Epidemiology

1
Epidemiology

• Science that studies when (incidence) and where
  diseases occur and how they are transmitted in
  populations
• Modern epidemiology began in the mid 1800s
• CDC, a branch of the U.S.P.H.S. is the main
  source of epidemiological information in the
  United States
• Headquartered in Atlanta, GA
• Publishes the MMWR, the Morbidity (incidence) and
  Mortality (deaths)
• With reportable disease, there is the phenomenon
  known as the iceberg effect

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Disease outbreaks

• Are categorized by their frequency of occurrence
• Pandemic- across the globe Ex AIDS, influenza
• Epidemic- pronounced increase in the number of
  cases, much more than would be expected in a
  population Ex influenza
• Endemic- seen in a specific region, constant
  number of cases over a long period of time Ex
  the common cold
• Sporadic- isolated cases , unpredictable, spread
  out over a wide area (occasional occurrence) Ex
  typhoid in the U.S.

3
Symptoms v signs of disease

• Is there a difference?
• Symptoms are subjective
• Changes in the patient are not apparent to the
  observer Ex pain, achiness, malaise
• Signs are objective changes that a physician can
  observe or measure
• Swelling, fever, paralysis
• A diagnosis is based on signs and symptoms
• A syndrome is a disease accompanied by specific
  signs and symptoms (Ex AIDS, the Gulf War
  syndrome)

4
Disease transmission

• Communicable diseases are spread from one host to
  another, either directly or indirectly Ex TB,
  chicken pox, typhoid fever
• Contagious diseases are EASILY spread from one
  person to another
• A non-communicable disease is not spread from one
  host to another
• Usually caused by microorganisms that would
  normally inhabit the body and only occasionally
  cause disease OR
• Microorganisms that reside outside the body and
  produce disease only when introduced into the
  body Ex Clostridium tetani introduced into
  puncture wounds

5
Stages of development of disease

• Incubation- the time interval between initial
  infection and the appearance of signs and
  symptoms
• Time of incubation depends on the microorganism,
  its virulence, the number of infecting organisms
  and the hosts resistance
• Rubella has a 2-3 week incubation period
• Cholera has a 1-3 day period

6

• Prodromal- relatively short
• Follows a period of incubation in some diseases
• Characterized by early, mild symptoms of the
  disease (malaise and achiness)

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• Period of illness
• Disease is acute
• Overt signs and symptoms are exhibited such as
  fever, chills, pharyngitis, lymphadenopathy and
  GI disturbance
• WBC count may rise or fall
• If patients immune system overcomes the
  pathogen, the illness ends OR the patient can be
  treated with meds successfully OR the patient
  dies

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• Period of decline when the signs and symptoms
  decline. Patient is vulnerable to a secondary
  infection
• Period of convalescence- person regains their
  strength and return to a healthy state
• People may serve as reservoirs of disease such
  as typhoid or cholera where the pathogenic
  organism can be carried for months or even years

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Reservoirs

• May be a living organism or an inanimate object
  that provides the pathogen with acceptable
  conditions for its survival, multiplication and
  opportunity for transmission
• May be human, animal or non-living
• Fomite- is an inanimate object that can serve as
  a reservoir Ex towels, diapers, contaminated
  syringes

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• Zoonoses- disease can be transmitted from wild or
  domestic animals to humans such as Lyme disease
  or rabies
• Transmission includes
• direct contact with infected animals
• direct contact with pet waste,
• contamination of food and water,
• consumption of infected animal products
• insect vectors
• Mechanical vectors are those which are passive
  carriers
• Biological vectors participate in the life cycle
  of the pathogen

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• Carrier is a person who transmits disease to
  another person
• Active- exhibit signs and symptoms
• Convalescent- recovered but continue to harbor
  the pathogen
• Asymptomatic- healthy, arent ill but carry the
  pathogen
• Incubation- are incubating the pathogen but are
  not exhibiting signs/symptoms of illness yet
• Chronic- harbor pathogen for months (or even a
  lifetime) after recovering

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Infectious disease transmission

• Depends on direct, indirect or droplet contact
• Direct is person to person, physical contact with
  susceptible host such as touching, kissing or
  sexual activity
• Examples include influenza, Hepatitis A,
  gonorrhea
• Direct contact of animal to person
• Examples of rabies and anthrax

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• Indirect contact transmitted from its reservoir
  ? acceptable host by a non-living object
• Example contaminated syringes are fomites for
  Hepatitis B and AIDS transmission
• Droplet contact- microbes are spread in droplet
  nuclei traveling only a short distance (lt1 M)
  discharged by sneezing, talking, laughing and
  coughing
• Examples influenza and pneumonia

14
Vehicle transmission

• Transmission of disease agents by a medium
• Water
• Food
• Air
• Waterborne- spread by water contaminated by
  untreated or under-treated sewage. Includes
  shigellosis and cholera
• Foodborne- foods are incompletely cooked, poorly
  refrigerated or prepared in unsanitary
  conditions. Includes tapeworm and food poisoning

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Vehicle transmission

• Airborne- droplet nuclei in dust that travels gt 1
  meter distance from reservoir to host
• May be discharged in spray from mouth/nose when
  coughing/sneezing
• Remain airborne for a period of time
• Tuberculosis
• Measles
• Dust can harbor pathogens such as Staph/Strept
• Fungal spores can cause histoplasmosis

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Vectors

• Animals that carry pathogens from one host to
  another
• Arthropods are the most important group of
  disease vectors
• Transmission is either biological or mechanical
• Mechanical - passive transport on the insects
  feet can make contact with the hosts food
• Biological arthropod bites an infected person
  or animal, ingests the infected blood, pathogen
  reproduces in the vector increasing in number as
  well as increasing the possibility of transmission

