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Background: Current National Advisory Committee on Immunization (NACI) guidance recommends human papillomavirus (HPV) vaccines be administered as a two or three-dose schedule. Recently, several large clinical trials have reported the clinical benefit of a single HPV vaccine dose. As a result, the World Health Organization released updated guidance on HPV vaccines in 2022, recommending a two-dose schedule for individuals aged 9-20 years, and acknowledging the use of an alternative off-label single dose schedule. Objective: The objective of this overview is to provide a detailed account of the available evidence comparing HPV vaccination schedules, which was considered by NACI when updating recommendations on HPV vaccines. Methods: To identify relevant evidence, existing systematic reviews were leveraged where possible. Individual studies were critically appraised, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence. Results: Available evidence suggests that a one, two, or three-dose HPV vaccine schedule may provide similar protection from HPV infection. While antibody levels against HPV vaccine types were statistically significantly lower with a single dose schedule compared to two or three doses, titres were sustained for up to 16 years. The clinical significance of lower antibody titres is unknown, as there is no established immunologic correlate of protection. Conclusion: While the available evidence on single-dose HPV vaccination schedules shows a one-dose schedule is highly effective, continued follow-up of single-dose cohorts will be critical to understanding the relative duration of protection for reduced dose schedules and informing future NACI guidance on HPV vaccines.
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Swine influenza A viruses pose a public health concern as novel and circulating strains occasionally spill over into human hosts, with the potential to cause disease. Crucial to preempting these events is the use of a threat assessment framework for human populations. However, established guidelines do not specify which animal models or in vitro substrates should be used. We completed an assessment of a contemporary swine influenza isolate, A/swine/GA/A27480/2019 (H1N2), using animal models and human cell substrates. Infection studies in vivo revealed high replicative ability and a pathogenic phenotype in the swine host, with replication corresponding to a complementary study performed in swine primary respiratory epithelial cells. However, replication was limited in human primary cell substrates. This contrasted with our findings in the Calu-3 cell line, which demonstrated a replication profile on par with the 2009 pandemic H1N1 virus. These data suggest that the selection of models is important for meaningful risk assessment.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Orthomyxoviridae Infections , Virus Replication , Animals , Swine , Orthomyxoviridae Infections/virology , Humans , Risk Assessment , Influenza, Human/virology , Influenza, Human/epidemiology , Cell Line , Influenza A Virus, H1N1 Subtype/physiology , Swine Diseases/virology , Disease Models, Animal , Influenza A Virus, H1N2 Subtype/genetics , Pandemics , Mice , Dogs , Epithelial Cells/virology , FemaleABSTRACT
PURPOSE: Expiratory muscle strength training (EMST) is increasingly being used to treat voice, cough, and swallowing deficits in a wide range of conditions. However, a multitude of aero-resistive EMST models are commercially available, and the absence of side-by-side comparative data interferes with clinicians' ability to assess which model is best suited to a particular client's needs. The primary aim of this research was to test and compare the pressure and flow parameters of six currently available EMST models to help inform clinical decision making. METHOD: We identified and tested five devices of each of six different EMST models to generate benchmark data for minimum trigger pressures across settings. The reliability was tested within each device and between five devices of the same model across settings using coefficient of variation. RESULTS: All six models required higher pressures to initiate flow at the highest setting compared to the lowest setting, as expected. Detailed descriptive statistics for each model/setting combination include average flow-triggering pressure for each model/setting and the variability across trials within a device and across devices of the same model. From these, ranked order of the least to most stable EMST model was derived. CONCLUSIONS: Systematic testing of several commercially available expiratory resistance training devices yielded clinical benchmarks and reliability data to aid clinicians in selecting an appropriate therapy device and regimen for a client based on their available airflow and air pressure as well as reliability of the device. These findings allow clinicians to directly compare key parameters across EMST devices.
