||Leishmaniasis is caused by
macrophage resident intracellular protozoan
parasites Leishmania donovani, Leishmania infantum and Leishmania chagasi. Parasite transmission occurs
through the bite of infected female phlebotomine
sandfly. Sandflies obtain infected blood while
sucking the blood from their parasite carrier hosts.
Four different forms of leishmaniasis with different
clinical manifestations occur in humans. Of these
different forms, visceral leishmaniasis (VL) which
is also known as Kala-Azar is the most severe and
has a mortality rate of almost 100% if not treated.
Frequent bouts of fever, weight loss, enlargement of
spleen and liver accompanied with anemia are
characteristic signs and symptoms of VL.
Various social and lifestyle changes have altered
the epidemiology of VL which was earlier predominant
only in underdeveloped tropical countries.
Leishmaniasis is presently endemic in all continents
except Australia. According to an earlier report of
World Health Organisation there are in excess of 12
million people affected by leishmaniasis world wide
and nearly 2 million new cases are added each year.
One third of the new cases of leishmaniasis are VL
and 90% of the VL cases are in five countries
Bangladesh, Brazil, India, Nepal and Sudan. Indian
alone accounts for 1/4th of the total world wide
Kala-Azar is a major public health problem in
certain part of India. Standard treatment involves
use of Antimonials and Sodium Stibogluconate.
Considerable resistance to the standard drugs has
compelled to look for alternative drugs.
AmphotericinB has been found clinically effective
even in resistant cases of Kala-Azar. Use of AmphotericinB,
however, is restricted due to its well known
Strategic suitability of lipid formulations of
AmphotericinB for the treatment of visceral
leishmaniasis emanates from several factors viz.
leishmania resides in the macrophages, liposomes are
rapidly taken up by the macrophages, AmphotericinB
is an effective antileishmanial drug, and
AmphotericinB can be formulated as liposomal
preparation. All of these facilitate targeted
delivery of Liposomal AmphotericinB to the desired
site for antiparasitic action and thus reduces the
toxicities of the AmphotericinB. Additionally
liposomes offer an amplification effect, through
concentrated encapsulation of numerous molecules in
each liposomes particle which are delivered at the
desired site of action. Liposomal AmphotericinB has
been used extensively throughout the world as the
best option for treatment of VL even in cases
resistant to standard drugs. FUNGISOME™ has been
shown to have proven advantage over conventional
drug regimen in the treatment of visceral leishmaniasis in India.
Tissue distribution of FUNGISOME™ has been studied
in experimental animals infected with Leishmania
donovani. At the maximum tolerated doses of
conventional AmphotericinB and FUNGISOME™ higher
levels of AmphotericinB were achieved in liver and
spleen in the mice treated with FUNGISOME™. In
comparison, conventional AmphotericinB was found to
be less effective at the tolerated doses.
Taking into consideration economy of the treatment,
number of dosage schedules have been clinically
evaluated which are comprehensively presented below.