Chagas Disease Reactivation Research Articles

Immunosuppression and Chagas disease; experience from a non-endemic country

Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality.

Reactivation of Chagas Disease in a Patient With Follicular Lymphoma Diagnosed by Means of Quantitative Real-Time Polymerase Chain Reaction.

We report a case of Chagas disease reactivation in a patient with stage IIb follicular lymphoma in the cecum. He was admitted to the hospital with neutropenia and fever. He had a history of right hemicolectomy 6 months earlier and had received the sixth cycle of chemotherapy with cyclophosphamide/doxorubicin/vincristine/prednisone/rituximab. Blood and urine cultures were negative, but the fever persisted. Reactivation of Chagas disease was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). Parasitic load was 577 950 parasite equivalents/mL. The patient began treatment with benznidazole 5 mg/k per day every 12 hours. After 1 month, the qRT-PCR control was undetectable. The patient completed 60 days of treatment and is currently asymptomatic. Trypanosoma cruzi qRT-PCR may become a useful diagnostic method for reactivation of Chagas disease.

Chagas disease reactivation in HIV-coinfected patients: Histopathological aspects

IntroductionChagas disease reactivation has been described in severely immunocompromised patients by various etiologies, including in HIV-coinfected patients. ObjectiveThis study aimed to perform histopathological and immunohistochemical evaluation of the brain, myocardium, esophagus and large bowel of autopsied patients with CHD and/or acquired immunodeficiency syndrome in comparison with control patients. Material and methodsAutopsy reports were reviewed from 1998 to 2012 and eight adult subjects were selected and divided into four groups: RE, CH, AI and CO. Sections of brain, myocardium, esophagus and large bowel were collected from each subject and processed for histological and immunohistochemical analysis. The histological sections stained with HE, Giemsa and picrosirius were used to quantify the density of inflammatory cells, the density of mast cells, and the percentage of collagen, respectively. Immunohistochemical analysis of IL17 and CD31 was performed. ResultsThe density of mast cells in the myocardium was significantly higher in the CH group than in the other groups. The density of mast cells in the esophagus and in the large bowel was significantly higher when compared to the other groups. The percentage of collagen in the esophagus, myocardium and large bowel was significantly lower in the RE group than in the CO group. The CH group had a higher percentage of collagen in the myocardium and in the large bowel in relation to the other groups. The density of cells immunostained with anti-IL17 was significantly higher in the large bowel and in the myocardium in the CH group than in the CO group. There was higher density of vessels immunostained with anti-CD31 in the myocardium and esophagus of the AI group than in the other groups. There were no significant correlations between the density of mast cells and percentage of collagen in the RE, CO, CH and AI groups. ConclusionBrain lesions observed in patients with CDR, as well as the higher density of cells immunostained with anti-IL17 at these sites, suggest that this cytokine was increasing local inflammation with subsequent tissue damage due to inflammation. Furthermore, the higher density of mast cells in the esophagus and large bowel of these subjects suggests that these cells might play a major role in esophageal and intestinal inflammation.

Acute chagas disease: new global challenges for an old neglected disease.

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management.

(715) - Cardiac Retransplantation: A Case Report in a Patient With Acute Reactivation of Chagas Disease

The indication for cardiac retransplantation is still a challenge. The lack of studies and protocols in the chagasic population invites a discussion. There is no description in the literature of cardiac retransplantation in patients affected by Chagas disease reactivation. Case Report: JPM, 36 years old, with a diagnosis of dilated cardiomyopathy due to Chagas disease, underwent heart transplant in August 2012. Showed mild rejection treated with methylprednisolone. Discharged on postoperative day 21 (POD) and readmitted after 32 days with hypotension, fever, and biventricular dysfunction.

Fatal chagas disease among solid-organ transplant recipients in Colombia.