Subject(s)
Exhalation , Resistance Training , Humans , Reproducibility of Results , Exhalation/physiology , Respiratory Therapy , Muscle Strength/physiologyABSTRACT
The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs). Canada's National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance. In this paper, we describe: structural adaptations in response to the accelerated pace and amount of work required to issue recommendations that were timed around product authorizations and dynamic epidemiology; technical adaptations in response to rapidly evolving evidence of variable quality which required close monitoring, and which promoted reliance on basic vaccine principles due to incomplete direct evidence; the need to provide nimble advice (e.g., off-label recommendations, preferential recommendations); communications adaptations (e.g. identify sustainable spokespeople for the committee, receive stakeholder feedback, and ensure urgent nuanced advice was communicated to a diverse audience); and research adaptations focussing on solutions to constrained supply (e.g. prioritisation, extended intervals, and heterologous schedules). The early pandemic vaccine experience has created a roadmap of lessons and adaptations that should be leveraged in future pandemic vaccine programs, and has highlighted the essential role of NITAGs to complement regulatory structures during pandemics to ensure timely, impactful, and evidence-informed public health vaccine guidance.
Subject(s)
COVID-19 , Vaccines , Humans , Pandemics/prevention & control , Advisory Committees , Health Policy , COVID-19/prevention & control , Canada/epidemiology , Immunization , Immunization ProgramsABSTRACT
Though there is evidence autism identification has been inequitable for populations who are culturally and linguistically minoritized, there is limited research that explains the issue of disproportionality and factors contributing to its occurrence, especially within an educational setting. To explore contributors to racial/ethnic disparities in autism special education eligibility, the current investigation evaluated child and evaluation characteristics as they relate to the absence of autism eligibility. Data were obtained from the Autism and Developmental Disabilities Monitoring (ADDM) Network Study and included children with behavioral characteristics consistent with autism and educational evaluation records. Despite documented characteristics consistent with autism, only 72% of the sample received educational services under autism eligibility. To characterize children without autism eligibility, hierarchical logistic regression was used to evaluate factors documented in evaluation records predicting the absence of autism eligibility. Factors influencing autism eligibility included behavioral characteristics documented, evaluation components completed, intellectual ability, and clinical diagnoses present. There was no unique contribution of race/ethnicity in predicting the absence of autism eligibility when accounting for these previous predictors, but many of these predictors differed by racial/ethnic group. Disproportionality in autism may be the manifestation of inequitable evaluation experiences, including experiencing less comprehensive evaluations, and not receiving an autism specific assessment. Though race/ethnicity did not uniquely contribute to the absence of autism eligibility above and beyond those combined factors, it is important to evaluate and reduce inequities experienced within the autism identification process for populations who are culturally and linguistically minoritized.
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Background: Ankle fracture surgeries are generally safe and effective procedures; however, as quality-based reimbursement models are increasingly affected by postoperative readmission, we aimed to determine the causes and risk factors for readmission following ankle fracture surgery. Methods: Ankle fracture cases were identified from the prospectively collected American College of Surgeons National Surgical Quality Improvement Program from 2013 to 2014. Demographics, comorbidities, and fracture characteristics were collected. Rates of 30-day adverse events and readmissions were determined as well as the causes for readmission. Multivariable logistic regression analyses were performed to identify risk factors associated with having any adverse events and being readmitted within 30 days of surgery. Results: There were 5056 patients included; 167 (3.3%) were open fractures. The rate of any postoperative adverse event was 5.2%. There were 116 unplanned readmissions, with a readmission rate of 2.3%. Of the 116 unplanned readmissions, 49 (42.2%) were for reasons related to the surgery or surgical site, with the most common causes being deep surgical site/hardware infections (12.9%), superficial site infections (11.2%), and wound disruption (6.9%). Most readmissions were for reasons unrelated to the surgical site (51.7%), including cardiac disorders (8.6%), pulmonary disorders (7.8%), and neurological/psychiatric disorders (6.9%). The cause of readmission was unknown for 6% of readmissions. With multivariable logistic regression, the strongest risk factors for readmission were a history of pulmonary disease (odds ratio [OR], 2.29), American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.28), and open fractures (OR, 2.04) (all P < .05). Conclusion: In this cohort of 5056 ankle fracture cases, 2.3% of patients were readmitted within 30 days, with at least 51.7% of all unplanned readmissions due to causes unrelated to the surgery or surgical site. Predictors of readmission included a history of pulmonary disease, higher ASA class, and open fractures. Based on these findings, we advocate close medical follow-up with nonorthopaedic providers after discharge for high-risk patients. Level of Evidence: Level III.
