Nodding syndrome is unlikely to be an autoimmune reaction to leiomodin-1 after infection by Onchocerca volvulus.

Nodding syndrome is a neurological disease of children in northern Uganda. Infection with the nematode parasite Onchocerca volvulus has been epidemiologically implicated as the cause of the disease. It has been proposed that an autoantibody directed against the human protein leiomodin-1 cross reacts with a tropomyosin-like nematode protein, thus suggesting that nodding syndrome is an autoimmune brain disease due to extra-cerebral parasitism. This hypothesis is dependent on constitutive neuronal expression of leiomodin-1. We tested this hypothesis by studying the distribution of leiomodin-1 in the normal human brain and other human tissues using immunohistochemistry. We found that immunostaining for leiomodin-1 follows a smooth muscle cell specific pattern. In the brain, it is confined to the smooth muscle cells of cerebral blood vessels and is not generally present in neurons or glia. However, immunoreactivity was identified in human Purkinje cell membrane and the body wall of C. elegans (as a proxy for Onchocerca volvulus) but only when immunostained with an antibody recognizing the N-terminal of leiomodin-1. Homology between leiomodin-1 and tropomodulin, specifically at the N-terminus, could explain why leiomodin-1 antibody cross reactivity between human Purkinje cells and C. elegans. However, we cannot provide proof confirming that the immunoreactivity in the membranes of Purkinje cells is specifically caused by the expression of tropomodulin. To overcome this limitation, further investigations using additional immunohistochemical and biochemical studies are required to corroborate our findings and provide more comprehensive evidence. Nevertheless, our findings do not support to the autoimmunity hypothesis involving Onchocerca volvulus and leiomodin-1. To gain a more comprehensive understanding of the cause and pathogenesis of NS, it is essential to explore alternative hypotheses.

The spectrum of disease and tau pathology of nodding syndrome in Uganda.

Nodding syndrome is an enigmatic recurrent epidemic neurologic disease that affects children in East Africa. The illness begins with vertical nodding of the head and can progress to grand mal seizures and death after several years. The most recent outbreak of nodding syndrome occurred in northern Uganda. We now describe the clinicopathologic spectrum of nodding syndrome in northern Uganda. The neuropathologic findings of 16 children or young adults with fatal nodding syndrome were correlated with the onset, duration and progression of their neurological illness. The affected individuals ranged in age from 14 to 25 years at the time of death with a duration of illness ranging from 6-15 years. All 16 cases had chronic seizures. In 10 cases, detailed clinical histories were available and showed that three individuals had a clinical course that was predominantly characterized by epilepsy, whereas the other seven individuals had progressive cognitive, behavioural and motor decline, in addition to epilepsy. The main neuropathologic findings included: tau pathology (16/16 cases), cerebellar degeneration (11/16 cases) and white matter degeneration (7/16 cases). The tau pathology was characterized by filamentous tau-positive deposits in the form of neurofibrillary tangles, pre-tangles and dot-like grains and threads in the neuropil. All cases showed some degree of tau pathology in the neocortex and in the locus coeruleus with frequent involvement of the substantia nigra and tegmental nuclei and lesser involvement of other grey matter sites, but there was a lack of glial tau pathology. The tau pathology in the neocortex showed a multifocal superficial laminar pattern. We conclude that nodding syndrome is a clinicopathological entity associated consistently with tau pathology, but our observations did not establish the cause of the disease, or an explanation for the tau pathology.

Nodding syndrome in Uganda is a tauopathy.

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.

A real-time medical cartography of epidemic disease (Nodding syndrome) using village-based lay mHealth reporters.

