Chagas Disease Prevention Research Articles

Modeling the impact of non-human host predation on the transmission of Chagas disease

In addition to the traditional transmission route via the biting-and-defecating process, non-human host predation of triatomines is recognized as another significant avenue for Chagas disease transmission. In this paper, we develop an eco-epidemiological model to investigate the impact of predation on the disease’s spread. Two critical thresholds, Rvp (the basic reproduction number of triatomines) and R0p (the basic reproduction number of the Chagas parasite), are derived to delineate the model’s dynamics. Through the construction of appropriate Lyapunov functions and the application of the Bendixson–Dulac theorem, the global asymptotic stabilities of the equilibria are fully established. The vector-free equilibrium E0 is globally stable when Rvp<1. E1, the disease-free equilibrium, is globally stable when Rvp>1 and R0p<1, while the endemic equilibrium E∗ is globally stable when both Rvp>1 and R0p>1. Numerical simulations highlight that the degree of host predation on triatomines, influenced by non-human hosts activities, can variably increase or decrease the Chagas disease transmission risk. Specifically, low or high levels of host predation can reduce R0p to below unity, while intermediate levels may increase the infected host populations, albeit with a reduction in R0p. These findings highlight the role played by non-human hosts and offer crucial insights for the prevention and control of Chagas disease.

Machine learning for predicting Chagas disease infection in rural areas of Brazil.

Chagas disease is a severe parasitic illness that is prevalent in Latin America and often goes unaddressed. Early detection and treatment are critical in preventing the progression of the illness and its associated life-threatening complications. In recent years, machine learning algorithms have emerged as powerful tools for disease prediction and diagnosis. In this study, we developed machine learning algorithms to predict the risk of Chagas disease based on five general factors: age, gender, history of living in a mud or wooden house, history of being bitten by a triatomine bug, and family history of Chagas disease. We analyzed data from the Retrovirus Epidemiology Donor Study (REDS) to train five popular machine learning algorithms. The sample comprised 2,006 patients, divided into 75% for training and 25% for testing algorithm performance. We evaluated the model performance using precision, recall, and AUC-ROC metrics. The Adaboost algorithm yielded an AUC-ROC of 0.772, a precision of 0.199, and a recall of 0.612. We simulated the decision boundary using various thresholds and observed that in this dataset a threshold of 0.45 resulted in a 100% recall. This finding suggests that employing such a threshold could potentially save 22.5% of the cost associated with mass testing of Chagas disease. Our findings highlight the potential of applying machine learning to improve the sensitivity and effectiveness of Chagas disease diagnosis and prevention. Furthermore, we emphasize the importance of integrating socio-demographic and environmental factors into neglected disease prediction models to enhance their performance.

A scoping review of triatomine control for Chagas disease prevention: current and developing tools in Latin America and the United States.

Chagas disease is an infectious disease of human and animal health concern, with 6-8 million chronic human infections and over 50,000 deaths throughout the Americas annually. Hematophagous insects of the subfamily Triatominae, also called kissing bugs, vector the protozoan parasite, Trypanosoma cruzi Chagas (Trypanosomatida: Trypanosomatidae),that causes Chagas disease. Despite the large human health burden, Chagas disease is a neglected tropical disease with inadequate funding for research and preventive practices. Given the resource-poor environment of most agencies trying to protect public health, it is critical to consider all control options for reducing vector populations and the risk of human exposure to T. cruzi to identify the most appropriate tools for each context. While numerous triatomine control methods exist, the literature lacks a compilation of the strategies used, a critical examination of their efficiency, and a particular focus on triatomine control in the United States compared to elsewhere in the Americas. Here, we present a review of the literature to assess historical intervention strategies of existing and developing triatomine control methods. For each method, we discuss progress in the field, future research to further advance the method, and limitations. While we found that pyrethroid insecticide is still the most commonly used method of triatomine and Chagas disease control, we suggest that complementing these techniques with alternative control methods in development will help to achieve Chagas disease reduction goals.

