Lucas Edel Donato

Background: Identification of risk and protective factors for canine visceral leishmaniasis (CVL) is essential to understand the epidemiology of the disease and direct prevention and control strategies. Building on a previous systematic review, this study presents new findings relating to the associations between CVL and a range of variables. Methods: The systematic review included articles from the previous review (up to September 2011) and additional studies published thereafter regarding factors associated with CVL in the American continent. The inclusion criteria encompassed studies that analyzed associations between CVL and socioeconomic, environmental, household-level, or dog-level variables, regardless of the diagnostic method employed. Meta-analyses were conducted using random-effects models and subgroup analyses, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to classify levels of evidence. Results: Of the 111 studies included in the analysis, the vast majority were cross-sectional (87.4%), conducted in Brazil (95.5%), and employed serological diagnostic tests alone (77.5%). The variables most consistently associated with CVL, based on moderate levels of evidence, were short-haired dogs, dogs dwelling in the peridomicile or with free access to the street, and proximity of the domicile to green areas. Male dogs, large dogs, ectoparasite-infested animals, dogs in contact with horses, and living in homes with yards also had higher odds of infection, although the levels of evidence were low. Other variables associated with CVL but assigned with very low levels of evidence included the presence of chickens, cats, sand flies, and other dogs in the dog environment; previous cases of CVL in the domicile; substandard custodianship; and guardians with poor education and low income. The quality of the studies has improved since the last review, although methodological limitations were still present, in particular, the absence of control for confounders. Conclusions: The analyses performed in this review strengthen the current knowledge of CVL and highlight the importance of further research to better understand some of the associated variables. Additional cohort and case–control studies are required, particularly those utilizing molecular diagnostics and adequate control for confounding factors. This review represents progress in understanding the determinants of CVL in the Americas and provides support for improving prevention and control strategies. Graphical

Understanding the distribution of tegumentary leishmaniasis (TL) in different periods enables the adequate conduction of actions at the public health level. The present study analyzes the spatiotemporal evolution of TL incidence rates in the municipalities of Brazil and identifies priority areas from 2001 to 2020. Notifications of new cases were analyzed employing space-time scan statistics and Local Indicators of Spatial Association. As TL incidence rates presented a downward trend in most Brazilian municipalities, spatiotemporal clusters of high relative risks (RR) were more frequent in the first decade of the series. There was a concentration of those clusters in the North and Northeast regions, mainly in the Legal Amazon area. More recent high-RR areas were identified in municipalities of different regions. The number of priority municipalities showed a stable trend in Brazil. There was a great concentration of such municipalities in the states of Acre, Mato Grosso, Rond & ocirc;nia, Par & aacute;, and Amap & aacute;, as well as large areas in Roraima, Amazonas, Maranh & atilde;o, and Tocantins, and smaller areas in the states of Goi & aacute;s, Cear & aacute;, Bahia, Minas Gerais, S & atilde;o Paulo, and Paran & aacute;. The present study contributes to the understanding of the historical evolution of TL in Brazil and subsidizes actions to combat the disease.

Aims: This study describes the spatio‐temporal dynamics of new visceral leishmaniasis (VL) cases notified in Brazil between 2001 and 2020.Methods and Results: Data on the occurrence of the disease were obtained by means of the Notifiable Diseases Information System of the Brazilian Ministry of Health. Joinpoint, temporal generalized additive models and conditional autoregressive (CAR) models were used to analyse the temporal evolution of the rates in Brazil, states and regions. Spatio‐temporal generalized additive and CAR models were used to identify the distribution of annual risks of VL occurrence in the Brazilian territory in relation to variation in the spatial average. There were 63,966 VL cases in the target period (3.198 cases/year), corresponding to a mean incidence rate of 1.68 cases/100,000 inhabitants. Of these, 4451 resulted in deaths, which gives a mean mortality rate of 0.12 deaths/100,000 inhabitants and a case fatality of 6.96%. The highest incidence rate was found in the North region, followed closely by the Northeast region, which presented the second and first highest mortality rates, respectively. For all of Brazil, and in the Northeast region, there were stability in the incidence rates, while the other regions showed an increasing trend in different time segments in the period: Central‐West up to 2011, North up to 2008, Southeast up to 2004, and South up to 2010. On the other hand, all regions experienced a reduction in incidence rate during the last years of the series. The Northeast region had the highest number of municipalities with statistically significant elevated relative risks. The spatio‐temporal analysis showed the highest risk area predominantly in the Northeast region in the beginning of the time series. From 2002 to 2018, this area expanded to the interior of the country.Conclusions: The present study has shown that VL has expanded in Brazil. However, the North and Northeast regions continue to have the highest incidence, and the risk of infection has decreased in recent years.

