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The relationship between genome biology and Chagas disease involves both the parasite Trypanosoma cruzi, its vectors (transmitting insects) and the human host. Understanding the genome of these organisms is fundamental to understanding the diversity, adaptation, transmission and evolution of the disease, in addition to influencing the susceptibility and severity of clinical manifestations.

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Chagas disease, caused by the parasite Trypanosoma cruzi, presents a diverse spectrum of clinical manifestations ranging from asymptomatic, indeterminate chronic infections to severe, acute presentations. The disease can be transmitted through diverse routes, including vectorial contact, congenital infection, blood transfusion, and even orally. These articles provides an in‐depth analysis of two case studies: one detailing an acute outbreak transmitted by contaminated food and beverages in Venezuela and another outlining a chronic case-control study focused on chronic Chagas heart disease (CCHD) in patients over 50 years of age. These case studies highlight the implications for timely diagnosis, management, and public health strategies.

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Chagas disease is an example of how global inequalities impact health. There is an urgent need for a bioethical approach that combines equitable access to treatment, responsible research, and combating the disease's social determinants while respecting the dignity of those affected.

In line with the fifth pillar of genomics, social and ethical implications, affected populations must be not only considered in scientific research but meaningfully included in decision-making processes, ensuring that genomic advances and healthcare innovations serve those most in need and do not reinforce existing disparities.

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1. Comprehensiveness

2. Scale

3. Rapid data release

4. Technology

5. Social and ethical implications

Following the 5 pillars of genomics, we evaluated each case study to verify whether each pillar was present or absent.

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Acute Phase Case Study: Oral Chagas Disease Outbreak in Venezuela

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Acute Phase Case Study: Oral Chagas Disease Outbreak in Venezuela

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The study documented 10 outbreaks across various regions, with a major outbreak occurring in Caracas involving 249 cases, predominantly affecting children (73.5% of cases) and showing a mortality rate of 4%. The oral route of transmission was clearly identified as the vector’s contamination of consumables such as açaí and sugar cane juices. This novel mode of transmission required a diagnostic strategy that combined the detection of both IgG and IgM antibodies via enzyme-linked immunosorbent assay (ELISA) with direct parasite identification among individuals at risk.

Their approach consisted of patient screening, identifications of at-risk individuals and vector identification, on which they pointed some key features of the outbreak, like age distribution, mortality and severity and diagnosis and follow-up.

They also pointed some implications in Venezuela, such as public health responses, diagnostic adaptation and preventive measures, due to the oral transmission outbreak.

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Update on oral Chagas disease outbreaks in Venezuela_ epidemiological, clinical and diagnostic approaches

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This technique allows the rapid and economical sequencing of large volumes of DNA and RNA (large data production at low cost, applying 1 of the 5 pillars of genomics) and is applied to the sequencing of the complete genome of Trypanosoma cruzi, making it possible to study the genetic diversity of this parasite. NGS facilitates transcriptomics, i.e. the analysis of gene expression at different stages of the parasite's life cycle and the comparison between different strains (DTUs - discrete typing units) to understand genetic variations, the parasite's virulence and its resistance.

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Optical microscope adapted with a smartphone to capture images of blood samples.

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Bioinformatics is essential for processing and analyzing NGS data, using algorithms and pipelines (sequence of processes and software tools that are used to analyze and process genomic data) to align genetic sequences (BWA, Bowtie), annotate genes (Prokka, RAST), identify genetic variants (GATK) and compare sequences to build phylogenetic trees.

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The DNA of a phage is injected into the bacterial cytoplasm and a protein complex is formed by Cas1 and Cas2. A phage DNA sequence, called a protospacer, is acquired from the phage DNA by the Cas1-Cas2 complex.

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It allows the precise modification of specific genes. In this case, this technique has been adapted experimentally for protozoa and is applied to the T. cruzi parasite to eliminate specific genes and observe the phenotypic consequence of this elimination, in order to investigate the function of genes related to its virulence and survival. It also allows mutant strains to be created for functional studies, with a focus on developing potential therapeutic targets, such as vaccines.

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The life cycle of Trypanosoma cruzi, which causes Chagas' disease, between hosts (insects and humans), indicating the parasite's stages of development.

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Proteomics focuses on the analysis of expressed proteins, identifying potential targets for therapies, while metabolomics studies the metabolites that are produced, offering clues about the parasite's metabolism and its possible vulnerabilities. Thus, these two methods are complementary for functional analysis. The techniques used for these studies are mass spectrometry, MALDI-TOF and high performance liquid chromatography (HPLC).

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Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi

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Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi

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Chapter Two - CRISPRing protozoan parasites to better understand the biology of diseases

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Chapter Two - CRISPRing protozoan parasites to better understand the biology of diseases

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CRISPRing protozoan parasites to better understand the biology of diseases - PubMed

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Precise gene editing techniques are paramount to gain deeper insights into the biological processes such as host-parasite interactions, drug resistance mechanisms, and gene-function relationships. Discovery of CRISPR-Cas9 system has spearheaded mechanistic understanding of protozoan parasite biology …

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Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease

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Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease

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Genomic surveillance: a potential shortcut for effective Chagas disease management

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Genomic surveillance: a potential shortcut for effective Chagas disease management

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Chagas disease, also known as Human American Trypanosomiasis, is an infectious disease caused by the parasite Trypanosoma cruzi and can be potentially fatal. Generally, this disease is strongly localized in Latin America, however it can be found in any part of the globe due to migration and new forms of transmission.

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A doença de Chagas, também conhecida como Tripanossomose Humana Americana, é uma doença potencialmente fatal, causada pelo parasita protozoário Trypanosoma cruzi (T. cruzi), encontrando-se maioritariamente em zonas endémicas da América Latina, onde é transmitida do vetor para o ser humano através do contacto com fezes de triatomíneos. Apesar de ser endémica na América Latina, em […]Ler mais

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The transmission of Chagas disease is highly related to the presence of the vector insect, better known as the triatomine (“barber”), which is infected with the parasite T. cruzi. Transmission occurs when the individual has contact with feces and/or urine from infected hematophagous triatomines. These insects begin by biting an exposed area of ​​skin where they defecate or urinate near the bite. The parasite later enters the body when the person instinctively spreads feces or urine by scratching the bitten area. This spread allows the parasite to enter the body through the skin or mucous membranes. Transmission of the parasite can also occur through the consumption of food/drinks infected with T. cruzi, during pregnancy or childbirth, through blood transfusions, laboratory accidents and organ transplants.

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Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi.

About 6 million to 7 million people worldwide are estimated to be infected with T. cruzi, the parasite that causes Chagas disease. The disease is found mainly in endemic areas of 21 continental Latin American countries, where it is mostly transmitted to humans and other mammals by contact with faeces or urine of triatomine bugs (vector-borne), known as 'kissing bugs', among many other popular names, depending on the geographical area.

Chagas disease is named after Carlos Ribeiro Justiniano Chagas, a Brazilian physician and researcher who discovered the disease in 1909. In May 2019, following up on decision of the 72 World Health Assembly, the World Chagas Disease Day was established to be celebrated on 14 April (the date of the year 1909 when Carlos Chagas diagnosed the first human case of the disease, a two-year-old girl called Berenice).

Distribution

Chagas disease was once entirely confined to continental rural areas of the Region of the Americas - (excluding the Caribbean islands). Mainly because of the increased population mobility in the last decades, most infected people live now in urban settings (urbanization) and the disease has been increasingly detected in the United States of America, Canada, and many European and some African, Eastern Mediterranean and Western Pacific countries.

Transmission

In Latin America, T. cruzi parasites are mainly transmitted by contact with faeces/urine of infected blood-sucking triatomine bugs. These bugs, that carry the parasites, typically live in the wall or roof cracks of homes and peridomiciliary structures, such as chicken coops, pens and warehouses, in rural or suburban areas. Normally they hide during the day and become active at night when they feed on animal blood, including human blood. They usually bite an exposed area of skin such as the face (hence its common name 'kissing bug'), and the bug defecates or urinates close to the bite. The parasites enter the body when the person instinctively smears the bug faeces or urine into the bite, or any other skin break, the eyes or the mouth.

