Version July 2025
INTRODUCTION —
Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi; the major manifestations are Chagas cardiomyopathy and gastrointestinal disease [1,2].
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 disease 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 —
Most immunosuppressed persons with T. cruzi infection are asymptomatic or have classic forms of disease such as chronic Chagas cardiomyopathy (see "Chagas disease: Chronic Trypanosoma cruzi infection"). Forms of Chagas disease unique to immunosuppressed hosts include reactivation of T. cruzi infection (in people with HIV and low CD4 counts and patients on immunosuppressive medications) and donor-derived infection in organ transplant recipients (table 1).
Reactivation of chronic Chagas disease in immunosuppressed patients — Reactivation of preexisting chronic T. cruzi infection can occur in individuals who become immunosuppressed due to HIV or administration of immunosuppressive medications (for solid organ or bone marrow transplantation) [3,4]. Rarely, T. cruzi reactivation has been reported during chemotherapy for lymphoma or leukemia, and among those taking immunosuppressive agents for rheumatologic diseases [5-8]. Reactivation forms a continuum from asymptomatic elevation of parasitemia levels to severe clinical disease [8-10]. The classic definition relies on demonstration of parasites in the peripheral blood by light microscopy or parasites in usually sterile fluids such as cerebrospinal fluid. Rising parasite loads by qPCR in blood are known to precede symptomatic reactivation by days to weeks and form the basis for prospective monitoring in patients known to be at risk of reactivation. (See 'Monitoring' below.)
Clinical manifestations
People 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 during the period 1989 to 2005, T. cruzi reactivation was observed in 21 percent of patients; the diagnosis was established based on symptoms and/or positive peripheral blood smear [11]. Even among patients without clinical manifestations of reactivation, the level of parasitemia is higher among patients with HIV than those without HIV [12].
The most commonly reported manifestations of symptomatic T. cruzi reactivation in patients with AIDS are meningoencephalitis and/or T. cruzi brain abscesses (chagomas) [11,13-15]. 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) [11,13,14,16]. Ring-enhancing cerebral lesions are the most common radiologic findings, though multiple nodular lesions with T2 hypodensity on MRI and punctate contrast enhancement have been reported. As many as 15 percent of patients may have normal brain imaging by both CT scan and MRI [13,15,17]. (See "Approach to the patient with HIV and central nervous system lesions".)
The second most commonly reported manifestation of reactivation in patients with HIV is acute myocarditis, sometimes superimposed on preexisting chronic Chagas heart disease [11,18]. Patients may present with new arrhythmias, pericardial effusions, acute cardiac decompensation, or accelerated progression of existing chronic cardiomyopathy [11,19].
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 [11].
Other manifestations of Chagas reactivation in the setting of HIV include skin lesions, erythema nodosum, and parasitic invasion of the peritoneum, stomach, or intestine [19,20].
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 [21-26]. CNS involvement can occur in transplant recipients with reactivation but is less frequent than among patients with reactivation attributable to immunosuppression from HIV [25,27-30].
Published cohort data enable some assessment of reactivation risk for renal and cardiac transplant recipients. In one Argentine study of 23 renal transplant recipients followed for up to seven years, five patients were diagnosed with reactivation based on microscopic parasitemia (21 percent) [26]. 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 cohort of 107 heart transplant recipients in Brazil, 22 (21 percent) patients experienced 32 episodes of reactivation; 23 (72 percent) had myocarditis based on endomyocardial biopsy histology [23]. Parasites were also demonstrated in skin lesions (8 patients), blood (11 patients) and CNS (1 patient); some patients had parasite found in more than one site. Four patients received benznidazole for 60 to 90 days just before or just after transplant; three had reactivation, leading the group to conclude that prophylactic antiparasitic treatment is unlikely to decrease risk of reactivation [31,32]. Post-transplant survival for Chagas disease patients was the same or better than for those transplanted for other etiologies [33].
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) [9]. (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 has similarities 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 [11,34]. However, a positive result by conventional PCR in blood does not prove reactivation; rising parasite load by quantitative PCR (qPCR) in serial specimens provides the earliest indicator [9,35,36]. Ideally, reactivation is detected by qPCR while the patient is still asymptomatic.
In patients with CNS disease, the parasite may be demonstrable by microscopy or PCR in CSF or brain biopsy [13,16,17]. Presence of skin lesions should prompt smears of lesion aspirate and/or stained biopsy specimens to evaluate for presence of T. cruzi organisms [37,38].
Monitoring — Patients with chronic Chagas disease who undergo solid organ or bone marrow transplantation warrant monitoring for reactivation. No data yet exist to support routine monitoring in patients with HIV and CD4 count <200, though some experts recommend following parasite load by qPCR in serial blood specimens until immune reconstitution is achieved [10,39-41].
For organ transplant recipients, the approach to monitoring consists of testing blood samples by microscopy and qPCR weekly for the first 2 months, twice monthly for the next 1 to 2 months, then monthly up to 6 months. Subsequently, monitoring intervals can be lengthened [42-44]. In addition, interval specimens are warranted in the setting of febrile episodes and suspected rejection crises [42,45]. The monitoring schedule for heart transplant recipients can be coordinated with the monitoring schedule for rejection [42,44,45]. The monitoring schedule can be modified; intensified immunosuppression may warrant increased frequency of monitoring.