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Biological transmission

• Some parasites reproduce in gut? feces or gut ?
  salivary gland
• Some protozoa and helminth parasites use vector
  as the host for an intermediate stage of their
  life cycle
• EX malaria (Plasmodium spp) where the vector is
  the mosquito

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Categories of infection

• Local infection is one that is confined to one
  site without spreading
• Focal infection is an infection at a site from
  which microbes can spread to other sites
• Metastatic is an infection at a site that spread
  from a focal infection

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Categories of infection

• Primary is the first infection in a healthy host
  which predisposes the host to a secondary
  infection
• Secondary infection is one that immediately
  follows a primary one
• Superinfection is an infection that results from
  the destruction of some of your normal flora that
  allows the survivors to grow out of control

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Categories of infection

• Acute infection- is one with a rapid onset of
  symptoms
• Chronic infection is one with a slow lengthy
  course
• Latent infection is one which disappears and
  reappears over time
• Subclinical infection is one without any
  noticeable symptoms, also called covert or
  inapparent

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Categories

• Exogenous infection is caused by microbes
  normally not found on the host
• Endogenous infection is caused by microbes that
  are part of your normal flora
• Nosocomial infection develops due to a stay at a
  medical facility
• Iatrogenic infections (a sub group of nosocomial)
  results from a healthcare procedure

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Categories

• Opportunistic infection is one that does not harm
  a healthy host but takes advantage of an
  unhealthy one
• Systemic infection is one that spreads via the
  blood or lymph
• Bacteremia is the presence of microbes in the
  blood without growth
• Septicemia is the presence of microbes in the
  blood with growth

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Categories

• Toxemia is the presence of toxins or poisons in
  the blood
• Viremia is the presence of viruses in the blood
• Pyogenic infection is one accompanied by pus
• Pyrogenic infection is one accompanied by fever
• Terminal infection is one that leads to the
  patients death

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Disease

• When the pathogen overcomes the host defense
  system, the microorganism can damage the host by
• Using the hosts nutrients
• Direct damage in the immediate vicinity of the
  invasion
• By producing toxins transported by blood and
  lymph
• By producing hypersensitivity reactions

25
Disease

• The ability of an infection to cause disease is
  pathogenic
• The invasion or colonization of the body by
  pathogenic organisms is infection
• Disease is caused when infection results in any
  impairment of all or part of the bodys
  functioning

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Disease

• Opportunistic pathogens are organisms of your
  normal flora that are disease-causing when your
  resistance is compromised by other diseases
• Pathogenic organisms cause disease even in
  healthy individuals
• Avirulent microbes cultured outside the host have
  either a decreased or no ability to cause disease
• The degree of a pathogens ability to cause
  disease is called virulence which is determined
  by the microbes invasiveness and toxigenicity

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Pathogenicity

• In order to be pathogenic, the microbe must
• Enter the body at the preferred portal of entry
• Mucous membranes of the respiratory or
  gastrointestinal tract
• Skin- some microbes get through hair follicles,
  sweat gland ducts, hookworm larvae burrow through
  intact skin
• Parenterally- deposited into tissue beneath skin
  or into mucous membranes when barriers are
  penetrated or injured (punctures, bites, wounds,
  cuts, splitting of skin due to drying or swelling
  are all parenteral)
• Must be the proper infectious dose of microbes

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Pathogenicity

• Microbe must have a means to adhere to cells at
  the point of entry
• Attachment between pathogen and host occurs by
  adhesions or ligands binding specifically to
  complementary surface receptors. Most adhesions
  are glycoproteins or lipoproteins
• Microbe must be able to penetrate or evade hosts
  defenses
• Capsules impair phagocytosis

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Pathogenicity

• Microbe can then cause disease by directly
  damaging cells, by using toxins or causing a
  hypersensitivity reaction
• Once attached to the proper portal of entry,
  pathogens use enzymes to penetrate and invade
  hosts tissues
• Coagulases- coagulate the fibrinogen in blood
  (fibrinogen?fibrin) protects the bacterium from
  phagocytosis and isolates it from other defenses
  example boils produced by Staphylococci

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Pathogenicity

• Kinases- bacterial enzymes that breakdown fibrin
  (dissolves clots) formed by the body to isolate
  the infection Example streptokinase, a
  fibrinolysin produced by Streptococcus pyogens
  has successfully been used to dissolve clots that
  form in coronary arteries causing a heart attack
• Hyaluronidase-hydrolyses hyaluronic acid, a
  polysaccharide that holds body cells together
  particularly connective tissue cells. Digestion
  causes blackening of wounds and allows the
  microorganism to spread Example Clostridia gas
  gangrene

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Pathogenicity

• Collagenase- breaks down collagen, a protein that
  forms the connective tissue of muscle and other
  organs
• IgA proteases- (IgA is an antibody produced by
  host which defends against adherence) Proteases
  destroy these antibodies Examples include N
  gonorrhea and N menigitidis
• Toxins poisons used by bacteria that cause
  damage to the host
• Toxemia- toxins in the blood
• Intoxication ingesting the toxins

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Toxins

• Types of toxins
• Exotoxins are secreted by bacteria into the
  surrounding media or are released in cell lysis
• Proteins produced by gram /- bacteria
• Soluble in body fluids- diffuse into blood and
  are transported throughout the body
• Destroy parts of hosts cell or inhibit metabolic
  functioning
• Are one of the most highly lethal substances

33
Toxins

• Are disease specific
• Botulism (neurotoxin) due to ingestion of the
  exotoxin
• Food poisoning due to Staphylococcus aureus is an
  enterotoxin
• Both of these are intoxications not infections
• Exotoxins are inactivated by heat/chemical
  treatment and lose their toxicity and are known
  as toxoids
• Both toxins and toxoids stimulate the body to
  produce antibody against the toxin (antitoxins)
• Inject toxoids as a vaccine such as tetanus and
  diphtheria

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Toxins

• Endotoxins are part of the outer portion of the
  cell wall of gram negative bacteria
• The outer membrane portion (LPS), lipid A is the
  endotoxin
• Released when gram bacteria die and during
  bacterial multiplication
• Are heat stable so they do not produce toxoids
• Rarely fatal- responsible for fever, shock,
  miscarriage
• Activate blood-clotting proteins causing the
  formation of small blood clots

35
Lines of defense

• To prevent infection, there are three lines of
  defense that your body uses
• First line- non-specific- skin and mucous
  membranes
• Second line- non-specific- macrophages, fever,
  complement, interferon
• Third line- specific target specific organisms
  with the production of B (antibody-producing) and
  T (cellular response) cells

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What might decrease a persons defense against
disease?

