WHAT if it were possible to get rid of malaria? Not just bring it
under control, but wipe it from the face of the Earth, saving 660,000
lives a year, stopping hitherto endless suffering, and abolishing a
barrier to economic development reckoned by the World Bank to cost
Africa $12 billion a year in lost production and opportunity? It is an
alluring prize, and one that Li Guoqiao, of Guangzhou University of
Chinese Medicine, thinks within reach.
Dr Li is one of the researchers who turned a Chinese herbal treatment
for the disease into artemisinin, one of the most effective
antimalarial drugs yet invented. Now he is supervising experiments in
the Comoros, using a combination drug therapy based on artemisinin, to
see if malaria can be eradicated from that island country. If it works,
he hopes to move on to somewhere on the African mainland, and attempt to
repeat the process there.
The current approach to dealing with malaria is to control the
mosquitoes (one of which is pictured above) that spread it—either by
killing them with chemical insecticides or by draining the bodies of
stagnant water that their larvae live in. That has worked in many
places. In Europe, for example, malaria once existed as far north as
Murmansk, in Russia. Now it is rare-to-non-existent. But it was never
the plague in Europe that it is in Africa, and on that continent
mosquito-control programmes may need a helping hand.
Dr Li’s approach is to attack not the mosquito, but the
disease-causing parasite itself. This parasite’s life cycle alternates
between its insect host (the mosquito) and its vertebrate one (human
beings). Crucially, as far as is known, humans are its only vertebrate
host. Deny it them and it will, perforce, wither away—an approach that
worked for the smallpox virus, which had a similarly picky appetite. In
the case of smallpox, a vaccine was used to make humans hostile
territory for the pathogen. Since there is no vaccine against malaria,
Dr Li is instead using drugs.
A combined assault
The drugs in question are artemisinin and a second antimalarial
called piperaquine—a combination made and sold under the brand name
“Artequick” by Artepharm, a firm based in Guangdong which Dr Li helped
found. Adding piperaquine to the mix reduces the risk of a strain of
parasite resistant to artemisinin evolving, because the chance that an
individual parasite will be immune to both forms of attack is
negligible. (A similar approach is employed in the combination therapies
used to treat HIV infection.)
To deny the parasites their human hosts long enough to exterminate
them in a given area, the researchers administer three doses of
Artequick, spaced a month apart. To add extra power, the first dose is
accompanied by a third drug, primaquine. Dr Li and his colleagues call
this approach Fast Elimination of Malaria through Source Eradication, or
FEMSE.
And it works—almost. The Comoros has three islands: Moheli, Anjouan
and Grande Comore. Before the experiment started, more than 90% of the
inhabitants of some villages on these islands had malaria. Song
Jianping, Dr Li’s lieutenant in the Comoros, blitzed Moheli with
Artequick in 2007. The number of cases there fell by 95%, though
reinfection from other islands caused a small subsequent rebound. In
2012 he did the same thing on Anjouan. There, the number of cases fell
by 97%. In October 2013 the campaign moved to Grande Comore, the most
populous island. When the process is complete there, nearly all of the
700,000 Comorans will have taken part in FEMSE.
Ninety-five percent, or even 97%, is not eradication. But it is an
enormous improvement and creates a position from which eradication can
be contemplated. To do that, though, means keeping an effective
surveillance programme permanently in being so that those who become
infected can be treated quickly, to stop them spreading the parasite.
That is especially important, in the view of Yao Kassankogno, the
World Health Organisation’s representative in the Comoros, because
eradicating malaria will stop people building up immunity to the disease
as children. Almost everyone in a place like the Comoros gets infected
as a child, and the immune systems of those who survive thus learn to
combat the disease, meaning that for many people subsequent bouts are
not much worse than catching a cold. If malaria did return after a
longish period of absence, Dr Kassankogno fears it could wreak havoc.
Whether FEMSE, or something similar, could be made to work on the
African mainland—or anywhere else that is not an isolated island—will
also depend on this sort of long-term monitoring, for in that case
leakage from the outside would mean even 100% local eradication would
not be enough to eliminate the parasites. In the case of the Comoros,
not everyone is convinced sufficient surveillance is happening. Dr
Kassankogno says the government’s current surveillance for the disease
is weak. Dr Song, however, says that his team has trained more than 200
Comorans to monitor rates of malaria, with a view to detecting and
preventing its return.
