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Viral infections 

Viral infections
Viral infections

Jeremy Hull

, Julian Forton

, and Anne Thomson

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The common cold

  • Recurrent viral infection of the pharynx, nasal passages, and ears occurs in all children.

  • Symptoms include:

    • nasal discharge, which is initially clear and profuse and which becomes thicker and yellow or green after a few days;

    • sneezing;

    • painful throat;

    • sore ears;

    • fever may be present and is commoner under the age of 4 years;

    • headache and malaise;

    • dry cough can occur, from stimulation of cough receptors in the pharynx. A productive-sounding cough indicates the presence of an LRTI.

  • Signs include:

    • often nothing to find;

    • a reddened pharynx, sometimes with pus;

    • bilateral injection (redness) of the tympanic membranes.

  • Symptoms usually persist for 7 days, although, in young children, they may continue for 2 weeks.

  • A yellow or green discharge reflects the presence of neutrophils (the colour is derived from neutrophil myeloperoxidase, an iron-containing enzyme), and not bacteria. Neutrophils are attracted to the upper airway by virus-induced cytokine release.

  • Epidemiological surveys have indicated that children between 1 and 5 years of age suffer an average of 6–8 viral URTIs each year, and some have as many as 12. Attendance at day-care is a risk factor. The number of infections decreases after 5 years of age, and adolescents and adults have 2–4 colds per year.

  • The commonest causative virus is rhinovirus. Others include enteroviruses, coronaviruses, RSV, HMP, human bocavirus (HBoV, a parvovirus identified in 2005), and PIV. Adenovirus and influenza virus are also common but usually cause more severe illness.

  • Infection is spread by droplets or direct contact, and the incubation period is usually between 2 and 4 days.

  • Colds are commoner in the winter months in temperate climates, when RSV, HMP, and PIV are the usual causes, but can occur at any time of year. The cause of the seasonality is not understood—people being in closer contact with each other in winter months (the overcrowding hypothesis) do not really stand up to scrutiny. An alternative is that cold air in the nasal passages reduces the ability of the airway epithelium to protect against viral infection.

  • No investigations are required.

  • There is no effective treatment.


  • Croup or laryngotracheobronchitis is caused by viral infection of the supraglottic, glottic, and subglottic airway.

  • PIV are responsible for 75% of croup episodes. The remainder are caused by any of the other respiratory viruses. Mycoplasma pneumoniae may rarely cause croup.

  • Croup tends to occur in epidemics in the autumn and winter in temperate climates.

  • Most affected children will have their first episode of croup before the age of 5 years, with a peak incidence at around 2 years of age.

  • Croup is common, and up to 5% of 2-year-olds will have at least one episode, for which their parents seek medical attention. Most episodes are mild, and only a minority of affected children require hospital treatment.

  • Symptoms arise because of narrowing of the subglottic space caused by viral-induced inflammation and oedema. Young children are probably principally affected, because narrowing caused by airway wall swelling has a proportionately greater effect on airways resistance when the starting airway size is small.

Symptoms and signs

Croup usually starts with a coryzal illness, often with a fever that is low grade but can be as high as 40°C. After 1–2 days, croup symptoms develop and usually last 3–7 days, but occasionally they persist for as long as 2 weeks. Typical symptoms are:

  • hoarse voice;

  • barking cough;

  • stridor.

Signs are those of subglottic airway obstruction with respiratory distress:

  • stridor, usually inspiratory, but biphasic in severe disease;

  • chest wall recession;

  • tachypnoea and tachycardia;

  • desaturation can occur and, in the context of a child with marked respiratory distress, is an ominous sign, since it indicates hypoventilation and accompanying CO2 retention. Urgent steps should be taken to improve the airway in children with hypoxaemia. Giving oxygen alone will not prevent a respiratory arrest. Occasionally, hypoxaemia will be seen in children with only mild respiratory distress, possibly reflecting secretion retention, patchy atelectasis, and resulting V/Q mismatch.

A number of croup scores are available to indicate croup severity. They are useful in research studies, but of limited value in clinical practice.

Spasmodic croup

The term spasmodic croup is used for children who present with croup-like episodes that typically come on suddenly without a preceding coryzal illness. Attacks often occur at night. Affected children tend to be older than those with typical croup and are more likely to have recurrent episodes. Recovery is usually quicker, and often symptoms have gone within 12 h. Children with spasmodic croup are said to be more likely to be atopic, and this has led to speculation that the airway oedema arises through allergy-mediated inflammation. The treatment of each episode is identical to that of other forms of croup.

Differential diagnosis

The differential diagnosis for a child with new-onset stridor includes other causes of acute airways obstruction and causes of pre-existing airway narrowing that have become more obvious during an acute viral respiratory tract infection. In practice, the diagnosis is usually straightforward in a previously well child who has a typical clinical course. When the illness is atypical, e.g. in children >5 years of age, or with significant systemic illness, or without a coryzal prodrome, or with pre-existing noisy breathing, other causes should be considered.

Other causes of acute airways obstruction are the following.

  • Laryngeal oedema caused by:

    • bacterial infection—epiglottitis or tracheitis;

    • irritants—aspirated caustic chemicals or smoke;

    • allergy—anaphylactic reactions;

    • C1 esterase deficiency—angio-oedema.

  • Laryngeal foreign body. Fortunately, this is rare. Objects small enough to fit through the vocal cords are usually small enough to pass to the main bronchi. Linear foreign bodies, such as fish bones, may become lodged in the larynx and still allow some air entry and cause croup-like symptoms. Larger objects, such as grapes, will usually cause complete laryngeal obstruction.

  • Airway compression by:

    • retropharyngeal abscess;

    • haemorrhage into cystic hygroma;

    • mediastinal lymph nodes, usually in the context of lymphoma;

    • trauma.

Possible pre-existing conditions are:

  • subglottic stenosis;

  • tracheal haemangioma;

  • subglottic cyst.

Narrowing of the mid to lower third of the trachea (due either to tracheal stenosis or a vascular ring) is less likely to cause stridor and croup-like symptoms.


  • For typical episodes of croup, no investigations are required. The diagnosis is clinical.

  • The commonest clinical question is whether children who have either prolonged illness or recurrent episodes of croup have underlying predisposing conditions requiring evaluation by bronchoscopy. In practice, when there are no interval symptoms (i.e. between episodes of croup or before the current episode started, the child had completely quiet breathing, even on exertion, and a normal voice), the likelihood of detecting any important airway pathology is extremely low, and bronchoscopy is not required.

    • An exception to this rule is when ‘croup’ occurs in infants <6 months of age. This group has a higher likelihood of an underlying airway pathology.

    • As in all children, where there is doubt, the safest option is always to look.


  • Most children with croup have mild disease with a barking cough and a runny nose. There may be mild chest wall retractions, but the child is otherwise well, and there is no stridor at rest. These children can be looked after at home. No specific treatment is needed, although regular paracetamol may be helpful if there is fever or a sore throat. Use of a single dose of oral corticosteroids is optional and varies with local practice. Parents should be warned that the disease can worsen, particularly at night, and that medical review may be required.

  • Children with moderate disease, characterized by stridor at rest, benefit from a dose of systemic (oral in most cases) corticosteroids (either 0.15 mg/kg of dexamethasone or 1 mg/kg of prednisolone; dexamethasone is more effective, with lower rates of re-presentation to emergency departments). These children need to be observed in hospital, until the stridor at rest has resolved. In some children, this will happen within 4 h, although the average is closer to 7 h.

