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Updated: December 2015
The Pandemic Influenza Laboratory Preparedness Network (PILPN) of the Canadian Public Health Laboratory Network (CPHLN) has developed this document, which is based on current best practices for the laboratory detection of influenza as well as the lessons learned from the 2009 H1N1 pandemic. Specifically, this Laboratory Annex to the Canadian Pandemic Influenza Preparedness: Planning Guidance for the Health Sector (CPIP) addresses issues related to appropriate sample type and specimen collection; laboratory testing; laboratory-based surveillance and data collection; communication issues; and pandemic preparedness.
In the context of the CPIP, “laboratory” refers to clinical laboratories. While the primary audience is clinical laboratory professionals, the document may serve as a practical reference for other stakeholders, such as front-line clinicians and epidemiologists. In addition, the Laboratory Annex highlights important aspects of the laboratory response, so that pandemic planners, decision-makers and other relevant stakeholders can be fully aware of the resources required to support that response. It is expected that this guidance will be adaptable to different situational and regional/jurisdictional contexts.
Consistent with the main body of the CPIP, this version of the Laboratory Annex incorporates lessons learned during and since the 2009 pandemic and provides a risk management approach to support a flexible and proportionate response.
As with the previous CPIP Laboratory Guidelines, nucleic acid amplification tests (NAAT) remain the pillar of the laboratory testing strategy because of their sensitivity, scalability and capacity to rapidly diagnose influenza.
Changes in the current version of the Laboratory Annex include the following:
In the event of pandemic influenza or the emergence of a novel subtype of influenza virus, laboratories will be instrumental in facilitating the delivery of rapid and appropriate public health responses. During a pandemic, laboratory testing will accomplish the following:
Primary detection assays to help with patient management and the public health response are provided by provincial public health laboratories (PHL) and many front-line hospital laboratories. While some hospital laboratories may also have the capacity for subtyping, this function is primarily the responsibility of the PHL.
Surveillance will require a coordinated approach from all levels - local, regional, provincial/territorial (PT) and national - to ensure that the data are adequately captured and interpreted. A statistically appropriate number of specimens should flow through the PHL to the National Microbiology Laboratory (NML) for further viral characterization, including AVR testing for those PHLs that do not have the capability or capacity.
There remain many uncertainties that influence how laboratories can prepare for the next pandemic:
Canada’s public health response to the 2009 H1N1 pandemic provides some valuable lessons learned vis-à-vis the potential role and contribution of laboratories in future outbreaks:
As noted in the main body of the CPIP, it is assumed that there will be geographic variability with regard to the timing and intensity of waves, although multiple jurisdictions will likely be affected simultaneously. The Canadian population is geographically dispersed, with large areas of rural or remote populations. Consequently, access to laboratory services (particularly NAATs) may be an issue in some communities within such regions, leading to delayed turnaround time. This may necessitate a collaborative response among different jurisdictions to help ensure that optimal laboratory testing is in place to guide both individual and community responses. For example, the Territories routinely rely on British Columbia and Alberta for influenza testing; therefore, testing strategies need to be tailored in these regions to encompass the logistics of transporting specimens in a timely fashion in order to obtain results that are useful for patient or outbreak management. It is also important that the samples transported be appropriate and sample integrity maintained to avoid even further delays due to laboratory rejection of samples deemed unfit for testing. The implications for laboratory testing need to be considered in any novel care delivery models.
Pandemic preparedness and response are intimately tied to public health and epidemiology objectives, together with the often competing patient care imperative. While front-line laboratories focus primarily on patient care, it is important that PHLs balance the needs of patient care with public health/epidemiology objectives.
In this context, ethical considerations promote a social justice approach that is based on trust, solidarity, reciprocity, stewardship, equity and fairness. The Laboratory Annex was developed through consideration of the guiding principles and approaches outlined in the main body of the CPIP, particularly focusing on the following:
As noted in the main body of the CPIP, one of the supporting objectives for Canada’s goals for pandemic preparedness and response is maintaining trust and confidence through support of evidence-informed decision-making by collection, analysis and sharing of surveillance and other scientific information. Having data-sharing agreements in place before the next pandemic will help achieve a coordinated and efficient flow of information through the laboratory system. It is important that FPT governments work together to develop and agree upon common sets of minimum data requirements needed to effectively support the surveillance systems required to guide the pandemic response and that laboratories are an intimate partner in these discussions.
