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Epidemiology of Leishmaniasis in the Time of Drug Resistance (the Miltefosine Era)

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Drug Resistance in Leishmania Parasites

Abstract

In the first edition of this chapter (Dujardin J-C, Decuypere S, Epidemiology of leishmaniasis in the time of drug resistance. In: Ponte-Sucre A, Padron-Nieves M, Diaz E (eds) Drug resistance in Leishmania parasites: consequences, molecular mechanism and possible treatments. Spinger, pp 65–83), we updated various aspects of leishmaniasis epidemiology, with a particular emphasis on their relation with parasite drug resistance (DR), with a focus on antimonials (SSG). We made a clear distinction between DR, a parasite phenotype measured in the laboratory and treatment failure (TF), a clinical phenotype assessed in the patient. In this second edition, the objective is to update knowledge (whatever the drug) in this domain and to focus on miltefosine (MIL), contrasting wherever relevant with SSG. In the first part, we present data on the current efficacy of MIL, highlighting the increase in TF, and only a few cases of DR. Then, we update information on the risk factors for (re)emergence and spreading of leishmaniasis, focusing on the link between DR and TF: among others, we discuss the role of asymptomatics and animals, the importance of co-infection (considering the usual suspect HIV but also newcomers as Leishmania RNA viruses (LRV)), and the risk related with massive human migrations and environmental changes. Finally, we review the advances made about tools for epidemiological surveillance of TF/DR, ranging from clinical ones to laboratory ones. Recommendations and perspectives for further research will be discussed at the end.

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References

  1. Dujardin J-C, Decuypere S. Epidemiology of leishmaniasis in the time of drug resistance. In: Ponte-Sucre A, Padron-Nieves M, Diaz E, editors. Drug resistance in Leishmania parasites. Consequences, molecular mechanism and possible treatments. Wienen: Springer; 2013. p. 65–83.

    Chapter  Google Scholar 

  2. Alvar J, Vélez ID, Bern C, Herrero M, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2002;7:e35671.

    Article  CAS  Google Scholar 

  3. SEARO/WHO. Health Ministers commit to eliminating kalar azar [media advisory]. New Delhi: WHO Regional Office for South-East Asia; 2014. http://www.searo.who.int/mediacentre/releases/2014/pr1581/en/

  4. WHO-TDR. Sustainable visceral leishmaniasis elimination requires research on infection reservoirs. TDR news item; 2016. http://www.who.int/tdr/news/2016/visceral-leishmaniasis-research/en/

  5. Sundar S, Jha TK, Thakur CP, Bhattacharya SK, et al. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med. 2002;347:1739–46.

    Article  PubMed  CAS  Google Scholar 

  6. Bhattacharya SK, Jha TK, Sundar S, Thakur CP, et al. Efficacy and tolerability of miltefosine for childhood visceral leishmaniasis in India. Clin Infect Dis. 2004;38:217–21.

    Article  PubMed  CAS  Google Scholar 

  7. Patra P, Guha SK, Maji AK, Saha P, et al. Efficacy of oral miltefosine in visceral leishmaniasis in rural West Bengal, India. Indian J Pharm. 2012;44:500–3.

    Article  CAS  Google Scholar 

  8. Sundar S, Singh A, Rai M, Prajapati VK, et al. Efficacy of miltefosine in the treatment of visceral leishmaniasis after a decade of use in India. Clin Infect Dis. 2012;55:543–50.

    Article  PubMed  CAS  Google Scholar 

  9. 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;56:1530–8.

    Article  PubMed  CAS  Google Scholar 

  10. Sundar S, Sinha P, Jha TK, Chakravarty J, et al. Oral miltefosine for Indian post-kala-azar dermal leishmaniasis: a randomised trial. Tropical Med Int Health. 2013;18:96–100.

    Article  CAS  Google Scholar 

  11. Ramesh V, Singh R, Avishek K, Verma A, et al. Decline in clinical efficacy of oral miltefosine in treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) in India. PLoS Negl Trop Dis. 2015;9:e0004093.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Sundar S, Singh A, Chakravarty J, Rai M. Efficacy and safety of miltefosine in treatment of post-kala-azar dermal leishmaniasis. Sci World J. 2015;2015:414378.

