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PubMed1992

Leishmaniasis: a rare cause of unexplained fever in a renal graft recipient.

We report a case of visceral leishmaniasis in a 38-year-old renal transplant recipient living in an endemic country. Antimonial derivatives induced a rapid remission. A review of the literature disclosed 8 cases of this association with a fatal fulminant outcome in 5 cases. We suggest that the specific immunosuppression used in renal transplant patients might facilitate the development of a dormant infection and in these patients the misleading presentation may delay the diagnosis. Moreover special caution with treatment of leishmaniasis must be taken in renal transplant because of possible interactions between antimony compounds and ciclosporin metabolites. In renal transplant patients living in endemic countries, visceral leishmaniasis should be kept in mind as a potential cause of unexplained long-standing fever and considered as an opportunistic infection.

Adult↗

PubMed2002

Antimony ethylene glycolate and catecholate compounds: structural characterization of polyesterification catalysts.

Antimony compounds are widely used as catalysts for the synthesis of the commercially important polymer poly(ethyleneterephthalate) by polycondensation of bis(hydroxyethyl)terephthalate. The precise nature of the antimony catalysts is, however, unknown. The present study has been conducted with a view to determining the nature of the catalytic species by structurally characterizing antimony ethylene glycolate compounds and related catecholate derivatives, namely [Sb(2)(OCH(2)CH(2)O)(3)](n), [Sb(OCH(2)CH(2)O)(OAc)](n), [pySb(1,2-O(2)C(6)H(4))](2)O, and [pyH][Sb(1,2-O(2)C(6)H(4))(2)].

Journal Article↗

PubMed2006

Effect of combination therapy with systemic glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis.

INTRODUCTION: Cutaneous leishmaniasis is a common parasitic disease in Iran, especially in Isfahan. First line treatment for this disease is antimonial compounds; however, owing to the intermittent failure of this treatment and its significant side-effects alternative therapeutic measures have been advocated. OBJECTIVE: Evaluating the efficacy of pentoxifylline plus glucantime in the treatment of cutaneous leishmaniasis. METHODS: This double-blind, randomized, controlled clinical trial with simple sampling was performed on 64 patients with cutaneous leishmaniasis referred to the Skin Diseases & Leishmaniasis Research Center from an endemic foci of L. major in Isfahan. The patients randomly were divided into two groups. One group was treated with systemic Glucantime (20 mg pentavalent antimony/kg/day) combined with pentoxifylline (400 mg three times daily) and the other group were treated with Glucantime (20 mg pentavalent antimony/kg/day) plus placebo (three tablets daily) for 20 days. Follow up lasted 3 months. Response to treatment was grouped as complete improvement (lesions had been flattened, no induration, and epidermal creases had appeared), partial improvement (reduction in lesion size, but without the appearance of epidermal creases) and poor response (no reduction in lesion size). RESULTS: Of 64 participants, 32 patients in the trial group and 31 patients in the control group were followed for 3 months. One patient in group B discontinued withdrew. After this time, complete improvement, partial improvement and poor response to treatment were 81.3%, 12.5% and 6.2% in the trial group and 51.6%, 29% and 19.4% in the control group, respectively. We also observed no adverse effect resulting from pentoxifylline. DISCUSSION: The result obtained by two therapeutic methods indicates that combined therapy with Glucantime and pentoxifylline is more effective than Glucantime alone (P < 0.05).

Adolescent↗

PubMed1991

Comparison of regimes of treatment of antimony-resistant kala-azar patients: a randomized study.

