• Anti-leishmanial drugs
• drug targets
• emerging therapies
• host directed therapies
• multi-drug therapy
• nanotechnology
• visceral leishmaniasis

• Humans
• Antiprotozoal Agents/adverse effects
• Antiprotozoal Agents/administration & dosage
• Antiprotozoal Agents/pharmacology
• Antiprotozoal Agents/economics
• Leishmaniasis/drug therapy
• Leishmaniasis/parasitology
• Animals
• Drug Resistance
• Drug Development
• Cost-Benefit Analysis
• Antimony/administration & dosage
• Antimony/adverse effects
• Phosphorylcholine/analogs & derivatives
• Phosphorylcholine/administration & dosage
• Phosphorylcholine/adverse effects
• Leishmania/drug effects
• Leishmania/isolation & purification

• Chemotherapeutic intervention
• Leishmania donovani
• Leishmaniasis
• Life-cycle
• Protozoan diseases
• Therapeutic targets
• alternative medication approach

• Leishmaniasis/drug therapy
• Humans
• Antiprotozoal Agents/therapeutic use
• Antiprotozoal Agents/pharmacology
• Leishmania/drug effects
• Animals
• Drug Repositioning
• Drug Resistance
• Drug Delivery Systems/methods
• Phosphorylcholine/analogs & derivatives

• Anti-leishmanial drugs
• drug treatment
• investigational drugs
• leishmaniasis
• plant-based investigational drug

• Humans
• Drugs, Investigational/pharmacology
• Drugs, Investigational/administration & dosage
• Antiprotozoal Agents/pharmacology
• Antiprotozoal Agents/administration & dosage
• Antiprotozoal Agents/adverse effects
• Leishmaniasis/drug therapy
• Drug Development
• Animals
• Drug Resistance
• Amphotericin B/pharmacology
• Amphotericin B/administration & dosage
• Amphotericin B/adverse effects
• Phosphorylcholine/analogs & derivatives
• Phosphorylcholine/pharmacology
• Phosphorylcholine/therapeutic use
• Phosphorylcholine/administration & dosage
• Drug Design

• Amphotericin B/pharmacology
• Amphotericin B/therapeutic use
• Animals
• Brazil
• Middle Aged
• Antiprotozoal Agents/pharmacology
• Antiprotozoal Agents/therapeutic use
• Humans
• Male
• Mice
• Drug Resistance
• Leishmania/drug effects
• Leishmania/isolation & purification
• Leishmania/classification
• Leishmania mexicana/drug effects
• Leishmania mexicana/isolation & purification
• Leishmaniasis, Cutaneous/drug therapy
• Leishmaniasis, Cutaneous/parasitology
• HIV Infections/complications
• HIV Infections/drug therapy
• Parasitic Sensitivity Tests
• Mice, Inbred BALB C
• Leishmaniasis, Diffuse Cutaneous/parasitology
• Leishmaniasis, Diffuse Cutaneous/drug therapy

• MR/P027989/1 Medical Research Council
• Fundação de Amparo à Pesquisa do Estado de São Paulo
• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão
• UK Research and Innovation
• PROCAD-Amazônia
• Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
• FAPESP

• Amphotericin B
• Drug susceptibility
• Leishmania
• Miltefosine
• Tegumentary leishmaniasis

Leishmaniases are human and animal parasitic diseases transmitted by phlebotomine sand flies. Globalization is an important driver of the burden and in the current dynamics of these diseases. A systematic review of articles published between 2000 and 2021 was conducted using the PubMed search engine to identify the epidemiology and clinical management of imported human leishmaniases as a fundamental step to better manage individual cases and traveler and migrant health from a global perspective. A total of 275 articles were selected, representing 10,341 human imported cases. Identified drivers of changing patterns in epidemiology include conflict and war, as well as host factors, such as immunosuppression, natural and iatrogenic. Leishmania species diversity associated with different clinical presentations implies diagnostic and treatment strategies often complex to select and apply, especially in non-endemic settings. Thus, diagnostic and management algorithms for medical clinical decision support are proposed. Increased surveillance of non-endemic cases, whether in vulnerable populations such as refugees/migrants and immunocompromised individuals or travelers, could improve individual health and mitigate the public health risk of introducing Leishmania species into new areas.

