Cost-effectiveness analysis of diagnostic-therapeutic strategies for visceral leishmaniasis in Brazil

Abstract INTRODUCTION: Visceral leishmaniasis (VL) is fatal if not diagnosed and treated. This study aimed to estimate the cost-effectiveness of diagnostic-therapeutic alternatives for VL in Brazil. METHODS: A decision model estimated the life expectancy and costs of six diagnostic-therapeutic strategies. RESULTS: IT LEISH + liposomal amphotericin B emerged the best option, presenting lower costs and higher effectiveness. DAT-LPC + liposomal amphotericin B showed an incremental cost-effectiveness ratio of US$ 326.31 per life year. CONCLUSIONS: These findings indicate the feasibility of incorporating DAT and designating liposomal amphotericin B as the first-line drug for VL in Brazil.

Combination therapy with liposomal amphotericin b (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate in a refractory visceral leishmaniasis case

Abstract Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.

Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary leishmaniasis results in low lethality, low incidence of relapse, and low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001-2013)

BACKGROUND American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. OBJECTIVES To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. METHODS Data were recovered from records of all ATL patients diagnosed during that period. FINDINGS Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. MAIN CONCLUSIONS Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.

Intralesional treatment with meglumine antimoniate in three patients with New World cutaneous leishmaniasis and large periarticular lesions with comorbidities

Abstract Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.

Standardization of intralesional meglumine antimoniate treatment for cutaneous leishmaniasis

Abstract INTRODUCTION: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS The technique is described in detail sufficient to enable replication. CONCLUSIONS: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.

Intralesional meglumine antimoniate for the treatment of localised cutaneous leishmaniasis: a retrospective review of a Brazilian referral centre

Although intralesional meglumine antimoniate (MA) infiltration is considered an option for cutaneous leishmaniasis (CL) therapy and is widely used in the Old World, there have been few studies supporting this therapeutic approach in the Americas. This study aims to describe outcomes and adverse events associated with intralesional therapy for CL. This retrospective study reviewed the experience of a Brazilian leishmaniasis reference centre using intralesional MA to treat 31 patients over five years (2008 and 2013). The median age was 63 years (22-86) and the median duration time of the lesions up to treatment was 16 weeks. In 22 patients (71%), intralesional therapy was indicated due to the presence of contraindications or previous serious adverse events with systemic MA. Other indications were failure of systemic therapy or ease of administration. Intralesional treatment consisted of one-six infiltrations (median three) for a period of up to 12 weeks. The initial (three months) and definitive (six months) cure rates were 70.9% and 67.7%, respectively. Most patients reported mild discomfort during infiltration and no serious adverse events were observed. In conclusion, these results show that the intralesional MA efficacy rate was very similar to that of systemic MA treatment, and reinforce the need for further studies with adequate design to establish the efficacy and safety of this therapeutic approach.

In vivo antileishmanial activity and chemical profile of polar extract from Selaginella sellowii

The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.

Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions ...

Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

Resolution of cttaneous leishmaniasis after acue eczema due to intralesional mmeglumine antimoniate / Resolução de leishmaniose cutânea após eczema agudo devido a antimoniato de meglumina intralesional

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.

Relatamos caso de paciente de 42 anos atendida em centro de referência em leishmanioses no Rio de Janeiro, Brasil, apresentando lesão de leishmaniose cutânea no antebraço direito. Iniciado tratamento com baixa dose de antimoniato de meglumina (AM) intramuscular (5 mg Sb5+/kg/dia), houve melhora após 28 dias, porém com desenvolvimento de eczema generalizado. Após 87 dias, notou-se piora da lesão. A paciente recusou o tratamento com anfotericina B. Infiltrou-se AM na lesão em duas sessões, resultando em eczema local com bolhas. Entretanto, 20 dias depois, tanto a úlcera quanto o eczema regrediram. A administração intralesional do AM deve ser utilizada com cautela em pacientes com hipersensibilidade cutânea a este fármaco.

Factors associaeed to adherence to different tratment schemes with meglumine aantimoniate in a clinical trial for cutaneous leishmaniasis / Fatores associados à adesão a diferentes esquemas de tratamento com antimoniato de meglumina em ensaio clínico para leishmaniose cutânea

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.

O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado. Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Recurrent cutaneous leishmaniasis / Leishmaniose recidiva cútis

We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment.

