Chagas Disease

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Diagnosis and reasoning

This patient has presented with a complex constellation of clinical findings: - Fever, headache, and constitutional symptoms for two weeks - A painless red lump on her right arm for the same duration - Recent foreign travel (to Costa Rica) just prior to the onset of the above symptoms The physical examination turns up some more clues: - The lesion on the right arm is found to be erythematous, indurated and nontender, with central edema - Mild hepatomegaly is also present When the above signs, symptoms, and timeline are interpreted together, the diagnosis which immediately comes to mind is Chagas disease, which is endemic in Costa Rica. Therefore, her further evaluation should include a complete blood count, liver profile, and microscopy of thick and thin blood films. The first of these shows lymphocytosis and eosinophilia, which is compatible with (but not specific to) the working diagnosis. However, blood films are confirmatory, showing parasitic forms suggestive of T. cruzi trypomastigotes. Note that given the strong possibility of Chagas disease, lack of historical or examination features of viral hepatitis, and normal liver profile, there is little justification for a viral hepatitis panel here. Antitrypanosomal therapy (i.e. with benznidazole or nifurtimox) is essential and should be commenced as soon as possible. As there is no evidence of secondary bacterial infection of the chagoma, antibacterial therapy is not indicated right now. Note that corticosteroids should be avoided, as they will suppress the immune system and potentially exacerbate the infection. Neither is there any rationale for isolation.


Discussion

Chagas disease, also known as American trypanosomiasis, is a tropical infectious disease caused by the protozoan agent Trypanosoma cruzi. The disease is endemic to Central and Latin America, with cases in other countries following travel to an endemic region. As per World Health Organization (WHO) statistics, around 18 million persons are infected worldwide, with another 100 million at risk of exposure. The triatomine bug ("kissing bug") is the primary insect vector for T. cruzi. The vector punctures the skin with a needle-like bloodsucking organ and then passes on the parasite by defecating on the wound. A local delayed-type hypersensitivity reaction then results in a chagoma. The parasite subsequently invades macrophages via phagocytosis. The infected cells subsequently lyse and release trypomastigotes into the blood. The infection then spreads systemically, showing tropism for muscular tissue, particularly that of the myocardium. Non-vector transmission may also occur. This may be following blood transfusions or organ transplantation; via congenital transmission; or rarely, via oral transmission following the ingestion of contaminated food or fruit. During the acute stage (i.e. the first 8 weeks post-infection), affected persons are asymptomatic, or only show nonspecific symptoms such as fever, headaches, bodyaches, fatigability, anorexia, nausea and vomiting. Upon examination, localized erythema and swelling (i.e. a chagoma) may be noted where the parasite entered the body. Hepatomegaly, splenomegaly, and regional lymphadenopathy may also be present. "Romaña's sign" is pathognomonic of Chagas disease. This involves swelling of the eyelids on the side of the face near the bite wound, or where bug feces were deposited or accidentally rubbed into the eye. In ~1% of persons, fulminant acute disease with myocarditis, pericardial effusions, and/or meningoencephalitis may occur. This is more common in infants, and in the immunocompromised. Unfortunately, even in countries where Chagas disease is endemic, most presentations are nonspecific, mimicking those caused by other diseases common in those regions (e.g. typhoid fever, brucellosis, acute schistosomiasis, kala-azar, infectious mononucleosis, cytomegalovirus infection, etc). The intermediate stage starts from 8 weeks onwards and may last for years. In this phase, the patient is asymptomatic, but inflammatory infiltrations persist in the heart and digestive tract, insidiously leading towards the onset of chronic Chagas disease. In the heart, chronic myocarditis can result in arrhythmias, thromboembolism, sudden death and cardiac insufficiency. Destruction of parasympathetic fibers in the digestive tract may result in dysphagia, reflux, megaesophagus, megacolon, and aspiration. Note that Chagas heart disease can be easily misdiagnosed for other causes of cardiomyopathy, such as alcoholism or beriberi. The diagnosis of Chagas disease depends on the stage of the disease. In the acute stage, trypomastigotes can be observed upon microscopy of freshly anticoagulated blood. Giemsa staining can be used to visualize the protozoan on a blood film. The intermediate and chronic stages have low levels of parasitemia. Therefore, serological studies are required to demonstrate a specific immune response. Suitable investigations include enzyme-linked immunosorbent assays (ELISA), indirect fluorescent antibody (IFA) testing, and blotting techniques. Note that the diagnosis should be confirmed using at least two separate techniques. Where symptoms are present, target-organ damage may also need to be evaluated. Based on these findings, the disease can then be classified as purely cardiac, purely digestive, or cardio-digestive. The parasitic infection can be treated using the antitrypanosomal agents benznidazole and nifurtimox, with the former being the drug of choice due to its lesser side effects. Earlier, these agents were mainly prescribed for the acute phase alone. However, they are now indicated in the indeterminate and chronic stages as well, particularly if the patient is young, or the cardiopathy is less severe, so as to reduce parasitemia and slow the evolution of the disease. Chagas cardiopathy can be treated with amiodarone, beta blockers, diuretics, or as a last resort, heart transplantation. In the case of megaesophagus, sublingual nitrates relax the lower esophageal sphincter and help ameliorate symptoms, while myotomy and fundoplication are definitive surgical measures reserved for highly symptomatic patients. Individuals with megacolon may benefit from high fiber diets, high fluid intake, laxatives, and enemas. Surgical bowel resection is the protocol for the most severe cases. Preventative measures are extremely important to control transmission. Public health education is paramount, particularly in high-risk populations. Vector control with insecticides lowers the population of triatomines. Blood and organ donor screening are necessary to prevent non-vector transmission.


Take home messages

  1. Chagas disease is endemic to Central America and South America and should be considered in patients hailing or immigrating from these areas.
  2. Acute infection features inflammation at the site of infection and/or nonspecific systemic symptoms. Rarely, serious cardiac or neurological disease can occur.
  3. The chronic sequela of the disease include cardiomyopathy, megacolon, and megaesophagus.
  4. Diagnosis in the acute stage is via microscopy of blood films. Serological techniques are preferred in chronic disease.
  5. The antitrypanosomal drugs nifurtimox or benznidazole are the agents of choice. Chagas heart disease and digestive tract disease, if present, require customized treatments.

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