Sinusitis Sinusitis is an extremely common part of

Sinusitis • Sinusitis is an extremely common part of the common cold syndrome • RVs have been detected in 50% of adult patients with sinusitis by RT-PCR of maxillary sinus brushings or nasal swabs • Frequency of association of RV infection with sinusitis suggests that common cold could be considered a rhinosinusitis

Sinusitis Signs and symptoms • Patient may complain of a ‘feeling of fullness’ and pressure over the involved sinuses, nasal congestion, and purulent nasal discharge • Other associated symptoms include sore throat, malaise, low grade fever, headache, toothache, and cough >1 weeks duration • Symptoms may last 10 – 14 days

Sinusitis Diagnosis • Based on clinical signs and symptoms • Physical examination may reveal patient described symptoms – palpate over sinuses, observe for structural abnormalities such a deviated nasal septum • Sinus radiographs may reveal cloudiness and air fluid levels • Limited coronal CT are more sensitive to inflammatory changes and bone destruction

Sinusitis Management/Treatment • 2/3 of untreated patients will improve symptomatically within 2 weeks • Antibiotics may be appropriate in certain patients • Supportive therapy such as humidification, antihistamines, analgesics, and/or vasoconstrictors may relieve congestion and fullness • OTC decongestant sprays for use of more than 5 days duration should be discouraged

Pharyngitis • Fewer than 25% of patients with a sore throat have true pharyngitis • Primarily seen in 5 – 18 year old population, it is common in adult women • Most common cause is viral; most common agent is rhinovirus; Self-limiting; usually lasts 3 -4 days • Group A, beta-hemolytic streptococcus is the primary bacterial pathogen in 1/3 cases • Early detection reduces incidence of acute rheumatic fever and post streptococcal pharyngitis

Pharyngitis • Sore throat is the prominent symptom • Erythema • Swelling of the affected tissues • Exudates: inflammatory cells overlaying mucous membranes • Low-grade fever, mild general symptoms • Difficult to differentiate from streptococcal infection Caused by the same viruses that cause common cold and Adenovirus, Enteroviruses and Influenza virus.

Viral Causes of Pharyngitis • • • Rhinoviruses Adenoviruses Coronaviruses Epstein-Barr Virus Herpes Simplex Virus Parainfluenza Viruses Respiratory Syncytial Virus Influenza Viruses Coxsackie Viruses

Adenoviruses

Adenoviruses 51 serotypes • Immunity correlates with the presence of type- specific neutralizing antibodies • Endemic or epidemic, often during summer • Incubation period 4 -7 days • Moderate to severe pharyngitis, sometimes exudative • Fever and systemic symptoms • Rhinitis and follicular conjunctivitis are common

Adenovirus 51 serotypes Pharyngo-conjunctival fever sporadic or epidemic association with swimming pools Epidemic acute respiratory disease in military recruits pneumonia in 10 -20% Pneumonia in immunocompromised patients BMT recipients: mortality 60% Nosocomial transmission: epidemic keratoconjunctivitis

Pathogenesis • Epithelial cells are the primary target. • E 1 B and E 4 proteins inhibit transport of host m. RNA from the nucleus to the cytoplasm causing cell death • The penton protein has been shown to be directly toxic to cells and it has been found in the blood of several fatal cases of adenoviurs pneumonia.

• Entry by the mouth, the nasopharynx or via the conjunctiva. • The lower stereotypes (1, 2, 5 and 6) are ubiquitous particularly in young children • Endemic spread takes place by the fecal oral route to new pools of susceptible infants and children.

