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Chagas Disease

Disease Details

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Description: Chagas disease is a tropical parasitic illness caused by Trypanosoma cruzi, transmitted primarily by triatomine bugs, and can lead to severe heart and digestive system complications if untreated.
Type: Type: Chagas disease is an infectious disease.
Type of genetic transmission: Chagas disease is not genetically transmitted; it is primarily spread through the bite of an infected triatomine bug (also known as a kissing bug). Other transmission routes include congenital transmission (from mother to baby), blood transfusions, organ transplants, consumption of contaminated food or drink, and accidental laboratory exposure.
Signs And Symptoms: Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years. The acute stage is often symptom-free. When present, the symptoms are typically minor and not specific to any particular disease. Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes. Sometimes, people develop a swollen nodule at the site of infection, which is called "Romaña's sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin. In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can involve inflammation of the heart muscle, fluid accumulation around the heart, and inflammation of the brain and surrounding tissues, and may be life-threatening. The acute phase typically lasts four to eight weeks and resolves without treatment.Unless treated with antiparasitic drugs, individuals remain infected with T. cruzi after recovering from the acute phase. Most chronic infections are asymptomatic, which is referred to as indeterminate chronic Chagas disease. However, over decades with the disease, approximately 30–40% of people develop organ dysfunction (determinate chronic Chagas disease), which most often affects the heart or digestive system.The most common long-term manifestation is heart disease, which occurs in 14–45% of people with chronic Chagas disease. People with Chagas heart disease often experience heart palpitations, and sometimes fainting, due to irregular heart function. By electrocardiogram, people with Chagas heart disease most frequently have arrhythmias. As the disease progresses, the heart's ventricles become enlarged (dilated cardiomyopathy), which reduces its ability to pump blood. In many cases the first sign of Chagas heart disease is heart failure, thromboembolism, or chest pain associated with abnormalities in the microvasculature.Also common in chronic Chagas disease is damage to the digestive system, which affects 10–21% of people. Enlargement of the esophagus or colon are the most common digestive issues. Those with enlarged esophagus often experience pain (odynophagia) or trouble swallowing (dysphagia), acid reflux, cough, and weight loss. Individuals with enlarged colon often experience constipation, and may develop severe blockage of the intestine or its blood supply. Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered reflexes or movement. While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.Signs and symptoms differ for people infected with T. cruzi through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, vomiting, shortness of breath, cough, and pain in the chest, abdomen, and muscles. Those infected congenitally typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as jaundice, respiratory distress, and heart problems. People infected through organ transplant or blood transfusion tend to have symptoms similar to those of vector-borne disease, but the symptoms may not manifest for anywhere from a week to five months. Chronically infected individuals who become immunosuppressed due to HIV infection can have particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or brain abscesses. Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum.
Prognosis: The prognosis for Chagas disease can vary depending on the stage and severity of the infection. In the acute phase, which occurs shortly after the initial infection, symptoms are often mild or asymptomatic, but severe cases can be life-threatening. If the disease progresses to the chronic phase, it can lead to serious complications like heart disease, digestive problems, and neurological disorders. Early detection and treatment with antiparasitic drugs can improve outcomes and prevent complications. Chronic cases may require additional treatments to manage symptoms and prevent further deterioration. Regular medical monitoring is essential for managing the disease effectively.
Onset: The onset of Chagas disease can be divided into two phases: acute and chronic. The acute phase occurs immediately after infection and can last for weeks to months. Symptoms during this phase might include fever, fatigue, body aches, headache, rash, loss of appetite, diarrhea, and vomiting, but many people may remain asymptomatic.

The chronic phase can occur years or even decades after the initial infection. During this phase, the disease can remain silent or lead to serious complications such as heart disease, digestive problems, and neurological issues.
Prevalence: Chagas disease, caused by the parasite Trypanosoma cruzi, primarily affects Latin America. The prevalence is estimated to be around 6 to 7 million people worldwide, with a significant number of cases in countries such as Brazil, Argentina, and Mexico. However, due to migration, cases are now also found in the United States, Canada, and Europe.
Epidemiology: In 2019, an estimated 6.5 million people worldwide had Chagas disease, with approximately 173,000 new infections and 9,490 deaths each year. The disease resulted in a global annual economic burden estimated at US$7.2 billion in 2013, 86% of which is borne by endemic countries. Chagas disease results in the loss of over 800,000 disability-adjusted life years each year.The endemic area of Chagas disease stretches from the southern United States to northern Chile and Argentina, with Bolivia (6.1%), Argentina (3.6%), and Paraguay (2.1%) exhibiting the highest prevalence of the disease. Within continental Latin America, Chagas disease is endemic to 21 countries: Argentina, Belize, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Uruguay, and Venezuela. In endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), and in Argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001. During Venezuela's humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease seroprevalence rates have increased. Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission.While the rate of vector-transmitted Chagas disease has declined throughout most of Latin America, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species. Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.Chagas exists in two different ecological zones: In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where T. cruzi also circulates in wild and domestic animals. T. cruzi commonly infects more than 100 species of mammals across Latin America including opossums (Didelphis spp.), armadillos, marmosets, bats, various rodents and dogs all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals. For entomophagous animals this is a common mode. Didelphis spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces. Veterinary transmission also occurs through vertical transmission through the placenta, blood transfusion and organ transplants.
Intractability: Chagas disease, caused by the parasite Trypanosoma cruzi, can be challenging to treat, particularly in the chronic phase. While antiparasitic medications like benznidazole and nifurtimox are effective during the acute phase, their efficacy decreases as the disease progresses. Chronic Chagas disease often involves complications such as heart and gastrointestinal issues that require separate management and are difficult to fully resolve. Therefore, Chagas disease can be considered intractable, especially in its later stages.
Disease Severity: The severity of Chagas disease varies depending on the phase of the infection. There are two phases: acute and chronic.