The Perception of the American Trypanosomiasis "Disease of Chagas" in the Traditional Community of the Brazilian Amazon

Objective: To evaluate the perception of residents of the Bacuri community in the municipality of Cachoeira do Arari, Pará, about American trypanosomiasis, known as Chagas disease, in order to expand awareness and control strategies for the disease, in addition to providing specific information about its main vector, the popular barber, and reduce the appearance of epidemiological cases in the region. Method: An “on-site” visit was carried out, applied to questionnaires composed of open and closed multiple-choice questions and in-depth interviews, with a descriptive statistical analysis being carried out with the aid of the Microsoft Excel 2010 program, calculating the relative and absolute frequency in a quantitative way. Theoretical reference: the research has its main theoretical bases in current scientific articles on the subject. Result and conclusion: The results showed that 98% of the participants said they knew the disease superficially and also did not receive visits from health agents, 68% said they only knew those in the chronic phase of the disease. As for the vector 72%, the appearance of these insects is common in the community. Implications of the research: this work is an important tool for raising awareness among traditional peoples of the Brazilian Amazon for the control and prevention of Chagas disease, in addition to expanding the range of information regarding the disease in the region. Originality/value: The research indicated that popular knowledge about the disease is of fundamental importance for its treatment and an alternative given the lack of awareness campaigns in the region, which portrays a reality within rural communities in the Brazilian Amazon.

Assessing the impact of host predation with Holling II response on the transmission of Chagas disease

Chagas disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi and transmitted by a broad range of blood-sucking triatomine species. Recently, it is recognized that the parasite can also be transmitted by host ingestion. In this paper, we propose a Chagas disease model incorporating two transmission routes of biting-defecation and host predation between vectors and hosts with Holling II functional response. The basic reproduction number R_v of triatomine population and basic reproduction numbers R_0 of disease population are derived analytically, and it is shown that they are insufficient to serve as threshold quantities to determine dynamics of the model. Our results have revealed the phenomenon of bistability, with backward and forward bifurcations. Specifically, if R_v&gt;1, the dynamic is rather simple, namely, the disease-free equilibrium is globally asymptotically stable as R_0&lt;1 and a unique endemic equilibrium is globally asymptotically stable as R_0&gt;1. However, if R_v&lt;1, there exists a backward bifurcation with one unstable and one stable positive vector equilibria, and bistability phenomenon occurs, revealing that different initial conditions may lead to disease extinction or persistence even if the corresponding R_0&gt;1. In conclusion, predation transmission in general reduces the risk of Chagas disease, whilst it makes the complexity of Chagas disease transmission, requiring an integrated strategy for the prevention and control of Chagas disease.

Prevention of congenital Chagas disease by screening of mothers and monitoring of serological tests of neonates: the seven years' experience.

Approximately 14000 immigrants coming from the Cochabamba area of Bolivia, with an increased risk of congenital Chagas Disease (CD), are currently living in Bergamo, Italy. According to the World Health Organization (WHO) recommendation (2011), prevention of congenital CD involves testing all pregnant women at risk of infection and performing follow-up of their newborns. In our study, all pregnant women of Latin American origin were tested for the presence of Trypanosoma cruzi antibodies and children, born to mothers found to be positive, were followed up after delivery. T. cruzi antibodies were detected using a chemiluminescence immunoassay. The test was also performed on siblings and fathers of children with CD, and women of childbearing age to prevent the congenital infection, as proposed by 2011 WHO recommendation. In the study period 1105 patients were tested for CD, using a serological test: 934 (85%) were females and 171 (15%) were males. Of the 62 newborns, from mothers who tested positive, 28 were females and 34 were males. The number of positive adults and siblings identified was 148 (14%). Among the adults and siblings born between 1991 and 2011 only 3 (2%) of females tested positive to serological test. All neonates, with the exception of one, were classified as non-infected according to the follow-up of index value of CD serology. This study confirms the usefulness of serological tests and of their index value as follow-up. The difference of positivity rate for CD antibodies between people born before and after 1990 should be further investigated to generate information that potentially improve the prevention and control of CD.

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.

