Risk factors for antimony treatment failure in American Cutaneous Leishmaniasis in Northwestern-Argentina.

BACKGROUND: To date, there is no specific literature available on the determinants for therapeutic failure (TF) with meglumine antimoniate (MA) in Northwestern-Argentina. This study aimed to identify epidemiological, clinical, and treatment-related factors that could be involved in TF. METHODOLOGY/PRINCIPAL FINDINGS: We performed a case-control study. Cases were represented by patients who showed TF after administration of the first course of MA treatment, whereas, controls were determined as patients who evolved towards healing after the first MA cycle received. Crude Odds Ratios and their corresponding 90% confidence intervals (CI) were calculated, and risk factors were then tested by multivariate analysis using logistic binary regression. Three hundred and eighty-four patients with a presumptive diagnosis of ACL were recruited, and 153 with a positive diagnosis were selected. We included in the study 71 patients, who underwent specific treatment with MA, presented complete data on response to treatment, and had a minimum post-treatment follow-up of 6 months in cutaneous leishmaniasis, and 12 months in mucosal leishmaniasis. Of these, 34 (47.9%) presented TF. In the initial analysis, TF was significantly associated with the geographical area of disease acquisition (p = 0.036), the presence of mucosal lesions (p = 0.042), the presence of concomitant skin and mucosal lesions (p = 0.002), and lesion age ≥ 6 months (p = 0.018). Risk factors influencing TF in the final multivariate model included the geographical area where the disease was acquired (adjusted Odd Ratio 8.062; 95% CI 1.914-33.959; p = 0.004), and lesion age ≥ 6 months (adjusted Odd Ratio 10.037; 95% CI 1.383-72.843; p = 0.023). CONCLUSIONS/SIGNIFICANCE: The results of the present study suggest the existence of some risk factors linked to TF in Northwestern-Argentina, which deserve further investigation. Herein we recorded a high percentage of TF and we described clinical and epidemiological characteristics associated with TF that could be taken into account improving the clinical management of patients.

[Alterations of immunological parameters in an autochthonous case of visceral leishmaniasis from the Northwest of Argentina]. / Afectación de parámetros inmunológicos en un caso de leishmaniasis visceral autóctono del Noroeste Argentino.

We report the alterations of immunological parameters of a patient with visceral leishmaniasis caused by Leishmania (Leishmania) infantum from the Northwest of Argentina during active disease and after achieving clinical recovery. We first demonstrated elevated amounts of IFN-y, IL-10, B-cell activating factor (BAFF) and IgG in plasma during active disease, which returned to control values after recovery. In relation to T cell profile, we measured CD27, CD28, CD45RO, CD57 and perforin. We found a highly differentiated phenotype, preferentially in active disease and among CD8+ T cells, consisting in increased numbers of late differentiated and terminal effector cells. Although this highly differentiated CD8+ T cell phenotype persisted after recovery, a clear increase of central memory cells was recorded for both T subsets at that point, suggesting signs of reversion toward a less differentiated profile. The composition of the B cell compartment was slightly modified during active disease. Herein we document the global impact of severe visceral leishmaniasis on immunological parameters, which tend to revert upon clinical recovery, suggesting signs of immune restoration accompanying clinical improvement. The evaluated parameters could eventually be used as biomarkers of clinical evolution of visceral leishmaniasis.

En el presente trabajo informamos la afectación de parámetros inmunológicos durante la etapa grave de la infección y luego de alcanzar la recuperación clínica en un paciente autóctono del Noroeste argentino con leishmaniasis visceral causada por Leishmania (Leishmania) infantum. Detectamos concentraciones plasmáticas elevadas de interferón-y, interleuquina 10, IgG y BAFF (B-cell activating factor) durante la enfermedad activa, que se normalizaron luego de la recuperación clínica. En relación al perfil de diferenciación y memoria de las células T, clasificamos las células según la expresión de CD27, CD28, CD45RO, CD57 y perforina. Encontramos un fenotipo altamente diferenciado analizando la población de linfocitos T CD8+, con porcentajes aumentados de células T de diferenciación tardía y efectoras terminales. Si bien el fenotipo T CD8+ persistió luego de la recuperación clínica, pudimos observar un claro aumento de células T de memoria central en ese punto de estudio, sugiriendo signos de una posible reversión hacia un perfil T menos avanzado. El compartimiento de células B CD19+ mostró cambios más leves en la composición de las subpoblaciones de memoria. Documentamos el compromiso global de parámetros inmunológicos en la etapa grave de la leishmaniasis visceral que tienden a revertir luego de la recuperación, sugiriendo posibles signos de reconstitución inmune acompañando a la mejoría clínica. Los parámetros evaluados podrían ser útiles como biomarcadores de la evolución clínica de la enfermedad.

