2014 Epilepsy Benchmarks Area III: Improve Treatment Options for Controlling Seizures and Epilepsy-Related Conditions Without Side Effects

The Epilepsy Benchmark goals in Area III focus on making progress in understanding and controlling seizures and related conditions as well as on developing biomarkers and new therapies that will reduce seizures and improve outcomes for individuals with epilepsy. Area III emphasizes a need to better understand the ways in which seizures start, propagate, and terminate and whether those network processes are common or unique in different forms of epilepsy. The application of that knowledge to improved seizure prediction and detection will also play a role in improving patient outcomes. Animal models of treatment-resistant epilepsy that are aligned with etiologies and clinical features of human epilepsies are especially encouraged as necessary tools to understand mechanisms and test potential therapies. Antiseizure therapies that target (either alone or in combination) novel or multiple seizure mechanisms are prioritized in this section of the Benchmarks. Area III goals also highlight validation of biomarkers of treatment response and safety risk, effective self-management, and patient-centered outcome measures as important areas of emphasis for the next five to ten years

Paediatric brought-in-dead at a tertiary health facility in South western Nigeria: Patterns and drivers

Background: ‘Brought- in-dead’ (BID) refers to the demise of an individual before presentation to a health facility. This study assessed the pattern of paediatric BID cases seen at a tertiary health facility in southwest Nigeria. Method: A cross-sectional, descriptive study was done at the Children Emergency Ward (CEW) of the hospital between January 2014 and December 2018. The patterns of BID cases and presumed causes of death were determined using a standardized checklist adapted from the WHO verbal autopsy instrument. Results: Ninety-eight BID cases were seen during the study, constituting 2.5% of total patients seen during the period. The median (IQR) age of cases was 24.0 (8.75 – 63.0) months and 72.4% were under-fives. Most had symptoms related to the haematologic (36.7%), respiratory (24.5%) or digestive (20.4%) systems. Severe anaemia 31(31.6%), gastroenteritis 19 (19.4) and aspiration 17 (17.3%) were the most common causes of death. The median (IQR) duration of illness before presentation was 3.0 (1.0 – 7.0) days but most presented from 4 – 7 days of illness. A significant relationship was found between the duration of illness and whether or not pre-hospital treatment was received (p < 0.0001). Unprescribed drugs purchased over the counter were the most commonly used treatment in 79.1% of cases (p < 0.0001). Conclusion: This study has highlighted the prevalence and pattern of paediatric BID in a tertiary health facility in southwest Nigeria and the factors that were associated with it. More efforts need to be geared towards community sensitization and pediatric health care to prevent factors drivingits menace

Abdominal ultrasonography in HIV/AIDS patients in southwestern Nigeria

<p>Abstract</p> <p>Background</p> <p>Though the major target of the HIV-virus is the immune system, the frequency of abdominal disorders in HIV/AIDS patients has been reported to be second only to pulmonary disease. These abdominal manifestations may be on the increase as the use of antiretroviral therapy has increased life expectancy and improved quality of life. Ultrasonography is an easy to perform, non invasive, inexpensive and safe imaging technique that is invaluable in Africa where AIDS is most prevalent and where sophisticated diagnostic tools are not readily available. Purpose: To describe the findings and evaluate the clinical utility of abdominal ultrasonography in HIV/AIDS patients in Ibadan, Nigeria</p> <p>Methods</p> <p>A Prospective evaluation of the abdominal ultrasonography of 391 HIV-positive patients as well as 391 age and sex-matched HIV-negative patients were carried out at the University College Hospital, Ibadan.</p> <p>Results</p> <p>Of the 391 cases studied, 260 (66.5%) were females; the mean age was 38.02 years, (range 15–66 years). The disease was most prevalent in the 4th decade with an incidence of 40.4%. Compared with the HIV-negative individuals, the HIV+ group of patients had a significantly higher proportion of splenomegaly (13.5% vs. 7.7%; p < 0.01), lymphadenopathy (2.0% vs. 1.3%; p < 0.70), and renal abnormalities (8.4% vs. 3.8%; p < 0.02). There were no differences in hepatic and pancreatic abnormalities between the HIV+ and HIV- groups. There were significantly fewer gallstones in the HIV+ group (1.4% vs. 5.1%; p < 0.01).</p> <p>Conclusion</p> <p>AIDS is a multi-systemic disease and its demographic and clinical pattern remains the same globally. Ultrasonography is optimally suited for its clinical management especially in Africa. Its accuracy and sensitivity may be much improved with clinico-pathologic correlation which may not be readily available in developing countries; further studies may provide this much needed diagnostic algorithms.</p