• 1. stress, fatigue, anxiety, depression and sleep
  deprivation all contribute to adrenalin release
  which over time, will suppress your immune system
• 2. age- very young have poorly developed immune
  systems and very old have inefficient ones
• 3. poor nutrition
• 4. occupational hazards- health related fields

37
What causes people to have resistance?

• Species differences- most infectious agents
  infect only one species
• Racial differences (not your stereotypical
  ones)refers to isolated groups of people. When
  populations interact, risk of encountering new
  infection emerging infectious diseases
• Innate resistance of some while others get sick

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First line of defense

• Skin and mucous membranes that guard against all
  antigens
• Skin
• Normally impermeable to bacteria
• Sweat contains lysozyme which kills bacteria
• Dry skin is inhibitory to bacteria and fungi,
  moist skin provides a better growth medium
• Salts secreted on skin inhibits most except Staph
  epidermidis and Staph aureus

39
First line of defense

• Sebum secreted contains fatty acids which inhibit
  bacteria and fungi
• Normal flora (harmless) that live on your skin
  and mucous membranes protect you by competitive
  inhibition, stimulate immune system development
  and help produce vitamins B and K
• Organisms enter in hair follicles, sweat glands,
  sebaceous glands, cuts and abrasions
• Mucous membranes- mucous secreted by membranes
  traps microbes and prevents the lining from
  dehydration
• Mucous contains lysozymes which attack microbes

40
First line of defense

• Each area of the body has its own normal flora or
  other nonspecific mechanism to protect you
• Sterile areas of the body include
• The heart and associated vessels
• The liver, kidneys, bladder and lungs
• The CSF (brain and spinal cord)
• Muscles, bone and sinuses
• Glands
• Internal eye, middle and inner ear

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Defenses of the body and associated diseases

• The normal flora of the skin is S. epidermidis,
  C. albicans, M. luteus, Corynebacterium spp.
• Common infectious diseases
• Propionibacterium acnes- primary cause of acne in
  adolescents and young adults
• S. aureus- if it enters hair follicle results in
  folliculitis (pimple) can cause
  bacteremia/septicemia in scalded skin syndrome
  especially in infants

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• S. pyogenes- can cause scarlet fever- sore
  throat, fever and rash caused by the toxin, this
  can lead to rheumatic fever
• Impetigo can be caused by S. aureus or S.
  pyogenes, is a highly contagious, pus-producing
  skin infection
• Pseudomonas aeruginosa is a serious problem in
  burns patients
• Rubella or German measles causes a rash of small
  red spots/light fever
• during the first three months of pregnancy
  causes congenital rubella syndrome (35 chance
  of severe fetal damage including deafness, heart
  defects, mental retardation and even death MMR
  prevents the infection

43

• Measles (rubeola) accompanied by raised rash and
  fever
• Presence of Kopliks spots on oral mucosa (tiny
  red patches with white central specks) are a
  diagnostic indicator
• Can be complicated by middle ear infection or
  encephalitis
• MMR is 95 effective

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• Chicken pox caused by varicella zoster virus
• A herpes virus
• Highly contagious, vesicles are filled with pus,
  rupture then form scab before healing
• Virus may remain latent in the dorsal root
  ganglion near the spine and reoccur as a painful,
  itching skin infection known as shingles. This
  is a reactivation of the same virus now
  affecting the cutaneous sensory nerves of the skin

45

• Small pox or variola
• First disease to which immunity was artificially
  induced
• No animal host reservoirs
• Last individual to be infected was in Somalia in
  1977

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• Warts caused by the human papilloma virus
• Medical treatment is cryotherapy, electric
  current desiccation, or TCA (trichloroacetic
  acid)
• Some skin and cervical cancers are associated
  with HPV
• Current vaccine in trials to prevent cervical
  cancer

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• Ringworm- dermatomycoses or fungal infection
  which grows on keratin
• Tinia capitis is ringworm of the scalp, common in
  young school children
• Transmitted by fomites, dogs.cats
• Tinea cruris is jock itch
• Tinea pedis is athletes foot
• Tinea unguium is nail fungus
• Itraconazole is the Rx which requires weeks of
  therapy

48

• Gas gangrene caused by Clostridium perfringes an
  obligate anaerobe
• Ferment carbs producing gases that swell tissue
  and release toxins
• Surgical removal of necrotic tissue/amputation
  are most common medical treatment
• Prompt treatment of serious wounds and
  precautionary antibiotic therapy is most
  effective in prevention
• Responds to penicillin

49

• Cat scratch fever- caused by gram- aerobic
  bacterium, Bartonella henselae
• Transmitted to humans mostly by scratch or bite
• Initial sign is a papule at infection site
• Swelling of lymph nodes, fever and malaise follow
  in a few weeks
• May require antibiotic therapy

50
Mouth

• On and around teeth, there are more than 300
  species of microbes that have been identified
• Dental caries- the most important cariogenic
  (cavity-causing) is Streptococcus mutans (gram
  cocci) Attaches to teeth with dextran formed by
  hydrolyzing sugars in the mouth
• Bacteria dextran plaque
• Also, lactobacillus which ferment lactic acid
  which breaks down tooth enamel

