| dc.description.abstract | 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. | en |
