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      Enfermedad de Chagas del sistema nervioso central en un paciente con SIDA demostrada por métodos cuantitativos moleculares Translated title: Chagas disease affecting the central nervous system in a patient with AIDS demonstrated by quantitative molecular methods

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          Abstract

          La reactivación de la infección por Trypanosoma cruzi es un diagnóstico infrecuente pero posible en pacientes con infección por VIH/SIDA y una lesión de tipo tumoral o granulomatosa en el sistema nervioso central. Presentamos el caso clínico de un paciente de 60 años con VIH/SIDA y recuentos bajos de linfocitos CD4, con síntomas cerebelosos y paresia leve, lesiones hipodensas supra e infratentoriales y serología positiva para Toxoplasma gondii y T. cruzi. Se trató empíricamente como una toxoplasmosis cerebral y con terapia antiretroviral, sin respuesta clínica. La enfermedad de Chagas cerebral se confirmó por RPC cuantitativa en el LCR. El paciente falleció a pesar de recibir terapia con nifurtimox. Apoyan la posibilidad de un Chagas cerebral en pacientes con VIH/SIDA, la exposición epidemiológica, la serología positiva y el patrón de distribución de las lesiones en las imágenes. El diagnóstico puede mejorarse con técnicas moleculares cuantitativas en LCR. A pesar de su mal pronóstico, se puede intentar una terapia específica junto al tratamiento antiretroviral.

          Translated abstract

          Although infrequent, Trypanosoma cruzi reactivation is possible among patients with HIV/AIDS infection that develop a tumor-like or granulomatous lesion in the CNS. We report the case of a 60 years old male patient with HIV/AIDS and low CD4 lymphocytes count with cerebellar symptoms and mild paresis, associated to supra and infratentorial hypodense lesions and positive serology tests both to T. gondii and Trypanosoma cruzi. Empirical therapy against toxoplasmosis was prescribed together with antiretroviral therapy but without a favorable response. Brain Chagas disease was confirmed by quantitative PCR in the CSF but he died despite nifurtimox treatment. Despite its rare occurrence, Chagas disease affecting the CNS is possible among patients with HIV/AIDS infection. Epidemiological exposure, a positive Chagas serological test and the image pattern of brain lesions support the suspicion. Diagnosis can be confirmed by molecular test in CSF samples, including new quantitative methods. Despite an adverse prognosis, specific therapy can be attempted besides antiretroviral treatment.

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          Most cited references 33

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          Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples.

          The aim of this study was to develop a real-time PCR technique to detect Trypanosoma cruzi DNA in blood of chagasic patients. Analytical sensitivity of the real-time PCR was assessed by two-fold serial dilutions of T. cruzi epimastigotes in seronegative blood (7.8 down to 0.06 epimastigotes/mL). Clinical sensitivity was tested in 38 blood samples from adult chronic chagasic patients and 1 blood sample from a child with an acute congenital infection. Specificity was assessed with 100 seronegative subjects from endemic areas, 24 seronegative subjects from non-endemic area and 20 patients with Leishmania infantum-visceral leishmaniosis. Real-time PCR was designed to amplify a fragment of 166 bp in the satellite DNA of T. cruzi. As internal control of amplification human RNase P gene was coamplified, and uracil-N-glycosylase (UNG) was added to the reaction to avoid false positives due to PCR contamination. Samples were also analysed by a previously described nested PCR (N-PCR) that amplifies the same DNA region as the real-time PCR. Sensitivity of the real-time PCR was 0.8 parasites/mL (50% positive hit rate) and 2 parasites/mL (95% positive hit rate). None of the seronegative samples was positive by real-time PCR, resulting in 100% specificity. Sixteen out of 39 patients were positive by real-time PCR (41%). Concordance of results with the N-PCR was 90%. In conclusion, real-time PCR provides an optimal alternative to N-PCR, with similar sensitivity and higher throughput, and could help determine ongoing parasitaemia in chagasic patients.
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            Real-time PCR for quantitative detection of Toxoplasma gondii.

            The protozoan Toxoplasma gondii is one of the most common infectious pathogenic parasites and can cause severe medical complications in infants and immunocompromised individuals. We report here the development of a real-time PCR-based assay for the detection of T. gondii. Oligonucleotide primers and a fluorescence-labeled TaqMan probe were designed to amplify the T. gondii B1 gene. After 40 PCR cycles, the cycle threshold values (C(T)) indicative of the quantity of the target gene were determined. Typically, a C(T) of 25.09 was obtained with DNA from 500 tachyzoites of the T. gondii RH strain. The intra-assay coefficients of variation (CV) were 0.4, 0.16, 0.24, and 0.79% for the four sets of quadruplicate assays, with a mean interassay CV of 0.4%. These values indicate the reproducibility of this assay. Upon optimization of assay conditions, we were able to obtain a standard curve with a linear range (correlation coefficient = 0.9988) across at least 6 logs of DNA concentration. Hence, we were able to quantitatively detect as little as 0.05 T. gondii tachyzoite in an assay. When tested with 30 paraffin-embedded fetal tissue sections, 10 sections (33%) showed a C(T) of <40 and were scored as positive for this test. These results were consistent with those obtained through our nested-PCR control experiments. We have developed a rapid, sensitive, and quantitative real-time PCR for detection of T. gondii. The advantages of this technique for the diagnosis of toxoplasmosis in a clinical laboratory are discussed.
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              Chagas disease in the immunosuppressed host.

               Caryn Bern (2012)
              This review examines recent literature on Chagas disease in the immunosuppressed host. Chagas disease in immunosuppressed patients may represent acute transmission in an organ recipient, or reactivation of chronic infection in an HIV-infected individual or patient receiving cardiac transplantation for Chagas cardiomyopathy. Transplantation of the kidney or liver from an infected donor resulted in transmission in 18-19 and 29%, respectively. Prospective monitoring usually detects acute infection before symptom onset; early treatment is highly effective. In heart transplant patients, reactivation symptoms include fever, myocarditis and skin lesions, and may mimic rejection. Approximately 20% of HIV- Trypanosoma cruzi infected patients experience reactivation; manifestations include meningoencephalitis and/or myocarditis. Transplantation of the heart from a T. cruzi-infected donor is contraindicated; use of other organs can be considered. Guidelines recommend prospective monitoring rather than prophylactic treatment in recipients. Posttransplant monitoring for acute infection or reactivation relies on PCR, culture and microscopy of blood specimens regularly for at least 6 months. Treatment employs standard courses of benznidazole or nifurtimox, and immune reconstitution for the HIV-coinfected patient. Case reports suggest some HIV-T. cruzi-infected patients may benefit from secondary prophylaxis, but more data are needed to determine efficacy and specific regimens.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rci
                Revista chilena de infectología
                Rev. chil. infectol.
                Sociedad Chilena de Infectología (Santiago, , Chile )
                0716-1018
                February 2017
                : 34
                : 1
                : 69-76
                Affiliations
                Santiago orgnameHospital Militar orgdiv1Servicio de Neurología Chile
                Santiago orgnameHospital Militar orgdiv1Servicio de Infectología Chile
                Santiago orgnameHospital Militar orgdiv1Servicio de Imagenología Chile
                orgnameInstituto de Salud Pública orgdiv1Sección Parasitología Chile
                Article
                S0716-10182017000100011
                10.4067/S0716-10182017000100011

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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                Figures: 0, Tables: 0, Equations: 0, References: 34, Pages: 8
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