The Challenges of Effective Leishmaniasis Treatment

  • Sarah Hendrickx
  • Louis Maes
  • Simon L. Croft
  • Guy CaljonEmail author


During the past decades, visceral leishmaniasis therapy has been faced with the rapid emergence of drug resistance against the pentavalent antimonials which had been used as mainstay of treatment for over 70 years. Even though cutaneous leishmaniasis cannot be linked to development of drug resistance, the huge species- and strain-specific variations in drug susceptibilities severely complicate effective treatment as well. A new challenge in leishmaniasis control has arisen with increasing numbers of treatment failures against all of the currently used anti-leishmanial standard drugs. The exact causes of these treatment failures are still not fully comprehended, but they are most likely a consequence of the complex interplay between parasite, host and drug. In this chapter, the generally accepted underlying factors of treatment failure are discussed along with their consequences for therapy, drug design and other related challenges.


Drug susceptibility Treatment failure/relapse PK-PD In vivo sanctuary sites Parasite-drug-host interaction 


  1. 1.
    Rijal S, Ostyn B, Uranw S, Rai K, et al. Increasing failure of miltefosine in the treatment of kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clin Infect Dis. 2013;56(11):1530–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Mueller M, Ritmeijer K, Balasegaram M, Koummuki Y, et al. Unresponsiveness to AmBisome in some Sudanese patients with kala-azar. Trans R Soc Trop Med Hyg. 2007;101(1):19–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Salih NA, van Griensven J, Chappuis F, Antierens A, et al. Liposomal amphotericin B for complicated visceral leishmaniasis (kala-azar) in eastern Sudan: how effective is treatment for this neglected disease? Tropical Med Int Health. 2014;19(2):146–52.CrossRefGoogle Scholar
  4. 4.
    Sundar S, More DK, Singh MK, Singh VP, et al. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis. 2000;31(4):1104–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Uliana SR, Trinconi CT, Coelho AC. Chemotherapy of leishmaniasis: present challenges. Parasitology. 2017;20:1–17.Google Scholar
  6. 6.
    Asin-Prieto E, Rodriguez-Gascon A, Isla A. Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents. J Infect Chemother. 2015;21(5):319–29.PubMedCrossRefGoogle Scholar
  7. 7.
    Maes L, Cos P, Croft S. The relevance of susceptibility tests, breakpoints and markers. In: Ponte-Sucre A, Diaz E, Padrón-Nieves M, editors. Drug resistance in Leishmania parasites. Vienna: Springer; 2013. p. 407–29.CrossRefGoogle Scholar
  8. 8.
    Bryceson A. A policy for leishmaniasis with respect to the prevention and control of drug resistance. Tropical Med Int Health. 2001;6(11):928–34.CrossRefGoogle Scholar
  9. 9.
    Senior K. Global health-care implications of substandard medicines. Lancet Infect Dis. 2008;8(11):666.PubMedCrossRefGoogle Scholar
  10. 10.
    Dorlo TP, Eggelte TA, de Vries PJ, Beijnen JH. Characterization and identification of suspected counterfeit miltefosine capsules. Analyst. 2012;137(5):1265–74.PubMedCrossRefGoogle Scholar
  11. 11.
    Dorlo TP, Eggelte TA, Schoone GJ, de Vries PJ, et al. A poor-quality generic drug for the treatment of visceral leishmaniasis: a case report and appeal. PLoS Negl Trop Dis. 2012;6(5):e1544.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Uranw S, Ostyn B, Dorlo TP, Hasker E, et al. Adherence to miltefosine treatment for visceral leishmaniasis under routine conditions in Nepal. Tropical Med Int Health. 2013;18(2):179–87.CrossRefGoogle Scholar
  13. 13.
    Caudron JM, Ford N, Henkens M, Mace C, et al. Substandard medicines in resource-poor settings: a problem that can no longer be ignored. Tropical Med Int Health. 2008;13(8):1062–72.CrossRefGoogle Scholar
  14. 14.
    Hendrickx S, Guerin PJ, Caljon G, Croft SL, et al. Evaluating drug resistance in visceral leishmaniasis: the challenges. Parasitology. 2016;109:1–11.Google Scholar
  15. 15.
    Frezard F, Demicheli C, Ribeiro RR. Pentavalent antimonials: new perspectives for old drugs. Molecules. 2009;14(7):2317–36.PubMedCrossRefGoogle Scholar
  16. 16.
