Doxycycline for the treatment of nodding syndrome: a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913. FINDINGS: Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups. INTERPRETATION: Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections. FUNDING: Medical Research Council (UK). TRANSLATION: For the Luo translation of the abstract see Supplementary Materials section.

Field investigation of high reported non-neonatal tetanus burden in Uganda, 2016-2017.

BACKGROUND: Despite providing tetanus-toxoid-containing vaccine (TTCV) to infants and reproductive-age women, Uganda reports one of the highest incidences of non-neonatal tetanus (non-NT). Prompted by unusual epidemiologic trends among reported non-NT cases, we conducted a retrospective record review to see whether these data reflected true disease burden. METHODS: We analysed nationally reported non-NT cases during 2012-2017. We visited 26 facilities (14 hospitals, 12 health centres) reporting high numbers of non-NT cases (n = 20) or zero cases (n = 6). We identified non-NT cases in facility registers during 1 January 2016-30 June 2017; the identified case records were abstracted. RESULTS: During 2012-2017, a total of 24 518 non-NT cases were reported and 74% were ≥5 years old. The average annual incidence was 3.43 per 100 000 population based on inpatient admissions. Among 482 non-NT inpatient cases reported during 1 January 2016-30 June 2017 from hospitals visited, 342 (71%) were identified in facility registers, despite missing register data (21%). Males comprised 283 (83%) of identified cases and 60% were ≥15 years old. Of 145 cases with detailed records, 134 (92%) were clinically confirmed tetanus; among these, the case-fatality ratio (CFR) was 54%. Fourteen cases were identified at two hospitals reporting zero cases. Among >4000 outpatient cases reported from health centres visited, only 3 cases were identified; the remainder were data errors. CONCLUSIONS: A substantial number of non-NT cases and deaths occur in Uganda. The high CFR and high non-NT burden among men and older children indicate the need for TTCV booster doses across the life course to all individuals as well as improved coverage with the TTCV primary series. The observed data errors indicate the need for data quality improvement activities.

Health worker perspectives of Smart Triage, a digital triaging platform for quality improvement at a referral hospital in Uganda: a qualitative analysis.

BACKGROUND: Effective triage at hospitals can improve outcomes for children globally by helping identify and prioritize care for those most at-risk of death. Paper-based pediatric triage guidelines have been developed to support frontline health workers in low-resource settings, but these guidelines can be challenging to implement. Smart Triage is a digital triaging platform for quality improvement (QI) that aims to address this challenge. Smart Triage represents a major cultural and behavioural shift in terms of managing patients at health facilities in low-and middle-income countries. The purpose of this study is to understand user perspectives on the usability, feasibility, and acceptability of Smart Triage to inform ongoing and future implementation. METHODS: This was a descriptive qualitative study comprising of face-to-face interviews with health workers (n = 15) at a regional referral hospital in Eastern Uganda, conducted as a sub-study of a larger clinical trial to evaluate Smart Triage (NCT04304235). Thematic analysis was used to assess the usability, feasibility, and acceptability of the platform, focusing on its use in stratifying and prioritizing patients according to their risk and informing QI initiatives implemented by health workers. RESULTS: With appropriate training and experience, health workers found most features of Smart Triage usable and feasible to implement, and reported the platform was acceptable due to its positive impact on reducing the time to treatment for emergency pediatric cases and its use in informing QI initiatives within the pediatric ward. Several factors that reduced the feasibility and acceptability were identified, including high staff turnover, a lack of medical supplies at the hospital, and challenges with staff attitudes. CONCLUSION: Health workers can use the Smart Triage digital triaging platform to identify and prioritize care for severely ill children and improve quality of care at health facilities in low-resource settings. Future innovation is needed to address identified feasibility and acceptability challenges; however, this platform could potentially address some of the challenges to implementing current paper-based systems.

Pan-African evolution of within- and between-country COVID-19 dynamics.

