In order to assess the one must
first take an overview of the whole of the whole disease. One must
understand the disease and its enormity on a global basis. Malaria is a
protozoan disease of which over 150 million cases are reported per annum.
In tropical Africa alone more than 1 million children under the age of
fourteen die each year from Malaria. From these figures it is easy to see
that eradication of this disease is of the utmost importance.

The disease is caused by one of four species of Plasmodium These four are
P. falciparium, P .malariae, P .vivax and P .ovale. Malaria does not only
effect humans, but can also infect a variety of hosts ranging from
reptiles to monkeys. It is therefore necessary to look at all the aspects
in order to assess the possibility of a vaccine. The disease has a long
and complex life cycle which creates problems for immunologists. The
vector for Malaria is the Anophels Mosquito in which the life cycle of
Malaria both begins and ends. The parasitic protozoan enters the
bloodstream via the bite of an infected female mosquito. During her
feeding she transmits a small amount of anticoagulant and haploid
sporozoites along with saliva. The sporozoites head directly for the
hepatic cells of the liver where they multiply by asexual fission to
produce merozoites. These merozoites can now travel one of two paths. They
can go to infect more hepatic liver cells or they can attach to and
penetrate erytherocytes. When inside the erythrocytes the plasmodium
enlarges into uninucleated cells called trophozites The nucleus of this
newly formed cell then divides asexually to produce a schizont, which has
6-24 nuclei. Now the multinucleated schizont then divides to produce
mononucleated merozoites . Eventually the erythrocytes reaches lysis and
as result the merozoites enter the bloodstream and infect more
erythrocytes. This cycle repeats itself every 48-72 hours (depending on
the species of plasmodium involved in the original infection) The sudden
release of merozoites toxins and erythrocytes debris is what causes the
fever and chills associated with Malaria.

Of course the disease must be able to transmit itself for survival. This
is done at the erythrocytic stage of the life cycle. Occasionally
merozoites differentiate into macrogametocytes and microgametocytes. This
process does not cause lysis and there fore the erythrocyte remains stable
and when the infected host is bitten by a mosquito the gametocytes can
enter its digestive system where they mature in to sporozoites, thus the
life cycle of the plasmodium is begun again waiting to infect its next
host. At present people infected with Malaria are treated with drugs such
as Chloroquine, Amodiaquine or Mefloquine. These drugs are effectiv e
ateradicating the exoethrocytic stages but resistance to them is becoming
increasing common. Therefore a vaccine looks like the only viable option.

The wiping out of the vector i.e. Anophels mosquito would also prove as an
effective way of stopping disease transmission but the mosquito are also
becoming resistant to insecticides and so again we must look to a vaccine
as a solution Having read certain attempts at creating a malaria vaccine
several points become clear. The first is that is the theory of Malaria
vaccinology a viable concept? I found the answer to this in an article
published in Nature from July 1994 by Christopher Dye and Geoffrey Targett.
They used the MMR (Measles Mumps and Rubella) vaccine as an example to
which they could compare a possible Malaria vaccine Their article said
that "simple epidemiological theory states that the critical fraction (p)
of all people to be immunised with a combined vaccine (MMR) to ensure
eradication of all three pathogens is determined by the infection that
spreads most quickly through the population; that is by the age of one
with the largest basic case reproduction number Ro. If a vaccine can be
made against the strain with the highest Ro it could provide immunity to
all malaria plasmodium "

Another problem faced by immunologists is the difficulty in identifying
the exact antigens which are targeted by a protective immune response.
Isolating the specific antigen is impeded by the fact that several
cellular and humoral mechanisms probably play a role in natural immunity
to malaria - but as is shown later there may be an answer to the dilemma.
While researching current candidate vaccines I came across some which
seemed more viable than others and I will briefly look at a few of these
in this essay. The first is one which is a study carried out in the
Gambia from 1992 to 1995.(taken from the Lancet of April 1995). The
subjects were 63 healthy adults and 56 malaria identified children from an
out patient clinic Their test was based on the fact that experimental
models of malaria have shown that Cytotoxic T Lymphocytes which kill
parasite infected hepatocytes can provide complete protective immunity
from certain species of plasmodium in mice. From the tests they carried
out in the Gambia they have provided, what they see to be indirect
evidence that cytotoxic T lymphocytes play a role against P falciparium in
humans Using a human leucocyte antigen based approach termed reversed
immunogenetics they previously identified peptide epitopes for CTL in
liver stage antigen-1 and the circumsporozoite protein of P falciparium
which is most lethal of the falciparium to infect humans. Having these
identified they then went on to identify CTL ...