American Visceral Leishmaniasis Research Articles

Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil.

In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Mechanisms Involved in the Arthropod Transmission of Leishmania spp.

Mechanisms Involved in the Arthropod Transmission of Leishmania spp.

Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil.

Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical-immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical-immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.

American visceral leishmaniasis in an ecotourism area

Visceral Leishmaniasis is a vector-borne disease that represents one of the most important public health problems in the world. This neglected tropical zoonosis shows an increasing urbanization process, since the end of the 1980s. The increase in ecotourism practices, mainly in regions nearby urban areas facilitates the interaction between companion animals, humans, and wildlife. Known as the land of the waterfalls, Carrancas is a 728 km² Brazilian municipality located at 1052m, in the southeast of Brazil. The region is surrounded by urban areas with autochthonous cases of Canine Visceral Leishmaniasis and lacking studies on the presence of vectors of Leishmania spp. The municipality is part of the most important ecotourism area, a renowned tourist destination in Brazil and abroad called Royal Road or “Estrada Real – ER. Due to the increasing number of travelers involved in ecotourism and exposing them to risk factors for diseases, we propose to investigate the presence of phlebotomine sandflies in a protected area in the southern state of Minas Gerais, which is constantly visited by tourists over the world. Six specimens of Lutzomyia longipalpis were captured in Carrancas. This is the first report of L. longipalpis in an ecotourism area south of Minas Gerais State. This record contributes to our knowledge of the geographical distribution of the main vector of American Visceral Leishmaniasis in Carrancas and alerts us to the need for permanent surveillance and health education at this location.

Ecological Aspects of the Phlebotominae Fauna (Diptera: Psychodidae) among Forest Fragments and Built Areas in an Endemic Area of American Visceral Leishmaniasis in João Pessoa, Paraíba, Brazil.

Sand flies are dipterans of medical importance, as some species are vectors of American visceral leishmaniasis (AVL). The municipality of João Pessoa (Paraíba, northeastern Brazil), is an endemic region for AVL, having high rates of human and canine cases. The main objective was to evaluate the sand fly fauna among forest fragments and built areas, and its relationship with environmental conditions. HP light traps were placed in the studied areas from March 2019 to July 2021. A total of 2141 specimens of phlebotomines were captured, comprising nine genera and ten species. Temperature and humidity were significant and positive only in built areas. The diversity composition among forest fragments and built areas was different and the AVL vector, Lutzomyia longipalpis, was the most prevalent species in built areas. The study showed that the built areas present differences in their richness and diversity of sand flies in relation to forest fragments, concluding that the conservation of forest areas, even if urban fragments, favors the diversity of phlebotomine species.

Visceral Leishmaniasis Urbanization in the Brazilian Amazon Is Supported by Significantly Higher Infection Transmission Rates Than in Rural Area.

This was an open cohort prospective study (2016-2018) that analyzed the prevalence and incidence rates of human Leishmania (L.) infantum chagasi-infection and the evolution of their clinical-immunological profiles in distinct urban and rural scenarios of American visceral leishmaniasis (AVL) in Pará State, in the Brazilian Amazon. These infection profiles were based on species-specific DTH/IFAT-IgG assays and clinical evaluation of infected individuals, comprising five profiles: three asymptomatic, Asymptomatic Infection [AI], Subclinical Resistant Infection [SRI], and Indeterminate Initial Infection [III]; and two symptomatic, Subclinical Oligosymptomatic Infection [SOI] and Symptomatic Infection [SI = AVL]. The two distinct scenarios (900 km away) were the urban area of Conceição do Araguaia municipality and the rural area of Bujaru municipality in the southeast and northeast of Pará State. Human populations were chosen based on a simple convenience sampling design (5-10% in each setting), with 1723 individuals (5.3%) of the population (32,464) in the urban area and 1568 individuals (8.9%) of the population (17,596) in the rural one. A serological survey (IFAT-IgG) of canine infection was also performed in both scenarios: 195 dogs in the urban area and 381 in the rural one. Prevalence and incidence rates of human infection were higher in the urban area (20.3% and 13.6/100 person-years [py]) than in the rural setting (14.1% and 6.8/100-py). The AI profile was the most prevalent and incident in both urban (13.4% and 8.1/100-py) and rural (8.3% and 4.2/100-py) scenarios, but with higher rates in the former. An III profile case evolved to SOI profile after four weeks of incubation and another to SI (=AVL) after six. The prevalence of canine infection in an urban setting (39.2%) was also higher (p < 0.05) than that (32%) in the rural zone. AVL urbanization in Pará State, in the Brazilian Amazon, has led to infection rates significantly higher than those in rural sites, requiring more intense control measures.

