Continental concerted efforts to control the seventh outbreak of Ebola Virus disease in Uganda: The first 90 days of the response.

On 20th September 2022, Uganda declared the 7th outbreak of Ebola virus disease (EVD) caused by the Sudan Ebola strain following the confirmation of a case admitted at Mubende Regional Referral Hospital. Upon confirmation, the Government of Uganda immediately activated the national incident management system to initiate response activities. Additionally, a multi-country emergency stakeholder meeting was held in Kampala; convening Ministers of Health from neighbouring Member States to undertake cross-border preparedness and response actions. The outbreak spanned 69 days and recorded 164 cases (142 confirmed, 22 probable), 87 recoveries and 77 deaths (case fatality ratio of 47%). Nine out of 136 districts were affected with transmission taking place in 5 districts but spilling over in 4 districts without secondary transmission. As part of the response, the Government galvanised robust community mobilisation and initiated assessment of medical counter measures including therapeutics, new diagnostics and vaccines. This paper highlights the response actions that contributed to the containment of this outbreak in addition to the challenges faced with a special focus on key recommendations for better control of future outbreaks.

Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda.

IMPORTANCE: Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks.

Genomic analysis, immunomodulation and deep phenotyping of patients with nodding syndrome.

The aetiology of nodding syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with nodding syndrome, investigate potential contributors to disease aetiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for nodding syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had nodding syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. CSF was non-inflammatory and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus-specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal aetiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention.

Uganda National Institute of Public Health: Establishment and Experiences, 2013-2021.

Uganda is an ecological hot spot with porous borders that lies in several infectious disease transmission belts, making it prone to disease outbreaks. To prepare and respond to these public health threats and emergencies in a coordinated manner, Uganda established the Uganda National Institute of Public Health (UNIPH) in 2013.Using a step-by-step process, Uganda's Ministry of Health (MOH) crafted a strategy with a vision, mission, goal, and strategic objectives, and identified value additions and key enablers for success. A regulatory impact assessment was then conducted to inform the drafting of principles of the bill for legislation on the Institute.Despite not yet attaining legal status, the UNIPH has already achieved faster, smarter, and more efficient and effective prevention, detection, and response to public health emergencies. Successes include a more coordinated multisectoral, disciplined, and organized response to emergencies; appropriate, timely, and complete information receipt and sharing; a functional national lab sample and results transportation network that has enabled detection and confirmation of public health events within 48 hours of alert; appropriate response to a confirmed public health event in 24-48 hours; and real-time surveillance of endemic- and epidemic-prone diseases.In this article, we document success stories, lessons learned, and challenges encountered during the unique staged process used to develop the components of the UNIPH. The creation of an integrated disease control center has proven to yield better collaboration and synergies between different arms of epidemic preparedness and response.

Operational analysis of the national sickle cell screening programme in the Republic of Uganda.

BACKGROUND: Sickle cell anaemia is a common global life-threatening haematological disorder. Most affected births occur in sub-Saharan Africa where children usually go undiagnosed and die early in life. Uganda's national sickle cell screening programme was developed in response to a 2014 sickle cell surveillance study that documented a high disease prevalence. OBJECTIVE: This study describes the temporal and financial aspects of Uganda's 2014-2019 sickle cell screening programme. METHODS: National sickle cell screening data from Uganda's Central Public Health Laboratories were used to calculate turn-around times (TATs) from sample collection to delivery, testing, and result reporting for blood samples collected from February 2014 to March 2019. The parameters affecting specific TATs were assessed. The exact programme expenditures were analysed to determine cost per test and per positive sickle cell disease case detected. RESULTS: A total of 278 651 samples were analysed. The median TAT from sample collection to laboratory receipt was 8 days (interquartile range [IQR]: 6-12), receipt to testing was 3 days (IQR: 1-7), and testing to result reporting was 6 days (IQR: 3-12). Altogether, the sample continuum averaged 16 days (IQR: 11-24). Lower level healthcare facilities were associated with longer sample delivery TATs. Calendar months (January and December) and larger sample volumes impacted testing and result reporting TATs. The cost per test was $4.46 (United States dollars [USD]) and $483.74 USD per positive case detected. CONCLUSION: Uganda's sickle cell screening programme is efficient and cost-effective. Universal newborn screening is the best strategy for detecting sickle cell anaemia in Uganda.

Trends in sickle cell trait and disease screening in the Republic of Uganda, 2014-2019.