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BACKGROUND: Recently, studies have suggested that influenza antibody titers decline with time since vaccination. Duration of vaccine protection is an important factor to determine the optimal timing of vaccination. OBJECTIVE: We aimed to systematically evaluate the implication of waning immunity on the duration of seasonal influenza vaccine antibody response. METHOD: Electronic databases and clinical trial registries were systematically searched to identify phase III/IV randomized clinical trials evaluating the immunogenicity of seasonal influenza vaccines measured by hemagglutination inhibition assay in healthy individuals six months of age and older. Meta-analyses were conducted to compare adjuvanted and standard influenza vaccine responses with time since vaccination. RESULTS: 1918 articles were identified, of which ten were included in qualitative synthesis and seven in quantitative analysis (children; n=3, older adults; n=4). All studies were deemed to be at low risk of bias, except one study deemed at high risk of bias due to missing outcome data. The majority of included studies found a rise in antibody titers at one-month followed by a decline at six-month post-vaccination. At six-months post-vaccination overall risk differences in seroprotection were significantly higher for children vaccinated with adjuvanted compared to standard vaccines (0.29; 95 % confidence interval (CI), 0.14-0.44). A small increase in seroprotection levels was observed among older adults vaccinated with an adjuvanted compared to standard vaccines, which remained constant over six-months (pre-vaccination: 0.03; 95 % CI, 0.00-0.09 and one- and six-months post-vaccination: 0.05; 95 % CI, 0.01-0.09). CONCLUSIONS: Our results found evidence of persistent antibody responses following influenza vaccination over the course of a typical influenza season. Even if influenza vaccine responses wane over a six-month period, vaccination likely still provides a significant advantage in protection, which may be enhanced with adjuvanted vaccines, particularly in children. Further research is needed to identify the exact timing when the decline in antibody response begins to better inform the optimal timing of influenza vaccination programs. TRIAL REGISTRATION: PROSPERO (CRD42019138585).
Subject(s)
Influenza Vaccines , Influenza, Human , Child , Humans , Aged , Seasons , Antibodies, Viral , Vaccination/methods , Adjuvants, Immunologic/therapeutic use , Hemagglutination Inhibition TestsABSTRACT
Viruses from a new species of piscichuvirus were strongly associated with severe lymphocytic meningoencephalomyelitis in several free-ranging aquatic turtles from 3 coastal US states during 2009-2021. Sequencing identified 2 variants (freshwater turtle neural virus 1 [FTuNV1] and sea turtle neural virus 1 [STuNV1]) of the new piscichuvirus species in 3 turtles of 3 species. In situ hybridization localized viral mRNA to the inflamed region of the central nervous system in all 3 sequenced isolates and in 2 of 3 additional nonsequenced isolates. All 3 sequenced isolates phylogenetically clustered with other vertebrate chuvirids within the genus Piscichuvirus. FTuNV1 and STuNV1 shared ≈92% pairwise amino acid identity of the large protein, which narrowly places them within the same novel species. The in situ association of the piscichuviruses in 5 of 6 turtles (representing 3 genera) with lymphocytic meningoencephalomyelitis suggests that piscichuviruses are a likely cause of lymphocytic meningoencephalomyelitis in freshwater and marine turtles.
Subject(s)
Turtles , United States/epidemiology , Animals , Central Nervous System , RNA, MessengerABSTRACT
Background: Influenza vaccination is recommended annually; however, some studies have raised questions regarding whether repeated influenza vaccine administration may have unintended negative consequences for seasonal protection. Methods: The National Advisory Committee on Immunization (NACI) Influenza Working Group undertook an overview of systematic reviews on the effects of repeated influenza vaccination on vaccine effectiveness, efficacy, and immunogenicity. A systematic assessment of programmatic factors was conducted according to established NACI methods. The NACI evidence-based process was used to critically appraise the available evidence and to review recommendations. Results: The evidence base consisted of four eligible systematic reviews/meta-analyses. Repeated vaccination, including the current season, was consistently more effective than no vaccination in the current season. The evidence showed no significant difference or predictable trend in vaccine efficacy or effectiveness between vaccinations in two consecutive seasons compared to vaccination in the current season only. Conclusion: Overall, NACI concluded that there is evidence to recommend annual influenza vaccination, irrespective of whether an individual received the seasonal influenza vaccine in previous seasons. It is neither currently feasible nor warranted to modify existing annual influenza vaccination programs to account for potential negative or positive interference. NACI continues to strongly recommend that seasonal influenza vaccine should be offered annually to everyone six months of age and older who does not have contraindications to the vaccine, irrespective of previous seasons' influenza vaccination status.
