Influenza in Primary Immunodeficiency (2013-2014 Season)
Typical influenza disease is characterized by abrupt onset of fever, aching muscles, sore throat, and non-productive cough. Additional symptoms may include runny nose, headache, a burning sensation in the chest, and eye pain and sensitivity to light. Typical influenza disease does not occur in every infected person. Someone who has been previously exposed to similar virus strains (through natural infection or vaccination) is less likely to develop serious clinical illness. Although many people think of influenza as the “flu” or just a common cold, it is really a specific and serious respiratory disease that can result in hospitalization and death.
The most frequent complication of influenza is bacterial pneumonia. Viral pneumonia is a less common complication but has a high fatality rate. Other complications include inflammation of the heart and worsening of pulmonary diseases (e.g., bronchitis). Reye’s syndrome is a complication that occurs almost exclusively in children—patients suffer from severe vomiting and confusion, which may progress to coma because of swelling of the brain. To decrease the chance of developing Reye’s syndrome, infants, children, and teenagers should not be given aspirin for fever reduction or pain relief.
Viruses cause influenza. There are two basic types, A and B, which can cause clinical illness in humans. Their genetic material differentiates them. Influenza A can cause moderate to severe illness in all age groups and infects humans and other animals. Influenza B causes milder disease and affects only humans, primarily children.
Subtypes of the type A influenza virus are identified by two antigens on the surface of the virus. These antigens can change, or mutate, over time. When a “shift” (major change) occurs, a new influenza virus is born and an epidemic is likely among the unprotected population. This happened when the novel H1N1 influenza virus appeared in March of 2009 and led to a major pandemic, lasting until the summer of 2010.
Influenza is transmitted from person to person by airborne droplets formed during coughing and sneezing. These droplets are inhaled or land on mucus membranes (lining of the nose or inside of the mouth or the conjunctiva). Influenza virus also can be transmitted orally. A person is most likely to pass on the virus during the period beginning one to two days before the onset of symptoms and ending four to five days after the onset. The incubation period of influenza is usually two days but can range from one to four days. For most people, the flu lasts only a few days, but some people get much, much sicker. Influenza is of particular concern in people with pre-existing heart and/or lung conditions, the elderly, children under 2 years of age and pregnant women.
Vaccination is the principal means of preventing influenza and its complications. Here are some additional steps that may help prevent the spread of respiratory illnesses like influenza:
The most effective way to avoid an infection with influenza is to receive the influenza vaccine annually. The CDC regularly updates its guidelines and now recommends that everyone over the age of six months be given the influenza vaccine every year. Influenza vaccines are safe and effective, and, contrary to a common misconception, they do not cause the flu. Because the influenza virus characteristically changes or mutates from year to year, each year it is necessary to prepare a new vaccine for protection from the new flu strains that are present that year. For this reason it is essential that everyone get immunized against the seasonal flu every year because last year’s vaccine may not be protective against this year’s virus strains. Currently there are two different types of seasonal flu vaccine available in the US—the inactivated or “killed” flu vaccine (the “flu shot”) and a live attenuated influenza vaccine (nasal spray). Both are highly effective in preventing influenza in normal individuals.
The influenza vaccine for the 2013-2014 season will once again guard against the pandemic A (H1N1) virus from 2009 and the A Victoria 2011 (H3N2) viruses used in last season’s vaccine. This year’s vaccine also includes a B/Massachusetts/2/2012-like virus in the traditional trivalent vaccine. This year for the first time, a limited quantity of seasonal influenza vaccine will be quadrivalent (four components), containing two A viruses and two B viruses. The quadrivalent vaccines will contain the three viruses listed above, plus a B/Brisbane/60/2008-like virus. The CDC recommends both the trivalent and quadrivalent type equally.
The most commonly used vaccine, often called the “flu shot,” is a killed virus vaccine that can be given to individuals ranging from six months to senior citizens. This inactivated vaccine can be used by everyone, even by individuals who are allergic to eggs. Because the vaccine virus is grown in eggs, there was concern in the past that egg-allergic individuals might be at risk if they received the vaccine. However, recent studies have shown that individuals allergic to eggs do not have a higher chance of a reaction to the vaccine than non-allergic individuals and therefore the previous recommendation that egg-allergic individuals not receive the killed virus vaccine has now been withdrawn. This year there is also a version of the flu vaccine that was prepared in cell culture and has had no contact with eggs in its preparation (Flublok).
The traditional influenza vaccine requires an injection and may cause local swelling and tenderness at the injection site. For children receiving the flu shot for the first time, two injections spaced about one month apart are required. These should preferably be given in September and October before the influenza season begins. In subsequent years, only a single vaccine dose is required. Children who only received a single dose of vaccine in the first year often do not develop protective immunity and therefore two doses should be given to the child in the second year.
The other vaccine is a live attenuated influenza virus (LAIV) vaccine that is administered by droplets given into the nose (FluMist). FluMist is the name given to the intranasal seasonal influenza virus vaccine. Attenuation means that the virus has been weakened so that it does not cause illness in normal healthy people.
