Monitoring Toxicity Associated with Parenteral Sodium Stibogluconate in the Day-Case Management of Returned Travellers with New World Cutaneous Leishmaniasi
Background Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach. Methodology We reviewed records of 67 consecutive NWCL patients, aged 17–61 years, treated as day-cases with 20 mg/kg/day SbV for up to 28 days at our UK centre. Data had been collected in a standardised format at the time of treatment using a care-record tool. Patients reported adverse-effects daily using a structured questionnaire. Blood tests and electrocardiograms were performed twice weekly to monitor for toxicity. Principal Findings Parenteral SbV treatment was associated with an early, significant suppression of mean lymphocyte and platelet counts. By day four of treatment, lymphocytes reduced by 0.53×109/L (CI 0.29×109/L to 0.76×109/L, p<0.001), and platelets by 31,000/μL (CI 16,000/μL to 46,000/μL, p<0.001). SbV was further associated with significant elevation of serum alanine transaminase concentrations, with a mean peak rise of 107 iu/L by day 13 (CI 52 iu/L to 161 iu/L, p<0.001). These disturbances were temporary and did not result in adverse clinical events. Patient-described symptoms were cumulative and at three weeks of treatment, 59.6% of patients experienced myalgia and 29.8% malaise. Treatment adherence and clinical outcomes were comparable to inpatient treatment studies. A total of 1407 individual doses of SbV resulted in only 26 nights' hospital admission, a saving of 1381 bed-days compared to inpatient treatment. Conclusions/Significance In specialist centres, NWCL patients aged below 65 years and without co-morbidities can be safely and effectively treated without hospital admission. This reduces the cost of treatment, and is much preferred by patients. Twice weekly blood and electrocardiographic monitoring may be surplus to requirement in clinically well, low-risk patients.
References
[1]
Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27: 305–18. doi: 10.1016/j.cimid.2004.03.004
[2]
Reithinger R, Dujardin J, Louzir H, Pirmez C, Alexander B (2007) Cutaneous leishmaniasis. Lancet Infect Dis 7: 581–96. doi: 10.1016/S1473-3099(07)70209-8
[3]
David C, Dimier-David L, Vargas F, Torrez M, Dedet JP (1993) Fifteen years if cutaenous and mucocutaneous leishmaniais in Bolivia: a retrospective study. Trans R Soc Trop Med Hyg 87: 7–9. doi: 10.1016/0035-9203(93)90398-A
[4]
Lawn SD, Whetham J, Chiodini PL, Kanagalingam J, Watson J, et al. (2004) New World mucosal and cutanous leishmaniasis: an emerging health problem among British travellers. Q J Med 97: 781–88. doi: 10.1093/qjmed/hch127
[5]
Bailey M, Green AD, Ellis CJ, O'Dempsey TJ, Beeching NJ, et al. (2005) Clinical Guidelines for the Management of cutaneous leishmaniasis in British military personnel. J R Army Med Corps 151: 73–80. doi: 10.1136/jramc-151-02-03
[6]
Ballou WR, McClain JB, Gordon DM, Shanks GD, Andujar J, et al. (1987) Safety and efficacy of high-dose sodium stibogluconate therapy of Amercian cutaneous leishmaniasis. Lancet 2: 13–6. doi: 10.1016/S0140-6736(87)93053-4
[7]
Saenz RE, Paz H, Berman JD (1990) Efficacy of ketoconazole against Lesihmania braziliensis panamensis cutaneous leishmaniasis. Am J Med 89: 147–55. doi: 10.1016/0002-9343(90)90292-L
[8]
Navin TR, Arana BA, Arana FE, de Mérida AM, Castillo AL, et al. (1990) Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala. Am J Trop Med Hyg 42: 43–50. doi: 10.1093/qjmed/hch127
[9]
Wortmann G, Miller RS, Oster C, Jackson J, Aronson N (2002) A randomized, double-blind study of the efficacy of a 10- or 20-day course of sodium stibogluconate for treatment of cutenous leishmaniasis in United States military personnel. CID 35: 261–7.
[10]
Herwaldt BL, Berman JD (1992) Recommendations for treating leishmaniasis with sodium stibogluconate (Pentostam) and review of pertinent clinical studies. Am J Trop Med Hyg 46: 296–306.
[11]
World Health Organisation Technical Report Series. Control of the leishmaniases. Report of a meeting of the WHO expert committee on the control of leishmaniases, Geneva, 22–226 March 2010.
[12]
Centers for Disease Control and Prevention website. Available: http://www.cdc.gov/parasites/leishmanias？is/health_professionals/index.html. Accessed 2012 May 24.