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Background: At the commencement of a pandemic, it is important to consider the impact of respiratory infections on the health system and the possibility of vaccine shortages due to increased demand. In the event of an influenza vaccine shortage, a strategy for administration of fractional influenza vaccine doses might be considered. This article reviews the available evidence for efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing, and summarizes the National Advisory Committee on Immunization (NACI) recommendations on fractional dosing strategies by public health programs in Canada. Methods: Two rapid literature reviews were undertaken to evaluate the efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing via the intramuscular or intradermal route. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. Results: There was limited evidence for the effectiveness of fractional influenza vaccine dosing. Fractional dosing studies were primarily conducted in healthy individuals, mainly young children and infants, with no underlying chronic conditions. There was fair evidence for immunogenicity and safety. Feasibility issues were identified with intradermal use in particular. Conclusion: NACI recommended that, in the event of a significant population-level shortage of influenza vaccine, a full-dose influenza vaccine should continue to be used, and existing vaccine supply should be prioritized for those considered to be at high risk or capable of transmitting to those at high risk of influenza-related complications or hospitalizations. NACI recommended against the use of fractional doses of influenza vaccine in any population.
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BACKGROUND: Systematic reviews (SRs) provide the highest level of evidence and inform evidence-based decision making in health care. Earlier studies found association with industry to be negatively associated with methodological quality of SRs. However, this has not been investigated in SRs on vaccines. METHODS: We performed a systematic literature search using MEDLINE and EMBASE in March 2020. The results were restricted to those published between 2016 and 2019 with no language restrictions. Study characteristics were extracted by one person and checked by an experienced reviewer. The methodological quality of the SRs was assessed with the AMSTAR 2 tool by multiple reviewers after a calibration exercise was performed. A summary score for each SR was calculated. The Mann-Whitney U test and Fisher's exact test were performed to compare both groups. RESULTS: Out of 185 SRs that met all inclusion criteria, 27 SRs were industry funded. Those were matched with 30 non-industry funded SRs resulting in a total sample size of 57. The mean AMSTAR 2 summary score across all SRs was 0.49. Overall, the median AMSTAR 2 summary score was higher for the non-industry funded SRs than for the industry-funded SRs (0.62 vs. 0.36; p < .00001). Lower ratings for industry funded SRs were consistent across all but one AMSTAR 2 item, though significantly lower only for three specific items. CONCLUSION: The methodological quality of SRs in vaccination is comparable to SRs in other fields, while it is still suboptimal. We are not able to provide a satisfactory explanation why industry funded SRs had a lower methodological quality than non-industry funded SRs over recent years. Industry funding is an important indicator of methodological quality for vaccine SRs and should be carefully considered when appraising SR quality.
Subject(s)
Journal Impact Factor , Vaccines , Cross-Sectional Studies , Humans , Publications , Research Design , Systematic Reviews as TopicABSTRACT
Avian paramyxoviruses (APMVs) (subfamily Avulavirinae) have been isolated from over 200 species of wild and domestic birds around the world. The International Committee on Taxonomy of Viruses (ICTV) currently defines 22 different APMV species, with Avian orthoavulavirus 1 (whose viruses are designated APMV-1) being the most frequently studied due to its economic burden to the poultry industry. Less is known about other APMV species, including limited knowledge on the genetic diversity in wild birds, and there is a paucity of public whole-genome sequences for APMV-2 to -22. The goal of this study was to use MinION sequencing to genetically characterize APMVs isolated from wild bird swab samples collected during 2016 to 2018 in the United States. Multiplexed MinION libraries were prepared using a random strand-switching approach using 37 egg-cultured, influenza-negative, hemagglutination-positive samples. Forty-one APMVs were detected, with 37 APMVs having complete polymerase coding sequences allowing for species identification using ICTV's current Paramyxoviridae phylogenetic methodology. APMV-1, -4, -6, and -8 viruses were classified, one putative novel species (Avian orthoavulavirus 23) was identified from viruses isolated in this study, two putative new APMV species (Avian metaavulavirus 24 and 27) were identified from viruses isolated in this study and from retrospective GenBank sequences, and two putative new APMV species (Avian metaavulavirus 25 and 26) were identified solely from retrospective GenBank sequences. Furthermore, coinfections of APMVs were identified in four samples. The potential limitations of the branch length being the only species identification criterion and the potential benefit of a group pairwise distance analysis are discussed. IMPORTANCE Most species of APMVs are understudied and/or underreported, and many species were incidentally identified from asymptomatic wild birds; however, the disease significance of APMVs in wild birds is not fully determined. The rapid rise in high-throughput sequencing coupled with avian influenza surveillance programs have identified 12 different APMV species in the last decade and have challenged the resolution of classical serological methods to identify new viral species. Currently, ICTV's only criterion for Paramyxoviridae species classification is the requirement of a branch length of >0.03 using a phylogenetic tree constructed from polymerase (L) amino acid sequences. The results from this study identify one new APMV species, propose four additional new APMV species, and highlight that the criterion may have insufficient resolution for APMV species demarcation and that refinement or expansion of this criterion may need to be established for Paramyxoviridae species identification.
