title: Prevalence and risk factors associated to pruritus in Plasmodium vivax patients using chloroquine in the Brazilian Amazon.
abstract: Chloroquine-induced pruritus has been described as a common adverse event in African patients being treated for Plasmodium falciparum malaria, and has been associated with treatment discontinuation in this setting. In Latin America, where Plasmodium vivax is the most common species causing malaria and chloroquine is still used as the first-line schizonticidal for treating this parasite infection, there are no reports on chloroquine-induced pruritus. This study aimed to estimate the frequency of pruritus and associated risk factors in P. vivax-infected patients treated with chloroquine in a reference centre in the Brazilian Amazon. In this cross-sectional study, patients who were prescribed with chloroquine for the treatment of microscopy-confirmed P. vivax infection in the past five days were actively asked about the occurrence of any level of pruritus and potential risk factors were investigated. Univariable and multivariable logistic regression was performed for the analysis of possible risk factors in two sets of patients: (1) all the patients interviewed and (2) restricted to patients with previous use of chloroquine. Among the 510 patients interviewed, 20.4% (95%CI: 16.9-23.9%) developed any level of pruritus during treatment with chloroquine. Most episodes of pruritus occurred during the first two days of treatment and the most common location was hands and feet. In multivariate analysis performed in the entire population, the only risk factors independently associated to pruritus were allergy history (adjusted odds ratio [AOR]: 1.83; 95%CI 1.02-3.31; p=0.044) and high parasitaemia (AOR: 1.96: 95%CI 1.22-3.13; p=0.005). In the analysis restricted to the 215 patients with previous use of chloroquine, previous chloroquine-induced pruritus was a strong predictor of pruritus occurrence (AOR: 11.84: 95%CI 3.15-44.47; p<0.001). Two patients (0.4%) interrupted treatment due to the severity of pruritus. Pruritus is a common adverse event in patients being treated with chloroquine for P. vivax malaria in the Brazilian Amazon. Host-parasite interaction may play a relevant role in the development of pruritus and concurs with the finding of strong association of pruritus with high parasitaemia and allergy history. Patients with previous chloroquine-induced pruritus had a high risk for developing pruritus. Due to its high frequency, this side effect cannot be neglected as it can have major implications on patients' compliance to treatment hampering elimination efforts in the region.
authors.affiliation: Universidade Nilton Lins, R. Marquês Monte Alegre, 1400, Manaus, AM 69058-040, Brazil. Electronic address: priballut@hotmail.com.
authors.forename: Priscilla C
authors.initials: PC
authors.lastname: Ballut
authors.forename: Andre M
authors.initials: AM
authors.lastname: Siqueira
authors.forename: Aline C B
authors.initials: AC
authors.lastname: Orlando
authors.forename: Marcia A A
authors.initials: MA
authors.lastname: Alexandre
authors.forename: Maria Graças C
authors.initials: MG
authors.lastname: Alecrim
authors.forename: Marcus V G
authors.initials: MV
authors.lastname: Lacerda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000009:adverse effects* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011537:Pruritus / Q000139:chemically induced* / Q000453:epidemiology*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000962:Antimalarials; D002738:Chloroquine
keywords: Adverse events; Amazon; Chloroquine; Malaria; Plasmodium vivax