Chapter 5

RESPIRATORY INFECTIONS

INFECTIONS OF THE RESPIRATORY TRACT

Most common entry point for infections

Upper respiratory tract

nose, nasal cavity, sinuses, mouth, throat

Lower respiratory tract

Trachea, bronchi, bronchioles, and alveoli in the lungs

RESPIRATORY TRACT

PROTECTIVE MECHANISMS

Normal flora: Commensal organisms

Limited to the upper tract

Mostly Gram positive or anaeorbic

Microbial antagonist (competition)

Clearance of particles and organisms from the respiratory tract

Cilia and microvilli move particles up to the throat where they are swallowed.

Alveolar macrophages migrate and engulf particles and bacteria in the alveoli deep in the lungs.

Protective Mechanisms

OTHER PROTECTIVE MECHANISMS

Nasal hair, nasal turbinates

Mucus

Involuntary responses (coughing)

Secretory IgA

Immune cells

RESPONSE TOWARDS FOREIGN PARTICLES

Ventilatory flow

Cough

Mucociliary clearance mechanisms

Mucosal immune system

SELECTED BACTERIAL INFECTIONS

Pharyngitis

Group A Strep - Streptococcus pyogenes

(Many viruses also cause this)

Pneumonia - Streptococcus pneumoniae

Diphtheria - Corynebacterium diphtheriae

Tuberculosis - Mycobacterium tuberculosis

Whooping cough - Bordetella pertussis

DISEASE OF UPPER RESPIRATORY TRACT

1. Pharyngitis and related infections

2. Diptheria

EXAMPLES OF COMMON INFECTIONS

Laryngitis

Streptococcal Pharyngitis

Scarlet Fever

Sinusitis

Diptheria

Otitis media

Advance stages – bacterial superinfection, mastoiditis, meningitis and brain abscess

LARYNGITIS

Most commomly upper respiratory viruses

Diphtheria

- C. diphtheriae produces a cytotoxic exotoxin causing tissues necrosis at site of infection with associated acute inflammation. Membrane may narrow airway and/ or slough off (asphyxiation)

STREPTOCOCCAL PHARYNGITIS (STREP THROAT)

Caused by group A beta-hemolytic streptococci of S.pyogenes

Also causing impetigo, erysipelas and endocarditis on skin

Causing inflammation of the mucous membrane and fever; tonsilitis and otitis media may also occur

Rapid diagnosis using enzyme immunoassays.

STREP THROAT

Fever

Tonsillitis

Enlarged lymph nodes

Middle-ear infection

REDDENING OF THROAT

STREPTOCOCCUS PYOGENES

Gram positive streptococci

Carried and transmitted from the throat

In Respiratory secretions

GROUP A STREP

Capsule -resistant to phagocytosis

Enzymes damage host cells

M protein adhesinThe M protein has many antigenic varietiesand thus, different strain of S.pyogenes cause repeat infections

ENZYME IMMUNOASSAYS

SCARLET FEVER

Caused by S. pyogenes producing erythrogenic toxin

The bacteriophage disturb the normal characterristic of bacteria that involving genetic mutation

Also associate with pharyngitis and skin infection that caused by the same bacteria

It is nowadays become mild and rare disease

SCARLET FEVER

Caused by ErythrogenicToxin secreted by S. pyogenes

SCARLET FEVER The erythrogenic

toxin is coded by a gene

lysogenic bacteriophage

within the genome of

S. pyogenes Rash is an inflammatory reaction to the toxin

SINUSITIS

Commonly caused by S. pneumoniae, Moraxella catarrhalis / H. influezae

can also caused by S. aureus / S.pyogenes

The sinus cavity will swelling and prevent drainage that resulting pressure and severe pain

Pt usually produce mucus, bacteria and phagocytic cells that collect in the sinuses

CONT.

Chronic stages caused by Bacteriodes

Mostly occur above the root of upper teeth which infection derived from oral cavity

Treatment by applying moist heat on particular area / drop an ephedrine / raise head to help drainage

Best antibiotic - penicillin

SINUSITIS

DIPTERIA

Until 1935, it leading infection to children of US

Vaccine used for children is DTaP vaccine

Diptheria Toxoid antibodies Production (DTaP)

Spread thru air bourne and resistant towards drying

The greyish toungue contain fibrin, dead tissues and bacterial cells that block the air passage

0.01mg of highly virulence toxin - fatal

CORYNEBACTERIUM DIPHTHERIAE

Aerobic Gram + bacillus Toxin inhibits protein synthesis of

cells to which it binds Destroyed cells and WBC form

"pseudomembrane" which blocks airways

SEVERE STAGE

UNDER MICROSCOPIC OBSERVATION

CORYNEBACTERIUM DIPHTHERIAE

To produce toxin, C. dithpheriae must be infected with a bacteriophage carrying the toxin gene

