Study Aid

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Study Aid

• Microbiology Dr. Felton Part 1

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Viruses Assoc. W/ Common Cold

• More than 90 of URT infxns caused by viruses.
• 1) Rhinovirus
• 2) Coronavirus
• 3) Parainfluenza virus
• 4) Influenza virus
• 5) Respiratory Syncitial virus (RSV)
• 6) Adenovirus

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Rhinovirus

• 30 of colds in adults
• Small RNA viruses related to poliovirus
• Members of picornavirus
• Grow optimally at 33 degrees
• Virus multiplies in cytoplasm of host
• No Envelope

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Coronavirus

• ssRNA
• Round or petal shaped projections around capsid
  resembling a crown
• Lipid envelope

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Respiratory syncitial virus

• RNA
• Envelope
• 2 Antigenic types
• Infects infants children more often than it
  does adults
• Occasionally causes bronchopneumonia, bronchitis
• Belongs to paramyxovirus group

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Myxoviruses

• Orthomyxoviruses
• Influenza virus
• All 3 antigenic types cause influenza
• Mild illness that resembles colds can also result

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Myxoviruses

• Paramyxoviruses
• Parainfluenza virus
• 4 Antigenic types
• ssRNA
• Enveloped
• Major cause of viral laryngitis pharyngitis in
  adults
• PaRaMyxovirus Parainfluenza
  RSV Mumps, Measles

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Adenovirus

• Military recruits

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Transmission of viruses that cause common colds

• Main source? young children
• Spread? mostly in home school
• Modes? Infectious secretions on skin
• Large particles of respiratory secretions
• Infectious droplet nuclei suspended in air

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Clinical characteristics of common cold

• Incubation period 48-72 hrs
• Sx. Run 5-7 days
• Complications are rare

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Diagnosis of common cold

• Pt. Self dx. Usually correct
• No way of differentiating etiology of cold

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Treatment of common cold

• Relief of sx.

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Sinusitis

• Inflammation of one or more of paranasal sinuses
• Frontal
• Ethmoidal
• Sphenoidal
• Maxillary

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Sinusitis

• Acute sinusitis most often follows rhinitis
  (viral)
• Most common bacterial Strep Pneumoniae,
  Haemophilus Influenza
• Anaerobes, S. Aureus, S. Pyogenes also cause it
• Chronic sinusitis commonly assoc. with Anaerobic
  bacteria
• Infxn. Of Maxillary sinuses may follow dental
  extractions

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Pathogenesis of sinusitis

• Obstruction impedes drainage
• Mucus converted into mucopus by bacterial
  multiplication in sinus cavities
• Pus also irritates underlying mucosa ? further
  edema aggravating obstruction

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Epidemiology of sinusitis

• 0.5 of URT infxns. are complicated by acute
  sinusitis
• Sinusitis most prevalent in fall, winter, spring
• Summer ? swimming
• More common in adults than children

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Clinical Manifestations of sinusitis

• Pressure over a sinus? acute sinusitis
• Facial pain purulent nasal discharge most
  constant
• Photophobia tearing may be present

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Diagnosis of sinusitis

• Can be made w/o radiographic exam w/ history of
  URT infxn or allergic rhinitis
• Pain and tenderness over sinus
• Purulent discharge in the corresponding meatus
• Specific etiology only w/ culture of exudate, or
  of a rinse by sinus puncture aspiration
• Cultures from nasal pus or rinsing of nose
  unreliable

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Treatment of sinusitis

• In most pt. Acute sinusitis responds well to
  antimicrobial therapy

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Pharyngitis

• Mostly viral
• Caused by both viral bacterial
• Bacterial (15-30) Mostly Strep.
  Pyogenes
• Viral Impt. To differentiate btwn. Viral Bac.
• Strep. Pyogenes can cause Rheumatic Fever, Acute
  Glomerulonephritis
• Viral Rhinovirus
  Coronavirus Adenovirus Herpes
  simplex
• Adenovirus and Herpes simplex are less common but
  more serious

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Epidemiology of pharyngitis

• Mostly winter months
• Some with annual periods of peak prevalence?
  Rhinovirus
• Reservoir in humans

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Clinical Presentation Pharyngitis w/ common cold

• Mild to moderate pharyngitis discomfort
  frequently present, but not primary complaint
• Pharynx maybe normal or mild erythema or edema
• Rhinorrhea post-nasal discharge usually present
• NO pharyngeal pain!
• NO dysphagia!
• Subsides 3-4 days

