Treatment of Cutaneous Leishmaniasis with Allopurinol and Stibogluconate

Martinez, Samuel; González, M.; Vernaza, María Elisa

doi:10.1093/clinids/24.2.165

Cited by 56 publications

(25 citation statements)

References 17 publications

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“…Published efficacy trials of pentavalent antimonial drugs using a regimen of 20 mg Sb/kg/d for 20 days in Colombia and the Americas, have documented an efficacy of 88 to 100% for the treatment of cutaneous leishmaniasis caused by species of the Leishmania Viannia subgenus. 5,8,[13][14][15][16]20 One group in the Colombian southwest and close to our study area, reported efficacy of meglumine antimonate with a 15-day regimen, to be 40%, 21,22 and close to the 36-37% efficacy of placebo reported by other investigators in other areas of Colombia. 8,20 All of these trials have involved young-adult populations primarily.…”

Section: Discussionsupporting

confidence: 83%

Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species.

Palácios¹,

Osório²,

Grajalew³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

116

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Abstract. Clinical response to supervised treatment of Colombian patients with cutaneous leishmaniasis was evaluated in a randomized controlled trial comparing 10 days versus 20 days of treatment with meglumine antimonate (20 mg Sb/kg/day). Masked examiners evaluated clinical response defined as 100% re-epithelialization of all lesions at 13 weeks and no relapses during 52 weeks of follow-up. The efficacy of meglumine antimonate for 10 days' treatment was 61% (28 of 46) compared to 67% (24 of 36) for 20 days. There was a significantly lower clinical response for children Ͻ 5 years in both 10-day (11%) and 20-day (25%) groups compared to patients aged 5-14 years (67% and 75%, respectively) and 15 years or more (81% and 83%, respectively). Overall efficacy of treatment schedules was comparable, but lower than expected, mainly because of low efficacy in children. Pathogenicity of infection and pharmacokinetics may affect the treatment response in children. New therapeutic alternatives should be evaluated in trials that include children and women.

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Section: Discussionsupporting

confidence: 83%

Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species.

Palácios¹,

Osório²,

Grajalew³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

116

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“…7 CF cure rates attained with the use of pentavalent antimony were compatible to those found by other authors. 14,22,23 In the case of MCF, these rates were smaller, thus reaffirming the greater difficulty found in the treatment of this form of the disease (Table 1). Results indicating otherwise might be derived, for instance, from methodologies different than the one employed in this study.…”

Section: Resultsmentioning

confidence: 71%

Estudo clínico, epidemiológico e terapêutico de 402 pacientes com leishmaniose tegumentar americana atendidos no Hospital Universitário de Brasília, DF, Brasil

Name

Borges

Nogueira

et al. 2005

An. Bras. Dermatol.

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BACKGROUND -American cutaneous leishmaniasis is a disease with high prevalence and incidence in Brazil. The Brazilian Central-Western Region currently holds the third largest incidence and the first growth rate of this disease in the country. OBJECTIVES -to evaluate clinical, epidemiological and treatment features of patients with American cutaneous leishmaniasis seen at the University Hospital of Brasília. METHOD -a case series study with 402 patients was carried out, spanning the period between January 1st, 1994 and February 28th, 2003. The following variables were studied: sex, age, occupation, state of origin, clinical features, diagnostic techniques, treatment with pentavalent antimony and side effects. Follow-up was one year after the end of treatment. RESULTS -the predominant group of patients was composed by male rural laborers who presented mainly the cutaneous form of the illness. The greatest efficacy of the antimony was observed in patients presenting the cutaneous form treated up to six months after the onset of symptoms, and in females in general (both differences were statistically significant in multivariate analysis). The early treatment of the mucocutaneous form also presented better results, although not statistically significant. Electrocardiographical alterations were more frequent in the group of patients receiving a 20mg SbV/Kg/day for a 30-day schedule than those with the same dosage for 20 days. Eosinophilia was found in 17.5%. CONCLUSIONS -Early treatment, female gender and cutaneous form presented higher levels of cure. Electrocardiographic changes rose as time of treatment was increased. The remarkable report of eosinophilia as a side effect of N-methylglucamine deserves further investigation. Keywords: Leishmaniasis, Mucocutaneous/diagnosis; Leishmaniasis, Mucocutaneous/epidemiology; Leishmaniasis, Mucocutaneous/therapy Resumo: FUNDAMENTOS -A leishmaniose tegumentar americana é doença em expansão no Brasil. A região Centro-Oeste é hoje a terceira em incidência e a primeira em crescimento da doença. OBJETIVOS -Avaliar pacientes com leishmaniose tegumentar americana atendidos no Hospital Universitário de