Three hundred twelve patients with antimony-resistant kala-azar were randomized into three groups. The first group (A) received pentamidine isethionate intravenously three times each week until parasitological cure was achieved. Group B received pentamidine concomitantly with a 20-day regimen of sodium stibogluconate. Group C received pentamidine injections that were followed by 20 days of sodium stibogluconate therapy. All patients became afebrile after 10 injections of pentamidine. Parasitologic cure was achieved in approximately 98% of the patients who had 33 or more injections of this drug. The addition of the antimony compound did not appear to enhance the rate of parasitologic cure. Three patients continued to have parasites after 40 injections of pentamidine. After six months, the rate of parasitologic cure was significantly higher in Group C (pentamidine followed by sodium stibogluconate) than in either Group A or B. Forty patients relapsed after apparent parasitologic cure and were successfully treated with five additional injections of pentamidine, followed by a course of antimony therapy. Minor side effects with pentamidine included an uneasy feeling during intravenous injection (12%), intestinal disturbances (6%), cellulitis (5%), abscess formation (1%), and allergic manifestations (2%). Major reactions to this drug included hyperglycemia (10%; reversible in 6% and irreversible in 4%), and delayed hypoglycemia (8%). Four deaths were associated with the administration of this compound. It is concluded that pentamidine is an effective but toxic drug for the treatment of antimony-resistant kala-azar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2001

Sb K-edge absorption fine structure of Sb2Te3.

In order to study the local structure of some antimony compounds, Sb K-edge XAFS spectra were measured for Sb2Te3 and InSb. The measurements were performed in the transmission mode at BL-01 of SPring-8. Though crystal structure of antimony telluride Sb2Te3 is known by X-ray diffraction analysis, the EXAFS analyses give controversial result on the Sb-Te distance and the coordination number of Sb2Te3. Comparing the observed XANES spectra for Sb2Te3 with FEFF8 calculation, we can explain the controversial results which are also supported by the observed X-ray powder diffraction.

Journal Article↗

PubMed2004

Liposomal amphotericin B and rHuGM-CSF for treatment of visceral leishmaniasis in AIDS.

In recent years, several reports have emphasized the increasing importance of visceral leishmaniasis as an opportunistic infection among HIV-positive patients in areas where both infections are endemic. Major challenges in the treatment of leishmaniasis include widespread resistance to pentavalent antimonial compounds, absence of safe chemotherapeutic agents, and treatment failure and relapses in HIV-leishmania coinfected patients. Despite the associated adverse reactions and the need for prolonged parenteral treatment, for several decades pentavalent antimony has remained the traditional, first-line therapy for kala-azar throughout the world. However conventional antimony treatment for visceral leishmaniasis has several main drawbacks, including the toxicity of pentavalent antimonials, the prolonged therapy required to achieve cure, and the risk of relapse even after initial good response. In recent years, the search for alternative treatment has led to the recognition of lipid associated amphotericin B formulations as powerful antileishmanial agents. Several observations have also suggested that GM-CSF can be used as an antileishmanial treatment. Indeed, GM-CSF induces potentially beneficial effects in visceral leishmaniasis, such as blood monocyte mobilization, macrophage activation, and amelioration of granulocytopenia. In this report, we describe the safety and efficacy of combination treatment with liposomal amphotericin B and rHuGM-CSF immunotherapy used for the therapy of visceral leishmaniasis in a patient with AIDS.

AIDS-Related Opportunistic Infections↗

PubMed1981

In vivo effect of a new mineral condensed ion (HPA 39) on murine Friend leukaemia.

HPA 39 is a tungsto-antimoniate compound, closely related to the mineral consensed ion HPA 23, from which it differs only by the presence of a potassium instead of a sodium ion inside the central cage. A single parenteral injection of HPA 39 on the same day as virus inoculation decreased the splenomegaly induced by Friend virus in DBA/2 mice and protected 90% of the infected animals against leukaemia. It also lowered the virus content in spleen extracts compared to untreated animals. The efficiency of treatment with HPA 39 on leukaemic mice at a late stage of the disease suggested that the compound may act at the cellular level as well as by inducing virus growth inhibition. HPA 39 also induced an early decrease of peripheral blood reticulocytes, and of the most differentiated erythroblasts in the bone marrow 1 day after injection of the compound. Mineral condensed ions therefore appear to have multiple biological effects both in vitro and in vivo.