Chagas disease continues to cause substantial morbidity and mortality in endemic areas in Latin America. Although there have been some well documented successes in halting the transmission of Chagas disease through preventive interventions to decrease vector-borne and blood-transfusion cases, this parasitic infection continues to be transmitted through these routes in some areas as well through perinatal and foodborne routes. In addition, transmission through solid-organ transplantation has been described in nonendemic settings due to the increasing globalization of Chagas disease to the United States of America, Europe, and other areas. Because there has been a concomitant increase in the number of solid-organ transplantations performed in Latin American settings endemic for American trypanosomiasis, there is increasing concern for the potential reactivation of Trypanosoma cruzi in a previously infected recipient and as a result of aggressive immunosuppression; or via transmission from organs donated by a latently infection donor transplanted onto an uninfected recipient. In this study, we report 2 cases of Chagas disease reactivation in 2 solid-organ transplant recipients in Northeastern Colombia, and we discuss the implications for screening as a crucial strategy for preventing transmission in endemic settings.

Trypanosoma cruzi persistence in the native heart is associated with high-grade myocarditis, but not with Chagas’ disease reactivation after heart transplantation

Chagas' disease reactivation (CDR) after heart transplantation (HTx) is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We investigated whether a detailed pathologic examination of the explanted heart at HTx with evaluation of myocarditis and parasitic persistence or load in the myocardium could be useful to identify patients at high risk of CDR. The native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group) were compared with the native hearts of 16 chagasic patients who never presented CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of myocarditis was evaluated semiquantitatively. Parasite persistence/load in the myocardium was investigated through immunohistochemistry for T cruzi antigens and by qualitative and quantitative real-time PCR for T cruzi DNA. The rate of high-grade myocarditis, parasite persistence, and the median of parasitic load and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 × 10(-3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%, 50%, 7.49×10(-3), and 17.800. There was no statistical difference between the groups. High-grade myocarditis was present in all 22 samples (100%) with parasite persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p = 0.003). Although associated with high-grade myocarditis, T cruzi parasite persistence in the myocardium of the native heart is not associated with the occurrence of CDR after HTx.

High Rate of Reactivation of Chagas Disease after Heart Transplantation in the United States

Purpose Chagas cardiomyopathy (CC) is a common indication for heart transplant (HTx) in endemic countries, but uncommon in the U.S. Given the potential for reactivation (react) of the causative agent Trypanosoma cruzi (TC) with immunosuppression, close monitoring for TC react is required.We sought to determine the rate of TC react in patients undergoing HTx for CC at a U.S. transplant center. Methods and Materials Serological testing for TC was performed using a whole epimastigote immunofluorescence assay and Chagatest ELISA recombinante v.3.0 (Wiener Laboratorios). After HTx, clinical surveillance for react comprised of: 1) serial clinical evaluation 2) echocardiography, and 3) heart biopsy to assess for presence of amastigotes. Positivity for any of these features was considered as clinical react of TC. Lab surveillance for react comprised of: 1) microscopy of a buffy coat blood sample for TC and 2) whole blood real-time polymerase chain reaction (PCR) testing for TC at the Reference Diagnostic Laboratory of the Division of Parasitic Diseases and Malaria at the CDC. All clinical reacts were treated. Reacts based on positive PCR results (“PCR reactivation”) were treated, except in 1 patient where repeat testing was negative. Results Between June 2006 and January 2011, 11 patients underwent HTx for CC. Two patients were lost to follow up. Two patients experienced clinical react, occurring 100 days and 216 days post-HTx. Four patients experienced PCR react at an average of 23 days post-HTx. Two patients with clinical react and 3 with PCR react were treated for TC (nifurtimox 1 patient and benznidazole 4 patients). One patient w/clinical react died due to cardiogenic shock, whereas the other 5 patients are alive at a median of 399 days post-HTx. Conclusions React of TC is common after HTx, occurring in 67% of patients, at an average of 68 days post-HTx. React is associated with mortality and therefore close clinical/laboratory monitoring is essential. Antibiotic prophylaxis requires further investigation.

