Pau Bosch-Nicolau1, Fernando Salvador2, Adrián Sánchez-Montalvá2, Clara Franco-Jarava3, Iria Arrese-Muñoz3, Elena Sulleiro4, Silvia Roure5, Lluis Valerio6, Inés Oliveira-Souto2, Núria Serre-Delcor2, Diana Pou2, Begoña Treviño2, María L Aznar2, Juan Espinosa-Pereiro7, Israel Molina8. 1. Tropical Medicine & International Health Unit Vall D'Hebron-Drassanes, Infectious Diseases Department, PROSICS Barcelona, University Hospital Vall D'Hebron, Barcelona, Spain; Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: pbosch@vhebron.net. 2. Tropical Medicine & International Health Unit Vall D'Hebron-Drassanes, Infectious Diseases Department, PROSICS Barcelona, University Hospital Vall D'Hebron, Barcelona, Spain. 3. Immunology Department, University Hospital Vall D'Hebron, Barcelona, Spain. 4. Microbiology Department, University Hospital Vall D'Hebron, Barcelona, Spain. 5. North Metropolitan International Health Unit, PROSICS Metropolitana Nord, Badalona, Spain; Infectious Diseases Department, Germans Trias I Pujol University Hospital, Badalona, Spain. 6. North Metropolitan International Health Unit, PROSICS Metropolitana Nord, Badalona, Spain. 7. Tropical Medicine & International Health Unit Vall D'Hebron-Drassanes, Infectious Diseases Department, PROSICS Barcelona, University Hospital Vall D'Hebron, Barcelona, Spain; Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain. 8. Tropical Medicine & International Health Unit Vall D'Hebron-Drassanes, Infectious Diseases Department, PROSICS Barcelona, University Hospital Vall D'Hebron, Barcelona, Spain; Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: imolina@vhebron.net.
Abstract
OBJECTIVES: Benznidazole is the first-line treatment for Chagas disease. Adverse events appear in more than 50% of patients, leading to discontinuation in approximately 15%. Cutaneous reactions are one of the most frequent adverse events. Human leucocyte antigen (HLA) genotyping studies identified an association between cutaneous reactions to benznidazole and carrying the specific allele HLA-B∗35:05. We designed the present study to prospectively confirm this association. METHODS: This is a prospective observational study including Chagas disease patients aged 18 years or more who accepted to receive benznidazole treatment following current guidelines. Allele genotyping of HLA-B was determined in all patients. Clinical and analytical follow up was performed at days 0, 7, 14, 30 and 60 of treatment. RESULTS: Two-hundred and seven individuals were included. Seventy per cent were female with a mean age of 45.1 (SD ± 9.86) years mainly from Bolivia (92.8%). In 102 (49.3%) cases a cutaneous reaction was diagnosed. Forty-eight (46.6%) were classified as mild, 37 (35.9%) as moderate and 18 (17.5%) as severe. Thirty-two (15.4%) patients had to definitively interrupt the treatment because of a cutaneous reaction. Female sex (OR 4.49; 95% CI 1.62-12.47), new-onset eosinophilia before cutaneous symptoms (OR 2.55; 95% CI 1.2-5.43) and carrying the HLA-B∗35 allelic group (OR 2.58; 95% CI 1.2-5.51) were all predictors of moderate to severe cutaneous reactions. No statistical significance was found when the specific allele HLA-B∗35:05 was analysed. CONCLUSIONS: Patients carrying the HLA-B∗35 allelic group are at higher risk of moderate to severe reactions when taking benznidazole treatment.
OBJECTIVES: Benznidazole is the first-line treatment for Chagas disease. Adverse events appear in more than 50% of patients, leading to discontinuation in approximately 15%. Cutaneous reactions are one of the most frequent adverse events. Human leucocyte antigen (HLA) genotyping studies identified an association between cutaneous reactions to benznidazole and carrying the specific allele HLA-B∗35:05. We designed the present study to prospectively confirm this association. METHODS: This is a prospective observational study including Chagas disease patients aged 18 years or more who accepted to receive benznidazole treatment following current guidelines. Allele genotyping of HLA-B was determined in all patients. Clinical and analytical follow up was performed at days 0, 7, 14, 30 and 60 of treatment. RESULTS: Two-hundred and seven individuals were included. Seventy per cent were female with a mean age of 45.1 (SD ± 9.86) years mainly from Bolivia (92.8%). In 102 (49.3%) cases a cutaneous reaction was diagnosed. Forty-eight (46.6%) were classified as mild, 37 (35.9%) as moderate and 18 (17.5%) as severe. Thirty-two (15.4%) patients had to definitively interrupt the treatment because of a cutaneous reaction. Female sex (OR 4.49; 95% CI 1.62-12.47), new-onset eosinophilia before cutaneous symptoms (OR 2.55; 95% CI 1.2-5.43) and carrying the HLA-B∗35 allelic group (OR 2.58; 95% CI 1.2-5.51) were all predictors of moderate to severe cutaneous reactions. No statistical significance was found when the specific allele HLA-B∗35:05 was analysed. CONCLUSIONS: Patients carrying the HLA-B∗35 allelic group are at higher risk of moderate to severe reactions when taking benznidazole treatment.
Authors: Melisa D Castro Eiro; María A Natale; Carlos A Vigliano; Susana A Laucella; María G Alvarez; Araceli Castro; Débora Seigelshifer; Rodolfo Viotti; Marisa Fernández; Luis Mazzuoccolo; Bruno Lococo; Graciela L Bertocchi; Gonzalo Cesar; María C Albareda; María J Elias; María B Caputo; Eduardo Gaddi; Jeanette Balbaryski Journal: Microbiol Spectr Date: 2022-08-08