Infectious Disease

Influenza A/H3N2 variant virus has been infecting swine and humans since July 2011 and is causing concern among federal and local health officials as the seasonal influenza season begins.

According to information on the CDC’s website, federal health officials are concerned about this variant because the virus may have already contributed to at least one death in September in an Ohio patient who had an underlying immunodeficiency.

Before the summer officially ended, officials with the agency reported 306 confirmed cases since the virus was first reported in 2011.

The variant virus appears to spread more easily to humans from pigs than other swine influenza viruses, and “children younger than 10 years old have little to no immunity against H3N2v virus,” according to the CDC.

Although the virus has not yet exhibited a sustained human-to-human transmission pattern, some clinicians are worried this variant could make this influenza season worse than years past, partially because the regular 2011-2012 influenza season was the mildest on record, according to the CDC. This makes delivering the message about influenza vaccination — particularly to those most at risk — all the more important, health officials told Infectious Disease News.

“The H3N2v virus could become an important player,” Pedro A. Piedra, MD, of Baylor College of Medicine, said. “It is another pig virus, for which our current influenza vaccine does not provide protection.”

Pedro A. Piedra, MD, of Baylor College of Medicine, said seasonal influenza vaccine will not protect against H3N2v.

Photo courtesy of Sanchez A, Baylor College of Medicine

Dominik Mertz, MD, of McMaster University in Canada, echoed Piedra’s comments during an interview with Infectious Disease News.

“We need to see where this new variant goes. It doesn’t look like it’s becoming a real public health issue, since we are not seeing too many person-to-person transmissions, but it is early. Regardless, it should not affect our continued vaccination recommendation efforts,” Mertz said.

Although Piedra said he has “little doubt” that the recently recommended universal influenza vaccination recommendations will keep under control the three strains that are contained within it, the new variant may require a new vaccine, should a sustained human-to-human transmission pattern occur.

Recommendations this year

Until such time as another vaccine may be needed, the CDC has partnered with the AAP and influenza advocacy groups to help promote awareness about the importance of getting the regular seasonal influenza vaccine.

“Partnering with the AAP, influenza advocacy groups and family led-organizations can help prevent influenza in children at highest risk,” Thomas R. Frieden, MD, CDC director, said in a statement earlier this season when the partnership was announced.

This year’s trivalent influenza vaccine contains A/California/7/2009 (H1N1)-like antigen, which is derived from influenza A/H1N1 2009 pandemic virus (pH1N1), along with the influenza A/Victoria/ 361/2011 (H3N2)-like antigen and influenza B/Wisconsin/1/2010-like antigen.

“The influenza A (H3N2) and B antigens are different than those contained in the 2010-2011 and 2011-2012 seasonal vaccines,” said Henry H. Bernstein, DO, of the Hofstra North Shore – Long Island Jewish Health System. Bernstein is the AAP Red Book online associate editor and a member of the Infectious Disease News Editorial Board.

Piedra said the two major influenza B lineages that are circulating has led to a quadrivalent vaccine, but that is not expected to be put into the market until next year’s influenza season.

An AAP statement issued at the beginning of this season called for influenza immunization of patients, physicians/nurses and all other health care personnel, along with identification of influenza infections to enable rapid treatment with antiviral medications. Regarding antiviral treatment, the AAP recommended against the use of amantadine and rimantadine because of persisting high levels of resistance but recommends the use of oseltamivir (Tamiflu, Roche) and zanamivir (Relenza, GlaxoSmithKline) when indicated.

The AAP statement also emphasized the importance of vaccinating children who have conditions that could increase the risk of influenza-related complications, which included all household contacts/care providers of children with high-risk conditions; all children aged younger than 5 years; all health care personnel; all pregnant woman and those who are considering pregnancy; and those who just delivered or are breast-feeding during influenza season.

The number of trivalent seasonal influenza vaccine doses to be administered during this influenza season will depend on the child’s age at the time the first dose was given and the child’s vaccine history, according to the AAP.

“The important thing is to educate on the need for vaccinations,” Piedra said, particularly in those most at risk for complications from influenza.

Mertz recently presented a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy that reviewed 255 studies on influenza that shines a light on those most at risk for influenza complications. That paper concluded: “In particular, older age, cardiopulmonary disease, and obesity increase the risk of influenza death.”

Mertz said his data also showed that as a group, children are at a lower risk for mortality compared with non-elderly adults during pandemic influenza. There was a trend for lower mortality rates for children aged younger than 5 years compared with older children.

“However, we had a pretty wide confidence interval, difficult to draw any definite conclusions,” he said.

Mertz also said his data can corroborate recently published data that showed children who have neurocognitive diseases were also at increased risk for mortality, making vaccination key in this population as well.

