Open access

Introductory Chapter: Leishmaniasis: An Emerging Clinical Syndrome

Written By

Farhat Afrin and Hassan A. Hemeg

Submitted: March 26th, 2018 Published: October 10th, 2018

DOI: 10.5772/intechopen.79662

Chapter metrics overview

1,077 Chapter Downloads

View Full Metrics

1. Introduction

Leishmaniasis comprises a broad-spectrum of neglected vector-borne diseases ranging in severity from the self-healing but disfiguring and stigmatizing cutaneous lesions to mucocutaneous and fatal visceral manifestations, depending on the species and host characteristics. This syndrome primarily afflicts the impoverished population of low-income countries falling in the tropics and subtropics. Globally, 0.7–1.2 million new cases of cutaneous leishmaniasis (CL) occur every year while for visceral leishmaniasis (VL), 200,000–400,000 new cases and 20,000–40,000 deaths are reported each year, with 95% of fatal cases occurring in only six countries, namely, India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil [1]. The disease is transmitted by the bite of female Phlebotomus sandflies that transmit the promastigotes, which are then transformed into amastigotes within the mammalian macrophages. The goal of World Health Organization is to eliminate this public health problem in the South-east Asia Region by 2020 [2]. Despite intensive research, live vaccines are the only effective vaccines till date against CL while none exists for the visceral form that is the most severe of the various clinical forms of leishmaniasis. Moreover, there is an upward trend in development of resistance to most of the currently available drugs [3]. The chemotherapeutic arsenal is associated with need for hospitalization and prolonged periods of treatment, coupled with high toxicity, which limits the application and patient compliance. Combinations of drugs have also been explored. Absence of vaccines, progressive emergence of HIV-Leishmania co-infection and relapse after treatment delineate the gravity of leishmaniasis affliction [4]. A recent report indicated relapse of post kala-azar dermal leishmaniasis (PKDL) 1 year after successful treatment of VL with miltefosine and paromomycin [5]. Antimony therapy is also not advised in elderly patients with CL due to severe adverse side effects [6]. The potential of the visceralizing species, Leishmania donovani to cause localized cutaneous lesions is also not fully understood [7].

This chapter gives a brief glimpse of the recent advances in immunopathogenesis and immune evasion strategies employed by the Leishmania parasite, vaccination and immunotherapeutic approaches, natural product-based drugs, nanomedicines, therapeutic targets and diagnosis of leishmaniasis. We have included citations of the latest research articles presenting the most recent results.


2. Immunopathogenesis and immune evasion strategies

Invasion of host macrophages by Leishmania triggers a multitude of signaling circuits to eliminate the pathogen. However, the parasite tries to subvert these defense mechanisms to create a safe haven for their survival. Leishmania secretes effector molecules to modulate the host immune transcriptome resulting in alterations in the host epigenome to alter cytokine and chemokine levels, their cross talks and downstream signaling hubs. This adversely affects the recruitment and activation of immune cells, respiratory burst and antigen presentation, leading to immune evasion. Leishmania amazonensis has been reported to induce histone deacetylase in infected macrophages, which contributes to down regulation of inducible nitric oxide synthase and subsequent parasite survival [8]. L. donovani infection causes hypoxic environment within the macrophages by activating hypoxia inducible factor-1α, that in turn up regulates micro RNA-210, while down regulating NF-κB mediated pro-inflammatory immune responses, to establish a safe niche for their survival [9].

Leishmania have evolved stratagems to neutralize macrophage defensive arsenals, the very heart of the immune system’s defensive machinery, resulting in replication of the parasites within the phagolysosomal vacuoles of the infected macrophages. Unfolding of these host-pathogen interactions will help in development of effective drug targets that would enable to modulate the host immune system to ameliorate the pathogenesis of infection. Besides the host immune profile and the intrinsic parasite factors that may influence the clinical manifestations of the disease, Leishmania virus RNA 1 (LRV1) infecting Leishmania guyanensis has been implicated to contribute to immunopathogenesis of American tegumentary leishmaniasis [10]. Studies have also indicated that gut microbiota egested during infected sandfly bites is an important determinant of Leishmania dissemination via triggering of inflammasomes, leading to IL-1β production that sustains the neutrophilic infiltrate harboring the parasites [11].


