RESUMEN
Tegumentary leishmaniasis due to Leishmania braziliensis is a parasitic disease that occurs in two stages after the infected sandfly bite: (1) a primary cutaneous lesion followed by (2) a secondary mucosal involvement generally resulting in severe facial deformities. In order to investigate the genetic and environmental factors involved in the development of the cutaneous lesion, a familial study was performed in a region of Bolivia in which the disease is endemic. Complete selection of 118 nuclear families (703 subjects, with 241 patients), each with at least one cutaneous affected subject, was achieved; 41 families were of native origin, and 77 (herein designated "migrant") recently had settled in the area. For the analysis, the trait under study was the time to onset of the primary cutaneous lesion. The start of the follow-up was birth, for native population, or date of arrival in the endemic area, for migrant population. Segregation analysis was performed by use of a model based on survival analysis methods that allows joint estimation of genetic and environmental effects and accounts for gene x covariate interactions. A significant effect of gender, home-forest distance, and forest-related activity was found. In the 77 migrant families there was evidence for a recessive major gene controlling the onset of the primary cutaneous lesion, with residual familial dependences and age x genotype interaction. Penetrance estimations show that young subjects are genetically more susceptible than older subjects, suggesting that this genetic component could concern mechanisms involved in the development of individual protection during childhood. There was also a significant genetic heterogeneity of the sample according to the native/migrant origin of the families, and no major-gene effect was found in the native subsample.
Asunto(s)
Leishmania braziliensis , Leishmaniasis Cutánea/genética , Adulto , Factores de Edad , Animales , Bolivia , Niño , Susceptibilidad a Enfermedades , Femenino , Humanos , Indígenas Sudamericanos/genética , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea Difusa/genética , Leishmaniasis Mucocutánea/genética , Masculino , Núcleo Familiar , Probabilidad , Factores de Tiempo , MigrantesRESUMEN
A survival analysis was performed on data from an endemic area of Bolivia where two populations, natives and highland migrants, were living, to investigate risk factors for onset of cutaneous leishmaniasis (CL) and its mucosal form (MCL). In a first data set (703 subjects with 242 CL patients), significant risk factors for CL were gender, native/migrant status, activity, and home-forest distance. The instantaneous risk of CL increased until adolescence in both populations, and rapidly decreased thereafter. This risk was 3-10 times higher in migrants than in natives until 20 years of age, and became similar thereafter. Environmental and behavioral factors did not seem sufficient to explain this contrast between the two populations, and this evolution with age may suggest differences in the mechanisms involved in the development of individual protection during childhood. In a second data set (446 CL patients with 34 mucosal forms) the native/migrant status was the main factor associated with the onset of mucosal form.