Wormwood and Artemisinin - A Malaria Medicine from Nature
Artemisia and Wormwood
Wormwood is the name used for herbaceous plants in the genus Artemisia. The plants are known for their extremely bitter taste. A chemical called artemisinin is extracted from the flowers, leaves and stems of one species of wormwood. Artemisinin is an important substance because it acts as an anti-malaria drug. It has been so successful in treating malaria that the scientist who discovered the chemical's effect was awarded a Nobel Prize for Physiology or Medicine in 2015.
The genus Artemisia plays several interesting roles in human life and culture. For example, Artemisia absinthium is an ingredient in the distilled alcoholic beverage known as absinthe. The drink is made from wormwood, anise, fennel, other spices and herbs, alcohol and water. Wormwood is also mentioned in the Book of Revelation in the Bible. Here its name is given to a star that falls to Earth, filling the waters with bitterness and killing people. There is preliminary evidence that artemisinin may be useful in destroying cancer cells. The most important use of wormwood at the moment is its role in fighting malaria, however.
When scientists write the scientific name for an organism, the genus is often abbreviated to one letter after it's been written in full at least once. For example, Plasmodium vivax may be abbreviated to P. vivax.
Malaria is a tropical and subtropical disease that is a risk in a large proportion of the planet. According to WHO (World Health Organization), almost half the world's population lives in an area where malaria is endemic. The disease is not only very unpleasant but is sometimes fatal. The good news is that the death rate is decreasing. The bad news is that the parasite that causes the disease is becoming resistant to anti-malaria drugs in some parts of its range.
Malaria is caused by five species of a one-celled parasite named Plasmodium. The parasite belongs to a group of organisms known as protozoans. Malaria caused by Plasmodium falciparum is more likely to be deadly than the disease caused by other species of its genus. Malaria produced by P. vivax. P. ovale and P. malariae is generally milder. P. knowlesi causes malaria in certain species of macaques. It was once thought to be unimportant with respect to humans, but it's now known to be a zoonotic species. Zoonotic organisms can infect both animals and humans. Most cases of human malaria are the result of a P. falciparum or P. vivax infection.
Key Facts about Malaria from WHO
According to the latest WHO estimates, released in September 2015, there were 214 million cases of malaria in 2015 and 438,000 deaths.— World Health Organization
Symptoms of Malaria
The symptoms of uncomplicated malaria generally appear ten to fifteen days after the bite of an infected mosquito but may not develop until as long as thirty days after the bite. Common symptoms include:
- a high fever
- chills that produce shaking
- a headache
- body aches
Unfortunately, the malaria parasite sometimes produces effects beyond the basic ones. Complicated malaria is a serious condition. Symptoms may include:
- serious anemia due to loss of red blood cells
- seizures, confusion and coma due to a complication known as cerebral malaria
- difficulty in breathing
- hypoglycemia (very low blood sugar)
- low blood pressure and cardiovascular collapse
- kidney failure
Another problem linked to malaria is that the parasite may stay in the liver in an inactive form after a person has apparently been cured of the disease. The dormant parasite may become active up to a year later, causing malaria symptoms once again.
Life Cycle of the Malaria Parasite
The malaria parasite requires both a human and a female mosquito in order to complete its life cycle. Only female mosquitoes suck blood, which is an essential factor in the transmission of the parasite between its two hosts. The females need the nutrients in blood to produce their eggs.
Plasmodium Life Cycle
Plasmodium exists in different forms, each with a different name. It changes from one form to another during its life cycle. The form of the parasite in a mosquito's saliva is known as a sporozoite.
- A female mosquito belonging to the genus Anopheles injects anticoagulant into a human's bloodstream during a bite. Sporozoites from her saliva enter the victim's blood during this process. The sporozoites travel to the liver and infect its cells.
- Each sporozoite produces merozoites, which break break out of the liver cells and enter red blood cells.
- Merozoites in the red blood cells produce more merozoites. These burst out of the red blood cells, destroying them and releasing toxins produced by the parasite's activities. This stage corresponds with the typical symptoms of malaria.
- Some merozoites produce male and female gametocytes instead of producing more merozoites.
- When a mosquito bites an infected human and sucks up blood, the red blood cells containing the gametocytes enter the insect's digestive tract.
- Inside the insect's gut, the gametocytes leave the red blood cells.
- The gametocytes become male and female gametes, which are the reproductive cells.
- A male and female gamete join to form a zygote.
- The zygote becomes an ookinete, which burrows into the wall of the mosquito's digestive tract and forms oocysts.
- The oocysts produce sporozoites, which enter the body cavity of the mosquito. This cavity is known as the hemocoel and contains fluid.
