Clinicians play a key role in controlling the spread of infectious disease through everyday good practices such as recommending appropriate vaccinations, judicious antibiotic prescribing, and by counselling patients on risk reduction strategies. They are often the first to see new cases of a disease that is reportable to public health authorities. Occasionally, astute clinicians may see cases that that could indicate the beginning of an outbreak. And at times they are called upon to collaborate with infection control or with public health teams to ensure good control practices and to arrest outbreaks of infectious disease. Clinicians must also be aware that they themselves or the equipment they use can transmit infection to their patients and must take steps to prevent this.
Clinicians are also well placed to recognize changing patterns of non-infectious disease, such as an unusually high number of injuries linked to a change in the built environment or to a new toy. In these cases, clinicians can also play a role in identifying and managing the situation, although the procedure for doing so may not be as clearly defined as that for infectious diseases.
After reading this chapter, you will be able to:
- Know the defining characteristics of an outbreak and how to recognize one when it occurs;
- Describe and understand the main steps in outbreak management and prevention;
- Demonstrate skills in effective outbreak management including infection control when the outbreak is due to an infectious agent;
- Describe the different types of infection control practices and justify which type is most appropriately implemented for different outbreak conditions;
- Demonstrate effective communication skills with patients and the community as a whole;
- Describe appropriate approaches to prevent or reduce the risk of the outbreak recurring;
- Advise relevant authorities if necessary (notifiable disease, reporting a dangerous situation) (MCC 78-8);
- Describe immunization procedures;
- Describe the main routes for the transmission of infectious diseases;
- Describe approaches to preventing infectious disease transmission;
- Summarize hazards of infection in the health care setting:
• Nosocomial infections
• Antimicrobial resistance
Linking these topics to the Medical Council exam objectives, especially section 78-5.
|Note: The colored boxes contain optional additional information; click on the box open it and to close it again.
Words in CAPITALS are defined in the Glossary
Dr. Rao suspects an outbreak
Dr. Rao received a phone call from Mrs. Richards’s long-term care home to say that she has had some diarrhea. He went to see her. She says she had some stomach pain last night but feels better today; she just had one bout of fairly liquid stool. Mrs. Richards thinks that other people in the home have been sick also. She heard that one resident had vomited two days ago and another had stomach cramps the other night.
Dr. Rao tries to get more precise information; he wants to know if this number of people with stomach complaints is greater than normal. He also realizes he should ask a whole series of questions: precisely who was sick, when, for how long, the location of the rooms of the sick people, if any of the staff have been sick, and if the Public Health department has been informed. However, the staff member now on duty was away for the last few days and knows only what was mentioned in the daily report.
More often than not, cases of notifiable diseases are sporadic, meaning that that they are not part of a larger transmission event. Nonetheless, clinicians play an important role in recognizingClinicians are often in the best position to recognize an OUTBREAK of disease (see the Definitions box). They may see an high number of people with the same disease, or patients may mention that they know other people with similar symptoms. Even if a clinician only sees a single case, this may be one of several in the region so reporting contributes to the detection of outbreaks. Filling in discharge summaries and death certificates, and reporting cases of notifiable disease (see: Notifiable disease) all contribute to health surveillance. Ensuring that the forms are completed accurately and submitted in a timely fashion makes a major contribution to outbreak detection and general health surveillance.
Depending on the type of organism involved, the conditions of spread and the target population, disease outbreaks can be acute and fast-moving, such as gastroenteritis in a nursery school or long-term care home, or they can evolve more slowly, such as the AIDS pandemic. Clinicians play a major role during outbreaks because they are usually the first point of contact with the affected population. Likewise, hospital infection prevention and control teams rely on the cooperation of hospital staff in preventing infections. Public health authorities, who are ultimately responsible for ensuring the detection and control of outbreaks, apply these basic actions in outbreak management and control:
- Establish the existence of an outbreak
- Confirm the diagnosis
- Define what constitutes a case and count cases as they occur
- Perform descriptive epidemiology to determine who is at risk
- Formulate hypotheses on the causes, and implement initial control measures
- Test the hypotheses through analysis of surveillance data or special studies
- Evaluate the response and re-adjust hypotheses and control measures if needed
- Communicate information on progress of the outbreak to partners and the public
- Plan for long-term prevention and control.
Note that these steps often overlap in time, so an outbreak response does not typically follow a step-by-step process.
Is it an outbreak?
It is important to identify an outbreak quickly so that it can be controlled before causing significant harms. A cluster of cases could be due to chance or might form the beginning of an outbreak that could then develop into a full EPIDEMIC. However, there is no hard and fast rule for defining an outbreak. For rare diseases and diseases in small populations an absolute increase of a very small number of cases could represent a large relative increase in an illness in the population. In a community where there are usually two cases of a given disease per month, four cases in one month (an absolute increase of only 2 cases, but a relative increase of 100%) may or may not constitute an outbreak. In such instances, it can be very difficult to decide how much time and money to spend on investigating something that might be just a chance occurrence. Analysing the complete history of each case helps, but consultation with epidemiologists or statisticians may be required.
Furthermore, biases may occur in documenting an outbreak. If a possible outbreak has been discussed on the news, and if clinicians are aware of this, they may be more assiduous than usual about requesting laboratory tests and reporting cases. If patients are aware, they may be more sensitive than usual to their symptoms and seek care (and hence their case gets reported) when they would not normally do so. In addition, case-finding or active surveillance (see Chapter 7), by public health workers may uncover cases that would not otherwise have been identified.
Endemic is the constant presence of a disease or infectious agent within a given area or population group.1
A Cluster is a collection of new cases of an uncommon disease that occur so closely together in space or time as to arouse suspicion that this is not merely a chance occurrence.1 Cluster applies to both communicable and non-communicable diseases.
An Outbreak describes a number of cases higher than would routinely be expected in a given season or place.2 An outbreak can also refer to a small, localized cluster of cases, usually of an infectious disease that may be a prelude to a broader epidemic.1
Epidemic is the occurrence of illness clearly in excess of normal expectancy.1 The number of new cases needed to declare an epidemic depends on the disease, the time, and the location. For example, a single case of yellow fever could be considered to be an epidemic in Canada, but it might not be in a tropical region.
Pandemic is an epidemic occurring over much of the world. Examples include influenza (1918–19 and 1957–58), cholera (1961 to present), AIDS (1988 to present), and tobacco addiction (current) and COVID-19 (2020-2022).1
The distinction between cluster, outbreak and epidemic is fluid, but cluster suggests a current lack of an epidemiological link between cases; outbreak suggests a narrower geographic distribution than an epidemic.
Great care is needed in deciding whether or not to declare an epidemic, balancing the value of alerting agencies to the need for control measures against possibly causing public panic. National and regional public health agencies are responsible for these decisions. A pandemic can only be declared after careful evaluation by the WHO, which may issue travel advisories, and such announcements are taken only after serious deliberation because of their potential impact on the economy of regions affected.
