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Respiratory System
Infections
Chapter 24
Respiratory System Infections
Encompass enormous variety of illnesses
Trivial to fatal
Divided into infections of
Upper respiratory
Head and neck
Uncomfortable but generally not life threatening
Lower respiratory
Chest
More serious
Can be life-threatening
Particularly in the immunocompromised
Normal Flora
Nasal cavity, nasopharynx and pharynx colonized by
numerous bacteria
Other sites are sterile
Numerous classes of organisms are present from
aerobes to anaerobes
Conjunctiva commonly have no bacteria
Organisms that do invade are swept into the
nasolacrimal duct (tear duct) and nasopharynx
Streptococcal Pharyngitis
Symptoms
Characterized by
Difficulty swallowing
Fever
Red throat with pus patches
Enlarged tender lymph nodes
Localized to neck
Most patients recover uneventfully in approximately
a week
Streptococcal Pharyngitis
Causative Agent
–
Streptococcus pyogenes
Gram-positive
Coccus in chains
β hemolytic
Complete hemolysis of red
blood cells
Commonly referred to as
group A streptococcus
Due to group A
carbohydrate in cell wall
Basis for identification from
other organisms
Streptococcal Pharyngitis
Pathogenesis due to numerous virulence factors
Streptolysin
Protein G
Complications of infection can occur during acute
illness
Scarlet fever
Acute glomerulonephritis
Acute rheumatic fever
Treatment
Penicillin is antibiotic of choice
Common Cold
Symptoms
Malaise
Scratchy mild sore throat
Runny nose
Cough and hoarsness
Nasal secretion
Initially profuse and watery
Later, thick and purulent
No fever
Unless complicated with secondary infection
Symptoms disappear in about a week
Common Cold
Causative Agent
30% to 50% caused by
rhinoviruses
More than 100 serotypes of
rhinoviruses
Non-enveloped
Single-stranded RNA genome
Common Cold
Pathogenesis
Virus attach to specific receptors on respiratory epithelial
cells and multiply in cells
Large number of viruses released from infected cells
Injured cells cause inflammation which stimulates profuse
nasal secretion, sneezing and tissue swelling
Infection is halted by inflammatory response, interferon
release, and immune response
Infection can extend to ears, sinuses and lower
respiratory tract before stopping
Treatment is supportive with OTC medications
Whooping Cough
Aka: Pertussis
Symptoms
Runny nose followed by bouts of uncontrollable
coughing
Termed paroxymal coughing
Severe cough can cause rupture of small blood vessels in the
eyes
Coughing spasm followed by characteristic “whoop”
Sound made by the forceful inspiration of air
Vomiting and seizure may occur
Whooping Cough
Causative Agent
–
Bordetella pertussis
Small
Encapsulated
Strictly aerobic
Gram-negative
Bacillus
Does not survive long
periods outside the host
Whooping Cough
Pathogenesis
Enters respiratory tract with inspired air and attaches
to ciliated cells
Organism colonizes structures of the upper and lower
respiratory tract
Mucus secretion increases which causes ciliary action
to decrease
Cough reflex is only mechanism for clearing
secretions
Whooping Cough
Video on web page
Whooping Cough
Pathogenesis
–
B. pertussis produces numerous
toxic products
Pertussis toxin - A-B toxin
B portion attaches to cell surface
A portion enters cell and inactivates
regulation of cAMP
Causes increased mucus
formation
Decreases phagocytic killing
Invasive adenylate cyclase
Increases production of cAMP
Increased mucus formation
Whooping Cough
Epidemiology
Spreads via infected respiratory droplets
Most infectious during runny nose period
Number of organisms decrease with onset of
cough
Classically disease of infants
Milder forms are seen in older children and adults
Often overlooked a persistent cold
Fosters transmission
Whooping Cough
Prevention
Vaccine directed at protection of infants
Prevents disease in 70% of individuals
Pertussis vaccine combined with diphtheria and tetanus
toxoids (DPT)
Injections given at 6 weeks, 4, 6,and 18 months, 5 years,
and now recommended for 12 year olds
Treatment
Erythromycin is effective at reducing symptoms if
given early
Tuberculosis
Causative Agent
Symptoms
Chronic illness
Mycobacterium tuberculosis (and M.