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Pharyngitis w/ Influenza

• Sore throat major complaint
• Coryza (catarrhal inflamm.) sx. May be present
• Temp. elevation common
• NO Edema!
• NO Erythema!
• NO pharyngeal exudate!
• NO painful cervical adenopathy!
• Subsides 3-4 days

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Pharyngoconjunctival Fever

• Commonly caused by adenoviruses
• More severe than pharyngitis assoc. with common
  cold
• Temp. elevation 5-6 days
• Sore throat
• Conjunctivitis (adenoviral) 1/3 cases.
  Follicular, bilateral
• Cough, hoarseness, substernal pain occurs in
  acute resp. disease in military recruits

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Adenovirus

• DNA
• Causes 3 types of resp. disease
• 1) Acute Febrile (self-limited)
• 2) Pharyngoconjunctival
• 3) Pertussis-like syndrome, indistinguishable
  from infx. W/ Bordetella Pertussis (whooping
  cough)
• Major etiologic agent of acute resp. disease and
  pharyngitis

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Acute Herpetic Pharyngits

• Primary infxn.w/ herpes simplex
• Presence of inflamm. exudate may mimic
  full-blown Strep. Pharyngitis
• Vesicles shallow ulcers of the palate are
  characteristic of herpetic infxn.
• Vesciles ulcers are present on the labial
  buccal mucosa when there is an associated
  gingivostomatitis

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HSV

• DNA
• Latent infxns.
• Recurrent fever blisters
• Lipid containing capsids inactivated by Ether!

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Herpangina

• Uncommon type of pharyngitis
• Coxsackieviruses
• Small vesicles on soft palate, uvula, ant.
  Tonsillar pillars
• Children severe, febrile illness w/ marked sore
  throat dysphagia

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Coxsackieviruses

• Member of picornaviruses
• Causes
• Aseptic Meningitis
• Myocarditis
• URT infxns.
• Picornaviruses (PERCH)
• Poliovirus
• Echovirus
• Rhinovirus
• Coxsackievirus
• Hepatitis A

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Infectious Mono.

• EB virus (Herpesvirus family)
• dsDNA
• Fever
• Cervical adenopathy
• Splenomegaly, ½ cases

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Streptococcal Pharyngitis

• Pharyngeal pain
• Dysphagia
• 39.4 degrees or greater temp.
• Fiery red pharyngeal membrane, thick exudate
  covers the post. Pharynx and tonsillar area
• Tender, enlarged cervical nodes
• Strep. Pyogenes? Erythematous rash of scarlet
  fever

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Anaerobic Pharyngitis

• Purulent exudate coats the membrane
• Foul odor of breath
• Abscess
• Pharyngeal pain severe
• Dysphagia
• Low grade fever
• Usually limited to one side
• When bilateral, partial obstruction of pharynx
  occurs

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Gonococcal Pharyngitis

• Mostly asymptomatic

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Diphtheria

• NO pharyngeal discomfort!
• Low grade temp. elevation

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Mycoplasma Pneumonia

• Mild
• No distinguishing clinical features
• Characteristically causes
• Bronchitis
• Atypical Pneumonia

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Diagnosis of Pharyngitis

• Main goal Separate strep. Pharyngitis from
  others.
• Exudate may suggest Strep. Pharyngitis, Vincents
  Angina, Pharyngoconjunctival fever, herpes
  simplex, infectious mono
• Small vesicles or ulcers suggests herepes simplex
  infection or herpangina

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Diagnosis of Pharyngitis

• Neisseria Gonorrheae? Thayer Martin Agar
• Vincents Angina? Crystal Violet stained smear
• Diphtheria? Loefflers medium
• Infectious Mono? Specific serological tests

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Laryngitis, Epiglottitis, Laryngotracheobronchitis

• Acute inflammatory diseases of the upper airway
• Common hazard? obstruction of airway
• Grave in the very young

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Etiology

• Bacteria viruses
• Individually or combination

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Haemophilus Influenza

• Small, pleomorphic, Gram neg. rod
• Non-motile, non-sporulating, capsualted
• Aerobic or facultative
• Requires iron prtoporphyrin compound (X factor),
  pyridine nucleotide (V factor)
• Virulence assoc. with capsulation
• Six antigenic types (a ? f)
• Type b formerly acctd. for almost all serious
  infections in humans
• Intro of vaccine reduced frequency in young
  children