Just as a local outbreak runs a natural course (see figures 7.1 to 7.5 in Chapter 7), so does a pandemic. As an example, Figure 11.1 illustrates the progression of influenza outbreaks into a pandemic, as described by the World Health Organization:
Epidemics of infectious disease can result from changes in either the agent, the host, or their environment:3
1. Agent: a micro-organism such as a virus of bacterium may evolve to become more communicable (or infectious). For example, SARS-CoV-2 virus (the cause of the COVID-19 pandemic) underwent many mutations to produce variants of different communicability. Similarly, micro-organisms have a number of mechanisms to alter their ability to cause symptoms of disease (PATHOGENICITY) or to cause severe disease (VIRULENCE ) (See Glossary for definitions). For example, Corynebacterium diphtheria must be infected with a specific bacteriophage in order to produce the diphtheria toxin that causes diphtheria. Plasmid exchange can confer antibiotic resistance in previously susceptible bacteria. Another example is the influenza virus, whose virulence may vary as its genetic composition drifts and shifts.
2. Host: The population at risk may change in a way that makes them more susceptible to the disease. For example, waning immunity may contribute to cases (and even outbreaks) of mumps, especially in cohorts with a single dose of vaccine.3 When a population is faced with a novel disease against which there is little immunity the results may be severe. For example, the introduction of smallpox – sometimes purposely – by Europeans to Indigenous populations of the Americas caused widespread and severe disease. Similarly, the severity of the 2002-03 North American epidemic of West Nile virus may have been in part due to the lack of immunity of the host birds in the region, as well as a lack of immunity in the human population (see Nerd’s corner).
3. Environment: The social environment may change to make transmission more or less likely. Troop movements and population upheavals during the 1914–1918 war brought many more people than usual into close contact with one another. This enhanced the transmission of the influenza virus that caused the 1918 pandemic. Changes in the physical environment may also contribute. For example, longer warm seasons have contributed to an increased incidence of Lyme disease by increasing tick habitats and activity.
West Nile virus in North America
West Nile virus was first documented in Uganda in 1937. In the 1990s, in Europe, the virus seemed to increase in virulence. In North America, it was first detected in birds in New York, and in 2002 and 2003, it caused an epidemic that was more widespread than on other continents. Reasons for its epidemic potential in North America may include: 4
- More virulent strain
- No previous immunity in birds – the primary host
- The carrier mosquito, Culex pipiens, mainly feeds on birds, but switches to feeding on humans in the fall when host birds migrate
- Age structure of non-immune individuals—older and more susceptible to neurological effects.
On May 18, 2000, a paediatrician at the Owen Sound hospital admitted a nine year-old girl with bloody diarrhea and a seven year-old boy with fever and abdominal pain who later developed bloody diarrhea. On investigating possible links, the attending paediatrician found that the children attended the same school. The same day, people from Walkerton started contacting their Public Utilities Commission because they suspected problems with the water supply.
On May 19th, having learned that more people in the community were suffering from diarrheal illnesses, and having conducted a food history with the parents of her two patients, the paediatrician suspected that they were suffering from water-borne Escherichia coli infection. She contacted the Bruce-Grey-Owen Sound Health Unit. Later that day, the managing director of a Walkerton retirement home also contacted the health unit to report that three residents had diarrheal disease.
The health unit contacted schools in the area and learned that abnormally high numbers of pupils were absent with illness. The unit also learned that the Walkerton emergency room had seen eight patients with diarrheal disease. At first, the pattern of disease suggested a food-borne outbreak, but, as many members of the public believed the outbreak to be due to contaminated water, the health unit also began to investigate the water supply.
The Walkerton outbreak was caused by contamination of the municipal water supply with E. coli and Campylobacter jejuni. By August 31st, 2000, it had killed seven people, caused Haemolytic-Uraemic Syndrome in 27 people and, it was estimated, made over 2,000 people ill. Poor supervision of water treatment combined with heavy rain, which had washed cattle effluent into the water supplying the treatment plant, were the major causes of the outbreak.
Factors contributing to Ebola outbreaks
Outbreaks of the Ebola virus in West Africa in 2013 and 2016 were worse than previous outbreaks; by April 2016, 11,310 people had died6. Before that the largest Ebola outbreak was in Uganda, killing 224 people. Of the factors that contributed to the severity of the 2013 – 2014 outbreak some were cultural and socio-economic:
- The outbreak started among impoverished, marginalized rural population groups who are forced to exploit the forest as their source of food and resources. This increases their risk of being infected by forest animals that carry the disease.
- The region had been decimated by years of civil conflict which left the economy and the public health system unequipped to respond adequately and early in the outbreak.
- Porous borders between neighbouring affected countries meant that a high level of intergovernmental cooperation was required
- Poor healthcare infrastructure in the affected areas meant that patients were being cared for in facilities that lacked the means to diagnose infection and prevent transmission.
- The traditional rites of bathing and touching the bodies of sick relatives enhanced spread to family members. Mistrust of health advice made it difficult to address these practices
For further information see the article by Bausch and Schwarz7. For a view from further upstream, see: Richardson et al.8
Steps 1 and 2 are often completed near or at the same time. Confirming the diagnosis is important because it informs the next steps of outbreak response, especially in deciding on disease control measures.
Step 2 consists of ensuring that the clinical and laboratory findings match, and point to a unifying diagnosis. For example, physicians may be alerted by their laboratory colleagues to a positive test for a reportable disease. It is important for physicians to consider the clinical presentation to ensure the result was not falsely positive. An example of this could a patient with a ‘reactive’ non-treponemal test but a non-reactive treponemal test for syphilis; reasons for a falsely reactive non-treponemal test may include chronic infections, autoimmune conditions, or others.
Step 2 may also include gathering further information on a confirmed diagnosis. For example, even after confirming a case of Invasive Meningococcal Disease (caused by Neisseria meningitidis), it is important for public health authorities to confirm the serotype to help guide further action. Although Invasive Meningococcal Disease is relatively rare in Canada, it is possible that two cases occur in the same community in a short period of time. Therefore, in addition to completing an epidemiological investigation, detailed serotype information about the microorganism can help public health authorities understand if two or more cases are linked.
Physicians are required by law to report cases of certain infectious diseases, yet, unfortunately, many cases are not reported. Reporting is necessary to direct attention to possible outbreaks or sporadic cases that require rapid action to control. The notifiable disease database can also be used to evaluate subsequent control measures, as well as to trace long-term fluctuations in incidence that reflect changing patterns of behaviour that may require intervention on several levels to control the disease.
