Visceral Leishmaniasis In Brazil Research Articles

Impact of the COVID-19 Pandemic Surveillance of Visceral Leishmaniasis in Brazil: An Ecological Study.

The aim of the study was to assess the impact of the COVID-19 pandemic on the notification of new VL cases in Brazil in 2020. It is an ecological and time-series study (2015-2020) with spatial analysis techniques, whose units of analysis were the 5570 Brazilian municipalities. The study population consisted of all new cases of VL recorded between 2015 and 2020. The P-score was calculated to estimate the percentage variation in new VL cases. Global and local univariate Moran's Indices and retrospective space-time scan statistics were used in spatial and space-time analyses, respectively. It was expected that there would be 3627 new cases of VL in Brazil in 2020, but 1932 cases were reported (-46.73%). All Brazilian regions presented a negative percentage variation in the registration of new VL cases, with the Southeast (-54.70%), North (-49.97%), and Northeast (-44.22%) standing out. There was spatial dependence of the disease nationwide in both periods, before and during the first year of the COVID-19 pandemic. There was a significant reduction in the incidence of new VL cases in Brazil during the first year of the COVID-19 pandemic. These findings reinforce the need for better preparedness of the health system, especially in situations of new epidemics.

Impact of 4% Deltamethrin-Impregnated Dog Collars on the Incidence of Human Visceral Leishmaniasis: A Community Intervention Trial in Brazil.

In Brazil, human visceral leishmaniasis (HVL) is caused by the protozoan parasite Leishmania infantum, primarily transmitted by the sand fly Lutzomyia longipalpis, with dogs acting as the main urban reservoir. This study aims to evaluate the effectiveness of 4% deltamethrin-impregnated dog collars (DMC) on HVL incidence. This is a community intervention study carried out from 2012 to 2015 in the municipalities of Araguaína, State of Tocantins, and Montes Claros, State of Minas Gerais, Brazil. Two areas in each were randomly allocated to either (1) culling seropositive dogs + residual insecticide spraying (control area-CA) or (2) culling seropositive dogs + residual insecticide spraying + DMC fitted to dogs every six months for two years (intervention area-IA). Cases of HVL (n = 1202) occurring from 2008 to 2020 were identified from the Brazilian Reportable Diseases Information System and georeferenced to the control and intervention areas. The HVL cases from 2008 to 2012 were considered as occurring in the "pre-intervention" period. Those cases from 2013 to 2016 and from 2017 to 2020 were regarded as occurring in the "intervention" and "post-intervention" periods, respectively. We used a mixed-effects Poisson regression model to estimate the effectiveness of the intervention, comparing the changes from the pre-intervention period to the intervention and post-intervention periods in the control and intervention areas. In Araguaína, there was a statistically significant reduction in the incidence of HVL in both the control and intervention areas, comparing both the intervention and post-intervention periods with the pre-intervention period. The intervention with DMC was significantly associated with a reduction in HVL when comparing the intervention and pre-intervention periods, yielding an effectiveness estimate of the DMC of 27% (IC95% 1-46%, p = 0.045). No differences were observed when comparing the pre- and post-intervention periods (p = 0.827). In Montes Claros, cases reduced in both the control and intervention areas from the pre-intervention period to the intervention period (p = 0.913). In the post-intervention period, the incidence increased in the control area, while cases continued to decrease in the DMC area (p = 0.188). The use of DMC was associated with a reduction of 27% in the incidence of HVL during the period of DMC delivery, indicating that DMC is effective as an additional strategy for controlling visceral leishmaniasis in Brazil. However, no significant reduction associated with DMC was detected after the intervention period, suggesting that a control program based on the large-scale deployment of DMC might have to be maintained for more extended periods without interruption.

