Lower Respiratory Tract Infections                        Reading: pg. 217 – 237

• Introduction
• Acute infections
  • Whooping cough
    • Bordetella pertussis
    • Treatment
    • Vaccine
  • Acute bronchitis
  • Acute exacerbations of chronic bronchitis
  • Bronciolitis
  • Respiratory syncytial virus
  • Hantavirus
  • Pneumonia (fig. 19.7, pg. 222)
    • Lobar
    • Bronchopneumonia
    • Interstitial
    • Lung abscess
    • Bacterial pneumonia (fig. 19.8, pg. 223)
    • Atypical pneumonia (fig. 19.11, pg. 225)
    • Viral (fig. 19.13, pg. 227)
      • Parainfluenza virus
      • Adenovirus
      • Influenza virus (fig. 19.16, pg. 229)
      • SARS-associated
      • Measles
        • Giant cell pneumonia (fig. 19.18, pg. 231)
        • Secondary bacterial infections
      • CMV
• Chronic infections
  • Tuberculosis
  • Fungal infections
    • Aspergillus fumigatus
    • Pneumocystis jiroveci
  • Cystic fibrosis
    • Pseudomonas aeruginosa
  • Lung abscess
  • Pleural effusion and empyema
• Parasitic infections

Lower respiratory tract infections

Introduction

p   Lower respiratory tract infections are:

n   Divided into acute and chronic infections

n   more serious or even fatal

n   Caused by wide range of organisms:

p  Viruses, bacteria, fungi and parasites

Acute infections

p   Sudden onset or shorter in duration

Whooping Cough

p   Causative Agent

n   Bordetella pertussis

p  Encapsulated

p  Strictly aerobic

p  Gram-negative rod

p  Fastidious - does not survive long periods outside host

p    Enters respiratory tract with inspired air and attaches to and destroy ciliated cells

p    Pathogenesis due to Pertussis toxin

n    Causes increased mucus formation à decreased ciliary action

n    Cough - only mechanism for clearing secretions

p    Symptoms:

n    Runny nose followed by bouts of uncontrollable coughing

n    Termed paroxymal coughing

n    followed by characteristic “whoop”

n    Sound made by the forceful inspiration of air

p     Spreads via respiratory droplets

n    Spread from adults to children (mild in adults)

p     Prevention

n    vaccination of infants

p   Prevents disease in 70% of individuals

p   Pertussis vaccine combined with diphtheria and tetanus toxoids (DPT)

§    Injections given at 6 weeks, 4, 6, and 18 months

p     Treatment

n   Supportive care is important especially for infants under 1 yr of age

n    Erythromycin

p   effective at reducing symptoms if given early

p   eliminates bacteria from respiratory secretions

p  Reduces infectivity of patient

Acute bronchitis

p    Inflammation of the tracheobrondial tree

p    Caused by:

n    Viruses: coronaviruses and rhinoviruses, influenza virus, adenovirus

n    Bacteria: Mycoplasma pneumoniae

p    Diagnosis is clinical presentation:

n    cough and excessive mucus production

p    Treatment is mainly symptomatic

n    Antibiotics may be given but effectiveness is uncertain

p    chronic bronchitis is exacerbated by cigarette smoking and inhalation of dust

p    Bacterial infections (S. pnuemoniae and H. influenzae)

p    Antibiotics helpful

Bronchiolitis

p    70% caused by Respiratory syncytial virus

p   Part of paramyxovirus family

p   ssRNA genome

p   Enveloped contain G protein for attachment to cells and fusion proteins (fuses viral envelope to host cell membrane)

§    Lacks hemagglutinin and neuraminidase

p    Symptoms

p   Incubation period 1 – 5 days

p   Runny nose

p   Cough and wheezing

p   Difficulty breathing

p   Fever - May or may not be present

p   Dusky colored skin - Due to poor oxygenation

p   Severe in infants – peak mortality at 3 months of age

Respiratory Syncytial Virus

p    Pathogenesis

n    Enters body through inhalation (droplets)

n    Infects nasopharynx and lower respiratory tract

n    Causes death and sloughing of infected cells

p   Bronchioles become obstructed by sloughing cells

§    Responsible for wheezing

n    necrosis of epithelial cells may lead to secondary pneumonia

p    Disease has an immunopathologic basis

n    Reaction of maternal Ab with virus antigen à production of histamines

n    Infants have underdeveloped cell mediated immunity needed to terminate the infection