In Canada, maintaining the notifiable disease information system is a provincial and territorial responsibility. The World Health Organization specifies those diseases that must be reported worldwide. The Public Health Agency of Canada specifies some that are notifiable nation-wide, while each province or territory can add other diseases to be reported in their region. Not all infectious diseases are notifiable. The Public Health Agency of Canada selects diseases as notifiable according to certain characteristics, such as:9
- Its interest to national or international regulations or prevention programmes
- Its national incidence
- Its severity
- Its communicability
- Its potential to cause outbreaks
- The socio-economic costs of its cases
- Its preventability
- The risk it poses in the public perception
- The need for a public health response
- Evidence that its pattern is changing.
Some provincial and territorial public health authorities require physicians to notify them when they suspect an outbreak of any infectious disease. Some lists include non-infectious diseases that can be caused by environmental hazards, such as poisoning with heavy metals or with carbon monoxide.
Physicians are required to notify the public health authority when history and clinical examination causes them to suspect a notifiable disease; they are not required to await the results of testing. Indeed, diseases that could pose an immediate, severe threat to the public’s health should be reported by telephone as soon a case is suspected. Laboratories notify the public health authority of cases of notifiable disease when test results are positive. Because some diseases are difficult to diagnose reliably without laboratory testing, and because others do not require testing, the list of laboratory-reportable disease differs slightly from that of physician-reportable disease.
A crucial early step in investigating a possible outbreak is to define what constitutes a case, as the case definition will be used in the search for more cases to draw a complete portrait of the outbreak. It is important to recognize that the criteria of a public health case definition may differ from those of a clinical diagnosis. The case definition details the symptoms, signs, history, or test results that indicate a probable case of disease. Clinicians may be asked to help in the search to uncover all cases, and they may also have valuable information linking the cases, which can suggest a possible cause.
Biological variation causes the presenting symptoms and signs for cases of any illness to vary. The case definition should neither be too broad nor too narrow. In an outbreak of gastroenteritis, for instance, some people may only have mild abdominal cramps, whereas others have diarrhoea and vomiting, with or without fever, muscle pain, headache, and dehydration. The case definition should therefore be neither too narrow nor too broad. If the definition includes people with any one of the full range of symptoms (fever, or muscle pain, or headache, etc.), it will include people whose symptoms are unrelated to the outbreak under investigation – an unduly sensitive test produces false positives. Conversely, if the case definition is too narrow (a specific test – fever plus muscle pain and headache), it may exclude some with the disease, underestimating the extent of the outbreak and possibly delaying the implementation of control measures. If, however, there are indications of a common exposure, for instance if a large proportion of the initial cases say they ate at the same restaurant, the common exposure can be included as a criterion in the case definition and the investigation could focus on identifying the particular foodstuff at the root of the problem.
A case definition is a set of criteria that must be fulfilled to identify a person to be included as a case of a particular disease as part of an outbreak. The criteria may include geographic, clinical, or laboratory criteria, and may be combined into a scoring system. The case definition is used to identify probable cases in epidemiological surveillance.1
Note that the purpose in using criteria to identify cases as part of infectious disease control differs from using criteria to identify cases in a clinical diagnosis. In infectious disease control, cases are identified so that they may be fully described and common factors among them may point to the source of the problem. In clinical situations, diagnostic criteria help to identify patients who are likely to benefit from treatment.
Step 4: Perform descriptive epidemiology
After identifying cases, it is important to systematically document and describe factors related to person, place, and time. Factors related to the ‘person’ may include demographics (e.g., age, sex), and other risk factors (e.g., medical comorbidities or health behaviours). Place-related factors can refer to the geographical distribution of cases or to places where exposure may have occurred. For example, a long-term care home may show public health authorities that cases of a gastrointestinal illness only occurred in one wing of the facility. Lastly, describing cases according to time gives important clues about an outbreak. The time-frame is illustrated in epidemic curves (the ‘epi curve’), histograms that portray the size and duration of an outbreak that plot numbers of cases on the y-axis by time on the x-axis (see epidemic curves in Chapter 7).
Person, place, and time factors are communicated together in epidemiological reports. Early in an outbreak, epidemiological reports can help public health authorities formulate hypotheses about who may be at risk. For example, during the 2022-2023 Mpox pandemic, epidemiological reports showed that the majority of cases were men between 20 and 50 years of age who reported intimate or sexual contact with a new and / or more than one male partner.11 This knowledge allowed for control measures, such as communications campaigns, that were more relevant for those at greater risk.
In addition to identifying populations at higher risk during an outbreak, the epidemiological patterns identified by public health authorities may indicate the likely source of the outbreak. This is generally sufficient to guide initial control measures.
Management of cases
In general, cases in an outbreak are managed by their usual physicians unless the size of the outbreak justifies setting up special clinics. Management includes preventing transmission of the disease by providing appropriate treatment, isolating patients or excluding them from certain high-risk settings, and education on health behaviors such as hand washing and respiratory hygiene. The clinician can consult the public health service for advice on controlling spread. In outbreak situations, public health officials keep health professionals and the public informed of the evolving situation and of the control procedures.
Management of contacts
To help control disease spread, public health authorities will manage close contacts of cases. Management of contacts depends on the disease but may include an assessment of symptoms to ensure they do not have the condition, providing post-exposure prophylaxis, counselling on when to seek medical care, or advice on health behaviours. In rare circumstances, contacts may be requested to quarantine or exclude themselves from certain higher-risk settings. For sexually transmitted infections, some public health services trace and treat the patient’s sexual contacts.
Acting on the physical or social environment is an important tool to help control outbreak. For example, an outbreak of gastrointestinal illness caused by E. coli contamination of drinking water requires remediation of the water supply and system. While that remediation is taking place, community members may be subject to a Boil Water Advisory to immediately reduce their risk. Another example would be the enhanced cleaning of surfaces in a long-term care home experiencing an outbreak of diarrheal illness.
Similarly, the social environment can contribute to outbreaks of disease and are a potential target for intervention. For example, during the COVID-19 pandemic, it was quickly recognized that indoor, crowded spaces increased the risk of transmission; this led to public health advice (and occasionally rules) on capacity limits to reduce this risk. Environmental interventions may also include removing a known hazard to eliminate the risk, as with cases of food-borne disease caused by a contaminated food product. Here, public health authorities coordinate with the implicated food producer and distributors or vendors (restaurants or grocery stores) to remove the product from circulation.
Infection prevention and control
Infection prevention and control actions undertaken by clinicians are critical to outbreak response. These actions include point of care risk assessments, using appropriate PPE, or diligent hand hygiene. These actions help reduce the risk of both clinicians and their patients.
People at risk from the outbreak—those likely to be exposed to the probable source—require credible information. This includes:
- Information about their risk and how to reduce it. For instance, forestry workers should be informed about the importance of adequate clothing, insect repellant, and performing ‘tick checks’ to help reduce their risk of Lyme disease.
- When to seek care. It is important for the public to know the symptoms of the disease, and also when and where to seek care. If they do not require acute care, it is helpful to provide advice on how to manage safely and comfortably at home.
- How to reduce the risk of propagation. This could include reminders to stay at home when feeling sick, regular hand washing and practicing good hand hygiene during the respiratory season.