    Article  CAS  Google Scholar 

  13. Ritmeijer K, Dejenie A, Assefa Y, Hundie TB, et al. A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis. 2006;43:357–64.

    Article  PubMed  CAS  Google Scholar 

  14. Wasunna M, Njenga S, Balasegaram M, Alexander N, et al. Efficacy and safety of AmBisome in combination with sodium stibogluconate or miltefosine and miltefosine monotherapy for African visceral leishmaniasis: phase II randomized trial. PLoS Negl Trop Dis. 2016;10:e0004880.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Mohebali M, Fotouhi A, Hooshmand B, Zarei Z, et al. Comparison of miltefosine and meglumine antimoniate for the treatment of zoonotic cutaneous leishmaniasis (ZCL) by a randomized clinical trial in Iran. Acta Trop. 2007;103:33–40.

    Article  PubMed  CAS  Google Scholar 

  16. Soto J, Arana BA, Toledo J, Rizzo N, et al. Miltefosine for new world cutaneous leishmaniasis. Clin Infect Dis. 2004;38:1266–72.

    Article  PubMed  CAS  Google Scholar 

  17. Soto J, Rea J, Balderrama M, Toledo J, et al. Efficacy of miltefosine for Bolivian cutaneous leishmaniasis. Am J Trop Med Hyg. 2008;78:210–1.

    Article  PubMed  Google Scholar 

  18. Vélez I, López L, Sánchez X, Mestra L, et al. Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis. Am J Trop Med Hyg. 2010;83:351–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. López L, Cruz C, Godoy G, Robledo SM, et al. Thermotherapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia. Rev Inst Med Trop Sao Paulo. 2013;55:S0036-46652013000300197.

    Google Scholar 

  20. Chrusciak-Talhari A, Dietze R, Chrusciak Talhari C, da Silva RM, et al. Randomized controlled clinical trial to access efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis Caused by Leishmania (Viannia) guyanensis in Manaus, Brazil. Am J Trop Med Hyg. 2011;84:255–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Machado PR, Ampuero J, Guimarães LH, Villasboas L, et al. Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial. PLoS Negl Trop Dis. 2010;4:e912.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Garcia Bustos MF, Barrio A, Parodi C, Beckar J. Miltefosine versus meglumine antimoniate in the treatment of mucosal leishmaniasis. Medicina (B Aires). 2014;74:371–7.

    Google Scholar 

  23. Cota GF, de Sousa MR, de Mendonça AL, Patrocinio A, et al. Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil. PLoS Negl Trop Dis. 2014;8:e2816.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Arevalo J, Ramirez L, Adaui V, Zimic M, et al. Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis. J Infect Dis. 2007;195:1846–51.

    Article  PubMed  CAS  Google Scholar 

  25. Yardley V, Croft SL, De Doncker S, Dujardin JC, et al. The sensitivity of clinical isolates of Leishmania from Peru and Nepal to miltefosine. Am J Trop Med Hyg. 2005;73:272–5.

    Article  PubMed  CAS  Google Scholar 

  26. Bhandari V, Kulshrestha A, Deep DK, Stark O, et al. Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. PLoS Negl Trop Dis. 2012;6:e1657.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Prajapati VK, Sharma S, Rai M, Ostyn B, et al. In vitro susceptibility of Leishmania donovani to miltefosine in Indian visceral leishmaniasis. Am J Trop Med Hyg. 2013;89:750–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Srivastava S, Mishra J, Gupta AK, Singh A, et al. Laboratory confirmed miltefosine resistant cases of visceral leishmaniasis from India. Parasit Vectors. 2017;10:49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Fernández OL, Diaz-Toro Y, Ovalle C, Valderrama L, et al. Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia. PLoS Negl Trop Dis. 2014;8:e2871.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Obonaga R, Fernández OL, Valderrama L, Rubiano LC, et al. Treatment failure and miltefosine susceptibility in dermal leishmaniasis caused by Leishmania subgenus Viannia species. Antimicrob Agents Chemother. 2014;58:144–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Mondelaers A, Sanchez-Cañete MP, Hendrickx S, Eberhardt E, et al. Genomic and molecular characterization of miltefosine resistance in Leishmania infantum strains with either natural or acquired resistance through experimental selection of intracellular amastigotes. PLoS One. 2016;11:e0154101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Shaw CD, Lonchamp J, Downing T, Imamura H, et al. In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterization. Mol Microbiol. 2016;99:1134–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. 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:e00611–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. 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;210:146–53.

