The Global Burden of Disease of Chagas Disease (American Trypanosomiasis)

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (1 October 2021) | Viewed by 29562

Special Issue Editors


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Guest Editor
1. College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
2. Department of Medicine, Division of Infectious Diseases, Anschutz Medical Center, University of Colorado, Aurora, CO, USA
3. Instituto Nacional de Salud, Hospital Infantil de México, Federico Gomez, México City, Mexico
Interests: vaccines; preventable diseases; neglected tropical diseases; tropical medicine; Chagas disease; cryptococcosis
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Guest Editor
Department of Medicine, Division of Infectious Diseases, Anschutz Medical Center, University of Colorado, Aurora, CO 80045, USA
Interests: tropical medicine; Chagas disease; cryptococcosis

Special Issue Information

Dear Colleagues,

Chagas disease (American trypanosomiasis), caused by the protozoan Trypanosoma cruzi, remains a significant cause of illness, disability, and death in Latin America. Due to the global migration of individuals from highly endemic areas and the latency of infection, Chagas disease has been identified in many countries. The disease remains predominantly a major neglected tropical disease of disenfranchised populations, reflecting the historical social and geopolitical realities that have prevailed in Mexico and Central and South America. An estimated 6–8 million infected individuals live in South America, Central America, and Mexico. In most endemic areas, vector-borne transmission is the most relevant form of human infection. As a result, large-scale vector-control programs, particularly in the Southern cone countries of South America, have reduced the incidence of Chagas disease [3–10]. Similarly, blood bank screening practices in endemic settings have decreased the number of infections acquired through this route [5,10]. Despite many achievements in reducing the overall burden of T. cruzi transmission in Latin America, there have been a series of recently documented reinfestations of previously insecticide-treated communities in parts of Venezuela, Colombia, and Bolivia [10]. Over the last few decades, the ingestion of foods or beverages contaminated with complete triatomines or their feces containing metacyclic trypomastigotes has been responsible for many cases of orally acquired Chagas disease. Chagas disease manifests most frequently as a cardiomyopathy; it is diverse and difficult to predict, with some patients remaining asymptomatic throughout their lifespan despite electrocardiographic or echocardiographic evidence of the disease, some presenting with signs, symptoms, and complications of progressive heart failure or life-threatening cardiac arrhythmias, and others dying unexpectedly without prior symptoms. Some other infected individuals may manifest gastrointestinal manifestations including esophageal or colonic dysfunction. The burden of disease of Chagas disease is substantial in terms of premature death, disability, and years lost in productivity.

This Special Issue will highlight various aspects of Chagas disease in endemic regions as well as other countries due to international migration from endemic countries. This Special Issue will explore new concepts in our understanding of Chagas disease, including:

  • The increasing identification of the oral transmission of Chagas disease;
  • Duration of antiparasitic therapy;
  • Shorter latency of Chagas disease;
  • Acute manifestations of Chagas disease.

Prof. Dr. Carlos Franco-Paredes
Dr. Andrés F. Henao-Martínez
Guest Editors

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Keywords

  • Chagas disease
  • American trypanosomiasis
  • Cardiomyopathy
  • Gastrointestinal
  • Esophageal dysfunction

Published Papers (6 papers)

