Pathogen Identification

Occurrence of a Disease

An occurrence of disease greater than would be expected at a particular time and place is called an outbreak.

Learning Objectives

Recognize the steps taken by epidemiologists when investigating disease outbreaks

Key Takeaways

Key Points

  • Outbreaks may also refer to endemics that affect a particular place or group, epidemics that affect a region in a country or a group of countries, or pandemics that describe global disease outbreaks.
  • The epidemiology profession has developed a number of widely accepted steps to investigate a disease occurrence.
  • Outbreak patterns, which can be useful in identifying the transmission method or source, and predicting the future rate of infection include common source, continuous source, point source, and propagated source.
  • Outbreaks can be behavioral risk related (e.g., sexually transmitted diseases, increased risk due to malnutrition) or zoonotic (e.g. the infectious agent is endemic to an animal population ).

Key Terms

  • outbreak: A term used in epidemiology to describe an occurrence of disease greater than would otherwise be expected at a particular time and place.
  • epidemic: A widespread disease that affects many individuals in a population.
  • pandemic: A disease that hits a wide geographical area and affects a large proportion of the population.

Occurrence of a Disease

Outbreak is a term used in epidemiology to describe an occurrence of disease greater than would otherwise be expected at a particular time and place. It may affect a small and localized group or impact thousands of people across an entire continent. Two linked cases of a rare infectious disease may be sufficient to constitute an outbreak. Outbreaks may also refer to endemics that affect a particular place or group, epidemics that affect a region in a country or a group of countries, and pandemics that describe global disease outbreaks.

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1918 Flu Victims: With masks over their faces, members of the American Red Cross remove a victim of the Spanish Flu from a house at Etzel and Page Avenues, St. Louis, Missouri.

The epidemiology profession has developed a number of widely accepted steps when investigating disease outbreaks. As described by the Centers for Disease Control and Prevention, these include the following:

  1. Verify the diagnosis related to the outbreak.
  2. Identify the existence of the outbreak (if the group of ill persons is normal for the time of year, geographic area, etc. ).
  3. Create a case definition to define who/what is included as a case.
  4. Map the spread of the outbreak.
  5. Develop a hypothesis (if there appears to be a cause for the outbreak).
  6. Study hypothesis (collect data and perform analysis).
  7. Refine hypothesis and carry out further study.
  8. Develop and implement control and prevention systems.
  9. Release findings to greater communities.

There are several outbreak patterns that can be useful in identifying the transmission method or source and predicting the future rate of infection.

  1. Common source – All victims acquire the infection from the same source (e.g. a contaminated water supply).
  2. Continuous source – Common source outbreak where the exposure occurs over multiple incubation periods.
  3. Point source – Common source outbreak where the exposure occurs in less than one incubation period.
  4. Propagated – Transmission occurs from person to person.

Each has a distinctive epidemic curve, or histogram of case infections and deaths.

Outbreaks can also be:

  1. Behavioral risk related (e.g. sexually transmitted diseases, increased risk due to malnutrition)
  2. Zoonotic – The infectious agent is endemic to an animal population.

Disease Severity and Duration

The severity and duration of diseases vary greatly and are important for epidemiological studies.

Learning Objectives

Discuss the severity and various types of disease duration, including: acute, chronic, flare-up, refractory, progressive, remission and a cure

Key Takeaways

Key Points

  • Severity of illness is defined as the extent of organ system derangement or physiologic decompensation of a patient, and in general an illness is classified into minor, moderate, major, and extreme.
  • In an infectious disease, the incubation period is the time between infection and the appearance of symptoms, the latency period is the time between infection and the ability to spread to another person, and the viral latency is the time the virus hides in the body in an inactive state.
  • Disease duration can encompass one or more of the following: an acute disease, a chronic disease, a flare-up, a refractory disease is a disease, a progressive disease, or a cure.
  • The scope of a disease, whether it is localized, disseminated, or systemic also affects its severity and duration.
  • The International Classification of Diseases (ICD) is known as a health care classification system that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease.

