Project description:Leishmaniasis is an important public health problem in the Americas. A Cochrane review published in 2009 analyzed 38 randomized controlled trials (RCT). We conducted a systematic review to evaluate the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis.All studies were extracted from PubMed, Embase, Lilacs (2009 to July, 2012 respectively), the Cochrane Central Register of Controlled Trials (6-2012) and references of identified publications. RCTs' risk of bias was assessed.We identified 1865 references of interest; we finally included 10 new RCTs. The risk of bias scored low or unclear for most domains. Miltefosine was not significantly different from meglumine antimoniate in the complete cure rate at 6 months (4 RCT; 584 participants; ITT; RR: 1.12; 95%CI: 0.85 to 1.47; I2 78%). However a significant difference in the rate of complete cure favoring miltefosine at 6 months was found in L. panamensis and L. guyanensis (2 RCTs, 206 participants; ITT; RR: 1.22; 95%CI: 1.02 to 1.46; I2 0%). One RCT found that meglumine antimoniate was superior to pentamidine in the rate of complete cure for L. braziliensis (80 participants, ITT; RR: 2.21; 95%CI: 1.41 to 3.49), while another RCT assessing L. guyanensis did not find any significant difference. Although meta-analysis of three studies found a significant difference in the rate of complete cure at 3 months favoring imiquimod versus placebo (134 participants; ITT; RR: 1.45; 95%CI: 1.12 to 1.88; I2 0%), no significant differences were found at 6 and 12 months. Thermotherapy and nitric oxide were not superior to meglumine antimoniate.Therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis are varied and should be decided according to the context. Since mucosal disease is the more neglected form of leishmaniasis a multicentric trial should be urgently considered.
Project description:Leishmaniasis is a major neglected tropical disease which contributes a huge economic burden on already meager economic resources. The World Health Organization (WHO) has estimated an annual incidence of 700,000--1,000,000 patients and about 20,000-30,000 deaths per year. Approximately 66,941 patients of cutaneous leishmaniasis are reported annually in the Americas. In recent years, Nicaragua has presented alarmingly high numbers of patients and elevated incidence rates. Unfortunately, there are no detailed spatial descriptions on the epidemiological situation of leishmaniasis in this country. The objective of this study is to present descriptive data about the epidemiology of leishmaniasis in Nicaragua in the context of the distribution of this neglected tropical disease (NTD) in the Americas. This paper also provides an epidemiological update on different forms of leishmaniasis found in the three administrative regions of Nicaragua and its municipalities. Health authorities from the Ministry of Health of Nicaragua (MINSA) provided the entomological and epidemiological information for the different forms of the disease from 2001 to 2018. Prevalence, incidence rates, clinical classification of disease, age groups, sex, and geographic distribution by municipality and department are described in this study. Approximately 90%-95% of the national patients corresponded to CL and 5-10% correspond to MCL. The disease is distributed in the three regions of the country, with a higher burden in the Departments of Jinotega, Matagalpa and Atlántico Norte. The municipalities with the highest proportion of patients were El Cuá (23.92%), Waslala (14.16), Santa Maria de Pantasma (9.62%), Rancho Grande (9.03%) and Siuna (7.67%). There is an expansion of spatial distribution of CL and MCL in the North Central and South Atlantic regions of the country. These results could inform interventional strategies to address the burden of leishmaniasis in Nicaragua, which would improve the likelihood of meeting the goals for the Leishmaniasis Plan of Action for the Americas.
Project description:BACKGROUND: Leishmania tropica is a causative agent of cutaneous leishmanaisis in the Middle East, North Africa and parts of southeastern Europe. Although transmission of L. tropica has been reported as anthroponotic, in Israel it was found to have a zoonotic pattern. FINDINGS: A one year old male Pekingese dog from Maale Adumim, a focus of L. tropica human cutaneous leishmaniasis near Jerusalem, was presented by its owner with a large proliferative red mucocutaneous lesion on the lip between the mouth and nose. Physical examination and a biochemistry panel were normal and a complete blood count showed mild leukocytosis with lymphocytosis and eosinophilia. A biopsy of the lesion was suggestive of the presence of Leishmania organisms. Serology for Leishmania sp. by ELISA was positive and an aspirate from the lesion showed a large number of Leishmania amastigotes. ITS1-HRM-PCR of the lesion was positive and sequencing indicated that infection was caused by L. tropica, which was also cultured from the lesion. Blood PCR was negative. The dog responded well to allopurinol treatment and its lesion shrunk considerably within one month of therapy and healed after two months. CONCLUSIONS: Only a few cases of dog infection with L. tropica have been described to date. They were reported from Morocco and Iran and involved infection of visceral organs. This is the first report of focal mucocutaneous L. tropica infection in a dog and its response to anti-leishmanial treatment. Domestic and wild canines should be evaluated for being possible animal reservoirs for human L. tropica infection in endemic areas or merely accidental hosts.
Project description:Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, and in vitro studies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators-if any-included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80 Leismania tropica infected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing and in vitro studies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, the in vitro synergistic effects of allylamines combined with triazole drugs warrant further exploration.
