Invited Article

Oseltamivir resistance in swine influenza: a brief discussion

Viroj Wiwanitkit
Wiwanitkit House, Bangkhae, Bangkok Thailand.

Swine flu, an atypical H1N1 influenza virus infection, is a new emerging infectious disease starting from Mexico in 2009, and is presently pandemic around the world. For treatment of this infection, oseltamivir is recommended as drug of choice. Generally, a big problem for using oseltamivir in treatment of classical H1NI influenza virus infection is drug resistance. In this brief paper, the author discusses on the situation of oseltamivir resistance in swine influenza. Briefly, the oseltamivir resistance of swine flu is expected to be possible due to many underlying factors. It is needed to perform surveillance on oseltamivir resistance in swine flu. Planning for management of case of emerging oseltamivir drug resistance is needed. (Wiwanitkit V. Oseltamivir resistance in swine influenza: a brief discussion. North Am J Med Sci 2009; 1: 96-98).

Keywords: H1N1; Swine flu; oseltamivir; influenza; virus infection; resistance

Correspondence to: Professor Viroj Wiwanitkit, Wiwanitkit House, Bangkhae, Bangkok Thailand 10160. Tel.: 6624132436. Email: wviroj@yahoo.com


Introduction
Influenza virus infection is classified as a common respiratory tract infection. Recently, atypical influenza virus infection became the global threaten. In early 2009, swine, atypical H1N1 influenza virus infection, originated in Mexico and spread to many countries around the world. This new atypical virus is the product of natural genetic reassortment of influenza virus from human beings, swine and bird [1]. At present, World Health Organization already documents for level VI, the highest level, and precaution for this new disease indicating for its worldwide pandemic situation. The present focus of medical scientists is how to control this new emerging disease. Also, for the infected cases, searching for the best treatment protocol is the focus of physicians around the world.  Generally, there are some specific drugs indicating for treatment of classical influenza. Oseltamivir and zanamivir are the two drugs that are confirmed for its present usefulness in treatment of classical H1N1 influenza virus infection. Oseltamivir, an oral antiviral drug, is presently recommended for treatment of swine flu. Here, the author discusses on the problem of usage of oseltamivir in the new pandemic influenza infection, drug resistance.

 

Table 1 Recommended dosage of oseltamivir and zanamivir in treatment and prevention for swine flu (according to the WHO recommendation)



Drugs

Treatment

Prevention

Oseltamivir

 

 

 

Zanamivir

(> 10 years) 75 mg bid  x 5 days
(6 - 9 years) 60 mg bid  x 5 days
(3 - 5 years) 45 mg bid  x 5 days
(1 -2 years) 30 mg bid  x 5 days
(6 – 11 months) 25 mg bid  x 5 days
(3 - 5 months) 20 mg bid  x 5 days

(< 3 months) 12 mg bid  x 5 days
(> 7 years) 10 mg bid  x 15 days

(> 10 years) 75 mg od  x 10 days*
(6 - 9 years) 60 mg od  x 10 days*
(3 - 5 years) 45 mg od  x 10 days*
(1 -2 years) 30 mg od  x 10 days*
(6 – 11 months) 25 mg od  x 10 days*
(3 - 5 months) 20 mg od x 10 days*

(< 3 months) 12 mg od  x 10 days*
(> 7 years) 10 mg od  x 10 days**
(> 7 years) 10 mg od  x 28 days***

* Either in cases with closed contact to the patients or in pandemic period; ** in cases with closed contact to the patients; *** in pandemic period.

Efficacy of oseltamivir in swine influenza
Since the starting of the pandemic situation of swine flu, oseltamivir has been recommended and used as the first line antiviral drug. No doubt that oseltamivir has a good efficacy in treatment. According to the recent publication in New England Journal of Medicine, the clinical usefulness of oseltamivir in treatment of swine flu can be confirmed [1]. Several publications also confirm the effectiveness of oseltamivir in treating swine flu [2–5]. The main question is why oseltamivir, which is primarily designed for classical influenza treatment, is still effective for treatment of swine flu. There are some reports explaining this query in view of molecular phenomenon. First, swine flu and classical influenza are still within the group of H1N1 influenza virus infection. The two pathogens have no significant difference in oseltamivir receptor. The similarity of the drug receptors between the two influenza infections are already confirmed in some recent publications [6–8]. The preserved drug receptor area is the main reason for retained susceptibility to oseltamivir in swine influenza [6–8]. However, the mutation in swine influenza still makes the change in required drug-viral interaction energy that will bring decreased efficacy in treatment [5].

Oseltamivir resistance in swine influenza
It is the present focus for clinical observation on oseltamivir resistance in swine influenza. In USA, oseltamivir is still confirmed for no drug resistance in the report from disease surveillances [9]. However, this does not mean that there will be no drug resistance. This observation is also similar in other countries [9 - 10]. If there is a significant mutation or genetic drift, the present oesltamivir will be useless. For classical influenza, the oseltamivir is already documented for drug resistance [11 – 13]. The problem is usually due to inappropriate use of antiviral drug, in cases without indication. This can also be expected in case of swine influenza. In addition, in case of pandemic situation, the new variant that is highly resistant to oseltamivir can be expected.

"How to mange" in case of emerging oseltamivir resistance swine influenza
"How to mange" in case of emerging oseltamivir resistance swine flu is a big interesting problem. If the generalized oseltamivir resistance occurs, it is no doubt that another preserved antiviral drug, zanamivir has to be used. This is based on the similar rationale to the case of H5N1 influenza, bird flu [14]. However, the expectation of a rapid resistance to zanamivir can be imagined since zanamivir is the drug in the same group as oseltamivir. This is the reason for the urgent need on new drug searching.

Conclusions
The situation of oseltamivir resistance in swine flu is the present concern of medical society. The oseltamivir resistance of swine flu is expected to be possible due to etiologies. Surveillance on oseltamivir resistance in swine flu is useful. In management of possible case of emerging oseltamivir drug resistance, a good planning is required at present.

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