Comment on: Unresponsiveness to AmBisome in some Sudanese patients with kala-azar.

he excellent paper by Mueller et al. (2007) gives us an idea f how difficult it is to perform clinical research in field conitions, however I believe that their final recommendation or the use of combined antileishmanial therapy could not e drawn from their study. They have seen that a group of failing patients to mBisome—–after a previous relapse with antimonials—–do espond to a second course of antimonials. They therefore ecommend combined or sequential therapy with both drugs n relapse cases. HIV co-infected patients tend to have a higher paraite burden, lower positive serology rates, frequent relapses nd a protracted course, despite different and multiple ntileishmanial therapies (Alvar et al., 1997). Very immunoompromised HIV patients with visceral leishmaniasis have mastigotes in their bone marrow, skin and other tissues, ven when they do not have clinically overt kala-azar. For hese cases, addition of effective antiretroviral therapy s pivotal for immune restoration and parasite clearance Russo et al., 2003). It is very likely that most of the failng patients to AmBisome in Mueller et al.’s study were o-infected with HIV: they had a higher parasite burden, ower positive serology rates, had had a relapse and showed protracted course. Unfortunately, HIV testing could not e performed in six of the patients owing to the extremely ifficult field conditions. To the best of my knowledge, combined antileishmanial herapy with AmBisome and antimonials has not been tested n randomised clinical trials. Sequential therapy has been sed in many HIV co-infected patients without significant uccess. Combination therapy might prevent the develpment of Leishmania resistance, but again clinical and re-clinical data are lacking. In addition, if failing patients esponded to a second course of antimonials the possibilty of resistance to this drug is very unlikely, although it s possible that AmBisome significantly lowered the parasite urden, facilitating clinical success of the second antimonial ourse. I believe that relapsing cases should be HIV tested and, f positive, the treatment approach should include secndary prophylaxis until antiretroviral therapy is available nd effective. If this is not possible, a second course of antionials compared with AmBisome therapy or even the use f oral miltefosine for refractory cases could be a better pproach instead of recommending combined therapy, until ore pre-clinical and clinical data are available. o i r a a Correspondence