Leishmaniasis: new insights from an old and neglected disease

Review

Abstract

Leishmaniases are a clinically heterogeneous group of diseases caused by protozoa of the genus Leishmania. There is growing evidence that the true incidence of the disease is underestimated, especially in hyperendemic regions. Moreover, climate changes together with the increasing movement of humans and animals raise concerns about the possible introduction of Leishmania infection in previously spared areas. The disease is emerging in immunocompromised patients undergoing bone marrow or solid organ transplantation or treatment with biologic drugs. Furthermore, the deployment of military troops and travel to endemic areas are associated with the observation of a growing number of patients with cutaneous disease. Improvement in diagnostic methods, both in the field and in specialized laboratories, has been obtained through the implementation of molecular amplification methods and using the rK39 antigen as the substrate. Finally, new therapeutic approaches are gaining attention, such as the use of miltefosine for cutaneous leishmaniasis and paromomycin for visceral leishmaniasis, as well as the use of various antileishmanial drugs in combination.

References

  1. 1.
    Al-Mutawakel K, Scutaru C, Shami A, Sakr M, Groneberg DA, Quarcoo D (2010) Scientometric analysis of the world-wide research efforts concerning Leishmaniasis. Parasit Vectors 3:14PubMedCrossRefGoogle Scholar
  2. 2.
    Pratt DM, David JR (1981) Monoclonal antibodies that distinguish between New World species of Leishmania. Nature 291:581–583PubMedCrossRefGoogle Scholar
  3. 3.
    Lainson R, Shaw JJ (1987) Evolution, classification and geographical distribution. In: Peters W, Killick-Kendrick R (eds) The leishmaniases in biology and medicine. Academic Press, London, pp 1–120Google Scholar
  4. 4.
    Rioux JA, Lanotte G, Serres E, Pratlong F, Bastien P, Perieres J (1990) Taxonomy of Leishmania. Use of isoenzymes. Suggestions for a new classification. Ann Parasitol Hum Comp 65:111–125PubMedGoogle Scholar
  5. 5.
    Bañuls AL, Hide M, Prugnolle F (2007) Leishmania and the leishmaniases: a parasite genetic update and advances in taxonomy, epidemiology and pathogenicity in humans. Adv Parasitol 64:1–109PubMedCrossRefGoogle Scholar
  6. 6.
    Lukes J, Mauricio IL, Schönian G, Dujardin JC, Soteriadou K, Dedet JP, Kuhls K, Tintaya KW, Jirků M, Chocholová E, Haralambous C, Pratlong F, Oborník M, Horák A, Ayala FJ, Miles MA (2007) Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy. Proc Natl Acad Sci USA 104:9375–9380PubMedCrossRefGoogle Scholar
  7. 7.
    Fraga J, Montalvo AM, De Doncker S, Dujardin JC, Van der Auwera G (2010) Phylogeny of Leishmania species based on the heat-shock protein 70 gene. Infect Genet Evol 10:238–245PubMedCrossRefGoogle Scholar
  8. 8.
    Schönian G, Mauricio I, Cupolillo E (2010) Is it time to revise the nomenclature of Leishmania? Trends Parasitol 26:466–469PubMedCrossRefGoogle Scholar
  9. 9.
    Bern C, Maguire JH, Alvar J (2008) Complexities of assessing the disease burden attributable to leishmaniasis. PLoS Negl Trop Dis 2:e313PubMedCrossRefGoogle Scholar
  10. 10.
    Singh SP, Reddy DC, Rai M, Sundar S (2006) Serious underreporting of visceral leishmaniasis through passive case reporting in Bihar, India. Trop Med Int Health 11:899–905PubMedCrossRefGoogle Scholar
  11. 11.
    Singh VP, Ranjan A, Topno RK, Verma RB, Siddique NA, Ravidas VN, Kumar N, Pandey K, Das P (2010) Estimation of under-reporting of visceral leishmaniasis cases in Bihar, India. Am J Trop Med Hyg 82:9–11PubMedCrossRefGoogle Scholar
  12. 12.
