A review of neuraminidase inhibitor susceptibility in influenza strains

Abstract

Influenza human infections are considered as a persistent global public health issue. Whereas vaccination is important for prevention, given its limitations, antiviral therapy is at the forefront of treatment, while it also plays a significant role in prevention. Currently, two classes of drugs, adamantanes (M2 blockers) and neuraminidase inhibitors (NAIs), are available for treatment and chemoprophylaxis of influenza infections. Given the resistance patterns of circulating influenza strains, adamantanes are not currently recommended. The current review mainly focuses on the development of resistance to NAIs among A and B subtypes of influenza virus strains over the last 5 years. ‘Permissive’ drift mutations and reassortment of viral gene segments have resulted in NAI oseltamivir-resistant A/(H1N1) variants that rapidly became predominant worldwide in the period 2007–2009. However, the prevalence of antiviral resistance to NAI zanamivir remains relatively low. In addition, the recently developed NAIs, peramivir and laninamivir, while licensed in certain countries, are still under evaluation and only a few reports have described resistance to peramivir. Although in 2014, the majority of circulating human influenza viruses remains susceptible to all NAIs, the emergence of oseltamivir-resistant influenza variants that could retain viral transmissibility, highlights the necessity for enhanced epidemiological and microbiological surveillance and clinical assessment of antiviral resistance.

Keywords::

• antiviral drugs
• epidemiology
• influenza
• neuraminidase inhibitor
• oseltamivir
• resistance
• susceptibility

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Influenza infections occur annually with an attack rate of 5–10% in adults and 20–30% in children, resulting in approximately 1 billion cases, 3–5 millions of severe illness and 250–500 thousands of deaths worldwide.

• Since 2010, neuraminidase inhibitors (NAIs) are the only recommended antiviral drugs for the treatment and prophylaxis of influenza A and B infections.

• NAIs action is achieved through their attachment and subsequent block of the enzymatic location of the neuraminidase glycoprotein of influenza viruses, preventing the release of viral progeny from infected cells.

• Four NAIs are currently licensed for the treatment and prevention of influenza since 1999: zanamivir, oseltamivir, permivir and laninamivir.

• The most widely used NAIs are zanamivir and oseltamivir, the latter causing the majority of resistance, especially after prolonged treatment.

• The most common mutation associated with oseltamivir resistance is the amino acid change H275Y in the neuraminidase protein.

• Only limited number of influenza strains exhibit zanamivir resistance.

• Oseltamivir resistance is reported among several types/subtypes of influenza A and B viruses.

• Early laboratory detection of oseltamivir-resistant strains is essential for the reduction of NAI’s resistance.

• Prolonged administration of oseltamivir without apparent clinical benefit should be avoided.

• Prophylactic measures are highly recommended for the infection control among immunocompromised patients.

• Vaccination against influenza is highly encouraged in order to reduce NAI’s usage.