  • Children with severe disease, with stridor at rest, associated with marked chest wall recession and tachycardia, should be treated with nebulized adrenaline plus systemic corticosteroids. Despite concerns in the past, there is no evidence that adrenaline results in worsening rebound of symptoms when its effects wear off. Using adrenaline improves the airway and gives time for the corticosteroids to work. A number of studies have shown that children showing significant improvement can be safely discharged from the emergency department 3–4 h after being given nebulized adrenaline.

  • Standard L-adrenaline, available in most hospitals, seems to work as well as racemic adrenaline. The usual dose of L-adrenaline is 0.5 mL/kg of 1 in 1000 adrenaline nebulized neat, up to a maximum of 5 mL. It can be repeated after 30 min. The effects last 2–3 h.

  • Humidified air does not help in moderate and severe croup. There are insufficient data on mild croup to be able to tell if it has an effect or not. The use of steam at home can be hazardous. Overall, the balance is in favour of not using it.

  • Nebulized budesonide has an onset of action within 30 min, compared to 60 min for oral dexamethasone. In terms of preventing subsequent admission to hospital, nebulized budesonide is slightly less effective than dexamethasone and more expensive.


  • In the vast majority of children, croup is a mild disease with an excellent outcome. For most children, symptoms will have sufficiently improved to allow discharge from hospital within 24 h. In others, stridor at rest can persist for as long as 2 weeks.

  • Deaths from airway obstruction at home are now very rare.

  • Up to 20% of children will have recurrent episodes. In the absence of interval symptoms, no further investigation is usually required.

  • In about one in 50 children admitted to hospital with croup, airway obstruction progresses, despite treatment. These children become agitated and poorly perfused, associated with worsening hypercarbia and hypoxaemia. Intubation is required. Once intubated, ventilation requirements are usually minimal. Occasionally, negative pressure pulmonary oedema can complicate severe croup. The mean duration of intubation is 5–7 days. Most units will use daily corticosteroids in this group of children and wait for a leak to develop around the ETT before extubation. If extubation fails, subsequent attempts should be carried out in an operating theatre, with an ENT surgeon available to inspect the airway to determine if there is significant underlying pathology.

Further information

Fitzgerald DA (2006). The assessment and management of croup. Paediatr Respir Rev 7, 73–81.Find this resource:

Moore M, Little P (2006). Humidified air inhalation for treating croup. Cochrane Database Syst Rev 3, CD002870.Find this resource:

Sparrow A, Geelhoed G (2006). Prednisolone versus dexamethasone in croup: a randomised equivalence trial. Arch Dis Child 91, 580–3.Find this resource:

Juvenile onset recurrent respiratory papillomatosis


  • Juvenile onset recurrent respiratory papillomatosis (JORRP) is caused by infection with HPV, usually HPV subtypes 6 or 11. HPV-11 is associated with more aggressive disease.

  • It is relatively rare, with a childhood incidence of 4–5/100 000.

  • The majority of children present before the age of 5 years, and, of these, 25% develop symptoms in infancy. It can rarely present in adolescence. The adult form of the disease is most common in the third decade of life.

  • Infection is thought to be acquired from the genital tract of infected mothers at the time of delivery. Disease in adolescence and adulthood is probably acquired through sexual activity.

  • Risk factors for acquiring the disease are:

    • mother with active genital condylomata (warts);

    • teenage mother;

    • first born child;

    • vaginal delivery.

  • In 50% of children, the papillomata are confined to the larynx, mostly around the vocal folds. In the remainder, infection can spread to the lower airways and lung parenchyma.

  • The papillomata are benign neoplasms. There is an undefined risk of malignant transformation to squamous cell carcinoma. For disease limited to the upper airway, the risk is low (<5%). The risk is probably higher in the more aggressive disease that has spread to the lower airway.

Symptoms and signs

  • Usual symptoms are hoarseness and/or stridor.

  • Decompensation of a compromised airway may occur over a few days, and children may present with acute severe respiratory distress. These children can have a nearly complete occluded larynx and require emergency tracheostomy.

  • There is often a delay in diagnosis—an average of just over 12 months.

  • Other modes of presentation include:

    • cough;

    • recurrent pneumonia;

    • dysphagia;

    • failure to thrive.

Differential diagnosis

The differential for a child with stridor, with/without a hoarse voice includes:

  • vocal cord palsy, caused by trauma, malignancy, or brainstem compression;

  • recurrent croup;

  • vascular ring;

  • airway haemangioma;

  • cystic hygroma;

  • laryngeal web;

  • subglottic stenosis.

These children may also have been misdiagnosed as having asthma or a recurrent chest infection.


  • Diagnosis is made by laryngoscopy, revealing typical cauliflower-like warts. If laryngeal papillomata are seen, further instrumentation of the airway should be avoided to prevent dissemination of the disease.

  • Biopsy of one of the lesions will allow histological confirmation of papilloma and to look for malignant change. PCR on the tissue can be used to identify and type the virus.

  • CXR is usually normal. It may show small nodules if there is disease in the lung parenchyma. If a bronchus has become obstructed, there may areas of collapse or consolidation.

  • CT of the chest can be useful in identifying papillomata in the trachea and bronchi and within the lung parenchyma. Healed papillomata can appear as cystic lesions.

  • If there is extensive lower airway disease, investigations to exclude immune deficiency should be carried out.

  • A staging system is available and can help to track the response to treatment. It assesses symptoms (stridor and hoarseness), the frequency of recurrence, and the number and distribution of lesions (graded as surface-raised or bulky).


  • Treatment is difficult, because of the propensity of the papillomata to recur. The rate and frequency of recurrence varies widely. Some children need only 1–2 excision procedures per year; others need treatment every few weeks.

  • Tracheostomy should be avoided, if possible, because of a risk of spreading the disease into the lower trachea. If a tracheostomy is needed, it should be removed as soon as the airway has been made safe.

  • The most widely used treatment is surgical excision. The goals of treatment are to provide a safe airway, whilst preserving the voice. Excision can be by direct resection or with a CO2 laser. If a laser is used, special precautions must be used to protect staff from the virus which can be released into the air during the procedure.

  • Eradication by surgery is not possible, and overly aggressive surgery can lead to permanent damage to the airway or voice.

  • Adjuvant therapy is needed in around 10% of children. It should be considered if:

    • > 4 surgical procedures are needed each year;

    • there is significant disease in the lower airways or lung parenchyma;

    • there is rapid re-growth with airway compromise;

    • interferon alfa, given daily for 1 month, then three times per week for 6 months, can reduce the severity of the disease during treatment, but the papillomata often recur, once treatment has stopped. Alternatives include indole-3-carbinol and cidofovir. The long-term safety of cidofovir is not known, but it does seem to be effective in some children, given either IV or as intralesional injections, when other treatments have failed;

    • lower airway involvement represents a serious complication, and there are no therapies proven to affect disease progression. A review of the literature in 2008 concluded that interferon was not effective and that case report evidence favoured IV cidofovir.


  • Delivery by Caesarean section in women with active genital condylomata probably reduces the risk but does not prevent the disease completely.

  • Vaccination of women against HPV is the most likely effective treatment. Effective vaccines have been developed against HPV-16 and HPV-18, the two most common subtypes associated with cervical cancer.


