Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant.

BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×1010 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS: Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, -76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132).

Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis.

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%-115%); tolbutamide, 80% (74%-86%); omeprazole, 55% (47%-65%); dextromethorphan, 77% (68%-86%); midazolam, 62% (49%-78%), and 117% (105%-130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.

Legislative framework for national contingency planning and response.

Contingency plans are a key tool to prevent and respond to events of different origins and nature that may affect animal health, animal welfare and veterinary public health needs. They should include a number of elements ranging from assessment and notification systems, financial arrangements and the role of national authorities. To help to ensure their effective and rapid implementation and prevent gaps, they should be based on a clear legal framework; this 'enabling legislation' will provide for basic requirements and the overall content of the plans. This paper first examines the basis of an effective and comprehensive legal framework for national contingency planning and response and considers the formal and substantive contents of such a framework. It then looks at different steps that can be taken to evaluate and strengthen existing national legislation. Finally, it describes the assistance role of the World Organisation for Animal Health in reviewing and developing national legislation.

Les plans d'urgence sont un outil essentiel de prévention et d'intervention se rapportant à des événements d'origine et de nature diverses qui peuvent avoir un impact sur la santé animale, le bien-être animal et la santé publique vétérinaire. Plusieurs aspects doivent être prévus dans cette planification, depuis les systèmes d'évaluation et de notification jusqu'aux dispositifs financiers en passant par le rôle joué par les autorités nationales. Les plans d'urgence doivent être soutenus par un cadre juridique clair afin d'assurer une mise en œuvre efficace et rapide et d'éviter les lacunes ; un tel cadre d'habilitation devra couvrir les exigences de base et l'essentiel du contenu des plans. Les auteurs décrivent d'abord les composantes essentielles requises pour qu'un cadre législatif recouvre de manière complète et efficace les plans nationaux d'urgence et d'intervention, ainsi que le contenu d'un tel cadre, tant sur la forme que sur le fond. Ils examinent ensuite les différentes mesures pouvant être prises par les pays pour évaluer et renforcer leur législation nationale. Enfin, ils décrivent le soutien apporté par l'Organisation mondiale de la santé animale aux pays souhaitant procéder à l'examen ou à l'améloration de leur législation nationale en la matière.

Los planes para casos de emergencia son una herramienta básica para prevenir y afrontar episodios de diferente naturaleza y origen que pueden afectar a la sanidad y el bienestar animales y a las necesidades de salud pública veterinaria. Estos planes deben cubrir una serie de temas que van desde los sistemas de evaluación y notificación hasta los mecanismos de financiación y la función de las autoridades nacionales competentes. Para que puedan ser aplicados rápida y eficazmente y evitar lagunas deben reposar en un ordenamiento jurídico claro, la «base legislativa¼ que sentará los requisitos básicos y el contenido general de los planes. Los autores exponen en primer lugar los elementos en que debe basarse un ordenamiento jurídico eficaz y completo, que encuadre la planificación nacional para casos de emergencia y las correspondientes medidas de respuesta, y explican la forma que debe revestir y cuál ha de ser su contenido. A continuación se detienen en las distintas medidas que se pueden adoptar para evaluar y mejorar la legislación nacional existente. Por último, describen la función que cumple la Organización Mundial de Sanidad Animal ayudando a los países a examinar y desarrollar su acervo legislativo.

Performance of Veterinary Services Pathway evolution and One Health aspects.

