Micro - 4th Asessment - Viral Infections Of The Respiratory Tract - 2007

Viral Infections of the Respiratory Tract

Fourth Medical,2007 .Prof. Widad Al-Nakib, FRCPath

Respiratory Infections are Common • Most are fairly mild, self-limiting and confined to the upper respiratory tract (URT). • Most are probably viral induced – at least initially. • However, in infants and children, URT infections may spread downwards and cause more severe infections and even death.

Respiratory Tract Infections

Upper Respiratory Tract (URT) Viral Infections 1.

Colds. Watery to mucoid, sometimes purulent nasal discharge “coryza”. Often preceded by a sore throat, sometimesaccompanied by fever and often followed by transient opportunist bacterial infection.

2.

Pharyngitis (“sore throat”). Generalised erythema of pharynx, not localised to the tonsils and not associated with coryza. Some fever present.

3.

Tonsilitis. Local infection of tonsils=red, swollen with exudate on the surface.

4.

Sinusitis & Otitis media. Painful inflammatory conditions of sinuses and middle ear. Drainage of these spaces may be impaired and lead to bacterial infection. (it is usually secondary to viral infection of the nose and pharynx.)

5. Influenza. Fever, myalgia, sore throat, headache, prostration – usually NOT much nasal discharge compared to a cold. Maybe some cough.

Lower Respiratory Tract (LRT) Viral Infections 1. Laryngo-Tracheo Bronchitis (Croup). An acute viral inflammation of larynx and trachea in small children. Often preceded by a “cold”. Accompanied by pyrexia, hoarseness, croaking cough, stridor, restlessness. Can be fatal. 2. Acute Bronchitis. Inflammation of bronchi, accompanied by fever, cough, wheezing and “noisy chest”. 3. Acute Bronchiolitis. Inflammation of terminal bronchioles in small children. Complete plugging of bronchiole with air resorption leads to collapse, and can be life-threatening. Usually preceded by coryzal symptoms which later develops into the major pulmonary illness. Clinically there is fever, rapid respiration, exhausting cough and wheezing. 4. Pneumonia & Bronchopneumonia. Acute respiratory disease accompanied by fever, restlessness and cyanosis. Often not much clinical “consolidation”. Again, can be life-threatening.

Bronchitis and Emphysema

Viruses Associated with Respiratory Infections Less Commonly Associated Viruses

Syndrome

Commonly Associated Viruses

Colds

Rhinoviruses, Coronaviruses

Influenza and parainfluenza viruses, enteroviruses, adenoviruses

Pharyngitis

Parainluenza viruses

Influenza viruses. CMV, EBV

Croup

Parainfluenza viruses

Influenza virus, RSV, hMPV, adenoviruses

Bronchitis

Parainfluenza viruses

RSV, Influenza viruses

Bronchiolitis

RSV, hMPV

Influenza and parainfluenza viruses, adenoviruses

Influenza

Influenza viruses

Parainfluenza viruses, adenoviruses

Bronchopneumonia Influenza virus, RSV, hMPV, Parainfluenza viruses, measles, VZV, Adenoviruses CMV SARS

SARS-coronavirus

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Influenza Virus • RNA virus, genome consists of 8 segments • enveloped virus, with haemagglutinin and neuraminidase spikes • 3 types: A, B, and C • Type A undergoes antigenic shift and drift. • Type B undergoes antigenic drift only and type C is relatively stable

Influenza Virus • Undergoes “antigenic shifts” and “antigenic drifts” with the haemagglutinin and neuraminidase proteins. • Antigenic “shifts” of the haemagglutinin results in pandemics. Antigenic “drifts” in the H and N proteins result in epidemics. • Usually causes a mild febrile illness. • Death may result from complications such as viral/bacterial pneumonia.

Epidemics and Pandemics

.Contd • Pandemics - influenza A pandemics arise when a virus with a new haemagglutinin subtype emerges as a result of antigenic shift. As a result, the population has no immunity against the new strain. Antigenic shifts had occurred 3 times in the 20th century. • Epidemics - epidemics of influenza A and B arise through more minor antigenic drifts as a result of mutation.

What Influenza Viruses Caused Past ? Pandemics • • • • •

1889–1891 H3N8 1918–1919 H1N1 1957–1958 H2N2 1968–1969 H3N2 This time H5NI

?’What Causes the ’Bird Flu

It is an influenza virus ,H5N1 sub-type •

So Why Are We So Afraid of the ?“’Bird Flu • Because the ‘Bird Flu’ is a new strain of influenza virus to humans and humans have no antibody against it to protect them? • So if the ‘Bird Flu’ virus adapts to grow in humans and it can spread from human to human it will cause infections world-wide, the so called “pandemic”, with very serious consequence and probably high mortality rate everywhere. • That is why the WHO is very worried and wants everybody to be prepared. In the 1918-1919 pandemic 40 million people died

So why is the ’Bird Flu” a serious ?disease in humans • The virus infects the lower respiratory tract causing pneumonia and multiple organ failure leading usually to death in these patients. Recent cases reported in the N. Eng. Med. shows that patients can present atypically with diarrhea, fever, encephalitis and usually die. Virus was found in faeces, blood and CSF

