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The National Defense Council Foundation
ARTEMISININ NEW HOPE FOR MALARIA VICTIMS
THE SCOURGE OF MALARIA
Malaria is one of the triumvirate of diseases that has devastated the developing world.
Along with AIDS and Tuberculosis, it has reached pandemic proportions in Asia and
Africa with some 120 million clinical cases reported annually. Although the vast majority
of Malaria deaths occur in Africa, at lease 40% of the World’s population has been
exposed to the parasite. Indeed, it is estimated that 300 million people carry the parasite.
This compares with around 40 million AIDS carriers and is exceeded only by
Tuberculosis which may be carried by as much as one-third of the world’s population.
What is particularly disturbing about Malaria, however, is that over the last century every
time a new drug has been developed to combat it, the parasite has adapted and developed
a resistance. In the 1950s quinine-based drugs such as Chloraquine and Primaquine
proved highly effective in combating Malaria, but today, anywhere from 50% to 90% of
Over the past fifteen years, the older quinine-based drugs were replaced as the treatment
of choice by Lariam (Mefloquine), a drug developed by the United States Army for
soldiers serving in Vietnam. Lariam was first produced at the Walter Reed Army Institute
of Research in 1963. Licensed to Swiss pharmaceutical giant Hoffman LaRoche, it was
approved for general use in May of 1989. Each year, thousands of civilians traveling
abroad as well as U.S. military and Peace Corps personnel take Lariam to protect them
PROBLEMS WITH LARIAM
However, like their predecessors, drugs such as Lariam are now also losing their
effectiveness. Moreover, serious side effects have been associated with Lariam, including
extreme neuropsychiatric disorders. These disorders are suspected of sparking a series of
murders at Ft. Bragg, N.C. by soldiers returning from Afghanistan where they were
administered the drug. Nor are those the only instances in which Lariam was suspected of
causing violent or psychotic behavior.
Concern over the possible neuropsychiatric side effects of Lariam caused the FDA to
require a change to the product’s label in 2002 that reads in part:
“Mefloquine may cause psychiatric symptoms in a number of patients ranging from
anxiety, paranoia and depression to hallucinations and psychotic behavior. On occasions
these symptoms have been reported to continue long after mefloquine has been stopped.
Rare cases of suicidal ideation and suicide have been reported though no relationship to
drug administration has been confirmed.”
What makes the concern over the growing drug resistance of the Malaria parasite an
even more urgent problem is that the increase in global travel, especially to areas such as
Africa and Southeast and Southwest Asia where Malaria is common raise the specter of
its return to the United States. Other tropical diseases such as the West Nile Virus have
already made there way here, and some fear it is only a matter of time before Malaria
In addition, U.S. forces are increasingly being sent to regions where Malaria is prevalent.
Therefore it is essential to have available a medication that is not only effective, but that
also is relatively free of side effects.
AN HERBAL SOLUTION?
Surprisingly, an answer to the pressing question of finding an effective Anti-Malarial has
been available for at least three decades, but it was largely ignored by Western medicine.
At about the same time the U.S. Army was looking for a new Malaria drug to give to
soldiers fighting in Vietnam, the Chinese military was engaged in the same task to protect
their own troops and those of North Vietnam. Their approach, however, was quite
China has a tradition of using herbal medicine that dates back over 2,000 years. In 1965,
Chinese military researchers began looking at traditional herbal remedies to see if they
could find one that was effective against the strain of Malaria endemic to Vietnam. In
short order they hit on an herb known as “sweet wormwood.”
Sweet wormwood had been used to treat a variety of illnesses in China for more than two
millennia. Normally administered as a tea, it had no noticeable side effects and seemed
quite effective. The Chinese military researchers were able to isolate the active ingredient
in sweet wormwood, a substance called Artemisinin, and to develop a simple process to
They found that Artemisinin was effective against all strains of Malaria, and more
important, its therapeutic action was stunningly rapid. In one clinical trial, it was found to
destroy 95% of the Malaria parasites in patients within twenty hours. The fever typically
accompanying a Malaria infection was gone within eight hours. Moreover, there were no
side effects. Other studies of Artemisinin confirmed its effectiveness and rapid action –
something particularly important for the treatment of very young children who account
But that wasn’t all of the good news concerning Artemisinin.
Because sweet wormwood is easy to cultivate and because the extraction process to
separate out the Artemisinin is simple, it was cheap to manufacture. In other words, it
was the perfect answer to the developing world’s Malaria pandemic.
Despite its promise, initially this new “miracle” cure was resisted by the World Health
Organization, UNICEF and the other international organizations trying to combat global
public health problems, largely due to a perceived lack of clinical investigation.
