Chemotherapy of visceral leishmaniasis in Kenya
A prospective randomised pilot study was carried out to find a cheaper, more effective and safe alternative drug for the treatment of visceral leishmaniasis in Kenya. This study was necessary because the current treatment of visceral leishmaniasis using a parenteral pentavalent antimonial compound, sodium stibogluconate (Pentostam, Wellcome trust Laboratories, U.K. Ltd), is prolonged and unsatisfactory. It has to be administered intravenously (IV) at a dose of 20mg Antimony (Sb)/kg bOdy weight (BW) daily for at least 30 days. Although this drug may be safe, it causes cardiotoxicity at high doses and cures only about 80% of patients who receive the initial treatment and about 20% of the initially cured patients experience relapses. Besides, the drug is very expensive costing about US $ 85 per 100ml bottle which is still insufficient to cure one adult patient. Previously, about 80 common drugs had been tried in vitro on L donovani in murine macrophages, 8 of uhich were selected for trials in infected hamsters after which only the following 3 treatment regimens were xxiii selected for the trials in pacien~s; Amlnosldlne (Gabbromicina or Gabbromicyne, Farmitalia carlo Erba, Italy) administered through ~he intra-muscular (1M) route at a dose of 14-16mg/kg Bw once daily for 20 days, Sodium stibogluconate administered through the IV route at a dose of 20mg Sb/kg Bw once daily for 20 days served as the control drug because it is the current drug of choice to treat visceral leishmaniasis, and the combination of aminosidine with sodium stibogluconate at the same doses as above. The dosage schedules for aminosidine used in this study to treat these patients were restricted to the normal doses employed in treatment of other conditions such as bacterial infections. The study was carried out in 56 patients with visceral leishmaniasis recruited from the Rift Valley Province and admitted to Kabarnet Hospital. The patients who gave informed consent and satisfied the inclusion criteria were randomised into the 3 treatment regimens above. Clinical and laboratory invest~gations were carried out before, during and after patients was conducted treatment. treatment. Follow at 2 and 6 up of cured months after xxiv The results from the 5~ patients indicat~d that thd combination treatment. or anlinosidine alone were more efficacious and cured patients in a shorter time than the standard drug sodium stibogluconate. These two treatment regimens had the advantage of reducing both the period of hospitalization and cost of treatment of visceral leishmaniasis. The standard drug takes at least 30 days to cure 80% of treated patients whereas aminosidine alone or when used in combination needed 19±1 and lS±2 days to cure 85% and 100% of the treated patients respectively. By using aminosidine alone or in combination with sodium stibogluconate, cure rates of 797. and 87% respectively were achieved as compared to 54% when the control drug, sodium stibogluconate alone, was used for the treatment of visceral leishmaniasis. When used alone, aminosidine showed no side effects, but when it was used in combination with sodium stibogluconate it produced minor side effects similar to those due to stibogluconate alone such as epistaxis. sodium When aminosidine alone or its combination with sodium stibogluconate were used, the present cost of treatment xxv decreased by 60X and 48X respectively. This was due to the lower cost of aminosidine and the shorter duration of hospitalization of patients resulting from the superior efficacy of these new treatment regimens for visceral leishmaniasis. Aminosidine alone had two extra advantages over the other treatment regimens: its intramuscular route of administration would enable the medical staff at Health Centres to treat visceral leishmaniasis instead of referring the patients to hospitals; and additional drugs were not required tor the treatment of pneumonia which is a common complication of visceral leishmaniasis. The experimental protocol only allowed for a shorter treatment period than that usually recommended for sodium stibogluconate. It may be correctly argued that this decision affected the ultimate cure rates. The fact .however, remains that under the same experimental conditions, aminosidine or its combination with sodium stibogluconate produced the best results. The results of this study therefore provide us with two new alternative treatment regimens for visceral leishmaniasis in Kenya. However, dose fOnYH"ta.hcrt studies for aminosidine will be required for this new indication.
CitationChunge, C.N(1989). Chemotherapy of visceral leishmaniasis in Kenya
SponsorhipUniversity of Nairobi
College of Agriculture and Veterinary Sciences, University of Nairobi
Phd - Thesis