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The Cochrane Database of Systematic... Apr 2009Pentavalent antimonial drugs are the most prescribed treatment for American cutaneous and mucocutaneous leishmaniasis. Other drugs have been used with varying success. (Meta-Analysis)
Meta-Analysis Review
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 STRATEGY
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; I(2)=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 12 mg/kg/day and 18 mg/kg/day for 14 days were better than aminosidine sulphate 12 mg/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.
Topics: Administration, Oral; Antiprotozoal Agents; BCG Vaccine; Humans; Hyperthermia, Induced; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Randomized Controlled Trials as Topic
PubMed: 19370612
DOI: 10.1002/14651858.CD004834.pub2 -
The Cochrane Database of Systematic... Oct 2008Cutaneous leishmaniasis is caused by a parasitic infection and is considered one of the most serious skin diseases in many developing countries. Antimonials are the most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cutaneous leishmaniasis is caused by a parasitic infection and is considered one of the most serious skin diseases in many developing countries. Antimonials are the most commonly prescribed treatment but other drugs have been used with varying success.
OBJECTIVES
To assess the effects of treatments for Old World cutaneous leishmaniasis (OWCL).
SEARCH STRATEGY
We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2008), MEDLINE (2003-April 2008), EMBASE (2005-April 2008), CINAHL (1982-August 2007), LILACS (from inception to April 2008) and ongoing trials databases (August 2007).
SELECTION CRITERIA
Randomised controlled trials assessing treatments in immuno-competent people with OWCL confirmed by smear, histology, culture or polymerase chain reaction.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data.
MAIN RESULTS
We included 49 trials involving 5559 participants. Reporting quality was generally poor and only two studies contained sufficiently similar data to pool.In Leishmania major infections, there was good RCT evidence of benefit of cure around 3 months after treatment when compared to placebo for 200 mg oral fluconazole (1 RCT n = 200, RR 2.78; 95% CI 1.86, 4.16), topical 15% paromomycin + 12% methylbenzethonium chloride (PR-MBCL) (1 RCT n = 60, RR 3.09; 95% CI 1.14, 8.37) and photodynamic therapy (1 RCT n = 60, RR 7.02; 95% CI 3.80, 17.55). Topical PR-MBCL was less efficacious than photodynamic therapy (1 RCT n = 65, RR 0.44; 95% CI 0.29, 0.66). Oral pentoxifylline was a good adjuvant therapy to intramuscular meglumine antimoniate (IMMA) when compared to IMMA plus placebo (1 RCT n = 64, RR 1.63; 95% CI 1.11, 2.39)In Leishmania tropica infections, there was good evidence of benefit for the use of 200 mg oral itraconazole for 6 weeks compared with placebo (1 RCT n = 20, RR 7.00; 95% CI 1.04, 46.95), for intralesional sodium stibogluconate (1 RCT n = 292, RR 2.62; 95% CI 1.78, 3.86), and for thermotherapy compared with intramuscular sodium stibogluconate (1 RCT n = 283, RR 2.99; 95% CI 2.04, 4.37).
AUTHORS' CONCLUSIONS
Most trials have been designed and reported poorly, resulting in a lack of evidence for potentially beneficial treatments. There is a desperate need for large well conducted studies that evaluate long-term effects of current therapies. We suggest the creation of an international platform to improve quality and standardization of future trials in order to inform clinical practice.
Topics: Animals; Anti-Infective Agents; Antiprotozoal Agents; Complementary Therapies; Cryotherapy; Hot Temperature; Humans; Laser Therapy; Leishmania major; Leishmania tropica; Leishmaniasis, Cutaneous; Photochemotherapy; Randomized Controlled Trials as Topic
PubMed: 18843677
DOI: 10.1002/14651858.CD005067.pub3 -
International Journal of Dermatology Feb 2008New World leishmaniasis is an important endemic disease and public health problem in developing countries. The increase in ecologic tourism has extended this problem to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
New World leishmaniasis is an important endemic disease and public health problem in developing countries. The increase in ecologic tourism has extended this problem to developed countries. Few drugs have emerged over the past 50 years, and drug resistance has increased, such that the cure rate is no better than 80% in large studies. Despite these data, there has been no systematic review with a meta-analysis of the therapy used in this important tropical disease. The aim of this study was to determine the best drug management in the treatment of cutaneous leishmaniasis (CL) in Latin America based on the best studies published in the medical literature.
