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

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

‘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

‘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

‘Flu - therapy Symptomatic Antivirals 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) Nice says that only given in patients at risk of complications and when flu circulating and early in disease.

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

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

Human Duck Pig Human Human Pandemic

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;360:2605-2615

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

Egon Schiele,The Family,1918.Oesterreichische Galerie, Vienna http://www.artchive.com/artchive/S/schiele/schiele_family.jpg.html Egon Schiele,The Family,1918.Oesterreichische Galerie, Vienna

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

Metapneumovirus First isolated 2001 children with Acute Respiratory Tract Infection Nat Med 2001;7:719-24. Contribution of ARTI to inc in winter deaths is well recognised

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.

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

Laboratory confirmation PCR

Other recently discovered respiratory viruses Bocavirus Various coronaviruses

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

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

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.

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