Cases Of Chagas Disease Research Articles

627. Outcomes of Military Blood Donors Screening Positive for Trypanosoma cruzi

Abstract Background First time blood donors at the Armed Service Blood Bank-San Antonio are screened for Trypanosoma cruzi infection with a chemiluminescent microparticle immunoassay (CMIA) followed by a confirmatory enzyme strip assay (ESA). In military populations, T. cruzi positivity on a screening test accounts for the fourth most common reason for post-donation deferral. With concerns for low positive predictive value in a low prevalence disease, this study evaluated the clinical outcomes and diagnostic work-up of blood donors who screened positive on T. cruzi CMIA testing.Table 1:Workup of 49 blood donors who screened positive for Trypanosoma cruzi infection Methods All blood donors from 2017-2022 were screened for T. cruzi antibodies with CMIA and deferred indefinitely if screening was positive, regardless of ESA result. All donors that initially screened positive for T. cruzi infection were evaluated to determine diagnostic work-up, further testing, specialty appointments seen, and final diagnosis of each case following their initial positive blood donation screen.Table 2:Clinical outcomes of 4 blood donors with positive T. cruzi screening test and confirmatory test Results Of 89,459 blood donors during the study period, 49 (57.3 per 100k donors) screened positive for Chagas disease on initial blood donation. Of those individuals, 4 (8%) had positive, 18 (36%) had indeterminate, and 30 (61%) had negative confirmatory tests. The evaluation varied significantly depending on the results of ESA testing, however there were no blood donors who met criteria for Chagas disease (Table 1). Evaluation of four donors with positive CMIA and ESA showed only one with repeat positivity on one assay, but all were ultimately deemed negative (Table 2). Conclusion While positive T. cruzi antibodies were a common reason for post-donation deferral in this cohort, there were no confirmed cases of Chagas disease, despite most patients receiving an extensive work-up. Patients with positive or indeterminate ESA received more specialty care and more confirmatory testing than those with a negative confirmatory test. This study demonstrates the need for higher specificity screening and confirmatory tests for T. cruzi in blood donors in low prevalence settings. Disclosures All Authors: No reported disclosures

Epidemiology of Chagas Disease in the United States of America: A Short Review and Some Comments.

The epidemiology of Chagas disease in humans has markedly changed within the past several decades in the United States of America. This report discusses autochthonous cases of Chagas disease as well as disease in immigrants from Latin American countries. Suggestions for epidemiology research and medical care are discussed given the evolving epidemiology of the disease in the United States of America.

ACUTE CHAGAS DISEASE IN THE MUNICIPALITY OF BELÉM/PARÁ

Chagas disease is a parasitic infection transmitted by hematophagous insects popularly known as “barbeiros”, “chupão” or “chupança”. The World Health Organization estimates that approximately 6 to 7 million people are infected worldwide, the vast majority of whom are in Latin America. In Brazil, the northern region is responsible for almost all cases. The general objective of this study is to demonstrate the incidence of acute Chagas disease in the city of Belém/Pará in the years 2021 and 2022. The specific objectives are to determine the type of contamination, verify the seasonality and relate the seasonality to the type of contamination. This is an epidemiological, retrospective, and descriptive study that uses publicly accessible data from the Department of Information Technology of the Unified Health System on notifications of cases of acute Chagas disease reported in 2021 and 2022. Thirty-five cases of Chagas disease were confirmed in the municipality of Belém during the period studied; the main means of contamination was oral transmission, with 31 confirmed cases. The months of August to November represented the period of highest incidence of the disease, with an increase mainly in cases of oral contamination. These results are probably related to the increased consumption of food contaminated with Trypanosoma cruzi. We conclude that acute Chagas disease represents a public health problem and that it is being neglected in combat, treatment, and prevention actions.

ANÁLISE TEMPORAL DA INCIDÊNCIA DE CASOS NOTIFICADOS DA DOENÇA DE CHAGAS NO BRASIL, NO PERÍODO DE 2010-2019

Chagas disease is caused by Trypanosoma cruzi and remains an important public health concern in Brazil, despite control measures adopted over the last few decades. The objective of this study is to carry out a temporal analysis of the incidence of reported cases of Chagas Disease in Brazil from 2010 to 2019, identifying trends and possible associated factors. Secondary data from the Notifiable Diseases Information System (SINAN) were used to calculate incidence rates by region and year. The statistical analysis included linear regression models to evaluate the temporal variation of notifications. The results indicate an overall reduction in notifications in the country during the period analyzed, with significant regional variations. The North region showed an increase in notifications, suggesting the need for greater surveillance and control strategies. In contrast, the Southeast and South regions maintained a stable downward trend, as a result of continued vector control measures. It is concluded that, although cases of Chagas disease are declining in much of Brazil, the disease still represents a public health challenge in some regions, especially in areas where oral transmission and vector synanthropy are on the rise.

