Malaria
1965 in Sarawak, Malaysia; other foci of infection have been
- leading parasitic disease that causes mortality worldwide
- 655000 deaths in 2010; 3.3 billion are at risk
- identified by the WHO as one of the three major infectious
disease threats, along with AIDS/HIV and TB
- causes more than 5 million deaths a year
- leads to decreased social and economic productivity and
contributes to a vicious cycle of poverty and disease
- Young children and pregnant women are mostly affected
- anemia is cause by chronic malaria, it is associated with
impaired physical and mental growth and development in
children
- Anemia, in pregnancy, is a leading contributor to maternal
morbidity and mortality, and is associated with risk of cardiac
failure and adverse perinatal outcomes
-Anemia from malaria is also exacerbated by anemia from
concomitant helminth infections in both children and pregnant
women.
In 2000, the United Nations (UN) adopted a blueprint named
Millennium Development Goals (MDGs).
- MDG 6 aims to reduce the burden of HIV/AIDS, malaria, and
other diseases. The malaria component of MDG 6 includes
reducing incidence and mortality rates of the disease, increasing
insecticide-treated bed net coverage among children below 5
years of age and increasing anti-malarial coverage among
children below 5 years of age.
Despite the high figures in mortality, the disease is curable if
promptly and adequately treated. The group of parasites
causing malaria belongs to the genus Plasmodium that is
transmitted by the bite of an infected female mosquito belonging
to the genus Anopheles. The four species that are medically
important to humans are Plasmodium falciparum, P. vivax, P.
ovale, and P. malariae. The first two are responsible for over
90% of all human malaria cases. More recently, P. knowlesi has
been described in humans in the Philippines and most of
Southeast Asia. P. knowlesi, considered the fifth human malaria
parasite, is normally a parasite of long-tailed macaques
(Macaca fascicularis), but humans working in nearby forest
fringe pose great risk for infection.
The first naturally acquired human infection was reported in
reported in Thailand and China as late as 2008. In the
Philippines, the first reported case of P. knowlesi was described
in 2006. Since then, the Research Institute for Tropical Medicine
(RITM) has reported nine cases of mixed malaria infection,
positive for P. knowlesi. The life cycle of P. knowlesi is
microscopically indistinguishable from P. malariae, and
differentiation is only achieved through polymerase chain
reaction (PCR) assay and molecular characterization. These
protozoans are pigment producers and are ameboid in shape,
with some being more ameboid than the others. Their asexual
cycle occurs in humans, the vertebrate and intermediate host,
while the sexual cycle occurs in the Anopheles mosquito, the
invertebrate and definitive host.
Parasite Biology
The asexual cycle in humans consists of schizogony, which
leads to the formation of merozoites, and gametogony, which
leads to the formation of gametocytes. The sexual cycle in the
mosquito involves sporogony, which leads to the formation of
sporozoites. The life cycles of all human species of malaria are
similar. The infected female Anopheles mosquito bites and
sucks blood from the human host. In the process, salivary fluids
containing sporozoites are also injected. These sporozoites, the
infective stage of the parasite, are immediately carried to the
liver and enter the parenchymal cells. The parasites then
commence exo-erythrocytic schizogony, which produces the
merozoites in varying duration and amounts, depending on the
species. Merozoites proceed to the
peripheral blood to enter the erythrocytes. Some merozoites of
P. vivax and P. ovale re-invade theliver cells forming
hypnozoites, while the other species do not. These dormant
exo-erythrocytic forms may remain quiet for years. Within the
red blood cell, the merozoite grows as a ring form developing
into a trophozoite. The trophozoite has an extended cytoplasm
and a large chromatin mass which further divides to form more
merozoites within schizonts. The merozoites of P. falciparum
develop in the parasitophorous vacuolar membrane (PVM)
within the mature red cells and modify the structural and
antigenic properties of these cells. The parasites feed on the
hemoglobin resulting in the production of pigment known as
hematin. Soon after, the erythrocytes rupture and the
merozoites are released into the blood, ready to enter new
erythrocytes. This asexual cycle is synchronous, periodic, and
speciesdetermined. Some merozoites develop into
microgametocytes (male) or macrogametocytes (female) which
are picked up by feeding female mosquitoes for completion of
the life cycle. In the gut of the mosquito, the male gametocytes
exflagellate and produce eight sperm-like microgametes which
may fertilize the female macrogamete to form a zygote. The
zygote becomes motile and penetrates the mosquito’s gut as an
ookinete, which then develops into an oocyst. The oocyst grows
and produces sporozoites, which escape from the oocyst and
enter the salivary glands of the mosquito. These sporozoites
may be injected into another human host when the mosquito
takes a blood meal. The entire developmental cycle in the
mosquito takes 8 to 35 days, depending to some extent on
ambient temperature. Morphologically, the early trophozoite
form is ring-shaped with a red chromatin dot and a scant amount
of blue cytoplasm when stained with Giemsa or Wright’s stain.
The trophozoite form has a large chromatin mass and a
prominent ameboid cytoplasm, which is spread through the
erythrocyte. The parasite develops into a schizont when the
chromatin has divided into two or more masses of chromatin
with small amounts of cytoplasm, the so-called merozoites. The
number of merozoites is species dependent. Clumps of pigment
accumulate in the middle of a mature schizont. The gametocyte
stage fills the entire red blood cell and is characterized by a large
chromatin mass and a blue cytoplasm with pigment. It is round
to banana-shaped. The microgametocyte has a lighter blue
cytoplasm, while the cytoplasm of the macrogametocyte is a
darker blue. Species identification depends on various
characteristics of these stages of development as described in
Table 2.5.’