CHAPTER  14   PRINCIPLES OF DISEASE AND EPIDEMIOLOGY

 

 

PATHOLOGY, INFECTION, AND DISEASE

 

Pathology is the scientific study of disease. It includes:

 

1. Etiology---the cause of the disease--disease-causing organisms are called pathogens

 

2. Pathogenesis---the manner in which the disease develops

 

3. Structural and functional changes brought about by the disease

 

4. Final effects of the disease on the body

 

 

Infection---invasion or colonization of the body by pathogenic microorganisms. This term is also used to describe the presence of normal flora organisms in an abnormal location.

 

Disease---an abnormal state in which part or all of the body is not properly adjusted or is incapable of performing its normal function--change from the state of health.

 

These 2 terms do not mean exactly the same thing. A disease can occur without the involvement of microorganisms. And an infection can occur without disease actually developing.

 

The location of microorganisms can be important. Escherichia coli in the intestine are considered normal and would not be classified as an infection. If some of the same organisms are transferred to the urinary tract, they usually cause disease and then their presence would be considered an infection.

 

 

NORMAL MICROBIOTA   (NORMAL FLORA)   

 

All animal bodies have a large population of microorganisms that are considered normal inhabitants. These are more or less permanent residents and do not produce disease under normal conditions. These microbes are known as normal flora or normal microbiota. The number of microbes in the normal flora is often greater that the total number of human cells.

 

Animals developing in utero are normally free of microorganisms. During the birth process and immediately after birth, characteristic microbial populations begin to appear.  Lactobacilli of the vagina are usually acquired first. Breathing and feeding bring in other types.

 

In addition to the normal flora, which are usually present at all times, transient microbes may appear and remain for days, weeks, or months, and then disappear.

 

Microbes in the form of normal flora are expected to be present in the following parts of the body:

 

Skin-secretions from sweat & oil glands may inhibit growth of some microbes, but large numbers of

          microbes that tolerate these factors are always present

Outer part of eye within the conjunctival sac

Nose & throat—some of these are potential pathogens, but competition and other factors keep the

          numbers of potentially dangerous microbes relatively low

Mouth—normal mouth flora are mostly gram positive, but in an unhealthy mouth the balance shifts to

          gram negative

Large intestine—contains the largest numbers of resident microbes in the body

Urinary system—lower urethra in both sexes often contains some microbes, but the

          urinary bladder should be sterile

Reproductive systems—no microbes in males except for lower urethra; large population of lactobacilli in

          the vagina which create an environment hostile to digestive tract bacteria

 

 

RELATIONSHIPS BETWEEN NORMAL MICROBIOTA AND HOST

 

Normal flora organisms are desirable because they can prevent the growth of large numbers of pathogens. This is called microbial antagonism and is mainly due to competition among microbes. If pathogens come along, normal flora may affect them in several ways:

   1. Compete for nutrients

   2. Produce substances harmful to the pathogens

   3. Influence pH or oxygen levels in a way harmful to the pathogens

 

When the balance is upset, pathogens which arrive or which have already been present but in numbers too small to cause disease take the opportunity to multiply. An example of this is the diarrhea or yeast infections often associated with taking antibiotics. The antibiotics may have a greater effect on the normal flora organisms than on the pathogens, thus upsetting the balance.

 

In the mouth, streptococci (not the species that causes “strep throat,” but others) produce compounds that prevent the growth of most other gram-positive and gram-negative cocci. In the large intestine, Escherichia coli organisms produce bacteriocins, which inhibit the growth of other related bacteria, such as Salmonella and Shigella.

 

Also in the large intestine, an organism called Clostridium difficile is normally found but in very small numbers. Normal flora organisms keep the C. difficile numbers down, but when the balance is disturbed the C. difficile may greatly outgrow the others, producing symptoms ranging from mild diarrhea to severe or fatal colitis.

 

The relationship between normal flora and the host is called symbiosis, which means living together. More specific types of symbiosis include:

·         Commensalism—relationship in which one organism is benefited and the other is unaffected. In this type of relationship with humans, bacteria live on secretions and sloughed-off cells but do not benefit or harm the host. Some bacteria normally found in the eye, the ear, and on the external genitals have this type of relationship.

·         Mutualism—both organisms benefit. Bacteria that live in the large intestine benefit by receiving shelter and a constant supply of nutrients. In return, they synthesize vitamins that humans cannot synthesize. Even though the bacteria are making these vitamins for their own use, the extra amounts that are produced are absorbed and used by the host.

·         Parasitism---one organism benefits and the other is harmed. Pathogens fit into this category.