51
Salivary glands

• Mumps are viral
• Target of the mumps virus are the parotid glands
• Characterized by swelling, fever and pain when
  swallowing
• May cause orchititis in males past puberty but
  sterility is rare
• Prevented with MMR immunization

52
Eyes

• Tears contain lysozyme and flush bacteria from
  the surface of the eye into nasolacrimal ducts
• Infectious eye diseases include
• Conjunctivitis pink eye a highly contagious
  inflammation of the conjunctiva caused by a wide
  variety of bacterial, viral and protozoal
  pathogens
• Increased incidence due to use of soft contact
  lenses worn for long periods of time
  (pseudomonads)

53
Eyes

• Haemophilis influenzae is the most common
  bacterial cause
• Viral conjunctivitis is usually caused by
  adenoviruses
• Neisseria gonorrheae (neonatal) is serious, often
  leading to blindness
• i silver nitrate has been replaced by
  antibiotics for newborns due to the fact that
  Chlamydia is often present with gonorrhea and
  does not respond to AgNO3

54
Eyes

• Trachoma caused by C. trachomatis
• Worldwide, it is the greatest single infectious
  agent causing preventable blindness
• 500 million cases worldwide with 7 million
  blinded
• Hand contact, sharing towels and flies can
  transmit this bacteria
• Leads to permanent scarring of the cornea

55
Respiratory tract

• Lower respiratory tract should contain NO normal
  flora
• Nose hairs and mucous in the nasopharynx which
  contains lysozyme traps bacteria before ti can
  enter lungs
• Ciliary escalator carries mucous upward
• S. epidermidis, alpha hemolytic streptococcus and
  sometimes Staph aureus are normally found in the
  upper respiratory tract

56
Respiratory tract

• Aerosol spread of infection of the respiratory
  tract can be from people sneezing, coughing,
  talking and laughing or from air conditioners,
  grocery mist sprayers and dental drills

57
Respiratory tract

• Whooping cough (Bordatella pertussis)
• Vaccination DTaP (acellular pertussis replaced P
  in 1996 with less side effects)
• Mucus accumulates because the cilia are damaged,
  patient is gasping for air between coughs which
  causes a whooping sound
• Coughing episodes may last up to 6 weeks
• In infants, irreversible brain damage may occur
  due to lack of oxygen
• Effectiveness of the vaccine is approx 12 years

58
Pharyngitis

• Strep throat (Streptococcus pyogenes) group a
  Beta- hemolytic
• Local inflammation and fever
• Lymph node swelling in neck
• Often accompanied by otitis media
• Penicillin effective
• 80 different serotypes so that immunity from one
  does not confer immunity to others

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Diphtheria

• Corynbacterium diphtheria, a gram non-endospore
  forming rod causes this
• Up to 1935, was the leading infectious killer of
  children in the U.S.
• Affects the upper respiratory tract with sore
  throat, fever, general malaise and neck swelling
• Characteristic gray membrane forms in the throat
  in response to the infection which can block the
  airway
• The D in DTaP is diphtheria toxoid

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Classic pneumonia

• Affects the lobes of the lung (lobar)
• Streptococcus pneumoniae, Staphlococcus aureus,
  Klebsiella pneumoniae
• High fever, difficulty breathing, chest pain
• Alveoli are filled with RBC, neutrophils and
  fluid
• Penicillin and fluoroquinolones are the drugs of
  choice
• Pneumonia vaccine from purified capsules of 23
  types is used for most susceptible (elderly)

61
Tuberculosis

• Consumption
• Commonly acquired by inhaling the bacillus
• Macrophages of healthy individuals become
  activated in the bacillus presence and are
  destroyed
• If infection progresses, host isolates the
  pathogens in a walled-off lesion, a tubercle,
  which shows up on X-rays

62
Tuberculosis

• If disease is arrested, the lesions will heal
• Of defenses fail, tubercle breaks down into the
  airways of the lung, CV system and lymphatic
  system
• Multiple drug regimen including rifampin
• Prolonged treatment is necessary, antibiotics
  only effective against growing cells (slow)

63
Tuberculosis

• Lack of patient compliance with medicine regimen
  has been the leading reason for the development
  of antibiotic resistant strains
• Mantoux test injects .1 ml of antigen, the
  reacting area of skin is measured, if , the
  patient undergoes chest x-ray
• BCG vaccine is live culture made avirulent by
  cultivation on artificial media

64
Tuberculosis

• In U.S. only recommended for children at high
  risk with negative skin tests
• Ineffective for adolescents and adults
• People who receive the vaccine will have skin
  tests

65
Legionnaires disease

• Legionellosis (Legionella pneumophila)
• 1976 identified a previously unknown bacteria,
  gram-, aerobic rod
• Characterized by high fever, cough, pneumonia
  symptoms
• Readily isolated from natural waters
• Grows in air conditioning cooling towers in
  hotels and hospitals
• Home sites include whirlpool spas, humidifiers
  and showers

66
Ornithosis

• Chlamydia psittaci
• Spread by contact with droppings and other
  exudates of fowl
• Fever, headache, chills
• Pet store employees/turkey farmers are at highest
  risk
• Parakeets and parrots sold commercially are
  usually disease-free

67
Influenza

• Classified into major groups according to antigen
  on their protein coat
• A type is responsible for pandemics
• B is responsible for geographically limited
  milder infections
• Strains are collected, analyzed and a decision is
  made concerning the composition of the vaccine
• Multivalent vaccine is aimed at several strains
  in circulation
• Viruses are grown in embryonic egg cultures
• Death from flu is usually due to a secondary
  bacterial infection