  • Short- and medium-term quality of life for children with frequently recurring disease is poor. Multiple hospital visits for treatment severely disrupt family life and education.

  • Remission can occur after several years, usually around the time of puberty.

  • A small proportion of children will develop malignant squamous cell carcinoma, which has a poor prognosis.

Further information

Gélinas JF, Manoukian J, Côté A (2008). Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature. Int J Pediatr Otorhinolaryngol 72, 433–52.Find this resource:

Shah KV, Stern WF, Shah FK, Bishai D, Kashima HK (1998). Risk factors for juvenile onset recurrent respiratory papillomatosis. Pediatr Infect Dis J 17, 372–6.Find this resource:

Acute viral bronchiolitis

Acute viral bronchiolitis is an LRTI of infants characterized by:

  • preceding coryzal symptoms;

  • progressive breathlessness with associated poor feeding;

  • cough;

  • evidence of respiratory distress, including chest wall recession and desaturation;

  • presence of inspiratory crepitations and/or wheeze on auscultation of the chest.


Viral infection of the lower airways provokes a host response that results in airway wall oedema, the production of inflammatory exudate, increased airway mucus, and a varying degree of bronchospasm. Taken together, these result in obstruction of the small airways and increased respiratory work.


  • The majority (60–70%) of episodes of bronchiolitis are caused by the RSV. Other viruses that can cause bronchiolitis are HMP, adenovirus, influenza virus, PIV, and HBoV.

  • RSV bronchiolitis is the single most important cause of severe LRTI in infants worldwide. The WHO estimates that 64 million children suffer from the infection each year, of whom 160 000 die.

  • In temperate climates, bronchiolitis occurs in winter epidemics. In tropical climates, bronchiolitis occurs year round but is more prevalent in the rainy season.

  • The mean age of affected infants is 4–6 months, with an equal sex incidence.

  • In developing countries, RSV accounts for about 40% of LRTIs in infants.

  • RSV is highly infectious, and nearly all children will have been infected by the virus by the end of their second RSV season. Spread is by respiratory droplets or direct contact with respiratory secretions. The first member of most households who becomes infected is a child attending day care or school. If there is an infant in the family, their likelihood of becoming infected after the virus is introduced is around 60–70%.

  • Nearly all infants will be symptomatic with coryzal symptoms, and 50–80% will develop a cough. One to 3% will develop more severe lower respiratory tract disease, requiring hospital admission, usually for oxygen therapy and assistance with feeding.

  • The incubation period for RSV bronchiolitis is 3–7 days. The duration of viral shedding is variable. In infants, shedding lasts on average for 10 days but may continue for as long as 30 days. In older children and adults, the duration of viral shedding is shorter (2–4 days) but again occasionally can be prolonged.

  • Some of the known risk factors for developing severe bronchiolitis are:

    • prematurity (probably because of missing out on the placental transfer of passive maternal immunity that occurs in the third trimester);

    • pre-existing heart or lung disease;

    • older siblings and attendance at day care—resulting in exposure to a higher viral load;

    • parental smoking.

  • Viral strain (RSV A, compared to RSV B) does not seem to be important in determining the disease severity.

  • Most infants who are admitted to hospital with severe disease are previously healthy infants born at full term, and the reasons why these infants develop severe disease are not fully understood. Genetic predisposition may play a role.

  • Following severe bronchiolitis (requiring hospital admission), 60% of infants will have subsequent wheezing episodes. In most studies, the effect of previous bronchiolitis on the risk of wheezing is lost by the age of 6–12 years. The interaction between early bronchiolitis and subsequent atopy is controversial.

Clinical features

  • The typical history is of a young infant who develops a ‘snuffly’ nose with some nasal discharge and sneezing. This progresses to episodes of coughing and fast breathing that together prevent normal feeding. There may be a fever, but this is not always present.

  • In infants under 6 weeks and older infants who were born prematurely, there is a risk of apnoea, which may be the presenting problem, before there is a noticeable respiratory distress.

  • Examination will usually show:

    • evidence of respiratory distress (tachypnoea, chest wall recession, use of accessory muscles, tachycardia);

    • desaturation, which is common in infants with bronchiolitis severe enough to cause chest wall recession;

    • fever, usually low grade (<38.5*C);

    • inspiratory crepitations on auscultation, with or without expiratory wheeze.

Differential diagnosis

  • A relatively rapid onset of respiratory distress in infants is likely to be caused by infection in a previously normal child. Occasionally, there will be an important underlying cause that may first come to medical attention as an apparent episode of bronchiolitis. These conditions include:

    • heart failure—usually associated with a left-to-right shunt and, more rarely, with superventricular tachycardia or a cardiomyopathy;

    • CF;

    • immune deficiency, often SCID;

    • congenital lung anomaly such as congenital lobar emphysema;

    • ILD.

  • Careful evaluation of the infant’s health before the acute episode may give clues to a pre-existing condition. When these are present, affected infants usually take longer to recover. Infants with prolonged or recurrent episodes of ‘bronchiolitis’ should be subject to further investigation.


  • Bronchiolitis is a clinical diagnosis. No investigations are needed routinely.

  • NPAs can be used to identify the causative virus. Analysis can be by enzyme-linked immunosorbent assay (ELISA), PCR, or cell culture. Multiplex PCR can assess for several viruses in the same test. Identifying the causative virus can provide some reassurance of the likely clinical course, but, given that RSV is highly prevalent, finding it in the upper respiratory tract does not mean that it is the sole cause of the infant’s respiratory distress. Viral identification can be useful in cohorting infected infants within hospitals and identifying new infection acquired after admission.

  • CXR is not needed routinely, as it will not affect management. Where the illness is atypical or prolonged, CXR may help identify the underlying pathology. If a CXR is performed, findings consistent with bronchiolitis include:

    • hyperinflation;

    • patchy atelectasis;

    • perihilar bronchial wall thickening.

  • Blood investigations are not normally required. Blood gas analysis will be needed in infants who are struggling, despite supplementary oxygen. The point at which the CO2 and pH are checked will vary with local practice but will usually be required in infants needing >50% of oxygen.


  • Hospital treatment will be needed for infants who are too breathless to feed or who are hypoxaemic (saturations <92%) in room air. Hospital admission should also be considered in less ill infants who are at heightened risk of developing severe disease, e.g. those born prematurely, those with pre-existing heart or lung disease, and those <12 weeks of age.

  • Treatment is supportive. No intervention has yet been shown to shorten the illness.

  • A UK-based randomized trial of nebulized 3% hypertonic saline is due to be published in 2014. Smaller studies have suggested that the length of stay for bronchiolitis may be reduced by the use of this treatment.

  • Feeding assistance is given by tube feeds or IV fluids, the choice depending on local practice and the disease severity. Some infants who are unable to feed will tolerate tube feeds (ideally orogastric, rather than NG). When respiratory distress is severe, tube feeding can make it worse and increase the risk of aspiration. At this point, IV fluids will be needed.

  • Oxygen can be given by nasal cannulae, either low-flow or, where higher oxygen concentrations are needed, by high-flow humidified systems using a head-box (see Viral infections Chapter 56).

  • Sick infants with bronchiolitis (as with other acute conditions) should be handled as little as possible. Being placed in the prone position seems to reduce the respiratory workload for some infants.

  • The use of inhaled beta-2 agonists and anticholinergic agent has been the subject of a Cochrane review.1 Neither is recommended for routine use. In older infants (>8 months) with coryza and wheeze, there is an overlap between true bronchiolitis (an LRTI) and wheeze associated with a viral URTI. In this group, it may be reasonable to try a bronchodilator and observe for benefit.

