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Glenn Wortmann - One of the best experts on this subject based on the ideXlab platform.
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Varicella zoster virus--specific immune response after treatment with Sodium Stibogluconate for cutaneous leishmaniasis.
The American journal of tropical medicine and hygiene, 2008Co-Authors: In-kyu Yoon, Josephine H. Cox, Yaling Zhou, Yvonne Lukes, Brian Reinhardt, Anais Valencia-micolta, Glenn WortmannAbstract:Sodium Stibogluconate has been associated with the reactivation of varicella zoster virus (VZV) in otherwise healthy adults who receive the drug as treatment for cutaneous leishmaniasis. Ten patients receiving daily Sodium Stibogluconate underwent phlebotomy at baseline and at day 10. Flow cytometry-based immunophenotyping, VZV-specific IgG levels, and lymphocyte proliferative responses and intracellular cytokine secretion to VZV, cytomegalovirus, tetanus toxoid, superantigen, and mitogens were performed at both time points. The absolute number of total leukocytes, total lymphocytes, and lymphocyte subsets decreased overall without predilection for any particular subset of lymphocytes, such that the percentage of the total lymphocyte population for each lymphocyte subset did not change significantly (except for a marginal increase in percentage of cytotoxic T cells). Antibodies to VZV were measured in seven patients before and after treatment, and did not change. Lymphocyte proliferative responses to VZV and other antigens and mitogens did not change from baseline. The mechanism for the increased rate of VZV reactivation after treatment with Sodium Stibogluconate remains undefined.
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VARICELLA ZOSTER VIRUS MENINGITIS COMPLICATING Sodium Stibogluconate TREATMENT FOR CUTANEOUS LEISHMANIASIS
The American journal of tropical medicine and hygiene, 2006Co-Authors: Joshua D. Hartzell, Naomi E. Aronson, Sudhir Nagaraja, Tim Whitman, Clifton A. Hawkes, Glenn WortmannAbstract:Sodium Stibogluconate (Pentostam; GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with Sodium Stibogluconate.
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Herpes Zoster and Lymphopenia Associated with Sodium Stibogluconate Therapy for Cutaneous Leishmaniasis
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1998Co-Authors: Glenn Wortmann, Naomi E. Aronson, John C. Byrd, Michael R. Grever, Charles N. OsterAbstract:A review of 84 patients with cutaneous leishmaniasis treated with Sodium Stibogluconate (Pentostam) at our institution revealed that three had developed herpes zoster during or shortly after receiving therapy. Because zoster has been associated with depressed cellular immunity, we prospectively followed serial lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who received Pentostam. By day 7 of therapy, the white blood cell count had fallen by a median of 1.15/mm 3 , the total lymphocyte count by a median of 804/mm 3 , and the CD4 lymphocyte count by a median of 306/mm 3 (67% of baseline; confidence interval, 52%-78%). An in vitro cell-viability assay demonstrated that Pentostam is not toxic to human mononuclear cells. The administration of Pentostam for the treatment of cutaneous leishmaniasis results in lymphopenia that may be related to the subsequent occurrence of herpes zoster.
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Safety and Efficacy of Intravenous Sodium Stibogluconate in the Treatment of Leishmaniasis: Recent U.S. Military Experience
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1998Co-Authors: Naomi E. Aronson, Max Grogl, Glenn Wortmann, Steven C. Johnson, Joan E. Jackson, Robert A. Gasser, Alan J. Magill, Timothy P. Endy, Philip E. Coyne, Paul M. BensonAbstract:The efficacy and toxicity of Sodium Stibogluconate (SSG) at a dosage of 20 mg/(kg . d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for I year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.
Robert N. Davidson - One of the best experts on this subject based on the ideXlab platform.
