Effect of regularly dosed paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW Study)Evaluating the effect of regularly-dosed paracetamol in improving kidney function in Plasmodium knowlesi malaria
The monkey parasite, Plasmodium knowlesi, is now the commonest cause of human malaria in Malaysia. Acute kidney injury (AKI) is a common complication and can kill. AKI of any cause can also have long-term health consequences, including increased risk of chronic kidney and cardiovascular disease, and increased mortality. Additional management strategies are therefore needed to prevent and reduce severity of AKI in malaria. In the related infection, falciparum malaria, haemolyis (breakdown of red blood cells) leads to release of toxic cell-free haemoglobin which contributes to AKI via oxidative damage. Paracetamol can inhibit this process, and in our small pilot study of Bangladeshi adults with falciparum malaria, regularly-dosed paracetamol was associated with improved kidney function at 72 hours. Larger studies are needed to confirm this effect. In knowlesi malaria, red cell-breakdown is greater than in falciparum malaria. Thus, paracetamol may be even more protective than in falciparum malaria.
This study is a randomised trial to assess whether paracetamol can prevent/reduce AKI in knowlesi malaria. Malaysian adults and children (>5y) hospitalised with knowlesi malaria will be randomly assigned to receive either regularly-dosed paracetamol, or no paracetamol, together with standard anti-malarial treatment. We will measure kidney function at enrolment, and daily thereafter, as well as other markers of kidney injury, red cell-breakdown and oxidative damage. The primary endpoint will be the relative change in creatinine at 72 hours, in patients who received paracetamol vs. no paracetamol. Secondary endpoints include the effect of paracetamol on markers of blood vessel and oxidative damage.
Paracetamol is cheap and widely available. If we demonstrate that regular dosing prevents or reduces kidney damage in knowlesi malaria, then this intervention could be readily implemented and will have substantial short and long-term benefits. Our findings may also be applicable to falciparum malaria and as other diseases with haemolysis-induced AKI.