    Das P, Samuels S, Desjeux P, Mittal A, Topno R, Siddiqui NA, Sur D, Pandey A, Sarnoff R (2010) Annual incidence of visceral leishmaniasis in an endemic area of Bihar, India. Trop Med Int Health 15(Suppl 2):4–11PubMedCrossRefGoogle Scholar
  13. 13.
    Dujardin JC, Campino L, Cañavate C, Dedet JP, Gradoni L, Soteriadou K, Mazeris A, Ozbel Y, Boelaert M (2008) Spread of vector-borne diseases and neglect of Leishmaniasis, Europe. Emerg Infect Dis 14:1013–1018PubMedCrossRefGoogle Scholar
  14. 14.
    Ready PD (2010) Leishmaniasis emergence in Europe. Euro Surveill 15:19505PubMedGoogle Scholar
  15. 15.
    Maroli M, Rossi L, Baldelli R, Capelli G, Ferroglio E, Genchi C, Gramiccia M, Mortarino M, Pietrobelli M, Gradoni L (2008) The northward spread of leishmaniasis in Italy: evidence from retrospective and ongoing studies on the canine reservoir and phlebotomine vectors. Trop Med Int Health 13:256–264PubMedCrossRefGoogle Scholar
  16. 16.
    Morosetti G, Bongiorno G, Beran B, Scalone A, Moser J, Gramiccia M, Gradoni L, Maroli M (2009) Risk assessment for canine leishmaniasis spreading in the north of Italy. Geospat Health 4:115–127PubMedGoogle Scholar
  17. 17.
    Biglino A, Bolla C, Concialdi E, Trisciuoglio A, Romano A, Ferroglio E (2010) Asymptomatic Leishmania infantum infection in an area of Northwestern Italy (Piedmont Region) where such infections are traditionally nonendemic. J Clin Microbiol 48:131–136PubMedCrossRefGoogle Scholar
  18. 18.
    Naucke TJ, Schmitt C (2004) Is leishmaniasis becoming endemic in Germany? Int J Med Microbiol 293:179–181PubMedGoogle Scholar
  19. 19.
    Naucke TJ, Menn B, Massberg D, Lorentz S (2008) Sandflies and leishmaniasis in Germany. Parasitol Res 103(Suppl 1):S65–S68PubMedCrossRefGoogle Scholar
  20. 20.
    Postigo JA (2010) Leishmaniasis in the World Health Organization Eastern Mediterranean Region. Int J Antimicrob Agents 36(Suppl 1):S62–S65PubMedCrossRefGoogle Scholar
  21. 21.
    Mosleh IM, Geith E, Natsheh L, Abdul-Dayem M, Abotteen N (2008) Cutaneous leishmaniasis in the Jordanian side of the Jordan Valley: severe under-reporting and consequences on public health management. Trop Med Int Health 13:855–860PubMedCrossRefGoogle Scholar
  22. 22.
    Romero GA, Boelaert M (2010) Control of visceral leishmaniasis in Latin America—a systematic review. PLoS Negl Trop Dis 4:e584PubMedCrossRefGoogle Scholar
  23. 23.
    Alvar J, Cañavate C, Gutiérrez-Solar B, Jiménez M, Laguna F, López-Vélez R, Molina R, Moreno J (1997) Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev 10:298–319PubMedGoogle Scholar
  24. 24.
    Kubar J, Marty P, Lelièvre A, Quaranta JF, Staccini P, Caroli-Bosc C, Le Fichoux Y (1998) Visceral leishmaniosis in HIV-positive patients: primary infection, reactivation and latent infection: impact of the CD4+ T-lymphocyte counts. AIDS 12:2147–2153PubMedCrossRefGoogle Scholar
  25. 25.
    Paredes R, Munoz J, Diaz I, Domingo P, Gurgui M, Clotet B (2003) Leishmaniasis in HIV infection. J Postgrad Med 49:39–49PubMedCrossRefGoogle Scholar
  26. 26.
