Visceral Leishmaniasis In Brazil Research Articles

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.

Epidemiological aspects of visceral leishmaniasis in Brazil and in international border regions

Objectives: To verify the number of visceral leishmaniasis (VL) cases in Brazil and its states and twin cities, with a focus on the state and twin city with the highest number of cases. We investigated social, demographic, laboratory and clinical aspects of these cases. Methodological design: We performed a descriptive study using a quantitative approach and data from 2010 to 2019 that were obtained through a public domain website, the Informatics Department of the Unified Health System. The incidence rate of VL cases was calculated per 100,000 inhabitants. software. Results: In Brazil, 35,886 VL cases were reported, with 2,834 cases in international border states and 148 cases in twin cities. The state and twin city with the highest number of cases were Mato Grosso do Sul (1,834 cases) and Corumbá (94 cases), respectively, with annual mean incidence rates of 6.4 and 8.3 cases per 100,000 inhabitants. In Mato Grosso do Sul and Corumbá, the disease was more frequent in male and brown-skinned individuals who had up to 8 years of education (age range: 1 to > 80 years old). Most of the cases occurred in urban areas, was diagnosed by laboratory tests and evolved to cure (p < 0.05). Conclusions: A high number of VL cases in Brazil was found during the period of study. The cases were distributed in 10 states with international borders and eight twin cities. These findings draw attention to the greater need for management programs to control and prevent VL.

In Vitro Susceptibility to Miltefosine of Leishmania infantum (syn. L.chagasi) Isolates from Different Geographical Areas in Brazil.

Treatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of Leishmania infantum from different geographic regions, using intracellular amastigote and promastigote assays. The EC50 for miltefosine of 13 of these strains evaluated in intracellular amastigotes varied between 1.41 and 4.57 μM. The EC50 of the 73 strains determined in promastigotes varied between 5.89 and 23.7 μM. No correlation between in vitro miltefosine susceptibility and the presence of the miltefosine sensitive locus was detected among the tested strains. The relatively low heterogeneity in miltefosine susceptibility observed for the 73 strains tested in this study suggests the absence of decreased susceptibility to miltefosine in Brazilian L. infantum and does not exclude future clinical evaluation of miltefosine for VL treatment in Brazil.

The effects of natural disasters on leishmaniases frequency: A global systematic review and meta-analysis

ObjectivesNatural disasters (NDs) may increase the outbreaks and transmissions of vector-borne diseases such as cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). However, the relationship between leishmaniases and NDs has not yet been clearly established. Here, we systematically reviewed all reported articles in this field to answer whether NDs increase the frequency of leishmaniases. MethodsAll the related articles published during January 2000 till January 2020 were reviewed. Moreover, all NDs and the associated leishmaniases frequencies reports in 17 leishmaniases endemic countries were searched to find any ND-leishmaniases relationship. ResultsAfter the initial screening, 39 articles on ND-leishmaniases were selected and systematically reviewed. These articles showed different frequencies of CL in the endemic areas before and after NDs in some regions of Pakistan and Iran and in case of VL in Brazil, Ethiopia, and Sudan. After thorough deliberation, four studies for CL-ND and five studies for VL-ND relationships were selected for meta-analysis. The results showed increases in the leishmaniases incidences after NDs, although not robustly. ConclusionThe lack of a strong leishmaniases-ND relationship could be attributed to the local compilations of such data in scattered regions of the endemic countries. Therefore, currently a substantial knowledge gap on leishmaniases-ND relationship is apparent.

Potential vectors of Leishmania spp. in an Atlantic Forest conservation unit in northeastern Brazil under anthropic pressure

