Effectiveness of Insecticide Spraying and Culling of Dogs on the Incidence of Leishmania infantum Infection in Humans: A Cluster Randomized Trial in Teresina, Brazil

Brazil. PLoS Negl Trop Dis 8(10): e3172. doi:10.1371/journal.pntd. 0003172 Effectiveness of Insecticide Spraying and Culling of Dogs on the Incidence of Leishmania infantum Infection in Humans: A Cluster Randomized Trial in Teresina, Brazil Guilherme L. Werneck 0 Carlos H. N. Costa 0 Fernando Ae cio Amorim de Carvalho 0 Maria do Socorro Pires e Cruz 0 James H. Maguire 0 Marcia C. Castro 0 Alon Warburg, The Faculty of Medicine, The Hebrew University of Jerusalem, Israel 0 1 Instituto de Estudos em Sau de Coletiva (UFRJ) e Departamento de Epidemiologia, Instituto de Medicina Social/IMS, Universidade do Estado do Rio de Janeiro (UERJ) , Maracana , Rio de Janeiro, Rio de Janeiro , Brasil , 2 Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Instituto de Doenc as Tropicais Nathan Portella and Universidade Federal do Piau , Teresina, Piau , Brasil , 4 Departamento de Bioqu mica e Farmacologia, Centro de Ciencias da Sau de, Universidade Federal do Piau , Teresina, Piau , Brasil , 5 Programa de Po s-Graduac a o em Ciencia Animal, Centro de Ciencias Agra rias, Universidade Federal do Piau , Teresina, Piau , Brasil , 6 Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts , United States of America Background: To evaluate the effect of insecticide spraying for vector control and elimination of infected dogs on the incidence of human infection with L. infantum, a randomized community intervention trial was carried out in the city of Teresina, Brazil. Methods/Principal Findings: Within each of ten localities in the city, four blocks were selected and randomized to 4 interventions: 1) spraying houses and animal pens with insecticide; 2) eliminating infected dogs; 3) combination of spraying and eliminating dogs, and 4) nothing. The main outcome is the incidence of infection assessed by the conversion of the Montenegro skin test (MST) after 18 months of follow-up in residents aged $1 year with no previous history of visceral leishmaniasis (VL). Reactions were measured at 48-72 h, induration of $5 mm considered positive. Interventions were executed after the baseline interview and repeated 6 and 12 months later. The effects of each type of intervention scheme on the incidence of infection were assessed by calculating relative risks and 95% confidence intervals using Poisson population-averaged regression models with robust variance. Among the 1105 participants, 408 (37%) were MST positive at baseline. Of the 697 negatives, only 423 (61%) were reexamined at the end of the follow-up; 151 (36%) of them converted to a positive MST. Only dog culling had some statistically significant effect on reducing the incidence of infection, with estimates of effectiveness varying between 27% and 52%, depending on the type of analysis performed. Conclusions/Significance: In light of the continuous spread of VL in Brazil despite the large scale deployment of insecticide spraying and dog culling, the relatively low to moderate effectiveness of dog culling and the non-significant effect of insecticide spraying on the incidence of human infection, we conclude that there is an urgent need for revision of the Brazilian VL control program. - Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: This study was funded by Health Surveillance Unit from the Brazilian Ministry of Health. GLW was partially funded by the Brazilian Research Council (CNPq 306267/2010-1 and 202088/2012-0). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Zoonotic visceral leishmaniasis (VL) is a severe neglected tropical disease leading to 4.5 to 6.8 thousand new cases each year in the Americas, mainly those living in poverty [1], [2]. In this region, the disease is caused by the protozoan parasite Leishmania infantum (syn = Leishmania chagasi), which is transmitted by the bite of female sandflies from the genus Lutzomyia, and dogs are considered the main source of infection in urban settings [3], [4]. Those who are infected usually exhibit no symptoms, but some 5 10% will develop clinical signs of the disease during the course of infection [5], [6]. Clinical VL is commonly characterized by fever, weight loss, hepatosplenomegaly, and pancytopenia, and is usually fatal if untreated [7], [8]. Malnutrition and genetic factors may play a role in the risk of developing clinical VL after infection [5], [9], [10]. Brazil accounts for some 90% of the disease burden in the Americas, with an estimate of 4.2 to 6.3 thousand cases per year Zoonotic visceral leishmaniasis (VL) constitutes a serious public health problem in the Americas, particularly in Brazil. The disease is caused by the protozoan parasite Leishmania infantum, which is transmitted by the bite of female sand flies, and dogs are the main source of infection. To decrease the risk of transmission, the Brazilian VL control program recommends residual insecticide spraying and environmental management for vector control, and culling of seropositive dogs in areas with moderate to high levels of transmission. Because there is a lack of scientific evidence supporting such interventions, we designed a study to assess the effectiveness of dog culling and residual insecticide spraying in the reduction of incidence of human VL infection. The results show that only dog culling had some statistically significant effect on reducing the incidence of infection, with estimates of effectiveness varying between 27% and 52%. In light of the continuous spread of VL in Brazil despite the large scale deployment of insecticide spraying and dog culling, the relatively low to moderate effectiveness of dog culling and the non-significant effect of insecticide spraying on the incidence of human infection, we conclude that there is an urgent need for revision of the Brazilian VL control program. and fatality rates around 7% [1]. A gradual process of VL urbanization started in the early 1980s in Brazil, initially causing epidemics in the cities of Teresina, Natal and Sao Luis, all located in the Northeast of the country, and later spreading to other major urban centers [11]. Between 2008 and 2010, 11,581 autochthonous VL cases were reported in 1,392 Brazilian municipalities, with 70% of cases occurring in only 165 municipalities, which had a total population of 40 million persons and included 12 state capitals and 52 cities with .100,000 inhabitants. Currently, the VL control program of the Brazilian Ministry of Health recommends two strategies for reducing the risk of transmission: (i) vector population control by means of residual insecticide spraying and (...truncated)