T. cruzi can also be transmitted by:

consumption of food or beverages contaminated with T. cruzi through, for example, contact with faeces or urine of infected triatomine bugs or marsupials (this kind of transmission typically causes outbreaks with more severe morbidity and higher mortality - infecting groups of people simultaneously with more frequent cases of severe disease and higher number of deaths);

blood or blood product transfusion from infected donors;

passage from an infected mother to her newborn during pregnancy or childbirth;

some organ transplants using organs from infected donors; and

laboratory accidents.

Signs and symptoms

Chagas disease presents itself in two phases. The initial acute phase lasts for about two months after infection. During the acute phase, a high number of parasites circulate in the blood but in most cases, symptoms are absent or mild and unspecific. In less than 50% of people bitten by a triatomine bug, characteristic first visible signs can be a skin lesion or a purplish swelling of the lids of one eye. Additionally, they can present fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain.

During the chronic phase, the parasites are hidden mainly in the heart and digestive muscle. Up to 30% of patients suffer from cardiac disorders and up to 10% suffer from digestive (typically enlargement of the oesophagus or colon), neurological or mixed alterations. In later years the infection can lead to sudden death due to cardiac arrhythmias or progressive heart failure caused by the destruction of the heart muscle and its nervous system.

Chagas disease patients are at risk of severe COVID-19 manifestations and should be a priority group to be vaccinated because the SARS-CoV-2 can cause myocarditis and the chronic Chagas disease typically originates a pro-thrombotic status, cardiac alterations and secondary thrombotic strokes.

To kill the parasite, Chagas disease can be treated with benznidazole and also nifurtimox. Both medicines are nearly 100% effective in curing the disease if given soon after infection at the onset of the acute phase, including the cases of congenital transmission. The efficacy of both diminishes, however, the longer a person has been infected and the adverse reactions are more frequent at older age. Treatment is also indicated for those in whom the infection has been reactivated (for example, due to immunosuppression), and for patients during the early chronic phase, including girls and women of childbearing age (before or after pregnancy) to prevent congenital transmission.

Infected adults, especially those with no symptoms, should be offered treatment because antiparasitic treatment can also prevent or curb disease progression. In other cases, the potential benefits of medication in preventing or delaying the development of Chagas disease should be weighed against the duration of treatment (up to 2 months) and possible adverse reactions (occurring in up to 40% of treated adult patients). Benznidazole and nifurtimox should not be taken by pregnant women or by people with kidney or liver failure. Nifurtimox is also contraindicated for people with a background of neurological or psychiatric disorders. Additionally, specific treatment for cardiac, or digestive or neurological manifestations may be required.

Control and prevention

Originally (more than 9 000 years ago), T. cruzi only infected wild mammals. It later spread to domestic mammals, including humans. The large reservoir of T. cruzi parasites in wild animals of the Americas means that the parasite cannot be eradicated. Instead, the control targets are elimination of the transmission to humans and early health-care access of the infected people.

There is no vaccine for Chagas disease. T. cruzi can infect many species of triatomine bugs, the vast majority of which are found in the Americas. Vector control has been the most effective method of prevention in Latin America. Blood screening is necessary to prevent infection through transfusion and organ transplantation and to increase detection and care of the affected population all over the world.

Depending on the geographical area, WHO recommends the following approaches to prevention and control:

spraying of dwellings and surrounding areas with residual insecticides;

house improvements and house cleanliness to prevent vector infestation;

personal preventive measures such as bednets, good hygiene practices in food preparation, transportation, storage and consumption;

development of contextualized information, education and communication activities for different actors and scenarios about preventative measures and surveillance tools;

screening of blood donors;

testing of organ, tissue or cell donors and receivers;

access to diagnosis and treatment of people with medical indication or recommendation to do antiparasitic treatment, especially children and women of child-bearing age before pregnancy; and

screening of newborns and other children of infected mothers without previous antiparasitic treatment to do early diagnosis and provide treatment.

The medical care cost of patients with chronic cardiac, digestive, neurologic or mixed forms of the disease has been calculated to be >80% higher than the cost of spraying residual insecticide to control vectors and prevent infection.

WHO response

Since the 1990s there have been important successes in parasite and vector control in Latin America, in the territories of the Southern Cone, Central America, Andean Pact and Amazonian Intergovernmental Initiatives, with the Pan American Health Organization Secretariat. These multinational initiatives led to substantial reductions in transmission and increased access to diagnosis and antiparasitic treatment.

In addition, the risk of transmission by blood transfusion has been extremely reduced through the universal screening in all blood banks of the continental Latin American countries. Most of the blood banks in the United States of America and most European and some Western Pacific countries with Chagas disease cases have also implemented universal screening in blood banks.

These advances have been possible because of the strong commitment of Member States affected by the disease and the strength of their research and control organizations, together with support from many international partners.

In 2005 the World Health Organization recognized Chagas disease as a neglected tropical disease (NTDs). This facilitated a greater recognition of the disease as a public health problem on the international scene and facilitated the fight against misinformation, the lack of social demand and the weak political commitment to solve the problems related with Chagas disease, as well as insufficient scientific research and development related with prevention, detection and comprehensive care, including diagnosis, treatment, medicine presentations, social aspects, information, education and communication tools.

In 2020 the road map for neglected tropical diseases 2021-2030 included five Chagas disease objectives:

1. verification of the interruption of vectorial domiciliary transmission;

2. verification of interruption of transfusion transmission;

3. verification of the interruption of transmission by organ transplants;

4. elimination of congenital Chagas disease;

5. 75% coverage of antiparasitic treatment of the eligible population.

At the same time, a series of additional challenges have to be faced. These include:

difficulty to maintain and consolidate advances made in disease control and prevention, especially in the context of the current COVID-19 sanitary and socioeconomic crises;

emergence of Chagas disease in regions previously considered to be free of the disease - such as the Amazon basin;

persistence in regions where control had been in progress, such as the Chaco region of Argentina and the Plurinational State of Bolivia;

spread of the disease mainly due to increasing population mobility between Latin America and the rest of the world;

people living with the disease in countries/areas where health systems have low awareness or experience;

prevention of the consequences of the lack of knowledge and awareness, existence of stigma and/or discrimination associated with the disease;

low case notification, week monitoring and surveillance and limited verification of control achievements; and

lack of access to diagnosis and treatment for millions of infected people.

To attain the goal of elimination of Chagas disease transmission and provide health care for infected or people suffering from the disease, both in endemic and non-endemic territories, WHO aims to increase networking at the global level and reinforce regional and national capacities, focusing on:

strengthening national information systems and world epidemiological surveillance;

raising awareness about Chagas disease and the challenges faced by affected populations;

develop innovative strategies aiming at disrupting vector-borne transmission (through One Health/Ecohealth approaches)

preventing transmission by blood transfusion and organ transplantation;

promoting the identification of most adequate diagnostic tests and algorithms/protocols to increase screening and diagnosis of infections;

expanding primary prevention of congenital transmission and case management of congenital and non-congenital infections;

promoting consensus on adequate updated case management, including co-infections and co-morbidities (such as COVID-19, HIV/AIDS, strongyloidiasis...); and,

promoting the development of multidimensional approaches.

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Argentina, Belize, Bolivia (Plurinational State of), Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela (Bolivarian Republic of).

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Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi . About 6 million to 7 million people worldwide are estimated to be infected with T. cruzi, the parasite that causes Chagas disease.

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1. The infected insect bites the person and defecates near the wound. Trypomastigotes present in feces penetrate the skin or mucous membranes.

2. Inside the body, trypomastigotes enter cells near the site of infection and transform into amastigotes.

3. Amastigotes multiply by binary fission and transform back into trypomastigotes, leaving the cells and entering the bloodstream.

4. Trypomastigotes can infect new cells in various tissues, restarting the intracellular cycle.

5. Another kissing bug infects a person by poking trypomastigotes into the blood.

6. In the insect's gut, trypomastigotes transform into epimastigotes, multiplying and then transforming into infectious metacyclic trypomastigotes, ready to infect another host.

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Causal Agent

Trypanosoma cruzi, is a parasitic protozoan that is the causative agent of Chagas disease (American trypanosomiasis). Currently, six distinct lineages of T. cruzi are classified into discrete typing units (TcI-VI), which vary in their geographic occurrence, host specificity, and pathogenicity.

