VIRAL INFECTIONS OF THE RESPIRATORY TRACT Influenza virus Rhinovirus Coronavirus Parainfluenza viruses Respiratory Syncytial viruses Adenovirus

ADENOVIRUSES Adenoviruses were first isolated from adenoids surgically removed from children in 1953

PROPERTIES Naked double stranded DNA virus Icosahedral symmetry 80 nm in diameter Capsid consist of 252 capsomeres (240 hexons, 12 pentons) Pentons make up the apices and possess projecting fibers. The fibers possess hemagglutinating activity and mediate the attachment of the virus to cellular receptors.

At least 47 serotypes of human adenoviruses are known and they are classified into 6 subgenera (A to F) on the basis of nucleotide sequence homology Adenoviruses share common epitopes on the hexons.

PATHOGENESIS Adenoviruses cause diseases that involve respiratory, urinary, gastrointestinal tracts and eye. Virus may be introduced through contact, respiratory droplets or ingestion. The association of particular types with specific disease syndromes is striking. After recovery of illness, adenoviruses may maintain latent persistent infections in the tonsils, the adenoids, and other lymphoid tissues.

CLINICAL SYNDROMES Wide variety of clinical syndromes, the majority of which concerns the respiratory tract. Adenovirus types Disease 1, 2, 3, 5, 7 Pharyngitis 1. 3, 7 Pharyngoconjunctival fever 2. 4, 7, 14, 21 Acute respiratory disease of recruits 3. 1, 2, 3, 7 Pneumonia 4. 3, 4, 11 Follicular conjunctivitis 5.

8, 19, 37 Epidemic keratoconjunctivitis 6. 5 Pertussis-like syndrome 7. 11, 21 Acute haemorrhagic cystitis 8. 40, 41 Acute infantile gastroenteritis 9. 1, 2, 5 Intussusception 10. 5, 34, 35 Severe disease in AIDS and other immunocompromized patients 11. 3, 7 Meningitis 12.

Pharyngoconjunctival FeverPharyngoconjunctival Fever –This disease is characterized by conjunctivitis, fever, pharyngitis and adenoidal enlargements. This is frequently associated with swimming pools. Acute Respiratory Disease (ARD) in Military RecruitsAcute Respiratory Disease (ARD) in Military Recruits –The crowding of people, allowing repeated exposure to highly infectious doses, and the strenuous physical exercise may account for the unusually high degree of severe infections. Characteristic symptoms include fever, malaise, sore throat, hoarseness and cough. Pneumonia develops in around 10% of cases.

Infections of the Eye Acute follicular conjunctivitisAcute follicular conjunctivitis, which is part of the syndrome of pharyngoconjunctival fever, can also occur as a separate entity. Epidemic keratoconjunctivitisEpidemic keratoconjunctivitis is a distinctly different syndrome. This syndrome is characterized by an aggressive conjunctivitis, pain, photophobia and lymphadenopathy followed by the development of superficial punctate keratitis.

Acute Hemorrhagic CystitisAcute Hemorrhagic Cystitis –Occurs predominantly in boys (6 – 15 years) –Acute dysuria –Haematuria –Adenovirus serotype 11 Infections of the gutInfections of the gut –Adenoviruses are associated with 4-15% of all children hospitalized with viral gastroenteritis. The enteric adenoviruses Ad40 and Ad41 are associated with 2/3rds of cases of adenovirus-associated diarrhea.

Adenovirus infection in immunocompromised patients Severe combined immunodeficiency (SCID) and immunocompromised hosts. - Children with SCID are prone to develop pneumonia and hepatitis with high mortality. AIDS - latent infections of the kidneys are occasionally seen in patients with AIDS. Members of subgenus D are often seen in the stools of AIDS patients. Bone marrow transplant recipients - These patients are vulnerable to activation of all latent DNA viruses. Adenovirus infections have been demonstrated in 8% of bone marrow transplant recipients.

LABORATORY DIAGNOSIS Virus Isolation –Adenovirus may be isolated from most body fluids and secretions; eye swabs, NPA, throat swabs, urine, faeces, and CSF. –Human embryonic kidney cells Hep-2 cells –Primary monkey kidney cells293 cells –CPE includes rounding, clustering of cells with refractile intranuclear inclusion bodies Detection of antigen by Immunoflurescence (IF) Serology –Infection of humans with any adenovirus type stimulates a rise in complement- fixing antibodies to adenovirus group antigens shared by all types. A four-fold or greater rise in these antibodies between acute phase and convalescent phase sera indicates recent infection. –The fastidious (no growth on cell cultures) enteric adenoviruses can be detected by direct examination of fecal samples by ELISA or latex agglutination tests.