p    Epidemiology

n    Outbreaks common in community and hospitals

n    Healthy adults and children usually suffer mild disease but readily spread virus

p    Prevention and Treatment

n    No vaccine

n    Isolation of sick individual best prevention

n    No effective antiviral medications

p   Ribavirin used for severe cases

Hantavirus Pulmonary Syndrome

p  Causative Agent

n   Hantavirus

p Sin Nombre virus found in outbreak of severe pulmonary disease

p ssRNA genome

p Enveloped

p Causes lifetime infection in wild rodents

p    Early symptoms

n    Fever

n    Muscle ache

p   Especially in the lower back

n    Nausea and vomiting

n    Diarrhea

p    Later symptoms

n    Unproductive cough

n    Increasing shortness of breath

n    Shock and death

p     Pathogenesis

n    Enters body via inhalation of dust contaminated with urine, feces and saliva of infected rodents

n    virus enters circulation

p   Carried throughout body

§    Infects cells that line capillaries

n    Inflammation causes capillaries to leak fluid into lungs

p   Causes suffocation and precipitous fall in blood pressure

n    Shock and death occur in over 40% of patients

p     Epidemiology

n    Emerging disease due to recent discovery

n    Most cases in United States occur west of Mississippi River

p   Caused by Sin Nombre virus

§    Virus carried by deer mouse

n    Outbreaks correlate with increase mouse population

p   Over 30% of mice become carriers

n    Person-to-person spread RARE

p   Prevention and Treatment

n   Prevention

p  minimizing exposure

§    Keep pet and human food in containers

§    Maximal ventilation when cleaning mouse droppings

§    Mop with disinfectant

§    Decrease rodent population

n   No proven antiviral treatment

p  Treatment limited to support care

Pneumonia

p   Immunocompromised individuals are most susceptible

p   Common cause of death in elderly

n   Older people who stay in bed > 3 days get pneumonia

p  Result in aspiration of vomit into lungs

p  Microbes reach lungs by inhalation, aspiration or via blood

§    as far down as the alveoli

p  Acid and bacteria can cause permanent damage to lungs

p  Can be deadly

p    Signs and symptoms of chest infection:

n    Fever

n    Chest pain

n    Sputum-producing cough

n    Shortness of breath

n    Difficulty and pain on breathing

p    Clinical diagnosis:

n    chest radiograph showing consolidation

n    Microscopic examination of sputum

p   Gram stain and culture of microbe

n    Serological tests for hard to grow organisms

p   Treatment

n   Antibiotics: penicillin and ampicillin

p   Prevention

n   Minimize crowding

n   Better ventilation

n   vaccination

4 types of Pneumonia

•            Lobar

n         Involves distinct region of lung

n         Immune response to infection leads to alveoli becoming consolidated with neutrophils and fibrin

•            Bronchopneumonia

n         More diffuse patchy consolidation

n         May spread throughout lung

•            Interstitial

n         Involves invasion of lung interstitium (viral infections)

•            Lung abscess

n         Necrotizing pneumonia

n         Destruction of lung tissue leads to formation of cavities

p          Outcome = respiratory distress

Pneumonia

p    Caused by variety of pathogens depending on:

n    patient’s age

p   In children – caused by viruses or secondary bacterial infection

p   Adults – bacterial pneumonia is more common

n    Previous or underlying disease

p   Individuals with cystic fibrosis - more prone to lower respiratory tract infections

n    Occupational and geographic factors

p   Important risk factors for adults

n    Fig. 19.7 Causative agents (risk factors) of pneumonia

p    Bacterial pneumonia

n    Classical cause

p   S. pneumoniae

n    other microbes associated with disease

Pneumococcal Pneumonia

p    80-90% of cases are due to

n    Streptococcus pnuemoniae

p   Gram-positive, diplococci

p   Thick polysaccharide capsule

§    Capsule responsible for virulence

§    80 serotypes based on capsular antigen

p   Organism is hard to culture

p    Atypical pneumonia

n    S. pneumoniae not found in sputum

n    Do not respond to penicillin treatment

p    Fig. 19.11 Causes of atypical pneumonia

n    Difficult to culture

n    Indirect test with antibodies

Mycoplasmal Pneumonia

p    Typical pneumoniae, mild disease

p    A.k.a. “walking pneumoniae”

p    Causative Agent

n    Mycoplasma pneumoniae

p   Small

p   lacks cell wall

n    Small infecting dose

n    attaches to and interferes with function of cilia

n    Inflammation à thickening of bronchial and alveolar walls à Causes difficulty in breathing