Afectación de parámetros inmunológicos en un caso de leishmaniasis visceral autóctono del Noroeste Argentino / Alterations of immunological parameters in an autochthonous case of visceral leishmaniasis from the Northwest of Argentina

Resumen En el presente trabajo informamos la afectación de parámetros inmunológicos durante la etapa grave de la infección y luego de alcanzar la recuperación clínica en un paciente autóctono del Noroeste argentino con leishmaniasis visceral causada por Leishmania (Leishmania) infantum. Detectamos concentraciones plasmáticas elevadas de interferón-γ, interleuquina 10, IgG y BAFF (B-cell activating factor) durante la enfermedad activa, que se normalizaron luego de la recuperación clínica. En relación al perfil de diferenciación y memoria de las células T, clasificamos las células según la expresión de CD27, CD28, CD45RO, CD57 y perforina. Encontramos un fenotipo altamente diferenciado analizando la población de linfocitos T CD8+, con porcentajes aumentados de células T de diferenciación tardía y efectoras terminales. Si bien el fenotipo T CD8+ persistió luego de la recuperación clínica, pudimos observar un claro aumento de células T de memoria central en ese punto de estudio, sugiriendo signos de una posible reversión hacia un perfil T menos avanzado. El compartimiento de células B CD19+ mostró cambios más leves en la composición de las subpoblaciones de memoria. Documentamos el compromiso global de parámetros inmunológicos en la etapa grave de la leishmaniasis visceral que tienden a revertir luego de la recuperación, sugiriendo posibles signos de reconstitución inmune acompañando a la mejoría clínica. Los parámetros evaluados podrían ser útiles como biomarcadores de la evolución clínica de la enfermedad.

Abstract We report the alterations of immunological parameters of a patient with visceral leishmaniasis caused by Leishmania (Leishmania) infantum from the Northwest of Argentina during active disease and after achieving clinical recovery. We first demonstrated elevated amounts of IFN-γ, IL-10, B-cell activating factor (BAFF) and IgG in plasma during active disease, which returned to control values after recovery. In relation to T cell profile, we measured CD27, CD28, CD45RO, CD57 and perforin. We found a highly differentiated phenotype, preferentially in active disease and among CD8+ T cells, consisting in increased numbers of late differentiated and terminal effector cells. Although this highly differentiated CD8+ T cell phenotype persisted after recovery, a clear increase of central memory cells was recorded for both T subsets at that point, suggesting signs of reversion toward a less differentiated profile. The composition of the B cell compartment was slightly modified during active disease. Herein wedocument the global impact of severe visceral leishmaniasis on immunological parameters, which tend to revert upon clinical recovery, suggesting signs of immune restoration accompanying clinical improvement. The evaluated parameters could eventually be used as biomarkers of clinical evolution of visceral leishmaniasis.

B-cell profile, B-cell activating factor concentration and IgG levels in human cutaneous and mucosal leishmaniasis.

AIMS: The aim of this study was to evaluate characteristics of B cells in human tegumentary leismaniasis (TL) analysing cutaneous leishmaniasis (CL), most prevalent form and mucosal leishmaniasis (ML), aggressive form characterized by the destruction of the oral-nasal-pharyngeal cavities. METHODS AND RESULTS: By flow cytometry analysis, we found decreased percentages of non-class-switched memory B cells in TL with the degree of the loss related to clinical severity. Using commercial ELISA, we reported high levels of B-cell activating factor (BAFF) and IgG preferentially in aggressive CL and markedly in ML together with decreased BAFF receptors in the latter. We also found lower levels of BAFF after clinical recovery suggesting a relation between BAFF and disease activity. Mucosal leishmaniasis history of therapeutic failure presented high levels of BAFF accompanied by detectable concentrations of IFN-γ and IL-6 (assayed by commercial ELISA and cytometric bead arrays respectively), cytokines involved in exaggerated inflammatory responses and tissue damage in TL. CONCLUSION: We demonstrate B-cell disturbances in TL with the degree of the alterations related to clinical severity. We suggest a relation between excess of BAFF and disease activity and point towards a possible implication of BAFF in the inflammatory phenomenon of ML.

