Abstract
Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. It is transmitted by phlebotomine female sand flies of the genera Phlebotomus and Lutzomyia in the old and new world, respectively. More than 20 well-recognized Leishmania species are known to infect humans and cause visceral (VL), cutaneous (CL) and mucocutaneous (ML) forms of the disease. Approximately 350 million people are at risk of contracting the disease and an estimated 1.6 million new cases occur annually. The disease mainly affects poor people in Africa, Asia and Latin America, and is associated with malnutrition, population migration, poor residency conditions, frail immune system and lack of resources. Previously, diagnosis of leishmaniasis relied mainly on invasive techniques of detecting parasites in splenic and bone marrow aspirates. Nevertheless, serological tests using the recombinant kinesin antigen (rK39) and molecular methods (polymerase chain reaction) are considered the best options for diagnosis today, despite problems related to varying sensitivities and specificities and field adaptability. Therapy of leishmaniasis ranges from local treatment of cutaneous lesions to systemic often toxic, therapy for disseminated CL, ML and VL. Agents with efficacy against leishmaniasis include amphotericin B, pentavalent antimonial drugs, paromomycin and miltefosine. No single therapy of VL currently offers satisfactory efficacy along with safety. This article provides a brief and updated systematic review on the epidemiology, diagnosis and treatment of this neglected disease.
References
1. Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012;7:e35671. 10.1371/journal.pone.0035671Search in Google Scholar
2. Mathers CD, Ezzati M, Lopez AD. Measuring the burden of neglected tropical diseases: The global burden of disease framework. PLoS Negl Trop Dis 2007;1:e114. 10.1371/journal.pntd.0000114Search in Google Scholar
3. Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol 2006;22:552-7. 10.1016/j.pt.2006.09.004Search in Google Scholar
4. Murray HW, Berman JD, Davies CR, Saravia NG. Advances in leishmaniasis. Lancet 2005;366:1561-77. 10.1016/S0140-6736(05)67629-5Search in Google Scholar
5. Nateghi Rostami M, Saghafipour A, Vesali E. A newly emerged cutaneous leishmaniasis focus in central Iran. Int J Infect Dis. 2013;17:e1198-206. 10.1016/j.ijid.2013.07.003Search in Google Scholar
6. Sutherst RW. Global change and human vulnerability to vector-borne diseases. Clin Microbiol Rev 2004;17:136-73. 10.1128/CMR.17.1.136-173.2004Search in Google Scholar
7. Quinnell RJ, Courtenay O. Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis. Parasitology 2009;136:1915-34. 10.1017/S0031182009991156Search in Google Scholar
8. Dey A, Singh S. Transfusion transmitted leishmaniasis: A case report and review of literature. Indian J Med Microbiol 2006;24:165-70. 10.1016/S0255-0857(21)02344-6Search in Google Scholar
9. Antinori S, Cascio A, Parravicini C, Bianchi R, Corbellino M. Leishmaniasis among organ transplant recipients. Lancet Infect Dis 2008;8:191-9. 10.1016/S1473-3099(08)70043-4Search in Google Scholar
10. Meinecke CK, Schottelius J, Oskam L, Fleischer B. Congenital transmission of visceral leishmaniasis (Kala Azar) from an asymptomatic mother to her child. Pediatrics 1999;104:e65. 10.1542/peds.104.5.e65Search in Google Scholar PubMed
11. Bern C, Maguire JH, Alvar J. Complexities of assessing the disease burden attributable to leishmaniasis. PLoS Negl Trop Dis 2008;2:e313. 10.1371/journal.pntd.0000313Search in Google Scholar