- The sporozoites travel to the mosquito's salivary glands. When the mosquito bites a human, the cycle begins again.
Artemisia and Artemisinin
Wormwood plants belong to the daisy family, whose scientific name is the Asteraceae. The family used to be known as the Compositae family because the flowers have a composite structure. Although a flower head of Artemisia looks like a single flower, it's actually an inflorescence consisting of many smaller flowers. The inflorescense of Artemisia is not as big and showy as those of many members of the daisy family, however. The leaves of wormwood are generally deeply divided into leaflets.
Artemisia is a widespread plant that occurs in many parts of the world. The common name used for some members of the genus is sagebrush rather than wormwood. The sagebrush species that is often associated with dry areas of the western United States is Artemisia tridentata.
Artemisinin is obtained from the sweet wormwood, or Artemisia annua. The artemisinin concentration is highest in the young plant. The plant is native to Asia but has been found growing wild in other parts of the world, including North America.
We owe the modern use of artemisinin in malaria treatment to Chinese traditional medicine and a very persistent scientist, as described below. China has a rich tradition of using nature to treat disease. Fourth-century Chinese doctors discovered that sweet wormword relieved fever and used it as a medicinal plant.
How Does Artemisinin Work?
It's not known for certain how artemisinin cures malaria. There are several theories, most of them relating to the peroxide bridge in the molecule. In the diagram below, the two oxygen atoms joined together inside the first polygon form the peroxide bridge. The bridge is sometimes known as an endoperoxide because it's part of the inner structure of the molecule. ("Endo" means "within".) This type of chemical structure is very unusual in the molecules of living things.
While inside red blood cells, Plasmodium feeds on hemoglobin, the red pigment that carries oxygen from the lungs to the tissue cells. Hemoglobin contains iron. A leading theory for the action of artemisinin states that the iron that is released from the hemoglobin reacts with the peroxide in the artemisinin. This leads to the production of very reactive forms of oxygen known as radicals. Radicals are also known as free radicals and reactive oxygen species, or ROS. The oxygen radicals are believed to damage and kill the parasite.
Tu Youyou and a Nobel Prize for Physiology or Medicine
Tu Youyou discovered the effect of artemisia (or qinghao as it's known in China) on malaria. She's a Chinese chemist who was born on December 30th, 1930. Her name is written as both Tu Youyou and Youyou Tu in the western literature. Her first or given name is Youyou and her surname or family name is Tu. In China, the surname is written before the first name.
Tu Youyou discovered a modern use of Artemisia rather than the herb itself. At the start of her research, a new malaria medicine was badly needed. Youyou performed a very diligent and comprehensive search of the literature relating to traditional Chinese medicine. She looked for materials with properties that might enable them to attack malaria and then tested them. She realized that sweet wormwood might be a suitable candidate, since it reportedly relieved intermittent fever. In the past, the plant was traditionally gathered early in the growing season, added to water and pounded in a mortar and pestle to extract the contents.
Youyou and her colleagues tried extracting the active principle of Artemisia (artemisinin or qinghaosu) with hot water, but the resulting liquid had no effect on mice with malaria. They then extracted artemisinin with cold water and were delighted to find that the liquid was a successful malaria cure. Youyou continued to explore the medication and made other significant discoveries.
Today semi-synthetic versions of artemisinin are used to treat malaria. Researchers have discovered ways to make artemisinin miore effective, such as by improving its solubility. The natural chemical is still used as a starting point, though.
Two other scientists won a 2015 Nobel Prize for Physiology or Medicine at the same time as Tu Youyou. William C. Campbell and Satoshi Omura received the award and part of the prize money for their discovery of a new therapy for roundworm infections.
Between 2000 and 2015, malaria incidence (the rate of new cases) fell by 37% globally. In that same period, malaria death rates fell by 60% globally among all age groups.— World Health Organization
Artemisinin on its own has treated malaria very successfully for many years and has saved many lives. It's currently given in combination with another drug, however. Artemisinin-based Combination Therapy, or ACT, is necessary because in some places the malaria parasite is becoming resistant to artemisinin. This is a worrying discovery. ACT provides both artemisinin and a second drug that works by a different mechanism. The goal is for the second drug to kill the parasite cells that survive the artemisinin attack.
At the moment, in most areas ACT is a good treatment for all types of malaria. It's especially useful for malaria caused by P. falciparum. In general, we seem to be winning the war against the disease. If ACT loses its effectiveness, however, the parasite may get the upper hand. There are other medications for malaria, but the parasite is developing resistance to them, too. Searching for new medicines and reducing the incidence of disease by reducing the number of mosquitoes are both very important practices. Malaria is an enemy that needs to be beaten.
© 2016 Linda Crampton
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