Management of respiratory viral infections

The Leeds Method of Management. April, 2008. Management of respiratory infections [online]. Leeds Regional Adult and Paediatric Cystic Fibrosis Units, St James's University Hospital, Leeds, UK. Available from http://www.cysticfibrosismedicine.com

Introduction

Most acute respiratory viral infections in people with cystic fibrosis (CF) are probably self limiting, but may be associated with significant clinical deterioration (Conway et al, 1992) and predispose to infection with P. aeruginosa (Johansen & Hoiby, 1992). Viral and bacterial infections may be synergistic in their capacity to cause airway inflammation and lung damage (Petersen et al, 1981). Coincidental respiratory syncytial virus (RSV) infections in patients with intermittent and chronic P. aeruginosa infection are associated with a significant rise in anti-pseudomonal antibody levels (Petersen et al, 1981). There are several possible mechanisms by which respiratory viruses may induce pulmonary damage in patients with CF. Viral infection may promote inflammatory cell recruitment and activation through intercellular adhesion molecules (Papi et al, 1999) and induce the expression of stress response genes such as heme-oxygenase-1 and genes encoding for antioxidant enzymes such as glutathione peroxidase (Choi et al, 1996). The latter can further affect already reduced epithelial lining fluid levels of glutathione in inflammatory conditions like CF (Roum et al, 1993)

Prevalence

There is a wide variation in the incidence of viral infections in groups of patients without CF. Falsey et al prospectively followed 540 adults aged over 21 years with a diagnosis of congestive cardiac failure or chronic pulmonary disease over a four year period using culture, PCR and serology (Falsey et al, 2005). Within this population of patients RSV and Influenza A infection developed annually in 4-10% and 0-5% respectively (Falsey et al, 2005). A recent 10 year retrospective study looking at the prevalence of positive viral serology in adult patients receiving intravenous antibiotics (3156 courses) found that the annual incidence of admissions per patient associated with viral infection was 4.9% (Clifton et al, 2008) (Table 1). Reassuringly, the presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term.

Diagnosis

Historically, the techniques used for the diagnosis of viral respiratory infection have been tissue culture, serology and immunofluorescence. Tissue culture was the gold standard, but all these techniques suffered from low sensitivities. Modern techniques are based upon molecular techniques such as polymerase chain reaction (PCR). These offer increased accuracy and more rapid turnover. A diagnosis of a viral infection can be made in a matter of hours rather than days.

To treat or not to treat?

We advise patients to take appropriate oral antibiotics at the first symptoms suggestive of a viral respiratory tract infection, (a varied combination of increased cough, wheeze or fever), because

1) Some of these ‘viral’ respiratory exacerbations may actually be due to bacteria, such as Haemophilus influenzae or Streptococcus pneumoniae. The extra antibiotic should therefore be active against these bacteria, e.g. amoxycillin (Amoxil®), cefaclor (Distaclor®), trimethoprim (Monotrim®), azithromycin (Zithromax®), or clarithromycin (Klaricid®).

2) The Copenhagen experience documents an increased incidence of new P. aeruginosa acquisition in the winter ‘viral’ months (Johansen & Hoiby, 1992) and it is generally agreed that viral induced respiratory tract damage may facilitate secondary bacterial infection.

The additional antibiotic is taken until the patient returns to his/her previous condition even if this takes two or three weeks. If the new symptoms, (most important being a new cough), do not settle we consider a different oral antibiotic or intravenous antibiotic treatment, and the need for further cultures and a chest X-ray.

Influenza A has a more significant impact on people with CF than on other individuals (Wat & Doull, 2003). There are a number of potential treatments available for infection with the influenza virus including the M2 ion blocking drugs amantadine and rimantadine and the newer neuraminidase inhibitors zanamivir and oseltamivir. A systematic review of these drugs in non-CF healthy adults suggested that the use of amantadine and rimantadine should be discouraged due to lack of proven efficacy, a poor side effect profile and the rapid development of viral resistance (Jefferson et al, 2006). In contrast, zanamivir and oseltamivir have been demonstrated to be effective in healthy non-CF adults for the prevention and treatment of influenza (Jefferson et al, 2006). An analysis of studies assessing the efficacy of antiviral drugs targeted against influenza A (e.g. oseltamivir, zanamivir) failed to show a significant benefit for ‘high risk’ (which includes those with CF) children in terms of reduction of duration of symptoms or number of secondary cases in contacts (Matheson et al, 2007).