METHODS
MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to CL and therapy. Articles with adequate data on cure and treatment failure, internal and external validity information, and more than four patients in each treatment arm were included.
RESULTS
Fifty-four articles met our inclusion criteria and 12 were included in the meta-analysis. Pentavalent antimonials were the most studied drugs, with a total of 1150 patients, achieving a cure rate of 76.5%. The cure rate of pentamidine was similar to that of pentavalent antimonials. Other drugs showed variable results, and all demonstrated an inferior response.
CONCLUSION
Although pentavalent antimonials are the drugs of choice in the treatment of CL, pentamidine showed similar results. Nevertheless, several aspects, such as cost, adverse effects, local experience, and availability of drugs to treat CL, must be considered when determining the best management of this disease, especially in developing countries where resources are scarce.
Topics: Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Developing Countries; Endemic Diseases; Humans; Leishmaniasis, Cutaneous; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Paromomycin; Pentamidine
PubMed: 18211479
DOI: 10.1111/j.1365-4632.2008.03417.x -
The American Journal of Tropical... Aug 2007Mucosal leishmaniasis (ML) is an important endemic disease and public-health problem in underdeveloped countries because of its significant morbidity and mortality.... (Review)
Review
Mucosal leishmaniasis (ML) is an important endemic disease and public-health problem in underdeveloped countries because of its significant morbidity and mortality. Increases in ecological tourism have extended this problem to developed countries. This form of leishmaniasis, caused by reactivation after primary cutaneous lesion, has a natural history of progressive destruction of the nasal septa and soft and hard palates, causing facial disfiguration and leading to respiratory disturbances. Treatment of ML, based on several therapies, depends on use of toxic compounds, and few drugs have emerged over the past 40 years. Drug resistance has increased, and the cure rate is no better than 70% in the largest studies. Despite these data, there has been no systematic review of therapies used to treat this important tropical disease. The aim of this study is to determine the best drug management for treatment of ML in Latin America based on the best studies offered by the medical literature. The MEDLINE, LILACS, EMBASE, Web of Science, and Cochrane Library databases were searched to identify articles related to ML and therapy. The studies were independently selected by 2 authors. Articles with sufficient data for cure and treatment failures, internal and external validity information, and > 4 patients in each treatment were included. Validation of this systematic review was based on guidelines to guarantee quality; 22 articles met our inclusion criteria. Stibogluconate achieved a 51% cure rate (76/150 patients), and 88% of patients treated with meglumine were cured (121 patients). Pentamidine and amphotericin were as effective as meglumine. Use of itraconazole and other therapies (pentoxifylline, allopurinol, or interferon-gamma) was controversial, and numbers of patients in some studies were insufficient for statistical analysis. Meglumine may be the drug of choice in the treatment of ML, as it offers similar cure rates when compared with amphotericin B and pentamidine. Cost, adverse effects, local experience, and availability of drugs to treat ML are strong points to be considered before determining the best management of this disease, especially in developing countries.
Topics: Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Humans; Itraconazole; Latin America; Leishmania; Leishmaniasis, Mucocutaneous; Meglumine; Paromomycin; Pentamidine
PubMed: 17690398
DOI: No ID Found -
Journal of the American Academy of... Aug 2007Cutaneous leishmaniasis (CL) is caused by different species of Leishmania and transmitted by the bite of infected sand flies. It is a health problem in many countries. (Review)
Review
BACKGROUND
Cutaneous leishmaniasis (CL) is caused by different species of Leishmania and transmitted by the bite of infected sand flies. It is a health problem in many countries.
OBJECTIVE
This study was performed to assess the evidence for the efficacy of different therapeutic modalities for acute Old World CL, which is usually caused by L major and L tropica.
METHODS
Evidence was reviewed according to the hierarchy of evidence. Because there have been no published systematic reviews on this topic to date, the primary source of evidence was individual randomized controlled trials (RCTs). Multiple databases were systematically searched. Using independent double review and published quality review criteria, articles were rated as good, fair, or poor. Treatment benefit data were tabulated, and conclusions were based on the rated strength of published evidence.