68
Common cold

• 50 caused by rhinoviruses
• 10-20 by coronaviruses
• 40 no known agent
• Accumulate immunities over lifetime
• Characteristics include sneezing, excessive nasal
  secretion and congestion

69
Otitis media

• Middle ear infection
• Pathogens cause the formation of pus which builds
  up pressure on the eardrum, painful and inflamed
• Frequent in children
• Pathogens which cause it are H. influenzae
  20-30, S. pneumoniae (35), S. pyogenes (8-10)
• Vaccine for S.pneumoniae intended to prevent
  pneumonia in children also lowers incidence of
  otitis media

70
Gastrointestinal tract

• Few bacteria in stomach due to high acid content
  (low pH1.5)
• Bacteria known as enteric
• Large 300 or gt of harmless, beneficial bacteria
  that keep pathogens in check and produce useful
  vitamins
• Large intestine has 1 x 109 bacteria /gram of
  feces which are mostly anaerobes or facultative
  anaerobes

71
Common infectious disease of the GI tract

• Viral enteritis rotavirus
• Most common cause of viral gastroenteritis
• 3 million cases annually in U.S.
• Incubate 2-3 days followed by low grade fever,
  diarrhea and vomiting
• Death in underdeveloped countries due to
  inadequate rehydration therapy
• Vaccine withdrawn over concerns with intestinal
  obstruction

72

• Food poisoning microbes (see earlier notes)
• Stomach ulcers
• Caused mainly by microaerophilic Helicobacter
  pylori (peptic ulcer disease)
• Also a carcinogenic bacteria (3 of cases)
• H. pylori can live in the highly acid stomach
  because it produces urease which converts urea
  into ammonia resulting in locally high pH where
  bacteria are growing

73
Hepatitis A?E

• A is a single stranded RNA which lacks an
  envelope
• Entrance is typically oral route and multiplies
  in the epithelial lining of the digestive tract
• Spreads to liver, kidney and spleen, shed in
  feces, detected in blood/urine
• Loss of apetite, malaise, nausea, diarrhea,
  fever, chills, abdominal discomfort
• Recovery grants lifelong immunity
• Inactivated vaccine recommended for travelers

74
Hepatitis B

• B is a double-stranded DNA
• Transmitted by blood transfusions, IDU, sexual
  activity and childbirth if birth mother is
• Serum of HBV patient has three distinct
  particles, largest of which is Dane particle, the
  complete virion
• Acute/chronic HBV 10 become chronic carriers
• Estimate that there are 2.5 million carriers in
  the U.S.

75
Hepatitis C

• Transfusion transmitted
• Enveloped, single stranded RNA
• 70-80 days between infection and detectable HCV
  antibodies
• Treatment with ribaviron/interferon therapy

76
Hepatitis D

• Must be infected with HBV
• Single strand RNA
• Higher incidence of liver damage, higher
  mortality rate than with only HBV infection
• Occurs in acute and chronic
• In acute, when HBV disappears so does HDV
• In chronic, superinfection with HDV with
  progressive liver damage

77
Hepatitis E

• Fecal-oral transmission
• Non-enveloped RNA virus
• HEV is endemic where sanitation is poor
• Does not cause liver disease but is responsible
  for a 20 mortality rare in infected pregnant
  women, reason is unknown

78
Urogenital tract

• Urine is sterile in kidneys, ureters, urinary
  bladder and the upper part of the urethra
• In females, after puberty, normal vaginal flora
  is primarily Lactobacillus acidophilus, Candida
  albicans, Enterococcus and Corynebacterium spp.
• From puberty to menopause, the pH of the vagina
  is 5
• Prepubescent and post menopausal pH 7 and the
  normal flora is Staphylococci and Streptococci

79
Common infections

• Cystitis- bladder infection and UTI
• 8X more common in females
• Most common are E coli, Staphylococcus
  saprophyticus and Proteus mirabilis
• Peurperal sepsis, a nosocomial infection begins
  in the uterus as a result of childbirth/abortion
• Cause is S. pyogenes which progresses to the
  abdominal cavity and then the blood

80
Urogenital infections

• Leptospirosis is passed to humans form
  domestic/wild animals
• Can cause severe kidney disease
• Spirochete Leptospira interrogans which are shed
  in the urine of the infected animal
• Pathogen enters through abrasions in skin and
  mucous membranes

81
Urogenital infections

• TSS or toxic shock syndrome
• Originally became known as a result of Staph
  aureus growth with the use of super absorbent
  tampon
• Toxin circulates in the bloodstream
• Trichomoniasis
• Caused by the anaerobic protozoan, T. vaginalis,
  frequently a normal inhabitant of the vagina in
  women and the urethra in males
• Overgrows when acid pH is disturbed
• Resulting discharge is profuse, greenish-yellow
  with a foul odor (irritation and itching)

82
Urogenital infections

• Gonorrhea
• Caused by the gram diplococci, Neisseria
  gonorrhoeae
• Greater than 60 of patients are 15-24 years old
• In males, painful urination and pus-containing
  discharge
• In females, cervix is infected, not vaginal walls
  so few women are aware of the infection, which
  may lead to PID
• Dangerous to infant passing through the birth
  canal (antibiotics for all newborns to prevent
  blindness)

83
Urogenital infections

• Syphilis
• Caused by gram spirochete, Treponema pallidum
• Transmitted through sexual contact
• Progresses in stages beginning with a painless
  chancre sore
• Secondary stage is characterized by skin rashes
• Latent period follows for 2-4 years

84

• Tertiary stage marked by lesions called gummas
• CV system is affected, aorta is weakened
• Congenital syphilis can be transmitted to fetus
  across the placental membrane
• NGU
• Any inflammation of the urethra not caused by N.
  gonorrhoeae
• Most common pathogen is Chlamydia trachomatis
  which often coinfects with gonorrhea