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Haemophilus Influenza

• HaEMOPhilus
• Epiglottitis Felton relavent
• Meningitis
• Otitis Media
• Pneumonia Felton relavent

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Corynebacterium Diphtheria

• Larynx and pharynx classical sites for
  localization of diphtheria infections

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Bordetella Pertussis

• Whooping cough special kind of bronchitis
  primarily in un-immunized children
• Small, ovoid, non-motile, non-sporeforming
• Gram Negative rod
• Fastidious requirement for growth
• Freshly isolated in phase I, virulent,
  encapsulated, piliated, produces several toxins
• Only phase I bacilli are suitable for prep. Of
  vaccines

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Strep. Pneumonia

• Major cause of bac. Pneumonia in adults and
  children
• Frequently recovered from sputum of pts. W/
  chronic bronchitis

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Parainfluenza Viruses

• Paramyxoviruses w/ binding sites for erythrocytes
• RNA core, Ether sensitive envelope
• Multiply in cytoplasm
• 4 types 1,2,3,4
• Types 1,2,3? Croup
• Types 1,3? Bronchitis, bronchopneumonia
• Types 1,3,4? Common cold, pharyngitis

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Influenza Viruses

• Typically cause lower resp. tract infxns both in
  adults and children

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Respiratory syncitial virus

• Can cause croup
• Usually causes bronchiolitis or bronchopneumonia
  in infants

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Acute Laryngitis

• Typically assoc. with common cold and influenzal
  syndrome
• Barking cough, hoarseness characteristic
  complaints
• Airway obstruction due to infxn of larynx and
  tracheobronchial tree more common in young
  children than in adults

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Diagnosis of acute laryngitis

• Clinical characteristics of illness
• Confirmed with exam of larynx

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Treatment of acute laryngitis

• Resting voice until hoarseness and aphonia have
  subsided
• Inhalation of moistened air (relief)
• No evidence of antimicrobial agents being useful!

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Epiglottitis

• Rapidly progressive cellulitis of epiglottis
  adjacent structures
• Frequency decreased dramatically since intro of
  vaccine against Haemophilus influenza type b

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Clinical Manifestations of epiglottitis

• Typical pt. 2-4 y.o.
• 6-12 hr. history of fever dysphagia
• Sore throat most prominent sx in older children
  and adults

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Diagnosis of epiglottitis

• Edematous cherry red epiglottis
• Lab leukocytosis, positive cultures of blood and
  epiglottis evidence of pneumonia on CXR
• Hib isolated in most pt.
• Hib occurs in up to 100 children w/ epiglottitis

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Treatment of epiglottitis

• Maintenance of adequate airway
• Control of infxn
• Blood epiglottis should be cultured, pt. should
  begin IV antibiotic therapy against Hib

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Immunity to epiglottitis

• Episode of Hib epiglottitis usually results in
  high levels of serum Ab to capsular polysacch.
• 2nd cases of epiglottits extremely rare!
• Vaccine against Hib available!

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Croup

• Age specific viral infxn of upper lower resp.
  tract.
• Inflammation in subglottis area
• Dyspnea on inspiration
• Characteristic stridulous notes of croup

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Etiology of croup

• Variety of viral agents
• Occasionally Mycoplasma pneumonia
• Parainfluenza Type 1 - most common
• Parainfluenza Type 3 - 2nd most common
• Influenza A ? broader range of children with a
  higher frequency of hospitalization tracheotomy.

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Epidemiology of croup

• Occurs mostly in children btwn. Ages 3 months 3
  years
• Peak 2nd yr of life
• More common among boys than girls

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Clinical Manifestations of croup

• Hoarseness, deepening, non-productive,
  brassy-tone cough
• Most children fever
• Resp. rate elevated
• Hallmark fluctuating course

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Diagnosis of croup

• Characteristic clinical picture
• Id of viral agent isolation in tissue culture
  by one of the newer techniques

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Acute Bronchitis

• Inflammatory condition of tracheobronchial tree
• Usually assoc. w/ generalized resp. infxn.
• Most commonly - winter

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Etiology of acute bronchitis

