INFLUENZA PNEUMONIA - TREATMENT

Question:
Should this child be treated with antivirals?

Answer:
If started promptly, antiviral medications may reduce complications of acute influenza. Four licensed influenza antiviral agents are available: amantadine, rimantadine, zanamivir, and oseltamivir. Both amantadine and rimantadine are M2-inhibitors and zanamivir and oseltamivir are neuraminidase inhibitors (1). Amantadine and rimantadine target the M2 membrane protein of influenza A virus and inhibit viral replication. Both drugs have therapeutic and prophylactic benefit against infection caused by influenza A virus. They reduce the severity and duration of infection, if given within 48 hours of the onset of symptoms, and are 70% to 90% effective in preventing illness caused by influenza A virus if given prophylactically during epidemics or outbreaks. (2). However, both are ineffective against infection caused by influenza B virus, and their use is limited by adverse effects (neurological and gastrointestinal), mainly with amantadine, and by the development and transmission of drug-resistant virus. (3)

Oseltamivir and zanamivir are routinely used for the treatment and prophylaxis against flu. Both, inhaled zanamivir and oral oseltamivir, are effective for treatment and prophylaxis of influenza A and B infection. Both are well tolerated and show limited potential for emergence of antiviral drug resistance. (2) Oseltamivir is given orally while zanamivir is given by the inhaled route. The virus attacks the lungs and replicates in the cells. These drugs act by blocking the release of new virus particles from the cells that the virus has infected. This prevents the spread of the virus to other cells in the lungs. Evidence for benefits from antiviral treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours of illness onset. However, some studies of oseltamivir treatment of hospitalized patients with seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset. Recommended duration of treatment is five days. Antiviral doses recommended for treatment of novel H1N1 influenza virus infection in adults or children 1 year of age or older are the same as those recommended for seasonal influenza. For treatment doses, see table 1. Oseltamivir is licensed for the treatment of influenza in individuals aged one year and above. However there have been insufficient clinical studies evaluating its use in infants. There is published evidence from Japan that it has been used safely at a dose of 2mg per kg twice daily in children under one year of age. (4-6)

Table 1: Antiviral medication dosing recommendations for treatment of influenza infection (Table extracted from IDSA guidelines for seasonal influenza.)

Drug		Treatment (for 5 days)
Oseltamivir
Adults		75 mg capsule twice per day
Children > 12  months	15 kg or  less	60 mg per day divided into 2 doses
	16-23 kg	90 mg per day divided into 2 doses
	24-40 kg	120 mg per day divided into 2 doses
	> 40 kg	150 mg per day divided into 2 doses
Children <3  months		12 mg twice daily
Children 3-5  months		20 mg twice daily
Children 6-11  months		25 mg twice daily
Zanamivir
Adults		Two 5 mg inhalations (10 mg total) twice a day
Children		Two 5-mg inhalations (10 mg total) twice a day  (age, 7 years or older)

Thus this child should be treated with oseltamivir in the doses mentioned above.

References:

1.		Influenza treatment - Wikipedia, the free encyclopedia. Available at URL: http://en.wikipedia.org/wiki/Influenza_treatment. Accessed on 17th September 2010
2.		Cox NJ, Subbarao K. Influenza. Lancet. 1999; 345: 1277-1282
3.		Gavin PJ, Thomson RB Jr. Review of Rapid Diagnostic Tests for Influenza. Clinical and Applied Immunology Reviews 4. 2003; 151-172
4.		Kiso M, Mitamura K, Sakai-Tagawa Y et al. Resistant Influenza A viruses in Children Treated with Oseltamivir. Lancet 2004; 364: 759-765
5.		Tamura D, Miura T, Kikuchi Y. Oseltamivir Phosphate in Infants Under 1 Year of Age with Influenza Infection. Paediatrics International 2005; 47: 484
6.		Okamato S, Kamiya I, Kishida K et al. Experience with Oseltamivir for Infants Younger than 1 year old in Japan. The Pediatric Infectious Disease Journal 2005; 24: 575-576.