Plasmodium (the genus of pathogens causing
> Eukaryotes >
Chromalveolata > Alveolata > Apicomplexa
Malaria infects 300-500 million and kills 1.5-2.7 million people each year,
making it by far the most serious of the diseases spread by insects. The
pathogens causing malaria are four species of Plasmodium and they are
transmitted from person to person by mosquitoes of the genus Anopheles.
The Plasmodium species causing malaria
- Plasmodium falciparum. Causes malignant tertian malaria, which
kills through cerebral malaria or renal failure. Fever occurs about every 48
hours but this periodicity is often masked because the stages are not always
synchronous. This periodicity is termed tertian because of fever on the first
day, no fever on the second and then a return of fever on the third day. Plasmodium
falciparum needs an average ambient temperature of at least 20ºC so is
found mainly in warmer parts of the world.
- Plasmodium vivax. Causes benign tertian malaria which rarely
kills. This species is not found in tropical Africa mainly because black
Africans lack the red cell surface Duffy antigen that P. vivax requires
for cell invasion. It can exist in places with an average summer temperature
of only 16ºC. Together with P. ovale is is considered a relapsing
malaria, so named because it can remain in a dormant hypnozoite stage for very
long periods (years) in the liver. The adaptive value of this ability is that
the parasite can persist in areas that experience long winters with no
opportunities for transmission.
- Plasmodium ovale. Causes a rare tertian malaria with a long
incubation period and relapses at three-month intervals. Found mainly in
tropical Africa but with sporadic reports from elsewhere. Life P. vivax, it
is a recurrent malaria with a dormant liver stage.
- Plasmodium malariae. Causes quartan malaria with fever returning
every 72 hours. It is remarkable in that it can persist in the blood of
a host for decades at very low densities, but it does not have a dormant stage
in the liver. Relapses can sometimes occur half a century after being
All four species are found in regions all round the world but they are
thought to have been introduced to the New World from Europe and Africa during
the sixteenth century. The distributions of P. vivax and P. ovale
There are about 422 species of Anopheles worldwide, many of them
sibling species that can only be identified using genetic techniques. Of these,
about 70 are malaria vectors but only about 40 are important. The ability to
transmit Plasmodium parasites depends on
- the mosquito living long enough for the parasite to complete its
- the mosquito's propensity to feed on humans; and
- whether or not the mosquito is physiologically suitable for the parasite.
However, most Anopheles are thought to be able to support normal
development of at least one of the Plasmodium species.
Life cycle of Plasmodium in humans and mosquitoes
skin of person
The female mosquito punctures the persons
skin and injects saliva containing Plasmodium sporozoites
pre-erythrocytic schizogonous cycle
The sporozoites are carried in the blood to
the person’s liver and enter liver parenchyma cells. The sporozoite
grows through feeding on the cell contents and changes to a schizont
which is the form that undergoes multiple division, termed schizogony.
This process of schizogony in the liver cell produces 2000-40000 separate
tiny individuals termed merozoites. A merozoite then either infects
another liver cell and repeats the cycle or it passes out of the liver
into the blood and enters the erythrocyte schizogonous cycle. The period
in the liver lasts 6-16 days.
erythrocyte schizogonous cycle (asexual)
A merozoite enters an erythrocyte (red
blood cell) and grows through feeding on the cell contents. The individual
is transformed into a schizont that undergoes the process of schizogony
to produce 6-24 merozoites (much less than the number produced in
the liver). The cycle is usually repeated a number of times so that the
number of infected erythrocytes in the blood stream increases enormously.
The duration of the cycle is the duration between successive bouts of
fever in the victim, each bout correlating with the simultaneous release
of the merozoites from the cells. This is because the release stimulates
the person’s immune system to produce cytokines which cause
fever. Erythrocytes are killed by being infected and the remains are
broken down in the spleen, a reason why the spleen is enlarged in people
Merozoites eventually stop multiplying and
transform into male and female individuals termed gametocytes.
