Parasites & Vectors最新文献

Background: Members of the genus Trichinella are muscle-dwelling zoonotic parasites of global importance for public health, animal husbandry, and trade. Trichinella chanchalensis (T13) is the newest species in the genus, first described in the Yukon and the Northwest Territories, for which the geographical distribution remains unknown due to limitations of the gold standard test for genotyping (multiplex polymerase chain reaction [PCR]). Our primary objective was to determine whether T. chanchalensis was present in Alaska, using a new molecular method that enables the description of the prevalence, co-infection, host associations, and risk factors for Trichinella spp. infection in wild carnivores.

Methods: Trichinella spp. larvae were recovered through artificial digestion of muscle and genotyped using next-generation sequencing (NGS).

Results: Trichinella spp. larvae were detected in 53/157 (34%) animals, namely wolverines (Gulo gulo), arctic foxes (Vulpes lagopus), red foxes (Vulpes vulpes), coyotes (Canis latrans), wolves (Canis lupus), brown bears (Ursus arctos), and polar bears (Ursus maritimus), but not in black bears (Ursus americanus) or lynx (Lynx canadensis). Prevalence was highest in polar bears and wolverines, while intensity (larvae per gram, LPG) was highest in red foxes, arctic foxes, and wolves. Most animals (65%) harbored single infections with Trichinella nativa, followed by mixed infections of T. nativa and Trichinella T6 (33%). A single wolverine was infected with T. nativa, T6, and T. chanchalensis. Combining NGS with statistical methods, we found no evidence of competition between T. nativa and T6 in host muscles. Trichinella spp. infection (primarily T. nativa) was the highest in the Northwestern region, whereas T6 infection probability was higher in the Interior and Southern regions, suggesting differences in environmental resistance even among these three taxa. In a single, highly infected brown bear, we detected a rare case of Trichinella spiralis of foreign origin based on whole-genome sequencing, suggesting illegal importation and disposal of meat.

Conclusions: We report a new geographical record for T. chanchalensis and a rare finding of T. spiralis in North American wildlife, and demonstrate the utility of new NGS methods for describing the ecology of parasites maintained in wildlife hosts commonly presenting as co-infections.

Background: Loiasis, caused by the nematode/filaria Loa loa, presents a major health burden in Central and West Africa. Despite the growing recognition of loiasis' medical significance, current antifilarial drugs remain inadequate in terms of efficacy and safety, particularly for individuals with hypermicrofilaremia. This systematic review aims to evaluate the efficacy of antifilarial treatment regimens for reducing L. loa microfilaremia and provide guidance on treatment strategies.

Methods: A systematic review was conducted to evaluate the efficacy of antifilarial treatment regimens on reducing L. loa microfilaremia. Data on the percentage reduction of microfilaremia from baseline to nadir were extracted for each treatment regimen.

Results: A total of 27 studies were included in the review, with treatment regimens involving albendazole (ALB), mebendazole (MBZ), ivermectin (IVM), diethylcarbamazine (DEC), levamisole, imatinib, and moxidectin, among others. ALB and MBZ showed dose- and duration-dependent efficacy, with extended treatment leading to up to a 98-100% microfilaremia reduction. IVM showed a dose-dependent effect, with single doses of 200-400 µg/kg reducing microfilaremia by 88-92%. DEC exhibited high efficacy, achieving up to a 100% microfilaremia reduction.

Conclusions: Antifilarial drug efficacy against L. loa microfilaremia varies by dosage and treatment duration, with IVM and DEC demonstrating rapid, high efficacy but presenting safety concerns for hypermicrofilaremic individuals. ALB and MBZ show efficacy with extended treatment but are slower acting. Further research is needed to optimize treatment regimens and assess clinical outcomes beyond microfilaremia reduction.

Background: Clonorchiasis, a neglected tropical zoonosis, is caused by chronic infection with Clonorchis sinensis (C. sinensis). This infection can lead to cholangitis, bile duct epithelial hyperplasia, periductal fibrosis, and cholangiocarcinoma (CCA). However, the underlying carcinogenic mechanisms of CCA remain poorly understood, and there is not a well-developed model for C. sinensis CCA.

