Managing diet better could aid in fight against side-effects of anti-parasitic drug
Adverse side-effects caused by the anti-parasitic drug quinine in the treatment of malaria could be controlled through diet; that's the finding of a new study from a team of scientists from Malaysia and the United Kingdom.
Writing in the Journal of Antimicrobial Chemotherapy, the researchers show that natural variation in our levels of the amino acid tryptophan has a significant influence on how we respond to quinine treatment. The lower our levels of tryptophan, the more likely it is that we will suffer side-effects.
As tryptophan is an essential amino acid that the body cannot produce itself, we control our level of tryptophan through the types of food we eat.
Quinine has been used in anti-malaria treatment since the 1600s, but despite its attributes it comes with a range of side-effects, from sickness and headaches to blindness, deafness and in rare cases, death.
Previous research from the team used a yeast model, which is a relatively close evolutionary neighbour of the human, and showed that quinine can block take-up of tryptophan, causing quinine toxicity in cells. This work provided new insight into the way quinine behaves and led the team to believe that a quinine/tryptophan combination therapy might allow the use of higher quinine dosages to improve the effectiveness of the drug and reduce the risk of adverse side-effects.
Now, building on this work, for their latest study the scientists screened malaria patients in several public hospitals in the Klang Valley in Malaysia and they discovered that quinine levels in patients receiving treatment for malaria were linked to patients' levels of tryptophan. They also showed that the incidence of adverse reaction to quinine was significantly lower in patients with high levels of tryptophan.
Lead researcher Dr Simon Avery from the University of Nottingham comments: '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. 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.'
According to the World Health Organization (WHO), about 3.3 billion people are at risk of malaria worldwide. In 2010 there were about 216 million cases of malaria and an estimated 655 000 people died from the disease.
Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. Symptoms of malaria include fever, headache, and vomiting, and usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs. Unfortunately, in many regions of the world, the parasites have developed resistance to a number of malaria medicines.
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 malnourished populations, would be especially at risk from this drug.
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Document Reference: Islahudin, F., et al. 'Quinine interactions with tryptophan and tyrosine in malaria patients, and implications for quinine responses in the clinical setting', J. Antimicrob. Chemother, 2012. doi:10.1093/jac/dks253
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