  • Nebulized adrenaline does seem to have short-term benefit, with temporary improvement in oxygen saturation and reduction of respiratory effort. There is no effect on the duration of illness or the need for mechanical ventilation. On this basis, it is not recommended for routine use. It may be of some value in sick infants, whilst arrangements are made for review by ICU staff.

  • Corticosteroids, either orally or inhaled, do not affect the course of the acute disease, nor the likelihood of subsequent wheezing illness, and their use is not indicated.

  • Nebulized ribavirin is effective at killing RSV and reducing the viral load in infected infants. Unfortunately, it does not significantly affect the clinical course of the illness, and this, combined with difficulties of administration (it needs to be nebulized 18 h in every 24 h), means that it is not used routinely. In some high-risk patients, particularly those with immune deficiency, it still has a role.

  • Antibiotics are not indicated routinely. The rate of dual infection with a bacterial pathogen is low. The presence of patchy consolidation on CXR is not an indication for prescribing antibiotics. In infants requiring mechanical ventilation, BAL studies have indicated the presence of lower airway bacteria in 20% of intubated infants, and antibiotics are routinely prescribed for ventilated infants with bronchiolitis in some ICUs, although there are no trials to show that this intervention is beneficial. Infants with bronchiolitis who have persistent or recurrent high fever should undergo further investigation, since it is unlikely that fever of this nature will be due primarily to bronchiolitis.

  • Nasal continuous positive airway pressure (CPAP) seems to be beneficial in some infants with severe disease, in terms of reducing the respiratory work and oxygen requirement. Whether it reduces the need for intubation and ventilation has not been subject to an RCT. The same can be said for high-flow oxygen therapy, which has replaced the use of CPAP in some units.

  • Mechanical ventilation is needed in a small proportion of infants. Indications are either recurrent apnoea or respiratory failure, despite the use of CPAP or high-flow oxygen therapy. The duration of ventilation varies but is typically 2–5 days.


  • The outcome is usually excellent. The duration of hospital treatment is around 3 days. Some infants have mild hypoxaemia during feeds or sleep, which can persist for several days after their oxygen saturation during wakefulness has returned to normal and after they have otherwise recovered. It is safe to stop monitoring saturations in these babies and allow them to go home.

  • Thirty to 60% of infants who have had severe bronchiolitis will have subsequent episodes of wheeze. Whether these episodes are causally related to the bronchiolitis or represent a shared predisposition remains unclear.

  • Deaths from bronchiolitis are rare in developed countries and, when they occur, nearly always do so in children with an underlying heart or lung disease.

  • Rarely, severe bronchiolitis/pneumonitis is associated with post-infectious BO. This is more common with adenoviral infection.

  • Infection with RSV does not generate protective immunity, and repeat infections are common. Subsequent infections are usually milder. It is possible, but unusual, for an infant to have two distinct episodes of bronchiolitis in a single season.


  • Strict hand washing in hospital is required to prevent spread. RSV is easily killed by alcohol and cannot survive for more than a few minutes on dry surfaces.

  • Vulnerable babies in hospital and at home should be protected from overattentive coryzal siblings.

  • Programmes to develop an RSV vaccine have been active for many years. They suffered a major setback in the 1960s when a formalin-inactivated vaccine resulted in enhanced disease. Newer live vaccines, given via the nasal route, do seem to provide protection, but not without causing some symptoms themselves. None has yet been licensed.

  • Passive immunization with humanized anti-RSV monoclonal antibody (palivizumab) reduces the risk of severe disease by 50% in high-risk children. No studies have been powered to detect an effect on mortality. Monthly injections are given for 5 months in temperate climates to provide protection through the RSV season.

Further information

American Academy of Pediatrics (2006). Diagnosis and management of bronchiolitis. Pediatrics 118, 1774–93.Find this resource:

Monto AS (2002). Epidemiology of viral respiratory infections. Am J Med 112 (Suppl. 6A), 4S–12S.Find this resource:

Viral pneumonia

  • The terms pneumonia and pneumonitis are often used interchangeably to indicate infection of the lung parenchyma. When CXR findings show areas of consolidation, the term pneumonia tends to be used, whereas, when there are streaky interstitial changes, pneumonitis is more often used. Both patterns can be seen in children with viral LRTI. The distinction between viral bronchiolitis and viral pneumonia is also arbitrary and based on the CXR appearance, rather than any distinct clinical features.

  • The clinical presentation of viral pneumonia does not differ from that of other community-acquired pneumonias (see Viral infections Chapter 17).

  • The likely causative viruses are:

    • RSV;

    • PIV;

    • influenza virus;

    • adenovirus;

    • HMP;

    • HBoV;

    • coronavirus.

  • In children with immune deficiency, CMV and (to a lesser extent) EBV are also important causes of pneumonia.

  • NPA analysed by PCR is the most likely method of successfully identifying the causative virus.

  • CXR findings are non-specific. Findings nearly always affect more than one lobe, and commonly changes are seen in all lobes. Possible findings include:

    • perihilar bronchial wall thickening;

    • air trapping with evidence of hyperinflation;

    • airspace disease with areas of consolidation;

    • streaky interstitial changes;

    • pleural effusions are rare.

  • CT scans are not often performed but may be required in the context of investigating children with respiratory disease of uncertain origin. Findings consistent with viral pneumonia are the same as those described for the CXR. In addition, small airways disease may result in a mosaic appearance, reflecting heterogeneous air trapping.

  • Treatment is supportive. In children with immune deficiency, specific antiviral drugs, such as ribavirin or ganciclovir, may be indicated.

  • The outcome is usually excellent. Rarely, persistent airway or lung damage may occur, resulting in long-term oxygen requirement and wheeze (see also Viral infections Chapter 36).

Cytomegalovirus pneumonia

Infection with CMV is common. The prevalence of seropositive individuals increases with age and varies widely, according to the socio-economic status, race, and geographical area. In the UK, about 50% of adults are infected. Recurrent infection or reactivation can also occur. The majority (95%) of infections in normal individuals are asymptomatic.

Spread of infection

Normal children

After primary infection in normal children, CMV is excreted from multiple sites (e.g. tears, urine, saliva) for months to years. CMV particles can remain infectious on plastic surfaces for several hours. Toddlers in day care frequently transmit CMV to each other and to adults with whom they have contact.

Mother to infant

CMV may be transmitted across the placenta and results in congenital infection in around 1% of live born infants. The risk of infection and symptomatic infection in infants of affected mothers is highest in mothers who acquire primary CMV infection during pregnancy. Most infected infants are asymptomatic, but around 10% suffer from CNS damage.

Immunocompromised children

In immunocompromised children, most clinically significant CMV disease is transmitted by blood products and transplanted tissue. Re-infection with a different strain of CMV and reactivation of latent infection can both occur in the immunocompromised. Spread of CMV in hospital by other routes is rare. The risk of CMV pneumonitis depends on the cause of immunosuppression. CMV pneumonitis is:

  • very common following lung transplantation. It can be difficult to separate CMV pneumonitis as a distinct infection from the effects of rejection and other infections. Highest risk (90–100%) occurs when the donor is CMV-positive and the recipient is CMV-negative; reactivation disease in recipient CMV-positive patients with a CMV-positive or CMV-negative donor is also common (60%);

  • common (10%) in allogeneic bone marrow or stem cell transplant recipients and has a high mortality (70%). Usually occurs 7–10 weeks after transplantation;

  • unusual in renal and liver transplants (around 2–5%), because of prophylactic and pre-emptive treatment;

  • rare and often mild in HIV-infected children;

  • very rare in children receiving chemotherapy for leukaemia and other childhood malignancies.

