Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations and the application of this study to the control of health problemsFootnote 40. The main purpose of infectious disease epidemiology is to assist in the prevention of infection through an understanding of its distribution (i.e., of person, place and time), factors that affect its natural history, and factors that influence the acquisition of disease.
Acquisition of infection is the result of a set of complex interrelationships between the infectious agent/infected source, the susceptible host and the environment. The "epidemiological triangle"Footnote 41 can be used to describe and understand the relationship between these three key elements. Figure 1 provides a visual representation of the interaction of the three elements as it relates to infectious disease, and influenza in particular. In this document, the relationship between the elements found in the epidemiological triangle will provide the basis for describing a) the process of exposure to and transmission of the influenza virus and b) interventions to minimize (prevent and control) transmission of the influenza virus among patients, HCWs, visitors, contractors, etc. while present (e.g., working, receiving care, visiting, volunteering) in healthcare settings.
Figure 1. Epidemiological Triangle – acquisition and transmission of infection
The infectious agent is a microorganism that causes, or has the potential to cause an infection. Characteristics of the infectious agent (e.g., pathogenicity, virulence, and infectious dose), symptoms and behaviours of the infected source may influence the possibility of exposure to, and transmission of, an infectious agent to a susceptible host. In the healthcare setting "infected source" describes a person with an infection caused by an infectious agent. The infected source may be a patient, HCW, visitor, etc.
A "susceptible host" is an individual not possessing sufficient immunity against a particular infectious agent to prevent contracting an infection when exposed to an infectious agent. A susceptible host must be exposed to an infectious agent/infected source in a manner that will enable the acquisition of an infection. The integrity of a susceptible host's internal defences, both innate (e.g., normal flora, intact skin, neutrophils, macrophages) and acquired (antibodies, cell-mediated responses), may impact the host's ability to prevent disease after exposure to the infectious agent. Host defences may be altered by age, co-morbidities, immunization status, genetic factors, medications, and invasive medical procedures that predispose the susceptible host to infection. In the healthcare setting, the susceptible host may be a patient, HCW, visitor, etc.
The "environment" includes all factors, external to either the susceptible host or the infected source, that may assist or impede the exposure to, or transmission of, the infectious agent from the infected source to the susceptible host. The environment may be conducive to the survival and transmission of the infectious agent, potentially increasing the size of the dose to which the host is exposed.
The environment may play a larger role than previously appreciated in the transmission of certain pathogensFootnote 42, reinforcing the importance of minimizing environmental contamination by patient excretions and secretions, avoiding unnecessary hand contact with environmental surfaces and ensuring that adequate resources (e.g., housekeeping personnel) are available for cleaning patient care equipment and horizontal surfaces in the patient's environment.
The environmental risk can be minimized by the use of the Hierarchy of Controls (i.e., engineering and administrative controls, as well as the availability and use of PPE). The concept of the Hierarchy of Controls will be utilized throughout this Annex and is described in detail in Section V.6. In healthcare settings, the impact of these control measures frequently overlap (e.g., the effectiveness of hand hygiene may be influenced by the placement of alcohol-based hand rubs [ABHRs] dispensers and dedicated hand washing sinks [engineering controls], policies and procedures for performing hand hygiene [administrative controls] and the availability and use of PPE [e.g., gloves]).
While the concepts of infected source and susceptible host are discussed below as occurring separately in individuals, it is critical to remember that each person (patient, HCW, etc.) has the potential to be either (e.g., a HCW may be a susceptible host who acquires influenza in the community and then becomes an infected source at work in the healthcare setting).
As per the assumptions in Section V.1., V.2., and V.3., the pandemic influenza virus will be a human influenza virus to which a large number of the population will be susceptible. The pandemic influenza virus is expected to be clinically and epidemiologically similar to other known influenza virus strains.
For a discussion regarding the potential characteristics of the pandemic influenza virus refer to the section entitled Public Health Assumptions (see Section V.1.). It should be noted that the actual virulence, pathogenicity, shedding, incubation period and period of communicability of a specific strain cannot be determined until the pandemic has been declared and sufficient epidemiologic information has been obtained. Further characterization of the influenza pandemic strain will continue to be developed as the pandemic progresses and new information becomes available.
