1

Respiratory infection - 1

Dr Paul McIntyre

2

Influenza - clinical presentation

• Fever: high, abrupt onset

• Malaise

• Myalgia• Headache• Cough• Prostration

3

‘Flu - aetiology• Classical flu

– 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

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

5

‘Flu - therapy

• Symptomatic– bed rest, fluids, paracetamol

• Antivirals– oseltamivir– zanamivir

• see NICE guidelines www.nice.org.uk– ‘flu circulating– risk of complications

– use in prophylaxis (additional to vaccine)

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

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

9

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med 2009;360:2605-2615

Comparison of H1N1 Swine Genotypes in Early Cases in the United States

10

Future threats

• Highly pathogenic avian flu is influenza A H5N1

• bird to human transmission seen– High mortality

• not readily transmitted human to human

11Egon 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 VirusPCR for Influenza A Virus

Influenza A RNAnegative samples

Influenza A RNA positive 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

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

20

Mycoplasma pneumoniae

• Common cause of community acquired pneumonia

• Older children, young adults

• Person to person spread

21

Coxiella burnetii (Q-fever)

• Diseases– pneumonia– pyrexia of unknown

origin (Q fever)

• Uncommon, sporadic zoonosis

• Sheep and goats• Complication

– culture negative endocarditis

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

– 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– >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

27

Metapneumovirus

• First isolated 2001 children with Acute Respiratory Tract Infection– Nat Med 2001;7:719-24.

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;43:5520-5.

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;350:443-50 (and editorial)

• 2% of cases of influenza-like illness– Emerging Infect Dis 2002;8:897-901

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• Chlamydia trachomatis

– 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.