Leishmaniasis Tegumentaria Americana en Salta: evaluación de métodos no invasivos para toma de muestra y validación del diagnóstico molecular / American Tegumentary Leishmaniasis in Salta: evaluation of non-invasive methods for sample collection and validation of molecular diagnosis

La Leishmaniasis Tegumentaria Americana (LTA) es una zoonosis endémica del Noroeste Argentino. Salta presenta la mayor incidencia del país. El control reside en un rápido diagnóstico y tratamiento temprano. Nuestro grupo colabora con hospitales de Salta­capital, implementando el diagnóstico parasitológico y molecular (PCRk). Se han presentado algunas dudas en aquellos pacientes con diagnóstico parasitológico negativo y molecular positivo. Otro inconveniente es la toma de muestra, hasta ahora el raspado (P) de lesiones demostró ser el método más efectivo. Pero genera incomodidad y presenta riesgos como el sangrado e infección. Es necesario probar técnicas menos invasivas. En base a esto los objetivos del trabajo fueron; Validar la técnica de diagnóstico PCRk y; Evaluar la sensibilidad de PCRk con muestras menos invasivas como impresiones en papel de filtro (PF) y/o uso de hisopos (H). A partir del análisis del diagnóstico de pacientes atendidos entre 2007-2017, se evaluó la idoneidad de la PCRk en la detección de casos clínicos dudosos. También se evaluó la sensibilidad analítica en diluciones de parásitos, y diagnóstica en pacientes atendidos entre 2017-2018, de la PCRk con PF, H con respecto a P. La PCRk exhibió una S; 99% y E; 87,8%, y una concordancia casi perfecta según el índice Kappa. Con respecto a la S analítica de la PCRk, con PF y H fue menor (3p/300µl) que con P (1p/300µl). PF resulto ser más sensible que H para LC, mientras que H mostró una máxima S y E en LMC. La PCRk de acuerdo a los parámetros evaluados, ha mostrado idoneidad diagnóstica para los casos de LTA en Salta. En conjunto con el frotis aporta información completa para la toma de decisiones respecto al tratamiento de los pacientes

American tegumentary leishmaniasis: T-cell differentiation profile of cutaneous and mucosal forms-co-infection with Trypanosoma cruzi.

American tegumentary leishmaniasis displays two main clinical forms: cutaneous (CL) and mucosal (ML). ML is more resistant to treatment and displays a more severe and longer evolution. Since both forms are caused by the same Leishmania species, the immunological response of the host may be an important factor determining the evolution of the disease. Herein, we analyzed the differentiation and memory profile of peripheral CD4(+) and CD8(+) T lymphocytes of patients with CL and ML and their Leishmania-T. cruzi co-infected counterparts. We measured the expression of CD27, CD28, CD45RO, CD127, PD-1 and CD57, together with interferon-γ and perforin. A highly differentiated phenotype was reflected on both T subsets in ML and preferentially on CD8(+) T cells in CL. A positive trend toward a higher T differentiation profile was found in T. cruzi-infected CL and ML patients as compared with Leishmania single infections. Association between CD8(+) T-cell differentiation and illness duration was found within the first year of infection, with progressive increase of highly differentiated markers over time. Follow-up of patients with good response to therapy showed predominance of early differentiated CD8(+) T cells and decrease of highly differentiated cells, while patients with frequent relapses presented the opposite pattern. CD8(+) T cells showed the most striking changes in their phenotype during leishmaniasis. Patients with long-term infections showed the highest differentiated degree implying a relation between T differentiation and parasite persistence. Distinct patterns of CD8(+) T differentiation during follow-up of different clinical outcomes suggest the usefulness of this analysis in the characterization of Leishmania-infected patients.

Clinical and epidemiological features of leishmaniasis in northwestern-Argentina through a retrospective analysis of recent cases.

