Old World Cutaneous Leishmaniasis Research Articles

Comparison of Intralesional Sodium Stibogluconate versus Intralesional Meglumine Antimoniate for the Treatment of Leishmania major Cutaneous Leishmaniasis.

Israel is endemic for Old-World cutaneous leishmaniasis. The most common species is Leishmania major. However, the available treatment options are limited. This study's objective was to compare the authors' experience with different antimony intralesional treatments of Leishmania major cutaneous leishmaniasis. A retrospective evaluation was undertaken for cases of Leishmania major cutaneous leishmaniasis treated by pentavalent antimony in a university-affiliated medical centre in Israel. The previous treatment of intralesional sodium stibogluconate (Pentostam®) was compared with the current treatment of meglumine antimoniate (Glucantime®). One hundred cases of cutaneous leishmaniasis were treated during the study period, of whom 33 were treated with intralesional sodium stibogluconate and 67 were treated with intralesional meglumine antimoniate. The patients were 78 males and 22 females, mean age 24 (range 10-67) and there was a total of 354 skin lesions. Within 3 months from treatment, 91% (30/33) of the intralesional sodium stibogluconate group and 88% (59/67) of the intralesional meglumine antimoniate group had complete healing of the cutaneous lesions after an average of 3 treatment cycles (non-statistically significant). In conclusion, the 2 different medications have the same efficacy and safety for treating cutaneous leishmaniasis. Pentavalent antimoniate intralesional infiltration treatment is safe, effective, and well tolerated with minimal side effects for Old-World cutaneous leishmaniasis.

Failure to Detect Leishmania in the Blood of Patients with Old-World Cutaneous Leishmaniasis: Implications for Blood Donation.

Cutaneous leishmaniasis (CL) is endemic in Israel, caused mainly by Leishmania major (L. major) and L. tropica. In addition, returning travelers import another leishmanial species such as L. braziliensis. Although we are dealing with a skin disease, the blood bank in Israel does not accept blood donations from people infected with CL in cases of multiple lesions due to the possibility of transfusion. Our purpose was to investigate the prevalence of Leishmania in the blood of patients with active or previous CL. This pilot study screened patients with active or previous CL for parasites in their blood. All patients were infected in Israel or were returning travelers with leishmaniasis acquired in Latin America. Patients were seen at the Sheba Medical Center. In addition, patients were seen at their homes in L. tropica and L. major endemic regions in Israel. Blood samples were taken from each patient for culture and polymerase chain reaction (PCR). Altogether 62 blood samples were examined (L. tropica = 26, L. major = 33, and L. braziliensis = 3). Twenty-seven patients had an active disease and 35 were recovered. All blood cultures and PCR were negative for parasites except one blood sample that was PCR positive for L. braziliensis. The findings of our study, although a small sample, suggest that people with active or recent CL caused by L. major and L. tropica, do not harbor parasites in their blood. Thus, their exclusion from blood donation should be revisited. Further studies are needed with larger sample size and highly sensitive tests.

Reversed Immunoglycomics Identifies α-Galactosyl-Bearing Glycotopes Specific for Leishmania major Infection.

