Background.We conducted a prospective cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario, Canada. Methods.Patients admitted ...to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study. Demographic and medical data were collected by patient and physician interview and chart review. The main outcome evaluated was death within 15 days after symptom onset. Results.Data were available for 512 of 541 eligible patients. There were 185 children (<15 years of age), none of whom died and none of whom were treated with antiviral drugs. The median age of the 327 adults was 77 years (range, 15–98 years), 166 (51%) were male, 245 (75%) had a chronic underlying illness, and 216 (71%) had been vaccinated against influenza. Of the 327 adult patients, 184 (59%) presented to the emergency department within 48 h after symptom onset, 52 (16%) required intensive care unit admission, and 27 (8.3%) died within 15 days after symptom onset. Most patients (292 patients; 89%) received antibacterial therapy; 106 (32%) were prescribed antiviral drugs. Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality (odds ratio, 0.21; 95% confidence interval, 0.06–0.80; P = .03). There was no apparent impact of antiviral therapy on length of stay in survivors. Conclusions.There is a significant burden of illness attributable to influenza in this highly vaccinated population. Treatment with antiviral drugs was associated with a significant reduction in mortality.
In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours ...were associated with the greatest risk of SARS-CoV transmission.
A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission.
45 laboratory-confirmed intubated SARS patients were identified. Of the 697 HCWs involved in their care, 624 (90%) participated in the study. SARS-CoV was transmitted to 26 HCWs from 7 patients; 21 HCWs were infected by 3 patients. In multivariate GEE logistic regression models, presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score > or = 20 (OR = 17.05, p = .009) and patient Pa0(2)/Fi0(2) ratio < or = 59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.
Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients.
Background. In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential ...benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. Methods. From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. Results. Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval CI, 8.7–15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio OR 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1–2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40–.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%–96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. Conclusions. Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established.
Isolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under ...monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-α/β) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.
Highlights • Routine pediatric PCV7 vaccination did not reduce in the incidence of IPD in adults in Toronto. • Use of PCV7 at 1 dose per child in the birth cohort resulted in significant reductions ...in PCV7 serotype IPD. • The case fatality rate of IPD decreased by 2% per year in Toronto between 1995 and 2011. • Post PCV13 program implementation, a substantial burden of IPD in adults will remain.
The evaluation of humoral protective immunity against SARS-CoV-2 remains crucial in understanding both natural immunity and protective immunity conferred by the several vaccines implemented in the ...fight against COVID-19. The reference standard for the quantification of antibodies capable of neutralizing SARS-CoV-2 is the plaque-reduction neutralization test (PRNT). However, given that it is a laboratory-developed assay, validation is crucial in order to ensure sufficient specificity and intra- and interassay precision. In addition, a multitude of other serological assays have been developed, including enzyme-linked immunosorbent assay (ELISA), flow cytometry-based assays, luciferase-based lentiviral pseudotype assays, and commercially available human ACE2 receptor-blocking antibody tests, which offer practical advantages in the evaluation of the protective humoral response against SARS-CoV-2. In this study, we validated a SARS-CoV-2 PRNT to assess both 50% and 90% neutralization of SARS-CoV-2 according to guidelines outlined by the World Health Organization. Upon validation, the reference-standard PRNT demonstrated excellent specificity and both intra- and interassay precision. Using the validated assay as a reference standard, we characterized the neutralizing antibody response in specimens from patients with laboratory-confirmed COVID-19. Finally, we conducted a small-scale multilaboratory comparison of alternate SARS-CoV-2 PRNTs and surrogate neutralization tests. These assays demonstrated substantial to perfect interrater agreement with the reference-standard PRNT and offer useful alternatives to assess humoral immunity against SARS-CoV-2.
SARS-CoV-2, the causal agent of COVID-19, has infected over 246 million people and led to over 5 million deaths as of October 2021. With the approval of several efficacious COVID-19 vaccines, methods to evaluate protective immune responses will be crucial for the understanding of long-term immunity in the rapidly growing vaccinated population. The PRNT, which quantifies SARS-CoV-2-neutralizing antibodies, is used widely as a reference standard to validate new platforms but has not undergone substantial validation to ensure excellent inter- and intraassay precision and specificity. Our work is significant, as it describes the thorough validation of a PRNT, which we then used as a reference standard for the comparison of several alternative serological methods to measure SARS-CoV-2-neutralizing antibodies. These assays demonstrated excellent agreement with the reference-standard PRNT and include high-throughput platforms, which can greatly enhance capacity to assess both natural and vaccine-induced protective immunity against SARS-CoV-2.