Leishmaniasis is a parasitic disease caused by hemoflagellates of the genus Leishmania and is transmitted to humans by the bite of infected phlebotomine sandflies. Depending on the Leishmania species, the disease has different clinical forms including cutaneous, mucocutaneous, and visceral manifestations. Previous studies performed in endemic zones of northwestern-Argentina, during epidemic outbreaks, have been important for detecting patients suffering from the acute phase of the disease, but have not given a complete representation of the clinical and epidemiological features in the region. Furthermore, due to the resurgence of leishmaniasis worldwide and in particular the large increase of international tourism to the region, it seems pertinent to update the current epidemiological and clinical profile of leishmaniasis in northwestern-Argentina. Here we present a retrospective analysis of 95 Leishmania positive cases, presenting between 2000 and 2014. Patients were derived from hospitals and diagnosed in our lab at the University of Salta, located in a non-endemic area in Salta, Argentina. We detected numerous extensive mucocutaneous cases (34/95, 35.8%) distinct from mucosal affected patients, some instances originating in locations with no previously reported human cases. Additionally patients suffering from concomitant diseases, besides leishmaniasis, were assessed. These included Chagas disease, syphilis, deep mycoses, tuberculosis, toxoplasmosis and intestinal parasitosis. This study updates the clinical and epidemiological features of leishmaniasis in northwestern-Argentina, and discusses the implications and management strategy for patients who acquire the disease in this region.

Visceral Leishmaniasis Caused by Leishmania infantum in Salta, Argentina: Possible Reservoirs and Vectors.

Cases of human visceral leishmaniasis (HVL) were not recorded until recently in the Chaco region of northwestern Argentina. Dogs were surveyed at the sites of infection of two HVL index cases in the Chaco region of Salta province. Canine cases (CanL) were diagnosed by two parasitological methods, two molecular methods targeting mini- and maxicircle DNA, and immunochromatographic dipstick. Among 77 dogs studied, 10 (13%) were found infected with Leishmania spp. In seven dogs and two humans, the infecting species was typed as Leishmania (Leishmania) infantum. The same genotype was detected in the human and two of the CanL. Although several diagnostic methods displayed weak or moderate agreement, the concordance values for serology versus maxicircle PCR were very good (Kappa index = 0.84). Sandflies captured in the area were identified as Lutzomyia migonei and Lu. cortelezzii/Lu. sallesi (cortelezzii complex). The focal appearance of leishmaniasis in dogs and humans in a sylvatic region and its relatively low prevalence of infection suggests that L. (L.) infantum transmission to dogs and humans may, in this region, stem from sylvatic reservoirs.

[Miltefosine versus meglumine antimoniate in the treatment of mucosal leishmaniasis]. / Miltefosina versus antimoniato de meglumina en el tratamiento de la leishmaniasis mucosa.

The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.

Miltefosina versus antimoniato de meglumina en el tratamiento de la leishmaniasis mucosa

El tratamiento convencional para la leishmaniasis tegumentaria es el antimoniato de meglumina, el cual presenta falla terapéutica creciente, producción de efectos adversos graves, y necesidad de administración parenteral, justificando la búsqueda de alternativas terapéuticas. Presentamos aquí los resultados preliminares de un ensayo clínico de fase II en pacientes con leishmaniasis mucosa, en el que se comparó la eficacia de miltefosina por vía oral con respecto a la del compuesto antimonial. La evaluación de la respuesta a los tratamientos se realizó mediante un seguimiento con videofibroscopia nasofaríngea, utilizándose un score de gravedad de lesiones mucosas para aplicar en cada momento del seguimiento de los pacientes. No se encontraron hasta ahora diferencias significativas entre el número de pacientes curados con miltefosina o con la quimioterapia convencional. Los resultados favorables de este trabajo sugieren que miltefosina podría constituir una alternativa terapéutica efectiva y segura en la región.(AU)

The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.(AU)

Miltefosina versus antimoniato de meglumina en el tratamiento de la leishmaniasis mucosa

El tratamiento convencional para la leishmaniasis tegumentaria es el antimoniato de meglumina, el cual presenta falla terapéutica creciente, producción de efectos adversos graves, y necesidad de administración parenteral, justificando la búsqueda de alternativas terapéuticas. Presentamos aquí los resultados preliminares de un ensayo clínico de fase II en pacientes con leishmaniasis mucosa, en el que se comparó la eficacia de miltefosina por vía oral con respecto a la del compuesto antimonial. La evaluación de la respuesta a los tratamientos se realizó mediante un seguimiento con videofibroscopia nasofaríngea, utilizándose un score de gravedad de lesiones mucosas para aplicar en cada momento del seguimiento de los pacientes. No se encontraron hasta ahora diferencias significativas entre el número de pacientes curados con miltefosina o con la quimioterapia convencional. Los resultados favorables de este trabajo sugieren que miltefosina podría constituir una alternativa terapéutica efectiva y segura en la región.