1. **Acute Phase**:
- This phase lasts for a few weeks or months after infection. Many people may remain asymptomatic or experience mild symptoms such as fever, fatigue, body aches, rash, and swelling at the infection site. Severe symptoms are rare but can include inflammation of the heart muscle or the brain and the lining around the brain.

2. **Chronic Phase**:
- This phase can last for decades or even for life. Most people remain asymptomatic; however, around 20-30% of infected individuals may develop serious complications over time. These can include cardiac problems (like heart failure, arrhythmias, or sudden cardiac arrest) and gastrointestinal issues (such as an enlarged esophagus or colon).

Severity is primarily determined by whether the disease progresses from the acute to the chronic phase and the extent of complications that develop during the chronic phase.
Healthcare Professionals: Disease Ontology ID - DOID:12140
Pathophysiology: In the acute phase of the disease, signs and symptoms are caused directly by the replication of T. cruzi and the immune system's response to it. During this phase, T. cruzi can be found in various tissues throughout the body and circulating in the blood. During the initial weeks of infection, parasite replication is brought under control by production of antibodies and activation of the host's inflammatory response, particularly cells that target intracellular pathogens such as NK cells and macrophages, driven by inflammation-signaling molecules like TNF-α and IFN-γ.During chronic Chagas disease, long-term organ damage develops over years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, T. cruzi is found frequently in the striated muscle fibers of the heart. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat. Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically macrophages and T cells. Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.In the heart, colon, and esophagus, chronic disease leads to a massive loss of nerve endings. In the heart, this may contribute to arrythmias and other cardiac dysfunction. In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction. Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.
Carrier Status: In Chagas disease, there is no "carrier status" in the typical sense seen in some other diseases. Chagas disease is caused by the parasite Trypanosoma cruzi, and once a person is infected, they can either enter an acute phase, which may be asymptomatic or mild, or a chronic phase that can lead to severe complications over time. A person infected with T. cruzi is always considered infected, even if they are asymptomatic, and would not be referred to as a "carrier" in the usual terminology.
Mechanism: Chagas disease, also known as American trypanosomiasis, is caused by the protozoan parasite Trypanosoma cruzi. The mechanism involves several stages:

1. **Transmission**: T. cruzi is primarily transmitted to humans through the feces of triatomine bugs, commonly known as "kissing bugs." The parasite can also be transmitted congenitally, through blood transfusions, organ transplants, consumption of contaminated food, and via laboratory incidents.

2. **Cell Invasion**: Once in the host, T. cruzi trypomastigotes penetrate various cells, commonly macrophages and fibroblasts. They invade through a variety of mechanisms, including parasitophorous vacuole formation.

3. **Intracellular Transformation**: Inside host cells, trypomastigotes transform into amastigotes. These amastigotes multiply by binary fission in the cytoplasm of the host cell.

4. **Cell Rupture and Dissemination**: After several multiplication cycles, amastigotes transform back into trypomastigotes, causing the host cell to rupture. The released trypomastigotes can then enter the bloodstream and infect new cells, continuing the cycle.

**Molecular Mechanisms**:
1. **Surface Molecules**:
- T. cruzi expresses glycoproteins like trans-sialidase and glycosylphosphatidylinositol (GPI)-anchored mucins that help in invasion, immune evasion, and adherence to host cells.

2. **Host Cell Interaction**:
- The parasite utilizes receptors on the host cell surface such as TGF-β and bradykinin receptors to facilitate entry.

3. **Immune Evasion**:
- T. cruzi can alter host immune responses through mechanisms such as the suppression of nitric oxide production, modulation of cytokine profiles, and inhibition of T cell activation.
- The parasite’s ability to exist intracellularly helps it avoid direct immune surveillance.