OBJECTIVE: Sickle cell disease is an important public health issue that is increasingly recognised as a substantial contributor to morbidity and early childhood mortality in sub-Saharan Africa. We aimed to provide information from large-scale, long-term sickle cell screening efforts in Africa. METHODS: We used nationally representative data from the centralised public health laboratory database in Uganda to examine epidemiological trends in sickle cell screening over a five-year period, comparing age and geographic adjustments to prevalence among different testing cohorts of children aged 0-24 months, and calculating screening coverage within high-burden districts. RESULTS: A total of 324 356 children aged 0-24 months were screened for sickle cell trait and disease from February 2014 to March 2019. A high national burden of sickle cell disease (0.9%) was confirmed among a cohort of samples co-tested with HIV. In the cohort of samples referred specifically for sickle cell testing, the overall prevalence of sickle cell disease was 9.7% and particularly elevated in high-burden districts where focused screening occurred. The majority of children were screened before age 4 months, but the sickle-specific cohort had a larger proportion of affected children tested between age 5-9 months, coincident with onset of disease signs and symptoms. Successful screening coverage of sickle cell disease births was achieved in several high-burden districts. CONCLUSIONS: Examination and analysis of national sickle cell screening trends in Uganda documents the successes of focused screening strategies as an important step towards universal screening. With this evidence and increased healthcare provider knowledge, Uganda can optimise sickle cell diagnosis and management across the country.

OBJECTIF: La drépanocytose est un problème important de santé publique, de plus en plus reconnu comme un contributeur important à la morbidité et à la mortalité infantile en Afrique subsaharienne. Notre objectif était de fournir des informations sur les efforts de dépistage de la drépanocytose à grande échelle et à long terme en Afrique. MÉTHODES: Nous avons utilisé des données représentatives nationales de la base de données centralisée des laboratoires de santé publique en Ouganda pour examiner les tendances épidémiologiques dans le dépistage de la drépanocytose sur une période de cinq ans, en comparant l'âge et les ajustements géographiques à la prévalence dans différentes cohortes de tests d'enfants âgés de 0 à 24 mois, et en estimant la couverture du dépistage dans les districts à forte charge. RÉSULTATS: Un total de 324.356 enfants âgés de 0 à 24 mois ont été dépistés pour le trait drépanocytaire et la maladie de février 2014 à mars 2019. Une charge nationale élevée de la drépanocytose (0,9%) a été confirmée dans une cohorte d'échantillons co-testés pour le VIH. Dans la cohorte d'échantillons référés spécifiquement pour le dépistage de la drépanocytose, la prévalence globale de la drépanocytose était de 9,7% et particulièrement élevée dans les districts à forte charge où un dépistage ciblé avait eu lieu. La majorité des enfants ont été dépistés avant l'âge de 4 mois, mais la cohorte spécifique pour la drépanocytose avait une plus grande proportion d'enfants affectés testés entre l'âge de 5 à 9 mois, coïncidant avec l'apparition des signes et symptômes de la maladie. Une bonne couverture de dépistage des naissances drépanocytaires a été obtenue dans plusieurs districts à forte charge. CONCLUSIONS: L'examen et l'analyse des tendances nationales du dépistage de la drépanocytose en Ouganda documentent les succès des stratégies de dépistage ciblé comme une étape importante vers le dépistage universel. Grâce à ces données et à une meilleure connaissance des prestataires de soins de santé, l'Ouganda peut optimiser le diagnostic et la prise en charge de la drépanocytose dans tout le pays.

Operational analysis of the national sickle cell screening programme in the Republic of Uganda

Background: Sickle cell anaemia is a common global life-threatening haematological disorder. Most affected births occur in sub-Saharan Africa where children usually go undiagnosed and die early in life. Uganda's national sickle cell screening programme was developed in response to a 2014 sickle cell surveillance study that documented a high disease prevalence. Objective: This study describes the temporal and financial aspects of Uganda's 2014­2019 sickle cell screening programme. Methods: National sickle cell screening data from Uganda's Central Public Health Laboratories were used to calculate turn-around times (TATs) from sample collection to delivery, testing, and result reporting for blood samples collected from February 2014 to March 2019. The parameters affecting specific TATs were assessed. The exact programme expenditures were analysed to determine cost per test and per positive sickle cell disease case detected. Results: A total of 278 651 samples were analysed. The median TAT from sample collection to laboratory receipt was 8 days (interquartile range [IQR]: 6­12), receipt to testing was 3 days (IQR: 1­7), and testing to result reporting was 6 days (IQR: 3­12). Altogether, the sample continuum averaged 16 days (IQR: 11­24). Lower level healthcare facilities were associated with longer sample delivery TATs. Calendar months (January and December) and larger sample volumes impacted testing and result reporting TATs. The cost per test was $4.46 (United States dollars [USD]) and $483.74 USD per positive case detected. Conclusion: Uganda's sickle cell screening programme is efficient and cost-effective. Universal newborn screening is the best strategy for detecting sickle cell anaemia in Uganda.

