Ambulance service recognition of health inequalities and activities for reduction: An evidence and gap map of the published literature.

Background: Emergency medical services (EMS) are often patients' first point of contact for urgent and emergency care needs. Patients are triaged over the phone and may receive an ambulance response, with potential conveyance to the hospital. A recent scoping review suggested disparities in EMS patient care in the United States. However, it is unknown how health inequalities impact EMS care in other developed countries and how inequalities are being addressed. Objectives: This rapid evidence map of published literature aims to map known health inequalities in EMS patients and describe interventions reducing health inequalities in EMS patient care. Methods: The search strategy consisted of EMS synonyms and health inequality synonyms. The MEDLINE/PubMed database was searched from 1 January 2010 to 26 July 2022. Studies were included if they described empirical research exploring health inequalities within ambulance service patient care. Studies were mapped on to the EMS care interventions framework and Core20PLUS5 framework. Studies evaluating interventions were synthesised using the United Kingdom Allied Health Professions Public Health Strategic Framework. Results: The search strategy yielded 771 articles, excluding duplicates, with two more studies added from hand searches. One hundred studies met the inclusion criteria after full-text review. Inequalities in EMS patient care were predominantly situated in assessment, treatment and conveyance, although triage and response performance were also represented. Studies mostly explored EMS health inequalities within ethnic minority populations, populations with protected characteristics and the core issue of social deprivation. Studies evaluating interventions reducing health inequalities (n = 5) were from outside the United Kingdom and focused on older patients, ethnic minorities and those with limited English proficiency. Interventions included community paramedics, awareness campaigns, dedicated language lines and changes to EMS protocols. Conclusions: Further UK-based research exploring health inequalities of EMS patients would support ambulance service policy and intervention development to reduce health inequality in urgent and emergency care delivery.

Interventions to improve executive functions in children aged 3 years and under: A systematic review.

BACKGROUND: Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions enhancing these capabilities could have critical import in improving outcomes. However, to develop interventions, it is necessary to identify specific EF skills that will vary with child age. Thus, we aimed to examine the characteristics and efficacy of interventions targeting EF in infancy and early childhood up to age 3. METHODS: A comprehensive search of PubMed, Embase, CINAHL and APA PsycINFO databases was performed for studies published before December 2022. Randomized and non-randomized studies of interventions designed to improve at least one EF skill in children ≤3 years were included. EF skills included attentional control, inhibition/self-regulation, activity initiation, working memory, cognitive flexibility, planning ability, problem-solving and performance monitoring. We independently extracted data, used the revised Cochrane Risk-of-Bias tool to assess the quality of the evidence and conducted Synthesis Without Meta-analysis (SWiM). The overall quality of the evidence and the strength of recommendations was determined using elements of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Thirty-five studies met inclusion criteria (original n = 7467). Studies were highly variable in the EF skill targeted, target subject (i.e., child, parent and teacher), nature and dosage of the intervention, and timing of outcome assessment. Most interventions focused on improving impulse control and self-regulation. The overall quality of evidence was low to moderate with a high risk of bias, though six studies had low risk of bias but yielded mixed findings of efficacy. CONCLUSIONS: The relatively small number of early EF intervention studies uses such variable methods that there is currently no converging evidence of efficacy to recommend a specific intervention. Thus, findings support the need for a more systematic, targeted approach to the design and implementation of early EF interventions for target populations.

Factors associated with delayed diagnosis of leprosy in an endemic area in Northeastern Brazil: a cross-sectional study.

This study aimed to investigate the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy in an endemic area in the Northeastern Brazil. This is a cross-sectional study of 120 individuals with leprosy. Demographic and clinical data and information on the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy were obtained. Delayed diagnosis in months was estimated for each participant by interviews. A multivariate Poisson's regression analysis was performed between the outcome and the independent variables. The median delay in the diagnosis of leprosy was 10.5 (4.0-24.0) months. Approximately 12.6% of participants had grade 2 disability (G2D) at the time of diagnosis. In the multivariate Poisson regression analysis, males, older age, low schooling level, residing in urban areas, multibacellar or tuberculoid leprosy, not seeking healthcare immediately after symptom onset, suspected leprosy, excessive referrals, and the need for three or more consultations to confirm the diagnosis were associated with longer diagnostic delay. This study found a significant delay in the diagnosis of leprosy in Arapiraca, Northeastern Brazil, which may explain the continuously high rate of G2D among new cases. Factors related to the individual and the health system were associated with longer diagnostic delay. Interventions to raise awareness of the disease among the general population and strengthen primary health care are urgently needed.

Factors associated with delayed diagnosis of leprosy in an endemic area in Northeastern Brazil: a cross-sectional study / Fatores associados ao atraso no diagnóstico da hanseníase em área endêmica no Nordeste do Brasil: um estudo transversal / Factores asociados con el diagnóstico tardío de la lepra en un área endémica del Nordeste de Brasil: un estudio transversal

Abstract: This study aimed to investigate the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy in an endemic area in the Northeastern Brazil. This is a cross-sectional study of 120 individuals with leprosy. Demographic and clinical data and information on the factors related to the individual and the health system that contribute to delayed diagnosis of leprosy were obtained. Delayed diagnosis in months was estimated for each participant by interviews. A multivariate Poisson's regression analysis was performed between the outcome and the independent variables. The median delay in the diagnosis of leprosy was 10.5 (4.0-24.0) months. Approximately 12.6% of participants had grade 2 disability (G2D) at the time of diagnosis. In the multivariate Poisson regression analysis, males, older age, low schooling level, residing in urban areas, multibacellar or tuberculoid leprosy, not seeking healthcare immediately after symptom onset, suspected leprosy, excessive referrals, and the need for three or more consultations to confirm the diagnosis were associated with longer diagnostic delay. This study found a significant delay in the diagnosis of leprosy in Arapiraca, Northeastern Brazil, which may explain the continuously high rate of G2D among new cases. Factors related to the individual and the health system were associated with longer diagnostic delay. Interventions to raise awareness of the disease among the general population and strengthen primary health care are urgently needed.

Resumo: Neste estudo objetivou-se investigar os fatores relacionados ao indivíduo e ao sistema de saúde que contribuem para o atraso no diagnóstico da hanseníase em uma área endêmica no Nordeste do Brasil. Trata-se de um estudo transversal que incluiu 120 pacientes com hanseníase. Foram obtidos dados demográficos, clínicos e informações sobre fatores relacionados ao indivíduo e ao sistema de saúde que contribuem para o atraso no diagnóstico da hanseníase. O atraso do diagnóstico em meses foi estimado para cada participante por meio de entrevistas. Foi realizada uma análise multivariada por regressão de Poisson entre o resultado e as variáveis independentes. A mediana de atraso no diagnóstico da hanseníase foi de 10,5 (4,0-24,0) meses. Aproximadamente 12,6% dos participantes apresentavam grau de incapacidade física 2 (GIF 2) no momento do diagnóstico. Na análise multivariada por regressão de Poisson, homens, idosos, baixa escolaridade, residir em área urbana, hanseníase multibacilar, hanseníase tuberculóide, não procurar atendimento imediatamente após perceber os primeiros sintomas, suspeita de hanseníase, encaminhamentos excessivos e três ou mais consultas necessárias para confirmação diagnóstica associaram-se ao maior atraso diagnóstico. Este estudo encontrou um atraso significativo no diagnóstico da hanseníase em Arapiraca, Nordeste do Brasil, o que pode explicar a taxa continuamente alta de GIF 2 entre os casos novos. Fatores relacionados ao indivíduo e ao sistema de saúde foram associados ao maior atraso no diagnóstico. Intervenções para aumentar a conscientização sobre a doença entre a população geral e fortalecer a atenção primária à saúde são urgentemente necessárias.

Resumen: El objetivo de este estudio fue investigar los factores relacionados con el individuo y el sistema de salud que contribuyen al diagnóstico tardío de la lepra en un área endémica del Nordeste de Brasil. Se trata de un estudio transversal que incluyó a 120 pacientes con lepra. Se obtuvieron datos demográficos, clínicos e informaciones sobre los factores relacionados con el individuo y el sistema de salud que contribuyen al diagnóstico tardío de la lepra. Se estimó el retraso del diagnóstico en meses para cada participante a través de entrevistas. Se realizó un análisis multivariante por regresión de Poisson entre el resultado y las variables independientes. La mediana de retraso en el diagnóstico de lepra fue de 10,5 (4,0-24,0) meses. Aproximadamente el 12,6% de los participantes tenían grado de discapacidad física 2 (GIF 2) en el momento del diagnóstico. En el análisis multivariante por regresión de Poisson se encontró que los hombres, ancianos, la baja escolaridad, vivir en área urbana, la lepra multibacilar, la lepra tuberculoide, no buscar atención médica inmediatamente tras notar los primeros síntomas, la sospecha de lepra, las derivaciones excesivas y la necesidad de tres o más consultas para confirmar el diagnóstico se asociaron con un mayor retraso del diagnóstico. Este estudio encontró un retraso significativo en el diagnóstico de la lepra en Arapiraca, Nordeste de Brasil, lo que puede explicar la tasa continuamente alta de GIF 2 entre los nuevos casos. Factores relacionados con el individuo y el sistema de salud se asociaron con el mayor retraso del diagnóstico. Intervenciones para aumentar la concienciación sobre la enfermedad entre la población general y fortalecer la atención primaria de salud son urgentemente necesarias.

