Enfermedad de Chagas en el sistema nervioso central en paciente con infección por VIH: dificultades diagnósticas y terapéuticas / Chagas disease in the central nervous system in patient infected with HIV: diagnostic and therapeutic difficulties

Chagas disease (ChD), caused by the protozoan Trypanosoma cruzi, is an endemic anthropozoonosis in Latin America, linked to deficients socio-economic and cultural aspects and is considered one of the neglected tropical diseases. We report a fatal case of Chagas disease reactivation with central nervous system involvement in a patient with HIV infection, whose diagnosis was confirmed by positive PCR (polymerase chain reaction) test of blood, with treatment response efficiency with benznidazol and management and etiologic treatment was difficult due to limited number of antitrypanosomal drugs and the occurrence of frequent and serious adverse effects.

La enfermedad de Chagas, causada por el protozoo Trypanosoma cruzi, es una antropo-zoonosis endémica en Latinoamérica, vinculada con aspectos socio-económico-culturales deficitarios y considerada una de las enfermedades desatendidas. Presentamos un caso fatal de una reactivación de la enfermedad de Chagas con afectación del sistema nervioso central en un paciente con infección por VIH. El diagnóstico se confirmó por reacción de polimerasa en cadena (RPC) positiva en sangre. Tuvo una buena respuesta al tratamiento con benznidazol. Las dificultades en el manejo del tratamiento etiológico se debieron al número limitado de medicamentos antitripanosomiásicos y la aparición de efectos adversos graves.

Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease / Avaliação do tratamento tripanossomicida em coorte de adultos chagásicos crônicos através de técnicas sorológicas convencionais e ELISA-F29

This work compared the time at which negative seroconversion was detected by conventional serology (CS) and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.

Este trabalho comparou os tempos de soroconversão negativos obtidos pela sorologia convencional (CS) e teste ELISA-F29 em uma coorte de pacientes chagásicos crônicos tratados com nifurtimox ou benznidazol. Um estudo retrospectivo foi realizado com soro preservado de 66 adultos chagásicos assintomáticos com acompanhamento clínico e sorológico semestral ao longo de um seguimento médio de 23 anos. 29 pacientes receberam tratamento tripanossomicida e 37 outras permaneceram sem tratamento. O teste ELISA-F29 usou um antígeno recombinante obtido por expressão do gene de uma proteína flagelar de Trypanosoma cruzi de ligação de cálcio em Escherichia coli. Entre os pacientes não tratados, 36 mantiveram os títulos da CS. Um paciente apresentou sorologia duvidosa em alguns controles. ELISA-F29 apresentou reatividade constante em 35/37 e foi negativo no paciente com CS flutuante. Os pacientes tratados foram agrupados de acordo com os títulos da CS, em três grupos: 13 tornaram-se negativos, 12 diminuíram e quatro permaneceram inalterados. ELISA-F29 foi negativo nos dois primeiros grupos. O tempo de negativização foi significativamente menor para o teste ELISA-F29 do que para CS (14,5 ± 5,7 e 22 ± 4,9 anos, respectivamente). A soroconversão negativa foi observada somente nos pacientes tratados. Os resultados obtidos confirmam que o teste ELISA-F29 é útil como um indicador precoce de soronegativação em pacientes crônicos tratados.

Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission / Tratamento etiológico de mulheres jovens infectadas com Trypanosoma cruzi e prevenção da transmissão congênita

The objective was to detect Trypanosoma cruzi infection in 32 children in Salta, Argentina, born to 16 chronically infected young women who were treated with benznidazole. Tests were performed to assess the efficacy of treatment after 14 years. At the end of the follow up, 87.5 percent of the women were non-reactive to EIA tests, 62.5 percent to IHA and 43.8 percent to IFA. 62.5 percent of the women were non-reactive according to two or three serological tests. No infected children were detected among the newborns of mothers treated before their pregnancy.

O objetivo foi detectar a infecção do Trypanosoma cruzi em 32 crianças nacidas de 16 jovens mulheres cronicamente infectadas e tratadas com benzinadol, em Salta, Argentina. Testes foram feitos para avaliar a eficácia após 14 anos do tratamento. Ao final do seguimento 87.5 por cento das mulheres foram não reativas ao EIA, 62.5 por cento ao IHA e 43.8 por cento ao IFA. 62.5 por cento das mulheres foram não reativas de acordo a 3 ou 2 testes serológicos. Nenhuma criança infectada foi detectada entre os recém-nascidos de mães tratadas antes da gravidez.