How Do Humans Get Infected with Avian ?Influenza Virus

Treatment • Amantidine is effective against influenza A if

given early in the illness. However, resistance to amantidine emerges rapidly • Rimantidine is similar to amantidine but but fewer neurological side effects. • Ribavirin is thought to be effective against both influenza A and B. • Neuraminidase inhibitors (Oseltamivir, Zanamivir) .They are highly effective and have fewer side effects than amantidine. Moreover, resistance to these agents emerge slowly

Prevention • Inactivated whole/split/subunit vaccines are available against influenza A and B. • The vaccine is normally trivalent, consisting of one A H3N2 strain, one A H1N1 strain, and one B strain. • The strains used are reviewed by the WHO each year. • The vaccine should be given to debilitated and elderly individuals who are at risk of severe influenza infection. • Oseltamivir or Zanamivir can be used for those who are allergic to the vaccine or during the period before the vaccine takes effect.

Parainfluenza viruses • Enveloped, pleomorphic morphology • 5 serotypes: 1, 2, 3, 4a and 4b • ssRNA virus • No common group antigen, HN, F proteins • Closely related to Mumps virus

Clinical Manifestations • Croup (laryngo-tracheo-bronchitis) - most common manifestation of parainfluenza virus infection. However other viruses may induce croup e.g. influenza, RSV and hMPV. Other conditions that may be caused by parainfluenza viruses include bronchiolitis, pneumonia, flu-like tracheo-bronchitis, and coryza-like illnesses.

(Respiratory Syncitial Virus (RSV • Most common cause of severe lower respiratory tract disease in infants, responsible for 50-90% of bronchiolitis and 5-40% of bronchopneumonia • Other manifestations include croup (10% of all cases). • In older children and adults, the symptoms are much milder: it may cause a coryza-like illness or bronchitis.

?Infants at Most Risk 1. Infants with congenital heart disease - infants who were hospitalized within the first few days of life with congenital disease are particularly at risk. 2. Infants with underlying pulmonary disease - infants with underlying pulmonary disease, especially bronchopulmonary dysplasia, are at risk of developing prolonged infection with RSV. 3. Immunocompromized infants - children who are immunosuppressed or have a congenital immunodeficiency disease may develop lower respiratory tract disease at any age.

(Human Metapneumovirus (hMPV Clinical symptoms associated with the new virus are similar to those caused by human respiratory syncytial virus (RSV) infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. By the age of 5 years most children are infected.

Adenoviruses Pharyngitis (1, 2, 3, 5, 7) Pharyngoconjunctival fever (3, 7) Acute respiratory disease of recruits (4, 7, 14, 21) Pneumonia (1, 2, 3, 7) Pertussis-like syndrome (5) Follicular conjunctivitis (3, 4, 11) Epidemic keratoconjunctivitis (8, 19, 37) Acute haemorrhaghic cystitis (11, 21) Acute infantile gastroenteritis (40, 41) Intussusception (1, 2, 5) Severe disease in AIDS and other immunocompromized patients (5, 34, 35, >41) Meningitis

Management • There is no specific antiviral therapy. • A vaccine is available against Adult Respiratory Distress Syndrome (ARDS). It consists “live” adenovirus 4, 7, and 21 in “enterically” coated capsules. It is given to new recruits into various arm forces around the world.

Common Cold Viruses • Common colds account for one-third to one-half of all acute respiratory infections in humans.

• Rhinoviruses are responsible for 30-50% of common colds, Coronaviruses for 10-30% of all respiratory infections.

• The rest are due to adenoviruses, enteroviruses, RSV, influenza, and parainfluenza viruses, which may cause symptoms indistinguishable to those of rhinoviruses and coronaviruses.

Laboratory Diagnosis of Respiratory Virus Infections •

Detection of Antigen - a rapid diagnosis can be made by the detection of viral antigen in nasopharyngeal aspirates, throat washings and other respiratory samples by IF and ELISA.

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RT-PCR- detecting the viral genome in respiratory secretions and other samples.

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Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs.

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Serology - a retrospective diagnosis may be made by detecting significant virus antibody (greater than 4-fold) between blood samples collected at the acute phase and one at the convalescent phase using serological assays such as CFT, HAI or EIA.

A ’Novel’ Coronavirus Associated with SARS

SARS-Corona virus • SARS-Coronavirus has recently been associated to be the cause of severe acute respiratory syndrome (SARS) with a relatively high mortality rate. The ‘new’ virus is thought to have jumped ‘ species’ and became able to infect man with serious consequences.

Methods Used to Identify the Causative Agent of SARS • Virus isolation in Vero cell lines • Viral antigen detection (directly in specimen and/or in culture) • Electron Microscopy • Amplifying the viral genome indirectly in specimen and/or in culture using RT-PCR

SARS-Corona Virus SARS remains an ongoing problem internationally, and the virus is to some extent is partially contained but may well spread internationally. If it does, the consequences will be quite devastating as currently, we do not have any treatment nor a vaccine to prevent it. However it remains a “hot” topic for research especially with regards to the development of a vaccine and antiviral chemotherapy.