Investigating One Health risks for human colonisation with extended spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study.

BACKGROUND: Low-income countries have high morbidity and mortality from drug-resistant infections, especially from enteric bacteria such as Escherichia coli. In these settings, sanitation infrastructure is of variable and often inadequate quality, creating risks of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales transmission. We aimed to describe the prevalence, distribution, and risks of ESBL-producing Enterobacterales colonisation in sub-Saharan Africa using a One Health approach. METHODS: Between April 29, 2019, and Dec 3, 2020, we recruited 300 households in Malawi for this longitudinal cohort study: 100 each in urban, peri-urban, and rural settings. All households underwent a baseline visit and 195 were selected for longitudinal follow-up, comprising up to three additional visits over a 6 month period. Data on human health, antibiotic usage, health-seeking behaviours, structural and behavioural environmental health practices, and animal husbandry were captured alongside human, animal, and environmental samples. Microbiological processing determined the presence of ESBL-producing E coli and Klebsiella pneumoniae, and hierarchical logistic regression was performed to evaluate the risks of human ESBL-producing Enterobacterales colonisation. FINDINGS: A paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites. A total of 11 975 samples were cultured, and ESBL-producing Enterobacterales were isolated from 1190 (41·8%) of 2845 samples of human stool, 290 (29·8%) of 973 samples of animal stool, 339 (66·2%) of 512 samples of river water, and 138 (46·0%) of 300 samples of drain water. Multivariable models illustrated that human ESBL-producing E coli colonisation was associated with the wet season (adjusted odds ratio 1·66, 95% credible interval 1·38-2·00), living in urban areas (2·01, 1·26-3·24), advanced age (1·14, 1·05-1·25), and living in households where animals were observed interacting with food (1·62, 1·17-2·28) or kept inside (1·58, 1·00-2·43). Human ESBL-producing K pneumoniae colonisation was associated with the wet season (2·12, 1·63-2·76). INTERPRETATION: There are extremely high levels of ESBL-producing Enterobacterales colonisation in humans and animals and extensive contamination of the wider environment in southern Malawi. Urbanisation and seasonality are key risks for ESBL-producing Enterobacterales colonisation, probably reflecting environmental drivers. Without adequate efforts to improve environmental health, ESBL-producing Enterobacterales transmission is likely to persist in this setting. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Multicenter Diagnostic Evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has given rise to numerous commercially available antigen rapid diagnostic tests (Ag-RDTs). To generate and to share accurate and independent data with the global community requires multisite prospective diagnostic evaluations of Ag-RDTs. This report describes the clinical evaluation of the OnSite COVID-19 rapid test (CTK Biotech, CA, USA) in Brazil and the United Kingdom. A total of 496 paired nasopharyngeal (NP) swabs were collected from symptomatic health care workers at Hospital das Clínicas in São Paulo, Brazil, and 211 NP swabs were collected from symptomatic participants at a COVID-19 drive-through testing site in Liverpool, United Kingdom. Swabs were analyzed by Ag-RDT, and results were compared to quantitative reverse transcriptase PCR (RT-qPCR). The clinical sensitivity of the OnSite COVID-19 rapid test in Brazil was 90.3% (95% confidence interval [CI], 75.1 to 96.7%) and in the United Kingdom was 75.3% (95% CI, 64.6 to 83.6%). The clinical specificity in Brazil was 99.4% (95% CI, 98.1 to 99.8%) and in the United Kingdom was 95.5% (95% CI, 90.6 to 97.9%). Concurrently, analytical evaluation of the Ag-RDT was assessed using direct culture supernatant of SARS-CoV-2 strains from wild-type (WT), Alpha, Delta, Gamma, and Omicron lineages. This study provides comparative performance of an Ag-RDT across two different settings, geographical areas, and populations. Overall, the OnSite Ag-RDT demonstrated a lower clinical sensitivity than claimed by the manufacturer. The sensitivity and specificity from the Brazil study fulfilled the performance criteria determined by the World Health Organization, but the performance obtained from the UK study failed to do. Further evaluation of Ag-RDTs should include harmonized protocols between laboratories to facilitate comparison between settings. IMPORTANCE Evaluating rapid diagnostic tests in diverse populations is essential to improving diagnostic responses as it gives an indication of the accuracy in real-world scenarios. In the case of rapid diagnostic testing within this pandemic, lateral flow tests that meet the minimum requirements for sensitivity and specificity can play a key role in increasing testing capacity, allowing timely clinical management of those infected, and protecting health care systems. This is particularly valuable in settings where access to the test gold standard is often restricted.