Symptoms and signs

Normal children

  • CMV infection is usually clinically silent.

  • When symptoms do occur, they present 9–60 days after primary infection.

  • Symptomatic cases are clinically indistinguishable from EBV infection, with fatigue, fever (up to 40*C), lymphadenopathy, hepatomegaly, splenomegaly, and lymphocytosis with atypical lymphocytes.

  • The illness can last several weeks. Hepatitis and atypical lymphocytes usually disappear after 6 weeks.

  • Lower respiratory tract involvement is very rare and, if found, strongly suggests the presence of immunosuppression.

Neonates and young infants

  • Congenital infection, when symptomatic, may cause intrauterine growth retardation (IUGR), hepatosplenomegaly, petechiae, jaundice, microcephaly, and intracranial calcification.

  • Pneumonitis as part of congenital infection is rare and, when present, should prompt a thorough search for other causes, before it is attributed to CMV.

  • Common laboratory abnormalities in congenital infection include hyperbilirubinaemia, increased hepatocellular enzymes, thrombocytopenia, and increased CSF protein. Neonates with symptomatic congenital infection have high rates of subsequent learning difficulties.

  • Acquired disease in infancy may be similar, but with a lower incidence of CNS disturbance. Occasionally, otherwise normal infants who acquire CMV infection post-natally (usually from breast milk) may present as miserable babies with tachypnoea, poor feeding, and poor weight gain. A careful search for an underlying primary immune deficiency should be made.

  • The risk of acquiring disease from breast milk is higher in preterm babies.

Immunocompromised children

CMV seroconversion and excretion of CMV in body fluids is commonly found after receipt of CMV-positive transplanted tissue or blood. The occurrence and severity of disease are variable. Important factors determining the disease severity are as follows.

  • Primary infection versus re-infection or reactivation. Primary infection (occurring in a previously CMV-negative child) is more severe.

  • Degree of immunosuppression. Patients deficient in CMI are at greatest risk of developing CMV disease.

  • Reason for immunosuppression. Children who have had organ transplantation, especially lung and bone marrow, are at greatest risk.

Symptoms and signs include:

  • fever, malaise, arthralgia;

  • macular rash;

  • hepatosplenomegaly.

Complications include:

  • retinitis;

  • gastrointestinal ulceration and enterocolitis;

  • hepatitis;

  • pneumonitis;

  • encephalitis;

  • graft rejection.


When it does occur, CMV pneumonia has the following characteristics.

  • Breathlessness and a non-productive cough.

  • Severity ranges from mild dyspnoea to severe respiratory insufficiency.

  • There may be an insidious onset, in which case there may be no fever.

  • Signs include tachypnoea, with or without chest wall recession and desaturation.

  • Breath sounds may be normal, or there may be inspiratory crackles.

  • CXR shows bilateral diffuse interstitial changes.

  • CT findings are non-specific, commonly showing small nodules and patchy consolidation, particularly in the lower lobes.


Diagnosis (Box 19.1) requires answers to the following three questions.

  • Is there evidence of CMV infection?

  • Is there evidence of CMV in the lungs?

  • Is the CMV in the lungs causing the disease?

The answer to the first question can be obtained by looking for CMV in the urine, saliva, and blood.

  • Tests for CMV include the following.

    • Culture methods, which can be combined with immunofluorescence to allow early detection (this test is sometimes called the ‘shell vial’ assay).

    • Detection of CMV antigen in peripheral blood mononuclear cells (PBMCs)—this test is called the pp65 antigen test. The antigenaemia test is semi-quantitative, according to the proportion of PBMCs that are stained for the CMV antigen.

    • CMV PCR tests in the past had poor specificity, but now appear to be reliable and sensitive, and are often the detection method of choice.

    • Serology is generally only useful in determining previous exposure to CMV, although CMV-specific IgM has been used to indicate recent infection.

  • CMV excretion in the saliva and urine is common in patients who are immunocompromised and is generally of little consequence.

  • The significance of CMV viraemia depends on the context and the level of viraemia. In allogeneic marrow transplant patients, any level of viraemia is significant, warrants treatment, and will be associated with CMV pneumonia in 60–70%.

  • Following organ transplant, up to 50% of patients can have low levels of viraemia. The presence of viraemia identifies those at greatest risk for CMV pneumonia. Pre-emptive treatment is started at a threshold level of CMV antigenaemia, e.g. 25 positive cells/2 x 105 PBMCs.

  • The absence of CMV virus in the bloodstream has a high negative predictive value for CMV disease, including pneumonia.

  • Negative tests for CMV in urine do not exclude lung infection but make it less likely.

  • CMV detection in the lungs requires BAL, transbronchial biopsy, or open lung biopsy. Lower airway cytology brushings can improve the yield of BAL alone.

  • Expectorated sputum or ETT aspirates are not acceptable. They will probably be contaminated with mouth and upper respiratory tract secretions where CMV is commonly found.

  • CMV may be found in the lung of 5–10% of normal adult subjects. The likelihood of CMV disease depends on the setting. Quantification of the viral load using PCR techniques can also predict disease. Higher viral loads in blood and lung are more likely to be associated with pneumonia.

Prevention and treatment

  • In immunosuppressed CMV-negative children, CMV-negative leucocyte-depleted blood should be used.

  • In transplant patients, it is usually not possible to avoid CMV-positive organs, because of limited supply.

  • High-dose prophylactic aciclovir and pre-emptive ganciclovir (when CMV is detected in routine blood samples) can be used in CMV-negative patients receiving CMV-positive tissue.

  • Treatment of CMV infection is with ganciclovir, with or without CMV Ig. Both CMV infection and ganciclovir depress the neutrophil count and increase the risk of fungal infection. The duration of therapy is 2–5 weeks.

  • Foscarnet or cidofovir can be used if ganciclovir is ineffective.

Varicella pneumonia

  • Primary infection with VZV causes clinically recognizable chickenpox in over 90% of subjects.

  • The incubation period is usually 10–14 days but can be as long as 21 days.

  • Children are infectious from 1–2 days before the rash appears, until the last spot has scabbed over or 5 days after the rash appeared, whichever is the longer.

  • Varicella-zoster spreads mainly by airborne droplets. The respiratory tract is the point of entry.

  • The virus replicates in local lymph glands for several days, before dissemination via the bloodstream to the viscera and skin. Spread back to the lungs occurs at this stage, and the child becomes infectious through the production of varicella-containing airborne droplets.

  • Primary varicella pneumonia can occur in immunocompetent individuals. It is more common in adults than children.

  • Pneumonia usually occurs 2–5 days after the appearance of the rash; rarely, it precedes the rash.

  • The presence of pneumonia is an indication of high levels of viraemia and may be associated with other organ involvement: hepatitis, arthritis, myocarditis, encephalitis.

  • Pneumonia is more likely in neonatal disease and in immunocompromised children, including those on long-term oral steroid therapy.

  • Secondary bacterial infections, particularly invasive GAS and Staphylococcus aureus, are important alternative causes of respiratory distress in a child with chickenpox. Both can cause pneumonia and empyema.


