The infection of millions of people with the protozoan parasite Trypanosoma cruzi is a public health concern. A new review article explains how treatments for Chagas’ disease remain marginally effective, and cardiac and gastrointestinal complications dominate the clinical picture.
Chagas’ disease is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted when the infected feces of the triatomine vector are inoculated through a bite site or through an intact mucous membrane of the mammalian host. Vectorborne transmission is limited to areas of North America, Central America, and South America. Both in endemic and in nonendemic areas, other infection routes include transfusion, organ and bone marrow transplantation, and congenital transmission. Infection is lifelong in the absence of effective treatment.
• How prevalent is Chagas’ disease?
Latin America has made substantial progress toward the control of Chagas’ disease. The estimated global prevalence of T. cruzi infection declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Serologic screening for T. cruzi is conducted in most blood banks in endemic Latin American countries and the United States, and some countries have systematic screening for congenital Chagas’ disease. Nevertheless, Chagas’ disease remains the most important parasitic disease in the Western Hemisphere, with an estimated disease burden, as measured by disability adjusted life-years, that is 7.5 times as great as that of malaria.
Figure 1. Life Cycle of Trypanosoma cruzi.
Figure 2. Estimated Prevalences of T. cruzi Infection.
• What cardiac and gastrointestinal sequelae are associated with chronic Trypanosoma cruzi infection?
The vast majority of acute infections are never detected. In persons who survive the acute phase, the cell-mediated immune response controls parasite replication, symptoms resolve spontaneously, and patent parasitemia disappears in 4 to 8 weeks. Persons then pass into the chronic phase of T. cruzi infection. Most persons remain asymptomatic but are infected for life. It is estimated that 20 to 30% of infected persons have progression over the course of years to decades to chronic Chagas’ cardiomyopathy. The earliest signs are typically conduction-system defects, especially right bundle-branch block or left anterior fascicular block. Chagas’ cardiomyopathy is highly arrhythmogenic and is characterized by sinus and junctional bradycardias, atrial fibrillation or flutter, atrioventricular blocks, and nonsustained or sustained ventricular tachycardia. Affected patients eventually have progression to dilated cardiomyopathy and congestive heart failure. Gastrointestinal Chagas’ disease is less frequent than Chagas’ cardiomyopathy, and predominantly affects the esophagus, colon, or both and results from damage to intramural neurons. The manifestations of esophageal disease range from asymptomatic motility disorders and mild achalasia to severe megaesophagus.
Morning Report Questions
Q: How is Chagas’ disease diagnosed?
A: In the acute phase, motile trypomastigotes can be detected by means of microscopic examination of fresh anticoagulated blood or buffy coat. Parasites may also be visualized on blood smears stained with Giemsa or other stains and can be grown with the use of hemoculture in a specialized medium. Polymerase chain reaction (PCR) is a sensitive diagnostic tool in the acute phase and is the best test for early detection of infection in the recipient of an organ from an infected donor or after accidental exposure. The diagnosis of chronic infection relies on IgG serologic testing, most commonly with the use of an enzyme-linked immunosorbent assay (ELISA) or immunofluorescent antibody assay (IFA). No single assay for chronic T. cruzi infection has high enough sensitivity and specificity to be used alone; positive results of two tests, preferably based on different antigens (e.g., whole-parasite lysate and recombinant antigens), are required for confirmation. The sensitivity of PCR in the chronic phase of Chagas’ disease is highly variable and depends on specimen volume and processing, population characteristics, and PCR primers and methods. Negative PCR results do not prove that infection is absent.
Figure 3. Phases of Trypanosoma cruzi Infection.
Q: What therapies are available for Chagas’ disease, and who is a candidate for treatment?
A: Nifurtimox and benznidazole, the only drugs with proven efficacy against T. cruzi infection, are not currently approved by the Food and Drug Administration but can be obtained from the CDC and used under investigational protocols. Benznidazole, a nitroimidazole derivative, is considered to be the first-line treatment, on the basis of a better side-effect profile than nifurtimox, as well as a more extensive evidence base for efficacy. Until the 1990s, only the acute phase of the infection was thought to be responsive to antiparasitic therapy. However, in the 1990s, two placebo-controlled trials of benznidazole involving children with chronic T. cruzi infection showed cure rates of approximately 60%, on the basis of conversion to negative serologic test results 3 to 4 years after treatment. Follow-up studies have suggested that the earlier in life children are treated, the higher the rate of conversion from positive to negative results of serologic assays (negative seroconversion). Over the past 15 years, there has been a growing movement toward broader treatment of chronically infected adults, including those with early cardiomyopathy. Most experts now believe that the majority of patients with chronic T. cruzi infection should be offered treatment, with exclusion criteria such as an upper age limit of 50 or 55 years and the presence of advanced irreversible cardiomyopathy. This change in standards of practice is based in part on nonrandomized, nonblinded longitudinal studies that have shown significantly decreased progression of cardiomyopathy and a trend to decreased mortality among adults treated with benznidazole, as compared with untreated patients.