• May be transmitted in swimming pools, via medical equipment (tonometer), and via respiratory droplets. • Site of initial replication is commonly the oropharynx and spread is mostly local. • Virermic spread is rare. • Latency has been shown to be common among humans (in tonsils and adenoids)

Adenovirus Clinical Syndromes • They infect the respiratory tract as well as the eye, gastrointestinal tract, urinary bladder, and the liver. • On occasions, these viruses may cause disease in other organs such as CNS and the pancreas. • Most human disease is associated with only one-third of the serotypes. • Many adenovirus infections are subclinical

Respiratory Disease • Endemic Adenovirus Respiratory Infections of young children - Represent 5% of the acute respiratory disease in children(<5 y) most commonly as pharyngitis or pharyngoconjunctival fever - Most common serotypes are 1, 2, 5 and 6 and occasionally 3, 4 and 7. - Responsible for 10% of the pneumonias of childhood. - Most patients recover but epidemics of adenovirus 7 have resulted in considerable mortality.

Acute Respiratory Disease • Primarily affects military recruits (types 4, 7 and occasionally 3). • Frequently occurs under conditions of fatigue and crowding. • Characterized by fever, pharyngitis, cervical adenitis, cough, hoarseness and rhinitis. • Some cases have had a fatal outcome (pneumonia).

• Pertussis – like syndrome - It is associated with adenovirus type 5. • Infections of the Eye - Acute follicular conjunctivitis types 3 and 7 but other types (1, 2, 4, 6, 9, 10, 15, 17, 20, 22) have been incriminated.

Epidemic Keratoconjunctivitis - Types 8, 11, 19 and 37. - Followed by corneal subepithelial infiltration which may persist for a long period but it resolves completely with return of visual acuity to normal. - Outbreaks can be traced to eye clinics where an instrument (Tonometer) or a solution acts as a vehicle.

Viral Causes of Pharyngitis • • • Rhinoviruses Adenoviruses Coronaviruses Epstein-Barr Virus Herpes Simplex Virus Parainfluenza Viruses Respiratory Syncytial Virus Influenza Viruses Coxsackie Viruses

Viral Infections of the Lower Respiratory Tract

Laryngotracheo Bronchitis (Croup) - An acute viral inflammation of larynx, trachea, and bronchi that is common in young children. - It is often preceded by a "cold". - Accompanied by pyrexia, hoarseness, croaking cough, stridor, restlessness (respiratory insufficiency). - Can be fatal - i. e. life-threatening disease.

Acute Bronchitis • Inflammation of bronchi, accompanied by fever, cough, wheezing and "noisy chest". • Respiratory virus infection associated with cough – Influenza virus: 75%– 93% of cases – Adenovirus: 45%– 90% – RVs: 32%– 60% – Coronaviruses: 10%– 50% • 40% of nonasthmatic patients with acute bronchitis had FEV 1 80% of predicted • Bronchial reactivity remained increased up to 5 weeks after an episode of acute bronchitis

Acute Bronchiolitis - Inflammation of terminal bronchioles in young 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. - Clinically, there is fever, rapid respiration, exhausting cough and wheezing.

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

Causative Agents • Paramyxoviruses - Parainfluenza viruses - Respiratory Syncytial Virus (RSV) - Measles virus • Influenza • Coronaviruses • Adenoviruses • Enteroviruses • Rhinoviruses

Parainfluenza Viruses

Pathogenesis and Pathology • Initially, the mucous membranes of the nose and throat are involved. • Obstruction of the paranasal sinuses and eustachian tubes may also occur. • Many patients with mild disease may have limited involvement of the bronchi as well. • In more extensive infections there is a tendency for HPIV-1 and 2 to involve the larynx and upper tarchea, resulting in croup.

• Such infections may extend also to the lower trachea and bronchi, with accumulation of inspissated mucous and resultant atelectasis and pneumonia. • When HPIV-3 produces severe disease, infection of the small air passage is likely with the development of bronchopneumonia, bronchiolitis, or bronchitis. • Lower respiratory tract involvement also occurs commonly during primary HPIV-1 and 2 infection; about 25% of primary infections produce bronchitis or pneumonia.