3. Current vaccination and immunotherapeutic approach

A major challenge to mitigation of this endemic disease is to achieve safe, efficacious and low-cost prophylactic or therapeutic vaccines with long-lasting protection. These vaccines should be effective against both stages of the parasite curbing its progression and accompanying pathology that stems from an imbalance between the pathogen and the host immune system. The plethora of candidate vaccines range from the live non-pathogenic vectors to the recombinant subunit vaccines, alone or together with adjuvants and/or delivery systems for induction of cell-mediated immunity. Some of these include Leishmania-activated C-kinase antigen (LACK) [12], Leishmania cysteine peptidase A, B in poly-lactic-co-glycolic acid (PLGA) nanoparticles [13], soluble Leishmania antigens in nanoliposomes co-delivered with saponin and imiquimod [14], DNA vaccine encoding ornithine decarboxylase [15]. Inclusion of salivary proteins in antileishmanial vaccines has been reported to result in a synergistic protective effect [16]. A live recombinant amastigote 2 antigen vaccine vector using Trypanosoma cruzi non-virulent strain, and live attenuated centrin gene–deleted Leishmania donovani [17] have been reported to induce strong T cell-mediated protective immune responses against VL and hence could represent promising alternatives for translation to human clinical trials [18]. Recombinant small myristoylated protein-3, a virulence factor has been found to be immunogenic in both mice and humans, with induction of protective immunity against murine VL [19]. In case of CL, intranasal immunization has been found to reduce numbers of CD4+Foxp3+ regulatory T cells with increased Th1 response and associated protection [20].

Immunotherapy on the other hand has been found to promote sterilizing cure. However, immunotherapeutic intervention with L. amazonensis antigens plus saponin was not found to maintain long-lasting low parasitism in dogs naturally infected with Leishmania infantum [21]. Therapy with anti-PDL-1 antibody has been found to promote parasite clearance with concomitant induction of protective immunity against VL by inhibiting autophagy, that is hijacked by Leishmania [22]. Immunotherapeutic approach with Th1 stimulating antigens (aldolase, enolase, p45 and triose phosphate isomerase) has also been attempted [23].

An emerging therapeutic modality for CL is photodynamic therapy of zinc porphyrin that results in loss of plasma membrane integrity and hyperpolarization of the mitochondrial membrane potential [24].


4. Therapeutic targets and inhibitors

Identification of new drug targets can contribute towards designing inhibitors and strengthen the pipeline for disease elimination. DNA topoisomerases that control the over- or under-winding of DNA have been reported as deadly targets for topoisomerase inhibitors that may act as potential antileishmanial drugs [25]. Computational tools using in silico approaches targeting key enzymes in metabolic pathways of Leishmania have led to identification of several potential druggable targets such as cytochrome P450 sterol 14α-demethylase [26], dihydrofolate reductase-thymidylate synthase [27], methylglyoxal degradation superpathway [28], trypanothione reductase [29]. Trypanothione reductase is absent in humans and neutralizes the reactive oxygen species generated inside the infected macrophages. Inhibitors such as chalcones that block the activity of these trypanosomatid enzymes may be effective in treatment of leishmaniasis [29]. β-carbonic anhydrase [30], acid phosphatases [31], uracil DNA glycosylase [32] and Type 2 NADH dehydrogenase [33] are other potential therapeutic targets that are being explored. NLR (NOD-Like Receptor) family member NOD2 has also been implicated as an essential therapeutic target [34].


5. Natural products as source of antileishmanial drugs

In view of looming chemotherapeutic drug resistance, natural products and scaffolds from medicinal plants are being emphasized as leads for drug discovery. Plant-based bioactive compounds have merit over synthetic compounds, considering their unique structural variety, providing an unlimited source of molecules and biological activities [35]. A host of plant extracts or oils and their phytoconstituents (alkaloids, terpenoids, quinones, flavonoids, saponins, phenylpropanoids, flavonoids, lignoids, naphthoquinones, iridoids, and more) have shown promise in vitro and/or in vivo [36, 37, 38, 39, 40, 41]. In some cases, the leishmanicidal effect is potentiated by immunomodulation [3, 42]. Besides plants, secondary metabolites from microorganisms such as fungi [43] and marine organisms have also been reported. Plant defensins have been found to eliminate Leishmania parasites via plasma membrane perturbation, mitochondrial membrane collapse, and reactive oxygen species induction [44].

