Assessment of Interferon-γ Levels and Leishmanin Skin Test Results in Persons Recovered for Leishmaniasis

Alimohammadian, Mohammad Hossein; Jones, Stephen L.; Darabi, F.; Riazi-Rad, Farhad; Ajdary, Soheila; A, Shabani; Rezaee, Mohammad Ali; Mohebali, Mehdi; Hosseini, Zohreh; Modabber, Farrokh

doi:10.4269/ajtmh.2012.11-0479

Cited by 18 publications

(18 citation statements)

References 25 publications

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“…The latter reported on an incremental increase in IFN-γ levels in cured individuals living in Northwest Ethiopia as compared to active patients but could not detect differences in IL-10 levels. Similar findings were reported in Turkish, Indian, Iranian, Spanish, and Bangladeshi VL patients [20,21,23,32,33], indicating a typical cellular hyporesponsiveness during active disease that restores after successful therapy, as was also reported in studies using peripheral blood mononuclear cell (PBMC). This was also reflected in the gradual increase in nonspecific PHA stimulation which suggests a broad mechanism of immunosuppression that merits further investigation.…”

Section: Discussionsupporting

confidence: 85%

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

Aleka

Ibarra-Meneses

Workineh

et al. 2020

Journal of Immunology Research

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Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.

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Section: Discussionsupporting

confidence: 85%

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

Aleka

Ibarra-Meneses

Workineh

et al. 2020

Journal of Immunology Research

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“…There is evidence that when LST data are supported with information on the production of antigen-specific interferon-γ (IFN-γ), this could better assist in determining whether a suspected case has been exposed to a Leishmania infection [ 21 ]. In contrast, it is reported that the LST is significantly more sensitive than IFN-γ levels in persons who have been cured of CL [ 22 ].…”

Section: Laboratory Diagnosismentioning

confidence: 99%

Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management

2015

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This review focuses on recent developments in the diagnosis, treatment, management, and strategies for the prevention and control of cutaneous leishmaniasis (CL) caused by both Old and New World Leishmania species. CL is caused by the vector-borne protozoan parasite Leishmania and is transmitted via infected female sandflies. The disease is endemic in more than 98 countries and an estimated 350 million people are at risk. The overall prevalence is 12 million cases and the annual incidence is 2–2.5 million. The World Health Organization considers CL a severely neglected disease and a category 1 emerging and uncontrolled disease. The management of CL differs from region to region and is primarily based on local experience-based evidence. Most CL patients can be treated with topical treatments, but some Leishmania species can cause mucocutaneous involvement requiring a systemic therapeutic approach. Moreover, Leishmania species can vary in their sensitivity to available therapeutic options. This makes species determination critical for the choice of treatment and the clinical outcome of CL. Identification of the infecting parasite used to be laborious, but now the Leishmania species can be identified relatively easy with new DNA techniques that enable a more rational therapy choice. Current treatment guidelines for CL are based on poorly designed and reported trials. There is a lack of evidence for potentially beneficial treatments, a desperate need for large well-conducted studies, and standardization of future trials. Moreover, intensified research programs to improve vector control, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are needed.

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“…The mean stimulation index values recorded after SLA challenge shows the cell-mediated immune response against Leishmania to be strongest in patients cured of VL. Differences in this response between patients cured of VL and CL have been reported previously, and might reflect a stronger systemic Th-1 response to occur in the former given the need to clear a much heavier parasite burden (Turgay et al, 2010 ; Alimohammadian et al, 2012 ). The patients with LLL—perhaps an evolved form of CL—showed the strongest immunological response before treatment, with Leishmania parasites present in affected lymph glands near the site of the Phlebotomus bite (Horrillo et al, 2015 ).…”

Section: Resultsmentioning

confidence: 64%

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

Botana

Matía

et al. 2018

Front. Cell. Infect. Microbiol.

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Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, Leishmania infantum infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an L. infantum-endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to Leishmania-specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples vs. 52% in cured VL samples, and IFAT in 90% vs. 56%; in the SLA-CPA, PBMC proliferation was seen in 16% vs. 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by L. infantum.

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Assessment of Interferon-γ Levels and Leishmanin Skin Test Results in Persons Recovered for Leishmaniasis

Cited by 18 publications

References 25 publications

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management

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

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