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treatment of kala azar in southern sudan using a 17 day regimen of Sodium Stibogluconate combined with paromomycin a retrospective comparison with 30 day Sodium Stibogluconate monotherapy
American Journal of Tropical Medicine and Hygiene, 2007Co-Authors: Yosef Melaku, Koert Ritmeijer, Simon M Collin, Kees Keus, Francis Gatluak, Robert N. DavidsonAbstract:Medecins sans Frontieres-Holland has treated > 67,000 patients with kala-azar (KA) in southern Sudan since 1989. In 2002, we replaced the standard regimen of 30 days of daily Sodium Stibogluconate (SSG) with a 17-day regimen of daily SSG combined with paromomycin (PM). We analyzed data for 4,263 primary KA patients treated between 2002 and 2005 in southern Sudan to determine the relative efficacy of the combination therapy regimen (PM/SSG). The initial cure rate among patients treated with PM/SSG was 97.0% compared with 92.4% among patients treated with SSG monotherapy. Relative efficacy of PM/SSG compared with SSG increased over the study period: odds of death in the PM/SSG group were 44% lower (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.37–0.84) in 2002, 78% lower (OR = 0.22, 95% CI = 0.10–0.50) in 2003, and 86% lower (OR = 0.14, 95% CI = 0.07–0.27) in 2004–2005. In remote field settings, 17 days of SSG combined with PM gives better survival and initial cure rates than 30 days of SSG monotherapy.
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A comparison of liposomal amphotericin B with Sodium Stibogluconate for the treatment of visceral leishmaniasis in pregnancy in Sudan
The Journal of antimicrobial chemotherapy, 2006Co-Authors: Marius Mueller, Manica Balasegaram, Youssif Koummuki, Koert Ritmeijer, Muriel Ramirez Santana, Robert N. DavidsonAbstract:Objectives: Little is known about the treatment of visceral leishmaniasis (VL) in pregnancy, especially in resource-poor settings. We present a series of pregnant women with VL treated with either Sodium Stibogluconate or liposomal amphotericin B (AmBisome), or both, in eastern Sudan over 16 months. Methods: We did a retrospective analysis of all pregnant VL patients treated in the Medecins sans Frontieres (MSF) Um el Kher centre between January 2004 and April 2005. We diagnosed VL with laboratory confirmation of clinical suspects, and recorded the outcomes of treatment for pregnant women and their foetuses. We carried out a manual search of relevant publications and a systematic search of the literature in the MEDLINE database. Results: We treated 23 women with Sodium Stibogluconate, 4 with AmBisome and Sodium Stibogluconate and 12 with AmBisome alone. There were 13 (57%) spontaneous abortions in the Sodium Stibogluconate monotherapy group, and none in either of the other two groups. All spontaneous abortions occurred in the first two trimesters. All patients, except one in the Sodium Stibogluconate group who defaulted, were discharged as cured in good clinical condition. Conclusions: AmBisome treatment for VL appears to be safe and effective for pregnant women and their foetuses. We recommend the use of AmBisome as first-line treatment for these patients.
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Comparison of generic and proprietary Sodium Stibogluconate for the treatment of visceral leishmaniasis in Kenya
Bulletin of the World Health Organization, 2001Co-Authors: Elinore Moore, Deidre Oflaherty, Hans Heuvelmans, Jill Seaman, Hans Veeken, Sjoukje De Wit, Robert N. DavidsonAbstract:OBJECTIVE: To compare the use of generic and proprietary Sodium Stibogluconate for the treatment of visceral leishmaniasis (kala-azar). METHODS: A total of 102 patients with confirmed kala-azar were treated in a mission hospital in West Pokot region, Kenya, with Sodium Stibogluconate (20 mg/kg/day for 30 days) - either as Pentostam® (PSM) or generic Sodium Stibogluconate (SSG); 51 patients were allocated alternately to each treatment group. FINDINGS: There were no significant differences in baseline demographic characteristics or disease severity, or in events during treatment. There were 3 deaths in the PSM group and 1 in the SSG group; 2 patients defaulted in each group. Only 1 out of 80 test-of-cure splenic aspirates was positive for Leishmania spp.; this patient was in the SSG group. Follow-up after > 6 months showed that 6 out of 58 patients had relapsed, 5 in the SSG group and 1 in the PSM group. No outcome variable was significantly different between the two groups. CONCLUSION: The availability of cheaper generic Sodium Stibogluconate, subject to rigid quality controls, now makes it possible for the health authorities in kala-azar endemic areas to provide treatment to many more patients in Africa.
