The Anatomy of a Parasite
By Jason Socrates Bardi
such cities as lie well to the sun and winds, and use good waters, feel
these changes less, but such as use marshy and pooly waters, and lie
well both as regards the winds and the sun, these all feel it more.
And if the summer be dry, those diseases soon cease, but if rainy, they
On Airs, Waters, an Places, 400 B.C.E.
The name malaria comes from the old French and Italian construction,
"mala" + "aria," which means "bad air."
People once thought that the disease was caused by swamp gasses, since
it seemed to be prevalent in wet, marshy places. Even though scientists
have known for more than 100 years that malaria is caused by a microscopic
parasite transmitted by a pest common to wet, marshy placesthe mosquito
Anopheles gambiaethe name, like the disease, persists.
Malaria is a nasty and often fatal disease and is one of the greatest
scourges of modern times. Indeed, one of the greatest challenges to global
public health today is the control of malaria.
Malaria Can Be Controlled
Once endemic in the southern United States and Mediterranean Europe,
malaria has largely been brought under control in these areas. However,
there are still occasional outbreaks, usually caused when travelers infected
in another country arrive in the United States or Europe where they are
bitten by a mosquito that then begins transmitting the disease to other
Southern California has witnessed over a dozen such cases in the last
50 years, including a large outbreak in San Diego County in August 1988
that infected 30 individuals. In total, about 1,200 cases of malaria are
diagnosed in the United States each year.
But these numbers are tiny compared to the global incidence. In many
parts of the world, not only is malaria a major cause of death and disabilityparticularly
among childrenit is a major drain on the economies of some of the
world's most impoverished nations.
In fact, some 40 percent of the world's population lives in areas where
malaria is endemic. The World Health Organization (WHO) estimates that
yearly 300 million acute cases of malaria occur and more than 1 million
people die of malaria each year. Most of these victims are children under
the age of five.
According to the WHO, in areas of intense transmission, young children
may have as many as six episodes of malaria each year; the disease consumes
nearly half of annual public health care expenditures; and some 45 million
years of productive human life is lost annually to the disease.
Malaria is also a contributing factor in global poverty. The disease
severely impacts the gross domestic product of many of the poorest countriesthe
broadest measure of a nation's economy. The Wellcome Trust estimates that
malaria costs the global economy the equivalent of more than $31 billion
each year through lost productivity and health costs.
Lifecycle of a Killer
The parasite Plasmodium, which causes malaria, has four distinct
lifecycles, and it is encountered, variously, in sporozoitic, merozoitic,
trophozoitic, and gametocytic forms.
When a mosquito bites a person with malaria, it ingests red blood cells
infected with Plasmodium "gametocytes," the pathogen's sexual stage.
Inside the gut of the mosquito, the male and female gametocytes mature
and mate to form "zygotes." The products of the zygote mitosis, "ookinetes"
migrate through the peritrophic matrix lining the mosquito stomach and
form into "oocysts". The oocysts enlarge as the nucleus divides, and eventually
rupture to release thousands of motile "sporozoites," which migrate to
the salivary glands of the mosquito.
If the mosquito then bites another person, the sporozoites are incidentally
injected from the mosquito's mouth into the person's blood. Within 30
minutes, the sporozoites travel to the person's liver, enter the liver's
hepatocyte cells, and transform into "merozoites" that grow, multiply,
and infect more cells.
During the time when the parasites are in the liver, the newly infected
person does not yet felt sick. After some timeanywhere from eight
days to several monthsthe parasites leave the liver and enter red
blood cells where, as "trophozoites," they grow and multiply.
The infected red blood cells eventually burst, freeing merozoites to
attack other red blood cells and releasing Plasmodium toxins into
the blood, making the person feel sick. If at this point another mosquito
bites this sick individual, it will ingest the tiny parasites, and after
a week or more, the mosquito can infect another person.
A New Hope
One major breakthrough in the fight against malaria has been an effort,
detailed in the current issue of the journal Nature, to complete the genome
sequence of Plasmodium falciparum. There are four types of human
malariaPlasmodium vivax, P. malariae, P. ovale and P. falciparumand
Plasmodium falciparum is one of the most common and the single
most deadly type of malaria pathogen.
The sequencing was difficult because many stretches of the genome of
Plasmodium falciparum are rich in AT pairs of DNA base, which
account for 82 percent of the genome sequence. This makes Plasmodium DNA
unstable, causing it to fall apart when the scientists tried to work with
it. Add to that the sheer number of bases that had to be sequenced, and
it is no wonder some in the field thought it could never be done. One
scientist who led the sequencing effort likened it to tearing up six Bibles,
scattering them over a football field, and piecing the pages together
The DNA pages of this particular pathogenic book were taken from a Dutch
schoolgirl who contracted malaria after spending one night with her parents
aboard a barge near Schiphol Airport, Amsterdam in July, 1979. Scientists
believe she was bitten by a mosquito that came in on a plane from Africa.
The samples taken from this girl's blood over 20 years ago have proven
indispensable because scientists were able to trick the tiny parasites
into going through their lifecycle in the laboratory.
Now finished, this major, six-year, $17.9-million effort involving 185
researchers from the United States, United Kingdom, and Australia was
complemented by two other large genome-sequencing efforts. Also reported
in this week's Nature is the complete genome sequence of the rodent parasite
Plasmodium yoelii yoelii.
In the current issue of the journal Science, another international
consortium of researchers reports the genomic sequence of the Anopheles
gambiae mosquito, the primary malaria animal "vector," which is responsible
for transmitting Plasmodium falciparum in up to 90 percent of malaria
Two different groups from The Scripps Research Institute also have reports
in the latest issues of Science and Nature that detail additional
work related to this project. The combined research of the hundreds of
scientists who have been involved in this effort should result in the
identification of new targets for the development of drugs, which may
be more effective than those under development today.
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Scientists have known for more than 100 years that
malaria is caused by a microscopic parasite transmitted by a pest common
to wet, marshy placesthe mosquito Anopheles gambiae.
Illustration courtesy of the Mandeville
Special Collections Library.