“Artemisinin”- A Major Breakthrough In Malaria Chemotherapy

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 populations live in areas with the risk of 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.

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 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 . 

In the past 36 years, out of all antimalarial drugs discovered during this period, artemisinin was the only natural product whose medicinal properties were known for more than 2000 years. The only one synthetic antimalarial drug, mefloquine, has been discovered during this period.

Since its discovery, artemisinin has distinguished itself as a rapidly acting plasmodial agent against the blood phase of P. falciparum, and  is potent against both chloroquine-sensitive and chloroquine-resistant strains of the parasite in vitro,in vivo animal studies, and most importantly, in humans. 1,2,4-trioxane is the basic pharmacophore responsible for antimalarial activity. 

Owing to the fact that the peroxy linkage is essential for the antimalarial activity of artemisinin activity of artemisine and its derivatives, many 1,2,4-trioxane have been synthesized in different laboratory from inexpensive and readily available starting material. 

References

• http://malaria.who.int/
• Qinghaosu Antimalarial Coordinating Research Group. Chin. Med. J. 1979, 92, 811.
• Meshnick, S. R.; Taylor, T. E.; Kamchonwongpaisan, S. Microbiol. Rev. 1996, 60, 301.