Biomarkers in Leishmaniasis

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About this Research Topic

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Background

Leishmaniasis is one of the deadliest and most neglected of all tropical diseases. Effective therapy is central to any strategy for controlling leishmaniasis. In addition, the identification and management of asymptomatic subjects has become an increasingly important challenge in control programs. Furthermore, human vaccination has been proposed as the best cost-effective protection measure against leishmaniasis. There is, therefore an essential need for biomarkers that can help in monitoring the success of treatment in patients with active disease, to identify the asymptomatic population in areas where Leishmania is endemic, and to assess specific cell immunity to Leishmania infection.

Biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Some of the most important characteristics to achieve are robustness, stability, and specificity.

Most identified biomarkers for leishmaniasis are indirect markers, i.e., as biochemical markers, cytokines circulating in sera/plasma, etc. As a result, these biomarkers are also found in patients suffering from common concomitant infections. For that reason, direct markers are more recommendable, such as parasite nucleoid acids, skin test, T-cell stimulation response to leishmanial antigens, whole blood assay or antigen-antibody tests.

Biomarkers of cure can indicate the initiation of a successful response, which could shorten the duration of treatment and prevent relapses. Further, it could help to adjust dosages and to research the effectiveness of new treatments or combinations of current drugs. Individual analysis of every patient is needed to evaluate the real changes of a biomarker along with the monitoring of a treatment.

The search of biomarkers for asymptomatic status is limited by the poor definition of an asymptomatic case: someone from an endemic area, having an immune response (either antibody or cellular) against Leishmania but remains healthy. For this reason, no reference method for asymptomatic detection exists. It is essential to know the real prevalence of Leishmania infection for VL control programs and the role of asymptomatic population as reservoirs and in transmission.

To complicate this scenario is important to highlight that biomarkers in leishmaniasis have to be defined depending on geographical area and the infective specie. In addition, immunodepression increases the risk of developing leishmaniasis, modifies the clinical spectrum of leishmaniasis and increases the rate of treatment failure and recurrences. For that reason, biomarkers are urgently needed for the follow-up of co-infected HIV/Leishmania patients and with other types of immunosuppression.
Although reports on new candidate biomarkers are numerous, qualification and verification are a final step before validation.

Through this process, the number of candidate biomarkers are diminishing and the number of samples needed increasing. For that reason, few validated biomarkers exist for asymptomatic infection or for following treatment of active disease caused by Leishmania.

Keywords: Asymptomatic, cure, treatment, vaccine, leishmaniasis

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