Canine serological survey and dog culling ant its relationship with Human Visceral leishmaniasis in an endemic urban area
Visceral leishmaniasis is an important but neglected disease that is spreading and is highly lethal when left untreated. This study sought to measure the Leishmania infantum seroprevalence in dogs, the coverage of its control activities (identification of the canine reservoir by serological survey, dog culling and insecticide spraying) and to evaluate its relationship with the occurrence of the disease in humans in the municipalities of Araçatuba and Birigui, state of São Paulo, Brazil.
... lo, Brazil. Methods: Information from 2006 to 2015 was georeferenced for each municipality and modeling was performed for the two municipalities together. To do this, latent Gaussian Bayesian models with the incorporation of a spatio-temporal structure and Poisson distribution were used. The Besag-York-Mollie models were applied for random spatial effects, as also were autoregressive models of order 1 for random temporal effects. The modeling was performed using the INLA (Integrated Nested Laplace Approximations) deterministic approach, considering both the numbers of cases as well as the coverage paired year by year and lagged at one and two years. Results: Control activity coverage was observed to be generally low. The behavior of the temporal tendency in the human disease presented distinct patterns in the two municipalities, however, in both the tendency was to decline. The canine serological survey presented as a protective factor only in the two-year lag model. Conclusions: The canine serological coverage, even at low intensity, carried out jointly with the culling of the positive dogs, suggested a decreasing effect on the occurrence of the disease in humans, whose effects would be seen two years after it was carried out. Background Visceral leishmaniasis (VL) is considered a neglected tropical disease. It presents a high fatality rate, which can attain 100% if left untreated [1, 2]. In Brazil, VL control is based on the Visceral Leishmaniasis Control Program (VLCP), the main strategies of which include the diagnosis and timely treatment of human cases, environmental management and chemical control of the vector with residual insecticide spraying, and the canine serological survey and the canine culling of positive dogs considered was the urban region of the municipalities of Araçatuba (21° 12′ 41″ S; 50° 25′ 34″ W) and Birigui (21º 17' 19" S; 50º 20' 24" W), plus a rural census tract of Birigui, as a connecting area between them (Fig 1) . The study area is located in the northwest of the state of São Paulo. We chose these municipalities as they were the first to present autochthonous HVL in the state of São Paulo and they are adjacent, thus allowing us to consider them as a single study area. Fig 1. Map of the study area composed of the municipalities of Birigui and Araçatuba. (A) Urban areas of the municipalities of Araçatuba and Birigui and rural area of the municipality of Birigui, State of São Paulo, Brazil. (B) Indication of the area of study, represented by the red rectangle, located in the State of São Paulo, Brazil, and South America. The map was made by the authors, through QGIS Software Development Team (QGIS 2.18.20), available at and using the layers obtained from the Brazilian Institute of Geography and Statistics (IBGE), available at . SOURCES OF INFORMATION AND GEOREFERENCING. To apply zoonosis control measures, the municipalities divide the urban area into sectors (denominated as "SUCEN Sectors") that were chosen as the units of analysis (Fig 1) . Additionally, the Brazilian Institute of Geography and Statistics (IBGE) provides the population census data every 10 years and they divide the area in a different track (nominated as IBGE census track). Thus, digital maps of the area were constructed referencing both SUCEN sectors and IBGE census track, using the latter for the rural area. The Zoonoses Control Center of the respective municipalities provided information according to the units of analysis and year of the human cases (residential address and year of occurrence), the control activities (number of dogs with seropositive tests for VL culled and number of properties sprayed with insecticide), and the surveillance measure (number of dogs evaluated in the canine serological survey). The diagnostic tests used to identify infected dogs are the TRdPP®-Bio-Manguinhos test for screening and the ELISA test as a test to confirm the previous results. The TRdPP®-Bio-Manguinhos advertises Another issue that must be considered is the lack of accuracy of available serological tests, especially for asymptomatic dogs. Grimaldi et al.  highlight the TRdPP®-Bio-Manguinhos presents high sensitivity (98%) for diagnosed dogs with symptoms, but low sensitivity to identify dogs without signs and symptoms (47%). Moreover, these authors discuss that the ELISA test, despite having reliable sensitivity (ranging from 93% to 100%) for symptomatic dogs, also presents less sensitivity for dogs without symptoms. It is noteworthy that, even using tests with low sensitivity for asymptomatic dogs, our results suggested an inverse relationship between HVL incidence and canine survey. Moreover, we were unable to consider controlling the model for HIV/AIDS incidence during the study period. HIV/ AIDS coinfection is known associated with higher risk of VL human symptomatic infection and has important epidemiological and clinical implications. In endemic areas, it is common for cases of VL to be asymptomatic. However, HIV coinfection increases the risk of developing symptomatic VL by between 100 and 2320 times . Since it was not possible to adjust our models for the incidence of HIV / AIDS, it is not possible to state what effect this variable would have on the relationship between the incidence of HVL and the canine serological survey coverage, an issue that needs to be investigated in new studies. Another limitation is the use of secondary data. Nevertheless, these data were indispensable and appropriate for the development of the study. It is worth noting that it is the health teams which make the decisions about the planning of the surveillance actions and control of VL in their respective municipalities based on this information. This information is essential for all involved in VL control efforts. Strengths of the study include the consideration of the spatial and temporal dependence of the phenomenon studied and, consequently, more accurate estimates were obtained than in studies that did not take these dimensions into account. The proximity of Araçatuba to Birigui is also worth mentioning as it made it possible to evaluate the relationship between HVL and control measures 15 more comprehensively and with greater study power, given the greater number of units of analysis. Conclusions Our study revealed that the canine serological survey in the municipalities of Araçatuba and Birigui, undertaken concomitantly with the canine culling of positive dogs, although with incomplete coverage, suggests a reduction in the risk for the occurrence of HVL of 34%, with the effects observed after two years of the implementation of these control measures. Therefore, the study suggest that, even when below the recommended levels, the control measures directed at the canine reservoir were effective for the control of HVL.