BackgroundPhlebotomines are a group of insects which include vectors of the Leishmania parasites that cause visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL), diseases primarily affecting populations of low socioeconomic status. VL in Brazil is caused by Leishmania infantum, with transmission mainly attributed to Lutzomyia longipalpis, a species complex of sand fly, and is concentrated mainly in the northeastern part of the country. CL is distributed worldwide and occurs in five regions of Brazil, at a higher incidence in the north and northeast regions, with etiological agents, vectors, reservoirs and epidemiological patterns that differ from VL. The aim of this study was to determine the composition, distribution and ecological relationships of phlebotomine species in an Atlantic Forest conservation unit and nearby residential area in northeastern Brazil.MethodsCenters for Disease Control and Shannon traps were used for collections, the former at six points inside the forest and in the peridomestic environment of surrounding residences, three times per month for 36 months, and the latter in a forest area, once a month for 3 months. The phlebotomines identified were compared with climate data using simple linear correlation, Pearson’s correlation coefficient and cross-correlation. The estimate of ecological parameters was calculated according to the Shannon-Wiener diversity index, standardized index of species abundance and the dominance index.ResultsA total of 75,499 phlebotomines belonging to 11 species were captured in the CDC traps, the most abundant being Evandromyia walkeri, Psychodopygus wellcomei and Lu. longipalpis. Evandromyia walkeri abundance was most influenced by temperature at collection time and during the months preceding collection and rainfall during the months preceding collection. Psychodopygus wellcomei abundance was most affected by rainfall and relative humidity during the collection month and the month immediately preceding collection time. Lutzomyia longipalpis abundance showed a correlation with temperature and the rainfall during the months preceding collection time. The Shannon trap contained a total of 3914 phlebotomines from these different species. Psychodopygus wellcomei, accounting for 91.93% of the total, was anthropophilic and active mainly at night.ConclusionsMost of the species collected in the traps were seasonal and exhibited changes in their composition and population dynamics associated with local adaptions. The presence of vectors Ps. wellcomei and Lu. longipalpis underscore the epidemiological importance of these phlebotomines in the conservation unit and surrounding anthropized areas. Neighboring residential areas should be permanently monitored to prevent VL or CL transmission and outbreaks.Graphical

Epidemiological profile and lethality of visceral leishmaniasis/human immunodeficiency virus co-infection in an endemic area in Northeast Brazil.

INTRODUCTION: The association of visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) infection is a concern worldwide, and this co-infection is linked to increased lethality. The Northeast is the region that mostly reports cases of VL in Brazil. The knowledge of risk factors associated with VL/HIV co-infection and its impact on lethality is extremely important. METHODS: The present study analyzed the epidemiologic features of cases with VL/HIV co-infection in the state of Pernambuco, Northeast of Brazil, from 2014 to 2018. RESULTS: There were 858 and 11,514 reported cases of VL and HIV infection, respectively. The average incidences of VL and HIV infection were 1.82 and 24.4/100,000 inhabitants, respectively. Of all reported cases of VL, 4.9% (42/858) also had HIV infection. There was an inverse spatial association between VL and HIV infection incidences. The lethality rates of VL, HIV infection, and co-infection were 9.9%, 26.1%, and 16.6%, respectively. Most of the patients were males and lived in urban areas. The cases of VL mostly occurred in children aged below 10 years, whereas the cases of HIV infection and VL/HIV co-infection were primarily observed in adults between 20 years and 39 years old. CONCLUSIONS: We defined the profile and areas with most cases of co-infection and found that the lethality of VL with co-infection increased in the current period. These findings contribute to applying efforts with a greater focus in these identified populations to prevent future deaths.

The spread of visceral leishmaniasis in Brazil: the first canine cases described in Ji-Paraná, Rondônia, Brazil.

Leishmaniases are zoonotic diseases caused by protozoa of the genus Leishmania. The disease has two clinical manifestations described in humans: visceral (VL) and cutaneous (CL) leishmaniasis. In Brazil, there has been an expansion of human VL. The participation of the dog as a reservoir of Leishmania infantum, the agent of VL, is important for the epidemiology of the disease since canine cases generally precede human cases. The present study aimed to evaluate the occurrence of Leishmania spp. infection in dogs in the municipality of Ji-Paraná by PCR assays using blood samples. Leishmania DNA was detected in two of the 105 studied dogs. The PCR products were sequenced and confirmed that the two samples (1.90%) correspond to L. infantum. The dogs had allochthonous history. Therefore, the positive results found here should serve as a warning to public health agencies. This is because Ji-Paraná is the third municipality to register cases of canine leishmaniasis (CanL) in Rondônia state. Thus, reinforcing the importance of expanding studies on the epidemiology and surveillance of VL in the region.

Knowledge, attitudes and practices concerning visceral leishmaniasis among residents of a sporadic transmission area in southeast Brazil.

