Biology subjects

Dumonteil, E.

Publications and source records attributed to Dumonteil, E..

5 recordsLinked to original sources

bioRxiv2025

Vampire bats in Belize harbor multiple Trypanosoma cruzi genotypes: implications for parasite transmission at the wildlife-domestic-human interface

BackgroundChagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease with complex sylvatic and domestic transmission cycles involving vectors, mammalian hosts, and humans. The common vampire bat (Desmodus rotundus) is an obligate blood-feeding species that frequently interacts with livestock and humans, yet their role in parasite maintenance in Central America remains poorly characterized. Methodology/Principal FindingsWe analyzed 205 blood samples from vampire bats collected at two sites in northern Belize over three years (2019, 2021, 2022). PCR screening revealed an overall T. cruzi prevalence of 41.5% and increasing infection risks over time. The amplicon-based next-generation sequencing of the parasite mini-exon locus identified 36 unique haplotypes belonging to five DTUs: TcI, TcIV, TcV, TcVI, and TcBat. TcBat was present in half of the samples sequenced. TcBat and TcVI, were detected in Belize for the first time. Belizean TcBat haplotypes clustered closely with Colombian reference sequences, and a subset formed a Belize-specific clade, indicating previously unrecognized TcBat diversity in the region; in contrast, Brazilian TcBat sequences were more distantly related. Conclusions/SignificanceVampire bats in Belize harbor diverse T. cruzi genotypes, including DTUs with established roles in human disease. Given their obligate blood diet, frequent feeding on livestock, and occasional biting of humans, vampire bats may serve as bridge hosts linking sylvatic, domestic, and human transmission cycles. Together with a recent report of an acute human Chagas disease case in northern Belize, these results underscore the need for integrated One Health surveillance of bats, vectors, livestock, and humans to better evaluate and mitigate the risk of Chagas disease in Central America. Author SummaryChagas disease, caused by the parasite Trypanosoma cruzi, is a major public health concern in the Americas but remains neglected in many regions, including Central America. The parasite is typically transmitted by kissing bugs, but wild mammals also serve as important hosts. Vampire bats (Desmodus rotundus) are unique because they feed exclusively blood and frequently bite livestock, and occasionally humans, creating opportunities for parasite transmission across different environments. In this study, we screened 205 vampire bats from northern Belize and found that over 40% were infected with T. cruzi. By sequencing parasite DNA, we discovered a surprising diversity of DTUs, including TcI, TcIV, TcV, TcVI, and TcBat. The detection of TcVI is particularly important, because this DTU, associated with human infections in South America, had not been previously reported in Belize. TcBat haplotypes were highly prevalent and genetically diverse. Our results show that vampire bats are important hosts of diverse T. cruzi genotypes in Belize and may act as bridge hosts between wildlife, livestock, human transmission cycles. Enhanced One Health surveillance across vectors, bats, domestic animals, and humans will be critical for understanding and preventing Chagas disease emergence in Central America.

