Clinical features and outcomes of influenza and RSV coinfections: a report from Canadian immunization research network serious outcomes surveillance network.

BACKGROUND: Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults. METHODS: A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization. RESULTS: Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes. CONCLUSIONS: Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.

Practical Guidance for Clinical Microbiology Laboratories: Viruses Causing Acute Respiratory Tract Infections.

Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans. This article is an American Society for Microbiology (ASM)-sponsored Practical Guidance for Clinical Microbiology (PGCM) document identifying best practices for diagnosis and characterization of viruses that cause acute respiratory infections and replaces the most recent prior version of the ASM-sponsored Cumitech 21 document, Laboratory Diagnosis of Viral Respiratory Disease, published in 1986. The scope of the original document was quite broad, with an emphasis on clinical diagnosis of a wide variety of infectious agents and laboratory focus on antigen detection and viral culture. The new PGCM document is designed to be used by laboratorians in a wide variety of diagnostic and public health microbiology/virology laboratory settings worldwide. The article provides guidance to a rapidly changing field of diagnostics and outlines the epidemiology and clinical impact of acute respiratory viral infections, including preferred methods of specimen collection and current methods for diagnosis and characterization of viral pathogens causing acute respiratory tract infections. Compared to the case in 1986, molecular techniques are now the preferred diagnostic approaches for the detection of acute respiratory viruses, and they allow for automation, high-throughput workflows, and near-patient testing. These changes require quality assurance programs to prevent laboratory contamination as well as strong preanalytical screening approaches to utilize laboratory resources appropriately. Appropriate guidance from laboratorians to stakeholders will allow for appropriate specimen collection, as well as correct test ordering that will quickly identify highly transmissible emerging pathogens.

Frailty Hinders Recovery From Influenza and Acute Respiratory Illness in Older Adults.

BACKGROUND: We examined frailty as a predictor of recovery in older adults hospitalized with influenza and acute respiratory illness. METHODS: A total of 5011 patients aged ≥65 years were admitted to Canadian Serious Outcomes Surveillance Network hospitals during the 2011/2012, 2012/2013, and 2013/2014 influenza seasons. Frailty was measured using a previously validated frailty index (FI). Poor recovery was defined as death by 30 days postdischarge or an increase of more than 0.06 (≥2 persistent new health deficits) on the FI. Multivariable logistic regression controlled for age, sex, season, influenza diagnosis, and influenza vaccination status. RESULTS: Mean age was 79.4 (standard deviation = 8.4) years; 53.1% were women. At baseline, 15.0% (n = 750) were nonfrail, 39.3% (n = 1971) were prefrail, 39.8% (n = 1995) were frail, and 5.9% (n = 295) were most frail. Poor recovery was experienced by 21.4%, 52.0% of whom had died. Frailty was associated with lower odds of recovery in all 3 seasons: 2011/2012 (odds ratio [OR] = 0.70; 95% confidence interval [CI], 0.59-0.84), 2012/2013 (OR = 0.72; 95% CI, 0.66-0.79), and 2013/2014 (OR = 0.75; 95% CI, 0.69-0.82); results varied by season, influenza status, vaccination status, and age. CONCLUSIONS: Increasing frailty is associated with lower odds of recovery, and persistent worsening frailty is an important adverse outcome of acute illness.

Performance of a Modified Two-Tiered Testing Enzyme Immunoassay Algorithm for Serologic Diagnosis of Lyme Disease in Nova Scotia.

Compared to the standard two-tiered testing (STTT) algorithm for Lyme disease serology using an enzyme immunoassay (EIA) followed by Western blotting, data from the United States suggest that a modified two-tiered testing (MTTT) algorithm employing two EIAs has improved sensitivity to detect early localized Borrelia burgdorferi infections without compromising specificity. From 2011 to 2014, in the Canadian province of Nova Scotia, where Lyme disease is hyperendemic, sera submitted for Lyme disease testing were subjected to a whole-cell EIA, followed by C6 EIA and subsequently IgM and/or IgG immunoblots on sera with EIA-positive or equivocal results. Here, we evaluate the effectiveness of the MTTT algorithm compared to the STTT approach in a Nova Scotian population. Retrospective chart reviews were performed on patients testing positive with the whole-cell and C6 EIAs (i.e., the MTTT algorithm). Patients were classified as having Lyme disease if they had a positive STTT result, a negative STTT result but symptoms consistent with Lyme disease, or evidence of seroconversion on paired specimens. Of the 10,253 specimens tested for Lyme disease serology, 9,806 (95.6%) were negative. Of 447 patients who tested positive, 271 charts were available for review, and 227 were classified as patients with Lyme disease. The MTTT algorithm detected 25% more early infections with a specificity of 99.56% (99.41 to 99.68%) compared to the STTT. These are the first Canadian data to show that serology using a whole-cell sonicate EIA followed by a C6 EIA (MTTT) had improved sensitivity for detecting early B. burgdorferi infection with specificity similar to that of two-tiered testing using Western blots.

Low Seroprevalence of Lyme Disease Among Multiple Sclerosis Patients in New Brunswick.

The signs and symptoms of Lyme neuroborreliosis can overlap with non-infectious degenerative diseases such as multiple sclerosis (MS). In this study, we assessed a cohort of MS patients in Atlantic Canada for serological evidence of Lyme disease (LD). No positive serology was identified using the recommended two-tiered algorithm.

Committee Opinion No. 399: Management of Tick Bites and Lyme Disease During Pregnancy.