The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.

In vivo antileishmanial efficacy of miltefosine against Leishmania (Leishmania) amazonensis.

Leishmaniasis, a disease caused by parasites of the Leishmania genus, constitutes a significant health and social problem in many countries and is increasing worldwide. The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI), and the presence of parasites in RFP, spleen, and liver, determined by polymerase chain reaction (PCR). Swiss mice, infected with Leishmania (Leishmania) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF produced a clear reduction in splenomegaly and was equal in reducing antibody titles in comparison with MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA.

Miltefosina versus antimoniato de meglumina en el tratamiento de la leishmaniasis mucosa. / [Miltefosine versus meglumine antimoniate in the treatment of mucosal leishmaniasis].

The conventional treatment for tegumentary leishmaniasis is meglumine antimoniate, which needs parenteral administration, has increased therapeutic failure, and produces serious adverse effects, justifying the search for therapeutic alternatives. We report here the preliminary results of a phase II clinical trial in patients with mucosal leishmaniasis, in which the efficacy of oral miltefosine versus the antimonial compound was assessed. The evaluation of response to the treatment was performed by monitoring with nasopharyngeal video-fibroscopy, using a score of mucosal injury severity for patients at each follow-up point. We found no significant differences so far between the number of patients cured with miltefosine or conventional chemotherapy. The favorable results of this study suggest that miltefosine could be an effective and safe oral therapeutic alternative in the region.

Desarrollo de una PCR en tiempo real para la cuantificación de leishmania SP en muestras de pacientes con leishmaniasis tegumentaria americana / Development of a real time PCR assay for the quantification of leishmania SP in samples from patients with american tegumentary leishmaniasis

INTRODUCCION: La leishmaniasis tegumentaria americana (LTA) es una enfermedad endémica reemergente en la provincia de Salta. Los recursos terapéuticos disponibles presentan serias limitaciones. Se han detectado numerosos casos de fallas terapéuticas debido a que el criterio de curación se basa en la evolución clínica de las lesiones.OBJETIVO: A fin de contar con un sistema adecuado para monitorear la enfermedad, se propuso optimizar una PCR en tiempo real (RT-PCR) basada en el uso de un agente intercalante y oligonucleótidos que amplifican secuencias del ADN del kinetoplasto (KADN), directamente de muestras de raspados de lesiones (en pacientes con LTA) contenidas en buffer TE (Tris-EDTA), sin extracción de ADN.METODOS: Para obtener una curva estándar (CE) se realizaron diluciones seriadas de parásitos (p) de cepas de referencia de especies que circulan en la zona. También se compararon 3 métodos de procesamiento de muestras (PM): Buffer de lisis, Insta-GeneTM Matrix (BIO-RAD) y TE. Luego se analizaron negativos para evaluar la especificidad y sensibilidad del sistema. Estas muestras provenían de raspados de lesiones cutáneas o mucocutáneas, tomados con palillos de madera en 300 μl TE.RESULTADOS: El límite de detección fue de 0,001 p/300 μl TE. La CE construida a partir de una cepa de Leishmania Viannia braziliensis mostró una pendiente de -3,40, eficiencia de amplificación de 96,66%, coeficiente de Pearson (R2) de 0,997 e intersección en la ordenada de 44,079. Al comparar los PM, el método de buffer TE fue el más eficiente. La RT-PCR desarrollada mostró un 100% de especificidad frente a muestras controles negativos y un 100% de sensibilidad frente a controles positivos.CONCLUSIONES: El sistema analizado es altamente sensible y permite detectar parásitos de Leishmania sp directamente de muestras clínicas provenientes de raspados de lesiones.