Leishmaniasis has been identified as a significant disease in tropical and subtropical regions of the world, with Iran being one of the disease-endemic areas. Various treatments have been applied for this disease, and amphotericin B (Amp B) is the second line of treatment. Side effects of this drug have been reported in various organs. The present study investigated the effects of different types of Amp B on fetal organs using in silico and in vivo assays (chicken embryos). In vivo analysis was done by checking pathological changes, angiogenesis, and apoptosis alterations on eggs treated by Amp B and AmBisome. In silico approach was employed to predict the affinity of Amp B and AmBisome to the vascular endothelial growth factor A (VEGF-A), its receptor (KDR1), apoptotic-regulator proteins (Bcl-2-associated X protein (Bax), B-cell lymphoma (Bcl-2), and Caspase-8. The ADME-toxicity prediction reveals that AmBisome possesses a superior pharmacological effect to Amp B. The best result of all the dockings in the Molegro Virtual Docker (MVD) was obtained between Bax, Bcl-2, Caspase-8, KDR1, and VEGF-A targets. Due to the lower Egap (HOMO–LUMO) of AmBisome, the chemical reactivity of AmBisome was higher than that of Amp B. In vivo analysis showed that embryos that received Amp B exhibited less vascular density than AmBisome. Amp B alone significantly increased the expression of apoptosis and decreased angiogenesis genes compared to AmBisome. The histopathology analysis of the treated embryos showed a reduction in the blood vessel collapse and an increase in degenerative and apoptotic–necrotic changes in the embryonic tissues. Overall, the results suggest the potential benefits of AmBisome over Amp B, which might be a better treatment strategy to treat leishmaniasis during pregnancy.

• amphotericin B
• angiogenesis
• apoptosis
• chick embryo
• in silico
• in vivo
• leishmaniasis
• toxicity

• Clinical manifestations
• Cutaneous leishmaniasis
• Diagnosis
• Diagnóstico
• Leishmaniasis cutánea
• Leishmaniasis mucocutánea
• Manifestaciones clínicas
• Mucocutaneous leishmaniasis
• Tratamiento
• Treatment

• asymptomatic visceral leishmaniasis
• autochthonous leishmaniasis
• climate change
• immunosuppression
• transfusion transmission
• travel-related leishmaniasis

• Clinical manifestations
• Cutaneous leishmaniasis
• Diagnosis
• Diagnóstico
• Leishmaniasis cutánea
• Leishmaniasis mucocutánea
• Manifestaciones clínicas
• Mucocutaneous leishmaniasis
• Tratamiento
• Treatment

M. tuberculosis and parasites of the genus Leishmania present the type II fatty acid biosynthesis system (FASII). The pentacyano(isoniazid)ferrate(II) compound, named IQG-607, inhibits the enzyme 2-trans-enoyl-ACP(CoA) reductase from M. tuberculosis, a key component in the FASII system. Here, we aimed to evaluate the inhibitory activity of IQG-607 against promastigote and amastigote forms of Leishmania (Viannia) braziliensis isolated from patients with different clinical forms of L. braziliensis infection, including cutaneous, mucosal and disseminated leishmaniasis. Importantly, IQG-607 inhibited the proliferation of three different isolates of L. braziliensis promastigotes associated with cutaneous, mucosal and disseminated leishmaniasis. The IC₅₀ values for IQG-607 ranged from 32 to 75 μM, for these forms. Additionally, IQG-607 treatment decreased the proliferation of intracellular amastigotes in infected macrophages, after an analysis of the percentage of infected cells and the number of intracellular parasites/100 cells. IQG-607 reduced from 58% to 98% the proliferation of L. braziliensis from cutaneous, mucosal and disseminated strains. Moreover, IQG-607 was also evaluated regarding its potential toxic profile, by using different cell lines. Cell viability of the lineages Vero, HaCat and HepG2 was significantly reduced after incubation with concentrations of IQG-607 higher than 2 mM. Importantly, IQG-607, in a concentration of 1 mM, did not induce DNA damage in HepG2 cells, when compared to the untreated control group. Future studies will confirm the mechanism of action of IQG-607 against L. braziliensis.