Leishmania infantum NTPDase1 and NTPDase2 play an important role in infection and nitric oxide production in macrophages

Leishmania infantum, the causative agent of American Visceral Leishmaniasis (VL), is known for its ability to modulate the host immune response to its own favor. Ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) represents a family of enzymes that hydrolyze nucleotides and are involved in nucleotide-dependent biological processes. L. infantum has two ENTPDases, namely LiNTPDase1 and LiNTPDase2. Here, we used genetic tools to overexpress or abolish the expression of LiNTPDase1 and -2 to assess their role in parasite growth in culture and macrophage infection. While LiNTPDase1 or 2-overexpressing clones showed no morphological or growth changes in promastigotes, LiNTPDase2 overexpression increased macrophage adhesion and infection by 50% and 30%, respectively. The individual LiNTPDase1 and 2 knockout mutants showed lag in growth profile, which was reversed by the addition of adenine and guanine to the culture media. Moreover, the morphology of the knockout mutants even in supplemented media was changed to an amastigote-like form. The double knockout of both genes was lethal and a mechanism of compensation of deletion of one isoform was detected in these mutants. Correspondingly, the absence of LiNTPDase1 or LiNTPDase2 led to a dramatic reduction in in vitro infection (∼90%). Interestingly, nitric oxide production was decreased in both knockout mutants during infection, which suggests that both LiNTPDases can inhibit macrophage responses against the parasite. Overall, our results show important roles of LiNTPDase1 and -2 concerning in vitro macrophage infection and reinforce their use as potential targets to control Leishmania infections.

Visceral leishmaniasis in a recent transmission region: 27.4% infectivity rate among seronegative dogs.

American visceral leishmaniasis (VL) is a parasitic disease whose main domestic reservoir in the urban environment is dog and is considered one of the most important zoonoses in the context of public health. Serological tests are typically used for the diagnostic screening of the disease. This study aimed to analyse the performance of different methodologies used in the diagnosis of VL in dogs sampled from a recent transmission area. The sample consisted of 52 dogs separated into groups based on the absence and presence of clinical signs of VL. The following serological techniques were carried out: the DPP® rapid test (RT), the ALERE® RT and an RT and immunoenzymatic assay with a recently developed protein (rKDDR-plus). In addition, molecular techniques were carried out with conjunctival swabs, and bone marrow aspirate samples and parasitological samples were obtained directly from bone marrow aspirates. It was concluded that 27.4% of seronegative dogs were infected, but the serological tests, used as screening tests, showed unsatisfactory sensitivity results (average: 51.2%) for dogs without clinical signs. It was suggested that polymerase chain reaction with conjunctival swabbing be used as a screening test for dogs without clinical signs, as this is a non-invasive collection technique with high-sensitivity values.

American visceral leishmaniasis in a state of northeastern Brazil: clinical, epidemiological and laboratory aspects.

In Brazil, American visceral leishmaniasis (AVL) has become a public health concern due to its high incidence and lethality. This study aimed to analyze the clinical, epidemiological, and laboratory aspects of AVL in a state of Brazil. This descriptive, cross-sectional, retrospective, and quantitative study of notified cases of AVL was carried out in Alagoas between 2008 and 2017 from data obtained from DATASUS/SINAN. Sociodemographic, clinical, and laboratory variables were analyzed. A descriptive analysis was performed using absolute values ​​and valid percentages, using tables and/or graphs. Data processing was performed using Stata 12.0®. Results with P <0.05 were considered statistically significant. During the study period, 352 cases of AVL were reported, of which 6.82% died and 38.92% had met a cure criterion. Male patients were predominant (66.76%). Of the total infected patients, 16.76% had attended only the 1st to the 4th grades, with those most affected aged 1 to 4 years (28.69%). Laboratory diagnostic criteria were most commonly used to confirm the notified cases (76.42%), whereas 51.70% and 8.52% of the cases had positive parasitological and immunofluorescence diagnoses, respectively. Finally, the study showed a higher prevalence of the disease in children, men and in rural residents. Although with low lethality, the expressive frequency of AVL in the State of Alagoas was still verified, since there was an increase in the number of cases during the years of the study.