Methods: A C. sinensis-infected Sprague-Dawley rat model, co-treated with N-nitrosodimethylamine, was established. The study comprised four groups: negative control (NC), C. sinensis infection (CS), N-nitrosodimethylamine induction (NDMA), and combined C. sinensis infection and N-nitrosodimethylamine induction (CSNDMA). Pathological damage to the hepatic ducts was evaluated at 10, 17, and 20 weeks after infection. The expression levels of the relevant genes and proteins were detected using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry, respectively. In addition, transcriptome sequencing was carried out on hepatic tissues infected for 20 weeks.

Results: Histopathological analysis using hematoxylin and eosin (H&E) and Masson staining revealed bile duct dilation, inflammatory infiltration, and collagen deposition in the liver tissue of both CS and CSNDMA groups, with the most severe manifestations observed in the CSNDMA group. The CSNDMA group exhibited the earliest onset of CCA, occurring at 10 weeks post infection, with an overall incidence of 63%, peaking at 71% by 20 weeks. The CS group showed a 37% incidence of CCA, while only one case was noted in the NDMA group at 20 weeks. Quantitative PCR demonstrated that C. sinensis infection induced upregulation of tumor-related markers in the liver, including CK19, PCNA, TP53, ITGB1, and MMP2, particularly when co-exposed to N-nitrosodimethylamine. Immunohistochemistry detected the significant overexpression of CK19, CK7, and PCNA along bile ducts. Transcriptome sequencing further indicated that C. sinensis significantly affected circadian rhythm and metabolic reprogramming in the liver, enriching pathways related to cancer, inflammation, and metabolism, including AMPK, PPAR, mTOR, and FoxO pathways.

Conclusions: C. sinensis can effectively promote the pathogenesis of CCA and significantly increase the expression of CCA-related genes (e.g., CK19 and CK7). The inflammation, disrupting circadian rhythms and altering energy metabolism caused by C. sinensis infection, may promote the progression of CCA. This study provides a foundational experimental basis for diagnosing and intervening in C. sinensis-related CCA.

Background: The cattle fever tick, Rhipicephalus microplus, is found in tropical and subtropical regions worldwide. Infestations of this tick lead to significant economic losses for cattle producers and dairy farmers, and the ticks can transmit a variety of pathogens that cause diseases such as babesiosis, anaplasmosis and theileriosis. The proteins Bm86, AQP1, AQP2 and VgR are expressed in various tick tissues, including the gut, salivary glands and ovaries. These proteins regulate essential physiological processes, including water balance (AQP1, AQP2), reproduction (VgR) and cell membrane integrity (Bm86).

Methods: Comprehensive bioinformatic and immunoinformatic analyses were conducted to evaluate Bm86, AQP1, AQP2 and VgR as potential vaccine targets against R. microplus. Specifically, we conducted studies on these proteins that included analysis of their physicochemical properties; topographical protein analyses; prediction of N-glycosylation sites, O-glycosylation sites, phosphorylation sites and B-cell and T-cell epitopes; and immune response simulation. The overall aim was to identify key epitopes and highlight their behavior within the host, representing a promising multicomponent vaccine formulation.

Results: The predictions for R. microplus Bm86, VgR, AQP1 and AQP2 proteins indicate strong antigenicity, low allergenicity and minimal toxicity, suggesting the potential for safe and effective immune response elicitation. The immune profile simulations for a cocktail of these proteins as vaccine candidates predicted consistently high levels of interferon-gamma and antibody isotypes, which could improve vaccine efficacy and control tick fitness and survivability in subsequent generations.

Conclusions: The application of immunoinformatic tools for anti-tick vaccination was validated for the investigation of combining R. microplus Bm86, VgR, AQP1 and AQP2 proteins as a potential cocktail vaccine candidate.

Concomitant immunity (CI) can be viewed as an example of coevolution between the microorganisms and their long-lived hosts. Such an ecological trade-off may be advantageous to both the microbe and the host, as it allows protozoa and helminths to maintain their genetic features while providing the host, particularly mammals, with long-standing protection against reinfection by the same microbe. In Leishmania infection, CI is the mechanism whereby parasites remain at low-level infection in the host, which develops a strong immune reaction that protects against reinfection. Mechanistically, several CD4⁺ T cell populations seem to be involved in such fine immune responses. While immunity against Leishmania, Plasmodium, Taenia, Schistosoma, and Echinococcus is well known, the mechanisms of CI involving these pathogens have been poorly studied. Finally, the phenomenon of CI should be carefully assessed in the design of novel vaccine preparations.