Differentiated models of HIV care (DMOC) aim to improve health care efficiency. We describe outcomes of five DMOC in KwaZulu-Natal, South Africa: facility adherence clubs (facility AC) and community ...adherence clubs (community AC), community antiretroviral treatment (ART) groups (CAG), spaced fast lane appointments (SFLA), and community pick up points (PuP). This retrospective cohort study included 8241 eligible patients enrolled into DMOC between 1/1/2012 and 31/12/2018. We assessed retention in DMOC and on ART, and viral load suppression (<1000 copies/mL). Kaplan-Meier techniques were applied to describe crude retention. Mixed effects parametric survival models with Weibull distribution and clustering on health center and individual levels were used to assess predictors for ART and DMOC attrition, and VL rebound (≥1000 copies/mL). Overall DMOC retention was 85%, 80%, and 76% at 12, 24 and 36 months. ART retention at 12, 24 and 36 months was 96%, 93%, 90%. Overall incidence rate of VL rebound was 1.9 episodes per 100 person-years. VL rebound rate was 4.9 episodes per 100 person-years among those enrolled in 2012-2015, and 0.8 episodes per 100 person-years among those enrolled in 2016-2018 (RR 0.12; 95% CI, 0.09-0.15, p<0.001). Prevalence of confirmed virological failure was 0.6% (38/6113). Predictors of attrition from DMOC and from ART were male gender, younger age, shorter duration on ART before enrollment. Low level viremia (>200-399 copies/mL) was associated with higher hazards of VL rebound and attrition from ART. Concurrent implementation of several DMOC in a large ART program is feasible and can achieve sustained retention on ART and VL suppression.
Abstract
Background
At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9–12 months ...regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions.
Methods
We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database.
Results
Our cohort included 117 patients; 68.4% (95% confidence interval CI: 59.3–76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50–57). Treatment success was achieved in 75.2% (95% CI: 66.5–82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8–20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range IQR 4.0–12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8–34.5) of participants.
Conclusions
An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.
An all-oral regimen, combining linezolid and bedaquiline, for the treatment of rifampicin-resistant tuberculosis shows good outcomes, irrespective of human immunodeficiency virus (HIV) status or CD4 level. Linezolid accounted for nearly half of severe adverse events and warrants close monitoring for myelosuppression and neuropathy.
There is renewed concern over the sustainability of disease control programmes, and re-emergence of policy recommendations to integrate programmes with general health systems. However, the ...conceptualization of this issue has remarkably received little critical attention. Additionally, the study of programmatic sustainability presents methodological challenges. In this article, we propose a conceptual framework to support analyses of sustainability of communicable disease programmes. Through this work, we also aim to clarify a link between notions of integration and sustainability. As a part of development of the conceptual framework, we conducted a systematic literature review of peer-reviewed literature on concepts, definitions, analytical approaches and empirical studies on sustainability in health systems. Identified conceptual proposals for analysis of sustainability in health systems lack an explicit conceptualization of what a health system is. Drawing upon theoretical concepts originating in sustainability sciences and our review here, we conceptualize a communicable disease programme as a component of a health system which is viewed as a complex adaptive system. We propose five programmatic characteristics that may explain a potential for sustainability: leadership, capacity, interactions (notions of integration), flexibility/adaptability and performance. Though integration of elements of a programme with other system components is important, its role in sustainability is context specific and difficult to predict. The proposed framework might serve as a basis for further empirical evaluations in understanding complex interplay between programmes and broader health systems in the development of sustainable responses to communicable diseases.
Il y a de nouveau des inquiétudes quant à la viabilité des programmes de contrôle des maladies et une réémergence des recommandations pour intégrer les programmes dans le système de santé global. Quoi qu’il en soit, la conception de cette question a reçu que peu d’attention. De plus, l’étude de la viabilité du programme est un défi méthodologique. Dans cet article, nous proposons un cadre conceptuel pour soutenir l’analyse de la viabilité des programmes des maladies transmissibles. A travers ce travail, nous essayons aussi de faire la distinction entre les notions d’intégration et de viabilité. Dans le cadre du développement du cadre conceptuel, nous avons systématiquement mené un examen méthodique de la documentation examinée par des pairs sur les concepts, les définitions, l’approche analytique et les études empiriques de la viabilité dans les systèmes de santé. Les propositions identifiées pour l’analyse de cette viabilité manquent d’une conceptualisation précise de ce qu’est un système de santé. A partir de concepts théoriques s’inspirant des sciences de durabilité et de cette étude, nous avons conceptualisé un programme pour les maladies transmissibles comme composant d’un système de santé, qui est vu comme un système adaptif complexe. Nous proposons cinq caractéristiques de programmation qui peuvent expliquer le potentiel de viabilité: leadership, capacité, interactions (notions d’intégration), flexibilité/adaptabilité et performance. Passer par l’intégration d’éléments d’un programme avec d’autres composants du système est important, le rôle joué pour la viabilité des programmes est spécifique à un contexte et est difficile à prédire. Le cadre proposé peut servir de base pour d’autres évaluations empiriques afin de comprendre l’interaction entre les programmes et les systèmes de santé, au sens large, dans le développement de réponses adéquates et durables aux maladies transmissibles