Effect of environmental variables on the incidence of Visceral Leishmaniasis in Brazil and Colombia

Visceral Leishmaniasis (VL) is the most severe of the three forms of Leishmaniasis. In the Americas, Brazil and Colombia present more than 90 % of the cases in the region. Our aim in this research was to estimate the association of the incidence rate of Visceral Leishmaniasis with the following environmental variables: the percentage of area suitable for the vector Lutzomyia longipalpis, the episodes of La Niña and El Niño, the Brazilian and Colombian biomes. Epidemiological data were obtained from the Brazilian Notifiable Diseases Information System and the Colombian National Public Health Surveillance System. Environmental data were downloaded from the NASA Giovanni web app, the Modis Sensor database, and the meteorological agencies of Australia, Japan, and the United States of America. Records of the presence of Lu. longipalpis were obtained from public databases and previous studies. As a result, the incidence per 10,000 inhabitants with LEBS for each El Niño-Southern Oscillation (ENSO) episode showed the largest values during El Niño 2015–2016, mainly in Brazil's Northeast and Central regions and the Northeast region of Colombia. Compared with the Neutral 2012–2014 episode, the episodes of El Niño 2015–2016 and La Niña 2010–2011 showed an average increase in the monthly incidence rate of VL, and the average increase was higher during El Niño 2015–2016 (aIRR = 2.304 vs.1.453) We found a positive association between the incidence rate of VL and the El Niño 2015–2016 episode and an impressive% of area suitable for the vector Lu. longipalpis in the Amazon region.An increase of 1 % in the area suitable for the vector Lu. longipalpis leads to an average rise of 0.8 % in the monthly incidence rate of VL. Our study shows a possible association between VL incidence and ENSO, with the most considerable incidence rates observed during El Niño 2015–2016 in Brazil's Northeast and Central regions and the Northeast region of Colombia. The present study is very important to better understand the Visceral Leishmaniasis transmission dynamics.

Therapeutic success and failure in using miltefosine to treat dogs naturally infected with Leishmania infantum.

In urban environments, domestic dogs (Canis familiaris) are a major reservoir for the parasite Leishmania infantum. Miltefosine has been used as the standard treatment for canine visceral leishmaniasis in Brazil. However, therapeutic failures have been reported. In the present study, two dogs (CG03 and CG06) with a diagnosis of infection by L. infantum underwent two cycles of treatment with miltefosine (Milteforan™ - Virbac®). Analyses showed increases in the parasite load of both CG03 and CG06, even after treatment. The clinical score of CG03 dropped from 1 to 0 (after one round of treatment), such that this dog became asymptomatic. CG06 showed clinical worsening, such that its score increased from 1 to 2. After the second therapeutic round, the parasite load in CG03 was found to have decreased, but it was still higher than before drug treatment even though this dog was physically asymptomatic. There was no decrease in the parasite load in CG06 and there was clinical worsening. The clinical response of these dogs to the treatment differed, but the parasite load remained high in both cases, which poses a risk to public health, making it essential take measures to prevent the sandfly vector from accessing the dog.

Spatial-temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020Distribución espaciotemporal de la leishmaniasis visceral en Brasil en el período 2007-2020

To analyze the dynamics of the spatial and temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020. This ecological study focused on the spatial pattern of visceral leishmaniasis cases in Brazil from 2007 to 2020 using data from the Information System for Notifiable Diseases (SINAN). The variables analyzed were the incidence rate of visceral leishmaniasis and the visceral leishmaniasis composite indicator (VLCI), from which triennial thematic maps were constructed. The global Moran index was calculated to assess the existence of spatial autocorrelation, and the local Moran index was used to identify areas with higher and lower risk of visceral leishmaniasis in Brazil. During the study period, there were 48 705 cases of visceral leishmaniasis, with an incidence rate of 25.53 cases per 100 000 population. There was spatial autocorrelation in all triennial blocks, with municipalities in the North and Northeast regions having an incidence equal to or greater than 50 cases per 100 000 population. Regarding the VLCI there was an increase in the number of municipalities classified as low risk for transmission, and a growing presence of state capitals with a classification of very high risk. The incidence of visceral leishmaniasis varied over the trienniums. The border region between the states of Tocantins, Maranhão, and Pará, along with the state of Ceará, stood out in the spatial distribution of the disease incidence and risk stratification by VLCI. These areas should be a priority for surveillance and control efforts for the disease.

Temporal trend in the incidence of human visceral leishmaniasis in Brazil.

