Malaria

1
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.

2
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.

3
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.

4
Malaria Life Cycle

• Mosquito infected with the malaria parasite bites
  human, passing cells called sporozoites into the
  humans 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.

5
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 mosquitos 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 mosquitos salivary glands.
• If this mosquito bites another human, the cycle
  begins again

6
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.

7
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.

8
mode of action of artemisinin
HEMOGLOBIN
HEME GLOBIN(PROTEIN PART)



HEMOZOIN

HEME
HEMOZOIN
9
Pharmacophore for antimalarial activity

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

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