Identifying Barriers and Facilitators for Home Reconstruction for Prevention of Chagas Disease: An Interview Study in Rural Loja Province, Ecuador

Chagas disease (CD) is a tropical parasitic disease spread by triatomine bugs, which are bugs that tend to infest precarious housing in rural and impoverished areas. Reducing exposure to the bugs, and thus the parasite they can carry, is essential to preventing CD in these areas. One promising long-term sustainable solution is to reconstruct precarious houses. Implementing home reconstruction requires an understanding of how householders construct barriers and facilitators they might encounter when considering whether to rebuild their homes. To understand barriers and facilitators to home reconstruction, we performed in-depth qualitative interviews with 33 residents of Canton Calvas, Loja, Ecuador, a high-risk endemic region. Thematic analysis was used to identify these barriers and facilitators. The thematic analysis identified three facilitators (project facilitators, social facilitators, and economic facilitators) and two major barriers (low personal economy and extensive deterioration of existing homes). The study findings provide important loci for assisting community members and for agents of change in home reconstruction projects to prevent CD. Specifically, the project and social facilitators suggest that collective community efforts (minga) are more likely to support home reconstruction intentions than individualist efforts, while the barriers suggest that addressing structural issues of economy and affordability are necessary.

A Questionnaire Integrated with the Digital Medical Record Improved the Coverage of a Control Program for Congenital Chagas Disease in Tuscany, Italy.

The leading route of Chagas disease transmission in nonendemic countries is congenital. However, policies concerning screening, prevention, and management of congenital Chagas disease are rare in these settings. Since 2012, serological screening for Chagas disease should be provided for pregnant women at risk in Tuscany, Italy according to a Regional resolution. Due to difficulties in the implementation, in November 2019, a checklist aimed at identifying pregnant women at risk for Chagas disease was introduced in digital clinical records at Careggi University Hospital, Florence, Italy. In order to evaluate the effectiveness of the "Chagas checklist", data about the number of deliveries by women at risk and their screening coverage between 2012 and June 2022 were collected. Out of 1348 deliveries by women at risk, 626 (47%) Trypanosoma cruzi serology tests were performed during the study period. The annual screening coverage increased from an average of 40.3% between 2012 and 2019 to 75.7% between 2020 and June 2022, underlining the big impact of the checklist. Four Chagas disease serological tests out of 626 (0.6%) resulted positive, corresponding to 2 affected women. No cases of congenital transmission occurred. The study showed that a simple digital tool led to a tangible improvement in the coverage of the screening program; its application in a setting where digital charts are available will contribute to the control and elimination of congenital Chagas disease.

Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates

Trypanosoma cruzi, the agent of Chagas disease, probably infects tens of millions of people, primarily in Latin America, causing morbidity and mortality. The options for treatment and prevention of Chagas disease are limited and underutilized. Here we describe the discovery of a series of benzoxaborole compounds with nanomolar activity against extra- and intracellular stages of T. cruzi. Leveraging both ongoing drug discovery efforts in related kinetoplastids, and the exceptional models for rapid drug screening and optimization in T. cruzi, we have identified the prodrug AN15368 that is activated by parasite carboxypeptidases to yield a compound that targets the messenger RNA processing pathway in T. cruzi. AN15368 was found to be active in vitro and in vivo against a range of genetically distinct T. cruzi lineages and was uniformly curative in non-human primates (NHPs) with long-term naturally acquired infections. Treatment in NHPs also revealed no detectable acute toxicity or long-term health or reproductive impact. Thus, AN15368 is an extensively validated and apparently safe, clinically ready candidate with promising potential for prevention and treatment of Chagas disease.

Chronic Chagas Disease-the Potential Role of Reinfections in Cardiomyopathy Pathogenesis.

Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections' role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections. Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the host's immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. Animal models suggest that reinfections lead to worse outcomes and increased mortality, while other studies showed an association between reinfections and lower parasitemia levels and subsequent infection protection. In some regions, the human risk of reinfections is 14% at 5years. Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes. Control efforts should be redirected to interventions that address structural poverty for the successful and sustainable prevention of Chagas disease.

Hansel, Gretel, and the Chinchorro: A Live Performance Entertainment Education Approach to Chagas Disease in Rural Ecuador

ABSTRACT Impoverished rural communities are disproportionately affected by a neglected tropical disease called Chagas disease. Because it is a disease that affects the poor, governments inconsistently respond and, when they respond, governments use insecticides that are expensive for the affected communities and unhealthy for their inhabitants. Primary prevention of Chagas disease is essential. The present study reports on an entertainment education approach that sought to raise awareness of Chagas and its insect vector, the triatomine bug. As part of our ongoing efforts in rural Ecuador, we worked with the children of Chaquizhca to create plays that would promote awareness of triatomine bugs and associate the bugs with Chagas disease. Through an analysis of the plays the children wrote, we demonstrate opportunities and challenges that local scale entertainment education approaches face in when adopting community-centered participatory approaches in rural communities.

