Are antimalarials safe to young children?
27 May 2014
Artemisinin based malaria drugs are viewed as safe, but animal safety studies raised concerns over their potential to cause damage to parts of the brain involved in hearing and balance. A group of scientists reviewed safety studies in humans and found a worrying lack of data from young children, the most vulnerable group. The results were published today in the American Journal of Tropical Medicine and Hygiene.
Artemisinin-based combination therapies (or ACTs) are highly effective antimalarials that have saved many lives and are the first-line treatment recommended by the WHO for uncomplicated malaria. Their safety is based on trials where treatment was given only once or twice, in adults and older children.
But in many parts of Africa – where safety is rarely monitored – younger children are at greater risk of getting malaria and may receive ACTs three or more times a year.
Animal data has shown the potential of artemisinins to damage parts of the brain involved in hearing and balance, particularly with high doses of oil-based products of artemisinins. Because of the lower doses used in humans, the implications of these findings were not clear.
Researchers from the Malawi-Liverpool-Wellcome Trust Clinical Research Programme reviewed the robustness of safety studies that examined specific neuro-auditory safety of ACTs in humans over the past decade.
Persistent lack of safety data is ‘concerning’
“Only 15 studies reported a neurological or auditory assessment”, explained the paediatrician and author Dr Virginia Ramos. “The lack of a standardized approach to drug adverse event monitoring hampered the ability to make a meaningful comparison of data collected in different studies.”
One of the project’s Principal Investigators, Dr Anja Terlouw from the Liverpool School of Tropical Medicine, said: “These highly effective antimalarials have saved many lives and are vital in the fight against malaria. But that fact shouldn’t stop us from monitoring any side-effects these drugs may have, particularly if these could be limited by a more targeted use of these drugs.”
“While there are a lot of published studies looking at efficacy of these drugs, this review highlights the persistent lack of a collective effort to obtain the required safety data in a standardized way, which is a concern,” she added.
Addressing young children’s hearing safety needs
So far, studies looking at single exposures have been reassuring in adults and children over five, but the review reveals the persistent lack of data from young children. "This knowledge gap should not merely be accepted after a decade of widespread use, but addressed as soon as possible,” Dr Ramos warned.
“Early evaluation and prevention of hearing impairment in childhood is essential as it can have severe adverse effects on speech, behaviour, linguistic understanding and language acquisition contributing to global disability,” she said.
To address this gap, scientists from the Malawi-Liverpool group and the ACT Consortium conducted a community-based study over two years in Chikhwawa district, Malawi – an area of high malaria transmission.
It involved 814 children aged 4-11 months, receiving one of two ACTs (lumefantrine-artemether or dihydroartemisinin-piperaquine). The published review shows that this remains the only study specifically designed to look at the effects in the nervous and auditory systems in this group of children receiving repeated ACT treatments.
”There are several challenges in determining this safety concern in young children, especially in remote settings where trained audiologists and equipment are not available,” explained Dr Carmen González, the paediatrician who supported the research. ”However, programmes to detect early-onset hearing loss are successful and can be implemented in developing settings by using tele-medicine”.
At the time of writing, the fieldwork for this trial has been completed and trial data is being prepared for analyses.
Photo credit: Helen Wong
Further information
- Watch a video and learn more about the ACTia study in Malawi: Safety of repeated drug use in children
- Read the article published in the American Journal of Tropical Medicine and Hygiene
- Learn more about the Malawi-Liverpool-Wellcome Trust Clinical Research Programme