Animals↗

PubMed1995

Activity of pentostam (sodium stibogluconate) against cutaneous leishmaniasis in mice treated with neutralizing anti-interferon-gamma antibody.

Studies with Leishmania donovani in the mouse have demonstrated that an intact T cell compartment is required for effective anti-leishmanial therapy using pentavalent antimony compounds such as Pentostam (sodium stibogluconate), suggesting that the in vivo efficacy of drug treatment is at least partially immune-based. Similarly, Leishmania-infected, immunodeficient human patients including those with acquired immunodeficiency syndrome (AIDS) generally relapse following therapy with antimonials. However, sodium stibogluconate is directly parasiticidal in vitro, in the absence of T cells or T cell products. Using a model of a cutaneous form of leishmaniasis, in which susceptible BALB/c mice were infected with Leishmania major, we investigated whether the antileishmanial activity of the drug demonstrated a requirement for interferon-gamma (IFN-gamma), a cytokine produced during a T helper cell type 1 (Th1) immune response and known to contribute to resistance to infection, and whether drug therapy affected the nature of the antileishmanial response. Lesion development was suppressed in mice treated from the onset of infection with sodium stibogluconate alone, and in animals treated with sodium stibogluconate plus a neutralizing anti-IFN-gamma antibody, and tissue parasite burdens were approximately 10,000-fold less at the end of therapy in both groups compared with controls. Lesion development was similarly suppressed in mice with established lesions treated with either sodium stibogluconate alone, or sodium stibogluconate plus anti-IFN-gamma antibody. The production of IFN-gamma by cells from infected animals was somewhat increased immediately following therapy with sodium stibogluconate, an effect that was not long-lasting, while interleukin-4 (IL-4) production was not affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Asymptomatic visceral leishmaniasis in a child with acute lymphoblastic leukaemia.

Visceral leishmaniasis was detected incidentally in a patient with acute lymphoblastic leukaemia in remission, during maintenance therapy. Absence of fever, a normal haemogram, normal serum globulins, a negative serology and testicular involvement were the hallmarks of the case. Treatment with sodium stibogluconate (20 mg/kg for 55 days) failed. Subsequent therapy with pentamidine resulted in complete parasite clearance. Prolonged therapy with pentavalent antimony compounds or a higher dose of second line drugs such as pentamidine are recommended for complete clearance.

Antimony Sodium Gluconate↗

PubMed1978

Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs.

Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.

Animals↗

PubMed2006

Varicella zoster virus meningitis complicating sodium stibogluconate treatment for cutaneous leishmaniasis.

Sodium stibogluconate (Pentostam(R); 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.

Adult↗

PubMed1997

Comparison of aminosidine (paromomycin) and sodium stibogluconate for treatment of canine leishmaniasis.

Twelve dogs naturally infected with Leishmania infantum were treated subcutaneously with aminosidine at a dose of 10 mg kg-1 per day for four weeks. Antimonial compounds were used as reference drugs in twelve Leishmania-infected dogs. Eleven of the twelve dogs submitted to aminosidine therapy responded within 30 days. The treatment with the aminoglycoside antibiotic presented a marked decrease of anti-Leishmania antibody titres than the controls. Aminosidine also reduced urinary protein, serum IgG, and circulating immune complex concentrations. Side effects were observed only in a dog with pre-existent renal lesions. This study proved that aminosidine is an effective, tolerable and safe drug for the treatment of canine leishmaniasis and that it could be used as a suitable substitute for antimonial therapy.

Amebicides↗

PubMed1999

Leishmaniasis.