molecular biology↗

bioRxiv2025

Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy

Background and AimsChagas disease, caused by Trypanosoma cruzi, is a vector-borne parasitic disease, with dogs acting as a major domestic host of the parasite. An immunotherapeutic vaccine would be an excellent tool to treat infections and prevent chronic cardiac disease in this host. Building on previous pre-clinical studies, we performed here the first randomized field trial of a vaccine against T. cruzi among client-owned dogs with natural infections. MethodsA total of 31 dogs with T. cruzi infection with diverse parasite strains were enrolled and received three doses of a vaccine composed of Tc24-C4 and TSA1-C4 recombinant proteins with MPLA (N=16) or saline control (N=15) and followed for up to six months to assess efficacy. ResultsBlood parasite burden and electrocardiographic (ECG) recordings as primary outcomes showed that therapeutic vaccination led to a significant decrease in parasite burden, prevented/stopped cardiac alterations and was safe. This clinical benefit was mediated by major changes in T cell activation and T cell receptor (TCR) repertoire, while antibody responses were minimally affected. In addition, vaccination also reprogrammed the ongoing trained immunity to reduce inflammation, suggesting a complex interplay between innate and T cells in its mechanism of action. ConclusionsThese results provide a strong support for the further development of a veterinary vaccine based on these antigens as well as a human therapeutic vaccine to prevent the progression of chronic cardiac disease from T. cruzi infection. Structured graphical abstractO_ST_ABSKey questionC_ST_ABSCan an immunotherapeutic vaccine against Trypanosoma cruzi control an ongoing infection and prevent the progression of chronic cardiac disease in naturally infected dogs? Key findingTherapeutic vaccination of chronically infected dogs led to a reduced blood parasite burden and prevented the progression of chronic cardiac disease (Primary outcomes). Correlates of vaccine efficacy included major changes in T cell repertoire/activation and changes in innate immunity to reduce inflammation. Take home messageImmunotherapeutic vaccination of dogs with natural infection with T. cruzi was safe and effective to control an ongoing infection with a broad diversity of parasite strains and prevented the progression of chronic cardiac disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/653529v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@17ce572org.highwire.dtl.DTLVardef@bba649org.highwire.dtl.DTLVardef@1a20405org.highwire.dtl.DTLVardef@1b61c7e_HPS_FORMAT_FIGEXP M_FIG C_FIG Translational perspectiveCurrent drug treatments for Chagas disease have major limitations due to significant adverse effects and a limited efficacy as chronic cardiac disease develops. A veterinary vaccine for dogs, a major domestic host of the parasite, would help reduce domestic transmission and improve dog health, as well as provide support for the development of a human immunotherapeutic vaccine to prevent the progression of chronic Chagasic cardiomyopathy.

microbiology↗

bioRxiv2022

Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in BALB/c mice.

BackgroundChagas disease (CD) is caused by Trypanosoma cruzi and affects 6-7 million people worldwide. Approximately 30% of chronic patients develop chronic chagasic cardiomyopathy (CCC) after decades. Benznidazole (BNZ), one of the first-line chemotherapy approved for CD, induces toxicity and fails to halt the progression of CCC in chronic patients. The recombinant parasite-derived antigens, including Tc24, Tc24-C4, TSA-1, and TSA-1-C4 with Toll-like receptor 4 (TLR-4) agonist-adjuvants reduce cardiac parasite burdens, heart inflammation, and fibrosis, leading us to envision their use as immunotherapy together with BNZ. Given genetic immunization (DNA vaccines) encoding Tc24 and TSA-1 induce protective immunity in mice and dogs, we propose that immunization with the corresponding recombinant proteins offers an alternative and feasible strategy to develop these antigens as a bivalent human vaccine. We hypothesized that a low dose of BNZ in combination with a therapeutic vaccine (TSA-1-C4 and Tc24-C4 antigens formulated with a synthetic TLR-4 agonist-adjuvant, E6020-SE) could provide antigen-specific T cell immunity and prevent cardiac fibrosis progression. Methodology/ Principal findingsWe evaluated the therapeutic vaccine candidate plus BNZ (25 mg/kg/day/7 days) given at days 72 and 79 post-infection (p.i) (early chronic phase). Fibrosis, inflammation, and parasite burden were quantified in heart tissue at day 200 p.i. (late chronic phase). Further, spleen cells were collected to evaluate antigen-specific CD4+ and CD8+ T cell immune responses, using flow cytometry. We found that vaccine-linked BNZ treated mice had lower cardiac fibrosis compared to the infected untreated control group. Moreover, cells from mice that received the immunotherapy had higher stimulation index of antigen-specific CD8+Perforin+ T cells as well as antigen-specific central memory T cells compared to infected untreated control. ConclusionsOur results suggest that the bivalent immunotherapy together with BNZ treatment protects mice against cardiac fibrosis and activates strong CD8+ T cell responses by in vitro restimulation, evidencing the induction of a long-lasting T. cruzi-immunity. Author summaryChagas disease (CD) is a neglected tropical disease caused by the parasite Trypanosoma cruzi, transmitted through contact with infected feces of vectors bugs. CD can induce cardiac abnormalities including the development of fibrosis and eventually death. Benznidazole (BNZ) is the first-line drug approved against CD, however, its toxicity and lack of efficacy in the chronic phase have limited its use. Previous studies have demonstrated the feasibility of reducing doses of BNZ given in combination with therapeutic vaccines during the acute phase of CD, which increases its tolerability and reduces adverse side effects. Considering that patients are often diagnosed until prolonged stages of the disease, its necessary to evaluate therapies given in the chronic phase of CD. In this study, we evaluated a vaccine formulated with the recombinant T. cruzi-antigens TSA-1-C4 and Tc24-C4 and the adjuvant E6020-SE in combination with a low dose of BNZ given during the chronic phase of T. cruzi-infection using a murine model. The authors found that the combination therapy protects mice against cardiac fibrosis, allow the activation of a CD8+ T cell response and induce a prolonged memory response against T. cruzi. This study supports the development of the vaccine-linked chemotherapy approach in order to prevent T. cruzi chronic infection.

