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Systemic and cerebrospinal fluid immune and complement activation in Ugandan children and adolescents with long‐standing nodding syndrome: a case‐control study

Ogwang, Rodney, Muhanguzi, Dennis, Mwikali, Kioko, Anguzu, Ronald, Kubofcik, Joe, Nutman, Thomas B, Taylor, Mark ORCID:, Newton, Charles R., Vincent, Angela, Conroy, Andrea L., Marsh, Kevin and Idro, Richard (2021) 'Systemic and cerebrospinal fluid immune and complement activation in Ugandan children and adolescents with long‐standing nodding syndrome: a case‐control study'. Epilepsia Open, Vol 6, Issue 2, pp. 297-309.

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Nodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type— head nodding— and associated with Onchocerca volvulus infection. We hypothesized that altered immune activation in the cerebrospinal fluid (CSF) and plasma of children with nodding syndrome may yield insights into the pathophysiology and progression of this seizure disorder.

We conducted a case‐control study of 154 children (8 years or older) with long‐standing nodding syndrome and 154 healthy age‐matched community controls in 3 districts of northern Uganda affected by nodding syndrome. Control CSF samples were obtained from Ugandan children in remission from haematological malignancy during routine follow‐up. Markers of immune activation and inflammation (cytokines and chemokines) and complement activation (C5a) were measured in plasma and CSF using ELISA or Multiplex Luminex assays. O. volvulus infection was assessed by serology for anti‐Ov16 IgG levels.

The mean (SD) age of the population was 15.1 (SD 1.9) years and the mean duration of nodding syndrome from diagnosis to enrolment was 8.3 (SD 2.7) years. Majority with nodding syndrome had been exposed to O. volvulus 147/154 (95.4%) compared to community children 86/154 (55.8%), OR 17.04 (95% CI 7.33, 45.58), p<0.001. C5a was elevated in CSF of children with nodding syndrome compared to controls, (p<0.0001). The levels of other CSF markers tested were comparable between cases and controls after adjusting for multiple comparisons. Children with nodding syndrome had lower plasma levels of IL10, APRIL, CCL5 (RANTES), CCL2, CXCL13, MMP‐9 compared to community controls (p<0.05 for all; multiple comparisons). Plasma CRP was elevated in children with nodding syndrome compared to community children and correlated with disease severity.

Nodding syndrome is associated with exposure to O. volvulus. Compared to controls, children with long‐standing symptoms of nodding syndrome show evidence of complement activation in CSF and altered immune activation in plasma.

Item Type: Article
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 850 Nematode infections (General)
WL Nervous System > WL 100 General works
WS Pediatrics > Diseases of Children and Adolescents > General Diseases > WS 200 General works
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):
Depositing User: Cathy Waldron
Date Deposited: 27 Jan 2021 18:14
Last Modified: 01 Jun 2021 10:00


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