Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is recognized by the World Health Organization (WHO) as one of the neglected tropical diseases. According to data from 2019 and published in the most recent Global Burden of Disease report in 2020, Chagas disease is one of the leading public health problems in the Western Hemisphere.¹ Although most affected individuals are asymptomatic, morbidity and mortality related to infections are due to cardiac, gastrointestinal, or neurological involvement. Chagas disease affects approximately 5.7 million people in Latin America and over 70 million people are estimated to be at risk.² Despite being historically restricted to rural areas of Latin America, Chagas disease is now an emerging public health problem in major cities of Latin America and in regions outside Latin America such as Spain, Italy, Japan, and the United States (U.S.).³

The U. S., compared to other countries worldwide, is home to the largest number of immigrants who are infected with Trypanosoma cruzi. Based on data from 2005, the Centers for Diseases Control and Prevention (CDC) estimates that approximately 300,000 foreign born immigrants from endemic countries in Latin America are infected, of whom 30,000 to 45,000 have heart disease, and to whom 63–315 infants are born congenitally infected each year.⁴ The most recent national estimate is of 238,091 cases of T. cruzi infection in the U.S. as of 2012 although it does not include undocumented immigrants who may account for as many as 109,000 additional cases.⁵ Importantly, not only immigrants are at risk for the disease in the U.S. T. cruzi circulates in a sylvatic cycle between mammals and local triatomine insects in at least 29 states, where human residents may be at risk for incidental infection.⁶ In fact, rare cases of locally acquired vector-borne T. cruzi infection in the U. S. have been documented, with the first cases of autochthonous infection reported in 1955.⁷

Chagas disease, caused by the protozoan parasite T. cruzi, is a vector-borne zoonotic disease. Triatomine insects act as vectors and acquire the parasite when they take a blood meal from an infected mammal. Infected triatomines pass the parasite in their feces when they defecate during or immediately after feeding. The parasites can infect mammals, including humans, by entering new hosts across mucosal surfaces or abraded skin. Furthermore, T. cruzi can be spread by blood transfusion, organ transplantation, from mother to fetus, or by ingestion of contaminated food or drink⁸ (Figure 1).

Once infection occurs, the host is infected for life. The initial acute phase of the disease is typically asymptomatic, but it may also present as a nonspecific, self-limited mononucleosis-like illness. If the disease is not treated at this stage, it enters the chronic phase of infection. Approximately 60–70% of chronically infected individuals remain asymptomatic which is referred to as the indeterminate form of chronic Chagas disease. The remaining 30–40% of patients will become symptomatic 10–30 years after initial infection – mainly with cardiac or digestive tract (or both) manifestations⁸ (Figure 2).

With this report, we summarize the available information about Chagas disease in Oklahoma and provide data that suggest the existence of locally acquired human cases in the State.

Chagas diseases in the U. S. is mainly a disease of Latin American immigrants who acquired the infection in their countries of origin. The burden of the disease caused by autochthonous transmission in the U.S. is unknown and likely underappreciated. The southern half of the U.S contains triatomines that are capable of supporting the parasitic lifecycle of T. cruzi. Contact with triatomines infected with T. cruzi has been reported within the U. S. and locally acquired cases of Chagas disease have been identified.^9–11 For example, in Texas approximately 50% of triatomines found near or inside houses were infected with T. cruzi.¹² Other forms of transmission such as through blood transfusion, organ transplantation, and congenital infection have also been described in the U.S.⁷

Despite the burden of the disease within the Hispanic community and the increasing number of reported cases of Chagas disease in the U.S., many barriers to care remain. For example, there is a widespread lack of awareness of the disease among public health professionals and clinical providers.^13–15 Additionally, there is an absence of effective screening programs for the disease among those at risk, few clinicians are experienced with its management, and access to care is challenging due to financial and other constraints. Chagas disease is currently a reportable condition in only seven states (Texas, Arizona, Arkansas, Tennessee, Mississippi, Louisiana, and Utah) and Los Angeles county.^16,17

Eleven species of triatomines are found in the U.S. and ten have been found to be naturally infected with T. cruzi with a prevalence of infection as high as that found in Latin America. For eight species, human contact has been documented.^7,11,18,19 Locally acquired Chagas disease might not be as rare an event as previously suspected, as detailed in a recent review of the published cases in the U.S. between 2000 and 2018. The authors found 76 published cases of confirmed or suspected locally acquired disease.¹¹ Rural residence, history of hunting or camping, and agricultural or outdoor work were suggested as risk factors.¹¹

Triatoma sanguisuga is the most widely distributed species of triatomine in the U. S. Importantly, this species has also been implicated in at least two of the cases of local transmission within the U. S. identified to date.^18,20,21 Based on one study, both T. sanguisuga and T. lecticularia may be effective vectors because approximately one-fourth of the late stage instars or nymphs and female adults of T. sanguisuga defecate within 2 minutes of feeding and all instars of T. lecticularia defecate within 10 minutes of feeding.²²

Based on data from 2005 and assuming a transmission risk of 1%–5%, the annual number of congenital Chagas disease cases in the U.S was estimated to be 63–315 cases. Other reports estimate 166–638 cases annually.^4,23 Although there is no systematic screening to identify congenital Chagas disease in the U.S., these estimates would place its incidence in the range of that for phenylketonuria (254 births per year) or congenital adrenal hyperplasia (121 births per year), which are conditions for which the American College of Genetics recommends newborn screening.⁴ Furthermore, an U.S. study showed that universal screening of pregnant women during prenatal care visits or at the time of birth is cost-effective even though only about 12% of pregnant woman are at risk.²⁴

Screening for Chagas disease in the U.S. is recommended for individuals born in continental Latin America, who have spent > 6 months in a rural area of Latin America, and/or who report exposure to triatomines.²⁵ Screening Latin America-born persons in primary care settings has been demonstrated to be highly cost-effective in non-endemic areas such as Europe.²⁶ The prevalence of Chagas disease among survey participants in a Latin America born population in Los Angeles County was 1.24% suggesting over 30,000 infected individuals live in the Los Angeles County alone.²⁷ In another study, the prevalence of infection was 19% among patients with non-ischemic cardiomyopathy residing in Los Angeles, but who had lived in Latin America for at least 12 months.²⁸

In the U.S., voluntary blood bank screening for chronic Chagas disease was initiated in 2007 as a safety measure.²⁹ The Food and Drug Administration (FDA) has approved immunoassays for blood donor testing: Abbott Prism Chagas chemiluminescent assay and the Ortho T. cruzi enzyme linked immunosorbent assay (ELISA), both for screening, and the Abbott ESA Chagas Test for confirmatory testing. All these tests detect T. cruzi specific IgG antibody. Blood donor testing is performed according to FDA guidance, issued in 2010. All donated units that test positive are retested in duplicate using the same screening test. A repeatedly reactive donation undergoes a confirmatory test by a different assay. Blood donors who have a positive screening result are deferred from donating blood products. For blood donors who tested positive on the screening test but negative on the second confirmatory test, donating blood may be allowed again under specific terms described in the December 2017 FDA guidance reentry testing algorithm.³⁰ Blood donors who test positive are informed about the likelihood and medical significance of infection with T. cruzi. All donors who repeatedly test reactive are counseled to seek a physician’s advice.

According to the WHO, diagnosis of chronic Chagas disease requires testing with two or more diagnostic tests as no one serologic assay has sufficient sensitivity and specificity to be used alone. Two serological tests based on different antigens and/or techniques are used in parallel to increase the accuracy of diagnosis. In some cases, the infection status remains difficult to resolve even after a third test.³¹ Several diagnostic serologic kits are FDA cleared, including three ELISA tests and one rapid diagnostic test (InBios Chagas Detect Plus). Several commercial laboratories offer diagnostic serologic testing for Chagas disease, but none offers more than one serologic assay for chronic Chagas disease diagnosis at this time. Currently, CDC’s Parasitic Diseases Reference Laboratory is the only laboratory in the U.S. performing two serological assays that meet the WHO recommended method for diagnosis. CDC performs reference laboratory diagnostic testing using the Chagatest recombinant v3.0 ELISA (Wiener, Rosario, Argentina) and a trypomastigote excreted or secreted antigen immune-blot (TESA IB).