对疾病控制项目可持续发展的担忧再一次引起人们的关注， 将这些项目与医疗体系整合在一起的政策建议也再次被提 出。然而，这个议题的概念化很少受到学术严谨的关注。此 外，对可持续发展的系统性研究方法也存在不足。本文中， 我们提出了一个可以支持对传染病项目可持续发展进行分析 的概念框架。通过这项研究，我们还希望明确整合概念与可 持续发展之间的关系。作为发展概念框架的一部分，我们对 同行评议的关于在医疗系统中可持续发展的概念、定义、分 析方法和实证研究的文章进行了系统的文献研究。医疗系统 中的可持续发展这一概念缺乏对医疗系统的明确定义。根据 可持续发展研究与我们的文献回顾中得到的理论框架，我们 将传染疾病控制项目定义为一个复杂的具有自适性的医疗系 统的一部分。并提出了五个可以支持可持续性的项目特点： 领导力、生产能力、互动（整合的概念）、机动性或适应性 以及表现。尽管与其他项目组成的整合也是很重要的，但这 种整合在可持续发展中受情境的影响很大并且很难预测。我 们提出的框架在传染疾病控制可持续发展中可以作为更深入 的理解项目与医疗系统之间复杂互动的实证判断基础。
Existe una renovada preocupación sobre la sostenibilidad de los programas de control de enfermedades y una reaparición de recomendaciones sobre políticas a fin de integrar los programas con los sistemas generales de salud. Sin embargo, la conceptualización de este asunto ha recibido muy poca atención crítica. Además, el estudio de la sostenibilidad programática presenta desafíos metodológicos. En este artículo, proponemos un marco conceptual a fin de apoyar el análisis de sostenibilidad de los programas de enfermedades contagiosas. A través de este trabajo tambien tenemos el objectivo de aclarar una conexión entre las nociones de integración y sostenibilidad. Como una parte del desarrollo del marco conceptual llevamos a cabo una revisión sistemática de la literatura indexada sobre conceptos, definiciones, enfoques analíticos y estudios empíricos referentes a la sostenibilidad de los sistemas de salud. Las propuestas conceptuales para el análisis de la sostenibilidad en sistemas de salud identificadas no tienen una conceptualización explícita acerca de que es un sistema de salud. Basándose en conceptos teóricos originados en ciencias de sostenibilidad y en nuestra revisión, conceptualizamos un programa de enfermedades contagiosas como un componente de un sistema de salud, el cual es visto como un sistema complejo adaptable. Proponemos cinco características programáticas que podrían explicar un potencial para la sostenibilidad: liderazgo, capacidad, interacciones (nociones de integración), flexibilidad/adaptabilidad y desempeño. Aunque la integración de elementos de un programa con componentes de otro sistema es importante, su papel en la sostenibilidad es especifico a su contexto y difícil de predecir. El marco propuesto podría servir como base para más evaluaciones empíricas en el entendimiento de una compleja interacción entre programas y sistemas más amplios de salud en el desarrollo de respuestas sostenibles a las enfermedades contagiosas.
Abstract
Background
Several factors have been associated with severity of COVID-19 disease, but there remains a paucity of data surrounding whether the nature of exposure is impactful. Evidence ...demonstrating the correlation between initial viral exposure dose and disease severity exists for many viral infections. Observational studies have suggested that the exposure context, which can be considered a proxy for magnitude of viral inoculum, may influence severity of COVID-19 infection. We aimed to assess whether having a known exposure, as a proxy for higher inoculum dose to COVID-19, was associated with more severe outcomes for individuals hospitalized with COVID-19.
Methods
We created a retrospective cohort of community-dwelling adults hospitalized for COVID-19 in south-central Ontario from April 1, 2020 - January 14, 2021. Individuals or next of kin were contacted to ascertain exposure history. The primary outcome was death, intensive care unit (ICU) admission, or mechanical ventilation (MV) within 30 days of admission. A multivariable logistic regression model was used to determine whether a known exposure was associated with worse outcomes.
Results
1097 individuals with community acquired COVID-19 required hospitalization; of these, 942 (86%) had available exposure data. In this group, the median age was 65, 44% were women, 84% lived in a private residence, 59% had a frailty score (FS) of 1 – 3 while 40% had a FS of 4 – 9, and 28% had a known exposure. Overall, the primary outcome occurred in 368/942 (39%) patients. Having a known exposure was not associated with worse outcome (OR 1.14, 95% CI 0.84–1.54, p = 0.41). Male gender (OR 1.41, 95% CI 1.06–1.89; p = 0.018), age (OR 1.01/year, 95% CI 1.00–1.03, p = 0.03), frailty (OR 1.22/point, 95% CI 1.09–1.36, p = 0.001) and living with at least one other person (OR 1.57, 95% CI 1.09–2.28, p = 0.017) were all associated with death, ICU admission, or MV within 30 days of admission.
Conclusion
While having a known exposure to a person with COVID-19 was not associated with worse outcome, the identified increased severity of illness associated with cohabitation suggests context of exposure may have a role in disease severity. This data and future studies can be used to guide public health recommendations to not only minimize transmission, but severity of COVID-19 infection.
Disclosures
All Authors: No reported disclosures
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