TREATMENT AND PREVENTION There is no specific antiviral chemotherapy against adenoviruses at present. Swimming pool-associated conjunctivitis can be prevented with adequate levels of chlorine in the water. Effective vaccines are available for use in the military against adult respiratory distress syndrome. These vaccines are not currently licensed for administration to civilians. Live attenuated Adenovirus types 4, 7, and occasionally 21 are packaged into enteric capsules only replicate once they reach the intestine, resulting in an asymptomatic infection of the intestine. The vaccine had been shown to be both safe and effective.

PARAMYOVIRUSES Measles virus Mumps virus Respiratory Syncytial virus Parainfluenza Viruses One piece of ssRNA, helical nucleocapsid and envelope Negative polarity genome

RESPIRATORY SYNCYTIAL VIRUS Pneumonia and bronchiolitis in infants Fusion protein causes cells to fuse, forming multinucleated giant cells (syncytia).

EPIDEMIOLOGY RSV causes outbreaks of respiratory infections every winter. RSV is a major nosocomial pathogen in pediatric wards. The pathogen may be introduced by infected infants who are admitted from the outside and adults, especially members of staff with mild infections.

TRANSMISSION Respiratory droplets and direct contact of contaminated hands with the nose or eye The incubation period is usually days The virus spreads along the epithelium of the respiratory tract, mostly by cell-to-cell transfer

CLINICAL FINDINGS young infantsRSV is the most common cause of severe lower respiratory disease in young infants. It is responsible for % of cases of bronchiolitis, % of pneumonias and bronchitis and less than 10% of croups in young children. Young children –otitis media Older children & adults –common cold like – disease InfantsInfants –Febrile URTI –Lower respiratory tract involvement –Worsening cough –Tachypnoea and dyspnoea In bronchiolitis, the respiratory rate may be elevated, with wheezing and hyperinflation. Cyanosis may be present in severe cases.

Risk groups for fatal RSV infection Infants with congenital heart disease Infants with underlying pulmonary disease –especially bronchopulmonary dysplasia Immunocompromized infants –children who are immunosuppressed or have a congenital immunodeficiency disease. Nephrotic syndrome and cystic fibrosis

Complications Apnea –occurs in approximately 20% of cases (premature infants). The apnea is non- obstructive and develops at the onset or within the first few days of illness. The most common complication is prolonged alterations in pulmonary function, which may lead to chronic lung disease in later life.

LABORATORY DIAGNOSIS Immunoflurescence on smears of respiratory secretions ELISA for detection of RSV antigens multinucleated giant cells or syncytiaIsolation in cell culture (multinucleated giant cells or syncytia) Rise of antibody titre.

TREATMENT All infants with RSV lower respiratory tract disease are hypoxemic and oxygen should be given to hospitalized infants Aerosolized ribavirin in severely ill infants RespiGam contains a high concentration of protective antibodies against RSV. It is given for the prevention in children under 24 months with bronchopulmonary dysplasia or a history of premature birth.

PARAINFLUENZA VIRUSES

Croup (Acute Laryngotracheobronchitis) and pneumonia in children Common cold – like disease in adults. 5 subtypes: 1, 2, 3, 4a and 4b Surface spikes consist of H, N and fusion proteins. H and N on the same spike while fusion protein is on a different spike.

EPIDEMIOLOGY Transmission: respiratory droplets, winter months. Croup is the commonest clinical manifestation of parainfluenza virus infection, caused by subtypes 1 and 2. –It occurs in children (below 3 years). Parainfluenza 3 is prone to produce bronchiolitis and pneumonia. The majority of infections with parainfluenza viruses are subclinical.

CLINICAL FINDINGS Croup –Harsh cough –Inspiratory stridor –Hoarse voice Patients are usually afebrile. About 80% of patients exhibit runny nose 1 to 3 days before the onset of the cough. Usually, respiratory symptoms subside within 1 or 2 days.

In addition to croup, parainfluenza viruses cause –common cold, –pharyngitis, –otitis media, –bronchitis –pneumonia. Other viruses can induce croup, such as influenza viruses, RSV, measles and chickenpox. Parainfluenza virus infections in adults are relatively uncommon, and symptoms are usually less severe in adults than children.

LABORATORY DIAGNOSIS Croup is a well-defined, easily recognized clinical entity. Cell culture isolation Immunoflurescence Antibody rising titre using HAI or ELISA

TREATMENT Hospital admission Nursing in plastic tents supplied with cool, moistened oxygen Severe respiratory obstruction may require endotracheal intubation followed by a tracheotomy.