GREY MEMBRANE

THE DIPHTHERIA OUTBREAK OF NOME, ALASKA, 1925

Heroic Alaska Dog Teams

AN “AB” TOXIN

B = binding subunit A = active subunit

which binds to and inhibits a eucaryotic ribosomal translation factor

Vaccine is diphtheria toxoid

OTITIS MEDIA

Uncomfortable common cold, that infecting nose or throat (otitis media)

85% infecting children below 3 yrs old

Best antibiotic from penicillin group

The antibiotics used were just reduction the duration of infection

CAUSES

S. pneumoniae

H. influenzae

S.pyogene

Moraxella catarrhalis

S.aureus

INFECTED

MIDDLE EAR

(OTITIS MEDIA)

DISEASES OF LOWER RESPIRATORY TRACT

1. Whooping cough

2. Tuberculosis

3. Pneumonia

WHOOPING COUGH

BORDETELLA PERTUSSIS

Gram negative cocco-bacillus

Capsule Adherence to ciliated

cells

Pertussis toxin is A-B toxin

PERTUSSIS (WHOOPING COUGH)

Cough

Violent coughing followed by whooping sound

Vaccine – it is made of

purified components

Not lifelong immunity – adult carriers

PNEUMONIA

BACTERIAL PNEUMONIABacterial, viral or fungal infection can cause

Inflammation of the lung with fluid filled alveoli

COMMUNITY ACQUIRED PNEUMONIA

Infection of the lung parenchyma in a person who is not hospitalized or living in a long-term care facility for ≥ 2 weeks

5.6 million cases annually in the U.S.

Estimated total annual cost of health care = $8.4 billion

Most common pathogen = S. pneumo (60-70% of CAP cases)

“NOSOCOMIAL” PNEUMONIA

Hospital-acquired pneumonia (HAP)

Occurs 48 hours or more after admission, which was not incubating at the time of admission

Ventilator-associated pneumonia (VAP)

Arises more than 48-72 hours after endotracheal intubation

“NOSOCOMIAL” PNEUMONIA

Healthcare-associated pneumonia (HCAP) Patients who were hospitalized in an acute care

hospital for two or more days within 90 days of the infection; resided in a nursing home or LTC facility; received recent IV abx, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic

Guidelines for the Management of Adults with HAP, VAP, and HCAP. American Thoracic Society, 2005

PATHOGENESIS

Inhalation, aspiration and hematogenous spread are the 3 main mechanisms by which bacteria reaches the lungs

Primary inhalation: when organisms bypass normal respiratory defense mechanisms or when the Pt inhales aerobic GN organisms that colonize the upper respiratory tract or respiratory support equipment

PATHOGENESIS

Aspiration: occurs when the Pt aspirates colonized upper respiratory tract secretions

Stomach: reservoir of GNR that can ascend, colonizing the respiratory tract.

Hematogenous: originate from a distant source and reach the lungs via the blood stream.

PATHOGENS

CAP usually caused by a single organism

Even with extensive diagnostic testing, most investigators cannot identify a specific etiology for CAP in ≥ 50% of patients.

In those identified, S. pneumo is causative pathogen 60-70% of the time

STREPTOCOCCUS PNEUMONIA

Most common cause of CAP

Gram positive diplococci

“Typical” symptoms (e.g. malaise, shaking chills, fever, rusty sputum, pleuritic hest pain, cough)

Lobar infiltrate on CXR

Suppressed host

25% bacteremic

ATYPICAL PNEUMONIA

#2 cause (especially in younger population)

Commonly associated with milder Sx’s: subacute onset, non-productive cough, no focal infiltrate on CXR

Mycoplasma: younger Pts, extra-pulm Sx’s (anemia, rashes), headache, sore throat

Chlamydia: year round, URI Sx, sore throat

Legionella: higher mortality rate, water-borne outbreaks, hyponatremia, diarrhea

VIRAL PNEUMONIA

More common cause in children

RSV, influenza, parainfluenza

Influenza most important viral cause in adults, especially during winter months

Post-influenza pneumonia (secondary bacterial infection)

S. pneumo, Staph aureus

OTHER BACTERIA

Anaerobes Aspiration-prone Pt, putrid sputum, dental disease

Gram negative Klebsiella - alcoholics

Branhamella catarrhalis - sinus disease, otitis, COPD

H. influenza

Staphylococcus aureus IVDU, skin disease, foreign bodies (catheters,

prosthetic joints) prior viral pneumonia

STREPTOCOCCUS PNEUMONIAE

Pneumococcus

Encapsulated

Often secondary infection following influenza virus

BACTERIAL PNEUMONIAStreptococcus pneumoniae• 2/3 of all pneumonia• Risk Factors- old age, season, underlying

viral infection, diabetes, alcohol and narcotic use

• Variable capsular antigen• Purified component (capsule) vaccine

Others that cause pneumonia:Mycoplasma pneumoniaeLegionella pneumophila

TUBERCULOSIS

MYCOBACTERIUM TUBERCULOSIS

Acid-fast bacillus – complex cell wall with “cord factor”