    Article  PubMed  CAS  Google Scholar 

  35. 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:e100220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Hirve S, Boelaert M, Matlashewski G, Mondal D, et al. Transmission dynamics of visceral Leishmaniasis in the Indian subcontinent – a systematic literature review. PLoS Negl Trop Dis. 2016;10:e0004896.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Nandy AM. Ten years of kala-azar in west Bengal, Part I. Did post-kala-azar dermal leishmaniasis initiate the outbreak in Parganas? Bull World Health Organ. 1992;70:341–6.

    PubMed  PubMed Central  Google Scholar 

  38. Bhattarai NR, Van der Auwera G, Rijal S, Picado A, et al. Domestic animals and epidemiology of visceral leishmaniasis, Nepal. Emerg Infect Dis. 2010;16:231–7.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Khanal B, Picado A, Bhattarai NR, Van Der Auwera G, et al. Spatial analysis of Leishmania donovani exposure in humans and domestic animals in a recent kala azar focus in Nepal. Parasitology. 2010;137:1597–603.

    Article  PubMed  Google Scholar 

  40. Singh N, Mishra J, Singh R, Singh S. Animal reservoirs of visceral leishmaniasis in India. J Parasitol. 2013;99:64–7.

    Article  PubMed  Google Scholar 

  41. Singh SP, Picado A, Boelaert M, Gidwani K, et al. The epidemiology of Leishmania donovani infection in high transmission foci in India. Tropical Med Int Health. 2010;15(Suppl 2):12–20.

    Article  Google Scholar 

  42. Alam MZ, Yasin G, Kato H, Sakurai T, et al. PCR-based detection of Leishmania donovani DNA in a stray dog from a visceral Leishmaniasis endemic focus in Bangladesh. J Vet Med Sci. 2013;75:75–8.

    Article  PubMed  CAS  Google Scholar 

  43. Stauch A, Sarkar RR, Picado A, Ostyn B, et al. Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and control. PLoS Negl Trop Dis. 2011;5:e1405.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ostyn B, Gidwani K, Khanal B, Picado A, et al. Incidence of symptomatic and asymptomatic Leishmania donovani infections in high-endemic foci in India and Nepal: a prospective study. PLoS Negl Trop Dis. 2011;5:e1284.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Chapman LA, Dyson L, Courtenay O, Chowdhury R, et al. Quantification of the natural history of visceral leishmaniasis and consequences for control. Parasit Vectors. 2015;8:521.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Das S, Matlashewski G, Bhunia GS, Kesari S, et al. Asymptomatic Leishmania infections in northern India: a threat for the elimination programme? Trans R Soc Trop Med Hyg. 2014;108:679–84.

    Article  PubMed  CAS  Google Scholar 

  47. Tiwary P, Kumar D, Singh RP, Rai M, et al. Prevalence of sand flies and Leishmania donovani infection in a natural population of female Phlebotomus argentipes in Bihar State, India. Vector Borne Zoonotic Dis. 2012;12:467–72.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Bhattarai NR, Das ML, Rijal S, van der Auwera G, et al. Natural infection of Phlebotomus argentipes with Leishmania and other trypanosomatids in a visceral leishmaniasis endemic region of Nepal. Trans R Soc Trop Med Hyg. 2009;103:1087–92.

    Article  PubMed  Google Scholar 

  49. Picado A, Singh SP, Rijal S, Sundar S, et al. Longlasting insecticidal nets for prevention of Leishmania donovani infection in India and Nepal: paired cluster randomised trial. BMJ. 2010;341:c6760.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Stauch A, Duerr HP, Dujardin JC, Vanaerschot M, et al. Treatment of visceral leishmaniasis: model-based analyses on the spread of antimony-resistant L. donovani in Bihar, India. PLoS Negl Trop Dis. 2012;6:e1973.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 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:e12211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Vanaerschot M, Decuypere S, Berg M, Roy S, et al. Drug-resistant microorganisms with a higher fitness – can medicines boost pathogens? Crit Rev Microbiol. 2013;39:384–94.