All healthy humans have high levels of natural anti-α-galactosyl (α-Gal) antibodies (elicited by yet uncharacterized glycotopes), which may play important roles in immunoglycomics: (a) potential protection against certain parasitic and viral zoonotic infections; (b) targeting of α-Gal-engineered cancer cells; (c) aiding in tissue repair; and (d) serving as adjuvants in α-Gal-based vaccines. Patients with certain protozoan infections have specific anti-α-Gal antibodies, elicited against parasite-derived α-Gal-bearing glycotopes. These glycotopes, however, remain elusive except for the well-characterized glycotope Galα1,3Galβ1,4GlcNAcα, expressed by Trypanosoma cruzi. The discovery of new parasitic glycotopes is greatly hindered by the enormous structural diversity of cell-surface glycans and the technical challenges of classical immunoglycomics, a top-down approach from cultivated parasites to isolated glycans. Here, we demonstrate that reversed immunoglycomics, a bottom-up approach, can identify parasite species-specific α-Gal-bearing glycotopes by probing synthetic oligosaccharides on neoglycoproteins. This method was tested here seeking to identify as-yet unknown glycotopes specific for Leishmania major, the causative agent of Old-World cutaneous leishmaniasis (OWCL). Neoglycoproteins decorated with synthetic α-Gal-containing oligosaccharides derived from L. major glycoinositolphospholipids served as antigens in a chemiluminescent enzyme-linked immunosorbent assay using sera from OWCL patients and noninfected individuals. Receiver-operating characteristic analysis identified Galpα1,3Galfβ and Galpα1,3Galfβ1,3Manpα glycotopes as diagnostic biomarkers for L. major-caused OWCL, which can distinguish with 100% specificity from heterologous diseases and L. tropica-caused OWCL. These glycotopes could prove useful in the development of rapid α-Gal-based diagnostics and vaccines for OWCL. Furthermore, this method could help unravel cryptic α-Gal-glycotopes of other protozoan parasites and enterobacteria that elicit the natural human anti-α-Gal antibodies.

Diel periodicity and visual cues guide oviposition behavior in Phlebotomus papatasi, vector of old-world cutaneous leishmaniasis.

BackgroundPhlebotomine sand flies are vectors of human leishmaniases, important neglected tropical diseases. In this study, we investigated diel patterns of oviposition behavior, effects of visual cues on oviposition-site selection, and whether these affect the attraction of gravid Phlebotomus papatasi (Scopoli), the vector of old-world cutaneous leishmaniasis, to olfactory cues from oviposition sites.Methodology/principal findingsTo evaluate these questions, we conducted a series of experiments using attraction and oviposition assays within free-flight test chambers containing gravid females entrained under a 14:10 hrs light:dark photoperiod. By replacing sticky-screens or moist filter papers every three hours, we showed that oviposition site search occurs mainly in the latest part of the night whereas peak oviposition occurs during the early part of the night. Behavioral responses to olfactory oviposition cues are regulated by time-of-day and can be disrupted by transient exposure to a constant darkness photoperiod. Gravid females, but not any other stage, age, or sex, were attracted to dark, round oviposition jars, possibly resembling rodent burrow openings. This visual attraction disappeared in the absence of an illumination source. Egg deposition rate was not affected by jar color. Olfactory cues had the strongest effect when the visual cues were minimal.Conclusion and significanceOur study showed, for the first time, that visual cues in the form of oviposition-site color, lighting level, and photoperiod are important in guiding the oviposition behavior of phlebotomine sand flies. Furthermore, such visual cues could modify the flies’ sensitivity to olfactory oviposition cues. Our results suggest that chemosensory and visual cues are complementary, with visual cues used to orient gravid females towards oviposition sites, possibly at long- to medium-ranges during crepuscular periods, while olfactory cues are used to approach the burrow in darkness and assess its suitability at close-range. Implications to sand fly control are discussed.

Interventions to treat cutaneous leishmaniasis in children: A systematic review.

BackgroundCase 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.MethodsWe 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.ResultsWe 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.ConclusionInformation 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.RegistrationThe protocol of this review was registered in the PROSPERO International register of systematic reviews, number CRD42017062164.

Eligibility criteria and outcome measures adopted in clinical trials of treatments of cutaneous leishmaniasis: systematic literature review covering the period 1991-2015.

