Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Malaria and the physiology of parasitic infections

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HLA-typing can provide valuable DNA-based evidence

contributing to the determination of identity in criminal cases.

This technology has been used in domestic criminal trials.

Additionally, it is a technology that has been applied interna-

tionally in the human-rights arena. For example, HLA-typing

had an application in Argentina following a military dictator-

ship that ended in 1983. The period under the dictatorship was

marked by the murder and disappearance of thousands who

were known or suspected of opposing the regime’s practices.

Children of the disappeared were often adopted by military

officials and others. HLA-typing was one tool used to deter-

mine non-parentage and return children of the disappeared to

their biological families.

HLA-typing has proved to be an invaluable tool in the

study of the evolutionary origins of human populations. This

information, in turn, contributes to an understanding of cul-

tural and linguistic relationships and practices among and

within various ethnic groups.

See alsoAntibody and antigen; Immunity, cell mediated;

Immunity, humoral regulation; Immunodeficiency disease

syndromes; Immunodeficiency diseases; Immunogenetics;

Immunological analysis techniques; Transplantation genetics

and immunology

MALARIA AND THE PHYSIOLOGY OF

PARASITIC INFECTIONSMalaria and the physiology of parasitic infections

Malaria is a disease caused by a unicellular parasite known as

Plasmodium.Although more than 100 different species of

Plasmodiumexist, only four types are known to infect humans

including, Plasmodium falciparum, vivax, malariae, and

ovale.While each type has a distinct appearance under the

microscope, they each can cause a different pattern of symp-

toms. Plasmodium falciparumis the major cause of death in

Africa, while Plasmodium vivaxis the most geographically

widespread of the species and the cause of most malaria cases

diagnosed in the United States. Plasmodium malariaeinfec-

tions produce typical malaria symptoms that persist in the

blood for very long periods, sometimes without ever produc-

ing symptoms. Plasmodium ovaleis rare, and is isolated to

West Africa. Obtaining the complete sequence of the

Plasmodiumgenome is currently under way.

The life cycle of Plasmodiumrelies on the insect host

(for example, the Anopheles mosquito) and the carrier host

(humans) for its propagation. In the insect host, the

Plasmodiumparasite undergoes sexual reproduction by unit-

ing two sex cells producing what are called sporozoites. When

an infected mosquito feeds on human blood, the sporozoites

enter into the bloodstream. During a mosquito bite, the saliva

containing the infectious sporozoite from the insect is injected

into the bloodstream of the human host and the blood that the

insect removes provides nourishment for her eggs. The para-

site immediately is targeted for a human liver cell, where it can

escape from being destroyed by the immune system. Unlike in

the insect host, when the sporozoite infects a single liver cell

from the human host, it can undergo asexual reproduction

(multiple rounds consisting of replication of the nucleusfol-

lowed by budding to form copies of itself).

During the next 72 hours, a sporozoite develops into a

schizont, a structure containing thousands of tiny rounded

merozoites. Schizont comes from the Greek word schizo,

meaning to tear apart. One infectious sporozoite can develop

into 20,000 merozoites. Once the schizont matures, it ruptures

the liver cells and leaks the merozoites into the bloodstream

where they attack neighboring erythrocytes (red blood cells,

RBC). It is in this stage of the parasite life cycle that disease

and death can be caused if not treated. Once inside the cyto-

plasmof an erythrocyte, the parasite can break down hemo-

globin (the primary oxygen transporter in the body) into

amino acids (the building blocks that makeup protein). A by-

product of the degraded hemoglobin is hemozoin, or a pig-

ment produced by the breakdown of hemoglobin.

Golden-brown to black granules are produced from hemozoin

and are considered to be a distinctive feature of a blood-stage

parasitic infection. The blood-stage parasitesproduce sch-

izonts, which rupture the infected erythrocytes, releasing

many waste products, explaining the intermittent fever attacks

that are associated with malaria.

The propagation of the parasite is ensured by a certain

type of merozoite, that invades erythrocytes but does not asex-

ually reproduce into schizonts. Instead, they develop into

gametocytes (two different forms or sex cells that require the

union of each other in order to reproduce itself). These game-

tocytes circulate in the human’s blood stream and remain qui-

escent (dormant) until another mosquito bite, where the

gametocytes are fertilized in the mosquito’s stomach to become

sporozoites. Gametocytes are not responsible for causing dis-

ease in the human host and will disappear from the circulation

if not taken up by a mosquito. Likewise, the salivary sporo-

zoites are not capable of re-infecting the salivary gland of

another mosquito. The cycle is renewed upon the next feeding

of human blood. In some types of Plasmodium,the sporozoites

turn into hypnozoites, a stage in the life cycle that allows the

parasite to survive but in a dormant phase. A relapse occurs

when the hypnozoites are reverted back into sporozoites.

An infected erythrocyte has knobs on the surface of the

cells that are formed by proteins that the parasite is producing

during the schizont stage. These knobs are only found in the

schizont stage of Plasmodium falciparumand are thought to be

contacted points between the infected RBC and the lining of

the blood vessels. The parasite also modifies the erythrocyte

membrane itself with these knob-like structures protruding at

the cell surface. These parasitic-derived proteins that provide

contact points thereby avoid clearance from the blood stream

by the spleen. Sequestration of schizont-infected erythrocytes

to blood vessels that line vital organ such as the brain, lung,

heart, and gut can cause many health-related problems.

A malaria-infected erythrocyte results in physiological

alterations that involve the function and structure of the ery-

throcyte membrane. Novel parasite-induced permeation path-

ways (NPP) are produced along with an increase, in some

cases, in the activity of specific transporters within the RBC.

The NPP are thought to have evolved to provide the parasite

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