Definition
Malaria is a parasitic infection transmitted through infected female Anopheles mosquitoes. The reason that
malaria is primarily transferred by female mosquitoes is that male Anopheles do not feed on blood. Female Anopheles
feed most often at night. It is common in tropical and subtropical parts of the Americas, Asia, and Africa. Every
year malaria infects approximately 400 million people and kills 1-3 million of those infected, most often children
in sub-saharan Africa. The disease is caused b the protozoan parasite Plasmodium, with the most serious
infections being caused by Plasmodium falciparum and Plasmodium vivax. The malaria parasites asexually
reproduce in red blood cells resulting in anemia, fever, chills, and nausea. As no vaccine is currently available,
prevention is largely limited to preventing bites from infected mosquitoes using spraying programs, mosquitoe nets,
insect repellants, and removing standing water where mosquitoes lay their eggs. Preventative medications must be
taken continuously to prevent infection. Active infection can be treated with antimalarial drugs such as quinine or
artemisinin derivatives. Drug resistance has become a growing problem however.
Malaria symptoms
Symptoms of malaria infection include fever, shivering, joint pain, vomiting, anemia, and convulsions. The usual
progression of symptoms is sudden coldness following by rigor and fever/sweating for 4-6 hours occurring every 2-3
days. Children with malaria often show signs of severe brain damage including abnormal posturing. Severe malaria is
usually caused by P. falciparum and usually appears 6-14 days following infection. Severe malaria can result in coma
and death if untreated, especially in children and pregnant women. Severe organ damage may also occur and infected
organs include the brain, liver, spleen, and kidneys. While P. falciparum can cause severe malaria, it is rarly
chronic. Chronic malaria, where disease relapse can occur months or years after exposure, is occasionally seen from
P. vivax or P. ovale infection due to latent parasites remaining in the liver.
Plasmodium life cycle
The main vector of Plasmodium transmission is the female Anopheles mosquito. The malaria parasite first enters the
mosquito when the mosquito feeds on an infected human carrier. Anopheles carries Plasmodium sporozoites in their
salivary glands. The parasite gametocytes differentiate into male or female gametes and come together in the
mosquito gut. An ookinete results that produces an oocyst in the gut wall. The oocyst eventually ruptures, releasing
more sporozoites which migrate to the salivary gland where they are available to infect a human host. The
sporozoites are injected into the human skin with mosquito saliva.
Once a human is infected, malaria develops in 2 phases, one phase involves the liver (hepatic) and the other
phase involves the red blood cells (erythrocytic). Sporozoites migrate to the liver, infecting hepatocytes
and multiplying asexually. This phase is known as a dormant phase since it is usually asymptomatic and lasts
from 6-15 days. In the liver, the sporozoites differentiate into merozoites which cause hepatocyte rupture.
The merozoites then infect red blood cells (RBCs). It is able to do this undetected by the host immune system
by wrapping itself in a coat of hepatocyte cell membrane.
Infection of the RBCs begins the erythrocytic stage of the life cycle. The parasites continue to multiply
asexually in the RBCs and occasionally break out to invade new RBCs. These waves of amplification produce
the typical waves of fever. The parasite evades the host immune system because it tends to remain inside
cells. Despite this tactic, infected RBCs are destroyed in the spleen. To avoid this, P. faciparum expresses
adhesive proteins called Plasmodium faciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of
infected RBCs causing them to stick to vessel walls. This sticking to vessel walls can give rise to hemorrhagic complications.
Evolutionary implications
Sickle-cell disease
Malaria has resulted in profound selective pressure on humans due to the high levels of morbidity and mortality.
Sickle-cell disease is the best studied of the selective pressures of malaria. Sickle-cell disease arises from a
mutation in the HBB gene encoding the beta globin subunit of hemoglobin. A single Glu-Val point mutation results
in polymerization of hemoglobin molecules deforming the RBCs into a sickle shape. These sickle cells are rapidly
destroyed by the spleen. This rapid destruction is actually an advantage in malaria infection because RBCs become
deformed and destroyed before daughter parasites can emerge. Individuals heterozygous for the sickle-cell mutation
(sickle-cell trait) usually have low levels of anemia, but also have a greatly reduced chance of developing serious
malaria infection. There are 4 haplotypes of sickle-cell trait, suggesting that the mutation has emerged independently at least 4 times.
Other selective pressures
In many regions, the gene frequency of the blood disorder beta-thalassemia is related to the level of malaria in
a given population. In one study, children with beta-thalassemia had a 50% reduced likelihood of developing clinical
malaria infection. Other genotypes that have conferred resistance to malaria include the lack of Duffy antigens
in indigenous people of west and central Africa, genetic deficiency in glucose-6-phosphate dehydrogenase (G6PD),
and interleukin-4 (IL4-524 T allele).