[13]
Oliveira LF, Schubach AO, Martins MM, Passos SL, Oliveira RV, et al. (2011) Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Trop 118: 87–96. doi: 10.1016/j.actatropica.2011.02.007
[14]
Aronson NE, Wortmann GW, Johnson SC, Jackson JE, Gasser RA Jr, et al. (1998) Safety and efficacy of intravenous sodium stibogluconate in treatment of leishmaniasis: recent U.S. military experience. Clin Infect Dis 27: 1457–64. doi: 10.1086/515027
[15]
Hepburn NC (1993) Thrombocytopaenia complicating sodium stibogluconate therapy for cutaneous leishmaniasis. Trans R Soc Trop Med Hyg 87: 691. doi: 10.1016/0035-9203(93)90298-5
[16]
Wortmann GW, Aronson NE, Byrd JC, Grever MR, Oster CN (1998) Herpes zoster and lymphopenia associated with sodium stibogluconate therapy for cutenous leishmaniasis. Clin Infect Dis 27: 509–12. doi: 10.1086/514689
[17]
Seaton RA, Morrison J, Man I, Watson J, Nathwani D (1999) Out-patient parenteral antimicrobial therapy-a viable option for the management of cutaneous leishmaniasis. Q J Med 92: 659–67. doi: 10.1093/qjmed/92.11.659
[18]
Hatzell JD, Aronson NE, Nagaraja S, Whitman T, Hawkes CA, et al. (2006) Varicella zoster virus meningitis complicating sodium stibogluconate treatment for cutaneous leishmaniasis. Am J Trop Med Hyg 74: 591–2. doi: 10.1093/qjmed/92.11.659
[19]
Lawn SD, Armstrong M, Chilton D, Whitty CJ (2006) Electrocardiographic and biochemical adverse effects of sodium stibogluconate during treatment of cutaneous and mucosal leishmaniasis among returned travellers. Trans R Soc Trop Med Hyg 100: 264–269. doi: 10.1016/j.trstmh.2005.03.012
[20]
Hepburn NC, Siddique I, Howie AF, Beckett GJ, Hayes PC (1993) Hepatotoxicity of sodium stibogluconate in leishmaniasis. Lancet 342: 238–9. doi: 10.1016/0140-6736(93)92327-P
[21]
Gasser RA Jr, Magill AJ, Oster CN, Franke ED, Gr？gl M, et al. (1994) Pancreatitis induced by pentavalent antimonial agents during treatment of leishmaniasis. Clin Infect Dis 18: 83–90. doi: 10.1093/clinids/18.1.83
[22]
McBride MO, Linney M, Davidson RN, Weber JN (1995) Pancreatic necrosis following treatment of leishmaniasis with sodium stibogluconate. Clin Infect Dis 21: 710. doi: 10.1093/clinids/21.3.710
[23]
Davidson RN (1998) Practical guide for the treatment of leishmaniasis. Drugs 56: 1009–18. doi: 10.2165/00003495-199856060-00005
[24]
Hepburn NC, Nolan J, Fenn L, Herd RM, Neilson JM, et al. (1994) Cardiac effects of sodium stibogluconate: myocardial, electrophysiological and biochemical studies. Q J Med 87: 465–72.
[25]
Chulay JD, Spencer HC, Mugambi M (1985) Electrocardiographic changes during treatment of leishmaniasis with pentavalent antimony (sodium stibogluconate). Am J Trop Med Hyg 34: 702–09.
[26]
Bryceson AD, Chulay JD, Mugambi M, Were JB, Gachihi G, et al. (1985) Visceral leishmaniasis unresponsive to antimonial drugs. II. Response to high dosage sodium stibogluconate or prolonged treatment with pentamidine. Trans R Soc Trop Med and Hyg 79: 705–14. doi: 10.1016/0035-9203(85)90199-3
[27]
Brostoff JM, Lockwood DN (2011) Glucocorticoids as a novel approach to the treatment of disabling side effects of sodium stibogluconate. J Clin Pharm Ther. 2011 Apr 4. doi: 10.1111/j.1365-2710.2011.01259.x. [Epub ahead of print].
[28]
Chrusciak-Talhari A, Dietze R, Talhari CC, da Silva RM, Yamashita EPG, et al. (2011) Randomised 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 84: 255–26. doi: 10.4269/ajtmh.2011.10-0155
[29]
Machado PR, Ampuero J, Guimaraes LH, Villasboas L, Rocha AT, et al. (2010) Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomised and controlled trial. PLoS Negl Trop Dis 4(12): e912. doi: 10.1371/journal.pntd.0000912