Updated Estimates and Mapping for Prevalence of Chagas Disease among Adults, United States.

We combined American Community Survey data with age-specific Trypanosoma cruzi prevalence derived from US surveys and World Health Organization reports to yield estimates of Chagas disease in the United States, which we mapped at the local level. In addition, we used blood donor data to estimate the relative prevalence of autochthonous T. cruzi infection. Our estimates indicate that 288,000 infected persons, including 57,000 Chagas cardiomyopathy patients and 43,000 infected reproductive-age women, currently live in the United States; 22-108 congenital infections occur annually. We estimated ≈10,000 prevalent cases of locally acquired T. cruzi infection. Mapping shows marked geographic heterogeneity of T. cruzi prevalence and illness. Reliable demographic and geographic data are key to guiding prevention and management of Chagas disease. Population-based surveys in high prevalence areas could improve the evidence base for future estimates. Knowledge of the demographics and geographic distribution of affected persons may aid practitioners in recognizing Chagas disease.

Modelling the dynamics of Trypanosoma rangeli and triatomine bug with logistic growth of vector and systemic transmission.

In this paper, an insect-parasite-host model with logistic growth of triatomine bugs is formulated to study the transmission between hosts and vectors of the Chagas disease by using dynamical system approach. We derive the basic reproduction numbers for triatomine bugs and Trypanosoma rangeli as two thresholds. The local and global stability of the vector-free equilibrium, parasite-free equilibrium and parasite-positive equilibrium is investigated through the derived two thresholds. Forward bifurcation, saddle-node bifurcation and Hopf bifurcation are proved analytically and illustrated numerically. We show that the model can lose the stability of the vector-free equilibrium and exhibit a supercritical Hopf bifurcation, indicating the occurrence of a stable limit cycle. We also find it unlikely to have backward bifurcation and Bogdanov-Takens bifurcation of the parasite-positive equilibrium. However, the sustained oscillations of infected vector population suggest that Trypanosoma rangeli will persist in all the populations, posing a significant challenge for the prevention and control of Chagas disease.

Waiting for a success story in prevention, control and treatment of Chagas disease in non-endemic countries

Waiting for a success story in prevention, control and treatment of Chagas disease in non-endemic countries

Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea?

Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.

CULTURAL KNOWLEDGE AND EXPERIENCES OF TRIATOMINES AND CHAGAS DISEASE IN THE CITY OF MÉRIDA, MEXICO

Human-k triatomine insects’ interaction is a milestone in Chagas Disease (CD) prevention and control. We studied and compared ethnoecology and cultural knowledge and experiences about triatomines and Chagas of two urban social groups, and of health technicians of the vector control program in Merida city, southeastern Mexico. We conducted semi-structure interviews: 24 participants living in very low marginalization index (VLMi) and 26 of very high marginalization index (VHMi) areas in Merida, and 15 health workers. Questions focused on ethno-ecology and health-related knowledge of blood-sucking insects, and experiences on triatomine bites and CD, same than treatment and diagnosis of both bites and the disease. A thematic content-analysis and descriptive statistics were followed. Triatomines were considered a health danger due to the perception of them as poisonous and causing infection. Participants of VLMi were more knowledgeable about CD compared to VHMi participants, but they had limited understanding of the overall to chronicity when compared to health technicians. VHMi showed a more elaborate ethno-ecological knowledge about triatomines and had more exposition to them. Across participants, a biased understanding about CD has been recorded, since it was given emphasis only on acute phase aspects but not on chronic symptomatology. Cultural knowledge about CD remains rather theoretical since it keeps a very unfamiliar disease due to the lack of individual and collectively shared experiences on therapeutic itineraries and illness. There is an urgent need to focus on CD also as a chronic disease by giving more visibility to its prevalence, more advances in diagnostic and treatment, a proper medical care need, as well as illness experiences, and its human impact.

Congenital Chagas disease: progress toward implementation of pregnancy-based screening.