    Alvar J, Aparicio P, Aseffa A, Den Boer M, Cañavate C, Dedet JP, Gradoni L, Ter Horst R, López-Vélez R, Moreno J (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21:334–359PubMedCrossRefGoogle Scholar
  27. 27.
    de la Rosa R, Pineda JA, Delgado J, Macías J, Morillas F, Mira JA, Sánchez-Quijano A, Leal M, Lissen E (2002) Incidence of and risk factors for symptomatic visceral leishmaniasis among human immunodeficiency virus type 1-infected patients from Spain in the era of highly active antiretroviral therapy. J Clin Microbiol 40:762–767CrossRefGoogle Scholar
  28. 28.
    ter Horst R, Collin SM, Ritmeijer K, Bogale A, Davidson RN (2008) Concordant HIV infection and visceral leishmaniasis in Ethiopia: the influence of antiretroviral treatment and other factors on outcome. Clin Infect Dis 46:1702–1709PubMedCrossRefGoogle Scholar
  29. 29.
    Gorski S, Collin SM, Ritmeijer K, Keus K, Gatluak F, Mueller M, Davidson RN (2010) Visceral leishmaniasis relapse in Southern Sudan (1999–2007): a retrospective study of risk factors and trends. PLoS Negl Trop Dis 4:e705PubMedCrossRefGoogle Scholar
  30. 30.
    Petrela R, Kuneshka L, Foto E, Zavalani F, Gradoni L (2010) Pediatric visceral leishmaniasis in Albania: a retrospective analysis of 1,210 consecutive hospitalized patients (1995–2009). PLoS Negl Trop Dis 4:e814CrossRefGoogle Scholar
  31. 31.
    Antinori S, Cascio A, Parravicini C, Bianchi R, Corbellino M (2008) Leishmaniasis among organ transplant recipients. Lancet Infect Dis 8:191–199PubMedCrossRefGoogle Scholar
  32. 32.
    Veroux M, Corona D, Giuffrida G, Cacopardo B, Sinagra N, Tallarita T, Giaquinta A, Zerbo D, Veroux PF (2010) Visceral leishmaniasis in the early post-transplant period after kidney transplantation: clinical features and therapeutic management. Transpl Infect Dis 12:387–391PubMedCrossRefGoogle Scholar
  33. 33.
    Weisser M, Khanlari B, Terracciano L, Arber C, Gratwohl A, Bassetti S, Hatz C, Battegay M, Flückiger U (2007) Visceral leishmaniasis: a threat to immunocompromised patients in non-endemic areas? Clin Microbiol Infect 13:751–753PubMedCrossRefGoogle Scholar
  34. 34.
    Xynos ID, Tektonidou MG, Pikazis D, Sipsas NV (2009) Leishmaniasis, autoimmune rheumatic disease, and anti-tumor necrosis factor therapy, Europe. Emerg Infect Dis 15:956–959PubMedCrossRefGoogle Scholar
  35. 35.
    Cascio A, Iaria M, Iaria C (2010) Leishmaniasis and biologic therapies for rheumatologic diseases. Semin Arthritis Rheum 40:e3–e5PubMedCrossRefGoogle Scholar
  36. 36.
    De Leonardis F, Govoni M, Lo Monaco A, Trotta F (2009) Visceral leishmaniasis and anti-TNF-α therapy: case report and review of the literature. Clin Exp Rheumatol 27:503–506PubMedGoogle Scholar
  37. 37.
    Mueller MC, Fleischmann E, Grunke M, Schewe S, Bogner JR, Löscher T (2009) Relapsing cutaneous leishmaniasis in a patient with ankylosing spondylitis treated with infliximab. Am J Trop Med Hyg 81:52–54PubMedGoogle Scholar
  38. 38.
    Kopterides P, Mourtzoukou EG, Skopelitis E, Tsavaris N, Falagas ME (2007) Aspects of the association between leishmaniasis and malignant disorders. Trans R Soc Trop Med Hyg 101:1181–1189PubMedCrossRefGoogle Scholar
  39. 39.
