Chagas Disease Prevalence in a Cohort of Neurocysticercosis Patients in a Nonendemic Setting

Abstract

In a cohort of mostly Central American immigrants with confirmed neurocysticercosis (NCC), 3.1% were confirmed positive for Chagas disease (CD). The majority were diagnosed with NCC before age 50. Entry to care for NCC is an opportunity for early detection and possible treatment for CD in those from endemic areas.

Neglected tropical diseases (NTDs) affect millions of people globally, disproportionately affecting rural and impoverished communities in endemic regions of the world, though they may be underrecognized in nonendemic countries [1, 2]. Two NTDs, Chagas disease (CD) and neurocysticercosis (NCC), are leading infectious causes of heart failure and epilepsy, respectively, in countries where they are endemic [3, 4]. US population-based prevalence estimates for both diseases are imprecise due to diagnostic challenges, lack of awareness, absence of national disease reporting, and social factors that inhibit access to care [5, 6]. US recommendations for screening, though recently published, have not yet been widely implemented [5]. No studies, to our knowledge, have systematically evaluated prevalence of coinfection with NCC and CD in US populations.

In countries where NCC is endemic, the coexistence of humans with pigs and poor sanitary conditions perpetuate the lifecycle of Taenia solium. In these communities, NCC affects 10% to 20% of the population [4]. Transmission of Trypanosoma cruzi, the protozoan responsible for CD, occurs principally in rural Latin American communities where adobe and thatched-roof housing provide habitats for the triatomine insect vector [3, 6]. Vertical transmission, transmission through food, and through infected tissues have been described [3]. The seroprevalence rate of endemic CD varies by country, with an estimated 13% of the total population of continental Latin America at risk [3]. Seroprevalence in nonendemic settings largely reflects migrant countries of origin [2, 7].

Coinfection by NCC and CD has the potential to occur in areas where the community shares endemicity to both parasites (eg, rural Latin American agricultural communities) and where transmission of the parasite is able to occur because of the presence of triatomine vector, pig husbandry, and/or poor sanitation.

Here, we assess the coprevalence of CD in a cohort of patients with NCC with geographic risk factors for both parasites.

METHODS

All patients included in this report provided written consent and were enrolled on a natural history protocol for NCC at the National Institutes of Health. Diagnosis of NCC was definitive in all cases based on the revised Del Brutto criteria [8]. Patients with multiple types of NCC were classified into racemose subarachnoid, ventricular, and parenchymal forms. None had been previously known, or suspected, to have CD.

Patients’ medical records were reviewed and screened for CD if they had previously reported residence in a country endemic for T. cruzi (Mexico, Central America, South America). Patients without prior self-described residence in an endemic region or without evidence of NCC were excluded. Stored frozen serum specimens for included patients were screened using the Chagas Detect Plus Rapid Test (InBios, Seattle, WA). Patients who screened positive by the rapid test underwent confirmatory testing by the US Centers for Disease Control and Prevention, using the Chagatest recombinant v3.0 enzyme-linked immunosorbent assay (ELISA; Weiner, Rosario, Argentina) and the CDC in-house trypomastigote excreted or secreted antigen immunoblot (TESA IB), which detects antibody reactivity to trans-sialidase antigens of T. cruzi. Positivity by the screening test and CDC testing were considered confirmed CD.

Patients with confirmed CD underwent a targeted history and physical exam, electrocardiogram with 30 second lead II rhythm strip, transthoracic echocardiogram with definity contrast, and 48-hour Holter monitoring.

RESULTS

A total of 98 patients with a history of NCC also reported prior residence in T. cruzi–endemic countries (Supplementary Table). Most had parenchymal disease (46%), followed by subarachnoid (41%) and ventricular (13%). Seventy-nine percent of these patients were aged <50 years at the time of referral for NCC. Central America (67%) and Mexico (18%) were the most common regions of exposure, and South America (13%) was the least common (Supplementary Table).