Lack of recognition of congenital Chagas disease in infants of mothers from endemic regions who are living in countries nonendemic for Trypanosoma cruzi infection suggests a high rate of underdiagnosis. Pregnancy is the optimal access point for identifying Chagas disease in at-risk mothers and their infants. In this review, we update progress toward implementation of pregnancy-based screening for congenital Chagas disease in nonendemic settings. International organizations have updated recommendations for diagnosis, treatment and prevention of congenital Chagas disease. Reports of successful implementation of pregnancy-based screening at some centers provide a model for optimizing diagnosis of congenital Chagas disease. Screening family members of index patients may identify additional T. cruzi-infected persons. Promising tests to augment current diagnostic modalities for maternal and congenital Chagas disease are in development. Universal or risk-based screening would be cost-effective. More healthcare providers are now aware that treatment of congenital Chagas disease is curative and are promoting efforts to make pregnancy-based screening for congenital Chagas disease a standard of care. Ongoing efforts to implement routine pregnancy-based screening for congenital Chagas disease in nonendemic regions will mutually benefit infants, their mothers and family members and can prevent potentially fatal Chagas cardiomyopathy.

IgG Subclass Analysis in Patients with Chagas Disease 4Years After Benznidazole Treatment.

In humans, Trypanosoma cruzi infection is controlled by a complex immune response. Immunoglobulin G (IgG) is important for opsonizing blood trypomastigotes, activating the classic complement pathway, and reducing parasitemia. The trypanocidal activity of benznidazole is recognized, but its effects on the prevention and progression of Chagas disease is not well understood OBJECTIVE: We aimed to evaluate the levels of total IgG and cross-specific IgG subclasses in patients with chronic Chagas disease of different clinical forms before and after 4years of benznidazole treatment. Eight individuals with the indeterminate form and nine with the cardiac form who completed the treatment protocol were evaluated. The levels of total IgG and IgG1, IgG2, IgG3, and IgG4 isotypes were quantified in the serum of each individual using the fluorescent immunosorbent assay. The results are expressed as relative fluorescence unit. Patients with chronic Chagas disease presented decreased levels of total IgG at 48months after benznidazole treatment. Increased IgG1 and decreased IgG3 levels were observed in patients with the cardiac form and those with exacerbated clinical forms. In addition, a decrease in the IgG3/IgG1 ratio was observed in individuals with the cardiac form of Chagas disease. Benznidazole administration in the chronic phase differentially changes IgG subclasses in patients with cardiac and indeterminate forms, and monitoring the IgG3 level may indicate the possible prognosis to the cardiac form or worsening of the already established clinical form.

Key Chagas disease missing knowledge among at-risk population in Spain affecting diagnosis and treatment

BackgroundChagas disease is endemic in Latin America and, over the last few decades, due to population movements, the disease has spread to other continents. Early diagnosis and treatment are critical in terms of improving outcomes for those living with Chagas disease. However, poor knowledge and awareness is one of barriers that affects access to Chagas disease diagnosis and treatment for the population at risk. Information regarding immigrants’ knowledge concerning Chagas disease control and prevention is insufficient in non-endemic countries and, therefore, this study sought to assess Chagas disease knowledge and awareness within the Bolivian community residing in Madrid.MethodsThis cross-sectional study was carried out in March–August 2017. A total of 376 Bolivians answered a structured questionnaire. A knowledge index was created based on respondents’ knowledge about transmission, symptoms, diagnosis, and place to seek treatment. Multivariate logistic regressions analyses were performed to assess the factors associated with respondents’ knowledge of Chagas disease.ResultsA total 159 (42.4%) of Bolivians interviewed about their knowledge of Chagas disease were men and 217 (57.6%) were women. Vinchuca was mentioned as mode of transmission by 71% of the Bolivians surveyed, while only 9% mentioned vertical transmission. Almost half of the Bolivians did not know any symptom of Chagas disease and only 47% knew that a specific blood test is necessary for diagnosis. Most of Bolivians were aware of the severity of Chagas disease, but 45% of Bolivians said that there is no cure for Chagas and 96% did not know any treatment. Based on the index of knowledge generated, only 34% of Bolivians had a good knowledge about Chagas disease transmission, symptoms, diagnosis and treatment. According to the multiple logistic regression analysis, knowledge regarding Chagas disease, diagnosis and treatment was significantly higher amongst older Bolivians who had secondary education at least, as well as amongst those who had already been tested for Chagas disease.ConclusionsThis study found that most of the Bolivian population living in Spain had poor knowledge about Chagas disease transmission, symptoms, diagnostic methods and treatment. A poor understanding of the disease transmission and management is one of the most important barriers when it comes to searching for early diagnosis and appropriate care.