Life Cycle

An infected triatomine insect vector (or "kissing" bug) takes a blood meal and releases trypomastigotes in its feces near the site of the bite wound. Trypomastigotes enter the host through the bite wound or intact mucosal membranes, such as the conjunctiva
. Inside the host, the trypomastigotes invade cells near the site of inoculation, where they differentiate into intracellular amastigotes

. The amastigotes multiply by binary fission

and differentiate into trypomastigotes, and then are released into the circulation as bloodstream trypomastigotes

. Trypomastigotes infect cells from a variety of tissues and transform into intracellular amastigotes in new infection sites. Clinical manifestations can result from this infective cycle. The bloodstream trypomastigotes do not replicate (different from the African trypanosomes). Replication resumes only when the parasites enter another cell or are ingested by another vector. The "kissing" bug becomes infected by feeding on human or animal blood that contains circulating parasites

. The ingested trypomastigotes transform into epimastigotes in the vector's midgut

. The parasites multiply and differentiate in the midgut

and differentiate into infective metacyclic trypomastigotes in the hindgut

. Other less common routes of transmission include blood transfusions, organ transplantation, transplacental transmission, and foodborne transmission (via food/drink contaminated with the vector and/or its feces).

Hosts/Vectors

Apart from humans, a number of mammals serve as reservoir hosts for T. cruzi, e.g. armadillos, opossums, raccoons, woodrats, some other rodents, and domestic dogs. Common triatomine vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus.

Geographic Distribution

T. cruzi is endemic in vectors and wildlife reservoirs throughout the Americas from the southern half of the United States down to Argentina. Chagas disease cases have been reported from South and Central American countries, particularly in rural, impoverished areas. There have been a small number of autochthonous cases of Chagas disease in the United States.

Clinical Presentation

Chagas disease has an acute phase and chronic phase. The acute phase is usually asymptomatic, but can present with nonspecific somatic symptoms. Rarely, the acute phase may be more severe with potential cardiac or neurologic symptoms and signs. Nodular lesions or furuncles, usually called chagomas, may develop around the vector's feeding site. Chagomas occurring on the on the eyelids are commonly referred to as palpebral and periocular firm swelling. Most acute cases resolve over a period of a few weeks or months into a subclinical chronic form of the disease ("indeterminate form"). Reactivation of Chagas disease from this asymptomatic form may occur in patients with HIV or those receiving immunosuppressive drugs.

The symptomatic chronic form ("determinate form") may not occur for years or even decades after initial infection. This may include cardiac or gastrointestinal involvement, which occasionally occur together. The many complications of chronic Chagas disease can be fatal. Amastigote invasion of smooth muscle can lead to megaesophagus, megacolon, and dilated cardiomyopathy.

T. cruzi amastigotes in heart tissue.

Trypomastigotes of T. cruzi are the only stage found circulating in human blood or CSF. In tissue, the parasite forms amastigotes characterized by a single nucleus and kinetoplast. The amastigotes of T. cruzi are morphologically indistinguishable from those of Leishmania spp.

Figure B: Higher magnification of Figure A.

Figure D: Higher magnification of Figure C.

Figure F: Higher magnification of Figure E. The amastigotes in this image appear to be transforming into trypomastigotes.

T. cruzi epimastigotes, from culture.

The epimastigote stage is not seen in humans but can be found in the midgut of triatomines that have ingested trypomastigotes from an infected host.

Triatomine bug, the T. cruzi vector.

Trypanosoma cruzi is transmitted by kissing bugs (Hemiptera: Reduviidae). The most common genera responsible for transmission of the disease are Triatoma, Rhodnius, and Panstrongylus. Infection usually occurs after bugs defecate on the bite site and are rubbed into the wound by the host scratching.

Morphology

In the acute stage of the disease, diagnosis may be made by the finding of trypomastigotes in circulating blood or cerebral spinal fluid (CSF). During the chronic stage, trypomastigotes are usually not found circulating in blood and serologic testing is recommended (see below). Amastigotes may be found in biopsy specimens stained with hematoxylin-and-eosin (H&E) or Giemsa.

Serology (Antibody Detection)

Positive IFA result with T. cruzi antigen (magnification 400x).

During the acute phase of illness, blood film examination generally reveals the presence of trypomastigotes. However, during the chronic phase of infection, parasitemia is low and immunodiagnosis is a useful technique for determining whether the patient is infected.

Diagnosis of chronic Chagas disease in suspected patients is based on serology performed with at least two different serologic tests. CDC utilizes an FDA-cleared enzyme immunoassay (EIA) based on recombinant T. cruzi antigens alongside an immunoblot (TESA) as the two first-line tests. If initial EIA and TESA results are discordant, a second specimen is requested and testing is repeated. If results of the second EIA and TESA are discordant, an immunofluorescence assay (IFA) is used as a "tie-breaker" test. Various serologic methods are commercially available in other countries for laboratory diagnosis of Chagas disease. The sensitivity and specificity of these tests are highly variable.

Molecular Testing

Molecular diagnosis of Chagas disease is performed for cases of suspected acute infection (including transfusion or transplant transmission), congenital Chagas disease, and for monitoring of suspected laboratory exposures. For chronic Chagas disease, serology is generally most appropriate, although molecular detection may be performed for re-activated cases associated with immunosuppression.

At CDC molecular detection of T. cruzi DNA is performed using a combination of two real-time PCR assays (TCZ and MNC). Acceptable specimen types are EDTA blood (minimum of 2.2 ml), heart biopsy tissue (in saline or paraffin-embedded) and, in cases of suspected central nervous system involvement, CSF.

References:

Bern C, Montgomery SP, Herwaldt B L, Marin-Neto JA, Dantas RO, Maguire JH, Acquatella H, Morillo C, Kirchhoff LV, Gilman RH, Reyes, PA, Salvatella R, Moore AC. Evaluation and Treatment of Chagas Disease in the United States. Aa Systematic Review. JAMA 2007 298 2171-81

Diez M, Favaloro L, Bertolotti A, Burgos JM, Vigliano C, Lastra MP, Levin MJ, Arnedo A, Nagel C, Schijman AG, Favaloro RR. Usefulness of PCR Strategies For Early Diagnosis of Chagas' Disease Reactivation and Treatment Follow-Up in Heart Transplantation. American Journal of Transplantation. 2007; 7: 1633-1640.

Afonso AM, Ebell MH, Tarleton RL. A systematic review of high quality diagnostic tests for Chagas disease. PLoS Negl Trop Dis. 2012; 6(11):e1881.

Qvarnstrom Y, Schijman AG, Veron V, Aznar C, Steurer F, da Silva AJ. Sensitive and specific detection of Trypanosoma cruzi DNA in clinical specimens using a multi-target real-time PCR approach. PLoS Neglected Tropical Diseases. 2012; 6: e1689.

Laboratory Safety

Standard safety protocols for handling blood and sharps ( https://www.cdc.gov/dpdx/diagnosticprocedures/blood/safety.html). The risk of needle-sticks should be seriously mitigated with all possible precautions; several symptomatic cases of laboratory-acquired T. cruzi infections following needles-ticks are known.

Suggested Readings

Bern, C., Kjos, S., Yabsley, M.J. and Montgomery, S.P., 2011. Trypanosoma cruzi and Chagas' disease in the United States. Clinical Microbiology Reviews, 24 (4), pp.655-681.

Pérez-Molina, J.A., Molina, I. 2018. Chagas disease. The Lancet, 391 (10115), pp.82-94.Treatment Information
https://kissingbug.tamu.edu/external icon

DPDx is an educational resource designed for health professionals and laboratory scientists. For an overview including prevention, control, and treatment visit www.cdc.gov/parasites/.

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division of parasitic diseases and malaria (dpdm)

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training and continuing education of laboratorians

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Trypanosoma cruzi, is a parasitic protozoan that is the causative agent of Chagas disease (American trypanosomiasis). Currently, six distinct lineages of T. cruzi are classified into discrete typing units (TcI-VI), which vary in their geographic occurrence, host specificity, and pathogenicity.

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Chagas disease has two phases.

