Our group has recently been applying different molecular tools towards the study of specific diagnostics and the genotypic behaviour of L. (V.) braziliensis subpopulations in patients with mucocutaneous leishmaniasis [20, 21]. These studies served as a basis for the present investigation, which aimed to explore the relationship between genetic diversity of L. (V.) braziliensis at inter and intrapatient levels presenting distinct clinical manifestations of ATL. At the same time, this study also aimed to evaluate such genetic diversity following two hypothetical scenarios: (i) the individual, by him/herself, acting as a biological filter whereby highly adapted populations are selected and (ii) eco-epidemiological interactions occurring in the endemic area as reflecting on the dynamics of the circulating populations of L. (V.) braziliensis. According to our conceptual model, the situation at intrapatient level takes into account the participation of both parasite virulence factors and the immunological system of the host and that the reactivation of the disease would reflect in the emergence of different parasite subpopulations. However, at the interpatient level circumstance is that heterogeneous subpopulations circulate among man and vectors as well as domestic and sylvatic animals in simple and complex epidemiological interactions. In such specific cases individuals would be exposed to distinct selective pressures, to the polyclonality of the initial inoculum and also to multiple independent infections. If the biological entity that evolves is the clonal lineage , one can imagine different clones being reshuffled and propagated in the natural circulating population, sharing different factors of virulence or competing for selective advantages such as distinct growth rates and differential tropisms [23, 24].
Genetic variability of L. (V.) braziliensis, demonstrated here by polymorphisms of kDNA signatures, was identified among the patients and among different lesions of the same patient. Phenetic analysis was adopted to evaluate the degree of heterogeneity of the kDNA minicircles and group them into genetic profiles of different levels of differentiation, from more similar to more divergent. Although this study did not uncover a relationship between parasite genotype and clinical manifestations of ATL, considerably divergent genetic profiles have been detected in nasal mucosal lesions of patients with ML. Schriefer et al.  noted that a higher frequency of a determined genotype of L. (V.) braziliensis in certain isolates of ML originated from the same endemic area in the state of Bahia.
This idea of multiple independent infections may be an explanation corroborated by data from patient 34, with DL, whose results display significant genetic diversity in the minicircles from distinct cutaneous and mucosal lesions collected both at the same time and also at different moments over a short period of time.
Despite the existence of heterogeneity, genotypic similarities between the samples from cutaneous and mucosal lesions were evident on the intrapatient level. The average of the coefficients of similarities (0.80) was also of major significance, indicating that the samples are genetically related. Therefore, the intrapatient genetic variability, less than that between different patients (77%), must be a result that is also in accordance with the percentage of shared intrapatient characters (89%).
Elegant studies have demonstrated that the host immune system plays an important role in the selection of parasite populations [26–28]. Considering this, it is possible that man may act as a biological filter towards the selection of parasite subpopulations most adapted to develop in the host organism, and in this case, subpopulations can be responsible for either cutaneous or mucosal pathologies as mentioned in our conceptual model.
From the epidemiological point of view, the complex cycle of transmissions in which the individuals are exposed is a very important factor for the possibility of reinfections through the accumulation of multiple independent infections in patients residing in endemic areas [8, 29]. The complexity of transmission cycles, involving sylvatic and domestic mammals together with the phlebotamine vectors surely contributes to the large diversity of the natural population of L. (V.) braziliensis[30, 31]. An understanding of the genetic diversity of circulating parasite populations in a specific endemic area, as well as an investigation of the clonality of the initial lesions, is fundamentally important and assists us in interpreting the inter and intrapatient variability.