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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
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
R. Colebunders, K. Coudere, N. Van der Moeren, A Hendy
(1) Landis JL, Palmer VS, Spencer PS. Nodding syndrome in Kitgum
District, Uganda: association with conflict and internal displacement. BMJ
(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
(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.
Jump to comment:
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.