Evaluación de ELISA F29 como marcador de eficacia del tratamiento etiológico en la enfermedad de Chagas / Assessment of ELISA F29 as a marker of etiological treatment efficacy for Chagas disease

A transversal study was performed on sera from chronic chagas ic patients treated with nifurtimox (Nx) or benznidazole (Bz), in order to evaluate the Trypanosoma cruzi flagellar calcium-binding protein (F29) as a marker for therapeutic effectiveness. An ELISA was used with these F29 recombinant antigen, and its relation to conventional serology (CS) and parasitological and clinical evolution was analysed. Sera from 118 patients with retrospective, serological, parasitological and clinical information was available, were analyzed. Patients were grouped into: A) 30 treated patients whose CS became negative after treatment; B) 34 treated patients whose CS remained positive; C) 54 untreated patients. A double-blind trial was conducted simultaneously in all serum samples, by means ofCS (indirect hemagglutination, direct agglutination and indirect immunofluorescence) and ELISA F29. The ELISA F29 test was non reactive in: 100 percent of group A, 82.4 percent of group B and 13 percent> of group C. The infected patients who presented electrocardiographic alterations compatible with chronic chagasic myocardiopathy (n = 11) were reactive for ELISA F29. All patients whose parasitological studies (xenodiagnosis and/or strout method) were positive presented a high reactivity to the ELISA F29 test. The correlation between ELISA F29 and CS was statistically significant (p < 005) in the treated group whose CS was non reactive (group A) and the untreated group (group C). As opposed to this, in the group of treated patients whose CS remained positive (group B), the ELISA F29 test was reactive only in a 17.6 percent>. These results suggest that the fast and user-friendly ELISA F29 test could be useful to monitor changes after trypanocidal treatment.

La proteína flagelar F29 es una proteína ligadora de calcio del Trypanosoma cruzi. En el presente trabajo se realizó un estudio transversal en sueros de pacientes con infección crónica por T. cruzi tratados con nifurtimox (Nx) o benznidazol (Bz) y no tratados, para evaluar el antígeno F29 como marcador de eficacia terapéutica. Se utilizó un ensayo inmuno-enzimático con la proteína recombinante F29 (ELISA F29) y se analizó su relación con la serología convencional (SC) y la evolución parasitológica y clínica en esos pacientes. Se estudiaron 118 sueros de pacientes que formaban parte de una cohorte, de los cuales se disponía de información retrospectiva, serológica, parasitológica y clínica. Los pacientes se dividieron en 3 grupos: A) 30 tratados negativizaron SC post-tratamiento; B) 34 tratados permanecieron con SC reactiva; C) 54 no tratados. Las muestras de suero se procesaron a doble ciego en forma simultánea mediante serología convencional (hemoaglutinación indirecta, aglutinación directa e inmunofluorescencia indirecta) y ELISA F29. El test ELISA F29 resultó no reactivo en: 100 por ciento del grupo A, 82,4 por ciento del grupo B y 13 por ciento del grupo C. Los infectados con alteraciones electrocardiográficas compatibles con miocardiopatía chagásica crónica (n = 11) fueron reactivos al ELISA F29. Los pacientes en quienes los estudios parasitológicos (xenodiagnóstico y/o strout) fueron (+) presentaron elevada reactividad al ELISA F29. La correlación entre ELISA F29 y SC en los pacientes tratados con SC no reactiva (grupo A) y no tratados (grupo C), fue significativa (p < 0,05). En cambio, en pacientes tratados que mantuvieron la SC reactiva (grupo B) el test de ELISA F29 fue reactivo sólo en 17,6 por ciento. Estos resultados sugieren que el test ELISA F29, rápido y sencillo, podría ser útil para monitorear cambios post-tratamiento tripanocida.

Papel de la insulina y andrógenos sobre la respuesta ovulatoria al citrato de clomifeno en el síndrome de ovarios poliquísticos / Paper of the insulin and androgens on its relation to clomiphene citrate ovulatory response in polycystic ovary syndrome

Con el objeto de evaluar la secreción de insulina estimulada por glucosa oral, andrógenos séricos y la respuesta ovulatoria al citrato de clomifeno en el síndrome de ovarios poliquísticos, 23 mujeres con diagnóstico de síndrome de ovarios poliquísticos y 10 mujeres normales fueron evaluadas en un estudio prospectivo realizado en el Hospital Universitario de Los Andes, Mérida, Venezuela. La respuesta de insulina durante una prueba de tolerancia a la glucosa fue expuesta como área de insulina bajo la curva. En todas las pacientes la ovulación fue inducida con clomifeno: 100 mg/día por 5 días. La ovulación fue evaluada por ultrasonido abdominal diario y cuantificación de progesterona sérica, la cual se logró en el 52,17 por ciento y una respuesta anovulatoria fue observada en el 47,83 por ciento de las pacientes. Dentro del grupo anovulatorio, el folculo luteinizado no roto fue observado en el 26,9 por ciento de las pacientes. No hubo diferencias significativas entre los grupos ovulatorio y anovulatorio. La androstenediona sérica fue significativamente más alta en el grupo anovulatorio que en el grupo ovulatorio. Probablemente los niveles elevados de insulina pueden contribuir al aumento de la síntesis ovárica de andrógenos, lo cual favorece la atresia folicular y por consiguiente, la anovulación y esterilidad