The initial phase is called the acute phase, lasting about two months after infection. At this stage, the affected individual is generally asymptomatic or may present mild symptoms such as fever, headache, enlarged lymph nodes, paleness, muscle pain, difficulty breathing, swelling and abdominal or chest pain. Two clear signs of this disease may appear at this stage. Chagoma, which is a nodular lesion at the site of entry of the parasite, and eyelid edema or Romaña's sign, if the chagoma is on the eyelid. Serious cardiac or neurological symptoms rarely appear at this stage. The acute phase usually resolves over a few weeks, but the parasite is not eliminated from the body without treatment, causing the disease to progress to the chronic phase.

The chronic phase may be silent for years after the initial infection. This phase includes damage to the cardiac, gastrointestinal and neurological levels. Individuals in this phase first present with cardiac disorders, enlargement of the esophagus or colon, and neurological changes. In the last years of life they present damage to the nervous system and heart muscles, leading to arrhythmias, heart failure and potentially death.

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Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi.

About 6 million to 7 million people worldwide are estimated to be infected with T. cruzi, the parasite that causes Chagas disease. The disease is found mainly in endemic areas of 21 continental Latin American countries, where it is mostly transmitted to humans and other mammals by contact with faeces or urine of triatomine bugs (vector-borne), known as 'kissing bugs', among many other popular names, depending on the geographical area.

Chagas disease is named after Carlos Ribeiro Justiniano Chagas, a Brazilian physician and researcher who discovered the disease in 1909. In May 2019, following up on decision of the 72 World Health Assembly, the World Chagas Disease Day was established to be celebrated on 14 April (the date of the year 1909 when Carlos Chagas diagnosed the first human case of the disease, a two-year-old girl called Berenice).

Distribution

Chagas disease was once entirely confined to continental rural areas of the Region of the Americas - (excluding the Caribbean islands). Mainly because of the increased population mobility in the last decades, most infected people live now in urban settings (urbanization) and the disease has been increasingly detected in the United States of America, Canada, and many European and some African, Eastern Mediterranean and Western Pacific countries.

Transmission

In Latin America, T. cruzi parasites are mainly transmitted by contact with faeces/urine of infected blood-sucking triatomine bugs. These bugs, that carry the parasites, typically live in the wall or roof cracks of homes and peridomiciliary structures, such as chicken coops, pens and warehouses, in rural or suburban areas. Normally they hide during the day and become active at night when they feed on animal blood, including human blood. They usually bite an exposed area of skin such as the face (hence its common name 'kissing bug'), and the bug defecates or urinates close to the bite. The parasites enter the body when the person instinctively smears the bug faeces or urine into the bite, or any other skin break, the eyes or the mouth.

T. cruzi can also be transmitted by:

consumption of food or beverages contaminated with T. cruzi through, for example, contact with faeces or urine of infected triatomine bugs or marsupials (this kind of transmission typically causes outbreaks with more severe morbidity and higher mortality - infecting groups of people simultaneously with more frequent cases of severe disease and higher number of deaths);

blood or blood product transfusion from infected donors;

passage from an infected mother to her newborn during pregnancy or childbirth;

some organ transplants using organs from infected donors; and

laboratory accidents.

Signs and symptoms

Chagas disease presents itself in two phases. The initial acute phase lasts for about two months after infection. During the acute phase, a high number of parasites circulate in the blood but in most cases, symptoms are absent or mild and unspecific. In less than 50% of people bitten by a triatomine bug, characteristic first visible signs can be a skin lesion or a purplish swelling of the lids of one eye. Additionally, they can present fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain.

During the chronic phase, the parasites are hidden mainly in the heart and digestive muscle. Up to 30% of patients suffer from cardiac disorders and up to 10% suffer from digestive (typically enlargement of the oesophagus or colon), neurological or mixed alterations. In later years the infection can lead to sudden death due to cardiac arrhythmias or progressive heart failure caused by the destruction of the heart muscle and its nervous system.

Chagas disease patients are at risk of severe COVID-19 manifestations and should be a priority group to be vaccinated because the SARS-CoV-2 can cause myocarditis and the chronic Chagas disease typically originates a pro-thrombotic status, cardiac alterations and secondary thrombotic strokes.

To kill the parasite, Chagas disease can be treated with benznidazole and also nifurtimox. Both medicines are nearly 100% effective in curing the disease if given soon after infection at the onset of the acute phase, including the cases of congenital transmission. The efficacy of both diminishes, however, the longer a person has been infected and the adverse reactions are more frequent at older age. Treatment is also indicated for those in whom the infection has been reactivated (for example, due to immunosuppression), and for patients during the early chronic phase, including girls and women of childbearing age (before or after pregnancy) to prevent congenital transmission.

Infected adults, especially those with no symptoms, should be offered treatment because antiparasitic treatment can also prevent or curb disease progression. In other cases, the potential benefits of medication in preventing or delaying the development of Chagas disease should be weighed against the duration of treatment (up to 2 months) and possible adverse reactions (occurring in up to 40% of treated adult patients). Benznidazole and nifurtimox should not be taken by pregnant women or by people with kidney or liver failure. Nifurtimox is also contraindicated for people with a background of neurological or psychiatric disorders. Additionally, specific treatment for cardiac, or digestive or neurological manifestations may be required.

Control and prevention

Originally (more than 9 000 years ago), T. cruzi only infected wild mammals. It later spread to domestic mammals, including humans. The large reservoir of T. cruzi parasites in wild animals of the Americas means that the parasite cannot be eradicated. Instead, the control targets are elimination of the transmission to humans and early health-care access of the infected people.

There is no vaccine for Chagas disease. T. cruzi can infect many species of triatomine bugs, the vast majority of which are found in the Americas. Vector control has been the most effective method of prevention in Latin America. Blood screening is necessary to prevent infection through transfusion and organ transplantation and to increase detection and care of the affected population all over the world.

Depending on the geographical area, WHO recommends the following approaches to prevention and control:

spraying of dwellings and surrounding areas with residual insecticides;

house improvements and house cleanliness to prevent vector infestation;

personal preventive measures such as bednets, good hygiene practices in food preparation, transportation, storage and consumption;

development of contextualized information, education and communication activities for different actors and scenarios about preventative measures and surveillance tools;

screening of blood donors;

testing of organ, tissue or cell donors and receivers;

access to diagnosis and treatment of people with medical indication or recommendation to do antiparasitic treatment, especially children and women of child-bearing age before pregnancy; and

screening of newborns and other children of infected mothers without previous antiparasitic treatment to do early diagnosis and provide treatment.

The medical care cost of patients with chronic cardiac, digestive, neurologic or mixed forms of the disease has been calculated to be >80% higher than the cost of spraying residual insecticide to control vectors and prevent infection.

WHO response

Since the 1990s there have been important successes in parasite and vector control in Latin America, in the territories of the Southern Cone, Central America, Andean Pact and Amazonian Intergovernmental Initiatives, with the Pan American Health Organization Secretariat. These multinational initiatives led to substantial reductions in transmission and increased access to diagnosis and antiparasitic treatment.

In addition, the risk of transmission by blood transfusion has been extremely reduced through the universal screening in all blood banks of the continental Latin American countries. Most of the blood banks in the United States of America and most European and some Western Pacific countries with Chagas disease cases have also implemented universal screening in blood banks.

These advances have been possible because of the strong commitment of Member States affected by the disease and the strength of their research and control organizations, together with support from many international partners.

In 2005 the World Health Organization recognized Chagas disease as a neglected tropical disease (NTDs). This facilitated a greater recognition of the disease as a public health problem on the international scene and facilitated the fight against misinformation, the lack of social demand and the weak political commitment to solve the problems related with Chagas disease, as well as insufficient scientific research and development related with prevention, detection and comprehensive care, including diagnosis, treatment, medicine presentations, social aspects, information, education and communication tools.

In 2020 the road map for neglected tropical diseases 2021-2030 included five Chagas disease objectives:

1. verification of the interruption of vectorial domiciliary transmission;

2. verification of interruption of transfusion transmission;

3. verification of the interruption of transmission by organ transplants;

4. elimination of congenital Chagas disease;

5. 75% coverage of antiparasitic treatment of the eligible population.