Among included patients, 5 (5.1%) were positive by Chagas Detect Plus. Of those, 3 were confirmed positive for CD on ELISA and TESA IB assays and were referred for ongoing CD care (Table 1). The other 2 patients with positive CD screens tested negative on both confirmatory tests. All 3 positive patients reported at least occasional residence in adobe homes in rural regions of their respective countries of prior residence (Table 1).

Table 1.

Summary of Confirmed Chagas Disease Cases

Patient	Demographics	Trypanosoma cruzi Testing and Risk Factors			Cardiac Findings
	Age at Study Entry (y), Sex
	Age at Chagas Disease Diagnosis (y)
	Type of NCC Disease
	Country of Exposure	Trypanosoma cruzi Chagatest, Recombinant v3.0 Enzyme-Linked Immunosorbent Assay Optical Densitya (Interpretation)	Trypomastigote Excreted-Secreted Antigen immunoblot	Type of Housing	Cardiac Symptoms	Initial EKG (Year Performed)	Current EKG (2021)	Holter Monitor Findings	Other (Year Performed)	Current Echocardiogram Findings (2021)
1	43, female	3.196 (reactive)	Weak positive	Brick, tile at primary home; adobe-walled home on some weekends	Atypical chest pain; presyncope; palpitations; dizziness	Nonspecific T-wave abnormalities (2001)	Non-specific T-wave abnormalities	Minimal ectopy: 37 supraventricular ectopic beats, 7 VEs, 2 brief runs of SVT	Chemical stress nuclear medicine single photon emission computed tomography: Normal LV size; no myocardial perfusion defects (2003)	Normal LV function; no wall motion abnormalities
	65
	Parenchymal NCC
	Bolivia
2	51, male	3.143 (reactive)	Positive	Adobe, clay tile roof	Dizziness; fatigue with exertion	Nonspecific abnormal T waves in inferior leads; prolonged QT segment (2013)	Sinus bradycardia (56 beats per minute)	Ectopic beats (935 supraventricular, 1 VE couplet, 9 SV couplets, 2 runs of SVT)	Not applicable	Mild LV dilatation; normal LV function; no wall motion abnormalities
	59
	Racemose subarachnoid NCC
	Honduras
3	37, male	3.214 (reactive)	Positive	Adobe, metal roof	None reported	RSRʹ configuration (V1, lead I); no evidence of conduction blocks (2007)	PVCs; nonspecific T-wave abnormalities	Significant ectopic beats: 2758 VE (2.1% of total beats); 4-beat run of VT	Exercise stress EKG (2021): Normal sinus rhythm with right bundle branch block, left posterior fascicular block at rest; findings of chronotropic incompetence; nonischemic clinical and EKG responses CT Heart: Nonobstructive coronary arterial disease with minimal (<25%) stenoses of the proximal and mid left anterior descending coronary artery and right coronary artery	Mild hypokinesis of basal inferolateral wall, with globally preserved ejection fraction; frequent ectopy noted
	51
	Racemose subarachnoid NCC
	El Salvador

Abbreviations: CTc computed tomography; EKG, electrocardiogram; LV, left ventricle; NCC, neurocysticercosis; PVC, premature ventricular contraction; QTc, corrected QT segment; SVT, supraventricular tachycardia; VE, ventricular ectopic beat; VT, ventricular tachycardia.

Reactive optical density, >0.330.

All 3 patients with CD had nonspecific abnormalities on initial electrocardiogram (EKG; performed 8–20 years prior to diagnosis) and upon repeat EKG following CD diagnosis. Patient 3 had nonischemic basal inferolateral hypokinesis on transthoracic echocardiogram, chronotropic incompetence on treadmill stress testing, and significant ventricular ectopy on Holter monitor, all of which was consistent with Chagas cardiomyopathy. Full cardiac evaluation results for each patient are shown (Table 1). Patient 1 reported a history of abdominal pain with chronic constipation. However, barium enema study was unremarkable, and esophagram demonstrated a small hiatal hernia.