Update of the Phlebotominae Fauna with New Records for Argentina and Observations on Leishmaniasis Transmission Scenarios at a Regional Scale

Phlebotominae are small insects distributed in the Americas from Canada to Argentina and Uruguay, counting with more than 500 neotropical species. Some of them have a vectorial role in the transmission of Leishmania Ross, the causative agent of leishmaniases, a group of worldwide distributed diseases with different clinical manifestations and transmission cycles. Our aim was to update the Phlebotominae fauna of Argentina and to make observations on the American Cutaneous (ACL) and Visceral Leishmaniasis (AVL) transmission scenarios, according to the distribution of proven or suspected Leishmania vector species and recent changes in land use. Primary data (entomological captures) and secondary data (review of 65 scientific publications with Phlebotominae records) were used. With 9 new records, 46 Phlebotominae species are now recorded through the area comprising 14 political jurisdictions and 6 phytogeographic provinces. Distribution maps were constructed for the 5 proven or incriminated Leishmania vector species, and the evidence supporting the vectorial incrimination of these species is discussed. Three main ACL transmission scenarios are described in the phytogeographic provinces of the Yungas, Chaco, and Paranaense, associated with deforestation processes, while the transmission scenarios of AVL are urban outbreaks and scattered cases in rural areas. We update the available knowledge on the Phlebotominae fauna present in Argentina, emphasizing its epidemiological relevance in the current context of the increasing frequency of ACL outbreaks and geographic spread of AVL.

Socio-economic and environmental factors associated with the occurrence of canine infection by Leishmania infantum in Teresina, Brazil.

American visceral leishmaniasis (AVL) is a zoonosis caused by protozoan parasites of the genus Leishmania. In Brazil, the disease is caused by Leishmania infantum and the main vector is the phlebotomine sandfly Lutzomyia longipalpis, found both in natural ecotopes and in the rural and urban environments, being very well adapted to the peridomestic environment. The domestic dog has been incriminated as the main reservoir of the parasite in the urban environment, but the control measures based on culling seropositive dogs have not shown to be effective to contain the spread of the disease throughout the country. Many studies evaluated risk factors for human visceral leishmaniasis but few focused on the socioeconomic and environmental factors associated with infection among dogs. Knowledge of these factors might help identify the conditions that contribute to the maintenance of transmission cycles in the urban environment and identify new targets for intervention. The objective of this study was to assess the association between socioeconomic and environmental factors and the occurrence of canine leishmaniasis at Teresina city, Brazil. This cross-sectional study was developed in ten districts of Teresina, involving 532 houses and 810 dogs. Peripheral blood samples were collected by vein punction using vacutainer tubes without anticoagulant for performing serological test (indirect immunofluorescence - IFI). Serum samples with IFI titers ≥1: 80 were considered positive. Owners of the selected dwellings were interviewed using a semi-structured questionnaire addressing socioeconomic and environment aspects. The association between variables and seropositivity was assessed through multilevel logistic regression models. Global seropositivity was 39%. There was no statistically significant difference between seropositivity and age and sex of animals, literacy of the household head, presence of other domestic animals or with household characteristic like water supply, inadequate sewage disposal system, type of floor and roof. Mixed-breed dogs and those living for a long time in houses with absence of masonry walls and presence of a kennel showed higher odds of seropositivity. These results suggest that some peridomestic characteristics, especially the absence of barriers that allow dogs to have free access to the street, in association with the presence of a kennel, might contribute to maintaining the infection cycle in urban areas. Intervention measures oriented to the management of the peridomestic environment and responsible dog possession could be useful tools for reducing disease burden in endemic area.

