Viral Infection Of The Respiratory Tract

RESPIRATORY DISEASES

VIRAL

Viruses Viruses are intracellular parasites that can pass through conventional bacteriological filters. -They contain a virus-specific nucleic acids but require the synthetic machinery of a host cell for replication and proliferation.

• Common respiratory viruses include the influenza viruses, respiratory syncytial virus, adenoviruses, and rhinoviruses. • Viruses are associated with the "common cold" and with the "flu" and are often the agents of pneumonia, bronchiolitis, and inner ear infections (otitis). Antibiotics are ineffective against viruses although there are some chemotherapeutic agents which may limit the severity of illness by suppressing viral replication.

This view of type a influenza virus shows several virions (one is circled) attached to an infected ciliated epithelial cell.----------------------------

---------This electron micrograph of respiratory syncytial virus (RSV) illustrat virions budding from an es fiveinfected cell. T he viral nucleic acid

The abnormalities of ciliary structure that appear in respiratory infections are distinctive from those characteristic of Primary Ciliary Dyskinesia(PCD) and although they may be commonly observed, They are less consistent and more focal in their distribution.

The figure below illustrates microtubular additions and deletions in cilia of a patient with a viral upper respiratory infection confirmed by culture. Note also that the central microtubules of two apparently normal cilia exhibit disorientation similar to that seen in cilia of patients with PCD.

What are common viral respiratory diseases? Common viral respiratory diseases are illnesses caused by a variety of viruses that have similar traits and affect the upper respiratory tract. The viruses involved may be the influenza viruses, respiratory syncytial virus (RSV), parainfluenza viruses, or respiratory adenoviruses.

How are the respiratory viruses spread? The viruses are spread directly by droplets coughed or sneezed into the air which are then inhaled, or indirectly by contaminated hands, handkerchiefs, toys, etc. which come in contact with the nose or eyes.

Respiratory viral diseases Respiratory infections are common, eg. colds in both adults and children. 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.

Upper Respiratory Tract diseases

Colds Main feature: watery to mucoid, sometimes purulent nasal discharge "coryza". Often preceded by a sore throat, sometimes accompanied by fever and often followed by transient opportunist bacterial infection.

COLDS

are probably most frequently caused by rhinoviruses but both enterovirus and coronavirus infections may cause a similar symptomatology. Respiratory syncytial virus (RSV) and parainfluenza virus infections may manifest themselves as common colds in adults but create more significant problems in the young age group.

Infections of the pharynx. A red, sore throat is one of the most common clinical signs of viral infection. Gingivostomatitis and tonsillitis may both have viral etiology. The herpes viruses may cause enanthems, with eruptions of the mucous membrane of the pharynx. Vesicular gingivostomatitis may result from both primary and recurrent herpes simplex infections. Herpangina with a few small blisters on the soft palate and the posterior wall of the throat or the tongue is seen in children or adolescents. Tonsillitis with a badly smelling greyish exudate covering the tonsils is seen in at least 50 per cent of cases of EBV induced infectious mononucleosis (IM). This is not a feature of CMV-induced IM. Tonsillitis may also occur in HSV induced gingivostomatitis. Tender, swollen tonsils may represent a lymphoid reaction of many virus infections and is a common finding in adenovirus infections

Common viral causes of upper respiratory tract infections and their laboratory diagnosis.   Clinical signs

Virus

Laboratory test

Specimen

Common cold a

Rhinovirus Coronavirus

Virus culture

NPW

Pharyngitisa

Adenovirus

Virus culture

NPW(Throatsw ab)

Pharyngitisa

Parainfluenzavi Virus culture rus 1-4

NPW

Pharyngitisa

Influenzavirus Virus culture A and B

NPW

Gingivostomatitis Pharyngitis Tonsillitis

HSV

HSV IgM/IgG Virus culture

Clotted blood Throat swab

Infectious mononucleosis EBV

EBV serology

Clotted blood

Infectious mononucleosis CMV

CMV IgM/IgG Virus culture

Clotted blood NPW

Infectious mononucleosis HHV6

HHV6 IgM/IgGPCR

Clotted bloodsaliva

Infectious mononucleosis Toxoplasma gondii Toxo IgM/IgG

Clotted blood

Pharyngitis/Koplik's spots Measles

Measles IgM/IgG Clotted blood

Herpangina/hand foot and Coxsackie A mouth disease

Virus culture

NPW/ stool throat swab

Primary HIV infection

HIV serology Culture/PCR

Clotted blood Heparinized blood

HIV

a

Laboratory testing is not routine on common, self limited illnesses.

Pharyngitis ("sore throat") Generalized erythema of pharynx, not localized to the tonsils and not associated with coryza. Some fever present.

Tonsilitis Local infection of tonsils = red, swollen with exudate on the surface. (Bacterial tonsilitis is quite common.)

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

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

Lower Respiratory Tract

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 (respiratory insufficiency). Can be fatal - ie. life-threatening disease.

Acute Bronchitis Inflammation of bronchi, accompanied by fever, cough, wheezing and "noisy chest".

