina (14,9 %), Anaplasma ovis (11,2 %), Ehrlichia ruminantium (9,2 %), Theileria mutans (8,4 %), Babesia bovis (2,2 %) et Anaplasma bovis (2 %). Cette étude fournit la première identification moléculaire des tiques infestant les ruminants domestiques au Malawi et documente les agents pathogènes transmis par les tiques associés. Notamment, Rhipicephalus appendiculatus a été identifié pour la première fois dans le sud du Malawi, ce qui affine les connaissances actuelles sur l'épidémiologie de la fièvre de la côte Est et souligne la nécessité de mettre à jour les méthodes de surveillance.
Visceral leishmaniasis (VL) remains a major public health challenge in East Africa, particularly in Ethiopia. Clinical trials on VL often exclude patients with severe comorbidities or laboratory abnormalities, limiting the generalizability of evidence used to guide real-world management. We comprehensively characterised the clinical profile, treatment outcomes, and mortality of VL patients treated in a referral centre. This prospective cohort study enrolled patients at the Leishmaniasis Research and Treatment Center (LRTC), University of Gondar (02/2023-06/2024). All VL cases fulfilling eligibility criteria underwent detailed clinical, laboratory, and radiological assessments. VL treatment followed WHO guidelines. Outcomes, adverse events, and supportive care measures were recorded during treatment and over a 12-month follow-up period. Patients meeting at least one exclusion criterion (e.g., comorbidities, clinical signs of severe VL) of standard phase III VL treatment trials were defined as trial-ineligible patients and compared with trial-eligible patients. A total of 314 VL patients, mostly young adult males (median age 22 years), were enrolled. Of these, 21 (6.7%) had HIV co-infection; 204 (65%) met ≥ 1 key exclusion criterion typically used in VL clinical trials. Trial-ineligible patients had high parasitemia, more concurrent infections, more pronounced clinical and laboratory abnormalities and a higher need of supportive care measures including systemic antibiotics and blood transfusion. Overall cure rate was 90.1%. Mortality after the first VL treatment course was 6.4%, ranging from 1.8% in trial-eligible patients to 8.8% in trial-ineligible patients. Leading causes of death included severe bacterial infections, acute liver failure and haemorrhagic complications. These findings underscore the severity and complexity of VL in routine care in our study population, and highlight the limitations of current trial populations to inform broader clinical practice. Strengthening supportive care and expanding research inclusivity designed to respond to the needs of this patient population are critical to achieve VL elimination targets.
Phlebotomine sand-fly-borne infections are an emerging threat to human and animal health in Mediterranean countries, highlighting the need for improved surveillance and control strategies. Dogs are ideal sentinel hosts owing to their central role in the transmission of zoonotic Leishmania infantum, frequent exposure to sand fly bites, capacity to develop antibodies to phleboviruses, and close contact with humans. This study reports cross-sectional surveys of antibodies to Leishmania, Toscana virus (TOSV), and Sicilian sand fly virus (SFSV) in dogs from Portugal, Spain, Italy, Croatian Istria, Turkey, and Israel, as well as antibodies to salivary proteins of Phlebotomus perniciosus (Portugal, Spain, and Italy) and Phlebotomus papatasi (Spain and Italy), conducted within the Climate Monitoring and Decision Support Framework for the Detection and Mitigation of Sand fly Diseases with Cost-Benefit and Climate Policy Measures (CLIMOS) project. Blood samples and epidemiological data were collected from 2500 dogs. Antibodies to Leishmania were detected by indirect immunofluorescence, phlebovirus antibodies by seroneutralization assays, and antibodies to P. perniciosus and P. papatasi salivary antigens by enzyme-linked immunosorbent assay (ELISA) using recombinant proteins rSP03B and rSP36, respectively. Sources of antibody variability were evaluated using mixed-effects logistic regression models. Antibodies to L. infantum, phleboviruses, and sand fly saliva were widely detected, although seroprevalence varied markedly by region. No Leishmania-seropositive dogs were found in Istria, parts of northern Spain, or several districts in Israel, whereas seroprevalence exceeded 30% in Sicily and in several Turkish and Spanish provinces. TOSV seropositivity was generally absent or below 5%, except in southern Spain (8-24%) and Muğla, Turkey (10%). SFSV exposure was highly focal, occurring mainly in Turkey (12%), Israel (12%), and Lisbon (7%). Exposure to P. perniciosus was very high in Portugal, Sicily, and most of Spain, while P. papatasi exposure was highest in Sicily and selected Spanish regions. Antibody variability was driven primarily by geographical location. The marked geographical heterogeneity observed confirms dogs as valuable sentinels for sand-fly-borne infections. These infections are highly clustered across Mediterranean regions, likely reflecting differences in sand fly density and infection rates. Understanding the drivers of this heterogeneity is essential for accurate risk mapping and effective control strategies.