The coronavirus disease 2019 (COVID-19) pandemic is heterogeneous throughout Africa and threatening millions of lives. Surveillance and short-term modeling forecasts are critical to provide timely information for decisions on control strategies. We created a strategy that helps predict the country-level case occurrences based on cases within or external to a country throughout the entire African continent, parameterized by socioeconomic and geoeconomic variations and the lagged effects of social policy and meteorological history. We observed the effect of the Human Development Index, containment policies, testing capacity, specific humidity, temperature, and landlocked status of countries on the local within-country and external between-country transmission. One-week forecasts of case numbers from the model were driven by the quality of the reported data. Seeking equitable behavioral and social interventions, balanced with coordinated country-specific strategies in infection suppression, should be a continental priority to control the COVID-19 pandemic in Africa.

Tracking and predicting the African COVID-19 pandemic.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is heterogeneous throughout Africa and threatening millions of lives. Surveillance and short-term modeling forecasts are critical to provide timely information for decisions on control strategies. We use a model that explains the evolution of the COVID-19 pandemic over time in the entire African continent, parameterized by socioeconomic and geoeconomic variations and the lagged effects of social policy and meteorological history. We observed the effect of the human development index, containment policies, testing capacity, specific humidity, temperature and landlocked status of countries on the local within-country and external between-country transmission. One week forecasts of case numbers from the model were driven by the quality of the reported data. Seeking equitable behavioral and social interventions, balanced with coordinated country-specific strategies in infection suppression, should be a continental priority to control the COVID-19 pandemic in Africa.

Prevalence and incidence of nodding syndrome and other forms of epilepsy in onchocerciasis-endemic areas in northern Uganda after the implementation of onchocerciasis control measures.

BACKGROUND: Around 2007, a nodding syndrome (NS) epidemic appeared in onchocerciasis-endemic districts of northern Uganda, where ivermectin mass distribution had never been implemented. This study evaluated the effect of community-directed treatment with ivermectin (CDTI) and ground larviciding of rivers initiated after 2009 and 2012 respectively, on the epidemiology of NS and other forms of epilepsy (OFE) in some districts of northern Uganda. METHODS: In 2012, a population-based community survey of NS/epilepsy was carried out by the Ugandan Ministry of Health in Kitgum and Pader districts. In August 2017, we conducted a new survey in selected villages of these districts and compared our findings with the 2012 data. In addition, two villages in Moyo district (where CDTI was ongoing since 1993) served as comparative onchocerciasis-endemic sites in which larviciding had never been implemented. The comparison between 2012 and 2017 prevalence and cumulative incidence were done using the Fisher's and Pearson's Chi-square tests at 95% level of significance. RESULTS: A total of 2138 individuals in 390 households were interviewed. In the selected villages of Kitgum and Pader, there was no significant decrease in prevalence of NS and OFE between 2012 and 2017. However, the cumulative incidence of all forms of epilepsy decreased from 1165 to 130 per 100 000 persons per year (P = 0.002); that of NS decreased from 490 to 43 per 100 000 persons per year (P = 0.037); and for OFE from 675 to 87 per 100 000 persons per year (P = 0.024). The median age of affected persons (NS and OFE) shifted from 13.5 (IQR: 11.0-15.0) years in 2012 to 18.0 (IQR: 15.0-20.3) years in 2017; P <  0.001. The age-standardized prevalence of OFE in Moyo in 2017 was 4.6%, similar to 4.5% in Kitgum and Pader. CONCLUSIONS: Our findings support the growing evidence of a relationship between infection by Onchocerca volvulus and some types of childhood epilepsy, and suggest that a combination of bi-annual mass distribution of ivermectin and ground larviciding of rivers is an effective strategy to prevent NS and OFE in onchocerciasis-hyperendemic areas.

Comparing static and outreach immunization strategies and associated factors in Uganda, Nov-Dec 2016.

