Screening, Diagnosis, and Management of Chagas Disease in the United States

May 5, 2025

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Introduction

This document is focused on the epidemiology, clinical aspects, diagnosis, and management of Chagas disease within the United States. The presentation aims to equip healthcare providers with the knowledge necessary for effective screening, diagnosis, and treatment of this often-overlooked parasitic infection. Dr. Clark emphasizes the importance of understanding risk factors to identify individuals who should be screened and provides detailed information on available diagnostic tools and treatment options.

Chagas Disease

Dr. Clark begins by expressing her enthusiasm for discussing Chagas disease, also known as American trypanosomiasis, highlighting the need for increased attention to this condition in the US. She outlines the presentation's objectives, which include understanding the epidemiology and risk factors for Chagas disease, particularly to identify candidates for screening, and discussing available treatments and eligibility criteria. She also discloses that none of her relevant affiliations pose a conflict of interest for this presentation.

Chagas disease is caused by a protozoan parasite called Trypanosoma cruzi (T. cruzi). Dr. Clark uses a poll to gauge the audience's initial understanding of the disease, with responses including "kissing bug," "parasite," "end organ," and "dilation tropics," alluding to key aspects of the infection. She then provides a visual representation of T. cruzi in a thin blood smear, illustrating its size relative to red blood cells, particularly relevant during the acute phase of infection.

Life Cycle and Transmission

To establish a fundamental understanding, Dr. Clark outlines the life cycle of T. cruzi. The vector of transmission is the triatomine bug, commonly known in the US as the kissing bug, and referred to as "chinches" in Mexico and Central America, and "benchuka" in South America. These bugs typically inhabit cracks and crevices in dwellings, particularly in rural endemic areas.

The transmission cycle begins when an infected triatomine bug takes a blood meal from a human or other mammal. During or shortly after feeding, the bug defecates, and the feces contain infective trypomastigotes. The parasite can enter the host's bloodstream through the bite wound, mucous membranes (such as the eyes), or skin that has been contaminated with the infected feces, especially if the bite site is scratched.

Once in the bloodstream, trypomastigotes circulate and invade various cells, with a predilection for muscle cells, most notably cardiac muscle cells. Inside these cells, they transform into amastigotes, which multiply. Eventually, the amastigotes burst out of the host cells as trypomastigotes, re-entering the bloodstream and potentially infecting other cells or being ingested by another kissing bug during a subsequent blood meal, thus continuing the cycle. Dr. Clark emphasizes that humans are not the only mammals affected; domestic animals like dogs and cats, as well as wild animals, can also be infected.

Further elaborating on transmission, Dr. Clark clarifies that it is not the bite itself but rather the infected feces that cause the infection. She reiterates the ways in which the parasite can enter the body after contact with the feces, including contamination of the bite site, rubbing the eyes, or through contaminated food and drink. She presents poll results indicating that the audience correctly identified several transmission routes.

Beyond vector-borne transmission, they are other important routes:

Congenital Transmission (Vertical Transmission): T. cruzi can be transmitted from a pregnant mother to her child during pregnancy, but not through breastfeeding.
Blood Transfusions: Although a significant historical route, the risk has been substantially reduced in endemic countries, including the US (since 2007), due to systematic blood supply screening.
Organ Donation: Transmission through infected organ transplants has occurred, leading to guidelines regarding which organs can be donated by individuals with Chagas disease. Heart and gastrointestinal tract donations are generally not recommended, while kidney and liver transplants may be considered with recipient consent.
Laboratory Accidents: Accidental exposure to T. cruzi in laboratory settings is a potential risk.
Contaminated Food or Drink: Outbreaks due to contaminated juices have been reported in South America, representing an emerging mode of transmission.

Epidemiology of Chagas Disease

Dr. Clark presents data on the estimated number of people living with Chagas disease in the United States, citing modeling studies that suggest a range of 200,000 to 300,000 individuals. She emphasizes that many of these cases are in immigrants from Latin America.

She displays a map highlighting the most endemic regions, primarily the southern cone of South America, with Bolivia being considered the epicenter. However, she notes that triatomine bugs are found throughout South America, Central America, Mexico, and the southern United States, leading to varying levels of endemicity across the Americas. Globally, an estimated six to eight million people are infected.

Dr. Clark mentions regional epidemiologic studies conducted in major US metropolitan areas like Los Angeles, Washington D.C., and Houston, which generally show a prevalence of about 1% in populations with similar demographics to Houston. She points out that prevalence rates can be significantly higher in specific populations, such as patients attending cardiology clinics who originate from endemic countries.