    Article  PubMed  Google Scholar 

  53. Vanaerschot M, Huijben S, Van den Broeck F, Dujardin JC. Drug resistance in vectorborne parasites: multiple actors and scenarios for an evolutionary arms race. FEMS Microbiol Rev. 2014;38:41–55.

    Article  PubMed  CAS  Google Scholar 

  54. Ouakad M, Vanaerschot M, Rijal S, Sundar S, et al. Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines. Parasitology. 2011;138:1392–9.

    Article  PubMed  CAS  Google Scholar 

  55. García-Hernández R, Gómez-Pérez V, Castanys S, Gamarro F. Fitness of Leishmania donovani parasites resistant to drug combinations. PLoS Negl Trop Dis. 2015;9:e0003704.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Leblois R, Kuhls K, François O, Schönian G, et al. Guns, germs and dogs: On the origin of Leishmania chagasi. Infect Genet Evol. 2011;11:1091–5.

    Article  PubMed  Google Scholar 

  57. Alvar J, Bashaye S, Argaw D, Cruz I, et al. Kala-azar outbreak in Libo Kemkem, Ethiopia: epidemiologic and parasitologic assessment. Am J Trop Med Hyg. 2007;77:275–82.

    Article  PubMed  Google Scholar 

  58. Al-Salem W, Herricks JR, Hotez PJ. A review of visceral leishmaniasis during the conflict in South Sudan and the consequences for East African countries. Parasit Vectors. 2016;9:460.

    Article  PubMed  PubMed Central  Google Scholar 

  59. “Annual Risk Analysis 2015” Frontex. 27 April 2015. p. 59.

    Google Scholar 

  60. Postigo JA. Leishmaniasis in the World Health Organization Eastern Mediterranean Region. Int J Antimicrob Agents. 2010;36(Suppl 1):S62–5.

    Article  PubMed  CAS  Google Scholar 

  61. Alp E, Erdem H, Rello J. Management of septic shock and severe infections in migrants and returning travelers requiring critical care. Eur J Clin Microbiol Infect Dis. 2016;35:527–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Papan C, Hübner J, von Both U. Infectious diseases in refugees and their minors arriving in Germany – what the GP needs to know [Article in German]. MMW Fortschr Med. 2017;158:58–62.

    Article  Google Scholar 

  63. Svárovská A, Ant TH, Seblová V, Jecná L, et al. Leishmania major glycosylation mutants require phosphoglycans (lpg2-) but not lipophosphoglycan (lpg1-) for survival in permissive sand fly vectors. PLoS Negl Trop Dis. 2010;4:e580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Seblova V, Myskova J, Hlavacova J, Votypka J, et al. Natural hybrid of Leishmania infantum/L. donovani: development in Phlebotomus tobbi, P. perniciosus and Lutzomyia longipalpis and comparison with non-hybrid strains differing in tissue tropism. Parasit Vectors. 2015;8:605.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Arce A, Estirado A, Ordobas M, Sevilla S, et al. Reemergence of leishmaniasis in Spain: community outbreak in Madrid, Spain, 2009 to 2012. Euro Surveill. 2013;18:20546.

    Article  PubMed  CAS  Google Scholar 

  66. Molina R, Jiménez MI, Cruz I, Iriso A, et al. The hare (Lepus granatensis) as potential sylvatic reservoir of Leishmania infantum in Spain. J Vet Parasitol. 2012;190:268–71.

    Article  CAS  Google Scholar 

  67. Perry MR, Wyllie S, Prajapati VK, Feldmann J, et al. Visceral leishmaniasis and arsenic: an ancient poison contributing to antimonial treatment failure in the Indian subcontinent? PLoS Negl Trop Dis. 2011;5:e1227.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Perry MR, Wyllie S, Raab A, Feldmann J, et al. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis. Proc Natl Acad Sci USA. 2013;110:19932–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  69. Perry M, Wyllie S, Prajapati V, Menten J, et al. Arsenic, antimony, and Leishmania: has arsenic contamination of drinking water in India led to treatment-resistant kala-azar? Lancet. 2015;385(Suppl 1):S80.