• The mechanisms responsible for localization and severity of human parainfluenza viruses' disease are not known. • Severe respiratory tract disease caused by HPIV 1, 2, and 3 generally occurs in the first 3 -5 years of life. • Primary infections and reinfections occur and most persons have had primary infections before the age of 5 years.

Clinical Features • Most infections are asymptomatic, especially in older children and adults. • The incubation period is 2 -6 days. • Fever and a spectrum of respiratory infections are caused by HPIVs; rhinorrhea/rhinitis, pharyngitis, croup, bronchiolitis and pneumonia.

• In children, the most common type of illness consists of rhinitis, pharyngitis, and bronchitis, usually with fever. • Severe acute laryngotracheobronchitis (Croup) is noted in only 2 -3% of primary HP 1 V 1 or 2 infections. • When croup develops, the initial symptoms of rhinitis, pharyngitis, fever, and cough progress.

• After several days, subglottic region becomes narrower, the cough worsens and becomes brassy, “seallike”, or barking, with hoarseness and stridor. • At this stage, most children recover uneventfully after 24 -48 hours. • In some children, however, air hunger develops, with cyanosis, sternal and intercostal retraction, and progressive airway obstruction.

• HP 1 V 3 is an important cause of bronchiolitis in young infants and children below 2 years of age. • When bronchiolitis or pneumonia develops, fever persists and the cough progresses and becomes somewhat productive. • It is accompanied by wheezing, tachypnea, retraction, and in severe cases cyanosis.

• A combined bronchopneumonia-croup syndrome occurs in some patients. • Rarely, parainfluenza viruses are associated with otitis media, parotitis, and aseptic meningitis. • Prolonged (persistent) and particularly severe infections are known to occur in the immunocompromised

Respiratory Syncitial Virus

• RSV is the most important cause of viral lower respiratory tract disease in infants and children worldwide. • RSV is also an important agent of disease in immunosuppressed adults and the elderly. • RSV grows poorly in tissue culture and most experimental animals, does not shut off host macromolecular synthesis, and it is unstable. • Consequently, research on RSV was impeded.

• RSV survives on surfaces for up to 6 hours and on gloves for less than 2 hours. • The virus loses activity with freeze-thaw cycles, in acidic conditions and with treatment by disinfectants. • Classified into two types, RSV-A and RSV-B, on the basis of variation in the G glycoprotein • RSV utilizes ICAM-1 as its receptor.

Pathogenesis • RSV is transmitted via large droplets, through fomites and via hands • The mechanism of virus spread from upper to lower respiratory tract is assumed to be via the respiratory epithelium or through aspirated secretions. • The virus is capable of cell-to-cell spread without emergence into the extracellular fluid. • Viremia has not been described during infection of normal infants and children

Pathogenesis • RSV causes the release of – Interleukins – Leukotrienes – Chemokines • This results in inflammation and tissue damage • Presence of eosinophils and eosinophilic cationic protein in blood is associated with recurrent wheezing episodes post RSV infection

Pathogenesis • Bronchiolitis – Virus induced necrosis of bronchiolar epithelium – Hypersecretion of mucous – Round cell infiltration and edema of the surrounding submucosa • This leads to – Formation of mucous plugs – Hyperinflation/collapse of distal airways • Can also result in interstitial pneumonia • Infants are particulary at risk due to small size of normal bronchioles

Pathology • Lower respiratory tract involvement (signs) usually appear 1 -3 days after the onset of illness (rhinorrhea) • Inflammatory infiltration, edema, and excessive mucous production cause obstruction of small bronchioles, with either collapse or emphysema of distal portions of the airway. • In those instances in which pneumonia occurs, the interalveolar walls thicken as a result of mononuclear cell infiltration, and the alveolar spaces may fill with fluid.

• There is usually a patchy appearance of these pathologic changes, even though disease may be widespread. • Severe infections are observed in: - Preterm infants (<35 weeks gestational age) - Those with chronic lung disease - Those with cyanotic congenital heart disease - Immunocompromised hosts.