Background: Sindbis virus (SINV) and Batai virus (BATV) are emerging zoonotic arboviruses with a growing number of detections in Europe. Recent SINV outbreaks in northern Europe and high BATV seroprevalence in sheep, goats, and cattle in Germany emphasise the threat they pose to both animal and human health. Despite their presence in countries of similar latitude and climate, neither of these viruses have been detected in the UK.

Methods: Zoos are strategic sentinel sites for disease surveillance because they are well monitored and possess a high diversity of animal species. Located in southeast England, where the climate and vector prevalence may provide suitable conditions for viral emergence, London Zoo was selected as the sampling site for SINV and BATV prevalence in mosquito samples between September 2022 and January 2024. In 2020, it was also the first location where Usutu virus was detected in the UK. Adult mosquitoes were collected during host-seeking and overwintering seasons while larvae were collected in the summer months.

Results: A total of 8477 mosquito specimens were analysed, representing all mosquito stages, i.e. including host-seeking and overwintering mosquitoes as well as adults that had emerged from larvae. Mosquitoes of the Culex pipiens/Culex torrentium complex were the most abundant, accounting for 97.5% of the total. Molecular analysis using quantitative polymerase chain reaction was performed to test for SINV and BATV; however, none of the samples tested positive.

Conclusions: These results suggest that neither SINV nor BATV actively circulated in the sampled area during the study period. The findings provide baseline data for arbovirus surveillance in the UK, particularly at London Zoo, which is home to diverse bird populations that might be potential sentinel populations for viral emergence. Future studies that obtain molecular and serological data on birds or mammals housed at the zoo would complement our surveillance efforts on the emergence or prevalence of SINV and BATV in the UK. This study focused on a single location, but extending sampling and monitoring to other sites across the UK, especially in the southeast, is crucial to strengthening the UK's preparedness and response strategies in case SINV and BATV emerge in the country in the future.

Background: Dogs are recognized as epidemiologically significant reservoirs for Trypanosoma cruzi, the causative agent of Chagas disease (CD), owing to their close association with humans and their role in sustaining the domestic and peridomestic transmission cycle. Canine seropositivity often correlates with human CD prevalence. However, the lack of commercial, high-performance diagnostic assays for canine infections remains a significant barrier to effective surveillance. Previously, our group demonstrated the diagnostic potential of four chimeric T. cruzi antigens in a phase I study, yielding results comparable to those observed in humans. The present phase II study expands upon these findings by evaluating these antigens in a larger canine cohort using indirect enzyme-linked immunosorbent assay (ELISA). The objective of this study was to assess the diagnostic performance of four chimeric recombinant T. cruzi antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) in immunoassays for the detection of anti-T. cruzi IgG in dogs with chronic Chagas disease.

Methods: Immunoassays were optimized by checkerboard titration. In this phase II study, the diagnostic performance of the IBMP antigens was evaluated using 1260 canine serum samples. Cross-reactivity was assessed in an additional 752 samples from dogs with unrelated infectious diseases. The performance of the chimeric antigens was compared with a commercial human-adapted assay (Gold ELISA Chagas).

Results: The Instituto de Biologia Molecular do Paraná (IBMP) antigens demonstrated area under the curve (AUC) values ranging from 89.0% to 97.4%, with diagnostic accuracy between 87.4% and 96%. IBMP-8.2 exhibited the highest sensitivity (90.3%), while IBMP-8.1, IBMP-8.3, and IBMP-8.4 achieved sensitivities of 74.8%, 72.6%, and 79.6%, respectively. The highest specificity was observed for IBMP-8.4 (99.6%), followed by IBMP-8.3 (99.0%), IBMP-8.2 (96.5%), and IBMP-8.1 (90.6%). The Gold ELISA Chagas assay showed a sensitivity of 62.3%, specificity of 98.6%, and accuracy of 89.9%. IBMP-8.2 exhibited the lowest cross-reactivity index (0.9%), closely approximating an ideal diagnostic assay.

Conclusions: The IBMP chimeric antigens demonstrated strong diagnostic performance for detecting T. cruzi infection in dogs, significantly enhancing immunoassay accuracy and minimizing diagnostic failures due to cross-reactivity. The combined use of these antigens represents a promising strategy to further improve sensitivity and specificity in future diagnostic applications.

