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Background. According to an estimate from the Centers for Disease Control and Prevention (CDC), Chagas disease (CD) may affect 1.31% of Latin American immigrants in the United States, with >300 000 cases. However, there is a lack of real-world data to support this estimate. Little is known about the actual prevalence of this neglected tropical disease in the United States, and the bulk of those infected are undiagnosed. Methods. From April 2008 to May 2014, we screened 4,755 Latin American-born residents of Los Angeles County. Blood samples were tested for serologic evidence of CD. We collected demographic data and assessed the impact of established risk factors on CD diagnosis, including sex, country of origin, housing materials, family history of CD, and awareness of CD. Results. There were 59 cases of CD, for an overall prevalence of 1.24%. Prevalence was highest among Salvadorans (3.45%). Of the 3,182 Mexican respondents, those from Oaxaca (4.65%) and Zacatecas (2.2%) had the highest CD prevalence. Salvadoran origin (aOR = 6.2; 95% CI = 2.8-13.5; P < .001), prior knowledge of CD (aOR = 2.4; 95% CI = 1.0-5.8; P = .047), and exposure to all 3 at-risk housing types (adobe, mud, and thatched roof) (aOR = 2.5; 95% CI = 1.0-6.4; P = .048) were associated with positive diagnosis. Conclusions. In the largest screening of CD in the United States to date outside of blood banks, we found a CD prevalence of 1.24%. This implies >30 000 people infected in Los Angeles County alone, making CD an important public health concern. Efficient, targeted surveillance of CD may accelerate diagnosis and identify candidates for early treatment. [ABSTRACT FROM AUTHOR]

Background. Nifurtimox is 1 of only 2 medications available for treating Chagas disease (CD) and currently the only drug available in the United States, but its safety and tolerance have not been extensively studied. This is the first study to evaluate tolerance of nifurtimox in US patients with CD. Methods. This investigation assessed side effects in a sample of 53 patients with CD, all Latin American immigrants, who underwent treatment with nifurtimox (8-10 mg/kg in 3 daily doses for 12 weeks) from March 2008 to July 2012. The frequency and severity of adverse events (AEs) was recorded. Results. A total of 435 AEs were recorded; 93.8% were mild, 3.0% moderate, and 3.2% severe. Patients experienced a mean of 8.2 AEs; the most frequent were anorexia (79.2%), nausea (75.5%), headache (60.4%), amnesia (58.5%), and >5% weight loss (52.8%). Eleven patients (20.8%) were unable to complete treatment. Experiencing a moderate or severe AE (odds ratio [OR], 3.82; P < .05) and Mexican nationality (OR, 2.29; P < .05) were significant predictors of treatment discontinuation, but sex and cardiac progression at baseline were not. Patients who did not complete treatment experienced nearly 3 times more AEs per 30-day period (P = .05). Conclusions. Nifurtimox produces frequent side effects, but the majority are mild and can be managed with dose reduction and/or temporary suspension of medication. The high frequency of gastrointestinal symptoms and weight loss mirrors results from prior investigations. Special attention should be paid during the early stages of treatment to potentially severe symptoms including depression, rash, and anxiety. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The US-based Center of Excellence for Chagas Disease performed an observational study on the safety and tolerance of benznidazole 5 mg/kg/day for 60 days in 30 adults with chronic Chagas disease. The side-effect profile was suboptimal, including 5 cases of debilitating neuropathy and an unusually high angioedema rate. [ABSTRACT FROM AUTHOR]

Chagas disease is now an active disease in the urban centers of countries of nonendemicity and endemicity because of congenital and blood and/or organ transplantation transmissions and the reactivation of the chronic disease in smaller scale than vectorial transmission, reported as controlled in countries of endemicity. Oral transmission of Chagas disease has emerged in unpredictable situations in the Amazon region and, more rarely, in areas of nonendemicity where the domiciliary triatomine cycle was under control because of exposition of the food to infected triatomine and contaminated secretions of reservoir hosts. Oral transmission of Chagas disease is considered when >1 acute case of febrile disease without other causes is linked to a suspected food and should be confirmed by the presence of the parasite after direct microscopic examination of the blood or other biological fluid sample from the patient. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Tolerance of benznidazole in a United States Chagas disease clinic" by D. Miller and colleagues that was published in the previous issue.

Presents the different medical aspects of Chagas' disease and its primary agent Trypanosoma cruzi. Background information on the spread of Chagas' disease in the Americas; Prevalence of the disease among kidney transplant patients; Methods of diagnosis and treatment of the disease.

A letter to the editor is presented in response to articles in previous issues regarding tolerance of patient of chagas' disease treated using benznidazole in MIlan, Italy and Los Angeles, California by Miller and colleagues, and Antinori and colleagues.

Reports that the Institute for OneWorld Health and the U.S. National Institutes of Health are developing CRA-3316 cysteine protease inhibitor from Celera Genomics to treat Chagas disease. Information on how the protease inhibitor can treat parasitic infections.