It is an ecological study that analyzed the time trend of visceral leishmaniasis incidence rates in Brazil using segmented time regression by joinpoints. There was a decreasing incidence rate of this disease in the country with an average annual percent change (AAPC) of -5 (CI95%: -9.1; -0.6) and a reduction of 1.69 cases/100 thousand inhabitants in 2007, and 0.91/100 thousand inhabitants in 2020. The Central-West region showed the highest reduction percent (AAPC: -9.1; CI95%: -13.8; -4.3), followed by the Southeast region (AAPC: -8.7; -14.6; -2.5). The North and South regions showed the largest number of joinpoints in the time series. The highest incidences were recorded in the male population, however, stable (AAPC: 2.14; CI95%: -8.3; 0). In the age group analysis, the trend was decreasing for the groups from 0 to 4 years old (AAPC: -7.7; CI95%: -12.6; -2.4), 5 to 9 years old (AAPC: -7.3; CI95%: -13.6; -0,4) and 10 to 14 years old (AAPC: -5.5; CI95%: -10.3; -0.3). It was found that although Visceral Leishmaniasis is an endemic disease in Brazil, there was a decrease in its incidence rate from 2007 to 2020.

The Program for the Control of Visceral Leishmaniasis in Brazil: The Effect of the Systematic Euthanasia of Seropositive Dogs as a Single Control Action in Porteirinha, a Brazilian City with an Intense Transmission of Visceral Leishmaniasis.

Porteirinha is endemic for visceral leishmaniasis (VL), with intense disease transmission of the disease. We evaluated the impact of canine euthanasia as a single control measure on the incidence of VL in humans and canines. A prospective observational cohort study was carried out over four years (1998-2002) in 8 of the 12 neighborhoods of the city. The dynamics of canine visceral leishmaniasis (CVL) transmission were evaluated for 2 years, before beginning the screening-culling intervention. The comparative morbidity index (CMI) was used to stratify areas with the greatest risk of CVL, and the spatial distribution of human and canine VL cases was compared using univariate and bivariate K-functions. Human cases conglomerated in three neighborhoods. Spatial clusters were detected for CVL in 1998, 2000, and 2001, but not in 1999, when greater spatial dispersion occurred. The screening and culling intervention reduced the number of human VL cases and decreased the incidence of CVL, mainly in neighborhoods with a high CMI. The systematic euthanasia of seropositive dogs was shown to be an effective control action of the Program for Control of Visceral Leishmaniasis (PCLV) in Brazil. The fundamental role of domestic dogs in the epidemiological chain of VL was reaffirmed.

Historical trend of Visceral Leishmaniasis in Brazil: epidemiological aspects and perspectives for the future

Historical trend of Visceral Leishmaniasis in Brazil: epidemiological aspects and perspectives for the future

Epidemiological indicators as prophylaxis tools for Canine Visceral Leishmaniasis in Brazil

Epidemiological indicators as prophylaxis tools for Canine Visceral Leishmaniasis in Brazil

Epidemiological profile of Visceral Leishmaniasis in Brazil between 2011-2020

The purpose of this study was to carry out an epidemiological analysis of Visceral Leishmaniasis cases registered by the Notifiable Diseases Information System (SINAN-DATASUS) in Brazil between the years 2011 and 2020. The variables verified were: year, region of notification, gender, age group, and disease progression. In the time range studied, 34,386 cases were registered in the Brazilian territory. The year 2017 stood out with the highest number of cases: 4,462, and 2020 presented the lowest number: 1,908. Such variations proved to be related to global climatic and epidemiological events: 2017 was evaluated as the 3rd hottest year in history by the North American Entity NOAA (National Oceanic Atmospheric Administration), with the consulted literature pointing to relations of growth in the incidence of high temperature climatic events. The year 2020 faced the COVID-19 pandemic break-out. There was a predominance of cases in the Northeast (54.96%), followed by the Southeast (18.67%), North (18.05%), Midwest (8.01%) and South (0.31%). The gender variable shows a predominance of incidence of 65.08% in males and 34.91% in females, which is compatible with the literature. Another parameter that remains within the literature is the age group, where the highest incidence in the 1-4 age group was 23.77%, remaining a disease that severely affects children. The percentages found are in line with the literature and the disease has changed its spread in the Northeast region of the country from about 90% to 55% in two decades, still remaining the most affected region of the country. The disease appears to be more widespread and urban in current studies. There are new and efficient multidisciplinary resources – pharmacological, geographic, climatic and environmental – which, if continued, expanded, and articulated, can strengthen the fight against this serious harm to human health.

