• 1

    Gangneux JP, 1999. Treatment of visceral leishmaniasis: recent modalities. Presse Med 28 :2057–2066.

  • 2

    Bora D, 1999. Epidemiology of visceral leishmaniasis in India. Nat Med J India 12 :62–68.

  • 3

    Sundar S, Singh VP, Sharma S, Makharia MK, Murray HW, 1997. Response to interferon-γ plus pentavalent antimony in Indian visceral leishmaniasis. J Infect Dis 176 :1117–1119.

    • Search Google Scholar
    • Export Citation
  • 4

    Thakur CP, Sinha GP, Pandey AK, Kumar N, Kumar P, Hasan SM, Narain S, Roy RK, 1998. Do the diminishing efficacy and increasing toxicity of sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar, India, justify its continued use as a first-line drug? Ann Trop Med Parasitol 92 :561–569.

    • Search Google Scholar
    • Export Citation
  • 5

    Jha SN, Singh NKP, Jha TK, 1991. Changing response to diamidine compounds in cases of kala-azar unresponsive to antimonial. J Assoc Physicians India 39 :314–316.

    • Search Google Scholar
    • Export Citation
  • 6

    Jha TK, Giri YN, Singh TK, Jha S, 1995. Use of amphotericin B in drug-resistant cases of visceral leishmaniasis in north Bihar. Am J Trop Med Hyg 52 :536–538.

    • Search Google Scholar
    • Export Citation
  • 7

    Sundar S, Jha TK, Thakur CP, Mishra M, Singh VR, Buffels R, 2002. Low-dose liposomal amphotericin B in refractory Indian visceral leishmaniasis: a multicenter study. Am J Trop Med Hyg 66 :143–146.

    • Search Google Scholar
    • Export Citation
  • 8

    Sundar S, Gupta LB, Makharia MK, Singh MK, Voss A, Rosenkaimer F, Engel J, Murray HW, 1999. Oral treatment of visceral leishmaniasis with miltefosine. Ann Trop Med Parasitol 93 :589–597.

    • Search Google Scholar
    • Export Citation
  • 9

    Jha TK, Sundar S, Thakur CP, Bachmann P, Karbwang J, Fisher C, Voss A, Berman J, 1999. Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis. N Engl J Med 341 :1795–1800.

    • Search Google Scholar
    • Export Citation
  • 10

    Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, Junge K, Bryceson A, Berman J, 2002. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 347 :1739–1746.

    • Search Google Scholar
    • Export Citation
  • 11

    Sundar S, Jha TK, Sindermann H, Junge K, Bachmann P, Berman J, 2003. Oral miltefosine treatment in children with mild to moderate Indian visceral leishmaniasis. Ped Infect Dis 22 :434–438.

    • Search Google Scholar
    • Export Citation
  • 12

    Bhattacharya SK, Jha TK, Sundar S, Thakur CP, Engel J, Sindermann H, Junge K, Karbwang J, Bryceson AD, Berman JD, 2004. Efficacy and tolerability of miltefosine for childhood visceral leishmaniasis in India. Clin Infect Dis 38 :217–221.

    • Search Google Scholar
    • Export Citation
  • 13

    More B, Bhatt H, Kukreja V, Ainapure S, 2003. Miltefosine: great expectations against visceral leishmaniasis. J Postgrad Med 49 :101–103.

    • Search Google Scholar
    • Export Citation
  • 14

    Bryceson A, 2001. A policy for leishmaniasis with respect to the prevention and control of drug resistance. Trop Med Int Health 6 :928–993.

    • Search Google Scholar
    • Export Citation
  • 15

    Prasad R, Kumar R, Jaiswal BP, Singh UK, 2004. Miltefosine: an oral drug for visceral leishmaniasis. Indian J Pediatr 71 :143–144.

  • 16

    Thakur CP, Sinha PK, Singh KR, Hassan SM, Narain S, 2000. Miltefosine in a case of visceral leishmaniasis: and rising incidence of this disease in India. Trans Royal Soc Trop Med Hyg 94 :696–697.

    • Search Google Scholar
    • Export Citation
  • 17

    Kinnamon KE, Steck EA, Loizeau PS, Hanson WL, Chapman WL Jr, Waits VB, 1978. The antileishmanial activity of lepidines. Am J Trop Med Hyg 27 :751–757.

    • Search Google Scholar
    • Export Citation
  • 18

    Chapman WL Jr, Hanson WL, Waits VB, Kinnamon KE, 1979. Antileishmanial activity of selected compounds in dogs experimentally infected with Leishmania donovani. Rev Inst Med Trop Sao Paulo 21 :189–193.

    • Search Google Scholar
    • Export Citation
  • 19

    White MR, Chapman WL Jr, Hanson WL, 1989. Chemotherapy with experimental visceral leishmaniasis in the opossum. J Parasitol 75 :176–178.

    • Search Google Scholar
    • Export Citation
  • 20

    Dietze R, Carvalho SF, Valli LC, Berman J, Brewer T, Milhous W, Sanchez J, Schuster B, Grogl M, 2001. Phase 2 trial of WR6026, an orally administered 8-aminoquinoline, in the treatment of visceral leishmaniasis caused by Leishmania chagasi. Am J Trop Med Hyg 65 :685–689.