85

• It is also (Chlamydia) the most common sexually
  transmitted pathogen
• Increases risk of cervical cancer
• Symptoms in males often mild which can lead to
  epididymitis
• In females, usually asymptomatic and may cause
  sterility due to scarred fallopian tubes

86
Herpes simplex viruses

• Can be transmitted when no lesions or symptoms
  are apparent
• HSV1- causes fever blisters (cold sores)
• HSV2- causes genital herpes
• Both are lifelong latent viruses
• HSV1 can be triggered by sunlight, stress and
  resides in the trigeminal nerve
• HSV2 outbreaks triggered by stress, injury,
  menstruation and resides in sacral nerve ganglia
• 88 chance of recurrence

87
Herpes

• Can cause whitlows which are infections of the
  finger caused by HSV. Nurses, doctors and
  dentists are prone to these
• Herpes gladiatorum is caused by skin contact
  among wrestlers
• Ocular herpes is keratitis

88

• Mothers with genital herpes infections are
  recommended to have C section since it can be
  fatal to newborns
• Newborns should not be kissed on the lips
• Newborn nursery workers should not be at work
  with herpes lesions
• There is no cure for herpes
• Can only alleviate the symptoms with acyclovir or
  other cyclovir antiviral drugs
• OTC (Abreva) for HSV1 can shorten the duration of
  symptoms

89

• Genital warts
• HPV or human papilloma virus
• Greatest danger is the connection with cervical
  cancer (99)
• Cytomegalovirus
• Opportunistic pathogen in immunocompromised
  patients
• A large herpes virus, carried by 80 of U.S.
  population
• Shed in semen and breast milk
• Associated with AIDS

90
HIV

• A retrovirus which is a pair of single stranded
  RNAs, the enzyme reverse transcriptase, and an
  envelope of phospholipid
• Modes of transmission
• Blood with 1000-100,000 virus particles/ml
• Sexually transmitted in semen with 10-50 virus
  particles
• Lesions from viral and bacterial diseases
  facilitate its transmission
• Transmission requires transfer of /direct contact
  with infected body fluids
• Anal intercourse is the most dangerous for sexual
  transmission
• 20X more likely to be transmitted form male to
  female in vaginal intercourse

91
HIV

• Not transmitted by insects or casual contact
  including kissing
• Evades immune system by cell?cell fusion of
  infected to uninfected
• Latent virions may remain in vacuoles, infected
  cell becomes long-lived memory T cell
• Virus is either latent or provirus (hidden in the
  chromosome of host cell) reason why antibodies
  dont inhibit progressive disease
• Undergoes rapid antigenic changes so they have a
  high mutation rate

92
Screening for HIV

• Done by ELISA test (enzyme linked immunoabsorbent
  assay which detects the presence of antibodies
• Then Western blot test is done to confirm the HIV
  infection
• If antigen is present in serum, antibody will
  combine and be visible as a colored band on a
  filter (ELISA is reverse, uses antibody)
• You are initially infective during the incubation
  period before your B cells have produced antibody

93
HIV

• Viral load tests can be done to quantify by PCR
  (very costly)
• Red Cross has instituted PCR
• Progression of disease- track helper T cell
  counts (Normal counts are 800-1000/mm3
• Typically takes 10 years? AIDS (200/mm3)

94
HIV

• Category A may be asymptomatic or have persistent
  lymphadenopathy
• Category B persistent C.albicans infections,
  persistent diarrhea and fever
• Category C clinical AIDS- C albicans in bronchi,
  lungs, cytomegalovirus eye infections, TB, PCP,
  toxoplasmosis of the brain, Kaposis sarcoma
  (caused by herpes virus8)
• TB is the 1 cause of death in AIDS patients

95
HIV

• Other conditions associated with HIV are weight
  loss, poor nutrient absorption, night sweats,
  fatigue, memory loss and dementia
• Prevention
• Only 20 of babies born to HIV mothers are
  infected
• Treatment with protease inhibitors and reverse
  transcriptase inhibitors
• HAART- highly active antiretroviral therapy is
  used, a combination of drugs, complex schedule
  which must be strictly adhered to
• Some people have an innate resistance

96
STORCH

• A group of infections to which unborn and newborn
  children are susceptible
• S-syphilis
• T-toxoplasmosis
• O-other (N. gonorrhoeae, Listeria monocytogenes,
  Leptospira interrogans, C. albicans, B.
  burgdorferi, HIV, varicella-herpes zoster,
  cytomegalovius, HBV, and S. pyogenes)

97
STORCH

• R- Rubella
• C- Chlamydia
• H- Herpes

98
Second line of defense

• Primarily WBC that phagocytize any foreign
  antigen that penetrates the first line of defense
• Also non-specific
• To understand the WBC, see what makes up whole
  blood
• Blood is a suspension of cells in fluid
• Fluid is plasma if blood is unclotted and serum
  if blood has been allowed to clot

99
Blood

• Cellular elements include
• RBCs or erythrocytes 5-6 million/mm3, main job is
  to carry oxygen in respiratory pigment,
  hemoglobin
• Platelets or thrombocytes are fragments of cells
  that become sticky if vessel is injured which
  assists in the clotting mechanism
• WBC or leucocytes which can be granular or
  agranular

100
WBC

• Granular WBCs are
• Neutrophils which are phagocytic and proliferate
  in the early stages of disease, the most common
  circulating WBC
• Eosinophils which are weakly phagocytic, release
  enzymes. Increase in is mostly seen in
  parasitic/fungal infections and allergic
  reactions
• Basophils are not phagocytic but release
  histamine in immediate types of allergic reactions

101
WBC

• Agranulocytes
• Monocytes which are highly phagocytic
• When they leave blood vessels, are known as
  macrophages
• increases in later stages of infection
• Are the antigen-presenting cells in the third
  line of defense which is specific
• Lymphocytes are the third line of defense
• B and T cells