INTRODUCTION: the government of Uganda aims at reducing childhood morbidity through provision of immunization services. We compared the proportion of children 12-33 months reached using either static or outreach immunization strategies and factors affecting utilization of routine vaccination services in order to inform policy updates. METHODS: we adopted the 2015 vaccination coverage cluster survey technique. The sample selection was based on a stratified three-stage sample design. Using the Fleiss formula, a sample of 50 enumeration areas was sufficient to generate immunization coverages at each region. A total of 200 enumeration areas were selected for the survey. Thirty households were selected per enumeration area. Epi-Info software was used to calculate weighted coverage estimates. facility. RESULTS: among the 2231 vaccinated children aged 12-23 months who participated in the survey, 68.1% received immunization services from a health unit and 10.6% from outreaches. The factors that affected utilization of routine vaccination services were; accessibility, where 78.2% resided within 5km from a health. 29.7% missed vaccination due to lack of vaccines at the health facility. Other reasons were lack of supplies at 39.2% and because the caretaker had other things to do, 26.4%. The survey showed 1.8% (40/2271) respondents had not vaccinated their children. Among these, 70% said they had not vaccinated their child because they were busy doing other things and 27.5% had not done so because of lack of motivation. CONCLUSION: almost 7 in 10 children aged 12-23 months access vaccination at health facilities. There is evidence of parental apathy as well as misconceptions about vaccination.

Qualitative evaluation of the outcomes of care and treatment for children and adolescents with nodding syndrome and other epilepsies in Uganda.

BACKGROUND: In 2012, the Ugandan Government declared an epidemic of Nodding Syndrome (NS) in the Northern districts of Gulu, Kitgum, Lamwo and Pader. Treatment guidelines were developed and NS treatment centres were established to provide symptomatic control and rehabilitation. However, a wide gap remained between the pre-defined care standards and the quality of routine care provided to those affected. This study is to qualitatively assess adherence to accepted clinical care standards for NS; identify gaps in the care of affected children and offer Clinical Support Supervision (CSS) to Primary Health Care (PHC) staff at the treatment centres; and identify psychosocial challenges faced by affected children and their caregivers. METHODS: This case study was carried out in the districts of Gulu, Kitgum, Lamwo and Pader in Uganda from September to December in 2015. Employing the 5-stage approach of Clinical Audit, data were collected through direct observations and interviews with PHC providers working in public and private-not-for-profit health facilities, as well as with caregivers and political leaders. The qualitative data was analysed using Seidel model of data processing. RESULTS: Clinical Audit and CSS revealed poor adherence to treatment guidelines. Many affected children had sub-optimal NS management resulting in poor seizure control and complications including severe burns. Root causes of these outcomes were frequent antiepileptic drugs stock outs, migration of health workers from their work stations and psychosocial issues. There was hardly any specialized multidisciplinary team (MDT) to provide for the complex rehabilitation needs of the patients and a task shifting model with inadequate support supervision was employed, leading to loss of skills learnt. Reported psychosocial and psychosexual issues associated with NS included early pregnancies, public display of sexual behaviours and child abuse. CONCLUSIONS: Despite involvement of relevant MDT members in the development of multidisciplinary NS guidelines, multidisciplinary care was not implemented in practice. There is urgent need to review the NS clinical guidelines. Quarterly CSS and consistent anticonvulsant medication are needed at health facilities in affected communities. Implementation of the existing policies and programs to deal with the psychosocial and psychosexual issues that affect children with NS and other chronic conditions is needed.

Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.

