10 April 2018 (Bangkok) – Giving paracetamol (acetaminophen) to patients ill with severe malaria made them less likely to develop potentially fatal kidney failure, say researchers in a recent study in Clinical Infectious Diseases.
The study reported for the first time that giving regular doses of paracetamol protects the kidney in adult patients with severe falciparum malaria. Each year severe malaria causes close to half a million deaths globally. Acute kidney injury (AKI) complicating severe malaria is an important cause for death. AKI occurs in 40 % of adults and at least 10 % of children with severe malaria, killing an estimated 40 % of these adults and 12-24 % of the children.
“This is an important finding, because acute kidney injury is a very common, often fatal complication in adult patients with severe malaria,” said Oxford Prof Arjen Dondorp, Head of Malaria Research at the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok. “Surprisingly simple and cheap paracetamol can protect the kidney in severe malaria and thus has the potential to reduce deaths from malaria.”
Noting that the numbers in African children with severe malaria and AKI may be underestimated because renal function was not systematically checked and cut-off values not well defined, Prof Dondorp said, “This finding now needs to be tested in African children with severe malaria.”
Funded by Wellcome and conducted by a MORU team with Bangladeshi collaborators at study sites in Chittagong and Ramu, Bangladesh, the study was led by Dr Katherine Plewes, a Vancouver, Canada-based MORU researcher.
An extensive series of earlier studies had linked the level of intravascular rupture of red blood cells (haemolysis) with oxidative stress markers (the haemoglobin released by the red blood cells is very oxidative) and kidney damage.
Dr Plewes had shown in an earlier paper that the frequent, often fatal complication of kidney failure was closely linked to the level of haemolysis. After another study in rats showed that paracetamol reduced the oxidative properties of haem, and protected the rat kidney, Dr Plewes and her team set up a clinical trial to test paracetamol as an inexpensive, safe intervention in patients with severe malaria.
Remarkably, this study showed that patients – especially those with a high level of haemolysis – who were given paracetamol developed less kidney failure than patients who weren’t given paracetamol.
“Paracetamol is potentially the first beneficial adjuvant therapy to be discovered for severe malaria,” said Dr Plewes. “We are now testing paracetamol in P. knowlesi malaria, a monkey malaria that easily skips species to humans and often causes renal failure, to confirm our study findings.”
Acetaminophen as a Renoprotective Adjunctive Treatment in Patients with Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial.Plewes K, Kingston HWF, Ghose A, Wattanakul T, Hassan MMU, Haider MS, Dutta PK, Islam MA, Alam S, Jahangir SM, Zahed ASM, Sattar MA, Chowdhury MAH, Herdman MT, Leopold SJ, Ishioka H, Piera KA, Charunwatthana P, Silamut K, Yeo TW, Lee SJ, Mukaka M, Maude RJ, Turner GDH, Faiz MA, Tarning J, Oates JA, Anstey NM, White NJ, Day NPJ, Hossain MA, Roberts LJ 2nd, Dondorp AM. Clin Infect Dis. 2018 Mar 12. doi: 10.1093/cid/ciy213. [Epub ahead of print]
Notes for editors
The Mahidol Oxford Tropical Medicine Research Unit (MORU), www.tropmedres.ac, is a research collaboration between Mahidol University in Thailand and the University of Oxford and the Wellcome Trust in the UK.
This research was funded with support from Wellcome. Katherine Plewes received support also from the Infectious Diseases Society of America ERF/NFID Young Investigator Merle A. Sande/Pfizer Fellowship in International Infectious Diseases; and the Clinician Investigator Program at the University of British Columbia, Canada.