At the same time, a series of additional challenges have to be faced. These include:

difficulty to maintain and consolidate advances made in disease control and prevention, especially in the context of the current COVID-19 sanitary and socioeconomic crises;

emergence of Chagas disease in regions previously considered to be free of the disease - such as the Amazon basin;

persistence in regions where control had been in progress, such as the Chaco region of Argentina and the Plurinational State of Bolivia;

spread of the disease mainly due to increasing population mobility between Latin America and the rest of the world;

people living with the disease in countries/areas where health systems have low awareness or experience;

prevention of the consequences of the lack of knowledge and awareness, existence of stigma and/or discrimination associated with the disease;

low case notification, week monitoring and surveillance and limited verification of control achievements; and

lack of access to diagnosis and treatment for millions of infected people.

To attain the goal of elimination of Chagas disease transmission and provide health care for infected or people suffering from the disease, both in endemic and non-endemic territories, WHO aims to increase networking at the global level and reinforce regional and national capacities, focusing on:

strengthening national information systems and world epidemiological surveillance;

raising awareness about Chagas disease and the challenges faced by affected populations;

develop innovative strategies aiming at disrupting vector-borne transmission (through One Health/Ecohealth approaches)

preventing transmission by blood transfusion and organ transplantation;

promoting the identification of most adequate diagnostic tests and algorithms/protocols to increase screening and diagnosis of infections;

expanding primary prevention of congenital transmission and case management of congenital and non-congenital infections;

promoting consensus on adequate updated case management, including co-infections and co-morbidities (such as COVID-19, HIV/AIDS, strongyloidiasis...); and,

promoting the development of multidimensional approaches.

---------------------------------------------------

Argentina, Belize, Bolivia (Plurinational State of), Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela (Bolivarian Republic of).

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Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi . About 6 million to 7 million people worldwide are estimated to be infected with T. cruzi, the parasite that causes Chagas disease.

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https://www.ihmt.unl.pt/glossary/chagas-disease-american-trypanosomiasis/

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A doença de Chagas, também conhecida como Tripanossomose Humana Americana, é uma doença potencialmente fatal, causada pelo parasita protozoário Trypanosoma cruzi (T. cruzi), encontrando-se maioritariamente em zonas endémicas da América Latina, onde é transmitida do vetor para o ser humano através do contacto com fezes de triatomíneos. Apesar de ser endémica na América Latina, em […]Ler mais

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Doença de Chagas (também conhecida como tripanossomíase americana)

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Doença de Chagas (também conhecida como tripanossomíase americana)

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https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)

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Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi.

About 6 million to 7 million people worldwide are estimated to be infected with T. cruzi, the parasite that causes Chagas disease. The disease is found mainly in endemic areas of 21 continental Latin American countries, where it is mostly transmitted to humans and other mammals by contact with faeces or urine of triatomine bugs (vector-borne), known as 'kissing bugs', among many other popular names, depending on the geographical area.

Chagas disease is named after Carlos Ribeiro Justiniano Chagas, a Brazilian physician and researcher who discovered the disease in 1909. In May 2019, following up on decision of the 72 World Health Assembly, the World Chagas Disease Day was established to be celebrated on 14 April (the date of the year 1909 when Carlos Chagas diagnosed the first human case of the disease, a two-year-old girl called Berenice).

Distribution

Chagas disease was once entirely confined to continental rural areas of the Region of the Americas - (excluding the Caribbean islands). Mainly because of the increased population mobility in the last decades, most infected people live now in urban settings (urbanization) and the disease has been increasingly detected in the United States of America, Canada, and many European and some African, Eastern Mediterranean and Western Pacific countries.

Transmission

In Latin America, T. cruzi parasites are mainly transmitted by contact with faeces/urine of infected blood-sucking triatomine bugs. These bugs, that carry the parasites, typically live in the wall or roof cracks of homes and peridomiciliary structures, such as chicken coops, pens and warehouses, in rural or suburban areas. Normally they hide during the day and become active at night when they feed on animal blood, including human blood. They usually bite an exposed area of skin such as the face (hence its common name 'kissing bug'), and the bug defecates or urinates close to the bite. The parasites enter the body when the person instinctively smears the bug faeces or urine into the bite, or any other skin break, the eyes or the mouth.

T. cruzi can also be transmitted by:

consumption of food or beverages contaminated with T. cruzi through, for example, contact with faeces or urine of infected triatomine bugs or marsupials (this kind of transmission typically causes outbreaks with more severe morbidity and higher mortality - infecting groups of people simultaneously with more frequent cases of severe disease and higher number of deaths);

blood or blood product transfusion from infected donors;

passage from an infected mother to her newborn during pregnancy or childbirth;

some organ transplants using organs from infected donors; and

laboratory accidents.

Signs and symptoms

Chagas disease presents itself in two phases. The initial acute phase lasts for about two months after infection. During the acute phase, a high number of parasites circulate in the blood but in most cases, symptoms are absent or mild and unspecific. In less than 50% of people bitten by a triatomine bug, characteristic first visible signs can be a skin lesion or a purplish swelling of the lids of one eye. Additionally, they can present fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain.

During the chronic phase, the parasites are hidden mainly in the heart and digestive muscle. Up to 30% of patients suffer from cardiac disorders and up to 10% suffer from digestive (typically enlargement of the oesophagus or colon), neurological or mixed alterations. In later years the infection can lead to sudden death due to cardiac arrhythmias or progressive heart failure caused by the destruction of the heart muscle and its nervous system.

Chagas disease patients are at risk of severe COVID-19 manifestations and should be a priority group to be vaccinated because the SARS-CoV-2 can cause myocarditis and the chronic Chagas disease typically originates a pro-thrombotic status, cardiac alterations and secondary thrombotic strokes.

To kill the parasite, Chagas disease can be treated with benznidazole and also nifurtimox. Both medicines are nearly 100% effective in curing the disease if given soon after infection at the onset of the acute phase, including the cases of congenital transmission. The efficacy of both diminishes, however, the longer a person has been infected and the adverse reactions are more frequent at older age. Treatment is also indicated for those in whom the infection has been reactivated (for example, due to immunosuppression), and for patients during the early chronic phase, including girls and women of childbearing age (before or after pregnancy) to prevent congenital transmission.

Infected adults, especially those with no symptoms, should be offered treatment because antiparasitic treatment can also prevent or curb disease progression. In other cases, the potential benefits of medication in preventing or delaying the development of Chagas disease should be weighed against the duration of treatment (up to 2 months) and possible adverse reactions (occurring in up to 40% of treated adult patients). Benznidazole and nifurtimox should not be taken by pregnant women or by people with kidney or liver failure. Nifurtimox is also contraindicated for people with a background of neurological or psychiatric disorders. Additionally, specific treatment for cardiac, or digestive or neurological manifestations may be required.

Control and prevention

Originally (more than 9 000 years ago), T. cruzi only infected wild mammals. It later spread to domestic mammals, including humans. The large reservoir of T. cruzi parasites in wild animals of the Americas means that the parasite cannot be eradicated. Instead, the control targets are elimination of the transmission to humans and early health-care access of the infected people.

There is no vaccine for Chagas disease. T. cruzi can infect many species of triatomine bugs, the vast majority of which are found in the Americas. Vector control has been the most effective method of prevention in Latin America. Blood screening is necessary to prevent infection through transfusion and organ transplantation and to increase detection and care of the affected population all over the world.

Depending on the geographical area, WHO recommends the following approaches to prevention and control:

spraying of dwellings and surrounding areas with residual insecticides;

house improvements and house cleanliness to prevent vector infestation;

personal preventive measures such as bednets, good hygiene practices in food preparation, transportation, storage and consumption;

development of contextualized information, education and communication activities for different actors and scenarios about preventative measures and surveillance tools;

screening of blood donors;

testing of organ, tissue or cell donors and receivers;

access to diagnosis and treatment of people with medical indication or recommendation to do antiparasitic treatment, especially children and women of child-bearing age before pregnancy; and

screening of newborns and other children of infected mothers without previous antiparasitic treatment to do early diagnosis and provide treatment.

The medical care cost of patients with chronic cardiac, digestive, neurologic or mixed forms of the disease has been calculated to be >80% higher than the cost of spraying residual insecticide to control vectors and prevent infection.

