1. Respiratory infection - 1
Dr Paul McIntyre
This is a big subject and requires some background reading.
TAKE NPA EQUIPMENT FROM BOTTOM DRAWER.

2. Influenza - clinical presentation
Fever: high, abrupt onset
Malaise
Myalgia
Headache
Cough
Prostration
Up to 40C
Generally feeling unwell
Muscle pain is marked
Headache marked, may early in epidemic be mistaken for meningitis.
Cough initially dry and painful, becomes productive but painless
Laryngo- tracheo - bronchitis
Interferon cause systemic symptoms, virus restricted to resp epithelium

3. ‘Flu - aetiology Classical flu ‘Flu- like illnesses
influenza A viruses
influenza B viruses
‘Flu- like illnesses
parainfluenza viruses
many others
Haemophilus influenzae
bacterium
not a primary cause of ‘flu
may be a secondary invader
More than 1 subtype of flu A circulating.
Flu - like illnesses occur outside of the major epidemics

4. ‘Flu - complications Primary influenzal pneumonia
seen most during pandemic years
can be disease of young adults
high mortality
Secondary bacterial pneumonia
more common in elderly and debilitated, pre-existing disease
cause of mortality in all influenza epidemics
Pandemics: multi continent epidemics
In 1918/19 pandemic mortality most common in young adults eg 60k of 110k US troops in trenches.
20 million dead in 1918/19

5. ‘Flu - therapy Symptomatic Antivirals
bed rest, fluids, paracetamol
Antivirals
oseltamivir
zanamivir
see NICE guidelines
‘flu circulating
risk of complications
use in prophylaxis (additional to vaccine)
Nice says that only given in patients at risk of complications and when flu circulating and early in disease.

6. Epidemiology of ‘flu Winter epidemics
Epidemics seen in association with minor mutations in the surface proteins of the virus
antigenic drift
Pandemics: rare, unpredictable, influenza A
antigenic shift
segmented genome
animal reservoir/mixing vessel
Drift classical Darwinian selection

7. Current pandemic planning assumption
the combination of “reasonable worst case” 30% Clinical Attack Rate and 0.1% Case Fatality Ratio would result in a total number of deaths of about 20,000, or about 1/30th of the total expected each year from all causes (about 600,000).
These are planning assumptions for forthcoming winter, not predictions

8. Human
Duck
Pig
Human
Human
Pandemic

9. Comparison of H1N1 Swine Genotypes in Early Cases in the United States
Figure 3. Comparison of H1N1 Swine Genotypes in Recent Cases in the United States. The triple-reassortant strain was identified in specimens from patients with infection with triple-reassortant swine influenza viruses before the current epidemic of human infection with S-OIV. HA denotes the hemagglutinin gene, M the M protein gene, NA the neuraminidase gene, NP the nucleoprotein gene, NS the nonstructural protein gene, PA the polymerase PA gene, PB1 the polymerase PB1 gene, and PB2 the polymerase PB2 gene.
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med 2009;360:

10. Future threats Highly pathogenic avian flu is influenza A H5N1
bird to human transmission seen
High mortality
not readily transmitted human to human

11. Egon Schiele,The Family,1918.Oesterreichische Galerie, Vienna
Egon Schiele,The Family,1918.Oesterreichische Galerie, Vienna

12. Lab confirmation of influenza
Direct detection of virus
PCR
Throat swabs in virus transport medium
Pernasal swabs in virus transport medium
other respiratory samples
Other labs may use immunofluorescence, antigen detection (near patient), virus culture

13. Lab confirmation of influenza
Direct detection of virus
PCR
Antibody detection
may need paired acute and convalescent bloods
often retrospective

14. PCR for Influenza A Virus
Influenza A RNA
positive samples
Influenza A RNA
negative samples

15. Prevention of ‘flu Vaccine killed vaccine
given annually to patients at risk of complications
given to health care workers

16. Antiviral as prophylaxis
antivirals after a contact with ‘flu
NICE guidelines
rarely used
During “containment phase” of first wave of pandemic.