Antimicrobial peptides have been reported to improve the therapeutic outcome of antileishmanial drugs [45]. Synergistic drug-natural product combinations have also been explored [46, 47].


6. Nanomedicines

In recent years, numerous advances in drug discovery have been made for treating leishmaniasis, exploiting nanotechnological approaches to target the immune cell phagolysosomes that harbors the Leishmania amastigotes. A plethora of nanoparticles have been reported to elicit protection with modulation of the immune response via reduction in anti-inflammatory cytokine IL-10, and increased nitric oxide production [48]. Recently, antileishmanial activity of sulphonamide nanoemulsions have been reported that target the leishmanial β-carbonic anhydrase [30]. Linalool-loaded gold nanoparticles have also been found to exhibit therapeutic effectiveness against Leishmania [49]. A short-course AmBisome regimen has been found to be safe and effective in the treatment of clinically diagnosed PKDL patients in Bangladesh, and may be considered as a viable option for routine programmatic use, contributing towards the VL elimination drive [50]. Biodegradable PLGA microparticles loaded with an antileishmanial nitrochalcone has proved therapeutic effectiveness when administered subcutaneously in BALB/c mice with cutaneous lesions [51].

Green nanoparticles, that is, plant-based synthesis of nanoparticles have an upper edge over the synthetic nanoparticles owing to their biosynthesis being rapid, eco-friendly, non-pathogenic and economical. An array of biogenic nanoparticles from plant extracts has been reported to have antileishmanial activity with boosting of anti-oxidant activity [52, 53].

Miltefosine- and ketoconazole-loaded nanoniosomes with improved antileishmanial activity have also been reported [54]. AmBisome-miltefosine combination therapy for VL-HIV co-infected patients has been reported in Ethiopia with 83.8% cure rate [55].


7. Diagnosis of leishmaniasis

A definitive diagnosis of leishmaniasis is crucial to guide timely and appropriate therapy. The disease is often confused with other co-endemic diseases and HIV co-infections may result in atypical clinical presentation [4]. Differential diagnosis of VL should be considered in patients of endemic areas after organ transplantation [56]. This underscores the need for highly sensitive and specific diagnostic modalities. In this regard, molecular techniques such as real-time polymerase chain reaction (qPCR)-based methods are gaining ground for detection and quantification of Leishmania as well as for species identification [57]. However, to rule out false negatives, combination of two PCR techniques is advisable in patients with cutaneous lesions [58]. For VL, serological diagnosis with recombinant antigen rK39-based immunochromatography and direct agglutination test based on the whole parasite antigens have been reported to have high sensitivity and specificity [59]. Nonetheless, amastigote detection in bone marrow aspirates and positive rK39 immunochromatographic test should be further validated by nested PCR [60]. Recently, a loop-mediated isothermal amplification (LAMP) assay based on 18S rDNA and the conserved region of minicircle kDNA has been implicated with high sensitivity for visceral as well as CL diagnostics [61]. Further, Leishmania urine antigen has been explored as a probable biomarker for predicting treatment failure and relapse in VL/HIV-coinfected patients [62].


8. Conclusions and future perspectives

To strengthen the leishmaniasis elimination drive, particular emphasis has to be laid on the diagnosis, chemotherapeutics and new targets identification and vaccination strategies for control of this endemic disease. This underscores renewed efforts to combat upcoming challenges in the quest for new drug targets in achieving definitive cure and/or safe, cost-effective prophylactic vaccines with long-lasting immunity against leishmaniasis. An effective therapeutic vaccine may further boost the immunosuppressed state and thus control the visceralizing form of leishmaniasis that is mainly harbored in the South Asian region.


Conflict of interest

The authors declare no conflict of interest.