102
Other second lines of defense

• Fever- can occur without infection
• Phagocytic cells release pyrogens which reset the
  temperature in the hypothalamus
• Fever response inhibits pathogens growth,
  stimulates the immune system and phagocytosis but
  rarely kills it
• Inflammatory response is marked by redness, heat,
  swelling and pain
• Neutrophils are the first to arrive followed by
  macrophages which engulf and destroy antigen

103
Second line

• Interferon- anti-viral protein produced by the
  virus-infected cells to warn neighboring cells
  which in turn will produce anti-viral proteins to
  destroy viral genetic material
• Not virus specific
• Are species specific
• Stimulate the NKCs
• Natural killer cells are lymphocytes capable of
  destroying virus infected cells
• Can attack large parasites
• Not immunologically specific
• Lyse cell on contact
• Function is enhanced by interferon

104
Systemic infections of the human body

• Anthrax- (Bacillus anthracis)
• Endospores inhaled into lungs have a high
  probability of entering bloodstream
• Initially low fever, coughing, chest pain for
  first few days
• As bacteria enter the blood. Septic shock in 2-3
  days usually killing patient in 24-36 hours
• Disease can be arrested in initial phase with
  antibiotics if anthrax is suspected
• Vaccine is inactivated form of protective antigen
  toxin designed to prevent the edema and entry of
  lethal toxins into cells (six injections over 18
  months)

105
Systemic diseases

• Infectious mononucleosis
• Mononucleosis refers to the lymphocytes with
  unusual lobed nuclei in acute infections
• Caused by Epstein-Barr virus
• Infection delayed into young adulthood becomes
  symptomatic, peaks in U.S. in 15-25 year olds
• College populations have high incidence
• Recovery complete in a few weeks and immunity is
  permanent
• Route of infection is transfer of saliva
• Incubation period is 4-7 weeks
• No recommended therapy, rarely fatal if spleen is
  ruptured

106

• Toxoplasmosis
• Caused by toxoplasma gondii

107
Nervous system diseases

• Poliomyelitis- polio viruses
• When infection occurs in adolescence/early
  adulthood, paralytic form occurs more frequently
• Primary mode of transmission is ingestion of
  water contaminated with feces containing virus
• Replicates in throat and small intestine
• If viremia persists, virus penetrates capillary
  walls and enters CNS where it kills motor
  neurons, particularly upper spinal cord
• Incidence in U.S. down markedly
• 1954- Salk vaccine inactivated with formalin
• Replaced by Sabin (1963) oral which contains
  three living attenuated strains
• In 2000, CDC recommended Salk IPV for routine
  childhood immunization

108
Botulism

• Caused by C. botulinum
• Produces exotoxin, the most potent of natural
  toxins
• Neurotoxin blocks the release of acetylcholine
  needed for transmission of impulses across
  synapse
• Nausea but no fever may precede neurological
  symptoms
• Double /blurred vision , difficulty swallowing
• May die from respiratory or cardiac failure

109
Nervous system infectious diseases

• Rabies caused by the Lyssavirus
• Almost always results in fatal encephalitis
• Acquired from bite or even a lick where viruses
  can enter through minute scratches
• Incubation time is usually long enough to allow
  immunity to develop from post-exposure
  vaccination
• Virus multiplies in skeletal muscle and enters
  and travels along peripheral nerves to CNS where
  it causes the encephalitis average incubation is
  30-50 days
• When paralysis sets in, disease is almost always
  fatal within a few days

110
Nervous system infectious diseases

• Hansens disease or leprosy
• Caused by Mycobacterium leprae
• Only bacterium that grows in the peripheral
  nervous system
• Also grows in skin cells
• Optimum growth temperature is 30 degrees, prefers
  outer, cooler portions of the body
• The progressive form has considerable necrosis of
  tissue
• Can be made non-contagious within a few days with
  antibiotic

111
Nervous system infectious disease

• Tetanus or lock jaw
• Caused by Clostridium tetani
• Obligately anaerobic endospore forming gram
  rod, commonly found in soil
• Potent neurotoxin tetanospasmin
• The toxin blocks the relaxation pathway of the
  opposing muscle so that both sets contract
• Muscles of the jaw affected early
• Death results from spasm of respiratory muscles
• Tetanus vaccine is a toxoid

112
Nervous system infectious diseases

• Bacterial meningitis
• Haemophilis influenzae in children lt 5 years old
• H. influenzae is a normal throat microbe. If it
  enters the bloodstream, can cause several
  diseases
• Hib has a vaccine

113
Nervous system infectious diseases

• Neisseria meningitidis and Strep pneumoniae are
  more common in gt5 years old
• Neisseria meningitidis has a polysaccharide
  capsule
• Carriers are reservoirs for infection
• Begins with a throat infection ? bacteremia
  ?meningitis
• Vaccine used in military and required by many
  colleges for incoming freshmen
• Antibiotics given to patients contacts
• S. pnemoniae is a common inhabitant of the
  nose/throat
• Encapsulated
• Leading cause of bacterial meningitis
• Conjugated vaccine

114
Third line of defense

• Made up of B and T lymphocytes
• Both develop from stem cells in the bone marrow
• B cells mature in the bone marrow
• T cells mature in the thymus gland

115
Humoral or antibody-mediated immunity

• B cells are responsible for this
• Produce antibodies that are found in blood plasma
  , lymph fluid and mucous secretions
• Primarily effective against bacteria, bacterial
  toxins, and viruses
• Antibodies are made of protein
• Made in response to an antigen which it
  recognizes and binds to
• There are five classes of antibodies

116
Antibodies

• Each plays a different role in the immune
  response
• IgG or gamma globulin is the most abundant in
  serum
• Accounts for 80 of ab in blood serum
• Can cross the placenta and confer passive
  immunity to fetus
• Protects against circulating bacteria/viruses,
  neutralizes toxins, triggers complement and when
  bound to antigen, enhances phagocytic cell
  effectiveness