    Antinori S, Gianelli E, Calattini S, Longhi E, Gramiccia M, Corbellino M (2005) Cutaneous leishmaniasis: an increasing threat for travellers. Clin Microbiol Infect 11:343–346PubMedCrossRefGoogle Scholar
  40. 40.
    Pavli A, Maltezou HC (2010) Leishmaniasis, an emerging infection in travellers. Int J Infect Dis 14:e1032–e1039PubMedCrossRefGoogle Scholar
  41. 41.
    Schwartz E, Hatz C, Blum J (2006) New world cutaneous leishmaniasis in travellers. Lancet Infect Dis 6:342–349PubMedCrossRefGoogle Scholar
  42. 42.
    Weina PJ, Neafie RC, Wortmann G, Polhemus M, Aronson NE (2004) Old world leishmaniasis: an emerging infection among deployed US military and civilian workers. Clin Infect Dis 39:1674–1680PubMedCrossRefGoogle Scholar
  43. 43.
    van Thiel PP, Leenstra T, de Vries HJ, van der Sluis A, van Gool T, Krull AC, van Vugt M, de Vries PJ, Zeegelaar JE, Bart A, van der Meide WF, Schallig HD, Faber WR, Kager PA (2010) Cutaneous leishmaniasis (Leishmania major infection) in Dutch troops deployed in northern Afghanistan: epidemiology, clinical aspects, and treatment. Am J Trop Med Hyg 83:1295–1300PubMedCrossRefGoogle Scholar
  44. 44.
    Lederman ER, Weld LH, Elyazar IRF, von Sonnenburg F, Loutan L, Schwartz E, Keystone JS (2008) Dermatologic conditions of the ill returned traveler: an analysis from the GeoSentinel Surveillance Network. Int J Infect Dis 12:593–602PubMedCrossRefGoogle Scholar
  45. 45.
    Pintado V, Martín-Rabadán P, Rivera ML, Moreno S, Bouza E (2001) Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore) 80:54–73CrossRefGoogle Scholar
  46. 46.
    López-Vélez R (2003) The impact of highly active antiretroviral therapy (HAART) on visceral leishmaniasis in Spanish patients who are co-infected with HIV. Ann Trop Med Parasitol 97(Suppl 1):143–147PubMedCrossRefGoogle Scholar
  47. 47.
    Mary C, Faraut F, Lascombe L, Dumon H (2004) Quantification of Leishmania infantum DNA by a real-time PCR assay with high sensitivity. J Clin Microbiol 42:5249–5255PubMedCrossRefGoogle Scholar
  48. 48.
    Antinori S, Calattini S, Piolini R, Longhi E, Bestetti G, Cascio A, Parravicini C, Corbellino M (2009) Is real-time polymerase chain reaction (PCR) more useful than a conventional PCR for the clinical management of leishmaniasis? Am J Trop Med Hyg 81:46–51PubMedGoogle Scholar
  49. 49.
    Bourgeois N, Bastien P, Reynes J, Makinson A, Rouanet I, Lachaud L (2010) ‘Active chronic visceral leishmaniasis’ in HIV-1-infected patients demonstrated by biological and clinical long-term follow-up of 10 patients. HIV Med 11:670–673PubMedCrossRefGoogle Scholar
  50. 50.
    Antinori S, Longhi E, Bestetti G, Piolini R, Acquaviva V, Foschi A, Trovati S, Parravicini C, Corbellino M, Meroni L (2007) Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired immune deficiency syndrome. Br J Dermatol 157:1032–1036PubMedCrossRefGoogle Scholar
  51. 51.
    Sinha S, Fernández G, Kapila R, Lambert WC, Schwartz RA (2008) Diffuse cutaneous leishmaniasis associated with the immune reconstitution inflammatory syndrome. Int J Dermatol 47:1263–1270PubMedCrossRefGoogle Scholar
  52. 52.
    Dettwiler S, McKee T, Hadaya K, Chappuis F, van Delden C, Moll S (2010) Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction. Am J Transpl 10:1486–1489CrossRefGoogle Scholar
  53. 53.