OBJECTIVE: Lyme disease is an emerging infection in Canada caused by the bacterium belonging to the Borrelia burgdorferi sensu lato species complex, which is transmitted via the bite of an infected blacklegged tick. Populations of blacklegged ticks continue to expand and are now established in different regions in Canada. It usually takes more than 24 hours of tick attachment to transfer B. burgdorferi to a human. The diagnosis of early localized Lyme disease is made by clinical assessment, as laboratory tests are not reliable at this stage. Most patients with early localized Lyme disease will present with a skin lesion (i.e., erythema migrans) expanding from the tick bite site and/or non-specific "influenza-like" symptoms (e.g., arthralgia, myalgia, and fever). Signs and symptoms may occur from between 3 and 30 days following the tick bite. The care of pregnant patients with a tick bite or suspected Lyme disease should be managed similarly to non-pregnant adults, including the consideration of antibiotics for prophylaxis and treatment. The primary objective of this committee opinion is to inform practitioners about Lyme disease and provide an approach to managing the care of pregnant women who may have been infected via a blacklegged tick bite. INTENDED USERS: Health care providers who care for pregnant women or women of reproductive age. TARGET POPULATION: Women of reproductive age. EVIDENCE: In November 2018, Medline, EMBASE, PubMed, and CENTRAL databases were searched for 2 main categories: (1) Lyme disease and (2) other tick-borne diseases. Because the main focus was Lyme disease, and considering the limited number of the articles, no further filters were applied for publication time or type of study. For other tick-borne diseases, the results were restricted to a publication date within the last 10 years (2008-2018). The search terms were developed using MeSH terms and keywords including Lyme Disease, Pregnancy, Pregnant Women, Pregnancy Complications, Ehrlichiosis, Anaplasmosis, Rocky Mountain Spotted Fever, Babesiosis, Tularemia, Powassan Virus, Encephalitis Viruses, Tick-Borne, Tick-Borne Diseases, Colorado Tick Fever, Q Fever, Relapsing Fever, and Southern Tick-Associated Rash Illness. All articles on Lyme disease and other tick-borne diseases with a target population of pregnant women were included; other groups and populations were excluded. VALIDATION METHODS: The content and recommendations of this committee opinion were drafted and agreed upon by the authors. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication.

Calibration and Evaluation of Quantitative Antibody Titers for Varicella-Zoster Virus by Use of the BioPlex 2200.

Most commercially available enzyme immunoassay-based methods have limited sensitivity to detect antibody responses to varicella-zoster virus (VZV) in vaccinated individuals, who produce lower antibody levels than those with natural infection. However, more sensitive methods are either not commercially available or less amenable to high-throughput testing. The BioPlex 2200 measles, mumps, rubella, and varicella (MMRV) IgG assay (Bio-Rad Laboratories, Hercules, CA) is an automated high-throughput platform based on the microsphere Luminex technology that measures antibodies against measles, mumps, rubella, and varicella viruses simultaneously. Although it has U.S. Food and Drug Administration approval as a qualitative diagnostic test for measles, mumps, rubella, and varicella virus immunity, in this study, we have validated the assay to produce quantitative titers (off label) against the VaccZyme VZV glycoprotein (VZVgp) low-level IgG kit (The Binding Site Ltd., Birmingham, UK) using the World Health Organization international standard. Here, we show that the BioPlex 2200 MMRV IgG assay has sensitivity superior to that of the Zeus enzyme-linked immunosorbent assay (ELISA) VZV IgG assay (Zeus Diagnostics, Branchburg, NJ). Using receiver operating characteristic (ROC) analysis and adjusting the cutoff levels, we improved the sensitivity of the quantitative BioPlex 2200 MMRV IgG assay to 97.4%, while maintaining 100% specificity.

High Seroprevalence of Jamestown Canyon Virus among Deer and Humans, Nova Scotia, Canada.

Using residual serum samples from Nova Scotia, Canada, we found that 87.8% of tested deer and an estimated 20.6% of the human population were infected with Jamestown Canyon virus. Human seropositivity reached 48.2% in 1 region. This virus may be an underrecognized cause of disease in Nova Scotia.

Risk acceptance of human T-lymphotropic virus infection in solid organ transplantation-A survey of Atlantic Canadian ambulatory patients.

BACKGROUND: Human T-lymphotropic virus (HTLV) has an estimated prevalence of 12 per 100 000 in the general Canadian population (with higher rates in distinct groups) and is most commonly transmitted by breast feeding, sexual intercourse, sharing injection tools, and blood transfusions. A minority of those infected will develop severe disease. Health Canada mandates that people who are positive for HTLV are not suitable to be solid organ donors. Given the apparent low-disease burden of HTLV in Canada, we explored HTLV risk tolerance among patients, in the context of organ transplantations. METHODS: Using telephone, and in-person questionnaires, we assessed willingness of patients to accept the risk of HTLV infection in hypothetical scenarios in which they required an organ transplant for survival. RESULTS: Seventy-four outpatients attending various medical clinics participated in the survey. In a standard gamble scenario, 37.5% of respondents would have accepted a solid organ transplant regardless of HTLV risk, as compared to 27.3% and 24.6% accepting organ transplantation if there was a risk of human immunodeficiency virus (HIV) or of human virus Y (HVY; a fictitious virus describing HTLV in terms of neurological outcomes), respectively. Similarly, the median longevity traded to ensure a virus-free organ was 4-5 years regarding all viruses, except for HVY, for which the median time exchanged to ensure a virus-free organ was 10 (out of a possible 20) years. CONCLUSIONS: These data suggest that patients, though willing to accept some risk of viral infection, would not be willing to forgo HTLV screening of solid organs.

Influenza a virus host shutoff disables antiviral stress-induced translation arrest.

Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5' caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.