The purpose of testing for influenza virus falls into two broad categories:
Population-based surveillance requires that laboratory networks have the capacity to detect and subtype the novel virus in order to differentiate it from common circulating influenza strains. Subtyping and characterization of strains may be particularly relevant if the emerging virus has a different antiviral susceptibility pattern and can help determine vaccine effectiveness and potential mismatch. To this end, it is recommended that a proportion of influenza isolates representing community-based cases, as well as isolates from hospitalized patients, be isolated in cell culture and submitted to the NML for further characterization, including antiviral resistance and antigenic variation. Laboratories equipped to readily determine the genome sequence will be able to characterize the virus in greater detail and identify the appearance of genotypes associated with an enhanced risk of mortality. It is anticipated that laboratories will also provide diagnostic support to research initiatives as required.
As noted in the main body of the CPIP, identifying planning assumptions is a way to deal with uncertainty. Although planning assumptions provide a useful framework for planning, they should not be regarded as predictions. In the absence of certainty, planning assumptions help to inform planning and decisions regarding the establishment of laboratory protocols and procedures, and stockpiling of materials and supplies that will be necessary during the pandemic response. Planning assumptions related to pandemic preparedness are found in the main body of the CPIP.
Several laboratory-specific planning assumptions are identified below:
|Key Triggers||Typical Accompanying Actions|
|Novel virus causing human cases detected anywhere in the world||
|Novel/pandemic virus (with sustained human transmission) first detected in Canada||
|End of the first waveTable 1 - Footnote 1 1||
Specimen type and collection: The ability to detect influenza virus depends on many factors:
While the shedding patterns of a novel influenza virus may be variable, because the population lacks immunity it is likely that the novel virus will behave in a way that is similar to what is seen in seasonal influenza with children. Specimens should be collected within 5 days of onset of symptoms and preferably within 48 hours. Sampling beyond 5 days may be considered in young children or the elderly, in the immunocompromised and in patients with persisting or worsening symptoms regardless of age.Footnote 2 Specimens should be collected from patients admitted to the hospital with suspected influenza regardless of symptom duration. While the ideal specimen will need to be defined as the pandemic progresses, suggested specimen types are outlined in Table 2.
|Nature of illness||Specimen of choice||Alternative specimens|
|Asymptomatic||Do not test.|
|Mild/moderate ILI||Nasopharyngeal swab (NPS)/nasopharyngeal aspirate (NPA)
Video demonstration of NPS/NPA collection can be accessed at:
Procedure for Nasopharyngeal Swabs and Aspirates
|Deep nasal swab WITH a throat swab or mid-turbinate swabTable 2 - Footnote 1 1
Throat swab and sputumTable 2 - Footnote 2 2
|Severe respiratory illness or lower respiratory tract infection||NPS AND endotracheal (ET) secretions or bronchoalveolar lavage (BAL) specimensTable 2 - Footnote 3 3 Table 2 - Footnote 4 4|
|Autopsy||Lung tissue or other tissues from suspected organ involvement. Specimens should be fresh or frozen at -70oC. DO NOT put into formalin fixative.|
Flocked swabs should be used to collect nasopharyngeal or nasal/throat combination specimens. Wooden shaft swabs are inhibitory to nucleic acid-based testing and are therefore not recommended.Footnote 3
Appropriate personal protective equipment (PPE) is recommended for collection of specimens. The infection control/occupational health guidelines may differ among PTs. For relevant PPE guidance, it is recommended that laboratories check with their infection prevention and control guidelines and with their local public health agencies, as well as the Canadian Biosafety Standards and Guidelines.
Specimen transport: Specimens should be collected and transported to the laboratory as soon as possible, preferably within 72 hours, on cold packs (+4oC). If a longer delay is anticipated, specimens should be frozen at -70oC or lower and transported on dry ice. However, freezing may affect the recovery of the virus if culture is required. Specimens should not be frozen at -20oC.
