Cumulative Plasmodium falciparum infections do not drive long-term telomere shortening in Kenyan children

Background Malaria is a severe and fatal disease in the non-immune, but severity lessens with increasing exposure. Children in endemic areas are at a particularly high-risk for malaria, often experiencing multiple sequential clinical and asymptomatic P. falciparum infections annually. Whether the associated persistent cellular activation has additional hidden costs, as reflected by cellular aging, has not been studied. Methods We measured correlations between telomere length (TL) in cross-sectional blood samples (2007, 2010 and 2013) and cumulative malaria and P. falciparum infection episodes in children from two longitudinal cohorts under active weekly surveillance for febrile malaria. TL was quantified by qPCR in 218 children from Junju, an area of moderate transmission, and 90 age-matched controls from Ngerenya, where P. falciparum transmission is no longer endemic. Results Although TL declined with age (independently of cumulative malaria exposure; linear effects model, p>0.05) in both cohorts, the decline was more pronounced in those with longer TL at baseline. Asymptomatic P. falciparum parasitaemia, at the time of the cross-sectional survey, was associated with a positive change in TL of 0.22 kb (95% confidence interval 0.02-0.42, p=0.03). Conclusion Overall, repeated asymptomatic and symptomatic P. falciparum malaria episodes were not associated with TL shortening in the children in our cohorts. The apparent increase in length with asymptomatic malaria was of marginal statistical significance and could have been a chance finding. Alternatively, the suppression of cellular activation and proliferation, recently reported in asymptomatic Plasmodium spp infections, preserves TLs from degrading.