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ALINGAN, MUAMIR A.
WHAT IS MALARIA
• A vector-borne infectious disease caused by protozoan
parasites.
• The term MALARIA originates from MEDIEVAL ITALIAN: MALA
ARIA – “BAD AIR”; and the disease was formerly called
ague or marsh fever due to its association with swamps.
• It is widespread in tropical and subtropical regions,
including parts of the Americas, Asia, and Africa.
• Historical records suggest malaria has infected humans
since the beginning of mankind.
• It has been infected humans for over 50,000 years, and
may have been a human pathogen for the entire history of
our species.
1880
A French army doctor
working in the military
hospital of Constantine
Algeria named Charles
Louise Alphonse Laveran
observed parasites for
the first time, inside
the red blood cells of
people suffering from
malaria. He therefore
proposed that malaria was
caused by this protozoan,
the first time protozoa
were identified as
causing disease.
1884
Ettore Marchiafava and
Angelo Celli, while
studying wet blood
smears from malarious
patients with the new
oil-immersion lens,
looked at unstained
blood and saw an active
amoeboid ring in the
red blood cells. They
then published this
finding and named it
Plasmodium.
A year later
Carlos Finlay, a Cuban
doctor treating patients
with yellow fever in
Havana, first suggested
that mosquitoes were
transmitting disease to
and from humans.
1898
It was Britain's Sir
Ronald Ross working in
India who finally proved
in 1898 that malaria is
transmitted by mosquitoes
NORMAL ANATOMY AND
PHYSIOLOGY
ETIOLOGY
PLASMODIUM
VIVAX
• P. Vivax is the most common
cause of infection, responsible
for about 80% of all malaria
cases.
PLASMODIUM
MALARIAE • However, P. Falciparum is the
most important cause of disease,
and responsible for about 15% of
infections and 90% of deaths.
PLASMODIUM
OVALE
The Parasite’s primary hosts and
transmission vectors are female
mosquitoes of the Anopheles genus.
Once in RBC,
merozoites reproduce
rapidly, producing
many more
merozoites, which
burst out of the RBC
& penetrate new
cells.
Some of these
merozoites form male
& female
gametocytes, which
can be picked up by
another mosquito.
Inside the gut of
the mosquito,
gametocytes will
The zygote then develops into an fertilize creating
Ready for
oocyst and ruptures to release zygote.
another cycle.
thousands of sporozoites.
Only female mosquitoes feed on
blood, thus males do not
transmit the disease. The
females of the Anopheles genus
of mosquito prefer to feed at
night. They usually start
searching for a meal at dusk,
and will continue throughout
the night until taking a meal.
sulfadoxine-pyrimethamine (Fansidar®)
mefloquine (Lariam®)
atovaquone-proguanil (Malarone®)
quinine
doxycycline
artemisin derivatives
primaquine
social mobilization
education sessions
JOURNALS Mosquito Nose Transplants Help Fight Malari
Main Category: Tropical Diseases
Also Included In: Biology / Biochemistry; Aid / Disasters
Article Date: 16 Feb 2010 - 9:00 PDTIn .
a new approach to combating malaria, a disease that affects half a billion people worlwide, US scientists
successfully transplanted most of the "nose" of the disease-spreading Anopheles mosquito into frogs'
eggs and fruit flies so they could analyse the insect's odorant receptors and find out how to lure it into
traps and even prevent it being able to detect and thereby target humans.
You can read about the two studies by researchers from Yale University in New Haven, Connecticut,
and Vanderbilt University in Nashville, Tennessee, in a report in the 3rd February online issue of the
journal Nature and there is also a complementary article in the Proceedings of the National Academy
of Sciences, PNAS.
The mosquito Anopheles gambiae is the major route through which humans in sub-Saharan Africa
become infected with malaria. While we know that the insect uses its sense of smell to find human
hosts, we know little about the underlying molecular process.
A mosquito's "nose" is in its antennae which carry nerve cells covered with odorant receptors that
react to different chemical compounds in the insect's environment. These receptors are similar to
those that give us our senses of smell and taste in our nose and on our taste buds.
Co-author Dr Laurence Zwiebel, professor of biological sciences at Vanderbilt, told the press
that:"We've successfully expressed about 80 percent of the Anopheles mosquito's odorant receptors
in frog's eggs and in the fruit fly antennae."
Zwiebel's lab at Vanderbilt is where they successfully transplanted the
receptors into frogs' eggs. The transplant into fruit-fly (Drosophila melanogaster) eggs
was done at the laboratory of John Carlson, Eugene Higgins Professor of Molecular,
Cellular and Developmental Biology at Yale and is written up as a complementary
study in PNAS.
Scientists have previously used frogs' eggs to study olfactory receptors in moths,
bees and fruit flies. For this study, the researchers injected DNA that codes for the
mosquito's olfactory receptors into a frog egg and waited for it to produce proteins.
Eventually the surface of the egg became covered with mosquito odorant receptors.