Transplante cardíaco na doença de Chagas

Among the several etiologies of heart failure, the chagasic myocardiopathy is considered the most aggressive. Once there is no treatment capable of reverting the disease evolution, the heart transplantation becomes the only option. We analyzed 107 patients with Chagas disease submitted to heart transplantation, aged between 11 and 62 years (42.7 ± 15.3 years). Patients with symptomatic megacolon and megaesophagus are automatically excluded from transplant programs due to a higher possibility of postoperative short and long term complications. The expectation of inferior results for the transplantation of chagasic patients in comparison with other myocardiopathies was not confirmed and, paradoxically, were found better survival rates. We noticed an immediate mortality rated in 17.7% (19 cases), whose main cause of death were: infection (6 cases, 31.5%), graft dysfunction (6 cases, 31.5%), rejection (4 cases 21,1%), sudden cardiopulmonary arrest (2 cases 10.5%) and ABO incompatibilities (1 case 5,3%). Late after transplant, 27 (25.2%) patients died, and the major causes were: rejection (6 cases, 22.2%), infection (6 casos, 22.2%), lymphoma (4 cases, 14.8%), Kaposi sarcoma (2 cases, 7.4%), constrictive pericarditis (2 cases, 7.4%) and Chagas disease reactivation in the central nervous system (1 case, 7.1%). Finally, the conclusions are: 1) heart transplantation is still the only way to modify the natural course of chagasic myocardiopathy, 2) early diagnosis coupled to the rapid introduction of benzonidazol leads to a pattern recognition of normal myocardial histology without sequelae and 3) the doses of immunosuppressants used should be lower than those used in other etiologies.

Reactivation of Chagas Disease by Immunosuppressive Therapy in a Patient With Systemic Lupus Erythematosus

Chagas disease is a zoonosis caused by the protozoan Trypanosoma cruzi. It presents as a chronic evolution and produces high morbidity and mortality in countries where the disease is endemic, as in ours. The skin disease is very rare and results from the reactivation of latent disease as a result of immunosuppression, presenting with acute, atypical, and severe lesions. We describe the case of a patient who was unaware of being a carrier of Chagas disease and presented reactivation after immunosuppressive therapy instituted to treat her systemic lupus erythematosus.

Reactivation of Chagas disease after a bone marrow transplant in Italy: first case report.

Chagas disease is a protozoan zoonosis caused by the haemoflagellate Trypanosoma cruzi (T. cruzi). In continental Latin America, it is transmitted to humans mainly by insect vectors (Triatominae). Transmission can also occur by blood transfusion1,2, transplantation of infected organs, tissues or cells1–3 or from mother to child1, even in countries in which the disease is not endemic. In Latin America about 8–10 million people are affected4 and it has been calculated that 667,000 disability-adjusted life years are lost annually5. Most of the infected people are not aware of their status because the disease frequently causes few or no symptoms during the acute phase and evolves commonly to a clinically silent (indeterminate) phase; only in 20–30% of patients is there progression to a chronic disease, affecting mainly the heart and digestive system. Given the growing amount of international travel and the overall increase in migratory flows, a not negligible number of imported cases are registered also in non-endemic areas6. Immunosuppression and immune deficiency states (e.g. a patient with human immunodeficiency virus infection or acquired immunodeficiency syndrome) can lead to reactivation of latent infection which, in some circumstances, may give rise to severe manifestations1. We report the first case of Chagas disease reactivation after a bone marrow transplant (BMT) recorded in Italy and the first ever in Europe in a patient of paediatric age.

