The Anatomy of a Parasite
By Jason Socrates
Bardi
"And
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 are protracted...."
——Hippocrates,
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 places—the mosquito Anopheles
gambiae—the 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 people.
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 disability—particularly among children—it
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 countries—the 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 time—anywhere
from eight days to several months—the 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 malaria—Plasmodium vivax,
P. malariae, P. ovale and P. falciparum—and 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 A–T
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 again.
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
cases worldwide.
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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