antimony-sodium-gluconate and Chronic-Disease

A 25-year-old woman of Yugoslavian origin came to Germany two years before and did not leave Germany since this time. She developed a phlebothrombosis during pregnancy which was treated surgically and with subsequent heparinisation. The pregnancy had to be terminated by section because of abnormal liver functions and increased blood pressure. These values returned to normal within two months. Further tests again showed raised liver function tests (GOT 57 U/l, GPT 71 U/l) and antibodies against smooth muscle and actin. Autoimmune hepatitis was diagnosed and prednisolone given (100 mg daily). In the subsequent 4 months the patient progressively lost more weight and a pancytopenia developed. Suspected of having a systemic haematological syndrome she was admitted to hospital.. Physical examination was unremarkable except for hepato- and splenomegaly (spleen 15.6 cm in diameter by sonography). Laboratory tests showed hypergammaglobulinaemia (50 g/l, 53%), increased WBC count, as well as decreased haemoglobin concentration and platelet count (900 WBC/microliter, Hb 10.9 g/l, 146,000 platelets/microliter). Bone marrow puncture unexpectedly revealed a large number of Leishmania donovani.. Five-valent antimony was administered (sodium stibogluconate 20 mg/kg daily intravenously as bolus for 14 days). She has been free of symptoms since then (follow-up period of one year).. Visceral leishmaniasis is a rare disease in Europe. Incubation periods of several years have been reported and the infection can be easily mistaken for other chronic liver disease, in this case for an autoimmune hepatitis. Leishmaniasis should be included in the differential diagnosis of unclear liver disease if there is a suggestive history (country of origin or journey into an endemic area).

Topics: Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Diagnosis, Differential; Female; Germany; Hepatitis, Viral, Human; Humans; Leishmania donovani; Leishmaniasis, Visceral; Pregnancy; Time Factors; Yugoslavia

Topics: Aged; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Biopsy; Chronic Disease; Dermatitis, Atopic; Facial Dermatoses; Female; Humans; Leishmania donovani; Leishmania infantum; Leishmaniasis; Treatment Outcome

In this work we report the activity seen with combination therapy using sodium antimony gluconate in liposomes composed of egg phosphatidyl choline and stearylamine for elimination of Leishmania donovani parasites from the liver and spleen of BALB/c mice with established and chronic infections.

Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Drug Carriers; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Leishmania donovani; Leishmaniasis, Visceral; Liposomes; Liver; Mice; Mice, Inbred BALB C; Phosphatidylcholines; Spleen

In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values, P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values, P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.

Topics: Acute Disease; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Female; Leishmaniasis, Visceral; Male; Mice; Mice, Inbred BALB C; Surface-Active Agents

Treatment of nonhealing forms of human leishmaniasis with antimonial drugs in combination with gamma interferon (IFN-gamma) may promote healing more effectively than conventional drug therapy. Although the natures of immune responses in patients prior to treatment are often unclear, it is generally assumed that such therapy also promotes a switch from a Th2-type response to a dominant Th1-type response. We have examined the efficacy of IFN-gamma therapy, in combination with drug therapy, to promote healing and a Th2-to-Th1 switch in highly susceptible BALB/c mice infected with Leishmania major. Short-term treatment with the antileishmanial drug sodium stibogluconate failed to significantly alter the course of disease or the immune response when it was given during the third and fourth weeks of infection. IFN-gamma therapy, administered over the same time period, also failed to induce cure or a Th1 dominant response. In contrast, mice treated with a combination of drug and IFN-gamma therapy resolved their infections and developed Th1-type responses. However, administration of an antibody to interleukin 12 (IL-12) reversed the therapeutic effects of therapy with drug plus IFN-gamma, suggesting that IFN-gamma promotes cure through an IL-12-dependent mechanism. Analysis of mRNA levels within parasitized lesions suggests that drug treatment plus IFN-gamma treatment, in addition to reducing parasite numbers, results in reduced levels of IL-4, IL-10, and transforming growth factor beta transcripts but increased levels of transcripts of the p40 chain of IL-12 and inducible nitric oxide synthase, which catalyzes the production of nitric oxide. Together, these results suggest that such immunotherapy may promote the development of a protective Th1-type response in susceptible mice by a mechanism which involves both suppression of regulatory cytokines and enhancement of IL-12 and nitric oxide production.

Topics: Animals; Antibodies, Protozoan; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Immunoglobulin G; Interferon-gamma; Interleukin-12; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Transforming Growth Factor beta

BALB/c mice with an acute or chronic Leishmania donovani infection were treated with intravenous sodium stibogluconate solution and the parasite suppressions determined in the spleen, liver and femur bone marrow. Antimony concentrations in these and other tissues were determined by hydride generation-atomic absorption spectrophotometry. There was little correlation between tissue antimony levels one hour after treatment and drug efficacy. It would appear that the peak tissue antimony concentration achieved soon after dosing, rather than the lower concentrations which are readily sustained in most tissues, is the most important factor in the antileishmanial activity of stibogluconate. A high peak antimony concentration occurred in the liver, where parasites were significantly suppressed, and was not observed in the two other sites of infection, where the parasites were apparently less susceptible to stibogluconate therapy.

Topics: Acute Disease; Animals; Antimony; Antimony Sodium Gluconate; Chronic Disease; Female; Leishmania donovani; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C

Mucosal leishmaniasis as an oral disease in the form of chronic periodontitis with involvement of the oral mucosa is described. Leishmania parasites were isolated from the oral lesions, lymph nodes, and bone marrow. The patient had a low-grade fever and hepatosplenomegaly that regressed along with the oral lesions after treatment with stibogluconate sodium.

Topics: Antimony Sodium Gluconate; Chronic Disease; Humans; Injections, Intravenous; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral; Male; Middle Aged; Periodontitis