In the last four decades, visceral leishmaniasis (VL) has undergone an urbanization process in Brazil. This research aimed to assess the knowledge, attitudes and practices concerning VL among residents of a sporadic transmission urban area in southeast Brazil. A community-based, cross-sectional quantitative study was conducted. Scores for knowledge, attitudes and practices concerning VL were evaluated and the bivariate analysis was performed. The analysis indicated that 29.9% had good knowledge, 5.2% had appropriate attitudes and 62.1% had appropriate practices. Notwithstanding that, pivotal practices for controlling VL had unsatisfactory individual frequencies. Good knowledge on VL was related to women, a higher level of education, a higher income, the place of residence and having pets. Appropriate attitudes were related to the place of residence. The practices had no significant associations with the sociodemographic and epidemiological variables. This study demonstrated that even in the area of disease transmission, knowledge on VL is very limited, including at the most basic level. In order to achieve effectiveness in actions against VL in Brazil, the participation of the affected communities is imperative, therefore popular health education interventions are necessary to improve the population's understanding of the disease and to avoid inappropriate attitudes and practices.

Epidemiological aspects and spatial patterns of human visceral leishmaniasis in Brazil.

Human visceral leishmaniasis (HVL) cases are important public health problems due to their zoonotic aspect, with high rates of morbidity and mortality in Brazil. The aim of this this study was to identify spatial patterns in both rates of HVL cases in Brazilian states during the period from 2006 to 2015. This is an ecological study, using geoprocessing tools to create choropleth maps, based on secondary data from open access platforms, to identify priority areas for control actions of the disease. Data were collected in 2017 and analysed according to the global and local Moran's I, using TerraView 4.2.2 software. Similar clusters were observed in neighbouring municipalities in thematic maps of HVL, suggesting spatial similarity in the distribution of the disease in humans mainly in the North and Northeast Regions, which concentrate the states with the highest rates of HVL. Heterogeneous spatial patterns were observed in the distribution of HVL, which show municipalities that need higher priority in the intensification of disease surveillance and control strategies.

How much does it cost to prevent and control visceral leishmaniasis in Brazil? Comparing different measures in dogs

Visceral leishmaniasis (VL) is an important zoonosis in Brazil. Dogs are considered the main domestic reservoirs of the disease in the country; hence, control measures are focused on these reservoirs. Despite efforts to prevent and control VL, important reductions in disease prevalence and incidence have not been identified, stimulating the development and application of new strategies. The choice and implementation of new control strategies can benefit from the application of mathematical models that allow the simulation of different strategies in different scenarios. Selecting the best strategy to be implemented is also supported by cost-effectiveness studies. Here we used the results of a mathematical model in which scenarios, including isolated use of the vaccine and insecticide-impregnated collar (IIC), both at different coverage rates, were simulated to conduct a cost-effectiveness study. The costs were calculated for each scenario considering a simulation period of four years. Collar application in both infected and non-infected animals was the most cost-effective strategy. For example, to reduce the prevalence in humans and dogs by approximately 70%, the costs ranged from $250,000 and $550,000 for the IICs and vaccination, respectively. Even in the scenario with 40% loss/replacement of IICs, this measure was more advantageous in terms of cost-effectiveness than vaccination. If the vaccine were applied with culling of seropositive tested dogs, then the measure became more effective with a reduced cost compared with the vaccine alone. The use of the three first consecutive vaccine doses had the greatest impact on the cost of the vaccination strategy. The advantage of using IICs is that there is no need for a prior diagnosis, unlike vaccination, reducing costs and facilitating implementation. The present study aims to contribute to strategies to reduce hosts infected with VL by reducing public expenditure.

Information differences across spatial resolutions and scales for disease surveillance and analysis: The case of Visceral Leishmaniasis in Brazil.

Nationwide disease surveillance at a high spatial resolution is desired for many infectious diseases, including Visceral Leishmaniasis. Statistical and mathematical models using data collected from surveillance activities often use a spatial resolution and scale either constrained by data availability or chosen arbitrarily. Sensitivity of model results to the choice of spatial resolution and scale is not, however, frequently evaluated. This study aims to determine if the choice of spatial resolution and scale are likely to impact statistical and mathematical analyses. Visceral Leishmaniasis in Brazil is used as a case study. Probabilistic characteristics of disease incidence, representing a likely outcome in a model, are compared across spatial resolutions and scales. Best fitting distributions were fit to annual incidence from 2004 to 2014 by municipality and by state. Best fits were defined as the distribution family and parameterization minimizing the sum of absolute error, evaluated through a simulated annealing algorithm. Gamma and Poisson distributions provided best fits for incidence, both among individual states and nationwide. Comparisons of distributions using Kullback-Leibler divergence shows that incidence by state and by municipality do not follow distributions that provide equivalent information. Few states with Gamma distributed incidence follow a distribution closely resembling that for national incidence. These results demonstrate empirically how choice of spatial resolution and scale can impact mathematical and statistical models.