    Article  PubMed  Google Scholar 

  70. Ostyn B, Uranw S, Bhattarai NR, Das ML, et al. Transmission of Leishmania donovani in the hills of Eastern Nepal, an outbreak investigation in Okhaldhunga and Bhojpur districts. PLoS Negl Trop Dis. 2015;9:e0003966.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Imamura H, Downing T, Van den Broeck F, Sanders MJ, et al. Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent. elife. 2016;5:e12613.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Rai K, Bhattarai NR, Vanaerschot M, Imamura H, et al. Single locus genotyping to track Leishmania donovani in the Indian subcontinent: application in Nepal. PLoS Negl Trop Dis. 2017;11:e0005420.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Siriwardana HV, Noyes HA, Beeching NJ, Chance ML, et al. Leishmania donovani and cutaneous leishmaniasis, Sri Lanka. Emerg Infect Dis. 2007;13:476–8.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Ginouvès M, Simon S, Bourreau E, Lacoste V, et al. Prevalence and distribution of Leishmania RNA virus 1 in Leishmania parasites from French Guiana. Am J Trop Med Hyg. 2016;94:102–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Adaui V, Lye LF, Akopyants NS, Zimic M, et al. Association of the endobiont double-stranded RNA virus LRV1 with treatment failure for human leishmaniasis caused by Leishmania braziliensis in Peru and Bolivia. J Infect Dis. 2016;213:112–21.

    Article  PubMed  CAS  Google Scholar 

  76. Cantanhêde LM, da Silva Júnior CF, Ito MM, Felipin KP, et al. Further evidence of an association between the presence of Leishmania RNA virus 1 and the mucosal manifestations in tegumentary leishmaniasis patients. PLoS Negl Trop Dis. 2015;9:e0004079.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Macedo DH, Menezes-Neto A, Rugani JM, Rocha AC, et al. Low frequency of LRV1 in Leishmania braziliensis strains isolated from typical and atypical lesions in the State of Minas Gerais, Brazil. Mol Biochem Parasitol. 2016;210:50–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Hajjaran H, Mahdi M, Mohebali M, Samimi-Rad K, et al. Detection and molecular identification of Leishmania RNA virus (LRV) in Iranian Leishmania species. Arch Virol. 2016;161:3385–90.

    Article  PubMed  CAS  Google Scholar 

  79. Zangger H, Hailu A, Desponds C, Lye LF, et al. Leishmania aethiopica field isolates bearing an endosymbiotic dsRNA virus induce pro-inflammatory cytokine response. PLoS Negl Trop Dis. 2014;8:e2836.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Hartley MA, Ronet C, Zangger H, Beverley SM, et al. Leishmania RNA virus: when the host pays the toll. Front Cell Infect Microbiol. 2012;2:99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Bourreau E, Ginouves M, Prévot G, Hartley MA, et al. Presence of Leishmania RNA virus 1 in Leishmania guyanensis increases the risk of first-line treatment failure and symptomatic relapse. J Infect Dis. 2016;213:105–11.

    Article  PubMed  CAS  Google Scholar 

  82. Yardley V, Ortuno N, Llanos-Cuentas A, Chappuis F, et al. American tegumentary leishmaniasis: is antimonial treatment outcome related to parasite drug susceptibility? J Infect Dis. 2006;194:1168–75.

    Article  PubMed  Google Scholar 

  83. Martínez DY, Verdonck K, Kaye PM, Adaui V, et al. Tegumentary leishmaniasis and coinfections other than HIV. PLOS Neglect Trop Dis. 2018;12(3):e0006125. https://doi.org/10.1371/journal.pntd.0006125

    Article  Google Scholar 

  84. Chiaramonte MG, Zwirner NW, Caropresi SL, Taranto NJ, et al. Trypanosoma cruzi and Leishmania spp. human mixed infection. Am J Trop Med Hyg. 1996;54:271–3.

    Article  PubMed  CAS  Google Scholar 

  85. O’Neal SE, Guimarães LH, Machado PR, Alcântara L, et al. Influence of helminth infections on the clinical course of and immune response to Leishmania braziliensis cutaneous leishmaniasis. J Infect Dis. 2007;195:142–8.

    Article  PubMed  Google Scholar 

  86. Parodi C, García Bustos MF, Barrio A, Ramos F, et al. American tegumentary leishmaniasis: T-cell differentiation profile of cutaneous and mucosal forms-co-infection with Trypanosoma cruzi. Med Microbiol Immunol. 2016;205:353–69.