RESULTS
In all, 50 RCTs met inclusion criteria consisting of 5515 patients in 119 study arms. Reviewed trials were highly variable in quality and methods and generally provide weak evidence for treatment of acute Old World CL.
LIMITATIONS
The quality of included studies was generally poor.
CONCLUSIONS
Well-designed randomized, double-blind, controlled trials should be designed and conducted to find better evidence for the treatment of acute Old World CL.
Topics: Administration, Topical; Antimony; Azoles; Cryotherapy; Humans; Leishmaniasis, Cutaneous; Paromomycin; Randomized Controlled Trials as Topic; Zinc Sulfate
PubMed: 17337090
DOI: 10.1016/j.jaad.2007.01.016 -
The Lancet. Infectious Diseases Dec 2005The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with... (Comparative Study)
Comparative Study Review
The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.
Topics: Animals; Antimony; Antiprotozoal Agents; Child; Clinical Trials as Topic; Drug Resistance; Humans; India; Leishmania donovani; Leishmaniasis, Visceral; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16310148
DOI: 10.1016/S1473-3099(05)70296-6 -
Veterinary Dermatology Aug 2005Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of... (Review)
Review
Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of efficacy of interventions for treatment or prevention of canine visceral leishmaniasis, and to propose recommendations for or against their use. Forty-seven articles describing clinical trials published between 1980 and 2004 fulfilled selection criteria. The evaluation of clinical trials provided good evidence for recommending the use of meglumine antimoniate at a minimum dosage of 100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the articles also provided fair evidence for recommending the use of pentamidine (4 mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks. There was insufficient evidence for recommending the use of allopurinol alone, amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was proposed due to its side effects. Evaluation of articles on repellent measures against sand fly vectors of leishmaniasis provided good evidence for recommending deltamethrin collars and fair evidence for recommending spot-on permethrin.
Topics: Animals; Antiprotozoal Agents; Dog Diseases; Dogs; Leishmaniasis, Visceral; Meglumine; Randomized Controlled Trials as Topic
PubMed: 16101793
DOI: 10.1111/j.1365-3164.2005.00460.x -
Archives of Environmental Health 1984The typical occupational cohort study includes all causes of mortality. However, emphasis is usually placed on the presence or absence of excess cancer mortality. A... (Review)
Review
The typical occupational cohort study includes all causes of mortality. However, emphasis is usually placed on the presence or absence of excess cancer mortality. A systematic review of completed occupational cohort studies to assess the findings and patterns of cardiovascular mortality would be useful. Although many of these studies will illustrate the "healthy worker effect" with deficits in mortality, particularly from cardiovascular causes, a thorough review should indicate certain exposures needing further research. A recently published study of heart disease mortality in the rubber industry illustrates the potential use of such a literature review with subsequent follow up. Production workers in the rubber industry have shown small excesses in CAHD mortality. A follow-up study at one plant confirmed the known association between carbon disulfide and atherosclerosis, as well as suggested two new causal associations between CAHD and the use of phenol and ethanol as solvents. What additional techniques can be used to generate hypotheses on heart disease and occupation? Some possibilities include: A recent article describes the use of the results of occupational disease surveillance systems for occupational cancer research. A review of such systems for heart disease would be equally useful. It would be useful to review the quality and quantity of occupational data that has been collected in prospective cohort studies, such as those in Framingham and Evans County. The importance of examining the association between occupational exposures and heart disease include: Assessing whether adequate protection is afforded by current limits on exposure to substances known to cause heart disease (carbon disulfide, nitrates, and carbon monoxide).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Animals; Antimony; Arsenic Poisoning; Carbon Disulfide; Carbon Monoxide Poisoning; Child; Cold Temperature; Coronary Disease; Fluorocarbons; Hot Temperature; Humans; Hydrocarbons; Middle Aged; Nitrates; Noise; Occupational Diseases; Pneumoconiosis; Radiation Effects; Vibration
PubMed: 6380427
DOI: 10.1080/00039896.1984.9939528