Leishmaniose visceral humana: um retrato da situação de casos em idosos e longevos

Aims: to analyze the current Brazilian and of the state of Rio Grande do Sul epidemiological situation of visceral leishmaniasis (LVH) in the elderly and verifythe mortality coefficient.Methods: This is a cross-sectional study with a secondary data source, taken from SINAN data from January 2013 to December 2017, with confirmed visceral leishmaniasis in Brazil and Rio Grande do Sul, which are tabulated in Excel and analyzed with Epiinfo 7.Results: cases of LVH in the elderly have increased in the last 5 years, within the Brazilian and the state of Rio Grande do Sul settings. Although not widely reported, it is frequent to compromise and increase the proportion of elderly people who die from LVH, which was 20,3% of the cases in the period from 2013 to 2017, demonstrating the seriousness of the infection in this public. In our study we also found a strong relation between age and the increase in the lethality coefficient, reaching 46.87% in 2016.Discussion: One of the recent strategies in the fight against HVL is the slaughter of dogs that contains the parasite responsible for the transmission of the disease, but this method of control has not been very effective. Thus, the immunoprophylactic measurement by Leish-Tec® vaccine has a favorable effect in the fight against the disease only in animals that are not in high transmission areas.

Social determinants of mortality due to visceral leishmaniasis in Brazil (2001-2015): an ecological study

INTRODUCTION: We aimed to analyze the relationship between visceral leishmaniasis mortality and social determinants of health (SDH).METHODS: This was an ecological study of all leishmaniasis-related deaths in Brazil, from 2001 to 2015. We analyzed 49 indicators of human development and social vulnerability. The association was tested using the classical and spatial regression model.RESULTS: Mortality was associated with indicators that expressed low human development and high social vulnerability: lack of garbage collection, low schooling, unemployment rate, low per capita income, and income inequality (Gini index).CONCLUSIONS: There was an association between high mortality by leishmaniasis and low SDH.

Visceral leishmaniasis lethality in Brazil: an exploratory analysis of associated demographic and socioeconomic factors.

INTRODUCTION: It is believed that delays in diagnosis and treatment of Visceral Leishmaniasis (VL) contribute significantly to the burden of VL lethality in Brazil. METHODS: This study included several parts: a descriptive cross-sectional study of the individual characteristics of deaths from disease; a descriptive ecological study of the spatial distribution of deaths from disease; and an ecological analytical study to evaluate the association between disease lethality rates and the demographic, socioeconomic, and health indicators. The study population comprised all cases diagnosed throughout the country per the National Disease Notification System (SINAN) and the total number of disease deaths recorded in the Mortality Information System (SIM) from 2007 to 2012. RESULTS: Of the 223 deaths from disease captured by pairing the databases, 59.1% were reported as "death from other causes". There were significant associations between VL lethality rate and municipalities with the highest proportion of vulnerable individuals (rate ratio (RR)=1.18, 95% confidence interval (CI): 1.01-1.27), with VL lower incidence rate (RR=0.62, 95% CI: 0.58-0.67) and a higher incidence rate of Acquired Immune Deficiency Syndrome (AIDS) (RR=1.20, 95% CI: 1.17-1.51). CONCLUSIONS: Linking the SINAN and SIM databases allowed the inclusion of 14% of otherwise underreported deaths from VL for the study period, showing that this method is useful for the surveillance of VL-related deaths. The size of the municipal population, proportion of the vulnerable population, incidence of disease, and the incidence of AIDS were associated with municipal lethality rates related to VL in Brazil.

Exposure to Leishmania spp. infection and Lutzomyia spp. in individuals living in an area endemic for visceral leishmaniasis in Brazil.

INTRODUCTION:This study aimed to investigate human exposure to Leishmania spp. infection and sandflies in an area endemic for the disease.METHODS:The presence of antibodies specific for Leishmania spp. and saliva of Lutzomyia spp. and that of L. infantum DNA in blood were evaluated.RESULTS: Antibodies against Leishmania spp. and sandfly saliva were observed in 20.8% and 37.7% of individuals, respectively. DNA of Leishmania spp. was amplified from the blood of one patient.CONCLUSIONS:The results suggest that Leishmania spp. infection may be underdiagnosed in this area.