    Article  PubMed  CAS  Google Scholar 

  87. Azeredo-Coutinho RB, Pimentel MI, Zanini GM, Madeira MF, et al. Intestinal helminth coinfection is associated with mucosal lesions and poor response to therapy in American tegumentary leishmaniasis. Acta Trop. 2016;154:42–9.

    Article  PubMed  Google Scholar 

  88. Ostyn B, Malaviya P, Hasker E, Uranw S, et al. Retrospective quarterly cohort monitoring for patients with visceral leishmaniasis in the Indian subcontinent: outcomes of a pilot project. Tropical Med Int Health. 2013;18:725–33.

    Article  Google Scholar 

  89. Siriwardana HV, Senarath U, Chandrawansa PH, Karunaweera ND. Use of a clinical tool for screening and diagnosis of cutaneous leishmaniasis in Sri Lanka. Pathog Glob Health. 2015;109:174–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Valencia C, Arévalo J, Dujardin JC, Llanos-Cuentas A, et al. Prediction score for antimony treatment failure in patients with ulcerative leishmaniasis lesions. PLoS Negl Trop Dis. 2012;6:e1656.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Bhattacharyya T, Ayandeh A, Falconar AK, Sundar S, et al. IgG1 as a potential biomarker of post-chemotherapeutic relapse in visceral leishmaniasis, and adaptation to a rapid diagnostic test. PLoS Negl Trop Dis. 2014;8:e3273.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Sudarshan M, Weirather JL, Wilson ME, Sundar S. Study of parasite kinetics with antileishmanial drugs using real-time quantitative PCR in Indian visceral leishmaniasis. J Antimicrob Chemother. 2011;66:1751–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Verma S, Singh R, Sharma V, Bumb RA, et al. Development of a rapid loop-mediated isothermal amplification assay for diagnosis and assessment of cure of Leishmania infection. BMC Infect Dis. 2017;17:223.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Van der Auwera G, Dujardin JC. Species typing in dermal leishmaniasis. Clin Microbiol Rev. 2015;28:265–94.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Fraga J, Montalvo AM, De Doncker S, Dujardin JC, et al. Phylogeny of Leishmania species based on the heat-shock protein 70 gene. Infect Genet Evol. 2010;10:238–45.

    Article  PubMed  CAS  Google Scholar 

  96. Montalvo AM, Fraga J, Monzote L, Montano I, et al. Heat-shock protein 70 PCR-RFLP: a universal simple tool for Leishmania species discrimination in the New and Old World. Parasitology. 2010;137:1159–68.

    Article  PubMed  CAS  Google Scholar 

  97. Montalvo AM, Fraga J, Maes I, Dujardin JC, et al. Three new sensitive and specific heat-shock protein 70 PCRs for global Leishmania species identification. Eur J Clin Microbiol Infect Dis. 2012;31:1453–61.

    Article  PubMed  CAS  Google Scholar 

  98. Fraga J, Veland N, Montalvo AM, Praet N, et al. Accurate and rapid species typing from cutaneous and mucocutaneous leishmaniasis lesions of the New World. Diagn Microbiol Infect Dis. 2012;74:142–50.

    Article  PubMed  CAS  Google Scholar 

  99. Montalvo AM, Fraga J, El Safi S, Gramiccia M, et al. Direct Leishmania species typing in Old World clinical samples: evaluation of 3 sensitive methods based on the heat-shock protein 70 gene. Diagn Microbiol Infect Dis. 2014;80:35–9.

    Article  PubMed  CAS  Google Scholar 

  100. Van der Auwera G, Maes I, De Doncker S, Ravel C, et al. Heat-shock protein 70 gene sequencing for Leishmania species typing in European tropical infectious disease clinics. Euro Surveill. 2013;18:20543.

    Article  PubMed  Google Scholar 

  101. Van der Auwera G, Ravel C, Verweij JJ, Bart A, et al. Evaluation of four single-locus markers for Leishmania species discrimination by sequencing. J Clin Microbiol. 2014;52:1098–104.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Van der Auwera G, Bart A, Chicharro C, Cortes S, et al. Comparison of Leishmania typing results obtained from 16 European clinical laboratories in 2014. Euro Surveill. 2016;21:30418.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Rodríguez-Brito S, Camacho E, Mendoza M, Niño-Vega GA. Differential identification of Sporothrix spp. and Leishmania spp. by conventional PCR and qPCR in multiplex format. Med Mycol. 2015;53:22–7.