    Simon I, Wissing KM, Del Marmol V, Antinori S, Remmelink M, Nilufer Broeders E, Nortier JL, Corbellino M, Abramowicz D, Cascio A (2011) Recurrent leishmaniasis in kidney transplant recipients: report of 2 cases and systematic review of the literature. Transpl Infect Dis. doi:10.1111/j.1399-3062.2011.00598.x Google Scholar
  54. 54.
    Reithinger R, Dujardin JC, Louzir H, Pirmez C, Alexander B, Brooker S (2007) Cutaneous leishmaniasis. Lancet Infect Dis 7:581–596PubMedCrossRefGoogle Scholar
  55. 55.
    Akilov OE, Khachemoune A, Hasan T (2007) Clinical manifestations and classification of Old World cutaneous leishmaniasis. Int J Dermatol 46:132–142PubMedCrossRefGoogle Scholar
  56. 56.
    Maniscalco M, Noto G, Zichichi L, Veraldi S (2007) Multifocal cutaneous leishmaniasis: a new clinical presentation of the disease. Acta Derm Venereol 87:275–276PubMedGoogle Scholar
  57. 57.
    Lindoso JA, Barbosa RN, Posada-Vergara MP, Duarte MI, Oyafuso LK, Amato VS, Goto H (2009) Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World. Br J Dermatol 160:311–318PubMedCrossRefGoogle Scholar
  58. 58.
    Antinori S, Calattini S, Longhi E, Bestetti G, Piolini R, Magni C, Orlando G, Gramiccia M, Acquaviva V, Foschi A, Corvasce S, Colomba C, Titone L, Parravicini C, Cascio A, Corbellino M (2007) Clinical use of polymerase chain reaction performed on peripheral blood and bone marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV-infected and HIV-uninfected patients: a single-center, 8-year experience in Italy and review of the literature. Clin Infect Dis 44:1602–1610PubMedCrossRefGoogle Scholar
  59. 59.
    Bensoussan E, Nasereddin A, Jonas F, Schnur LF, Jaffe CL (2006) Comparison of PCR assays for diagnosis of cutaneous leishmaniasis. J Clin Microbiol 44:1435–1439PubMedCrossRefGoogle Scholar
  60. 60.
    Verma S, Kumar R, Katara GK, Singh LC, Negi NS, Ramesh V, Salotra P (2010) Quantification of parasite load in clinical samples of leishmaniasis patients: IL-10 level correlates with parasite load in visceral leishmaniasis. PLoS One 5:e10107PubMedCrossRefGoogle Scholar
  61. 61.
    Romero I, Téllez J, Suárez Y, Cardona M, Figueroa R, Zelazny A, Gore Saravia N (2010) Viability and burden of Leishmania in extralesional sites during human dermal leishmaniasis. PLoS Negl Trop Dis 4:e819CrossRefGoogle Scholar
  62. 62.
    Srivastava P, Dayama A, Mehrotra S, Sundar S (2011) Diagnosis of visceral leishmaniasis. Trans R Soc Trop Med Hyg 105:1–6PubMedCrossRefGoogle Scholar
  63. 63.
    Boelaert M, El-Safi S, Hailu A, Mukhtar M, Rijal S, Sundar S, Wasunna M, Aseffa A, Mbui J, Menten J, Desjeux P, Peeling RW (2008) Diagnostic tests for Kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent. Trans R Soc Trop Med Hyg 102:32–40PubMedCrossRefGoogle Scholar
  64. 64.
    Pattabhi S, Whittle J, Mohamath R, El-Safi S, Moulton GG, Guderian JA, Colombara D, Abdoon AO, Mukhtar MM, Mondal D, Esfandiari J, Kumar S, Chun P, Reed SG, Bhatia A (2010) Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. PLoS Negl Trop Dis 4:e822CrossRefGoogle Scholar
  65. 65.
    Sundar S, Chakravarty J, Agarwal D, Rai M, Murray HW (2010) Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med 362:504–512PubMedCrossRefGoogle Scholar
  66. 66.
    Sundar S, Agrawal G, Rai M, Makharia MK, Murray HW (2001) Treatment of Indian visceral leishmaniasis with single or daily infusions of low dose liposomal amphotericin B: randomised trial. BMJ 323:419–422PubMedCrossRefGoogle Scholar
  67. 67.