Sensitive and Specific Detection of Trypanosoma cruzi DNA in Clinical Specimens Using a Multi-Target Real-Time PCR Approach

BackgroundThe laboratory diagnosis of Chagas disease is challenging because the usefulness of different diagnostic tests will depend on the stage of the disease. Serology is the preferred method for patients in the chronic phase, whereas PCR can be successfully used to diagnose acute and congenital cases. Here we present data using a combination of three TaqMan PCR assays to detect T. cruzi DNA in clinical specimens.Methods/Principal FindingsIncluded in the analysis were DNA extracted from 320 EDTA blood specimens, 18 heart tissue specimens, 6 umbilical cord blood specimens, 2 skin tissue specimens and 3 CSF specimens. For the blood specimens both whole blood and buffy coat fraction were analyzed. The specimens were from patients living in the USA, with suspected exposure to T. cruzi through organ transplantation, contact with triatomine bugs or laboratory accidents, and from immunosuppressed patients with suspected Chagas disease reactivation. Real-time PCR was successfully used to diagnose acute and Chagas disease reactivation in 20 patients, including one case of organ-transmitted infection and one congenital case. Analysis of buffy coat fractions of EDTA blood led to faster diagnosis in six of these patients compared to whole blood analysis. The three real-time PCR assays produced identical results for 94% of the specimens. The major reason for discrepant results was variable sensitivity among the assays, but two of the real-time PCR assays also produced four false positive results.Conclusions/SignificanceThese data strongly indicate that at least two PCR assays with different performances should be combined to increase the accuracy. This evaluation also highlights the benefit of extracting DNA from the blood specimen's buffy coat to increase the sensitivity of PCR analysis.

Chagas disease: a threat to safe blood transfusion

Chagas disease affects approximately 8 million infected people in Mexico and Central and South America and causes 12 500 deaths annually; 41 200 new cases are reported annually (2006). Coordinated multicenter programmes have decreased about 70% of new infections in South America due to the interruption of vectorial and decreased blood transfusion transmissions. Migration of the infected population from rural areas to urban centres in endemic and non‐endemic countries led to the urbanization and globalization of Chagas disease. Chagas disease is now an emerging disease in non‐endemic areas, where congenital, blood and organ transplant transmissions are associated with reactivation of chronic Chagas disease in patients under immunosuppression or HIV infection. Recent initiatives in non‐endemic countries have been implemented to control its transmission by blood transfusion and transplants of organs. Most of the infected people were asymptomatic individuals in the chronic phase of the disease, characterized by and low and intermittent parasitemia and diagnosed by serological tests. In endemic countries, universal mandatory screening tests for detection of Trypanosoma cruzi antibodies dramatically reduced blood transfusion transmission. In non‐endemic countries, where transfusion represents the most important way of transmission, different strategies have been registered: (1) blood donor selection and deferral; (2) blood donation testing; (3) blood donation testing in people who lived in endemic areas. Questionnaires containing well‐defined questions help to identify patients from endemic areas and their epidemiological data but are of limited value since they depend on donor information. High‐performance serologic tests were reported for the detection of anti‐T. cruzi antibodies like ELISA with epimastigotes or trypomastigotes or recombinant antigens, chemiluminescent, immunoblot and radioimmunoprecipitation assays. Almost 100% of sensitivity and specificity were registered when tested in samples of well‐defined chronic chagasic patients but gold standards are not validated in circumstances of low prevalence of the disease. Additionally, their value in cases of inconclusive results (one positive test and other negative or doubtful results) was not known. Unfortunately, molecular methods are less sensitive than serology for the chronic phase of the disease (45–100% sensitivity) and were not reliable for screening tests in blood banks. Perspectives of the reduction of parasites by photochemical treatment and ultraviolet (crystal violet, methylene blue, amotosalen, riboflavin, thiopirilium) were reported sometimes with slight changes in the blood products. However, the main challenge is to demonstrate their value for prevention of a broad spectrum of agents transmitted by blood transfusion (including príon disease) and inactivation of low parasite load. In summary, questionnaires including specific questions about donor epidemiology and high‐performance serologic tests have been useful for blood bank screening. The cost–benefit–effectiveness analyses of universal serologic screening vs. serologic screening of selected donors depend on the prevalence of positive donors and should be evaluated in different regions. Finally, as pathogen inactivation methods may represent remarkable improvement in blood bank transfusion, efforts from the academia are necessary to prove their safety and effectiveness, and from blood banking–transfusion medicine community and public regulators to their implementation aiming to increase the safety of blood transfusion for patients around the world.

