Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

OBJECTIVE: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. METHODS: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). RESULTS: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. CONCLUSION: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

The Selvester QRS score as an estimative of myocardial injury in acute chagasic patients from the Brazilian Amazon.

BACKGROUND: In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment. METHODS: The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide (< 3 points: no myocardial injury,> 3: points × 3% = % of the predicted LV infarction). RESULTS: A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment. CONCLUSION: This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region.

An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region.

BACKGROUND: American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, pentamidine isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. MATERIALS AND METHODS: This study was conducted as a controlled, randomized, open-label clinical trial for a total number of 159 patients with CL. Individuals aged 16-64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. RESULTS: From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p<0.0001) and two-dose groups (p = 0.03). No serious adverse events occurred. CONCLUSION: The present study shows that PI is a safe drug and its efficacy varied with the number of doses. The administration of PI in patients with ACL, predominantly caused by L. guyanensis, was mostly efficient in three or two doses of 7 mg/kg. TRIAL REGISTRATION: ClinicalTrials.gov NCT02919605.

Trypanosoma cruzi I and IV stocks from Brazilian Amazon are divergent in terms of biological and medical properties in mice.

BACKGROUND: In the Brazilian Amazon, clinical and epidemiological frameworks of Chagas disease are very dissimilar in relation to the endemic classical areas of transmission, possibly due to genetic and biological characteristics of the circulating Trypanosoma cruzi stocks. Twenty six T. cruzi stocks from Western Amazon Region attributed to the TcI and TcIV DTUs were comparatively studied in Swiss mice to test the hypothesis that T. cruzi clonal structure has a major impact on its biological and medical properties. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen parameters were assayed in mice infected with 14 T. cruzi strains belonging to DTU TcI and 11 strains typed as TcIV. In comparison with TcI, TcIV stocks promoted a significantly shorter pre-patent period (p<0.001), a longer patent period (p<0.001), higher values of mean daily parasitemia (p = 0.009) and maximum of parasitemia (p = 0.015), earlier days of maximum parasitemia (p<0.001) and mortality (p = 0.018), higher mortality rates in the acute phase (p = 0.047), higher infectivity rates (p = 0.002), higher positivity in the fresh blood examination (p<0.001), higher positivity in the ELISA at the early chronic phase (p = 0.022), and a higher positivity in the ELISA at the late chronic phase (p = 0.003). On the other hand TcI showed higher values of mortality rates in the early chronic phase (p = 0.014), higher frequency of mice with inflammatory process in any organ (p = 0.005), higher frequency of mice with tissue parasitism in any organ (p = 0.027) and a higher susceptibility to benznidazole (p = 0.002) than TcIV. Survival analysis showing the time elapsed from the day of inoculation to the beginning of the patent period was significantly shorter for TcIV strains and the death episodes triggered following the infection with TcI occurred significantly later in relation to TcIV. The notable exceptions come from positivity in the hemocultures and PCR, for which the results were similar. CONCLUSION/SIGNIFICANCE: T. cruzi stocks belonging to TcI and TcIV DTUs from Brazilian Amazon are divergent in terms of biological and medical properties in mice.

[Clinical and diagnostic aspects of American tegumentary leishmaniosis in soldiers simultaneously exposed to the infection in the Amazon Region]. / Aspectos clínicos e diagnósticos da leishmaniose tegumentar americana em militares simultaneamente expostos à infecção na Amazônia.

Military exercises in the forest of the Amazon region constitute an important factor in the incidence of American cutaneous leishmaniasis in this region. This report describes 48 cases of American tegumentary leishmaniosis. All these patients acquired the disease after military exercises in the Amazon. The mean incubation time was 27.6 days. The lesions were predominantly in the upper extremities, face and neck. The majority of patients presented two lesions. Ulcers were the most common clinical manifestation. The diagnosis was obtained through skin smears of the lesions. A total of 43 cases (89.6 %) were found to be positive.