Causes TB: lungs

bones, other organs

Airborne, (milk, v. rare)

MYCOBACTERIUM TUBERCULOSIS

Thick lipid coat

of “Mycolic fatty acids”

Grows very slowly

Resists killing by macrophages and grows in them

TUBERCULE FORMATION

A tubercle in the lung is a “granuloma”

consisting of a central core of TB bacteria inside an enlarged macrophage, and an outer wall of fibroblasts, lymphocytes, and neutrophils

TUBERCULOSIS

Primary

Lung tubercles, caseous, tuberculin skin reaction

Secondary (reactivation)

Consumption: Coughing and chronic weight loss

Dissemination

Extrapulmonary TB (lymph nodes, kidneys, bones, genital tract, brain, meninges)

TUBERCULOSISElimination requires long antibiotic treatment with “cocktail” of antibiotics because

of the resistance that develops.

MULTI-DRUG RESISTANTMYCOBACTERIUM

TUBERCULOSIS

TB SKIN TEST

HOW DOES TUBERCULOSIS DEVELOP?

There are two possible ways a person can become sick with TB disease:

The first applies to a person who may have had been infected with TB but is perfectly healthy. The person can get infected again if they have a another disease such as HIV or cancer or they may get infected if they use drugs/alcohol.

The other way it TB can develop, happens much more quickly. Sometimes when a person first breathes in the TB germs, the body is unable to protect itself against the disease. The germs then develop into active TB disease within weeks.

WHO GETS TUBERCULOSIS?

Anyone can get tuberculosis. Some people are at higher risks than others. The people who have more of a chance getting TB are:

People who share same breathing space

Poor people/homeless people

Prisoners

Alcoholics or Drug users

People with medical conditions (cancer, diabetes)

Specially people with aids

PRIMARY TUBERCULOSIS PNEUMONIA

This is an uncommon type of TB as pneumonia is infectious. People who have it, have high fevers and productive coughs. It occurs most often in extremely young children and the elderly. This type is also found in HIV and Aids infected people.

THE THREE STAGES

There are three stages in the disease of tuberculosis. These three stages are identified from mild to extreme danger which is death. The first mild stage can get cured easily as long as the patient gets medication on time and takes good care. The second stage is more dangerous and the patient has to be really careful and that is were the symptoms should be considered. The third stage is extremely dangerous and there is no cure which means death. The third stage is the stage were nothing should go wrong and the patient will slowly begin to vomit blood and eventually die.

WHO DISCOVERED TUBERCULOSIS?

In 1882, Robert Koch discovered TB and soon he found out that it was caused by a microorganism Mycobacterium tuberculosis. After discovering that this disease was infectious, he started to consider treatments. Many treatments were tried but none were discovered until the year of 1943 were the activity of streptomycin was discovered.

VIRUS INFECTIONS

Respiratory syncytial virus (“RSV”)

Influenza virus

Fungal Infections•Coccidiodomycosis (Valley Fever)

Coccidioides immitis

THE COMMON COLD

Also known as coryza

Caused by viral infection

Show symptoms as other cold but secretion might consist of pus and blood mucus

Leads to 2ndary infection – sinusitis, bronchitis and otitis media

In serious case – likely as whooping cough and respiratory

RESPIRATORY SYNCYTIAL VIRUS

Enveloped (membrane) RNA virus

Spread by respiratory droplets

Community outbreaks in late fall to spring

Upper respiratory tract infection – epithelial cells

May be fatal in infants

INFLUENZA VIRUS AN ENVELOPED RNA VIRUS

Structure

Influenza Virus

New human strains every year• Mutations

Pandemic strains Genetic Recombinant Viruses•1957 Asian Flu H2N2•1968 Hong Kong Flu H3N2•1977 Russian Flu H1N1

Bird FluDirectly from birds•?? H5N1

‘H’ AND ‘N’ FLU GLYCOPROTEINS

H – Hemagglutinin • Specific parts bind to host

cells of the respiratory mucosa• Different parts are

recognized by the host antibodies• Subject to changes

N - Neuraminidase • Breaks down protective

mucous coating • Assist in viral release

INFLUENZA

Epidemics and pandemics, mostly in winter Upper respiratory tract infection –

epithelial cells Multivalent killed virus vaccine with strains

from the previous year (Grown in embryonated eggs)

Bird flu (H5N1) pandemic in birds

COCCIDIOIDES IMMITIS Soil fungus in

American Southwest

Cause of Valley Fever

Highly infectious

COCCIDIOIDES IMMITIS LIFE CYCLE

COCCIDIOIDES IMMITIS

Valley Fever usually a flu-like illness

Can spread to bones, skin, meninges

100,000 new cases/yr in SW