Plasma Tau as a Biomarker for Neurocognitive Impairment in Pediatric Malaria

Malaria infection, illustration.
Researchers sought to determine whether acutely elevated tau levels are associated with future neurocognitive impairment in children after cerebral malaria and severe malarial anemia.

Plasma tau, which indicates injury to neuronal axons, is higher among children with cerebral malaria (CM) and severe malarial anemia (SMA), according to study findings published in JAMA Network Open.

Research is limited regarding pediatric patients with axonal injury, which occurs in acute disorders and in infections, including CM. Patients who survive CM tend to have persistent neurocognitive impairment (NCI) and children with SMA develop long-term NCI. Predicting NCI in CM is crucial for stemming future NCI in children in countries where malaria is common, according to the researchers.

The objective of the current study was to determine whether plasma tau can be a proxy marker of NCI after CM and SMA to limit the use of lumbar punctures to obtain CSF biomarkers.

Researchers assessed 467 pediatric patients with CM (n=182 aged 4.02±1.92 years, 41% girls) or SMA (n=162 aged 3.45±1.60 years, 36% girls), and also a control group of community children (n=123 aged 3.94±1.92 years, 53% girls) at Mulago Hospital in Uganda from March 2008 through October 2015. They measured total tau levels between August and September 2018 with a single-molecule array HD-1 analyzer with lower limit of tau detection of 0.024 picograms per milliliter (pg/mL).

Overall cognition, attention, and memory of children with CM or SMA at 1 week, 6 months, 1 year, and 2 years following hospital discharge were assessed. Control group individuals were assessed at enrollment and follow-up.

Children younger than 5 years were assessed with the Mullen Scales of Early Learning, the Early Childhood Vigilance Test, and the Color Object Association Test. Children aged at least 5 years were evaluated with the Kaufman Assessment Battery for Children and the Test of Variables of Attention.

Plasma tau levels greater than 6.43 pg/mL were associated with tripled (OR 3.06 P =.048) mortality in children with CM younger than 5 years. Plasma tau levels were associated with lower cognition scores at the 2 year follow-up appointment in children with CM who were younger than 5 years at baseline and follow-up (β = −0.80 P =.003). Those with CM who were younger than 5 years at baseline but older at follow-up tended to perform more poorly in assessments of attention (β = −1.08; P =.003) and working memory (β = −1.39 P =.001).

Study limitations included the utilization of 1 study cohort, lack of serial tau testing at follow-up points, and a need for additional study of mechanisms associated with NCI in patients with SMA.

“In this study, plasma tau, a marker of injury to neuronal axons, was elevated in children with CM or SMA and was associated with mortality and persistent NCI in children with CM younger than 5 years,” the researchers stated.

They also added that if more studies confirm plasma tau is a biomarker for neurological injury, a plasma tau point-of-care test could help identify children with the greatest risk of future NCI, “and therefore with the greatest needed for acute cognitive rehabilitation.”


Datta D, Bangirana P, Opoka RO, et al. Association of plasma tau with mortality and long-term neurocognitive impairment in survivors of pediatric cerebral malaria and severe malarial anemia. JAMA Network Open. Published online December 10, 2021. doi:  10.1001/jamanetworkopen.2021.38515