Minor cough and coryza are common in chickenpox. More persistent coughing and breathlessness suggest pneumonia.


Tachypnoea and occasionally inspiratory crepitations. Cyanosis may be present.


  • The diagnosis of chickenpox is usually made clinically. If confirmation is required in high-risk patients, immunostaining of vesicular fluid is possible.

  • When pneumonia is present, CXR will show diffuse bilateral nodular densities with bilateral linear opacities. After recovery, the nodules may calcify.

  • Lobar pneumonia or pleural collection is more likely to be caused by either GAS or Staphylococcus aureus.


IV aciclovir for 10–14 days should be used in children with immunosuppression. Evidence of benefit for treating varicella pneumonia in immunocompetent children is lacking, but most paediatricians would probably use it.


  • An effective vaccine is now available and should be given to all children, when there is time, before immunosuppression occurs. In children <13 years, a single dose is needed. For older children, two doses, 4–8 weeks apart, should be given.

  • Post-exposure zoster immunoglobulin (ZIG) is effective in prevention or ameliorating chickenpox when given within 72 h of exposure. ZIG is in short supply in some regions, and its rational use requires knowledge of the levels of anti-zoster IgG in the patient’s blood. If the immune status of the child is not known, this may need to be checked before ZIG is given.


In previously healthy children, clinically apparent pneumonia is rare, and outcomes are generally good. In immunosuppressed children with varicella pneumonia, mortality can be as high as 10%.

Adenovirus pneumonia

  • Large population-based surveys have suggested that adenovirus accounts for 5–10% of URTIs and LRTIs in infants and children.

  • Most infections are asymptomatic or very mild, and, by 4 years of age, about half of all children will have serological evidence of previous adenovirus infection.

  • Severe pneumonia can occur. It is more common in infants and in immunocompromised children when it can be fatal.

  • Infections also occur in older children and young adults, particularly in crowded, stressful conditions. Up to 20% of military recruits develop symptomatic adenoviral respiratory infection, requiring hospital treatment.

  • Fifty-one different adenovirus serotypes have been described, divided into six subgroups A–F, based on their DNA sequence and their ability to agglutinate erythrocytes. Immunity appears to be serotype-specific.

  • Adenovirus type 7 (Ad7), a group B virus, like all adenovirus types, usually causes mild URTI but is also the most frequently isolated type from patients with severe or fatal respiratory infection.

  • Adenovirus can infect epithelial cells from many different tissues, usually causing cell lysis. Occasionally, chronic latent infection occurs, especially in lymphoid tissue, and adenovirus may be cultured from the pharynx and stool of asymptomatic children.

Symptoms and signs

Symptomatic adenoviral infection can cause a wide variety of symptoms, generally not lasting >7 days. Infections can affect the upper and lower airway, causing simple colds, croup, bronchiolitis, or pneumonia. Most respiratory infections are caused by serotypes 3, 4, and 7. Respiratory symptoms include:

  • runny nose;

  • cough;

  • fever;

  • sore throat;

  • croup;

  • conjunctivitis;

  • breathlessness.

The physical signs are those seen in any viral respiratory tract infection and depend on the nature and severity of the infection. Acute conjunctivitis and exudative tonsillitis are more commonly seen with adenoviral infection than most of the other respiratory viruses and may provide a clue to the diagnosis. Conjunctivitis affects both eyes (usually one, then the other) and usually causes only mild discomfort. A more severe keratoconjunctivitis (caused predominantly by serotypes 8, 19, and 37) can occur, causing a red, painful eye for several weeks.

Other illnesses caused by adenovirus include watery diarrhoea, especially in infants, intussusception, haemorrhagic cystitis, hepatitis, and encephalitis.


  • Imaging studies: CXR and chest CT scans in children with acute adenoviral LRTI show non-specific bilateral reticulonodular shadowing. In children with severe pneumonia that has become prolonged, mosaic air trapping may be seen, consistent with small airways obstruction. Pleural effusions can occur as part of the acute systemic illness.

  • The presence of adenovirus in respiratory secretions (NPA or BAL) can be detected by culture, combined with immunofluorescence, or by PCR. Both are reliable tests. As noted, adenovirus may be cultured from asymptomatic children, and detected adenovirus may not necessarily be the cause of respiratory symptoms, although, in the absence of other causes, it is a reasonable assumption, particularly in a child under the age of 5 years.

  • Serology is often unhelpful. Most clinical laboratory tests will not provide the serotype, and, without paired sera 4 weeks apart, it is hard to interpret the results. It may be worth storing sera for later analysis.

  • Blood investigations may show:

    • decreased white cell count;

    • anaemia;

    • elevated transaminases;

    • deranged coagulation.


  • Treatment is supportive. Some children will progress to respiratory failure and require mechanical ventilation.

  • In immunodeficient children, antiviral agents, such as ribavirin and cidofovir, sometimes combined with pooled human Ig, have been used, with variable success.


Adenovirus vaccines have been developed by the US military and appear to be effective. These live attenuated virus vaccines were given orally and resulted in a significant reduction in outbreaks of adenoviral infection amongst army personnel, although, for financial reasons, production ceased in 1996. Adenoviral vaccine is not available for use in children.


  • Adenoviral infections are usually mild, self-limiting illnesses.

  • Adenovirus is more likely to cause severe lung disease than most of the other respiratory viruses, including disease severe enough to cause respiratory failure. A small number of these children, especially neonates and immunocompromised children, will die from their pneumonia, and a proportion will be left with long-term lung damage, usually in the form of BO.

Measles pneumonia

  • Measles virus is a paramyxovirus, the same family that includes RSV, HMP, and PIV.

  • Measles is spread by respiratory droplets. The incubation period is 10–14 days. The initial infection and viral replication take place in airway epithelial cells of the upper and lower respiratory tracts. After 2–4 days’ infection, there is a primary viraemia, after which the infection spreads to the lymph nodes and generalized lymphadenopathy develops. After a further period of replication, secondary viraemia occurs, with dissemination of the virus to various organs, including back to the lungs and the skin causing the typical rash.

  • Measles virus infection is exclusive to humans—there is no animal host. In immunized communities, it is commonest in 2–3-year-olds. In non-immunized communities, the incidence peaks at 5–10 years of age. It tends to occur in seasonal epidemics, usually in the early spring in temperate climates. Attack rates are very high, and 90% of susceptible individuals will become infected after exposure to the virus.

  • Measles infection is associated with depression of host immunity, including lymphopenia, which can last for weeks to months after the infection and which predisposes to subsequent bacterial infection, most commonly, otitis media and bronchitis or pneumonia.

  • Typical measles symptoms are as follows.

    • A prodrome of fever, runny nose, conjunctivitis, and dry cough occurs during the initial respiratory tract infection and is indistinguishable from any viral coryza, except that Koplik’s spots may be seen on the buccal mucosa. A croup-like illness can occur.

    • After 2–4 days, a florid macular, blanching red rash appears, spreading downwards from the head and neck to cover the whole body. The initial spots are discrete and pinpoint, but, as they become more numerous, they enlarge and become confluent.

    • The rash usually lasts around 3 days, after which fever settles and the rash resolves.

    • Common complications are bacterial bronchitis and pneumonia and otitis media. Diarrhoea is also common, particularly in poorly nourished children, as is corneal ulceration associated with vitamin A deficiency. Encephalitis occurs in one in 5000. Subacute sclerosing panencephalitis is very rare and occurs 4–10 years after the initial infection.