This post-transplant monitoring schedule can also be used for other immunocompromised patients, such as those with hematologic malignancies or for hematopoietic cell transplant candidates [8,27].
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 [35,36]. In addition, heart transplant recipients should have endomyocardial biopsy tissue specimens evaluated for histological demonstration of acute myocarditis in the transplanted heart [38,44].
Donor-derived acute Chagas disease in organ transplant recipients — Transplant recipients who receive an organ from a donor infected with T. cruzi may develop acute T. cruzi infection. However, transmission is not universal and rates vary by organ [8]. Cohort studies of kidney transplants from infected donors describe transmission rates ranging from 12 to 19 percent [26].
Hearts from known infected donors are never transplanted in Latin America. Four heart transplants have occurred in the United States from donors with unknown infection status at the time of the transplant [46-49]. Three of the four recipients became infected, but the diagnosis was not suspected until acute symptoms developed; all three infected recipients died. One heart transplant from a known infected donor was performed with informed consent [47]. The recipient was monitored by serial PCR, found to be infected 3 weeks post-transplant and had a good clinical outcome with antitrypanosomal treatment. Based on these sparse data and the known tropism of the parasite, the transmission risk is likely higher for hearts than for other organs [42,48].
Clinical manifestations — Clinical manifestations and prognosis are determined by the patient's degree of immunosuppression and by how early T. cruzi parasitemia is detected. Prospective serial monitoring enables diagnosis of acute infection before symptoms develop [8]. However, if the patient is not monitored, they may develop myocarditis, CNS mass lesions, and/or graft dysfunction. Symptoms can include fever, malaise, anorexia, hepatosplenomegaly, acute myocarditis, and decreased cardiac function. Two reported patients presented with fulminant myocarditis and congestive heart failure [50,51].
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 [26,47].
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. In the case of febrile episodes or suspected rejection, additional specimens should be evaluated [26,48,52]. If immunosuppression worsens (eg, decrease in CD4 count, addition of immunosuppressive agent), the risk of Chagas reactivation increases and more frequent screening may need to be resumed [42,53].
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 — Treatment of Chagas disease is composed of restoring immunocompetence and providing antitrypanosomal therapy. For people with HIV, ART should be (re)started as soon as possible and in solid organ transplant recipients, iatrogenic immunosuppression should be minimized as much as possible. The optimal approach to anti-trypanosomal therapy for Chagas disease in immunocompromised patients and the efficacy of secondary prophylaxis remain uncertain [4,54]. 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 [26-28,55]. 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 [9].
●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 [11].
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 2 and table 3). Issues related to antitrypanosomal drugs are discussed further separately. (See "Chagas disease: Antitrypanosomal drug therapy".)
For people with HIV, after treatment for symptomatic reactivation, many experts recommend secondary prophylaxis with benznidazole (2.5 to 5 mg/kg/day three times weekly) until CD4 cell count reaches 200 [40,56,57].
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 people with HIV who have epidemiological risk factors for T. cruzi infection [58-60]. (See "Chagas disease: Epidemiology, screening, and prevention", section on 'Summary of screening recommendations'.)
Recommendations from United States, Spanish, and Latin American advisory bodies generally agree that organs from T. cruzi-infected donors, except for heart and small bowel, can be transplanted, as long as appropriate informed consent and post-transplantation monitoring can be assured [42,45,53,61,62]. Prophylactic treatment carries a high likelihood of side effects and may mask infection if it occurs. Most experts therefore recommend monitoring and initiating antitrypanosomal treatment only if acute T. cruzi infection is detected [42]. (See 'Monitoring' above.)
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 [4,42].
In people with HIV, optimization of antiretroviral therapy is the most important means of preventing T. cruzi reactivation. People with chronic T. cruzi infection, HIV, and CD4 counts >200 cells/microL are eligible for antitrypanosomal treatment based on the same criteria as other persons with chronic Chagas disease. (See "Acute and early HIV infection: Treatment" and "Chagas disease: Chronic Trypanosoma cruzi infection".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately [62]. (See "Society guideline links: Opportunistic infections in individuals 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 iatrogenically, eg, via immunosuppressive regimens for solid organ or hematopoietic cell transplantation. Rarely, T. cruzi reactivation has been reported during chemotherapy for lymphoma or leukemia. (See 'Reactivation of chronic Chagas disease in immunosuppressed patients' above.)
●Clinical manifestations
•People with HIV – The most reported manifestations of symptomatic T. cruzi reactivation in patients with CD4 count <200 cells/microL 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 'People 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 immunosuppression from uncontrolled HIV. (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 load 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 support routine monitoring 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 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, decreased cardiac function, 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 – Immunocompetence should be restored (eg, via starting/re-starting anti-retroviral therapy for people with HIV or decreasing iatrogenic immunosuppressive medications whenever possible). 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 2 and table 3). (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.)