    • Search Google Scholar
    • Export Citation
  • 21

    Sherwood JA, Gachihi GS, Muigai RK, Skillman DR, Mugo M, Rashid JR, Wasunna KM, Were JB, Kasili SK, Mbugua JM, Kirigi G, Shaefer KU, Oster CN, Fleckenstein LL, Berman JD, Brewer TG, Roberts CR, Johnson AJ, Schuster BG, 1994. Phase 2 efficacy trial of an oral 8-aminoquinoline (WR6026) for treatment of visceral leishmaniasis. Clin Infect Dis 19 :1034–1039.

    • Search Google Scholar
    • Export Citation
  • 22

    Wasunna MK, Rashid JR, Mbui J, Kirigi G, Kinoti D, Lodenyo H, Felton JM, Sabin AJ, Horton J, 2005. A phase II dose-increasing study of sitamaquine for the treatment of visceral leishmaniasis in Kenya. Am J Trop Med Hyg 73: 871–876.

    • Search Google Scholar
    • Export Citation
  • 23

    Chulay JD, Bryceson AD, 1983. Quantitation of amastigotes of Leishmania donovani in smears of splenic aspirates from patients with visceral leishmaniasis. Am J Trop Med Hyg 32 :475–479.

    • Search Google Scholar
    • Export Citation
  • 24

    National Cancer Institute, 2003. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Cancer Therapy Evaluation Program. Available at: http://ctep.cancer.gov/reporting/ctc.html.

  • 25

    Caravaca F, Munoz A, Pizarro JL, Saez de Santamaria J, Fernandez-Alonso J, 1991. Acute renal failure in visceral leishmaniasis. Am J Nephrol 11 :350–352.

    • Search Google Scholar
    • Export Citation
  • 26

    De Brito T, Hoshino-Shimizu S, Neto VA, Duarte IS, Penna DO, 1975. Glomerular involvement in human kala-azar. A light, immunofluorescent, and electron microscopic study based on kidney biopsies. Am J Trop Med Hyg 24 :9–18.

    • Search Google Scholar
    • Export Citation
  • 27

    Dutra M, Martinelli R, de Carvalho EM, Rodrigues LE, Brito E, Rocha H, 1985. Renal involvement in visceral leishmaniasis. Am J Kidney Dis 6 :22–27.

    • Search Google Scholar
    • Export Citation
  • 28

    Weisinger JR, Pinto A, Velazquez GA, Bronstein I, Dessene JJ, Duque JF, Montenegro J, Tapanes F, de Rousse AR, 1978. Clinical and histological kidney involvement in human kala-azar. Am J Trop Med Hyg 27 :357–359.

    • Search Google Scholar
    • Export Citation
  • 29

    Duarte MI, Silva MR, Goto H, Nicodemo E, Amato Neto V, 1983. Interstitial nephritis in human kala-azar. Trans Royal Soc Trop Med Hyg 77 :531–537.

    • Search Google Scholar
    • Export Citation
  • 30

    Salgado Filho N, Ferreira TM, Costa JM, 2003. Involvement of the renal function in patients with visceral leishmaniasis (kala-azar). Rev Soc Bras Med Trop 36 :217–221.

    • Search Google Scholar
    • Export Citation
  • 31

    Maru M, 1979. Clinical and laboratory features and treatment of visceral leishmaniasis in hospitalized patients in Northwestern Ethiopia. Am J Trop Med Hyg 28 :15–18.

    • Search Google Scholar
    • Export Citation
  • 32

    Mary C, Ange G, Dunan S, Lamouroux D, Quilici M, 1993. Characterization of a circulating antigen involved in immune complexes in visceral leishmaniasis patients. Am J Trop Med Hyg 49 :492–501.

    • Search Google Scholar
    • Export Citation
 
 
 

 

 
 
 

 

 

 

 

 

 

A PHASE II DOSE-RANGING STUDY OF SITAMAQUINE FOR THE TREATMENT OF VISCERAL LEISHMANIASIS IN INDIA

View More View Less
  • 1 Kala-azar Research Center, Muzaffarpur, India; Kala-azar Medical Research Center, Banaras Hindu University, Varanasi, India; Balaji Uthan Sansthan, Patna, India; GlaxoSmithKline, Greenford, United Kingdom; Liverpool University, Liverpool, United Kingdom

This randomized, open label, multicenter study assessed the dose-response and safety profile for oral sitamaquine in 120 Indian subjects with visceral leishmaniasis (VL). Patients aged 5–64 years (mean age 21.2 years) received one of four sitamaquine doses (1.5, 1.75, 2.0, or 2.5 mg kg−1 day−1) daily for 28 days. At Day 180 in the intent-to-treat population, final cure (primary efficacy outcome) was achieved in 92 of 106 (87%) patients overall and 25 of 31 (81%), 24 of 27 (89%), 23 of 23 (100%), and 20 of 25 (80%) patients at doses of 1.5, 1.75, 2.0, or 2.5 mg kg−1 day−1 sitamaquine, respectively. Sitamaquine was generally well tolerated. The most common adverse events during the active treatment phase were vomiting (8% [10 of 120]), dyspepsia (8% [9 of 120]) and cyanosis (3% [4 of 120]). Nephrotic syndrome (3% [3 of 120]) and glomerulonephritis (2% [2 of 120]) were also reported and require further investigation. Oral sitamaquine demonstrated efficacy in Indian VL and was well tolerated.

Author Notes

Reprint requests: Tara K. Jha, Kala-azar Research Center, Muzaffarpur, 842 001 India, Telephone: 91-621-261-283, Fax: 91-621-261-425, E-mail: dr_tkjha@hotmail.com.
Save