Revisão sistemática e meta-análise da prevalência de Leishmania spp. em vetores da leishmaniose tegumentar americana no Brasil e mapeamento de áreas prioritárias para sua vigilância na região Nordeste do país

Abstract

American cutaneous leishmaniasis (ACL) is a neglected disease whose transmission involves complex interactions among different protozoan species of the genus Leishmania, sand fly vectors, and vertebrate hosts in diverse ecological settings. This dissertation is organized into an introductory chapter of general considerations, followed by two chapters written in the format of scientific articles, which investigate the ecology and epidemiology of ACL. The second chapter presents a systematic review and meta-analysis focusing on natural Leishmania spp. infection prevalence and blood meal sources of vectors in Brazil. Data from 71 studies were synthesized, revealing a pooled prevalence of 2.17% (n=52,315 specimens). The vectors of greatest epidemiological importance were Nyssomyia whitmani (3.54%) and N. umbratilis (1.71%), with the latter standing out as the main vector of L. (V.) guyanensis in the Amazon. N. whitmani demonstrated trophic and parasitic plasticity, with infection by different Leishmania species and an infection rate for L. (V.) braziliensis of 1.03%. Blood meal analysis revealed a high frequency of detection for animal groups commonly found in peridomestic settings, such as birds (35.75%) and humans (21.35%), suggesting vector interaction with anthropized environments. The third chapter focused on mapping ATL risk in Northeast Brazil (2013-2024), integrating ecological niche modeling, spatial autocorrelation analysis, and space-time scanning. The vector suitability model (AUC = 0.86 ± 0.02) identified precipitation of the coldest quarter as the main environmental determinant, with high suitability in eastern Maranhão, northern Piauí, and the Atlantic Forest coastal strip. Disease incidence showed strong positive spatial autocorrelation [Moran's (I) coefficient = 0.55; p < 0.05], forming High-High clusters concentrated in the states of Maranhão (58.1% of municipalities), Bahia (36.5%), and Ceará (13.5%). Space-time scanning detected 18 recent (2021-2024) high-risk clusters, with notable clusters in the states of Bahia [Relative Risk (RR) = 29.7] and Ceará (RR = 70.6). Bivariate LISA analysis demonstrated that high-incidence clusters spatially overlap areas of high forest cover (I = 0.32) and extreme social vulnerability, especially lack of urban

infrastructure (I = 0.13) and low human capital (I = 0.09), with high concentration in Maranhão. The confluence of high vector suitability and high incidence identified priority municipalities for surveillance in Maranhão (40.4%) and Bahia (35.8%). In summary, these findings confirm that ACL transmission is driven by a combination of specific vector species with ecological plasticity and distinct epidemiological profiles, and spatially defined hotspots where environmental suitability converges with critical socioeconomic vulnerability. The identification of N. whitmani and N. umbratilis as key vectors, along with the precise mapping of priority areas in Maranhão, Bahia, and Ceará, provides support for the implementation of integrated surveillance and control strategies, focused on the municipalities and epidemiological scenarios with the highest identified risk.