Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy.

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Drug Resistance in Leishmaniasis

The group of diseases known as the leishmaniases are caused by obligate intracellular protozoa of the genus Leishmania ([39][1]). Natural transmission of leishmania is carried out by a certain species of sandfly of the genus Phlebotomus (Old World) or Lutzomyia (New World). These are present in

Laboratory Diagnosis of Visceral Leishmaniasis

In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.

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Use of antimony in the treatment of leishmaniasis: current status and future directions.

Leishmaniasis is a spectrum of diseases ranging in severity from cutaneous (CL), post-kala-azar dermal (PKDL), and diffuse cutaneous (DCL) to mucocutaneous (MCL) and visceral (VL) infections that are endemic in 86 tropical and subtropical countries around the world, accounting for 75,000 deaths per year. Different forms of leishmaniases are generally caused by different distinct species of Leishmania having a digenetic life cycle alternating between an aflagellated amastigote form replicative within the macrophages of the host and a flagellated promastigote form that multiplies within the gut of the sandfly. VL, MCL, PKDL, DCL, and CL forms of the disease can be arranged on a priority basis in accordance with the humoral immune responses of host. Generally, the cell-mediated immunity, particularly the delayed-type hypersensitivity to leishmanial antigens, is associated with CL, MCL, PKDL, and cured VL cases. The serodiagnosis of leishmaniasis appears to be an alternative to parasite detection in b...

Serodiagnosis of Leishmaniasis

Cell-mediated immune (CMI) response in 16 Indian kala-azar (KA) and 12 post-kala-azar dermal leishmaniasis (PKADL) patients was studied in detail by in vitro lymphocyte transformation experiments and by in vivo skin testing. Peripheral blood lymphocytes of active KA patients failed to be stimulated by leishmania antigen. On the other hand, lymphocytes from a majority of the active KA patients could be stimulated by phytohemagglutinin. Active KA patients also failed to show delayed type hypersensitivity reaction to leishmanin, although 72% of them showed delayed type hypersensitivity to a purified protein derivative of tuberculin. Longitudinal studies indicated that antigen-specific CMI response usually appeared in treated KA patients after 12 to 20 weeks of antileishmanial drug therapy, although individual variations were noted. CMI response in PKADL patients was variable as about two-thirds of them showed positive sensitization to leishmania antigen in either in vivo or in vitro tests. Usually, patients with newly acquired PKADL exhibited better CMI response than those with chronic PKADL. However, lymphocytes from all of these patients could be stimulated normally by phytohemagglutinin. Results presented in this study show an impairment of CMI response in active KA which appears to be more specific to leishmania than generalized in nature. Moreover, restoration of specific T-cell responsiveness was aided by antileishmanial drug therapy which resulted in the reduction of antigenic load by parasite destruction and a concomitant decrease in circulating antibody levels, particularly that of the immunoglobulin G class. We suggest that the protection afforded by specific CMI response against Leishmania donovani infection may not be absolute and probably depends on other host-related factors leading to parasite destruction and patient recovery.

https://iai.asm.org/content/iai/42/2/702.full.pdf

Bhattacharya Pk

Papers

The role of counter immunoelectrophoresis as a diagnostic tool in kala-azar.

Clinical profile of cases of kala-azar in Bihar.

Immunological response in Indian kala-azar.

Haematological investigations in kala-azar patients in Bihar.