Interleukin-6 (\u3cem\u3eIL-6\u3c/em\u3e) rs1800796 and Cyclin Dependent Kinase Inhibitor (\u3cem\u3eCDKN2A/CDKN2B\u3c/em\u3e) rs2383207 Are Associated with Ischemic Stroke in Indigenous West African Men

Background—Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub – Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. Aim—Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6 and CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Methods—Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 24 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men = 198; Women = 231) and stroke– free (N=483) controls (Men = 236; Women = 247). Results—Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans = 8.6%) was significantly associated with ischemic stroke in men (OR = 2.006, 95% CI = [1.065, 3.777], p = 0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans = 1.7%) was also associated with ischemic stroke in men (OR = 2.550, 95% CI = [1.027, 6.331], p = 0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. Conclusion—Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry

Geographic determinants of reported human Campylobacter infections in Scotland

<p><b>Background:</b> Campylobacteriosis is the leading cause of bacterial gastroenteritis in most developed countries. People are exposed to infection from contaminated food and environmental sources. However, the translation of these exposures into infection in the human population remains incompletely understood. This relationship is further complicated by differences in the presentation of cases, their investigation, identification, and reporting; thus, the actual differences in risk must be considered alongside the artefactual differences.</p> <p><b>Methods:</b> Data on 33,967 confirmed Campylobacter infections in mainland Scotland between 2000 and 2006 (inclusive) that were spatially referenced to the postcode sector level were analysed. Risk factors including the Carstairs index of social deprivation, the easting and northing of the centroid of the postcode sector, measures of livestock density by species and population density were tested in univariate screening using a non-spatial generalised linear model. The NHS Health Board of the case was included as a random effect in this final model. Subsequently, a spatial generalised linear mixed model (GLMM) was constructed and age-stratified sensitivity analysis was conducted on this model.</p> <p><b>Results:</b> The spatial GLMM included the protective effects of the Carstairs index (relative risk (RR) = 0.965, 95% Confidence intervals (CIs) = 0.959, 0.971) and population density (RR = 0.945, 95% CIs = 0.916, 0.974. Following stratification by age group, population density had a significant protective effect (RR = 0.745, 95% CIs = 0.700, 0.792) for those under 15 but not for those aged 15 and older (RR = 0.982, 95% CIs = 0.951, 1.014). Once these predictors have been taken into account three NHS Health Boards remain at significantly greater risk (Grampian, Highland and Tayside) and two at significantly lower risk (Argyll and Ayrshire and Arran).</p> <p><b>Conclusions:</b> The less deprived and children living in rural areas are at the greatest risk of being reported as a case of Campylobacter infection. However, this analysis cannot differentiate between actual risk and heterogeneities in individual reporting behaviour; nevertheless this paper has demonstrated that it is possible to explain the pattern of reported Campylobacter infections using both social and environmental predictors.</p&gt

Dihydroartemisinin-Piperaquine and Artemether-Lumefantrine for Treating Uncomplicated Malaria in African Children: A Randomised, Non-Inferiority Trial

BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443

Using combined diagnostic test results to hindcast trends of infection from cross-sectional data

Infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. Following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. It is thus critical to obtain accurate information concerning the origin of the outbreak and its forward trajectory. However, there is often a lack of situational awareness that may lead to over- or under-reaction. There is a widening range of tests available for detecting pathogens, with typically different temporal characteristics, e.g. in terms of when peak test response occurs relative to time of exposure. We have developed a statistical framework that combines response level data from multiple diagnostic tests and is able to ‘hindcast’ (infer the historical trend of) an infectious disease epidemic. Assuming diagnostic test data from a cross-sectional sample of individuals infected with a pathogen during an outbreak, we use a Bayesian Markov Chain Monte Carlo (MCMC) approach to estimate time of exposure, and the overall epidemic trend in the population prior to the time of sampling. We evaluate the performance of this statistical framework on simulated data from epidemic trend curves and show that we can recover the parameter values of those trends. We also apply the framework to epidemic trend curves taken from two historical outbreaks: a bluetongue outbreak in cattle, and a whooping cough outbreak in humans. Together, these results show that hindcasting can estimate the time since infection for individuals and provide accurate estimates of epidemic trends, and can be used to distinguish whether an outbreak is increasing or past its peak. We conclude that if temporal characteristics of diagnostics are known, it is possible to recover epidemic trends of both human and animal pathogens from cross-sectional data collected at a single point in time

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

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Objectives: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors. Design: Cross-sectional study. Setting and participants: Plasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples. Outcome measures: Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality. Results: Vitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (<25 nmol/L) were prevalent in COVID-19 (29.3% and 44.4%, respectively), influenza A (47.3% and 37.6%) and critical illness survivors (30.2% and 56.8%). In COVID-19 and influenza A, total 25(OH)D measured early in illness was lower in patients who received IMV (19.6 vs 31.9 nmol/L (p<0.0001) and 22.9 vs 31.1 nmol/L (p=0.0009), respectively). In COVID-19, biologically active free 25(OH)D correlated with total 25(OH)D and was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators. Conclusions: Vitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes