Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole [POS] in the Treatment of Asymptomatic Chronic Chagas Disease [P05267] [STOP CHAGAS]: NCT01377480).

Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF) and benznidazole (BNZ) are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30–60 days. Other useful drugs are itraconazole and posaconazole. The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished. At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease. In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.

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Four hundred four patients with chronic Chagas' disease were treated with itraconazole (6 mg/kg of body weight/day for 120 days), allopurinol (8.5 mg/kg of body weight/day for 60 days), or with a placebo of pure starch. Patients were monitored over a period of four years by clinical examination, serology, xenodiagnosis, hemoculture, and electrocardiogram. Drug tolerance was good, with only four treatments discontinued due to side effects that subsided after suspension of treatment. Parasitologic cure was evident in 44% of the those treated with allopurinol and 53% of those treated with itraconazole, and the electrocardiographic evaluation showed normalization in 36.5% and 48.2 %, respectively, of patients with chronic or recent cardiopathy.

To identify Trypanosoma cruzi clones from chronically infected individuals, they were transferred to triatomines by the xenodiagnosis test (XD) with Triatoma infestans. Polymerase chain reaction (PCR) and hybridization assays were performed to detect minicircle DNA in human blood samples and triatomine feces, using probes to determine the T. cruzi clones present. T. cruzi clone 19 (TcI) resulted the most prevalent in humans, with a frequency of 0.70 compared with a frequency of 0.53 in triatomines. T. cruzi clone 39 (TcIId) was the most prevalent in T. infestans, with a frequency of 0.65 compared with 0.33 in humans. The T. cruzi clone 43 (TcIIe) was not detected in blood samples; nevertheless, it was present at a rate of 0.17 in T. infestans feces. In conclusion, the T. cruzi clones are associated to each host, suggesting that selective amplification of clones occurs in human and triatomines.

Eleven years after they had been given itraconazole or allopurinol for the treatment of chronic American trypanosomiasis, 109 adult patients were checked for electrocardiographic abnormalities and evidence of Trypanosoma cruzi infection. The parasitological investigations included xenodiagnosis, in which the faeces of Triatoma infestans that had fed on the patients were checked under the microscope for flagellates. In addition, a PCR-based assay and a hybridization assay were used to test blood samples from the patients, and faeces from the Tri. infestans that had fed on the patients, for Try. cruzi DNA. For the data analysis, the patients were divided into four groups known as normal/normal, abnormal/normal, normal/abnormal and abnormal/abnormal, according to whether the patients had been found to have normal or abnormal electrocardiograms (ECG) shortly before the first treatment and to have normal or abnormal ECG when checked at the 11-year follow-up. The 51 normal/normal and 24 normal/abnormal patients were assumed to have been in the 'indeterminate' phase of the disease when they were treated, whereas the 16 abnormal/normal and 18 abnormal/abnormal patients all had evidence of chagasic cardiopathy at that time. When checked 11 years post-treatment, 40 (78.4%), 17 (70.8%), 14 (87.5%) and 17 (94.4%) of these patients, respectively, were each found positive for Try. cruzi in at least one of the parasitological tests. The hybridization assay, whether applied to human blood or bug faeces, appeared a significantly more sensitive test than the PCR-based assays or microscopically assessed xenodiagnosis (P<0.05). Only the 21 patients who appeared to be negative for Try. cruzi could be considered parasitologically cured (although all still appeared to have anti-Try. cruzi antibodies in their blood). Only 13 of these parasitologically cured patients (seven of those treated with itraconazole and six of those given allopurinol) had normal ECG at the 11-year follow-up. In Chile at least, itraconazole, which caused fewer adverse effects than the allopurinol while being no less effective at preventing cardiopathy, appears to be the drug of choice to treat chronic American trypanosomiasis in adults.

BACKGROUNDVector transmission of Trypanosoma cruzi appears to be interrupted in Chile; however, data show increasing incidence of Chagas' disease, raising concerns that there may be a reemerging problem.OBJECTIVETo estimate the actual risk in a changing world it is necessary to consider the historical vector distribution and correlate this distribution with the presence of cases and climate change.METHODSPotential distribution models of Triatoma infestans and Chagas disease were performed using Maxent, a machine-learning method.FINDINGSClimate change appears to play a major role in the reemergence of Chagas' disease and T. infestans in Chile. The distribution of both T. infestans and Chagas' disease correlated with maximum temperature, and the precipitation during the driest month. The overlap of Chagas' disease and T. infestans distribution areas was high. The distribution of T. infestans, under two global change scenarios, showed a minimal reduction tendency in suitable areas.MAIN CONCLUSIONThe impact of temperature and precipitation on the distribution of T. infestans, as shown by the models, indicates the need for aggressive control efforts; the current control measures, including T. infestans control campaigns, should be maintained with the same intensity as they have at present, avoiding sylvatic foci, intrusions, and recolonisation of human dwellings.

Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite’s genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N-terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite.