5 Jun

Influenza types A and  B are  discussed in Chapter 3.

Every year, immunologists and  epidemiologists prepare a vaccine combination based on  an  educated guess. The  new vaccine must be  developed and  produced rapidly to  meet expected needs. Pandemics, such  as those in 1917–1919, 1957, 1968,  1977,  and  1997,  present even  more  challenges, particu- larly with the  need  for safety, quality, and  efficacy  of the  vac- cine.  Most  influenza  vaccines are  influenza virus grown in embryonated hen’s eggs, purified and  inactivated. Concerns of this type  of vaccine are  that it takes 7–8 months of lead  time to produce the  vaccine. Often a single 15 mg heamagglutinin dose  may  not  confer  sufficient immunity. On the  other hand, whole virus vaccines are  more  immunogenic than split or sub- unit vaccines. H5 vaccines may  need  an adjuvant (96). Soluble, recombinant forms  of influenza A virus have been  suggested (97). Other suggestions for improved vaccines are  better vac- cine production technologies, reverse genetics technology, and novel  adjuvants to  improve immunogenicity (98).  Currently, the  trivalent inactivated vaccines are  available as  subvirion (split), purified surface antigen (subunit), and  whole  virus preparations.

Those  who  are  most  at risk for influenza complications are  the  very  young  and  the  very  elderly. More  than 80%  of children and  young  adults who received influenza vaccination developed high  levels  of antibody titers (99).  Whole-virus influenza vaccines should not  be given  to children <12 years old,  due  to  increased potential for  febrile reactions (100). Therefore, for children 1–16  years old, the  inactivated triva- lent influenza vaccines are  well tolerated and  provided 91.4% efficacy  for influenza A H1N1  and  77.3% efficacy  for influenza A H3N2  (101).

Vaccination in the  elderly has  been  shown to lessen the risk of complications, hospitalization and  death (102,103). In children and  young  adults, the  influenza  vaccine has  been 70–90% effective in preventing influenza during controlled tri- als  with a  good  match between the  vaccine and  circulating influenza strains  (104,106). In  the  elderly, inactivated virus vaccines have less efficacy due to the declining integrity of eld- erly  immune systems. Only  17% of persons over  65 years are expected to increase antibody titers to all three vaccines com- ponents and  46%  fail  to  respond to  any  of them. Perhaps a prophylactic treatment, such  as neuraminidase inhibitors can be used to boost  immunogenicity (107). A study of vaccination in  low-risk elderly persons demonstrated  a  58%  efficacy  in preventing laboratory-confirmed influenza (108). When stud- ied  in  elderly nursing home  residents, influenza vaccine is 30–40%  effective in  preventing influenza illness, but  is  also 50–60%  effective in preventing pneumonia or hospitalization and  80%  effective in  preventing death  (109,110). Immunity following influenza vaccination begins within 1–2 weeks and rarely persists beyond 1 year (111). Protective antibody levels may  only  last 4 months or  less  in  certain elderly patients (112).  In  addition, the  strains of influenza may  differ  signifi- cantly from  one season to the  next, thus increasing the  need for annual vaccinations.

Influenza immunization is  indicated for  anyone aged ³6 months who is at increased risk for complications of influ- enza or  is  in  contact with those individuals (i.e.  caregivers, medical personnel). The  at-risk population includes persons ³65  years of age,  residents of nursing homes, those with chronic pulmonary or  cardiovascular disorders, and  persons with HIV.  Vaccination is  also  indicated for  individuals who desire to decrease their risk for influenza infection. The immu- nization regimen consists of one  dose  given  each  year, from September through mid-November, to prepare for the  winter’s influenza activity. Administration of the  vaccine is still  recom- mended after mid-November if influenza activity has   not peaked in  the  community. Previously unvaccinated children <9 years of age should receive 2 vaccine doses at least 1 month apart to develop sufficient antibody levels  (100).

Adverse Effects

These symptoms typically begin  within 6–12  hours and  per- sist   for  1–2  days. In  one  clinical trial,  the   incidence of adverse effects  did  not  differ  between the  vaccinated group and  placebo (113).

Fever. Malaise. Headache. Arthralgia. Myalgia.

Guillain-Barré  syndrome  (GBS). A significantly in- creased frequency of GBS  was  found  with the  1976 swine influenza vaccine (114), but  more  recent investi- gations show  an  extremely small risk of GBS with the current vaccines, which is slightly more  than one extra case  per  1 million vaccinees (100).

Immediate allergic  reactions. Hives, angioedema, or systemic anaphylaxis rarely occur  after vaccination

(115).  These hypersensitivity reactions are  most  likely due to residual egg-protein exposure to sensitive patients.

Special Considerations

Egg  allergies. The  majority of egg-allergic subjects can safely receive immunization, but  those with a history of anaphylactic reaction to eggs  or previous influenza vaccines should discuss their history of such  allergies with their physician before  a decision is made regard- ing vaccination (100).

New  Developments  in Influenza Vaccines

A new  intranasal  vaccine was  recently approved as  an  alter- native form  of influenza vaccination. The  cold-adapted, live attenuated, trivalent influenza virus vaccine (FluMist) is able to replicate in the  cooler nasal passages and  stimulate mucosal as  well  as  systemic immunity, similar to  natural infection. However, the  altered virus is unable to grow  in  the  warmer temperatures of the lower respiratory tract. Clinical studies in children have shown the  vaccine to  be 93%  effective in  pre- venting culture-positive influenza A and  B infections (116). Also, the  vaccinated group had  21% fewer  febrile illnesses and 30% fewer  cases of febrile otitis media when compared with placebo. Adverse reactions  were  mild  and  included rhinor- rhea, fever, and  lethargy. A similar study in  adults demon- strated 23% fewer  days  of severe febrile illness and  25% fewer days  of febrile upper respiratory tract  illness (117).  This resulted in 28% fewer  missed work days  and  41% fewer  physi- cian  visits.  The  intranasal vaccine first became available for the  2003–2004 influenza season.

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