12. Bern C, Amann J, Haque R, Chowdhury R, Ali M, Kurkjian KM, et al. Loss of leishmanin skin test antigen sensitivity and potency in a longitudinal study of visceral leishmaniasis in Bangladesh. Am J Trop Med Hyg 2006;75:744-8. 10.4269/ajtmh.2006.75.744Search in Google Scholar
13. Elnaiem DA, Hassan HK, Ward RD. Phlebotomine sandflies in a focus of visceral leishmaniasis in a border area of eastern Sudan. Ann Trop Med Parasitol 1997;91:307-18. 10.1080/00034983.1997.11813143Search in Google Scholar
14. Bucheton B, Kheir MM, El-Safi SH, Hammad A, Mergani A, Mary C, et al. The interplay between environmental and host factors during an outbreak of visceral leishmaniasis in eastern Sudan. Microbes Infect 2002;4:1449-57. 10.1016/S1286-4579(02)00027-8Search in Google Scholar
15. Alvar J, Bashaye S, Argaw D, Cruz I, Aparicio P, Kassa A, et al. Kala-azar outbreak in Libo Kemkem, Ethiopia: Epidemiologic and parasitologic assessment. Am J Trop Med Hyg 2007;77:275-82. 10.4269/ajtmh.2007.77.275Search in Google Scholar
16. Seaman J, Mercer AJ, Sondorp E. The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: Course and impact from 1984 to 1994. Int J Epidemiol 1996;25:862-71. 10.1093/ije/25.4.862Search in Google Scholar PubMed
17. Elnaiem DA, Hassan MM, Maingon R, Nureldin GH, Mekawi AM, Miles M, et al. The Egyptian mongoose, Herpestes ichneumon, is a possible reservoir host of visceral leishmaniasis in eastern Sudan. Parasitology 2001;122:531-6. 10.1017/S0031182001007594Search in Google Scholar PubMed
18. Dereure J, El-Safi SH, Bucheton B, Boni M, Kheir MM, Davoust B, et al. Visceral leishmaniasis in eastern Sudan: Parasite identification in humans and dogs; host-parasite relationships. Microbes Infect 2003;5:1103-8. 10.1016/j.micinf.2003.07.003Search in Google Scholar PubMed
19. Ready PD. Leishmaniasis emergence in Europe. Euro Surveill 2010;15:19505. 10.2807/ese.15.10.19505-enSearch in Google Scholar
20. Kafetzis DA, Maltezou HC. Visceral leishmaniasis in paediatrics. Curr Opin Infect Dis 2002;15:289-94. 10.1097/00001432-200206000-00012Search in Google Scholar PubMed
21. van Griensven J, Carrillo E, López-Vélez R, Lynen L, Moreno J. Leishmaniasis in immunosuppressed individuals. Clin Microbiol Infect 2014;20:286-99. 10.1111/1469-0691.12556Search in Google Scholar PubMed
22. Chitimia L, Muñoz-García CI, Sánchez-Velasco D, Lizana V, Del Río L, Murcia L, et al. Cryptic Leishmaniosis by Leishmania infantum, a feature of canines only? A study of natural infection in wild rabbits, humans and dogs in southeastern Spain. Vet Parasitol 2011;181:12-6. 10.1016/j.vetpar.2011.04.016Search in Google Scholar PubMed
23. Michel G, Pomares C, Ferrua B, Marty P. Importance of worldwide asymptomatic carriers of Leishmania infantum (L. chagasi) in human. Acta Trop 2011;119:69-75. 10.1016/j.actatropica.2011.05.012Search in Google Scholar PubMed
24. Singh OP, Hasker E, Sacks D, Boelaert M, Sundar S. Asymptomatic Leishmania infection: A new challenge for Leishmania control. Clin Infect Dis 2014;58:1424-9. 10.1093/cid/ciu102Search in Google Scholar PubMed PubMed Central
25. Jarvis JN, Lockwood DN. Clinical aspects of visceral leishmaniasis in HIV infection. Curr Opin Infect Dis 2013;26:1-9. 10.1097/QCO.0b013e32835c2198Search in Google Scholar PubMed
