1 Respiratory infection - 1 Dr Paul McIntyre. 2 Influenza - clinical presentation Fever: high, abrupt onset Malaise Myalgia Headache Cough Prostration.

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Respiratory infection - 1

Dr Paul McIntyre

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Influenza - clinical presentation

• Fever: high, abrupt onset

• Malaise• Myalgia• Headache• Cough• Prostration

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‘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

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‘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

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‘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)

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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

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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

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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

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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

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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

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Lab confirmation of influenza

• Direct detection of virus– PCR

• Antibody detection– may need paired acute and convalescent bloods– often retrospective

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PCR for Influenza A VirusPCR for Influenza A Virus

Influenza A RNAnegative samples

Influenza A RNA positive samples

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Prevention of ‘flu

• Vaccine– killed vaccine– given annually to patients at risk of

complications– given to health care workers

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Antiviral as prophylaxis

• antivirals after a contact with ‘flu– NICE guidelines– rarely used

• During “containment phase” of first wave of pandemic.

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Other causes of community acquired pneumonia

• Microbiological causes (all bacteria)– Mycoplasma pneumoniae– Coxiella burnetii– Chlamydia

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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

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Lab confirmation of mycoplasma, coxiella and

Chlamydophila psittaci• By serology

– send acute and convalescent bloods to lab– gold top vacutainer

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Mycoplasma pneumoniae

• Common cause of community acquired pneumonia

• Older children, young adults

• Person to person spread

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Coxiella burnetii (Q-fever)

• Diseases– pneumonia

– pyrexia of unknown origin (Q fever)

• Uncommon, sporadic zoonosis

• Sheep and goats• Complication

– culture negative endocarditis

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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

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Bronchiolitis• Clinical presentation

– 1st or 2nd year of life– Fever– Coryza– Cough– Wheeze

• Severe cases– grunting PaO2

– Intercostal / sternal indrawing

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Bronchiolitis - complications

• Respiratory and cardiac failure– prematurity– pre-existing respiratory or cardiac disease

• Scottish Intercollegiate Guidelines Network– SIGN guideline 91

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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

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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

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Metapneumovirus

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

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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.

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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

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Laboratory confirmation

• PCR

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Other recently discovered respiratory viruses

• Bocavirus

• Various coronaviruses

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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

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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

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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.

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Lecture objectives

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