Animals, and the health systems which ensure their protection, play a vital role in the security and economic and social well-being of humanity, and are therefore a key component of the One Health concept. For global and national health security, prevention is better than cure, and targeting 'risk at source' in animal populations is a vital strategy in safeguarding the planet from risks of emerging zoonoses and antimicrobial resistance (AMR). Neglected zoonoses - such as rabies and brucellosis - continue to have a significant global impact on human health and are also best managed at their animal source. The World Organisation for Animal Health (OIE) has built international consensus on the principles of good governance and the quality of Veterinary Services, which are incorporated within its international standards. The OIE has a proven track record in the provision of Member Country support based on these standards, especially since the advent of its flagship Performance of Veterinary Services (PVS) Pathway programme in 2006-2007. To date, approximately 140 countries have benefited from the structured and sustainable process of animal health systems evaluation and planning afforded by the PVS Pathway. The PVS Tool, the basic methodology upon which the PVS Pathway is based, addresses One Health by evaluating the Veterinary Authority's ability to coordinate with other Competent Authorities that have a role to play in One Health, most notably public health, food safety, and environmental authorities. Despite the undoubted success of the PVS Pathway, the OIE felt that it was time to consider how the programme might be developed to adapt to new challenges. Consequently, during 2017-2018, the OIE embarked on a process of PVS evolution, during which it carried out extensive consultation and further tailored the PVS Pathway to a changing global context. These improvements, which include both fundamental adaptations to the PVS Pathway methods and the development of new PVS Pathway activities targeting topics such as multisectoral collaboration, rabies and AMR, have further strengthened and embedded the One Health approach within the PVS Pathway.

Parce qu'ils jouent un rôle crucial pour la sécurité et le bien-être économique et social de l'humanité, les animaux et les systèmes sanitaires en charge de leur protection sont une composante clé du concept Une seule santé. En matière de sécurité sanitaire à l'échelle du monde ou d'un pays, il vaut toujours mieux prévenir que guérir ; c'est pourquoi la stratégie consistant à cibler le risque à sa source est la seule qui puisse protéger la planète contre les zoonoses émergentes et le développement de l'antibiorésistance. L'impact sur la santé publique des zoonoses négligées comme la rage et la brucellose reste important et c'est également à leur source animale que les interventions visant à les contrôler sont les plus efficaces. L'Organisation mondiale de la santé animale (OIE) a forgé un consensus international autour des principes de bonne gouvernance et de qualité des Services vétérinaires et les a inscrites au coeur de ses normes internationales. L'OIE a démontré sa capacité à apporter aux Pays membres un soutien basé sur ces normes, en particulier depuis la création en 2006­2007 du Processus sur les Performances des Services vétérinaires (PVS), son programme phare. À ce jour, près de 140 pays ont bénéficié d'une procédure structurée d'évaluation et de planification durable de leurs systèmes de santé animale, grâce au Processus PVS. L'Outil PVS, instrument méthodologique du Processus PVS, couvre certains aspects relevant de l'approche Une seule santé en évaluant les capacités de concertation des Autorités vétérinaires avec d'autres autorités compétentes ayant un rôle à jouer dans ce contexte, en particulier celles en charge de la santé publique, de la sécurité sanitaire des aliments et de la protection de l'environnement. En dépit de la réussite incontestée du Processus PVS, l'OIE a estimé que le temps était venu d'envisager l'évolution de ce programme afin de l'adapter aux nouveaux défis. En conséquence, l'OIE a lancé en 2017­2018 la phase d'Évolution du Processus OIE à travers de larges consultations visant à adapter le Processus PVS aux mutations du contexte mondial. Les améliorations apportées, qui portent à la fois sur les fondements méthodologiques et sur la conception de nouvelles activités du Processus PVS dédiées à des sujets tels que la collaboration multisectorielle, la rage et la résistance aux agents antimicrobiens ont renforcé l'approche Une seule santé ainsi que son ancrage dans le Processus PVS.