Dr. Rao reminds the staff…
Mumps in the Maritimes
In Halifax, Nova Scotia, in 2006 and 2007, two successive outbreaks of mumps affected a total of 34 people.10 Although there was no obvious link between the outbreaks, they were thought to be part of a group of outbreaks that occurred in North-Eastern USA and Québec, and which may have originated in the UK. The Nova Scotia outbreaks were managed by voluntary isolation of the cases for nine days after symptoms appeared. Households and other contacts of the cases were immunized. All cases had previously been immunized against mumps, although many had received only one dose of vaccine. It was decided not to immunize all those at risk of the illness because:
- Mumps immunization levels were already high
- Spread of the outbreak was limited and slow, and there was no evidence of spread to unimmunized groups
- It was assumed that herd immunity was effective because of high immunization levels and the limited spread of the disease (See Glossary HERD IMMUNITY)
- Experience with a similar outbreak in the UK showed vaccination had a poor cost-benefit ratio
- The population at risk was large.
Once there is a hypothesis concerning the cause of the outbreak, it should be tested. If removing the suspected source is followed by a decline in the outbreak, the hypothesis may be correct, although the decline could still be serendipitous. A case-control study could be carried out in the case of food-borne outbreaks in a limited population. For example, in an outbreak associated with a social gathering, guests can be asked about the foods they ate and about their symptoms. The risk associated with each food can be calculated and can indicate the culprit. In cases where the population at risk is larger or more dispersed, it can be difficult to identify all those at risk, so clinicians may be required to contribute in case-finding or by providing data on their patients.
Dr. Snow and the pump
John Snow was a British physician considered by many to be the father of epidemiology. He identified the source of the London cholera outbreak of 1854 that killed 500 people over a ten day period. Snow plotted the location of the cholera deaths on a map and interviewed seventy-seven surviving cases. He noticed that a water pump located on Broad Street was in the centre of the area where most cases lived. Cases in outlying areas also tended to draw their water on Broad Street, ironically because of its reputation for pure water.
Although, at the time, cholera was thought to be caused by bad air, Snow’s work led him to suspect an association with water. He convinced the local council to remove the handle of the Broad Street pump and, according to legend, this stopped the epidemic. In fact, although Snow’s work was a breakthrough in surveillance, hypothesis formation, and intervention, the epidemic was almost over by the time the handle was removed.
Once the cause of the outbreak has been confirmed, the initial control measures may need to be adjusted. For example, if the incidence of cases does not decrease as anticipated, more stringent control measures may be required. Similarly, if the source cannot be identified, more epidemiological detective work may be required.
Outbreak evaluations should be designed to indicate the possible long-term preventive actions and ways of improving response to future similar outbreaks.
Legislative controls are sometimes needed. For instance, the 2008 outbreak of listeriosis in Canada resulted in discussion of legislative control on food manufacturers. At other times, adequate application of controls and guidelines is needed. For instance, in the case of the water borne illnesses in the Kashechewan First Nations community (see Chapter 10 Illustration box: “An environmental hazard …”), recommendations to prevent further problems included upgrading the water treatment plant as well as the water treatment processes, training of personnel, and improved procedures for identifying and correcting problems.
Immunization plays a critical role in the long-term control of many diseases. Broadly speaking, there are two types of immunization; passive and active. Passive immunization increases the body’s resistance to illness via antibodies. Antibodies are initially passed from mothers to their children during pregnancy when they cross the placental barrier, then during lactation when they are secreted in breast milk. They can also be acquired via blood transfusion and by the administration of immune globulin after exposure to disease. Antibodies acquired by passive immunization wane rapidly and no memory of the antigen is retained so the protection it offers does not last.
Active immunization uses the body’s own defences to produce a longer lasting protection. It is a response to the introduction of antigens into the body. Active immunization can be characterized as ‘natural’ when a person is infected with an immunogenic microbe (natural antigen) or ‘artificial’ when a person is protected by vaccination. Although immunity may decline after active immunization, although at a slower rate than after passive immunization and the immune system retains a ‘memory’ of the antibody so it can mount a rapid response when it meets the antigen again.
When a vaccine for a disease exists, it is the preferred method of immunization. In most cases, vaccination produces a similar level of protection or benefit with far less risk than ‘natural’ immunization. Unfortunately, we do not have a vaccine for every communicable disease; a list of immunizing agents is shown in the Canadian Immunization Guide,13 a list that will continue to grow.
Vaccination is effective and is one of the safest interventions in medicine. Vaccines are absolutely contraindicated in very few situations. One is when there has been an anaphylactic reaction to a previous dose of the same vaccine. A second and third apply to live attenuated vaccines only: these should not be given to people who are immunosuppressed and they should not be given to pregnant women.
Despite their excellent safety profile, Adverse Events Following Immunization (AEFI) do occur. An AEFI includes any untoward event that occurred following immunization but does not necessarily have a causal relationship to the vaccine. Most reactions are minor and do not preclude giving the same vaccine subsequently. Such reactions may include pain or swelling at the injection site, rash or fever after injection. Rare but serious AEFIs may include allergic (e.g., anaphylaxis) or neurological (e.g., seizure) reactions. While these are not absolute contraindications to future vaccination, they should cause careful assessment of the patient and the risks and benefits of future vaccination must be analysed. Because serious or unexpected AEFIs are reportable to public health authorities, there is often a public health practitioner to assist in AEFI assessments. Reporting AEFIs is also critical to maintain Canada’s (including individual provinces and territories) robust AEFI surveillance system that allows for rapid identification and response to ‘safety signals’, or worrisome trends in AEFIs.14
Some vaccine side-effects
Whooping cough & neurological disorders
Whole cell pertussis vaccine has been available and widely used since the 1940’s. However, it was commonly associated with several adverse effects including local swelling and pain, and with systemic effects such as drowsiness, fretfulness and anorexia. Rarely there were more severe effects such as convulsions, certain neurological manifestations and encephalopathy. Experts still do not agree if the more severe side effects are related to the vaccine. Nonetheless, in view of the concern, an acellular vaccine was developed.13 Although the acellular vaccine is slightly less effective and is more expensive, it has largely supplanted the whole cell vaccine in countries that can afford it, including Canada.
