Case-Control Study of Nodding Syndrome in Acholiland: Urinary Multi-Mycotoxin Screening.

Jennifer Duringer,Peter Spencer,Rajarshi Mazumder,A Morrie Craig,Valerie Palmer

doi:10.3390/toxins13050313

Jennifer Duringer, Peter Spencer + Show 3 more

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https://doi.org/10.3390/toxins13050313

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Abstract

This case-control study adds to the growing body of knowledge on the medical, nutritional, and environmental factors associated with Nodding Syndrome (NS), a seizure disorder of children and adolescents in northern Uganda. Past research described a significant association between NS and prior history of measles infection, dependence on emergency food and, at head nodding onset, subsistence on moldy maize, which has the potential to harbor mycotoxins. We used LC-MS/MS to screen for current mycotoxin loads by evaluating nine analytes in urine samples from age-and-gender matched NS cases (n = 50) and Community Controls (CC, n = 50). The presence of the three mycotoxins identified in the screening was not significantly different between the two groups, so samples were combined to generate an overall view of exposure in this community during the study. Compared against subsequently run standards, α-zearalenol (43 ± 103 µg/L in 15 samples > limit of quantitation (LOQ); 0 (0/359) µg/L), T-2 toxin (39 ± 81 µg/L in 72 samples > LOQ; 0 (0/425) µg/L) and aflatoxin M1 (4 ± 10 µg/L in 15 samples > LOQ; 0 (0/45) µg/L) were detected and calculated as the average concentration ± SD; median (min/max). Ninety-five percent of the samples had at least one urinary mycotoxin; 87% were positive for two of the three compounds detected. While mycotoxin loads at NS onset years ago are and will remain unknown, this study showed that children with and without NS currently harbor foodborne mycotoxins, including those associated with maize.

Highlights

Nodding Syndrome (NS) is a brain disorder of childhood and adolescence that has been present over the past 20–25 years in epidemic form in northern Uganda andSouth Sudan [1,2,3,4,5,6]
Results should be viewed semi-quantitatively, as samples were compared against subsequently run matrix-matched standards. α-Zearalenol was detected in 93 of the 100 samples; of those, only 15 exceeded the limit of quantitation (LOQ), with mean concentration ± standard deviation (SD) of 43 ± 103 μg/L
We carried out a multi-mycotoxin screen for nine analytes in the urine of children with

Summary

Introduction

Nodding Syndrome (NS) is a brain disorder (tauopathy) of childhood and adolescence that has been present over the past 20–25 years in epidemic form in northern Uganda andSouth Sudan [1,2,3,4,5,6]. Severe food shortages, vermiform infection, and lack of medicine and immunization are common to NS-affected populations in these areas. Children with this disease are born normally and undergo unremarkable perinatal development before growth slows and the child becomes physically and mentally stunted, coincident with behavioral changes, periodic head nodding, and convulsions. In northern Uganda (Acholiland), an epidemic of NS (1997–2015) was associated with civil war-related movement of the population to internal displacement camps, where conditions were squalid, infectious disease rampant, and food quality very poor [10]. In March 2014, a case-control study of medical, nutritional, and other risk factors associated with NS among 5–18 year-old

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