Leonard Krilov, MD, FAAP
Asif Noor, MD, FAAP
Influenza outbreaks are unpredictable. This year’s flu season has hit the entire country hard. Influenza activity spiked earlier than expected this year. It is widespread and already associated with 37 pediatric deaths nationwide. Over the past month newsflashes of healthy children succumbing to flu are depicting an alarming situation. The impact is comparable to the 2009 H1N1 Pandemic in terms of its rampant spread.
As a pediatrician you play a crucial role during such an outbreak. Not only do you treat the flu stricken children, you transform into an advocate for flu prevention through vaccination. In this blog we address the two common issues faced by the pediatricians, i) understanding the effectiveness of this year’s flu vaccine, and ii) when to consider oseltamivir for treatment.
What are the circulating strains in New York State? Influenza virus belongs to the orthomyxoviridae family and has two clinically significant antigenic types: influenza A and B. Influenza A is further subtyped based on the nature of surface proteins, the hemagglutinin (HA) and neuraminidase (NA) which are spike-like projections from the surface. Genetic mutations in the HA antigen and to a lesser extent NA antigen are responsible for the severity and epidemic potential of outbreaks. This season the main circulating strain is influenza A H3N2 (77%), followed by H1N1 (15%), and influenza B (8%) based on testing at the New York State Department of Health, Wadsworth Center.
What strains are in the flu vaccine? The composition of the flu vaccine is reviewed annually and updated based on the circulating influenza strains. Influenza vaccine for this season includes: A/Michigan/45/2015 (H1N1)pdm09-like virus, A/Hong Kong/4801/2014 (H3N2)-like virus, and B/Brisbane/60/2008-like virus. The quadrivalent vaccine containing two influenza B viruses contain the above three viruses and a B/Phuket/3073/2013-like virus.
How is the effectiveness of flu vaccine measured? The effectiveness of the flu vaccine depends upon the match between the vaccine strain and the circulating strain. The estimate is, however, calculated by the number of cases prevented by the flu vaccine. This year the circulating H3N2 strain is similar to last year’s strain and is included in the vaccine. The reason H3N2 strain is still the predominant virus responsible for the flu outbreak is due to its ability to undergo constant mutations of the genetic material, known as antigenic drift. It can change from one season to another and even during the same season. This phenomenon is particularly true if the predominant strain is H3N2 and if the vaccine production is egg-based (less stable vaccine). The vaccine effectiveness studies since 2009 have shown that when the vaccine and circulating virus are well matched the flu vaccine provides better protection against influenza B and influenza A H1N1 as compared to H3N2. Thus the severe and widespread nature of flu activity this year is likely a result of the predominant H3N2 strain which underwent drifting.
What is the estimated effectiveness of flu vaccine this year? The vaccine effectiveness studies from 2005-2017 showed that if the vaccine and circulating H3N2 are not well matched the vaccine effectiveness is close to 23%. Before this flu reached the Northern hemisphere, Australia had a bad flu season, in which the predominant strain was H3N2 and the vaccine effectiveness was only 10%. It is still too early in the season to provide estimated vaccine effectiveness in United States. The Centers of Disease Control and Prevention conducts observational studies at 5 outpatient sites across the country to measure the vaccine effectiveness. The effectiveness implies ability of the flu vaccine to prevent infection. It is calculated as the odds of vaccination among outpatients with influenza-like illness and laboratory confirmed influenza infection to the odds of vaccination in outpatients with influenza-like illness but are negative influenza test.
If the vaccine is not a good match to the predominant H3N2 circulating strain, should one continue to advocate for vaccination? Yes, the match is not ideal for this year, but the antibody production from the vaccine strain will continue to provide some degree of protection against the circulating strain. This protection might not prevent the occurrence of infection but the vaccine will reduce the probability of a further severe infection, hospitalization, and even death.
When should one prescribe antivirals? The two classes of antivirals approved for treatment of influenza are neuraminidase inhibitors which includes oseltamivir (oral) and zanamivir (inhalation) and the adamantanes (amantadine and rimantadine; high resistance is seen). Oseltamivir remains the treatment of choice. It is approved for neonates as young as 2 weeks of age. Oseltamivir’s resistance to the circulating viruses over the past few years is around 1%. One of the limiting factors of its use in children is the associated nausea and vomiting. The recommendations for treatment are limited to:
- Any child who is admitted to the hospital due to severe, complicated, or progressive respiratory disease irrespective of immunization status and duration of illness ≥48 hours.
- Outpatient therapy should be offered to any child at risk of complications such as children less than 2 years or underlying medical problems. Treatment should be offered to symptomatic siblings less than 6 months of age. In addition it can be used for term and preterm infants after birth based on limited pharmacokinetics and safety data. Best outcome is seen with early treatment started within the first 48 hours.
- Premavir is an intravenous formulation for treatment of influenza reserved for severe cases when oral oseltamivir cannot be used.
In this hard hit flu season, some of the other important recommendations regarding flu vaccinations are as below:
- The inactivated flu vaccine is recommended for children ≥6 months and older. Both trivalent and quadrivalent preparations are available. The live nasal influenza vaccine is not recommended for this 2017-18 season due to lack of effectiveness.
- One should continue to offer influenza vaccination while flu activity is present in the community.
- The only contraindication to vaccination is a severe anaphylaxis to a prior influenza vaccination. A history of mild (hives) or severe hypersensitivity (anaphylaxis) to eggs is not a contraindication. If there is a history of severe egg allergy then the vaccine should be administered by a healthcare worker who is able to recognize and treat anaphylaxis reactions.
- Prophylaxis with oseltamivir should be recommended to close contacts that are at higher risk of developing influenza complication. Prophylaxis is not recommended in infants less than 3 months of age unless the situation is judged as critical.
- A cell grown vaccine by the name of Flucelvax is available for children 4 years of age and above. It might provide better protection against H3N2 but the main benefit is flexibility in manufacturing.
In this particularly difficult flu season, one should continue to be an advocate for the flu vaccine to lessen the severity and extent of the outbreak.
(Dr. Leonard Krilov, MD, FAAP is Chairman of Pediatrics and Chief of the Division of Pediatric Infectious Disease at NYU Winthrop Hospital. He is the Co-chair of the Infectious Disease Committee of the NYS AAP Chapter 2. Dr. Asif Noor, MD, FAAP is Pediatric Infectious Disease Attending at NYU Winthrop Hospital and member of NYS AAP Chapter 2)