FluMist is approved for individuals ranging from 2 to 49 years old. Administration does not require any injections. However, since it is a live virus vaccine, it has some theoretical risk for patients with defective immunity. It is the general recommendation that patients with severe T-cell disorders, such as Severe Combined Immune Deficiency (SCID) and DiGeorge Syndrome, and B-cell disorders with hypogammaglobulinemia/agammaglobulinemia, such as X-Linked Agammaglobulinemia (XLA) and Common Variable Immune Deficiency (CVID), not be given this form of influenza vaccine (FluMist). There is no reason to expect that FluMist poses any risk for patients with Chronic Granulomatous Disease (CGD) or complement disorders. Patients with HIV infection and immunodeficiency have been given this live agent vaccine without problem, but there have been no studies of patients with primary immunodeficiency diseases.
As with any live virus vaccine, concern has been raised about the possible spread of the vaccine virus from an immunized person to a close contact such as a family member with primary immunodeficiency disease. Safety studies have indicated that the risk of spread of the vaccine virus is very low and we are not aware of a single instance of a patient with primary immunodeficiency disease developing an influenza infection as a result of contact with a FluMist immunized individual, despite several million doses of this vaccine being used each year for the past several years. As a general recommendation only patients with the most severe forms of primary immunodeficiency diseases (babies with untreated SCID) should avoid contact with individuals recently immunized with FluMist.
The CDC Advisory Committee on Immunization Practices (ACIP) issued the following recommendation concerning FluMist (LAIV) use in individuals in close contact with patients with impaired immune systems: “The flu shot is preferred for people (including healthcare workers and family members) in close contact with anyone who has a severely weakened immune system (requiring care in a protected environment, such as a bone marrow transplant unit). People in close contact with those whose immune systems are less severely weakened (including those with HIV) may get LAIV.”
Primary Immunodeficiency Family Plan
For families with a member who has a primary immunodeficiency, we recommend that all members of the family should be given the inactivated (killed) vaccine. The vaccines usually become available in August or September. Studies have shown that immunization can still be effective when given well into February or March in some years, so it is important to ask for the vaccine even if the New Year has passed.
Why do we recommend that everyone be immunized? First, some patients with a primary immunodeficiency may benefit from the vaccine. Even if they do not, there is little down side to receiving the inactivated vaccine. Family members who are able to respond to the vaccine will be protected. Even if the patient with primary immunodeficiency does not respond to the immunization, he or she will benefit from having everyone else in the family protected from infection and not susceptible to bringing the virus home with them. We want to create a “protective cocoon” of immunized persons surrounding our patients so that they have less chance of being exposed. It would be a good strategy to encourage employers to provide influenza immunization programs at the place of work and schools to similarly encourage immunization of the student body to further extend this “cocoon.”
Individuals with primary immunodeficiency have the same risk of contracting flu as does the rest of the population. The same type of anti-viral medicine, i.e., Tamiflu or Relenza, which is effective for people with normal immune systems, would be effective for patients with primary immunodeficiency diseases who get influenza. Note that Ig replacement therapy may not protect against new strains of the influenza virus since the Ig contained in the currently available lots of IVIG or SCIG was obtained from donors several months ago, probably before the newer strains of influenza had circulated thru the donor population to result in antibody formation.
Influenza can be diagnosed rapidly by a test done in physician offices. If the test is positive, it is recommended that persons immediately begin anti-virus treatment. Speed is important in this situation since the antiviral medications are most effective if begun within 48 hours of the onset of the illness. It would be a good idea to discuss with your physician plans for dealing with influenza before you get sick so that you are prepared. If you do become ill, you should contact your doctor immediately about initiating treatment. However, it would be wise to contact your physician first, before going to their office, an urgent care facility or emergency room.
During the flu season, you may want to stay away from crowded public places, such as shopping malls, if you are concerned about exposure. Most people can get information from the national media and from their physicians on other ways to prevent exposure, as well as when to use additional precautionary measures.
What do I do if there is influenza in the schools or at my workplace?
There is no single recommendation that is applicable to every situation. Some medical advisors recommend that unless influenza is in their classroom children with primary immunodeficiency diseases should go to school. If there is a known direct contact with secretions from a flu-affected child or adult by the individual with primary immunodeficiency, some medical advisors suggest that the patient should go on Tamiflu once a day for 10 days. If the individual with primary immunodeficiency disease develops symptoms of influenza, that person should be treated with Tamiflu twice a day for 5 days. Relenza could also be used as the anti-viral treatment. The same treatment recommendations should apply to adults with CVID or other primary immunodeficiency diseases. As stated earlier, only patients with the most severe forms of primary immunodeficiency diseases (babies with untreated SCID) need to strictly avoid contact with individuals recently immunized with FluMist. If you have any questions, please contact your specialist.
Revised October 2013