Flu and GBS
In 1976 – 1977 a swine flu vaccine was associated with a small increase in the risk of developing Guillain-Barré syndrome (GBS). Approximately one case arose in every 100,000 people vaccinated, an association that had not been noted before. In the years since then, studies have identified even smaller risks associated with flu vaccines and the development of GBS, approximately one to two cases for every million people vaccinated. Indeed, much larger increases have been associated with influenza infection (in addition to the morbidity and potential complications of infection).16, 17
No vaccine provides 100% protection. For example, conjugated Meningococcal C vaccine is approximately 97% effective for infants within one year of vaccination, with effectiveness decreasing to 68% after a year.18 However, if the disease can be transmitted only between people and if enough people in a population are vaccinated, vaccines can break the chain of transmission and protect even those in whom the vaccine is not effective. This is known as herd immunity and can be useful in protecting people who have an absolute contraindication to vaccine – vaccinating people who come into contact with them can protect them even if they cannot be vaccinated themselves. Furthermore, if the chain of transmission can be broken, it may be possible to eliminate the disease altogether. Smallpox, a highly virulent infection, was eradicated in 1979.15 At the time of writing, polio remains endemic only in two countries: Afghanistan and Pakistan. Measles has been eliminated in Canada since 1998.20 Unfortunately, as long as vaccine preventable disease is present somewhere in the world, it can travel quite easily so that global vaccination levels must remain high until the disease is completely eradicated.
Most wealthy countries are able to maintain high levels of childhood vaccination. Lower-income countries face economic, geographic and political barriers to providing vaccines. As illustrated by the outbreaks of diphtheria during and after the break-up of the Soviet Union, war, civil unrest and the associated population movements disrupt vaccination programmes and create opportunity for increased transmission.16 Myths and misconceptions about vaccination can also disrupt vaccine uptake. Due to public anxiety about whooping cough vaccine in 1975 coverage fell from 80% to 60% in the United Kingdom. This was followed by whooping cough epidemic, resulting in 12 deaths in 1978.17 Similarly, an article published in the Lancet in 1978 created a scare about a link between measles vaccine and autism spectrum disorder. Although this article was later shown to be fraudulent and subsequent studies failed to show any link, fears about vaccine persist. Other arguments against vaccination are also put forward: see Table 11.1 for the more common ones.
|The real situation
|Vaccine-preventable diseases had already begun to disappear before vaccines were introduced.
|True: better housing, nutrition, hygiene and sanitation reduced the incidence of disease, but the diseases still exist (along with poor housing, diet, etc.) and vaccine is the most effective way of protecting those at risk against them.
|The majority of people who get the disease have been vaccinated
|True: this is because vaccine uptake is high and protection is not 100%. However, those who have been vaccinated usually have a milder form of the disease.
|Certain batches of vaccines are associated with higher incidence of adverse events.
|More reports of adverse events often mean better reporting. The vaccine surveillance system is in place so that adverse events can be quickly recognised and linked to a vaccine batch number. Batches with greater than expected adverse events are recalled.
|Vaccines cause many harmful side effects.
|Vaccines are among the safest interventions available. Many cause minor side effects such as soreness at the injection site. Most serious side-effects are so rare that their incidence is difficult to measure.
|Vaccine-preventable diseases have been virtually eliminated from wealthier countries, so there is no need for vaccination.
|It only takes one infected traveller from a country where the disease is occurring to cause an outbreak here.
|Multiple vaccinations can overload the immune system.
|If the immune system can manage the daily onslaught of the numerous antigens it comes into contact with, a few extra in the form of vaccines will not harm it.
Our environment is full of microbes – fungi, protozoa, bacteria and viruses – that can infect us and cause disease. All that is needed is a source of infection, a mode of transmission and a susceptible person with a portal of entry into the body. The microbes that cause infectious disease are found the soil, air, water and food – as are the causes of environmental disease (see Chapter 10). Microbes can also inhabit other people, animals and insects, and they can contaminate inanimate objects, medications and medicinal fluids.
The body uses both its innate and adaptive immune system to protect itself against infectious disease. The innate immune system can include physical and chemical barriers such as intact skin that prevents microbes entering the body, or gastric acid that inactivates many potential pathogens. If a pathogen does succeed in getting though these barriers the innate immune system also includes phagocytosis of the invading pathogen, a molecular response (e.g., the complement system) to help destroy an invading microbe, and the inflammatory response. Additionally, the ‘second line of defense’ – the adaptive immune system – provides protection against the pathogen both during the current and future exposures due cell-mediated and humoral immunity.24
Three main routes of transmission are summarized in Figure 11.2. Infections can be spread directly from an infected or colonised person to a susceptible person through direct contact with skin or mucosa or by direct contact with blood or other body fluids: for example, shaking hands, kissing, sexual contact, and sharing needles. Spread also includes sneezing or coughing, when the respiratory tract secretions of an individual land on the mucous membranes (eyes, nose, mouth) of another.
Indirect contact transmission can happen when microbes remain viable in the environment at least long enough to be transmitted. They may settle on a surface and get picked up by a susceptible person. Variations on contact transmission include transmission by a vector – a living organism capable of transmitting the infection (the hands of healthcare personnel may be considered as vectors or as agents of indirect contact spread). Other vectors would include, for instance, the mosquitoes that spread malaria or Zika virus. Finally, transmission by contaminated medications or other agents used in patient care could also be considered as a form of spread by indirect contact.
Airborne particles can also transmit disease. Particles can be generated by coughing or sneezing or by some medical procedures. The size of these particles and the force with which they are expelled determine how far they can travel. Usually, and without significant air movement (e.g. from fans or wind), particles from about 50 to 100 μm do not travel much more than 2 metres from their source, those between 10 and 50 μm can travel within an average-sized hospital room (although the concentration of particles within the room may not be uniform. Those less than 10 μm can become suspended in the air for longer periods of time to create a uniform concentration within a room, with the smallest particles (e.g. <2 μm) able to travel outside the room. The resilience of the organism determines how long the particles remain infectious. For instance, Bordetella pertussis becomes nonviable after a short period in the air so it is chiefly spread by droplets. Mycobacterium tuberculosis is resilient enough to be spread in very small airborne particles.
Microbes may use more than one method of transmission – those that are expelled in droplets may land on surfaces and remain there until touched by a susceptible person and get passed on by indirect contact. Alternatively, some respiratory viruses may have both direct and indirect transmission.
Other organisms that are normally present in the environment, cause infectious disease that is generally not transmissible from person to person. Examples include Clostridium tetani, present in the soil, which can enter the body via a penetrating wound. Legionella, ubiquitous in our environment, can contaminate humidifiers and water systems whence they become airborne, enter the respiratory tract and cause Pontiac fever or Legionnaires’ disease.
The results of coming into contact with a microbe include:
- Colonisation – the microbe lives and may multiply but does not cause a reaction; the person becomes a ‘healthy carrier’
- Infection – the microbe causes a reaction that may be clinical with associated signs and symptoms or subclinical with only biochemical indication of infection
- Carrier state – in spite of the host’s reaction and an improvement in their clinical condition, the infection remains and may be passed on. The person may be an ‘incubating carrier’ or a ‘convalescent carrier’.
Terms relating to transmission of infection
Vector – a living organism (usually an insect) that transmits an infectious disease. The pathogens that cause vector-borne diseases usually require the insect to complete their lifecycles. Examples include malaria, the Zika virus or Yellow Fever virus.
