Acute Chagas Disease Research Articles

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.

Oral Chagas disease outbreak by bacaba juice ingestion: A century after Carlos Chagas' discovery, the disease is still hard to manage.

Orally transmitted acute Chagas disease (ACD) primarily affects low-visibility and low-income individuals in tropical and subtropical zones. Managing ACD remains challenging even after more than 100 years of its discovery. Its spread to non-endemic areas has made it a global health issue. The aim of this work is to demonstrate the difficulties encountered in handling a real-life situation. This report examines an outbreak of 39 cases of ACD due to oral transmission by bacaba juice ingestion that occurred in Pedro do Rosário, Maranhão, Brazil. A clinical and epidemiological investigation, including an entomological search, was conducted. Diagnosis criteria included positive peripheral blood smear (PBS), seroconversion of IgG, and a two-fold increase in IgG titer (laboratory criteria); and clinical findings, epidemiological exposure, and at least one positive IgG test (clinical-epidemiological criteria). In-house conventional polymerase chain reaction (PCR) was performed on 33 samples. All patients were treated with benznidazole. After 4.5 years, IgG levels were reassessed in 26 individuals. The mean age was 33.6 years, with no gender difference. The mean incubation period was 13.8 days, and the mean between symptom onset and treatment was 16.6 days. The most common symptoms were fever and lymphadenopathy (90%). Diagnostic success rates were 66.6% (laboratory criteria), 23% (clinical-epidemiological criteria), and 10.2% (high clinical suspicion despite negative tests). Test positivity rates were 69.7% (PBS), 91.4% (serology), and 100% (PCR). There were no deaths. Serological cure was achieved in 34.6% of cases, and IgG titers decreased in 15.3%. We encountered several barriers in managing ACD, including population vulnerability, reliance on outdated diagnostic techniques, lack of standardized molecular biology methods, and limited therapeutic options. This report underscores the importance of rapid surveillance and early treatment to prevent fatalities. We recommend the standardization of conventional PCR in diagnostic routines.

Exploring Trypanosoma cruzi transmission dynamics in an acute Chagas disease outbreak using next-generation sequencing

BackgroundChagas disease (CD), caused by Trypanosoma cruzi, poses a major global public health challenge. Although vector-borne transmission is the primary mode of infection, oral transmission is increasingly concerning.MethodsThis study utilized long-amplicon-based sequencing (long-ABS), focusing on the 18S rRNA gene, to explore T. cruzi’s genetic diversity and transmission dynamics during an acute CD outbreak in Colombia, an area without domestic infestation.ResultsAnalyzing samples from five patients and five T. cruzi-positive marsupial samples, we identified coinfections between T. cruzi and Trypanosoma rangeli, mixed T. cruzi DTUs, suggesting possible links between human and marsupial T. cruzi infections. Coexistence of TcI, TcIV and T. rangeli suggests marsupial secretions as the possible source of T. cruzi transmission. Our investigation revealed diversity loss in DTUs TcIV and T. rangeli in humans after infection and in marsupial samples after culture.ConclusionThese findings provide significant insights into T. cruzi dynamics, crucial for implementing control and prevention strategies.Graphical abstract

Acute Chagas disease outbreaks in Colombia in 2019

This study seeks to address the critical knowledge gap surrounding the acute phase of Chagas disease in Colombia, with a specific focus on cases reported in 2019. The acute phase of Chagas disease is a pivotal period for intervention, yet it remains poorly understood, particularly in regions where oral transmission is presumed to be a significant factor. By analyzing these recent cases, our research aims to provide a deeper understanding of the dynamics of Chagas disease during its acute phase in Colombia in 2019. This understanding is essential not only for improving disease management and treatment strategies but also for enhancing public health responses to this neglected tropical disease. In particular, our study highlights the importance of identifying and addressing the unique challenges posed by oral transmission routes, which have been increasingly recognized within Colombia's Chagas disease landscape.

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.

Health-disease Process of Acute Chagas Disease According to One Health Approach

Health-disease Process of Acute Chagas Disease According to One Health Approach

Comparative analysis of health-related fitness in patients with acute versus chronic Chagas disease.