4. **Oxidative Stress Management**:
- T. cruzi possesses antioxidant enzymes like superoxide dismutase and trypanothione reductase to combat oxidative stress within the host cell.

These mechanisms contribute to the parasite's ability to establish infection, sustain cellular invasion, and evade or manipulate the host immune system.
Treatment: Chagas disease treatment involves antiparasitic medications, specifically benznidazole and nifurtimox, which are most effective during the acute phase. Chronic phase treatment focuses on managing symptoms and complications, such as heart failure or digestive issues, often requiring a multidisciplinary approach.
Compassionate Use Treatment: For Chagas disease, compassionate use treatment and off-label or experimental treatments may include:

1. **Benznidazole and Nifurtimox**: While these medications are the standard treatment for the acute phase, they may also be used under compassionate use or experimental protocols for chronic Chagas disease in regions where standard treatment is not approved or accessible.

2. **AmBisome (Liposomal Amphotericin B)**: Some studies have explored its use for Chagas disease, particularly for patients who cannot tolerate first-line treatments.

3. **Posaconazole and E1224 (Fosravuconazole)**: Investigational treatments targeting Trypanosoma cruzi, the parasite causing Chagas disease, showing some efficacy in clinical trials.

4. **Azithromycin and Other Antibiotics**: Evaluated in combination with antiparasitic drugs to enhance treatment efficacy.

These treatments might be available through clinical trials or special access programs for patients who do not have other therapeutic options.
Lifestyle Recommendations: For Chagas disease, lifestyle recommendations include:

1. **Avoiding Endemic Areas**: When possible, avoid travel to areas where Chagas disease is common, particularly rural parts of Latin America.
2. **Improving Housing Conditions**: In endemic areas, improve housing conditions to prevent infestation by the Triatomine bugs (kissing bugs) that transmit the disease. This includes sealing cracks in walls and roofs, and using bed nets.
3. **Regular Screening**: For individuals at risk, such as those living in or having lived in endemic areas, regular medical screening can help in early detection and treatment.
4. **Food Safety**: Avoid consuming raw or undercooked foods that might be contaminated with the parasites that cause Chagas disease.
5. **Personal Protective Measures**: Use insect repellent, wear protective clothing, and take other measures to reduce the risk of bug bites.
6. **Blood and Organ Donation Precautions**: Ensure that blood transfusions and organ transplants are screened for Chagas disease to prevent transmission.

By adopting these lifestyle recommendations, the risk of contracting or spreading Chagas disease can be significantly reduced.
Medication: The primary medications used to treat Chagas disease are:

1. **Benznidazole**: This is the most commonly used drug and is effective in the acute phase of the disease. It can also be used in the chronic phase, though its efficacy decreases.

2. **Nifurtimox**: This is an alternative medication, also primarily used in the acute phase, and can be used in the chronic phase with varying effectiveness.

Both medications can have side effects and their use should be monitored by a healthcare professional.
Repurposable Drugs: For Chagas disease, there are some drugs initially approved for other conditions that have been considered for repurposing. These include:

1. **Posaconazole**: An antifungal agent, initially developed to treat fungal infections.
2. **E1224 (Fosravuconazole)**: A prodrug of ravuconazole, another antifungal agent.
3. **Itraconazole**: Another antifungal medication.
4. **Amiodarone**: Originally used for cardiac arrhythmias, has shown some antiparasitic activities.

Repurposing existing drugs can help reduce the time and cost associated with drug development, potentially providing new therapeutic options for Chagas disease. However, their efficacy and safety for treating Chagas disease require thorough clinical evaluations.
Metabolites: Chagas disease, caused by the parasite Trypanosoma cruzi, leads to various metabolomic changes in the host. Some key metabolites affected include trypanothione, which is crucial for the parasite's antioxidant defense, and metabolic pathways involving amino acids, nucleotides, and lipids. Alterations in these metabolic processes contribute to the disease pathology and progression.
Nutraceuticals: Nutraceuticals, or dietary supplements, have not been established as effective treatments for Chagas disease. This disease, caused by the parasite *Trypanosoma cruzi*, primarily requires antiparasitic medications such as benznidazole or nifurtimox. Nutraceuticals might support general health but should not be considered a substitute for these targeted therapies.
Peptides: In the context of Chagas disease, there is ongoing research into the use of peptides for both diagnosis and treatment. Peptides can serve as biomarkers to detect the presence of Trypanosoma cruzi, the parasite that causes the disease. Additionally, therapeutic peptides are being explored to target and neutralize T. cruzi.

Nanotechnology (nan) is also being investigated for potential applications in Chagas disease. Nanoparticles can be used to improve the delivery and efficacy of drugs, making them more effective in reaching and eliminating the parasite. Nanotechnological approaches may also enhance diagnostic techniques through more sensitive and specific detection methods.