bovis in AIDS)
Symptoms include
Gram-positive cell wall
Slight fever with night sweatsSlender bacillus
Progressive weight loss
Chronic productive cough
Acid fast due to mycolic acid in cell
wall
Slow growing
Sputum often blood streaked
Generation time 12 hours or more
Resists most prevention methods of
control
Tuberculosis
Pathogenesis
Usually contracted by inhalation of airborne organisms
Bacteria are taken up by pulmonary macrophages in
the lungs
Resists destruction within phagocyte
Organism prevents the fusion of phagosome with
lysosomes; allows multiplication in protected vacuole
Tuberculosis
Pathogenesis
Organisms are carried to lymph nodes
About 2 weeks post infection intense immune reaction
occurs
Macrophages fuse together to make large
multinucleated cell
Macrophages and lymphocytes surround large cell
and form a tubercle of connective tissue
This is an effort to wall off infected tissue
Activated macrophages release into infected tissue
Causes death of tissue resulting in formation of
“cheesy” material (biofilm)
Tuberculosis
Epidemiology
Estimated 10 million
Americans infected
Rate highest among nonwhite, elderly, immigrant poor
people
Small infecting dose
As little as ten inhaled
organisms
Factors important in
transmission
Frequency of coughing,
adequacy of ventilation,
degree of crowding
Tuberculosis
Epidemiology
Tuberculin skin test used to
detect those infected
Small amount of tuberculosis
antigen is injected under the
skin
Injection site becomes red and
firm if infected
Positive test does not indicate
active disease
Tuberculosis
Prevention
Treatment
Vaccination for tuberculosis Antibiotic treatment is given in cases of active
widely used in many parts tuberculosis
of the world
Two or more medications are given together to
reduce potential antimicrobial resistance
Vaccine known as Bacillus
of Calmette and Guérin
Antimicrobials include Rifampin and Isoniazid
(INH)
BCG derived from
Mycobacterium bovis
Gives weak, partial
immunity against
tuberculosis
Both target actively growing organisms
and metabolically inactive intracellular
organisms
Therapy is pronged, lasting at least 6 months
Vaccine not given in United Multi-drug resistant strains have
States because it
arisen in the U. S. and Russia that
eliminates use of tuberculin
have spread to other countries
test as diagnostic tool
Seasonal Influenza
Symptoms
Influenza Type A
Short incubation period
Averaging 2 days
Headache
Fever
Muscle pain
Dry cough
Acute symptoms abate within a week
Cough, fatigue and generalized weakness may linger
Seasonal Influenza
Causative Agents
Influenza A virus
Belong to orthomyxovirus
Single-stranded RNA genome
Genome divided into 8 gene segments
Spiked envelope
H spike – hemagglutinin (subtypes H1-H16)
Aids in attachment
Only H1, H2 and H3 viruses circulate in humans
N spikes – neuraminidase (subtypes N1-N9)
Cleaves H protein to allow fusion of viral and cellular
membranes (i.e., entry into the cell)
Requires cellular enzyme trypsin to facilitate infection
Influenza B & C viruses only circulate in humans
Influenza A Transmission Cycle
Adaptation/
reassortment
with swine
influenza viruses
Circulates with
limited pathology
Transmission to
domestic fowl
Transmission
to humans
Pathogenesis
Seasonal Influenza
Acquired through inhalation of infected respiratory secretions
Virus attaches to host cells via hemagglutinin spikes
Once attached viral envelope fuses with host membrane, leading to viral
replication within the cell
Mature viruses bud from host cell
Budding allows mature virus to pick up envelope
Infected cells die and slough off
Host immunity quickly controls viral spread
Anti-HA neutralizing IgG is protective
Mortality rate is low
However, hundreds of thousands or millions of people are infected each year in
the U. S.
On average, about 30,000 Americans, mostly elderly and very young children,
die from influenza each year
Seasonal Influenza
Epidemiology
Outbreaks occur in United States every year
Vaccines are formulated months in advance using
prominent circulating strains
2010-2011 vaccine strains
Type / Geographic origin / Strain/ Year isolated (H & N genes)
A/California/7/2009 (H1N1)-like (the same strain as was used
for 2009 H1N1 monovalent vaccines)
A/Perth/16/2009 (H3N2)-like
B/Brisbane/60/2008-like
Pandemics occur periodically
Most famous pandemic of 1918 (Spanish flu)
Spanned the globe in 9 months
Pandemics have higher than normal morbidity
Seasonal Influenza
Epidemiology
Spread caused by major
antigenic changes
Antigenic drift
Consists of amino acid changes
in spikes (point mutations)
Particularly hemagglutinin
Antigenic shift
Represent more dramatic changes
Virus strains are drastically antigenically
different from previous strains, importantly
in the hemagglutinin
Changes minimize effectiveness New virus comes from genetic reof immunity to previous strains
assortment
Ensures enough susceptible
people are available for
continued virus survival
Occurs when two different viruses
infect a cell at the same time
Genetic mixing results in new virus
that is often more virulent
Seasonal Influenza
Seasonal Influenza
Prevention and Treatment
Vaccine can be 80% to 90% effective
New vaccine required every year
Due to antigenic drift
Antiviral medications are 70% to 90% effective
Include amantadine, rimantadine, and Tamiflu
Must be taken early
Not a substitute for vaccine
Avian Influenza
There are hundreds, if not thousands, of influenza A
viruses circulating in nature
Seasonal influenza occurs from mammalian viruses
Pigs in SE Asia are frequently a source of these
viruses
New reassortants arise every year, but most are not
pathogenic to humans
Avian influenza viruses routinely circulate among wild
birds
Some species can be infected without conspicuous
pathology
These species often carry the viruses along migratory
routes, exposing other birds
Avian Influenza
Most avian influenza viruses are highly inefficient at
infecting humans
However, some cultures have domestic birds and pigs in
close periodomestic proximity
This practice increases the chance of
Reassortment with mammalian influenza viruses
1957, 1967 pandemic strains were reasortant mammalian
viruses with avian segments (antigenic shift)
Emergence of mutant avian strains that can infect
humans
1918 pandemic strain was an avian virus that adapted to
efficient human to human transmission (antigenic drift)
Avian Influenza
Rescue of the 1918 pandemic strain
Virology did not exist in 1918
The virus could not be isolated, thus went extinct
when the pandemic ended
In 2005 a group resurrected the 1918 strain from
bodies buried in Alaskan permafrost
Viral genome sequencing indicated it was an avian
influenza A virus
It was also infectious...