WHO response

Since the 1990s there have been important successes in parasite and vector control in Latin America, in the territories of the Southern Cone, Central America, Andean Pact and Amazonian Intergovernmental Initiatives, with the Pan American Health Organization Secretariat. These multinational initiatives led to substantial reductions in transmission and increased access to diagnosis and antiparasitic treatment.

In addition, the risk of transmission by blood transfusion has been extremely reduced through the universal screening in all blood banks of the continental Latin American countries. Most of the blood banks in the United States of America and most European and some Western Pacific countries with Chagas disease cases have also implemented universal screening in blood banks.

These advances have been possible because of the strong commitment of Member States affected by the disease and the strength of their research and control organizations, together with support from many international partners.

In 2005 the World Health Organization recognized Chagas disease as a neglected tropical disease (NTDs). This facilitated a greater recognition of the disease as a public health problem on the international scene and facilitated the fight against misinformation, the lack of social demand and the weak political commitment to solve the problems related with Chagas disease, as well as insufficient scientific research and development related with prevention, detection and comprehensive care, including diagnosis, treatment, medicine presentations, social aspects, information, education and communication tools.

In 2020 the road map for neglected tropical diseases 2021-2030 included five Chagas disease objectives:

1. verification of the interruption of vectorial domiciliary transmission;

2. verification of interruption of transfusion transmission;

3. verification of the interruption of transmission by organ transplants;

4. elimination of congenital Chagas disease;

5. 75% coverage of antiparasitic treatment of the eligible population.

At the same time, a series of additional challenges have to be faced. These include:

difficulty to maintain and consolidate advances made in disease control and prevention, especially in the context of the current COVID-19 sanitary and socioeconomic crises;

emergence of Chagas disease in regions previously considered to be free of the disease - such as the Amazon basin;

persistence in regions where control had been in progress, such as the Chaco region of Argentina and the Plurinational State of Bolivia;

spread of the disease mainly due to increasing population mobility between Latin America and the rest of the world;

people living with the disease in countries/areas where health systems have low awareness or experience;

prevention of the consequences of the lack of knowledge and awareness, existence of stigma and/or discrimination associated with the disease;

low case notification, week monitoring and surveillance and limited verification of control achievements; and

lack of access to diagnosis and treatment for millions of infected people.

To attain the goal of elimination of Chagas disease transmission and provide health care for infected or people suffering from the disease, both in endemic and non-endemic territories, WHO aims to increase networking at the global level and reinforce regional and national capacities, focusing on:

strengthening national information systems and world epidemiological surveillance;

raising awareness about Chagas disease and the challenges faced by affected populations;

develop innovative strategies aiming at disrupting vector-borne transmission (through One Health/Ecohealth approaches)

preventing transmission by blood transfusion and organ transplantation;

promoting the identification of most adequate diagnostic tests and algorithms/protocols to increase screening and diagnosis of infections;

expanding primary prevention of congenital transmission and case management of congenital and non-congenital infections;

promoting consensus on adequate updated case management, including co-infections and co-morbidities (such as COVID-19, HIV/AIDS, strongyloidiasis...); and,

promoting the development of multidimensional approaches.

---------------------------------------------------

Argentina, Belize, Bolivia (Plurinational State of), Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela (Bolivarian Republic of).

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Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi . About 6 million to 7 million people worldwide are estimated to be infected with T. cruzi, the parasite that causes Chagas disease.

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https://www.cdc.gov/dpdx/trypanosomiasisamerican/index.html

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Causal Agent

Trypanosoma cruzi, is a parasitic protozoan that is the causative agent of Chagas disease (American trypanosomiasis). Currently, six distinct lineages of T. cruzi are classified into discrete typing units (TcI-VI), which vary in their geographic occurrence, host specificity, and pathogenicity.

Life Cycle

An infected triatomine insect vector (or "kissing" bug) takes a blood meal and releases trypomastigotes in its feces near the site of the bite wound. Trypomastigotes enter the host through the bite wound or intact mucosal membranes, such as the conjunctiva
. Inside the host, the trypomastigotes invade cells near the site of inoculation, where they differentiate into intracellular amastigotes

. The amastigotes multiply by binary fission

and differentiate into trypomastigotes, and then are released into the circulation as bloodstream trypomastigotes

. Trypomastigotes infect cells from a variety of tissues and transform into intracellular amastigotes in new infection sites. Clinical manifestations can result from this infective cycle. The bloodstream trypomastigotes do not replicate (different from the African trypanosomes). Replication resumes only when the parasites enter another cell or are ingested by another vector. The "kissing" bug becomes infected by feeding on human or animal blood that contains circulating parasites

. The ingested trypomastigotes transform into epimastigotes in the vector's midgut

. The parasites multiply and differentiate in the midgut

and differentiate into infective metacyclic trypomastigotes in the hindgut

. Other less common routes of transmission include blood transfusions, organ transplantation, transplacental transmission, and foodborne transmission (via food/drink contaminated with the vector and/or its feces).

Hosts/Vectors

Apart from humans, a number of mammals serve as reservoir hosts for T. cruzi, e.g. armadillos, opossums, raccoons, woodrats, some other rodents, and domestic dogs. Common triatomine vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus.

Geographic Distribution

T. cruzi is endemic in vectors and wildlife reservoirs throughout the Americas from the southern half of the United States down to Argentina. Chagas disease cases have been reported from South and Central American countries, particularly in rural, impoverished areas. There have been a small number of autochthonous cases of Chagas disease in the United States.

Clinical Presentation

Chagas disease has an acute phase and chronic phase. The acute phase is usually asymptomatic, but can present with nonspecific somatic symptoms. Rarely, the acute phase may be more severe with potential cardiac or neurologic symptoms and signs. Nodular lesions or furuncles, usually called chagomas, may develop around the vector's feeding site. Chagomas occurring on the on the eyelids are commonly referred to as palpebral and periocular firm swelling. Most acute cases resolve over a period of a few weeks or months into a subclinical chronic form of the disease ("indeterminate form"). Reactivation of Chagas disease from this asymptomatic form may occur in patients with HIV or those receiving immunosuppressive drugs.

The symptomatic chronic form ("determinate form") may not occur for years or even decades after initial infection. This may include cardiac or gastrointestinal involvement, which occasionally occur together. The many complications of chronic Chagas disease can be fatal. Amastigote invasion of smooth muscle can lead to megaesophagus, megacolon, and dilated cardiomyopathy.

T. cruzi amastigotes in heart tissue.

Trypomastigotes of T. cruzi are the only stage found circulating in human blood or CSF. In tissue, the parasite forms amastigotes characterized by a single nucleus and kinetoplast. The amastigotes of T. cruzi are morphologically indistinguishable from those of Leishmania spp.

Figure B: Higher magnification of Figure A.

Figure D: Higher magnification of Figure C.

Figure F: Higher magnification of Figure E. The amastigotes in this image appear to be transforming into trypomastigotes.

T. cruzi epimastigotes, from culture.

The epimastigote stage is not seen in humans but can be found in the midgut of triatomines that have ingested trypomastigotes from an infected host.

Triatomine bug, the T. cruzi vector.

Trypanosoma cruzi is transmitted by kissing bugs (Hemiptera: Reduviidae). The most common genera responsible for transmission of the disease are Triatoma, Rhodnius, and Panstrongylus. Infection usually occurs after bugs defecate on the bite site and are rubbed into the wound by the host scratching.

Morphology

In the acute stage of the disease, diagnosis may be made by the finding of trypomastigotes in circulating blood or cerebral spinal fluid (CSF). During the chronic stage, trypomastigotes are usually not found circulating in blood and serologic testing is recommended (see below). Amastigotes may be found in biopsy specimens stained with hematoxylin-and-eosin (H&E) or Giemsa.

Serology (Antibody Detection)

Positive IFA result with T. cruzi antigen (magnification 400x).

During the acute phase of illness, blood film examination generally reveals the presence of trypomastigotes. However, during the chronic phase of infection, parasitemia is low and immunodiagnosis is a useful technique for determining whether the patient is infected.