  1. 1. Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7(5):e35671
  2. 2. Karunaweera ND, Ferreira MU. Leishmaniasis: Current challenges and prospects for elimination with special focus on the South Asian region. Parasitology. 2018;145(4):425-429
  3. 3. Dumetz F, Cuypers B, Imamura H, Zander D, D’Haenens E, Maes I, et al. Molecular preadaptation to antimony resistance in Leishmania donovani on the Indian subcontinent. mSphere. 2018;3(2):e00548-e00517
  4. 4. de Lima Henn GA, Júnior ANR, Colares JKB, Mendes LP, Silveira JGC, Lima AAF, et al. Is visceral Leishmaniasis the same in HIV-coinfected adults? The Brazilian Journal of Infectious Diseases. 2018;22(2):92-98
  5. 5. Pandey K, Goyal V, Das V, Verma N, Rijal S. PKDL development after combination treatment with miltefosine and paromomycin in a case of visceral leishmaniasis: First ever case report. Journal of Medical Microbiology and Immunology Research. 2018;2(1)
  6. 6. do Lago AS, Nascimento M, Carvalho AM, Lago N, Silva J, Queiroz JR, et al. The Elderly Respond to Antimony Therapy for Cutaneous Leishmaniasis Similarly to Young Patients but Have Severe Adverse Reactions. The American Journal of Tropical Medicine and Hygiene. 2018;98(5):1317-1324
  7. 7. Siriwardana YD, Deepachandi B, Ranasinghe S, Soysa P, Karunaweera N. Evidence for Seroprevalence in human localized cutaneous leishmaniasis caused by Leishmania donovani in Sri Lanka. BioMed Research International. 2018;2018:9320367
  8. 8. Calegari-Silva TC, Vivarini ÁC, Pereira RM, Dias-Teixeira KL, Rath CT, Pacheco AS, et al. Leishmania amazonensis downregulates macrophage iNOS expression via histone: Deacetylase 1 (HDAC1): A novel parasite evasion mechanism. European Journal of Immunology. 2018;48(7):1188-1198
  9. 9. Kumar V, Kumar A, Das S, Kumar A, Abhishek K, Verma S, et al. Leishmania donovani activates hypoxia inducible factor-1α and miR-210 for survival in macrophages by downregulation of NF-κB mediated pro-inflammatory immune response. Frontiers in Microbiology. 2018;9:385
  10. 10. Borges AF, Gomes RS, Ribeiro-Dias F. Leishmania (Viannia) guyanensis in tegumentary leishmaniasis. Pathogens and Disease. 2018;76(4):fty025
  11. 11. Dey R, Joshi AB, Oliveira F, Pereira L, Guimarães-Costa AB, Serafim TD, et al. Gut Microbiota Egested during Bites of Infected Sand Flies Augments Severity of Leishmaniasis Via Inflammasome-Derived IL-1β. 2018
  12. 12. Fernández L, Carrillo E, Sánchez-Sampedro L, Sánchez C, Ibarra-Meneses AV, Jimenez MA, et al. Antigenicity of leishmania-activated C-kinase antigen (LACK) in human peripheral blood mononuclear cells, and protective effect of prime-boost vaccination with pCI-neo-LACK plus attenuated LACK-expressing Vaccinia viruses in hamsters. Frontiers in Immunology. 2018;9
  13. 13. Noormehr H, Hosseini AZ, Soudi S, Beyzay F. Enhancement of Th1 immune response against Leishmania cysteine peptidase A, B by PLGA nanoparticle. International Immunopharmacology. 2018;59:97-105
  14. 14. Emami T, Rezayat SM, Khamesipour A, Madani R, Habibi G, Hojatizade M, et al. The role of MPL and imiquimod adjuvants in enhancement of immune response and protection in BALB/c mice immunized with soluble Leishmania antigen (SLA) encapsulated in nanoliposome. Artificial Cells, Nanomedicine, and Biotechnology. 2018:1-10
  15. 15. Kumar A, Dikhit MR, Amit A, Zaidi A, Pandey RK, kumar Singh A, et al. Immunomodulation induced through ornithine decarboxylase DNA immunization in Balb/c mice infected with Leishmania donovani. Molecular Immunology. 2018;97:33-44
  16. 16. Martin-Martin I, Chagas AC, Guimaraes-Costa AB, Amo L, Oliveira F, Moore IN, et al. Immunity to LuloHya and Lundep, the salivary spreading factors from Lutzomyia longipalpis, protects against Leishmania major infection. PLoS Pathogens. 2018;14(5):e1007006
  17. 17. Banerjee A, Bhattacharya P, Dagur PK, Karmakar S, Ismail N, Joshi AB, et al. Live attenuated Leishmania donovani centrin gene–deleted parasites induce IL-23–dependent IL-17–protective immune response against visceral leishmaniasis in a murine model. The Journal of Immunology. 2018;200(1):163-176
  18. 18. Almeida APM, Machado LF, Doro D, Nascimento FC, Damasceno L, Gazzinelli RT, et al. New vaccine formulations containing a modified version of the amastigote 2 antigen and the non-virulent Trypanosoma cruzi CL-14 strain are highly antigenic and protective against Leishmania infantum challenge. Frontiers in Immunology. 2018;9:465
  19. 19. Oliveira MP, Martins VT, Santos TT, Lage DP, Ramos FF, Salles B, et al. Small myristoylated protein-3, identified as a potential virulence factor in Leishmania amazonensis, proves to be a protective antigen against visceral leishmaniasis. International Journal of Molecular Sciences. 2018;19(1):129
  20. 20. Bezerra IPS, Abib MA, Rossi-Bergmann B. Intranasal but not subcutaneous vaccination with LaAg allows rapid expansion of protective immunity against cutaneous leishmaniasis. Vaccine. 2018;36(18):2480-2486
  21. 21. Viana KF, Lacerda G, Teixeira NS, Cangussu ASR, Aguiar RWS, Giunchetti RC. Therapeutic vaccine of killed Leishmania amazonensis plus saponin reduced parasite burden in dogs naturally infected with Leishmania infantum. Veterinary Parasitology. 2018;254:98-104
  22. 22. Habib S, El Andaloussi A, Elmasry K, Handoussa A, Azab M, Elsawey A, et al. PDL-1 blockade prevents T cell exhaustion, inhibits autophagy, and promotes clearance of Leishmania donovani. Infection and Immunity. 2018;86(6):e00019-e00018
  23. 23. Yadav NK, Joshi S, Ratnapriya S, Sahasrabuddhe AA, Dube A. Immunotherapeutic potential of Leishmania (Leishmania) donovani Th1 stimulatory proteins against experimental visceral leishmaniasis. Vaccine. 2018;36(17):2293-2299
  24. 24. Andrade C, Figueiredo R, Ribeiro K, Souza L, Sarmento-Neto J, Rebouças J, et al. Photodynamic effect of zinc porphyrin on the promastigote and amastigote forms of Leishmania braziliensis. Photochemical & Photobiological Sciences. 2018;17(4):482-490
  25. 25. Elmahallaw E, Garcia-Estrada C, Carbajo-Andres R, Balana-Fouce R. DNA topoisomerases of Leishmania parasites; druggable targets for drug discovery. Current Medicinal Chemistry. 2018
  26. 26. Shokri A, Abastabar M, Keighobadi M, Emami S, Fakhar M, Teshnizi SH, et al. Promising antileishmanial activity of novel imidazole antifungal drug Luliconazole against Leishmania major: In vitro and in silico studies. Journal of Global Antimicrobial Resistance. 2018. pii: S2213-7165(18)30091-2
  27. 27. Vadloori B, Sharath A, Prabhu NP, Maurya R. Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A. BMC Research Notes. 2018;11(1):246
  28. 28. Chávez-Fumagalli MA, Schneider MS, Lage DP, Tavares GSV, Mendonça DVC, Santos TTO, et al. A computational approach using bioinformatics to screening drug targets for Leishmania infantum species. Evidence-Based Complementary and Alternative Medicine. 2018;2018
  29. 29. Ortalli M, Ilari A, Colotti G, De Ionna I, Battista T, Bisi A, et al. Identification of chalcone-based antileishmanial agents targeting trypanothione reductase. European Journal of Medicinal Chemistry. 2018;2018:6813467
  30. 30. da Silva Cardoso V, Vermelho AB, Ricci Junior E, Almeida Rodrigues I, Mazotto AM, Supuran CT. Antileishmanial activity of sulphonamide nanoemulsions targeting the β-carbonic anhydrase from Leishmania species. Journal of Enzyme Inhibition and Medicinal Chemistry. 2018;33(1):850-857
  31. 31. Dorsey BM, McLauchlan CC, Jones MA. Evidence that speciation of oxovanadium complexes does not solely account for inhibition of Leishmania acid phosphatases. Frontiers in Chemistry. 2018;6:109