Key Terms

  • severity: the degree of something undesirable; badness or seriousness.
  • duration: an amount of time or a particular time interval

Severity of illness is defined as the extent of organ system derangement or physiologic decompensation of a patient. It gives a medical classification into minor, moderate, major, and extreme that is meant to provide a basis for evaluating hospital resource use or to establish patient care guidelines.

In an infectious disease, the incubation period is the time between infection and the appearance of symptoms. The latency period is the time between infection and the ability of the disease to spread to another person, which may precede, follow, or be simultaneous with the appearance of symptoms. Some viruses also exhibit a dormant phase, called viral latency, in which the virus hides in the body in an inactive state.

Disease duration can be one of the following:

  1. An acute disease is a short-lived disease, like the common cold.
  2. A chronic disease is one that lasts for a long time, usually at least six months. During that time, it may be constantly present, or it may go into remission and periodically relapse. A chronic disease may be stable (does not get any worse) or it may be progressive (gets worse over time). Some chronic diseases can be permanently cured. Most chronic diseases can be beneficially treated, even if they cannot be permanently cured.
  3. A flare-up can refer to either the recurrence of symptoms or an onset of more severe symptoms.
  4. A refractory disease is a disease that resists treatment, especially an individual case that resists treatment more than is normal for the specific disease in question.
  5. A progressive disease is a disease whose typical natural course is the worsening of the disease until death, serious debility, or organ failure occurs. Slowly progressive diseases are also chronic diseases; many are also degenerative diseases. The opposite of progressive disease is stable disease or static disease: a medical condition that exists, but does not get better or worse.
  6. A cure is the end of a medical condition or a treatment that is very likely to end it, while remission refers to the disappearance, possibly temporarily, of symptoms. Complete remission is the best possible outcome for incurable diseases.

The scope of a disease also affects its severity and duration:

  1. A localized disease is one that affects only one part of the body, such as athlete’s foot or an eye infection.
  2. A disseminated disease has spread to other parts; with cancer, this is usually called metastatic disease.
  3. A systemic disease is a disease that affects the entire body, such as influenza or high blood pressure.

The International Classification of Diseases (most commonly known by the abbreviation ICD) is according to its publisher, the United Nations-sponsored World Health Organization, and is considered “the standard diagnostic tool for epidemiology, health management and clinical purposes. ” It is known as a health care classification system that provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or disease. Under this system, every health condition can be assigned to a unique category and given a code, up to six characters long. Such categories can include a set of similar diseases.The International Classification of Diseases is published by the World Health Organization (WHO) and is used worldwide for morbidity and mortality statistics, reimbursement systems, and automated decision support in health care. This system is designed to promote international comparability in the collection, processing, classification, and presentation of these statistics. The ICD is a core classification of the WHO Family of International Classifications (WHO-FIC).

Extent of Host Involvement

Host-pathogen interactions are the interactions taking place between a pathogen (e.g. virus, bacteria) and their host (e.g. humans, plants).

Learning Objectives

Differentiate between primary and opportunistic pathogens in regards to host involvement

Key Takeaways

Key Points

  • All pathogens damage their host to some extent, usually resulting in an infectious disease from the interplay between the pathogens and the defenses of the hosts they infect.
  • Clinicians classify infectious microorganisms or microbes according to the status of host defenses – either as primary pathogens or as opportunistic pathogens.
  • Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence is, in part, a necessary consequence of their need to reproduce and spread.
  • Organisms which cause an infectious disease in a host with depressed resistance are classified as opportunistic pathogens.

Key Terms

  • host: A cell or organism which harbors another organism or biological entity, usually a parasite.
  • pathogen: Any organism or substance, especially a microorganism, capable of causing disease, such as bacteria, viruses, protozoa, or fungi. Microorganisms are not considered to be pathogenic until they have reached a population size that is large enough to cause disease.

