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06.RESPIRATORY TRACT INFECTIONS1. RESPIRATORY TRACT INFECTINOS2. DEFENSE MECHANISMS (RT) – CELL TYPES ALONG THE TRACT3. MECHANISMS OF DEFENSE (RT)4. PATHS ENABLING INFECTIOUS COLONIZATION OF RTA. Remotely-produced toxin mediates damage B. Breach intact epithelium – broken epithelium C. System infect...

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06.12.18

RESPIRATORY TRACT INFECTIONS 1. RESPIRATORY TRACT INFECTINOS

2. DEFENSE MECHANISMS (RT) – CELL TYPES ALONG THE TRACT

3. MECHANISMS OF DEFENSE (RT)

4. PATHS ENABLING INFECTIOUS COLONIZATION OF RT A. Remotely-produced toxin mediates damage B. Breach intact epithelium – broken epithelium C. System infections to the blood and then to the RT

5. VIRUSES, ADVANTAGES i.

Acquired through close contact

ii.

Acquired during childhood

iii.

Often virtually asymptomatic

iv.

Transient

v.

Leading to sustained protective immune responses

vi.

Viruses have low survival in the environment

vii.

A few vaccines available

6. VIRUSES, DISADVANTAGES

2

i.

Normally diagnosed on clinical presentation (serology and PCR becoming more common)

ii.

Generic early symptoms (fever, malaise, rash)

iii.

Some viruses are immediately life-threatening (e.g. SARS – severe acute respiratory syndrome)

iv.

Only a few vaccines available

v.

Antiherpetic/antiretroviral drugs can be effective but problems with efficacy and treatment resistance (e.g. acyclovir)

vi.

Few other treatments are available

vii.

Clinical presentations in immunocompromised patients are extreme

viii.

Potential for persistence, virus reactivation, oncogenesis (e.g. tumours, HBV, and HCV)

ix.

Survive for longer than one may expect

x.

Multiple varieties for every virus

xi.

Often airborne or present in bodily fluids

7. TYPES OF PATHOGENS OF THE RESPIRATORY TRACT A. The professionals (invaders) i.

Successfully infect the normal respiratory tract

B. Microbiota (secondary invaders) i.

Opportunistic pathogen (infect when host defences down) e.g. fungi

8. SYSTEMIC/DEEP MYCOSES COMMONLY AIRBORNE

3

9. THE PROFESSIONALS (INVADERS) AND COLONIZATION METHODS A. Adhesion to mucosa i.

Influenza virus

ii.

Rhinovirus (Picornaviridae)

B.

Adhesion to cilia i.

Streptococcus pyogenes

ii.

Streptococcus pneumoniae

C.

Resist alveolar macrophage i.

Bordetella pertussis

ii.

Mycobacterium tuberculosis

D.

10.

Damage local tissues (also remote) i.

Legionella pneumophila

ii.

Corynebacterium diphtheriae

SECONDARY INVADERS

4

11.

COMMON COLD Nasopharyngitis = rhinitis + pharyngitis + fever A. Common cold I i.

Inflammation of the nose mucous membrane

ii.

Diagnosis: clinical

iii.

Aerosol; contact

iv.

Everyone; 1billilon/year in the US

v.

Rhinovirus, replication 33oC

vi.

Flu: hemagglutinin binds to epithelial cell neuraminic acid – destruction

vii.

Mainly viruses: Rhinoviruses (2/3rd of cases), Coronaviruses (CoV), Influenza (flu), Parainfluenza (epiglottis & laryngotracheitis), Respiratory Syncytial Viruses (RSV; bronchiolitis & pneumonia)

B. Pharyngitis/tonsillitis I i.

Inflammation pharynx mucous membrane & lymphoid tissue

ii.

Diagnosis; clinical

iii.

Aerosol; contact – plus

iv.

Infection/destruction of epithelial mucosa

v.

Common cold viruses and Coxsackie virus A (Herpangina), EBV, HSV

vi.

Streptococcus pyogenes, Corynebacterium diphtheriae, Neisseria gonorrhoea, Mycoplasma pneumoniae Generic features: malaise and fever C. Common Cold II i.

Mild; self-limiting (48h)

ii.

Stuffy/nasal discharge

iii.

Sneezing

iv.

Face swelling

v.

Sore throat

vi.

Symptomatic: anti-decongestants, analgesi

vii.

Antibiotics

viii.

Influenza vaccines: H1N1 (Hemagglutinin neuraminidase)

D. Pharyngitis/tonsillitis II

5

i.

Sore throat

ii.

Headache

iii.

Swollen neck lymph nodes

iv.

Joint pain/muscle aches

v. vi.

12.

Symptomatic: pain killers, humidifier, salt water gargles, warm soothing liquids Antibiotics

MORE HERPEVIRIDAE Generic features: malaise and fever (mild) A. Epstein-Barr Virus (EBV) i.

Young adults; incidence in 90% of the population

ii.

Atypical lymphocytes (T lymph.) – like leukaemia but no anaemia

iii.

Self-limiting

iv.

Subclinical/debilitating

v.

Rash (rubelliform)

vi.