An Urban Case of Canine Visceral Leishmaniasis in the Municipality of Pereira, Colombia

American visceral leishmaniasis (VL) is caused by Leishmania infantum/chagasi, transmitted by the sandflies Lutzomyia longipalpis and Lu. evansi. Dogs are the main reservoir and source for zoonotic infections in humans. Therefore, it is of utmost importance to diagnose such diseases in domestic animals to maintain public health. In 2019, the authors of the present study observed intracellular amastigotes in Giemsa-stained bone marrow smear using a real-time qPCR (parasite load was 484,336 DNA copies/mL), a canine visceral leishmaniasis (CVL) case caused by L. infantum/chagasi, in a 22-month-old male, English bulldog from Pereira, Colombia, a municipality not previously considered endemic for CVL nor human VL. Therefore, further field studies are necessary to determine if there is a low-grade circulation of this parasite among dogs and other animal reservoirs in the area, also entomological surveys are of utmost importance, as well as highlighting the clinical suspicion of this disease in domestic animals and humans.

First Report of Canine Infection by Leishmania (Viannia) guyanensis in the Brazilian Amazon.

The American cutaneous (CL) and visceral leishmaniasis (VL) are zooanthroponoses transmitted by sand flies. Brazil records thousands of human leishmaniasis cases annually. Dogs are reservoirs of Leishmania infantum, which causes VL, but their role in the transmission cycle of CL is debatable. Wild mammals are considered reservoirs of the aetiological agents of CL (Leishmania spp.). Objective: To describe the aetiology of leishmaniasis in dogs in an endemic area for CL and VL in the Amazon, Brazil. Methods: Clinical evaluation and blood collection of 40 dogs from the villages Ubim (20) and Socorro (20), city of Tomé-Açu, state of Pará, were carried out. The DNA extracted from the blood was used for PCR with Leishmania-specific primers targeting the hsp70-234 gene sequence. Products were sequenced (ABI3500XL), and the sequences were aligned, edited (BioEdit), and analyzed (Blastn). Results: Of the 34 amplified samples, 21 were sequenced, namely Leishmania infantum (12), L. guyanensis (5), L. braziliensis (3), and Leishmania sp. (01). Conclusion: Given the diversity of circulating pathogens, elucidation of the role of the dog in the Leishmania spp. cycle in Amazonian villages is imperative to the surveillance of CL in the region. We present the first report in Brazil, confirmed by sequencing, of canine infection by L. guyanensis, a species highly resistant to treatment in humans, with the drug of first choice (Glucantime®).

Doenças tropicais negligenciadas e as vulnerabilidades socioambientais nas capitais amazônicas

O presente estudo avalia a situação epidemiológica das doenças tropicais negligenciadas (DTN) com maior ocorrência na Amazônia e sua associação com as vulnerabilidades socioambientais. Foi realizado um estudo ecológico, descritivo, no período entre 2007 e 2016 acerca das DTN notificadas, além de dados sobre o Índice de Desenvolvimento Humano Municipal (IDHM), saneamento básico e o crescimento populacional nas capitais da Amazônia Legal. Os dados obtidos foram organizados em planilhas Excel para a aplicação da estatística descritiva, análise de componentes principais (PCA) e análise hierárquica de agrupamentos (HCA). As doenças notificadas foram dengue, tuberculose, leishmaniose tegumentar americana, esquistossomose, leishmaniose visceral e doença de Chagas. Todas as capitais apresentaram, ao menos, quatro DTN. Estes dados foram confirmados através do PCA e HCA, que constataram que as DTN identificadas puderam ser agrupadas por similaridades entre os valores. A maioria das capitais apresentaram crescimento populacional e IDHM elevados nos últimos anos, no entanto, os serviços de esgotamento sanitário e abastecimento de água deixam a desejar. O estudo mostrou que há uma associação entre as doenças notificadas e os dados de crescimento populacional e saneamento básico, os quais podem evidenciar uma negligência geográfica. Uma forma de mudar essa realidade epidemiológica na Amazônia é elaborando políticas públicas, com planejamento financeiro direcionado para a realização de projetos viáveis e eficazes que ofereçam serviços constantes de saneamento básico, água potável e educação em saúde para esta população.

Lutzomyia longipalpis, Gone with the Wind and Other Variables.