 

OPPORTUNISTIC MICROORGANISMS

 

Under certain circumstances, relationships between organisms can change. For example, common strains of Escherichia coli are harmless or beneficial in the large intestine. However, E. coli is a very common cause of urinary tract infections if it gains access to that area. Although unusual, it also can cause infections in the lungs, spinal cord, or wounds. Opportunistic pathogens are organisms that do not ordinarily cause disease in their natural habitat in a healthy person, but in case of broken skin, damaged mucous membranes, or a weakened host, these same organisms can cause serious disease. Most AIDS patients die of infections caused by opportunistic pathogens that take advantage of the weakened immune system. One type of pneumonia, caused by Pneumocystis jiroveci, is seldom seen except in AIDS patients, although we have all probably been exposed to the organism.

 

Many people carry organisms that are regarded as pathogens, but may not be causing their disease in that particular host. This includes echoviruses, adenoviruses, Neisseria meningitidis, and Streptococcus pneumoniae.

 

 

 

COOPERATION AMONG MICROORGANISMS

 

In some situations, microbes cooperate with each other in causing disease. Synergism means that the effect of two microbes together is greater than the effects of either acting alone. For example, pathogens that cause periodontal disease may attach to receptors on the streptococci that are considered normal flora of the mouth, not to the teeth or gums themselves.

 

 

ETIOLOGY OF INFECTIOUS DISEASES (THE WAY THEY ARE CAUSED)

 

Although not all diseases are infectious (caused by microorganisms), those that are due to microbes are the topic of this section. The requirements for establishing a specific pathogen as the causative agent of a particular disease are known as Koch Postulates:

   1. The same pathogen must be present in every case of the disease.

   2. The pathogen must be isolated from the diseased host and grown in pure culture.

   3. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible lab animal (or apple!).

   4. The inoculated animal must develop the disease, and the original pathogen must be isolated from it.

 

 

EXCEPTIONS TO KOCH’S POSTULATES

 

Characteristics of some microorganisms and some diseases make it impossible to exactly follow Koch’s postulates:

 

   1. Some microbes cannot be grown on artificial lab media. Treponema pallidum (syphilis) and Mycobacterium leprae (leprosy) are examples. Rickettsias and viruses also cannot be grown on artificial media. For these, Koch’s postulates must be modified. The suspected pathogen may have to be grown in cell culture or in a laboratory animal.

 

   2. Some diseases are not always caused by the same pathogen. Nephritis, pneumonia, meningitis, and peritonitis may be caused by a number of different pathogens, but still present similar signs and symptoms.

 

   3. Some pathogens can cause more than one disease condition. Mycobacterium tuberculosis, for example, can infect the bones instead of the lungs. Streptococcus pyogenes commonly causes “strep throat,”  but it can also cause scarlet fever or puerperal (childbed) fever.

 

   4. Some agents do not grow in any way except a human host. This brings up a question of ethics.

 

 

CLASSIFYING INFECTIOUS DISEASES

 

Diseases cause:

   Symptoms---changes not apparent to an observer

   Signs---changes that can be observed or measured

A syndrome is a group of signs and symptoms that always accompanies a particular disease.

 

Infectious diseases may be classified in several ways:

 

   1. How the disease is spread

      a. Communicable disease—a disease that spreads from one host to another, either directly or indirectly

 

      b. Contagious disease---easily spread from one person to another

 

      c. Noncommunicable disease---not spread from one host to another

 

 

    2. Occurrence of the disease  

 

      a. Incidence of a disease—the fraction of a population that contracts the disease in a particular time period

 

      b. Prevalence of a disease—the fraction of a population having the disease at a specified time

 

     c. Frequency of occurrence

         1) Sporadic disease---occurs only occasionally

         2) Endemic disease—always present in a particular population

         3) Epidemic disease---many people come down with the disease within a short time period

         4) Pandemic disease—worldwide epidemic

 

   3. Severity or duration of the disease

      a. Acute disease---develops rapidly and lasts only a short time

      b. Chronic disease---develops more slowly and may continue or recur for long periods

      c. Subacute disease---intermediate between acute and chronic

      d. Latent disease---causative agent enters the body but remains dormant for some period of time. Later the agent becomes active and causes symptoms

 

Immunity of the population can determine the rate at which a disease spreads and the number of individuals involved. Vaccination can produce a large number of immune persons in a population, making it unlikely that even susceptible persons will come in contact with the disease-causing agent. When many immune people are present in a community, this is called herd immunity. The fewer sick people there are, the less likely the disease will spread to susceptible people.

