South African Traditional Medicines Research Unit
Current projects 4 - 5
- The
in- vitro immunostimulation of medicinal plants used for treatment of malaria
in South Africa
Supervisors:
Prof. P.I. Folb, Prof. E.G. Shephard
Researcher:
Ms Noluntu Qodi
Over the past hundred
years, malaria has been one of the most serious and complex health problems
facing humanity. Approximately 300 million people in the world are infected
by the disease and between 1 and 1.5 million people die from it every year
(WHO, Division of Control of Tropical diseases).
The malaria infection
is caused by parasites entering the bloodstream. There are four species of
malarial parasites that infect human beings namely:
- Plasmodium falciparum;
- Plasmodium vivax;
- Plasmodium malariae;
and
- Plasmodium ovale.
Previous research has
focused primarily on Plasmodium falciparum as it is responsible for most deaths.
This parasite causes the most complicated form of malaria, which is cerebral
malaria. Certain strains of P.falciparum are also resistant to chloroquine,
which is used to treat malaria.
The resistance of the
malarial parasite to chloroquine and other drugs prompts the search for chemotherapeutic
agents with novel modes of action.
Many malaria victims world-wide,
especially those living in developing countries, consult traditional healers,
using medicinal plants in an attempt to combat the illness.
Medicinal plants researched
to date were usually selected on the basis of their traditional reputation
for efficacy in the treatment of malaria and other diseases.
Malarial drugs such as
quinine and artemisinin have also been derived from plants and continue to
be effective in treating malaria.
Some medicinal plants
used by traditional healers to treat malaria and ailments such as pneumonia
and fever, have been analysed in laboratories for anti-malarial activities
without any success. This loss of activity could be due to the purification
step, whereby the researcher searches for the pure Compound. Alternatively,
healers could be using such plants as immuno-stimulants rather than as anti-malarial
agents.
The purpose of this study
will be to look at the specific medicinal plants used by healers in the treatment
of malaria, for immuno-stimulatory activity.
Apart from being specifically
stimulatory or suppressive, certain agents have been shown to possess activity
which normalises or modulates pathophysiological processes and are hence called
immunomodulatory agents (Wagner, 1983).
Suppressive and cytotoxic
activity affecting the function of the immune system has been reported for
many of synthetic and natural therapeutic agents (Muftuogony, 1984).
Specific objectives:
As mentioned
previously, the main purpose of this project is to study the activity of some
medicinal plants, used in the treatment of malaria, on the immune system.
The immune system is known
to be involved in the aetiology as well as pathophysiological mechanisms of
many diseases. Immunology is thus one of the most rapidly developing areas
of biomedical research and shows great promise with regard to the prevention
and treatment of a wide range of disorders (M.Zauddin et al,1996).
Plasmodia parasites invade
the bloodstream after a mosquito bite, as well as liver hepatocytes, where
they develop into merozoites. This stage takes about 9-16 days and the merozoites
are subsequently released, invading red blood cells via adhesion molecules
present on their surfaces.
Because the invasion process
is essential for the parasite's survival, and the merozoite adhesion molecules
that mediate the process are exposed on the surface during invasion, these
adhesion molecules are candidates for asexual stage malarial vaccines.
If the plants are found
to be modulators of the immune processes, isolation of each plant's pure compound
and its structure will be studied in detail, as well as the toxicity of its
compounds.
The production of soluble
mediators due to the immuno-stimulation will be compared with that of phytohemagglutinin.
Control of diseases by immunological means has two primary objectives, namely:
- the development and
improvement of protective immunity; and
- the avoidance of undesired
immunological side reactions (M. Ziauddin et al, 1996).
- A
study of the natural history of plasmodium chabaudi chabaudi infections
in experimental mice, with special reference to the influence of traditional
medicines on the immune response.
Project
leaders: Prof. P. I. Folb, Prof. B. Ryffel, Dr P. Smith
Researcher: Bonginkosi Gumede, Paul Waako
Plasmodium chabaudi chabaudi
infections in mice have been shown to have strong analogies, at the immunological
level, to P. falciparum infections in humans.
This model has been used
to investigate the mechanism of the development of immunity [1] and is therefore
a broadly experimental model for studying the development of immunity during
malaria infections.
In order to gain a better
insight into protective immunity in vivo, various murine malaria experimental
systems have been developed with parasites isolated from African wild rodents.
In this study, we will
be using the experimental model Plasmodium chabaudi chabaudi (Pcc). With this
parasite, the genetic background of the host influences the course of the
infection. In some inbred mice strains, Pcc develop a fatal infection course,
whereas other strains are able to control and clear the parasites. Similar
genetic predisposition has been shown in humans [2].
In this study, we will
be studying the natural history of the disease in immune competent mice and
in immune knockout mice. This will assist in investigating the effect of artesunate,
which is an artemisinin derivative from the Artemisia annua plant, and the
effect of some traditional medicines, which have been shown in our pharmacology
plant research laboratory to have some antimalarial activity.
This research might lead
to the discovery of new drugs or therapies for malaria. Since the Pcc model
has been broadly used for studying the development of immunity, this research
may enable us to work on the promising possibility of new vaccine development.
Specific objectives:
The purpose
of this research is to establish a reproducible experimental model of P. chabaudi
chabaudi in our laboratory, and to describe the natural history of the disease
in wild type and immune-competent C3H mice.
The immunological basis
of the normal resistance of the mouse to Plasmodium Chabaudi infections will
be explored by comparing the natural history of the infection in immune competent
mice with that in:
- interferon gamma deficient
mice;
- tumor necrosis factor
deficient mice;
- ICAM-1 deficient mice;
and
- ICAM-2 deficient mice.
The possible therapeutic
effects of artesunate, and of two or more traditional medicines with known
antimalarial activity, will be determined. |