Although Chagas disease causes high levels of morbidity, the muscle function and tolerance to physical activity in Chagas disease patients are still not completely understood. To compare health-related fitness of patient groups with acute Chagas disease versus chronic Chagas disease. We conducted a cross-sectional study involving 18 patients. The data were obtained from patient´s records, and functional capacity was measured with the sixminute walk test, the peripheral muscle strength with handgrip strength, and respiratory muscle strength using the maximum inspiratory pressure and the maximum expiratory pressure. The 18 patients were divided in two groups: acute Chagas disease (n=9) and chronic Chagas disease (n=9). The distance walked in the six-minute walk test was lower than the predicted distance walked in both groups (p < 0.0001). The maximum expiratory pressure was lower than the predicted one (p = 0.005), and statistically significant for chronic Chagas disease patients (p = 0.02). Heart rate increased faster in the chronic Chagas disease group within the first two minutes of the six-minute walk test (p = 0.04). The sixminute walk test in the acute Chagas disease group presented a strong correlation with peripheral muscle strength (p = 0.012) and maximum inspiratory pressure (p = 0.0142), while in the chronic Chagas disease group, only peripheral muscle strength and maximum inspiratory pressure were correlated (p = 0.0259). The results suggest lowered functional capacity and reduced respiratory and peripheral muscle strength in patients with Chagas disease, although no differences were observed between groups. The early increase in heart rate during exercise in the chronic Chagas disease group implies a greater myocardial overload.

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.

Profile of interstitial cells of Cajal in a murine model of chagasic megacolon.

Disorders of gastrointestinal motility are the major physiologic problem in chagasic megacolon. The contraction mechanism is complex and controlled by different cell types such as enteric neurons, smooth muscle, telocytes, and an important pacemaker of the intestine, the interstitial cells of Cajal (ICCs). The role of ICCs in the progression of acute and chronic Chagas disease remains unclear. In the present work, we investigate the aspects of ICCs in a long-term model of Chagas disease that mimics the pathological aspects of human megacolon. Different subsets of ICCs isolated from Auerbach's myenteric plexuses and muscle layers of control and Trypanosoma cruzi infected animals were determined by analysis of CD117, CD44, and CD34 expression by flow cytometer. Compared with the respective controls, the results showed a reduced frequency of mature ICCs in the acute phase and three months after infection. These results demonstrate for the first time the phenotypic distribution of ICCs associated with functional dysfunction in a murine model of chagasic megacolon. This murine model proved valuable for studying the profile of ICCs as an integrative system in the gut and as a platform for understanding the mechanism of chagasic megacolon development.

Vascular Growth Factor Inhibition with Bevacizumab Improves Cardiac Electrical Alterations and Fibrosis in Experimental Acute Chagas Disease.

Chagas disease (CD) caused by Trypanosoma cruzi is a neglected illness and a major reason for cardiomyopathy in endemic areas. The existing therapy generally involves trypanocidal agents and therapies that control cardiac alterations. However, there is no treatment for the progressive cardiac remodeling that is characterized by inflammation, microvasculopathy and extensive fibrosis. Thus, the search for new therapeutic strategies aiming to inhibit the progression of cardiac injury and failure is necessary. Vascular Endothelial Growth Factor A (VEGF-A) is the most potent regulator of vasculogenesis and angiogenesis and has been implicated in inducing exacerbated angiogenesis and fibrosis in chronic inflammatory diseases. Since cardiac microvasculopathy in CD is also characterized by exacerbated angiogenesis, we investigated the effect of inhibition of the VEGF signaling pathway using a monoclonal antibody (bevacizumab) on cardiac remodeling and function. Swiss Webster mice were infected with Y strain, and cardiac morphological and molecular analyses were performed. We found that bevacizumab significantly increased survival, reduced inflammation, improved cardiac electrical function, diminished angiogenesis, decreased myofibroblasts in cardiac tissue and restored collagen levels. This work shows that VEGF is involved in cardiac microvasculopathy and fibrosis in CD and the inhibition of this factor could be a potential therapeutic strategy for CD.

Acute Chagas Disease Presenting as Preseptal Cellulitis.

Chagas disease, also known as American trypanosomiasis, is caused by Trypanosoma cruzi, a parasite transmitted by hematophagous triatomine insects (subfamily Triatominae) belonging to the Reduviidae family, order Hemiptera. Infection occurs through contact with the feces of the infected vector at the site of its bite or on intact mucosa. [Pediatr Ann. 2023;52(10):e394-e397.].

Acute Chagas Disease Outbreak among Military Personnel, Colombia, 2021.

We report an acute Chagas disease outbreak among soldiers in Colombia. Trypanosoma cruzi infection was confirmed through parasitology, serology, and molecular methods. Among 9 affected soldiers, 2 died; 7 were hospitalized and received benznidazole treatment, which produced favorable outcomes. Personnel patrolling rural areas in Colombia could be at increased risk for Chagas disease.

Oral transmission of Chagas disease from a One Health approach: A systematic review.

