Leishmaniasis Disease - Proteins, Assays & ELISA Kits

Leishmaniasis is a parasitic disease that is found in southern Europe, the tropics, and subtropics. The protozoan parasites, Leishmania, are the causative agents of leishmaniases. There are over 20 different species of Leishmania that infect humans. This parasite is transmitted to humans through the bite of phlebotomine sand flies. There are over 1.3 million cases of leishmaniasis every year, causing 20-30,000 deaths.

Following infection, Leishmania parasites interact with the cells of the mononuclear phagocytic system, namely, dendritic cells and macrophages. Although uncommon, Leishmania can be transmitted from person to person via blood transfusions, infected needles or syringes, or congenitally from mother to baby. It is important to note that not everyone who becomes infected develops the disease, some can be infected without displaying any clinical signs or symptoms of leishmaniasis.

There are three different clinical types of leishmaniasis; cutaneous, visceral, and mucosal. Cutaneous leishmaniasis (CL) is the most common type. It is characterized by sores on the skin which can develop anywhere between a week to a month following infection. This can lead to scarring or secondary infections. Visceral leishmaniasis (VL) or Kala-Azar, is the most severe form of the disease. It can develop from 10 days up to a year following the bite of the sandfly. Visceral leishmaniasis affects internal organs, namely, the spleen, liver and bone marrow. The mucosal form of the disease is the least common (ML). It results in partial or complete destruction of the mucous membranes in the nose, mouth or throat, and can occur as a complication of cutaneous leishmaniasis. Currently, there are no vaccines available to treat humans.

Peroxiredoxins are vital for parasitic defence mechanisms, subsequently, their absence can be detrimental. Cytosolic peroxiredoxin has proven to be essential in the protection of Leishmania against peroxides. To ensure the survival and persistence of Leishmania, their resistance to host microbicidal responses is crucial.

Heavily glycosylated soluble acid phosphatases (SAPs) are present on the surface of Leishmania species. Their rate of release is dependent on the particular Leishmania species. SAPs play an important role in the modulation of the host environment via dephosphorylation, as well as, the preparation of nutrients for the parasite. In addition, they are resistant to proteolytic degradation. This is beneficial to the parasite as the sandfly midgut has a low pH and contains large amounts of digestive enzymes.

Studies in hamster models have been carried out to determine specific biomarkers that indicate the cure of CL. Results have shown that high levels of TGFbeta1 are associated with active disease. In addition, increased EGF levels have been linked with the cure of lesions. Overall, it has been suggested that the EGF/TGFbeta1 ratio may act as a potential biomarker of infection or response to treatment.

For the development of a vaccine available against human leishmaniasis, determination of biomarkers that correlate with the degree of protection achieved are crucial. It has been reported that high levels of granzyme B are associated with increased protection against CL. Thus, granzyme B could be a strong biomarker for the assessment of the effectiveness of vaccines.

Previous studies have indicated that serum levels of macrophage activators, neopterin and sCD40L, are reduced in patients with active VL, and increased in asymptomatic patients. Therefore, these biomarkers could be used for the prediction of disease progression in VL patients.

T helper 1 (Th1) and T helper 2 (Th2) cell development is an important branch point in the immune response. It is a key determinant of the human immune response to an infectious pathogen which can lead to either protection of the host or dissemination of disease. Th1 cells produce IFN-gamma, IL-2 and IL-12, while Th2 cells produce IL-4, IL-6, IL-10, IL-13, and TGF-Beta.

The interaction between the Leishmania parasite and host immune cells generates an exacerbated proinflammatory response. This plays a vital role in the development of leishmaniasis clinical manifestations. In response to Leishmania, numerous cells at the site of infection release chemokines, namely, MIP-1A, MIP-1B and MIP-2. Subsequently, inflammatory cells such as neutrophils are recruited.

Various cytokines and the lipid mediator leukotriene B4 (LTB4) are involved in inflammation during leishmaniasis. The cytokines TNF and IL-1 are produced by macrophages upon recognition of a pathogen, in this case, Leishmania. These cytokines induce the expression of adhesion molecules, thus promoting inflammation. During leishmaniasis, phagocytes are stimulated to produce the anti-inflammatory cytokine, IL-10. When expressed in large quantities, IL-10 can have deleterious effects, leading to reduced production of Th1-related cytokines, such as IL-12 and IFN-Gamma. This may cause premature suppression of innate and acquired immune responses. In addition, through polarization of CD4+ T cells, IL-4 defines the cell profile and modulates the response from surrounding cells during Leishmania infection.

The pathogenesis of chronic viral and non-viral infections in humans is thought to be impacted by an imbalance of Th1 and Th2 cells. This can be noted in diseases such as leishmaniasis, leprosy, HIV, and viral hepatitis.

The immunometabolism field presents novel opportunities to interfere with pathological conditions. Pentavalent antimonials are compounds used for the treatment of leishmaniasis. Leishmania-killing mechanisms, such as the disturbance of fatty acids beta-oxidation or apoptosis, have been attributed to these compounds. Antimonials inhibit the glycolysis pathway, directly acting on infected macrophages. Thereafter, these compounds elicit an oxidative/nitrosative stress response against internalised parasites. Assay Genie provides Glycolysis and Fatty Acid Oxidation immunometabolism assay kits that would support leishmaniasis research.

Many experimental models including dog, hamster, mouse, and non-human primate models have been developed to characterize the immune response to leishmaniasis. The golden Syrian hamster is highly susceptible to infection with VL and thus, is considered the best animal model for the study of VL infection. Assay Genie offers a wide range of animal model ELISA kits with the potential to support the advancing field of leishmaniasis research.