19 Upper respiratory tract infections Flashcards
Introduction
We distinguish between upper and lower respiratory tract, even though it is a continuum. Some organisms have a preference (e.g nasopharynx - cornaviruses/ rhinoviruses)
Proximal to distal - Rhinitis, sinusitis, pharyngitis, laryngitis, tracheitis, bronchitis, bronchilotis, pneumonia
Some microorganisms are restricted to surface of epithelium. Some spread to other parts of body before returning to respiratory tract/ oropharynx/ salivary glands e.g mumps
What are “professional “ invaders, and “secondary invaders”
Professional successfully infect the normal healthy respiratory tract, and can evade local host defences, e.g attachment mechanisms for respiratory viruses
Secondary invaders cause disease only only when host defences are already impaired e.g staph aureus after influenza
Normal flora of respiratory tract
Common >50% people
Occasional <10% people
Streptococci Neisseria spp Moraxella Corynebacterium Bacteroides Candida albicans Haemophilus influenzae
Streptococcus pneumoniae
Streptococcus pyogenes
Neisseria meningitidis
Normal flora of respiratory tract
Uncommon <1% people
Residents in latent state in tissues
Corynebacterium diptheria
Klbesiella pneumoniae
Pseudomonas
E. Coli
Pneumocystis jirovecii Mycobacterium TB CMV EBV HSV VZV
Pathogens which gain access via upper respiratory tract through the surface
Short incubation period. Local defences breeched, and infection established before adaptive immune response active
Rhinoviruses Influenza Streptococci in throat Chlamydia (conjunctivitis) Diptheria Pertussis Candida albicans
Pathogens which gain access via upper respiratory via spreading through body
Little or no entry in respiratory system. Pathogen spreads throughout body, returns to surface for final multiplication and shedding. Adaptive immune system important in recovery, longer incubation (weeks)
Measles - respiratory tract Mumps - salivary gland Rubella EBV - salivary gland CMV - salivary gland
Professional invaders
What are examples of pathogens which -
- Adhere to normal mucosa (in spite of mucociliary system)
- Ability to interfere with cilia
Respiratory viruses - influenza, rhinovirus
Strep pyogenes
Strep pneumoniae
Chlamydia
Bordetella pertussis
Mycoplasma pneumoniae
Strep pneumoniae (pneumolysin)
Professional invaders
What are examples of pathogens which -
- Resist destruction by alveolar macrophage
- Damage local mucosa/ submucosal tissues
Legionella
TB
Corynebacteriym diptheriae (toxin) Strep pneuomniae (pneumolysin)
Secondary invaders
What are examples of pathogens which -
- Infect after initial damage by respiratory virus
- Infect when local defences impaired (e.g cystic
fibrosis) - Infect in chronic bronchitis, local foreign body or tumour
Staph aureus
Strep pneumoniae
Staph aureus
Pseudomonas
Haemophilus influenzae
Strep pneumoniae
Secondary invaders
What are examples of pathogens which -
- Infect when immune response depressed
- Infect when resistance depressed - elderly, alcoholism, CKD, liver disease
Pneumocystis jirovecii
CMV
TB
Strep pneumoniae
Staph aureus
Haemophilus influenzae
Respiratory viruses cause common cold. They induce flow of virus rich fluid (rhinorrhoea), and sneezing triggers release of virus particles into air - aerosol transmission.
Most respiratory viruses have surface molecules which allows them to bind to microvilli, so they are not washed away in normal respiratory secretions.
Once first cell is infected, virus progeny from spread to neighbouring cells and via surface secretions to new sites on mucosal surface. Damage to epithelial cells and release of inflammatory mediators such as bradykinin lead to cold type symptoms
How are most virus infections diagnosed?