Trypanosoma cruzi Discrete Typing Units in Chagas disease patients from endemic and non-endemic regions of Argentina

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.

Usefulness of qualitative polymerase chain reaction for Trypanosoma cruzi DNA in endomyocardial biopsy specimens of chagasic heart transplant patients

Chagas' disease reactivation (CDR) after heart transplantation is characterized by relapse of the infectious disease, with direct detection of Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. CDR affecting the myocardium induces lymphocytic myocarditis and should be distinguished from acute cellular rejection in endomyocardial biopsy (EMB) specimens. We performed retrospectively qualitative polymerase chain reaction for T cruzi DNA using 2 sets of primers targeting nuclear DNA (nDNA) or kinetoplast DNA (kDNA) in 61 EMB specimens of 11 chagasic heart transplant recipients who presented with CDR. Thirty-five EMB specimens were obtained up to 6 months before (pre-CDR group) and 26 up to 2 years after the diagnosis of CDR. The control group consisted of 6 chagasic heart transplant recipients with 18 EMB specimens who never experienced CDR. Amplification of kDNA occurred in 8 of 35 (22.9%) EMB specimens of the pre-CDR group, in 5 of 18 (27.8%) of the control group, and in 17 of 26 (65.4%) EMB specimens obtained after the successful treatment of CDR. Amplification of nDNA occurred in 3 of 35 (8.6%) EMB specimens of the pre-CDR group, 0 of 18 (0%) of the control group, and 6 of 26 (23.1%) EMB specimens obtained after the successful treatment of CDR. Amplification of kDNA in EMB specimens is not specific for the diagnosis of CDR, occurring also in patients with no evidence of CDR (control group). However, amplification of nDNA occurred in a few EMB specimens obtained before CDR, but in none of the control group specimens. Qualitative PCR for T cruzi DNA in EMB specimens should not be used as a criterion for cure of CDR because it can persist positive despite favorable clinical evolution of the patients.

Meningoencefalitis chagásica en un paciente con infección por VIH/SIDA con sobrevida a tres años: Caso clínico

Immunocompromised patients as those with renal transplant, hematological neoplasia or cancer and HIV/AIDS infection can suffer acute reactivation of Chagas disease. Central nervous system (CNS) evolvement (cerebral tumor or chagoma and diffuse meningoencephalitis) is similar to other opportunistic infections that present with cerebral expansive processes like toxoplasmosis or CNS primary lymphoma. Survival is infrequent, depending on antiparasitic therapy and early starting antiretroviral therapy. The case of an HIV/AIDS positive patient that evolved with a chagasic meningoencephalitis and improved after beginning early antiparasitic therapy and antiretroviral therapy antiretroviral is described.

Benznidazole alters the pattern of Cyclophosphamide-induced reactivation in experimental Trypanosoma cruzi-dependent lineage infection

The factors involved in the reactivation of chronic Chagas disease infection are not clear enough and may be related to host immune unbalance and/or parasite genetic diversity. To evaluate the role of the Trypanosoma cruzi genetic background in the Chagas disease reactivation, we inoculated Cyclophosphamide-immunosupressed (CyI) Swiss mice with clonal stocks from T. cruzi I (Cuica cl1, P209 cl1, Gamba cl1, SP104 cl1), T. cruzi II (IVV cl4, MVB cl8) and T. cruzi (Bug2148 cl1, MN cl2) lineages. We used the parasitemia as the parameter for Chagas disease reactivation and observed that CyI animals infected with T. cruzi stocks showed no reactivation and those infected with T. cruzi II stocks showed only 5% of reactivation. In contrast, immunosuppressed mice infected with stocks from T. cruzi I lineage showed 77.5 and 51.25% reactivation of the infection when Cyclophosphamide treatment was performed 60 and 180 days after inoculation, respectively. Next, we evaluated the efficacy of the Benznidazole (Bz) pre-treatment in reducing or preventing the recurrence of the infection in these CyI animals. In general, the percentage of the parasite recurrence was not altered among the CyI mice that received the Bz pre-treatment during the acute phase of the infection. Interestingly, when pre-Bz treatment was performed during the chronic phase, we observed two different patterns of response: (i) an increased protection among the animals inoculated with the SP104 cl1 (genotype 19) and Cuica cl1 (genotype 20) stocks; (ii) an increased percentage of parasitemia reactivation among mice inoculated with Gamba cl1 (genotype 19) and P209 cl1 (genotype 20) T. cruzi stocks. Our results corroborate our hypothesis by showing that the T. cruzi genetic background in combination with specific Bz treatment has an important role in the Chagas disease reactivation in immunosuppressed animals.