Main Routes of Entry and Genomic Diversity of SARS-CoV-2, Uganda.

We established rapid local viral sequencing to document the genomic diversity of severe acute respiratory syndrome coronavirus 2 entering Uganda. Virus lineages closely followed the travel origins of infected persons. Our sequence data provide an important baseline for tracking any further transmission of the virus throughout the country and region.

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies.

Family Health Days program contributions in vaccination of unreached and under-immunized children during routine vaccinations in Uganda.

BACKGROUND: We explored the contributions of the Family Health Days (FHDs) concept, which was developed by the Uganda Ministry of Health (MOH) and UNICEF as a supplementary quarterly outreach program in addition to strengthening the routine expanded program for immunization (EPI), with the aim to increase coverage, through improved access to the unimmunized or unreached and under-immunized children under 5 years. METHOD: A cross-sectional descriptive study of the Uganda MOH, Health Management Information Systems (HMIS) and UNICEF in house FHDs data was conducted covering six quarterly implementations of the program between April 2012 and December 2013. The FHDs program was implemented in 31 priority districts with low routine vaccination coverage from seven sub-regions in Uganda in a phased manner using places of worship for service delivery. RESULTS: During the six rounds of FHDs in the 31 districts, a total of 178,709 and 191,223 children received measles and Diphtheria-Pertussis-Tetanus (DPT3) vaccinations, respectively. The FHDs' contributions were 126% and 144% for measles and 103% and 122% for DPT3 in 2012 and 2013, respectively of the estimated unreached annual target populations. All implementing sub-regions after two rounds in 2012 attained over and above the desired target for DPT3 (85%) and measles (90%). The same was true in 2013 after four rounds, except for Karamoja and West Nile sub-regions, where in some districts a substantial proportion of children remained unimmunized. The administrative data for both DPT3 and measles immunization showed prominent and noticeable increase in coverage trend in FHDS regions for the months when the program was implemented. CONCLUSION: The FHDs program improved vaccination equity by reaching the unreached and hard-to-reach children and bridging the gap in immunization coverage, and fast tracking the achievement of targets recommended by the Global Vaccine Action Plan (GVAP) for measles and DPT3 (85% and 90% respectively) in implementing sub-regions and districts. The FHDs is an innovative program to supplement routine immunizations designed to reach the unreached and under immunized children.

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers.

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.

Prevalence of protective tetanus antibodies and immunological response following tetanus toxoid vaccination among men seeking medical circumcision services in Uganda.

INTRODUCTION: Tetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV). OBJECTIVE: To determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision. METHODS: We enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response. RESULTS: Mean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35-0.53) on day 0, 3.86IU/ml (CI 3.60-4.11) on day 14, 4.05IU/ml (CI 3.81-4.29) on day 28, and 4.48IU/ml (CI 4.28-4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years. CONCLUSION: Insufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years.

Nodding syndrome may be an autoimmune reaction to the parasitic worm Onchocerca volvulus.

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.

Rapid reduction of maternal mortality in Uganda and Zambia through the saving mothers, giving life initiative: results of year 1 evaluation.

BACKGROUND: Achieving maternal mortality reduction as a development goal remains a major challenge in most low-resource countries. Saving Mothers, Giving Life (SMGL) is a multi-partner initiative designed to reduce maternal mortality rapidly in high mortality settings through community and facility evidence-based interventions and district-wide health systems strengthening that could reduce delays to appropriate obstetric care. METHODS: An evaluation employing multiple studies and data collection methods was used to compare baseline maternal outcomes to those during Year 1 in SMGL pilot districts in Uganda and Zambia. Studies include health facility assessments, pregnancy outcome monitoring, enhanced maternal mortality detection in facilities, and population-based investigation of community maternal deaths. Population-based evaluation used standard approaches and comparable indicators to measure outcome and impact, and to allow comparison of the SMGL implementation in unique country contexts. RESULTS: The evaluation found a 30% reduction in the population-based maternal mortality ratio (MMR) in Uganda during Year 1, from 452 to 316 per 100,000 live births. The MMR in health facilities declined by 35% in each country (from 534 to 345 in Uganda and from 310 to 202 in Zambia). The institutional delivery rate increased by 62% in Uganda and 35% in Zambia. The number of facilities providing emergency obstetric and newborn care (EmONC) rose from 10 to 25 in Uganda and from 7 to 11 in Zambia. Partial EmONC care became available in many more low and mid-level facilities. Cesarean section rates for all births increased by 23% in Uganda and 15% in Zambia. The proportion of women with childbirth complications delivered in EmONC facilities rose by 25% in Uganda and 23% in Zambia. Facility case fatality rates fell from 2.6 to 2.0% in Uganda and 3.1 to 2.0% in Zambia. CONCLUSIONS: Maternal mortality ratios fell significantly in one year in Uganda and Zambia following the introduction of the SMGL model. This model employed a comprehensive district system strengthening approach. The lessons learned from SMGL can inform policymakers and program managers in other low and middle income settings where similar approaches could be utilized to rapidly reduce preventable maternal deaths.