  32. 32. Mishra A, Khan M, Jha PK, Kumar A, Das S, Das P, et al. Oxidative stress-mediated overexpression of uracil DNA glycosylase in Leishmania donovani confers tolerance against antileishmanial drugs. Oxidative Medicine and Cellular Longevity. 2018;2018:4074357
  33. 33. Stevanović S, Perdih A, Senćanski M, Glišić S, Duarte M, Tomás AM, et al. In silico discovery of a substituted 6-methoxy-quinalidine with Leishmanicidal activity in Leishmania infantum. Molecules. 2018;23(4):772
  34. 34. Jawed JJ, Saini P, Majumdar S. Exploring the role of immune-modulators in pathogen recognition receptor NOD2 mediated protection against visceral leishmaniasis. World Academy of Science, Engineering and Technology. International Journal of Medical and Health Sciences. 2018;5(3)
  35. 35. Varela M, Fernandes J. Natural products: Key prototypes to drug discovery against neglected diseases caused by Trypanosomatids. Current Medicinal Chemistry. 2018
  36. 36. Simoben CV, Ntie-Kang F, Akone SH, Sippl W. Compounds from African medicinal plants with activities against selected parasitic diseases: Schistosomiasis, trypanosomiasis and leishmaniasis. Natural Products and Bioprospecting. 2018:1-19
  37. 37. de Lima Moreira F, Riul TB, de Lima Moreira M, Pilon AC, Dias-Baruffi M, Araújo MS, et al. Leishmanicidal effects of piperlongumine (Piplartine) and its putative metabolites. Planta Medica. 2018
  38. 38. dos Santos Sales V, Monteiro ÁB, de Araújo Delmondes G, do Nascimento EP. Antiparasitic activity and essential oil chemical analysis of the piper Tuberculatum Jacq fruit. Iranian Journal of Pharmaceutical Research. 2018;17(1):268-275
  39. 39. Zafar S, Ur-Rehman F, Shah ZA, Rauf A, Khan A, Humayun Khan M, et al. Potent leishmanicidal and antibacterial metabolites from Olea ferruginea. Journal of Asian Natural Products Research. 2018:1-9
  40. 40. Krstin S, Sobeh M, Braun MS, Wink M. Anti-parasitic activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae. Medicine. 2018;5(2):37
  41. 41. Monzote L, Geroldinger G, Tonner M, Scull R, De Sarkar S, Bergmann S, et al. Interaction of ascaridole, carvacrol, and caryophyllene oxide from essential oil of Chenopodium ambrosioides L. with mitochondria in Leishmania and other eukaryotes. Phytotherapy Research. 2018
  42. 42. Domeneghetti L, Demarchi I, Caitano J, Pedroso R, Silveira T, Lonardoni M. Calophyllum brasiliense modulates the immune response and promotes Leishmania amazonensis intracellular death. Mediators of Inflammation. 2018;2018:6148351
  43. 43. Peretz A, Zabari L, Pastukh N, Avital N, Masaphy S. In vitro antileishmanial activity of a black Morel, Morchella importuna (ascomycetes). International Journal of Medicinal Mushrooms. 2018;20(1):71-80
  44. 44. Souza GS, de Carvalho LP, de Melo EJT, Gomes VM, AdO C. The toxic effect of Vu-Defr, a defensin from Vigna unguiculata seeds, on Leishmania amazonensis is associated with reactive oxygen species production, mitochondrial dysfunction, and plasma membrane perturbation. Canadian Journal of Microbiology. 2018;64(999):1-10
  45. 45. Fragiadaki I, Katogiritis A, Calogeropoulou T, Brückner H, Scoulica E. Synergistic combination of alkylphosphocholines with peptaibols in targeting Leishmania infantum in vitro. International Journal for Parasitology: Drugs and Drug Resistance. 2018;8(2):194-202
  46. 46. Khanra S, Kumar YP, Dash J, Banerjee R. In vitro screening of known drugs identified by scaffold hopping techniques shows promising leishmanicidal activity for suramin and netilmicin. BMC Research Notes. 2018;11(1):319
  47. 47. Vieira-Araújo FM, Rondon FCM, Vieira ÍGP, Mendes FNP, de Freitas JCC, de Morais SM. Sinergism between alkaloids piperine and capsaicin with meglumine antimoniate against Leishmania infantum. Experimental parasitology. 2018;188:79-82
  48. 48. Halder A, Shukla D, Das S, Roy P, Mukherjee A, Saha B. Lactoferrin-modified Betulinic acid-loaded PLGA nanoparticles are strong anti-leishmanials. Cytokine. 2018. pii: S1043-4666(18)30208-4