Premature deaths by visceral leishmaniasis in Brazil investigated through a cohort study: A challenging opportunity?

BackgroundVisceral Leishmaniasis (VL) is the most severe form of leishmaniasis because it can lead to death. In the Americas, 96% of cases are in Brazil, and despite efforts, the fatality rate has increased in the past years. We analyzed deaths associated to VL in Brazil and investigated the factors that could influence on the timeliness of fatal outcome with emphasis on time (tStoD).MethodologyThe registered deaths by VL were sourced from the Brazilian National Notification System from 2007–2014. Through a retrospective cohort study, univariate and multivariable Cox proportional hazards model analysis were performed and investigated the factors that could influence the time (tStoD). These factors were analyzed through survival models.ResultsOut of the 1,589 reported deaths, the median for onset of the symptoms and the case notification date (tStoN) is 25 days (10–61), and for date of case notification and death (tNotD) is 9 days (4–17). The time (tStoN) to event investigation for HIV non-infected individuals was 1.4 (1.16–1.68) greater than the HIV positive group. At the same time peri-urban and urban area were 0.83 (0.47–1.44) and 1.33 (1.16–1.52), respectively. The explorations revealed apparent differences between the time to event investigation (both for tStoN and tNotD) and the age at the onset of the symptoms. According to the tStoN the rate of notification is 1.73 times greater in patients under 5 years old at the onset of the clinical symptoms compared to older patients.ConclusionVL patients under 5 years old were diagnosed earlier and had shorter survival. It could mean that in younger population, although properly diagnosed, the fatality pattern might be related to the severity of the disease. Main host characteristics were evaluated, and age and co-infections seem to have an impact in the disease progression.

Effectiveness of the mass use of deltamethrin-impregnated dog collars for preventing transmission of canine leishmaniasis by Lutzomyia spp.: A cluster randomized controlled trial

Visceral leishmaniasis (VL) is a zoonosis that greatly impacts public health, especially in developing countries. The effectiveness of deltamethrin-impregnated dog collars for preventing transmission of canine leishmaniasis (CanL) by the sand fly Lutzomyia spp. in countries with high incidence of the disease, such as Brazil, remains unknown. A cluster randomized controlled trial was carried out to evaluate the effectiveness of these collars in preventing infection of dogs with Leishmania infantum.Two areas were selected in a municipality endemic for VL in Brazil: an experimental area (EA) and a control area (CA). In both areas, blood samples were collected from dogs for detection of CanL. Seronegative dogs from the EA received collars impregnated with deltamethrin 4%. After six months, the dogs were retested for CanL and the incidence of the disease, the relative risk, and the effectiveness of collaring determined. In the baseline survey, 1020 dogs from the EA and 589 from the CA were examined. The prevalence calculated for EA was 4.41% (CI95% 3.27–5.91), and 7.13% (CI95% 5.25–9.59) for CA. In the second evaluation, 454 dogs from the EA and 292 from the CA were examined. The person-time incidence calculated for EA was 3.51% (CI95% 1.30–7.48), and for CA was 11.81% (CI95% 7.03–18.23). The difference between the calculated incidences was statistically significant (p = 0.009). The relative risk was 0.2972 (CI95% 0.1204-0.7339; p = 0.009), and the efficacy of the proposed measure was estimated in 70.27%.This report evaluated the effectiveness of the mass use of deltamethrin-impregnated dog collars in areas of transmission of VL by Lutzomyia spp. Collaring was able to protect dogs and may represent an effective strategy that could be implemented to control infection in both dogs and humans in Brazil and perhaps other countries where Lutzomyia spp. is the main vector of the disease.

Natural infection by Leishmania infantum in the Lutzomyia longipalpis population of an endemic coastal area to visceral leishmaniasis in Brazil is not associated with bioclimatic factors.