    Article  PubMed  CAS  Google Scholar 

  104. Karani M, Sotiriadou I, Plutzer J, Karanis P. Bench-scale experiments for the development of a unified loop-mediated isothermal amplification (LAMP) assay for the in vitro diagnosis of Leishmania species’ promastigotes. Epidemiol Infect. 2014;142:1671–7.

    Article  PubMed  CAS  Google Scholar 

  105. Zangger H, Ronet C, Desponds C, Kuhlmann FM, et al. Detection of Leishmania RNA virus in Leishmania parasites. PLoS Negl Trop Dis. 2013;7:e2006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Kulshrestha A, Bhandari V, Mukhopadhyay R, Ramesh V, et al. Validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of Leishmania donovani. Parasitol Res. 2013;112:825–8.

    Article  PubMed  Google Scholar 

  107. Pérez-Victoria FJ, Sánchez-Cañete MP, Seifert K, Croft SL, et al. Mechanisms of experimental resistance of Leishmania to miltefosine: implications for clinical use. Drug Resist Updat. 2006;9:26–39.

    Article  PubMed  CAS  Google Scholar 

  108. Hefnawy A, Berg M, Dujardin JC, De Muylder G. Exploiting knowledge on Leishmania drug resistance to support the quest for new drugs. Trends Parasitol. 2017;33:162–74.

    Article  PubMed  CAS  Google Scholar 

  109. Dumetz F, Imamura H, Sanders M, Seblova V, et al. Modulation of aneuploidy in Leishmania donovani during adaptation to different in vitro and in vivo environments, and its impact on gene expression. MBio. 2017;8(3):pii e00599–17.

    Article  Google Scholar 

  110. Prieto Barja P, Pescher P, Bussotti G, Dumetz F, et al. Asexual maintenance of genetic diversity in the protozoan pathogen Leishmania donovani. Nat Ecol Evol. 2017;1(12):1961–9.

    Article  PubMed  Google Scholar 

  111. Alam MZ, Kuhls K, Schweynoch C, Sundar S, et al. Multilocus microsatellite typing (MLMT) reveals genetic homogeneity of Leishmania donovani strains in the Indian subcontinent. Infect Genet Evol. 2009;9:24–31.

    Article  PubMed  CAS  Google Scholar 

  112. Dumetz F, Cuypers B, Imamura H, Zander D, et al. (2018) Molecular pre-adaptation to antimony resistance in Leishmania donovani of the Indian subcontinent. mSphere (in press)

    Google Scholar 

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Acknowledgments

The research in the Molecular Parasitology Unit here quoted received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 642609, the Flemish Fund for Scientific Research (12Q8115N and G.0.B81.12), the Kaladrug-R consortium from the European Union Framework Program (FP7-222895), the Belgian Science Policy Office (TRIT, P7/41), the Department of Economy, Science and Innovation in Flanders (ITM-SOFIB) and the Belgian Cooperation Agency (DGD; institutional collaboration with Instituto de Medicina Tropical A.von Humboldt in Lima and with Instituto Pedro Kouri in La Havana).

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  1. Molecular Parasitology Unit, Institute of Tropical Medicine, Antwerp, Belgium

    Jean-Claude Dujardin

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  1. Jean-Claude Dujardin
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Correspondence to Jean-Claude Dujardin .

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  1. Institute of Experimental Medicine, Universidad Central de Venezuela, Caracas, Venezuela

    Alicia Ponte-Sucre

  2. Escuela Luis Razetti Fac de Medicine, Universidad Central de Venezuela, Caracas, Venezuela

    Maritza Padrón-Nieves

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Dujardin, JC. (2018). Epidemiology of Leishmaniasis in the Time of Drug Resistance (the Miltefosine Era). In: Ponte-Sucre, A., Padrón-Nieves, M. (eds) Drug Resistance in Leishmania Parasites. Springer, Cham. https://doi.org/10.1007/978-3-319-74186-4_4

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