• Animals
• Ferrous Compounds/pharmacology
• Isoniazid/analogs & derivatives
• Isoniazid/pharmacology
• Leishmania braziliensis/drug effects
• Leishmania braziliensis/growth & development

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results.

• leishmania
• leishmania treatment
• recombinant antigens
• vaccine

Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication.

We conducted a retrospective analysis of data from a French centralized referral treatment program and from the “LeishMan” European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines.

From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28–803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3–27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03–32]) while infection with other species had no impact on outcome.

In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease.

Cutaneous and muco-cutaneous leishmaniasis (CL/MCL) are disfiguring diseases caused by a worldwide distributed parasite called Leishmania and its 20 species. Clinical manifestations span a wide continuum from single nodular lesion to disseminated form with mucosal involvement. Though local treatment with cryotherapy and intralesionnal antimony or topical formulations of paromomycin is generally adequate in most of situations, some patients with complex CL/MCL require systemic therapy. No convenient regimen has been proved to be safe and effective for all infecting species, all clinical forms and all patients (e.g. children, pregnant women, adults with comorbidities or immunosuppression). In this study, the authors examined in returning travelers with CL/MCL the effectiveness of an antifungal agent “liposomal amphotericin B” (L-AmB), which is highly effective in visceral leishmaniasis. Surprisingly, rates of healing were lower than in previous reports in this unselected population that reflects clinical practice in non-endemic countries. The observations also suggest that some Leishmania species (namely, L. infantum) may be more susceptible to L-AmB than others. Occurrence of adverse events should raises the question of the benefit-risk balance of L-AmB in CL/MCL. Careful attention to comorbidities and adoption of strict protocols for administration are pre-requisites for the use of L-AmB in patients with CL/MCL.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amphotericin B/administration & dosage
• Amphotericin B/adverse effects
• Amphotericin B/therapeutic use
• Antiprotozoal Agents/administration & dosage
• Antiprotozoal Agents/adverse effects
• Antiprotozoal Agents/therapeutic use
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Leishmania/classification
• Leishmania/drug effects
• Leishmaniasis, Cutaneous/drug therapy
• Leishmaniasis, Cutaneous/parasitology
• Leishmaniasis, Mucocutaneous/drug therapy
• Leishmaniasis, Mucocutaneous/parasitology
• Male
• Middle Aged
• Retrospective Studies
• Travel
• Treatment Outcome

• Leishmania (V.) braziliensis
• cutaneous leishmaniasis
• fluconazole
• pentavalent antimony

• Adolescent
• Adult
• Antimony/administration & dosage
• Antimony/adverse effects
• Antimony/therapeutic use
• Antiprotozoal Agents/administration & dosage
• Antiprotozoal Agents/adverse effects
• Antiprotozoal Agents/therapeutic use
• Brazil
• Female
• Fluconazole/administration & dosage
• Fluconazole/adverse effects
• Fluconazole/therapeutic use
• Humans
• Leishmania braziliensis/drug effects
• Leishmania braziliensis/genetics
• Leishmaniasis, Cutaneous/diagnosis
• Leishmaniasis, Cutaneous/drug therapy
• Leishmaniasis, Cutaneous/parasitology
• Male
• Middle Aged
• Treatment Outcome
• Young Adult

Early treatment of leishmaniasis is critical to achieve cure, prevent psychological and social distress, and prevent transmission of disease. Untreated Leishmaniasis-cutaneous leishmaniasis, mucocutaneous leishmaniasis and visceral leishmaniasis - results in disfiguring scars and high rates of morbidity and mortality in highly endemic regions of the world. However, cure rates with available therapeutics are limited due to cost, therapeutic toxicity and the growing rate of resistance. New therapeutic targets for medications and vaccine development are under investigation to provide improved healing and efficacy for the treatment of Leishmania spp.

