Version May 2024
INTRODUCTION — Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi; the major manifestations are Chagas cardiomyopathy and gastrointestinal disease [1].
Issues related to Chagas in the setting of immunosuppression are reviewed here. Issues relating to acute and chronic Chagas infection are discussed separately. (See "Chagas disease: Acute and congenital Trypanosoma cruzi infection" and "Chagas disease: Chronic Trypanosoma cruzi infection".)
Issues related to epidemiology and prevention of Chagas disease are discussed separately. (See "Chagas disease: Epidemiology, screening, and prevention".)
Issues related to cardiac and gastrointestinal Chagas are discussed separately. (See "Chronic Chagas cardiomyopathy: Clinical manifestations and diagnosis" and "Chronic Chagas cardiomyopathy: Management and prognosis" and "Chagas gastrointestinal disease".)
FORMS OF DISEASE — Forms of Chagas disease in immunosuppressed hosts include reactivation of T. cruzi infection (in patients with HIV and patients on immunosuppressive medications) and donor-derived infection in organ transplant recipients.
Reactivation of chronic Chagas in immunosuppressed patients — Reactivation of preexisting chronic T. cruzi infection can occur in patients who become immunosuppressed due to HIV or administration of immunosuppressive medications (for solid organ or bone marrow transplantation) [2,3]. Rarely, T. cruzi reactivation has been reported during chemotherapy for lymphoma or leukemia [4-6].
Clinical manifestations
Patients with HIV — Reactivation of T. cruzi infection can occur in the setting of HIV/AIDS, usually when the CD4 count falls below 200 cells/microL and can cause severe disease with high risk of mortality. Reactivation is rare in patients coinfected with T. cruzi and HIV who achieve immune reconstitution with antiretroviral therapy (ART).
In one series including 53 patients with HIV and T. cruzi infection followed for 1 to 190 months, T. cruzi reactivation was observed in 21 percent of patients; the diagnosis was established based on symptoms and/or positive peripheral blood smear [7]. Even among patients without clinical manifestations of reactivation, the level of parasitemia is higher among patients with HIV than those without HIV [8].
The most commonly reported manifestations of symptomatic T. cruzi reactivation in patients with AIDS are meningoencephalitis and/or T. cruzi brain abscesses (chagomas) [7,9,10]. The presentation may be confused with central nervous system (CNS) toxoplasmosis and should be considered in the differential diagnosis of patients with HIV infection and CNS symptoms or mass lesions on imaging (image 1) [7,9-11]. The most common appearance on imaging is that of one or more hypodense lesions [9]. (See "Approach to the patient with HIV and central nervous system lesions".)
The second most common reported manifestation of reactivation in patients with HIV is acute myocarditis, sometimes superimposed on preexisting chronic Chagas heart disease [7,12]. Patients may present with new arrhythmias, pericardial effusions, acute cardiac decompensation, or accelerated progression of existing chronic cardiomyopathy [7,13].
Acute meningoencephalitis and myocarditis can occur simultaneously. In one Brazilian cohort, cardiac reactivation was as frequent as CNS disease; cardiac reactivation may be subtle and can mimic progression of chronic Chagas cardiomyopathy [7].
Other manifestations of Chagas reactivation in the setting of HIV include skin lesions, erythema nodosum, and parasitic invasion of the peritoneum, stomach, or intestine [8,13].
Transplant recipients — Transplant recipients with preexisting chronic T. cruzi infection can experience reactivation. Clinical manifestations include fever, myocarditis, symptoms suggestive of rejection, and/or dermatologic manifestations, including inflammatory panniculitis and skin nodules [14-19]. CNS involvement can occur in transplant recipients with reactivation but is less frequent than among patients with reactivation attributable to HIV infection [18,20,21].