  49. 49. Jabir MS, Taha AA, Sahib UI. Linalool loaded on glutathione-modified gold nanoparticles: A drug delivery system for a successful antimicrobial therapy. Artificial Cells, Nanomedicine, and Biotechnology. 2018;Apr 4:1-11
  50. 50. den Boer M, Das AK, Akhter F, Burza S, Ramesh V, Ahmed B-N, et al. Safety and effectiveness of short-course AmBisome in the treatment of post-kala-azar dermal leishmaniasis (PKDL): A prospective cohort study in Bangladesh. Clinical Infectious Diseases. 2018
  51. 51. de Jesus Sousa-Batista A, Pacienza-Lima W, Arruda-Costa N, CAB F, Ré MI, Rossi-Bergmann B. Depot subcutaneous injection with chalcone CH8-loaded poly (lactic-co-glycolic acid) microspheres as a single-dose treatment of cutaneous leishmaniasis. Antimicrobial Agents and Chemotherapy. 2018;62(3):e01822-e01817
  52. 52. El-khadragy M, Alolayan EM, Metwally DM, El-Din MFS, Alobud SS, Alsultan NI, et al. Clinical efficacy associated with enhanced antioxidant enzyme activities of silver nanoparticles biosynthesized using Moringa oleifera leaf extract, against cutaneous leishmaniasis in a murine model of Leishmania major. International Journal of Environmental Research and Public Health. 2018;15(5):1037
  53. 53. Ovais M, Khalil AT, Raza A, Islam NU, Ayaz M, Saravanan M, et al. Multifunctional theranostic applications of biocompatible green-synthesized colloidal nanoparticles. Applied Microbiology and Biotechnology. 2018;102(10):4393-4408
  54. 54. Nazari-Vanani R, Vais RD, Sharifi F, Sattarahmady N, Karimian K, Motazedian M, et al. Investigation of anti-leishmanial efficacy of miltefosine and ketoconazole loaded on nanoniosomes. Acta Tropica. 2018;185:69-76
  55. 55. Abongomera C, Diro E, de Lima Pereira A, Buyze J, Stille K, Ahmed F, et al. The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study. PLoS Neglected Tropical Diseases. 2018;12(5):e0006527
  56. 56. Sánchez FC, Sánchez TV, Díaz MC, Moyano VS, Gallego CJ, Marrero DH, editors. Visceral leishmaniasis in renal transplant recipients: Report of 2 cases. Transplantation Proceedings. 2018;50(2):581-582
  57. 57. Galluzzi L, Ceccarelli M, Diotallevi A, Menotta M, Magnani M. Real-time PCR applications for diagnosis of leishmaniasis. Parasites & Vectors. 2018;11(1):273
  58. 58. Merino-Espinosa G, Rodríguez-Granger J, Morillas-Márquez F, Tercedor J, Corpas-López V, Chiheb S, et al. Comparison of PCR-based methods for the diagnosis of cutaneous leishmaniasis in two different epidemiological scenarios: Spain and Morocco. Journal of the European Academy of Dermatology and Venereology. 2018
  59. 59. Bangert M, Flores-Chávez MD, Llanes-Acevedo IP, Arcones C, Chicharro C, García E, et al. Validation of rK39 immunochromatographic test and direct agglutination test for the diagnosis of Mediterranean visceral leishmaniasis in Spain. PLoS Neglected Tropical Diseases. 2018;12(3):e0006277
  60. 60. Shrestha M, Pandey BD, Maharjan J, Dumre SP, Tiwari PN, Manandhar KD, et al. Visceral leishmaniasis from a non-endemic Himalayan region of Nepal. Parasitology Research. 2018;117(7):2323-2326
  61. 61. Adams ER, Schoone G, Versteeg I, Gomez MA, Diro E, Mori Y, et al. Development and evaluation of a novel LAMP assay for the diagnosis of cutaneous and visceral leishmaniasis. Journal of Clinical Microbiology. 2018;56(7). pii: e00386-18
  62. 62. Van Griensven J, Mengesha B, Mekonnen T, Fikre H, Takele Y, Adem E, et al. Leishmania antigenuria to predict initial treatment failure and relapse in visceral leishmaniasis/HIV coinfected patients: An exploratory study nested within a clinical trial in Ethiopia. Frontiers in Cellular and Infection Microbiology. 2018;8:94

Written By

Farhat Afrin and Hassan A. Hemeg

Submitted: March 26th, 2018 Published: October 10th, 2018