Regarding local transmission within the US, Dr. Clark acknowledges that while the number of reported cases is small, it does occur. She highlights that case detection relies on passive surveillance, as there are no active studies looking for domestically acquired cases in individuals who have never left the US. A study of reported cases between 2000 and 2018 identified 76 domestically acquired cases.

Data from US blood donor screening (2007-2019) revealed that about one in 30,000 donors tested positive for T. cruzi antibodies, with a low percentage of these individuals seeking medical assistance. Dr. Clark cautions that blood donor screening data may underestimate the true prevalence, as individuals at highest risk are often less likely to donate blood. The state with the highest number of positive blood donations was California, followed by Texas, Florida, and New York, likely reflecting large immigrant populations from endemic areas.

Focusing on local transmission in Texas, the presenter shows a map indicating the presence of four different triatomine species in the state, which facilitates local transmission. Data from the Texas Department of State Health Services (2013-2020) show counties with reported locally acquired human cases (red outlines), counties where T. cruzi-positive kissing bugs were found (hashtags), and counties where infected animals (mostly dogs) were detected (blue). Notably, 50% of the 1,000 kissing bugs submitted in Texas tested positive for T. cruzi. Dr. Clark concludes that locally acquired cases are possible in other southern states where the vector and parasite are present.

Clinical Presentations of Chagas Disease

Congenital Chagas Disease: Occurs when T. cruzi is transmitted from an untreated mother with chronic Chagas disease to her baby during pregnancy, with an estimated 1-5% risk per pregnancy. Neonates with congenital Chagas disease may be asymptomatic but can also be very ill. Dr. Clark references an MMWR report detailing the first diagnosed case in the US. This condition is largely preventable with maternal treatment before pregnancy.
Acute Chagas Disease: More common in children living in endemic areas who are exposed to infected triatomines. Most acute infections are asymptomatic. When symptoms occur, they are often non-specific, flu-like symptoms. A characteristic but uncommon sign is Romana's sign, a painless swelling of the eyelid resulting from parasite entry through the conjunctiva. Swelling at the bite site, called a chagoma, can also occur and may last for several weeks. During the acute phase, the host's immune system typically controls the parasitemia, but the parasites can migrate to muscle tissues.
Chronic Chagas Disease: Develops after the acute phase (typically within two months of infection). The initial chronic phase is asymptomatic and is termed the indeterminate form. This phase can last for many years. However, 20-30% of individuals with chronic Chagas disease will eventually develop cardiac manifestations (Chagas cardiomyopathy) decades after infection, characterized by dilated cardiomyopathy and a spectrum of other cardiac issues. Approximately 10% will develop gastrointestinal (GI) disease, primarily megaesophagus (difficulty swallowing, dysphagia) and megacolon (chronic constipation). These GI manifestations often start subtly.
T. cruzi Reactivation Disease: Occurs in individuals with chronic Chagas disease who become immunocompromised, such as those with advanced HIV or transplant recipients on immunosuppressive therapy. The lack of cellular immunity allows T. cruzi to proliferate to high levels, leading to potentially fatal disease.

Screening and Diagnosis of Chronic Chagas Disease

The US FDA has cleared four serologic tests for Chagas disease. Dr. Clark highlights the hemogen cruzi IGG ELISA, which is the test used by LabCorp, the contracted laboratory for Harris Health. While readily available, the hemogen test has known performance limitations. The Texas Department of State Health Services (TDSHS) is unique in offering two distinct tests (hemogen and WEER) for confirmation. A rapid test (Inbios) is cleared but has a newer, uncleared generation. The Ortho Abbott test is approved only for blood donor screening.

Also, she addresses a question about the progression from acute to chronic Chagas disease, explaining that it is believed that if infected with T. cruzi, an individual will develop chronic Chagas disease. Seroconversion (becoming IGG positive) typically occurs within a couple of months of infection, assuming a normal immune system. However, she reiterates the limitations of current serologic tests, which may not always detect antibodies, especially against non-South American strains. Without appropriate management, individuals will remain IGG positive for life.

Given resource limitations, the CDC recommends screening with one test. This is the practice in Harris Health, where the hemogen test is ordered. However, a positive screening test must be confirmed with a different test. In Texas, this is done by sending the patient's serum to the TDSHS, which performs both hemogen and WEER tests for free. If these results are discordant, the TDSHS forwards the sample to the CDC for further testing using three different assays, with two positive results required for a confirmed diagnosis.