Infected sources include all individuals present in the healthcare setting who are infected with the pandemic influenza virus and are within the period of communicability (see Section V.1.a.), including patients, HCWs, visitors, etc. The identification of infected sources may be difficult as individuals infected with the pandemic influenza virus may be able to transmit influenza up to 24 hours before symptom onset (see Section V.1.a.). The similarity of influenza symptoms to other respiratory illnesses may also make it difficult to definitively diagnose influenza.
In general, factors that increase the source’s ability to transmit infection include the frequency of coughing and sneezing, the concentration of infectious agents in the respiratory secretions, and the stage of illnessFootnote 43. Infected sources, who are unable to comply with respiratory hygiene (e.g., children and individuals with cognitive impairment) are more likely to expose and potentially transmit their infection to othersFootnote 44 Footnote 45.
Susceptible hosts include all non-immune individuals in the healthcare setting including HCWs, patients and visitors who may be exposed to an infected source or environmental contamination. Susceptible hosts that become infected with the pandemic influenza virus may in turn become infected sources. Note that the pandemic influenza viral strain is likely to be a new strain with most individuals likely to be susceptible at the beginning of the pandemic.
The risk of pandemic influenza infection and subsequent disease will be dependent on the likelihood of exposure to and susceptibility of a specific hostFootnote 5.
The environment includes the physical area in which interactions and/or activities bring an infectious agent/infected source together with a susceptible host. During a pandemic wave, the increase in the number of infected sources (i.e., surge) will greatly increase the risk of exposure of a susceptible host. In the healthcare setting this means bringing a person with influenza or object contaminated with the influenza virus and a susceptible host together in a way that may allow the influenza virus to pass from the source to the host. For example, an infected individual’s hands may be “the environmental factor“that brings infected source and susceptible host together.
In most healthcare organizations, the areas with the greatest risk will be where patient care is delivered.
The following information is based on the Public Health Assumptions discussed in Section V.1., specifically, that the incubation period and communicability of the pandemic virus may be similar to other known human influenza viruses. However, the exact nature of the pandemic influenza virus and pandemic influenza infection (e.g., period of communicability, severity of illness) may be unclear until an actual influenza pandemic occurs. The three modes of potential respiratory pathogen exposure/transmission (i.e., contact, droplet, and airborne) (see Figure 2) will be discussed separately; however, these modes of transmission do overlap. The recommendations in this document will interpret and apply evidence for contact, droplet and airborne as a continuum.
Exposure to an influenza virus occurs when a susceptible host comes into contact with an infected source or contaminated environment (e.g., inanimate/animate objects or via virus particles in the air). Figure 2 illustrates the continuum of infectious agent exposure that may be relevant to a susceptible host when touching an infected source or a contaminated environment (e.g., less than two metres away from an infected source, face-to-face) and when a susceptible host inhales an infectious agent (as an aerosol or droplet)Footnote 46-48.
Pandemic influenza virus will be a human influenza virus to which there is global susceptibility. The pandemic influenza virus will likely behave clinically and epidemiologically similar to other known seasonal influenza virus strains.
Figure 2: Exposure to Particles Develped by the ANNEX F Working Group, 2008; * See Glossary
Figure 3 Deposition regions of the respiratory tract for the various particle sizesFootnote 49. Used with Permission.
Recent literature has demonstrated that aerosols contain both droplets and airborne sized particles that can be found in the air at close proximity to a coughing/sneezing source (less than two metres)Footnote 46-54. In addition, a portion of larger particles (droplets) may desiccate (become smaller) while in the air and become, in effect, droplet nuclei. Polymerase Chain Reaction (PCR) has identified influenza ribonucleic acid (RNA) in small aerosols produced by persons with influenza; however, the relationship between the presence of these small segments of influenza RNA to the actual infectivity of small aerosol particles has not been demonstratedFootnote 39 Footnote 49.