    Sundar S, Jha TK, Thakur CP, Mishra M, Singh VP, Buffels R (2003) Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: a multicenter study. Clin Infect Dis 37:800–804PubMedCrossRefGoogle Scholar
  68. 68.
    Syriopoulou V, Daikos GL, Theodoridou M, Pavlopoulou I, Manolaki AG, Sereti E, Karamboula A, Papathanasiou D, Krikos X, Saroglou G (2003) Two doses of a lipid formulation of amphotericin B for the treatment of Mediterranean visceral leishmaniasis. Clin Infect Dis 36:560–566PubMedCrossRefGoogle Scholar
  69. 69.
    Bhattacharya SK, Sinha PK, Sundar S, Thakur CP, Jha TK, Pandey K, Das VR, Kumar N, Lal C, Verma N, Singh VP, Ranjan A, Verma RB, Anders G, Sindermann H, Ganguly NK (2007) Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J Infect Dis 196:591–598PubMedCrossRefGoogle Scholar
  70. 70.
    Ritmeijer K, Dejenie A, Assefa Y, Hundie TB, Mesure J, Boots G, den Boer M, Davidson RN (2006) 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 43:357–364PubMedCrossRefGoogle Scholar
  71. 71.
    Sindermann H, Engel KR, Fischer C, Bommer W (2004) Oral miltefosine for leishmaniasis in immunocompromised patients: compassionate use in 39 patients with HIV infection. Clin Infect Dis 39:1520–1523PubMedCrossRefGoogle Scholar
  72. 72.
    Soto J, Arana BA, Toledo J, Rizzo N, Vega JC, Diaz A, Luz M, Gutierrez P, Arboleda M, Berman JD, Junge K, Engel J, Sindermann H (2004) Miltefosine for New World cutaneous leishmaniasis. Clin Infect Dis 38:1266–1272PubMedCrossRefGoogle Scholar
  73. 73.
    Mohebali M, Fotouhi A, Hooshmand B, Zarei Z, Akhoundi B, Rahnema A, Razaghian AR, Kabir MJ, Nadim A (2007) Comparison of miltefosine and meglumine antimoniate for the treatment of zoonotic cutaneous leishmaniasis (ZCL) by a randomized clinical trial in Iran. Acta Trop 103:33–40PubMedCrossRefGoogle Scholar
  74. 74.
    Soto J, Rea J, Balderrama M, Toledo J, Soto P, Valda L, Berman JD (2008) Efficacy of miltefosine for Bolivian cutaneous leishmaniasis. Am J Trop Med Hyg 78:210–211PubMedGoogle Scholar
  75. 75.
    Vélez I, López L, Sánchez X, Mestra L, Rojas C, Rodríguez E (2010) Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis. Am J Trop Med Hyg 83:351–356PubMedCrossRefGoogle Scholar
  76. 76.
    van Thiel PP, Leenstra T, Kager PA, de Vries HJ, van Vugt M, van der Meide WF, Bart A, Zeegelaar JE, van der Sluis A, Schallig HD, van Gool T, Faber WR, de Vries PJ (2010) Miltefosine treatment of Leishmania major infection: an observational study involving Dutch military personnel returning from northern Afghanistan. Clin Infect Dis 50:80–83PubMedCrossRefGoogle Scholar
  77. 77.
    Machado PR, Ampuero J, Guimarães LH, Villasboas L, Rocha AT, Schriefer A, Sousa RS, Talhari A, Penna G, Carvalho EM (2010) Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial. PLoS Negl Trop Dis 4:e912PubMedCrossRefGoogle Scholar
  78. 78.
    Chrusciak-Talhari A, Dietze R, Chrusciak Talhari C, da Silva RM, Gadelha Yamashita EP, de Oliveira Penna G, Lima Machado PR, Talhari S (2011) Randomized controlled clinical trial to assess efficacy and safety of miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis in Manaus, Brazil. Am J Trop Med Hyg 84:255–260PubMedCrossRefGoogle Scholar
  79. 79.
