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American Trypanosomiasis (Chagas Disease; Trypanosoma cruzi )
American trypanosomiasis or Chagas disease is caused by the protozoan Trypanosoma cruzi . Its natural vectors are the reduviid insects, specifically triatomines , variably known as wild bedbugs, assassin bugs, or kissing bugs. It can also be transmitted orally from contaminated food, vertically from mother to child, and through blood transfusion or organ transplantation. Signs and symptoms of acute Chagas disease are usually nonspecific, whereas chronic disease may manifest as cardiomyopathy or severe gastrointestinal (GI) dilation and dysfunction.
Etiology
American trypanosomiasis is caused by Trypanosoma cruzi , a parasitic, flagellated kinetoplastid protozoan. The main vectors for T. cruzi are insects of the family Reduviidae, subfamily Triatominae, which includes Triatoma infestans, Rhodnius prolixus, and Panstrongylus megistus.
Life Cycle
T. cruzi has 3 recognizable morphogenetic phases: amastigotes, trypomastigotes, and epimastigotes ( Figs. 313.1 and 313.2 ). Amastigotes are intracellular forms found in mammalian tissues that are spherical and have a short flagellum but form clusters of oval shapes (pseudocysts) within infected tissues. Trypomastigotes are spindle-shaped, extracellular, nondividing forms that are found in blood and are responsible for both transmission of infection to the insect vector and cell-to-cell spread of infection. Epimastigotes are found in the midgut of the vector insect and multiply in the midgut and rectum of arthropods, differentiating into metacyclic forms. Metacyclic trypomastigotes are the infectious form for humans and are released onto the skin of a human when the insect defecates close to the site of a bite, entering through the damaged skin or mucous membranes. Once in the host, these multiply intracellularly as amastigotes, which then differentiate into bloodstream trypomastigotes and are released into the circulation when the host cell ruptures. Bloodborne trypomastigotes circulate until they enter another host cell or are taken up by the bite of another insect, completing the life cycle.
Epidemiology
Natural transmission of Chagas disease occurs in North and South America, most frequently in continental Latin America. The disease may arise elsewhere because of migration and transmission through contaminated blood. World Health Organization (WHO) and Pan-American Health Organization–led efforts in large-scale vector control, blood donor screening to prevent transmission through transfusion, and case finding and treatment of chronically infected mothers and newborn infants have effectively halted transmission in a number of areas of South America. The number of cases has dropped from a peak of 24 million in 1984 to a current estimate of 6-7 million, with about 10,000 deaths annually. Overall vectorial transmission continues to drop, although challenges remain, including the emergence of disease in new areas thought to be Chagas free, along with reemergence in previously controlled areas.
Infection is divided into 2 main phases: acute and chronic ( Table 313.1 ). Acute infection is asymptomatic in up to 95% of infected individuals, but can manifest as fever, lymphadenopathy, organomegaly, myocarditis, and meningoencephalitis. Chronic infection in 60–70% of patients is indeterminate, meaning the patient is asymptomatic but has a positive antibody titer. Approximately 30% of infected persons proceed to chronic determinate or symptomatic T. cruzi infection. The T. cruzi genome has been fully sequenced and contains 12,000 genes, the most widely expanded among trypanosomatids, and may reflect its ability to invade a wide variety of host tissues. Significant variability has been also found, along with extensive epigenetic modification of surface proteins, which may contribute to immune evasion. Six discrete typing units (DTUs) are recognized, referred to as TcI to TcVI. A newly described 7th type called Tcbat has recently been identified. DTUs may differ in geographic distribution, predominant vector, and hosts and may also differ in disease manifestations and response to treatment.
Table 313.1
Clinical Features and Diagnosis of Chagas Disease
From Pérez-Molina J, Molina I: Chagas disease, Lancet 391:82–92, 2018 (Table 2).