Particles with a diameter of 0.1Ám to 10Ám may penetrate as far as the alveolar ducts (i.e., beyond the upper respiratory system) but may also be deposited at any point in the respiratory tract (Figure 3). Aerosols with a larger diameter (10Ám -100Ám) can be deposited on influenza receptors, which are predominantly found in the upper airway (e.g., nasopharynx).
Receptors for human influenza virus are predominantly located on the nasopharyngeal mucosa. Transmission of infection occurs when influenza viruses penetrate a susceptible host's defences and are deposited on viral receptors in the upper respiratory tractFootnote 49. Transmission of the human influenza virus depends on the exposure of a susceptible host to a sufficient concentration (infectious dose) and attachment to a receptor of viable human strain viral particlesFootnote 50. Published clinical observationsFootnote 50 Footnote 51 suggest that influenza transmission usually occurs when the susceptible host and infectious source are within close proximity (less than two metres)Footnote 46-54.
Human-to-human transmission of the influenza virus appears to be similar to the transmission of other human influenza viruses (e.g., seasonal influenza) occurring primarily either directly or indirectly through close unprotected contact with large respiratory droplets. The contribution of close range exposure to smaller droplet nuclei to transmission of influenza is unknown, but may be more prominent under special conditions (e.g., aerosol-generating procedures). Therefore, IPC precautions for patients with suspected, probable or confirmed pandemic influenza virus infection, as well as those with other respiratory pathogens that cause ILI symptoms, should focus on controlling the spread of respiratory dropletsFootnote 46-54.
Exposure to the influenza virus does not necessarily result in its transmission and subsequent infection. A susceptible host may come in contact with (i.e., be exposed to) an infectious agent/infected source and NOT acquire influenza infection (i.e., transmission does not occur). The probability of infection (transmission) is dependent on a number of factors, including host mucosal immunity, infectious dose, viability and virulence of the infectious agent, and the effective implementation of Routine Practices and Additional Precautions within an organization's healthcare service environment.
Pandemic influenza contact exposure may occur, when infectious agents are transferred through direct physical contact between an infected source and a susceptible host or through the transfer of the infectious agent to a susceptible host via an intermediate objectFootnote 2 Footnote 3.
Infectious agents, including influenza and other respiratory viruses that are expelled in large droplets, remain viable in droplets that settle on objects in the immediate environment of the patient. In one study, both influenza A and B viruses were shown to survive on hard, non-porous surfaces for 24 to 48 hours, on cloth, paper and tissue for eight to twelve hours and on hands for five minutesFootnote 52. Hands can be contaminated with influenza virus by contact with an infected source or by contact with contaminated inanimate surfaces or objects in the immediate environment of a source with influenza infection. Contact exposure includes direct and indirect contact:
Figure 5: Indirect contact where there is contact with an inanimate object which may serve as the vehicle for transmission of pathogens
Pandemic influenza contact transmission may occur when contact exposure leads to an infectious dose of viable pandemic influenza particles from an infected/contaminated source being inoculated onto mucus membranes, (i.e., eyes, nose and mouth) and overcomes other host defences.
Pandemic influenza droplet exposure may occur when droplets containing an infectious agent are propelled a short distance (less than two metres)Footnote 46-54 through the air and deposited on a person's mucous membranesFootnote 2 Footnote 3. Infectious droplets are generated naturally from an infected source primarily during coughing and sneezingFootnote 50-54, or through AGMPs (see Section V.4.4.4.). AGMPs may also result in the generation of smaller infectious droplets, which can travel further than those generated spontaneously from patientsFootnote 54-58.
Pandemic influenza droplet transmission may occur when droplets that contain an infectious dose of viable influenza particles are propelled a short distance (less than two metres)Footnote 46-54 through the air and come into contact with influenza virus receptors in the susceptible host's upper airway, and overcome other host defences.
Pandemic influenza airborne exposure may occur if small particles (i.e., aerosols containing droplet nuclei) with viable influenza virus are generated and propelled over short or long distances and then inhaled by a susceptible host. Aerosols containing viable influenza virus may be generated naturally from an influenza infected source during coughing and sneezing. However, the contribution of close range exposure to small aerosols carrying viable influenza viruses is not well documented but is theorized to be more common during AGMPs. Airborne exposure may result almost immediately after generation i.e., the direct projection of an aerosol containing viable amounts of influenza virus through the air, and directly captured by a host's respiratory system. Exposure may also occur for longer periods as droplet nuclei can remain suspended in the air for a period of timeFootnote 39 Footnote 49 Footnote 53-73 before settling out of the air during which time a host may inhale the suspended aerosol.