Mycoplasmal Pneumonia

p   Epidemiology

n   spread by aerosolized droplets

n   Accounts for approximately one-fifth of bacterial pneumonias

p  Peak incidence in young people

n   Immunity is not permanent

Viral Pneumonia

p   Fig. 19.13 viruses that cause pneumonia

Pneumonia

p   Parainfluenza

n   4 types that cause respiratory infections

n   Have different antigens causing different clinical effects

p   Adenovirus

n   41 antigenic types

n   Causes both upper and lower respiratory tract infections (pharyngitis to atypical pneumonia)

Influenza

Influenza virus

p   Orthomyxovirus

n   Causes endemic, epidemic and pandemic influenza

n   3 types – distinguished by group specific antigen

p  Influenza A:

§    causes epidemics, pandemics

§    Involves animal reservoir (birds, swine)

p  Influenza B:

§    Causes only epidemics, does not involve animal hosts

p  Influenza C:

§    Does not cause epidemics

§    Only cause minor respiratory illness

n   Single-stranded RNA genome

p  divided into 8 segments

n   Spiked envelope

p  H spike – hemagglutinin

§    Aids in attachment

p  N spikes – neuraminidase

§    Aids in viral spread

n   Current avian influenza A virus (H5N1)

p   undergo genetic changes as passed among host species

n   Antigenic drift

p  changes in H and N antigen

p  minimize effectiveness of immunity to previous strains

n   Antigenic shift

p  sudden dramatic change due to recombination between different virus strains

p  new virus often more virulent

p  can infect previously immune populations

p  can lead to pandemic

p   Epidemiology

n   Transmission through droplet inhalation especially during winter months due to

p  People being close together indoors

p  Decreased host resistance

n   Outbreaks occur in every year

p  10,000 to 40,000 deaths

n   Pandemics occur periodically

p  Most “famous” pandemic of 1918

§    Spanned the globe in 9 months

p  Pandemics have higher than normal morbidity

p    Pathogenesis

n    Virus attaches to host cells via hemagglutinin spikes

p   viral envelope fuses with host membrane

§    Virus enters and replicates within cell

n    Mature viruses bud from host cell picking up envelope

n    Infected cells die and slough off

p   Destroy mucociliary escalator

n    Host immunity quickly controls viral spread

n    Small number of people die from influenza

p   Widespread

p   Symptoms:

n   1-3 days incubation

n   Chills, fever, malaise, muscle aches, runny nose, dry cough

n   Due to direct viral damage and Inflammatory responses

p   Predisposes host to secondary bacterial infections (bronchitis, pneumonia)

n   S. aureus, H. influenzae

p    Diagnosis:

n    Serological tests, PCR, culture

p    Prevention

n    Vaccine

p   egg grown viruses

p   Purified H and N antigens

n    New vaccine required every year

p   Due to antigenic drift

n    Recommended for those at high risk

n    Antiviral agents – reduces severity, effective as prophylaxis

p   Rimantadine or amantadine – inhibit replication of influenza virusA

p   Zanamivir and oseltamivir – inhibit neuramidase of influenza A and B

SARS-associated

p     Severe acute respiratory syndrome

n    Caused by SARS-associated coronavirus

p     First reported in 2002 in China

p     Symptoms:

n    2-7 days incubation

n    High fever

n    Difficulty breathing

n    Chest X-ray consistent with pneumonia

p     Transmission:

n    Person to person (in families or hospital staffs caring for SARS patients)

p     Infection control

n    Face mask

n    Checking for fever in the community and at airports

Measles

p   Causes Giant cell pneumonia

n   due to impaired cell-mediated immune response

p    Secondary bacterial infections

n    Viruses replicates in lower respiratory tract cause damage that leads to secondary infections

p    Symptoms

n    10-14 days incubation

n    Fever, runny nose, conjunctivitis, cough and characteristic rash

p    Treatment

n    Ribavirin may be used

n    Antibiotics used to treat bacterial secondary infections

p    Prevention

n    Highly effective vaccine - MMR (measles, mumps, and rubella)

