Browsing by Autor "David Paz"

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Cuantificación de niveles de INF-y - IL-13 y células T CD4+, CD8+ en pacientes con leishmaniasis tegumentaria con falla terapéutica
(2013) Amilcar Flores León; Ernesto Rojas Cabrera; Marisol Córdova Rojas; Mary Cruz Torrico; David Paz
Objetivos: se realiza un estudio del estatus inmunologico, cuantificando el perfil de citoquinas Th1 (INF-γ) y Th2 (IL-13) y celulas T CD3+, CD4+ y CD8+ como variables que puedan brindar informacion sobre el vinculo y/o asociacion a la falla terapeutica. Metodos: se cuantifico los niveles de INF-γ , IL-13, CD4 + y CD8+ en tres grupos de estudio: a) Pacientes con LT y falla terapeutica (RESISTENTES), b) Pacientes tratados que respondieron al tratamiento de forma exitosa (SENSIBLES) c) Pacientes sanos (GRUPO CONTROL). Resultados: los resultados indican, que la respuesta especifica inmune de los pacientes Resistentes y Sensibles esta polarizada hacia la respuesta TH1 y los valores de los Linfocitos T CD4+ y CD8+ estaban por debajo de los valores normales en los tres grupos de estudio. Los niveles de produccion de INF- γ fue mayor que la IL-13, siendo mas pronunciada en pacientes Resistentes que Sensibles en respuesta al Ag de Leishmania, la tipificacion de las cepas que fueron aisladas de los pacientes resistentes, identificaron a: Leishmania brasiliensis y Leishmania guayanensis. Conclusiones: en relacion a la falla terapeutica de los pacientes resistentes, estarian tambien involucrados los factores relacionados al parasito y otros factores extrinsecos al huesped. Palabras claves: leishmaniasis cutanea; fracaso del tratamiento; citocinas; recuento de linfocito CD4; interferones. Objectives: is a study of the immune status, quantifying the Th1 cytokine profile (IFN-γ) and Th2 (IL-13) and CD3 + T cells, CD4 + and CD8 + as variables that can provide information on the link and / or association therapeutic failure. Methods: we quantified the levels of INF-γ, IL-13, CD4 + and CD8 + in three study groups: a) patients with LT and therapeutic failure (RESISTANT), b) Treated patients who responded to treatment successfully (SENSITIVE ) c) healthy patients (CONTROL GROUP). Results: the results indicate that the specific immune res ponse of resistant and sensitive patients is polarized toward the TH1 response and values of CD4 + T lymphocytes and CD8 + were below normal values in the thr ee groups. The levels of IFN-γ production was higher than IL-13, being more pronounced in patients resistant to sensitive in response to Leishmania Ag, the typing of the strains that were isolated from patients resistant identified: Leishmania brasi liensis and guayanensis Leishmania. Conclusions: regarding treatment failure resistant patients, would also be involved factors related to the parasite and other extrinsic factors to the host.
Inhaled Pentamidine for Bolivian Mucosal Leishmaniasis
(American Society of Tropical Medicine and Hygiene, 2025) Jaime Soto; Patrícia Gutiérrez; Paula Soto; Jaime Escobar; David Paz; Daniela Rivero; Alejandro Villalba; Jonathan Berman
Aerosolized pentamidine is Food and Drug Administration approved to treat Pneumocystis pneumonia via a route that does not lead to systemic absorption or toxicity. Because Leishmania is also susceptible to pentamidine and mucosal leishmaniasis is also an infection of the respiratory tract, we performed a pilot study of aerosolized pentamidine (300 mg for 10 days over approximately 4 weeks) for mucosal leishmaniasis caused by Bolivian Leishmania braziliensis with a 2-year follow-up. Of 15 patients, 6 of 7 patients with initially mild disease were cured, 3 of 4 patients with initially moderate disease relapsed at the 18- to 24-month follow-up visits, and 3 of 4 patients with initially severe disease failed early after treatment. This study suggests that inhaled pentamidine may be useful as a well-tolerated treatment of mild mucosal leishmaniasis and that to rule out relapse, mucosal leishmaniasis follow-up should extend to 2 years.
Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis
(American Society of Tropical Medicine and Hygiene, 2016) Jaime Soto; David Paz; Daniela Rivero; Paula Soto; Jorge Alberto Morales Quispe; Julia Toledo; Jonathan Berman
A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization-recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 μg/mm(2)lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain-ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 μg/mm(2)[ILPenta-240-3]). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta-240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 μg/mm(2)lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days.
Treatment of Bolivian Leishmania braziliensis Cutaneous and Mucosal Leishmaniasis
(American Society of Tropical Medicine and Hygiene, 2022) Jaime Soto; Patrícia Gutiérrez; Paula Soto; David Paz; Eduardo Cayhuara; Carmen Molina; Mia Sánchez; Jonathan Berman
Although infection with Leishmania braziliensis is perhaps the key reason to treat New World cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML), the total literature contains relatively few reported cases. With the aim of supplementing the meager clinical information available, we searched the records of Jorochito (Dermatology) Hospital, Bolivia, for the years 1999-2020 and identified treatment records for 1,696 naive CL patients and 355 naive ML patients. Because follow-up was poor for this real-world treatment experience in the developing world, only 255 CL patients (15%) and 114 ML patients (32%) attended follow-up at Hospital. We therefore engaged in an Active Search for "lost" patients, located a further 542 CL patients (32%) and 142 ML patients (44%), thus eventually accomplished follow up on 697 CL patients (41%) and 256 ML patients (72%). Granular adverse event data derived from hospital records is listed for the 902 CL and 86 ML patients administered Glucantime intramuscularly, the 401 CL and 202 ML patients administered Glucantime intravenously, and the 163 CL and 89 ML patients administered miltefosine orally. Efficacy was obtained from hospital records for patients seen at hospital and from patient recall communicated by telephone for the patients found in the Active Search. The overall CL cure rate was 508 of 697 CL patients (73%) with follow-up: intramuscular Glucantime-196/293 (67%); intravenous Glucantime-90/126 (71%); intralesional Glucantime-34/54 (63%); oral miltefosine-52/69 (75%). The overall ML cure rate was 161 of 256 ML patients (63%) with follow-up: intramuscular Glucantime-26/48 (54%); intravenous Glucantime-66/104 (63%); intravenous amphotericin B deoxycholate-19/35 (54%); oral miltefosine-50/71 (70%). We offer this extensive adverse event and efficacy experience as useful guides for clinicians presented with a L. braziliensis infection. The cure rates also illustrate the quandary of New World CL and ML chemotherapy: sufficiently high to be useful but nevertheless needing augmentation with new agents.
Treatment of New World Mucosal Leishmaniasis: Randomized Comparison of Glucantime®, Liposomal Amphotericin B, and Miltefosine
(American Society of Tropical Medicine and Hygiene, 2026) Jaime Alberto Restrepo Soto; Paula Soto; David Paz; Daniela Rivero; Martha Sánchez; María Clara Arteaga; Jonathan Berman
New World Mucosal Leishmaniasis (ML) is predominantly caused by Leishmania braziliensis. We performed the first randomized trial of the three recommended agents for this disease-intravenous pentavalent antimony (Sb), intravenous liposomal amphotericin B (LAMB), oral miltefosine-with 24-month follow-up. Upon study enrollment, disease was scored by the number of sites (oro-nasal-palate, pharynx, larynx) and degree of disease at each site (maximum score = 60.) Our criterion for "cure" was ≥90% diminution in the enrollment score. Cure rates were 20/40 (50%) for Sb, 18/40 (45%) for LAMB, and 23/40 (57%) for miltefosine. Cure was highly dependent on whether the patient was being treated for the first time (39/55 = 71% cure) or undergoing repeat treatment (22/63 = 35% cure). The primary reason for the low cure rate for repeat patients was laryngeal disease at enrollment. For all patients, naïve patients, and repeat patients, the miltefosine cure rate was highest but not statistically so. A curative score at 2-6 months of follow-up had a predictive value of 94% for cure. It is notable that 14 of the 57 treatment failures (25%) were attributable to relapses occurring more than 24 months after therapy completion. Myalgias/arthralgias/general bodily discomfort occurred for LAMB and Sb patients; diarrhea and motion sickness occurred for miltefosine patients; Electrocardiogram abnormalities (occasionally severe) were seen in LAMB and Sb patients. When choosing a treatment of a ML patient, cure rates in part based on disease location and absence/presence of previous treatment, route of administration, tolerability, and cost should be considered. Patients should be followed for ≥2 years.