It is well established that visceral leishmaniasis (VL; also known as Kala azar) causes immunosuppression, and a successful drug treatment is associated with the development of cell-mediated immunity. Therefore combining a drug with an immune enhancer can provide a better approach for the treatment of the disease. Keeping this in mind, the in vivo antileishmanial efficacy of immunochemotherapy was evaluated with the use of a 78 kDa antigen with or without monophosphoryl lipid A (MPL-A) along with a traditional drug sodium stibogluconate (SSG) in Leishmania donovani infected BALB/c mice. Mice were infected intracardially with promastigotes of L. donovani, and 30 days after infection, these animals were given specific immunotherapy (78 kDa/78 kDa+MPL-A) or chemotherapy (SSG) or immunochemotherapy (SSG+78 kDa/SSG+78 kDa+MPL-A). Animals were euthanased on 1, 15 and 30 post-treatment days. The antileishmanial potential of the immunochemotherapy was revealed by significant reduction in the parasite burden (P<0·001). These animals were also found to exhibit increased delayed type hypersensitivity (DTH) responses, higher IgG2a levels, lower IgG1 levels and greater cytokine (IFN-γ and IL-2) concentrations compared with chemotherapy or immunotherapy alone, pointing towards the generation of a strong protective (Th1) type of immune response. Immunochemotherapy with SSG+78 kDa+MPL-A was found to be most effective in protecting mice against VL and therefore can be an alternative option for treatment of VL.

Co-treatment of mice infected with different strains of Leishmania donovani with a non-ionic surfactant vesicle formulation of buthionine sulfoximine (BSO-NIV), and sodium stibogluconate (SSG), did not alter indicators of Th1 or Th2 responses but did result in a significant strain-independent up-regulation of IL6 and nitrite levels by stimulated splenocytes from treated mice compared to controls. The efficacy of BSO-NIV/SSG treatment was dependent on the host being able to mount a respiratory burst indicating that macrophages are important in controlling the outcome of treatment. In vitro studies showed that SSG resistance was associated with a greater resistance to killing by activated macrophages, treatment with hydrogen peroxide or potassium antimony tartrate. Longitudinal studies showed that a SSG resistant (SSG-R) strain was more virulent than a SSG susceptible (SSG-S) strain, resulting in significantly higher parasite burdens by 4 months post-infection. These results indicate that SSG exposure may favour the emergence of more virulent strains.

The role of the essential nutrients, vitamins A,B (complex), C and E and iron, as prophylactic as well as supportive therapy in experimental visceral leishmaniasis (VL), was studied in hamsters. Prophylactic administration of vitamin C (50, 100 and 250 mg/kg) from day15 to day 0 (15 doses) significantly reduced the intake of Leishmania donovani in hamsters but had no therapeutic effect. In contrast, vitamins A,B complex and E and iron, whether used prophylactically or therapeutically, promoted parasite multiplication. The efficacy of sodium stibogluconate, a reference antileishmanial drug, was appreciably improved in animals administered prophylactically with vitamin C. However, supplementation of vitamin C during established infections resulted in reduced drug action. The results show that the prophylactic use of vitamin C may prevent the onset of leishmania infection and cautions against the indiscriminate use of nutrient supplements such as vitamin A, B complex, and E and iron in VL endemic areas.

The diagnosis of visceral leishmaniasis must be based upon a demonstration of the parasite in tissues of the patient. The best diagnostic test is a splenic aspirate, which is safe, highly sensitive and specific if the technique described in this paper is used and both smears and cultures of the aspirate are performed. Peripheral blood and nasal exudate have parasites in smears and/or cultures in 75 and 40% of Kenyan visceral leishmaniasis patients, respectively. Sodium stibogluconate (Pentostam) is the preferred treatment for visceral leishmaniasis. Recent Clinical Research Centre trials of different schedules of treatment with sodium stibogluconate are discussed. Currently, we recommend sodium stibogluconate, 20 mg/kg once daily for 30 days, for initial treatment. For patients who have not responded to initial treatment with sodium stibogluconate or have relapsed after initially responding to this treatment, we recommend sodium stibogluconate, 20 mg/kg once daily for 60 days. Further studies are now underway comparing the combination of allopurinol plus sodium stibogluconate versus sodium stibogluconate alone for unresponsive or relapsed patients.