Epidemiology of glaucoma in sub-saharan Africa: prevalence, incidence and risk factors.

PURPOSE: The purpose of this study is to review the epidemiology of different types of glaucoma relevant to Sub-Saharan Africa (SSA) and to discuss the evidence regarding the risk factors for onset and progression of glaucoma, including risk factors for glaucoma blindness. METHODS: Electronic databases (PubMed, MedLine, African Journals Online- AJOL) were searched using the full text, Medical Subject Headings (MeSH) terms, author(s) and title to identify publications since 1982 in the following areas: population-based glaucoma prevalence and incidence studies in SSA and in African-derived black populations outside Africa; population-based prevalence and incidence of blindness and visual impairment studies in SSA including rapid assessment methods, which elucidate the glaucoma-specific blindness prevalence; studies of risk factors for glaucoma; and publications that discussed public health approaches for the control of glaucoma in Africa. RESULTS: Studies highlighted that glaucoma in SSA is a public health problem and predominantly open-angle glaucoma. It is the second-leading cause of blindness, has a high prevalence, an early onset and progresses more rapidly than in Caucasians. These factors are further compounded by poor awareness and low knowledge about glaucoma even by persons affected by the condition. CONCLUSION: Glaucoma care needs to be given high priority in Vision 2020 programs in Africa. Many questions remain unanswered and there is a need for further research in glaucoma in SSA in all aspects especially epidemiology and clinical care and outcomes involving randomized controlled trials. Genetic and genome-wide association studies may aid identification of high-risk groups. Social sciences and qualitative studies, health economics and health systems research will also enhance public health approaches for the prevention of blindness due to glaucoma

Protective Effect of Chemically Characterized Polyphenol-Rich Fraction from Apteranthes europaea (Guss.) Murb. subsp. maroccana (Hook.f.) Plowes on Carbon Tetrachloride-Induced Liver Injury in Mice

Apteranthes europaea (Guss.) Murb. subsp. maroccana (Hook.f.) Plowes (A. europaea) is a medicinal plant widely used in traditional medicines to treat various diseases including hepatic pathogenesis. This study was conducted to evaluate the protective effect of chemically characterized polyphenol-rich fraction from A. europaea on carbon tetrachloride-induced liver injury in mice. The chemical characterization of A. europaea polyphenol-rich fraction was carried out using HPLC-DAD (high-performance liquid chromatography (HPLC) with a diode-array detector (DAD)). Carbon tetrachloride (CCl4) was used to induce liver injuries in mice as described in previous works. A polyphenol-rich fraction from A. europaea was used at a dose of 50 mg/Kg to study its hepatoprotective effect. Next, histopathological and biochemical alterations were investigated. The HPLC analysis revealed the presence of several phenolic compounds: gallic acid, methyl gallate, rutin, ferulic acid, and resorcinol. Regarding the mice treated with a polyphenol-rich fraction from A. europaea up to 50 mg/Kg and carbon tetrachloride, no significant biochemical nor histological alterations occurred in their liver; meanwhile, serious biochemical and histopathological changes were noted for liver recovered from the mice treated with carbon tetrachloride only. In conclusion, A. europaea extract is a promising source of hepatoprotective agents against toxic liver injury

Risk factors for open-angle glaucoma in Nigeria: results from the Nigeria National Blindness and Visual Impairment Survey.

BACKGROUND: The glaucoma-specific blindness prevalence in Nigeria (0.7 %, 95 % CI 0.6-0.9 %) among those aged ≥40 years is one of the highest ever reported. This study determined the risk factors for open-angle glaucoma (OAG) in adults examined in the Nigeria National Blindness and Visual Impairment Survey. METHODS: A nationally representative sample of 13,591 people aged ≥40 years in 305 clusters in Nigeria were examined (response rate 90.4 %) between January 2005 to June 2007. Everyone had logMAR visual acuity measurement, Frequency Doubling Technology (FDT) visual field testing, autorefraction, A-scan biometry and optic disc assessment. Full ocular examination (n = 6397), included Goldmann applanation tonometry. Values for defining glaucoma using International Society of Geographical and Epidemiological Ophthalmology criteria were derived from the study population. Disc images were graded by Moorfields Eye Hospital Reading Centre. Socio-demographic factors (age, gender, ethnicity, literacy and place of residence), ocular parameters (intraocular pressure [IOP], axial length and mean ocular perfusion pressure [MOPP]) and systemic parameters (blood pressure, blood glucose and body mass index [BMI]) were assessed for association with OAG. RESULTS: Thirteen thousand eighty-one (96 %) of 13,591 participants had vertical cup:disc ratio measured in at least one eye. 682 eyes of 462 participants were classified as OAG, with 12,738 controls. In univariate analyses the following were associated with OAG: increasing age, male gender, Igbo and Yoruba ethnic groups, illiteracy, longer axial length, higher IOP, lower MOPP, greater severity of hypertension and low BMI (underweight). In multivariate analysis, increasing age (odds ratio [OR] 1.04, 95 % CI 1.03-1.05), higher IOP (OR 1.22, 95 % CI 1.18-1.25) and Igbo ethnicity (OR 1.73, 95 % CI 1.18-2.56) were independent risk factors for OAG. CONCLUSION: Case detection strategies for OAG should be improved for those aged ≥40 years and for ethnic groups most at risk as a public health intervention