Subject(s)
Animals, Wild , Avulavirus Infections , Avulavirus , Bird Diseases , Animals , Animals, Wild/virology , Avulavirus/genetics , Avulavirus/isolation & purification , Avulavirus Infections/epidemiology , Avulavirus Infections/veterinary , Avulavirus Infections/virology , Bird Diseases/epidemiology , Bird Diseases/virology , Birds , Phylogeny , Retrospective Studies , Sentinel Surveillance/veterinary , United States/epidemiologyABSTRACT
Over the last several years, the recommended use of the live-attenuated influenza vaccine (LAIV) for children has evolved in the United States (US) in response to evidence of a potential decrease in LAIV effectiveness based on post-market monitoring. These issues were not observed in Canada or elsewhere; consequently, recommendations from Canada's National Advisory Committee on Immunization (NACI) and the US Advisory Committee on Immunization Practices (ACIP) on whether to use LAIV differed for two influenza seasons (2016-2017 and 2017-2018). This retrospective describes how NACI arrived at its recommendations in response to post-market signals of reduced LAIV performance from the US in 2013-2014 and again in 2015-2016. NACI's experience with LAIV marks the first time in Canada where a preferential recommendation on the use of an influenza vaccine in a routine immunization program was reversed. This experience highlights the importance of ongoing post-market monitoring of vaccines, international collaboration and careful consideration of local context to inform vaccine recommendations. NACI's capacity for timely responses to post-market vaccine performance signals will facilitate responsiveness to similar post-market monitoring signals from the coronavirus disease 2019 (COVID-19) vaccines.
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BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to provide an easily administered patient-outcome questionnaire that was adaptable to a variety of medical and surgical subspecialties. Numerous authors have examined the effectiveness of PROMIS in various areas of spine surgery. Our goal was to systematically review PROMIS scores compared with legacy patient-reported outcomes measures (PROMs) in spinal surgery and spine pathology. METHODS: A systematic search of the PubMed, EMBASE, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed, yielding 254 unique studies reporting on "PROMIS" in "spine." Each study was independently reviewed. A total of 16 studies were selected for inclusion. RESULTS: The pooled sample size yielded a total of 4268 patients. In the cervical population, PROMIS physical function (PF; |r| = .47-.87, pain intensity (PIn; |r| = .61-.74), pain interference (PIf; |r| = .65-.88), and pain behavior (PB; |r| = .59-.74) correlated with the Neck Disability Index (NDI). PROMIS PF also strongly correlated with the modified Japanese Orthopaedic Association scale (mJOA; |r| = .61-.72). Among patients with lumbar pathology and adult spinal deformities, PROMIS PF (|r| = .53-.85), PIn (|r| = .73-.78), PIf (|r| = .59-.89), and PB (|r| = .58-.82) strongly correlated with the Oswestry Disability Index (ODI). PF (|r| = .51-.78), PIf (|r| = .60-.70), and anxiety (|r| = .73) also strongly correlated with the Scoliosis Research Society (SRS)-22 and SRS-30. When comparing measures of global health, PROMIS PF was strongly correlated with the Short Form (SF)-12 and SF-36 (|r| = .50-.85). On average, all PROMIS domains required less time to complete (49.6-56 seconds) than the ODI (176 seconds), NDI (190.3 seconds), SF-12 (214 seconds), and SF-36 physical function domains (99 seconds). The responsiveness of the PROMIS PF, PIf, and PB was comparable to that of legacy measures ODI, NDI, and SF-12. CONCLUSIONS: The PROMIS PF, PIn, PIf, and PB demonstrated moderate to strong correlations with NDI, mJOA, ODI, SRS, and SF-12 measures in various populations of spine patients. All PROMIS domains had decreased time to completion and similar responsiveness compared with legacy measures. LEVEL OF EVIDENCE: 2. CLINICAL RELEVANCE: These results highlight the potential of PROMIS as a valid and reliable tool to assess patient-reported outcomes in spinal surgery patients and support more widespread use of PROMIS in spine.