To document the sources of heterogeneity in outcomes and shortcomings in trial designs reported by previous systematic reviews. Systematic review of clinical trials of CL treatments published since 1991, to assess and compare eligibility criteria and outcome measures in trials (any type of treatment) of CL (any form) reported before and after the publication of the CONSORT statement. We identified 106 eligible trials published between 1991 and 2015, 74% after the 2001 CONSORT statement; 58% (n=63) were on Old-World CL and 37% (n=40) in New-World CL; overall, 11531 patients enrolled in 243 treatment groups on 30 different treatments. Both requirements and definitions for eligibility and outcome criteria varied. Compliance with CONSORT requirements increased for studies published after the 2010 update. As for entry criteria, 94% of studies had a requirement for sex (74% of those enrolling also women excluded those who were pregnant or lactating), 69% for age (variable age ranges), 99% parasitological confirmation, 43% prior duration of illness (14% excluded cases with previous episodes), 46% defined the number, 28% the size and 13% the type of lesions (27% with restrictions as to their anatomical location). Follow-up ranged 1-24months, with 14% and 91% of studies, respectively, having defined initial and final cure. This review documents changes in reporting before and after the publication of the CONSORT statement. Lack of standardisation, compounded with the small number of trials relative to the magnitude of the disease in its multiple forms, and with the range of treatments tested explains why evidence to inform treatment guidelines is generally weak for CL. Adopting standardised methodologies will improve the quality and consistency of clinical trials, and ultimately yield better treatments for CL.

Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation.

IntroductionProgress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL).Materials and methodsUsing a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings.ResultsFindings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized.ConclusionsThe consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments.

Interventions for Old World cutaneous leishmaniasis.

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.To assess the effects of treatments for Old World cutaneous leishmaniasis (OWCL).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).Randomised controlled trials assessing treatments in immuno-competent people with OWCL confirmed by smear, histology, culture or polymerase chain reaction.Two authors independently assessed trial quality and extracted data.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).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.

Interventions for Old World cutaneous leishmaniasis.

Interventions for Old World cutaneous leishmaniasis.

Miltefosine for Mucosal and Complicated Cutaneous Old World Leishmaniasis: A Case Series and Review of the Literature.

Complicated Old World cutaneous leishmaniasis (OWCL) and Old World mucosal leishmaniasis (OWML) constitute an indication for systemic treatment. To date, there no controlled clinical studies that compare treatment options for these diseases. We compiled a case series of 24 cases successfully treated with miltefosine. We conclude that oral miltefosine is an effective treatment option for both OWCL and OWML.

Attraction and oviposition preferences of Phlebotomus papatasi (Diptera: Psychodidae), vector of Old-World cutaneous leishmaniasis, to larval rearing media.

BackgroundAs part of a project aimed at developing oviposition attractants for the control and surveillance of Phlebotomus papatasi (a vector of Old-World cutaneous leishmaniasis), we tested the hypothesis that gravid sand flies are attracted to chemical cues emanating from the growth medium of conspecific larvae - predominantly larvae-conditioned host feces that represents a suitable oviposition site. We report the results of a systematic assessment of media from various developmental stages of the sand fly using oviposition and olfactometer behavioral assays.MethodsWe conducted multiple-choice oviposition assays in 500 mL Nalgene jars. Six treatments were placed on separate filter paper discs at the bottom of the jar: 2nd/3rd larval instar medium, 4th larval instar/pupae medium, frass from expired colonies, larval food (aged rabbit chow and rabbit feces mix), rabbit feces, and a solvent (water) control. Fifty gravid females were introduced into each jar. Cumulative number of eggs laid on each filter paper per jar was counted at different time intervals from digital images. Attraction of gravid sand flies to these six treatments was assayed with a 3-chamber linear olfactometer. Twenty gravid females were transferred to the middle chamber of the olfactometer and their distribution in treatment and control chambers was recorded after 3 h.ResultsAlmost no eggs were oviposited during the first 72 h following a blood-meal. Cumulative egg deposition increased drastically in the next 24 h (hours 73–96), with a slight non-significant increasing trend thereafter. Comparing mean cumulative egg deposition among the six treatments, we found that significantly more eggs were oviposited on 2nd/3rd larval rearing medium followed by 4th instar/pupae rearing medium. Oviposition preference did not vary over time. The olfactometer results were consistent with the oviposition assays, with 2nd/3rd larval rearing medium being the most attractive, followed by 4th instar/pupae rearing medium.ConclusionThe key finding of this study is that gravid, laboratory reared, Ph. papatasi sand flies are significantly more attracted to rearing medium of the most biologically active larval stages (2nd/3rd instar and 4th instar/pupae). This finding indicates that sand fly-digested host food and feces is attractive to gravid females and suggests that the larvae and larval gut microbiome may be involved in conditioning the oviposition substrate and possibly the production of oviposition attractants and stimulants.