Diagnosis of chronic Chagas disease in suspected patients is based on serology performed with at least two different serologic tests. CDC utilizes an FDA-cleared enzyme immunoassay (EIA) based on recombinant T. cruzi antigens alongside an immunoblot (TESA) as the two first-line tests. If initial EIA and TESA results are discordant, a second specimen is requested and testing is repeated. If results of the second EIA and TESA are discordant, an immunofluorescence assay (IFA) is used as a "tie-breaker" test. Various serologic methods are commercially available in other countries for laboratory diagnosis of Chagas disease. The sensitivity and specificity of these tests are highly variable.

Molecular Testing

Molecular diagnosis of Chagas disease is performed for cases of suspected acute infection (including transfusion or transplant transmission), congenital Chagas disease, and for monitoring of suspected laboratory exposures. For chronic Chagas disease, serology is generally most appropriate, although molecular detection may be performed for re-activated cases associated with immunosuppression.

At CDC molecular detection of T. cruzi DNA is performed using a combination of two real-time PCR assays (TCZ and MNC). Acceptable specimen types are EDTA blood (minimum of 2.2 ml), heart biopsy tissue (in saline or paraffin-embedded) and, in cases of suspected central nervous system involvement, CSF.

References:

Bern C, Montgomery SP, Herwaldt B L, Marin-Neto JA, Dantas RO, Maguire JH, Acquatella H, Morillo C, Kirchhoff LV, Gilman RH, Reyes, PA, Salvatella R, Moore AC. Evaluation and Treatment of Chagas Disease in the United States. Aa Systematic Review. JAMA 2007 298 2171-81

Diez M, Favaloro L, Bertolotti A, Burgos JM, Vigliano C, Lastra MP, Levin MJ, Arnedo A, Nagel C, Schijman AG, Favaloro RR. Usefulness of PCR Strategies For Early Diagnosis of Chagas' Disease Reactivation and Treatment Follow-Up in Heart Transplantation. American Journal of Transplantation. 2007; 7: 1633-1640.

Afonso AM, Ebell MH, Tarleton RL. A systematic review of high quality diagnostic tests for Chagas disease. PLoS Negl Trop Dis. 2012; 6(11):e1881.

Qvarnstrom Y, Schijman AG, Veron V, Aznar C, Steurer F, da Silva AJ. Sensitive and specific detection of Trypanosoma cruzi DNA in clinical specimens using a multi-target real-time PCR approach. PLoS Neglected Tropical Diseases. 2012; 6: e1689.

Laboratory Safety

Standard safety protocols for handling blood and sharps ( https://www.cdc.gov/dpdx/diagnosticprocedures/blood/safety.html). The risk of needle-sticks should be seriously mitigated with all possible precautions; several symptomatic cases of laboratory-acquired T. cruzi infections following needles-ticks are known.

Suggested Readings

Bern, C., Kjos, S., Yabsley, M.J. and Montgomery, S.P., 2011. Trypanosoma cruzi and Chagas' disease in the United States. Clinical Microbiology Reviews, 24 (4), pp.655-681.

Pérez-Molina, J.A., Molina, I. 2018. Chagas disease. The Lancet, 391 (10115), pp.82-94.Treatment Information
https://kissingbug.tamu.edu/external icon

DPDx is an educational resource designed for health professionals and laboratory scientists. For an overview including prevention, control, and treatment visit www.cdc.gov/parasites/.

Page last reviewed:

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division of parasitic diseases and malaria (dpdm)

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training and continuing education of laboratorians

# data[].attributes.attachment_link.description
Trypanosoma cruzi, is a parasitic protozoan that is the causative agent of Chagas disease (American trypanosomiasis). Currently, six distinct lineages of T. cruzi are classified into discrete typing units (TcI-VI), which vary in their geographic occurrence, host specificity, and pathogenicity.

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The article highlights that the genomic structure and organization of T. cruzi are determinants of its ability to infect, persist and cause disease in humans. Genome biology allows us to understand:

1. The genetic diversity and adaptability of the parasite:
T. cruzi has a highly dynamic and compartmentalized genome, with a huge variety of multigene families that encode surface proteins (e.g., trans-sialidases, mucins, MASPs). These are essential for cell invasion, immune evasion and disease chronicity.

2. Regulation of parasite gene expression:
T. cruzi does not regulate gene expression by traditional promoters, but by post-transcriptional mechanisms (control of mRNA processing and stability). This unique characteristic influences how the parasite responds to changes in the host environment, contributing to the long-term persistence of the infection.

3. Therapeutic implications:
Understanding the T. cruzi genome allows us to identify molecular targets for drugs, vaccines and new therapeutic approaches. Genetic variability also explains the natural resistance to some treatments, which reinforces the importance of genomics in the fight against the disease.

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Addressing the Chalenges of Chagas Disease

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Addressing the Chalenges of Chagas Disease

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Stigma, Social Exclusion and Mental Health

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Stigma, Social Exclusion and Mental Health

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Chagas disease is commonly associated with poverty and marginalised rural communities, leading to significant social stigma. This stigma can result in discrimination, shame, and even denial of the disease, discouraging individuals from seeking diagnosis and treatment. Such social exclusion further exacerbates health inequalities and violates principles of dignity and respect.

The psychological burden of Chagas disease is often overlooked. Fear of disease progression, limited treatment options, and associated stigma can lead to anxiety, depression, and isolation. Ethical healthcare practice must consider mental health support as a component of holistic care for affected individuals.

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Neglected tropical diseases: tackling stigmatization, discrimination and mental health through a person-centred approach

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WHO recently published its guide on the mental health of people with neglected tropical diseases. The work analyses the combined social and economic implications and evidences how pain, disability and stigma put people affected by NTDs at high risk of mental depression, anxiety and even suicidal thoughts.
Other themes associated with disability, stigmatization and discrimination were also discussed during last week’s webinar hosted by the NTD Department.

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One of the major ethical concerns is the unequal access to diagnosis, treatment, and follow-up care. Despite the disease affecting millions, investment in research and therapeutic innovation has been historically low due to its classification as a neglected tropical disease. This neglect reflects systemic injustice and highlights the need for distributive justice in global health.

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Ethical dimensions of neglected tropical disease programming

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Ethical Responsibility in Research and Innovation

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Ethical Responsibility in Research and Innovation

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There is a moral obligation to prioritise scientific research that benefits underserved populations. Commercial disinterest in drug development for Chagas disease should not override the ethical imperative to advance accessible and effective treatments. Public and global health institutions must advocate for increased funding and international collaboration.

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“Manifesto” for Advancing the Control and Elimination of Neglected Tropical Diseases

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This paper establishes a direct link between Chagas disease and genome biology by showing that susceptibility to developing the chronic cardiac form of the disease (chronic Chagas cardiomyopathy (CCC)) may be partly determined by inherited genetic variants.

Genetics and predisposition to disease
The study used a genome-wide biology approach — a GWAS (Genome-Wide Association Study) — to look for genetic variants associated with a greater or lesser likelihood of developing CCC. In other words, a genome analysis method was applied to understand the variation in individuals' response to infection.

Identification of relevant genetic loci
Loci associated with genes (SAC3D1, SNX15, BAFT2, FERMT3) that have functions linked to cardiovascular and immunological mechanisms were identified, reinforcing the idea that the host genome affects the development of the severe form of the disease.

Applications of genomics in personalized medicine
This research shows how genomics can be used to identify at-risk individuals, which may in the future enable more personalized screening and treatment strategies.

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Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications 

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Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications 

# data[].attributes.attachment_link.title
Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications

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Chagas disease caused by the parasite Trypanosoma cruzi affects millions of people. Although its first genome dates from 2005, its complexity hindered a complete assembly and annotation. However, the new sequencing methods have improved genome annotation of some strains elucidating the broad genetic diversity and complexity of this parasite. Here, we reviewed the genomic structure and regulation, the genetic diversity, and the analysis of the principal multi-gene families of the recent genomes for several strains. The telomeric and sub-telomeric regions are sites with high recombination events, the genome displays two different compartments, the core and the disruptive, and the genome plasticity seems to play a key role in the survival and the infection process. Trypanosoma cruzi (T. cruzi) genome is composed mainly of multi-gene families as the trans-sialidases, mucins, and mucin-associated surface proteins. Trans-sialidases are the most abundant genes in the genome and show an important role in the effectiveness of the infection and the parasite survival. Mucins and MASPs are also important glycosylated proteins of the surface of the parasite that play a major biological role in both insect and mammal-dwelling stages. Altogether, these studies confirm the complexity of T. cruzi genome revealing relevant concepts to better understand Chagas disease.

