Asymptomatic immune responders to Leishmania among HIV positive patients

Concomitant infection with human immunodeficiency virus (HIV) and the Leishmania parasite is a growing public health problem, the result of the former spreading to areas where the latter is endemic. Leishmania infection is usually asymptomatic in immunocompetent individuals, but the proportion of HIV+ individuals in contact with the parasite who remain asymptomatic is not known. The aim of the present work was to examine the use of cytokine release assays in the detection of asymptomatic immune responders to Leishmania among HIV+ patients with no previous leishmaniasis or current symptomatology. Eighty two HIV+ patients (all from Fuenlabrada, Madrid, Spain, where a leishmaniasis outbreak occurred in 2009) were examined for Leishmania infantum infection using molecular and humoral response-based methods. None returned a positive molecular or serological result for the parasite. Thirteen subjects showed a positive lymphoproliferative response to soluble Leishmania antigen (SLA), although the mean CD4+ T lymphocyte counts of these patients was below the normal range. Stimulation of peripheral blood mononuclear cells (PBMC) or whole blood with SLA (the lymphoproliferative assay and whole blood assay respectively), led to the production of specific cytokines and chemokines. Thus, despite being immunocompromised, HIV+ patients can maintain a Th1-type cellular response to Leishmania. In addition, cytokine release assays would appear to be useful tools for detecting these individuals via the identification of IFN-gamma in the supernatants of SLA-stimulated PBMC, and of IFN-gamma, MIG and IL-2 in SLA-stimulated whole blood. These biomarkers appear to be 100% reliable for detecting asymptomatic immune responders to Leishmania among HIV+ patients. Author summary The proportion of patients with HIV+ who have at some time been infected with the Leishmania parasite, but who remain asymptomatic, is unknown. It is important to be able to identify such patients to determine the prevalence of asymptomatic leishmaniasis in the HIV+ population, and because these persons are at increased risk of developing symptomatic visceral leishmaniasis. In the present work, a population of HIV+ patients showing a cellular immune response to Leishmania infantum was identified. These subjects all showed a clear Th1-type response when their PBMC or blood were stimulated in vitro with soluble Leishmania antigen (SLA). Cytokine release assays and the detection of IFN-gamma, MIG and IL-2 (specific biomarkers for immunity to Leishmania) were found to be useful for detecting this population of HIV+ patients. New studies with larger numbers of patients are needed to confirm the present results.