Evaluation and validation of a PrintrLab-based LAMP assay to identify Trypanosoma cruzi in newborns in Bolivia: a proof-of-concept study

Vertical transmission of Trypanosoma cruzi represents approximately 20% of new Chagas disease cases. Early detection and treatment for women of childbearing age and newborns is a public health priority, but the lack of a simple and reliable diagnostic test remains a major barrier. We aimed to evaluate the performance of a point-of-care loop-mediated isothermal amplification (LAMP) assay for the detection of Tcruzi. In this proof-of-concept study, we coupled a low-cost 3D printer repurposed for sample preparation and amplification (PrintrLab) to the Eiken Tcruzi-LAMP prototype to detect vertically transmitted Tcruzi, which we compared with standardised PCR and with the gold-standard algorithm (microscopy at birth and 2months and serological study several months later). We screened pregnant women from two hospitals in the Bolivian Gran Chaco province, and those who were seropositive for Tcruzi were offered the opportunity for their newborns to be enrolled in the study. Newborns were tested by microscopy, LAMP, and PCR at birth and 2months, and by serology at 8months. Between April 23and Nov 17, 2018, 986mothers were screened, among whom 276were seropositive for Tcruzi (28·0% prevalence, 95% CI 25·6-31·2). In total, 224infants born to 221seropositive mothers completed 8months of follow-up. Congenital transmission was detected in nine of the 224newborns (4·0% prevalence, 1·9-7·5) by direct microscopy observation, and 14more cases were diagnosed serologically (6·3%, 3·6-10·3), accounting for an overall vertical transmission rate of 10·3% (6·6-15·0; 23of 224). All microscopy-positive newborns were positive by PrintrLab-LAMP and by PCR, while these techniques respectively detected four and five extra positive cases among the remaining 215 microscopy-negative newborns. The PrintrLab-LAMP yielded a higher sensitivity than microscopy-based analysis. Considering the simpler use and expected lower cost of LAMP compared with PCR, our findings encourage its evaluation in a larger study over a wider geographical area. Inter-American Development Bank.

The Development of a One-Step RT-qPCR for the Detection and Quantification of Viable Forms of Trypanosoma cruzi in Açai Samples from Areas at Risk of Chagas Disease through Oral Transmission.

Currently, approximately 70% of new cases of Chagas disease (CD) in Brazil are attributed to oral transmission, particularly through foods such as açaí, bacaba, and sugarcane juice, primarily in the northern and northeastern regions of the country. This underscores the imperative need to control the spread of the disease. The methods utilized to conduct quality control for food associated with outbreaks and to assess the potential for the oral transmission of CD through consuming açaí primarily rely on isolating the parasite or inoculating food into experimental animals, restricting the analyses to major research centers. While there are existing studies in the literature on the detection and quantification of T. cruzi DNA in açaí, the evaluation of parasites' viability using molecular methods in this type of sample and differentiating between live and dead parasites in açaí pulp remain challenging. Consequently, we developed a molecular methodology based on RT-qPCR for detecting and quantifying viable T. cruzi in açaí pulp samples. This protocol enables the stabilization and preservation of nucleic acids in açaí, along with incorporating an exogenous internal amplification control. The standardization of the RNA extraction method involved a simple and reproducible approach, coupled with a one-step RT-qPCR assay. The assay underwent validation with various T. cruzi DTUs and demonstrated sensitivity in detecting up to 0.1 viable parasite equivalents/mL in açaí samples. Furthermore, we investigated the effectiveness of a bleaching method in eliminating viable parasites in açaí samples contaminated with T. cruzi by comparing the detection of DNA versus RNA. Finally, we validated this methodology using açaí pulp samples positive for T. cruzi DNA, which were collected in a municipality with a history of oral CD outbreaks (Coari-AM). This validation involved comparing the detection and quantification of total versus viable T. cruzi. Collectively, our findings demonstrate the feasibility of this methodology in detecting viable forms of T. cruzi in açaí pulp samples, emerging as a crucial tool for monitoring oral outbreaks of Chagas disease resulting from açaí consumption.