Fomite – an inanimate object that becomes contaminated and thus transmits disease, as with improperly sterilized equipment used for surgeries or procedures like colonoscopies.
Zoonosis – a disease that can be transmitted from animal to man (and vice versa). Examples include campylobacter, anthrax, Ebola, rabies and avian influenza. While the prions that cause Bovine spongiform encephalitis are not usually considered to be microbes, the illness can still be classified as a zoonosis.
Anthrax on a Scottish island
For well over a century Bacillus anthracis has been investigated as a possible biological weapon: it can remain viable in unfavorable environments, it is easily dispersed and inhalation of spores can result in serious illness.
In 1942, the British tested Anthrax bombs on the small, uninhabited Scottish island of Gruinard. By the 1980s, the level of contamination was falling, but it was estimated that the island would remain contaminated for another 50 years. Intense political pressure led to the decision to decontaminate it by irrigating with formaldehyde and seawater. Gruinard was declared safe in 1990, more than 50 years after the last test was carried out.
Prevention of infectious disease transmission starts with the epidemiological triad – the agent-host-environment described in Chapter 2. Interventions include:
- Destruction or weakening of the agent outside the body (e.g., by cleansers, incineration)
- Destruction or weakening of the agent inside the body (e.g., use of appropriate antibiotic or antiviral for an appropriate length of time)
- Physical barriers (e.g., masks, or long pants when hiking in regions that have Lyme disease)
- Decrease opportunity for transmission (e.g., by isolating infective cases, quarantine of contacts, coughing into one’s sleeve, prompt adequate treatment of cases)
- Increase specific resistance (e.g., immunization, prophylaxis)
- Increase general resistance (e.g., nutrition, exercise)
- Hygiene and sanitation (e.g., clean water, sewers, adequate housing)
- Vector control (e.g., drainage of mosquito breeding sites, hand hygiene, and respect of infection control measures by health care providers)
- Health programmes (e.g., free immunization programmes with call/recall system, partner notification for sexually transmissible infections).
A geographer’s perspective
Jacques May, a medical geographer, was the first to propose the ecological model of health. He viewed disease as a reduction in survival caused by maladjustment of a person to the environment.20 The capacity of individuals to adjust to their environment is genetic, although it is generally mediated by the traits and behaviors associated with their culture. As an example, May cited the high haemoglobin levels found in people who live at high altitudes. For them high haemoglobin is a necessary adaption to low oxygen pressure. If a similar haemoglobin level were found in someone living at sea level, it could indicate disease.
These ideas led to the development of May’s model of the elements of transmissible disease, which include:21
- Agent: causes the disease (e.g., Plasmodium causing malaria);
- Vector: transmits the agent to the host (e.g., Anopheles mosquito in malaria);
- Geogens: physical environmental factors (e.g., humidity, temperature, vegetation which allow the survival of Plasmodium and Anopheles);
- Host: susceptible human.
In developing preventive strategies for specific diseases, it is important consider the following characteristics:
- The incubation period: the delay between infection and appearance of first symptoms or signs. People exposed to an infectious disease should be observed for symptoms during this period. Knowing the incubation period can help in differential diagnosis. Thus, a case of gastroenteritis that occurs soon after eating a suspect food is likely to be caused by a toxin, such as that produced by Staphylococcus, whereas a delay of a day or more likely indicates an infectious agent, such as Norovirus.
- Window period: the time between infection and when the infection can be detected. Some diseases, for instance HIV infection, have a long window period, yet can be transmitted during it. In the early stages of HIV infection, negative tests can falsely reassure the patient, who may continue risky behaviour, putting others at risk.
- Period of communicability: the time during which a person can transmit a pathogen. To prevent transmission, appropriate precautions should be taken through the whole of this period. Some organisms, such as the hepatitis B virus or Salmonella typhi can cause a chronic carrier state in which the patient, having apparently recovered from the disease, continues to transmit it to susceptible people (see the Link box).
- Attack rate: the proportion of exposed persons who become infected. This is a marker of infectivity, which refers to the ability of an organism to invade, survive, and multiply in the host. For instance, HIV is a fragile organism and not very infective. By contrast, measles is highly infective even before the characteristic rash appears, and most non-immune people who come into any contact with a case will develop the disease, so that routine immunization is the best means of reducing transmission.
- Pathogenicity: the proportion of infected persons who develop clinical disease. For instance, young children can develop antibodies to hepatitis A without showing signs of the disease. This happens far less frequently in adults, so hepatitis A is less pathogenic in children than it is in adults. Another example is Corynebacterium diphtheriae, which produces diphtheria only when it is carrying the bacteriophage that produces the toxin that causes diphtheria.
- Virulence: the proportion of persons with clinical disease who become severely ill or die – an indicator of severity. The virus that causes the common cold is not virulent; Ebola virus is.
- Case fatality: of all the persons who contract a disease, the proportion that die of it. The more virulent the disease, the higher the case-fatality rate is likely to be and the more urgent it becomes to control its spread. For this reason, physicians who suspect a virulent disease, such as meningococcal illness, should notify the public health authorities as soon as possible by telephone, whereas the notification of less virulent diseases is not so urgent.
- Herd immunity: the resistance of a group or community to invasion and spread of an infectious agent. If enough people in the community are immune to an agent, the chain of transmission is very likely to be broken before the agent reaches non-immune people. So, the immunity of the “herd” protects non-immune members. This happens only with agents that are transmitted directly from person to person.
Hospitals and other health care settings are gathering points for large numbers of people whose immune systems are compromised by stress, illness and medications. These people are often in close contact with health care workers who are also caring for other ill people. Invasive procedures, such the insertion of catheters and cannulas or surgical operations provide additional portals of entry into the body. For microbes, this is an opportunity to reproduce easily and exchange the latest plasmids and nucleic acids that confer antimicrobial resistance. Even those not normally pathogenic can lead to nosocomial illnesses and prolonged hospital stays.
Infection control in a health care setting begins with estimating the risk of transmission of disease. This takes into account the types of patients and illnesses being treated and the type of care being provided. For instance, facilities offering cancer care need to put more resources into infection control than those offering general outpatient care.
Combatting the spread of infectious disease in health care setting involves three levels of action:19 engineering, administrative and personal protection. Engineering actions refer to adaptations of the physical environment such as accessible hand sanitizer dispensers and wash-hand basins, the provision of single rooms with private toilets, ventilation, surfaces that are easily cleaned etc. Administrative actions refer to policies and practices around cleaning and building maintenance as well as ensuring adequate resources, like sterile packs, gowns and masks. It also refers to ensuring that the facility has an infection control team, adequate education of personnel on the control of infections and the provision of occupational health services such as immunization and rapid response to needle-stick injuries.