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Research

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10 pages, 1783 KiB  
Article
Lopinavir and Nelfinavir Induce the Accumulation of Crystalloid Lipid Inclusions within the Reservosomes of Trypanosoma cruzi and Inhibit Both Aspartyl-Type Peptidase and Cruzipain Activities Detected in These Crucial Organelles
by Leandro S. Sangenito, Miria G. Pereira, Thais Souto-Padron, Marta H. Branquinha and André L. S. Santos
Trop. Med. Infect. Dis. 2021, 6(3), 120; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6030120 - 01 Jul 2021
Cited by 4 | Viewed by 3941
Abstract
Several research groups have explored the repositioning of human immunodeficiency virus aspartyl peptidase inhibitors (HIV-PIs) on opportunistic infections caused by bacteria, fungi and protozoa. In Trypanosoma cruzi, HIV-PIs have a high impact on parasite viability, and one of the main alterations promoted [...] Read more.
Several research groups have explored the repositioning of human immunodeficiency virus aspartyl peptidase inhibitors (HIV-PIs) on opportunistic infections caused by bacteria, fungi and protozoa. In Trypanosoma cruzi, HIV-PIs have a high impact on parasite viability, and one of the main alterations promoted by this treatment is the imbalance in the parasite’s lipid metabolism. However, the reasons behind this phenomenon are unknown. In the present work, we observed by transmission electron microscopy (TEM) that the treatment of T. cruzi epimastigotes with the HIV-PIs lopinavir and nelfinavir induced a huge accumulation of crystalloid-shaped lipids within the reservosomes, most of them deforming these key organelles. As previously reported, those structures are characteristic of lipid inclusions formed mostly of cholesterol and cholesterol-esters. The fractionation of nontreated epimastigotes generated two distinct fractions enriched in reservosomes: one mostly composed of lipid inclusion-containing reservosomes (Fraction B1) and one where lipid inclusions were much less abundant (Fraction B2). Interestingly, the extract of Fraction B2 presented enzymatic activity related to aspartyl-type peptidases 3.5 times higher than that found in the extract obtained from Fraction B1. The cleavage of cathepsin D substrate by this class of peptidases was strongly impaired by pepstatin A, a prototypical aspartyl PI, and the HIV-PIs lopinavir and nelfinavir. In addition, both HIV-PIs also inhibited (to a lesser extent) the cruzipain activity present in reservosomes. Finally, our work provides new evidence concerning the presence and supposed participation of aspartyl peptidases in T. cruzi, even as it adds new information about the mechanisms behind the alterations promoted by lopinavir and nelfinavir in the protozoan. Full article
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9 pages, 613 KiB  
Article
Experiences with Diagnosis and Treatment of Chagas Disease at a United States Teaching Hospital—Clinical Features of Patients with Positive Screening Serologic Testing
by Peter Hyson, Lilian Vargas Barahona, Laura C. Pedraza-Arévalo, Jonathan Schultz, Luisa Mestroni, Maria da Consolação Moreira, Matthew Taylor, Carlos Franco-Paredes, Esther Benamu, Poornima Ramanan, Anis Rassi, Jr., Kellie Hawkins and Andrés F. Henao-Martínez
Trop. Med. Infect. Dis. 2021, 6(2), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020093 - 31 May 2021
Cited by 5 | Viewed by 5417
Abstract
Chagas disease (CD) is the third most common parasitic infection globally and can cause cardiac and gastrointestinal complications. Around 300,000 carriers of CD live in the U.S., with about 3000 of those in Colorado. We described our experience in diagnosing CD at a [...] Read more.