Avian Influenza
Tumpey et al.,
310:77. 2005
Lungs from Mice Infected with Rescued 1918 H1N1 Pandemic Virus
1918 Strain
1918 Strain
1918 Strain with
Texas 1991 H
segment
1918 Strain
1918
Strain(HN)/Texas
1991 Strain hybrid
Texas 1991
strain (control)
Avian Influenza
Feature
SI1
H5N1 AI2
1918 H1N13
Transmission efficiency
High
Very low/none
High
Replication site
Upper and lower
respiratory tract
Lower RT only
Likely upper &
lower RT
Viral CPE4
Limited
Substantial
Substantial
Immunopathology
Limited
Substantial
Substantial
Kills embyronated chicken eggs?
No
Yes
Yes
Requires trypsin for infection of
cell cultures?
Yes
No
No
Vaccine
Yes
No
N/A
Fatality rate
0.03% (U.S.)
57% (global)
About 1-2% (U.S)
Demographic
Young children,
elderly
Young adults
Young adults
1 Seasonal
influenza
2 Currently circulating H5N1 avian influenza virus
3 Rescued 1918 pandemic H1N1 avian influenza virus
4 Cytopathic effect (damage directly caused by the virus)
Red - more pathogenic feature
Green - less pathogenic feature
Hantavirus (Cardio)Pulmonary Syndrome
Symptoms
Early symptoms
Causative Agents
Hantaviruses
Fever
Includes Sin Nombre virus found in
initial outbreak
Muscle ache
Especially in the lower back
Nausea and vomiting
Diarrhea
Later symptoms
Unproductive cough
Belong to bunyavirus family
Single-stranded RNA genome
Divided into 3 segments
Enveloped
Causes apathogenic, lifetime infection in
rodent hosts
Increasing shortness of breath Death in humans is caused by cardiac
failure from severe hypotension
Capillary leak syndrome in lungs
Shock and death
Hantavirus Pulmonary Syndrome
Pathogenesis
Enters body via inhalation of dust contaminated with
urine, feces and saliva of infected rodents
Viremia
Mechanism unknown
Carried throughout body
Infects capillary endothelial cells
Inflammation causes capillaries to leak fluid into lungs
Causes hypoxia and hypotension
Cardiac shock and death occurs in over 36% of patients
Hantavirus Pulmonary Syndrome
Hantavirus disease is a T cell cytokine-mediated
immunopathology
TNF
IFNγ
Normal
Hantavirus Infection
Interleukin-1
Interleukin-2
Lymphotoxin
Proinflammatory
cytokines
•Immune cell infiltrates
•No viral damage to the lung epithelium
Hantavirus Pulmonary Syndrome
Epidemiology
Emerging disease due to recent
discovery
Most cases in United States occur
west of Mississippi River
Principally caused by Sin Nombre virus
Deer mice (Peromyscus maniculatus)
are the reservoir
Outbreaks causality with increase
rodent populations
Many, if not all, infected deer mice
become persistently infected
Person-to-person transmission does
not occur
Notable exception: Andes hantavirus in
South America (Argentina, Chile)
Hantavirus Pulmonary Syndrome
Prevention and Treatment
Prevention is directed towards minimizing
exposure
Keep pet and human food in containers
Maximal ventilation when cleaning mouse droppings
Mop with disinfectant
NEVER use brooms or vacuums
Wear N-100 HEPA-filtered mask
Lethal traps and poisons to decrease rodent
population
No effective antiviral treatment (nor would it
work anyway)
Treatment limited to supportive care
Extracorporeal membrane oxygenation (ECMO)