Socio-environmental factors associated with the occurrence of triatomines (Hemiptera: Reduviidae) in an endemic municipality in northern Minas Gerais, Brazil.

Triatomines are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. The study aimed to evaluate the association between sociodemographic and environmental factors, and changes in land use and cover, with the occurrence and abundance of triatomines by census sectors in an endemic municipality of northern Minas Gerais, Brazil. The study was conducted in Montes Claros, located in the north of Minas Gerais, Brazil. The entomological data used in the study were collected by active surveillance in the rural area from 2015 to 2019 and by passive surveillance in the urban area from 2009 to 2019. Data on sociodemographic and environmental factors and changes in land use and land cover were obtained from the urban and rural census sectors. A total of 1404 triatomines, belonging to eight species, were captured in domiciles in the rural area (2015-2019) and 277 triatomines in domiciles in the urban area (2009-2019) of the municipality of Montes Claros. The variables the number of domiciles, household economic income, pavement, NDVI, deforestation, unchanged, and anthropic proved to be positively associated with the occurrence and/or number of triatomines in census sectors, within the models. The occurrence of triatomines in the domestic environment of the municipality of Montes Claros should be considered a public health problem, as it suggests a potential risk of establishment and transmission of T. cruzi to domestic animals, farm animals, and humans.

Influence of anthropic changes and environmental characteristics on the occurrence of Tegumentary Leishmaniasis in Montes Claros, Minas Gerais, Brazil, between 2012 and 2019.

This is an ecological study that investigated the influence of environmental, socioeconomic characteristics and changes in land use and cover on the occurrence of Tegumentary Leishmaniasis (TL) in the city of Montes Claros. The relationships between the number of cases of TL, which occurred between 2012 and 2019, in each census sector and the standardized covariates (Number of properties, altitude, Brazilian Deprivation Index, Normalized Difference Vegetation Index (NDVI), proportion of sector (PS) deforested, PS that underwent other anthropic alterations and unaltered PS) were evaluated with ecological Bayesian Models. Four multivariate models were constructed, with similar quality of adjustments, but Model 1 was the most parsimonious. Model 1 revealed that for each one-unit increase of standard deviation (SD) in the log of the number of properties, at the altitude and root of the deforested PS, corresponds to an increase of 44%, 34% and 24.5% in the number of cases of TL, respectively. The variable NDVI, included in models 3 and 4, was positively associated with the increase in the number of TL cases, being that for each one-unit increase in the NDVI was verified an increase of 21.3% and 20.2% respectively in the models. This study showed that the spatial distribution of TL cases in the city of Montes Claros occurs in a heterogeneous way and our findings support the hypothesis that socio-environmental characteristics and deforestation influence the occurrence of this disease in the studied area. Thus, these factors must be considered for the development of disease control strategies.

Laboratorial algorithm for serological diagnosis of visceral leishmaniasis using rK39-ICT, DAT-LPC and FC-Simplex IgG1.

The performance of distinct serological tests (rK39-ICT, IFAT, DAT-LPC, FC-Simplex IgG1) was assessed and a laboratorial algorithm was proposed for accurate diagnosis of VL. DAT-LPC and FC-Simplex IgG1 showed outstanding accuracy (AUC = 0.93) to identify VL patients. The use of a sequential serological algorithm (rK39-ICT screening followed by DAT-LPC or FC-Simplex IgG1) improved the global accuracy for VL (97.2%) diagnosis. An alternative approach for diagnosis of VL has been also assessed for interchangeable use of serum/whole blood lysate samples in DAT-LPC and FC-Simplex IgG1. Our data showed an outstanding agreement for the results obtained with whole blood lysate samples as compared to serum samples (DAT-LPC =100%; FC-Simplex IgG1 = 99%). Together, these findings provide insights to improve the current overall accuracy of VL diagnosis and present innovative laboratorial tests and alternative samples from use in public health services.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial.

BACKGROUND: There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. METHODS: A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. RESULTS: 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). CONCLUSIONS: Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. TRIAL REGISTRATION: ClinicalTrials.gov NCT01310738.

Mapping B-cell epitopes for the peroxidoxin of Leishmania (Viannia) braziliensis and its potential for the clinical diagnosis of tegumentary and visceral leishmaniasis.

The search toward the establishment of novel serological tests for the diagnosis of leishmaniasis and proper differential diagnosis may represent one alternative to the invasive parasitological methods currently used to identify infected individuals. In the present work, we investigated the potential use of recombinant peroxidoxin (rPeroxidoxin) of Leishmania (Viannia) braziliensis as a potential antigen for the immunodiagnosis of human tegumentary (TL) and visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL). Linear B-cell epitope mapping was performed to identify polymorphic epitopes when comparing orthologous sequences present in Trypanosoma cruzi, the agent for Chagas disease (CD), and the Homo sapiens and Canis familiaris hosts. The serological assay (ELISA) demonstrated that TL, VL and CVL individuals showed high levels of antibodies against rPeroxidoxin, allowing identification of infected ones with considerable sensitivity and great ability to discriminate (specificity) between non-infected and CD individuals (98.46% and 100%; 98.18% and 95.71%; 95.79% and 100%, respectively). An rPeroxidoxin ELISA also showed a greater ability to discriminate between vaccinated and infected animals, which is an important requirement for the public campaign control of CVL. A depletion ELISA assay using soluble peptides of this B-cell epitope confirmed the recognition of these sites only by Leishmania-infected individuals. Moreover, this work identifies two antigenic polymorphic linear B-cell epitopes of L. braziliensis. Specific recognition of TL and VL patients was confirmed by significantly decreased IgG reactivity against rPeroxidoxin after depletion of peptide-1- and peptide-2-specific antibodies (peptide 1: reduced by 32%, 42% and 5% for CL, ML and VL, respectively; peptide-2: reduced by 24%, 22% and 13% for CL, ML and VL, respectively) and only peptide-2 for CVL (reduced 9%). Overall, rPeroxidoxin may be a potential antigen for the immunodiagnosis of TL, VL or CVL, as it has a higher agreement with parasitological assays and is better than other reference tests that use soluble Leishmania antigens for diagnosing CVL in Brazil (EIE-LVC, Bio-manguinhos, FIOCRUZ).