This study reports a new therapeutic approach for canine giardiasis, the most common intestinal protozoan infection caused by Giardia intestinalis. It is based on the use of the probiotic strain Lactobacillus johnsonii CNCM I-4884 and, in particular, its bile salt hydrolase enzymatic activities. Clinical trials in dogs demonstrated that daily administration of L. johnsonii CNCM I-4884 significantly reduced Giardia cyst shedding after 14 days. These results highlight the potential of this probiotic as a promising alternative to antimicrobials, such as nitroimidazoles or benzimidazoles, for the treatment of giardiasis in dogs. Moreover, they provide a novel approach for the veterinary industry to develop innovative products targeting this parasite. In addition to its direct anti-Giardia effect, L. johnsonii CNCM I-4884 may also act as an adjuvant therapy, supporting intestinal homeostasis, enhancing host defense mechanisms, and promoting recovery of gut balance during or after antiparasitic treatments. This dual role suggests that the strain could be considered not only as a complementary therapy but, in specific cases, as a potential stand-alone probiotic treatment for canine giardiasis.

In this report, we summarize the main outputs of the final workshop on multisectoral approaches (MSAs) to vector-borne diseases (VBDs) supported by the Special Programme for Research and Training in Tropical Diseases. We discussed the results of case studies from different countries investigating the collaboration between sectors such as health, education, environment, agricultural, and water and sanitation, among others, to combat VBDs such as malaria and arboviral diseases. Over 4 days, principal investigators of case studies presented their outcomes and invited experts highlighted the importance of MSA for effective control of VBDs. This multisectoral approach is novel and adds value to the research field by using a comprehensive strategy through coordinated efforts to address difficult public health topics, like vector-borne disease prevention and treatment. The participants had the opportunity to brainstorm and propose solutions related to limited financial resources to support MSA activities, the difficulty of engaging and collaborating with stakeholders from nonhealth sectors, and the sustainability of engaging committees that work across disciplines. Discussions emphasized the necessity of MSA and the importance of innovative technologies and multidisciplinary research, including strategic solutions that can help countries develop, implement, and sustain MSA for the prevention and control of VBDs. The workshop concluded with a commitment to strengthen international partnerships and implement comprehensive MSA to effectively control VBDs in marginalized communities.

Background: Borrelia burgdorferi, the causative agent of Lyme disease, is a zoonotic vector-borne pathogen transmitted by various Ixodes tick species. Lyme disease, while commonly asymptomatic, can induce fever and intermittent lameness in dogs. Highly effective acaricidal products with a rapid onset of action along with prompt removal of attached ticks are important aspects of successful Lyme disease prevention strategies.

Methods: Two studies were conducted with a total of 30 dogs each. Dogs were randomized to receive a control sham dose, Credelio Quattro, or Credelio. Treatment was administered on Day 0 in a fed state. On Day 28, all dogs were experimentally infested with wild-caught adult Ixodes scapularis. Blood samples for B. burgdorferi antibody analysis utilizing the SNAP 4Dx Plus and Lyme Quant C₆ tests were collected on Days 27, 49, 63, 77, 91, and 105. Skin biopsies were collected from four different areas of heavy tick attachment from each dog for polymerase chain reaction (PCR) detection of B. burgdorferi on Day 104 or 105.

Results: All control dogs demonstrated adequate I. scapularis infestation rates on Day 33 in both studies. In Study 2, on Day 27, one control dog tested positive for B. burgdorferi on the Lyme Quant C₆ test, prior to experimental tick infestation, and therefore was excluded from analysis. A total of eight out of 10 (Study 1) and nine out of nine (Study 2) control dogs tested positive for B. burgdorferi on at least one test after Day 27. One dog in the Credelio Quattro-treated group tested positive for B. burgdorferi on SNAP 4Dx Plus on Day 105 in Study 1 but was negative on all other tests and study days. None of the dogs treated with Credelio tested positive for B. burgdorferi at any point during either study.

Conclusions: The laboratory studies described herein confirm that a single dose of lotilaner, at the minimum effective dosage of 20 mg/kg, administered as Credelio Quattro, in combination with moxidectin, praziquantel, and pyrantel or Credelio, is effective for the prevention of transmission of B. burgdorferi from infected I. scapularis for a full month in dogs.