Viral PCR used these days
Use throat swabs
Avoid nasopharyngeal aspirates, as risks aerosol production of pathogen
What is the attachment mechanism for the following viruses and what disease can it cause
- Rhinovirus (>100 types)
- Enteroviruses including:
Coxsackie virus A (24 types)
Echoviruses (34 types)
Enteroviruses (116 serotypes)
capsid protein binds to ICAM-1 (intercellular adhesion molecules expressed on wide variety of normal cells) - common cold
Capsid protein binds to ICAM-1
Common cold, hand foot and mouth
What is the attachment mechanism for the following viruses
- Influenza (A, B, C)
- parainfluenza (1,2,3,4)
- RSV (A, B)
Haemagglutinin binds neuraminic acid containing protein on cell surface
Viral envelope proteins binds to glycoside on cell
G protein on virus attaches to receptor on cell
What is the attachment mechanism for the following viruses and what disease does it cause
- Coronaviruses (several types)
- Adenovirus (41 types)
Viral envelope protein binds to glycoprotein receptors on cell - common cold, SARS, Middle East respiratory syndrome coronavirus (MERS CoV)
Penton fibre binds to cell receptor
Pharyngitis, conjunctivitis, bronchitis
Common viruses which cause acute pharnygitis 8
Viruses inevitably encounter the submucosal lymphoid tissue that form a defensive risk around the oropharynx.
Rhinoviruses Coronavirus Adenovirus Influenza Parainfluenza - more severe than common cold Enteroviruses including Coxsackie A16 - small vesicles on hard palate/ tongue (hand, foot and mouth) EBV HSV1 - hard palate/ tongue vesicles
Common bacteria which cause acute pharyngitis
Streptococcus pyogenes - usually 5-10 years old
Neisseria gonorrhoeae - often asymptomatic
Corynebacterium diptheriae - can be severe
Haemophilus influenzae - epiglottitis
Borrelia vincentti - Vincent’s angina
Routes of transmission for CMV
CMV humans are natural hosts
Saliva Blood Organ donor Urine Semen/ cervical Breast milk
CMV causes silent infection, often asymptomatic.
Spreads to lymphoid tissues, then systemically via circulating lymphocytes and monocytes to involve lymph nodes/ spleen and epithelial cells of salivary gland/ kidney tubules/ cervix/ semen, where it is shed to outside world.
How does CMV cause disease
Inhibits T-cell response by interfering with MHC class I expression Induces Fc receptors on infected cells to help spread
Causes no illness in children, mild disease in adults. Cell mediated immunity helps keep virus at bay, but cannot clear it, remains throughout life. Can cause disease one immunity impaired
How does CMV spread to foetus
Primary infection during pregnancy allows spread of virus from blood to placenta, then to foetus. 18% foetus symptomatic at birth. CMV second only to Down’s syndrome as cause of intellectual disability
What are symptoms of CMV
In immunodeficiency such as HIV, bone marrow/ solid organ transplant
Interstital pneumonitis with infiltrating infected mononuclear cells
CNS
Retinitis
GI - colitis, hepatitis
Diagnosis of CMV
Cannot diagnose clinically, as usually asymptomatic
CMV IgM/ IgG. Not very helpful in immunosuppressed patient.
Use CMV DNA level monitoring if CMV positive prior to immunosuppression
Pneumonitis - bronchoalveolar lavage for CMV DNA/ Antigen detection
Colitis - biopsy
Treatment CMV
Treatment CMV pneumonitis
CMV vaccine has been trialled, as it is big cause of intellectual disability, and morbidity in immunosuppressed. CMV glycoprotein B vaccine helps generate antibodies to reduce future viraemia if becomes infected
Ganciclovir
Foscarnet
Anti-virals reduce viral replication, do not eliminate virus
CMV pneumonitis is immunopathological process, CMV specific or normal human immunoglobulin is given to help block Tc-cell response to pneumocytes expressing the target antigens. Also give anti-virals
EBV humans are natural host. Virus is morphologically identical to other herpesviruses, but antigenically distinct.
What are the antigens?
How is it transmitted
Viral capsid antigen (VCA)
EBV associated nuclear antigen (EBNA)
Exchange of saliva - e.g kissing
Therefore peaks occur in children (sub-clinical), and 14-20 years old
Explain local body spread of EBV infection from initial infection
What is incubation period
EBV replicates in local B lymphocytes after attaching to C3d (CD21) receptor, in oropharynx. Virus also infects oropharyngeal epithelial cells. Virus is shed from lymphocytes/ epithelial cells into salivary gland
B lymphocytes spread via blood to liver/ lymph nodes/ spleen
4-7 weeks
What is immune response to EBV?