Paciente do sexo masculino, 18 anos. Dois anos após tratamento insuficiente para leishmaniose tegumentar americana, apresentou, na mesma localização, lesão formada por cicatriz atrófica central e nódulos verrucosos na periferia. Era imunocompetente, hígido e negava qualquer trauma local. O diagnóstico de leishmaniose recidiva cutis foi feito através de cultura do aspirado da lesão. Realizou tratamento com N-metilglucamina (20mgSbV/kg/dia) associado à pentoxifilina (1200mg/dia) durante 30 dias alcançando cura clínica. Os casos semelhantes requerem atenção diferenciada pela dificuldade ao tratamento.

Potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime / A utilidade da terapia de oxigenação hiperbárica e própolis em potencializar a atividade leishmanicida do glucantime

In this study we investigated the efficacy of hyperbaric oxygen (HBO) therapy, alone or combined with the pentavalent antimonial glucantime on Leishmania amazonensis infection. In parallel, the effect of Brazilian red propolis gel (propain) alone or combined with glucantime on L. amazonensis infection was evaluated. The inhibition of the infection in macrophages treated with glucantime in combination with HBO exposition was greater than that of macrophages treated with glucantime alone or HBO alone. The susceptible mouse strain BALB/c infected in the shaved rump with L. amazonensis treated with glucantime and exposed to HBO showed: time points in the course of the disease in which lesions were smaller than those of mice treated with glucantime alone and revascularization of the skin in the lesion site; interferon-gamma (IFN-g) levels were not elevated in lymph node cells from these animals. Propain alone was not efficient against lesions, although less exudative lesions were observed in animals treated with propain alone or combined with glucantime. These results reveal the potential value of HBO and red propolis in combination with glucantime for treating cutaneous leishmaniasis and encourage further studies on the effect of more aggressive HBO, propolis and glucantime therapies on different mouse models of leishmaniasis.

Nesse trabalho foi avaliada a eficácia da terapia da oxigenação hiperbárica (HBO), aplicada em combinação ou não com o tratamento com glucantime, durante a infecção com Leishmania amazonensis. O efeito de gel da própolis vermelha de origem brasileira (propaina) aplicado em combinação ou não com o tratamento com glucantime, também foi avaliado durante infecção com esse parasita. A inibição da infecção de macrófagos tratados com glucantime em combinação com HBO foi maior que a de macrófagos tratados apenas com glucantime ou HBO. A linhagem murina susceptível, BALB/c, infectada no dorso com L. amazonensis, tratada com glucantime e exposta a HBO, mostrou durante o curso da doença, fases em que as lesões eram menores do que a de camundongos apenas tratados com glucantime; observou-se revascularização da pele da lesão e baixa produção de interferon-gama em células de linfonodos desses animais. O tratamento com propaina não foi eficiente na cura das lesões, apesar de lesões menos exsudativas serem observadas em animais tratados com propaina ou propaina combinada ao tratamento com glucantime. Os resultados demonstram que tanto HBO como a própolis vermelha em combinação com glucantime, são promissoras no tratamento da leishmaniose cutânea. Novos estudos devem ser realizados para avaliar tratamentos e outros protocolos em diferentes modelos murinos da leishmaniose.

[Side effects of meglumine antimoniate in cutaneous leishmaniasis: 15 cases]

Leishmaniasis is wide spread parasitic disease considered to be endemic in 88 countries in both old and new world. The standard treatment remains Meglumine antimoniate. We study the side effects of systemic meglumine antimoniate in cutaneous leishmaniasis. We conduct a retrospective study covering 3-year period [2002- 2005]. All medical reports of cutaneous leishmaniasis treated by systemic Meglumine antimoniate are reviewed. The study comprise 63 patients all treated by systemic meglumine antimoniate at the dose of 60mg/kg/day for 10-15 days. Side effects were noted in 15 cases [12 females and 3 males] .The subject's age range from 11 to 78 years. Stibio-intolerance [fever, rash, arthralgia, abdominal pain] was observed in 12 cases and stibio-toxicity in 3 cases: precordialgies 1 case, hyperamylasemia and increase liver enzyme: 1 case, pancytopenia, renal and hepatic failure leading to death: 1 case, skin eruption: 7 cases, pruritis and erythema in the site of injection: 5 cases, urticaria: 1 case. Meglumine antimoniate was stopped in 13 cases Meglumine antimoniate is the generally recommended treatment of cutaneous leishmaniasis. In spite of the rarity of Glucantime's side effects, we recommend a careful survey especially in older patients