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia

OBJECTIVES: SARS-CoV-2 transmission in Sub-Saharan Africa has probably been underestimated. Population-based seroprevalence studies are needed to determine the extent of transmission in the continent. METHODS: Blood samples from a cohort of Gambian pregnant women were tested for SARS-CoV-2 total receptor binding domain (RBD) IgM/IgG before (Pre-pandemic: October-December 2019), and during the pandemic (Pre-wave1: February-June 2020; Post-wave1: October-December 2020, Post-wave2: May-June 2021; and Post-wave3: October-December 2021). Samples reactive for SARS-CoV-2 total RBD IgM/IgG were tested in specific S1- and nucleocapsid (NCP) IgG assays. RESULTS: SARS-CoV-2 total RBD IgM/IgG seroprevalence was 0.9% 95%CI (0.2, 4.9) in Pre-pandemic; 4.1% (1.4, 11.4) in Pre-wave1; 31.1% (25.2, 37.7) in Post-wave1; 62.5% (55.8, 68.8) in Post-wave2 and 90.0% (85.1, 93.5) in Post-wave3. S-protein IgG and NCP-protein IgG seroprevalence also increased at each Post-wave period. Although S-protein IgG and NCP-protein IgG seroprevalence was similar at Post-wave1, S-protein IgG seroprevalence was higher at Post-wave2 and Post-wave3, [prevalence difference (PD) 13.5 (0.1, 26.8) and prevalence ratio (PR) 1.5 (1.0, 2.3) in Post-wave2; and 22.9 (9.2, 36.6) and 1.4 (1.1, 1.8) in Post-wave3 respectively, p<0.001]. CONCLUSION: SARS-CoV-2 transmission in The Gambia during the first three COVID-19 waves was high, differing significantly from official numbers of COVID-19 cases reported. Our findings are important for policy makers in managing the near-endemic COVID-19

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for CrossCohort Comparisons of COVID-19 Sera

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glyco-protein (VSVDG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n . 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week. IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We there-fore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.Fil: Oguntuyo, Kasopefoluwa. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Stevens, Christian S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hung, Chuan Tien. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ikegame, Satoshi. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Acklin, Joshua A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kowdle, Shreyas S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Carmichael, Jillian C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Chiu, Hsin Ping. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Azarm, Kristopher D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Haas, Griffin D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Amanat, Fatima. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Klingler, Jéromine. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Baine, Ian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Arinsburg, Suzanne. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Bandres, Juan C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Siddiquey, Mohammed N. A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Schilke, Robert M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Woolard, Matthew D.. State University of Louisiana; Estados UnidosFil: Zhang, Hongbo. State University of Louisiana; Estados UnidosFil: Duty, Andrew J.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kraus, Thomas A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Moran, Thomas M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Tortorella, Domenico. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lim, Jean K.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hioe, Catarina E.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Zolla Pazner, Susan. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ivanov, Stanimir S.. State University of Louisiana; Estados UnidosFil: Kamil, Jeremy. State University of Louisiana; Estados UnidosFil: Krammer, Florian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lee, Benhur. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: González López Ledesma, María Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Costa Navarro, Guadalupe Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Pallarés, H. M.. No especifíca;Fil: Sanchez, Lautaro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Perez, P.. No especifíca;Fil: Ostrowsk, M.. No especifíca;Fil: Villordo, S. M.. No especifíca;Fil: Alvarez, D. E.. No especifíca;Fil: Caramelo, J. J.. No especifíca;Fil: Carradori, J.. No especifíca;Fil: Yanovsky, M. J.. No especifíca

Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies

LNPK encodes a conserved membrane protein that stabilizes the junctions of the tubular endoplasmic reticulum network playing crucial roles in diverse biological functions. Recently, homozygous variants in LNPK were shown to cause a neurodevelopmental disorder (OMIM#618090) in four patients displaying developmental delay, epilepsy and nonspecific brain malformations including corpus callosum hypoplasia and variable impairment of cerebellum. We sought to delineate the molecular and phenotypic spectrum of LNPK-related disorder. Exome or genome sequencing was carried out in 11 families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals, including review of previously reported patients. We identified 12 distinct homozygous loss-of-function variants in 16 individuals presenting with moderate to profound developmental delay, cognitive impairment, regression, refractory epilepsy and a recognizable neuroimaging pattern consisting of corpus callosum hypoplasia and signal alterations of the forceps minor ('ear-of-the-lynx' sign), variably associated with substantia nigra signal alterations, mild brain atrophy, short midbrain and cerebellar hypoplasia/atrophy. In summary, we define the core phenotype of LNPK-related disorder and expand the list of neurological disorders presenting with the 'ear-of-the-lynx' sign suggesting a possible common underlying mechanism related to endoplasmic reticulum-phagy dysfunction

Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone

Background Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. Methods We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase–polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. Results Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient. Conclusions The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.