They then tested the engineered egg's reaction to being exposed to various odorant
chemicals. They floated the egg in a buffer solution in a voltage clamp (so they could
measure changes in the egg's electrical properties) and dissolved the chemicals one
by one in the solution. They detected a measurable electrical response in the egg.
Guirong Wang, lead author of the PNAS study, and a senior researcher in Zwiebel's
lab, said:"The frog egg system is relatively rapid, highly sensitive and allows us to do
very precise measurements of odorant response."
Wang, who personally conducted several thousand measurements of egg responses
to changes in odorant, described this method as a "medium throughput system",
because although they could set it up quite quickly, they had to make the odorant
solutions by hand, which took much longer.
Antioxidants May Help Prevent Malaria Complications That Damage Brain
Using an experimental mouse model for malaria, an international group of scientists has discovered that adding
antioxidant therapy to traditional antimalarial treatment may prevent long-lasting cognitive impairment in cerebral
malaria. Their findings were published online June 24, 2010, in the journal PLoS Pathogens.
Malaria, an infection caused by parasites that invade liver and red blood cells, is transmitted to humans by the
female Anopheles mosquito. Malaria is one of the leading infectious diseases worldwide, affecting more than 400
million people and causing more than 2 million deaths each year, mainly among African children. Recently, the
U.S. Centers for Disease Control and Prevention (CDC) issued a report on 11 laboratory-confirmed cases of
malaria among U.S. emergency responders and those traveling in the United States from Haiti.
Cerebral malaria is a severe, potentially fatal neurologic complication of infection by the most-feared malarial
parasite, Plasmodium falciparum. Recent studies of children with cerebral malaria indicate that cognitive deficits,
which may impair memory, learning, language, and mathematical abilities, persist in many survivors even after
the infection itself is cured.
"Cerebral malaria and its molecular mechanisms are under intense study, but the cognitive dysfunction that can
persist in survivors in the aftermath of successful treatment has gone unrecognized until recently," says Guy A.
Zimmerman M.D., professor and associate chair for research in the University of Utah School of Medicine's
Department of Internal Medicine and a contributor to the study. "This complication may impose an enormous
social and economic burden because of the number of people at risk for severe malaria worldwide. Our findings
demonstrate that, by using experimental models of cerebral malaria in mice, we can explore mechanisms of
cognitive damage and also examine potential treatments for reducing or preventing neurologic and cognitive
impairment."
Zimmerman and colleagues in Brazil studied the persistence of cognitive damage in mice with documented
cerebral malaria after cure of the acute parasitic disease with chloroquine, an antimalarial therapy. By
administering a battery of behavioral tests to these mice, post-doctoral fellow Patricia Reis, Ph.D., determined
that impairment in memory skills was still present 30 days after the initial malaria infection. Cognitive deficits that
persist for years after the episode of cerebral malaria have also been reported in 11 percent to 28 percent of
children who survive the infection.
"Although we believe that long-term cognitive dysfunction after cerebral malaria is initiated by injury to the brain
during the initial period of untreated infection, it is possible that the mechanisms for persistent cognitive deficits
are independent of those that cause neurological injury and death during acute cerebral malaria," says
Zimmerman. "Future research is aimed at clarifying this point. However, we have been able to demonstrate that
oxidative stress is present in the brains of mice infected with cerebral malaria."
Malaria And Algae Linked To Common Ancestor By 'Little Brown Balls'
Unconspicuous "little brown balls" in the ocean have helped settle a long-standing debate
about the origin of malaria and the algae responsible for toxic red tides, according to a new study
by University of British Columbia researchers.
In an article published this week in the Proceedings of the National Academy of Sciences Early
Edition, UBC Botany Prof. Patrick Keeling describes the genome of Chromera and its role in
definitively linking the evolutionary histories of malaria and dinoflalgellate algae.
"Under the microscope, Chromera looks like boring little brown balls," says Keeling. "In fact, the
ocean is full of little brown and green balls and they're often overlooked in favour of more
glamorous organisms, but this one has proved to be more interesting than its flashier cousins."
First described in the journal Nature in 2008, Chromera is found as a symbiont inside corals.
Although it has a compartment - called a plastid - that carries out photosynthesis like other algae
and plants, Chromera is closely related to apicomplexan parasites - including malaria. This
discovery raised the possibility that Chromera may be a "missing link" between the two.
Now Keeling, along with PhD candidate Jan Janouskovec, postdoctoral fellow Ales Horak and
collaborators from the Czech Republic, has sequenced the plastid genome of Chromera and
found features that were passed down to both apicomplexan and dinoflagellate plastids, linking
the two lineages.
"These tiny organisms have a huge impact on humanity in very different ways," says Keeling.
"The tool used by dinoflagellates and Chromera to do good - symbiosis with corals - at some
point became an infection mechanism for apicomplexans like malaria to infect healthy cells.
"Resolving their evolutionary origins not only settles a long-standing scientific debate but could
ultimately provide crucial information for tackling diseases and environmental concerns."
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