Cutaneous Leishmaniasis of the Lid: A Report of Nine Cases

Leishmaniasis is a parasitic disease caused by Leishmania species and is classified into three forms; cutaneous, mucocutaneous, and visceral. The eyelid is a rare site involved by leishmaniasis and only makes up 2.5% of cases with cutaneous leishmaniasis (CL). Although CL can affect both upper and lower lids on either their outer or inner aspects, the lateral canthus is most often affected. The most common aspect of lid leishmaniasis is chalazion-like lesions but ulcerous, phagedenic, cancer-like forms, and unilateral chronic granulomatous blepharitis may be observed. When the lid is involved, the disease is usually self-limiting; healing usually takes up to one year, hence early diagnosis and treatment are important. The diagnosis is based on a high index of suspicion regarding the endemicity of the disease in the region. Response to treatment in lid CL cases is quite satisfactory. In this article, we report nine cases of lid leishmaniasis with satisfactory responses to intralesional meglumine antimoniate.

O uso da associação azitromicina e N-metil glucamina no tratamento da leishmaniose cutânea causada por Leishmania (Leishmania) amazonensis em camundongos C57BL6 / The use of azythromycin and N-methyl glucamine for the treatment of cutaneous Leishmaniasis caused by Leishmania (Leishmania) amazonensis in C57BL6 mice

FUNDAMENTOS: O tratamento de primeira escolha da leishmaniose tegumentar americana é a N-metil-glucamina que tem alta toxicidade, exige administração parenteral e nem sempre cura. A azitromicina mostrou ação in vitro e resultado contraditório na doença humana. OBJETIVO: Verificar se a associação N-metil-glucamina+azitromicina é mais eficaz do que N-metil-glucamina no tratamento da leishmaniose experimental. MÉTODOS: 25 camundongos inoculados com a cepa C57BL/6 de L. (L.) amazonensis foram divididos em dois grupos. Um foi tratado com 400mgSbV/kg/dia de N-metil-glucamina associado a 200mg/kg/dia de azitromicina durante 20 dias, e o outro com N-metil-glucamina, na mesma dose, durante o mesmo tempo. Foi feita avaliação clínica e parasitológica com análise estatística. RESULTADO: Na avaliação clínica, pesquisa de amastigotas e das culturas, não houve diferença estatística. Verificou-se, entretanto, diferença significante no resultado das culturas realizadas através de diluição limitante, que desfavoreceu a associação NMG+ azitromicina. CONCLUSÃO: A associação N-metil-glucamina e azitromicina não demonstrou mais eficácia do que o N-metil-glucamina em uso isolado.

BACKGROUND: The first choice treatment for cutaneous Leishmaniasis is N-methyl glucamine: it has high toxicity, requires parenteral administration and cure is not always reached. Azythromycin showed in vitro action and controversial results in humans with the disease. OBJECTIVE: To verify if the association of N-methyl-glucamine - azythromycin is more effective than N-methyl-glucamine alone for the treatment of experimental Leishmaniasis. METHODS: Twenty-five C57BL/6 mice were inoculated with L. (L.) amazonensis strain and divided into two groups. One group was treated with 400mgSbV/kg/day of N-methyl glucamine and 200mg/kg/day of azythromycin for 20 days and the other group received the same dose of N-methyl glucamine alone during the same period of time. Clinical and parasitological evaluations were submitted to statistical analyses. RESULTS: There was no statistical difference in clinical analysis, in amastigotes investigation and in cultures. There were significant differences in cultures using limiting dilution, which showed lower efficacy of the association N-methyl glucamine -azythromycin. CONCLUSION: N-methyl glucamine-azythromycin association was not more effective than N-methyl glucamine alone.

Comparison of Thymus vulgaris (Thyme), Achillea millefolium (Yarrow) and propolis hydroalcoholic extracts versus systemic glucantime in the treatment of cutaneous leishmaniasis in balb/c mice.