Personal protection is most evident at the level of interaction between patient and health care worker. At this level routine infection control practice includes:
- Hand hygiene
- Assessing the risk of disease transmission before any contact with a patient
- If a patient is likely to transmit disease to others, educating on how to reduce this likelihood and limiting contact between this patient and others. For instance, in family practice seeing patients with a possible respiratory infection at the end of the day and putting them directly into an examination room to limit their time with others in the waiting room
- Setting up facilities and patient care in a way that reduces the contact between patients. In hospital practice this might mean separate facilities for accommodating inpatients and ambulatory patients
- Using appropriate aseptic techniques and single use equipment
- Using masks, gowns and eye protection where necessary
- Safety techniques for handling and disposing of sharps
- Properly cleaning clinics and areas used by patients as well as proper handling of used linen and clinical waste
- Educating patients, their families and visitors about the risk of disease transmission and how to avoid it
- Managing visitors to reduce their exposure to transmissible disease as well as their contact with other patients.
Certain situations require additional precautions to reduce the risk of transmission, depending on the mode of transmission of the organism. Table 11.2 lists some examples. Young children and others who are unable to comply with restrictions and people with incontinence may pose additional risk and should be treated accordingly.
|Mode of spread
|Examples of organisms and conditions
|Antibiotic resistant organisms, e.g. MRSA;
Acute vomiting or diarrhoea;
|Identify at triage;
May need to separate from other patients.
Gloves for contact;
Gown if soiling is likely;
Clean and disinfect equipment and surfaces after patient leaves.
|Identify at triage;
Put in a single room; Post alert at entrance;
Surgical mask and eye protection for any contact;
Clean and disinfect equipment and surfaces after patient leaves.
|Identify at triage;
Put in a single room, close the door and open the window if possible;
Alert notice at room entrance.
N95 respirator if tuberculosis suspected;
Only immune staff should provide care.
|Cases of acute respiratory infections, for example croup, RSV, influenza, or pneumonia should be treated as droplet and contact spread.
Dr. Rao calls public health
Microbes can rapidly develop resistance to threats; this became evident as antimicrobials came into use in the 1920s and 1930s. Until about the 1970s, pharmaceutical science was able to keep ahead by developing new antimicrobials that bypassed resistance. But the development of antimicrobials effective against resistant strains is now slowing so that antimicrobial resistance has become a worldwide problem.
Several factors encourage the growth of antimicrobial resistance:
- Inappropriate use: antimicrobials for self-limiting infections; using the latest antimicrobial instead of an effective older one, broad spectrum antimicrobials instead of appropriate narrow spectrum ones.
- Inadequate use: too low a dose, too short a course, missed doses, poor choice of route of administration, anything that can expose infecting microbes to an antimicrobial without eradicating them allows the survival of microbes that have some resistance to the antimicrobial. This is a particular problem with infections such as tuberculosis, which require a patient to continue therapy for several months.
- Use of antimicrobials in veterinary practice as a preventive measure or for promoting growth: intensive modern farming means that animals are raised in conditions that promote the spread of infection. Antimicrobials are often added to animal feed to prevent the loss of livestock (and profits) and to promote growth (and profits). This continuous, low level dose encourages the emergence of resistant strains which can then infect humans directly or pass resistance on to other microbes which infect humans.
To reduce the spread of resistance, physicians should reflect on their prescribing habits and educate patients on the proper use of antibiotics and the reasons for this. Physicians should make sure that their diagnosis is correct. A patient who presents with a cough and a runny nose may have an allergy rather than an infection. Even if she has an infection, as long as the symptoms are mild, it is likely to be viral and self-limiting. In neither case are antibiotics indicated. In hospitals, where patients are sicker and antimicrobials are used intensively for prolonged periods, attention to infection control practices reduces the spread of resistance.
Survival of the fittest microbe24
As with all life, microbes are subject to evolutionary pressures. Survival of the strain depends on its efficiency in spreading from one host to another. Microbes whose transmission depends on close proximity between the host and a susceptible person do not benefit from being highly virulent, for they require the host to be fit enough to move around and transport them to new hosts. A good example is the common cold, which does not incapacitate enough to limit the host’s mobility; however, the agent does irritate the upper respiratory tract, causing the coughing and sneezing that efficiently transmit it via droplets. Another example is the female pinworm. She deftly deposits her eggs around a child’s anus along with an allergen that causes itching. The child scratches, the eggs get on the fingers, and are then transferred to toys or other people. Microbes that cause sexually transmitted infections are spread by intermittent close contact so benefit from a different strategy. Gonorrhoea, chlamydia, and syphilis can infect silently while their hosts continue an active sex-life, thus ensuring continued spread.
Pathogens that depend on an intermediate vector (such as a flea or mosquito) for transmission can spread even from an immobilised host as long as the vector remains relatively healthy. These pathogens benefit from reproducing rapidly in their host because the more microbes the host is carrying, the more likely it is that one will be transferred to a passing vector. Plasmodium can be present in large numbers in the blood stream during the periodic, high fevers that characterize malaria and that typically confine the patient to bed. The sicker the patient, the less able he is to stop a mosquito from feeding on his blood and picking up the plasmodium parasite to transmit to the next victim. Similarly, agents able to survive for long periods outside of human hosts can afford to be virulent. Bacillus anthracis and Clostridium tetani are examples of microbes that survive for years in the soil and can kill people rapidly. Again, their ability to reproduce quickly helps the bacteria spread; the patient dies with a high bacterial load and the bacteria return to the soil to patiently await another host.
In general, a disease that spreads via attendants (such as nurses or physicians who carry the pathogen from patient to patient but are not themselves infected) tends towards high virulence. And yet, if the spread is to continue, the microbe can’t incapacitate the attendant, so the transmitted dose has to be small. A small dose of a less virulent pathogen might not establish infection. Following this logic, creating barriers to the transmission of certain community acquired microbes may eventually reduce their virulence while providing immediate control of outbreaks. This is because in order to overcome the barriers, the microbes have to infect their hosts for longer periods of time, keeping the hosts in good enough health to transmit the infection. In theory, therefore, it may be possible to stimulate organisms to evolve into less virulent forms. It is possible that one of the reasons for the huge impact of the 1918–1919 influenza pandemic was that the virus appeared at a time that favoured the transmission of a virus that would be poorly transmissible under normal social conditions.
We are surrounded by microbes that are fully capable of evolving ways to escape our interventions. Public health counteracts outbreaks in the population using surveillance to detect them and by implementing the steps of outbreak control. Vaccination is one of the best ways of controlling and, in some cases, even eliminating vaccine-preventable diseases. Health care is the source of nosocomial disease and contributes to antibiotic resistance. Clinicians must ensure that they are not increasing the transmission of infectious disease.
1. List the steps of outbreak control.
a. establish the existence of an outbreak;
b. define what constitutes a case and identify cases;
c. formulate hypotheses on the causes and implement initial control measures;
d. test hypotheses through analysis of surveillance data or special studies;
e. draw conclusions, re-adjust hypotheses and control measures if needed;
f. plan for long-term prevention and surveillance.