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A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy

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A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy

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Chronic Phase Case Study: Chronic Chagas Heart Disease in Older Patients

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Chronic Phase Case Study: Chronic Chagas Heart Disease in Older Patients

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Chronic Chagas heart disease represents one of the most severe long-term complications of T. cruzi infection. A case-control study conducted between 1997 and 2005 in Belo Horizonte, Brazil, evaluated factors associated with chronic Chagas heart disease in patients over the age of 50. This investigation provides critical insights into risk factors and the epidemiological profile of chronic cardiac involvement in Chagas disease.

The study involved 90 patients over 50 years old, divided into two groups, a case group where 46 patients were diagnosed with chronic Chagas heart disease based on abnormal ECGs findings, and a control group with 44 patients with undetermined forms of the chronic disease.

The research deployed both univariate and multivariate statistical methods to analyze a wide range of variables, such as social and demographic characteristics, epidemiological variables and clinical variables.

The investigation identified two primary risk factors independently associated with the development of chronic Chagas heart disease, such as age, with patients aged over 60 years demonstrated a threefold higher risk (Odds Ratio [OR] = 2.89) for developing CCHD compared to their younger counterparts and family history, with a positive family history of Chagas heart disease was significantly linked with the condition, with an OR of 2.833. Other factors, notably systemic hypertension and gender, did not show any statistically significant correlation with the disease outcome. The low statistical power associated with skin color was noted due to the small sample size.

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Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

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In a medical context, an "acute case" refers to a disease or condition that develops quickly and lasts a short period, typically requiring immediate or short-term care.

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A "chronic case" refers to a disease or condition that lasts for a prolonged period, typically three months or longer, and may worsen over time.

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To sum up, Chagas disease continues to be a public health concern, especially in regions with less access to medical care.

Through genome biology, we have begun to better understand how the Trypanosoma cruzi parasite works, how it survives in the human body and how it adapts so well to its environment.

Modern technologies, such as genome sequencing, CRISPR-Cas9 editing and bioinformatics tools, are helping us to find new targets for treatment and improve diagnosis.

The case studies we analyzed show that these technologies are already making a difference, especially in the development of more precise therapies.

But, as we have also seen, it is essential to think about the ethical aspects. Not everyone has access to new technologies, and the use of gene editing raises important questions about safety, privacy and fairness. Science has a fundamental role to play, but it must be used responsibly and fairly.

In short, fighting Chagas disease doesn't just depend on technology - it also requires social awareness, global collaboration and a real commitment to the populations most affected.

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Ethical dimensions of neglected tropical disease programming

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Ethical dimensions of neglected tropical disease programming

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Ethical dimensions of neglected tropical disease programming

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Chagas disease persists primarily in communities with limited political and economic power, making it a clear issue of social justice. Ethical responses should uphold the rights of these populations, ensuring fair access to health information, prevention strategies, and medical care. Tackling Chagas disease is a biomedical challenge and a call to defend human rights.

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The genome of Chagas disease vectors, mainly triatomines such as Triatoma infestans, Rhodnius prolixus and others, plays a fundamental role in the adaptation, dispersal and competence of these insects to transmit Trypanosoma cruzi. Genomic alterations and characteristics directly influence the biology, ecology and vectorial capacity of these insects.

1. Genes related to hematophagy

The genome of Rhodnius prolixus reveals specific adaptations to the habit of feeding on blood, essential for the transmission of Trypanosoma cruzi. Expansions in genes involved in host detection (olfactory and taste receptors), blood digestion (proteolytic enzymes) and neutralization of heme toxicity stand out. Genes encoding salivary proteins with anticoagulant and immunomodulatory functions were also identified, facilitating feeding and infection.

2. Changes in immunological pathways

Despite having immunological pathways such as Toll, R. prolixus has an incomplete IMD pathway, which limits the response against certain infections. Interestingly, although it controls the gut microbiota, the insect does not appear to activate mechanisms that are effective against T. cruzi, suggesting that the parasite can escape or tolerate vector immunity—a possible coevolutionary adaptation.

3. Genomic interactions with bacterial symbionts

Integrated and actively transcribed sequences of bacterial origin (Wolbachia) were detected in the genome of R. prolixus, indicating horizontal gene transfer. These genes may influence the insect's immunity, metabolism or vector competence, indirectly affecting the interaction with T. cruzi and the disease transmission capacity.

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Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection

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Genome of Rhodnius prolixus, an insect vector of Chagas disease, reveals unique adaptations to hematophagy and parasite infection

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Update on oral Chagas disease outbreaks in Venezuela_ epidemiological, clinical and diagnostic approaches

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Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

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1. Comprehensiveness -> Present
The study involves broad surveillance and patient data collection across multiple outbreaks. Serological and PCR-based diagnostic tools imply use of genomic sequences and patient-level data integration.

2. Scale -> Moderate
The study tracks multiple outbreaks involving hundreds of cases across Venezuela, but it's still relatively local. There's no mention of large-scale genomic data mining or national databanks.

3. Rapid Data Release -> Limited
While the paper refers to timely public health responses and outbreak publications (some via ProMED), it doesn’t emphasize systematic open data sharing in genomic repositories.

4. Technology -> Present
Use of ELISA, PCR, and molecular genotyping (e.g., DTU typing) shows incorporation of molecular technologies that are accessible and essential in outbreak response.

5. Social and Ethical Implications -> Present
The paper emphasizes food safety, vulnerability of children, education of health workers, and surveillance failures. It frames Chagas disease as both a public health issue and a socio-epidemiological concern—touching on equity, rural health, and systemic preparedness.

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Update on oral Chagas disease outbreaks in Venezuela_ epidemiological, clinical and diagnostic approaches

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1. Comprehensiveness -> Present
The study uses structured clinical, demographic, and epidemiological datasets. It’s not genome-wide, but it is thorough in its data integration.

2. Scale -> Limited
It involves a total of 90 patients, therefore an in-depth but small-scale study. Computational power was likely minimal and no genomic or high-throughput datasets were generated or used.

3. Rapid Data Release -> No mention
There's no mention of data sharing, and the study is retrospective. No open data infrastructure is discussed.

4. Technology -> Low
The study is more clinical-epidemiological. It relies on traditional diagnostics (ECG, imaging, serology), not genomic technologies.

5. Social and Ethical Implications -> Present
Discusses social determinants like rural origin, limited access to care, and under-recognition of disease in older populations. Emphasizes the need for tailored strategies for vulnerable aging patients, which reflects ethical considerations in care delivery.

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Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

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It is a high-throughput DNA sequencing technology that has revolutionized genetic research and medicine. It allows large amounts of DNA to be sequenced simultaneously, providing genetic information on a large scale.

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An enzyme called Cas9 acts like a “molecular scissors”. It is used to cut and modify sections of DNA associated with a disease or any kind of defect that needs to be repaired.

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Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (American trypanosomiasis). This parasite is transmitted mainly through the feces of triatomine insects, known as “barbers” or “kissing bugs”

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Rhodnius prolixus is a hematophagous insect known as the “kissing bug”. This insect is especially notable for being a main vector of Chagas disease, a serious illness caused by the protozoan Trypanosoma cruzi. During feeding, Rhodnius prolixus can transmit the parasite by defecating near the area of the bite, allowing the parasite to enter the body through the skin.

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IMD pathway (Imd signaling pathway) is a crucial immunological pathway in insects and some arthropods, responsible for defense against Gram-negative bacteria. This pathway is activated when peptidoglycan recognition proteins (PGRPs) detect DAP-type peptidoglycan, triggering a signaling cascade that culminates in the production of antimicrobial peptides and other infection-fighting effectors.

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Post-transcriptional mechanism refers to the processes that occur after RNA transcription, but before translation into proteins. These mechanisms regulate gene expression at the RNA level and include modifications such as alternative splicing, the addition of a poly-A tail, RNA editing and the export of RNA from the nucleus to the cytoplasm.