Abstract
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-γ in the supernatants of SLA-stimulated PBMC, and of IFN-γ, 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.
Highlights
Leishmaniasis is a neglected, vector-borne disease associated with high morbidity, caused by protozoan pathogens of the genus Leishmania
It is important to be able to identify such patients to determine the prevalence of asymptomatic leishmaniasis in the human immunodeficiency virus (HIV)+ population, and because these persons are at increased risk of developing symptomatic visceral leishmaniasis
Among the present HIV+ subjects, none of whom showed any clinical manifestation of Leishmania infection, there was a group of 13 (15.85%) asymptomatic immune responders (ARI subjects) with a stimulation index (SI) of 2.39 in the soluble Leishmania antigen (SLA)-CPA test (Fig 1A)
Summary
Leishmaniasis is a neglected, vector-borne disease associated with high morbidity, caused by protozoan pathogens of the genus Leishmania. In visceral leishmaniasis (VL), the most serious form of the disease (fatal if untreated), the parasite is systemically disseminated. VL is hypoendemic in the Mediterranean region, where the causal agent is Leishmania infantum [1]. In 2017, nearly 160,000 people were diagnosed with HIV in the WHO European Region, marking another year of alarming new HIV numbers [2]. The number of reported cases of Leishmania/HIV co-infection increased rapidly during the 1990s, a consequence of the spread of the HIV pandemic, increased awareness among reporting institutions, and the growing geographical overlap between the two diseases [4]
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