In 1903, Leishman and Donovan separately described the protozoan now called Leishmania donovani in splenic tissue from patients in India with the life-threatening disease now called visceral leishmaniasis. Almost a century later, many features of leishmaniasis and its major syndromes (ie, visceral, cutaneous, and mucosal) have remained the same; but also much has changed. As before, epidemics of this sandfly-borne disease occur periodically in India and elsewhere; but leishmaniasis has also emerged in new regions and settings, for example, as an AIDS-associated opportunistic infection. Diagnosis still typically relies on classic microbiological methods, but molecular-based approaches are being tested. Pentavalent antimony compounds have been the mainstay of antileishmanial therapy for half a century, but lipid formulations of amphotericin B (though expensive and administered parenterally) represent a major advance for treating visceral leishmaniasis. A pressing need is for the technological advances in the understanding of the immune response to leishmania and the pathogenesis of leishmaniasis to be translated into field-applicable and affordable methods for diagnosis, treatment, and prevention of this disease.

Amphotericin B↗

PubMed2000

American tegumentary leishmaniasis (ATL) in Rio de Janeiro State, Brazil: main clinical and epidemiologic characteristics.

BACKGROUND: Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasis (ATL) induced by Leishmania (Viannia) braziliensis. Objective Our purpose was to describe the main clinical and epidemiologic characteristics of the disease in Rio de Janeiro State. METHODS: Patients from endemic areas of Rio de Janeiro State attending the Evandro Chagas Hospital were included in the study. A general physical, dermatologic, and otorhinolaryngologic examination was performed in all patients, as well as a Leishmanin skin test. Skin biopsy specimens were obtained and utilized for touch preparations (stained with Leishman dye), culture in special media (Nicolle, Nevy and McNeal; NNN), and histopathologic examination after hematoxylin and eosin stain. Positive cultures were identified with regard to species by the isoenzyme technique. Therapy with pentavalent antimonial compounds was employed in all cases. Eco-epidemiologic characteristics were studied through regular field visits to endemic foci. RESULTS: Cutaneous disease was present in 87.2% of patients, and mucosal disease in only 12.7%. A single ulcerative cutaneous lesion was the most common clinical presentation. Demonstration of the parasite was always difficult and culture in special media gave the best results for diagnosis. The species involved in transmission was Leishmania (Viannia) braziliensis. Vectors included phlebotomine sand flies (Diptera: Psychodidae) of the genus Lutzomyia, and the most common species was Lutzomyia intermedia, captured mainly on the external walls of houses. CONCLUSIONS: ATL in Rio de Janeiro is mostly a cutaneous disease. In general, the cases showed great sensitivity to antimony. A pattern of peridomestic transmission seems to be the rule.

Animals↗

PubMed2000

South American cutaneous leishmaniasis of the eyelids: report of five cases in Rio de Janeiro State, Brazil.

PURPOSE: To describe American cutaneous leishmaniasis of the eyelids and highlight the main clinical and diagnostic features of lesions, which are rare in this location. DESIGN: Retrospective, noncomparative case series METHODS: Leishmanin skin test, touch preparations, histopathologic analysis, and culture in appropriate media were used for clinical confirmation and parasitologic diagnosis. Positive cultures were identified by the iso-enzymes technique. All patients were treated with pentavalent antimony applied intramuscularly. RESULTS: Leishmanin skin test was positive in all five patients. Touch preparations, histopathologic analysis, and culture were performed in four patients. Touch preparations were positive (presence of Leishman's bodies) in two patients; histopathologic analysis showed a granulomatous infiltrate in four patients and parasite was present in two patients; culture was positive in three patients, and in two the parasite was identified as Leishmania (Viannia) braziliensis. Therapy was effective for all patients. CONCLUSIONS: Cutaneous leishmaniasis of the eyelids is uncommon in the Americas. The disease may present diagnostic difficulties when appearing in nonendemic areas. The clues for diagnosis are the clinical aspect of lesions, the epidemiologic data, and a positive Leishmanin skin test. Demonstration of parasite is not always possible. Pentavalent antimonial compounds are the therapy of choice. Formerly, transmission of leishmaniasis occurred only when humans penetrated forested areas and became an incidental host. Now, eyelid lesions are part of the changing pattern in the transmission of the disease. With the increase in ecotourism, these lesions may begin to be seen in air travelers returning to other parts of the world.