If -70oC/dry ice is not available, the specimens should remain at +4oC and shipped as soon as possible. Recent data suggest that when extracted RNA is being transported alone, it will remain stable at +4oC.Footnote 4 Specimens should be transported as diagnostic specimens as per the usual practice for seasonal influenza specimens, and no enhanced precautions are necessary.
It is important to ensure that the specimen tube and requisition are completed correctly and fully, with matching patient names and unique identifiers, and relevant clinical and epidemiological information.
Surge Capacity: Many laboratories underestimated the pressures that the increase in testing demand during the 2009 pandemic would put on the pre-analytical process within the laboratory. The following issues should be considered in planning for the next pandemic:
A number of methods are available for the detection of influenza, each of which has varying abilities. NAAT protocols, such as conventional reverse transcriptase polymerase chain reaction (RT-PCR) or real-time RT-PCR (rRT-PCR), with their high sensitivity, rapid turnaround time and potential strain characterization capability, together with high throughput and the ability for automation, are the method of choice for pandemic influenza testing. Table 3 below summarizes the testing options available for detection and characterization of influenza; additional detail regarding the various testing methods is provided after the table.
|Test||Method||Time to perform the test||SensitivityTable 3 - Footnote 1 1||Subtyping||Cost||Throughput|
|NAAT (RT-PCRTable 3 - Footnote 2 2)||RNA detection||
|Viral culture||Virus isolation||2-10 days||About 30%||YesTable 3 - Footnote 3 3||$$||+|
|Direct immuno-fluorescence assays (DIFA) or indirect immuno-fluorescence assays (IIFA)||Antigen detection||2-4 h||47%-93%||No||$$||++|
|Rapid influenza detection tests||Antigen detection||0.5 h||10%-69%||No||$$$||++|
It is recommended that provincial laboratories have procedures in place for both the detection and subtyping of influenza viruses. Specimens positive for influenza A from patients with epidemiological and clinical features that suggest a novel subtype of influenza should be subtyped for common seasonal influenza viruses using RT-PCR. PHLs or designated laboratories should perform rapid subtyping of positive specimens. Specimens that are repeatedly positive for influenza but cannot be subtyped or have a unique genome sequence should be forwarded to the NML for further characterization. As the pandemic evolves, subtyping may remain an important aspect of testing to support ongoing surveillance requirements and may be important in patient management if the antiviral susceptibility profile is different from that of seasonal strains. However, if the pandemic virus becomes the dominant circulating strain, subtyping may have limited value.
It is recommended that a continued effort be made to decentralize NAATs and establish additional capacity in hospital laboratories. To support this effort, it is recommended that PHLs take appropriate initiatives and help establish additional testing sites in the respective jurisdictions, as well as mechanisms to help ensure that central reporting of results takes place. It is further recommended that laboratories should optimize reporting strategies such that both positive and negative results are reported expeditiously.While NAAT assays are the most sensitive detection method, there are many commercially available kits for the detection of influenza, including a number of multiplex assays, with varying degrees of analytical sensitivity. Recent data show that the analytical sensitivity of a number of commercial assays for the detection of H7N9 virus is poor compared with the in-house assays used at most PHLs, which are based on the Centers for Disease Prevention and Control kit.Footnote 11 Footnote 12 It is imperative that the performance of commercial assays in their ability to detect novel pathogens be assessed when novel influenza strains are identified.Footnote 13
Because the NML has the technical capacity for antigenic characterization and is required to conduct surveillance reporting to the WHO, the NML will be the primary laboratory for this type of testing. However, once reference antisera become available, there will be an option for subtyping and antigenic characterization, using haemagglutination inhibition assays and neutralization assays, to be carried out by laboratories with the appropriate containment facilities, as dictated by the containment level requirements of the novel strain (see Viral Characterization below).
RIDT-based testing may have a role in monitoring outbreaks in some settings and may be the only option for timely determination of the presence of influenza in remote communities. Data from Ontario during the 2011-2012 influenza season suggest that although RIDTs have a sensitivity of 59% and 35% for the detection of H3 and influenza B viruses respectively using individual specimens, they have an overall sensitivity of 78.9% for detecting H3 outbreaks when testing up to four samples per outbreak.Footnote 31
If RIDTs are used to assess influenza activity, the test limitations must be clearly understood and testing sites should train health care professionals in optimal specimen collection and testing procedures.Footnote 32 The local PHL could provide assistance in validating RIDT assays and provide confirmatory testing by NAAT for positive RIDT results early in the pandemic and in outbreaks with negative RIDT results. If these tests are to be used, it is recommended that the relevant communities ensure that they have a stockpile of the test kits and the appropriate collection swabs.
|≤5% PositivityTable 4 - Footnote 1 1||>5% PositivityTable 4 - Footnote 2 2|
|Surveillance||Temporal and geographic representation. PHLs are requested to submit to the NML 10% of positive isolates obtained from community-based sampling, such as the Sentinel Physician Network.||Temporal and geographic representation. PHLs are requested to submit to the NML two random positive specimens per week obtained from community-based sampling.
Outbreak of influenza A in a new jurisdiction or institution.
|Clinical application/criteria||Failed therapy - ICU patient, 10 days post-treatmentTable 4 - Footnote 3 3
Positive test of patient with ILI while receiving or after having received prophylaxis
Positive test in a traveler returning from an area where resistance is endemic
Persistent infection in people with immune compromising conditions
Nosocomial transmission in clinical areas with people with immune compromising conditions
Positive test from a case in contact with an infected person with an immune compromising condition
Clinical failure in a patient being treated with antivirals
The definition of clinical failure in the treatment of influenza infection has not been established. A study of treatment outcomes of patients infected with the H5N1 virus showed that treatment failure was associated with persistent high viral load after 48 hours of therapy.Footnote 34 Laboratories performing real-time RT-PCR (rRT-PCR) for influenza have the potential to assess viral loads in patient specimens obtained after antiviral therapy, but in most cases this approach has not been adequately validated and is not routinely available.
Routine repeat RT-PCR is not recommended. While there are data outlining the shedding patterns of influenza in infected patients, the clinical implication of a positive RT-PCR in patients receiving antivirals is not clear. Canadian data from a study of household contacts during the first wave of the 2009 pandemic suggest that although only 13% of pH1N1-positive patients had live virus isolated in cell culture at 8 days after infection, the virus could be detected by RT-PCR in 74% of patients.Footnote 35 A similar German study over a 4-year period (2007-2011) revealed that patients can shed live virus (isolated in cell culture) for 4-6 days after infection, and RT-PCR can be positive for up to 9 days.Footnote 36 In a Vietnam study, the median time to a negative RT-PCR in oseltamivir-treated patients was 2.6 days, and less than 7% of treated individuals were RT-PCR positive 5 days after treatment. No specimens were culture positive after 5 days of treatment.Footnote 37 These cases were considered clinically mild, suggesting that for those with an uncomplicated course of illness, the virus will have cleared in the majority of patients by 5 days. Therefore, in patients whose follow-up respiratory specimens have no detectable virus, the treatment can be deemed successful. However, the significance of positive results is not well understood.
Although routine repeat RT-PCR testing is NOT recommended, repeat testing would be appropriate if suspected failure of treatment, based on the clinical response to treatment (e.g. someone with worsening disease despite 10 days of antivirals and no other obvious cause, such as bacterial superinfection), occurs. In such cases, it is recommended that follow-up specimens, including ET suction and BAL specimens, be collected for testing by RT-PCR, and specimens showing substantial concentrations of virus be forwarded for AVR testing.
Detection of other respiratory viruses
Canadian experience during the 2009 pandemic and in previous influenza seasons has demonstrated that a number of other respiratory viruses, such as parainfluenza and rhinovirus, can co-circulate with influenza virus, causing considerable morbidity. To avoid inappropriate assignment of morbidity and mortality to influenza, some effort directed at detection of other respiratory viral agents is warranted. Because resource issues may be a problem in many laboratories, broad routine testing for other viruses by all laboratories may not be feasible. Therefore, when influenza testing is negative, a prioritized sampling method is recommended, especially for patients with severe acute respiratory infection, people with immune compromising conditions, children under 5 years of age admitted with ILI, or ILI outbreaks in closed settings such as nursing homes.Footnote 38
It is recommended that laboratories work with their laboratory information system to ensure that newly developed assays can be appropriately reported. It is important that front-line laboratories coordinate with the provincial PHLs to make report data and specimens available for surveillance purposes. Changes in laboratory testing may be required to adapt to the increasing demand. To help ensure a timely communication of such changes, it is recommended that laboratories have a communication strategy to inform clinicians and other end-users of the changes and how these changes may affect surveillance or patient care. Although developing consistent messaging during an evolving health crisis is challenging, the dissemination of this information is a greater challenge if the infrastructure has not been developed beforehand. Achieving effective communication strategies during seasonal influenza is essential so that they can be drawn upon in times of crisis.