17. Other causes of community acquired pneumonia
Microbiological causes (all bacteria)
Mycoplasma pneumoniae
Coxiella burnetii
Chlamydia
Not viruses

18. Mycoplasma, coxiella and Chlamydophila psittaci
Therapy
all respond to tetracycline and macrolides (eg clarithromycin)
Mortality
varies with pathogen, but generally lower than classical bacterial pneumonia
Often known as “atypical pneumonia”
relates to presentation and response to therapy in the pre-antibiotic era

19. Lab confirmation of mycoplasma, coxiella and Chlamydophila psittaci
By serology
send acute and convalescent bloods to lab
gold top vacutainer
Antibody tests

20. Mycoplasma pneumoniae
Common cause of community acquired pneumonia
Older children, young adults
Person to person spread
Only one of the 3 causes of atypical pneumonia described today that is common in UK

21. Coxiella burnetii (Q-fever)
Diseases
pneumonia
pyrexia of unknown origin (Q fever)
Uncommon, sporadic zoonosis
Sheep and goats
Complication
culture negative endocarditis
Occasional outbreaks

22. Chlamydia and respiratory disease
Chlamydophila psittaci causes Psittacosis
previously called Chlamydia psittaci
uncommon, sporadic zoonosis
caught from pet birds
parrots, budgies, cockatiels
psittacosis usually presents as pneumonia

23. Bronchiolitis Clinical presentation Severe cases
1st or 2nd year of life
Fever
Coryza
Cough
Wheeze
Severe cases
grunting
PaO2
Intercostal / sternal indrawing

24. Bronchiolitis - complications
Respiratory and cardiac failure
prematurity
pre-existing respiratory or cardiac disease
Scottish Intercollegiate Guidelines Network
SIGN guideline 91

25. Bronchiolitis Aetiology Lab confirmation Therapy
>90% cases due to Respiratory Syncytial Virus
Lab confirmation
By PCR on throat or pernasal swabs
(direct IF on NPA in some labs)
Therapy
supportive
nebulised ribavirin no longer used

26. Bronchiolitis - epidemiology and control
Epidemics every winter
Very common
No vaccine
Nosocomial spread in hospital wards
cohort nursing
handwashing, gowns, gloves
Passive immunisation
poor efficacy and cost-effectiveness
Passive immunisation with a monoclonal antibody preparation has not been shown to reduce mortality and so is not widely used.

27. Metapneumovirus
First isolated 2001 children with Acute Respiratory Tract Infection
Nat Med 2001;7:
Contribution of ARTI to inc in winter deaths is well recognised

28. Epidemiology Most children antibody positive by age 5
found in a wide range of ages
Virus is newly discovered, not new
World-wide distribution
Highest incidence in winter
8% of samples in Canadian children’s hospital
J Clin Micro 2005;43:

29. Association with disease
May be sole pathogen isolated
Possibly second only to RSV in bronchiolitis
Similar symptoms to RSV in both children and adults
Range of severity from mild to requiring ventilation
Incidence of asymptomatic infection low (in children at least)
Williams JV et al. NEJM 2004;350: (and editorial)
2% of cases of influenza-like illness
Emerging Infect Dis 2002;8:

30. Laboratory confirmation
PCR

31. Other recently discovered respiratory viruses
Bocavirus
Various coronaviruses

32. Current Respiratory tests
Samples for PCR: Throat swabs in viral transport medium, bronchoalveolar lavage (BAL), endotracheal aspirate etc
Flu A, Flu B, parainfluenza 1-3, metapneumo, adeno, RSV

33. Chlamydia trachomatis and Chlamydophila pneumoniae and respiratory disease
STI which can cause infantile pneumonia
diagnosed by PCR on urine of mother or pernasal / throat swabs of child
Chlamydophila pneumoniae
person to person (formerly Chlamydia pneumoniae)
mostly mild respiratory infections
may be picked up by test for Psittacosis

34. Microbiology Problem Solving Session
Remember to bring the relevant pages from the study guide with you to the class.
Code for the classroom’s cloakroom is 1245
Worthwhile looking at tuberculosis diagnosis and management before coming along.
Remember to wash your hands before leaving the classroom as other students use live bacteria in their practicals in that room.

35. Lecture objectives
An understanding of the epidemiology, presentation, management and prevention of many of the most important viral and “atypical” causes of respiratory infection.