Aged↗

PubMed2004

Exponential spread of hepatitis C virus genotype 4a in Egypt.

Hepatitis C virus (HCV) infects >10% of the general population in Egypt, in which intravenous injection with an antimony compound for endemic schistosomiasis in the past has been implicated. To simulate the epidemic history of HCV in Egypt, sera were obtained from 3608 blood donors at 13 governorates in or surrounding the Nile valley during 1999. The prevalence of antibody to HCV (anti-HCV) and genotypes was determined in them, and the molecular evolutionary analysis based on the neutral theory was applied to HCV isolates of genotype 4a, which is outstandingly prevalent in Egypt and indigenous there. Of 3608 sera, 317 (8.8%) were positive for anti-HCV. The molecular evolutionary analysis on 47 HCV genotype 4a isolates of carriers from various districts in Egypt indicated that the spread of HCV-4a would have increased exponentially during the 1940s through 1980 when oral medications became available. In conclusion, the estimated spread time is consistent with the duration of intravenous antimony campaigns in Egypt.

Adult↗

PubMedDate not supplied

Kala-azar--new developments in diagnosis and treatment.

Kala-azar is an endemic disease in many parts of India. Traditionally, diagnosis of this disease was based on demonstrating the parasites in various tissues like bone marrow or splenic aspirates. However, lack of high sensitivity of these methods led to the use of various immunodiagnostic methods in the diagnosis of kala-azar. Antigen detection and polymerase chain reaction to detect parasitic DNA have been found to be useful in patients with an underlying immunosuppressive disease like AIDS. For treating kala-azar, pentavalent antimonial compounds are still the first-line agents. However, due to increasing resistance to this agent, many patients at present require other drugs including amphotericin B and pentamidine. Toxic effects of these second-line agents have led to development of drug delivery systems like liposomal amphotericin B, which has shown uniform efficacy in clinical trials. Combining stibogluconate with either paromomycin or interferon-gamma has also been shown to be useful in many patients with drug-resistant kala-azar.

Amphotericin B↗

PubMed2003

Arsenic sensing and resistance system in the cyanobacterium Synechocystis sp. strain PCC 6803.

Arsenic is one of the most important global environmental pollutants. Here we show that the cyanobacterium Synechocystis sp. strain PCC 6803 contains an arsenic and antimony resistance operon consisting of three genes: arsB, encoding a putative arsenite and antimonite carrier, arsH, encoding a protein of unknown function, and arsC, encoding a putative arsenate reductase. While arsB mutant strains were sensitive to arsenite, arsenate, and antimonite, arsC mutants were sensitive only to arsenate. The arsH mutant strain showed no obvious phenotype under the conditions tested. In vivo the arsBHC operon was derepressed by oxyanions of arsenic and antimony (oxidation state, +3) and, to a lesser extent, by bismuth (oxidation state, +3) and arsenate (oxidation state, +5). In the absence of these effectors, the operon was repressed by a transcription repressor of the ArsR/SmtB family, encoded by an unlinked gene termed arsR. Thus, arsR null mutants showed constitutive derepression of the arsBHC operon. Expression of the arsR gene was not altered by the presence of arsenic or antimony compounds. Purified recombinant ArsR protein binds to the arsBHC promoter-operator region in the absence of metals and dissociates from the DNA in the presence of Sb(III) or As(III) but not in the presence of As(V), suggesting that trivalent metalloids are the true inducers of the system. DNase I footprinting experiments indicate that ArsR binds to two 17-bp direct repeats, with each one consisting of two inverted repeats, in the region from nucleotides -34 to + 17 of the arsBHC promoter-operator.

Antimony↗