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

Ibarra-Meneses, Ana Victoria; Ghosh, Prakash; Hossain, Faria; Chowdhury, Rajashree; Mondal, Dinesh; Alvar, Jorge; Moreno, Javier; Carrillo, Eugenia

doi:10.3389/fcimb.2017.00200

Cited by 41 publications

(43 citation statements)

References 22 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%

“…Therefore, techniques such as the whole blood stimulation assay (WBA) which measures the in vitro cell-mediated immune response after stimulation with soluble Leishmania antigens have been proposed to monitor disease recovery [19,20]. Recent findings in cross-sectional studies of Ethiopia, Spain, and Bangladesh further enforced the idea that gradual increases in IFN-γ or in IFN-γ-induced protein 10 (IP-10 or CXCL10), monokine induced by IFN-γ (MIG or CXCL9), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein 1 (MCP-1 or CCL2) levels in soluble Leishmania antigen-(SLA-) stimulated whole blood could indicate that treatment has been successful and could be targeted as biomarkers of clinical cure in VL [20][21][22][23]. The search for a robust marker is still ongoing, as different cytokines and chemokines have been proposed, but vary by geographical area, Leishmania strain, and outcome identification (asymptomatic, active, cured).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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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“…Studies with biomarkers may prove useful in anticipating reactivation in coinfected individuals. 28 Thus, severe infections and mortality would likely decrease with early intervention, and the high cost and the discomfort of unnecessary treatments would be avoided.…”

Section: Visceral Leishmaniasis In Hiv-infected Patients In Brazilmentioning

confidence: 99%

Visceral Leishmaniasis in Hospitalized HIV-Infected Patients in Pernambuco, Brazil

Guedes

Medeiros

Silva

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Common in four continents, visceral leishmaniasis (VL) is an important but neglected disease. Human immunodeficiency virus (HIV) infection increases the risk of developing VL in people from leishmaniasis-endemic areas, with worse prognosis when there is coinfection. We conducted a cross-sectional study to determine the prevalence of HIV/VL coinfection in patients admitted in three referral hospitals for HIV/acquired immunodeficiency syndrome (AIDS) in Pernambuco, Brazil, and to compare epidemiological, clinical, and laboratory characteristics among HIV/VL coinfected and HIV mono-infected individuals. The sample consisted of HIV patients aged 18 years or more, in a period of data collection of 6 months. We performed four Leishmania tests-polymerase chain reaction (PCR), direct agglutination test, rK39, and latex agglutination test-and individuals with at least one positive test were considered coinfected. The HIV/VL coinfection prevalence we found was 16.9%. We observed large variation in prevalence according to the Leishmania test used, with low coincidence of positive tests. The most frequent symptoms found were weight loss (75.6%), fever (67.6%), and cough (55.3%). When we compared HIV/VL coinfected and HIV mono-infected groups we did not observe statistically significant differences. Low educational level (P = 0.004) and pallor (P = 0.009) were more frequent in the coinfected group. Serum albumin level was higher in coinfected individuals (P = 0.

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“…Both the LST and the in vitro peripheral blood mononuclear cell proliferation assay (CPA) involving soluble Leishmania antigen (SLA) are used interchangeably since they have good agreement (98-100%), although the latter is laborious and time-consuming [53]. However, a simpler cellular test currently in use for identifying asymptomatic people in the field is the whole blood stimulation assay and the subsequent detection of cytokines and chemokines in stimulated plasma, which reaches a very high specificity and sensitivity by monitoring the specific expression of IL-2 for L. infantum and MIG for L. donovani in WBA, while IP-10 production has been described as being useful for both [54]. IL-2 has been already tested in the field [45].…”

Section: Leishmaniasismentioning

confidence: 99%

Implications of asymptomatic infection for the natural history of selected parasitic tropical diseases

et al. 2020

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Progress has been made in the control or elimination of tropical diseases, with a significant reduction of incidence. However, there is a risk of re-emergence if the factors fueling transmission are not dealt with. Although it is essential to understand these underlying factors for each disease, asymptomatic carriers are a common element that may promote resurgence; their impact in terms of proportion in the population and role in transmission needs to be determined. In this paper, we review the current evidence on whether or not to treat asymptomatic carriers given the relevance of their role in the transmission of a specific disease, the efficacy and toxicity of existing drugs, the Public Health interest, and the benefit at an individual level, for example, in Chagas disease, to prevent irreversible organ damage. In the absence of other control tools such as vaccines, there is a need for safer drugs with good risk/benefit profiles in order to change the paradigm so that it addresses the complete infectious process beyond manifest disease to include treatment of non-symptomatic infected persons.

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

Cited by 41 publications

References 22 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

Visceral Leishmaniasis in Hospitalized HIV-Infected Patients in Pernambuco, Brazil

Implications of asymptomatic infection for the natural history of selected parasitic tropical diseases

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