In one study of 23 renal transplant recipients in Argentina followed for up to seven years, five patients were diagnosed with reactivation based on microscopic parasitemia (21 percent) [19]. Of these patients, two had skin lesions and one of these also had panniculitis; the other three patients were asymptomatic. Reactivation was diagnosed 35 to 97 days post-transplant in four of the five patients; the fifth had reactivation detected 29 months after transplantation. In a series of 31 patients who received cardiac transplantation for end-stage Chagas cardiomyopathy in the United States, one was diagnosed with symptomatic reactivation while 18 remained asymptomatic but had evidence of reactivation based on rising parasite load in quantitative polymerase chain reaction (PCR) monitoring; all 19 patients with reactivation survived to the end of follow-up (median 60 weeks) [22]. (See "Chronic Chagas cardiomyopathy: Management and prognosis", section on 'Cardiac transplantation'.)
Diagnosis — Reactivated Chagas infection should be suspected in immunosuppressed individuals with relevant symptoms (CNS symptoms, myocarditis, and/or skin lesions) with a history of prior exposure to areas of Latin America with vector-borne transmission of Chagas disease.
The approach to diagnosis of reactivated Chagas disease is similar to the approach to diagnosis of acute T. cruzi infection; tools include PCR and light microscopy of fresh whole blood or buffy coat for detection of circulating trypomastigotes [7,23]. However, a positive result by conventional PCR does not prove reactivation; rising parasite numbers by quantitative PCR in serial specimens provide the earliest indicator [22,24,25]. (See "Chagas disease: Acute and congenital Trypanosoma cruzi infection", section on 'Acute T. cruzi infection'.)
Presence of skin lesions should prompt smears of lesion aspirate and/or stained biopsy specimens to evaluate for presence of T. cruzi organisms [26,27].
Monitoring — Patients with chronic Chagas disease who undergo solid organ or bone marrow transplantation warrant monitoring for reactivation. There are no data to suggest that routine monitoring is indicated for patients with HIV [28].
The approach to monitoring consists of testing blood samples (by microscopy and PCR) weekly for the first 2 months, twice monthly for the next month, then monthly up to 6 months. Subsequently, monitoring intervals can be lengthened [29-31]. In addition, interval specimens are warranted in the setting of febrile episodes and suspected rejection crises [29,32]. The monitoring schedule for heart transplant recipients can be coordinated with the monitoring schedule for rejection [29,31,32].
Laboratory testing should include microscopy of fresh whole blood or buffy coat for circulating trypomastigotes and quantitative PCR in peripheral blood. A positive result by conventional PCR does not prove reactivation, but rising parasite numbers by quantitative PCR in serial specimens provide the earliest indicator [24,25]. In addition, heart transplant recipients should have endomyocardial biopsy tissue specimens evaluated for histological demonstration of acute myocarditis in the transplanted heart [27,31].
Donor-derived acute Chagas in organ transplant recipients — Transplant recipients who receive an organ from a donor infected with T. cruzi may develop acute T. cruzi infection, although transmission under these circumstances appears to be fairly uncommon. In series of 16 recipients of kidney transplants from infected donors, three acquired T. cruzi infection (19 percent) [19]. More than 20 cases of Chagas disease transmission by solid organ transplantation have been documented in the literature (at least 15 kidney, 1 kidney and pancreas, 4 liver, 3 heart transplants) [19,33-43]. Hearts from known infected donors are never transplanted in Latin America; all such transplants have occurred in the United States from donors with unknown infection status at the time of the transplant [34,40,41]. In one study, three of the four heart recipients became infected; based on these sparse data and the known tropism of the parasite, the transmission risk is likely higher for hearts than for other organs [29,41].
Clinical manifestations — Among the 10 organ recipients for whom data were available in published reports, the period from transplantation to onset of symptoms of acute T. cruzi infection ranged from 23 to 300 days (mean 103 days; median 62 days). Symptoms included fever, malaise, anorexia, hepatosplenomegaly, acute myocarditis, and decreased cardiac function. Two of the reported patients presented with fulminant myocarditis and congestive heart failure [33,43].
Diagnosis — Ideally, donor-derived acute T. cruzi infection is detected via monitoring, prior to onset of symptoms. (See 'Monitoring' below.)