Host-pathogen interactions are the interactions that take place between a pathogen (e.g. virus, bacteria ) and their host (e.g. humans, plants). By definition, all pathogens damage their host to some extent. Infectious diseases result from the interplay between the pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from the presence of any pathogen depends upon the ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen.

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Clostridium tetani: Clostridium tetani are pathogenic bacteria.

Clinicians therefore classify infectious microorganisms or microbes according to the status of host defenses – either as primary pathogens or as opportunistic pathogens.

Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans; however many serious diseases are caused by organisms acquired from the environment or which infect non-human hosts.

Organisms which cause an infectious disease in a host with depressed resistance are classified as opportunistic pathogens. Opportunistic diseases may be caused by microbes that are ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts or from the environment as a result of traumatic introduction. An opportunistic disease requires impairment of host defenses, which may occur as a result of several factors such as genetic defects, exposure to antimicrobial drugs or immunosuppressive chemicals, exposure to ionizing radiation, or as a result of an infectious disease with immunosuppressive activity. Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host.

Identification of Microbes Based on Molecular Genetics

Modern nucleic acid-based microbial detection methods make it possible to identify microbes that are associated with a disease.

Learning Objectives

Describe the components of Molecular Koch’s postulates

Key Takeaways

Key Points

  • Nucleic acid -based detection methods are very sensitive.
  • Molecular Koch’s postulates are a set of experimental criteria that must be satisfied to show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen.
  • After virulent factors have been identified, it is possible to develop a vaccine against the factors.
  • For many pathogenic microorganisms, it is not currently possible to apply molecular genetic techniques to a gene in question.

Key Terms

  • genetic: Relating to genetics or genes.
  • nucleic acid: Any acidic, chainlike biological macromolecule consisting of repeating units of phosphoric acid, sugar, and purine and pyrimidine bases; they are involved in the preservation, replication, and expression of hereditary information in every living cell.
  • virulent: Highly infectious, malignant, or deadly.
  • genetics: the branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA

Modern nucleic acid-based microbial detection methods make it possible to identify microbes that are associated with a disease. Nucleic acid-based detection methods are very sensitive, and they can often detect the very low levels of viruses that are found in healthy people without disease.

The use of these new methods has led to revised versions of Koch’s postulates. Molecular Koch’s postulates are a set of experimental criteria that must be satisfied to show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen. Genes that satisfy molecular Koch’s postulates are often referred to as virulence factors (i.e., what makes the pathogen virulent). The following set of Koch’s postulates for the 21st century have been suggested:

  1. A nucleic acid sequence belonging to a putative pathogen should be present in most cases of an infectious disease. Microbial nucleic acids should be found, preferentially in those organs or gross anatomic sites known to be diseased and not in those organs that lack pathology.
  2. Fewer, or no, copies of the pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease.
  3. With resolution of the disease, the copy number of pathogen-associated nucleic acid sequences should decrease or become undetectable. With clinical relapse, the opposite should occur.
  4. When sequence detection predates disease, or the sequence copy number correlates with severity of disease or pathology, the sequence-disease association is more likely to be a causal relationship.
  5. The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms.
  6. Tissue-sequence correlates should be sought at the cellular level. Efforts should be made to demonstrate specific in situ hybridization of microbial sequence to areas of tissue pathology and to visible microorganisms or to areas where microorganisms are presumed to be located.
  7. These sequence-based forms of evidence for microbial causation should be reproducible.

Once virulent factors have been identified, it is possible to develop a vaccine against the factors. illustrates how the avian flu vaccine was developed using reverse genetic techniques.

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Reserve genetics: Avian flu vaccine development by reverse genetics technique.

For many pathogenic microorganisms, it is not currently possible to apply molecular genetic techniques to a gene in question. Testing a candidate virulence gene requires a relevant animal model of the disease being examined and the ability to genetically manipulate the microorganism that causes the disease. Suitable animal models are lacking for many important human diseases. Additionally, many pathogens cannot be manipulated genetically.