10 results on '"Parrado, Rudy"'
Search Results
2. New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial.
- Author
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Torrico, Faustino, Gascón, Joaquim, Barreira, Fabiana, Blum, Bethania, Almeida, Igor C, Alonso-Vega, Cristina, Barboza, Tayná, Bilbe, Graeme, Correia, Erika, Garcia, Wilson, Ortiz, Lourdes, Parrado, Rudy, Ramirez, Juan Carlos, Ribeiro, Isabela, Strub-Wourgaft, Nathalie, Vaillant, Michel, Sosa-Estani, Sergio, and BENDITA study group
- Subjects
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CHAGAS' disease , *CHOLECYSTITIS , *THERAPEUTICS , *FEBRILE neutropenia , *TERMINATION of treatment , *BREAST cancer , *SERODIAGNOSIS , *RESEARCH , *COMBINATION drug therapy , *HETEROCYCLIC compounds , *RESEARCH methodology , *MEDICAL cooperation , *EVALUATION research , *IMIDAZOLES , *DRUG administration , *TREATMENT effectiveness , *COMPARATIVE studies , *RANDOMIZED controlled trials , *TRYPANOSOMIASIS , *BLIND experiment , *RESEARCH funding , *DRUG side effects , *PARASITES - Abstract
Background: Current treatment for Chagas disease with the only available drugs, benznidazole or nifurtimox, has substantial limitations, including long treatment duration and safety and tolerability concerns. We aimed to evaluate the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole, in the treatment of Chagas disease.Methods: We did a double-blind, double-dummy, phase 2, multicentre, randomised trial in three outpatient units in Bolivia. Adults aged 18-50 years with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results, were randomly assigned (1:1:1:1:1:1:1) to one of seven treatment groups using a balanced block randomisation scheme with an interactive response system. Participants were assigned to benznidazole 300 mg daily for 8 weeks, 4 weeks, or 2 weeks, benznidazole 150 mg daily for 4 weeks, benznidazole 150 mg daily for 4 weeks plus fosravuconazole, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, or placebo, with a 12-month follow-up period. The primary endpoints were sustained parasitological clearance at 6 months, defined as persistent negative qualitative PCR results from end of treatment, and incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Primary efficacy analysis was based on the intention-to-treat and per-protocol populations and secondary efficacy analyses on the per-protocol population. Safety analyses were based on the as-treated population. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03378661.Findings: Between Nov 30, 2016, and July 27, 2017, we screened 518 patients, and 210 were enrolled and randomised. 30 patients (14%) were assigned to each treatment group. All 210 randomised patients were included in the intention-to-treat population, and 190 (90%) were included in the per-protocol population. In the intention-to-treat analysis, only one (3%) of 30 patients in the placebo group had sustained parasitological clearance at 6 months of follow-up. Sustained parasitological clearance at 6 months was observed in 25 (89%) of 28 patients receiving benznidazole 300 mg daily for 8 weeks (rate difference vs placebo 86% [95% CI 73-99]), 25 (89%) of 28 receiving benznidazole 300 mg daily for 4 weeks (86% [73-99]), 24 (83%) of 29 receiving benznidazole 300 mg daily for 2 weeks (79% [64-95]), 25 (83%) of 30 receiving benznidazole 150 mg daily for 4 weeks (80% [65-95]), 23 (85%) of 28 receiving benznidazole 150 mg daily for 4 weeks plus fosravuconazole (82% [67-97]), and 24 (83%) of 29 receiving benznidazole 300 mg weekly for 8 weeks plus fosravuconazole (79% [64-95]; p<0·0001 for all group comparisons with placebo). Six patients (3%) had ten serious adverse events (leukopenia [n=3], neutropenia [n=2], pyrexia, maculopapular rash, acute cholecystitis, biliary polyp, and breast cancer), eight had 12 severe adverse events (defined as interfering substantially with the patient's usual functions; elevated alanine aminotransferase [n=4], elevated gamma-glutamyltransferase [n=2], elevated aspartate aminotransferase [n=1], neutropenia [n=3], leukopenia [n=1], and breast cancer [n=1]), and 15 (7%) had adverse events that led to treatment discontinuation (most of these were in the groups who received benznidazole 300 mg daily for 8 weeks, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, and benznidazole 150 mg daily for 4 weeks plus fosravuconazole). No adverse events leading to treatment discontinuation were observed in patients treated with benznidazole 300 mg daily for 2 weeks or placebo. There were no treatment-related deaths.Interpretation: Benznidazole induced effective antiparasitic response, regardless of treatment duration, dose, or combination with fosravuconazole, and was well tolerated in adult patients with chronic Chagas disease. Shorter or reduced regimens of benznidazole could substantially improve treatment tolerability and accessibility, but further studies are needed to confirm these results.Funding: Drugs for Neglected Diseases initiative (DNDi).Translation: For the Spanish translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]- Published
- 2021
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3. Predominance of hybrid discrete typing units of Trypanosoma cruzi in domestic Triatoma infestans from the Bolivian Gran Chaco region.