    Dhillon GP, Sharma SN, Nair B. Kala-azar elimination programme in India. J Indian Med Assoc. 2008;106(10):664, 6–8.Google Scholar
  17. 17.
    Purkait B, Kumar A, Nandi N, Sardar AH, et al. Mechanism of amphotericin B resistance in clinical isolates of Leishmania donovani. Antimicrob Agents Chemother. 2012;56(2):1031–41.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Cojean S, Houze S, Haouchine D, Huteau F, et al. Leishmania resistance to miltefosine associated with genetic marker. Emerg Infect Dis. 2012;18(4):704–6.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Hendrickx S, Boulet G, Mondelaers A, Dujardin JC, et al. Experimental selection of paromomycin and miltefosine resistance in intracellular amastigotes of Leishmania donovani and L. infantum. Parasitol Res. 2014;113(5):1875–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Srivastava S, Mishra J, Gupta AK, Singh A, et al. Laboratory confirmed miltefosine resistant cases of visceral leishmaniasis from India. Parasit Vectors. 2017;10(1):49.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Vanaerschot M, Dumetz F, Roy S, Ponte-Sucre A, et al. Treatment failure in leishmaniasis: drug-resistance or another (epi-) phenotype? Expert Rev Anti-Infect Ther. 2014;12(8):937–46.PubMedCrossRefGoogle Scholar
  22. 22.
    Rai K, Cuypers B, Bhattarai NR, Uranw S, et al. Relapse after treatment with miltefosine for visceral leishmaniasis is associated with increased infectivity of the infecting Leishmania donovani strain. MBio. 2013;4(5):e00611–e006113.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Ouakad M, Vanaerschot M, Rijal S, Sundar S, et al. Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines. Parasitology. 2011;138(11):1392–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Vanaerschot M, De Doncker S, Rijal S, Maes L, et al. Antimonial resistance in Leishmania donovani is associated with increased in vivo parasite burden. PLoS One. 2011;6(8):e23120.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Vanaerschot M, Maes I, Ouakad M, Adaui V, et al. Linking in vitro and in vivo survival of clinical Leishmania donovani strains. PLoS One. 2010;5(8):e12211.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Hendrickx S, Beyers J, Mondelaers A, Eberhardt E, et al. Evidence of a drug-specific impact of experimentally selected paromomycin and miltefosine resistance on parasite fitness in Leishmania infantum. J Antimicrob Chemother. 2016;71(7):1914–21.PubMedCrossRefGoogle Scholar
  27. 27.
    Turner KG, Vacchina P, Robles-Murguia M, Wadsworth M, et al. Fitness and phenotypic characterization of miltefosine-resistant Leishmania major. PLoS Negl Trop Dis. 2015;9(7):e0003948.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hendrickx S, Inocencio da Luz RA, Bhandari V, Kuypers K, et al. Experimental induction of paromomycin resistance in antimony-resistant strains of L. donovani: outcome dependent on in vitro selection protocol. PLoS Negl Trop Dis. 2012;6(5):e1664.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    McConville MJ, Saunders EC, Kloehn J, Dagley MJ. Leishmania carbon metabolism in the macrophage phagolysosome - feast or famine? F1000Res. 2015;4(F1000 Faculty Rev):938.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Saunders EC, Ng WW, Kloehn J, Chambers JM, et al. Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism. PLoS Pathog. 2014;10(1):e1003888.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Mandell MA, Beverley SM. Continual renewal and replication of persistent Leishmania major parasites in concomitantly immune hosts. Proc Natl Acad Sci U S A. 2017;114(5):E801–10.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kloehn J, Saunders EC, O’Callaghan S, Dagley MJ, et al. Characterization of metabolically quiescent Leishmania parasites in murine lesions using heavy water labeling. PLoS Pathog. 2015;11(2):e1004683.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Grimm W. Storage conditions for stability testing in the EC, Japan and USA; the most important market for drug products. Drug Dev Ind Pharm. 1993;19(20):2795–830.CrossRefGoogle Scholar
  34. 34.
    Sundar S, Mehta H, Suresh AV, Singh SP, et al. Amphotericin B treatment for Indian visceral leishmaniasis: conventional versus lipid formulations. Clin Infect Dis. 2004;38(3):377–83.PubMedCrossRefGoogle Scholar
  35. 35.