Epidemiological analysis of cases of acute Chagas Disease in Brazil between 2007 and 2022

Epidemiological analysis of cases of acute Chagas Disease in Brazil between 2007 and 2022

Drastic reduction in the notification of acute cases of Chagas disease in the Northeast region of Brazil. Epidemiological evaluation in the period 2001–2021

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi (T. cruzi), is a neglected disease endemic to some Latin American countries, including Brazil. Soon after infection, individuals develop an acute phase, which in most cases is asymptomatic and may go undetected. However, when CD is detected early, notification in the Notifiable Diseases Information System (SINAN), is mandatory. This study aimed to evaluate the information registered in the SINAN database and to determine the epidemiological profile of acute CD in Northeast Brazil, an endemic region, from 2001 to 2021. According to this survey, 1,444 cases of acute CD were reported in the Northeastern region of Brazil during this period. During the first six years, referred to as period 1, 90.24% of the notifications were registered, while the number of notifications significantly decreased in the subsequent years, referred to as period 2. Most individuals diagnosed with acute CD were Afro-Brazilian adults. All known routes of infection by the parasite were reported. Vector-borne transmission was predominant during period 1 (73.29%) and oral transmission during period 2 (58.87%). All nine states in Northeast Brazil reported cases in both periods. A higher incidence of disease was reported in Rio Grande do Norte (RN) during period 1, and in Maranhão (MA) during period 2. Our results show that CD remains a significant public health challenge.

Trypanosoma cruzi in domestic and wild mammals in the northeast region of Colombia

Trypanosoma cruzi hosts can serve as a source of infection for animals, vectors, and humans, contributing to the establishment of Chagas disease (CD) in a given area. Traditionally, the Department of Córdoba has not been considered a transmission area for CD; however, the report of several acute cases of Chagas disease highlights the importance of studying the dynamics of disease transmission in this region. This study aimed to detect T. cruzi in domestic and wild mammals in the department of Córdoba. In 2017, a cross-sectional descriptive study was conducted in six villages in two municipalities in the department of Córdoba. Blood samples from dogs living in the zones were collected in EDTA vacutainer tubes for domestic mammals. Wild mammals were collected using Sherman and Tomahawk traps and mist nets in crops and peridomiciles. T. cruzi DNA was detected using the kinetoplast DNA (kDNA) variable region and the tandem repeat satellite region of T. cruzi as molecular targets. We sampled 168 dogs and 146 wild mammals. The detected prevalence of T. cruzi was 6.37%; the TcI lineage was found in D. marsupialis, H. anomalus, and one canine. A specimen of D. marsupialis with TcI and TcII lineages was also identified. T. cruzi DNA was detected in domestic and wild animals in the study area, indicating the circulation of the parasite in peridomestic environments. D. marsupialis may represent an important host in maintaining this region's wild and domestic cycle.

Prevalence of Maternal Chagas Disease and Vertical Transmission Rates in Bolivia: A Systematic Review and Meta-Analysis.

Bolivia has one of the highest burdens of Chagas disease in the world. Vertical transmission from mother to infant accounts for a growing number of cases. We performed a systematic review of articles assessing the prevalence of Chagas disease in pregnant women and rates of vertical transmission to infants in Bolivia. Studies were not excluded based on year of publication or language. Random-effects analyses were performed to estimate a pooled prevalence of maternal Chagas disease and pooled vertical transmission rate. Our search yielded 21 articles describing over 400,000 cases of Chagas disease among pregnant women in Bolivia. The reported prevalence of maternal Chagas disease ranged from 17.3% to 64.5%, with a pooled prevalence of 33.0% (95% CI, 27.4-38.7%). The prevalence of maternal Chagas disease trended down over time (P = 0.006), decreasing by approximately 25% to 30% over the last 40 years. Vertical transmission rates ranged from 2.0% to 13% with a pooled average of 6.2% (95% CI, 4.4-7.5%); rates did not significantly change over time. Our study is the first systematic review and meta-analysis of Chagas disease maternal prevalence and vertical transmission in Bolivia. Our findings indicate that maternal Chagas disease has fallen in prevalence but still affects 20% to 30% of pregnant women and poses a considerable risk of vertical transmission. Pregnant women and infants are an important target for public health interventions to limit the mortality and morbidity of Chagas disease and to reduce intergenerational spread.