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Ethiopian visceral leishmaniasis: generic and proprietary Sodium Stibogluconate are equivalent; HIV co-infected patients have a poor outcome
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2001Co-Authors: Koert Ritmeijer, Jill Seaman, Hans Veeken, Yosef Melaku, G. Leal, R. Amsalu, Robert N. DavidsonAbstract:We evaluated generic Sodium Stibogluconate (SSG) (International Dispensary Association, Amsterdam) versus Pentostam (Sodium Stibogluconate, GlaxoWellcome, London) under field conditions in Ethiopian patients with visceral leishmaniasis (VL; kala-azar). The 199 patients were randomly assigned to Pentostam (n = 104) or SSG (n = 95) in 1998/99; both drugs were given at 20 mg/kg intra-muscularly for 30 days. A clinical cure after 30-days treatment was achieved in 70.2% (Pentostam) and 81.1% (SSG). There were no significant differences between the 2 drugs for the following parameters: frequency of intercurrent events (vomiting, diarrhoea, bleeding or pneumonia) or main outcome (death during treatment and death after 6-month follow-up; relapse or post kala-azar dermal leishmaniasis at 6-months follow-up). Twenty-seven patients had confirmed co-infection with HIV. On admission, HIV co-infected VL patients were clinically indistinguishable from HIV-negative VL patients. The HIV co-infected VL patients had a higher mortality during treatment (33.3% vs 3.6%). At 6-month follow-up, HIV-positive patients had a higher relapse rate (16.7% vs 1.2%), a higher death rate during the follow-up period (14.3% vs 2.4%), and more frequent moderate or severe post kala-azar dermal leishmaniasis (27.3% vs 13.3%). Only 43.5% of the HIV-positive patients were considered cured at 6-months follow-up vs 92.1% of the HIV-negative patients. HIV-positive patients relapsing with VL could become a reservoir of antimonial-resistant Leishmania donovani.
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A randomized comparison of branded Sodium Stibogluconate and generic Sodium Stibogluconate for the treatment of visceral leishmaniasis under field conditions in Sudan.
Tropical medicine & international health : TM & IH, 2000Co-Authors: Hans Veeken, Jill Seaman, Koert Ritmeijer, Robert N. DavidsonAbstract:OBJECTIVE To compare the outcome of treatment of Sudanese kala-azar patients treated under field conditions with either branded Sodium Stibogluconate (SSG) (Pentostam GlaxoWellcome) or generic SSG (Albert David Ltd, Calcutta, supplied by International Dispensary Association, Amsterdam). METHOD Randomised comparison. 271 patients were treated with Pentostam and 245 with generic SSG. RESULTS No statistically significant differences in cure rate or mortality were detected between Pentostam and generic SSG. No differences in side-effects between the two drugs were noted. The initial cure rate at the time of discharge was 93.7 and 97.6%, respectively; the death rate during treatment 5.9 and 2.4%. Six months follow up was achieved in 88.5% of the discharged patients. Two patients had died in the Pentostam group and two had died in the generic SSG group, giving a final death rate of 7.5 and 3.7%. The number of relapses in the Pentostam and generic SSG groups were 3 and 1, respectively. The final cure rates, calculated at 6 months after discharge, were 91.3% and 95.9%. CONCLUSION No difference was observed in the performance of generic SSG compared to Pentostam for the treatment of visceral leishmaniasis in Sudan. Generic SSG can be routinely and safely used for the treatment of kala-azar. Generic SSG costs only 1/14 of the price of Pentostam. The use of generic SSG may make treatment of kala-azar affordable for national governments in Africa.
Joshua D. Hartzell - One of the best experts on this subject based on the ideXlab platform.
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VARICELLA ZOSTER VIRUS MENINGITIS COMPLICATING Sodium Stibogluconate TREATMENT FOR CUTANEOUS LEISHMANIASIS
The American journal of tropical medicine and hygiene, 2006Co-Authors: Joshua D. Hartzell, Naomi E. Aronson, Sudhir Nagaraja, Tim Whitman, Clifton A. Hawkes, Glenn WortmannAbstract:Sodium Stibogluconate (Pentostam; GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with Sodium Stibogluconate.
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Case 4-2005: Sodium Stibogluconate for cutaneous leishmaniasis.
The New England journal of medicine, 2005Co-Authors: Joshua D. Hartzell, Naomi AronsonAbstract:To the Editor: In Case 4-2005 (Feb. 10 issue),1 a discussant states that Sodium Stibogluconate (Pentostam, GlaxoSmithKline, United Kingdom) is available in the United States only from the Centers f...
Yusuf Ozbel - One of the best experts on this subject based on the ideXlab platform.