Project description:Pentavalent antimonials (Sb5) and miltefosine are the first-line drugs for treating cutaneous leishmaniasis in Colombia; however, toxicity and treatment duration negatively impact compliance and cost, justifying an active search for better therapeutic options. We compared the efficacy and safety of thermotherapy and meglumine antimoniate for the treatment of cutaneous leishmaniasis in Colombia.An open randomized Phase III clinical trial was performed in five military health centres. located in northwestern, central and southern Colombia. Volunteers with parasitological positive diagnosis (Giemsa-stained smears) of cutaneous leishmaniasis were included. A single thermotherapy session involving the application of 50°C at the center and active edge of each lesion. Meglumine antimoniate was administered intramuscularly at a dose of 20?mg Sb5/kg weight/day for 20?days.Both groups were comparable. The efficacy of thermotherapy was 64% (86/134 patients) by protocol and 58% (86/149) by intention-to-treat. For the meglumine antimoniate group, efficacy by protocol was 85% (103/121 patients) and 72% (103/143) by intention-to-treat, The efficacy between the treatments was statistically significant (p 0.01 and < 0.001) for analysis by intention to treat and by protocol, respectively. There was no difference between the therapeutic response with either treatment regardless of the Leishmania species responsible for infection. The side effects of meglumine antimoniate included myalgia, arthralgia, headache and fever. Regarding thermotherapy, the only side effect was pain at the lesion area four days after the initiation of treatment.Although the efficacy rate of meglumine antimoniate was greater than that of thermotherapy for the treatment of cutaneous leishmaniasis, the side effects were also greater. Those factors, added to the increased costs, the treatment adherence problems and the progressive lack of therapeutic response, make us consider thermotherapy as a first line treatment for cutaneous leishmaniasis.
Project description:Miltefosine is an oral agent used for cutaneous leishmaniasis treatment. An open-label, randomized, phase III clinical trial was carried out in the Colombian army population. Miltefosine, 50 mg capsule was taken orally three times per day for 28 days (N = 145) or meglumine antimoniate, 20 mg/kg body weight per day for 20 days by intramuscular injection (N = 143). The efficacy of miltefosine by protocol was 69.8% (85/122 patients) and 58.6% (85/145 patients) by intention to treat. For meglumine antimoniate, the efficacy by protocol was 85.1% (103/121 patients) and 72% (103/143 patients) by intention to treat. No association was found between drug efficacy and L. (V.) braziliensis or L. (V.) panamensis species of Leishmania responsible for infection. Adverse gastrointestinal events were associated with the use of miltefosine, the meglumine antimoniate treatment was associated with adverse effects on the skeletal musculature, fever, cephalea, and higher toxicity in kidney, liver, pancreas, and hematological system.
Project description:BACKGROUND:Case management in children with cutaneous leishmaniasis (CL) is mainly based on studies performed in adults. We aimed to determine the efficacy and harms of interventions to treat CL in children. METHODS:We conducted a systematic review of clinical trials and cohort studies, assessing treatments of CL in children (?12 years old). We performed structured searches in PubMed, CENTRAL, LILACS, SciELO, Scopus, the International Clinical Trials Registry Platform (ICTRP), clinicaltrials.gov and Google Scholar. No restrictions regarding ethnicity, country, sex or year of publication were applied. Languages were limited to English, Spanish and Portuguese. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A qualitative summary of the included studies was performed. RESULTS:We identified 1092 records, and included 8 manuscripts (6 Randomized Clinical Trials [RCT] and 2 non-randomized studies). Most of the articles excluded in full-text review did not report outcomes separately for children. In American CL (ACL), 5 studies evaluated miltefosine and/or meglumine antimoniate (MA). Their efficacy varied from 68-83% and 17-69%, respectively. In Old-World CL (OWCL), two studies evaluated systemic therapies: rifampicin and MA; and one study assessed efficacy of cryotherapy (42%, Per Protocol [PP]) vs intralesional MA (72%, PP). Few studies (4) provided information on adverse events (AEs) for children, and no serious AEs were reported in participants. Risk of bias was generally low to unclear in ACL studies, and unclear to high in OWCL studies. CONCLUSION:Information on efficacy of treatment for CL in children is scarce. There is an unmet need to develop specific formulations, surveillance of AEs, and guidelines both for the management of CL and clinical trials involving the pediatric population. REGISTRATION:The protocol of this review was registered in the PROSPERO International register of systematic reviews, number CRD42017062164.
Project description:Acre has reported the highest incidence of American cutaneous leishmaniasis (ACL) in Brazil in recent years. The present study seeks to identify high and low risk agglomerations of ACL in space and space-time during the period from 2007 to 2013 in Acre, and also to characterize the occurrence of the disease in time and according to sociodemographic variables.This is an ecological study, the study population of which consisted of autochthonous ACL cases notified in the municipalities of Acre by an epidemiological surveillance system. Scan statistics of SaTScan™ software were used to identify spatial and space-time clusters. In addition, the cases were characterized by sex, age, home situation (in a rural or urban area), and temporal tendency.Acre reported an incidence rate of 12.4 cases per 10 000 inhabitant-years in the study period, with the rates varied greatly (standard deviation of 21.8) among their 22 municipalities. One agglomeration of high risk and three of low risk were detected in space and space-time. Four of the five micro-regions of Acre presented a stationary temporal tendency. The profile of transmission varied according to the micro-region. Generally speaking, the disease occurred more often among young people, those of male gender, and those living in rural areas.Acre has stood out within the Brazilian national context due to its high rates of ACL incidence in the central region of the Acre Valley. The high rates in the micro-region of Brasiléia are related to the disease's intra/peridomiciliary occurrence, and it would seem that the municipality of Sena Madureira is approaching a transmission pattern similar to that of Brasiléia. In other micro-regions, the profile of the disease's transmission is mainly related to the forest/sylvatic cycle of ACL.