Patients 1 and 3 were aged <50 years at the time of NCC diagnosis and treatment, though were aged >50 years at the time of CD diagnosis.

DISCUSSION

The greatest prevalence of CD occurs in the 21 Latin American countries where the parasite is endemic [3]. The typical natural history of CD involves a subclinical acute phase, followed by a chronic phase with cardiac or gastrointestinal manifestations in up to 30% of those infected [3, 6, 9]. Left untreated, arrhythmias, heart failure, and embolic stroke are some of the most consequential complications, typically occurring years to decades after infection [3, 6, 9]. NCC also often has a long latency following infection before symptoms develop [1, 4]. Due to the long incubation period of CD and NCC and immigration patterns, healthcare providers in nonendemic areas are increasingly diagnosing and managing these diseases [1].

Despite having overlapping epidemiology, no US data exist on the burden of coparasitism by T. cruzi and T. solium. In the present study, we sought to understand the frequency of T. cruzi infection in a cohort of Latin American immigrants diagnosed with NCC in a nonendemic setting. While the sample size of the present study was small and represents a population emigrating mostly from Central American countries (67.4% of the cohort), the overall CD prevalence of 3.1% in NCC-infected patients is significant. The CD prevalence in this cohort is higher than among Latin American migrants in other major US cities, including a CD prevalence nearly 1% in a primary care setting in Boston and approximately 1.2% among a sample from Los Angeles County [2, 10]. A recent latent class analysis of Latin American immigrants in the Washington, DC, area found a weighted seroprevalence rate of 3.8% [7], though in a population that includes more patients from highly endemic regions of South America.

Current Pan-American Health Organization guidelines support offering antitrypanosomal treatment to adults aged <50 years with chronic CD without advanced cardiomyopathy and to children with chronic CD [11]. The majority of our cohort was aged <50 years at the time of referral for NCC, including 2 of the patients with confirmed CD. One of these patients now has clear evidence of CD-associated cardiomyopathy, while the other 2 now exhibit nonspecific EKG abnormalities potentially associated with CD, demonstrating that previously normal EKGs do not exclude the diagnosis. Their ages at presentation to our center are in keeping with observations in other series that suggest that NCC tends to occur among younger adult immigrant populations from Latin America, often prior to the fourth decade of life [1, 4]. By contrast, symptomatic chronic CD and its sequelae have generally been described as occurring later in life in endemic regions, with some series describing typical ages of presentation in the fifth decade of life and beyond [9]. CD antiparasitic therapy is ideal prior to the onset of clinically demonstrable disease. Therefore, given that a significant coprevalence of NCC and CD exists, patients who enter treatment for NCC who have CD risk factors should be routinely screened for CD. As illustrated by our CD-infected patients, early identification of asymptomatic CD is a critical opportunity for antiparasitic therapy and surveillance for progression to end-organ disease among infected patients and is a cost-effective intervention [12]. It may also decrease risk of vertical transmission of CD in pregnant patients.

There were several limitations to this study. Its observational and retrospective nature and small sample size limit conclusions about the interplay between CD and NCC among our cohort. These NCC patients overrepresent the most severe manifestations of NCC (subarachnoid and ventricular disease) and may not reflect the coparasitism risk profile of an NCC-infected population seeking care in the general community. Finally, this study may have underestimated the coprevalence of these infections as the Chagas Detect Plus screening test may be a less sensitive assay in those with discrete typing unit TcI, found from Mexico to northern South America where 95% of the patients in this study would have acquired CD [7].

In summary, we demonstrate that in this US-based cohort of Latin American immigrants with NCC, a significant proportion also had CD. Screening patients with NCC at the time of presentation provides an opportunity for earlier diagnosis and, potentially, treatment of CD.

Supplementary Data

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Financial support. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.