U. NOTTINGHAM (UK) — Scientists say they may be able to avoid the side effects of treating malaria with quinine by changing what patients eat.
Research suggests that variation in levels of tryptophan, an essential amino acid, affect how individuals respond to quinine treatment. Lower levels of tryptophan appear to increase the likelihood of side effects, which can include headaches, blindness, deafness, and even death.
The new findings published in the Journal of Antimicrobial Chemotherapy reinforce a discovery made three years ago.
Using a yeast model, which is a relatively close evolutionary neighbor of the human, a research team showed that quinine can block take-up of tryptophan, causing quinine toxicity in cells.
That finding offered new insight into the way quinine behaves and led Simon Avery of the University of Nottingham to believe that a quinine/tryptophan combination therapy might allow the use of higher quinine dosages to improve its effectiveness and reduce the risk of adverse side-effects at the same time.
A year later the team received funding to screen malaria patients in several public hospitals in the Klang Valley in Malaysia.
They found that quinine levels in patients receiving treatment for malaria were linked to the patients’ levels of tryptophan. The incidence of adverse reaction to quinine was significantly lower in patients with high levels of tryptophan.
“This new work with malaria patients shows that our earlier suggestions are largely borne out in the clinic. That is, natural variation in human levels of the amino acid tryptophan can have a marked bearing on patient responses to quinine therapy,” Avery says.
“One potential application stems from the fact that tryptophan levels can be modified by diet, possibly offering a cheap and simple way of manipulating adverse quinine responses in patients.”
About 3.3 billion people—half the world’s population—are at risk of malaria. In 2010 there were about 216 million cases of malaria and an estimated 655,000 people died from the disease. In Africa, malaria is a leading cause of death in children.
The body uses tryptophan to make the brain chemical serotonin—which is thought to produce healthy sleep and a stable mood—so a lack of tryptophan, induced by quinine, could also explain why many of quinine’s toxic effects are localized to the head region.
This on-going research fits well with evidence that quinine reactions are more severe in malnourished individuals. Tryptophan is abundant in meat but limited in yams, a staple food crop in the tropics where malaria is prevalent.
If quinine severely reduces tryptophan uptake, then it follows that people with pre-existing tryptophan deficiency, a common occurrence in undernourished populations, would be especially at risk from the drug.
Kang-Nee Ting from the Schools of Biology in the UK and Biomedical Sciences in Malaysia and Richard Pleass now at the University of Liverpool contributed to the research.
Source: University of Nottingham