Leishmaniasis is a vector-borne disease transmitted through sand fly vectors carrying protozoan parasites from the genus Leishmania. The leishmanin skin test (LST), used to detect exposure to Leishmania parasites, is no longer available due to a lack of well-characterised antigens. Towards reintroducing the LST, we previously developed a preparation of the leishmanin antigens using a freeze-thaw (FT) process, which induced a delayed-type hypersensitivity (DTH) response in hosts exposed to Leishmania parasites. The storage of FT preparation antigens requires refrigeration, which is not practical for use in field settings. We developed a safe, simple and scalable antigen extraction process and a phenol-free lyophilised-LST antigen formulation that obviates the need for a cold-chain under Good Laboratory Practice conditions (GLP-LSTLyo). The immunogenicity of GLP-LSTLyo was evaluated in murine models of Leishmania infections in support of two distinct use cases: (i) to detect latent infections of Leishmania in endemic areas and (ii) as a surrogate of vaccine-induced immunogenicity. Towards this goal, leishmanisation with wild-type Leishmania major and immunisation of mice with the live-attenuated L. major vaccine strain lacking the centrin gene (LmCen-/-) were used as animal models. The GLP-LSTLyo antigen was administered, and its ability to induce a DTH response was monitored for 48 h. Additionally, the potency of the GLP-LSTLyo was assessed by immune phenotyping of the cells isolated from the DTH tissue via flow cytometry. Only the DTH sites from pre-exposed animals, but not the excipient controls, showed enrichment for predominantly CD8+ T cells, along with CD4+ T cells and macrophages, consistent with previous studies. Additionally, in an interferon gamma release assay (IGRA), stimulation of whole blood collected from healed, active cutaneous leishmaniasis (CL) cases in a Leishmania endemic area in Brazil with GLP-LSTLyo induced IFN-γ and IL-10. These results demonstrated the potency of our formulation in IGRA studies, which could aid immunogenicity studies in vaccine trials, and surveillance studies in both endemic and emerging areas of Leishmania infection. These studies are supported by funding from GHIT Fund, Japan, CIHR, Canada, intramural funding from the FDA, and FIOCRUZ and INCT-DT Brazil.
To analyze Chinese and English publications pertaining to Oncomelania hupensis control from 2005 to 2024, so as to decipher the research status and hotspots of O. hupensis control. Chinese and English publications pertaining to O. hupensis control from 2005 to 2024 were retrieved in the Web of Science Core Collection Database and China National Knowledge Infrastructure. The annual number of publications was analyzed from 2005 to 2024, and the author and institution cooperation networks were mapped using the software CiteSpace 6.3.1. Keywords were extracted from publications to map the co-occurrence, burst and timeline of keywords to identify the research hotspots of O. hupensis control. A total of 158 English publications and 771 Chinese publications were included for bibliometric analyses. The overall output of English publications was relatively small from 2005 to 2024, the annual average publication was 7.90 publications. Parasites & Vectors was the most productive journal by the number of publications (21 publications). The three most productive authors included Li Shizhu (24 publications), Zhou Xiaonong (13 publications), and Yang Kun (12 publications), and the three most productive institutions included Chinese Center for Disease Control and Prevention (49 publications), the WHO (27 publications), and Fudan University (25 publications). The annual average number of Chinese publications was high from 2005 to 2015 (57.73 publications), and reduced to 15.11 publications during the period from 2016 to 2024, with Chinese Journal of Schistosomiasis Control as the most productive journal (241 publications). The three most productive authors included Wang Wanxian (18 publications), Sun Qixiang (16 publications), and Dai Jianrong (16 publications), and the three most productive institutions included Jiangsu Institute of Parasitic