Phlebotominae Fauna (Diptera: Psychodidae) and the Spatial Distribution of Species in Sergipe, Brazil.

Some sand fly species are the vectors responsible for the transmission of Leishmania spp. (Kinetoplastida: Trypanosomatidae), the etiological agent of leishmaniasis, and in the state of Sergipe, the two main forms of the disease (visceral and cutaneous) are recorded. Few works show information about the species that form the Phlebotominae fauna in Sergipe. This study aimed to update and determine how they are distributed throughout the state. The study used data from surveys about phlebotomines in Sergipe, from the Program of Surveillance and Control of Visceral Leishmaniasis, carried out by the Central Public Health Laboratory of Sergipe, from 2008 to 2018, along with review and original data from 2022. The commentary on this information was developed with focus on the species that can be vectors for the disease. Sergipe has, up to now, 27 registered species of phlebotomines from 12 genera, 15 of them are of sanitary relevance. Twenty two of these species are in the mesoregion East, 19 in the Agreste, and 11 in the Sertão of Sergipe. The species with the greatest distribution was Evandromyia lenti (Mangabeira, 1938), present in 74.6% of the municipalities of Sergipe, followed by Lutzomyia longipalpis (Lutz & Neiva, 1912), the main vector of the etiological agent of visceral leishmaniasis in Brazil, present in 68% of the municipalities studied. This study expands the number and distribution of species recorded in the state. This information can contribute to disease containment plans and support health education actions aimed at the control of leishmaniasis in Sergipe.

3'Nucleotidase/nuclease is required for Leishmania infantum clinical isolate susceptibility to miltefosine.

Miltefosine treatment failure in visceral leishmaniasis in Brazil has been associated with deletion of the miltefosine susceptibility locus (MSL) in Leishmania infantum. The MSL comprises four genes, 3'-nucleotidase/nucleases (NUC1 and NUC2); helicase-like protein (HLP); and 3,2-trans-enoyl-CoA isomerase (TEI). In this study CRISPR-Cas9 was used to either epitope tag or delete NUC1, NUC2, HLP and TEI, to investigate their role in miltefosine resistance mechanisms. Additionally, miltefosine transporter genes and miltefosine-mediated reactive oxygen species homeostasis were assessed in 26 L.infantum clinical isolates. A comparative lipidomic analysis was also performed to investigate the molecular basis of miltefosine resistance. Deletion of both NUC1, NUC2 from the MSL was associated with a significant decrease in miltefosine susceptibility, which was restored after re-expression. Metabolomic analysis of parasites lacking the MSL or NUC1 and NUC2 identified an increase in the parasite lipid content, including ergosterol; these lipids may contribute to miltefosine resistance by binding the drug in the membrane. Parasites lacking the MSL are more resistant to lipid metabolism perturbation caused by miltefosine and NUC1 and NUC2 are involved in this pathway. Additionally, L.infantum parasites lacking the MSL isolated from patients who relapsed after miltefosine treatment were found to modulate nitric oxide accumulation in host macrophages. Altogether, these data indicate that multifactorial mechanisms are involved in natural resistance to miltefosine in L.infantum and that the absence of the 3'nucleotidase/nuclease genes NUC1 and NUC2 contributes to the phenotype. MRC GCRF and FAPES.

Factors associated with Leishmania infantum infection in dogs from urban areas endemic for visceral leishmaniasis in Brazil