RESISTANCE AND REVERSAL
In 2002, Dr. Dennis Carroll, a health advisor to the Agency for International
Development called Artemisinin “… not ready for prime time …”
The World Bank and UNICEF objected to the herbal remedy claiming it was “too
At the time, a dose of Artemisinin sold for around $2 whereas a single dose
of Lariam costs from $4.50 to $6.00, making this statement somewhat incongruous
Suddenly, last April, Dr. Carroll reversed himself and became a cheerleader for
In large part it was due to the development of what is termed “ACT”
Under this approach Artemisinin is combined with a
pharmaceutical product – usually a drug called Lumefantrine that is produced by
Novartis, the huge Swiss drug conglomerate. Novartis sells the combination under the
two different brand names: “Coartem” in the developing world and in the West under the
With the involvement of a major pharmaceutical firm, Artemisinin therapy quickly
gained acceptance. In no small degree this may have because the involvement of a major
Western pharmaceutical firm made scientists more willing to accept it as a treatment.
What is particularly important about Artemisinin becoming available, however, is that
conventional pharmaceutical remedies are rapidly losing their effectiveness.
In Uganda, for example, a country which had not previously had a significant drug
resistance problem, the number of Malaria cases not responding to existing
pharmaceutical products rose from 6% in 2000 to 31% in 2003. Similar patterns of
rapidly growing drug resistance are being experienced elsewhere.
RATIONALE FOR THE COMBINATION
The reason a “combined drug therapy
” is recommended is the belief that using
Artemisinin in combination with Lumefantrine will protect the herb against losing its
Use of this approach has generated enough confidence in the world health community
that institutions such as the World Health Organization, the Global Fund for AIDS
Tuberculosis and Malaria and the U.S. Agency for International Development are
providing grants to farmers to grow more sweet wormwood so that sufficient supplies of
HOW ARTEMISININ WORKS
But how does Artemisinin work? The answer to this question may have implications for
global health that go far beyond its effectiveness against Malaria.
Artemisinin contains a bioactive peroxide molecule. It is this molecule that is the key to
its effectiveness against the Malaria parasite. Malaria grows in the body’s erythrocytes, or
red blood cells. Hemoglobin, a major component of red blood cells, contains large
amounts of “unbound
” or free iron. The iron plays a crucial role in the function of red
blood cells to transport oxygen throughout the body. The peroxide molecule in
Artemisinin reacts with the iron in the red blood cells to create free radicals that in turn
destroy the parasite’s membranes, killing it. This mechanism may be the reason why
Malaria parasites are unable to develop a resistance to Artemisinin.
The belief that oxygen plays a key role in the Artemisinin anti-malaria mechanism has
been reinforced by studies of derivatives of the substance that do not contain the peroxide
molecule. These were found to be ineffective against malaria. Further, when other drugs
such as miconazole and doxorubicin that also generate free radicals through an oxygen
interaction were used in conjunction with Artemisinin, its effect was enhanced.
Conversely when substances that retard free radical creation such as vitamin E were used
In a separate study where the antioxidant defenses of rats were manipulated, it was
discovered that those with weaker antioxidant defenses were more resistant to the Malaria
parasite, whereas those with enhanced antioxidant defenses were more vulnerable to the
But why is it so important that Artemisinin transport oxygen to cells? The answer lies in
the research of German Nobel Laureate Otto Warburg.
A POSSIBLE CANCER CURE?
Warburg won the Nobel Prize in 1928 for describing the way a cancer cell functions. A
key element of his research was to establish that cancer cells were “anaerobic
.” That is to
say that they required an ABSENCE
of oxygen to survive. Since 1928, countless
researchers have worked to find a way to transport oxygen to cancer cells. To date,
however, no successful therapy has been developed. This situation, however, may soon
Professor Henry Lai and Assistant Professor Narendra Singh of the University of
Washington have been conducting in vitro experiments to determine the effectiveness of
Artemisinin in fighting cancer. A study concerning their research published in the
Journal Life Sciences
described how the compound killed virtually all human breast
cancer cells exposed to it within sixteen hours.
According to Dr. Lai, “Not only does it appear to be effective, but it’s very selective
continued “it’s highly toxic to the cancer cells, but has a marginal impact on normal
Dr. Lai has been investigating the potential of Artemisinin in regard to treating various
types of cancer for over seven years with consistently promising results. He has
developed a “cocktail
” consisting of holotransferrin, a substance that binds with a cancer
cells “transferring receptors
,” the part of the cell that absorbs iron and a water soluble
form of Artemisinin. Cancer cells normally absorb much more iron than healthy cells.
Therefore the chemical cocktail is attracted to the diseased cells and brings the
Although full-scale human trials have not been conducted as yet, in one animal trial, a
dog with severe bone cancer was completely cured within five days of being given the
According to Dr. Lai, Artemisinin could open the door to a whole new era of cancer
treatment. Patients could be given a prescription for a pill they could take at home
without the need to go through expensive hospital-based treatments.
“That would be very easy, and this [Artemisinin] could make that possible. The
cost is another plus – at $2 a dose, it’s very cheap. And with millions of people
who have already taken Artemisinin for Malaria we have a track record
“The fascinating thing is that this was something the Chinese used thousands of
years ago. We simply found a different application.”
The real question is not whether Artemisinin will eventually become part of the arsenal
for fighting cancer as it has become part of the arsenal for fighting Malaria. Given the
amazing results of Dr. Lai’s research, it undoubtedly will. The real question is when.
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