CLASSIFICATION OF INFECTIONS ACCORDING TO THE EXTENT OF HOST INVOLVEMENT

 

Local infection—limited to a relatively small area of the body

 

Systemic (generalized) infection—microbes or their products are spread throughout the body by blood or lymph

 

Focal infection—agents of infection enter a blood or lymphatic vessel and spread to other specific parts of the body where they remain confined

 

Sepsis—toxic condition arising from the spread of microbes or their toxins from a focus of infection

Bacteremia—presence of bacteria in the blood

Septicemia--the bacteria are not only present in the blood but are multiplying there

Toxemia--the presence of toxins in the blood

Viremia—presence of viruses in the blood

 

Primary infection—acute infection causing the initial illness

 

Secondary infection—caused by an opportunistic pathogen after the primary infection has weakened the body’s defenses

 

Subclinical infection—no noticeable illness but carrying the microbe—people with this type of infection can spread the microbe to others, some of whom may develop clinical cases of the disease

 

 

PATTERNS OF DISEASE

 

Sequence of events:

1. Existence of reservoir

2. Transmission of pathogen to susceptible host

3. Invasion of the host by the microbe

4. Multiplication of the microbe

5. Injury to the host

 

A predisposing factor is one that makes the host more susceptible to the disease.

1. Gender                                                                  11. Occupation

2. Genetic background                                            12. Chemotherapy

3. Climate & weather                                               13. Emotional disturbance   

4. Inadequate nutrition

5. Fatigue

6. Age

7. Environment

8. Habits

9. Lifestyle

10. Preexisting illness

 

DEVELOPMENT OF DISEASE

 

1. Incubation period—time between initial infection and first appearance of signs or symptoms. This can vary due to:

    a. Microorganism involved

    b. Virulence of infecting microbes

    c. Original number of invaders

    d. Resistance of the host

 

2. Prodromal period—early, mild symptoms

 

3. Illness—patient shows signs & symptoms of the disease. Usually the resistance of the host overcomes the pathogen and recovery begins.

 

4. Decline—patient improves and signs and symptoms taper off. Secondary infections may appear during this phase.

 

5. Convalescence—recovery occurs and person returns to original state of health.

 

The infected person can spread the disease through all of these periods of the infection.

 

 

SPREAD OF INFECTION

 

RESERVOIRS OF INFECTION

1. Human reservoirs—many people carry pathogens and transmit them to others, directly or indirectly. These people may have signs and symptoms of the disease; or they may be in a period without signs and symptoms, either before or after the disease develops. Others may be carriers without ever developing signs or symptoms of the disease--these are called asymptomatic carriers.

 

2. Animal reservoirs—zoonoses are diseases which are primarily diseases of animals, but can be transmitted to humans. (See Table 14.2 P. 432). About 150 zoonoses have been identified, and these diseases spread to humans in various ways:

    a. Direct contact with infected animals

    b. Direct contact with waste of pets (cleaning kitty box, for example)

    c. Contamination of food or water

    d. Contact with contaminated hides, feathers, or fur

    e. By consuming infected animal products

    f. By insect vectors

 

3. Nonliving reservoirs—the two main examples are soil and water.

    a. Soil—fungus organisms (ringworm & systemic infections); Clostridium botulinum, C. tetani are common

    b. Water—Vibrio cholerae, Salmonella typhi, other gastrointestinal diseases.  Usually the water has become contaminated by feces of humans or animals.

    c. Improperly prepared or stored foods

 

TRANSMISSION OF DISEASE

 

1. Contact transmission—spread of an agent of disease by direct contact, indirect contact, or droplet.

    a. Direct contact---person-to-person transmission with no intermediate object involved. Respiratory diseases, staphylococcal infections, hepatitis A, measles, smallpox, STDs including AIDS. Rabies & anthrax spread from animals to people.

    b. Indirect contact—a nonliving object transmits the disease from its reservoir to a new susceptible host. The term for an object involved is fomite. Examples would be hankies, bedding, diapers, eating & drinking utensils, money, thermometers, contaminated syringes, etc.

    c. Droplet—discharged by coughing, sneezing, talking, laughing, etc. Droplets travel less than 1 meter from reservoir to host. Examples of diseases are influenza, pneumonia, and whooping cough.

 

2. Vehicle transmission—transmission of disease by water, food, air, blood & other body fluids, etc.

    a. Waterborne transmission—pathogens usually originate in untreated or poorly treated sewage. Diseases: cholera, shigellosis, leptospirosis.

    b. Foodborne transmission—transmission in foods that are incompletely cooked, poorly refrigerated, and contaminated in preparation. Food poisoning and tapeworm infestations.

    c. Airborne transmission—spread of agents by droplets that travel more than 1 meter from the reservoir to the new host.  Measles and tuberculosis are examples.

    d. Dust particles—staphylococci, streptococci, fungal spores.