The mosquito bites the person, injecting
saliva and sucking up blood containing the gametocytes. Any other Plasmodium
stages such as merozoites are digested in the mosquito’s gut but the
Female gametocytes transform into macrogametes,
a process that includes the reduction of the chromosomes to the haploid
number. The nucleus of the male gametocyte divides up into several
elongate protoplasmic processes that radiate from the surface of the male
gametocyte. Each of these processes becomes a male gamete termed a microgamete
which is equivalent to a mammalian spermatozoon. The process by which the
microgametes break away from the surface of the male gametocyte is termed exflagellation.
A microgamete fertilizes a macrogamete to
form a zygote.
The zygote transforms into a motile ookinete
which penetrates the wall of the midgut and settles under the membrane
separating the midgut from the haemocoel where it forms into a non-motile oocyst.
exterior of midgut
The oocyst grows and its contents
divides into about 10000 elongate sporozoites. This process does
not occur unless temperatures are from 16 to 33 ºC. The sporozoites burst
out of the oocyst into the haemocoel and many of them find there way to
the salivary glands.
skin of person
The cycle is repeated by the mosquito
biting another person and injecting the infected saliva.
Prevention and control of malaria
The lesson from the now abandoned global malaria eradication campaign was
that malaria cannot be dealt with as a single and uniform worldwide problem,
susceptible to one global control strategy (Collins & Paskewitz 1995).
Insecticides. Insecticidal control methods target a week link in the
transmission cycle which is that the mosquito needs to stay alive for quite a
long time for complete parasite development to take place. However, mosquitoes
soon build up resistance to particular insecticides and so new, usually more
expensive ones, constantly need to be formulated. Insecticides are used in three
main ways for controlling mosquitoes:
Breeding habitat modification. Drainage, filling, levelling,
intermittent flushing, and aquatic plant control are cost-effective options
for removing larval aquatic breeding habitat. Economic development projects
(e.g. building dams) need to ensure that they don't increase larval breeding
Biological control agents. There are a few successful cases of fish
being introduced to water bodies to eat mosquito larvae. For instance, the North
American fish Gambusia affinis reduced malaria incidence in Italy and
Greece and its introduction into 3800 wells in India reduced the number of wells
containing larvae by 75%.
Development of malaria vaccines. This has been complicated by both
scientific and political difficulties and so far no effective vaccines are
Genetic modification. The idea here is to use DNA techniques to replace
a highly competent vector population with one that is engineered to be an
incompatible host for the malaria parasite. There has already been success in
splicing into the genome of Anopheles stephensi a gene that provides
resistance to Plasmodium. This gene encodes a peptide that seems to block
receptors in the gut and salivary glands of the mosquito that are used by Plasmodium
for replication . Experiments showed that mosquitoes with this gene were unable
to infect mice with malaria. A similar exercise is now under way to splice this
gene into the genome of Anopheles gambiae which is the main culprit for
transmitting malaria in Africa (see news report in Science 293:
2370-2371, Sept. 2001). There is also a huge project underway to map the entire
genome of A. gambiae.
- Spraying of insecticide on larval habitats. When a large proportion
of the larval habitat can be identified, larval control can be very
- Insecticide impregnated bed nets. Recent studies have shown that
impregnation of bed nets with pyrethroid insecticides can be effective in
controlling mosquitoes and preventing bites. However, in many cases this
approach does not reduce the infection rate because the mosquitoes are
feeding outdoors in the early evening before people have gone to bed.
- Residual insecticides in home interiors. Formulations with
long-term residual activity are sprayed on surfaces that the mosquito is
likely to encounter such as walls in houses and huts. However, some species
of Anopheles often rest outdoors after a blood meal.
History of malaria
Collins, F.H. & Paskewitz, S.M. 1995.
Malaria: current and future prospects for control. Annual Review of
Entomology 40: 195-219.
Gullan, P.J. & Cranston, P.S. 1994. The
Insects: An Outline of Entomology. Chapman & Hall, London.
Service, M.W. 1993. Mosquitoes (Culicidae). In: Medical
Insects and Arachnids (eds R.P. Lane and R.W. Crosskey). Chapman and
Hall, London, pp. 120-240.