Feb 15, 2008 (CIDRAP News) The current influenza season is showing signs of becoming a tough one, with flu activity now widespread in 44 states and many of the circulating viruses differing from those in the vaccine, the Centers for Disease Control and Prevention (CDC) reported today.
Dr. Joe Bresee, chief of the epidemiology and prevention branch in the CDC's Influenza Division, said it's too early to tell if this season will be unusually bad, but so far it is looking worse than the past two or three seasons, which were relatively mild.
Speaking at a news briefing, Bresee said influenza A/H3N2 has become the predominant flu subtype in the United States, and the record over the past 25 years shows that seasons dominated by H3N2 tend to be worse than those dominated by type A/H1N1 or type B.
The CDC released more evidence today that many H3N2 and B viruses making people ill differ from the strains in the vaccine, though the H1N1 viruses continue to match the vaccine. The agency first reported the problem last week.
The agency also reported that 4.6% of all the flu viruses analyzed so far showed signs of resistance to oseltamivir (Tamiflu), the most commonly used antiviral flu drug. That represents a "real increase" in resistance but is not yet a major worry, Bresee said.
So far this season, 10 children have died of flu, 9 of them since Jan 1, Bresee reported. Four of those children had Staphylococcus aureus coinfections, a complication that the CDC recently asked physicians to watch for and report.
Flu spreading nationwide
For the week that ended Feb 9, 44 states reported widespread flu activity and 5 reported regional activity, according to today's CDC report, a Morbidity and Mortality Weekly Report (MMWR) early release. By comparison, in the last three seasons the number of states reporting widespread or regional activity peaked at between 41 and 48.
In another sign of a worsening epidemic, 33% of specimens tested for flu last week were positive, the report says. In the previous three seasons, the peak percentages of positive specimens ranged from 23% to 28%. Also, 5.7% of all outpatient visits to sentinel healthcare providers last week were for influenza-like illness. The peak percentage of visits for flu-like illness in the last three seasons never exceeded 5.4%.
Bresee said the current epidemic looks worse than the past two or three in terms of hospitalizations and deaths. However, "It's not an atypical season if you look back over many years," he said.
"The reasons are probably multiple, but you can't discount the fact that in seasons where we have a predominant H3N2 virus in circulation, we tend to have more disease in those seasons," Bresee said.
Since Sep 30, the CDC has subtyped 2,299 influenza A viruses and found that 55% were H3N2 and 45% were H1N1, the MMWR report says. H1N1 viruses predominated through mid-January, but H3N2 strains have taken over since then, it states.
Not a great year for the vaccine
The CDC has analyzed 250 viruses this season to determine how well they match up with the vaccine, the report says. Of 65 H3N2 isolates, 53 (81%) were characterized as A/Brisbane/10/2007-like, a variant that has evolved from the H3N2 strain in the vaccineA/Wisconsin/67/2005. Yesterday the World Health Organization (WHO) recommended that the Brisbane strain replace the Wisconsin strain in next season's northern hemisphere vaccine.
Of 68 type B viruses characterized by the CDC, only 4 (6%) belonged to the B/Victoria lineage represented in the vaccine, and only 1 of the 4 was the same strain as in the vaccine (B/Malaysia/2506/2004). The other 64 isolates (94%) belonged to the Yamagata lineage, the CDC reported.
In contrast, the circulating H1N1 viruses continue to match up well with the vaccine. Of 117 isolates tested, 107 (91%) were similar to the vaccine strain, A/Solomon Islands/3/2006-like, the MMWR report says.
Concerning the circulating H1N1 viruses, the CDC report contrasts with yesterday's WHO report. The WHO said "the majority" of recent H1N1 isolates tested globally differed from the Solomon Islands strain and were similar to a strain known as A/Brisbane/59/2007. The WHO advised using the latter in next year's vaccine.
Overall, said Bresee, "Slightly more than half of the viruses we looked at in our lab are somewhat different from the vaccine strains and may not be well covered by the vaccine strains." But what percentage of the viruses in circulation are not covered by the vaccine is unknown, since the isolates tested by the CDC aren't necessarily a representative sample, he said.
Bresee said the vaccine still should provide some protection despite the mismatches with two of three circulating strains.
Ideally, a vaccine that covers the circulating strains should provide 70% to 90% protection, he said. Under the circumstances, "We'd expect the 70 to 90% to be a bit lower this year. . . . Even in years when the vaccine virus doesn't match perfectly against the circulating strains, we do see some effectiveness. This is particularly important in patients who have conditions where they're more likely to get severely ill."
Bresee said the CDC has heard anecdotal reports of flu cases in people who had been vaccinated, but that's not unusual for any year. "Even in years when the vaccine matches less well against the circulating strains, we know the vaccine will tend to make the illness milder," he added.
Tamiflu resistance increases
The CDC has tested 350 flu viruses and found that 16 (4.6%) had a mutation that confers resistance to oseltamivir, according to today's report. All the resistant isolates were H1N1; they made up 8.1% of the 198 H1N1 viruses tested. In contrast, less than 1% of H1N1 viruses tested last years showed resistance. The increased resistance to the drug was first reported about 2 weeks ago.
"The level [of resistance] we're seeing is certainly higher than we've seen in the past, and we think it's a real increase," Bresee said. But he said the overall resistance levels are still considered very low and certainly not high enough to warrant changing the CDC's recommendation to use oseltamivir to treat flu patients. There have been no reports of increased resistance to zanamivir (Relenza), the other drug in the class known as neuraminidase inhibitors.
Resistance to the older flu drugs, amantadine and rimantadine, remains high this season, and the CDC continues to advise against using them for flu, the CDC report says.
Deaths in children
Concerning the 10 children who have died of flu so far this season, Bresee said, "We've seen somewhere between 44 and 73 cases in the last 3 years, so the finding of 10 this late in the season is not totally unexpected. We may see more before the season is finished."
Saying the 10 deaths are still under investigation, Bresee couldn't list which flu subtypes were involved.
Feb 15 MMWR update on flu activity
Feb 14 CIDRAP News story "WHO advises total makeover for 2008-09 flu vaccine"
Feb 8 CIDRAP News story "CDC says influenza B strain doesn't match vaccine"
Feb 7 CIDRAP News story "Europe reports further increase in Tamiflu resistance"