BACKGROUND: Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O.volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O.volvulus or its symbiont, Wolbachia, cross-reacting with human neuron proteins and that doxycycline, which kills Onchocerca through effects on Wolbachia, may be used as treatment. METHODS: This will be a two-arm, double-blind, placebo-controlled, randomised phase II trial of doxycycline 100 mg daily for six weeks in 230 participants. Participants will be patients' ages≥8 years with nodding syndrome. They will receive standard of care supportive treatment. All will be hospitalised for 1-2 weeks during which time baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised. Participants will then be randomised to either oral doxycycline (Azudox®, Kampala Pharmaceutical Industries) 100 mg daily or placebo. Treatment will be initiated in hospital and continued at home. Participants will be visited at home at 2, 4 and 6 weeks for adherence monitoring. Study outcomes will be assessed at 6, 12, 18 and 24-month visits. Analysis will be by intention to treat. The primary efficacy outcome measure will be the proportion of patients testing positive and the levels or titires of antibodies to host neuron proteins (HNPs) and/or leiomodin at 24 months. Secondary outcome measures will include effect of the intervention on seizure control, inflammatory markers, cognitive function, disease severity and quality of life. DISCUSSION: This trial postulates that targeting O.volvulus through drugs which kill Wolbachia can modify the pathogenic processes in nodding syndrome and improve outcomes. Findings from this study are expected to substantially improve the understanding and treatment of nodding syndrome. TRIAL REGISTRATION: Registered with clinicaltrials.gov ID: NCT02850913 on 1st August, 2016.

The natural history of nodding syndrome.

Nodding syndrome is a poorly understood acquired disorder affecting children in sub-Saharan Africa. The aetiology and pathogenesis are unknown, and no specific treatment is available. Affected children have a distinctive feature (repeated clusters of head nodding) and progressively develop many other features. In an earlier pilot study, we proposed a five-level clinical staging system. The present study aimed to describe the early features and natural history of nodding syndrome and refine the proposed clinical stages. This was a retrospective study of the progressive development of symptoms and complications of nodding syndrome. Participants were a cohort of patients who had been identified by community health workers and were referred for treatment. A detailed history was obtained to document the chronological development of symptoms before and after onset of head nodding and a physical examination and disability assessment performed by a team of clinicians and therapists. A total of 210 children were recruited. The mean age at the onset of head nodding was 7.5 (SD: 3.0) years. Five overlapping clinical stages were recognised: prodromal, head nodding, convulsive seizures, multiple impairments, and severe disability stages. Clinical features before the onset of head nodding (prodromal features) included periods of staring blankly or being inattentive, complaints of dizziness, excessive sleepiness, lethargy, and general body weakness, all occurring two weeks to 24 months before nodding developed. After the onset of head nodding, patients progressively developed convulsive seizures, cognitive and psychiatric dysfunction, physical deformities, growth arrest, and eventually, in some patients, severe disability. The description of the natural history of nodding syndrome and especially the prodromal features has the potential of providing a means for the early identification of at-risk patients and the prompt initiation of interventions before extensive brain injury develops. The wide spectrum of symptoms and complications emphasises the need for multi-disciplinary investigations and care.

Factors that affect immunization data quality in Kabarole District, Uganda.

INTRODUCTION: Reliable and timely immunization data is vital at all levels of health care to inform decisions and improve program performance. Inadequate data quality may impair our understanding of the true vaccination coverage and also hinder our capability to meet the program objectives. It's therefore important to regularly assess immunization data quality to ensure good performance, sound decision making and efficient use of resources. METHODS: We conducted an immunization data quality audit between July and August 2016. The verification factor was estimated by dividing the recounted diphtheria, pertussis and tetanus third dose vaccination for children under 1 year (DPT3<1 year) by reported DPT3<1 year. The quality of data collection processes was measured using quality indices for the 3 different components: recording practices, storage/reporting, monitoring and evaluation. These indices were applied to the different levels of the health care service delivery system. Quality index score was estimated by dividing the total question or observation correctly answered by the total number of answers/ observations for a particular component. RESULTS: The mean health center verification factor was 87%. Sixty five percent (32/49) of the health centers had consistent data, 27% (13/49) over reported and 4% (2/49) under-reported. Health center 11s and 111s contributed to over-reporting and under-reporting. All the health centers' reports were complete and timely between January and June and from November to December. The mean quality indices for the 3 different componets assessed were; recording practices 66%, storing/reporting 75%, monitoring and evaluation 43%. There was a weak positive correlation between the health center verifaction factor and quality index though this was not statistically significant (r = 0.014; p = 0.92). CONCLUSION: Lower level health centers contributed significantly to the inconsistencies in immunization data; there were wide variation between the quality indices of recording practices, storage/reporting, monitoring and evaluation. We recommended that District Local Governments and Ministry of Health focus on improving data quality at lower levels of health service delivery.

