Intervention Review

You have free access to this content

Interventions for American cutaneous and mucocutaneous leishmaniasis

  1. Urbà González 1,*,
  2. Mariona Pinart1,
  3. Mónica Rengifo-Pardo2,
  4. Antonio Macaya3,
  5. Jorge Alvar4,
  6. John A Tweed2

Editorial Group: Cochrane Skin Group

Published Online: 15 APR 2009

Assessed as up-to-date: 25 JAN 2009

DOI: 10.1002/14651858.CD004834.pub2

Database Title

Additional Information

How to Cite

González U, Pinart M, Rengifo-Pardo M, Macaya A, Alvar J, Tweed JA. Interventions for American cutaneous and mucocutaneous leishmaniasis. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD004834. DOI: 10.1002/14651858.CD004834.pub2.

Author Information

  1. 1

    Hospital Plató, Department of Dermatology, Research Unit for Evidence-based Dermatology, Barcelona, Catalunya, Spain

  2. 2

    University of Nottingham, c/o Cochrane Skin Group, Nottingham, UK

  3. 3

    Bellvitge Hospital, Barcelona, Fleixa Llarga s/n l'hospitalet de Llobregat, Barcelona, Spain

  4. 4

    World Health Organization, Control of Neglected Tropical Diseases (WHO/CDS/NTD/IDM), Geneva 27, Switzerland

*Urbà González , Department of Dermatology, Research Unit for Evidence-based Dermatology, Hospital Plató, c/ Plato 21, Barcelona, Catalunya, 08006, Spain. urba.gonzalez@hospitalplato.com .

Publication History

  1. Publication Status: New
  2. Published Online: 15 APR 2009

SEARCH

ARTICLE TOOLS

View Full Article (HTML) Summary (64K)Standard (1040K)Full (1309K)
 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Pentavalent antimonial drugs are the most prescribed treatment for American cutaneous and mucocutaneous leishmaniasis. Other drugs have been used with varying success.

Objectives

To assess the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis.

Search methods

We searched the Cochrane Skin Group Specialised Register (January 2009), the Register of Controlled Clinical Trials in The Cochrane Library (Issue 1,2009), MEDLINE (2003 to January 2009), EMBASE (2005 to January 2009), LILACS (from inception to January 2009), CINAHL (1982-May 2007) and other databases.

Selection criteria

Randomised controlled trials (RCTs) assessing treatments for American cutaneous and mucocutaneous leishmaniasis.

Data collection and analysis

Two authors independently assessed trial quality and extracted data.

Main results

We included 38 trials involving 2728 participants. Results are based on individual studies or limited pooled analyses. There was good evidence in:

Leishmania braziliensis and L. panamensis infections:

Intramuscular (IM) meglumine antimoniate (MA) was better than oral allopurinol for 28 days (1RCT n=127, RR 0.39; 95% CI 0.26, 0.58). Intravenous (IV)MA for 20-days was better than 3-day and 7-day IVMA plus 15% paromomycin plus 12% methylbenzethonium chloride (PR-MBCL) or 7-day IVMA (1RCT n= 150, RR 0.24; 95% CI 0.11, 0.50; RR 0.69; 95% CI 0.53, 0.90; RR 0.64; 95% CI 0.44, 0.92 respectively). Oral allopurinol plus antimonials was better than IV antimonials (2RCT n= 168, RR 1.90; 95% CI 1.40, 2.59; I2=0%).

L. braziliensis infections:

Oral pentoxifylline plus IV sodium stibogluconate (SSG) was better than IVSSG (1RCT n= 23, RR 1.66; 95% CI 1.03, 2.69); IVMA was better than IM aminosidine sulphate (1RCT n= 38, RR 0.05; 95% CI 0.00, 0.78) and better than IV pentamidine isethionate (1RCT n= 80, RR 0.45; 95% CI 0.29, 0.71). Intramuscular MA was better than Bacillus Calmette-Guérin (1RCT n= 93, RR 0.46; 95% CI 0.32, 0.65).

L .panamensis infections:

Oral allopurinol was better than IVMA (1RCT n= 58, RR 2.20; 95% CI 1.34, 3.60). Aminosidine sulphate at doses of 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days (1RCT n= 60, RR 0.23; 95% CI 0.07, 0.73; RR 0.23; 95% CI 0.07, 0.73 respectively). Oral ketoconazole for 28 days, oral miltefosine and topical PR-MBCL were better than placebo.

Authors' conclusions

Most trials have been designed and reported so poorly that they are inconclusive. There is a need for large well conducted studies that evaluate long-term effects of current therapies to improve quality and standardization of methods.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Interventions for American cutaneous and mucocutaneous leishmaniasis.