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“…Current evidence indicates that purine analogues alone or in combination with other chemotherapeutic agents are very effective against almost any fast-growing cells (22,41). Allopurinol, a purine analogue, has been used to treat leishmaniasis alone (34,48) or combined with other drugs (21,35,36,39,47). It should be pointed out, however, that the efficacy of allopurinol monotherapy remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Purine Nucleobase Transport in Amastigotes of Leishmania mexicana : Involvement in Allopurinol Uptake

Al-Salabi

Koning

2005

Antimicrob Agents Chemother

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Nucleobase and nucleoside transporters play central roles in the biochemistry of parasitic protozoa, as they lack the ability to synthesize purines de novo and are absolutely reliant upon purine salvage from their hosts. Furthermore, such transporters are potentially critical to the pharmacology of these important human pathogens, because they mediate the uptake of purine analogues, as well as some nonpurine drugs, that can be selectively cytotoxic to the parasites. We here report the first identification and characterization of a purine nucleobase transporter in Leishmania amastigotes. Uptake of [ 3 H]hypoxanthine by Leishmania mexicana amastigotes was mediated by a single high-affinity transporter, LmexNBT1, with a K m of 1.6 ؎ 0.4 M and high affinity for adenine, guanine, and xanthine but low affinity for nucleosides and pyrimidine nucleobases. Allopurinol, an antileishmanial hypoxanthine analogue, was apparently taken up by the same transporter. Using Parasitic protozoa of the genus Leishmania are the etiological agents of leishmaniasis. Some 12 million people throughout the world suffer from leishmaniasis, ranging from the disfiguring cutaneous form to often-fatal visceral leishmaniasis. Leishmania species are sandfly-transmitted protozoan parasites. The life cycle is divided into promastigotes and metacyclics in the insect vectors and amastigotes in their mammalian hosts, which are responsible for all clinical manifestations.Most of the currently available antileishmanial drugs have been discovered empirically, as until recently insufficient information was known about the biochemistry, physiology, and molecular biology of these parasites and the interactions with their hosts (23). The limitations of the current treatment for leishmaniasis, as a result of drug resistance and the severe side effects of most of the existing therapeutic agents, and the urgent need for new therapeutic approaches, are well documented (12,56,60).The development of a rational therapeutic strategy for the treatment and prevention of parasitic disease depends on exploitation of fundamental biochemical disparities between parasite and host, such as the inability of protozoan parasites to synthesize purines de novo (5). Current antiprotozoal agents often derive selectivity from selective accumulation by the parasite rather than the host cell (15). The selectivity and the efficacy of purine antimetabolites can be achieved by the cell surface transporters that mediate access to the cell, as substrate recognition by nucleobase transporters is strikingly different in humans and kinetoplastids such as Trypanosoma brucei (58) and Leishmania major promastigotes (2). Purine and pyrimidine antimetabolites have been highly successful against many viral infections as well as malignancies (27) and show great promise against protozoal infections as well (reviewed in references 14, 17, and 23). Allopurinol, a purine nucleobase analogue, is clinically used against various manifestations of leishmaniasis (1,13,39).Whereas purine transporters in prom...

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Treatment of Cutaneous Leishmaniasis with Allopurinol and Stibogluconate

Cited by 56 publications

References 17 publications

Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species.

Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species.

Estudo clínico, epidemiológico e terapêutico de 402 pacientes com leishmaniose tegumentar americana atendidos no Hospital Universitário de Brasília, DF, Brasil

Purine Nucleobase Transport in Amastigotes of Leishmania mexicana : Involvement in Allopurinol Uptake

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