RESUMO
Visceral leishmaniasis (VL) in northeast Brazil is a disease caused by infection with the protozoan Leishmania chagasi. Infection leads to variable clinical outcomes ranging from asymptomatic infection to potentially fatal disease. Prior studies suggest the genetic background of the host contributes to the development of different outcomes after infection, although it is not known if ancestral background itself influences outcomes. VL is endemic in peri-urban areas around the city of Natal in northeast Brazil. The population of northeast Brazil is a mixture of distinct racial and ethnic groups. We hypothesized that some sub-populations may be more susceptible than others to develop different clinical outcomes after L. chagasi infection. Using microsatellite markers, we examined whether admixture of the population as a whole, or markers likely inherited from a distinct ethnic background, differed between individuals with VL, individuals with an asymptomatic infection, or individuals with no infection. There was no apparent significant difference in overall population admixture proportions among the three clinical phenotype groups. However, one marker on Chr. 22 displayed evidence of excess ancestry from putative ancestral populations among different clinical phenotypes, suggesting this region may contain genes determining the course of L. chagasi infection.
Assuntos
Leishmania/fisiologia , Leishmaniose Visceral/etnologia , Leishmaniose Visceral/genética , Animais , Brasil/etnologia , Humanos , Leishmaniose Visceral/parasitologia , Repetições de MicrossatélitesRESUMO
The protozoan Leishmania chagasi can cause disseminated, fatal visceral leishmaniasis (VL) or asymptomatic infection in humans. We hypothesized that host genetic factors contribute to this variable response to infection. A family study was performed in neighborhoods of endemicity for L. chagasi near Natal in northeastern Brazil. Study subjects were assessed for the presence of VL or asymptomatic infection, which was defined by a positive delayed-type hypersensitivity (DTH) skin test response to Leishmania antigen without disease symptoms. A genomewide panel of 385 autosomal microsatellite markers in 1254 subjects from 191 families was analyzed to identify regions of linkage. Regions with potential linkage to the DTH response on chromosomes 15 and 19, as well as a novel region on chromosome 9 with potential linkage to VL, were identified. Understanding the genetic factors that determine whether an individual will develop symptomatic or asymptomatic infection with L. chagasi may identify proteins essential for immune protection against this parasitic disease and reveal strategies for immunotherapy or prevention.
Assuntos
Cromossomos Humanos Par 15 , Cromossomos Humanos Par 19 , Imunidade Inata/genética , Leishmania/patogenicidade , Leishmaniose/imunologia , Adolescente , Animais , Brasil , Criança , Pré-Escolar , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 15/imunologia , Cromossomos Humanos Par 15/parasitologia , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 19/imunologia , Cromossomos Humanos Par 19/parasitologia , Doenças Endêmicas , Feminino , Ligação Genética , Humanos , Hipersensibilidade Tardia/genética , Hipersensibilidade Tardia/imunologia , Lactente , Leishmaniose/fisiopatologia , Masculino , FenótipoRESUMO
Peri-urban visceral leishmaniasis (VL) caused by Leishmania chagasi is emerging in a new epidemiologic pattern in Brazilian cities. We studied peri-urban VL in endemic neighborhoods surrounding Natal, Brazil, identified through hospitalized individuals with VL. Clinical and environmental information obtained for 1106 members of 216 families living in endemic neighborhoods enabled us to identify 4 groups: VL: individuals with current or prior symptomatic visceral leishmaniasis (n = 135); DTH+: individuals with positive delayed-type hypersensitivity response with no history of VL (n = 390); Ab +: individuals with negative DTH response and seropositive (n = 21); DTH -: individuals with negative DTH and seronegative (n = 560). The mean +/-SD age of VL was 9.3+/-12.3 y. The gender distribution was nearly equal below age 5, but skewed toward males at higher ages. Acutely infected VL subjects had significantly lower hematocrits, neutrophils, and eosinophils than other categories. AB+ subjects also had lower eosinophil counts than others, a possible immune marker of early infection. VL was not associated with ownership of dogs or other animals, raising the question whether the reservoir differs in peri-urban settings. This new pattern of L. chagasi infection enables us to identify epidemiological and host factors underlying this emerging infectious disease.
Assuntos
Anticorpos Antiprotozoários/sangue , Doenças Transmissíveis Emergentes/epidemiologia , Leishmania/imunologia , Leishmaniose Visceral/epidemiologia , População Urbana , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/parasitologia , Doenças Transmissíveis Emergentes/fisiopatologia , Feminino , Humanos , Hipersensibilidade Tardia , Lactente , Recém-Nascido , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distribuição por SexoRESUMO
The sensitivity and specificity of a Leishmania chagasi recombinant K39 (rK39)-based enzyme-linked immunosorbent assay (ELISA) for visceral leishmaniasis (VL) was assessed in Natal, Brazil. Anti-rK39 antibodies were detected in 93.3% of patients with parasitologically confirmed VL (n = 120) and in 33 others with clinically diagnosed disease. Anti-rK39 antibodies decreased significantly following treatment. The presence of antibodies was inversely correlated with development of a positive leishmanin skin test result. Anti-rK39 antibodies were detected in only 2.9% of asymptomatic subjects with a positive skin test result (n = 168). They were not detected in healthy controls (n = 30) or in persons with Chagas' disease (n = 13) or active tuberculosis (n = 31). Antibodies were found in only one of 13 patients with cutaneous leishmaniasis. In contrast, an ELISA using total L. chagasi promastigote antigen was sensitive, but not specific. The results indicate that the rK39-based ELISA is a sensitive and specific diagnostic test for symptomatic VL and can differentiate progressive from self-resolving infection.