Safe and sound?
A more immediate concern is the safety of the drugs. Artemisinin and
piperaquine are pretty safe, but primaquine ruptures red blood cells in
people with a deficiency of an enzyme called G6PD. That can kill. And a
lot of Africans—in particular, 15% of Comorans—are G6PD-deficient.
Andrea Bosman, the head of the diagnosis, treatment and vaccines unit
of the global malaria programme at the World Health Organisation, is
critical of the experiment’s approach to looking for side-effects. He
says neither the scientists running it nor the Comoran government have
been monitoring side-effects from the drugs in a systematic way. That,
in Dr Bosman’s view, not only risks harming participating Comorans, it
is also a missed opportunity to learn lessons from the project that
would be of help to other countries in the fight against malaria.
Dr Song does not, however, believe side-effects will be a problem,
because the dose he uses is so low. He also says he has seen no evidence
of side-effects, though one hospital in Grande Comore said that the
number of patients it treated doubled in the week after the
drug-administration programme began, with people reporting nausea,
fever, stomach and back pain, headaches and chills. These are symptoms
of red-blood-cell rupture, but some are also common side-effects of
artemisinin, so would be expected anyway.
Four deaths that occurred shortly after people took the drugs have
been reported. There is no evidence that these were any more than
coincidence, but family members seem reluctant to talk about them with
journalists. Fouad Mhadji, the country’s health minister, shows no
similar reluctance. He says the four in question died of natural causes:
“One of them had the problem of cancer. One had the problem of
hepatitis B. The flu was not only in the Comoros. It was also in the
region of the Indian Ocean.”
There is also the question of informed consent to the drugs. Smallpox
vaccination permanently protected the person being vaccinated. There
was thus an individual as well as a collective benefit to offset any
possible side-effects. Prophylactic drug treatment protects only for as
long as the drugs stay in the body—which is a few weeks (and explains
the need for three rounds of treatment). Dr Song’s results suggest the
benefit is real. But it is a collective benefit. That changes the moral
calculus. On the one hand, there is the risk of healthy people being
harmed by side-effects. On the other, there is the risk of their
free-riding, by taking the collective benefits while not taking the
drugs themselves.
To avoid such free-riding, a lot of official encouragement to
participate has happened—encouragement some people regard as tipping
over into pressure and propaganda. In a public meeting in Niumadzaha, a
village in the south of Grande Comore, for example, the chief doctor of
the local health centre shouted through a megaphone: “This drug is safe
and effective. You are not being used as guinea pigs. The WHO would not
allow this administration to happen if you were being used as guinea
pigs.”
Certainly, there is a lot riding on the project. Dr Mhadji says FEMSE
will save the Comoros $11m a year in direct and indirect costs (for
comparison, its annual health-care budget is $7.6m), as well as
preserving many lives that would otherwise have been lost and saving
survivors from the brain damage malaria can cause. The eradication of
malaria will also, he hopes, make the Comoros more attractive as a
destination for tourists.
Others hope to profit, too. Artepharm has high expectations of
Artequick and is using the drug’s success in the Comoros in its
marketing campaigns in South America, South-East Asia and Africa.
Moreover, the arm of the Chinese government that administers that
country’s foreign aid, and is thus helping pay for the project, is the
Ministry of Commerce—for Chinese largesse is more explicitly tied to the
promotion of the country’s business than is aid from most Western
countries.
Not that the West is a disinterested party, for Western firms, too,
manufacture artemisinin-based malaria therapies. On that point Dr Mhadji
has strong views. He dismisses criticism of the experiment as fuelled
by competition between Western and Chinese pharmaceutical companies.
As Nick White, a malaria researcher at Oxford University’s School of
Tropical Medicine who has been working for years on eradicating malaria,
says, “This research is radical. It is controversial. It is led by a
very famous Chinese physician and investigator. There are lots of very
serious questions here and a lot of unknowns.” Or, as Oscar Wilde more
succinctly put it, “The truth is rarely pure and never simple.”
