Lymphoproliferative response after stimulation with soluble leishmania antigen (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients

Abstract

The introduction of HAART resulted in the decrease of Leishmania/HIV co-infection cases; nevertheless, the number of relapses remains high and secondary prophylaxis is recommended. However, secondary prophylaxis is not necessary in all patients, and presents a high risk of toxicity and an elevated cost. Our aim was to study whether specific cellular response to Leishmania infantum (measured by cell proliferation response after stimulation with soluble Leishmania antigen (SLA)), could be a useful tool to attempt a secondary prophylaxis withdrawal. In June 2009 an outbreak of leishmaniasis by Leishmania infantum was declared in the southeast of Madrid, and since January 2013, we recruited 10 HIV+ patients that had been treated for visceral leishmaniasis. 6 patients had positive SLA-cell proliferation test. The mean CD4 cell counts of those patients with positive SLA were 140 cel/mm3 and 40 cel/mm3 in those with negative SLA test. 3 patients with positive SLA-cell proliferation test (CD4 count: 336, 307, 625) were not on prophylaxis, and the other 3 patients (CD4 count: 152, 189, 359) were on secondary prophylaxis that was withdrawn after the positive SLA-cell proliferation test with no posterior relapses (mean follow up 60 weeks). From the 4 patients, which had negative SLA-cell proliferation test and continued on prophylaxis, 3 had positive PCR for Leishmania at the end of the follow-up and 2 presented clinical relapses. The performance of SLA-cell proliferation test can be a useful tool that can permit us to try withdrawal of the prophylaxis in Leishmania/HIV co-infected patients with low CD4 counts under clinical supervision, diminishing risk of toxicity and cost.

New insights into leishmaniasis in the immunosuppressed

“…The measurement of the cell-mediated immune response in SOT recipients may help to confirm recovery following VL treatment and to assess the risk of relapse and necessity of secondary prophylaxis. Analysis of Leishmania -specific cell immunity in 5 SOT recipients patients that remained relapse-free after VL treatment showed positive lymphoproliferation and IFN-γ production after in vitro cell stimulation [ 35 ], in a similar way to that reported for HIV-positive patients after VL treatment [ 37 ].…”

IFN-γ, IL-2, IP-10, and MIG as Biomarkers of Exposure to Leishmania spp., and of Cure in Human Visceral Leishmaniasis

“…Assessments should also be made in the pediatric population. Cell-mediated immunity tests have recently been proposed for the follow-up of patients co-infected with HIV/ Leishmania (Castro et al, 2016). Since IP-10 identifies HIV/tuberculosis-infected patients, despite their low CD4 counts (Azzurri et al, 2005; Kassa et al, 2016), it might be used to monitor for relapses of leishmaniasis in HIV/ Leishmania -infected patients.…”

Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease

“…Unfortunately, PCR and serological tests are not good indicators of cure (WHO, 2017 ). PCR detects parasites in active VL, but after the first doses of treatment their numbers can fall dramatically (Castro et al, 2016 ) while clinical manifestations of disease remain. Further, the non-detection of peripheral blood parasites does not necessarily mean that the spleen, liver, or bone marrow are parasite-free, which might allow for the reactivation of clinical disease months later, as repeatedly reported in immunosuppressed patients (van Griensven et al, 2014 ).…”

“…Indeed, the proliferation of blood mononucleocytes (PBMC) after challenge with soluble leishmanial antigen (the soluble Leishmania antigen cell proliferation assay [SLA-CPA]) (Singh and Sundar, 2014 ; Carrillo et al, 2015 ), and increased IFN-γ secretion by these cells (Hailu et al, 2004 ; Kumar et al, 2014 ), provide in vitro markers that might be used to assess early response to treatment. In fact, PBMC proliferation has been shown a useful indicator of the existence of Leishmania -specific T cell memory clones in HIV+ patients, sufficient to keep the parasitic infection under control and avoid relapsing VL (Castro et al, 2016 ). The value of IFN-γ in monitoring the cellular immune response has previously been reported in VL caused by L. infantum (Cillari et al, 1995 ; Adem et al, 2016 ; Ibarra-Meneses et al, 2017 ).…”