  • Diagnosis is often made on symptoms and signs. Confirmation can be obtained by measuring measles IgM, which will be positive in all children 4 days after the onset of the rash, and often earlier. PCR is also sensitive and specific, either from nasopharyngeal samples, throat swabs, or urine (90% of children excrete the measles virus in the urine), collected any time from illness onset to 12 days after the rash has resolved.


  • The first site of infection with measles is the respiratory tract, and measles always causes respiratory disease. Often this is confined to coryzal symptoms or croup during the prodrome, but the damaged airway epithelium is prone to secondary bacterial infection, causing a more persistent bronchitis. Small airways can be obstructed by inflammatory debris, resulting in areas of collapse that can also develop secondary bacterial pneumonia. Likely bacteria causing secondary pneumonia are Staphylococcus aureus, Streptococcus pyogenes, and Pneumococcus.

  • Primary measles pneumonia can also occur with infection of alveolar cells and interstitial cells with measles virus. Adjacent infected cells can fuse together, forming syncytial giant cells. Giant cell formation is not isolated to measles pneumonia and can be seen with RSV and parainfluenza pneumonia.

  • Primary pneumonia will occur during the early course of the disease, within 2 days of the onset of the rash. Secondary bacterial infection often occurs after the initial fever and rash have resolved and is accompanied by recurrence of fever and systemic disturbance.

  • When pneumonia occurs, it is usually associated with widespread airway epithelial cell damage and consequent airway wall oedema and airways obstruction. This will contribute to increased respiratory work.

  • CXR is usually typical of a viral pneumonia, with increased perihilar bronchial wall thickening, evidence of air trapping, and patchy atelectasis. There may also be evidence of hilar adenopathy. Secondary bacterial infection may cause lobar consolidation.

  • Occasionally, measles pneumonia may occur in a child who does not have a typical measles rash.


Treatment is supportive. Antibiotics should be used for secondary bacterial infection. The antibiotic selected should cover Staphylococcus aureus and streptococcal species. In malnourished children, high-dose vitamin A reduces morbidity and mortality associated with measles.


  • Effective vaccination is available. Since measles has only one strain and only infects humans, it should be possible to eradicate it from human populations in the same way that small pox has been eradicated.

  • Where there are effective national vaccine programmes against measles, the annual incidence is very low, and most of these cases are due to immigration of non-vaccinated individuals.


Measles is usually a self-limiting disease. Most children are miserable and unwell for 3–5 days, following which they make a full recovery. It is hard to estimate the frequency of respiratory complications. Pneumonia has been reported to affect 3–30% of infected children. Of those with pneumonia, 5–10% will develop respiratory failure and some will die. Mortality is much higher in malnourished children in resource-poor communities. In 1999, measles accounted for 800 000 deaths per year worldwide. In 2004, this figure had halved since the more widespread use of the measles vaccine.


  • Influenza infection causes an illness characterized by:

    • fever;

    • muscle aches;

    • headache;

    • cough.

  • Several different respiratory viruses, as well as bacteria such as Mycoplasma and Chlamydophila, can cause a flu-like illness that is impossible to distinguish clinically from an influenza infection.

  • Influenza is a seasonal illness, with the majority of cases occurring in a 6–8-week period during the winter months. The incidence of infection varies widely from year to year, affecting between 0 and 45% of the childhood population. On average, 5–10% of children are infected each winter. Attack rates are highest in children.

  • Immunity is strain-specific. Influenza strains vary from year to year, based on alteration of the surface glycoproteins haemagglutinin and neuraminidase. As a consequence, repeated infection often occurs several times in an individual’s life. Previous infection or vaccination may provide some protection against related strains and limit the severity of the illness. When a completely new strain arises, there will be no existing protection within the population, and a pandemic is more likely.

  • Three major subgroups of influenza are recognized—A, B, and C. Influenza A and B both cause epidemic flu. Influenza A infection tends to be more severe. Influenza C causes sporadic infection. Influenza A viruses are further divided, according to the haemagglutinin (H1–9) and neuraminidase (N1–3) types. Each year, one or two subtypes of influenza A may be in circulation with one type of influenza B.

  • Infection is by respiratory droplets, either directly or via contact with a contaminated object. Influenza viruses can survive on environmental surfaces, especially non-porous materials, for up to 48 h. Symptoms appear 1–3 days after infection. Viral shedding and infectivity persist for 5–7 days. Infectivity is highest in the 24 h after symptoms appear.

  • Influenza viruses on the skin or hard surfaces are easily killed by washing with soap and water, alcohol-based cleaners, and cleaning with normal household detergents.

Symptoms and signs

  • Influenza infection nearly always results in a noticeable illness. In the majority of children, it is not debilitating, but usually worse than a regular cold.

  • Symptoms typically start abruptly, usually with fever, sore throat, chills, aches, and headache. A feeling of weakness and fatigue is common. Although rhinitis can occur, it is not usually a predominant symptom. There may be a dry cough and conjunctivitis. Influenza infections are less distinctive from other respiratory tract infections in younger children.

  • In addition to the typical flu-like illness, influenza infection can cause bronchiolitis, pneumonia, and croup.

  • Examination findings are usually limited to fever and a red throat. There may be evidence of croup or pneumonia.

  • Young infants may present with severe illness, resembling bacterial septicaemia.

  • In a typical illness, fever will last 2–4 days. Return to full health may take several days or weeks. Cough may also persist for several days.


  • During the flu season, the diagnosis of flu-like illness is made on the basis of clinical signs and symptoms.

  • Confirmation of influenza infection can be obtained from NPA or throat swab. These can be processed by viral culture, direct immunofluorescence, or PCR. Near-patient testing kits are available but have limited specificity and add little to the clinical diagnosis.


  • Secondary bacterial pneumonia is the most common complication and responsible for most deaths. Infection arises because of viral-mediated damage to the airway surface and usually occurs 3–4 days after the onset of symptoms. The most likely bacterial pathogens are Staphyloccocus aureus and Streptococcus pyogenes. Secondary bacterial infections should be suspected when there is prolonged fever, recrudescence of fever, or worsening respiratory distress.

  • Primary influenza pneumonia is relatively rare but can cause a severe necrotizing disease, resulting in respiratory failure.

  • Multiorgan failure with a septicaemia-like illness has been observed with avian influenza infection. This does not appear to represent the consequences of secondary bacterial infection but rather is caused by an overwhelming viral disease.

  • Myositis with myoglobinuria, encephalitis, and myocarditis may also occur.


  • For previously healthy children, treatment is supportive, with oral fluids, antipyretics, and bed rest.

  • For infection in high-risk groups (children with heart disease, lung disease, immunocompromise), antiviral agents should be used. Amantadine (a viral ion channel blocker) is no longer recommended, because of readily acquired viral resistance. Two neuraminidase inhibitors are available—oseltamivir and zanamivir. These drugs inhibit the release of the virus from infected cells and thus limit the spread of the virus in the airways. To be effective, they must be given within 48 h of the onset of symptoms. Their use reduces the illness duration by 30% (1–1.5 days) and illness severity. Oseltamivir is taken orally, either as a capsule or suspension, and is licensed for all children >12 months of age. Zanamivir is a dry powder for inhalation for use in children >12 years of age.