    Wasan KM, Wasan EK, Gershkovich P, Zhu X, et al. Highly effective oral amphotericin B formulation against murine visceral leishmaniasis. J Infect Dis. 2009;200(3):357–60.PubMedCrossRefGoogle Scholar
  36. 36.
    Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–97.PubMedCrossRefGoogle Scholar
  37. 37.
    Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect Dis Clin N Am. 2009;23(4):791–815.CrossRefGoogle Scholar
  38. 38.
    Wijnant GJ, Van Bocxlaer K, Yardley V, Murdan S, et al. Efficacy of paromomycin-chloroquine combination therapy in experimental cutaneous leishmaniasis. Antimicrob Agents Chemother. 2017;61(8). pii: e00358-17.
  39. 39.
    Sundar S, Chakravarty J. An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother. 2015;16(2):237–52.PubMedCrossRefGoogle Scholar
  40. 40.
    Van Bocxlaer K, Yardley V, Murdan S, Croft SL. Topical formulations of miltefosine for cutaneous leishmaniasis in a BALB/c mouse model. J Pharm Pharmacol. 2016;68(7):862–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Garnier T, Mantyla A, Jarvinen T, Lawrence J, et al. In vivo (coloque en cursiva) studies on the antileishmanial activity of buparvaquone and its prodrugs. J Antimicrob Chemother. 2007;60(4):802–10.PubMedCrossRefGoogle Scholar
  42. 42.
    Van Bocxlaer K, Yardley V, Murdan S, Croft SL. Drug permeation and barrier damage in Leishmania-infected mouse skin. J Antimicrob Chemother. 2016;71(6):1578–85.PubMedCrossRefGoogle Scholar
  43. 43.
    Voak AA, Harris A, Qaiser Z, Croft SL, et al. Treatment of experimental visceral leishmaniasis with single-dose liposomal amphotericin B – pharmacodynamics and biodistribution at different stages of disease. Antimicrob Agents Chemother. 2017. pii: AAC.00497-17.
  44. 44.
    Hailu A, Musa A, Wasunna M, Balasegaram M, et al. Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial. PLoS Negl Trop Dis. 2010;4(10):e709.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Ostyn B, Hasker E, Dorlo TP, Rijal S, et al. Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia. PLoS One. 2014;9(6):e100220.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Dorlo TP, Rijal S, Ostyn B, de Vries PJ, et al. Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure. J Infect Dis. 2014;210(1):146–53.PubMedCrossRefGoogle Scholar
  47. 47.
    Castro MD, Gomez MA, Kip AE, Cossio A, et al. Pharmacokinetics of miltefosine in children and adults with cutaneous leishmaniasis. Antimicrob Agents Chemother. 2017;61(3). pii: e02198-16.Google Scholar
  48. 48.
    Kip AE, Rosing H, Hillebrand MJ, Blesson S, et al. Validation and clinical evaluation of a novel method to measure miltefosine in leishmaniasis patients using dried blood spot sample collection. Antimicrob Agents Chemother. 2016;60(4):2081–9.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Burkhart PV, Sabate E. Adherence to long-term therapies: evidence for action. J Nurs Scholarsh. 2003;35(3):207.PubMedGoogle Scholar
  50. 50.
    Geli P, Laxminarayan R, Dunne M, Smith DL. “One-size-fits-all”? Optimizing treatment duration for bacterial infections. PLoS One. 2012;7(1):e29838.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Croft SL, Olliaro P. Leishmaniasis chemotherapy—challenges and opportunities. Clin Microbiol Infect. 2011;17(10):1478–83.PubMedCrossRefGoogle Scholar
  52. 52.
    Hastings IM, Watkins WM, White NJ. The evolution of drug-resistant malaria: the role of drug elimination half-life. Philos Trans R Soc Lond Ser B Biol Sci. 2002;357(1420):505–19.CrossRefGoogle Scholar
  53. 53.
    Jarvis JN, Lockwood DN. Clinical aspects of visceral leishmaniasis in HIV infection. Curr Opin Infect Dis. 2013;26(1):1–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Nissapatorn V, Sawangjaroen N. Parasitic infections in HIV infected individuals: diagnostic & therapeutic challenges. Indian J Med Res. 2011;134(6):878–97.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Lindoso JA, Cota GF, da Cruz AM, Goto H, et al. Visceral leishmaniasis and HIV coinfection in Latin America. PLoS Negl Trop Dis. 2014;8(9):e3136.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Burza S, Sinha PK, Mahajan R, Lima MA, et al. Risk factors for visceral leishmaniasis relapse in immunocompetent patients following treatment with 20 mg/kg liposomal amphotericin B (Ambisome) in Bihar, India. PLoS Negl Trop Dis. 2014;8(1):e2536.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Monge-Maillo B, López-Vélez R. Miltefosine for visceral and cutaneous leishmaniasis: drug characteristics and evidence-based treatment recommendations. Clin Infect Dis. 2015;60(9):1398–404.PubMedGoogle Scholar
  58. 58.
