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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., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Antitrypanosomal treatment with Benznidazole (BZ) or Nifurtimox may be recommended for patients with chronic Chagas disease (CD) to reduce the onset or progression of symptoms. However, such treatment has limited efficacy and high level of toxic effects. In addition, the current cure biomarker (serology conversion) precludes any treatment assessment unless a prolonged follow-up is arranged. PCR is thus the most useful, alternative surrogate marker for evaluating responses to treatment. The aim of this study is to describe the usefulness of real-time PCR in monitoring BZ treatment within a large cohort of chronic CD cases in Barcelona., Methodology/principal Findings: A total of 370 chronic CD patients were monitored with real-time PCR post-BZ treatment. The median follow-up was 4 years (IQR 2.2-5.3y), with a median of 3 clinical visits (IQR 2-4). Only 8 patients (2.2%) presented with at least one incident of positive real-time PCR after treatment and were therefore considered as treatment failure. Four of those failure patients had completed full course treatment, whereas the remaining cases had defaulted with a statistical difference between both groups (p = 0.02). Half of the failure patients had undergone less than 4 years of follow-up monitoring all presented with parasitemia before treatment., Conclusions/significance: BZ treatment failure was highly infrequent in our cohort. BZ discontinuation was a risk factor for positive real-time PCR results during clinical follow-up. Regular testing with real-time PCR during follow-up allows for early detection of treatment failure in patients with chronic CD., Competing Interests: The authors have declared that no competing interests exist.

Background: Current therapeutic options for Chagas' disease are limited to benznidazole and nifurtimox, which have been associated with low cure rates in the chronic stage of the disease and which have considerable toxicity. Posaconazole has shown trypanocidal activity in murine models., Methods: We performed a prospective, randomized clinical trial to assess the efficacy and safety of posaconazole as compared with the efficacy and safety of benznidazole in adults with chronic Trypanosoma cruzi infection. We randomly assigned patients to receive posaconazole at a dose of 400 mg twice daily (high-dose posaconazole), posaconazole at a dose of 100 mg twice daily (low-dose posaconazole), or benznidazole at a dose of 150 mg twice daily; all the study drugs were administered for 60 days. We assessed antiparasitic activity by testing for the presence of T. cruzi DNA, using real-time polymerase-chain-reaction (rt-PCR) assays, during the treatment period and 10 months after the end of treatment. Posaconazole absorption was assessed on day 14., Results: The intention-to-treat population included 78 patients. During the treatment period, all the patients tested negative for T. cruzi DNA on rt-PCR assay beyond day 14, except for 2 patients in the low-dose posaconazole group who tested positive on day 60. During the follow-up period, in the intention-to-treat analysis, 92% of the patients receiving low-dose posaconazole and 81% receiving high-dose posaconazole, as compared with 38% receiving benznidazole, tested positive for T. cruzi DNA on rt-PCR assay (P<0.01 for the comparison of the benznidazole group with either posaconazole group); in the per-protocol analysis, 90% of the patients receiving low-dose posaconazole and 80% of those receiving high-dose posaconazole, as compared with 6% receiving benznidazole, tested positive on rt-PCR assay (P<0.001 for the comparison of the benznidazole group with either posaconazole group). In the benznidazole group, treatment was discontinued in 5 patients because of severe cutaneous reactions; in the posaconazole groups, 4 patients had aminotransferase levels that were more than 3 times the upper limit of the normal range, but there were no discontinuations of treatment., Conclusions: Posaconazole showed antitrypanosomal activity in patients with chronic Chagas' disease. However, significantly more patients in the posaconazole groups than in the benznidazole group had treatment failure during follow-up. (Funded by the Ministry of Health, Spain; CHAGASAZOL ClinicalTrials.gov number, NCT01162967.).

Background: Chagas disease is no longer limited to Latin America and is becoming frequent in industrialised countries in Europe and United States., Methods: A descriptive study of Latin American immigrants in Barcelona attending two centres for imported diseases during a period of 3 years. The main outcome was the identification of Trypanosoma cruzi-infected individuals in a non-endemic country and the characterization of their clinical and epidemiological features., Results: A total of 489 Latin American patients participated in the study. Forty-one percent were infected by T. cruzi, and the most frequent country of origin was Bolivia. All T. cruzi infected patients were in chronic stages of infection. 19% of cases had cardiac disorders and 9% had digestive disorders., Conclusions: A high percentage of participants in this study were infected by T. cruzi and various factors were found to be associated to the infection. It is important to improve clinical and epidemiological knowledge of T. cruzi infection in non-endemic countries and to develop appropriate screening and treatment protocols in these settings.

Summary: For geographical and historical reasons, Spain is receiving an increasing number of immigrants. The aim of this study was to evaluate some epidemiological aspects and the main public health issues of communicable diseases in Barcelona''s immigrant population. From 2001 to 2004, a population of immigrants from tropical, subtropical regions and Eastern Europe was attended to in our centre. Each patient was offered a complete screening for tropical and common diseases. The prevalence and demographical characteristics of eight diseases with a potential risk of transmission in our setting were studied: latent and active tuberculosis, syphilis, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), Chagas disease, Giardia intestinalis and Entamoeba histolytica/Entamoeba dispar. In all, 2464 immigrants mainly from sub-Saharan Africa were seen. Among the patients who underwent the screening, 46.5% had a positive tuberculin skin test (⩾10mm), incidence of active tuberculosis was 324.7/100,000 immigrants in the period of the study, 6.4% had a positive syphilis serology, 7.7% had a positive HBsAg, 3.1% had a positive serology for HCV and 2.8% were HIV positive, 41 patients from Latin America with risk factors for American Trypanosomiasis were screened for Chagas disease by immunofluorescence assay and 34% had a positive result; 5.4% of stools parasitological tests were positive for G. intestinalis; 4.2% for E. histolytica/E. dispar. Communicable diseases in immigrant population could lead to emerging and re-emerging infections in the European Union with important issues for public health. European countries may have to establish guidelines for screening of infectious diseases in immigrants from low-income countries. [Copyright &y& Elsevier]