Pandemic influenza airborne transmission may occur when viable viral particles contained in aerosolized secretions from an infected source are propelled a short distance (less than two metres)Footnote 46-54 through the air, are inhaled, come into contact with influenza virus receptors in the susceptible host's upper airway and cause disease. Polymerase Chain Reaction (PCR) has identified influenza RNA in small aerosols produced by persons with influenza; however, the viability (infectivity) of these small segments of influenza RNA has not been demonstrated, thus, the clinical importance of influenza airborne transmission remains controversialFootnote 50 Footnote 51 Footnote 58.
AGMPs (see Section V.6.2.4. and Section VII.1.5.4.) are medical procedures that can generate aerosols as a result of manipulation of a person’s airway. There are several types of AGMPs associated with a documented increased risk of tuberculosis (TB) or SARS transmission. It should be acknowledged that there is an evidence base and consensus of opinion regarding the spread of infection via droplets and aerosols by these procedures for TB or SARS. Further research may provide additional evidence regarding the hazards that exist from AGMPs, and performed when other organisms are presentFootnote 9. The risk of infection transmission via droplet nuclei and aerosols may increase during AGMPs because of the potential to generate a high volume of respiratory aerosols that may be propelled over a longer distance than that involved in natural dispersion patternFootnote 46 Footnote 60. These procedures include:
There is debate as to whether other medical procedures that result in the generation of aerosols or cough induction lead to the transmission of infection. To date, however, there is no published literature that documents the transmission of respiratory infections, including TB, SARS and influenza, as a result of these procedures. Examples of such procedures include:
High-frequency oscillatory ventilation
Nasopharyngeal swabs, Nasopharyngeal aspirates
NOTE: AGMPs performed on patients with no symptoms of influenza should be carried out using RPAP recommendations.
The probability of airborne exposure to an infectious aerosol is influenced by several factors in addition to the proximity of the infected source and susceptible host. These include the particle sizes containing the infectious agent, the viability of the infectious agent, and the animate and inanimate environment of a room (e.g., the concentration of the viral particles in the aerosol, the concentration of aerosol in the room, the relative humidity, the direction of air flow and the number of air changes per hour in the room).
Particles of a variety of sizes are expelled from the human airway during coughing, sneezing, talking, and medical procedures. The initial size of these particles and the distance they will be propelled is dependent on the force generated by the individual or the procedure. Large particles (greater than 10 Ám diameter) will fall quickly (in a few seconds) to the groundFootnote 46 Footnote 49 Footnote 54. However, smaller particles may remain suspended for a significantly longer time: tens of seconds for a droplet of 10 Ám diameter and minutes or hours longer for smaller droplet nuclei. The particles that remain aloft for minutes or hours (less than 10 Ám diameter) can be carried by air currents over a measurable distance, including beyond the room, and are considered to represent an airborne exposure. To date there is no human evidence to suggest that viable infectious influenza virus particles are carried measurable distances beyond the two metreFootnote 46-54 bed space.
The likelihood of airborne exposure to the pandemic influenza virus will depend, principally on the size of the particles in aerosols (see Figure 2) generated by the infected source. Airborne exposure is highly dependent on environmental factors, (i.e., humidity and air changes per hour in the room). Influenza virus particles have been detected in the airspace (less than two metres)Footnote 46-54 around a person with diagnosed influenza using polymerase chain reaction; however, viability (and thus infectivity) of these viral particles is unknownFootnote 71 Footnote 72.
Note: The previous one metre recommendation for spatial separation was extrapolated from studies regarding the transmission of meningococcal diseaseFootnote 73 from coughing and sneezing. However, studies of individuals who expelled respiratory droplets through coughs and/or sneezes demonstrate that the distance these respiratory droplets travel approaches two metresFootnote 46-54.