Los animales y los sistemas sanitarios que velan por su protección cumplen una función vital para la seguridad y el bienestar económico y social de la humanidad, razón por la cual constituyen un elemento básico del concepto de Una sola salud. Desde el punto de vista de la seguridad sanitaria del mundo y de los países, más vale prevenir que curar, y el hecho de ir a combatir un riesgo en las poblaciones animales en las que tiene su origen es una estrategia indispensable para salvaguardar al planeta de los peligros que entrañan las zoonosis emergentes y la resistencia a los antimicrobianos. La mejor forma de luchar contra zoonosis desatendidas como la rabia o la brucelosis, que en todo el mundo siguen repercutiendo sensiblemente en la salud humana, pasa por atacarlas en su origen animal. La Organización Mundial de Sanidad Animal (OIE) ha sabido suscitar un consenso internacional en torno a los principios de buen gobierno y calidad de los Servicios Veterinarios, integrados ahora en sus normas internacionales. La OIE goza de contrastada experiencia en la prestación de apoyo a los Países Miembros basándose en estas normas, especialmente desde la instauración en 2006­2007 de su emblemático programa llamado Proceso PVS (Prestaciones de los Servicios Veterinarios). Hasta la fecha, alrededor de 140 países han podido beneficiarse del procedimiento estructurado y sostenible de evaluación y planificación de los sistemas de sanidad animal que se propone a través del Proceso PVS. La Herramienta PVS aporta la metodología básica en que descansa el Proceso PVS: con ella se trabaja en clave de Una sola salud evaluando la capacidad de la Autoridad Veterinaria del país para coordinarse con las demás autoridades competentes que cumplen alguna función relacionada con Una sola salud, sobre todo las de salud pública, seguridad sanitaria de los alimentos y medio ambiente. Pese al indiscutible éxito cosechado por el Proceso PVS, la OIE estimó llegado el momento de plantearse hacia dónde hacer evolucionar el programa para adaptarlo a nuevas problemáticas. Obrando en consecuencia, en 2017 y 2018 la OIE se embarcó en un proceso de «evolución del PVS¼ durante el cual celebró vastas consultas y adaptó aún más el Proceso PVS a un panorama mundial en constante evolución, incorporándole mejoras que incluyen a la vez una serie de ajustes básicos en los métodos del Proceso PVS y la creación de nuevas actividades encuadradas en él sobre temas como la colaboración multisectorial, la rabia o la resistencia a los antimicrobianos, mejoras que a la postre han servido para potenciar la filosofía de Una sola salud e integrarla aún más en el Proceso PVS.

Medical students and personal smartphones in the clinical environment: the impact on confidentiality of personal health information and professionalism.

BACKGROUND: Smartphones are becoming ubiquitous in health care settings. The increased adoption of mobile technology such as smartphones may be attributed to their use as a point-of-care information source and to perceived improvements in clinical communication and efficiency. However, little is known about medical students' use of personal smartphones for clinical work. OBJECTIVE: The intent of the study was to examine final-year medical students' experience with and attitudes toward using personal mobile technology in the clinical environment, with respect to the perceived impact on patient confidentiality and provider professionalism. METHODS: Cross-sectional surveys were completed by final-year medical students at the University of Toronto. Respondents were asked about the type of personal mobile phone they use, security features on their personal phone, experiences using their personal phone during clinical rotations, and attitudes about using their personal phone for clinical work purposes. RESULTS: The overall response rate was 45.4% (99/218). Smartphone ownership was prevalent (98%, 97/99) with the majority (86%, 85/99) of participants using their personal phones for patient-related communication during clinical rotations. A total of 26% (26/99) of participants reported not having any type of security feature on their personal phone, 94% (90/96) of participants agreed that using their personal phone for clinical work makes them more efficient, and 86% (82/95) agreed that their personal phone allows them to provide better patient care. Although 68% (65/95) of participants believe that the use of personal phones for patient-related communication with colleagues poses a risk to the privacy and confidentiality of patient health information, 22% (21/96) of participants still use their personal phone to text or email identifiable patient data to colleagues. CONCLUSIONS: Our findings suggest that the use of personal smartphones for clinical work by medical students is prevalent. There is a need to more fully address the threat to patient confidentiality posed by the use of unsecured communication devices such as smartphones.

Electronic immunization data collection systems: application of an evaluation framework.

BACKGROUND: Evaluating the features and performance of health information systems can serve to strengthen the systems themselves as well as to guide other organizations in the process of designing and implementing surveillance tools. We adapted an evaluation framework in order to assess electronic immunization data collection systems, and applied it in two Ontario public health units. METHODS: The Centers for Disease Control and Prevention's Guidelines for Evaluating Public Health Surveillance Systems are broad in nature and serve as an organizational tool to guide the development of comprehensive evaluation materials. Based on these Guidelines, and informed by other evaluation resources and input from stakeholders in the public health community, we applied an evaluation framework to two examples of immunization data collection and examined several system attributes: simplicity, flexibility, data quality, timeliness, and acceptability. Data collection approaches included key informant interviews, logic and completeness assessments, client surveys, and on-site observations. RESULTS: Both evaluated systems allow high-quality immunization data to be collected, analyzed, and applied in a rapid fashion. However, neither system is currently able to link to other providers' immunization data or provincial data sources, limiting the comprehensiveness of coverage assessments. We recommended that both organizations explore possibilities for external data linkage and collaborate with other jurisdictions to promote a provincial immunization repository or data sharing platform. CONCLUSIONS: Electronic systems such as the ones described in this paper allow immunization data to be collected, analyzed, and applied in a rapid fashion, and represent the infostructure required to establish a population-based immunization registry, critical for comprehensively assessing vaccine coverage.

The good, bad, and ugly of online recruitment of parents for health-related focus groups: lessons learned.

BACKGROUND: We describe our experiences with identifying and recruiting Ontario parents through the Internet, primarily, as well as other modes, for participation in focus groups about adding the influenza vaccine to school-based immunization programs. OBJECTIVE: Our objectives were to assess participation rates with and without incentives and software restrictions. We also plan to examine study response patterns of unique and multiple submissions and assess efficiency of each online advertising mode. METHODS: We used social media, deal forum websites, online classified ads, conventional mass media, and email lists to invite parents of school-aged children from Ontario, Canada to complete an online questionnaire to determine eligibility for focus groups. We compared responses and paradata when an incentive was provided and there were no software restrictions to the questionnaire (Period 1) to a period when only a single submission per Internet protocol (IP) address (ie, software restrictions invoked) was permitted and no incentive was provided (Period 2). We also compared the median time to complete a questionnaire, response patterns, and percentage of missing data between questionnaires classified as multiple submissions from the same Internet protocol (IP) address or email versus unique submissions. Efficiency was calculated as the total number of hours study personnel devoted to an advertising mode divided by the resultant number of unique eligible completed questionnaires . RESULTS: Of 1346 submitted questionnaires, 223 (16.6%) were incomplete and 34 (2.52%) did not meet the initial eligibility criteria. Of the remaining 1089 questionnaires, 246 (22.6%) were not from Ontario based on IP address and postal code, and 469 (43.1%) were submitted from the same IP address or email address (multiple submissions). In Period 2 vs Period 1, a larger proportion of questionnaires were submitted from Ontario (92.8%, 141/152 vs 75.1%, 702/937, P<.001), and a smaller proportion of same IP addresses (7.9%, 12/152 vs 47.1%, 441/937, P<.001) were received. Compared to those who made unique submissions, those who made multiple submissions spent less time per questionnaire (166 vs 215 seconds, P<.001), and had a higher percentage of missing data among their responses (15.0% vs 7.6%, P=.004). Advertisements posted on RedFlagDeals were the most efficient for recruitment (0.03 hours of staff time per questionnaire), whereas those placed on Twitter were the least efficient (3.64 hours of staff time per questionnaire). CONCLUSIONS: Using multiple online advertising strategies was effective for recruiting a large sample of participants in a relatively short period time with minimal resources. However, risks such as multiple submissions and potentially fraudulent information need to be considered. In our study, these problems were associated with providing an incentive for responding, and could have been partially avoided by activating restrictive software features for online questionnaires.

Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005).

COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18-65 years. South Africa's first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs. VE against asymptomatic and symptomatic infection was 90.6% for WT, 6.7% for Beta and 77.1% for Delta. No cases of severe COVID-19 were documented ahead of unblinding. Safety was consistent with the interim analysis, with no new safety concerns identified. Notably, South Africa's Delta wave occurred ≥ 9 months after primary series vaccination, suggesting that primary series AZD1222 vaccination offers a good durability of protection, potentially due to an anamnestic response. Clinical trial identifier: CT.gov NCT04444674.

Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial.

BACKGROUND: COVID-19 vaccine rollout is lagging in Africa, where there has been a high rate of SARS-CoV-2 infection. We aimed to evaluate the effect of SARS-CoV-2 infection before vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days. METHODS: We did an unmasked post-hoc immunogenicity analysis after the first and second doses of AZD1222 in a randomised, placebo-controlled, phase 1b-2a study done in seven locations in South Africa. AZD1222 recipients who were HIV-uninfected, were stratified into baseline seropositive or seronegative groups using the serum anti-nucleocapsid (anti-N) immunoglobulin G (IgG) electroluminescence immunoassay to establish SARS-CoV-2 infection before the first dose of AZD1222. Binding IgG to spike (anti-S) and receptor binding domain (anti-RBD) were measured before the first dose (day 0), second dose (day 28), day 42, and day 180. Neutralising antibody (NAb) against SARS-CoV-2 variants D614G, beta, delta, gamma, and A.VOI.V2, and omicron BA1 and BA.4 variants, were measured by pseudovirus assay (day 28, day 42, and day 180). This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. FINDINGS: Of 185 individuals who were randomly assigned to AZD1222, we included 91 individuals who were baseline seropositive and 58 who were baseline seronegative, in the final analysis. In the seropositive group, there was little change of anti-S IgG (and anti-RBD IgG) or neutralising antibody (NAb) titres at day 42 compared with at day 28. Anti-S (and anti-RBD) IgG geometric mean concentrations (GMCs) were higher throughout in the seropositive compared with the seronegative group, including at day 180 (GMCs 517·8 [95% CI 411·3-651·9] vs 82·1 [55·2-122·3] BAU/mL). Also D614G NAb geometric mean titres (GMTs) were higher in the seropositive group than the seronegative group, as was the percentage with titres of at least 185 (80% putative risk reduction threshold [PRRT] against wild-type-alpha COVID-19), including at day 180 (92·0% [74·0-99·0] vs 18·2% [2·3-51·8). Similar findings were observed for beta, A.VOI.V2, and gamma. For delta, BA.1, and BA.4, NAb GMTs and the proportion with titres above the PRRT were substantially higher in the seropositive compared with seronegative group at day 28 and day 42, but no longer differed between the groups by day 180. INTERPRETATION: A single dose of AZD1222 in the general African population, where COVID-19 vaccine coverage is low and SARS-CoV-2 seropositivity is 90%, could enhance the magnitude and quality of antibody responses to SARS-CoV-2. FUNDING: The Bill & Melinda Gates Foundation, the South African Medical Research Council, the UK Research and Innovation, the UK National Institute for Health Research, and the South African Medical Research Council. TRANSLATION: For the Zulu translation of the abstract see Supplementary Materials section.

Measurement of a superconducting energy gap in a homogeneously amorphous insulator.

We present tunneling spectroscopy measurements that directly reveal the existence of a superconducting gap in the insulating state of homogenously disordered amorphous indium oxide films. Two films on both sides of the disorder induced superconductor to insulator transition show the same energy gap scale. This energy gap persists up to relatively high magnetic fields and is observed across the magnetoresistance peak typical of disordered superconductors. The results provide useful information for understanding the nature of the insulating state in the disorder induced superconductor to insulator transition.

Influenza vaccination coverage across ethnic groups in Canada.