There are gaps in the knowledge of the factors associated with canine visceral leishmaniasis (CVL). Moreover, there is a need for studies conducted with appropriate sample selection and with standardized diagnostic methods, to assess the current infection status of animals. This study analyzed factors associated with Leishmania infantum infection in dogs from urban areas endemic for CVL in Brazil. Data from four cities in different regions of the country (Fortaleza, Brasília, Palmas, and Bauru) were included, encompassing a large and heterogeneous sample group. Dogs were considered infected if they had positive results in parasitological tests (skin lesion culture, histological or immunohistochemical analysis of skin). Data analysis consisted of logistic regression with adjustment for the effect of cities as cluster variables, using generalized estimating equations. The canine positivity for L. infantum was 9.8%. Bauru had the highest percentage (18.7%), followed by Brasília (8.4%), Fortaleza (7.9%), and Palmas (4%). Male animals were twice as likely to be infected as females (Confidence Interval (CI): 1.5–2.8). Dogs living outdoors were 1.5 times more likely to be positive (CI: 1.4–1.6). Dogs living in households rearing chickens were 40% less likely to be infected (CI: 0.5–0.8). A significant multiplicative interaction indicated that a protective association between purebred and CVL was stronger among dogs older than seven years. These findings provide evidence for the role of individual and environmental factors on L. infantum infection in dogs from endemic urban areas. They may be used for identifying groups of animals at higher risk for delivering control interventions.

Isolation, typing, and drug susceptibility of Leishmania (Leishmania) infantum isolates from dogs of the municipality of Embu das Artes, an endemic region for canine leishmaniasis in Brazil.

The parasitic protozoa Leishmania (Leishmania) infantum is the etiological agent of human visceral leishmaniasis and canine leishmaniasis in South America, where Brazil is the most affected country. This zoonotic disease is transmitted by the bite of an infected phlebotomine sand fly and dogs constitute the main domestic reservoir of the parasite. In this study, we screened 2348 dogs of the municipality of Embu das Artes, Brazil, for antibodies against the parasite. Prevalence for canine leishmaniasis seropositivity was 2.81%, as assessed using a Dual-Path Platform rapid test for canine leishmaniasis. Twenty-five seropositive dogs were euthanized for parasite isolation and 14 isolates were successful obtained. Nucleotide sequencing of the internal transcribed spacer confirmed the isolates to be L. (L.) infantum, and very low sequence variability was observed among them. The in vitro susceptibility to miltefosine and paromomycin was assessed and moderate variation in paromomycin susceptibility was found among the isolates in the promastigote and intracellular amastigote stages. On the other hand, in vitro susceptibility to miltefosine of these isolates was homogenous, particularly in the amastigote stage (EC50 values from 0.69 to 2.07μM). In addition, the miltefosine sensitivity locus was deleted in all the isolates, which does not corroborate the hypothesis that the absence of this locus is correlated with a low in vitro susceptibility. Our findings confirm that the municipality of Embu das Artes is endemic for canine leishmaniasis and that isolates from this region are susceptible to paromomycin and miltefosine, indicating the potential of these drugs to be clinically evaluated in the treatment of human visceral leishmaniasis in Brazil.

Replacement of Leishmania (Leishmania) infantum Populations in an Endemic Focus of Visceral Leishmaniasis in Brazil.

Visceral leishmaniasis is an important global health problem with an estimated of 50,000 to 90,000 new cases per year. VL is the most serious form of leishmaniasis as it can be fatal in 95% of the cases if it remains untreated. VL is a particularly acute problem in Brazil which contributed with 97% of all cases reported in 2020 in the Americas. In this country, VL affects mainly the poorest people in both urban and rural areas and continues to have a high mortality rate estimated around 8.15%. Here, we performed a temporal parasite population study using whole genome sequence data from a set of 34 canine isolates sampled in 2008, 2012 and 2015 from a re-emergent focus in Southeastern Brazil. Our study found the presence of two distinct sexual subpopulations that corresponded to two isolation periods. These subpopulations diverged hundreds of years ago with no apparent gene flow between them suggesting a process of rapid replacement during a two-year period. Sequence comparisons and analysis of nucleotide diversity also showed evidence of balancing selection acting on transport-related genes and antigenic families. To our knowledge this is the first population genomic study showing a turn-over of parasite populations in an endemic region for leishmaniasis. The complexity and rapid adaptability of these parasites pose new challenges to control activities and demand more integrated approaches to understand this disease in New World foci.

Use of soil moisture active passive satellite data and WorldClim 2.0 data to predict the potential distribution of visceral leishmaniasis and its vector Lutzomyia longipalpis in Sao Paulo and Bahia states, Brazil.