A recent review of the performance of the FDA cleared serological tests in the U.S. showed a wide range of sensitivity and specificity that varied according to the country of origin of the person being tested.³² Importantly, none of these tests had optimal performance characteristics in the population examined and a diagnostic algorithm akin to what is used in syphilis or HIV testing (i.e. highly sensitive screening test followed by a highly specific confirmatory test) is recommended.³²

Benznidazole and nifurtimox are the only currently available drugs for the treatment of Chagas disease. Both drugs produce side effects in the majority of patients with some toxicities being severe enough to require treatment discontinuation.²⁵ Prior to 2017, neither drug had been FDA approved and each was released as an investigational new drug (IND) through protocols at CDC. On August 29, 2017, benznidazole obtained FDA approval for the treatment of Chagas disease in children 2 to 12 years of age.³³ The drug became commercially available May 14, 2018 and as of that date the drug is no longer available through the CDC-sponsored IND program.³³ Nifurtimox was approved by FDA August 7, 2020 for treatment of children birth to less than 18 years of age and became commercially available in October of that year.

Although substantial progress in the control of domestic transmission of the disease has been accomplished, Chagas disease continues to be a major public health problem in endemic countries.⁴⁴ For example, there are still regions in Latin America where greater than 95% of the population older than 30 years of age and close to 20% of the pregnant women population are infected by the parasite.^45,46

Several factors including but not limited to poverty, political instability, violence, and climate change have spurred migration of humans from endemic to non-endemic areas of the world. In the U.S. and only considering foreign born immigrants from endemic countries that are legally in the country, an estimated 238,092 people live with T. cruzi infection. If undocumented immigrants are considered, the estimated total number of cases will increase to between 326,000 and 347,000.⁵ Taking into account the most recent prevalence data of Chagas disease in Latin America,² the U.S. is home to more people infected with T. cruzi than 16 of the 21 endemic Latin American countries. Approximately 16.3% of Oklahoma residents (i.e. 645,000 people) were born outside of the U.S. with most originating from Mexico (approximately 110,000 people). There is also a relatively large community from Guatemala, Honduras, El Salvador, Argentina, and Venezuela totaling close to 20,000 people from these 5 countries.¹⁰ Oklahoma ranks 27^th in regards to the states with the most people living infected with T. cruzi with estimated cases greater or similar to states where Chagas disease is a reportable condition^5,16 and similar to the number of infected people living in Belize.² The total annual cost to the State, taking into account the most recent estimate of 1,407 infected immigrants, is of approximately $18,641,343 – $24,540,594.^5,44

Chagas disease continues to be a neglected disease, both in Latin American and non-endemic countries such as the U.S. The disease mainly affects people living in poverty in Latin America and the immigrant and vulnerable population in developed countries. Challenges in diagnosing and treating Chagas disease are therefore similar in both endemic and non-endemic regions. Lack of funding for education of both people at risk and healthcare providers, provision of screening programs (i. e. pregnant woman), assurance of access to culturally sensitive healthcare for those chronically infected, and distrust in the government programs are some of the most important barriers that we identified in Oklahoma and which are also shared by other states in the nation.^41,47

Further research in Oklahoma might focus on identifying the risks for infection in domesticated animals and humans. There is also a pressing need to better understand the prevalence of the disease in specific patient populations such as foreign-born immigrants from endemic areas in Latin America and pregnant women. Finally, efforts to study the burden of cardiomyopathy attributed to Chagas disease in Oklahoma, especially among those originating from endemic areas, is also recommended.

Improving the care of those infected by the parasite in Oklahoma needs to be urgently addressed. Awareness of the disease in the healthcare community can be improved by partnerships between health departments, universities, and other professional organizations. Many of the important public health aspects of the disease could be addressed by making Chagas disease in animals and humans a reportable condition in Oklahoma.

The implementation of published screening guidance,^25,48 improvement of access to testing, and the creation of a patient registry and referral network to centers with the infrastructure needed to provide culturally-competent care irrespective of the insurance or immigration status will help address some of the barriers to care. Investment in this might reduce the fragmentation of care and unify efforts to address Chagas disease across institutions and stimulate needed research of this neglected entity. In the interim, patients that have tested positive for the disease can schedule an appointment in the Infectious Diseases Institute in the University of Oklahoma Health Sciences Center. Furthermore, the Oklahoma State University is currently collecting triatomine insects from Oklahoma and surrounding areas and testing them for the presence of T. cruzi and the origin of the insect’s most recent blood meal.