• Common during influenza epidemics
• Rhinoviruses important cause
• Military recruits Adenovirus major cause
• Measles virus severe form of disease
• Mycoplasma pneumonia B. Pertussis nonviral
  causes of severe acute bronchitis

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Clinical Manifestations of acute bronchitis

• Cough begins early, prominent as illness
  progresses
• Frequency duration of cough prolonged in cig.
  Smokers
• Adults Influenza virus, Adenovirus, M.
  Pneumonia temp. elevation

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Diagnosis of acute bronchitis

• A diagnosis of exclusion
• Complete history info on exposure to toxic
  substances and cigarette use

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Treatment of acute bronchitis

• Symptoms

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Chronic Bronchitis

• Cough chronic, excessive secretion of mucus is
  present in the tracheobronchial tree not due to
  asthma or TB.
• It is a clinical diagnosis!
• Coughed sputum 3 consecutive months for more
  than 2 successive years

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Etiology of chronic bronchitis

• Causes not elucidated completely
• 3 factors important
• Cigarette smoking
• Infxn
• Inhalation of dust or fumes

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Epidemiology of chronic bronchitis

• 10-25 adults
• More common in men
• More common 40 y.o.
• Recurrent resp. infxns and persistent chronic
  bronchitis might signal presence of
  immunodeficiency

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Clinical Manifestations of chronic bronchitis

• Incessant cough
• Emphysema often present
• Pt. Tend to be obese!

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Relationship of chronic bronchitis to Bac. Infxn.

• Bac. Infxn does not appear to initiate disease.
• Bac. Significant in penetrating disease
• Pathogenic bac. Cultured in 82 pts.
• Chronic colonization of airways sputum w/
  unencapsulated strains of H. Influenza or w/
  pneumococci occurs in at least ½ of affected pts.
• 25-50 acute exacerbations related to viral agents

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Bronchiolitis

• Acute lower resp. illness
• Viral
• Occur w/in 1st 2yrs of life

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Etiology of bronchiolitis

• Viruses
• Occasionally M. Pneumonia
• 87 of isolates
• RSV, Parainfluenza 13
• Adenoviruses
• Rhinoviruses
• M. Pneumonia
• In hospitalized cases, RSV even higher

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Epidemiology of bronchiolitis

• Definite seasonal pattern
• Mirrors pattern of RSV
• Peak attack rate 2-10 mths age
• Significant levels of hospital admission of
  infants within 1st year of life esp. due to RSV

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Clinical Manifestations of bronchiolitis

• Coryza, cough herald onset
• Mild fever common
• Dehydration common from paroxysms of coughing,
  may trigger vomiting
• Acute course 3-7 days

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Diagnosis of bronchiolitis

• Clinical and epidemiologic findings
• Specific dx. - Viral isolation from a nasal wash

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Therapy of bronchiolitis

• Oxygen admin
• Supportive care
• Aerosolized ribavirin severe bronchiolitis due
  to RSV
• NO vaccine available!

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Influenza

• Acute, febrile disease
• Fever, malaise, headache, myalgia
• Uncomplicated case self limited
• Affected individuals recover completely within
  a week

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Etiology of Influenza

• 3 Serotypes A, B, C
• Influenza A Pandemic Influenza
• Influenza B Localized epidemics
• Influenza C Sporadic Mild
• Pandemic An epidemic so widely spread that vast
  numbers of people in different countries are
  affected.

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Morphologic Characteristics of Influenza

• Enveloped virus
• Irregular shape
• Segmented genome w/ 8 pieces RNA
• 8 RNA? 8 mRNA? 8 proteins (structure)
• Surface projections or spikes
• Glycoproteins ?hemagglutinins (H) or
  neuraminidases (N) -
• determine antigenic subtypes of influenza
  virus

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Hemagglutinins (HA)

• HA spike site of attachment of virus to host
  cells to initiate infxn
• HA one of major antigens of virus
• HA contains common (to subtypes) strain
  specific antigens
• HA Most frequently involved in antigenic
  variation
• Specific Ab to HA prevent initiation of infxn or
  hemagglutination

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Neuraminidase (NA)

• Other important antigen of virus
• Contains antigens common to each subtype and
  variation within a subtype

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Epidemiology of Influenza

• Antigenic variation
• Ability to change surface antigens
• Frequent w/ Influenza A
• Less frequent w/ Influenza B
• Not assoc. w/ Influenza C
• Involves only HA NA
• HA most important
• Antigenic variation? Antigenic drift or Antigenic
  shift