BACKGROUND: The success of influenza vaccination campaigns may be suboptimal if subgroups of the population face unique barriers or have misconceptions about vaccination. We conducted a national study to estimate influenza vaccine coverage across 12 ethnic groups in Canada to assess the presence of ethnic disparities. METHODS: We pooled responses to the Canadian Community Health Survey between 2003 and 2009 (n = 437 488). We estimated ethnicity-specific self-reported influenza vaccine coverage for the overall population, for people aged 65 years and older, and for people aged 12-64 years with and without chronic conditions. We used weighted logistic regression models to examine the association between ethnicity and influenza vaccination, adjusting for sociodemographic factors and health status. RESULTS: Influenza vaccination coverage ranged from 25% to 41% across ethnic groups. After adjusting for sociodemographic factors and health status for people aged 12 years and older, all ethnic groups were more likely to have received a vaccination against influenza than people who self-identified as white, with the exception of those who self-identified as black (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.88-1.15). Compared with white Canadians, Canadians of Filipino (OR 2.00, 95% CI 1.67-2.40) and Southeast Asian (OR 1.66, 95% CI 1.36-2.03) descent had the greatest likelihood of having received vaccination against influenza. INTERPRETATION: Influenza vaccine coverage in Canada varies by ethnicity. Black and white Canadians have the lowest uptake of influenza vaccine of the ethnic groups represented in our study. Further research is needed to understand the facilitators, barriers and misconceptions relating to vaccination that exist across ethnic groups, and to identify promotional strategies that may improve uptake among black and white Canadians.

Barriers to the use of reminder/recall interventions for immunizations: a systematic review.

BACKGROUND: Although many studies have demonstrated the benefits of reminder/recall (RR) measures to address patient under-immunization and improve immunization coverage, they are not widely implemented by healthcare providers. We identified providers' perceived barriers to their use from existing literature. METHODS: We conducted a systematic review of relevant articles published in English between January 1990 and July 2011 that examined the perceptions of healthcare providers regarding barriers to tracking patient immunization history and implementing RR interventions. We searched MEDLINE, PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Academic Search Premier, and PsychINFO. Additional strategies included hand-searching the references of pertinent articles and related reviews, and searching keywords in Google Scholar and Google. RESULTS: Ten articles were included; all described populations in the United States, and examined perceptions of family physicians, pediatricians, and other immunization staff. All articles were of moderate-high methodological quality; the majority (n=7) employed survey methodology. The most frequently described barriers involved the perceived human and financial resources associated with implementing an RR intervention, as well as low confidence in the accuracy of patient immunization records, given the lack of data sharing between multiple immunization providers. Changes to staff workflow, lack of appropriate electronic patient-tracking functionalities, and uncertainty regarding the success of RR interventions were also viewed as barriers to their adoption. CONCLUSIONS: Although transitioning to electronic immunization records and registries should facilitate the implementation of RR interventions, numerous perceived barriers must still be overcome before the full benefits of these methods can be realized.

Comments on a skeleton design paradigm for a demosponge.

The ball-shaped marine sponge Cinachyrellalevantinensis is 3-5 cm in diameter. It filters large quantities of seawater for feeding. Sponges contain numerous, hydrated, brittle amorphous SiO2 spicules of several types that form 70-80% by weight of the sponge. We performed mechanical tests to determine the functionality of the sponge skeleton. The potential effect of habitat on skeleton properties was investigated by comparing sponges from 0.5 m and 30 m depth. We determined how spicules contribute to maintaining the strength and macroscopic structural integrity of a sponge, and studied their deformation mechanisms under external loading, and their microscopic design parameters. Compression tests of cylindrical samples cut from sponges revealed their macroscopic deformation mechanisms. Experiments solely with the organic material (following spicules dissolution) revealed the contribution of the spicules to the load carrying capacity and structural integrity of the sponge. Cantilever bending tests of anchored spicules determined the strength of individual spicules, the sponge's main skeletal elements. As the strength of brittle spicules is statistical in nature, we used Weibull Statistics to define their strength and evaluate their Young's modulus. Shallow and deep-water sponges did not differ significantly neither in response to compression, nor in spicule strength under bending and tension. Spicule weight fraction within a sponge was significantly higher in shallow-water individuals. We conclude that the structural integrity and strength of this sponge's skeleton is derived from its low-strength, small spicules, produced by a cost-effective process. The operating deformation of the spicules (bending) and their design parameters make them highly efficient.