Chagas disease (CD) is the third most common parasitic infection globally and can cause cardiac and gastrointestinal complications. Around 300,000 carriers of CD live in the U.S., with about 3000 of those in Colorado. We described our experience in diagnosing CD at a Colorado teaching hospital to revise screening eligibility criteria. From 2006 to 2020, we reviewed Trypanosoma cruzi (TC) IgG serology results for 1156 patients in our institution. We identified 23 patients (1.99%) who had a positive test. A total of 14/23 (60%) of positive serologies never had confirmatory testing, and 7 of them were lost to follow up. Confirmatory testing, performed in 9 patients, resulted in being positive in 3. One additional case of CD was identified by positive tissue pathology. All four confirmed cases were among patients born in Latin America. While most of the testing for CD at our institution is part of the pretransplant screening, no confirmed cases of CD derived from this strategy. Exposure risk in this population is not always documented, and initial positive results from screening are not always confirmed. The lack of standardized screening protocols for CD in our institution contributes to underdiagnosis locally and in health systems nationwide. Given a large number of individuals in the U.S. with chronic CD, improved screening is warranted. Full article
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15 pages, 3539 KiB  
Article
Elevated Pediatric Chagas Disease Burden Complicated by Concomitant Intestinal Parasites and Malnutrition in El Salvador
by Melissa S. Nolan, Kristy O. Murray, Rojelio Mejia, Peter J. Hotez, Maria Jose Villar Mondragon, Stanley Rodriguez, Jose Ricardo Palacios, William Ernesto Murcia Contreras, M. Katie Lynn, Myriam E. Torres and Maria Carlota Monroy Escobar
Trop. Med. Infect. Dis. 2021, 6(2), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020072 - 07 May 2021
Cited by 8 | Viewed by 6677
Abstract
The eradication of the vector Rhodnius prolixus from Central America was heralded as a victory for controlling transmission of Trypanosoma cruzi, the parasite that causes Chagas disease. While public health officials believed this milestone achievement would effectively eliminate Chagas disease, case reports [...] Read more.
The eradication of the vector Rhodnius prolixus from Central America was heralded as a victory for controlling transmission of Trypanosoma cruzi, the parasite that causes Chagas disease. While public health officials believed this milestone achievement would effectively eliminate Chagas disease, case reports of acute vector transmission began amassing within a few years. This investigation employed a cross-sectional serosurvey of children either presenting with fever for clinical care or children living in homes with known triatomine presence in the state of Sonsonate, El Salvador. Over the 2018 calendar year, a 2.3% Chagas disease seroprevalence among children with hotspot clustering in Nahuizalco was identified. Positive serology was significantly associated with dogs in the home, older participant age, and a higher number of children in the home by multivariate regression. Concomitant intestinal parasitic infection was noted in a subset of studied children; 60% having at least one intestinal parasite and 15% having two or more concomitant infections. Concomitant parasitic infection was statistically associated with an overall higher parasitic load detected in stool by qPCR. Lastly, a four-fold higher burden of stunting was identified in the cohort compared to the national average, with four-fifths of mothers reporting severe food insecurity. This study highlights that polyparasitism is common, and a systems-based approach is warranted when treating Chagas disease seropositive children. Full article
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Review