American cutaneous and mucocutaneous leishmaniasis, a disfiguring and stigmatising disease affecting Central and South American regions, is caused by a parasite transmitted by sandflies. Pentavalent antimonial drugs (sodium stibogluconate (Pentostam, Stibanate, SSG) and meglumine antimoniate (Glucantime, MA)) have been used since the 1940s as first-line therapeutic agents for cutaneous leishmaniasis worldwide. However, other treatments have been used because these are expensive, toxic and painful, and because resistance is emerging.

We assessed 38 trials involving different interventions.

In L. braziliensis and L. panamensis infections there was good evidence that intramuscular (IM) MA was better than oral allopurinol for 28 days, that 20-day intravenous (IV) MA was better 7-day IVMA and also better than 3 or 7-day IVMA with paromomycin plus 12% methylbenzethonium chloride (PR-MBCL). Oral allopurinol plus intravenous antimonials was better than intravenous antimonials.

There was reasonable randomised controlled trial (RCT) evidence in L. braziliensis infections that oral pentoxifylline plus IVSSG was better than IVSSG alone; IVMA was better than IM aminosidine sulphate and IV pentamidine isethionate; and IMMA was better than the Bacillus Calmette-Guérin vaccine. Regarding L. panamensis infections, oral ketoconazole for 28 days and oral miltefosine and topical PR-MBCL were all better than placebo; oral allopurinol better than IVMA, aminosidine sulphate 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days.

There was complete absence of RCT evidence on alternative treatments, surgery, oral itraconazole and fluconazole, oral antibiotics like rifampicin, metronidazole and cotrimoxazole, intravenous or topical amphotericin B, oral dapsone, photodynamic therapy, promoting healing therapies, laser, and cryotherapy treatments. Moreover, none of the studies reported quality of life, "microbiological or histopathological cure of skin lesions", changes in ability to detect the parasite by diagnostic methods (e.g. smear or culture) or mortality.

No general consensus on optimal treatment has been achieved but alternatives to intramuscular or intravenous treatments are under active investigation.

The evidence base for the treatment of American cutaneous and mucocutaneous leishmaniasis has many limitations due to poor design and reporting of clinical trials. Because resources are limited for clinical research into neglected diseases, there is a need for prioritising properly designed clinical trials. Therefore, we suggest the creation of an international strategy to improve the quality and standardization of future trials for a better evidence-based strategic approach in the future.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

皮膚及黏膜美洲利氏曼原蟲病的治療

最常用來治療皮膚及黏膜美洲利氏曼原蟲病的藥物為含五價銻金屬的藥品。其他藥物治療則成效不一。

目標

想要評估對於皮膚及黏膜美洲利氏曼原蟲病治療的效果。

搜尋策略

我們搜尋了the Cochrane Skin Group Specialised Register (2009年1月), the Register of Controlled Clinical Trials in The Cochrane Library (2009年 Issue 1), MEDLINE 資料庫 (2003年到2009年1月), EMBASE 資料庫 (2005年到2009年1月), LILACS 資料庫 (從創辦到2009年1月), CNINAHL 資料庫 (1982年到2007年5月) 和其他的資料庫。

選擇標準

選擇關於評估皮膚及黏膜美洲利氏曼原蟲病治療的隨機對照試驗 (RCTs) 。

資料收集與分析

由兩位作者獨立地評估試驗的品質以及資料分析。

主要結論

我們收納了38篇試驗，包涵2728位參與者。從各篇研究的結論和有限的彙集分析獲得結論。有很好的證據顯示:對於 Leishmania braziliensis 和 L. panamensis 的感染:肌肉注射 meglumine antimoniate (MA) 比口服allopurinol,28天 有效 (1篇RCT, n = 127, 相對危險性 0.39; 95% 信賴區間 0.26, 0.58) 。靜脈注射 MA,20天 比 靜脈注射 MA,3天或7天,加上15% paromomycin 加上 12% methylbenzethonium chloride (PRMBCL) 以及 靜脈注射 MA,7天 來得有效 (1篇RCT, n = 150, 相對危險性 0.24; 95% 信賴區間 0.11, 0.50; 相對危險性 0.69; 95% 信賴區間 0.53, 0.90; 相對危險性 0.64; 95% 信賴區間 0.44, 0.92) 。口服 allopurinol 加上 antimonials 比 靜脈注射 antimonials 來得有效 (2篇RCT, n = 168, 相對危險性 1.90; 95% CI信賴區間 1.40, 2.59; I2 = 0%) 。對於 L. braziliensis 的感染: 口服 pentoxifylline 加上靜脈注射 sodium stibogluconate (SSG) 比 單純靜脈注射 SSG 來得有效 (1篇RCT, n = 23, 相對危險性 1.66; 95% 信賴區間 1.03, 2.69) 。靜脈注射 MA 比 肌肉注射 aminosidine sulphate 有效 (1篇RCT, n = 38, 相對危險性 0.05; 95% 信賴區間 0.00, 0.78) 也比靜脈注射 pentamidine isethionate 有效 (1篇RCT, n = 80, 相對危險性 0.45; 95% 信賴區間 0.29, 0.71) 。肌肉注射 MA 比 Bacillus CalmetteGuerin 有效 (1篇RCT, n = 93, 相對危險性 0.46; 95% 信賴區間 0.32, 0.65) 。 對於 L. panamensis 的感染: 口服 allopurinol 比 靜脈注射 MA 來得有效 (1篇RCT, n = 58, 相對危險性 2.20; 95% 信賴區間 1.34, 3.60) 。 Aminosidine sulphate 以 12毫克/公斤/天 和 18毫克/公斤/天的劑量使用14天 比 aminosidine sulphate以 12毫克/公斤/天 的劑量使用7天有效 (1篇RCT, n = 60, 相對危險性 0.23; 95% 信賴區間 0.07, 0.73; 相對危險性 0.23; 95% 信賴區間 0.07, 0.73) 。 口服 ketoconazole 28天, 口服 miltefosine 和 表皮塗抹 PRMBCL 則比安慰劑有效。