Seroprevalence of Trypanosoma cruzi among children from Veracruz, Mexico: Epidemiological baseline for a control model based on Chagas disease active transmission

Introduction. In 2021, the Secretaría de Salud de México and the Pan American Health Organization launched an initiative to interrupt intra-domiciliary vector transmission of Trypanosoma cruzi based on the prevalence of Chagas disease in children. The Mexican State of Veracruz was leading this initiative. Objective. To estimate the seroprevalence of T. cruzi infection among children under 15 years of age from rural areas of Veracruz, México. Materials and methods. We identified eight localities of high priority from the Municipality of Tempoal, Veracruz, for baseline serology. Blood samples were collected on filter paper from 817 individuals between June and August 2017, for screening with a third-generation enzyme immunoassay. Reactive cases were confirmed by indirect hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence tests on peripheral blood serum samples. We calculated seroprevalence and 95% confidence intervals (CI). Results. We confirmed Chagas disease cases in children under 15 years of age with a seroprevalence of 1,9% (95 % CI = 1,12-3,16) in the localities of Citlaltepetl, Cornizuelo, Cruz de Palma and Rancho Nuevo. Conclusions. These results indicate recent transmission of T. cruzi in these communities and allow to establish an epidemiological baseline for the design and implementation of a model focused on geographical areas with active transmission to advance toward the elimination of intra-domiciliary vector transmission of this parasite in Mexico.

Comparative evaluation of lateral flow assays to diagnose chronic Trypanosoma cruzi infection in Bolivia.

Bolivia has the highest incidence of Chagas disease (CD) worldwide. Caused by the parasite Trypanasoma cruzi, CD is generally a chronic condition. Diagnosis is logistically and financially challenging, requiring at least two different laboratory-based serological tests. Many CD cases are missed; in Bolivia it is estimated just 6% of individuals chronically infected with T. cruzi get diagnosed. Achieving control on the way to elimination of CD requires a radical simplification of the current CD testing pathways, to overcome the barriers to accessing CD treatment. We aimed to generate unbiased performance data of lateral flow assays (LFAs) for T. cruzi infection in Bolivia, to evaluate their usefulness for improving T. cruzi diagnosis rates in a precise and efficient manner. This retrospective, laboratory-based, diagnostic evaluation study sought to estimate the sensitivity/specificity of 10 commercially available LFAs for T. cruzi, using the current CD diagnostic algorithm employed in Bolivia as the reference test method. All tests were blinded at the study site and performed by three operators. In total, 470 serum samples were tested, including 221 and 249 characterized as CD-positive/-negative, respectively. The LFAs were scored according to their relative importance using a decision-tree-based algorithm, with the mean decrease in Gini index as the scoring metric. The estimates of sensitivities ranged from 62.2-97.7% (95% confidence interval (CI) lower bound 55.0-94.7%); for specificities the range was 78.6-100% (95% CI lower bound 72.0-97.5%); 5/10 and 6/10 tests had sensitivity >90% and specificity >95%, respectively. Four LFAs showed high values of both sensitivity (93-95%) and specificity (97-99%). The agreement between 6 LFAs and the reference tests was almost perfect (Kappa 0.83-0.94). Most LFAs evaluated thus showed performances comparable with current laboratory-based diagnostic methods.

Subcellular particles for characterization of host-parasite interactions

Parasitic diseases remain a major global health problem for humans. Parasites employ a variety of strategies to invade and survive within their hosts and to manipulate host defense mechanisms, always in the pathogen's favor. Extracellular vesicles (EVs), membrane-bound nanospheres carrying a variety of bioactive compounds, were shown to be released by the parasites during all stages of the infection, enabling growth and expansion within the host and adaptation to frequently changing environmental stressors. In this review, we discuss how the use of existing nanotechnologies and high-resolution imaging tools assisted in revealing the role of EVs during parasitic infections, enabling the quantitation, visualization, and detailed characterization of EVs. We discuss here the cases of malaria, Chagas disease and leishmaniasis as examples of parasitic neglected tropical diseases (NTDs). Unraveling the EVs' role in the NTD pathogenesis may enormously contribute to their early and reliable diagnostic, effective treatment, and prevention.

