Clonal diversity in the expression and stability of the metastatic capability of Leishmania guyanensis in the golden hamster

Metastatic disease is a major concern of dermal leishmaniasis caused by Lei shmania of the Viannia subgenus. The golden hamster provides an experimenta l model of systemic dissemination and cutaneous metastasis of Leishmania Vi annia. We have exploited this model to examine the expression of parasite v irulence in cloned populations derived from a strain of L. guyanensis previ ously shown to be highly metastatic in the hamster. Metastatic capacity man ifested as dissemination throughout the lymphoid organs; cachexia and secon dary cutaneous lesions were found to differ among clones, yielding a spectr um of virulence. The metastatic phenotype of clonal populations was stable over 5 sequential passages in hamsters. In addition, the low or high propen sity to disseminate and produce cutaneous metastatic lesions was reproduced . Capacity to disseminate from the inoculation site was conserved following subcloning of metastatic clones that had been passaged in culture for seve ral generations: clinical manifestations, cachexia, and cutaneous metastati c lesions were variably expressed. Dissemination of parasites and cachexia were significantly related (P = 0.004. Overall, cachexia was an earlier man ifestation of dissemination than cutaneous metastases (P < 0.001). The repr oducible expression of virulence phenotypes by discrete populations of Leis hmania in the golden hamster provides an experimental model for clinically relevant expression of virulence in human leishmaniasis.