Lutzomyia longipalpis (Lutz & Neiva) is the main vector of Leishmania infantum (Nicolle) in America, associated in turn with the current spread and urbanization of American visceral leishmaniasis (AVL). The vector distribution in AVL foci shows a spatial-temporal clustering despite the different epidemiological contexts. The factors associated with the macroscale distribution of Lu. longipalpis as a landscape stratification are discussed in the framework of the process of their adaptation to anthropized environments. On the other hand, the fact that Lu. longipalpis is clustered in only a few hot spots or critical sites suggests that microscale approaches that describe the trap surrounding environment and the availability of refuges and food sources are better at explaining the uneven distribution of this vector, and should contribute, together with macroscale variables, to design operational control strategies. With regard to temporal distribution and climatic or vegetation data obtained by remote sensing as variables to explain and forecast the abundance of Lu. longipalpis, it is necessary to take into account the time lags in relation to the life cycle of the vector, the difference between the level of daily activity and actual abundance, and the differences in critical variables and thresholds according to the region or season. In conclusion, this review shows that it is feasible to characterize the distribution of Lu. longipalpis at focus level and within it to identify the main critical sites, proposing a sequential cost-effectivity strategy for urban AVL surveillance and control.

Clinical and Immunological Features of Human Leishmania (L.) infantum-Infection, Novel Insights Honduras, Central America.

Leishmania (Leishmania) infantum is the etiological agent of both American visceral leishmaniasis (AVL) and non-ulcerated cutaneous leishmaniasis (NUCL) in Honduras. Although AVL is the most severe clinical form of infection, recent studies have shown that human immune response to parasite infection can result in a clinical-immunological spectrum. The overall prevalence rate of infection and clinical-immunological profiles of the L. (L.) infantum infection in Amapala municipality, South Honduras was determined. We examined 576 individuals with diagnosis based on combined ELISA (IgG/IgM) and DTH assays. We also used genus-specific kDNA PCR and Hsp70 PCR-RFLP for NUCL cases. Clinical evaluation found 82% asymptomatic and 18% symptomatic individuals. All symptomatic cases (n = 104) showing NUCL were positive for parasites. We identified L. (L.) infantum species in 100% of the skin lesion scrapings and in 90% of the blood samples from NUCL cases studied. A total of 320 asymptomatic individuals were exposed (ELISA+ and/or DTH+), providing an overall L. (L.) infantum prevalence of 73.6%. Clinical, parasitological, and immunological evaluations suggest seven infection profiles, three asymptomatic and four symptomatic. This represents the first report on clinical and immunological features of human L. (L.) infantum-infection in Amapala municipality, Honduras.

New record of preclinical diagnosis of American visceral leishmaniasis in Amazonian Brazil encourages optimizing disease control

The clinical-immunological spectrum of human Leishmania (L.) infantum chagasi-infection in Amazonian Brazil has recently been reviewed based on the combined use of the delayed-type hypersensitivity (DTH) and indirect fluorescence antibody test (IFAT-IgG/IgM), both with homologous L. (L.) infantum chagasi-antigens, and associated with the clinical evaluation of infected individuals. This diagnostic approach has allowed to identify the broadest clinical-immunological spectrum of human L. (L.) infantum chagasi-infection composed by five clinical-immunological profiles of infection: three asymptomatic, 1) Asymptomatic Infection (AI) [DTH+/++++, IFAT−], 2) Subclinical Resistant Infection (SRI) [DTH+/++++, IFAT+/++], and 3) Indeterminate Initial Infection (III) [DTH−, IFAT+/++], and two symptomatic ones, 4) Symptomatic Infection (SI) [=American visceral leishmaniasis - AVL] and, 5) Subclinical Oligosymptomatic Infection (SOI), both with the same immune profile [DTH−, IFAT+++/++++]. Herein, we confirm for the third time the preclinical diagnosis of AVL through IgM-antibody response in an early asymptomatic case of infection (profile III), a 17-year-old boy who evolved to AVL (=profile SI) six weeks after the initial infection diagnosis, confirming that the combined use of DTH and IFAT-(IgG/IgM) assays associated with the clinical evaluation of infected individuals is potentially useful for monitoring human L. (L.) infantum chagasi-infection in endemic areas as well as optimizing AVL control.

Cutaneous parasitism in patients with American visceral leishmaniasis in an endemic area.

