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Study: Oseltamivir-Resistant Pandemic Flu Cases In The US

 

 

 

# 5191

 

 

Unlike its seasonal cousin (which has all but vanished), the 2009 novel H1N1 virus remains largely susceptible to the antiviral medication oseltamivir (Tamiflu).

 

During a 14-month period (April 2009-June 2010) 6,740 H1N1 samples were submitted to US surveillance systems for testing, and of those, only 37 (.5%) proved resistant to oseltamivir.

 

That’s the encouraging news from a study, published yesterday, in the CDC’s  EID Journal.

 

The link, and an excerpt describing the patient profile follow.  Go ahead and read it. 

 

I’ll be back with a bit more when you return.

 

 

Characteristics of Patients with Oseltamivir-Resistant Pandemic (H1N1) 2009, United States

Graitcer SB, Gubareva L, Kamimoto L, Doshi S, Vandermeer M, Louie J, et al. Characteristics of patients with oseltamivir-resistant pandemic (H1N1) 2009, United States. Emerg Infect Dis. 2011 Feb; [Epub ahead of print]

 

(EXCERPT)

 

Most patients infected with oseltamivir-resistant pandemic (H1N1) 2009 viruses were hospitalized (81%), had a severe immunocompromising condition (76%), and had been exposed to oseltamivir before collection of the specimen tested for antiviral resistance (89%) (Table); 9 (30%) had received oseltamivir as chemoprophylaxis, and 21 (70%) had received oseltamivir as treatment.

 

Four patients with oseltamivir-resistant pandemic (H1N1) 2009 virus infection had no documented exposure to oseltamivir before collection of the specimen for testing, including exposure to family members receiving oseltamivir.

 

No epidemiologic links were found between the 4 patients.

 

For now, the good news is that the 2009 H1N1 virus remains overwhelmingly sensitive to Tamiflu.

 

But of course, the same could have been said about the old seasonal H1N1 virus back in 2006-2007, when 99% of isolates tested showed good sensitivity to oseltamivir.

 

Resistance is usually caused by a mutation, known as H275Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275

 

(Note: some scientists use 'N2 numbering' (H274Y) and some use 'N1 numbering' (H275Y)).

 

Back in 2007, the belief was that the mutation that made the virus resistant to Tamiflu (H275Y), also reduced its biological fitness – suggesting that mutated versions of the viruses were unlikely to spread widely.

 

 

But those hopes were dimmed when, by the end of the 2007-2008 flu season, nearly 13% of H1N1 isolates tested the United States were resistant to the drug.

 

By December of 2008 nearly all seasonal H1N1 isolates tested around the world carried the H275Y mutation that conferred Tamiflu resistance.

 


Thus far, it appears that most of these resistant 2009 H1N1 strains have developed in immuno-compromised patients as so-called `spontaneous mutations’ – not as the result of contracting a circulating and already-resistant virus.

 

 

Human-to-human transmission of an oseltamivir-resistant novel H1N1 virus has only rarely been demonstrated.  A couple of reports on those include:

 

NEJM: Community Cluster Of Tamiflu Resistant H1N1
WER Review: Oseltamivir Resistance In Pandemic H1N1

 

 

Today, the news is good; resistance in novel H1N1 is rare.  But pharmacological victories over constantly evolving viruses (and bacteria) tend to be fleeting, and so the need for new classes of antivirals is great.  

 

The authors sum of their report this way:

 

Although the number of patients with oseltamivir-resistant pandemic (H1N1) 2009 virus infections was small in the United States during this period, this is the largest case-series published and confirms findings from reports with smaller samples (8–10).

 

Although all patients in our comparison group of patients with oseltamivir-susceptible pandemic (H1N1) 2009 were hospitalized, most patients in the oseltamivir-resistant group were also hospitalized. Finally, we do not have a comparison group of patients with immunocompromising conditions and oseltamivir-susceptible pandemic (H1N1) 2009 virus infections; thus, risk factors for infection with oseltamivir-resistant infection among patients with immunocompromising conditions cannot be determined.

 

The finding of oseltamivir-resistant pandemic (H1N1) 2009 viruses associated with oseltamivir treatment highlights the need for new antiviral agents and new treatment strategies.

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