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.

Complete cure of experimental visceral leishmaniasis with amphotericin B in stearylamine-bearing cationic liposomes involves down-regulation of IL-10 and favorable T cell responses.

Abstract: Visceral leishmaniasis caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of liver, spleen, and bone marrow. Most available drugs are toxic. Moreover, relapse after seemingly successful therapy remains a chronic problem. In this study, we evaluated a new therapeutic approach based on combination of a low dose of amphotericin B (AmB) in association with suboptimum dose of stearylamine (SA)-bearing cationic liposomes, itself having leishmanicidal activity. We demonstrate that a single-shot therapy with this formulation caused clearance of parasites from liver and spleen below the level of detection in the selected piece of the organs of BALB/c mice. The combination was superior to free AmB and AmBisome for therapy, as well as for prevention of relapse and reinfection. Besides having better killing activity, AmB in SA liposomes, in contrast to AmBisome, maintained the immunomodulatory effect of free AmB on CD4+ and CD8+ T cells for IFN-γ production, at the same time reducing the toxic effects of the drug, reflected through decline in TNF-α. In addition, IL-10 was down-regulated to almost negligible levels, most efficiently through therapy with SA-bearing cationic liposomes-AmB. This IL-10-deficient environment of IFN-γ-secreting T cells probably up-regulated the enhanced IL-12 and NO production observed in splenic culture supernatants of these mice, correlating with prolonged disease suppression better than free AmB and AmBisome. The ability of the formulation to elicit protective immunity was reconfirmed in a prophylactic model. Our results emphasize the requirement of effective immune stimulation, additionally, by antileishmanials for persistent disease protection, demonstrated by this liposomal AmB formulation.

Autoantibody production by patients infected with Leishmania.

Abstract: Sera from 29 patients with visceral leishmaniasis and 14 patients with cutaneous leishmaniasis were tested against a panel of nine nuclear antigens employing an enzyme-linked immunosorbent assay (ELISA). Anti- Sm, RNP, SS-A and SS-B antibodies were present in high titres in 83, 86, 36 and 73 per cent of the patients with visceral leishmaniasis and in 7, 14, 25 and 25 per cent of the patients with cutaneous leishmaniasis. One serum from a patient with visceral leishmaniasis which reacted strongly with Sm, RNP, SS-A and SS-B was examined by immunoblotting on extractable nuclear antigen from Hela cells. This serum binds to nine different antigenic bands (16, 23, 29, 30, 40, 50, 58, 100 and 115 kD). These same antigens were recognized by serum from a patient with systemic lupus erythematosus. The binding of visceral leishmaniasis serum antibodies to ribonucleoproteins was inhibited by prior incubation of serum with either leishmanial membrane antigens, from four different species of Leishmania, or intact cells of Leishmania donovani, implying molecular resemblance between common leishmanial antigens and ribonuclear antigens. It seems that appearance of autoantibodies to ribonucleoproteins in sera of patients infected with Leishmania is not only due to simply polyclonal activation of lymphocytes, but is also the result of a molecular mimicry between leishmanial antigens and ribonucleoproteins.

Efficacy of the triazole SCH 56592 against Leishmania amazonensis and Leishmania donovani in experimental murine cutaneous and visceral leishmaniases.

Abstract: Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe oral therapy would be ideal. We examined the efficacy of SCH 56592, an investigational triazole antifungal agent, against cutaneous infection with Leishmania amazonensis and visceral infection with Leishmania donovani in BALB/c mice. Mice were infected in the ear pinna and tail with L. amazonensis promastigotes and were treated with oral SCH 56592 or intraperitoneal amphotericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highly efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day. The means of tail lesion sizes were 0.32 ± 0.12, 0.11 ± 0.06, 0.17 ± 0.07, and 0.19 ± 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphotericin B recipients, respectively (P = 0.0003, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. These studies indicate very good activity of SCH 56592 against cutaneous leishmaniasis due to L. amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c mice.

Isolation of Leishmania mexicana amazonensis from the bone marrow in a case of American visceral leishmaniasis.

Abstract: The first documented human case of visceral leishmaniasis caused by L mexicana amazonensis is reported Leishmania were isolated from bone marrow aspirate material from a typical visceral leishmaniasis patient Further characterization by isoenzyme electrophoresis and by a panel of species- and subspecies-specific monoclonal antibodies established its classification as L m amazonensis

Visceral leishmaniasis in HIV-1-infected individuals: a common opportunistic infection in Spain?

Abstract: Physicians examined the records of 47 adults with visceral leishmaniasis (VL) and HIV-1 infection who were patients at 3 urban teaching hospitals in the Andalucia region in southern Spain between January 1986 and November 1991. They wanted to identify the clinical biological and epidemiological features of VL in HIV-1 positive patients. 96% of the cases were diagnosed with both infections during the last 2 years of the study period and 79% between January and November 1991. All the patients had risk factors for HIV infection (65.9% IV drug use 21.3% sexual contact and 12.8% blood transfusion). 70% exhibited the classic symptoms of VL (fever enlarged liver and spleen and depressed counts of blood cells). Most patients were already very immunocompromised when VL was diagnosed. 87% had a total lymphocyte count of less than 1000 x 1 million/1 and a CD4 lymphocyte count of less than 200 x 1 million/1. In fact 66% had full blown AIDS prior to diagnosis of VL. VL was the first severe infection in 10 cases. 68% also suffered from opportunistic infections especially candidiasis extrapulmonary tuberculosis and Pneumocystis carinii pneumonia. Microscopic examination of Leishmania amastiogotes in tissue samples led to a diagnosis in 94% of cases isolation of motile amastigotes in culture of bone marrow aspirate in 2% and microscopic and culture in 4%. Just 46% completed a full course of treatment (pentavalent antimony allopurinol and/or pentamidine). Only 38% had a microbiological response. Immunofluorescence detected sizeable titers (>1:40) of antileishmanial antibodies in just 31% of cases. 17% experienced clear clinical improvement. Physicians in endemic areas should consider VL in every HIV-1 infected patient with fever hepatosplenomegaly or hematological abnormalities to avoid underdiagnosis of leishmaniasis.