    Musa AM, Younis B, Fadlalla A, Royce C, et al. Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. PLoS Negl Trop Dis. 2010;4(10):e855.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Sundar S, Chakravarty J. Liposomal amphotericin B and leishmaniasis: dose and response. J Global Infect Dis. 2010;2(2):159–66.CrossRefGoogle Scholar
  60. 60.
    Boothe DM. Interpreting culture and susceptibility data in critical care: perks and pitfalls. J Vet Emerg Crit Care (SanAntonio). 2010;20(1):110–31.CrossRefGoogle Scholar
  61. 61.
    Rex JH, Goldberger M, Eisenstein BI, Harney C. The evolution of the regulatory framework for antibacterial agents. Ann N Y Acad Sci. 2014;1323:11–21.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Duru V, Khim N, Leang R, Kim S, et al. Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations. BMC Med. 2015;13:305.Google Scholar
  63. 63.
    Inocencio da Luz RA, Vermeersch M, Dujardin JC, Cos P, et al. In vitro sensitivity testing of Leishmania clinical field isolates: preconditioning of promastigotes enhances infectivity for macrophage host cells. Antimicrob Agents Chemother. 2009;53(12):5197–203.PubMedCentralCrossRefGoogle Scholar
  64. 64.
    Hendrickx S, Eberhardt E, Mondelaers A, Rijal S, et al. Lack of correlation between the promastigote back-transformation assay and miltefosine treatment outcome. J Antimicrob Chemother. 2015;70(11):3023–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Grogl M, Thomason TN, Franke ED. Drug resistance in leishmaniasis: its implication in systemic chemotherapy of cutaneous and mucocutaneous disease. Am J Trop Med Hyg. 1992;47(1):117–26.PubMedCrossRefGoogle Scholar
  66. 66.
    Ramesh V, Katara GK, Verma S, Salotra P. Miltefosine as an effective choice in the treatment of post-kala-azar dermal leishmaniasis. Br J Dermatol. 2011;165(2):411–4.Google Scholar
  67. 67.
    Palumbo E. Treatment strategies for mucocutaneous leishmaniasis. J Global Infect Dis. 2010;2(2):147–50.CrossRefGoogle Scholar
  68. 68.
    Moore EM, Lockwood DN. Treatment of visceral leishmaniasis. J Global Infect Dis. 2010;2(2):151–8.CrossRefGoogle Scholar
  69. 69.
    Fortin A, Hendrickx S, Yardley V, Cos P, et al. Efficacy and tolerability of oleylphosphocholine (OlPC) in a laboratory model of visceral leishmaniasis. J Antimicrob Chemother. 2012;67(11):2707–12.PubMedCrossRefGoogle Scholar
  70. 70.
    Nettey H, Allotey-Babington GL, Somuah I, Banga NB, et al. Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats. J Microencapsul. 2017;34(1):21–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Balaraman K, Vieira NC, Moussa F, Vacus J, et al. In vitro and in vivo antileishmanial properties of a 2-n-propylquinoline hydroxypropyl beta-cyclodextrin formulation and pharmacokinetics via intravenous route. Biomed Pharmacother. 2015;76:127–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Loeuillet C, Bañuls AL, Hide M. Study of Leishmania pathogenesis in mice: experimental considerations. Parasit Vectors. 2016;9:144.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Loría-Cervera EN. Animal models for the study of leishmaniasis. Rev Inst Med Trop Sao Paulo. 2014;56(1):1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ponte-Sucre A. Physiological consequences of drug resistance in Leishmania and their relevance for chemotherapy. Kinetoplastid Biol Dis. 2003;2(1):14.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Kedzierski L, Sakthianandeswaren A, Curtis JM, Andrews PC, et al. Leishmaniasis: current treatment and prospects for new drugs and vaccines. Curr Med Chem. 2009;16(5):599–614.PubMedCrossRefGoogle Scholar
  76. 76.
