Onchocerciasis-Associated Epilepsy, an Additional Reason for Strengthening Onchocerciasis Elimination Programs

A high prevalence of epilepsy is reported in many onchocerciasis-endemic regions. In this paper we discuss recent epidemiological and clinical aspects as well as public health implications of onchocerciasis-associated epilepsy (OAE) and propose a strategy to reduce the burden of disease. OAE probably presents in a variety of clinical manifestations, including the nodding syndrome and the Nakalanga syndrome. The most common clinical presentation, however, is generalized (primarily tonic-clonic) seizures. A characteristic of OAE is the onset of seizures between the ages of 3 and 18 years and clustering in certain families and villages close to rapid-flowing black-fly-infested rivers. A strategy combining active surveillance for epilepsy with early treatment with antiepileptic drugs and prevention of onchocerciasis by increasing the geographical and therapeutic coverage of community-directed treatment with ivermectin (CDTi) may considerably decrease the burden of disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/epi4.12054

Onchocerciasis-associated epilepsy: From recent epidemiological and clinical findings to policy implications.

Nodding syndrome is an epidemic neurologic disorder of unknown cause that affects children in the subsistence-farming communities of East Africa We report the neuropathologic findings in five fatal cases (13–18 years of age at death) of nodding syndrome from the Acholi people in northern Uganda Neuropathologic examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre-tangles, neuropil threads, and dot-like lesions involving the cerebral cortex, subcortical nuclei and brainstem There was preferential involvement of the frontal and temporal lobes in a patchy distribution, mostly involving the crests of gyri and the superficial cortical lamina The mesencephalopontine tegmental nuclei, substantia nigra, and locus coeruleus revealed globose neurofibrillary tangles and threads We conclude that nodding syndrome is a tauopathy and may represent a newly recognized neurodegenerative disease

/pdf/nodding-syndrome-in-uganda-is-a-tauopathy-53c8f45ien.pdf

Nodding syndrome in Uganda is a tauopathy.

Environmental, dietary and case-control study of Nodding Syndrome in Uganda: A post-measles brain disorder triggered by malnutrition?

Background
The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.
Methods
PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome.
Results
Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and
analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including
nodding and Nakalanga syndromes.
Conclusion
Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.

/pdf/onchocerca-volvulus-and-epilepsy-a-comprehensive-review-zsv45cwcra.pdf

Onchocerca volvulus and epilepsy: A comprehensive review using the Bradford Hill criteria for causation.

OBJECTIVE: To determine environmental factors associated with Nodding Syndrome (NS), a treatable but otherwise progressive form of epilepsy in east Africa.
BACKGROUND: Uncontrollable head nodding, often food-associated, was first described in Tanzania in the 1960s, with reports from 1934 (Afr. Health Sci. 13:176-82, 2013). Many develop generalized seizures. Large outbreaks of NS occurred in South Sudan (from 1991) and Uganda (from 1997), the latter affecting thousands of children. Common risk factors include population displacement, food insecurity, and systemic infection with Onchocerca volvulus, transmitted by Simulium (blackfly) in these and other sub-Sahara regions where NS is not reported.
DESIGN/METHODS: In March 2014, we conducted a case-control study of NS in Tumangu, Kitgum, Uganda. Subjects included children with probable NS (n=50) and age- and gender-matched community Controls living in epilepsy-free households (n=50). Data included a dietary questionnaire at NS onset (reported here) and urine/plasma analyses (in progress). Cases were identified by local healthcare workers and defined as 5-18 year-old persons with episodes of repetitive head nodding. Logistic regression was used to evaluate association.
RESULTS: Reported NS onset was 2000-2013, with peaks in 2003 and 2008. Month of onset was non-uniform, with all-year-aggregated peaks in April and June that were not correlated with rainfall pattern or blackfly peak biting periods. Ten locally harvested staples were limited in January to May, and food insecurity in Internally Displaced Person camps began in March and peaked in June. Eating emergency food [OR=4.0 (1.3-12.4), P=0.0162], moldy maize [OR=4.0 (1.0-16.0), P=0.0496], emergency red sorghum [OR 2.4 (0.9-6.5), P=0.0848], and (pesticide-coated) painted seed [OR 2.3 (0.9-5.8), P=0.0696], was more likely in cases than in controls.
CONCLUSIONS: Exposure to plant components with chemical substances of natural origin (mycotoxins) and synthetic origin (pesticide) are possible risk factors for NS in northern Uganda.
Study Supported by: Grant R01 NS079276 to P.S.S. Disclosure: Dr. Mazumder has nothing to disclose. Dr. Palmer has nothing to disclose. Dr. Spencer has received personal compensation for activities as a consultant for a chemical company. Dr. King has nothing to disclose. Dr. Stadnik has nothing to disclose. Dr. Lasarev has nothing to disclose. Dr. Kabahenda has nothing to disclose. Dr. Kitara has nothing to disclose. Dr. Stadler has nothing to disclose.

Ryan C. Stadnik

Papers

Environmental, dietary and case-control study of Nodding Syndrome in Uganda: A post-measles brain disorder triggered by malnutrition?

Nodding Syndrome in Uganda: Risk Factors at Disease Onset (P2.321)