Chagas Disease in Texas: Still a Neglected Disease?
Jennifer Seltzer, PharmD
June 19, 2012
Chagas disease, named for Brazilian physician Carlos Chagas in 1909, is an infectious disease caused by the protozoan parasite, Trypanosoma cruzi. Chagas disease is also known as American trypanosomiasis because the parasite is found only in the Americas, primarily in rural Latin America where there is widespread poverty. T. cruzi is transmitted to humans and other mammals through contact with the feces of a handful of large, blood-sucking triatomine bug species infected with T. cruzi; Triatoma infestans, Rhodnius prolixus, and Triatoma dimidiata are the most common vectors that transmit T. cruzi to man.1, 2 These insects, found primarily in houses made from mud, adobe, straw, or palm thatch, hide in the walls and roofs during the day, but emerge at night to feed on human faces, earning them the name "kissing bugs".1 T. cruzi can also be transmitted congenitally from mother to infant as well as through transfusing contaminated blood components, transplanting infected donor organs, laboratory accidents, or, rarely, through ingesting contaminated food and/or drink.1, 3 Approximately 8 to 10 million people are infected in Mexico, Central America, and South America and it is estimated that about 300,000 infected persons have immigrated and live in the United States. A disproportionate number of infected persons in the United States reside in Texas and along the Gulf coast.4 In the U.S., Chagas disease is considered one of the neglected parasitic infections identified by the Centers for Disease Control (CDC) for public health action.1
Following exposure, the incubation period for Chagas disease is 1-2 weeks, although with transfusion- and transplant-associated disease, the incubation period may last up to 4 months.3, 5 The clinical manifestations of Chagas disease are divided into acute and chronic phases: the acute phase lasts between 8 and 12 weeks while the chronic phase lasts for the lifetime of the host. The acute phase is usually asymptomatic but may present with mild, self-limiting symptoms such as fever, malaise, and liver or spleen enlargement. A chagoma - inflammation and edema at the site of inoculation by the parasite – may develop in a minority of patients, typically on the face or extremities.1-3, 5 Inoculation occurring in the conjunctiva manifests as a characteristic unilateral, nonpainful upper and lower eyelid edema that lasts for a few weeks known as Romaña's sign.1, 3, 5 Potentially life-threatening, severe, acute infection occurs rarely (< 1% of patients) and presents as myocarditis, pericardial effusion or meningoencephalitis.3 Congenitally infected infants may present with Chagas disease signs either at birth or several weeks after delivery (e.g., hypotonia, fever, hepatosplenomegaly, anemia, low Apgar scores, prematurity). Symptoms, if present, dissipate in approximately 90% of T. cruzi infections regardless of whether patients receive antitrypanosomal drug therapy.2 During this acute phase, there is active parasite replication and microscopically observable parasitemia, but numbers significantly decrease within 4 to 8 weeks due to host immune defense mechanisms, signifying the end of the acute phase.2, 3, 5
Chronic Chagas disease is diagnosed through serologic testing, which confirms the presence of IgG antibodies to T. cruzi.3 Most infected patients have chronic indeterminate Chagas disease, characterized by the presence of T. cruzi serum antibodies, the absence of clinically evident disease (e.g., normal electrocardiogram, normal radiologic evaluation of the chest, esophagus and colon), and few parasites identified in the bloodstream.2 Approximately 20-30% of infected patients, however, will develop a determinate form of chronic Chagas disease that exhibits cardiac, digestive, or cardiodigestive symptoms 10 to 30 years after the initial infection.2, 3 The heart is impacted far more commonly than the gastrointestinal system in chronic determinate Chagas disease (20%-30% vs 10%-15% of infected individuals, respectively). Early cardiac symptoms include conduction abnormalities (e.g., right bundle branch block, left ventricular wall motion abnormalities), while later manifestations include heart block, arrhythmias, cardiac failure, thromboembolism, and sudden death.2, 5, 6 Megaesophagus and/or megacolon comprise the predominant gastrointestinal symptoms for chronic determinate Chagas disease. Chronic T. cruzi infections can be re-activated with or without symptoms in those immunosuppressed due to malignancy, chemotherapy, organ transplantation, immunosuppressive medications, or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).2, 7
The purpose of Chagas disease treatment is to eliminate T. cruzi and reduce/minimize disease symptoms. Clinical and parasitological cures are achieved in 60% to 85% of patients treated with antitrypanosomal medications. Treatment is recommended for all patients with acute documented infection, immunosuppression, and congenital infections, as well as all children with chronic infection and adults 19 to 50 years of age without Chagas heart disease. Treatment is optional for adults older than 50 years as efficacy has not been proven in this age group. Antitrypanosomal therapy is not effective in advanced Chagas heart disease, and is contraindicated for use in pregnancy or patients with severe renal or hepatic dysfunction. While evidence is lacking for antitrypanosomal therapy benefit in Chagas gastrointestinal disease, drug therapy should be used in this patient population to minimize the development or progression of heart disease.1, 2, 5, 7
The only drugs with documented effectiveness in Chagas disease are benznidazole, a nitroimidazole derivative, and nifurtimox, a nitrofuran compound. Benznidazole is considered first-line therapy due to better tolerability and more current efficacy data. In children less than 12 years of age, benznidazole 10 mg/kg/ day is given orally in two divided doses for 60 days, while children 12 years of age and older and adults receive benznidazole doses of 5-7 mg/kg/day orally in two divided doses for 60 days. Nifurtimox doses are as follows: 15-20 mg/kg/day orally in three to four divided doses for 90 days (children 10 years of age and younger); 12.5-15 mg/kg/day orally in three to four divided doses for 90 days (children 11-16 years of age); and 8-10 mg/kg/day orally in three to four divided doses for 90 to 120 days (children 17 years of age and older, adults). Common benznidazole adverse effects are dermatitis and peripheral neuropathy, while typical adverse effects associated with nifurtimox use include frequent gastrointestinal complaints (e.g., nausea, vomiting, abdominal discomfort), irritability, insomnia, and disorientation. In the U.S., antitrypanosomal therapy is only available through the CDC.1, 2, 5, 7
Authors have recently found resemblances between Chagas disease and the early HIV/AIDS years: both diseases affect impoverished people, both are chronic conditions, both require expensive therapy, and both are highly stigmatizing. To prevent and/or improve potential health disparities with Chagas disease, public health efforts are aimed toward improved vector control strategies, health education, and available drug therapy for this disease state.4
Advances have been made in Chagas disease management, including pesticide control to eliminate disease spread in endemic areas and blood donor screening. Gaps remain, however, in efficiently supplying effective antitrypanosomal therapy as well as determining which patients will develop Chagas cardiomyopathy and which will remain asymptomatic. Future research will target more rapid diagnostic testing for Chagas disease and improvements in effective, tolerable, life-saving treatments to better equip healthcare professionals to manage this emerging Texas health problem.