26. Alvar J, Aparicio P, Aseffa A, Den Boer M, Cañavate C, Dedet JP, et al. The relationship between leishmaniasis and AIDS: The second 10 years. Clin Microbiol Rev 2008;21:334-59. 10.1128/CMR.00061-07Search in Google Scholar PubMed PubMed Central
27. Clemente WT, Faria LC, Romanelli RM, Lima SS, Cortes JR, Oliveira AP, et al. Visceral leishmaniasis in liver transplant recipients from an endemic area. Transplantation 2011;91:806-8. 10.1097/TP.0b013e31820c4574Search in Google Scholar PubMed
28. Bouchekoua M, Trabelsi S, Ben Abdallah T, Khaled S. Visceral leishmaniasis after kidney transplantation: Report of a new case and a review of the literature. Transplant Rev (Orlando) 2014;28:32-5. 10.1016/j.trre.2013.10.007Search in Google Scholar PubMed
29. Xynos ID, Tektonidou MG, Pikazis D, Sipsas NV. Leishmaniasis, autoimmune rheumatic disease, and anti-tumor necrosis factor therapy, Europe. Emerg Infect Dis 2009;15:956-9. 10.3201/eid1506.090101Search in Google Scholar PubMed PubMed Central
30. Guedes-Barbosa LS, Pereira da Costa I, Fernandes V, Henrique da Mota LM, de Menezes I, Aaron Scheinberg M. Leishmaniasis during anti-tumor necrosis factor therapy: Report of 4 cases and review of the literature (additional 28 cases). Semin Arthritis Rheum 2013;43:152-7. 10.1016/j.semarthrit.2013.01.006Search in Google Scholar PubMed
31. Erre GL, Mesina P, Tonelli N, Passiu G. Visceral Leishmaniasis among immunosuppressed patients with rheumatic diseases. Clin Exp Rheumatol 2010;28:590-1. Search in Google Scholar
32. Bogdan C. Leishmaniasis in rheumatology, haematology and oncology: Epidemiological, immunological and clinical aspects and caveats. Ann Rheum Dis 2012;71 Suppl 2:i60-6. 10.1136/annrheumdis-2011-200596Search in Google Scholar
33. Singh SP, Picado A, Boelaert M, Gidwani K, Andersen EW, Ostyn B, et al. The epidemiology of Leishmania donovani infection in high transmission foci in India. Trop Med Int Health 2010;15:12-20. 10.1111/j.1365-3156.2010.02519.xSearch in Google Scholar
34. Srivastava P, Dayama A, Mehrotra S, Sundar S. Diagnosis of visceral leishmaniasis. Trans R Soc Trop Med Hyg 2011;105:1-6. 10.1016/j.trstmh.2010.09.006Search in Google Scholar
35. Zijlstra EE, Ali MS, el-Hassan AM, el-Toum IA, Satti M, Ghalib HW, et al. Kala-azar: A comparative study of parasitological methods and the direct agglutination test in diagnosis. Trans R Soc Trop Med Hyg 1992;86:505-7. 10.1016/0035-9203(92)90086-RSearch in Google Scholar
36. Sundar S, Rai M. Laboratory diagnosis of visceral leishmaniasis. Clin Diagn Lab Immunol 2002;9:951-8. 10.1128/CDLI.9.5.951-958.2002Search in Google Scholar
37. Thakur CP. A comparison of intercostal and abdominal routes of splenic aspiration and bone marrow aspiration in the diagnosis of visceral leishmaniasis. Trans R Soc Trop Med Hyg 1997;91:668-70. 10.1016/S0035-9203(97)90516-2Search in Google Scholar
38. Sarker CB, Alam KS, Jamal MF, Rahman S, Huq MH, Musa AK, et al. Sensitivity of splenic and bone marrow aspirate study for diagnosis of kala-azar. Mymensingh Med J 2004;13:130-3. Search in Google Scholar
39. Siddig M, Ghalib H, Shillington DC, Petersen EA. Visceral leishmaniasis in the Sudan: Comparative parasitological methods of diagnosis. Trans R Soc Trop Med Hyg 1988;82:66-8. 10.1016/0035-9203(88)90265-9Search in Google Scholar
40. Lightner LK, Chulay JD, Bryceson AD. Comparison of microscopy and culture in the detection of Leishmania donovani from splenic aspirates. Am J Trop Med Hyg 1983;32:296-9. 10.4269/ajtmh.1983.32.296Search in Google Scholar PubMed