T cells respond to infected B cells. T-cells appear as atypical lymphocytes on blood film. T-cells destroy infected B cells to gradually clear the infection. This cause lymphadenopathy
Immune response usually weak, and produces no clinical symptoms in children.
IFN-gamma produced by T-cells and NK cells contribute to symptoms. Infected B cells produce polyclonal antibodies and other auto-antibodies, which can cause AIHA
What are clinical features and severe complications
Fever Sore throat Petechiae on hard palate Lymphadenopathy Splenomegaly Lethargy Hepatitis
Severe complications -
aseptic meningitis
airway obstruction
haemophagocytic syndrome
How does EBV remain latent
Acts against complement and IFN
Produces it’s on fake IL-10, which interferes with hosts normal IL-10
Prevents apoptosis of infected cells
How to diagnose EBV
Treatment
Usually clinical diagnosis
VCA IgM/ VCA IgG in serum
EBNA IgG appears few weeks after symptoms
Atypical lymphocytes on blood film
Heterophil antibodies to horse/ sheep erythrocytes in monospot test
Antivirals not used in immunocompetent
Antivirals only work on lytic part of infection
Which cancers are associated with EBV (4)
Burkitt’s lymphoma in Africa/ PNG. Restricted to certain areas, so clear that EBV alone does not cause lymphoma. Co-carinogen malaria, weaknes T-cell control of EBV infection, and possibly increases activation of B cells. This increased B-cell turnover can lead to neoplastic transformation
B-cell lymphoma - usually if primary EBV vaccination post-transplant. EBV DNA found in tumour cells, which also show translocation of c-myc oncogene
Post-transplant lymphoproliferative disorder - due to uncontrolled B-cell proliferation related to EBV
Nasopharyngeal carcinoma - SE asia. EBV DNA in tumour cells. Co-carcinogen may be ingested nitrosamines from preserved fish
What are compliciations of strep pyogenes infection
Peritonsilar abscess - quinsy
Otitis media/ sinusitis/ mastoiditis
Scarlet fever - certain strains produce erythrogenic toxin , which localises in skin, and causes erythematous rash. Rash, sore throat, red cheeks, swollen tongue. Then get skin desquamination. Highly contagious
Impetigo/ erysipelas/ cellulitis
Pneumonia
Rheumatic fever - antibodies formed to antigens in streptococcal cell wall, cross-react with sarcolemma of heart. Myocarditis develops after 2-4 weeks. Duckett-Jones criteria for diagnosis
Rheumatic heart disease - repeated attacks strep pyogenes with different M types can damage heart valves. May need prophylaxis. Most common cause heart disease in resource poor settings
Glomerulonephritis - immuno complexes form which are deposited in glomeruli. Immune cells are recruited, and cytokines released, causes inflammation. Develop oedema/ HTN 1-2 weeks after sore throat
Diagnostic criteria for rheumatic fever
Revised Duckett-Jones criteria
Acute RF -
2 major or
1 major plus 2 minor
Major - Carditis Arthritis Chorea - jerky motion Erythema marginatum - pink rings come and go Subcutaneous nodules
Minor - Polyarthalgia Fever Raised CRP/ ESR Prolonged PR interval on ECG
Diagnosis of strep pyogenes
Treatment
Throat swab
Blood culture
GAS are sensitive to penicillin
Which bacteria cause Group A Strep
16% of schoolchildren carry GAS in throat during winter
Strep pyogenes
Strep anginosis
Strep dysgalactiae
How does mumps spread?
What is it’s route through the body
When are patients with mumps infectious?
Airborne droplets/ salivary secretions
Multiply in epithelium of respiratory tract
Spread to local lymph nodes - multiplies there
Primary viraemia
Spread to salivary gland/ testes/ pancreas/ CNS/ kidneys - replication causes oedema and symptoms
Infected patient is contagious from 3 days before symtpom onset, to 6 days after symptom onset
Age of peak incidence of mumps
Incubation period of mumps
Symptoms of mumps
Reinfection can occur after primary infection, or after MMR vaccine
5-14 years old
16-18 days
Painful/ swollen parotid glands
Fever
Orchitis
Pancreatitis
Diagnosis of mumps
Treatment
Prevention
viral RNA throat swab/ CSF/ urine
Mumps IgM
Symptomatic treatment
MMR live attenuated vaccine
Acute otitis media occurs due to purulent material building up leading to a bulging, red, tympanic membrane which may rupture and discharge.