Acute Bronchiolitis Inflammation of terminal bronchioles in small children. Bronchiole diameter is larger during inspiration than during expiration and this leads to hyperinflation of air sacs distal to bronchiole. Complete plugging of bronchiole with air resorption leads to collapse. These features can be seen on x-ray. These changes cause respiratory embarrassment and can be life-threatening. Bronchiolitis appears in seasonal epidemics in Britain but it can be seen all the year round in the Red Cross Childrens' Hospital, in the poorer communities of the Cape

Pneumonia & Bronchopneumonia Acute respiratory disease accompanied by fever, restlessness and cyanosis. Often not much clinical "consolidation". Again, can be lifethreatening.

Viral respiratory pathogens

PARAMYXOVIRUSES

General Properties of the Paramyxoviruses The whole important group of Paramyxoviruses is fairly homogeneous. Morphology Generally fairly similar to influenza: roughly spherical sometimes filamentous, easily distorted. A bit larger than influenza virus - 100-300nm. Composed of inner helical nucleocapsid containing protein/RNA, contained within a membranous envelope studded with "spikes" of: Haemagglutinin (Haemadsorption) and Neuraminidase (Haemolysis)

Primary infections usually occur in (early) childhood, with some resultant degree of protection against developing clinical disease later on in life. However, re-infections do occur in adulthood, but disease is subclinical or very minor. Spread The human paramyxoviruses are essentially diseases of man only, and are spread by droplets from the nose and mouth to fairly close contacts. Many of them are fairly highly infectious and go around the community in epidemics - often seasonal, eg. Winter coughs and colds. Fomites might also assist spread.

Virions are enveloped and enclose a helical nucleocapsid containing single-stranded RNA. Most virions are roughly spherical (about 200nm in diameter) but they can be much larger and more pleomorphic. The virus envelope is a lipid bilayer, studded with virus encoded glycoproteins which have properties of haemagglutination and fusion (the F protein).

PARA-INFLUENZA Types 1, 2, 3 and 4

All types can cause minor infections in children and adults. Types 1, 2 and 3 may be associated with more severe lower respiratory tract disease in children. For instance, in an American series of cases, 30% of acute laryngo-tracheobronchitis (LTB) cases yielded para-influenza viruses. Type 1 is especially associated with LTB, sometimes also type 2. Paraflu's have also been isolated from patients with pneumonia.

The virus grows locally in the respiratory tract lining of the URT and it may then spread down into the lungs. IgA type antibodies are induced. These are present in the respiratory secretions and seem to be more important than the IgG antibodies in the serum with regard to protection. However, IgA antibodies do not cross the placenta and babies thus have no maternal protection against this type of infection. Primary infections with para-influenza viruses usually occur in the first year or years of life. Re-infection usually causes only minor infection of the URT - one of the causes of a common cold in children and adults.

Respiratory Syncytial virus - (RSV)

This is an unusual but very important member the Paramyxovirus group: while it resembles the other members morphologically, no haemagglutinin or neuraminidase or haemolytic properties have been detected,and there is no antigenic similarity to other members. In cell cultures it readily induces many large syncytia with cytoplasmic inclusions - hence its name.

Clinical RSV was first isolated from chimpanzees with colds, and it was soon found to cause colds in man as well. (Chimps were probably infected by their human handlers.) However, it was also found to be associated with severe pulmonary infections in infants - especially Bronchiolitis. RSV is the prime cause of Bronchiolitis

RHINO VIRUSES (Common Cold virus)

Over 100 serotypes of this Picorna virus family are responsible for about 50% of common colds. Clinical An inhalational infection of the URT. Incubation period is short: 1 to 3 days followed by headache, sore throat, fullness in the nose. Then there is a profuse watery discharge from the nose which gradually thickens and becomes mucopurulent and decreases in volume. The infection resolves in about a week. Following a rhinovirus cold, there is a short period of immunity to all colds but prolonged immunity to the specific serotype causing the recent infection.

Complications A cold may temporarily upset the mucosal cilia and predisposes to secondary invaders especially bacterial infections, eg. sinusitis (pneumococcus, haemophilus, etc) and bronchitis and possibly pneumonia. These may require antibiotic treatment. Epidemiology An infected person is infectious in the first two days of coryza. Colds are readily acquired from breathing room air from a room crowded with coldy people. Wet cold weather per sé does not cause colds, but may predispose to infection from other persons. Colds are ubiquitous around the world except in very isolated communities. Prevention The enormous diversity of cold-causing viruses essentially rules out a vaccine. Vitamin C and bacterial vaccines are unproven.

INFLUENZA VIRUSES

The virion is generally rounded but may be long and filamentous. A single-stranded RNA genome is closely associated with a helical nucleoprotein (NP), and is present in eight separate segments of ribonucleoprotein (RNP), each of which has to be present for successful replication.

The segmented genome is enclosed within an outer lipoprotein envelope. An antigenic protein called the matrix protein (MP 1) lines the inside of the envelope and and is chemically bound to the RNP. The envelope carries two types of protruding spikes. One is a box-shaped protein, called the neuraminidase (NA), of which there are nine major antigenic types, and which has enzymic properties as the name implies.

The other type of envelope spike is a trimeric protein called the haemagglutinin (HA) (illustrated on the right) of which there are 13 major antigenic types. The haemagglutinin functions during attachment of the virus particle to the cell membrane, and can combine with specific receptors on a variety of cells including red blood cells. The lipoprotein envelope makes the virion rather labile - susceptible to heat, drying, detergents and solvents.

Influenza: a virus replication cycle

end of respiratory viral diseases