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doi:10.1038/nindia.2015.130 Published online 23 September 2015

Spice cure to cerebral malaria

K. S. Jayaraman

Turmeric could hold the clue to a cure for cerebral malaria 
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Researchers report complete cure for cerebral malaria in experimental mice with a therapy that includes curcumin, the yellow component isolated from turmeric (Curcuma longa), widely used in Indian cuisine1.

The study by scientists at the Indian Institute of Science (IISc) in Bangalore and the National Institute of Immunology in New Delhi raises hope for combating this severe neurological complication of infection with Plasmodium falciparum. The illness that affects the brain has very high mortality (15–20%) despite the availability of artemisinin-based therapy recommended by the World Health Organization (WHO).

In experimental mice with cerebral malaria, the researchers found that "arteether-curcumin (AC) combination therapy, even after the onset of symptoms, provided complete cure."  According to the researchers, migration of T- lymphocytes (a type of white blood cell that plays a central role in cell-mediated immunity) and falciparum parasite-infected Red Blood Cells (pRBCs) into the brain are both necessary to precipitate the disease.

"We have been able to simultaneously target both these parameters with AC combination therapy," Govindarajan Padmanabhan of IISc, who led the research, told Nature India.

The researchers designed two modules — first, to study the effect of curcumin alone before the onset of symptoms in mice with cerebral malaria and second, to study the effect of AC treatment after the onset of symptoms. The study, they say, provides "experimental evidence for the first time" that curcumin alone was able to eliminate the symptoms of cerebral malaria and delay the death of mice by 15- 20 days.

Though the curcumin treated animals did not show neurological symptoms, they eventually died of anaemia due to parasite build-up in blood. But the AC combination therapy "given even after the onset of symptoms provided complete cure by counteracting all the changes characteristic of cerebral malaria and preventing parasite build-up in blood."

Padmanabhan said the potential of curcumin to reduce T- cell as well as pRBC sequestration in the brain makes it an "ideal adjunct drug to prevent and treat cerebral malaria." In the present study all the animals were protected against mortality and are still living after six months, Padmanabhan said, when a single sub-optimal dose of arteether and three oral doses of curcumin were used. A full dose of arteethter, along with three oral doses of curcumin, could prove beneficial in the treatment of cerebral malaria in humans, the researchers say.

The curcumin-artimisinin combination — which now has a US patent No. 7,776,911 — comes close to WHO’s ideal prescription of a drug combination because curcumin is cheap, has been part of the Indian diet for ages, and is non-toxic. "In a phase-1 clinical trials, curcumin was given at a dose of 8 grams per day for 3 months without any side effects," Padmanabhan said.


References

1. Dende, C. et. al. Simultaneously targeting inflammatory response and parasite sequestration in brain to treat experimental cerebral malaria. Sci. Rep. 5, 12671 (2015) doi: 10.1038/srep12671