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Clinical and serological follow-up in dogs with visceral leishmaniosis treated with allopurinol and Sodium Stibogluconate.
Veterinary parasitology, 2005Co-Authors: Serdar Pasa, Seray Ozensoy Toz, Huseyin Voyvoda, Yusuf OzbelAbstract:Seven dogs with parasitologically proven clinical visceral leishmaniosis (Leishmania infantum infection) were treated with a combination of allopurinol and Sodium Stibogluconate. The dogs received first orally 15 mg/kg of allopurinol every 12 h until the clinical signs improved, in the following 1 month period allopurinol at same dose and subcutaneously 30 mg/kg of Sodium Stibogluconate combination were given daily and at the end of the combined treatment, allopurinol was continued alone at the same dose till the end of 8 months. During the treatment period, dogs were supported by additional proteins, vitamins, and minerals. A long acting insecticide (collar or drop) was also used in order to prevent further parasite transmission. Follow-up was maintained by clinical, clinicopathological evaluation, and parasitological examination of lymph node, serology using the indirect immunofluorescent antibody test (IFAT). Before treatment commenced, the most important clinical signs were exfoliative dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight loss, and ocular lesions. Clinicopathological findings included commonly anaemia, hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment, amastigotes were seen in six of the seven dogs by examination of lymph node aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months treatment, remission of clinical signs, restoration to normal of clinicopathological abnormalities were noticed. Lymph node aspiration was performed on three out of the seven dogs at the end of the treatment because of the very small sizes of the lymph nodes, and no amastigotes were observed. Although the mean IFAT-titer of the dogs were significantly (P < 0.001) lower compared with pretreatment, IFAT-titers of dogs were still positive. No relapses occurred during treatment period and a 6-24-month duration after the end of therapy. Based on the above results, long-term use of allopurinol combined with Sodium Stibogluconate together with support treatment concluded to have enough therapeutic efficacies in the treatment of dogs with visceral leishmaniosis. Observations of the cases for possible relapses were still going on and insecticide application was carefully carrying on in order preventing a possible re-infection.
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Clinical and serological follow-up in dogs with visceral leishmaniosis treated with allopurinol and Sodium Stibogluconate
Veterinary Parasitology, 2005Co-Authors: Serdar Pasa, Seray Ozensoy Toz, Huseyin Voyvoda, Yusuf OzbelAbstract:Abstract Seven dogs with parasitologically proven clinical visceral leishmaniosis ( Leishmania infantum infection) were treated with a combination of allopurinol and Sodium Stibogluconate. The dogs received first orally 15 mg/kg of allopurinol every 12 h until the clinical signs improved, in the following 1 month period allopurinol at same dose and subcutaneously 30 mg/kg of Sodium Stibogluconate combination were given daily and at the end of the combined treatment, allopurinol was continued alone at the same dose till the end of 8 months. During the treatment period, dogs were supported by additional proteins, vitamins, and minerals. A long acting insecticide (collar or drop) was also used in order to prevent further parasite transmission. Follow-up was maintained by clinical, clinicopathological evaluation, and parasitological examination of lymph node, serology using the indirect immunofluorescent antibody test (IFAT). Before treatment commenced, the most important clinical signs were exfoliative dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight loss, and ocular lesions. Clinicopathological findings included commonly anaemia, hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment, amastigotes were seen in six of the seven dogs by examination of lymph node aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months treatment, remission of clinical signs, restoration to normal of clinicopathological abnormalities were noticed. Lymph node aspiration was performed on three out of the seven dogs at the end of the treatment because of the very small sizes of the lymph nodes, and no amastigotes were observed. Although the mean IFAT-titer of the dogs were significantly ( P
Marc Ouellette - One of the best experts on this subject based on the ideXlab platform.