CMV

p   Causes interstitial pneumonia in immunocompromised patients

n   Bone marrow transplant recipients

Chronic infections

Tuberculosis

p    Causative Agent

n    Mycobacterium tuberculosis

p   Acid fast (mycolic acid in cell wall)

p   Slow growing

§    Generation time 12 hours or more

p   Resists most prevention methods of control

p    1990’s – drug resistant strain

n    In homeless and HIV infected individuals

n    Hard to contain

p    Symptoms

n    Chronic illness

p   Fatigue

p   Progressive weight loss

p   Chronic productive cough

§    Sputum often blood stained due to tissue damage

p    Complications due to:

n    Ability of M. tuberculosis to colonizes any site in body

n    Local spread (into pleural cavity – pleural effusion)

n    dissemination via lymphatics and bloodstream

p   Leads to necrosis and destruction of other organs (kidney)

p   Contracted by inhalation of airborne organisms

n   taken up by pulmonary macrophages in lungs

p  Resists destruction (prevents fusion of phagosome with lysosomes)

p  multiplies in protected vacuole

p  tubercle formed in an effort to wall off infected tissue

n   Activated macrophages

p  Causes death of tissue resulting in formation of “cheesy” material seen in X-rays

p    Epidemiology

n    10 million Americans infected

p   highest among non-white, elderly, poor people

n    Small infecting dose

p   As little as ten organisms

n    Factors important in transmission

p   Frequency of coughing, adequacy of ventilation, degree of crowding

p    Diagnosis

n    Clinical signs and symptoms

n    Chest X-rays

n    Positive TB test

n    Microscopic examination of Ziehl-Neelsen stain of sputum à acid-fast rods

n    Culture (6 weeks)

n    PCR

p    Tuberculin test

n   Purified protein derivative (PPD) of M. tuberculosis injection under skin

n   Positive test

p  Injection site becomes red and firm

p  does not indicate active disease

p   Treatment

n   Antibiotic treatment given in cases of active tuberculosis

p  Two or more medications used to reduce resistance

p  Antimicrobials include

§    Rifampin and Isoniazid (INH)

§    Both target actively growing organisms and metabolically inactive intracellular organisms

p  Therapy is prolonged

§    Lasting at least 6 months

p    Prevention

n    Improved social conditions

n    Vaccination for tuberculosis widely used in many parts of the world

p   Vaccine = Bacillus of Calmette and Guérin (BCG)

§    derived from Mycobacterium bovis

§    Does not prevent infection

§    Gives partial immunity against tuberculosis

p   Vaccine not given in United States 

§    eliminates use of tuberculin test

n    Chemoprophylaxis – recommended for people in contact with cases of tuberculosis (1 year isoniazid)

Fungal infections

p   opportunistic infections in people with impaired immune response

p   Aspergillus fumigatus

n   Allergic bronchopulmonary aspergillosis

p  allergic react to presence of fungi

n   Aspergilloma

p  in patients with pre-existing lung conditions

p  growth of fungi leading to respiratory problems

n   Disseminated aspergillosis

p  invasive disease in immunocompromised patients

p   Pneumocystis jiroveci

n   Spread by droplet transmission

n   High frequency in AIDS patients

n   Associated with interstitial pneumonia

Cystic fibrosis

p   Common inherited disorder in Caucasians

p   Lungs infected by several invaders

n   Most common = Pseudomonas aeruginosa

p  Grows in the lungs

p  Damage to lungs due to immunological responses

p  Impossible to eradicate from lung

p   Lung abscess

n   Necrotizing pneumonia due to mixture of bacteria including anaerobes

n   Bacteriodes and Fusobacterium

p   Pleural effusion and empyema

n   Infection of pleural cavity that can lead to empyema (purulent exudate)

n   S. aureus, Gram – rods, and some anaerobes

Parasitic infections

p    Some parasites may localize in the lung or involve lung during stage in their development

n    Damage may be due to high numbers but is usually due to immunopathologic response of host