The burden of tetanus in Uganda.

BACKGROUND: The successful scale-up of safe male circumcision (SMC) in Uganda has been hinged on client's safety and quality of services. However, after the recent three tetanus deaths after circumcision a review of all tetanus cases in one of the hospitals where the cases occurred was initiated. This was to ascertain the potential for an association between tetanus infection and circumcision. Routinely collected national data were also reviewed to determine the burden of tetanus in Uganda and contextualize these incidents. METHODS: A review of medical charts of tetanus cases identified from the inpatients registry at Masafu hospital, Busia district for the period 2009/2010-2013/2014. Data were abstracted from the inpatients registries, charts and HMIS annual reports, and a key informant interview conducted with the in-charge of the ward that treats tetanus patients. All quantitative data were captured in an electronic database. Routine facility data from the National District health Information Software-2 (DHIS-2) for all the 112 districts were also used. Descriptive analysis and Poisson regression models were used for statistical analysis using STATA version 13.0. RESULTS: Data from the routine DHIS-2 showed a high and increasing burden of tetanus from the emergency/out-patient department records over the 4 year period, highest among females aged 5+ years in all the regions. At the Masafa hospital, the chart review revealed a total of 25 tetanus cases and all were males. Nearly a third (32 %) was aged 7-15 years, with no evidence of circumcision apart from only one case. The rate of tetanus infection among male inpatients over the review period was 2-6 per 1000. The case fatality rate was nearly a half (47.4 %) with deaths occurring within 2 days after admission, and rates of patients' self-discharge against medical advice were high, 36.8 %. The most common tetanus entry wounds were due to road traffic accidents, followed by diabetic foot. Anti-tetanus serum was only not readily available. CONCLUSION: The burden of tetanus is increasing, especially among females aged 5+ years. Tetanus entry wounds among the inpatients in Masafa hospital were mostly due to road traffic accidents, and young males. The tetanus case fatality was very high (47.4 %) and so was patient requested discharge. There is a need to do more to protect the population against tetanus infection, especially among females, and males who need either initial or booster tetanus immunization as SMC is scaled up.

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.

Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study.

BACKGROUND: Sickle cell disease contributes substantially to mortality in children younger than 5 years in sub-Saharan Africa. In Uganda, 20,000 babies per year are thought to be born with sickle cell disease, but accurate data are not available. We did the cross-sectional Uganda Sickle Surveillance Study to assess the burden of disease. METHODS: The primary objective of the study was to calculate prevalence of sickle cell trait and disease. We obtained punch samples from dried blood spots routinely collected from HIV-exposed infants in ten regions and 112 districts across Uganda for the national Early Infant Diagnosis programme. Haemoglobin electrophoresis by isoelectric focusing was done on all samples to identify those from babies with sickle trait or disease. FINDINGS: Between February, 2014, and March, 2015, 99,243 dried blood spots were analysed and results were available for 97,631. The overall number of children with sickle cell trait was 12,979 (13·3%) and with disease was 716 (0·7%). Sickle cell numbers ranged from 631 (4·6%) for trait and 23 (0·2%) for disease of 13,649 in the South Western region to 1306 (19·8%) for trait and 96 (1·5%) for disease of 6581 in the East Central region. Sickle cell trait was seen in all districts. The lowest prevalence was less than 3·0% in two districts. Eight districts had prevalence greater than 20·0%, with the highest being 23·9%. Sickle cell disease was less common in children older than 12 months or who were HIV positive, which is consistent with comorbidity and early mortality. INTERPRETATION: Prevalence of sickle cell trait and disease were high in Uganda, with notable variation between regions and districts. The data will help to inform national strategies for sickle cell disease, including neonatal screening. FUNDING: Cincinnati Children's Research Foundation.