Visceral leishmaniasis (VL) is a neglected tropical disease transmitted by Lutzomyia longipalpis, a sand fly widely distributed in Brazil. Despite efforts to strengthen national control programs reduction in incidence and geographical distribution of VL in Brazil has not yet been successful; VL is in fact expanding its range in newly urbanized areas. Ecological niche models (ENM) for use in surveillance and response systems may enable more effective operational VL control by mapping risk areas and elucidation of eco-epidemiologic risk factors. ENMs for VL and Lu. longipalpis were generated using monthly WorldClim 2.0 data (30-year climate normal, 1-km spatial resolution) and monthly soil moisture active passive (SMAP) satellite L4 soil moisture data. SMAP L4 Global 3-hourly 9-km EASE-Grid Surface and Root Zone Soil Moisture Geophysical Data V004 were obtained for the first image of day 1 and day 15 (0:00-3:00 hour) of each month. ENM were developed using MaxEnt software to generate risk maps based on an algorithm for maximum entropy. The jack-knife procedure was used to identify the contribution of each variable to model performance. The three most meaningful components were used to generate ENM distribution maps by ArcGIS 10.6. Similar patterns of VL and vector distribution were observed using SMAP as compared to WorldClim 2.0 models based on temperature and precipitation data or water budget. Results indicate that direct Earth-observing satellite measurement of soil moisture by SMAP can be used in lieu of models calculated from classical temperature and precipitation climate station data to assess VL risk.

Tissue Specific Dual RNA-Seq Defines Host-Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum.

ABSTRACTVisceral leishmaniasis is associated with hepato-splenomegaly and altered immune and hematological parameters in both preclinical animal models and humans. We studied mouse experimental visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani in BALB/c mice using dual RNA-seq to investigate the transcriptional response of host and parasite in liver and spleen. We identified only 4 species-specific parasite expressed genes (SSPEGs; log2FC >1, FDR <0.05) in the infected spleen, and none in the infected liver. For the host transcriptome, we found 789 differentially expressed genes (DEGs; log2FC >1, FDR <0.05) in the spleen that were common to both infections, with IFNγ signaling and complement and coagulation cascade pathways highly enriched, and an additional 286 and 186 DEGs that were selective to L. donovani and L. infantum infection, respectively. Among those, there were network interactions between genes of amino acid metabolism and PPAR signaling in L. donovani infection and increased IL1β and positive regulation of fatty acid transport in L. infantum infection, although no pathway enrichment was observed. In the liver, there were 1,939 DEGs in mice infected with either L. infantum or L. donovani in comparison to uninfected mice, and the most enriched pathways were IFNγ signaling, neutrophil mediated immunity, complement and coagulation, cytokine-chemokine responses, and hemostasis. Additionally, 221 DEGs were selective in L. donovani and 429 DEGs in L. infantum infections. These data show that the host response for these two visceral leishmaniasis infection models is broadly similar, and ∼10% of host DEGs vary in infections with either parasite species.IMPORTANCE Visceral leishmaniasis (VL) is caused by two species of Leishmania parasites, L. donovani in the Old World and L. infantum in the New World and countries bordering the Mediterranean. Although cardinal features such as hepato-splenomegaly and alterations in blood and immune function are evident, clinical presentation may vary by geography, with for example severe bleeding often associated with VL in Brazil. Although animal models of both L. donovani and L. infantum have been widely used to study disease pathogenesis, a direct side-by-side comparison of how these parasites species impact the infected host and/or how they might respond to the stresses of mammalian infection has not been previously reported. Identifying common and distinct pathways to pathogenesis will be important to ensure that new therapeutic or prophylactic approaches will be applicable across all forms of VL.

Lethality among individuals infected with visceral leishmaniasis in Brazil: a retrospective study (2007-2018).