Trypanosomatid diversity in a bat community of an urban area in Campo Grande, Mato Grosso do Sul, Brazil

Bats have a long evolutionary history with trypanosomatids, but the role of these flying mammals on parasite transmission cycles in urban areas, especially for Trypanosoma and Leishmania species, remains poorly known. The objective of this study was to evaluate the species richness of trypanosomatids parasitizing a bat community in Campo Grande (CG), a state capital within the Cerrado of the Brazilian Midwest. We evaluated 237 bats of 13 species by means of hemoculture and molecular detection in spleen samples. The bat community of CG appears to participate in the transmission cycles of various species of trypanosomatids. We report an overall trypanosomatid detection rate of 34.2% (n=81), involving 11 out of 13 sampled bat species. We identified six species of trypanosomatids from 61 bats by analyzing SSU rRNA and/or kDNA: Trypanosoma cruzi DTU TcI, T. c. marinkellei, T. dionisii, Leishmania infantum, L. amazonensis, and T. janseni, with this latter being detected by hemoculture for the first time in a bat species. We also detected a Molecular Operational Taxonomic Unit, Trypanosoma sp. DID, in the phyllostomids Glossophaga soricina and Platyrrhinus lineatus. The highest trypanosomatid richness was observed for Sturnira lilium, which hosted three species: L. infantum, T. dionisii and T. janseni. Given that visceral leishmaniasis is endemic in CG, special focus should be placed on L. infantum. Moreover, L. amazonensis and T. cruzi warrant attention, since these are zoonotic parasites responsible for human cases of tegumentary leishmaniasis and Chagas disease, respectively. In this respect, we discuss how bat communities may influence the Leishmania spp. transmission in endemic areas.

Novel species of Triatoma (Hemiptera: Reduviidae) identified in a case of vectorial transmission of Chagas disease in northern Belize

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient’s home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel species of Triatoma in Belize indicates an increased risk of transmission to humans in the region and warrants expanded surveillance and further investigation.

Oral Chagas Disease in Colombia-Confirmed and Suspected Routes of Transmission.

Chagas disease (CD) remains endemic throughout many regions of Colombia despite implementing decades of vector control strategies in several departments. Some regions have had a significant decrease in vectorial transmission, but the oral ingestion of Trypanosoma cruzi through consumption of contaminated food and drink products is increasingly described. This form of transmission has important public health relevance in Colombia due to an increase in reported acute CD cases and clinical manifestations that often lead to significant morbidity and mortality. Oral CD in Colombia has been associated with the consumption of contaminated fruit juices, such as palm wine, sugar cane, or tangerine juice and water for consumption, or contaminated surfaces where food has been prepared. Another interesting route of oral transmission includes ingestion of unbeknownst infected armadillos' blood, which is related to a traditional medicine practice in Colombia. Some earlier reports have also implemented consumption of infected bush meat as a source, but this is still being debated. Within the Amazon Basin, oral transmission is now considered the principal cause of acute CD in these regions. Furthermore, new cases of acute CD are now being seen in departments where CD has not been documented, and triatomine vectors are not naturally found, thus raising suspicion for oral transmission. The oral CD could also be considered a food-borne zoonosis, and odoriferous didelphid secretions have been implemented in contaminating the human dwelling environment, increasing the risk of consumption of infectious metacyclic trypomastigotes. In this article, we will discuss the complex transmission dynamics of oral CD in Colombia and further examine the unique clinical manifestations of this route of infection. New insights into the oral transmission of Trypanosoma cruzi are being discovered in Colombia, which can help bring increased awareness and a better understanding of this neglected tropical disease to reduce the burden of CD throughout Latin America.

An Outbreak of Acute Chagas Disease Possibly Spread through Oral Transmission Involving Animal Reservoirs in Eastern Colombia.