Diseases (55 publications), Chinese Center for Disease Control and Prevention (47 publications), and Hubei Uni-versity (38 publications). Among the 158 English publications, molluscicidal effect, climate change, geographic information, biological control, machine learning were current research hotspots, and the Yangtze River and elimination were emerging research hotspots. Among the 771 Chinese publications, molluscicidal effect, niclosamide, comprehensive management, molluscicide, effectiveness evaluation, marshland, and endophyte were current research hotspots, and the future research hotspots shifted to molluscicidal effect and pyriclobenzuron. Limited attention is paid to the research on O. hupensis control across the world. The Yangtze River, elimination, molluscicidal effect, and pyriclobenzuron may be future research hotspots. High attention is recommended to be paid to the research on O. hupensis control, and development of diverse approaches for O. hupensis control is of urgent needs. We should continue to attach importance to the control research of O. hupensis and strengthen the exploration of diverse snail extermination and control methods. ［摘要］ 目的 对2005—2024年发表的钉螺控制相关研究中英文文献进行分析, 了解该领域的研究现状和热点。方法 分别在Web of Science核心合集数据库和中国期刊全文数据库中检索2005—2024年发表的有关钉螺控制研究的英 文和中文文献, 使用CiteSpace 6.3.1软件分析各年发文情况, 并构建作者、机构合作网络图谱; 提取文献关键词绘制关键 词共现、突现和时间线图谱, 分析钉螺控制研究热点。结果 共纳入158篇英文文献和771篇中文文献进行文献计量学 分析。2005—2024年英文文献发文量总体较少, 年均发文量为7.90篇; 《Parasites & Vectors》是刊载文献最多的期刊 (21 篇); 发文量居前3位的作者分别为Li Shizhu (24篇)、Zhou Xiaonong (13篇)、Yang Kun (12篇), 居前3位的机构分别是中 国疾病预防控制中心 (49篇)、WHO (27篇)、复旦大学 (25篇)。2005—2015年中文文献年均发文量为57.73篇, 2016— 2024年降至15.11篇; 《中国血吸虫病防治杂志》是刊载文献最多的期刊 (241篇); 发文量居前3位的作者分别为王万贤 (18篇)、孙启祥 (16篇)、戴建荣 (16篇), 排名前3位的机构分别是江苏省血吸虫病防治研究所 (55篇)、中国疾病预防控 制中心 (47篇)、湖北大学 (38篇)。158篇英文文献中, 灭螺效果 (molluscicidal activity)、气候变化 (climate change)、地理 信息 (geographic information)、生物控制 (biological control)、机器学习 (machine learning) 是目前的研究热点, 长江 (Yangtze River) 和消除 (elimination) 是新的研究热点。771篇中文文献中, 灭螺效果、氯硝柳胺、综合治理、灭螺剂、效果评价、江 滩、内生真菌是目前的研究热点, 未来研究热点转向灭螺效果和吡螺脲。结论 国内外对钉螺控制研究的关注度较低, 长江、消除、灭螺效果、吡螺脲可能是今后的研究热点, 应继续重视钉螺控制研究, 加强对多样化灭螺、控螺方式的探讨。.
Reliable assessment of antimalarial drug efficacy is crucial for an effective response to emerging drug resistance, and therapeutic efficacy studies (TESs) are the primary means of estimating in vivo efficacy. The accuracy of such estimates rests on correctly classifying recurrent infections developed during follow-up as recrudescences or new infections. Genotyping is used to guide classification, but polyclonal infections and alleles matching by chance make classification challenging, especially in high transmission settings. Match-counting algorithms currently recommended by the World Health Organization are unreliable and produce biased results, necessitating the development of principled statistical approaches. Modern genotyping methods, such as multiplexed amplicon sequencing, hold great potential for resolving recurrences and motivate the need for corresponding statistical methods able to utilize the rich data they provide. We propose an Adaptive Statistical framework for Therapeutic Efficacy and Recrudescence (Aster) that delivers accurate and consistent results by explicitly incorporating the complexity of infection, population allele frequencies, and imperfect detection of alleles in minority strains. Using an identity-by-descent approach, Aster accounts for alleles matching by chance and for a background infection relatedness structure that can otherwise lead to misclassification. The flexible framework can also use external information, such as parasite density and performance characteristics of a genotyping panel. Using simulations, we show that Aster dramatically outperforms match-counting algorithms in a wide variety of transmission settings and demonstrates consistently balanced performance that improves with more informative genotyping panels. Aster is implemented in a fast, fully scalable, and user-friendly R software package, asterTES, and provides accurate estimates of treatment failure for TES with any type of genotyping data, facilitating reliable evaluation of drug efficacy and effective management of malaria.