Early ribavarin treatment reduces the incidence and severity of reactive airway disease as well as respiratory illness-related hospitalisation in infants without CF and early respiratory syncitial virus infection (Edell et al, 2002), but there are no reports of its use in patients with CF.

Influenza vaccine generates a satisfactory immune response in patients with CF, but there is no evidence that it reduces morbidity or mortality due to influenza infection (Dharmaraj et al, 2007). We recommend annual influenza vaccination for all patients and advise that, if at all possible, they should avoid close contact with people with acute viral like illnesses in an effort to reduce the transmission of viral respiratory infections.

Negative serology
94.9%
Influenza A 2.0%
Influenza B 0.9%
Adenovirus 1.5%
RSV 0.5%
Influenza A and RSV 0.03%
M. pneumoniae 0.2%
C. psittacosis 0.1%
C. burnetii 0.0%
Table 1. Serology results from a 10 year retrospective study looking at the prevalence of positive viral serology in adult patients receiving intravenous antibiotics (3156 courses) (Clifton et al, 2008)
 

Key points

• Viral infection can be associated with significant clinical deterioration

• Anti-viral agents may have a role in the treatment of viral infections

Recommendations

• Avoid close contact with people with acute viral type symptoms

• Viral infections should be covered with additional oral antibiotic adminstration and treated with intravenous antibiotics if symptoms do not settle

• Annual influenza vaccination

 

References

Choi AM, Knobil K, Otterbein SL, et al. Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation. Am J Physiol 1996; 271: L383-L391. [PubMed]

Clifton IJ, Kastelik JA, Peckham DG, et al. Ten years of viral and non-bacterial serology in adults with cystic fibrosis. Epidemiol Infect 2008; 136: 128-134.[PubMed]

Conway SP, Simmonds EJ, Littlewood JM. Acute severe deterioration in cystic fibrosis associated with infuenza A virus infection. Thorax 1992; 47: 112-114. [PubMed]

Dharmaraj P, Tan A, Smyth R. Vaccines for preventing influenza in people with cystic fibrosis. Cochrane Database Syst Rev 2007; 3: CD001753. [Link]

Edell D, Khoshoo V, Ross G, et al. Early ribavarin treatment of bronchiolitis: effect on long-term respiratory morbidity. Chest 2002; 122: 935-939. [PubMed]

Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005; 352: 1749-1759. [PubMed]

Jefferson T, Demichell V, Rivetti D, et al. Antivirals for influenza in healthy adults: systematic review. Lancet 2006; 367: 303-313. [PubMed]

Johansen HK, Hoiby N. Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis. Thorax 1992; 47: 109-111. [PubMed]

Matheson NJ, Harnden AR, Perera R, et al. Neuramidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst Rev 2007; 1: CD002744. [PubMed]

Papi A, Johnston SL.. Rhinovirus infection induces expression of its own receptor intercellular adhesion molecule 1 (ICAM-1) via increased NF-kappaB-mediated transcription. J Biol Chem 1999; 274: 9707-9720. [PubMed]

Petersen NT, Hoiby N, Mordhorst CH, et al. Respiratory infections in cystic fibrosis patients caused by virus, chlamydia and mycoplasma - possible synergism with Pseudomonas aeruginosa. Acta Paediatr Scand 1981 Sep;70(5):623-8. [PubMed]

Roum JH, Buhl R, McElvaney NG, et al. Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol 1993; 75: 2419-2424. [PubMed]

Wat D, Doull I. Respiratory virus infections in cystic fibrosis. Paediatr Respir Rev 2003; 4: 172-177. [PubMed]

 

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