Contextualization of psychological treatments for government health systems in low-resource settings: group interpersonal psychotherapy for caregivers of children with nodding syndrome in Uganda.

BACKGROUND: Evidence for the effectiveness of psychological treatments in low- and middle-income countries is increasing. However, there is a lack of systematic approaches to guide implementation in government health systems. The objective of this study was to address this gap by employing the Replicating Effective Programs (REP) framework to guide contextualization of a psychological treatment in the Uganda public health system for caregivers of children affected by nodding syndrome, a neuropsychiatric disorder endemic to Sub-Saharan Africa associated with high morbidity and disability. METHODS: To contextualize a psychological treatment, we followed the four components of the REP framework: pre-conditions, pre-implementation, implementation, and maintenance and evolution. A three-step process involved reviewing health services available for nodding syndrome-affected families and current evidence for psychological treatments, qualitative formative research, and analysis and documentation of implementation activities. Stakeholders included members of affected communities, health care workers, therapists, local government leaders, and Ministry of Health officials. Detailed written, audio, and video documentation of the implementation activities was used for content analysis. RESULTS: During the pre-condition component of REP, we selected group interpersonal therapy (IPT-G) because of its feasibility, acceptability, effectiveness in the local setting, and availability of locally developed training materials. During the pre-implementation component, we adapted the training, logistics, and technical assistance strategies in conjunction with government and stakeholder working groups. Adaptations included content modification based on qualitative research with caregivers of children with nodding syndrome. During the implementation component, training was shortened for feasibility with government health workers. Peer-to-peer supervision was selected as a sustainable quality assurance method. IPT-G delivered by community health workers was evaluated for fidelity, patient outcomes, and other process-level variables. More than 90% of beneficiaries completed the treatment program, which was effective in reducing caregiver and child mental health problems. With the Ministry of Health, we conducted preparatory activities for the maintenance and evolution component for scale-up throughout the country. CONCLUSIONS: The REP framework provides a systematic approach to guide contextualization of psychological treatments for delivery in low-resource public health systems. Specific recommendations are provided for REP's application in global mental health. TRIAL REGISTRATION: ISRCTN11382067 ; 08/06/2016; retrospectively registered.

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial - challenges, enablers and lessons learned.

A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research.

Is nodding syndrome an Onchocerca volvulus-induced neuroinflammatory disorder? Uganda's story of research in understanding the disease.

Nodding syndrome is a devastating neurological disorder, mostly affecting children in eastern Africa. An estimated 10000 children are affected. Uganda, one of the most affected countries, set out to systematically investigate the disease and develop interventions for it. On December 21, 2015, the Ministry of Health held a meeting with community leaders from the affected areas to disseminate the results of the investigations made to date. This article summarizes the presentation and shares the story of studies into this peculiar disease. It also shares the results of preliminary studies on its pathogenesis and puts into perspective an upcoming treatment intervention. Clinical and electrophysiological studies have demonstrated nodding syndrome to be a complex epilepsy disorder. A definitive aetiological agent has not been established, but in agreement with other affected countries, a consistent epidemiological association has been demonstrated with infection by Onchocerca volvulus. Preliminary studies of its pathogenesis suggest that nodding syndrome may be a neuroinflammatory disorder, possibly induced by antibodies to O. volvulus cross-reacting with neuron proteins. Histological examination of post-mortem brains has shown some yet to be characterized polarizable material in the majority of specimens. Studies to confirm these observations and a clinical trial are planned for 2016.