The approach to diagnosis of donor-derived acute T. cruzi infection is the same as the approach to diagnosis of acute Chagas infection; tools include PCR and/or light microscopy of fresh whole blood or buffy coat for detection of circulating trypomastigotes. (See "Chagas disease: Acute and congenital Trypanosoma cruzi infection", section on 'Diagnosis'.)
Monitoring — Identification of donor infection before or after organ transplantation should prompt careful post-transplant monitoring of the recipients. Patients whose infection is detected early through monitoring have excellent response to treatment and good clinical outcomes [19,40].
Monitoring consists of evaluation for evidence of infection in the recipient by microscopy and PCR, if available. Microscopy should be performed on a fresh specimen as soon as possible after collection, when trypomastigotes are still motile and therefore more readily detected. After two hours at room temperature, motility would be expected to fall. PCR is more sensitive than microscopy. In the United States, the Centers for Disease Control and Prevention (CDC) act as a reference laboratory for T. cruzi PCR (Division of Parasitic Diseases Public Inquiries line, 404-718-4745; for emergencies after business hours, 770-488-7100; email [email protected]).
Monitoring should consist of weekly specimens for two months, every two weeks for the third month, and then monthly until six months post-transplantation, when the monitoring interval can be lengthened if no evidence of infection has been detected [29]. In the case of febrile episodes or suspected rejection, additional specimens should be evaluated [19,41,42].
Additional issues related to laboratory diagnosis of acute and chronic T. cruzi infection are discussed separately. (See "Chagas disease: Acute and congenital Trypanosoma cruzi infection" and "Chagas disease: Chronic Trypanosoma cruzi infection".)
TREATMENT AND PREVENTION
Treatment — The optimal approach to management of Chagas disease in immunocompromised patients and the efficacy of secondary prophylaxis remain uncertain [3,44]. Data are limited to observational studies:
●Among transplant patients with reactivated infection, treatment with benznidazole accelerated improvement in clinical symptoms and reduced intensity of parasitemia [19-21,45]. In a United States cohort study including 19 patients who underwent cardiac transplant and developed reactivation, patients responded well to treatment and no evidence of decreased survival was observed [22].
●In a small series of patients with HIV and T. cruzi coinfection, a course of benznidazole therapy resulted in improvement of clinical manifestations and decreased parasitemia [7].
Antitrypanosomal therapy is warranted for all patients with reactivated T. cruzi infection and for all patients with donor-derived acute T. cruzi infection. Antitrypanosomal drugs include benznidazole and nifurtimox; in general, benznidazole is better tolerated so is favored as the first-line treatment for Chagas disease. Dosing and adverse effects are outlined in the tables (table 1 and table 2). Issues related to antitrypanosomal drugs are discussed further separately. (See "Chagas disease: Antitrypanosomal drug therapy".)
Prevention — Monitoring and timely treatment of T. cruzi reactivation depends on early recognition. For that reason, Chagas disease screening should be included in the evaluation of transplant candidates and patients with HIV who have epidemiological risk factors for T. cruzi infection [46-48]. (See "Chagas disease: Epidemiology, screening, and prevention", section on 'Summary of screening recommendations'.)
Transplantation of kidney or liver from a known infected donor can be undertaken with informed consent and post-transplant monitoring. Transplantation of the heart from a known infected donor is contraindicated [29].
Routine presumptive antitrypanosomal treatment is not generally recommended for patients at risk of reactivation (such as patients with HIV and patients with previously untreated T. cruzi infection awaiting organ transplant) or for prevention of donor-derived acute T. cruzi infection [3,29].
Presumptive treatment is unlikely to be curative and carries substantial risk of adverse effects. In addition, establishing the presence of infection is important for long-term management; presumptive treatment would preclude this evaluation. Therefore, close monitoring is warranted as described above; detection of acute infection or reactivation should prompt initiation of treatment. (See 'Monitoring' above and 'Monitoring' above.)