Reactivation of Chagas disease with central nervous system involvement: peripheral blood smear evidence

Reactivation of Chagas disease with central nervous system involvement: peripheral blood smear evidence

Evolução fatal da co-infecção doença de Chagas/Aids: dificuldades diagnósticas entre a reagudização da miocardite e a miocardiopatia chagásica crônica

Chagas disease is a type of parasitosis caused by the protozoan Trypanosoma cruzi, and it is transmitted by triatomine insects. This disease is found between the southern United States to Argentina and approximately 14 million people in Latin America are believed to be infected, predominantly with the chronic form of the disease. Reactivation of Chagas disease can occur among immunosuppressed patients, as has been observed among AIDS patients. In one such case, we observed cardiac decompensation with severe ventricular dysfunction and arrhythmias. This case was thought to be reactivation of Chagas disease in the myocardium, since the xenodiagnosis was positive. Specific treatment for Trypanosoma cruzi was administered, consisting of benznidazole, but the course of treatment was not completed because the patient died due to cardiopathic complications. The necropsy showed the usual stigmas of chronic Chagas cardiopathy, such as fibrosing myocarditis and a decreased number of neurons in the digestive system. There were no amastigote forms of Trypanosoma cruzi in any of the tissue samples studied. Therefore, reactivation of Chagas disease was not demonstrated but, rather, the natural evolution of chronic Chagas cardiopathy was demonstrated.

Reactivation of Chagas disease with central nervous system involvement in HIV-infected patients in Argentina, 1992–2007

The objective of this study was to evaluate clinical and microbiological characteristics of Chagas disease (ChD) with central nervous system (CNS) involvement in AIDS patients. This was a retrospective study of clinical and laboratory findings of HIV-infected patients with a confirmed diagnosis of ChD involving the CNS during the period 1992-2007 at the "Francisco J. Muñiz" Infectious Diseases Hospital, Buenos Aires, Argentina. Of a total of 15 patients, 14 were male and the median age was 33 years (range 25-54 years). Seven out of nine had lived in a Chagas endemic area and 7/10 were intravenous drug users (IDUs). The disease was reactivated during corticosteroid therapy in three patients. Clinical manifestations were: headache (11/15), focal neurological deficits (9/15), fever (9/15), meningismus (7/15), seizures (7/15), altered mental status (5/15), and cardiac involvement (3/10). The median CD4 T-cell count at the time of reactivation was 64cells/microl (range 1-240). Twelve of 14 had positive serology for Trypanosoma cruzi; the two negative were IDUs. Cerebrospinal fluid (CSF) findings (median (range)): cell count 5/mm(3) (2-90), protein level 0.68g/l (0.1-1.84), and glucose level 0.45g/l (0.13-0.73). CSF direct examination for T. cruzi was positive in 11/13. Neuroimaging findings showed a single hypodense lesion in 7/14 and normal images in 2/14. Twelve patients were treated with benznidazole. The global mortality was 79% (11/14). ChD reactivation should be considered as a differential diagnosis of meningoencephalitis in HIV patients with low CD4 T-cell counts, previous residency in an endemic area, and/or IDUs. Whenever possible, lumbar puncture should be performed because of the high accuracy for early diagnosis.