41. Artan R, Yilmaz A, Akçam M, Aksoy NH. Liver biopsy in the diagnosis of visceral leishmaniasis. J Gastroenterol Hepatol 2006;21:299-302. 10.1111/j.1440-1746.2006.04172.xSearch in Google Scholar PubMed
42. Babiker ZO, Davidson R, Mazinda C, Kipngetich S, Ritmeijer K. Utility of lymph node aspiration in the diagnosis of visceral leishmaniasis in Sudan. Am J Trop Med Hyg 2007;76:689-93. 10.4269/ajtmh.2007.76.689Search in Google Scholar
43. Gatti S, Gramegna M, Klersy C, Madama S, Bruno A, Maserati R, et al. Diagnosis of visceral leishmaniasis: The sensitivities and specificities of traditional methods and a nested PCR assay. Ann Trop Med Parasitol 2004;98:667-76. 10.1179/000349804225011488Search in Google Scholar PubMed
44. Brustoloni YM, Cunha RV, Dorval ME, Oshiro ET, Pontes ER, Oliveira AL, et al. Comparison of conventional methods for diagnosis of visceral leishmaniasis in children of the Center-West Region of Brazil. Braz J Infect Dis 2007;11:106-9. 10.1590/S1413-86702007000100023Search in Google Scholar PubMed
45. Liberopoulos E, Kei A, Apostolou F, Elisaf M. Autoimmune manifestations in patients with visceral leishmaniasis. J Microbiol Immunol Infect 2013;46:302-5. 10.1016/j.jmii.2012.01.016Search in Google Scholar PubMed
46. Makaritsis KP, Gatselis NK, Ioannou M, Petinaki E, Dalekos GN. Polyclonal hypergammaglobulinemia and high smooth-muscle autoantibody titers with specificity against filamentous actin: Consider visceral leishmaniasis, not just autoimmune hepatitis. Int J Infect Dis 2009;13:e157-60. 10.1016/j.ijid.2008.08.011Search in Google Scholar PubMed
47. Saitis A, Gatselis NK, Dalekos GN. Leishmaniasis-associated haemophagocytic syndrome revisited: Not an uncommon clinical presentation of leishmaniasis. J Med Cases 2012;3:315-8. Search in Google Scholar
48. Voulgari PV, Pappas GA, Liberopoulos EN, Elisaf M, Skopouli FN, Drosos AA. Visceral leishmaniasis resembling systemic lupus erythematosus. Ann Rheum Dis 2004;63:1348-9. 10.1136/ard.2003.014480Search in Google Scholar PubMed PubMed Central
49. Galvão-Castro B, Sá Ferreira JA, Marzochi KF, Marzochi MC, Coutinho SG, Lambert PH. Polyclonal B cell activation, circulating immune complexes and autoimmunity in human american visceral leishmaniasis. Clin Exp Immunol 1984;56:58-66. Search in Google Scholar
50. Cota GF, de Sousa MR, de Freitas Nogueira BM, Gomes LI, Oliveira E, et al. Comparison of parasitological, serological, and molecular tests for visceral leishmaniasis in HIV-infected patients: A cross-sectional delayed-type study. Am J Trop Med Hyg 2013;89:570-7. 10.4269/ajtmh.13-0239Search in Google Scholar PubMed PubMed Central
51. Reed SG, Shreffler WG, Burns JM Jr, Scott JM, Orge Mda G, Ghalib HW, et al. An improved serodiagnostic procedure for visceral leishmaniasis. Am J Trop Med Hyg 1990;43:632-9. 10.4269/ajtmh.1990.43.632Search in Google Scholar PubMed
52. Cañavate C, Herrero M, Nieto J, Cruz I, Chicharro C, Aparicio P, et al. Evaluation of two rK39 dipstick tests, direct agglutination test, and indirect fluorescent antibody test for diagnosis of visceral leishmaniasis in a new epidemic site in highland Ethiopia. Am J Trop Med Hyg 2011;84:102-6. 10.4269/ajtmh.2011.10-0229Search in Google Scholar PubMed PubMed Central
53. de Assis TS, Braga AS, Pedras MJ, Oliveira E, Barral A, de Siqueira IC, et al. Multi-centric prospective evaluation of rk39 rapid test and direct agglutination test for the diagnosis of visceral leishmaniasis in Brazil. Trans R Soc Trop Med Hyg 2011;105:81-5. 10.1016/j.trstmh.2010.09.004Search in Google Scholar PubMed
