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Malaria

Malaria is a vector borne parasitic disease caused by the
genus Plasmodium, affecting over 100 countries of the
tropical and subtropical regions of the world.

Four different Plasmodium species infect humans and cause
distinct disease patterns:
P. falciparum (malaria tropica),
P. vivax (malaria tertiana),
P. malariae (malaria tertiana) and
P. Ovale (malaria quartana)

P. falciparum and P. vivax account for 95% of malaria
infections. Of these two parasites, P. falciparum is the most
deadly one, causing cerebral malaria which, if remain
untreated, leads to coma and ultimately death of the patient.

40% of the world population live in areas with the risk of
malaria.
Malaria

Around 300-500 million clinical cases of malaria are reported
every year, of which more than a million die of severe and
complicated cases of malaria.

Malaria is known to kill one child every 30 sec, 3000 children per
day under the age of 5 years.

Malaria ranks third among the major infectious diseases in
causing deaths after pneumococcal acute respiratory infections
and tuberculosis, and accounts for approximately 2.6% of the
total disease burden of the world.

Although malaria has been widely eradicated in many parts of the
world, the global number of cases continues to rise. The most
important reason for this alarming situation is the rapid spread
of malaria parasites that are resistant to antimalarial drugs.
Malaria

Malaria parasites are transmitted from one person to
another by the female anopheline mosquito.

The males do not transmit the disease as they feed only on plant
juices.

There are about 380 species of anopheline mosquito, but only 60
or so are able to transmit the parasite.
Malaria Life Cycle

Mosquito infected with the malaria parasite bites human,
passing cells called sporozoites into the human’s
bloodstream.

Sporozoites travel to the liver. Each sporozoite undergoes
asexual reproduction, in which its nucleus splits to form two
new cells, called merozoites.

Merozoites enter the bloodstream and infect red blood cells.

In red blood cells, merozoites grow and divide to produce
more merozoites, eventually causing the red blood cells to
rupture. Some of the newly released merozoites go on to
infect other red blood cells.
Malaria Life Cycle

Some merozoites develop into sex cells known as male and
female gametocytes.

Another mosquito bites the infected human, ingesting the
gametocytes.

In the mosquito’s stomach, the gametocytes mature. Male and
female gametocytes undergo sexual reproduction, uniting to
form a zygote.

The zygote multiplies to form sporozoites, which travel to the
mosquito’s salivary glands.

If this mosquito bites another human, the cycle begins again
Artemisinin: A major breakthrough in
malaria chemotherapy

In 1967, the Chinese government launched a program to discover new
antimalarial drugs from indigenous plants.

The first written record of the antipyretic activity of tea-brewed leaves of
Artemisia annua ( See Fig. ) was described in "The Handbook of Prescriptions
for Emergency Treatments" written by Ge Hong (281-340 A.D.).

In 1971, Chinese researchers isolated, by extraction at low temperature from A.
annua (Sweet wormwood), a stable easily crystallizable compound that they
named Qinghaosu and later on named artemisinin 8.
15
4
14
5 H
O2
6
7
5a
8a 8
O
13 O
12a
12
H
11 O 10
9 16
3
1
O
8
MODE OF ACTION OF ARTEMISININ

Digestion of hemoglobin releases heme. Free heme is toxic
due to its ability to destabilize and lyse membranes, as well as
inhibiting the activity of several enzymes.

The free heme destabilises the food vacuolar membrane and
other membranes and leads to the death of the parasite.

For this reason the parasite convert the free Heme to
Hemozoin.
MODE OF ACTION OF ARTEMISININ
HEMOGLOBIN
HEME +GLOBIN(PROTEIN PART)
HEMOZOIN
HEME
HEMOZOIN
O
Pharmacophore for antimalarial
activity
O
O

1,2,4-trioxane is the basic pharmacophore responsible for antimalarial activity.
H
H
O
O
O O
O
O
H
O
O
O
O
O
O
H
O
1,2,4-Trioxane
O
O
Deoxyartemisinin
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