Alphavirus chikungunya (CHIKV) is an arthritogenic virus whose innate recognition is primarily driven by pathogen associated molecular patterns (PAMPs) or damage associated molecular patterns (DAMPs), sensed by a variety of pattern recognition receptors (PRRs) such as Toll-like receptors (TLR), and cytosolic RIG-like receptors. CHIKV infection elicits a multifaceted interplay between viral replication strategies and host innate immune recognition. Among these pathways, TLR-mediated sensing emerges as a central axis of antiviral defense, orchestrating type I interferon responses and inflammatory cascades that determine the balance between viral clearance and immunopathology. In parallel, inflammasomes such as NLRP3 amplify the IL-1β/IL-18 axis, being a major contributing factor for the establishment of chronic joint inflammation. The transition from self-limited rapid resolving infection to chronic disease is largely determined by the cytokine and chemokine milieu. It is known that acute infection is characterized by high levels of IL-6, TNF-α, and IL-1β, which drive fever, myalgia, and joint inflammation; and chemokines such as CCL2 (MCP-1) were shown to recruit monocytes and macrophages to inflamed joints, whereas CXCL9/10 (MIG/IP-10) enhance T-cell trafficking, contributing to viral clearance but also sustaining tissue inflammation. In this review, we aim to consolidate the current knowledge on the molecular pathways that sense CHIKV infection and trigger the antiviral innate response that can act as both protective and pathogenic. By integrating viral evasion strategies and host factors, we provide a comprehensive framework for understanding innate immunity in CHIKV infection, its implications for therapeutic design, and important gaps that can guide future studies.
Effective diagnosis of Schistosoma haematobium is critical for disease management. However, current tools often lack sensitivity for low-intensity infections, a challenge noted in the recent WHO Roadmap for Neglected Tropical Diseases. This study aimed to evaluate a novel cell-free DNA (cfDNA) quantitative Polymerase Chain Reaction (qPCR) assay, utilizing 20 µl of plasma with crude DNA extraction. This approach intends to improve diagnostic accuracy and lower implementation barriers for molecular tests in field settings. We compared its performance against urine filtration microscopy and the Up-converting Reporter Particle Lateral Flow Circulating Anodic Antigen (UCP-LF CAA) test in pregnant women from Lambaréné, Gabon. A prospective cross-sectional study was conducted on 296 pregnant women in Gabon. EDTA blood, urine, and stool samples were collected from December 2018 to November 2020. Urine samples were analyzed by urine filtration microscopy and UCP-LF CAA. The cfDNA qPCR assay was performed retrospectively on 20 µl of frozen plasma using a simplified DNA extraction method. Diagnostic accuracy was assessed via sensitivity, specificity, and agreement measures. Bayesian latent class analysis (BLCA) was used to estimate test performance in the absence of a gold standard. Diagnostic positivity varied: 24.3% by cfDNA qPCR, 18.6% by urine filtration microscopy, and 20.9% by UCP-LF CAA. Agreement between tests was limited. BLCA indicated qPCR to be the most sensitive (74.0%, 95% CrI: 57.2-90.8), followed by UCP-LF CAA (65.7%, 95% CrI: 49.0-82.8). Microscopy was the most specific (94.9%, 95% CrI : 89.6-99.3). Estimated prevalence ranged between 22.5 and 27.1%. Receiver operating characteristic (ROC) analysis confirmed good individual performance (AUC 0.837-0.868), with performance improving when combining any two tests (AUC up to 0.931). This study validates the high sensitivity of a novel cfDNA qPCR approach using only 20 µl of plasma, demonstrating performance comparable to microscopy and UCP-LF CAA. While microscopy maintains high specificity, combining it with a high-sensitivity test such as qPCR or UCP-LF CAA provides significant diagnostic improvement. Further optimizing the specificity of this streamlined qPCR assay brings us closer to a highly accurate, feasible point-of-care diagnostic crucial for schistosomiasis control programs in resource-limited settings.
