Thrombocytopenia May Mediate Disease Severity in Plasmodium Falciparum Malaria Through Reduced Transforming Growth Factor Beta-1 Regulation of Pro- and Anti-Inflammatory Cytokines

Document Type



Paediatrics and Child Health (East Africa)



Transforming growth factor beta-1 (TGF-β1) is an important regulator of inflammation. Platelets are a major source of TGF-β1, and are reduced in severe malaria. However, the relationships between TGF-β1 concentrations and platelet counts, pro- and anti-inflammatory cytokine and chemokine concentrations, and disease severity in malaria have not been characterized.


Platelet counts and serum concentrations of TGF-β1 and interleukin-1beta (IL–1β), IL-6, IL-10, interferon (IFN)–γ, tumor necrosis factor (TNF)- α and RANTES were measured at the time of presentation in Ugandan children with cerebral malaria (CM, n=75), uncomplicated malaria (UM, n=67) and healthy community children (CC, n=62).


TGF-β1 concentrations decreased with increasing severity of disease (median concentrations (25th, 75th percentile) in ng/ml in CC, 41.4 (31.6, 57.4), UM, 22.7 (14.1, 36.4), CM, 11.8 (8, 21), P for trend<0.0001). In children with CM or UM, TGF-β1 concentrations correlated positively with platelet count (CM, P<0.0001, UM, P=0.0015). In children with CM, TGF-β1 concentration correlated negatively with IFN-γ, IL-6, and IL-10 and positively with RANTES concentrations (all P<0.01). TGF-β1 concentration was not associated with death or adverse neurologic or cognitive outcomes in children with CM.


TGF-β1 concentrations decrease with increasing P. falciparum disease severity. In cerebral malaria, thrombocytopenia correlates with decreased TGF-β1, and decreased TGF-β1 correlates with cytokine/chemokine changes associated with increased disease severity and death. Thrombocytopenia may mediate disease severity in malaria through reduced TGF-β1-mediated regulation of cytokines associated with severe disease.


This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

The Pediatric infectious disease journal