INTRODUCTION: The american tegumentary leishmaniasis (ATL) is an endemic, re-emergent disease in the Province of Salta. The therapeutic resources which are available have serious limitations. Numerous treatment failures have been detected due to the fact that the evaluation of chemotherapy is based on the clinical outcome of lesionsOBJECTIVE: In order to find a system for the correct follow-up of the disease, the study aimed at optimized the real time PCR (RT-PCR) based on intercalating agent and primers that amplify kinetoplastic DNA sequences (KDNA), directly on samples from skin lesion scrappings (from patients with ATL) contained in buffer TE, without DNA purification..METHODS: To obtain a stardard curve (SC) serial dilutions of parasites (p) were made (from reference strains of species that circulate in the region). 3 different methods of sample processing (SP) were compared: Lysis buffer, Insta-GeneTM Matrix (BIO-RAD) and TE (Tris-EDTA). The study evaluated the specificity and sensibility of the system by analyzing positive (by conventional PCR) and negative clinical samples. These samples were from cutaneous or mucocutaneous lesion scrapings, taken with toothpicks in 300 μl TE.RESULTS: The detection limit was 0.001 p/300 μl TE. The SC built with a Leishmania Viannia braziliensis strain showed a slope of -3.40, amplification efficiency of 96.66%, Pearson coefficient (R2) of 0.997 and 44.079 x-intersection. When comparing the SP, the buffer TE method was the most efficient one. With respect to positive and negative control samples, this RT-PCR showed a sensitivity and specificity of 100% respectively.CONCLUSIONS: This system is highly sensitive and allows to detect Leishmania sp parasites directly from clinical samples of lesion scrapings.

Detección, tratamiento y control de niños infectados con trypanosoma cruzi: estudio transversal en centros de atención primaria de Salta, Argentina / Detection, treatment and control of children infected with trypanosoma cruzi: cross-sectional study in centers of primary care of Salta, Argentina

INTRODUCCION: En la ciudad de Salta, la transmisión vectorial de la Enfermedad de Chagas se ha interrumpido desde 1970. Sin embargo, la transmisión congénita continúa debido a la presencia de mujeres infectadas en edad fértil.OBJETIVO: El estudio se propuso: a) incentivar la búsqueda de madres seropositivas, b) diagnosticar y tratar a los niños infectados, c) probar posibles marcadores precoces de curación a fin de evaluar en menor tiempo la efectividad del tratamiento.METODOS: Se trabajó en coordinación con Centro de Atención Primaria de la Salud de la ciudad de Salta. Se aplicaron métodos serológicos convencionales y no convencionales.RESULTADOS: La seroprevalencia en embarazadas en la ciudad de Salta en 2010 fue de 3,1% (61/1946). Se analizaron 57 niños y se encontraron 16 infectados con Trypanosoma cruzi, diagnosticados por microhematocrito o por serología convencional según la edad. Se aplicó tratamiento según las Normas Nacionales de Atención al Infectado Chagásico. Se evaluó la efectividad del tratamiento en 33 niños (edad promedio: 9,6 años), que habían sido tratados durante 2007-2008. El 21,2% (7/33) de esos niños fueron negativos por hemaglutinación en el postratamiento; además, se detectaron 3 antígenos recombinantes como posibles marcadores precoces de cura: Ag SAPA (p=0,0000182), Ag 13 (p=0,0026) y Ag 1 (p=0,02).CONCLUSIONES: Se recomienda el tratamiento y su seguimiento en todos los niños infectados.

INTRODUCTION: In the city of Salta, the vector transmission of Chagas disease has been interrupted since 1970. Nevertheless, congenital transmission is still a problem due to infected women in fertile age.OBJECTIVE: The aims of this study were: a) to search for seropositive mothers, b) to diagnose and to treat infected children, c) to test new antigens in order to detect early markers of treatment effectiveness.METHODS: The study was conducted in coordination with Centers of Primary Health Care in Salta. Conventional and non-conventional serological techniques were applied.RESULTS: During 2010, the Chagas disease prevalence in pregnant women was 3.1% (61/1946). Besides, 16 trypanosoma cruzi-infected children were found, out of 57 analyzed (diagnosed by microhematocrit or by conventional serology, depending on the age). Treatment was applied according to national care guidelines for Chagas disease infected patients. The efficiency of treatment was evaluated in 33 children (average: 9.6 years old), which had been treated during 2007-2008. From these, 21.2% (7/33) were negative for hemagglutination in the post-treatment; and 3 recombinant antigens were detected as possible good markers of treatment effectiveness: Ag SAPA (p=0.0000182), Ag 13 (p=0.0026) and Ag 1 (p=0.02).CONCLUSIONS: Treatment and follow-up should be performed in all infected children.