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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.
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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.

Dec 17, 2015

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Spencer Goodwin
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Page 1: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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.

Page 2: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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

Page 3: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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.

Page 4: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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.

Page 5: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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

Malaria Life Cycle

Page 6: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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.

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Page 7: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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.

Page 8: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

MODE OF ACTION OF ARTEMISININ

HEMOGLOBIN HEME +GLOBIN(PROTEIN PART)

HEMOZOIN

HEME HEMOZOIN

Page 9: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

Pharmacophore for antimalarial activity

1,2,4-trioxane is the basic pharmacophore responsible for antimalarial activity.

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1,2,4-Trioxane

Deoxyartemisinin

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Page 10: Malaria  Malaria is a vector borne parasitic disease caused by the genus Plasmodium, affecting over 100 countries of the tropical and subtropical regions.

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