- Author
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Perez E, Monje M, Chang B, Buitrago R, Parrado R, Barnabé C, Noireau F, and Brenière SF
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- Animals, Bolivia epidemiology, Chagas Disease epidemiology, Chagas Disease parasitology, DNA, Protozoan, Female, Genotype, Glucose-6-Phosphate Isomerase genetics, Humans, Insect Control, Male, Phylogeny, Protozoan Proteins genetics, Triatoma parasitology, Trypanosoma cruzi genetics
- Abstract
In the Gran Chaco region the reinfestation by Triatoma infestans remains a major problem for control of Chagas disease. Trypanosoma cruzi the agent of the illness presents a broad genetic intraspecific variability which is poorly documented in the Bolivian Gran Chaco. This work presents the identification of the discrete typing units (DTUs) currently recognized for T. cruzi in T. infestans populations collected before and after residual insecticide spraying in four villages in this region. Before spraying, of 84 samples, the frequencies of the DTUs identified by using the multiplex PCR based on the non transcribed spacer of the mini-exon gene (MMPCR) were 0.21 for TcI, 0.70 for TcII/TcV/TcVI, and 0.17 for TcIII/TcIV and no significant difference was observed after spraying (76 samples). Moreover 13% of the total sample corresponds to T. infestans specimens with mixed infection of DTUs of which three were TcII/TcV/TcVI with TcIII/TcIV. The partial sequences of T. cruzi Gpi gene obtained from 14 PCR products agree the MMPCR DTU identification and allowed to precise the occurrence of TcIII, TcII and hybrid TcV/TcVI stocks which were not discriminated by the MMPCR. Given the high prevalence of hybrid stocks, the authors ask whether the recombination event at the origin of hybrids would have taken place in the Gran Chaco where the putative parents are also present., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2013
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4. Sand fly fauna in Chapare, Bolivia: an endemic focus of Leishmania (Viannia) braziliensis.
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Bustamante M, Diaz M, Espinoza J, Parrado R, Reithinger R, and García AL
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- Animals, Bolivia, Female, Humans, Leishmania braziliensis, Male, Population Density, Seasons, Biodiversity, Leishmaniasis, Cutaneous transmission, Psychodidae
- Abstract
Data on the distribution and abundance of Lutzomyia spp. (Diptera: Psychodidae) in Bolivia is scarce. Sand flies from an area of Leishmania (Viannia) braziliensis endemicity in the Isiboro-Secure National Park in the Department of Cochabamba were captured and identified to species. In total, 945 sand flies (789 females and 156 males) belonging to 15 species were collected from the four collection points in two study villages in 2007. With 549 (58.1%) specimens, Lutzomyia shawi was the most abundant species, followed by Lutzomyia (Trichophoromyia) sp. (22.2%), Lutzomyia llanosmartinsi (8.3%), Lutzomyia antunesi (4.3%), and Lutzomyia olmeca (2.1%). Abundance and species composition varied between rainy and dry seasons, with 99.3% of all sand flies being collected outdoors. Because of species abundance and confirmed Leishmania infection in previous entomological collections, we believe Lu. shawi is the vector of L. (Viannia) braziliensis in Isiboro-Secure National Park.
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- 2012
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5. Co-Infection of Leishmania (Viannia) braziliensis and HIV: report of a case of mucosal leishmaniasis in Cochabamba, Bolivia.
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Torrico F, Parrado R, Castro R, Marquez CJ, Torrico MC, Solano M, Reithinger R, and García AL
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- Adult, Animals, Anti-Infective Agents therapeutic use, Bolivia epidemiology, HIV Infections epidemiology, Humans, Leishmaniasis, Mucocutaneous epidemiology, Male, HIV Infections complications, Leishmania braziliensis, Leishmaniasis, Mucocutaneous complications, Leishmaniasis, Mucocutaneous pathology
- Abstract
We describe the first case of Leishmania/HIV co-infection reported in Bolivia. Initially hospitalized with a diagnosis of pneumonia and bronchitis, the patient had numerous cutaneous and mucosal lesions caused by Leishmania (Viannia) braziliensis. The patient was also diagnosed as severely immunocompromised because of HIV infection.
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- 2009
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6. Leishmaniases in Bolivia: comprehensive review and current status.
- Author
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García AL, Parrado R, Rojas E, Delgado R, Dujardin JC, and Reithinger R
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- Animals, Bolivia epidemiology, Humans, Insect Vectors classification, Leishmania classification, Leishmaniasis diagnosis, Leishmaniasis parasitology, Psychodidae classification, Leishmaniasis epidemiology, Leishmaniasis therapy
- Abstract
The leishmaniases are protozoan, zoonotic diseases transmitted to human and other mammal hosts by the bite of phlebotomine sandflies. Bolivia has the highest incidence of cutaneous leishmaniasis (CL) in Latin America (LA), with 33 cases per 100,000 population reported in 2006. CL is endemic in seven of the country's nine administrative departments. Visceral leishmaniasis (VL) is comparatively rare and is restricted to one single focus. Most CL cases are caused by Leishmania (Viannia) braziliensis (85% cases); VL is caused by L. (L.) infantum. Seven sandfly species are incriminated as vectors and Leishmania infections have been detected in several non-human mammal hosts. Transmission is associated with forest-related activities, but recently, cases of autochthonous, urban transmission were reported. Because most cases are caused by L. (V.) braziliensis, Bolivia reports the greatest ratio (i.e., up to 20% of all cases) of mucosal leishmaniasis to localized CL cases in LA. Per national guidelines, both CL and VL cases are microscopically diagnosed and treated with pentavalent antimony.