作者結論

大多數試驗的設計和報告都相當差強人意，因此無法得到很好的結論。我們需要一個大型的有良好設計的研究，來評估目前治療方法的長期效果，以改善我們治療的品質並建立標準的治療方法。

翻譯人

本摘要由馬偕醫院楊兆傑翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

皮膚及黏膜美洲利氏曼原蟲病，是ㄧ種有損外型且被蒙上污名的疾病，主要發生在中美和南美洲，是由砂蠅所傳染的寄生蟲病。含五價銻金屬的藥物[sodium stibogluconate (Pentostam, Stibanate, SSG) 和 meglumine antimoniate (Glucantime, MA)]自1940年代起，就被廣泛地當作第一線治療皮膚利氏曼原蟲病的藥物。但是，由於這種治療昂貴、有毒、疼痛，而且出現了抗藥性，其他種的治療也有被使用。我們評估了38篇試驗，其中包含了不同的治療方法。對於 L. braziliensis and L. panamensis 的感染，有很好的證據顯示肌肉注射 MA 比 口服 allopurinol for 28天 有效， 靜脈注射20天MA比 靜脈注射7天MA 和 靜脈注射3天或7天MA加上 paromomycin 和 12% methylbenzethonium chloride (PRMBCL) 有效。口服 allopurinol 加上靜脈注射 antimonials 比 單純靜脈注射 antimonials 有效。很合理的，隨機對照試驗的證據顯示，對於 L. braziliensis 的感染，口服 pentoxifylline加上靜脈注射 SSG 比單純靜脈注射 SSG 有效; 靜脈注射 MA 比肌肉注射 aminosidine sulphate 和靜脈注射 pentamidine isethionate 有效; 而且肌肉注射 MA 比 Bacillus CalmetteGuerin 疫苗有效。對於 L. panamensis 的感染, 口服 ketoconazole 28天和 口服 miltefosine 和 表皮塗抹 PRMBCL 都比安慰劑來得好; 口服 allopurinol 比靜脈注射 MA 有效, aminosidine sulphate 12毫克/公斤/天 和 18毫克/公斤/天使用14天 比 aminosidine sulphate 12毫克/公斤/天使用7天 有效。 對於其他的替代療法、手術、口服 itraconazole 和 fluconazole、口服 抗生素如rifampicin, metronidazole 和 cotrimoxazole、靜脈注射或表皮塗抹的 amphotericin B、口服 dapsone、照光治療、promoting healing therapies, 雷射, 和 冷凍治療，則完全沒有隨機對照試驗的證據。此外，沒有研究報告出以下幾點的不同，包括使用藥物後的生活品質、 ‘微生物學上的’ 或者 ‘組織病理學上的’ 皮膚病灶痊癒、利用診斷法 (如抹片或培養) 偵測到寄生蟲感染的比率或者死亡率。對於最佳的治療法沒有一致的共識，但對於肌肉注射或者靜脈注射治療則有不錯的研究。因為臨床試驗的設計和報告都相當差強人意，對於皮膚及黏膜美洲利氏曼原蟲病治療的實證有許多限制。由於罕見疾病的病例數有限，所以需要良好設計的試驗。因此，我們建議能建立起跨國際的試驗並訂出標準策略，來改善未來實証醫學研究的品質與標準化。

View Full Article (HTML) Summary (64K)Standard (1040K)Full (1309K)