| GEOGRAPHIC DISTRIBUTION | CLINICAL SIGNS/SYMPTOMS | DIAGNOSIS | |
|---|---|---|---|
| ACUTE FORMS * | |||
| Vectorial | Endemic countries | Incubation period: 1-2 wk Signs of portal of entry: indurated cutaneous lesion (chagoma) or palpebral edema (Romaña sign) Most cases are mild disease (95–99%) and unrecognized. Persistent fever, fatigue, lymphadenopathy, hepatomegaly, splenomegaly, morbilliform rash, edema In rare cases, myocarditis or meningoencephalitis Anemia, lymphocytosis, elevated AST/ALT concentrations Risk of mortality: 0.2–0.5% |
Direct parasitological methods: patent parasitemia up to 90 days Microscopic examination of fresh blood, Giemsa-stained thin and thick blood films, or buffy coat Concentration methods: microhematocrit and Strout method PCR techniques Serology is not useful. |
| Congenital | Endemic and nonendemic countries | Incubation period: birth to several weeks Most are asymptomatic or have mild disease. Prematurity, low birthweight, abortion, neonatal death Fever, jaundice, edema, hepatomegaly, splenomegaly, respiratory distress syndrome, myocarditis, meningoencephalitis Anemia and thrombocytopenia Risk of mortality: <2% |
Direct parasitological methods Concentration methods: microhematocrit, Strout method Direct microscopy also useful PCR: most sensitive technique Serology: after 9 mo or later |
| Oral | Restricted areas of endemic countries (Amazon basin) and local outbreaks | Incubation period: 3-22 days Fever, vomiting, periocular edema, dyspnea, fever, myalgia, prostration, cough, splenomegaly, hepatomegaly, chest pain, abdominal pain, digestive hemorrhage Risk of mortality: 1–35% |
Same as for vectorial. |
| Transfusion and transplant | Endemic and nonendemic countries | Incubation period: 8-160 days; persistent fever Clinical characteristics similar to those of vectorial cases (excluding portal of entry signs) Risk of mortality is variable and depends on the severity of baseline disease. |
Same as for vectorial. PCR techniques usually yield positive results days to weeks before trypomastigotes are detectable in blood. Tissue samples are needed in some circumstances. |
| Reactivation in HIV-infected patients | Endemic and nonendemic countries | Behaves as other opportunistic infections Reactivation with <200 CD4 cells per µL (mostly with <100) Affects CNS (75–90%) as single or multiple space-occupying lesions or as severe necrohemorrhagic meningoencephalitis Cardiac involvement (10–55%): myocarditis, pericardial effusion or worsening of previous cardiomyopathy Risk of mortality: 20% |
Direct parasitological methods, as in vectorial cases. Parasite can be found in CSF, other body fluids, and tissue samples. PCR: not useful for diagnosis of reactivation Serology: indicative of chronic infection and helpful in cases of suspected disease |
| Reactivation in other immunosuppressed patients | Endemic and nonendemic countries | Reactivation after transplantation or in patients with hematologic malignancies Clinical characteristics similar to those of patients who undergo transfusion and those with panniculitis and other skin disorders Risk of mortality is variable and depends on severity of baseline disease and prompt diagnosis. |
Direct parasitological methods, as in vectorial cases. Parasite can be found in tissue samples. PCR: increasing parasite load detected with real-time PCR in serial specimens could be indicative of a high risk of reactivation. |
| CHRONIC FORMS | |||
| Indeterminate | Endemic and nonendemic countries | Asymptomatic Normal chest radiograph and 12-lead ECG. |
Serology: detection of IgG PCR: low sensitivity |
| Cardiac and gastrointestinal | Endemic and nonendemic countries | Cardiac manifestations: fatigue, syncope, palpitations, dizziness, stroke; late manifestations: chest pain (atypical), dyspnea, edema, left ventricular dysfunction, congestive heart failure; alterations in 12-lead ECG, echocardiography, or other heart function tests Gastrointestinal: dysphagia, regurgitation, severe constipation (dilated esophagus or colon); alterations in esophageal manometry, barium swallow, or barium enema |
Serology: detection of IgG PCR: low sensitivity |
ALT, Alanine transaminase; AST, aspartate transaminase; CNS, central nervous system; CSF, cerebrospinal fluid; ECG, electrocardiogram; PCR, polymerase chain reaction.
T. cruzi infection is primarily a zoonosis, and humans are incidental hosts. T. cruzi has a large sylvan reservoir and has been isolated from numerous animal species. The presence of reservoirs and vectors of T. cruzi and the socioeconomic and educational levels of the population are the most important risk factors for vector-borne transmission to humans. Insect vectors are found in rural, wooded areas and acquire infection through ingestion of blood from humans or animals with circulating trypomastigotes.
Housing conditions are very important in the transmission chain. Incidence and prevalence of infection depend on the adaptation of the triatomines to human dwellings, as well as the vector capacity of the species. Animal reservoirs of reduviid bugs include dogs, cats, rats, opossum, guinea pigs, monkeys, bats, and raccoons. Humans often become infected when land in enzootic areas is developed for agricultural or commercial purposes. An estimated 238,000 immigrants from endemic countries living in the United States are likely infected with T. cruzi . Increasing cases of autochthonous transmission in the United States have also been reported and confirmed with molecular typing, particularly from California, Louisiana, Texas, and Georgia, although these numbers remain small. One study found that 5.2% of Latin America immigrants in Los Angeles with conduction abnormalities on electrocardiogram (ECG) were seropositive for T. cruzi .
Humans can be infected transplacentally, occurring in 10.5% of infected mothers and causing congenital Chagas disease. Transplacental infection is associated with premature birth, fetal wastage, and placentitis. Disease transmission can occur through blood transfusions in endemic areas from asymptomatic blood donors. Seropositivity rates in endemic areas are as high as 20%. The risk for transmission through a single blood transfusion from a chagasic donor is 13–23%. Blood screening for Chagas disease in the United States was started in 2006 and has detected >2,200 seropositive cases since February 2017 ( www.aabb.org ). Percutaneous injection as a result of laboratory accidents is also a documented mode of transmission. Oral transmission through contaminated food is an increasingly important method of transmission as vector transmission is successfully interrupted by control programs. Although breastfeeding is an uncommon mode of transmission, women with acute infections should not nurse until they have been treated.
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