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Antigenic Drift

• Minor changes frequently occur within an
  influenza subtype
• Every year or every few years
• HA H1,H2,H3
• NA N1, N2
• Antigenic drift results from mutation(s)
  affecting the RNA segment coding for either HA or
  NA, more commonly HA

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Antigenic Shift

• Herald pandemic influenza
• NEW viruses popn. has no immunity
• Mxn Genetic reassortment of genome segments
  betwn. different strains of virus

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Clinical Manifestation of Influenza

• Incubation period 1-3 days
• Begins abruptly, fever 39-40 degrees
• Chills common
• Headaches severe
• Conjunctiva congested
• Sense of extreme prostration w/ myalgia
• Cough scantily productive

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Clinical Manifestations of Influenza

• If no complications fever abates in 3-4 days,
  recovery complete w/in a week
• Infants sx. mild, resemble common cold or URT
  infxn
• Old people pts. W/ underlying chronic resp.,
  cardiovasc., metabolic, renal disease, pregnant
  women, course of influenza may worsen rapidly
• Pneumonia complicating influenza - secondary bac.
  Infxn caused by
• S. aureus, H. Influenza, S. pneumonia, or S.
  pyogenes

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Immunity to Influenza

• Secretory Ab develop in resp tract
• Predominantly IgA
• Interferon freq. Detected
• Time of appearance of interferon
• improvement of sx. decrease in virus titers

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Immunity to Influenza

• Neutralizing, HA-inhibition (HAI), complement Ab
  develop in serum of pts.
• Development of anti-NA Ab parallels that of HAI
  Ab.
• HAI Neutralizing Ab persist for months years
  with gradual decline
• HLA restricted cytotoxic T lymphocytes also play
  a role in recovery from influenza virus infxn

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Complications of Influenza

• Myocarditis or severe myositis occasionally
  occurs
• Myoglobinuria encephalopathy
• Postinfluenza asthenia pts. take weeks to
  return to full activity
• Reyes Syndrome Often fatal encephalopathy,
  mostly

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Prevention of Influenza

• Vaccination principal method
• New strains causing disease around the world are
  grown w/ attenuated older vaccine strains in eggs
• Recombinants that grow to high yield and carry
  the new HA and NA antigens are selected for use
  in vaccines

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Pneumonia

• Inflammatory disease of pulmonary parenchyma
  (functional part of organ).
• Abnormal density CXR
• 50 of LRT infxns are bacterial in origin

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Acute Pneumonia Etiology

• Common Bacterial
• Strep. Pneumonia
• S. Aureus
• H. Influenza
• Anaerobic bac.
• Enterobacteriaceae
• P.Aeruginosa
• Legionella

93
Etiology of Acute Pneumonia

• Common Viral - Children
• RSV
• Parainfluenza 1,2,3
• Influenza A

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Etiology of Acute Pneumonia

• Common viral adults
• Influenza A
• Influenza B
• Adenovirus 4,7 (military recruits)
• Others Fungal, Rickettsial, Bacteria-like,
  Parasitic

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Diagnosis of Acute Pneumonia

• Good history
• Look for defects in host resistance predispose
  pt. to pneumonia possible exposure to specific
  pathogens

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Diagnosis of Acute Pneumonia

• Gram stain exam and culture of sputum mainstay
  of eval.
• Mucopurulent sputum most commonly with
  bacterial pneumonias
• Large s of epithelial cells reflect
  contamination
• Neutrophils indicate acute inflammation
• Gram stain helpful in selection of initial
  antimicrobial therapy
• Some cases transtracheal aspiration may be
  necessary to id pathogen

97
Pneumonia Syndromes

• Acute community-acquired pneumonia
• Pt. In mid 50s
• Midwinter or early spring
• Most pt. One or more chronic underlying diseases
• Majority due to
• S. pneumonia
• Others Legionella pneumophila, H. Influenza, S.
  Aureus

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Aspiration Pneumonia

• Setting states of altered consciousness, normal
  gag swallowing reflexes not present
• Anaerobic bac. mostly seen
• Anaerobic bac. In combo with aerobes or
  facultatives 2nd most seen

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Atypical Pneumonia Syndrome

• Symptom complex representing disease caused most
  commonly by Mycoplasma
• Age 5, adolescent, young adult greatest risk
• Others
• Parainfluenza virus
• EB Virus
• RSV
• Adenovirus