• Leishmania
• Visceral
• Cutaneous
• Mucocutaneous
• Amphoterecin
• Vaccine

Leishmaniasis is a neglected infectious disease caused by several different species of protozoan parasites of the genus Leishmania. Current strategies to control this disease are mainly based on chemotherapy. Despite being available for the last 70 years, leishmanial chemotherapy has lack of efficiency, since its route of administration is difficult and it can cause serious side effects, which results in the emergence of resistant cases. The medical-scientific community is facing difficulties to overcome these problems with new suitable and efficient drugs, as well as the identification of new drug targets. The availability of the complete genome sequence of Leishmania has given the scientific community the possibility of large-scale analysis, which may lead to better understanding of parasite biology and consequent identification of novel drug targets. In this review we focus on how high-throughput analysis is helping us and other groups to identify novel targets for chemotherapeutic interventions. We further discuss recent data produced by our group regarding the use of the high-throughput techniques and how this helped us to identify and assess the potential of new identified targets.

Leishmaniasis is a vector borne disease caused by protozoa of the genus Leishmania. Human leishmaniasis is not endemic in Australia though imported cases are regularly encountered. This study aimed to provide an update on the molecular epidemiology of imported leishmaniasis in Australia. Of a total of 206 biopsies and bone marrow specimens submitted to St Vincent’s Hospital Sydney for leishmaniasis diagnosis by PCR, 55 were found to be positive for Leishmania DNA. All PCR products were subjected to restriction fragment length polymorphism analysis for identification of the causative species. Five Leishmania species/species complexes were identified with Leishmania tropica being the most common (30/55). Travel or prior residence in a Leishmania endemic region was the most common route of acquisition with ~47% of patients having lived in or travelled to Afghanistan. Cutaneous leishmaniasis was the most common manifestation (94%) with only 3 cases of visceral leishmaniasis and no cases of mucocutaneous leishmaniasis encountered. This report indicates that imported leishmaniasis is becoming increasingly common in Australia due to an increase in global travel and immigration. As such, Australian clinicians must be made aware of this trend and consider leishmaniasis in patients with suspicious symptoms and a history of travel in endemic areas. This study also discusses the recent identification of a unique Leishmania species found in native kangaroos and a potential vector host which could create the opportunity for the establishment of a local transmission cycle within humans.

• cutaneous leishmaniasis
• kala azar
• leishmaniasis
• visceral leishmaniasis

• Cutaneous leishmaniasis
• Mucosal leishmaniasis
• Travelers
• Visceral leishmaniasis

• Adult
• Amphotericin B/therapeutic use
• Antiprotozoal Agents/therapeutic use
• Cuba
• Emigrants and Immigrants
• Female
• Humans
• Leishmania guyanensis/drug effects
• Leishmania guyanensis/physiology
• Leishmaniasis, Cutaneous/diagnosis
• Leishmaniasis, Cutaneous/drug therapy
• Leishmaniasis, Cutaneous/parasitology
• Male
• Middle Aged
• Panama
• Travel
• United States

• Antiprotozoal Agents/therapeutic use
• Disease Outbreaks/prevention & control
• Global Health
• Humans
• Leishmaniasis, Cutaneous/drug therapy
• Leishmaniasis, Cutaneous/ethnology
• Leishmaniasis, Mucocutaneous/drug therapy
• Leishmaniasis, Mucocutaneous/ethnology
• Practice Guidelines as Topic
• Travel