Laxity toward immunization

Piedra said he is particularly concerned about a potential pushback from those who choose not to be immunized against influenza vaccine this year because last year was so mild. This could complicate matters if the newer variant were to spread beyond those who have contact with swine.

The unanswered question, according to Piedra, is why last year’s influenza season was so mild. He said the answer to that question may take years to derive, but it could be related to the universal influenza vaccination recommendations. Another reason could be related to the cyclical nature of influenza itself.

Dominik Mertz

Piedra said taking a universal vaccination approach led to decreases in other pathogens, such as rotavirus and pneumococcal disease, so it is probable that influenza followed suit. However, as is also typical with implementation of universal vaccination recommendations, there is generally a public reluctance to get vaccinated. As has been seen with other diseases, less people see influenza, the less they may be inclined to protect themselves against it.

Influenza strain prediction

Another issue related to a mild influenza season, Piedra said, is the perception that influenza vaccine is unnecessary. Part of that perception stems from the way the vaccine is developed. Every year, officials with the FDA’s Vaccines and Related Biologics Advisory Committee make their “most educated guess” about what the primary influenza strains will be for that year, but it is always subject to change.

“You are trying to make a prediction of what will circulate on what one is observing in the Southern Hemisphere and that can differ from what we see in the Northern Hemisphere,” Piedra said. “We’re not always perfect. And it has been my experience that anybody who really tries to predict influenza seasons with 100% accuracy can always be proved wrong.”

When public health officials are proved wrong, the public can perceive it as a sign that these vaccines, and the people making the recommendations, are untrustworthy.

Therefore, William Schaffner, MD, of Vanderbilt University School of Medicine in Nashville, Tenn., and former president of the National Foundation for Infectious Diseases, said it is important for clinicians to be “vaccine advocates,” adding that there is a significant difference between being a vaccine provider and vaccine advocate.

“There’s a difference between a doctor or nurse saying, ‘I’d like you to consider getting a flu vaccine,’ compared with, ‘I want every one of my patients protected against influenza, and you are not leaving here without your influenza vaccine,’” said Schaffner, an Infectious Disease News Editorial Board member.

He said the difference in vaccine uptake with these two approaches is significant.

Variant strain considerations

Regarding the influenza A/H3N2 variant strain of influenza, officials with the CDC recommended that since no vaccine currently exists, people at high risk for influenza complications should avoid contact with pigs, and use common-sense approaches such as frequent hand washing at agricultural events that may exhibit swine.

“It’s important that people remember the common sense, simple steps that can be taken to protect their health as we would with any flu season,” said Dean Sienko, MD, of the Michigan Department of Community Health, which reported a patient with the new variant in August. The patient had come into contact with the variant at a county fair.

“Washing your hands, covering your nose and mouth when you sneeze or cough, and staying home when you feel sick are some of the best ways to protect yourself and others from becoming ill,” Sienko said.

For patients with suspected H3N2v infection, CDC officials recommended that clinicians obtain a nasopharyngeal swab or aspirate from the patient, place the swab or aspirate in viral transport medium, and contact their state or local health department to arrange transport and request a timely diagnosis at a state public health laboratory. Clinicians should also consider reverse-transcription polymerase chain reaction (RT-PCR) testing for patients with influenza-like illness who report recent swine exposure and for those who can be epidemiologically linked to confirmed cases of H3N2v influenza.

Rapid testing can be unreliable

The CDC also warned in an official health advisory about the potential unreliability of rapid diagnostic tests for the newer variants: “A negative rapid influenza diagnostic test result does not exclude infection with H3N2v or any influenza virus. In addition, a positive test result for influenza A cannot confirm H3N2v virus infection because these tests cannot distinguish between influenza A virus subtypes (they do not differentiate between human influenza A viruses and H3N2v virus). Therefore, respiratory specimens should be collected and sent for RT-PCR testing at a state public health laboratory.”

Rapid diagnostic tests for influenza may not be able to detect the novel influenza A H1N1 as well, according to a CDC study conducted at the beginning of the 2009 pandemic. Results of a CDC analysis indicated that although the rapid tests were capable of detecting influenza A H1N1 virus from respiratory specimens that contained high levels of virus, the overall sensitivity rate was only 40% to 69% when compared with PCR. Furthermore, the results showed that the sensitivity rate declined significantly among specimens with lower virus levels.

Pandemic prevention

As the influenza season is now in full swing, Schaffner said he has his “fingers crossed that this variant will not be the next influenza pandemic, but we all have to wait and see.” He added it is important for clinicians to remain apprised about the guidelines, as well as ongoing data about who is most at risk, and to advise patients accordingly.
— by Colleen Zacharyczuk