Laboratories should anticipate that industry may inquire about access to specimens and expertise in developing or assessing new assays. Consequently, it is recommended that policies regarding industry interactions, including MTA templates, be developed before the next pandemic to expedite the process. With increased laboratory test volumes, laboratories will also need to plan for the archiving/storage or removal of larger than normal numbers of specimens.
Accreditation programs require participation in influenza proficiency programs by all laboratories performing any type of influenza diagnosis. The NML provides proficiency panels to assess the diagnostic sensitivity and specificity of tests available at PHLs and other viral diagnostic laboratories. The NML and PHLs share reagent lots designed to diagnose circulating or emerging influenza subtypes. The NML also provides at least one influenza proficiency panel per year to Canadian laboratories that wish to participate in NAAT identification of current influenza A strains.
As the 2009 pandemic highlighted, a novel virus may require new testing protocols. Appropriate validation and verification of these methods or of current commercially available assays are essential to achieve accurate test results. As a network, the provincial PHLs and the NML will continue to work collaboratively, sharing reagents and specimens to help laboratories meet this requirement.
As the pandemic evolves, it is anticipated that the diagnostic capabilities of laboratories will be strained. However, it will be important to continue quality assurance activities, such as participation in proficiency panels distributed by the NML. The NML will be responsible for providing the guidance and materials required.
The PILPN recommends participation in other accredited proficiency programs, such as those of the College of American Pathologists.
International experience with the 2009 pandemic indicated that, from a laboratory perspective, the novel virus did not behave significantly differently from seasonal influenza strains. However, how the next novel influenza virus will behave remains unknown. In addition, at the beginning of the pandemic, when the virus is not widely circulating, there may be a greater chance of exposure to the virus in the laboratory setting than in the community. The Centre for Biosecurity (CB) at PHAC is responsible for providing guidance and the initial biosafety advisory on how diagnostic specimens and virus will be handled. The CB biosafety advisory may be revised as further information becomes available. Laboratories should expect that manipulation of virus culture will be restricted to CL3 facilities and that the processing of diagnostic specimens for NAATs will require CL2 with enhanced precautions. An additional biosafety consideration is influenza vaccination.Footnote 39 It is recommended that all laboratory workers be vaccinated as per the recommendations established for use of the pandemic vaccine.
The NML is responsible for the following:
PHLs are responsible for the following:
Front-line laboratories are responsible for the following:
This section discusses another important tool for pandemic planning: the use of multiple planning scenarios specifically intended to support the planning principles and approaches of evidence-informed decision-making, proportionality, flexibility and a precautionary/protective approach.
Planning scenarios provide a starting point to think through the implications and risks that would be associated with pandemics of varying population impact. Scenarios can also be used for exercises and training in support of pandemic plans. To help with risk identification, four pandemic planning scenarios have been developed that describe potential pandemic impacts varying from low to high.
When using these scenarios for pandemic planning purposes, laboratories would want to consider the full aspects of testing: pre-analytical, analytical and post-analytical components, including accessioning, reporting, laboratory information systems, storage of specimens, potential absenteeism and cross-training requirements.
Each laboratory would also define a testing volume baseline. While this may be simply an estimation equivalent to the volume that is expected in a routine influenza season, defining baseline volumes can be challenging. Laboratories may wish to consider the seasonal variation that occurs and the evolution of testing methodology, leading to changes in algorithms (who to test) and protocols. Many laboratories have changed their testing algorithms since the 2009 pandemic and therefore may not be able to provide a true baseline calculation. If laboratory testing algorithms and protocols are relatively consistent for a period of 3 years or more, the average or median of the test volumes over those years can be determined. However, if the testing algorithms and protocols have changed, it may be necessary for laboratories to model test volume estimates according to their historical low-, medium- and high-volume influenza seasons.