Visceral leishmaniasis (VL) is a public health problem with a high prevalence and lethality in Brazil. This study aims to estimate the lethality and associated factors in individuals with VL and assess survival time, emphasizing VL/HIV coinfection. This retrospective study has 37,583 individuals notified and confirmed with VL in the Sistema de Informação de Agravos de Notificação (SINAN) between 2007 and 2018 (Brazil). Lethality was evaluated considering VL deaths, deaths from other causes (OC), and non-deaths. We performed a multinomial logistic regression, with non-death as the benchmark category. We conducted a survival analysis (Kaplan-Meier method), emphasizing VL/HIV coinfection. Most individuals were young, male, mixed race, low schooling level, and urban dwellers. The lethality rate was 10.2% (VL and OC deaths) and 7.8% (VL deaths). The prevalence of HIV infection was 8.81%. A higher likelihood of VL and OC deaths was observed in older age groups, females, and with a higher number of symptoms. A higher likelihood of OC deaths was identified in individuals with HIV. A lower likelihood of VL and OC deaths was observed for individuals on VL therapy. The mean survival time was longer for VL/HIV individuals, who had a lower survival rate than those with VL. The data point to the need for attention to the timely diagnosis of VL and HIV and adequate pharmacological treatment in this population.

The first case of canine visceral leishmaniasis in the southern region of Santa Catarina, an emerging focus of visceral leishmaniasis in Brazil: regional report or reflection of the reality of a country?

Visceral leishmaniasis is among the most neglected diseases in the world and especially affects poor populations of some developing or underdeveloped countries, with human disease being a factor in the occurrence of thousands of deaths every year. Visceral leishmaniasis affect domestic dogs, main reservoirs of the Leishmania parasite in urban environments. Thus, the aim of this study was to analyze the prevalence of canine visceral leishmaniasis in two non-endemic municipalities located in southern Santa Catarina, as well as to identify the main risk factors for infection in dogs. A cross-sectional study was carried out with dogs living in two Zoonoses Control Centers located in the cities of Tubarão and Criciúma. Blood samples were collected and analyzed by real-time PCR for detection of Leishmania infection. Clinical examination and evaluation of the characteristics of the canine population were also carried out. A total of 107 dogs were evaluated, of which 19% were positive for Leishmania, and 85% of the positive cases were asymptomatic. In conclusion, we highlight the detection of cases of canine visceral leishmaniasis in two cities that had not yet reported cases. The high rate of positive asymptomatic animals suggests the maintenance of the parasite in the environment.

Leishmania infantum Infection Modulates the Jak-STAT Pathway in Lutzomyia longipalpis LL5 Embryonic Cells and Adult Females, and Affects Parasite Growth in the Sand Fly

Phlebotomine sand flies (Diptera, Psychodidae) belonging to the Lutzomyia genus transmit zoonoses in the New World. Lutzomyia longipalpis is the main vector of Leishmania infantum, which is the causative agent of visceral leishmaniasis in Brazil. To identify key molecular aspects involved in the interaction between vector and pathogens and contribute to developing disease transmission controls, we investigated the sand fly innate immunity mediated by the Janus kinase/signal transducer and activator of transcription (Jak-STAT) pathway in response to L. infantum infection. We used two study models: L. longipalpis LL5 embryonic cells co-cultured with L. infantum and sand fly females artificially infected with the parasite. We used qPCR to follow the L. longipalpis gene expression of molecules involved in the Jak-STAT pathway. Also, we modulated the Jak-STAT mediated immune response to understand its role in Leishmania parasite infection. For that, we used RNAi to silence the pathway regulators, protein inhibitor of activated STATs (PIAS) in LL5 cells, and STAT in adult females. In addition, the pathway suppression effect on parasite development within the vector was assessed by light microscopy in late-phase infection. The silencing of the repressor PIAS in LL5 cells led to a moderate increase in a protein tyrosine phosphatase 61F (PTP61F) expression. It suggests a compensatory regulation between these two repressors. L. infantum co-culture with LL5 cells upregulated repressors PIAS, suppressor of cytokine signaling (SOCS), and PTP61F. It also downmodulated virus-induced RNA-1 (VIR-1), a pathway effector, indicating that the parasite could repress the Jak-STAT pathway in LL5 cells. In Leishmania-infected L. longipalpis females, STAT and the antimicrobial peptide attacin were downregulated on the third day post-infection, suggesting a correlation that favors the parasite survival at the end of blood digestion in the sand fly. The antibiotic treatment of infected females showed that the reduction of gut bacteria had little effect on the Jak-STAT pathway regulation. STAT gene silencing mediated by RNAi reduced the expression of inducible nitric oxide synthase (iNOS) and favored Leishmania growth in sand flies on the first day post-infection. These results indicate that STAT participated in the iNOS regulation with subsequent effect on parasite survival.