Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to prevent the development of or progression of clinical manifestations, and to reduce morbidity and mortality.

Class Summary

These agents are used to treat infections caused by the protozoan T cruzi.

Benznidazole (Rochagan, Radanil)

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Nitroimidazole antimicrobial. Generates radical species in both aerobic and anaerobic conditions that are capable of damaging parasitic DNA. Inhibits DNA, RNA, and protein synthesis within the T cruzi parasite. Studies suggest benznidazole is reduced by a type I nitroreductase (NTR) enzyme of T cruzi, producing a series of short-lived intermediates that may promote damage to several macromolecules, including DNA. Approved by the FDA for treatment of Chagas disease in children aged 2-12 years. There is a general consensus in favor of antiparasitic treatment for all cases of acute or reactivated Chagas disease, for chronic T cruzi infection of children up to age 18 years, and for all women of child‑bearing age. Data regarding the efficacy of treating adults aged 50 years or younger with benznidazole are of low quality, and thus such treatment is controversial. As noted, there is a general consensus that persons who already have developed cardiac or gastrointestinal symptoms should not be given antiparasitic treatment. Repeated PCR testing can be used to look for treatment failure.

Nifurtimox (Lampit)

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Trypanocidal drug that acts on circulating trypomastigotes, as well as intracellular amastigotes. The mechanism of action may depend on the formation of nitro anion radicals, but precise details are not known. Approved by the FDA for treatment of Chagas disease in children from birth to age 18. The guidance regarding which groups of T cruzi‑infected persons can be treated with nifurtimox are the same as those listed above for benznidazole. As is the case for persons treated with the latter, evidence of treatment failure can be sought with repeated PCR testing.

Follow-up

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Media Gallery

Chagas disease (American trypanosomiasis). The trypomastigote is the infective flagellated form of the parasite found in the blood of the mammalian hosts (blood trypomastigote) and in the hindgut of vectors (metacyclic trypomastigote). Image courtesy of Peter Darben, MD.
Chagas disease (American trypanosomiasis). The epimastigote form of Trypanosoma cruzi is the multiplying stage of the parasite that grows in the gut of the insect vector and also in cell-free culture medium as shown here. Image courtesy of Peter Darben, MD.
Chagas disease (American trypanosomiasis). Megacolon.
Life cycle of triatomines. Courtesy of the CDC.
Trypanosoma cruzi trypomastigotes in a mouse blood smear (Giemsa, x625). Courtesy of Dr. Herbert B Tanowitz, New York, NY.
Rhodnius prolixus, a common vector of Trypanosoma cruzi. Eggs, first- and second-stage nymphs, and adult.
Trypanosoma cruzi in heart muscle of a child who died of acute Chagas disease in Texas. (H&E, x900).
Chest radiograph of a Bolivian patient with chronic Trypanosoma cruzi infection, congestive heart failure, and rhythm disturbances. Pacemaker wires can be seen in the area of the left ventricle.
Barium swallow radiographic study of a Brazilian patient with chronic Trypanosoma cruzi infection and megaesophagus. The markedly increased diameter of the esophagus and its failure to empty are typical findings in patients with megaesophagus caused by Chagas disease. Courtesy of Dr. Franklin A. Neva, Bethesda, MD.
Air-contrast barium enema of a Bolivian patient with chronic Chagas disease and megacolon. The markedly increased diameters of the ascending, transverse, and sigmoid segments of the colon are readily apparent.
Natural course of American trypanosomiasis. Courtesy of Dr. Patricia Paredes, Guadalajara, Jal., Mexico.
Footnote 1. Mexico, as well as all nations of Central and South America, are endemic for Chagas disease. Chagas disease is not endemic in any of the Caribbean Islands. Women who were born in Chagas endemic countries or who have resided therein for a substantial period are at geographic risk for having Chagas disease and should be screened serologically.{Edwards MS, Montgomery SP. Congenital Chagas disease: progress toward implementation of pregnancy-based screening. Curr Opin Infect Dis. 2021 Oct 1. 34 (5):538-545}. In addition, women who are not themselves at geographic risk but whose mothers are at such a risk and are not known to be seronegative are in turn considered to be at risk for Chagas disease. Footnote 2. The two approaches useful in this regard are microscopic examination of anticoagulated blood and polymerase chain reaction (PCR). Serologic testing of newborns is not useful because assays for specific immunoglobulin G (IgG) will yield a positive result, reflecting the mother’s chronic infection, and because immunoglobulin M (IgM) assays lack acceptable levels of sensitivity and specificity. Footnote 3. All children born to at risk women should be tested serologically since several studies indicate that the rate of congenital Chagas disease in babies born to infected mothers is 2%-10%. Footnote 4. The latter should include periodic monitoring for signs and symptoms of chronic cardiac and gastrointestinal Chagas disease followed by appropriate interventions, when indicated. The usefulness of specific drug treatment in adults with chronic Trypanosoma cruzi infections has not been clearly demonstrated and is a matter of ongoing debate. Footnote 5. The parasitologic cure rate in babies with congenital Chagas disease approaches 100% when a full course of treatment is given during the first year of life. Footnote 6. The sensitivities of microscopic examination of anticoagulated blood and PCR are less than 100%. Thus, the occasional baby who tests negative in these approaches immediately after birth may actually be infected with T cruzi. Serologic testing for specific IgG should be delayed until maternal IgG has disappeared.

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Author

Louis V Kirchhoff, MD, MPH Professor of Internal Medicine (Infectious Diseases), Epidemiology, and Psychiatry, University of Iowa, Roy J and Lucille A Carver College of Medicine and College of Public Health; Staff Physician, Medical Service, Iowa City Veterans Affairs Medical Center

Louis V Kirchhoff, MD, MPH is a member of the following medical societies: American Association of Blood Banks, American Society of Tropical Medicine and Hygiene

Disclosure: Received salary from Goldfinch Diagnostics Inc. for equity owner; Received royalty from Abbott Laboratories, Inc. for licensed technology.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John W King, MD Professor of Medicine, Chief, Section of Infectious Diseases, Director, Viral Therapeutics Clinics for Hepatitis, Louisiana State University School of Medicine in Shreveport; Consultant in Infectious Diseases, Overton Brooks Veterans Affairs Medical Center

John W King, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Association of Subspecialty Professors, Infectious Diseases Society of America, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, International Immunocompromised Host Society, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Mary D Nettleman, MD, MS, MACP Professor and Chair, Department of Medicine, Michigan State University College of Human Medicine

Mary D Nettleman, MD, MS, MACP is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical and Translational Research, Infectious Diseases Society of America, Society of General Internal Medicine

Disclosure: Nothing to disclose.