Jan. 28, 2014, 4:15 p.m.
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.”