54. Bern C, Haque R, Chowdhury R, Ali M, Kurkjian KM, Vaz L, et al. The epidemiology of visceral leishmaniasis and asymptomatic leishmanial infection in a highly endemic Bangladeshi village. Am J Trop Med Hyg 2007;76:909-14. 10.4269/ajtmh.2007.76.909Search in Google Scholar
55. Maia Z, Lírio M, Mistro S, Mendes CM, Mehta SR, Badaro R. Comparative study of rK39 Leishmania antigen for serodiagnosis of visceral leishmaniasis: Systematic review with meta-analysis. PLoS Negl Trop Dis 2012;6:e1484. 10.1371/journal.pntd.0001484Search in Google Scholar PubMed PubMed Central
56. Kumar R, Pai K, Pathak K, Sundar S. Enzyme-linked immunosorbent assay for recombinant K39 antigen in diagnosis and prognosis of Indian visceral leishmaniasis. Clin Diagn Lab Immunol 2001;8:1220-4. 10.1128/CDLI.8.6.1220-1224.2001Search in Google Scholar PubMed PubMed Central
57. Houghton RL, Petrescu M, Benson DR, Skeiky YA, Scalone A, Badaró R, et al. A cloned antigen (recombinant K39) of Leishmania chagasi diagnostic for visceral leishmaniasis in human immunodeficiency virus type 1 patients and a prognostic indicator for monitoring patients undergoing drug therapy. J Infect Dis 1998;177:1339-44. 10.1086/515289Search in Google Scholar PubMed
58. Sundar S, Maurya R, Singh RK, Bharti K, Chakravarty J, Parekh A, et al. Rapid, noninvasive diagnosis of visceral leishmaniasis in India: Comparison of two immunochromatographic strip tests for detection of anti-K39 antibody. J Clin Microbiol 2006;44:251-3. 10.1128/JCM.44.1.251-253.2006Search in Google Scholar PubMed PubMed Central
59. Sundar S, Singh RK, Bimal SK, Gidwani K, Mishra A, Maurya R, et al. Comparative evaluation of parasitology and serological tests in the diagnosis of visceral leishmaniasis in India: A phase III diagnostic accuracy study. Trop Med Int Health 2007;12:284-9. Search in Google Scholar
60. Boelaert M, El-Safi S, Hailu A, Mukhtar M, Rijal S, Sundar S, et al. 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 2008;102:32-40. 10.1016/j.trstmh.2007.09.003Search in Google Scholar PubMed
61. Sundar S, Agrawal S, Pai K, Chance M, Hommel M. Detection of leishmanial antigen in the urine of patients with visceral leishmaniasis by a latex agglutination test. Am J Trop Med Hyg 2005;73:269-71. 10.4269/ajtmh.2005.73.269Search in Google Scholar
62. Ruiter CM, Veer CV, Leeflang MM, Deborggraeve S, Lucas C, Adams ER. Major article: Molecular tools for diagnosis of visceral leishmaniasis: Systematic review and meta-analysis of diagnostic test accuracy. J Clin Microbiol 2014;52:3147-55. 10.1128/JCM.00372-14Search in Google Scholar PubMed PubMed Central
63. Antinori S, Calattini S, Longhi E, Bestetti G, Piolini R, Magni C, et al. 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 2007;44:1602-10. 10.1086/518167Search in Google Scholar PubMed
64. Salam MA, Mondal D, Kabir M, Ekram AR, Haque R. PCR for diagnosis and assessment of cure in kala-azar patients in Bangladesh. Acta Trop 2010;113:52-5. 10.1016/j.actatropica.2009.09.005Search in Google Scholar PubMed
65. Pourabbas B, Ghadimi Moghadam A, Pouladfar G, Rezaee Z, Alborzi A. Quantification of Leishmania infantum kinetoplast DNA for monitoring the response to meglumine antimoniate therapy in visceral leishmaniasis. Am J Trop Med Hyg 2013;88:868-71. 10.4269/ajtmh.12-0440Search in Google Scholar PubMed PubMed Central
