Nodding Syndrome and Autism Spectrum Disorder

Nodding syndrome (NS) is a devastating childhood neurological disorder seen in clusters in Eastern Africa but of uncertain nosology. It is characterized by repetitive head nodding, atonic seizures, cognitive decline, and school dropout, wasting and stunted growth and it occurs in children subject to internal displacement, food insecurity, and exposure to infectious diseases, contaminated environment and with a number of repetitive behavioral abnormalities. On the other hand autism spectrum disorders (ASD) is a group of behaviorally defined neurodevelopmental disorders with lifelong consequences. They are defined by impairments in communication and social interaction along with restrictive and repetitive behaviors. It is a complex disorder associated with a wide range of disparate and seemingly unrelated factors such as; maternal exposure to various chemical substances, maternal exposure to child abuse, maternal evidence of Diabetes, autoimmune diseases, age of either parents at conception, exposure of infants to various chemical substances, low vitamin D levels of the infant at birth, gender of the infant and a large number of genetic factors. There are a number of similarities in the clinical, biochemical and behavioral findings in children with NS and ASD

Could Nodding Syndrome (NS) in Northern Uganda be an environmentally induced alteration of ancestral microbiota?

Hippocrates stated in 460-C.370 BC that, "All diseases begin in the Gut." This statement may be beginning to have meanings in the advent of new diseases such as Nodding Syndrome (NS) and Autism Spectrum Disorder (ASD). Interestingly, a recent publication from China in the journal of microbiology in 2017 suggests that high grain diet had dynamically shifted the composition of mucosa-associated microbiota and induced mucosal Injuries in the colon of Sheep. NS is a devastating childhood neurological disorder characterized by atonic seizure, cognitive impairment, head nodding, wasting and stunted growth. In addition, NS in Northern Uganda is clustered in time (those who were in IDPs), in space (discretely observed on either sides of the two rivers of Aswa and Pager) and in person (onset mainly between the ages of 5-15 years) and therefore exhibits spatial temporality. The first case of NS was noticed in Kitgum district in 1997, one year after the reported displacement of that community into IDP. Prior to that internal displacement, there were no reported cases of NS. The same scenario occurred in the IDPs of Odek, Gulu district where the population was displaced into IDPs in 2001 and approximately a year later in 2002, cases of NS began to appear. In the IDPs, children that eventually developed NS fed nearly exclusively on food ration provided by relief agencies and roughly a year later, cases of NS began to appear. In the other East African countries, there were no reported cases of NS prior to internal displacement and dependence on food ration. The observed common factors in the three East African regions where NS occurs at endemic proportion are perhaps: Internal displacement and feeding on relief food. These researchers suggest that NS may have perhaps resulted from dietary and environmental factors during IDPs which may have been foreign to their GIT and links this observation to the concept of microbiota-gut-brain axis

Reduced plasma concentrations of vitamin B6 and increased plasma concentrations of the neurotoxin 3-hydroxykynurenine are associated with nodding syndrome: a case control study in Gulu and Amuru districts, Northern Uganda

Introduction: Nodding syndrome was first reported in Uganda in 2003 among internally displaced populations. Risk factors for the syndrome remain unknown. We therefore explored vitamin B6 deficiency and resulting high 3-hydroxykynurenine (3-HK) levels as risk factor for nodding syndrome in Northern Uganda. Methods: Case-control study conducted in Gulu and Amuru districts. Cases were children/young adults with nodding syndrome. Healthy children/young adults were recruited as controls from same community as cases. Data on socio-demographic and other risk factors was collected using questionnaires. Whole blood was collected in EDTA tubes for assay of 3-HK and vitamin B6 using sandwich ELISA. Conditional logistic regression model was used to assess associations. Results: 66 cases and 73 controls were studied. Factors associated with nodding syndrome were being positive for 3-HK (AOR=4.50, p=0.013), vitamin B6 concentration below mean (AOR=7.22, P=0.001), child being taken care of by mother only (AOR=5.43, p=0.011), child being taken care of by guardian (AOR=5.90, p=0.019) and child consuming relief food at weaning (AOR=4.05, p=0.021). Conclusion: Having low vitamin B6 concentration which leads to a build up of 3-hydroxykynurenine concentration in cases as a main risk factor. Therefore, cases should be treated with vitamin B6 and community members should be sensitise to ensure adequate dietary intake of vitamin B6 so that the risk of nodding syndrome among children is averted. We encourage future prospective intervention study to be conducted to assess the effect of low vitamin B6 on the development of nodding syndrome via raised 3-HK concentration.Pan African Medical Journal 2016; 2

Letter to the editors Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda

Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus (OV). These findings suggest a neuro-inflammatory cause of NS and they are   important findings in the search for the cause of Nodding Syndrome. These   observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus. Many clinical and  epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease,   Onchocerciasis, some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with (OV infection (using positive skin snips), we observe that (OV is generally endemic in many parts of Sub Saharan  Africa and Latin America and that to date, no NS cases have been recorded in thoseregions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda. Key words: Nodding Syndrome, Onchocerca Volvulus, Uganda, Gul

Nodding Syndrome (NS) in Northern Uganda: A Probable Metabolic Disorder

Aims: To conduct an epidemiological study to establish the association between malnutrition, metabolic disorder and Onchocerciasis to Nodding Syndrome (NS) in Northern Uganda. Study Design: Case-control study design. Place and Duration of Study: Odek and Atiak sub counties in Gulu and Amuru districts between 10th to 20th June 2012. Methodology: We recruited consecutively 101 children with probable NS in the 2 sub counties in Gulu and Amuru districts. Controls were from the same population but without symptoms of NS and were matched by age, sex and residents. History and physical examinations were conducted; anthropometry, blood samples and skin snips were obtained from cases and controls. Researchers were pediatricians, psychiatrists, nurses, laboratory scientists and epidemiologists. The research proposal was approved by the Ministry of Health and the IRB of Gulu University. Results: There was a statistically significant association between NS with malnutrition (t=0.142; p=0.044), Onchocerciasis (Χ 2 = 152.74, p<0.001; OR 7.025 95% CI 3.891, 12.682) and High Anion Gap (Χ 2=146.752, p<0.001; OR 6.313 95%CI 4.027, 9.895). Conclusion: Nodding syndrome is associated with metabolic disorder in young children who are malnourished and infected with Onchocerciasis

Community-based training of medical students is associated with malaria prevention and treatment seeking behaviour for children under 5 years in Uganda: a study of MESAU-MEPI COBERS in Uganda

Abstract Background Four university medical training institutions in Uganda have trained students at off-site health facilities under community-based education and Research Service (COBERS) programme for over 5 years. One of the major components of COBERS placement is for the students to provide health education in the communities about malaria as a major public health disease in Uganda. This study seeks to assess if targeted community-based medical education programme is associated with better prevention and treatment seeking behaviours in the management of malaria, a leading cause of morbidity and mortality of children under five in Uganda. Methods A cross-sectional survey was done to compare communities around health facilities where medical students were placed at COBERS sites with communities around similar health facilities where medical students were not placed (non-COBERS sites). We randomly selected two villages near each health facility and consecutively selected 10 households per village for interviews using nearest-neighbour method. We used a structured questionnaire to interview household heads on malaria prevention and treatment seeking behaviour for children under 5 years. We performed univariate analysis to determine site and demographic characteristics and performed a multivariate logistic regression to assess association between dependant and independent variables. Results Five hundred twenty-three (66.8%) of the children under 5 years in COBERS communities slept under Insecticide Treated Nets (ITNs) the night before survey compared with 1451 (57.8%) in non-COBERS communities (AOR = 0.66, p = 0.017). 100 (60.0%) of children under 5 years in COBERS communities sought care for fever within 24 h of onset compared with 268 (47.0%) in non-COBERS communities (AOR = 0.71, P = 0.009). Conclusion The presence of COBERS in communities is associated with improved malaria prevention and treatment-seeking behaviour for parents of children under 5 years. Further study needs to be done to determine the long-term impact of COBERS training program on malaria control and prevention in Uganda, along with other effects of COBERS