Now Australian researchers have found combining the drug with another preparation, Primaquine, seems to restore its effect.
New Scientist magazine reports that new malaria drugs are needed badly.
The parasite which causes the disease - Plasmodium falciparum - has proved extraordinarily adept at evolving to combat many of the drugs currently on the market.
And those that are in use, known as artemisinin-based combination therapies, are expensive - and thus not readily available in the poorest countries where need is greatest.
Last week UNICEF, the United Nations Children’s Fund, warned that ۶ million people in Ethiopia, many of them children under five, were at risk of contracting malaria.
Toxic compound
Chloroquine - which is far cheaper than more modern malaria drugs - works by blocking the way the parasite breaks down human haemoglobin contained in red blood cells.
If the haem molecules remain in an uncrystallised form, they are toxic to the parasite, and kill it.
However, to be effective chloroquine must reach a high concentration in the digestive apparatus of the parasite.
Research by the Liverpool School of Hygiene and Tropical Medicine showed resistant forms of the parasite can effectively neutralise the drug by developing a mechanism that drains chloroquine away from the key area, preventing it from reaching the necessary concentration.
This means that while the drug may ease malaria symptoms, it will not cure the infection.
A team from La Trobe University in Melbourne tested the effect of combing chloroquine with primaquine, a drug normally used to treat a less severe form of malaria.
On its own, primaquine has no effect on P. falciparum, but it is structurally similar to chloroquine.
The La Trobe team believes that primaquine acts to block the pores on the surface of the parasite’s digestive apparatus - thus preventing chloroquine from leaking out.
Researcher Dr Leann Tilley said: “If you put chloroquine and primaquine together at the right concentration in the lab, it’s as effective on chloroquine-resistant parasites as chloroquine is on sensitive parasites.”
Dr Tilley, who presented her work to a meeting of the Australian Society for Microbiology in Canberra, plans to start field trials of the drug combination soon, perhaps in Indonesia.
Possible complication
Professor Ron Behrens, of the London School of Hygiene and Tropical Medicine, said primaquine was not suitable for all patients, as it could trigger the break down of red blood cells in people with an enzyme deficiency.
He said testing people for the deficiency before administering the drug combination could push costs up.
Professor Behrens said: “It is an interesting biochemical process that they have uncovered, but my anxiety is that primaquine is not an easy drug to use widely.
“However, it may be that now they have found a mechanism, they will be able to find other safer drugs to use in combination with chloroquine.”
Dr Tilley said cheap tests for the enzyme deficiency were available, but agreed they would add to the cost of treatment.
“Any trial which we set up to test the efficacy of the treatment will also need to assess the potential risk to the patients with this deficiency.”
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