Visceral leishmaniasis

About: Visceral leishmaniasis is a research topic. Over the lifetime, 7486 publications have been published within this topic receiving 184865 citations. The topic is also known as: Kala-Azar & viscus leishmaniasis.

Treatment of visceral leishmaniasis

Abstract: Growing antimony resistance in patients with visceral leishmaniasis (VL) over last two decades, especially in Indian subcontinent, renders this cheap and easily available drug useless for a vast majority of patients. Use of the second line drug pentamidine isethionate, a toxic drug with declining efficacy, has largely been abandoned. Thus, in these areas amphotericin B remains the only drug; although it cures > 97% patients, infusion-related adverse events are common and occasionally serious toxicity, such as myocarditis, or death can occur. In recent years India has been the center for clinical development of new anti-leishmanial drugs like lipid formulations of amphotericin B, new drugs like parenterally administered aminosidine and oral miltefosine. The alkyl phospholipid compound miltefosine is the first effective oral compound for VL and is likely to be marketed soon. In addition to the monotherapy, efforts in development of combination chemotherapy are needed if the menace of drug resistance is to be contained.

Synergistic Effect of Interferon-γ and Mannosylated Liposome-Incorporated Doxorubicin in the Therapy of Experimental Visceral Leishmaniasis

Abstract: Active targeting of doxorubicin to macrophages was studied by incorporating it in mannose-coated liposomes by use of visceral leishmaniasis in BALB/c mice as the model macrophage disease. Mannosylated liposomal doxorubicin was more effective than liposomal doxorubicin or free doxorubicin. Because leishmaniasis is accompanied by immunosuppression, immunostimulation by interferon (IFN)-gamma was evaluated to act synergistically with mannosylated liposomal doxorubicin therapy. Combination chemotherapy with a suboptimal dose of IFN-gamma resulted in possibly complete elimination of spleen parasite burden. Analysis of mRNA levels of infected spleen cells suggested that targeted drug treatment together with IFN-gamma, in addition to greatly reducing parasite numbers, resulted in reduced levels of interleukin (IL)-4 but increased levels of IL-12 and inducible nitric oxide synthase. Such combination chemotherapy may provide a promising alternative for the cure of leishmaniasis, with a plausible conversion of antiparasitic T cell response from a Th2 to Th1 pattern indicative of long-term resistance.

Immunity to Visceral Leishmaniasis Using Genetically Defined Live-Attenuated Parasites

Abstract: Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL) Drug treatments are expensive and often result in the development of drug resistance No vaccine is available against leishmaniasis Subunit Leishmania vaccine immunization in animal models has shown some efficacy but little or none in humans However, individuals who recover from natural infection are protected from reinfection and develop life-long protection, suggesting that infection may be a prerequisite for immunological memory Thus, genetically altered live-attenuated parasites with controlled infectivity could achieve such memory In this paper, we discuss development and characteristics of genetically altered, live-attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL In addition, we discuss the challenges and other considerations in the use of live-attenuated parasites

Linking in vitro and in vivo survival of clinical Leishmania donovani strains.

Abstract: Background Leishmania donovani is an intracellular protozoan parasite that causes a lethal systemic disease, visceral leishmaniasis (VL), and is transmitted between mammalian hosts by phlebotomine sandflies Leishmania expertly survives in these ‘hostile’ environments with a unique redox system protecting against oxidative damage, and host manipulation skills suppressing oxidative outbursts of the mammalian host Treating patients imposes an additional stress on the parasite and sodium stibogluconate (SSG) was used for over 70 years in the Indian subcontinent Methodology/Principal Findings We evaluated whether the survival capacity of clinical L donovani isolates varies significantly at different stages of their life cycle by comparing proliferation, oxidative stress tolerance and infection capacity of 3 Nepalese L donovani strains in several in vitro and in vivo models In general, the two strains that were resistant to SSG, a stress encountered in patients, attained stationary phase at a higher parasite density, contained a higher amount of metacyclic parasites and had a greater capacity to cause in vivo infection in mice compared to the SSG-sensitive strain Conclusions/Significance The 2 SSG-resistant strains had superior survival skills as promastigotes and as amastigotes compared to the SSG-sensitive strain These results could indicate that Leishmania parasites adapting successfully to antimonial drug pressure acquire an overall increased fitness, which stands in contrast to what is found for other organisms, where drug resistance is usually linked to a fitness cost Further validation experiments are under way to verify this hypothesis

Human visceral leishmaniasis in Alpes-Maritimes, France: epidemiological characteristics for the period 1985–1992

Abstract: In 8 years (1985-1992), 65 cases of human visceral leishmaniasis (HVL) have been diagnosed in the department of Alpes-Maritimes, France, 56 of them having been infected locally. The annual frequency has increased from 3 cases in 1985 to 15 cases in 1992. There is a low rate of paediatric cases (29%) and a predominance of males among adult cases (85%). Since 1986, 19 cases of co-infection with Leishmania and human immunodeficiency virus 1 have been reported, corresponding to 40% of adult cases and to 30% of the total cases. The frequency of co-infections is stable at about 3 per annum. Isoenzymatic identification of the strains isolated from patients confirmed Leishmania infantum zymodeme MON-1 as responsible for most if not all HVL in the department of Alpes-Maritimes; 42 of the 44 strains isolated belonged to that zymodeme.