66. Cruz I, Chicharro C, Nieto J, Bailo B, Cañavate C, Figueras MC, et al. Comparison of new diagnostic tools for management of pediatric Mediterranean visceral leishmaniasis. J Clin Microbiol 2006;44:2343-7. 10.1128/JCM.02297-05Search in Google Scholar
67. Deborggraeve S, Boelaert M, Rijal S, De Doncker S, Dujardin JC, Herdewijn P, et al. Diagnostic accuracy of a new Leishmania PCR for clinical visceral leishmaniasis in Nepal and its role in diagnosis of disease. Trop Med Int Health 2008;13:1378-83. 10.1111/j.1365-3156.2008.02154.xSearch in Google Scholar
68. Bern C, Adler-Moore J, Berenguer J, Boelaert M, den Boer M, Davidson RN, et al. Liposomal amphotericin B for the treatment of visceral leishmaniasis. Clin Infect Dis 2006;43:917-24. 10.1086/507530Search in Google Scholar
69. Sundar S, Mehta H, Suresh AV, Singh SP, Rai M, Murray HW. Amphotericin B treatment for Indian visceral leishmaniasis: Conventional versus lipid formulations. Clin Infect Dis 2004;38:377-83. 10.1086/380971Search in Google Scholar
70. Meyerhoff A. U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clin Infect Dis 1999;28:42-8. 10.1086/515085Search in Google Scholar
71. Lachaud L, Bourgeois N, Plourde M, Leprohon P, Bastien P, Ouellette M. Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum. Clin Infect Dis 2009;48:16-22. 10.1086/595710Search in Google Scholar
72. Jarvis JN, Lockwood DN. Clinical aspects of visceral leishmaniasis in HIV infection. Curr Opin Infect Dis 2013;26:1-9. 10.1097/QCO.0b013e32835c2198Search in Google Scholar
73. Molina I, Falcó V, Crespo M, Riera C, Ribera E, Curran A, et al. Efficacy of liposomal amphotericin B for secondary prophylaxis of visceral leishmaniasis in HIV-infected patients. J Antimicrob Chemother 2007;60:837-42. 10.1093/jac/dkm294Search in Google Scholar
74. Yardley V, Croft SL. A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis. Int J Antimicrob Agents 2000;13:243-8. 10.1016/S0924-8579(99)00133-8Search in Google Scholar
75. Hamill RJ. Amphotericin B formulations: A comparative review of efficacy and toxicity. Drugs 2013;73:919-34. 10.1007/s40265-013-0069-4Search in Google Scholar PubMed
76. Moyssakis I, Vassilakopoulos TP, Sipsas NV, Perakis A, Petrou A, Kosmas N, et al. Reversible dilated cardiomyopathy associated with amphotericin B treatment. Int J Antimicrob Agents 2005;25:444-7. 10.1016/j.ijantimicag.2005.02.015Search in Google Scholar
77. Georgiadou SP, Kontoyiannis DP, Sipsas NV. Subclinical tumor lysis-like syndrome during treatment of visceral leishmaniasis with low-dose intermittent liposomal amphotericin B. Central Eur J Med 2012;7:305-9. 10.2478/s11536-011-0147-5Search in Google Scholar
78. den Boer M, Davidson RN. Treatment options for visceral leishmaniasis. Expert Rev Anti Infect Ther 2006;4:187-97. 10.1586/14787210.4.2.187Search in Google Scholar
79. Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, et al. Failure of pentavalent antimony in visceral leishmaniasis in India: Report from the center of the Indian epidemic. Clin Infect Dis 2000;31:1104-7. 10.1086/318121Search in Google Scholar
80. Rijal S, Chappuis F, Singh R, Bovier PA, Acharya P, Karki BM, et al. Treatment of visceral leishmaniasis in south-eastern Nepal: Decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline. Trans R Soc Trop Med Hyg 2003;97:350-4. 10.1016/S0035-9203(03)90167-2Search in Google Scholar
81. Sundar S. Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 2001;6:849-54. 10.1046/j.1365-3156.2001.00778.xSearch in Google Scholar PubMed