Phonon emission induced dynamic fracture phenomena.

We use molecular dynamics simulations to calculate the phonon energy emitted during rapid crack propagation in brittle crystals. We show that this energy is different for different crack planes and propagation directions and that it is responsible for various phenomena at several length scales: energetically preferred crack systems and crack deflection at the atomic scale, reduced maximum crack speed with volume at the micrometer scale, and the inability of a crack to attain the theoretical limiting speed at the macroscale. We propose to include the contribution of this energy in the Freund equation of motion of a dynamically propagating crack.

A cost comparison of electronic and hybrid data collection systems in Ontario during pandemic and seasonal influenza vaccination campaigns.

BACKGROUND: During the pandemic (H1N1) 2009 influenza vaccination campaign, health regions in Canada collected client-level immunization data using fully electronic or hybrid systems, with the latter comprising both electronic and paper-based elements. The objective of our evaluation was to compare projected five-year costs associated with implementing these systems in Ontario public health units (PHUs) during pandemic and seasonal influenza vaccination campaigns. METHODS: Six PHUs provided equipment and staffing costs during the pandemic (H1N1) 2009 influenza vaccination campaign and staffing algorithms for seasonal campaigns. We standardized resources to population sizes 100,000, 500,000 and 1,000,000, assuming equipment lifetime of five years and public health vaccine administration rates of 18% and 2.5% for H1N1 and seasonal campaigns, respectively. Two scenarios were considered: Year 1 pandemic and Year 1 seasonal campaigns, each followed by four regular influenza seasons. Costs were discounted at 5%. RESULTS: Assuming a Year 1 pandemic, the five-year costs per capita for the electronic system decrease as PHU population size increases, becoming increasingly less costly than hybrid systems ($4.33 vs. $4.34 [100,000], $4.17 vs. $4.34 [500,000], $4.12 vs. $4.34 [1,000, 000]). The same trend is observed for the scenario reflecting five seasonal campaigns, with the electronic system being less expensive per capita than the hybrid system for all population sizes ($1.93 vs. $1.95 [100,000], $1.91 vs. $1.94 [500,000], $1.87 vs. $1.94 [1,000, 000]). Sensitivity analyses identified factors related to nurse hours as affecting the direction and magnitude of the results. CONCLUSIONS: Five-year cost projections for electronic systems were comparable or less expensive than for hybrid systems, at all PHU population sizes. An intangible benefit of the electronic system is having data rapidly available for reporting.

Approaches to immunization data collection employed across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign.

OBJECTIVES: A critical component of the 2009 H1N1 vaccination campaign was the collection of immunization data at the point of care. To meet reporting requirements and to ensure timely availability of coverage information, many jurisdictions across Canada employed new or modified approaches to vaccine data collection. The objective of this study was to observe and characterize the range of influenza immunization data collection approaches used across Canada. METHODS: As part of a multi-stage observational study, the research team visited immunization clinics at which tasks related to data collection and management were observed. Tasks included registration, medical history collection and review, vaccine record-keeping, proof of vaccination preparation, and data entry. Field notes were analyzed in order to understand the data collection mechanisms that comprised each information system as a whole. RESULTS: Data collection mechanisms were grouped into two categories: electronic systems (9/38), in which all data were captured on computer; and hybrid systems (29/38), comprised of computerized and paper-based data collection tasks. Observed systems included stand-alone databases, immunization registries, and electronic health records. Organizations incorporated magnetic card reader technology, telephone registration, and pre-populated fields into data collection approaches. Electronic systems captured a greater number of data elements. CONCLUSION: Canadian jurisdictions employed a range of data collection approaches during the H1N1 vaccination campaign. System characteristics can have important implications for on-site efficiency and organization as well as program planning and evaluation. The systems observed have been described in detail to allow vaccine providers and planners to learn from what has been done elsewhere.

