An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda

Abstract

IntroductionNodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda.MethodsIn December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations.ResultsSurveillance identified 224 cases; most (95%) were 5–15-years-old (range = 2–27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6–46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1) = 14·4 (2·7, 78·3)], exposure to munitions [AOR1 = 13·9 (1·4, 135·3)], and consumption of crushed roots [AOR1 = 5·4 (1·3, 22·1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%).ConclusionNS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.

Unravelling the mysterious onchocerciasis—nodding syndrome link: new developments and future challenges

“…Some cases having NS-like clinical features have been described in a number of onchocerciasis-endemic African countries (1), however it is in Northern Uganda (2) and Southern Sudan (3) were epidemic proportions have been noted. First described by Louise Jilek-Aall in Tanzania in the 1960s (4), NS core clinical features are the atonic seizures manifesting as repetitive head nodding episodes (5), often occurring in association with taking a meal or by cold weather, and may be trailed or heralded by other seizure types, behavioural difficulties and deteriorating cognitive function (5)(6)(7).…”

“…Whereas an epidemiological association has consistently been demonstrated between infections with the nematode parasite Onchocerca volvulus (OV), transmitted to humans by the black fly (Simulium sp.) (with a higher sero-positivity prevalence seen among NS cases as well as in those from the affected geographical areas) the evidence regarding its contribution as a cause of NS has been inconclusive (2,5,10). This has stemmed from the lack of proof of microfilariae and adult OV worms' capacity to invade the central nervous system, in spite of some reports of cerebral spinal fluid (CSF) infestation by microfilariae (16).…”

“…Notably, studies have shown a lack of evidence of CSF inflammation (5,10) in NS and it seems unrelated to a known viral infectious aetiology (2,5,10). A plausible explanation for a negative CSF inflammation finding however, could be related to the timing in which the children having NS are identified.…”

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

“…84 The cause of NS remains unknown but there appears to be an unexplained link with Onchocerciasis infection. [88][89][90] The African Programme for Onchocerciasis Control, which operated in the three afflicted countries, adopted mass drug administration of ivermectin in 1997. However, it was not always possible to operate in conflict-affected regions.…”

Reducing neurodevelopmental disorders and disability through research and interventions

“…This condition is characterized by episodes of repetitive nodding (dropping forward of the head) often coupled with seizure-like behaviours (for example, convulsions or staring spells) that occur during attempted feeding 32,33 . Nodding syndrome is also characterized by stunted brain growth, including significant brain atrophy near the hippocampal and glia matter of the brain and significant cerebellar involvement.…”