title: Longitudinal Visuomotor Development in a Malaria Endemic Area: Cerebral Malaria and Beyond.
abstract: Paediatric cerebral malaria is the most serious complication of Plasmodium falciparum infection. While the majority recover, long-term cognitive impairment has been highlighted as a significant and neglected problem. Persistent or serious deficits in processes such as attention or behavioural inhibition should be manifest in changes to performance on oculomotor tasks. Therefore we investigated the impact of cerebral malaria on the development of reflexive pro-saccades and antisaccades. In a longitudinal study, 47 children previously admitted with retinopathy-confirmed cerebral malaria (mean age at admission 54 months), were compared with 37 local healthy controls (mean ages at first study visit 117 and 110 months respectively). In each of three or four test sessions, over a period of up to 32 months, participants completed 100 prosaccade tasks and 100 antisaccade tasks. Eye movements were recorded using infrared reflectance oculography; prosaccade, correct antisaccade and error prosaccade latency, and antisaccade directional error rate were calculated. Hierarchical linear modelling was used to investigate the effect of age and the influence of cerebral malaria on these parameters. Data were also collected from an independent, older group (mean age 183 months) of 37 local healthy participants in a separate cross-sectional study. Longitudinal data exhibited the expected decrease in latency with age for all saccade types, and a decrease in the antisaccade directional error rate. Hierarchical linear modelling confirmed that age had a statistically significant effect on all parameters (p< = 0.001). However, there were no statistically significant differences between the cerebral malaria and control groups. Combining groups, comparison with the literature demonstrated that antisaccade directional error rate for the Malawi sample was significantly higher than expected, while latencies for all saccade types were indistinguishable from published. The high directional error rate was also confirmed in the older, healthy Malawian participants from the cross sectional study. Our observation of similar oculomotor performance in cerebral malaria and control groups at long follow-up periods suggests that cerebral malaria survivors are not at a generally increased risk of persistent cognitive deficits. Our data raise questions about the prevailing hypothesis that cerebral malaria has gross impacts on the development of processes such as attention and behavioural inhibition. More importantly, our novel finding of a clear difference in antisaccade performance between all of the Malawi participants and published data suggests that the Malawian paediatric population as a whole faces serious challenges to cognitive development beyond cerebral malaria.
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, William Duncan Building, Liverpool, L7 ATX, United Kingdom.
authors.forename: Paul C
authors.identifier: http://orcid.org/0000-0002-2578-7335
authors.initials: PC
authors.lastname: Knox
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, William Duncan Building, Liverpool, L7 ATX, United Kingdom.|Malawi-Liverpool-Wellcome Trust Clinical Research Programme, PO Box 30096, Blantyre, Malawi.
authors.forename: Ian J C
authors.initials: IJ
authors.lastname: MacCormick
authors.affiliation: University of Malawi College of Medicine, College of Medicine, P/Bag 360 Chichiri, Blantyre, Malawi.
authors.forename: Emme
authors.initials: E
authors.lastname: Mbale
authors.affiliation: University of Malawi College of Medicine, College of Medicine, P/Bag 360 Chichiri, Blantyre, Malawi.
authors.forename: Macpherson
authors.initials: M
authors.lastname: Malewa
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, William Duncan Building, Liverpool, L7 ATX, United Kingdom.|Department of Biostatistics, University of Liverpool, Waterhouse Building, Liverpool, L69 3GL, United Kingdom.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Czanner
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, William Duncan Building, Liverpool, L7 ATX, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Harding
mesh_terms: D000293:Adolescent; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005133:Eye Movements / Q000502:physiology; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D016779:Malaria, Cerebral / Q000150:complications / Q000175:diagnosis*; D008295:Malawi; D008297:Male; D009802:Oculomotor Nerve / Q000254:growth & development* / Q000502:physiology; D012438:Saccades / Q000502:physiology