The spread of pathogens through trade in small ruminants and their products.

While the international trade in small ruminants and small ruminant products is small relative to the trade in bovine, swine and poultry products, it is still economically important. In addition to wool, it includes some unique products (such as goat and sheep milk cheeses, cashmere fibre and karakul pelts) and the sheep/goat meat trade plays a large part in sustaining livelihoods in several regions of the world. The trade in small ruminants and their products also merits consideration because sheep and goats may transmit zoonotic diseases such as Rift Valley fever, Crimean Congo haemorrhagic fever, brucellosis and listeriosis. They also may transmit highly infectious livestock diseases, such as peste des petits ruminants, to naïve populations of small ruminants in other countries. This can have dramatic consequences, particularly for poor people whose livelihood often depends on small ruminants. In addition, sheep and goats can serve as an important source of foot and mouth disease (FMD) for cattle. This has enormous global trade implications and it is important, therefore, that sheep and goats be considered in FMD control programmes aimed at improving access to trade.

Acquisition and Transmissibility of U.S. Soybean dwarf virus Isolates by the Soybean Aphid, Aphis glycines.

Soybean dwarf virus (SbDV) exists as several distinct strains based on symptomatology, vector specificity, and host range. Originally characterized Japanese isolates of SbDV were specifically transmitted by Aulacorthum solani. More recently, additional Japanese isolates and endemic U.S. isolates have been shown to be transmitted by several different aphid species. The soybean aphid, Aphis glycines, the only aphid that colonizes soybean, has been shown to be a very inefficient vector of some SbDV isolates from Japan and the United States. Transmission experiments have shown that the soybean aphid can transmit certain isolates of SbDV from soybean to soybean and clover species and from clover to clover and soybean with long acquisition and inoculation access periods. Although transmission of SbDV by the soybean aphid is very inefficient, the large soybean aphid populations that develop on soybean may have epidemiological potential to produce serious SbDV-induced yield losses.

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial.

BACKGROUND: People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. METHODS: In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18-65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. FINDINGS: Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9-298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7-204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained. INTERPRETATION: ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta. FUNDING: The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council.

Expression of structurally diverse Qa-2-encoded molecules on the surface of cloned cytotoxic T lymphocytes.

Extracts of 125I-labeled cloned murine cytotoxic T lymphocytes (CTL) were immunoprecipitated with alloantisera to the cloned CTL and rabbit antisera to beta-2 microglobulin. Polyacrylamide gel electrophoresis (PAGE) of the specific precipitates revealed, as expected, 125I-labeled components that corresponded to products of class I genes of the major histocompatibility complex (MHC). However, additional class I gene products of relatively low apparent molecular weight (Mr) were also observed. Similar analyses of spleen cells from a variety of MHC-congenic mouse strains suggested that the class I molecules of relatively low Mr are encoded in the Qa-2 region of the MHC, and this was confirmed by immunoprecipitation with a monoclonal antibody to Qa-2. Surprisingly, however, the cell surface Qa-2 molecules of different CTL clones differed in Mr, in isoelectric focusing (IEF) pattern, and in the number of distinguishable molecules expressed per clone: some clones seemed to express only a single Qa-2-encoded molecule while others expressed two distinct ones. Treatment of the immunoprecipitated Qa-2 with endoglycosidase F (Endo F) resulted in a decrease in Mr of approximately 5,000-6,000, corresponding to the expected loss of N-linked oligosaccharides, but the decrease did not eliminate structural variability among the clones. Structural diversity of the Qa-2-encoded molecules expressed on CTL could arise because CTL clones differ (a) in the particular Qa-2 genes they express, (b) in the way they splice Qa-2 gene transcripts or, perhaps, (c) in Endo F-resistant oligosaccharides on their Qa-2 molecules.