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.

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.

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.

Chagas disease, discovered in 1909 by the Brazilian physician Carlos Chagas, is a parasitic infection caused by the hemoflagellated protozoan Trypanosoma cruzi [¹ x 1 Chagas, C. Nova tripanozomiase humana. Estudos sobre a morfolojía e o ciclo evolutivo de Schizotrypanum cruzi n. gen., n. sp., ajente etiolójico de nova entidade mórbida do homen. Mem Inst Oswaldo Cruz. 1909; 1: 159–218 Crossref | Google Scholar See all References ]. Despite all the efforts to eradicate the disease, an estimated 10 million people are infected worldwide and 10 000 people die annually due to chagasic cardiomyopathy [² x 2 World Health Organization. Chagas disease (American trypanosomiasis). Data available on http://www.who.int. (Last accessed on 1st May 2013.) Google Scholar See all References ]. Originally, Chagas disease was an endemic disease of Latin America affecting rural and poor populations living in adobe houses. Progressive urbanization of this rural population since the 1940s has made Chagas disease an urban disease, causing an important change in the social groups affected by this disease [³ x 3 Coura, JR and Viñas, PA. Chagas disease: a new worldwide challenge. Nature. 2010; 465: S6–S7 Crossref | PubMed | Scopus (271) | Google Scholar See all References ]. The increase in mobility of populations during the last decades is the reason for the spread of Chagas disease outside endemic countries. As a consequence, Chagas disease has emerged as an important public health problem in other countries, mainly in Europe and North America [⁴ x 4 Schmunis, GA and Yadon, ZE. Chagas disease: a Latin American health problema becoming a world health problem. Acta Trop. 2010; 115: 14–21 Crossref | PubMed | Scopus (390) | Google Scholar See all References ].

Human infections by the gastrointestinal helminth Strongyloides stercoralis and the enteric protozoans Giardia duodenalis, Cryptosporidium spp. and Blastocystis spp. are not formally included in the list of 20 neglected tropical diseases prioritised by the World Health Organization. Although largely underdiagnosed and considered of lower public health relevance, these infections have been increasingly demonstrated to cause significant morbidity and even mortality globally, particularly among children living in resource-poor settings. In this cross-sectional survey the prevalence, frequency and molecular diversity of S. stercoralis, G. duodenalis, Cryptosporidium spp. and Blastocystis spp. were investigated in a school children population in the province of Benguela (Angola). A total of 351 stool samples were collected during January to June 2015. The presence of S. stercoralis and G. duodenalis was confirmed by qPCR methods. Giardia duodenalis assemblages and sub-assemblages were determined by multilocus sequence-based genotyping of the glutamate dehydrogenase and β-giardin genes of the parasite. Detection and identification of Cryptosporidium and Blastocystis species and subtypes was carried out by amplification and sequencing of a partial fragment of the small-subunit ribosomal RNA gene of both protozoan. Analyses of risk factors potentially associated with the transmission of these pathogens were also conducted. Prevalences of S. stercoralis, G. duodenalis, Cryptosporidium spp., and Blastocystis spp. were estimated at 21.4% (95% CI: 17.1–25.7%), 37.9% (95% CI: 32.8–43.0%), 2.9% (95% CI: 1.1–4.5%) and 25.6% (95% CI: 21.18–30.2%), respectively. Overall, 64.1% (225/351) of the children were infected by at least one of the pathogens investigated. Sequence analyses of the 28 G. duodenalis isolates that were successfully genotyped allowed the identification of sub-assemblages AI (14.3%), AII (14.3%), BIII (7.1%) and BIV (25.0%). Discordant typing results AII/AIII and BIII/BIV were identified in 7.1% and 14.3% of the isolates, respectively. A total of five additional isolates (17.9%) were identified as assemblage B. Three Cryptosporidium species including C. hominis (70%), C. parvum (20%) and C. canis (10%) were found circulating in the children population under study. A total of 75 Blastocystis isolates were assigned to the subtypes ST1 (30.7%), ST2 (30.7%), ST3 (36.0%), ST5 (1.3%) and ST7 (1.3%), respectively. Children younger than seven years of age had significantly higher risk of infections by protozoan enteropathogens (PRR: 1.35, P < 0.01), whereas being underweight seemed to have a protective effect against these infections (PRR: 0.74, P = 0.005). The burden of disease attributable to human strongyloidiasis, giardiosis, cryptosporidiosis and blastocystosis in Angola is considerably higher than initially estimated in previous surveys. Surveillance and control of these infections should be jointly tackled with formally considered neglected tropical diseases in order to maximize effort and available resources. Our data also demonstrate the added value of using molecular diagnostic methods in high transmission areas.

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.