Why is more common children?
Most common viral/ bacterial organisms
Eustachian tube is open more widely, and is shorter
RSV - most common Strep pneumoniae H Influenzae M Catarrhalis S pyogenes
Signs of acute otitis media
Treatment
If acute attacks of otitis media are not properly treated, can develop chronic suppurative otitis media
Fever
Bulging tympanic membrane
Fluid may persists in ear after treatment (glue ear), can can cause hearing and learning difficulties
Analgesia
Antibiotics if systemic involvement - amox/ clari
Causes of otitis externa
Treatment
External canal has bacterial flora similar to that of skin, so pathogens are usually different to otitis media
S Aureus
Candida albicans
Proteus
Pseudomonas
Neomycin/ chloramphenicol drops
Causes of acute sinusitis
Treatment
Same as otitis media: RSV - most common Strep pneumoniae H Influenzae M Catarrhalis S pyogenes
Viral cause most common by far. If duration more than ten days, likely to be bacterial in origin.
Amox/ co-amox/ clari empirically
Consider CT if considering complications
Acute epiglottiitis seen in young children. Hib vaccine has reduced incidence
What is the most common cause
What is main complication
Treatment
H Influenzae capsular type B
Spreads from nasopharynx to expiglottis causing severe inflammation and oedema. Can look similar to diptheria
Airway obstruction - may need intubation
Antibiotics e/g cefotaxime
Oraal cavity is continous with pharynx, but is different as has teeth, which specific bacteria attach to. 1 litre of saliva per day produced. Contains lysozyme, lactoperoxidase, antibodies to help find infection
When does candida albicans establish infection
Treatment oral candida
Prolonged antibiotic courses
Immunocompromised - HIV/ chemotherapy
Nystatin
Fluconazole
Which bacteria cause dental caries
How does it gain competitive advantage
Bacteria form dental plaque on tooth surface by synthesising glucan (polysaccharide) which forms matrix between streptococci. Removed with brushing, but re-establishes after few hours.
Bacteria use dietary sugar to form lactic acid, which decalcifies teeth, and proteolytic enzymes to break down enamel and cause tooth cavity
90% people colonised with this bacateria, so may be regarded as most prevalent infectious disease in resource-rich countries
Step mutans
Produces bacteriocins which kill other bacteria
Reduces pH to 4.0 to kill other bacteria
Gingival crevice forms between gums and tooth margin, can develop peridontal disease
Which bacteria cause peridontal disease
In disease, gingival crevice increases in size, and becomes a pocket of exudate. Activated macrophages release cytokines which activates peridontal fibroblasts and matrix metalloproteinases causing collagen degredation. Structures supporting teeth such as ligaments weaken, and tooth becomes looser. Gums bleed easily and then recede. Major cause of tooth loss
Actinomyces viscosus
Actinobacillus
Fusobacteriym
Bacteroids
Treatment of:
- Mastoiditis
- Otitis externa
- Otitis media
- Quinsy
- Mastoiditis - contact ENT
- Otitis externa - no treatment
- Otitis media - most cases viral, just analgesia. If chronic (>4 days) then amoxicillin or clarithromycin for 5 days
- Quinsy - benzylpenicillin and metronidazole, clindamicin second line
In sore throat/ pharyngitis, how do you decide who should get treatment
What is treatment
Beware EBV which when given penicillin can cause rash
Patients with 3 of 5 centor criteria (history of fever, purulent tonsils, cervical adenopathy, absence of cough, age) or history of otitis media may benefit more from antibiotics.
PenV
Clarithromycin
Co-amoxiclav if EBV
Treatment of:
- epiglottitis
- acute sinusitis
- chronic sinusitis
- whooping cough
- Epiglottitis - Cefotaxime
- acute sinusitis - usually viral, nsaisds
- chronic sinusitis - co-amoxiclav, clarithromycin, doxycyline
- whooping cough - antibiotics have little effect in paroxysmal stage. Clarithromycin