100
Chronic Pneumonia

• Pulmonary parenchymal infectious or
  non-infectious agent, present for weeks to months
• Abnormal CXR
• Chronic or progressive pulmonary sx

101
Etiology Chronic Pneumonia

• Mixed aerobic-anaerobic bac.
• Mycobacteria
• Fungi
• Protozoa
• Worms
• Non-infectious
• Neoplasia
• Sarcoidosis
• Vasculitis
• Chemicals
• Radiation
• Recurrent pulmonary infarction
• Fibrosing alveolitis

102
Epidemiology of chronic pneumonia

• Elderly at higher risk
• Pt. With Diabetes or COPD at higher risk
• Sex likely to play role in determining occupation
  or avocation ultimately likelihood of exposure
  to certain infectious agents
• Race of pt. maybe important
• Certain occupations hobbies suspicion
• Travelled?
• Drinks?
• Personal habits

103
Legionnaires Disease

• Form of pneumonia discrete outbreaks or as
  sporadic cases
• 1st recognized American Legion Convention in
  Philadelphia July 1976
• Only caused by Legionella pneumophilia
• Pontiac Fever acute resp. illness caused by
  legionella but without pneumonia

104
Etiology of Legionnaires Disease

• Fastidious
• Filamentous
• Flagellated
• Gram negative rod
• Isolated from lung or pleural fluid
• Legionella grown on charcoal-yeast extract or
  supplemented Mueller-Hinton medium
• Can be isolated from inoculated embryonated eggs
• 9 serogroups exists most clinical isolate?
  serogroup 1

105
Epidemiology of Legionnaires Disease

• Widely distributed in soil water
• Contaminated water systems
• Disease acquired by inhalation of aerosols
  contaminated with organisms
• Person to peron x-mission not documented!
• Attack rate for Legionnaires disease higher in
  elderly, chronic lung disease, malignancies,
  renal failure, immunosuppression
• Cause 5,000-10,000 cases of pneumonia annually
  in the U.S.

106
Diagnosis of Legionnaires Disease

• Isolated from sputum using charcoal-yeast extract
  agar, transtracheal aspirates used for culture
• Detection of L. pneumophilia antigens in urine
• Most often indirect immunofluorescence detect
  anti-Legionella Ab in pt. Serum
• 4 fold or greater rise in titer ? diagnostic

107
Prevention of Legionnaires Disease

• Hyperchlorination of cooling towers and potable
  water ineffective
• superheat and flush tx. Of water distribution
  systems currently used
• No vaccine available!

108
Hantavirus Pulmonary Syndrome

• 1st found to cause resp infxn in 1993
• Prior to that, only known human disease caused by
  Hantavirus was Koren hemorrhagic fever
• 1st few cases seen in Navajo Indian population
• Now, 100 cases seen
• New strain called Sin Nombre
• Infxn begins with febrile prodrome? pulmonary
  edema? hypotension/shock
• Fatality 50
• Virus carried by deer mouse, and other rodents,
  excretes virus in saliva, urine, feces

109
Lung Abscesses

• Lung abscessNecrotizing Pneumonia
• Early manifestation pneumonia
• In absence of therapy? lung abscess

110
Etiology Lung Abscess

• Similar to aspiration pneumonia
• Mixed anaerobic bacteria seen in most cases
• Fusobacterium nucleatum
• Bacteroides melaningenicus
• Peptostreptococci
• Microaerophilic streptococci

111
Clinical Features Lung Abscess

• Cough - almost all pt.
• When abscess drains into bronchial tree
  copious, foul-smelling sputum
• Chest pain common
• Fever majority of pts.

112
Diagnosis Lung Abscess

• Exam of sputum - crucial

113
Empyema

• Purulent inflammatory exudate of pleural cavity
  that maybe acute or chronic
• Most commonly direct spread of bronchopulmonary
  infxns
• Also, complication of thoracic surgery

114
Etiology Empyema

• Most common Staph Aureus
• Various Gram negatives
• P. aeruginosa
• Klebsiella pneumonia
• E. coli

115
Diagnosis Empyema

• Requires aspiration of pleural fluid
• Gram stain of pleural fluid

116
Treatment Empyema

• Surgical drainage of purulent exudate
• Plus, antibiotics