Plasmodium vivax poses a major obstacle to malaria elimination because this parasite can lie dormant in the liver for weeks to months before reactivating and causing a relapse of infection. These dormant forms (hypnozoites) cannot be detected using standard diagnostics, but P vivax exposure in the previous 9 months and, by proxy, hypnozoite carriage, can be inferred using serological markers. In this study, we aimed to examine how genetic variation in P vivax affects the utility of these markers and whether redesigned antigens could improve performance. In this observational diagnostic accuracy study, we analysed global P vivax genetic data to assess variation in leading serological markers (n=14). Accordingly, we expressed new haplotypes that better reflect global sequence diversity for eight antigens, compared with the commonly used reference strain (Sal-1). Antibody responses against these were tested using samples from cohorts in Brazil and Thailand, with magnitude assessed in relation to how recently participants had a qPCR-detectable blood-stage P vivax infection. We compared the ability of the haplotypes versus the reference to correctly identify individuals infected within the previous 9 months. Extensive global genetic diversity was identified in two P vivax antigens, MSP5 (π=14·8 × 10-3) and DBPII (π=7·7 × 10-3). Several antigens had large numbers of circulating haplotypes, with the percentage with similar sequence identity to the reference Sal-1 ranging from 0·4% (MSP5) to 99% (S16). Samples for immune analysis were previously collected between April 2013 and June 2014, with 774 and 923 participants included in the current analysis from Thailand and Brazil, respectively. Two antigens showed strong differences in immunogenicity by region and construct (RBP2a and DBPII). However, for most proteins (five of eight: MSP5, RiPR, PTEX150, Pv-fam-a, and RBP2b), these differences had no significant effect on the accuracy of identifying recent exposure. Affected performance (eg, RBP2a) was overcome by adding multiple antigens into the classification model. Even highly diverse antigens can be effective serological markers. Our findings highlight the importance of testing the effect of genetic diversity and suggest practical strategies to ensure consistent performance across regions. Australian National Health and Medical Research Council.
Leishmaniasis is caused by the Leishmania parasite, leading to cutaneous lesions or infections of internal organs. The therapy is challenging, and the search for new medications and alternative therapies continues. This study investigates the impact of quercetin-loaded microemulsion (MEs-QCT) on Leishmania major (L. major) in culture media and compares it with the effects of quercetin (QCT). We used the standard strain of L. major in this experiment. MEs formulations were created with an oily phase, a surfactant, a co-surfactant, and distilled water. Transmission electron microscopy (TEM) and Scatterscope were employed to analyze the MEs. The MTT test was employed to assess the survival rates of promastigotes and macrophages (MΦs). MEs-QCT demonstrated the highest efficacy against L. major promastigotes. The IC50 values for QCT, MEs-QCT, and MEs were determined to be 315.3, 130, and 1378 μg/mL, respectively. The findings of this study indicate that MEs-QCT possesses a greater potential for amastigote lethality compared to QCT and the control group. In all time periods, the proportion of MΦs mortality was lower in MEs-QCT than in QCT. The results showed that MEs-QCT had a higher effect with less toxicity compared to QCT. Leishmania is a parasite that causes leishmaniasis, a serious and occasionally fatal illness. Through the bite of an infected sand fly, this parasite can infect both people and animals. Leishmaniasis can damage the skin and internal organs. The most prevalent type of leishmaniasis, cutaneous leishmaniasis, can cause skin lesions and ulcers on exposed body regions that last for a year or longer. These ulcers can leave lifelong scars even though they are typically not lethal. Glucantime is administered by injection, either systemically or locally at the location of the wound or bite. Because local and repeated injections around the medication’s wounds produce excruciating pain over an extended period of time, researchers are searching for a better alternative to the current treatments. The materials are found in leaves, plants, fruits, and vegetables. Quercetin is one substance that has antiviral, anti-inflammatory, antioxidant, and anticancer properties. It is found in many fruits, vegetables, leaves, seeds, and grains. This study was designed because quercetin seems to be a promising therapy option for leishmaniasis.