Implementation of Early Detection and Intervention for Cerebral Palsy in High-Risk Infant Follow-Up Programs: U.S. and Global Considerations.

Early detection and intervention for cerebral palsy is best practice for all high-risk infants according to international guidelines, consensus statements and research-supported evidence. It allows support for families and optimization of developmental trajectories into adulthood. All phases of implementation of CP early detection can be found across the world in high-risk infant follow-up programs, demonstrating feasibility and acceptability through standardized implementation science. The largest clinical network for CP early detection and intervention in the world has now sustained an average age at detection less than 12 months corrected age for more than 5 years. Targeted referrals and interventions for CP can now be offered to patients in optimal periods of neuroplasticity, and new therapies researched as the age of detection decreases. Implementation of guidelines and incorporation of rigorous CP research studies both allow high-risk infant follow-up programs to fulfill their mission of improving outcomes of those with the most vulnerable developmental trajectories from birth.

Efficacy, Safety, Patient Experience, and Tolerability of Risankizumab Administered by On-Body Injector for Moderate to Severe Crohn's Disease.

INTRODUCTION: In patients with moderate to severe Crohn's disease (CD), intravenous induction and subcutaneous maintenance dosing with risankizumab was efficacious and well tolerated. Long-term management of CD via self-administration of risankizumab using an on-body injector (OBI) may improve treatment adherence through convenience and ease of use. METHODS: Within the FORTIFY maintenance study, 46 patients from the United States (US) sites participated in an open-label extension Substudy and received 180 mg or 360 mg risankizumab delivered subcutaneously via OBI [360 mg (2.4 mL, 150 mg/mL) or 180 mg (1.2 mL, 150 mg/mL)]. At the Week 0 visit, patients were trained (pre-injection) by site staff, using Instructions for Use (IFU) and a training video, to self-administer risankizumab at Weeks 0 (on site), 8 (at home), and 16 (on site). Key objectives of the Substudy 4 were to assess OBI usability (observer rating of successful self-administration), hazard-free self-injection at Weeks 0 and 16, and patient rating of acceptability using the Self-Injection Assessment Questionnaire (SIAQ) at Weeks 0, 8, and 16. Additionally, the proportion of patients in clinical remission (CD Activity Index < 150) was collected at Weeks 0 and 16. RESULTS: All patients successfully self-administered risankizumab via OBI, including two patients who successfully self-administered with a second OBI (i.e., required two injection attempts). Acceptability of self-injection was high. Two patients (n = 2) experienced a use-related hazard. Stable clinical remission was observed with both risankizumab doses. Two patients experienced injection site reactions; neither was related to the OBI per investigator's assessment. Two device-related adverse events related to topical adhesive reactions were reported, both mild and resolved. No new safety risks were observed. CONCLUSION: The efficacy and safety of maintenance risankizumab delivered via OBI and OBI usability support the use of this device in patients with moderate to severe CD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03105102 (FORTIFY).

Evaluation of eight lateral flow tests for the detection of anti-SARS-CoV-2 antibodies in a vaccinated population.

BACKGROUND: Rapid determination of an individual's antibody status can be beneficial in understanding an individual's immune response to SARS-CoV-2 and for initiation of therapies that are only deemed effective in sero-negative individuals. Antibody lateral flow tests (LFTs) have potential to address this need as a rapid, point of care test. METHODS: Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. Samples were analysed on eight different brands of antibody LFT and an automated chemiluminescent microparticle immunoassay (CMIA) that identifies anti-spike antibodies which was used as our reference standard. RESULTS: All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n = 60), AZD1222 (AstraZeneca, n = 31), mRNA-1273 (Moderna, n = 2) and Undeclared Vaccine Brand (n = 2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. CONCLUSIONS: These tests are demonstrated to be highly sensitive to detect raised antibody levels in vaccinated individuals. RDTs are low cost and rapid alternatives to ELISA based systems.

Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: An observational cohort study.

BACKGROUND: The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the United Kingdom National Health Service (NHS). We conducted an observational cohort study of SARS-CoV-2 infection in frontline healthcare workers (HCW) working in an acute NHS Trust during the first wave of the pandemic, to answer emerging questions surrounding SARS-CoV-2 infection, diagnosis, transmission and control. METHODS: Using self-collected weekly saliva and twice weekly combined oropharyngeal/nasopharyngeal (OP/NP) samples, in addition to self-assessed symptom profiles and isolation behaviours, we retrospectively compared SARS-CoV-2 detection by RT-qPCR of saliva and OP/NP samples. We report the association with contemporaneous symptoms and isolation behaviour. RESULTS: Over a 12-week period from 30th March 2020, 40·0% (n = 34/85, 95% confidence interval 31·3-51·8%) HCW had evidence of SARS-CoV-2 infection by surveillance OP/NP swab and/or saliva sample. Symptoms were reported by 47·1% (n = 40) and self-isolation by 25·9% (n = 22) participants. Only 44.1% (n = 15/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of a positive result and only 29·4% (n = 10/34) reported self-isolation periods. Overall agreement between paired saliva and OP/NP swabs was 93·4% (n = 211/226 pairs) but rates of positive concordance were low. In paired samples with at least one positive result, 35·0% (n = 7/20) were positive exclusively by OP/NP swab, 40·0% (n = 8/20) exclusively by saliva and in only 25·0% (n = 5/20) were the OP/NP and saliva result both positive. CONCLUSIONS: HCW are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections. Without routine asymptomatic SARS-CoV-2 screening, it is likely that HCW with SARS-CoV-2 infection would continue to attend work. Saliva, in addition to OP/NP swab testing, facilitated ascertainment of symptomatic and asymptomatic SARS-CoV-2 infections. Combined saliva and OP/NP swab sampling would improve detection of SARS-CoV-2 for surveillance and is recommended for a high sensitivity strategy.

An investigation of Mycobacterium bovis and helminth coinfection in the European badger Meles meles.

We investigated the relationship between the presence of helminth parasites in European badgers, and their tuberculosis (TB) status, culled as part of the bovine TB eradication programme in Ireland. Data on the worm burden or faecal egg or larval count was available for all helminth taxa recorded. Lymph node tissue samples were taken from the badgers and tested for TB. We then explored the correlation, in full-grown badgers, between the likelihood of M. bovis infection and both the prevalence and burden of certain helminth species. Specifically, our analyses focused upon the gastrointestinal species, Uncinaria criniformis and Strongyloides spp. We found that male badgers were more likely to have TB than female badgers, and that badgers infected with U. criniformis or Strongyloides spp. were more likely to have TB than badgers without such helminth infections. There was a suggestion that badgers with higher U. criniformis worm burdens were more likely to have TB than those with lesser burdens. Although our sampling protocols did not allow us to determine which infection came first, it strongly suggests that once badgers are infected with either gastrointestinal helminths or TB, they are likely to become coinfected. As Ireland works towards a national TB-free status, it will be important to appreciate the implications of such coinfection.

Multicenter Diagnostic Evaluation of a Novel Coronavirus Antigen Lateral Flow Test among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 103 PFU/mL (Alpha), 2.5 × 102 PFU/mL (Delta), 2.5 × 103 PFU/mL (Gamma), and 1.0 × 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 104 copies/mL, 9.0 × 105 copies/mL, 1.7 × 106 copies/mL, and 1.8 × 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods. IMPORTANCE Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.

A novel, magnetic bead-based extraction method for the isolation of antimicrobial resistance genes with a case study in river water in Malawi.

AIMS: The environment is increasingly recognized as an important reservoir of antimicrobial resistance genes (ARGs), which can be identified using molecular platforms. Yet, environmental surveillance remains an underutilised tool as there is no agreement on the best strategy for sample processing. We aim to develop a low-cost extraction method independent to commercial kits or reagents. METHODS AND RESULTS: We present a novel, magnetic bead-based method for the isolation of ARGs from river water named MagnaExtract. We present this with analytic limit of detection as well as a case study in Southern Malawi. Here we compare the DNA yield from MagnaExtract with commercially available QIAGEN kits and the crude boil and spin method, using a high-resolution melt analysis PCR panel designed for the detection of third-generation cephalosporin and carbapenem-resistant genes from 98 water samples. CONCLUSION: The MagnaExtract method is comparable, and in some instance's superior to commercially available kits for the isolation of ARGs from river water samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The MagnaExtract approach offers a simple, affordable, high yielding extraction method that could be used for the detection of ARGs from river water samples in surveillance campaigns in East Africa.

Streptococcus pneumoniae colonization associates with impaired adaptive immune responses against SARS-CoV-2.

BackgroundAlthough recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, cases of coinfection with Streptococcus pneumoniae in patients with coronavirus disease 2019 (COVID-19) during hospitalization have been reported infrequently. This apparent contradiction may be explained by interactions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pneumococci in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses.MethodsHere, we investigated the relationship of these 2 respiratory pathogens in 2 distinct cohorts of health care workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and patients with moderate to severe disease who presented to the hospital. We assessed the effect of coinfection on host antibody, cellular, and inflammatory responses to the virus.ResultsIn both cohorts, pneumococcal colonization was associated with diminished antiviral immune responses, which primarily affected mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients.ConclusionOur findings suggest that S. pneumoniae impair host immunity to SARS-CoV-2 and raise the question of whether pneumococcal carriage also enables immune escape of other respiratory viruses and facilitates reinfection.Trial registrationISRCTN89159899 (FASTER study) and ClinicalTrials.gov NCT03502291 (LAIV study).

Twelve lateral flow immunoassays (LFAs) to detect SARS-CoV-2 antibodies.

BACKGROUND: There are an abundance of commercially available lateral flow assays (LFAs) that detect antibodies to SARS-CoV-2. Whilst these are usually evaluated by the manufacturer, externally performed diagnostic accuracy studies to assess performance are essential. Herein we present an evaluation of 12 LFAs. METHODS: Sera from 100 SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) positive participants were recruited through the FASTER study. A total of 105 pre-pandemic sera from participants with other infections were included as negative samples. RESULTS: At presentation sensitivity against RT-PCR ranged from 37.4 to 79% for IgM/IgG, 30.3-74% for IgG, and 21.2-67% for IgM. Sensitivity for IgM/IgG improved ≥ 21 days post symptom onset for 10/12 tests. Specificity ranged from 74.3 to 99.1% for IgM/IgG, 82.9-100% for IgG, and 75.2-98% for IgM. Compared to the EuroImmun IgG enzyme-linked immunosorbent assay (ELISA), sensitivity and specificity ranged from 44.6 to 95.4% and 85.4-100%, respectively. CONCLUSION: There are many LFAs available with varied sensitivity and specificity. Understanding the diagnostic accuracy of these tests will be vital as we come to rely more on the antibody status of a person moving forward, and as such manufacturer-independent evaluations are crucial.

Drivers of Resistance in Uganda and Malawi (DRUM): a protocol for the evaluation of One-Health drivers of Extended Spectrum Beta Lactamase (ESBL) resistance in Low-Middle Income Countries (LMICs).

In sub-Saharan Africa (sSA), there is high morbidity and mortality from severe bacterial infection and this is compounded by antimicrobial resistance, in particular, resistance to 3rd-generation cephalosporins. This resistance is typically mediated by extended-spectrum beta lactamases (ESBLs). To interrupt ESBL transmission it will be important to investigate how human behaviour, water, sanitation, and hygiene (WASH) practices, environmental contamination, and antibiotic usage in both urban and rural settings interact to contribute to transmission of ESBL E. coli and ESBL K. pneumoniae between humans, animals, and the environment. Here we present the protocol for the Drivers of Resistance in Uganda and Malawi (DRUM) Consortium, in which we will collect demographic, geospatial, clinical, animal husbandry and WASH data from a total of 400 households in Uganda and Malawi. Longitudinal human, animal and environmental sampling at each household will be used to isolate ESBL E. coli and ESBL K. pneumoniae. This will be complimented by a Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) survey and structured observations to understand the contextual and psychosocial drivers of regional WASH practices. Bacterial isolates and plate sweeps will be further characterised using a mixture of short-,long-read and metagenomic whole-genome sequencing. These datasets will be integrated into agent-based models to describe the transmission of EBSL resistance in Uganda and Malawi and allow us to inform the design of interventions for interrupting transmission of ESBL-bacteria.