BACKGROUND: Disease surveillance in rural regions of many countries is poor, such that prolonged delays (months) may intervene between appearance of disease and its recognition by public health authorities. For infectious disorders, delayed recognition and intervention enables uncontrolled disease spread. We tested the feasibility in northern Uganda of developing real-time, village-based health surveillance of an epidemic of Nodding syndrome (NS) using software-programmed smartphones operated by minimally trained lay mHealth reporters. METHODOLOGY AND PRINCIPAL FINDINGS: We used a customized data collection platform (Magpi) that uses mobile phones and real-time cloud-based storage with global positioning system coordinates and time stamping. Pilot studies on sleep behavior of U.S. and Ugandan medical students identified and resolved Magpi-programmed cell phone issues. Thereafter, we deployed Magpi in combination with a lay-operator network of eight mHealth reporters to develop a real-time electronic map of child health, injury and illness relating to NS in rural northern Uganda. Surveillance data were collected for three consecutive months from 10 villages heavily affected by NS. Overall, a total of 240 NS-affected households and an average of 326 children with NS, representing 30 households and approximately 40 NS children per mHealth reporter, were monitored every week by the lay mHealth team. Data submitted for analysis in the USA and Uganda remotely pinpointed the household location and number of NS deaths, injuries, newly reported cases of head nodding (n = 22), and the presence or absence of anti-seizure medication. CONCLUSIONS AND SIGNIFICANCE: This study demonstrates the feasibility of using lay mHealth workers to develop a real-time cartography of epidemic disease in remote rural villages that can facilitate and steer clinical, educational and research interventions in a timely manner.

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

Nodding Syndrome (NS) is an epileptic encephalopathy characterized by involuntary vertical head nodding, other types of seizures, and progressive neurological deficits. The etiology of the east African NS epidemic is unknown. In March 2014, we conducted a case-control study of medical, nutritional and other risk factors associated with NS among children (aged 5-18years) of Kitgum District, northern Uganda (Acholiland). Data on food availability, rainfall, and prevalent disease temporally related to the NS epidemic were also analyzed. In NS Cases, the mean age of reported head nodding onset was 7.6years (range 1-17years). The epidemiologic curve of NS incidence spanned 2000-2013, with peaks in 2003 and 2008. Month of onset of head nodding was non-uniform, with all-year-aggregated peaks in April and June when food availability was low. Families with one or more NS Cases had been significantly more dependent on emergency food and, immediately prior to head nodding onset in the child, subsistence on moldy plant materials, specifically moldy maize. Medical history revealed a single significant association with NS, namely prior measles infection. NS is compared with the post-measles disorder subacute sclerosing panencephalitis, with clinical expression triggered by factors associated with poor nutrition.

Musculoskeletal disorder risk factors among nursing professionals in low resource settings: a cross-sectional study in Uganda.

BACKGROUND: Musculoskeletal disorders (MSD) constitute one of the main occupational hazards among health care workers. However, few epidemiological studies on work related MSD among nursing professionals have been carried out in Africa. The purpose of this study was to assess the work related musculoskeletal disorders and associated risk factors among nursing professionals in Uganda. METHODS: This was a cross-sectional study of MSD among 880 nursing professionals from five selected hospitals in Uganda. Data was collected using a questionnaire adapted from the Dutch Musculoskeletal and Nordic Musculoskeletal questionnaires. Descriptive (mean, standard deviation and percentages) and inferential (Chi square test and logistic regression analysis) statistics were used to analyse data. Alpha level was set at p < 0.05. RESULTS: A total of 741 completed questionnaires were analysed (response rate 85.4%). The average age of the respondents was 35.4 (SD 10.7) years and a majority were female (85.7%). The average working hours per week was 43.7 (SD 18.9 hours). The 12-month period-prevalence of MSD at anybody site was 80.8%. The most common site of MSD was the lower back (61.9%). Significant risk factors for reported MSD included often working in a slightly bent posture (adjOR 2.25, 95% CI 1.20-4.26), often working in a slightly twisted posture for long (adjOR 1.97, 95% CI 1.03-3.77), mental exhaustion (adjOR 2.05, 95% CI 1.17-3.5), being absent from the work station for more than 6 months due to illness or an accident (adjO|R, 4.35, 95% CI 1.44-13.08) and feeling rested after a break (adjOR 2.09, 95% CI 1.16-3.76). CONCLUSIONS: Musculoskeletal disorders affect more than 80% of nursing professionals in Uganda with the most commonly, affected site being the lower back. Significant risk factors for MSD include; being absent from the work station for more than 6 months due to illness or an accident, working in awkward postures, pushing/pulling of heavy loads and mental exhaustion. There is a need for greater advocacy, better working conditions and adoption of strategies to reduce occupational injuries.