A feverish response

Nov 18th 2004 | BEIJING AND GUILIN
From The Economist print edition

A Chinese herbal medicine is effective against malaria. But there is not
enough of it to go round

TAKE a walk through the countryside around Guilin, a bustling town in the
Guangxi region of southern China, and your eyes are immediately drawn up
towering
limestone peaks and down fast-flowing rivers. But one of the most remarkable
things in this dramatic landscape is one of the easiest to overlooka common
plant which the Chinese call qinghao, and which western botanists have dubbed
Artemisia annua. Artemisia holds the key to beating malaria, a disease that
strikes at least 300m people a year, and kills around a million, mainly young
children, throughout sub-Saharan Africa and south Asia. But Artemisia is also
at
the centre of a storm in international public health, as rising prices and
short supplies threaten global efforts to loosen malaria's grasp on the
developing world.

Artemisia has been used in Chinese medicine for more than a thousand years,
to treat everything from malaria to skin complaints. In the 1960s, Chinese
military scientists started screening hundreds of traditional herbs, including
Artemisia, in an effort to protect their soldiers from malaria. One of the
researchers, Tu Youyou, now director of the Qinghaosu Research and Development
Centre at the China Academy of Traditional Chinese Medicine, managed to extract
and
characterise a chemical called artemisinin that gives the plant's leaves
their anti-malarial punch.

Since then, scientists have developed chemical processes to convert
artemisinin into more potent derivatives. These are good at killing malarial
parasites
in the {*filter*}, but their activity wanes after a few hours. So they are best
given alongside another anti-malarial medicine, such as lumefantrine, which
attacks the parasites in a different way and over a longer period of timean
approach called artemisinin-class combination therapy (ACT). This double whammy
has
proved extraordinarily effective at treating malaria. Trials in several
African countries, as well as in India, Vietnam, Indonesia and Peru, have shown
that
at least 90% of malaria patients treated with ACT over three days recover
from the disease.

ACT has become even more important now that other anti-malarial {*filter*}, such
as chloroquine, are losing their effectiveness because malarial parasites have
evolved resistance to them. So far, resistance is not a problem with ACT, in
part because combining {*filter*} makes it much less likely that mutations in the
parasite will enable it to survive. Since 2001, the World Health Organisation
(WHO) has recommended that countries where drug resistance occurs switch to
ACT.
But international efforts to make the switch were sluggish until earlier this
year, when a stinging paper published in the Lancet accused the WHO and the
Global Fund to Fight AIDS, Tuberculosis and Malaria of medical
malpractice
for continuing to approve and fund proposals from poor countries to treat
malaria using older, cheaper {*filter*} instead of ACT.

While denying the charge, both agencies have now sprung into action. Getting
countries to switch to ACT is not only a question of securing the {*filter*}, but
also of training doctors in how to use them, and setting up surveillance
systems to monitor resistance. The WHO estimates that the world will need 132m
courses of ACT treatment (which cost up to $2.40 each) in 2005a four-fold
increase
over this yearand almost double that number in 2006. So far, the Global Fund

has set aside $205m to help finance the shift, with the promise of more to
come.

The biggest problem, at the moment, is getting enough artemisinin. Artemisia
grows like a weed across China and South-East Asia, but the best plants are
found only in certain parts of China, such as Guangxi and Hunan, which produce
most of the world's supply, and in Vietnam. The supply chain starts with local
farmers, who harvest the leaves in August, when they are richest in
artemisinin, and sell then to a handful of companies, mainly Chinese, which
extract the
chemical and change it into one of the more active derivatives. The chemicals
are then sold to the likes of Novartis, a Swiss drug giant, which produce the
combination therapies.

Just meeting this year's demand is proving tricky. The problem, says Yan
Xiaohua, the president of Guilin Pharmaceuticals, one of China's leading
producers
of artemisinin and its derivatives, is not that there are too few plants, but
that the price of leaves has shot through the roof. The reason is simple, he
says. Once the WHO made its forecast of future demand public in the spring,
the news filtered through to farmers, who quickly tripled the price of leaves,
thus jacking up the price of artemisinin and its derivatives as well. This has
caused particular headaches for Novartis, whose Chinese supplier, Kunming
Pharmaceuticals, failed to deliver the promised quantities. That means that
Novartis will only be able to fill half its promise of 10m courses of treatment
by
the end of the year.

The good news is that Mr Yan and others are optimistic that Artemisia prices
will stabilise next year. But producers are far from certain whether they can
rise to the WHO's ambitious expectations for the next two years. This week,
UNICEF, the United Nations' children's fund, and the WHO called an emergency
meeting in Copenhagen to discuss how to boost production and to keep prices
under
control.

One way would be to increase the production of Artemisia. In China, firms
such as Guilin Pharmaceuticals are trying to cultivate the plantboth on
their
own plantations and through contracts with local farmersrather than relying
on
wild leaves. Chongqing Holley, a sister company of Kunming's, has set up a
research laboratory in Hunan to help it identify high-yielding plants and
establish a seed bank. As Mr Yan points out, farming Artemisia not only gives
firms
more control over their supply, but also helps reduce the loss of biodiversity
that comes from picking wild plants. The WHO is also keen to see Artemisia
farmed elsewhere in the world. There are pilot projects to do this in Tanzania,

Kenya and Mozambique, but it will take time before the quantity and quality of
their production can make a real dent in the supply problem.

As Jeffrey Li, the head of Novartis's Chinese operation, points out, there is
also a shortage of facilities that can produce high quality artemisinin and
its derivatives. Novartis has been working with Kunming Pharmaceuticals and
Holley Pharmaceuticals to upgrade their production capacity. But the great hope

is to find a way of synthesising artemisinin in the laboratory, thereby freeing

drugmakers from the vagaries of nature. Jonathan Vennerstrom, a researcher at
the University of Nebraska, has come up with a five-step chemical process to
make compounds that can mimic the action of artemisinin derivatives. One of
them, called OZ-277, has proved more effective than artemisinin itself in both
the test-tube and in animal models of malaria. It was also shown to be safe in
recent trials in human volunteers, and a full clinical trial in Thailand is
planned soon. If this trial is successful, then further testing is planned to
see how well the new molecule performs in combination therapy. If OZ-277 lives
up to expectations, then such a therapy might be ready for market by 2008, at
less than $1 a course.

In the meantime, the world will have to meet its growing demand for
artemisinin the old-fashioned way, from nature. The trouble, according to
Fatoumata
Nafo-Traor, the director of the Roll Back Malaria department at the WHO, is
that
without more money up front, companies in the business of supplying
artemisinin are reluctant to make the $25m-30m investment that it would take to
start
planting on a large scale. Although the Global Fund has earmarked money for
this purpose, the way it is disbursed means that the process is too slow and
too
fragmented to give firms that sort of reassurance.

What is needed, experts say, is a commitment from an organisation such as the
World Bank to provide the hundreds of millions of dollars needed to buy ACT,
and a centralised global purchasing body to co-ordinate the orders. As the
Chinese proverb has it, He who plants a garden, plants happiness. With
enough
money, and better co-ordination, the world could have a bumper harvest of
Artemisiawhich would be good for poor farmers in China and poor patients in
Africa too.