Using the pandemic planning scenarios framework, Table 5 outlines the impact related to influenza testing. However, it is recommended that laboratories consider the impact on other services, such as blood cultures, bacterial cultures and antimicrobial testing, all of which may increase with increasing hospitalization due to influenza. While these values are more difficult to quantify, it would be prudent for laboratories to prepare for an increase in these secondary tests.
|Nature of impact||A
|Basic virus characteristics||Low transmission and virulence||High transmission/low virulence||High virulence/low transmission||High transmission and virulence|
|Nature and scale of illness||Similar numbers to those in moderate or severe seasonal influenza outbreaks.
Mild to moderate clinical features (in most cases).
|Higher number of cases than in large seasonal outbreak but similar clinical profile.
Overall increased numbers needing medical care and with severe disease.
|Similar number of cases to large seasonal outbreak but illness is more severe.
Overall increased numbers needing medical care and with severe disease.
|Large numbers of people ill, high proportion with severe disease.|
|Impact on testing||BaselineTable 5 - Footnote 1 1 (1x)||5x||7.5x||>10x|
Collaboration is one of the guiding principles that underpin Canadian pandemic preparedness and response activities and decision-making. It is essential that the various aspects of pandemic preparedness and response are integrated where necessary to achieve an effective and coordinated response. To this end, the Laboratory Annex strives to identify the key linkages and interrelationships that will contribute to an effective and coordinated response.
It is important for laboratories and public health decision-makers to be engaged during the interpandemic period in order to establish awareness and understanding of laboratory functions, the requirements associated with influenza detection and the contextual relationship of the laboratory as one of the pillars of an effective pandemic response; this will, in turn, facilitate the rapid decision-making processes that are required during a pandemic.
On a practical level, data-sharing agreements among different laboratories in the PT, among the PTs, as well as between the PTs and PHAC, need to be clarified to achieve the seamless transfer of data that will support ongoing surveillance activities. It is imperative that these agreements address intellectual property, copyright issues and other publication issues.
Some key inter-relationships between the Laboratory Annex and other aspects of pandemic preparedness and response are outlined below.
To ensure that the data are comparable and interpreted correctly, it is imperative that epidemiologists understand the nuances of testing and how testing is delivered differently across the country. It is equally important that laboratories understand the needs of the epidemiologists and the data they require to conduct risk assessments and effectively analyze the progression of the pandemic.
Because surveillance is a cornerstone of pandemic planning and preparedness, surveillance during a health emergency should utilize and build upon pre-existing surveillance infrastructures and data-sharing agreements. Every year, ILI is an important cause of morbidity and mortality in the population, and significant resources are expended annually on influenza vaccination and response management. Other viruses also cause respiratory illness each year, and there is limited knowledge of the relative impact of these other viral agents on morbidity and mortality and how best to manage infected individuals. Ensuring effective and functional surveillance for seasonal influenza and other respiratory viruses in Canada during the interpandemic period serves to optimize capacity for a pandemic response.
Given that rapid advances in diagnostic technologies will continue to improve the ability to accurately diagnose and identify influenza, novel influenza strains and other circulating viruses, the development and routine use of a broad-based network through which to understand the epidemiology of circulating respiratory viruses and to measure their health impact will also serve to build capacity within Canada. Such a network, ideally consisting of a coordinated sentinel network and hospital-based surveillance, would not only enhance capacity to evaluate existing interventions (e.g. vaccines, antivirals and cohorting practices) in the health outcomes of individuals infected with respiratory viruses but could also serve as the foundation for the surveillance response during a pandemic, providing strategic information to track and respond to the outbreak in near real time. Further information regarding the surveillance aspects of pandemic influenza planning can be found in the Surveillance Annex of the CPIP.
Understanding the performance characteristics, benefits and limitations of different testing methods is imperative to help patient management. Continued collaboration with relevant clinical groups will help to ensure that clinicians understand the different testing methods and any preferences for use.