She reiterates that individuals with any one of the following risk factors should be screened:

Lived in any part of continental Latin America for six months or more.
Seen triatomine bugs living in or around their home.
Have a mother who grew up in an endemic country (due to the risk of congenital transmission).

Treatment and Management of Chagas Disease

Exist effective drugs to treat Chagas disease. The two available anti-trypanosomal drugs are benznidazole and nifurtimox. However, their effectiveness is greater the closer the treatment is to the time of infection, making them more effective in children and those recently infected. The criteria used in their clinic to determine treatment eligibility for confirmed positive patients:

Acute Chagas Disease: Always treated, regardless of age or other health issues.
T. cruzi Reactivation Disease: Always treated, as it can be fatal.
Reproductive-Age Women: Generally offered treatment to reduce the risk of congenital transmission in future pregnancies and to prevent end-organ damage.
Adults Up to Age 50 Without Established Structural Heart Disease: Generally offered treatment.
Individuals at Risk for Iatrogenic Immunosuppression: Screening and treatment should be considered in consultation with an infectious disease provider.A

Treatment is generally not offered to asymptomatic individuals over the age of 50 without a strong indication, as the perceived benefit may not outweigh the potential side effects. For individuals with established structural heart disease, current data suggest that anti-parasitic treatment does not prevent disease progression, although this remains controversial. In cases of isolated GI disease (without heart disease), treatment is offered to prevent the development of cardiac complications. Anti-trypanosomal treatment is contraindicated during pregnancy, except in life-threatening situations like T. cruzi reactivation.

Benznidazole: Available in the US through ExceLUS, which has an excellent patient assistance program providing the drug free of charge for uninsured patients in their clinic.
Nifurtimox: Available through Bayer and is becoming available on the formulary at Harris Health, primarily for treating potential T. cruzi reactivation cases due to the need for rapid access.

Both drugs require a 60-day treatment course and have significant potential side effects, including rash, gastrointestinal distress, and peripheral neuropathy, which can lead to treatment discontinuation. Benznidazole generally has a better side effect profile than nifurtimox. Due to the side effects, close monitoring with safety labs and clinical assessments every two weeks is essential during the 60-day treatment. Dr. Clark briefly mentions ongoing research exploring shorter treatment durations.

Important Resources and Harris Health Initiatives

United States Chagas Disease Providers Network: Established to connect healthcare providers who manage Chagas disease and to link patients with these providers. The network's website contains provider contact information and resources for patients.
CDC Website: Offers extensive information on Chagas disease, including a CME-accredited course for clinicians ("What Clinicians Need to Know About Chaga's Disease"). The CDC also provides patient handouts in English and Spanish.

Dr. Clark specifically addresses Chagas disease testing within Harris Health. The screening test, Trapano Cruzie IGG (hemogen test), is electronically orderable in Epic. If the screening test is positive, a referral to the Tropical Medicine Clinic should be placed and can be expedited by directly in-basket messaging Dr. Clark. In the clinic, the diagnosis will be confirmed, counseling provided, cardiac screening performed, and treatment offered if eligible.

Dr. Clark announces a new immigrant health screening order set that debuted in Harris Health Epic on September 30th. This order set includes T. Cruz GG testing for patients who have resided in continental Latin America for more than six months. She acknowledges the collaborative effort involved in developing this order set and highlights initiatives to implement Chagas disease screening at various Harris Health clinics, including MLK and Northwest. She encourages feedback on the new order set for potential improvements.

Questions and Answers

Key points from the Q&A include:

Risk of Reactivation with Chemotherapy: While short-term immunosuppression due to solid tumor chemotherapy may not pose a significant risk, individuals with prolonged and profound immunosuppression, such as those with advanced lymphomas or those receiving chemotherapy for it, are at risk of T. cruzi reactivation. Screening is recommended in these populations.
Screening Hematologic Malignancy Patients: Screening with serology is generally recommended, but it's important to note that the accuracy of serologic tests may be compromised in individuals with impaired B-cell function. PCR testing may become a future recommendation in this population.
Cost of Antibody Testing: The cost to Harris Health for the hemogen test is relatively low (around $5), and patients with a gold card may have the cost covered depending on their level. For HIV patients undergoing screening covered by Ryan White funds, testing should not be charged. Confirmatory testing through the TDSHS and CDC is free.
Age-Based Screening Recommendations: In the US, the recommendation is to screen anyone with risk factors (lived in an endemic country for >6 months) regardless of age. Screening older individuals can help identify other infected family members who may be eligible for treatment.

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