- Published
- 2009
7. Leishmaniasis in Chaparé, Bolivia.
- Author
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Rojas E, Parrado R, Delgado R, Reithinger R, and Garcia AL
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- Adolescent, Adult, Aged, Bolivia epidemiology, Child, Child, Preschool, Communicable Diseases, Emerging transmission, Epidemiologic Methods, Female, Humans, Leishmaniasis transmission, Male, Middle Aged, Young Adult, Communicable Diseases, Emerging epidemiology, Leishmaniasis epidemiology
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- 2009
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8. Multiprimer PCR system diagnosis of pulmonary tuberculosis in Cochabamba, Bolivia.
- Author
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Parrado R, Lozano D, Garcia L, Torrico MC, Delgado R, Torrico F, Laserna M, and Reithinger R
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- Bolivia, Humans, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis growth & development, Sensitivity and Specificity, Sputum microbiology, Tuberculosis, Pulmonary microbiology, Bacteriological Techniques methods, Mycobacterium tuberculosis isolation & purification, Polymerase Chain Reaction methods, Tuberculosis, Pulmonary diagnosis
- Published
- 2008
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9. Epidemiological monitoring of American tegumentary leishmaniasis: molecular characterization of a peridomestic transmission cycle in the Amazonian lowlands of Bolivia.
- Author
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Garcia AL, Tellez T, Parrado R, Rojas E, Bermudez H, and Dujardin JC
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- Animals, Bolivia, Female, Humans, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Insect Vectors parasitology, Leishmania braziliensis isolation & purification, Leishmania guyanensis isolation & purification, Leishmaniasis, Cutaneous transmission, Psychodidae parasitology
- Abstract
Human-made and environmental changes constitute a major risk factor for the (re-)emergence and spread of leishmaniasis; surveillance of the transmission cycle is essential in this context. This study integrated entomological and molecular parasitological techniques to document the transmission pattern of a peridomestic focus of Leishmania in the Isiboro Secure area of Bolivia. First the spatial distribution and relative density of phlebotomine sand flies, genus Lutzomyia, were established. Lutzomyia shawi was the predominant species in domestic and peridomestic environments (90% from all collections). Second, direct application of the hsp70 PCR to sand fly extracts detected Leishmania infections in Lu. shawi only, and gave an estimated infection rate of 0.21 to 0.38%. The cleavage of the hsp70 amplicon with restriction enzymes (hsp70 PCR-RFLP) allowed identification of Le. (V.) braziliensis and Le. (V.) guyanensis in Lu. shawi captured in the same village. These two parasite species were also found in humans from the study region, supporting the co-existence of two transmission cycles involving the same sand fly species. This study demonstrated the use of PCR-RFLP in the identification of Leishmania in sand fly pools which could lead to the development of methods for screening large sand fly populations in Latin America.
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- 2007
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10. [Estimation of the parasitemia in Trypanosoma cruzi human infection: high parasitemias are associated with severe and fatal congenital Chagas disease].
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Torrico MC, Solano M, Guzmán JM, Parrado R, Suarez E, Alonzo-Vega C, Truyens C, Carlier Y, and Torrico F
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- Animals, Birth Weight, Bolivia epidemiology, Chagas Disease diagnosis, Female, Hematocrit instrumentation, Hematocrit methods, Humans, Infant, Newborn, Male, Mice, Sensitivity and Specificity, Umbilical Cord, Chagas Disease congenital, Chagas Disease parasitology, Parasite Egg Count methods, Parasitemia mortality, Trypanosoma cruzi isolation & purification
- Abstract
The aim of this study was to validate the method of microhematocrit tube, as a rapid method to estimate the parasitemia in blood and to associate the parasites concentration with the morbidity and mortality of new born children with congenital Chagas diseases. Our results were determined experimentally and shown that the detection limit of the microhematocrit tube method is 40 parasites/ml when at least one of the four observed tubes is positive. Besides, it was also established that when the four examined tubes are positive the parasitemia in blood reaches more than 100 parasites/ml. It is important to highlight the modification made by our laboratory in the microscopic observation of the microhematocrit tubes with respect to the methodology used by previous investigators. A positive association exists between a high number of parasites in blood and the morbi-mortality of the newly born children with congenital chagas. The results of positive association between the parasitic load and the morbility and mortality could constitute an argument to understand the possible role of the parasite in the pathology of the disease.
- Published
- 2005
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