Chagas disease (CD) is a parasitic infection caused by the parasite Trypanosoma cruzi. Reports of CD cases associated with oral transmission have increased, particularly in Colombia, Brazil, and Venezuela. In this investigation, parasitological, serological, and molecular tests were conducted on samples obtained from humans, mammal reservoirs, and hosts involved in the assessment of a suspected oral transmission outbreak in Cubara, Boyaca, Colombia. Seropositivity was observed in 60% (3 of 5) of index patients and 6.4% (5 of 78) of close contacts. Trypanosoma cruzi DNA was detected by quantitative polymerase chain reaction in 100% of index cases, 6.4% (5 of 78) of close contacts, 60% (6 of 10) of canines, and 100% (5 of 5) of opossums. In all index cases, the TcI lineage was identified, along with two cases of mixed infection (TcI/TcII-TcVI). Hemoculture revealed a flagellate presence in 80% of opossums, whereas all triatomine bugs tested negative. Our findings suggest a potential oral transmission route through contamination with opossum secretions.

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review.

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Seroprevalence of Strongyloides stercoralis, human T-lymphotropic virus, and Chagas disease in the Peruvian Amazon: a cross-sectional study.

Strongyloides stercoralis infections, human T-lymphotropic virus (HTLV) infections, and Chagas diseases occur throughout many regions of Central and South America, including Peru. This study aimed to evaluate the seroprevalence of S. stercoralis, HTLV, and Chagas disease in Iquitos (Peruvian Amazon) and the associated epidemiological conditions for S. stercoralis seroprevalence in Iquitos. A population-based cross-sectional study was conducted from May 1 to June 15, 2020, to assess the seroprevalence of S. stercoralis [lysate antigen ELISA (enzyme linked immunosorbent assay)], HTLV (recombinant antigen ELISA), and Chagas disease (crude and recombinant antigen ELISAs). Of the 396 included individuals, 257 were seropositive for S. stercoralis (a 64.9% prevalence, 95% confidence interval [CI] 60.0% to 69.4%). In the multivariable analysis, seropositivity for S. stercoralis was higher in women (odds ratio [OR] 1.60, 95% CI 1.03 to 2.66) and residents of Punchana (OR 3.47, 95% CI 1.51 to 7.93), whereas residence in Iquitos was associated with lower positivity (OR 0.52, 95% CI 0.32 to 0.85). In total, four individuals were positive for HTLV (1.0% seroprevalence, 95% CI 0.3% to 2.7%), and none were positive for Chagas disease (0.0% seroprevalence, 95% CI 0.0% to 1.2%). The seroprevalence of S. stercoralis in Iquitos is high, particularly among women and residents of Punchana. The presence of HTLV infection indicates that the virus is circulating in Iquitos. This study found no cases of Chagas disease.

The transcriptome landscape of 3D-cultured placental trophoblasts reveals activation of TLR2 and TLR3/7 in response to low Trypanosoma cruzi parasite exposure.

Vertical transmission of Trypanosoma cruzi (T. cruzi) become a globalized health problem accounting for 22% of new cases of Chagas disease (CD). Congenital infection is now considered the main route of CD spread in non-endemic countries where no routine disease testing of pregnant women is implemented. The main mechanisms that lead to fetal infection by T. cruzi remain poorly understood. Mother-to-child transmission may occur when bloodstream trypomastigotes interact with the syncytiotrophoblasts (SYNs) that cover the placenta chorionic villi. These highly specialized cells function as a physical barrier and modulate immune responses against pathogen infections. To model the human placenta environment, we have previously used a three-dimensional (3D) cell culture system of SYNs that exhibits differentiation characteristics comparable to placental trophoblasts. Further, we have shown that 3D-grown SYNs are highly resistant to T. cruzi infection. In this work, we used RNA sequencing and whole transcriptome analysis to explore the immunological signatures that drive SYNs' infection control. We found that the largest category of differentially expressed genes (DEGs) are associated with inflammation and innate immunity functions. Quantitative RT-PCR evaluation of selected DEGs, together with detection of cytokines and chemokines in SYNs culture supernatants, confirmed the transcriptome data. Several genes implicated in the Toll-like receptors signaling pathways were upregulated in 3D-grown SYNs. In fact, TLR2 blockade and TLR3/7 knockdown stimulated T. cruzi growth, suggesting that these molecules play a significant role in the host cell response to infection. Ingenuity Pathway Analysis of DEGs predicted the activation of canonical pathways such as S100 protein family, pathogen induced cytokine storm, wound healing, HIF1α signaling and phagosome formation after T. cruzi exposure. Our findings indicate that SYNs resist infection by eliciting a constitutive pro-inflammatory response and modulating multiple defense mechanisms that interfere with the parasite's intracellular life cycle, contributing to parasite killing and infection control.