Current Status of Malaria Vaccinology


In order to assess the current status of malaria vaccinology 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 effective at eradicating
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. In case the of MMR
this is measles with Ro of around 15 which implies that p> 1-1/Ro » 0.93
Gupta et al points out that if a population of malaria parasite consists of a
collection of pathogens or strains that have the same properties as common
childhoodviruses, the vaccine coverage would be determined by the strain with
the largest Ro rather than the Ro of the whole parasite population. While
estimates of the latter have been as high as 100, the former could be much lower.


The above shows us that 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