BACKGROUND & OBJECTIVES: Leishmaniasis is a parasitic disease transmitted by sand flies. Many investigations are performed to find an effective and safe treatment for leishmaniasis. In this study, we evaluated the efficacy of herbal extracts of Thymus vulgaris (Thyme) and Achillea millefolium (Yarrow), propolis hydroalcoholic extract and systemic glucantime against cutaneous leishmaniasis in Balb/c mice. METHODS: A total of 45 mice were randomised into five groups each including nine mice. They were treated with pure ethanol 70 degrees, systemic glucantime, Achillea millefolium hydroalcoholic extract, Thymus vulgaris hydroalcoholic extract and propolis hydroalcoholic extract for six weeks. The statistical tests including student t-test were used for analysis. Data were analyzed by SPSS software, ver 13.00. RESULTS: Mean of ulcer size reduction were -17.66, -22.57, 43.29, 36.09 and 43.77% for the alcohol, glucantime, yarrow, thyme and propolis groups, respectively. The results were suggestive that Thymus vulgaris, Achillea millefolium and propolis hydroalcoholic extracts were significantly more effective in reduction of ulcer size as compared with glucantime (p = 0.006, 0.002 and 0.008, respectively). INTERPRETATION & CONCLUSION: Our results are suggestive that Thymus vulgaris, Achillea millefolium and propolis extracts are effective for treatment of cutaneous leishmaniasis in mice. Regarding these results, we suggest that efficacy of these extracts alone or in combination are evaluated against human cutaneous leishmaniasis as a randomized clinical trial.

A comparative study between the efficacy of systemic meglumine antimoniate therapy with standard or low dose plus oral omeprazole in the treatment of cutaneous leishmaniasis.

BACKGROUND & OBJECTIVES: Pentavalent antimony compounds are the first line of drugs in the treatment of cutaneous leishmaniasis. However, because of their potential toxic effects, many investigations are performed to find an effective and safe treatment for cutaneous leishmaniasis patients. Our objective in this investigation was to compare the effect of oral omeprazole and low dose systemic meglumine antimoniate (MA) and standard dose of systemic MA in the treatment of cutaneous leishmaniasis. METHODS: This was a randomized double-blinded clinical trial. In 150 patients with cutaneous leishmaniasis who were randomly divided into three groups and were treated with: (i) MA 60 mg/kg/day/ IM and oral placebo for three weeks; (ii) MA 30 mg/kg/day/IM and oral omeprazole 40 mg/day for three weeks; and (iii) MA 30 mg/kg/day/IM and oral placebo for three weeks. All the patients were visited every two weeks from the beginning of the trial up to six weeks and then at 8 and 12 weeks. The effectiveness of the treatment was classified in three levels as complete response, partial response and no response. Data were analyzed by SPSS 10 using KI square, Mann-Whitney, Kaplan-Mayer and ANOVA tests. RESULTS: Rate of complete response for three months (12 weeks) after starting the treatments was 93% for the group treated with standard dose of glucantime and placebo, 89% for the group treated with omeprazole and low dose glucantime and 80% for the group treated with low dose glucantime and placebo and these differences were significant (p < 0.05). The highest response rate was for the group treated with standard dose of glucantime and placebo. INTERPRETATION & CONCLUSION: Although oral omeprazole and low dose of systemic MA showed less efficacy in comparison to standard dose of systemic MA in the treatment of cutaneous leishmaniasis, it still can be considered as a replacement therapy in high risk patients (such as patients with heart, kidney and/or liver disease) under close supervision of physician.

Estudo comparativo entre miltefosina oral e antimoniato de N-metil glucamina parenteral no tratamento da leishmaniose experimental causada por Leishmania (Leishmania) amazonensis / Comparative study between oral miltefosine and parenteral N-metil glucamine antimoniate for the treatment of experimental leishmaniasis caused Leishmania (Leishmania) amazonensis

Vinte e cinco camundongos infectados com Leishmania amazonensis foram tratados com antimoniato de N-metil glucamina e miltefosina oral. Critérios: medidas das patas, pesquisa de amastigotas e culturas após-tratamento. Miltefosina: 2,43mm e glucamina 3,46mm (p=0,05). Miltefosina: esfregaços e culturas negativos. Glucamina: 2 esfregaços positivos e culturas positivas (p<0,05). Concluímos que miltefosina foi semelhante à glucamina.

Twenty-five mice were infected with Leishmania amazonensis and treated with glucamine and oral miltefosine. The criteria used were pad measurements and investigations of amastigotes and cultures after treatment. Measurements: miltefosine 2.43 mm and glucamine 3.46 mm (p: 0.05). Miltefosine smears and cultures were negative. Glucamine produced two positive smears and the cultures were positive (p < 0.05). Miltefosine was similar to or better than glucamine.