  • For previously healthy children who develop severe illness, it is likely that symptoms will have been present for >48 h and antiviral therapies are unlikely to help. At this stage, their disease will be largely due to the consequence of viral damage, rather than active viral replication.

  • Antibiotics should be used when secondary bacterial infection is suspected. During epidemics of severe disease, there may be a role for using antibiotics from the onset of flu-like symptoms to prevent secondary bacterial infection.

  • Some children will require intensive care and mechanical ventilation for respiratory failure, usually as a consequence of primary viral, or secondary bacterial, pneumonia.

Influenza pandemics

  • The term seasonal influenza refers to the expected burden of disease each winter. When there are more cases than usual, the term epidemic is used; there is no strict boundary when epidemic proportions are reached. It reflects a combination of disease incidence and disease severity. The term pandemic is used when there are widespread epidemics around the world. Pandemics occur when:

    • a new influenza subtype arises, for which there is no existing immunity;

    • the new strain infects humans, causing serious disease;

    • the new strain spreads easily from person to person.

  • There have been three pandemics in the last 100 years: in 1918 (Spanish flu), 1957 (Asian flu), and 1968 (Hong Kong flu).

  • Avian flu (H5N1) fulfils the first two requirements for a pandemic strain, but person-to-person spread is rare. Nevertheless, some form of a virulent influenza virus crossing the species barrier from birds or pigs to man is the most likely source of the next pandemic strain. It is most likely that this will arise in Asia where cohabitation between livestock, poultry, and people is common.

  • Pandemic preparedness plans have been developed in many countries to deal with the next pandemic. The UK plan assumes that 25% of the population will be infected, with a case fatality of 0.4–2.5% resulting in 20 000–700 000 excess deaths. A pandemic of this proportion could severely disrupt all major services and businesses. The key elements of the preparedness plan are as follows.

    • Measures to minimize the spread of infection. These will include advice about avoiding crowds and staying at home if symptoms develop. There are also likely to be restrictions on national and international travel. Strict hygiene measures will limit spread within homes and hospitals.

    • Provision of necessary medical services. This will include ensuring that health care workers stay well by priority provision of antiviral therapy. Non-essential treatment will be postponed to deal with the large numbers of people who will seek medical attention, and non-medical support workers will be trained to triage potential cases and to supply antiviral treatments using simple algorithms. In order for sufficient supplies of antiviral treatment to be available, countries have stockpiled drugs. In the UK, there are sufficient stocks for 25% of the population to receive a 5-day treatment course of oseltamivir. Algorithms to determine access to limited intensive care services may also be required.

  • Once a pandemic strain has been identified, it will take 4–6 months to produce significant quantities of vaccine. This will not be quick enough to protect most populations from the initial season but may protect those uninfected for subsequent seasons.


  • An inactivated influenza vaccine is available (given as an IM injection) and, on average, provides 70% protection from an influenza infection. This varies from year to year and depends on how well matched the vaccine is to the prevalent strain of influenza.

  • Each year, a new vaccine is designed, based on predictions of which strains are most likely to be prevalent. The vaccine usually contains two subtypes of influenza A and one of influenza B. Strain inclusion is determined by a group in the World Health Organization (WHO), based on the analysis of strains collected over the previous winter and the identification of new strains that have the potential to spread. Production of the vaccine starts in March each year and is usually complete by October. The selected vaccine strains are grown, using hens’ eggs. Children with severe allergy to egg should not be given the vaccine. Protection takes 2 weeks to develop after vaccination.

  • The public health value of widespread immunization in otherwise healthy adults and children is debatable, and, in most seasons, it has been hard to show objective evidence of benefit.

  • Targeted immunization in at-risk groups, such as those with chronic lung disease, including asthma and CF, seems reasonable (although the benefits have not been proven).

  • A live attenuated vaccine, given as a nasal spray, is also available and has similar efficacy to that of the inactivated formulations made with the same strains of virus.

  • Neuraminidase inhibitors can provide 2–5-fold protection against influenza infection when taken daily during the influenza season. In most countries (including the UK and USA), they are not recommended for use in this way, even in high-risk groups. Although viral resistance to neuraminidase inhibitors is rare, widespread prophylactic use may increase the likelihood of a pandemic of a resistant strain.


The prognosis for children with seasonal Influenza infection is excellent. The majority of the mortality from seasonal influenza is in the elderly (in the UK, there are an estimated 12 000 excess influenza-related deaths each year). During the 1918 pandemic, the majority of the morbidity and mortality was in young adults of working age. This may reflect both the virulence of that particular strain and a possible partial immunity in older people because of repeated prior influenza infections. The 1957 and 1968 pandemics more closely resembled the impact of seasonal influenza, with the greatest effects on the elderly. The virulence and severity of the next pandemic strain is hard to predict. The avian influenza strain (H5N1) has a case fatality of 30–50%.

Further information

Department of Health UK. Available at: <>.

Health Protection Agency Influenza Pandemic Contingency Plan. Available at: <>.

Jefferson T (2006). Influenza vaccination: policy versus evidence. BMJ 333, 912–15.Find this resource:

Severe acute respiratory syndrome

  • Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV). Closely related viruses have been found in animals, and it has been suggested that SARS-CoV arose through the mutation of one of these viruses, allowing it to cross the species barrier and infect humans.

  • SARS was first identified as an epidemic that occurred in 2003. A total of 8000 people became unwell, and 774 died. The index case was a doctor from China who was visiting Hong Kong. The disease spread to Singapore and Toronto by air travel. Over 100 health care workers caring for affected patients became infected themselves. Since 2003, there have been no further outbreaks.

  • SARS appears to be spread by respiratory droplets, either directly or via fomites.

  • The incubation period is 2–10 days. In adults, the disease had three phases.

    • Phase 1: a flu-like illness with fever, myalgia, headache, coryza, and occasionally diarrhoea. During this phase, viral replication occurs. It lasts 2 days and is followed by transient improvement.

    • Phase 2: recurrence or persistence of fever, with worsening cough and respiratory distress and developing hypoxaemia. CXR consistent with bronchopneumonia (bronchial wall thickening plus patchy consolidation). The viral load is already decreasing during this phase, and the illness is related to an inflammatory host response. Systemic corticosteroids appear to be helpful in this stage.

    • Phase 3: ARDS with diffuse alveolar damage, sometimes leading to pulmonary fibrosis.

  • Children, particularly those under the age of 12 years, were much less severely affected than adults. Very few progressed to phase 3 of the illness. Less than 10% of all those affected by SARS were children, and, of these, only 5% required hospital treatment and <1% needed mechanical ventilation. No child died. The reasons why children had milder disease are not known.

  • Treatment requires early recognition, triage, and cohorting with strict infection control measures to prevent spread of the infection. Current recommendations are to use broad-spectrum antibiotics in children with fever and pneumonia to prevent secondary bacterial infection. Systemic corticosteroids should be tried if there is progressively worsening disease. Ribavirin has been tried and found to be ineffective.

  • At follow-up, about 10% of children requiring hospital care for pneumonia had mild restrictive or obstructive lung disease. Whether this will further improve with time is not known. This outcome is probably not different from that in any severe viral pneumonia.

Further information

Li AM, Ng PC (2005). Severe acute respiratory syndrome (SARS) in neonates and children. Arch Dis Child Fetal Neonatal Ed 90, F461–5.Find this resource:


1 Kellner JD, Ohlsson A, Gadomski AM, Wang EE (2000). Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2, CD001266.