Interleukin-2 expression in lupoid and usual types of old world cutaneous leishmaniasis.

Background:Interleukin (IL)-2 plays a central role in T cell-dependent immune responses.Objectives:We conducted this study to determine and compare IL-2 expression in lupoid and usual types of Old World Cutaneous Leishmaniasis (OWCL), using immunohistochemistry.Patients and Methods:Thirteen paraffin-embedded specimens of lupoid and 12 specimens of usual types of OWCL were used. A mouse monoclonal anti IL-2 antibody was used for staining by the envision technique.Results:There were strongly stained discrete foci of staining through inflammatory infiltrates of dermis and also in basal layers of epidermis and adnexal structures, with a distinctive pattern of hot spot activity foci (mean of 9.31 ± 6.4 versus 8.17 ± 6.9 foci per HPF for lupoid and usual types, respectively). The expression of IL-2 had no correlation with the pattern of granulomatous inflammation (tuberculoid, sarcoidal or mixed suppurative).Conclusions:Interleukin-2 takes part in the immunological response of the granulomatous reaction of OWCL and is not statistically different between lupoid and usual types (P = 0.674).

Therapeutic Options for Old World Cutaneous Leishmaniasis and New World Cutaneous and Mucocutaneous Leishmaniasis

Estimated worldwide incidence of tegumentary leishmaniasis (cutaneous leishmaniasis [CL] and mucocutaneous leishmaniasis [MCL]) is over 1.5 million cases per year in 82 countries, with 90% of cases occurring in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria. Current treatments of CL are poorly justified and have sub-optimal effectiveness. Treatment can be based on topical or systemic regimens. These different options must be based on Leishmania species, geographic regions, and clinical presentations. In certain cases of Old World CL (OWCL), lesions can spontaneously heal without any need for therapeutic intervention. Local therapies (thermotherapy, cryotherapy, paromomycin ointment, local infiltration with antimonials) are good options with less systemic toxicity, reserving systemic treatments (azole drugs, miltefosine, antimonials, amphotericin B formulations) mainly for complex cases. The majority of New World CL (NWCL) types require systemic treatment (mainly with pentavalent antimonials), either to speed the healing or to prevent dissemination to oral-nasal mucosa as MCL (NWMCL). These types of lesions are potentially serious and always require systemic-based regimens, mainly antimonials and pentamidine; however, the associated immunotherapy is promising. This paper is an exhaustive review of the published literature on the treatment of OWCL, NWCL and NWMCL, and provides treatment recommendations stratified according to their level of evidence regarding the species of Leishmania implicated and the geographical location of the infection.

Both combined oral azithromycin plus allopurinol and intramuscular Glucantime yield low efficacy in the treatment of Old World cutaneous leishmaniasis: a randomized controlled clinical trial

Old World cutaneous leishmaniasis (OWCL) is an endemic and major health problem in Iran. The optimal treatment of OWCL is unknown, and current treatments are not ideally effective and have many adverse effects. To compare the efficacy and tolerability of combined oral azithromycin and allopurinol with intramuscular Glucantime in the treatment of OWCL, we conducted a prospective randomized clinical trial. A total of 86 patients with OWCL were assigned and divided randomly into two groups; they received a combination of azithromycin capsule 10 mg/kg/d and allopurinol tablet 10 mg/kg/d for two months or IM injection of Glucantime 20 mg/kg of antimony daily for 20 days. All patients were followed for two months after termination of treatment. Although immediately at the end of the treatment period, complete response was seen in 27.8% of patients on combination therapy vs. 0% in the Glucantime group. The combination of azithromycin and allopurinol had a better outcome; two months after the end of the treatment period, complete, partial, and no responses were seen in 38.9%, 22.2%, and 38.9% in combination therapy and 40%, 31.4%, and 28.6% in the Glucantime group. There was no significant difference between the response rate in both groups after two months (P = 0.5). No severe adverse effect occurred. This study demonstrated that the efficacy of combined oral azithromycin and allopurinol at the above doses and duration was similar to that of IM Glucantime in the treatment of OWCL.