2. What are the advantages of immunization in the control of infectious disease?
3. A hospital patient has contracted Clostridium difficile. What precautions should be taken?
- Why have antibiotic-resistant strains of bacteria become a problem in recent years?
- What precautions should a clinician take against the spread of infectious disease in a clinic setting?
- Why is the common cold not a notifiable disease?
- What diseases are notifiable in your province Territory?
- Porta M, editor. A dictionary of epidemiology. New York (NY): Oxford University Press; 2008.
- Kelsey JL, Whittemore AS, Evans AS, Thompson WD. Methods in observational epidemiology. New York: Oxford University Press; 1996.
- Government of Canada. Mumps vaccines: Canadian immunization guide for health professionals. Ottawa: Health Canada; 2021 [Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-14-mumps-vaccine.html]
- Bouchard C, Dibernardo A, Koffi J, Wood H, Leighton PA, Lindsay LR. Increased risk of tick-borne diseases with climate change. Ottawa: Public Health Agency of Canada; 2019 [Available from: https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2019-45/issue-4-april-4-2019/article-2-increased-risk-tick-borne-diseases-climate-change.html]
- Kilpatrick AM, Kramer LD, Jones MJ, Marra PP, Daszak P. West Nile virus epidemics in North America are driven by shifts in mosquito feeding behavior. Plos Biology. 2006;4(4):e82.
- O’Connor DR. Report of the Walkerton Inquiry: the events of May 2000 and related issues. Toronto, Ontario: Office of the Attorney General; 2002 [Available from: http://www.attorneygeneral.jus.gov.on.ca/english/about/pubs/walkerton/part1/]
- Centers for Disease Control and Prevention. 2014 Ebola outbreak in West Africa – case counts. Atlanta: CDC – Centers of Disease Control and Prevention; 20216 [Available from: https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html]
- Bausch DG, Schwarz L. Outbreak of Ebola virus disease in Guinea: where ecology meets economy. PLOS Neglected Tropical Diseases [Internet]. 2014 2016, December; 8(7):[e3056 p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117598/]
- Richardson ET, Barrie MB, Kelly JD, Dibba Y, Koedoyoma S, Farmer PE. Biosocial approaches to the 2013-2016 Ebola pandemic. Health and Human Rights Journal [Internet]. 2016 2016, December; 18(1):[115-28 pp.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070685/
- Doherty JA. Final report and recommendations from the National Notifiable Diseases Working Group. Canadian Communicable Disease Report. 2006;32(19).
- Ontario Agency for Health Protection and Promotion (Public Health Ontario). Enhanced epidemiological summary: Mpox in Ontario – May 1, 2022 to July 31, 2023. Toronto, Ontario: King’s Printer for Ontario; 2023 [Available from: https://www.publichealthontario.ca/-/media/Documents/M/2022/monkeypox-episummary.pdf?rev=54bb06cfbe8548e7a66454985d89daf7&sc_lang=en]
- Watson-Creed G, Saunders A, Scott J, Lowe L, Pettipas J, Hatchette TF. Two successive outbreaks of mumps in Nova Scotia among vaccinated adolescents and young adults. Canadian Medical Association Journal. 2006;175(5):483-8.
- Public Health Agency of Canaada. Canadian Immunization Guide: Part 4. Immunizing agents. Ottawa: Government of Canada; 2023 [Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines.html]
- Public Health Agency of Canaada. Canadian adverse events following immunization surveillance system (CAEFISS). Ottawa: Government of Canada; 2023 [Available from: https://www.canada.ca/en/public-health/services/immunization/canadian-adverse-events-following-immunization-surveillance-system-caefiss.html]
- Centers for Disease Control. Pertussis vaccination: Use of acellular pertussis vaccines among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1997;47(RR-7):1-25.
- Centers for Disese Control and Prevention. Guillain-Barré syndrome and vaccines. Atlanta, GA: Centers for Disease Control and Prevention; 2023 [Available from: https://www.cdc.gov/vaccinesafety/concerns/guillain-barre-syndrome.html]
- Vellozzi C, Iqbal S, Brodetr K. Guillain-Barré syndrome, influenza and influenza vaccination: the epidemiologic evidence. Clinical Infectious Diseases. 2014;58(8):1149-55.
- Public Health Agency of Canaada. Meningococcal vaccines: immunogenicity, efficacy and effectiveness. Ottawa: Government of Canada; 2023 [Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html#p4c12a4]
- World Health Organization. Emergencies preparedness, response: Frequently asked questions and answers on smallpox. Geneva: WHO; 2016 [Available from: http://www.who.int/csr/disease/smallpox/faq/en/]
- Public Health Agency of Canaada. Measles in Canada Ottawa: Government of Canada; 2019 [Available from: https://www.canada.ca/en/public-health/services/diseases/measles/measles-in-canada.html]
- Centers for Disease Control. Diphtheria in the former Soviet Union: Reemergence of a pandemic disease. Emerging Infectious Diseases. 1998;4(4):539-50.
- Public Health England. Pertussis: the Green Book, chapter 24. 2016 December, 2016. In: Immunisation against infectious disease [Internet]. London: Gov.UK. Available from: https://www.gov.uk/government/publications/pertussis-the-green-book-chapter-24]
- World Health Organization. Global vaccine safety: Six common misconceptions about immunization. Geneva: WHO; 2016 [Available from: http://www.who.int/vaccine_safety/initiative/detection/immunization_misconceptions/en/]
- BC Centre for Disease Control. Communicable disease control manual, Chapter 2: Immunization. Appendix F – principles of immunology. Vancouver BC: Immunization Programs & Vaccine Preventable Diseses Service; 2009 [Available from: http://www.bccdc.ca/resource-gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Epid/CD%20Manual/Chapter%202%20-%20Imms/Appendix_F_PrinciplesImmunology.pdf]
- Public Health Agency of Canada. Routine practices and additional precautions for preventing the transmission of infection in healthcare settings. Ottawa: Public Health Agency of Canada; 2012 [Available from: http://publications.gc.ca/site/eng/440707/publication.html.
- May JM. The ecology of human disease. Annals of the New York Academy of Sciences. 1960;84(Culture, Society, and Health):789-94.
- Curtis S. Health and inequality: Geographical perspectives. London, Thousand Oaks, New Delhi: Sage Publications; 2004.
- Soper GA. The curious career of typhoid Mary. Bulletin of the New York Academy of Medicine [Internet]. 1939; 15(10):[698-712 pp.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1911442/pdf/bullnyacadmed00595-0063.pdf]
- Provincial Infectious Diseases Advisory Committee (PIDAC). Infection prevention and control for clinical office practice. Toronto: Public Health Ontario; 2015 [Available from: http://www.publichealthontario.ca/en/eRepository/IPAC_Clinical_Office_Practice_2013.pdf]
- Ewald PW. Guarding against the most dangerous emerging pathogens. Emerging Infectious Diseases. 1996;2(4):245-57.