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Optimal strategies for integration of clinical practice guidelines into electronic medical records and its impact on processes of care and clinical outcomes in diabetic patients are not well understood. A systematic review of CINAHL, MEDLINE, PubMed, and Cochrane Library databases in August 2016, November 2017, and June 2020 was conducted. Studies investigating integration of diabetes guidelines into ambulatory care electronic medical records reporting quantitative results were included. After screening 15,783 records, 21 articles were included. Lipid and blood pressure control consistently improved with guideline integration, but A1c control remained equivocal. Electronic guideline integration improved microvascular complication screening, vaccination, and documentation of cardiovascular risk factors, while medication prescription and blood pressure, lipid, and A1c documentation did not improve. Studies employing a combination of electronic record intervention strategies were associated with improvement in monitoring and attainment of guideline and screening targets. Thus, strategies employing combinations of interventions to incorporate guidelines into electronic records may improve processes of care and some clinical outcomes.
Subject(s)
Diabetes Mellitus/therapy , Electronic Health Records , Practice Guidelines as Topic , Humans , Treatment OutcomeABSTRACT
We report whole-genome sequencing of influenza A virus (IAV) with 100% diagnostic sensitivity and results available in <24-48 h using amplicon-based nanopore sequencing technology (MinION) on clinical material from wild waterfowl (n = 19), commercial poultry (n = 4), and swine (n = 3). All 8 gene segments of IAV including those from 14 of the 18 recognized hemagglutinin subtypes and 9 of the 11 neuraminidase subtypes were amplified in their entirety at >500× coverage from each of 16 reference virus isolates evaluated. Subgenomic viral sequences obtained in 3 cases using Sanger sequencing as the reference standard were identical to those obtained when sequenced using the MinION approach. An inter-laboratory comparison demonstrated reproducibility when comparing 2 independent laboratories at ≥99.8% across the entirety of the IAV genomes sequenced.
Subject(s)
Bird Diseases/diagnosis , Influenza A virus/isolation & purification , Influenza in Birds/diagnosis , Nanopore Sequencing/veterinary , Orthomyxoviridae Infections/veterinary , Swine Diseases/diagnosis , Whole Genome Sequencing/veterinary , Animals , Animals, Wild , Bird Diseases/virology , Chickens , Ducks , Influenza A virus/genetics , Influenza in Birds/virology , Nanopore Sequencing/methods , Orthomyxoviridae Infections/diagnosis , Orthomyxoviridae Infections/virology , Poultry Diseases/diagnosis , Poultry Diseases/virology , Sus scrofa , Swine , Swine Diseases/virology , Turkeys , Whole Genome Sequencing/methodsABSTRACT
Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of IB is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. Although serotyping requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV, and it is inefficient at detecting multiple viruses in a single sample. We describe herein a MinION-based, amplicon-based sequencing (AmpSeq) method that genetically categorized IBV from clinical samples, including samples with multiple IBVs. Total RNA was extracted from 15 tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer's instructions into a 1D MinION sequencing library, and then sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in 3 of 5 samples containing 2 IBV lineages. Additionally, 1 sample contained 3 IBV lineages, and AmpSeq accurately detected 2 of the 3 lineages. Strain identification, including detection of different IBVs from the same lineage, was also possible with this AmpSeq method. Our results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.
Subject(s)
Chickens , Coronavirus Infections/veterinary , Infectious bronchitis virus/isolation & purification , Poultry Diseases/diagnosis , Sequence Analysis, RNA/veterinary , Spike Glycoprotein, Coronavirus/analysis , Animals , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Poultry Diseases/virology , Sequence Analysis, RNA/methodsABSTRACT
RNA viruses rapidly mutate, which can result in increased virulence, increased escape from vaccine protection, and false-negative detection results. Targeted detection methods have a limited ability to detect unknown viruses and often provide insufficient data to detect coinfections or identify antigenic variants. Random, deep sequencing is a method that can more fully detect and characterize RNA viruses and is often coupled with molecular techniques or culture methods for viral enrichment. We tested viral culture coupled with third-generation sequencing for the ability to detect and characterize RNA viruses. Cultures of bovine viral diarrhea virus, canine distemper virus (CDV), epizootic hemorrhagic disease virus, infectious bronchitis virus, 2 influenza A viruses, and porcine respiratory and reproductive syndrome virus were sequenced on the MinION platform using a random, reverse primer in a strand-switching reaction, coupled with PCR-based barcoding. Reads were taxonomically classified and used for reference-based sequence building using a stock personal computer. This method accurately detected and identified complete coding sequence genomes with a minimum of 20× coverage depth for all 7 viruses, including a sample containing 2 viruses. Each lineage-typing region had at least 26× coverage depth for all viruses. Furthermore, analyzing the CDV sample through a pipeline devoid of CDV reference sequences modeled the ability of this protocol to detect unknown viruses. Our results show the ability of this technique to detect and characterize dsRNA, negative- and positive-sense ssRNA, and nonsegmented and segmented RNA viruses.
Subject(s)
High-Throughput Nucleotide Sequencing/veterinary , RNA Viruses/isolation & purification , Sequence Analysis, RNA/veterinary , Whole Genome Sequencing/veterinary , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, RNA/methods , Whole Genome Sequencing/methodsABSTRACT
BACKGROUND: Canada's National Advisory Committee on Immunization (NACI) provides guidance on the use of vaccines in Canada. To support the expansion of its mandate to include considerations for vaccine acceptability when making recommendations, the NACI Secretariat developed a matrix of factors that influence acceptability. To inform and validate the matrix, we systematically reviewed evidence for factors that influence vaccine acceptability, and for interventions aimed at improving acceptability. METHODS: On 10-11 October 2018 we searched four bibliographic databases, the Theses Canada Portal, and ClinicalTrials.gov. Two reviewers agreed on the included studies. From each study, we extracted information about the participants, intervention or exposure, comparator, and relevant outcomes. Due to heterogeneity in the reported factors and acceptability indicators we synthesized the findings narratively. We appraised the certainty of evidence using GRADE. For each vaccine-preventable disease we populated a matrix of factors for which there was evidence of an influence on acceptability. RESULTS: One hundred studies (>1 million participants) contributed data relevant to the public, 16 (6191 participants) to healthcare providers, and three (84 participants) to policymakers. There were 43 intervention studies (~2 million participants). Across vaccines, we identified low certainty evidence for 70 factors relevant to the general population, 56 to high-risk groups, and 30 to healthcare providers. The perceived safety and importance of the vaccine, vaccination history, and receiving a recommendation from a healthcare provider were common influential factors. We found low certainty evidence that reminders for childhood vaccines and policies or delivery models for rotavirus vaccines could improve uptake and coverage. Evidence for other interventions was of very low certainty. CONCLUSIONS: The NACI vaccine acceptability matrix is useful for categorizing acceptability factors for the general public. Reminder systems may improve the uptake of childhood vaccines. Policies that make the rotavirus vaccine universally available and easily accessible may improve coverage. FUNDING: This systematic review was completed under contract to the Public Health Agency of Canada, Contract #4600001536.
Subject(s)
Rotavirus Vaccines , Canada , Child , Humans , Immunization , Reminder Systems , VaccinationABSTRACT
Natural language processing (NLP) is a subfield of artificial intelligence devoted to understanding and generation of language. The recent advances in NLP technologies are enabling rapid analysis of vast amounts of text, thereby creating opportunities for health research and evidence-informed decision making. The analysis and data extraction from scientific literature, technical reports, health records, social media, surveys, registries and other documents can support core public health functions including the enhancement of existing surveillance systems (e.g. through faster identification of diseases and risk factors/at-risk populations), disease prevention strategies (e.g. through more efficient evaluation of the safety and effectiveness of interventions) and health promotion efforts (e.g. by providing the ability to obtain expert-level answers to any health related question). NLP is emerging as an important tool that can assist public health authorities in decreasing the burden of health inequality/inequity in the population. The purpose of this paper is to provide some notable examples of both the potential applications and challenges of NLP use in public health.