 

3. Vectors—these are animals that carry pathogens from one host to another. Often they are arthropods (insects, ticks, mites). A few examples of diseases transmitted by vectors are: malaria, yellow fever, Lyme disease, and Rocky Mountain spotted fever.

    a. Mechanical transmission—pick up the pathogen and carry it on feet or other body parts.

    b. Biological transmission—pathogen must undergo a necessary stage of development inside the body of the vector.

 

 

 

NOSOCOMIAL INFECTIONS

These are infections acquired in the hospital.  5 - 15% of hospital patients are affected (about 2 million people per year) and about 20,000 people per year die of these infections. Several factors acting together are involved:

 

    1. Microorganisms in the hospital environment—in spite of major efforts to control

them, large numbers of pathogens live in hospitals. Common  organisms include:

      a. Staphylococcus aureus

      b. Escherichia coli

      c. Pseudomonas aeruginosa

     d. Enterococcus

Unfortunately, many of the strains found in hospitals are resistant to antibiotics.

 

    2. Compromised host---patients weakened by other illnesses or conditions, including broken skin and a suppressed immune system. Invasive procedures such as anesthesia and surgery also increase the risk.

 

    3. Chain of transmission in the hospital

      a. Direct contact transmission from hospital staff to patient

      b. Patient to patient

      c. Fomites

      d. Ventilation system

 

 

 

CONTROL OF NOSOCOMIAL INFECTIONS

 

Accredited hospitals are have an infection control committee, an infection control nurse, or an epidemiologist. Their job is to identify problem sources, check equipment for contamination, check sterilization procedures, etc.

 

Some means of controlling infection include:

1. Education of staff

2. Handwashing!!!!! and gloves

3. Aseptic techniques where appropriate

4. Careful handling of contaminated materials

5. Isolation where appropriate

 

 

 

 

 

EMERGING INFECTIOUS DISEASES

 

These are “new” diseases, identified in  one of these ways:

   1. The disease presents symptoms that are clearly distinctive from all other diseases

   2. Improved diagnostic techniques may allow the identification of a new pathogen

   3. A local disease becomes widespread

   4. A rare disease becomes common

   5. A mild disease becomes more severe

   6. An increase in life span permits a new disease to develop

 

Remember, the causative agent itself is usually not new, but just one that has not previously been recognized. Examples ( Table 14.6 P. 439 for others):

MICROORGANISM

YEAR

DISEASE

BACTERIA

 

 

Borrelia burgdorferi

1975

Lyme disease

Legionella pneumophila

1976

Legionnaire’s disease

Escherichia coli O157:H7

1982

Food poisoning involving production of dangerous toxins

FUNGI

 

 

Pneumocystis carinii

1981

Pneumonia, esp. in AIDS patients

PROTOZOA

 

 

Cryptosporidium parvum

1976

Cryptosporidiosis

VIRUSES

 

 

HIV

1983

AIDS

Hepatitis C virus

1989

Hepatitis

Hantavirus

1993

Hantavirus pulmonary syndrome

Ebola virus

1975

Ebola fever

West Nile virus

1999

West Nile encephalitis

PRIONS

 

 

Bovine spongiform encephalitis agent

1996

Mad cow disease

 

 

 

Factors which may contribute to the emergence of new infectious diseases include:

   1. Familiar microorganisms change--new strains appear

   2. The widespread use of antibiotics and pesticides encourages the growth of resistant microbes and resistant insects and ticks that carry them

   3. Global warming may change the distribution and survival of organisms and vectors

   4. Modern rapid transportation encourages the spread of disease

   5. Previously unrecognized infections may appear when ecological changes occur

   6. Animal populations may affect the incidence of disease

   7. Lack of proper vaccination and failure to report infectious disease may affect handling of a disease outbreak

 

The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have plans related to emerging diseases:

   1. To detect, promptly investigate, and monitor emerging infectious diseases

   2. To expand research on ecological and environmental factors, microbial changes and adaptations, and host interactions

   3. To enhance communication of public health information and prevention strategies

   4. To establish plans to monitor and control emerging diseases worldwide

 

 

 

EPIDEMIOLOGY

 

This is the science that studies when and where diseases occur and how they are transmitted. This science began when Dr. John Snow traced an outbreak of cholera to contaminated water in London in 1848-1849.

 

In modern medicine, epidemiologists collect all possible data related to an outbreak of disease:

   1. Etiology (causative agent)

   2. Age & sex of patients

   3. Occupation

   4. Personal habits

   5. Socioeconomic status

   6. History of immunization

   7. What do these people have in common?

   8. Where did each one come in contact with the agent?

    9. Is the disease seasonal, yearly, etc.?     

 

The next step is controlling the disease, which may include