Clinical and public health laboratories also support the clinical management of individuals through testing. However, as noted in the planning assumptions, it is anticipated that resources will be constrained, and consequently clinical testing priorities will need to be re-evaluated as the pandemic progresses. Once the novel strain becomes widespread in the community, testing may not be indicated for the clinical management of those with uncomplicated ILI. It will be important for clinicians in all health care settings to be aware of the guidelines for laboratory testing and, in a timely manner, of any changes to the guidelines (i.e. restrictions on testing) to prevent laboratories from being overwhelmed with requests for confirmation of diagnosis. Clinicians should be made aware of the appropriate requisitions to use, their labelling and the laboratories to which specimens should be sent.
Canada has stockpiles of antiviral drugs comprising oseltamivir and zanamivir, the latter included mainly as a hedge against resistance to oseltamivir. Laboratory testing should be undertaken when antiviral resistance is suspected (see the circumstances outlined in Table 4).
Unique challenges related to laboratory activities exist in First Nations and remote or isolated communities and must be considered in pandemic preparedness and response planning. It is critical, therefore, for community pandemic planners, along with laboratory experts and PT partners, to collaborate in order to promote seamless transfer of information and determine feasible options in providing communities with access to testing. Community pandemic planners in these communities need to be familiar with established testing guidelines and processes to ensure that laboratory specimens are dealt with appropriately.
One challenge that can be anticipated is obtaining timely access to diagnostics, which can often be difficult because of infrastructure limitations and delays in transportation to reference laboratories. Planners and front-line health care providers must consider geographic location and weather conditions when planning the transport of laboratory specimens, which are time- and temperature-sensitive. Extreme temperature fluctuations and time delays in transporting specimens may adversely affect laboratory test results (e.g. if a specimen is frozen and thawed, PCR testing may be falsely negative). It is advised that every effort be made to transport specimens without delay.
PHLs will be the gatekeepers to reference testing. To ensure that the flow of testing results information and specimens is appropriate, it is important that front-line laboratories are or can be integrated into the surveillance system. As stated previously, this includes prior development of data-sharing agreements and MTAs.
Any issues related to the performance of commercial assays and the availability of reagents must be communicated to the appropriate vendors. It is important that processes are in place for the rapid approval of necessary equipment and reagents to support the laboratory response. Collaboration between laboratories and their procurement departments will help meet laboratory needs.
Research plays a key role in addressing knowledge gaps about the influenza virus and effective influenza prevention, treatment and control strategies. Identification of key questions regarding the development of protocols before the next pandemic is important. To help available resources to be mobilized quickly, advance planning is required. Such advance planning considerations could include establishing mechanisms for rapid-response research prior to the pandemic being declared, leveraging existing partnerships between public health agencies, clinical and academic institutions, etc. It is important that laboratories be involved in this planning, as they can support research by providing data gathered from routine or reference testing or by performing additional testing to answer research questions. Strengthening the existing scientific capacity in the PHLs would also help to ensure that the infrastructure exists to address diagnostic questions and to support ongoing clinical studies and vaccine effectiveness.
It is recommended that laboratories consider advance planning for the infrastructure required to support research in collaboration with public health agencies, academic and clinical institutions, as well as for protocols for the use of specimens and the requirement for informed consent. This would include, but would not be limited to, the development of MTAs and data-sharing agreements, particularly regarding intellectual property, copyright and other publication issues, as well as processes to support the dissemination of information to end-users.
With each health emergency, there is an opportunity to review and reassess planning. The development of the Laboratory Annex has allowed PILPN to review the experiences of the last pandemic in order to improve the guidance documents for the next one. When a novel influenza virus is detected in humans for the first time (such as the recent identification of H7N9), CPHLN and PILPN meet to review protocols and ensure that Canada can detect this novel pathogen should the need arise. CPHLN and PILPN will participate in any table top exercise led by PHAC to test the current preparedness and ability to respond, and PILPN will oversee the review of the Laboratory Annex every 2 years and incorporate new developments as they arise.
Assumptions about Demands for Testing
Recommended Testing Procedures/Capacity
Each PHL or designated laboratory should be able to provide or advise on appropriate specimen collection.
Business Continuity Plan
Minimum Requirements for Timely Communication