Genetic Dissection of the Canq1 Locus Governing Variation in Extent of the Collateral Circulation

<div><h3>Background</h3><p>Native (pre-existing) collaterals are arteriole-to-arteriole anastomoses that interconnect adjacent arterial trees and serve as endogenous bypass vessels that limit tissue injury in ischemic stroke, myocardial infarction, coronary and peripheral artery disease. Their extent (number and diameter) varies widely among mouse strains and healthy humans. We previously identified a major quantitative trait locus on chromosome 7 (<em>Canq1</em>, LOD = 29) responsible for 37% of the heritable variation in collateral extent between C57BL/6 and BALB/c mice. We sought to identify candidate genes in <em>Canq1</em> responsible for collateral variation in the cerebral pial circulation, a tissue whose strain-dependent variation is shared by similar variation in other tissues.</p> <h3>Methods and Findings</h3><p>Collateral extent was intermediate in a recombinant inbred line that splits <em>Canq1</em> between the C57BL/6 and BALB/c strains. Phenotyping and SNP-mapping of an expanded panel of twenty-one informative inbred strains narrowed the <em>Canq1</em> locus, and genome-wide linkage analysis of a SWRxSJL-F2 cross confirmed its haplotype structure. Collateral extent, infarct volume after cerebral artery occlusion, bleeding time, and re-bleeding time did not differ in knockout mice for two vascular-related genes located in <em>Canq1</em>, <em>IL4ra</em> and <em>Itgal</em>. Transcript abundance of 6 out of 116 genes within the 95% confidence interval of <em>Canq1</em> were differentially expressed >2-fold (p-value<0.05÷150) in the cortical <em>pia mater</em> from C57BL/6 and BALB/c embryos at E14.5, E16.5 and E18.5 time-points that span the period of collateral formation.</p> <h3>Conclusions</h3><p>These findings refine the <em>Canq1</em> locus and identify several genes as high-priority candidates important in specifying native collateral formation and its wide variation.</p> </div

Impact of mothers’ socio-demographic factors and antenatal clinic attendance on neonatal mortality in Nigeria

Neonatal death is often referred to maternal complications during pregnancy, and other exogenous factors that exist around the time of birth or shortly after birth. The United Nations Sustainable Development Goals (UNSDG)-Goal 3, Targets 3.2 aimed at ending preventable deaths of newborns by demanding that all countries should reduce neonatal mortality to 12 per 1000 live births by 2030. The objective of the study was to examine the relationship between mothers’ socioeconomic and demographic factors on neonatal deaths in Nigeria. The study used quantitative data from the 2013 Nigeria Demographic and Health Surveys (NDHS). The data analyzed consisted of 26,826 women aged 15–49 years who had a live or dead birth within the 5 years preceding the survey. STATA 12 computer software was used to carry out data analyses. Data analyses were at univariate (frequency distribution), bivariate (chi-square) and due to the dichotomous nature of the outcome variable (i.e., whether a child was born alive or dead during the delivery; coded as (1, 0), a binary logistic regression was carried out to examine the relationships between various socio-demographic factors, antenatal clinic attendance and neonatal mortality in Nigeria. The results, among others, revealed that background factors of the women such as age, region, residence, education, and wealth status have a significant association with neonatal mortality (P < 0.05). The study also found that adequate antenatal clinic attendance helps to reduce neonatal deaths. The study recommended that women should be encouraged to observe regular antenatal clinic visits during pregnancy and also go for institutional delivery for possible reduction of neonates and infant deaths in Nigeria

Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria.

Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the SARS-CoV-2 B.1.1.318 and B.1.525 (Eta) variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave in Nigeria emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Data from this study show how regional connectivity of Nigeria drove the spread of these variants of interest to surrounding countries and those connected by air-traffic. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission, as bidirectional transmission within and between African nations are grossly underestimated as seen in our import risk index estimates

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century