Is the glass half full or half empty? A qualitative exploration on treatment practices and perceived barriers to biomedical care for patients with nodding syndrome in post-conflict northern Uganda.

BACKGROUND: Nodding syndrome has increasingly become an issue of public health concern internationally. The etiology of the disorder is still unknown and there are yet no curative treatments. We explored perceptions about treatment practices and barriers to health seeking for nodding syndrome in Pader and Kitgum districts in northern Uganda in order to provide data necessary for informing policy on treatment adherence and rehabilitations. METHODS: We used focus group discussions and individual interviews to gain deep insights into help-seeking and treatment practices for nodding syndrome. Purposive sampling was used to identify information-rich participants that included village health teams, community members not directly affected with nodding syndrome, district leaders, healthcare professionals, and caregivers of children affected with nodding syndrome. We used qualitative content analysis to analyze data and presented findings under distinct categories and themes. RESULTS: Caregivers and communities sought care from multiple sources including biomedical facilities, traditional healers, traditional rituals from shrines, and spiritual healing. Nodding syndrome affected children reportedly have showed no enduring improvement with traditional medicines, traditional rituals, and prayers. A substantial minority of participants reported minimal improvements in symptoms of convulsions with use of western medicines. Challenges involved in health seeking included; (1) health system factors e.g. long distances to facilities, frequent unavailability of medicines, few healthcare providers, and long waiting times; (2) contextual and societal challenges e.g. lack of money for transport and medical bills, overburdening nature of the illness that does not allow time for other activities, and practical difficulties involved in transporting the physically deformed and mentally retarded children to the health facilities. CONCLUSIONS: Help-seeking for nodding syndrome is pluralistic and include use of traditional and biomedical practices. Western medicines admittedly showed at least short term control on nodding syndrome symptoms, especially convulsions and led in a few cases to regain of functional abilities. However, multiple barriers hinder health seeking and interfere with adherence to biomedical treatments. Regarding cure, there are hitherto no treatments participants perceive cure nodding syndrome.

Patients with nodding syndrome in Uganda improve with symptomatic treatment: a cross-sectional study.

OBJECTIVES: Nodding syndrome (NS) is a poorly understood neurological disorder affecting thousands of children in Africa. In March 2012, we introduced a treatment intervention that aimed to provide symptomatic relief. This intervention included sodium valproate for seizures, management of behaviour and emotional difficulties, nutritional therapy and physical rehabilitation. We assessed the clinical and functional outcomes of this intervention after 12 months of implementation. DESIGN: This was a cross-sectional study of a cohort of patients with NS receiving the specified intervention. We abstracted preintervention features from records and compared these with the current clinical status. We performed similar assessments on a cohort of patients with other convulsive epilepsies (OCE) and compared the outcomes of the two groups. PARTICIPANTS: Participants were patients with WHO-defined NS and patients with OCE attending the same centres. OUTCOME MEASURES: The primary outcome was the proportion of patients with seizure freedom (≥1 month without seizures). Secondary outcome measures included a reduction in seizure frequency, resolution of behaviour and emotional difficulties, and independence in basic self-care. RESULTS: Patients with NS had had a longer duration of symptoms (median 5 (IQR 3, 6) years) compared with those with OCE (4 (IQR 2, 6) years), p<0.001. The intervention resulted in marked improvements in both groups; compared to the preintervention state, 121/484 (25%) patients with NS achieved seizure freedom and there was a >70% reduction in seizure frequency; behaviour and emotional difficulties resolved in 194/327 (59%) patients; 193/484 (40%) patients had enrolled in school including 17.7% who had earlier withdrawn due to severe seizures, and over 80% had achieved independence in basic self-care. These improvements were, however, less than that in patients with OCE of whom 243/476 (51.1%) patients were seizure free and in whom the seizure frequency had reduced by 86%. CONCLUSIONS: Ugandan children with NS show substantial clinical and functional improvements with symptomatic treatments suggesting that NS is probably a reversible encephalopathy.