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9 pages, 266 KiB  
Review
Screening for Chagas Disease during Pregnancy in the United States—A Literature Review
by Elizabeth G. Livingston, Ryan Duggal and Sarah Dotters-Katz
Trop. Med. Infect. Dis. 2021, 6(4), 202; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6040202 - 26 Nov 2021
Cited by 2 | Viewed by 2807
Abstract
Obstetrician-gynecologists in the United States have little clinical experience with the epidemiology, pathophysiology, diagnosis, and treatment of Chagas disease. The number of US parturients born in Central and South America has continued to increase over the last 20 years, making US obstetricians more [...] Read more.
Obstetrician-gynecologists in the United States have little clinical experience with the epidemiology, pathophysiology, diagnosis, and treatment of Chagas disease. The number of US parturients born in Central and South America has continued to increase over the last 20 years, making US obstetricians more and more likely to care for Chagas-infected mothers who may never be identified until dealing with long-term consequences of the disease. A literature search demonstrates that few US obstetric care providers recognize the risk of vertical transmission for the neonate and the missed opportunity of infant treatment to decrease disease prevalence. Most women will be asymptomatic during pregnancy, as will their neonates, making routine laboratory screening a necessity for the identification of at-risk neonates. While the benefits of treating asymptomatic women identified in pregnancy are not as clear as the benefits for the infants, future health screenings for evidence of the progression of Chagas disease may be beneficial to these families. The literature suggests that screening for Chagas in pregnancy in the US can be done in a cost-effective way. When viewed through an equity lens, this condition disproportionately affects families of lower socioeconomic means. Improved education of healthcare providers and appropriate resources for diagnosis and treatment can improve this disparity in health outcomes. Full article
10 pages, 291 KiB  
Review
Chagas Disease in People with HIV: A Narrative Review
by Eva H. Clark and Caryn Bern
Trop. Med. Infect. Dis. 2021, 6(4), 198; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6040198 - 09 Nov 2021
Cited by 8 | Viewed by 3197
Abstract
Many questions remain unanswered regarding the epidemiology, pathophysiology, diagnosis, treatment, and monitoring of Trypanosoma cruzi infection in people with HIV (PWH). The reported prevalence of T. cruzi infection in PWH living in endemic countries ranges from 1–28% and is likely similar in at-risk [...] Read more.
Many questions remain unanswered regarding the epidemiology, pathophysiology, diagnosis, treatment, and monitoring of Trypanosoma cruzi infection in people with HIV (PWH). The reported prevalence of T. cruzi infection in PWH living in endemic countries ranges from 1–28% and is likely similar in at-risk US populations. While classic cardiac and gastrointestinal presentations of chronic Chagas disease occur in PWH, PWH are additionally at risk for a severe and often fatal form of T. cruzi-mediated disease called reactivation disease. T. cruzi reactivation typically occurs in PWH with low CD4 counts and poor virologic control. National HIV guidelines in several endemic South American countries recommend that all PWH be screened for T. cruzi infection at the time of HIV diagnosis; however, this recommendation is not widely implemented. The early detection of T. cruzi infection in PWH is critical as the sequelae of Chagas disease, including T. cruzi reactivation, may be preventable through the restoration of robust cellular immunity via the initiation of antiretroviral therapy and the appropriate use of antitrypanosomal therapy. Full article
15 pages, 628 KiB  
Review
A Rapid Review on the Efficacy and Safety of Pharmacological Treatments for Chagas Disease
by Cody J Malone, Immaculate Nevis, Eduardo Fernández and Ana Sanchez
Trop. Med. Infect. Dis. 2021, 6(3), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6030128 - 12 Jul 2021
Cited by 9 | Viewed by 4862
Abstract
Chagas disease remains a neglected tropical disease, causing significant burden in the Americas and countries that receive immigrants from endemic nations. Current pharmaceutical treatments are suboptimal, not only varying drastically in efficacy, depending on the stage of disease, but also presenting significant risk [...] Read more.
Chagas disease remains a neglected tropical disease, causing significant burden in the Americas and countries that receive immigrants from endemic nations. Current pharmaceutical treatments are suboptimal, not only varying drastically in efficacy, depending on the stage of disease, but also presenting significant risk of adverse events. The objective of this review is to provide a timely update on the efficacy and safety of current trypanocidals. Eligible studies published from January 2015 to December 2020 were retrieved by one reviewer from six electronic databases. Ana-lysis was done with review management software and risk of bias was assessed using tools appropriate for the type of study (i.e., experimental or observational). Thirteen studies (10 observational and three RCTs) were included in the analysis. All 13 studies tested Benznidazole (BNZ) or Nifurtimox (NFX), and two studies also tested Posaconazole (POS) or E1224 (Ravucanazole). BNZ was found to be the most efficacious trypanocidal drug compared to Nifurtimox, POS, and E1224; it also resulted in the highest percentage of adverse effects (AEs) and treatment discontinuation due to its toxicity. Adults experienced higher frequency of neurological AEs while taking BNZ or NFX compared to children. Children had a higher frequency of general AEs compared to adults while taking BNZ. Overall, BNZ is still the most efficacious, but development of new, less toxic drugs is paramount for the quality of life of patients. Studies testing combination therapies and shorter regimens are needed, as is the devising of better clinical parameters and laboratory biomarkers to evaluate treatment efficacy. Considering the variability in methodology and reporting of the studies included in the present analysis, we offer some recommendations for the improvement and replicability of clinical studies investigating pharmacological treatment of Chagas disease. These include full disclosure of methodology, standardization of outcome measures, and always collecting and reporting data on both the efficacy of trypanocidals and on safety outcomes. Full article
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