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Modulation of Gene Expression in Human Macrophages Treated with the Anti-Leishmania Pentavalent Antimonial Drug Sodium Stibogluconate
Antimicrobial agents and chemotherapy, 2007Co-Authors: Karima El Fadili, Michel J. Tremblay, Michael Imbeault, Nadine Messier, Gaétan Roy, Benjamin Gourbal, Marc J. Bergeron, Danielle Légaré, Marc OuelletteAbstract:Within the mammalian host, Leishmania donovani is an obligatory intracellular protozoan parasite that resides and multiplies exclusively in the phagolysosomes of macrophages. Leishmania control relies primarily on chemotherapy, with the mainstay being pentavalent antimony (SbV) complexed to carbohydrates in the form of Sodium Stibogluconate (Pentostam) or meglumine antimoniate (Glucantime). The mode of action of SbV is still not known precisely. To explore the effect of SbV on macrophage gene expression, a microarray analysis was performed using Affymetrix focus arrays to compare gene expression profiles in noninfected and L. donovani-infected THP-1 monocytic cells treated or not treated with Sodium Stibogluconate. Under our experimental conditions, SbV changed the expression of a few host genes, and this was independent of whether cells were infected or not infected with Leishmania. Leishmania infection had a greater effect on the modulation of host gene expression. Statistical analyses have indicated that the expression of eight genes was modified by at least twofold upon SbV treatment, with six genes upregulated and two genes downregulated. One gene whose expression was affected by SbV was the heme oxygenase gene HMOX-1, and this change was observed both in the monocytic cell line THP-1 and in primary human monocyte-derived macrophages. Another pathway that was affected was the glutathione biosynthesis pathway, where the expression of the glutamate-cysteine ligase modifier subunit was increased upon SbV treatment. Our analysis has suggested that, under our experimental conditions, the expression of a few genes is altered upon SbV treatment, and some of these encoded proteins may be implicated in the yet-to-be-defined mode of action of SbV.
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hiv 1 replication is stimulated by Sodium Stibogluconate the therapeutic mainstay in the treatment of leishmaniasis
The Journal of Infectious Diseases, 2007Co-Authors: Corinne Barat, Marc Ouellette, Chenqi Zhao, Michel J. TremblayAbstract:Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound Sodium Stibogluconate is a drug of choice for the treatment of leishmaniasis. Because Sodium Stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV-1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory-adapted and clinical strains of HIV-1, we report that Sodium Stibogluconate induces an increase in HIV-1 transcription and virus replication in primary CD4(+) T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor- kappa B and activator protein 1, as well as the Syk, Jun, and mitogen-activated protein kinase/extracellular signal-related kinase signal-transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV-1-infected patients.
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HIV‐1 Replication Is Stimulated by Sodium Stibogluconate, the Therapeutic Mainstay in the Treatment of Leishmaniasis
The Journal of infectious diseases, 2006Co-Authors: Corinne Barat, Marc Ouellette, Chenqi Zhao, Michel J. TremblayAbstract:Leishmaniasis is an important opportunistic disease among patients infected with human immunodeficiency virus (HIV)-1. The pentavalent antimony compound Sodium Stibogluconate is a drug of choice for the treatment of leishmaniasis. Because Sodium Stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and such inhibitors can promote HIV-1 replication, we tested the effect of this compound on virus gene expression. Using pseudotyped reporter viruses and fully infectious laboratory-adapted and clinical strains of HIV-1, we report that Sodium Stibogluconate induces an increase in HIV-1 transcription and virus replication in primary CD4(+) T cells and in thymic histocultures. This activation is a slow process and appears to involve the transcription factors nuclear factor- kappa B and activator protein 1, as well as the Syk, Jun, and mitogen-activated protein kinase/extracellular signal-related kinase signal-transduction pathways. In addition, the effect seems to be partly mediated by a soluble factor. Altogether, these findings might reveal clinical implications for the treatment of leishmaniasis in HIV-1-infected patients.
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Gene Amplification in Leishmania tarentolae Selected for Resistance to Sodium Stibogluconate
Antimicrobial agents and chemotherapy, 1998Co-Authors: Anass Haimeur, Marc OuelletteAbstract:Leishmania tarentolae promastigotes were selected step by step for resistance to Sodium Stibogluconate (Pentostam). Mutants resistant to antimony-containing drugs and cross-resistant to arsenite were therefore obtained. Amplification of one common locus was observed in several independent Sodium Stibogluconate-resistant mutants, and the locus amplified was novel. The copy number of the amplified locus was related to the level of resistance to pentavalent antimony. The gene responsible for antimony resistance was isolated by transfection and was shown to correspond to an open reading frame coding for 770 amino acids. The putative gene product did not exhibit significant homology with sequences present in data banks, and the putative role of this protein in antimony resistance is discussed.