117
Antibodies

• IgM (macro)
• Is 5-10 of serum antibodies
• First to respond to initial exposure to antigen
• Responsible for response to ABO antigens in
  transfusion reactions
• IgA is 10-15 serum antibodies
• Most abundant in the body since its most common
  form is in mucous membranes and body secretions
  including tears, mucous, saliva, breast milk
• Probably prevents the attachment of pathogens to
  mucosal surfaces (respiratory pathogens)

118
Antibodies

• IgD .2 of total serum antibodies
• Found in blood and lymph and on B cell surface
• No known function in serum but acts as antigen
  receptors on B cell surface
• IgE .0002 of total serum antibodies
• Binds tightly to receptors on mast cells and
  basophils, cells which participate in allergic
  reactions
• When allergen reacts with IgE antibodies attached
  to mast cells/basophils, histamine is released
• Can be helpful (parasitic worms) or harmful
  (hayfever to anaphylactic shock)

119
Ways in which antibodies work

• Agglutination- cause antigens to clump together
• Aggregate of cells into clumps that are easier to
  ingest by phagocytes
• Opsonization- antigen is coated with antibodies
  that enhance its digestion and lysis by
  phagocytic cells
• Neutralization- (IgG) antibodies inactivate virus
  by blocking their attachment to host cell and
  neutralize bacterial toxins by blocking their
  active sites

120
Ways in which antibodies work

• Complement fixation- pair of antibody molecules
  attach to antigen forming an AgAb complex
• This binds to and activates C-1
• C-1 activates other complements C-4, C-2 and C-3
• C-3 fragments to initiate opsonization

121
Types of B cells

• Plasma cells
• Activated by antigen
• The B cell divides and differentiates into a
  clone of cells that produce antibody against one
  specific antigen
• Short-lived lt one week
• Undergo apoptosis or programmed cell death

122
B cells

• Memory cells
• Some activated B cells do not produce Ab
• Persist as long-lived memory cells
• Years later, when exposed to same Ag, will
  differentiate into Ab-producing plasma cells
• B cells reside in lymph nodes, spleen and other
  lymphoid tissue in the body (Peyers patches,
  tonsils, appendix)

123
Mechanisms to obtain antibodies

• Active immunity
• Long-lasting
• Takes several weeks
• Anamnestic, specific, tolerant
• Can be conferred by
• Actually getting the infection and recovering
• Vaccination

124
Vaccines

• Dead or weakened bacteria or viruses or weakened
  toxins
• Used to effect an antibody response (serum titer)
• Attenuated is better than killed or chemically
  inactivated because they are avirulent, mutated
  strains which possess the important surface
  antigens
• Vaccines usually begin at 2 months for baby
• Any passive antibodies from mother across
  placenta is gone by one month

125
Childhood vaccinations

• DTaP- diphtheria, tetanus, pertussis
• IPV or OP- inactivated polio vaccine or oral
  polio
• MMR- measles, mumps, rubella
• HepB- first dose is now given sometimes before
  baby leaves hospital
• HepA- certain states/regions for high risk
• Hib for Haemophilis influenzae

126
Childhood vaccinations

• Varicella- chicken pox
• PCV- pneumococcal conjugate vaccine
• Influenza- recommended annually for children lt6
  months with certain risk factors

127
Passive immunity

• Person gets antibody pre-made by donor
• Gives immediate protection
• Only temporary, there are no memory cells
• Gamma globulin shots used to provide passive
  immunity
• Two ways to achieve passive immunity include
• Trans-placental IgG or in colostrum (mothers
  milk) as IgA
• Receive antiserum (gamma globulins) or antitoxins
  (antibodies against toxin) made by other animals
  (human or horse)

128
Cellular immunity

• Refers to cell-mediated immunity based on the
  activity of T cells which mature in the thymus
• More effective against intracellular bacteria and
  viruses, fungi, protozoa and helminths
• Have antigen receptors
• Most numerous lymphocyte population in the body
• Bodys ability to make new T cells decreases with
  age beginning with adolescence

129
T cells

• Two subsets are CD4 and CD8
• CD4 includes helper T cells and delayed
  hypersensitivity T cells
• TH stimulate B cells to increase antibody
  production
• They are the favorite host of HIV
• First to arrive and begin rejection of grafted
  tissue transplants

130
T cells

• Delayed hypersensitivity T cells (TD) associated
  with allergic reactions such as poison ivy,
  contact dermatitis, cosmetic/chemical allergies
• TB skin test-protein component of bacteria
  injected into skin
• If recipient has/had TB infection, inflammatory
  reaction to injection will appear 1-2 days
• Later, typical of delayed hypersensitivity
  reactions
• Itchy, red, swollen skin in several hours ?days
  after exposure to allergen

131
T cells

• CD8 cells
• Tc cytotoxic T cells both anti-viral and
  anti-cancer
• After helper T cells, cytotoxic T cells take over
  the rejection of foreign transplanted tissue
• Binds to MHC antigen complex on cells surface
  releasing perforin which causes cell lysis
• Cancer cells may develop non-self antigen on
  surface which marks them for destruction
• Suppressor T cells (Ts) regulate the immune
  response by turning it off when antigen is no
  longer present

132
Third line

• Macrophages are considered necessary for the
  third line of defense because they act as the
  antigen-presenting cell for B/T lymphocytes
• Show B/T cells what they have phagocytized so
  lymphocytes can further attack antigens

133
Applications of third line of defense

• Vaccination programs-purposely expose person to
  antigen so that Ab are developed for any future
  exposure
• Herd immunity or herd health concept- vaccinate
  as many as possible which will reduce the chances
  of unvaccinated people being exposed to each