In patients with HIV, optimization of antiretroviral therapy is the most important means of preventing T. cruzi reactivation. (See "Acute and early HIV infection: Treatment".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opportunistic infections in adults with HIV" and "Society guideline links: Chagas disease".)
SUMMARY AND RECOMMENDATIONS
●Reactivation of disease – Reactivation of preexisting chronic Trypanosoma cruzi infection can occur in patients who become immunosuppressed due to HIV or immunosuppressive regimens for solid organ or bone marrow transplantation. Rarely, T. cruzi reactivation has been reported during chemotherapy for lymphoma or leukemia. (See 'Reactivation of chronic Chagas in immunosuppressed patients' above.)
●Clinical manifestations
•Patients with HIV – The most commonly reported manifestations of symptomatic T. cruzi reactivation in patients with AIDS are meningoencephalitis and/or T. cruzi brain abscesses (chagomas). The presentation may be confused with central nervous system (CNS) toxoplasmosis and should be considered in the differential diagnosis of patients with HIV infection and CNS symptoms or mass lesions on imaging. (See 'Patients with HIV' above.)
•Transplant recipients – Clinical manifestations of T. cruzi reactivation among transplant recipients include fever, myocarditis, symptoms suggestive of rejection, and/or dermatologic manifestations, including inflammatory panniculitis and skin nodules. CNS involvement can occur but is less frequent than among patients with reactivation attributable to HIV infection. (See 'Transplant recipients' above.)
●Diagnosis – The diagnosis of reactivation is confirmed by detection of circulating trypomastigotes in the peripheral blood; quantitative polymerase chain reaction (PCR) on serial specimens is a useful technique to show rising parasite load. A positive result on conventional PCR does not prove reactivation, but quantitative PCR assays that indicate rising parasite numbers over time provide the earliest and most sensitive indicator of reactivation. (See 'Diagnosis' above.)
●Monitoring for reactivation of disease – Patients with chronic Chagas disease who undergo solid organ or bone marrow transplantation warrant monitoring for reactivation. There are no data to suggest that routine monitoring is indicated for patients with HIV. (See 'Monitoring' above.)
●Donor-derived acute Chagas disease
•Clinical manifestations – Organ transplant recipients who receive an organ from a donor infected with T. cruzi may develop acute T. cruzi infection; transmission under these circumstances appears to be fairly uncommon, except when the organ involved is the heart. Transplantation of the heart from a known infected donor is contraindicated. The period from transplantation to onset of symptoms of acute T. cruzi infection has ranged from 23 to 300 days (mean 103 days; median 62 days). Symptoms included fever, malaise, anorexia, hepatosplenomegaly, acute myocarditis, and decreased cardiac function. Two patients presented with fulminant myocarditis and congestive heart failure. (See 'Clinical manifestations' above.)
•Monitoring for acute Chagas disease – Identification of donor infection following organ transplantation should prompt careful post-transplant monitoring of the recipients. The approach to monitoring consists of testing blood samples (for microscopy and PCR) weekly for the first two months, twice monthly for the next month, then monthly up to six months. Subsequently, monitoring intervals can be lengthened. (See 'Monitoring' above.)
●Treatment – Antitrypanosomal therapy is warranted for all patients with reactivated T. cruzi infection and for all patients with donor-derived acute T. cruzi infection. Antitrypanosomal drugs include benznidazole and nifurtimox; in general, benznidazole is better tolerated so is favored as the first-line treatment for Chagas disease (table 1 and table 2). (See 'Treatment' above and "Chagas disease: Antitrypanosomal drug therapy".)
●Prevention – We suggest NOT administering presumptive antitrypanosomal therapy for patients at risk for T. cruzi reactivation or donor-derived acute T. cruzi infection (Grade 2C). Presumptive treatment is unlikely to be curative in this setting and carries substantial risk of adverse effects. In addition, establishing the presence of infection is important for long-term management; presumptive treatment would preclude this evaluation. (See 'Prevention' above.)
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