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• Cause of the nodding syndrome
  Robert Colebunders
  Published on: 8 December 2014

• Published on: 8 December 2014

  Cause of the nodding syndrome

  • Robert Colebunders, Professor

  Landis et al. describe a temporal association between wartime conflict, internal displacement, and Nodding syndrome (NS)(1). They raise infectious, nutritional and neuropsychiatric elements as possible causal factors. The authors, however, do not mention a key factor that may have played a major role during the NS epidemic in northern Uganda: a lack of ivermectin treatment in onchocerciasis endemic areas.

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  Landis et al. describe a temporal association between wartime conflict, internal displacement, and Nodding syndrome (NS)(1). They raise infectious, nutritional and neuropsychiatric elements as possible causal factors. The authors, however, do not mention a key factor that may have played a major role during the NS epidemic in northern Uganda: a lack of ivermectin treatment in onchocerciasis endemic areas.

  Mass-distribution of ivermectin is routinely used to interrupt onchocerciasis transmission in endemic foci, and an association between NS and onchocerciasis has repeatedly been reported (2). NS only occurs in onchocerciasis hyperendemic areas, and other forms of epilepsy are also thought to be highly prevalent in many of these regions(3).

  During the civil war in northern Uganda (1986-2006/2008), there was no access to ivermectin in districts affected by NS, and it was only after the war that ivermectin treatment programmes were established. Ivermectin has been distributed annually in NS-affected districts since 2008, and biannually since 2012 (2). This has coincided with a dramatic drop in the number of new NS cases, and no new cases were officially reported in 2013 (4). The ivermectin distribution programme in northern Uganda was supplemented by control measures targeting blackflies (Simuliidae), the vectors of onchocerciasis, in late-2012. The Achwa and Pager rivers were initially treated with larvicides applied from boats and light aircraft, and larval breeding sites are now being treated with the organophosphate, temephos, at predefined points along the rivers (2). We believe that this integrated approach, targeting both the vectors of onchocerciasis and the parasite in the human population, has contributed to the reduction of NS cases in northern Uganda.

  The link between NS and onchocerciasis appears to be further reinforced by a recent study which suggests that an antibody-mediated autoimmune response to leiomodin-1 may be involved in the etiology of NS. Johnson et al. have demonstrated that antibodies against leiomodin-1 are more likely to be present in NS cases than in controls (5). These antibodies are also present in the cerebrospinal fluid of certain patients with NS, are neurotoxic in vitro, and cross-react with Onchocerca volvulus -specific proteins.

  We do not believe that NS can be explained by events only related to war. In the Mahenge NS-focus in Tanzania, there is no recent history of conflict or household internment. Hypotheses regarding NS etiology should be based on information from all affected regions.

  Further research is needed to explore whether NS is caused by an auto -immune reaction in response to Onchocerca volvulus infection; whether the species or strain of Onchocerca is unique in NS-affected areas, or whether NS is caused by a currently unidentified agent transmitted by blackflies (6).

  R. Colebunders, K. Coudere, N. Van der Moeren, A Hendy

  Reference List

  (1) Landis JL, Palmer VS, Spencer PS. Nodding syndrome in Kitgum District, Uganda: association with conflict and internal displacement. BMJ Open 2014;4(11):e006195.

  (2) Colebunders R, Post R, O'Neill S, Haesaert G, Opar B, Lakwo T et al. Nodding syndrome since 2012: recent progress, challenges and recommendations for future research. Trop Med Int Health 2014 October 28.

  (3) Pion SD, Kaiser C, Boutros-Toni F, Cournil A, Taylor MM, Meredith SE et al. Epilepsy in onchocerciasis endemic areas: systematic review and meta-analysis of population-based surveys. PLoS Negl Trop Dis 2009;3(6):e461. (4) Ministry of Health, Uganda. Weekly epidemiological bulletin. 2014.

  (5) Johnson T, Tyagi R, Lee PR, Leea M-h, Johnson KR, Kowalak J, Medynets M, Hategan A, Nutman TB, Sejvar J, Makumbi I, Aceng JR, Dowell SF, Nath A. Detection of auto-antibodies to leiomodin-1 in patients with nodding syndrome. j.jneuroim , 103. 2014.

  (6) Colebunders R, Hendy A, Nanyunja M, Wamala JF, van OM. Nodding syndrome-a new hypothesis and new direction for research. Int J Infect Dis 2014 August 23;27C:74-7.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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