82. Herwaldt BL, Berman JD. Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies. Am J Trop Med Hyg 1992;46:296-306. 10.4269/ajtmh.1992.46.296Search in Google Scholar PubMed
83. Bhattacharya SK, Sinha PK, Sundar S, Thakur CP, Jha TK, Pandey K, et al. Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J Infect Dis 2007;196:591-8. 10.1086/519690Search in Google Scholar PubMed
84. Sundar S, Olliaro PL. Miltefosine in the treatment of leishmaniasis. Clinical evidence for informed clinical risk management. Ther Clin Risk Manag 2007;3:733-40. Search in Google Scholar
85. Seifert K, Pérez-Victoria FJ, Stettler M, Sánchez-Cañete MP, Castanys S, Gamarro F, et al. Inactivation of the miltefosine transporter, LdMT, causes miltefosine resistance that is conferred to the amastigote stage of Leishmania donovani and persists in vivo. Int J Antimicrob Agents 2007;30:229-35. 10.1016/j.ijantimicag.2007.05.007Search in Google Scholar PubMed
86. Pérez-Victoria FJ, Sánchez-Cañete MP, Seifert K, Croft SL, Sundar S, Castanys S, et al. Mechanisms of experimental resistance of Leishmania to miltefosine: Implications for clinical use. Drug Resist Updat 2006;9:26-39. 10.1016/j.drup.2006.04.001Search in Google Scholar PubMed
87. Sundar S, Singh A, Rai M, Prajapati VK, Singh AK, Ostyn B, et al. Efficacy of miltefosine in the treatment of visceral leishmaniasis in India after a decade of use. Clin Infect Dis 2012;55:543-50. 10.1093/cid/cis474Search in Google Scholar
88. Pandey BD, Pandey K, Kaneko O, Yanagi T, Hirayama K. Relapse of visceral leishmaniasis after miltefosine treatment in a Nepalese patient. Am J Trop Med Hyg 2009;80:580-2. 10.4269/ajtmh.2009.80.580Search in Google Scholar
89. Rijal S, Ostyn B, Uranw S, Rai K, Bhattarai NR, Dorlo TP, 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. 10.1093/cid/cit102Search in Google Scholar
90. Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. N Engl J Med 2007;356:2571-81. 10.1056/NEJMoa066536Search in Google Scholar
91. Musa AM, Younis B, Fadlalla A, Royce C, Balasegaram M, Wasunna M, et al. Paromomycin for the treatment of visceral leishmaniasis in Sudan: A randomized, open-label, dose-finding study. PLoS Negl Trop Dis 2010 26;4:e855. 10.1371/journal.pntd.0000855Search in Google Scholar
92. Monge-Maillo B, López-Vélez R. Topical paromomycin and gentamicin for new world cutaneous leishmaniasis in Panama. Am J Trop Med Hyg 2014;90:1191. 10.4269/ajtmh.14-0040aSearch in Google Scholar
93. Sundar S, Rai M, Chakravarty J, Agarwal D, Agrawal N, Vaillant M, et al. New treatment approach in Indian visceral leishmaniasis: Single-dose liposomal amphotericin B followed by short-course oral miltefosine. Clin Infect Dis 2008;47:1000-6. 10.1086/591972Search in Google Scholar
94. Melaku Y, Collin SM, Keus K, Gatluak F, Ritmeijer K, Davidson RN. Treatment of kala-azar in southern Sudan using a 17-day regimen of sodium stibogluconate combined with paromomycin: A retrospective comparison with 30-day sodium stibogluconate monotherapy. Am J Trop Med Hyg 2007;77:89-94. 10.4269/ajtmh.2007.77.89Search in Google Scholar
95. Sundar S, Sinha PK, Rai M, Verma DK, Nawin K, Alam S, et al. Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: An open-label, non-inferiority, randomised controlled trial. Lancet 2011; 377:477-86. 10.1016/S0140-6736(10)62050-8Search in Google Scholar
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