Visceral leishmaniasis (VL) is a zoonosis caused by the protozoan Leishmania infantum and in Brazil is transmitted mainly by the bite of Lutzomuyia longipalpis sand flies. Data about the presence, distribution, natural infection rate, seasonal and monthly dynamics of the vector population are important for optimizing the measures to control VL in endemic areas. This study aimed to identify sand fly fauna in an endemic area for VL to detect the prevalence of L. infantum infection in the Lu. longipalpis population and to elucidate the influence of bioclimatic factors on the monthly fluctuations of this vector. HP light traps were monthly set in the intradomicile and peridomicile of residences located in the central and beachfront areas of Camaçari, a VL endemic area. The sand fly collection was conducted in two periods: i) period 1—between December 2011 and November 2012 and ii) period 2—August 2014 and July 2015. Sand fly species were identified and detection of L. infantum infection by qPCR was performed in pools of female Lu. longipalpis. For the first time, the parasite load of positive pools was correlated with the number of Lu. longipalpis captured per month in both periods. Correlation analyses between the monthly fluctuation of the sand fly population and bioclimatic indices of the municipality in both collection periods were also performed. In both evaluated periods, more than 98% of the collected sand flies were Lu. longipalpis, confirming the predominance of this species in the region. It was captured mostly in the beachfront area in all months evaluated (99%). For the period 1, Leishmania DNA was detected in 81% of tested pools representing a minimal infection rate of 9.6%. In the period 2, 40% of the pools were positive with a minimal infection rate of 10.2%. Infected sand flies were only detected in the beachfront area in both periods. The parasite load was low and did not vary in the evaluated months despite the number of collected sand flies. No correlation was observed for climatic factors in both areas of Camaçari. These findings emphasize the high risk of Leishmania transmission in Camaçari regardless of the season and that other factors, aside from bioclimatic elements, are influencing the sand fly population monthly fluctuation.

Treatment for human visceral leishmaniasis: a cost-effectiveness analysis for Brazil.

To estimate the cost-effectiveness of strategies for the treatment of VL in Brazil. Cost-effectiveness study comparing three therapeutic options: meglumine antimoniate (MA), liposomal amphotericin B (LAMB) and a combination of LAMB plus MA (LAMB plus MA), from public health system and societal perspectives. An analytical decision-making model was used to compare strategies for the following outcomes: early therapeutic failure avoided at 30days, days of hospitalisation avoided and VL cure at 180days. The efficacy and safety parameters of the drugs came from a randomised, open-label trial and the cost data came from a cost-of-illness study, both carried out in Brazil. For all outcomes analysed, the LAMB strategy was more effective. The MA strategy was inferior to the LAMB plus MA strategy for the outcomes early therapeutic failure avoided and cure. When only LAMB and MA were compared from a societal perspective, a cost of US$ 278.56 was estimated for each additional early therapeutic failure avoided, a cost of US$ 26.88 for each additional day of hospitalisation avoided and a cost of US$ 89.88 for each additional case of cured VL, for the LAMB strategy vs. MA. In Brazil, the LAMB strategy proved to be cost-effective for treating VL, considering a GDP per capita as the willingness-to-pay threshold, for all of the outcomes analysed in comparison to MA.

Development and Clinical Evaluation of Loop-Mediated Isothermal Amplification (LAMP) Assay for the Diagnosis of Human Visceral Leishmaniasis in Brazil.

Visceral leishmaniasis (VL) is considered a major public health concern in Brazil and several regions of the world. A recent advance in the diagnosis of infectious diseases was the development of loop-mediated isothermal amplification (LAMP). The aim of this study was to develop and evaluate a new LAMP assay for detection of K26 antigen-coding gene of L. donovani complex. A total of 219 blood samples of immunocompetent patients, including 114 VL cases and 105 non-VL cases, were analyzed for the diagnosis of VL in the present study. Diagnostic accuracy was calculated against a combination of parasitological and/or serological tests as a reference standard. The results were compared to those of kDNA Leishmania-PCR. The detection limit for the K26-Lamp assay was 1fg L. infantum purified DNA and 100 parasites/mL within 60 min of amplification time with visual detection for turbidity. The assay was specific for L. donovani complex. Sensitivity, specificity, and accuracy were 98.2%, 98.1%, and 98.2%, respectively, for K26-LAMP and 100%, 100%, and 100%, respectively, for kDNA Leishmania-PCR. Excellent agreement was observed between K26-LAMP and kDNA Leishmania-PCR assays (K = 0.96). A highly sensitive and specific LAMP assay targeting K26 antigen-coding gene of L. donovani complex was developed for diagnosis in peripheral blood samples of VL patients.