To analyse acute Chagas disease (CD) outbreaks through a qualitative systematic review and discuss the determinants for its prevention and control. Review of studies in which clinical cases of oral transmission were confirmed by parasitological and/or serological tests that included an epidemiological investigation of sources of infection, vectors and reservoirs. Thirty-two outbreaks (1965-2022) were analysed. The main foods involved in oral transmission outbreaks are homemade fruit juices. Different species of vectors were identified. Reservoirs were mainly dogs, rodents and large American opossums (didelphids). Under a One Health approach, environmental changes are one of the factors responsible of the rise of oral transmission of CD. Entomological surveillance of vectors and control of the changes in wild and domestic reservoirs and reinforcement of hygiene measures around food in domestic and commercial sites are needed.

Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 μg/mL; LC50 26.73 ± 1.2 μg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

Immunization with a Trypanosoma cruzi cyclophilin-19 deletion mutant protects against acute Chagas disease in mice

Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi. This protein in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation whereas in the intracellular amastigotes it participates in generating ROS promoting the growth of parasites. We have generated a parasite mutant with depleted expression of Cyp19 by removal of 2 of 3 genes encoding this protein using double allelic homologous recombination. The mutant parasite line failed to replicate when inoculated into host cells in vitro or in mice indicating that Cyp19 is critical for infectivity. The mutant parasite line also fails to replicate in or cause clinical disease in immuno-deficient mice further validating their lack of virulence. Repeated inoculation of mutant parasites into immuno-competent mice elicits parasite-specific trypanolytic antibodies and a Th-1 biased immune response and challenge of mutant immunized mice with virulent wild-type parasites is 100% effective at preventing death from acute disease. These results suggest that parasite Cyp19 may be candidate for small molecule drug targeting and that the mutant parasite line may warrant further immunization studies for prevention of Chagas disease.

Genetic Ablation and Pharmacological Blockade of Bradykinin B1 Receptor Unveiled a Detrimental Role for the Kinin System in Chagas Disease Cardiomyopathy.

Chagas disease, the parasitic infection caused by Trypanosoma cruzi, afflicts about 6 million people in Latin America. Here, we investigated the hypothesis that T. cruzi may fuel heart parasitism by activating B1R, a G protein-coupled (brady) kinin receptor whose expression is upregulated in inflamed tissues. Studies in WT and B1R-/- mice showed that T. cruzi DNA levels (15 days post infection-dpi) were sharply reduced in the transgenic heart. FACS analysis revealed that frequencies of proinflammatory neutrophils and monocytes were diminished in B1R-/- hearts whereas CK-MB activity (60 dpi) was exclusively detected in B1R+/+ sera. Since chronic myocarditis and heart fibrosis (90 dpi) were markedly attenuated in the transgenic mice, we sought to determine whether a pharmacological blockade of the des-Arg9-bradykinin (DABK)/B1R pathway might alleviate chagasic cardiomyopathy. Using C57BL/6 mice acutely infected by a myotropic T. cruzi strain (Colombian), we found that daily treatment (15-60 dpi) with R-954 (B1R antagonist) reduced heart parasitism and blunted cardiac injury. Extending R-954 treatment to the chronic phase (120-160 dpi), we verified that B1R targeting (i) decreased mortality indexes, (ii) mitigated chronic myocarditis, and (iii) ameliorated heart conduction disturbances. Collectively, our study suggests that a pharmacological blockade of the proinflammatory KKS/DABK/B1R pathway is cardioprotective in acute and chronic Chagas disease.

SPATIAL DISTRIBUTION OF ACUTE CASES OF CHAGAS DISEASE REPORTED FROM 2010 TO 2020 IN THE STATE OF AMAZONAS

This study aimed to investigate the epidemiology of acute cases of Chagas disease notified in the State of Amazonas between the period from 2010 to 2020. Data were obtained from the portal of the Sistema de Informação de Agravos de Notificação- SINAN, considering the number of cases per municipality of notification. 140 cases of Acute Chagas Disease were notified, distributed in 23 of the 62 municipalities of the State of Amazonas, 82 (59%) were male individuals, with a greater predominance in the age group of 20-39 years old, having 45 (32.1%) cases. As for the race/color variable, the highest number was among brown people with 101 (72.1%) notifications. The oral route prevailed as the main form of disease transmission with 93 (66.4%) records. Infection by the oral route of T. cruzi is the most important route of transmission of CD in the State of Amazonas, the occurrence of transmission is associated in most cases with the consumption of foods such as açaí juice and has been reported frequently over the years between municipalities.