NEW LIFE FOR OLD DRUGS (Trypanosomiasis)

BIOTEC at GOLIAT.UGR.ES BIOTEC at GOLIAT.UGR.ES
Sat May 11 05:25:03 EST 1996


                          NEW LIFE FOR OLD DRUGS

     Trypanosomiasis is a devastating parasitic disease of
African cattle transmitted by tsetse flies. The protozoan
parasites, known as trypanosomes, live in the bloodstream and are
transmitted to other cattle by the bloodsucking habits of the
tsetse fly. Over 120 million cattle are at risk from this disease
in 37 African countries. In 35 of these countries control is
principally achieved by treating the cattle with trypanocidal
drugs to cure existing infections and to prevent future
infections. Unfortunately there are only three drugs available
for this purpose and they all have been in use for nearly forty
years. Economic factors make international pharmaceutical
companies unwilling to invest in the development of new drugs so
the best use must be made of what is available. We must give new
life to the old drugs. Every year millions of doses  of these
existing drugs are used by African farmers and in most cases they
work very well and their is a high demand for them by farmers.
However in some situations they are less than fully effective.
The reasons for this have recently been examined by a group of
international Scientists based in Glasgow University Veterinary
School and funded by the European Union Science and Technology
for Development Programme. Probably the most important factor
limiting the effectiveness of drugs is the development of drug
resistance by some populations of typanosomes. The detection of
these populations can be difficult because there is no simple
test available. At the moment the only tests that can be used in
most African countries involves taking samples of trypanosomes
from treated cattle and testing the parasites in laboratory mice
which are subsequently treated with graded doses of drug. However
extrapolating the results from mice to cattle can be hazardous
and inaccurate. The Glasgow group of Scientists have taken a
different approach. They have developed a highly sensitive
immunological assay for detecting trypanocidal drugs in the blood
of treated cattle. To do this antibodies to the drugs had to be
produced. The drugs themselves do not stimulate the production
of anti-drug antibodies but if the drugs are conjugated with a
protein anti-drug antibodies can be produced. These antibodies
can the be used in the test to measure drug concentrations. A
reliable and sensitive assay, which can measure drug levels down
to 0.5 nanogram of drug per millilitre of plasma has been
achieved. How does this assay test for drug resistance?. This can
be achieved by knowing the levels of drugs which should normally
be effective, this is above 1 nanogram/ml, so if parasites are
detected in the blood of cattle with drug levels above this they
must be drug resistant.
     Fortunately the drug detection test, using an enzyme linked
immunosorbent assay (ELISA) and parasite detection tests are easy
to perform and do not require expensive equipment. They are
therefore ideally suited to African laboratories and the test is
already being used in two East African countries. The drug
detection test can be also used to monitor drug levels in
different groups of cattle kept under various methods of
husbandry and in this way the ideal treatment regimens can be
developed.
     What happens when trypanosomes become drug resistant? Well,
no-one really knows the full story but the Glasgow group have
shown that for drugs to be effective a normal immune response
must be present. Trypanosome populations in mice, which have been
immunosuppressed quickly become drug resistant whilst
trypanosomes in normal mice do not. It has also been shown that
once the parasites become drug resistant there is a reduced
accumulation of drug in trypanosomes and this in turn is caused
by alterations in drug transport. Evidence suggests that specific
receptors on the surface of the trypanosome are involved and
these are somehow altered in drug resistant parasites. These
studies may one day lead to even simpler tests for drug
resistance and new ways of overcoming drug resistance, thereby
helping still further to give new life to these old but valuable
drugs.
For further information about this project contact the project
leader Prof. P.H. Holmes, Unversity of Glasgow Vetarinary School,
Glasgow G61 1QH.



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