Dynamics of Parasite Clearance in Cutaneous Leishmaniasis Patients Treated with Miltefosine

Parasite loads were quantified in repeated skin biopsies from lesions of 2 patients with Old-World cutaneous leishmaniasis (CL) caused by Leishmania major and L. infantum during and after treatment with miltefosine. Miltefosine induced a rapid therapeutic effect on both infections with an initial decline of parasites of ∼1 log/week for the L. major infection. These observations illustrate the usability of quantifying parasite loads in skin lesions as a pharmacodynamic measure and quantitative descriptor of drug effect for CL supporting clinical assessment.

Diagnosis and therapy of cutaneous and mucocutaneous Leishmaniasis in Germany

The incidence of cutaneous and mucocutaneous Leishmaniasis (CL/MCL) is increasing globally, also in Germany, although the cases are imported and still low in number. The current evidence for the different therapies has many limitations due to lack of sufficient studies on the different Leishmania species with differing virulence. So far there is no international gold standard for the optimal management. The aim of the German joint working group on Leishmaniasis, formed by the societies of Tropical Medicine (DTG), Chemotherapy (PEG) and Dermatology (DDG), was to establish a guideline for the diagnosis and treatment of CL and MCL in Germany, based on evidence (Medline search yielded 400 articles) and, where lacking, on consensus of the experts. As the clinical features do not necessarily reflect the involved Leishmania species and, as different parasite species and even geographically distinct strains of the same species may require different treatments or varying dosages or durations of therapy, the guidelines suggest for Germany to identify the underlying parasite prior to treatment. Because of relevant differences in prognosis and ensuing therapy species should be identified in i) New World CL/MCL (NWCL/ MCL) to distinguish between L. mexicana-complex and subgenus Viannia, ii) in suspected infections with L. mexicana-complex to distinguish from L. amazonensis, and iii) in Old World CL (OWCL) to distinguish between L. infantum and L. major, L. tropica, or L. aethiopica. A state-of-the-art diagnostic algorithm is presented. For recommendations on localized and systemic drug treatment and physical procedures, data from the accessible literature were adjusted according to the involved parasite species and a clinical differentiation into uncomplicated or complex lesions. Systemic therapy was strictly recommended for i) complex lesions (e. g. > 3 infected lesions, infections in functionally or cosmetically critical areas such as face or hands, presence of lymphangitis), ii) lesions refractory to therapy, iii) NWCL by the subgenus Viannia or by L. amazonensis, iv) in MCL and v) in recalcitrant, or disseminating or diffuse cutaneous courses. In e. g. infection with L. major it encompasses miltefosine, fluconazole and ketoconazole, while antimony or allopurinol were here considered second choice. Local therapy was considered appropriate for i) uncomplicated lesions of OWCL, ii) L. mexicana-complex and iii) pregnant women. In e. g. infection with L. major it encompasses perilesional antimony, combined with cryotherapy, paromomycin 15 %/in methylbenzethoniumchlorid 12 % and thermotherapy. The group also stated that there is an urgent need for improving the design and the way of publishing of clinical trials in leishmaniasis.

Two Cases of Old World Cutaneous Leishmaniasis in Australian Travelers Visiting Morocco

Two cases of Old World cutaneous leishmaniasis (OWCL) acquired by travelers to Morocco are described. In Australia, OWCL is more frequently seen in migrants rather than returned travelers. The patients were treated with sodium stibogluconate and fluconazole. Optimal treatment is not established, particularly in returned travelers, but identification of Leishmania species can help with the selection of appropriate therapy.

Interventions for Old World cutaneous leishmaniasis

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. To assess the effects of treatments for Old World cutaneous leishmaniasis (OWCL). 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). Randomised controlled trials assessing treatments in immuno-competent people with OWCL confirmed by smear, histology, culture or polymerase chain reaction. Two authors independently assessed trial quality and extracted data. 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). 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.