Dogs are the main reservoirs in the domestic transmission cycle of visceral leishmaniasis, and the diagnosis is essential for the effectiveness of the control measures recommended by the Brazilian Ministry of Health. We assessed the diagnostic performance of the ELISA-Vetlisa/BIOCLIN prototype with serum samples from 200 dogs, in triplicate, including symptomatic, oligosymptomatic, asymptomatic, and healthy dogs, originated by two distinct panels (A and B) characterized by parasitological tests as the reference standard. In this study, the prototype kit showed a 99% sensitivity (95%CI: 94.5-100.0) and a 100% specificity (95%CI: 96.4-100.0). The sensitivity of the prototype kit did not vary significantly with the clinical status of the dogs. Considering the final result classification (positive or negative), agreement between the results of repeated tests was almost perfect (kappa = 0.99; 95%CI: 0.98-1.00). ELISA-Vetlisa/BIOCLIN is a promising option for the serological diagnosis of canine visceral leishmaniasis in Brazil.

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.

The large number of activities contributing to zoonoses surveillance and control capability, on both human and animal domains, and their likely heterogeneous implementation across administrative units make assessment and comparisons of capability performance between such units a complex task. Such comparisons are important to identify gaps in capability development, which could lead to clusters of vulnerable areas, and to rank and subsequently prioritize resource allocation toward the least capable administrative units. Area-level preparedness is a multidimensional entity and, to the best of our knowledge, there is no consensus on a single comprehensive indicator, or combination of indicators, in a summary metric. We use Bayesian spatial factor analysis models to jointly estimate and rank disease control and surveillance capabilities against visceral leishmaniasis (VL) at the municipality level in Brazil. The latent level of joint capability is informed by four variables at each municipality, three reflecting efforts to monitor and control the disease in humans, and one variable informing surveillance capability on the reservoir, the domestic dog. Because of the large volume of missing data, we applied imputation techniques to allow production of comprehensive rankings. We were able to show the application of these models to this sparse dataset and present a ranked list of municipalities based on their overall VL capability. We discuss improvements to our models, and additional applications.

Visceral leishmaniasis (VL) is a neglected tropical disease of public health relevance in Brazil. To prioritize disease control measures, the Secretaria de Vigilância em Saúde of Brazil’s Ministry of Health (SVS/MH) uses retrospective human case counts from VL surveillance data to inform a municipality-based risk classification. In this study, we compared the underlying VL risk, using a spatiotemporal explicit Bayesian hierarchical model (BHM), with the risk classification currently in use by the Brazil’s Ministry of Health. We aim to assess how well the current risk classes capture the underlying VL risk as modelled by the BHM. Annual counts of human VL cases and the population at risk for all Brazil’s 5564 municipalities between 2004 and 2014 were used to fit a relative risk BHM. We then computed the predicted counts and exceedence risk for each municipality and classified them into four categories to allow comparison with the four risk categories by the SVS/MH. Municipalities identified as high-risk by the model partially agreed with the current risk classification by the SVS/MH. Our results suggest that counts of VL cases may suffice as general indicators of the underlying risk, but can underestimate risks, especially in areas with intense transmission. According to our BHM the SVS/MH risk classification underestimated the risk in several municipalities with moderate to intense VL transmission. Newly identified high-risk areas should be further evaluated to identify potential risk factors and assess the needs for additional surveillance and mitigation efforts.

É efetuada uma avaliação técnica e jurídica dos aspectos relacionadas ao controle da leishmaniose visceral no Brasil, com destaque para o tratamento de cães infectados, a eutanásia de cães soro reagentes e diagnósticos laboratorial da leishmaniose visceral canina (LVC).