    Eberhardt E, Mondelaers A, Hendrickx S, Van den Kerkhof M, et al. Molecular detection of infection homogeneity and impact of miltefosine treatment in a Syrian golden hamster model of Leishmania donovani and L. infantum visceral leishmaniasis. Parasitol Res. 2016;115(10):4061–70.PubMedCrossRefGoogle Scholar
  77. 77.
    Forestier CL. Imaging host-Leishmania interactions: significance in visceral leishmaniasis. Parasite Immunol. 2013;35(9–10):256–66.PubMedCrossRefGoogle Scholar
  78. 78.
    Yurdakul P, Dalton J, Beattie L, Brown N, et al. Compartment-specific remodeling of splenic micro-architecture during experimental visceral leishmaniasis. Am J Pathol. 2011;179(1):23–9.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Rouault E, Lecoeur H, Meriem AB, Minoprio P, et al. Imaging visceral leishmaniasis in real time with golden hamster model: monitoring the parasite burden and hamster transcripts to further characterize the immunological responses of the host. Parasitol Int. 2017;66(1):933–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Lewis MD, Fortes Francisco A, Taylor MC, Burrell-Saward H, et al. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection. Cell Microbiol. 2014;16(9):1285–12300.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Michel G, Ferrua B, Lang T, Maddugoda MP, et al. Luciferase-expressing Leishmania infantum allows the monitoring of amastigote population size, in vivo, ex vivo and in vitro. PLoS Negl Trop Dis. 2011;5(9):e1323.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Moreira ND, Vitoriano-Souza J, Roatt BM, Vieira PMA, et al. Parasite burden in hamsters infected with two different strains of Leishmania (Leishmania) infantum: “Leishman Donovan units” versus real-time PCR. PLoS One. 2012;7(10):e47907.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Satow MM, Yamashiro-Kanashiro EH, Rocha MC, Oyafuso LK, et al. Applicability of kDNA-PCR for routine diagnosis of American tegumentary leishmaniasis in a tertiary reference hospital. Rev Inst Med Trop Sao Paulo. 2013;55(6):393–9.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Nicodemo AC, Amato VS, Tuon FF, Souza RM, et al. Usefulness of kDNA PCR in the diagnosis of visceral leishmaniasis reactivation in co-infected patients. Rev Inst Med Trop Sao Paulo. 2013;55(6):429–31.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Ceccarelli M, Galluzzi L, Migliazzo A, Magnani M. Detection and characterization of Leishmania (Leishmania) and Leishmania (Viannia) by SYBR green-based real-time PCR and high resolution melt analysis targeting kinetoplast minicircle DNA. PLoS One. 2014;9(2):e88845.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Maes L, Beyers J, Mondelaers A, Van den Kerkhof M, et al. In vitro ‘time-to-kill’ assay to assess the cidal activity dynamics of current reference drugs against Leishmania donovani and Leishmania infantum. J Antimicrob Chemother. 2017;72(2):428–30.PubMedCrossRefGoogle Scholar
  87. 87.
    Seifert K, Escobar P, Croft SL. In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent. J Antimicrob Chemother. 2010;65(3):508–11.PubMedCrossRefGoogle Scholar
  88. 88.
    Koniordou M, Patterson S, Wyllie S, Seifert K. Snapshot profiling of the antileishmanial potency of lead compounds and drug candidates against intracellular Leishmania donovani amastigotes, with a focus on human-derived host cells. Antimicrob Agents Chemother. 2017;61(3). pii: e01228-16.Google Scholar
  89. 89.
    Tegazzini D, Diaz R, Aguilar F, Pena I, et al. A replicative in vitro assay for drug discovery against Leishmania donovani. Antimicrob Agents Chemother. 2016;60(6):3524–32.Google Scholar
  90. 90.
    Duenas-Romero AM, Loiseau PM, Saint-Pierre-Chazalet M. Interaction of sitamaquine with membrane lipids of Leishmania donovani promastigotes. Biochim Biophys Acta. 2007;1768(2):246–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sarah Hendrickx
    • 1
  • Louis Maes
    • 1
  • Simon L. Croft
    • 2
  • Guy Caljon
    • 1
    Email author
  1. 1.Laboratory for Microbiology, Parasitology and Hygiene (LMPH)University of AntwerpWilrijk (Antwerp)Belgium
  2. 2.Department of Immunology and Infection, Faculty of Infectious and Tropical DiseasesLondon School of Hygiene and Tropical MedicineLondonUK

Personalised recommendations