    Keynan Y, Larios OE, Wiseman MC, Plourde M, Ouellette M, Rubinstein E (2008) Use of oral miltefosine for cutaneous leishmaniasis in Canadian soldiers returning from Afghanistan. Can J Infect Dis Med Microbiol 19:394–396PubMedGoogle Scholar
  80. 80.
    González U, Pinart M, Reveiz L, Rengifo-Pardo M, Tweed J, Macaya A, Alvar J (2010) Designing and reporting clinical trials on treatments for cutaneous leishmaniasis. Clin Infect Dis 51:409–419PubMedCrossRefGoogle Scholar
  81. 81.
    Amato VS, Tuon FF, Siqueira AM, Nicodemo AC, Neto VA (2007) Treatment of mucosal leishmaniasis in Latin America: systematic review. Am J Trop Med Hyg 77:266–274PubMedGoogle Scholar
  82. 82.
    Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK (2007) Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med 356:2571–2581PubMedCrossRefGoogle Scholar
  83. 83.
    Hailu A, Musa A, Wasunna M, Balasegaram M, Yifru S, Mengistu G, Hurissa Z, Hailu W, Weldegebreal T, Tesfaye S, Makonnen E, Khalil E, Ahmed O, Fadlalla A, El-Hassan A, Raheem M, Mueller M, Koummuki Y, Rashid J, Mbui J, Mucee G, Njoroge S, Manduku V, Musibi A, Mutuma G, Kirui F, Lodenyo H, Mutea D, Kirigi G, Edwards T, Smith P, Muthami L, Royce C, Ellis S, Alobo M, Omollo R, Kesusu J, Owiti R, Kinuthia J; Leishmaniasis East Africa Platform (LEAP) group (2010) Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial. PLoS Negl Trop Dis 4:e709PubMedCrossRefGoogle Scholar
  84. 84.
    Chappuis F, Alirol E, Worku DT, Mueller Y, Ritmeijer K (2011) High mortality among older patients treated with pentavalent antimonials for visceral leishmaniasis in East Africa and rationale for switch to liposomal amphotericin B. Antimicrob Agents Chemother 55:455–456PubMedCrossRefGoogle Scholar
  85. 85.
    Musa AM, Younis B, Fadlalla A, Royce C, Balasegaram M, Wasunna M, Hailu A, Edwards T, Omollo R, Mudawi M, Kokwaro G, El-Hassan A, Khalil E (2010) Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. PLoS Negl Trop Dis 4:e855PubMedCrossRefGoogle Scholar
  86. 86.
    Kim DH, Chung HJ, Bleys J, Ghohestani RF (2009) Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials. PLoS Negl Trop Dis 3:e381PubMedCrossRefGoogle Scholar
  87. 87.
    Olliaro PL (2010) Drug combinations for visceral leishmaniasis. Curr Opin Infect Dis 29:595–602CrossRefGoogle Scholar
  88. 88.
    van Griensven J, Balasegaram M, Meheus F, Alvar J, Lynen L, Boelaert M (2010) Combination therapy for visceral leishmaniasis. Lancet Infect Dis 10:184–194PubMedCrossRefGoogle Scholar
  89. 89.
    Meheus F, Balasegaram M, Olliaro P, Sundar S, Rijal S, Faiz MA, Boelaert M (2010) Cost-effectiveness analysis of combination therapies for visceral leishmaniasis in the Indian subcontinent. PLoS Negl Trop Dis 4:e818CrossRefGoogle Scholar
  90. 90.
    Sundar S, Sinha PK, Rai M, Verma DK, Nawin K, Alam S, Chakravarty J, Vaillant M, Verma N, Pandey K, Kumari P, Lal CS, Arora R, Sharma B, Ellis S, Strub-Wourgaft N, Balasegaram M, Olliaro P, Das P, Modabber F (2011) Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial. Lancet 377:477–486PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Clinical Sciences L. Sacco, Section of Infectious Diseases and ImmunopathologyUniversità degli Studi di MilanoMilanoItaly

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