INTRODUCTION: Visceral leishmaniasis (VL) represents a public health concern in several areas of the world. In the American continent, VL transmission is typically zoonotic, but humans with active VL caused by Leishmania infantum are able to infect sandflies. Thus, individuals with cutaneous parasitic infections may act as reservoirs and allow interhuman transmission. Additionally, the skin may be responsible for reactivation of the disease after therapy. This study’s objective was to evaluate cutaneous parasitism in humans with VL in an American endemic area. METHODS: A cross-sectional hospital-based study was conducted in northeast Brazil from October 2016 to April 2017. Biopsies of healthy skin for histopathology and immunohistochemistry were performed prior to treatment in all study patients. RESULTS: Twenty-two patients between the ages of five months to 78 years were included in the study. Seven patients (31.8%) tested positive for HIV. Only one patient had cutaneous parasitism, as confirmed by immunohistochemistry prior to treatment. Parasitism was not detected after treatment. CONCLUSIONS: Cutaneous parasitism in the healthy skin of humans with visceral leishmaniasis, although unusual, may be a source of infection for phlebotomine sandflies.

Spatio-temporal distribution of human American visceral leishmaniasis in the Western region of Sao Paulo State, from 2004 to 2018.

ABSTRACTLeishmaniasis comprises a group of zoonotic diseases caused by protozoa belonging to the Leishmania genus, noting that the visceral form is the most severe and lethal, if untreated. Nowadays visceral leishmaniasis is widespread in Brazil and the Adamantina microregion, located in the west of Sao Paulo State, has been affected by Human American Visceral Leishmaniasis (HAVL) since 2004. We evaluated the epidemiological profile of HAVL in the Adamantina microregion through a Geographic Information Systems (GIS) and established its incidence rate by location and time. Notified cases were provided by the Sao Paulo State Epidemiological Surveillance Center. Home addresses of patients who tested positive to HAVL were converted into geographic coordinates through the Google Geocoding Application Programming Interface submitted to ArcMap 10.5 System for georeferencing. Kernel spatial analyses were performed to obtain the incidence distribution and the total area involvement rate. From 2004 to 2018, 325 cases of HAVL were diagnosed in 11 of the 12 municipalities belonging to the of Adamantina microregion. The disease has disseminated to the Northwest and East-Southeast directions, taking place along the Comandante Joao Ribeiro de Barros highway, with higher incidences rates in the municipalities where the highway passes. HAVL incidence was higher in children aged between 0 to 9 years and in the elderly; there was no difference in relation to sex and the majority of cases were located in urban areas. The determination of the epidemiological profile and the the spread of disease patterns can indicate possible areas of vulnerability, in order to contribute to the management and prevention of the disease through a strategic resources optimization.

CXCL10 treatment promotes reduction of IL-10+ regulatory T (Foxp3+ and Tr1) cells in the spleen of BALB/c mice infected by Leishmania infantum

American visceral leishmaniasis is caused by the protozoan Leishmania infantum. The control of the disease depends on the magnitude of the Th1 cell response and IL-10 producing regulatory T cells. Administration of chemokine, such as CXCL10, has shown promising results in the leishmaniasis treatment. Previous studies from our group have shown that CXCL10 induces a reduction in parasite burden in the spleen and a decrease in IL-10 and TGF-β production in L. infantum-infected BALB/c mice. This work investigated whether CXCL10-treatment reduces IL-10 + Treg cell populations (CD4+CD25+Foxp3+ and Tr1) and induces morphological changes in the spleen. BALB/c mice were infected and treated or not with CXCL10 on the 1st, 3rd and 7th days of infection. CXCL10-treatment was able to reduce the parasite load in the spleen in L. infantum-infected BALB/c mice and this decrease in the number of parasites correlated with the decrease in size of this organ in treated animals compared to untreated animals. 7, 23, and 45 days post-treatment (p.t.), the phenotype and frequency of IL-10 + Treg cells were evaluated by flow cytometry, and the morphological changes of the spleen were analyzed by optical microscopy. After 7 and 23 days p.t., CXCL10-treated animals showed a significant reduction of CD25-Foxp3−IL-10+ (Tr1) cells in the spleen when compared to untreated animals, whereas CD4+CD25+Foxp3+IL-10+ Treg cells reduced later at 23rd and 45th days p.t. Furthermore, while untreated animals showed a significant positive correlation between IL-10 production and Tr1 cells, in CXCL10-treated group this correlation was negative. Thus, these findings show that treatment with CXCL10 chemokine in L. infantum-infected BALB/c mice results in suppression of IL10+ Treg (Foxp3+ and Tr1) cells in the spleen, associated with a reduction in parasite load and splenomegaly.