immunology↗

bioRxiv2020

Polymorphism and selection pressure of SARS-CoV-2 vaccine and diagnostic antigens: implications for immune evasion and serologic diagnostic performance

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6-7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.

microbiology↗

bioRxiv2018

Estimating the current burden of Chagas disease in Mexico: a systematic review of epidemiological surveys from 2006 to 2017

BackgroundIn Mexico, estimates of Chagas disease prevalence and burden vary widely. Updating surveillance data is therefore an important priority to ensure that Chagas disease does not remain a barrier to the development of Mexicos most vulnerable populations.\n\nMethodology/Principal FindingsThe aim of this systematic review was to analyze the literature on epidemiological surveys to estimate Chagas disease prevalence and burden in Mexico, during the period 2006 to 2017. A total of 2,764 articles were screened and 38 were retained for the final analysis. Epidemiological surveys have been performed in most of Mexico, but with variable geographic coverage. Based on studies reporting confirmed cases, i.e. using at least 2 serological tests, the national seroprevalence of Trypanosoma cruzi infection was 2.26% [95% Confidence Interval (CI) 2.12-2.41], suggesting that there are 2.71 million cases in Mexico. Studies focused on pregnant women, which may transmit the parasite to their newborn during pregnancy, reported a seroprevalence of 1.00% [95% CI 0.87-1.14], suggesting that there are 22,930 births from T. cruzi infected pregnant women per year, and 1,445 cases of congenitally infected newborns per year. Children under 18 years had a seropositivity rate of 1.49% [95% CI 1.20-1.85], which indicate ongoing transmission. Finally, cases of T. cruzi infection in blood donors have also been reported in most states, with a national seroprevalence of 0.51% [95% CI 0.49-0.53].\n\nConclusions/SignificanceOur analysis suggests a disease burden for T. cruzi infection higher than previously recognized, highlighting the urgency of establishing Chagas disease surveillance and control as a key national public health priority in Mexico, to ensure that it does not remain a major barrier to the economic and social development of the countrys most vulnerable populations.\n\nAuthor summaryIn Mexico, estimates of Chagas disease prevalence and burden vary widely due to the ecology and epidemiology of this disease resulting of many geographical, ecological, biological, and social interactions. Better data are thus urgently needed to help develop appropriate public health programs for disease control and patient care. In this study we analyzed published data on T. cruzi seroprevalence infection in Mexico between 2006 and 2017. This systematic review shows a national seroprevalence of T. cruzi infection of 2.26% [95%CI 2.12-2.41], with over 2.71 million cases in Mexico, which is higher than previously recognized. The presence of T. cruzi infection in specific subpopulations such as pregnant women, children and blood donors also informs on specific risks of infection and call for the implementation of well-established control interventions. This work confirms the place of Mexico as the country with the largest number of cases, highlighting the urgency of establishing Chagas disease control as a key national public health priority.

epidemiology↗