Age tied to severity, mortality in knowlesi malaria
In malaria caused by Plasmodium knowlesi, age appears to be strongly associated with parasitaemia, systemic inflammation, endothelial activation, microvascular dysfunction and disease severity, according to a recent study.
“This suggests that ageing exacerbates these processes, contributing to the increased severity of disease that occurs in older adults with P. knowlesi malaria,” said researchers.
On the other hand, “[i]n falciparum malaria, endothelial activation is also associated with increasing age independent of parasite biomass, suggesting that … this may contribute to differences in disease severity and manifestations that occur in older compared to younger patients,” they added.
Investigators categorized 276 malaria patients according to the type of disease: those with knowlesi malaria (n=146; 99 nonsevere and 47 severe; median age 48 years) and those with falciparum malaria (n=130; 109 nonsevere and 21 severe; median age 27 years). Fifty controls were included in the study.
In patients with knowlesi malaria, significantly more patients in the >60 years old age group (56 percent; n=19) had severe disease compared with the 46 to 60 years old (41 percent; n=18) and 12 to 45 years old (15 percent; n=10; p<0.0001) age groups. No significant severity difference according to age was observed in falciparum malaria patients (p=0.196). [J Infect Dis 2017;215:1908-1917]
Age was also significantly positively associated with parasitaemia in knowlesi malaria patients (p<0.0001), with median parasite counts of 4,756, 8,925 and 34,017 parasites/µL in the 12 to 45, 46 to 60 and >60 years old age groups, respectively (p<0.0001). Again, no such significant correlation was apparent in the falciparum malaria patients.
In a bivariate model, both age (odds ratio [OR], 1.03; p=0.034) and parasitaemia (OR, 1.74; p<0.0001) predicted severe knowlesi malaria.
In knowlesi malaria, but not falciparum malaria, patients, interleukin (IL)-6 levels (p=0.001) and its ratio with IL-10 (IL-6/IL-10; p<0.001) were both significantly higher and correlated with age after controlling for disease severity and parasitaemia.
All three markers for endothelial activation were similarly significantly elevated in all knowlesi malaria patients, but only angiopoietin-2 levels showed significant associations with age (p<0.001) after controlling for disease severity and parasite load.
Microvascular function was also significantly impaired in patients with severe knowlesi malaria compared to those with nonsevere disease (median, 3.52 vs 6.07 units/second; p<0.001). Moreover, functional impairment was significantly associated with increasing age (p=0.018) after adjusting for disease severity and parasite biomass.
The link between worse malaria severity and mortality and increasing age has been extensively established in falciparum malaria, with various large-scale Southeast Asian studies outlining differences in manifestation, hospitalization rates and fatality risks, according to researchers. [Clin Infect Dis 2008;47:151-157; Clin Infect Dis 2003;36:990-995; J Infect Dis 1998;178:592-595]
The link between age and disease severity has also been established in various other infectious diseases like influenza and hepatitis A, which “suggests that age-related changes in innate immunity play a fundamental role in these differing disease presentations,” explained researchers. [Clin Microbiol Rev 2001;14:38-58; JAMA 2004;292:1333-1340; Methods Mol Biol 2016; 1435:235-247].
In this vein, the current study also finds that “ageing may play an important role in the host response to malaria, resulting in greater severity of disease in older adults,” with parasite biomass, microvascular function, endothelial activation and inflammation being the main factors that mediate the effect of ageing on disease severity, researchers said.