Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with
, 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
antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with
antigens and suggests that patients may benefit from immunomodulatory therapies.
Summary 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
New pathogens emerge each year, some of which have high mortality and the potential for efficient transmission--eg, severe acute respiratory syndrome (SARS),1 Middle East respiratory syndrome ...coronavirus,2 and avian influenza A H7N9.3 Existing pathogens are becoming resistant to available antibiotics and several are now resistant to virtually all available treatment.4 There is also the potential threat of intentional release of biological agents, which can be developed or synthesised biologically and disseminated at low cost and with little scientific expertise.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Nodding syndrome is a complex epilepsy disorder characterized by atonic seizures. • It is associated with multiple physical and functional disabilities and psychiatric manifestations. • ...There is a consistent epidemiological association with infection by the parasite Onchocerca volvulus. • Preliminary studies suggest it is a neuroinflammatory disorder induced by antibodies to O. volvulus cross-reacting with neuron proteins. • Studies to confirm these observations and a treatment trial are planned for 2016.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
ObjectifLa 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.MéthodesNous 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.RésultatsUn 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.ConclusionsL'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.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite the discovery of vaccines, the control, and prevention of Coronavirus disease 2019 (COVID-19) relied on non-pharmaceutical interventions (NPIs). This article describes the development and ...application of the Public Health Act to implement NPIs for COVID-19 pandemic control in Uganda.
This is a case study of Uganda's experience with enacting COVID-19 Rules under the Public Health Act Cap. 281. The study assessed how and what Rules were developed, their influence on the outbreak progress, and litigation. The data sources reviewed were applicable laws and policies, Presidential speeches, Cabinet resolutions, statutory instruments, COVID-19 situation reports, and the registry of court cases that contributed to a triangulated analysis.
Uganda applied four COVID-19 broad Rules for the period March 2020 to October 2021. The Minister of Health enacted the Rules, which response teams, enforcement agencies, and the general population followed. The Presidential speeches, their expiry period and progress of the pandemic curve led to amendment of the Rules twenty one (21) times. The Uganda Peoples Defense Forces Act No. 7 of 2005, the Public Finance Management Act No. 3 of 2015, and the National Policy for Disaster Preparedness and Management supplemented the enacted COVID-19 Rules. However, these Rules attracted specific litigation due to perceived infringement on certain human rights provisions.
Countries can enact supportive legislation within the course of an outbreak. The balance of enforcing public health interventions and human rights infringements is an important consideration in future. We recommend public sensitization about legislative provisions and reforms to guide public health responses in future outbreaks or pandemics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Tetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV).
To determine the prevalence of ...tetanus toxoid antibodies following vaccination among men seeking circumcision.
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.
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK