Adrián Sánchez-Montalvá

Trypanosoma cruzi infection in a non-endemic country: epidemiological and clinical profile.

Chagas disease has been increasingly diagnosed in non-endemic countries. This is a prospective observational study performed at the Tropical Medicine Units of the International Health Program of the Catalan Health Institute, Barcelona (PROgrama de Salud Internacional del Instituto Catalán de la Salud, PROSICS Barcelona, Spain), that includes all patients with Chagas disease who attended from June 2007 to May 2012. Clinical and epidemiological data were collected. Overall, 1274 patients were included, the mean age of the patients was 37.7 years, 67.5% were women and 97% came from Bolivia. Thirteen patients had immunosuppressive conditions. The prevalence of cardiac involvement was 16.9%, lower than in previous studies performed in endemic areas (20-60%). Cardiac alterations were found in 33.8% of symptomatic and 14.1% of asymptomatic patients. The prevalence of digestive involvement was 14.8%. The rate of digestive involvement is very different among previous studies because of different diagnostic tools and strategies used. Barium enema alterations were found in 21.4% of symptomatic and 10.3% of asymptomatic patients, and oesophageal alterations were found in 3.7% of symptomatic and in 2.3% of asymptomatic patients. As shown in previous studies, Chagas disease in non-endemic countries affects younger patients and has lower morbidity.

Usefulness of Strongyloides stercoralis serology in the management of patients with eosinophilia.

Strongyloides stercoralis infection is being increasingly diagnosed out of endemic areas. The aim of this study is to evaluate the usefulness of S. stercoralis serology for the management of probable strongyloidiasis in patients presenting with eosinophilia. Overall, 147 patients were included, 89 (60.5%) patients had a positive S. stercoralis serology. Strongyloides stercoralis larvae were detected only in 15 (10.2%) patients. Twenty-eight patients had human immunodeficiency virus infection. Eighty patients received ivermectin 200 mcg/Kg/day for 2 days, and follow-up 6 months after treatment could be performed in 32 patients: 26 (81.3%) patients reached the response to treatment criteria (negative serology 6 months after treatment or when by enzyme-linked immunosorbent assay the optical density ratio of post-treatment to pre-treatment decreased to 0.6), and 11 (34.4%) patients fulfilled the cure criteria (negative serology 6 months after treatment). Strongyloides stercoralis serology is a useful diagnostic tool both in the diagnosis of probable strongyloidiasis and follow-up after treatment.

Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers

ABSTRACT Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.

Posaconazole versus benznidazole for chronic Chagas' disease.

To the Editor: In the CHAGASAZOL study, Molina et al. (May 15 issue)1 report on the use of posaconazole, as compared with benznidazole, in adults with chronic Trypanosoma cruzi infection. Significantly more patients receiving posaconazole had treatment failure than those receiving benznidazole. Benznidazole showed sustained trypanocidal activity in 94% of patients who completed treatment and follow-up. The major problem was discontinuation of benznidazole because of allergic dermatitis (in 19% of patients). In order to improve the side-effect profile of benznidazole, we have adopted the following strategies. First, we avoid the use of a daily dose of more than 300 mg, which in our patients seemed to be the cutoff for an increased incidence of side effects. Since the recommended dose of benznidazole for adults is 5 mg per kilogram of body weight per day for 60 days, patients weighing more than 60 kg would typically receive more than 300 mg daily. So in such patients, we administer a fixed dose of 300 mg per day for a total number of days that is equivalent to their weight.2 Second, in patients in whom mild-to-moderate allergic dermatitis develops, we administer low-dose systemic glucocorticoids (20 mg per day of oral prednisone or its equivalent for 10 days, followed by 10 mg per day for 10 more days) without interrupting benznidazole therapy.2,3 In a series of 35 patients who had discontinued benznidazole because of severe dermatitis but still wanted to be treated, we reinitiated benznidazole along with prednisone, with a prednisone dose of 20 mg per day for the first 14 days, followed by 10 mg per day during the remaining days of treatment. With this regimen, 72% of the patients completed the full course of therapy with little or no dermatitis. Anis Rassi, M.D. Anis Rassi, Jr., M.D., Ph.D.

The use of posaconazole against Chagas disease.

Purpose of review The current therapeutic scenario against Chagas disease has been recently updated with the use of the triazoles in clinical trials and several experimental assays (in-vitro and in-vivo models) which are bringing novel and promising evidence for the treatment of Chagas diseases, mainly in its chronic phase. We pretend to analyze all the evidence extracted from the in-vitro and in-vivo assays, and try to understand the poor outcome of posaconazole (POS) in the clinical experience. Recent findings POS is the drug with more advanced development in both experimental model and clinical trial. Despite the promising results initially obtained in the animal model, the clinical trial did not meet expectations. Nevertheless, it has documented the activity against Trypanosoma cruzi either in the animal model or in humans. Also new treatment strategies, combination or sequential schemes, have been evaluated in the animal model. Summary POS has been tested in humans showing activity against T. cruzi, but not enough to reach cure by itself. Those results represent one of the most important breakthroughs in the treatment of Chagas disease, and open a window to new strategies as combination therapies or even sequential treatments.

Immunosuppression and Chagas disease; experience from a non-endemic country

Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality.

ESBL-Producing Salmonella enterica Serovar Typhi in Traveler Returning from Guatemala to Spain

We report a case of typhoid fever in a traveler returning to Spain from Guatemala that was caused by Salmonella enterica serovar Typhi which produced an extended-spectrum β-lactamase (ESBL). This finding demonstrates the presence of ESBL-producing S. enterica ser. Typhi strains in the Americas. Enhanced surveillance is necessary to prevent further spread.

ReviewZika feverFiebre del Zika

Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome.Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between zika infection and complications, such as microencephaly or Guillem-Barre syndrome.

Experimental and Clinical Treatment of Chagas Disease: A Review

Abstract. Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi that infects a broad range of triatomines and mammalian species, including man. It afflicts 8 million people in Latin America, and its incidence is increasing in nonendemic countries owing to rising international immigration and nonvectorial transmission routes such as blood donation. Since the 1960s, the only drugs available for the clinical treatment of this infection have been benznidazole (BZ) and nifurtimox (NFX). Treatment with these trypanocidal drugs is recommended in both the acute and chronic phases of CD. These drugs have low cure rates mainly during the chronic phase, in addition both drugs present side effects that may result in the interruption of the treatment. Thus, more efficient and better-tolerated new drugs or pharmaceutical formulations containing BZ or NFX are urgently needed. Here, we review the drugs currently used for CD chemotherapy, ongoing clinical assays, and most-promising new experimental drugs. In addition, the mechanism of action of the commercially available drugs, NFX and BZ, the biodistribution of the latter, and the potential for novel formulations of BZ based on nanotechnology are discussed. Taken together, the literature emphasizes the urgent need for new therapies for acute and chronic CD.

Evaluation of Cytokine Profile and HLA Association in Benznidazole Related Cutaneous Reactions in Patients With Chagas Disease

BACKGROUND Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients. METHODS Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment. RESULTS Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B*3505 allele (45.5% vs 15.4%, P = .033). No differences in benznidazole serum concentration were found. CONCLUSIONS Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B*3505 allele could be associated with moderate-severe cutaneous reaction.