Jaundice

vii.

Lymphadenopathy/splenomegaly

viii.

Sore throat

ix.

Soft palate petechiae

x.

Mouth ulcers

xi.

Neurological, liver, kidney dysfunction

xii.

Oncovirus – e.g. Burkitt lymphoma; nasopharyngeal carcinomas

B.

Cytomegalovirus (CMV) i.

Childhood (primary)

ii.

Saliva, blood, urine, semen, secretions, and milk

iii.

Asymptomatic

iv.

Pharyngitis

v.

Pneumonia (immunocomplex)

vi.

Glandular fever-like-lymphadenopathy

vii.

May lead to retinitis and blindness

viii.

Foetal damage (blood placenta transmission)

13.

STREPTOCOCCUS – ‘INVASION’ INFECTIONS (PHARYNGITIS) 2005, >616 million GAS pharyngitis/yr Primarily (not exclusively) affects 5-15 yr old

6

i.

Gram +ve ovococci bacterium

ii.

Nose/throat microflora

iii.

Contact with infected individuals

iv.

Groups A Streptococci (GAS)

v.

7

E.g. S. phyogenes-beta-haemolytic

14.

BACTERIAL – PHARYNGITIS/TONSILITIS (STREP THROAT) Generic features: malaise and fever (pyrexia) i.

Throat soreness

ii.

Headache

iii.

Patchy exudates

iv.

Cervical lymphadenopathy

v.

Chills

vi.

Orally:

15.

-

Mucositis & gingivitis

-

Erythema & discomfort

-

Petechiae on soft palate

SCARLET FEVER – TOXIN MEDIATED DAMAGE Streptococcus pyogenes (Group A Streptococci) i.

Pharyngitis & tonsillitis

ii.

Numerous deep red papules – rough skin

iii.

Orally: -

Generalise oedema, uvula elongation, diffuse petechiae, strawberry tongue (tongue becomes white and filiform papillae (erythematous and enlarged)

iv.

Spe A (pyrogenic exotoxin); influence immune system & skin blood vessels

v.

Streptococcus Toxic Shock Syndrome (STSS)

16.

INFLUENZA (ORTHOMYXOVIRUS) i.

Clinical diagnosis

ii.

Aerosol inhalation

iii.

Community- &healthcare infection

iv.

Complications in children and elderly

v.

Highly infectious

vi.

Whole respiratory tract

vii.

Sore throat

viii.

Nasal congestion

8

ix.

Headache

x.

Tiredness

xi.

Dry cough

xii.

Myalgia

xiii.

Typically self-limiting

17.

PNEUMONIA I Aerosol inhalation; microbiota aspiration; blood

18.

i.

Common cause of infection-related death

ii.

Agents: -

More common: professional virus – children + bacteria

-

Secondary; bacteria – adults

iii.

480,000 cases of adult pneumonia in the UK

iv.

Risk factors: -

Age

-

Influenza primary infection leading to secondary bacterial pneumonia

JOHN DOE’S SYMPTOMS

9

19.

PNEUMONIA II A. Common: Streptococcus pneumoniae B.

More atypical: i.

Mycoplasma pneumoniae

ii.

Legionella pneumophila (no sputum; GI symptoms)

iii.

S. aureus (after influenza) – ‘pandemic terror’

C.

Even more atypical: i.

Chlamydophila pneumoniae

ii.

Coxiella burnetiid

iii.

Moraxella catarrhalis (opportunistic)

iv.

Mycobacterium tuberculosis

v.

Klebsiella pneumoniae

20.

PNEUMONIA DIAGNOSIS I A. Clinical diagnosis - easy B.

Differential diagnosis – difficult: i.

Acute bronchitis, tuberculosis, pneumocystis pneumonia

ii.

Pneumonia severity (clinical skill)

C. Particularly in hospital-acquired: i.

Sputum contains bacteria which may not be linked to pneumonia

ii.

Atypical serology

21.

PNEUMONIA DIAGNOSIS II A. (acute pneumonia): i.

Respiratory rate >30

ii.

Bacteraemia

iii.

Low blood pressure 60/90 mmHg

B.

Laboratory i.

C-Reactive Protein (CRP)

ii.

WBC counts (high counts indicate infection)

iii.

Sputum: (blood/colour/consistency) microscopy, culture & sensitivity

iv.

Chest X-Ray, CT Scan

v.

Serology (urine antigen test – pneumococcus & legionella)

10

vi.

22.

PCR [Haemophilus, Chlamydia, Mycoplasma (expensive)]

BRONCHITIS Inflammatory condition of the tracheobronchial tree i.

Clinical; sputum (yellow/green)

ii.

Aerosol inhalation; microbiota aspiration

iii.

Lower respiratory tract pathogens: mycoplasma pneumoniae, adenoviruses, CoV

iv.

“All-star” respiratory tract pathogens: streptococcus pneumoniae, haemophilus influenzae, staphylococcus aureus

v.

RSV – Bronchiolitis

vi.

Cough (dry, maybe sputum)

vii.

Shortness of breath

viii.

Difficulty/pain breathing

ix.

Secondary infections

x.

Anitbiotics

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