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Seasonal Flu Vaccine


GENERAL FLU INFO
10-20% of pop gets it every year
up to 50% institutionalized pop gets it
problem: cost and stress
30-40,000 die/year
healthcare workers are largest vector group
vaccine ineffective vs avian flu
pts most contagious before sx (day 2 & 3)
vaccination & antiviral drugs are the only public health measures available for pandemic flu

TYPES OF FLU
three genera: A, B, C
A is human, divided by hemagglutinin and neuraminidase
H1N1 and H3N2 are most common
antigenic drift constant: random mutations cause new variations
B in humans and seals
epidemics every few years
C in humans and pigs
sporadic
less severe URI's

CDC RECOMMENDATIONS
annual vaccination for everyone except with CIs
more strongly recommends flu vaccine annual after age 50
recommends fall and winter vaccinations
indications: CV & pulm dz, chronic metabolic dz incl DM2, renal & hepatic dysfx
indications: hemoglobinopathies, immunocompromised
indications: cognitive dysfunction, spinal cord injury, seizure disorder (aspiration risk)
incidations: pregnancy during the influenza season, anyone who wants to avoid flu
no data on asplenia and flu
indications: health-care personnel, incl long term care/assisted living, childcare workers
indications: residents of nursing homes, assisted living, etc, anyone living with fragile pt

TWO TYPES OF SEASONAL VACCINE AVAILABLE
both kinds contain three viruses: A (H3N2), A (H1N1), & B virus
does not protect vs 2009 H1N1 (swine flu) separate vaccine expected by Oct 09
viruse selections change each year based on estimates re: which viruses will circulate
1) NASAL SPRAY
live, weakened flu virus that does not cause flu
LAIV = “live attenuated influenza vaccine” = FluMist®
for: healthy, nonpregnant adults under 50 w/o indications, and children over 2
2) FLU SHOT containing inactivated/killed virus
needle in arm
for pts over 5 mo incl healthy pts and those with chronic conditions
attenuated influenza vaccine = FluMist®
not so health people get inactivated virus

CDCs LIST OF WHO SHOULD GET VACCINE ANNUALLY
children age 6mo--19yr
pregnant females
contacts of children under 6 months of age
adults over 50
pts w/ chronic medical conditions
people in nursing homes and long term care facilities
healthcare workers and their household contacts
those with high risk for complications from flu & their household contacts
WHERE I DISAGREE WITH THE CDC
children should not be vaccinated prior to 1 year of age
vaccines should not be given to females between age 5 and 21 dt risk of AI dz

CDC LIST OF WHO SHOULD NOT GET VACCINE
chicken egg allergy
previous severe reaction to influenza vaccine (incl GBS within 6 wks)
kids under 6 mo
pts with moderate-severe illness with fever

EFFECTIVENESS
depends on ability of pt to develop immune response
depends on match of selected strains with actual challenge viruses
flu shot and nasal spray both supposed to be "effective" (CDC)
vaccine well-matched to flu strain can prevent 80% in normal healthy adults
difficult to match vaccines to exact annual flu strain
virus can mutate in the midst of an epidemic
typical seasonal vaccines reduce incidence in healthy adults by only about 50%
vaccines mainly prevent flu among healthy adults
the % of a vaccinated population who develop severe disease, miss work, require hospitalization is SAME as in an unvaccinated population
a 2004 meta-analysis concluded: "There is not enough evidence to decide whether routine vaccination to prevent influenza in healthy adults is effective (Demicheli; Jefferson)."
another recent meta-analysis: immunization does not reduce mortality in elders (Simonsen)
challenges CDC assertion that immunization in nursing homes reduces winter mortality
published in The Lancet
mortality from flu in pts over 70 was unchanged or increased 1980-2002
over 70 group accounts for 75% of all influenza mortality
during 1980-2002, elders immunized 15%-->65%

SIDE EFFECTS DIFFER BY TYPE OF VACCINE ADMINISTERED
SHOT
because virus is inactivated you can't get flu from this
at site of injx: soreness, redness, or swelling
fever, aches, lasting 1-2 days
rare allergic rxns
can file for injury compensation from the National Vaccine Injury Compensation Program (VICP)
LAIV (FluMist®)
viruses are weakened and do not cause severe symptoms but may be transmissible
kids: runny nose, wheezes, headache, vomiting, muscle aches, fever
adults: runny nose, headache, sore throat, cough

INFLUENZA SYMPTOMS
fever, sore throat, ha myalgia, chills, anorexia, fatigue
unprod cought, runny/stuffy nose
usu better in a week
cough & malaise may persist
kids may have febrile seizures
illness mb more severe in kids

COMPLICATIONS
risks in very young or old: exacerbation of chronic pulm dz, pneumo (strep, staph)
other: reyes synd, myocarditis, pericarditis, encephalopathy, encephalitis, traverse myelitis, guillain barre syndrome
incidence of guillain barre is 1 case/million vaccinees: may be coincidental

HISTORICAL PERSPECTIVE
non-pandemic seasonal influenza epidemics in the U.S.-->approx 36,000 deaths/yr
influenza pandemics occur in regular cycles
pandemics occur when a strain circulates for which people have little or no immunity
20th century pandemics in 1918, 1957, and 1968
1918 "Spanish" FLU-->500,000 death in the U.S
killed 50-100 million people globally in approx 18 mo
pop that died were young with active immune response
died of cytokine storm, superinfection with Strep penumoniae
average of 7-11 days for people to die (more like bacterial pattern)(soldiers 10 days)
antibiotics and serum therapy not available
1957 Asian flu-->70,000 US patients died
1957 pandemic strain was identified in February, vaccine was in production by May
available in limited supply by August (USHHS), epidemic kicked off bigtime in Sept
usu flu epidemics hit hardest in Dec
early seasonal appearance typical for new strains
may be followed by more waves of the epidemic over 6mo
1968 Hong Kong flu-->33,000 US pts died
1976 swine flu outbreak: some got guillain barre without vaccine
more people got flu from vaccine than not
1976 vaccine caused significant morbidity
more than 1000 individuals were paralyzed before it was removed from the marketplace

VACCINE
gap btw IDing new strain and vaccine availability is 6-9mo now (CDC b)
vaccine takes 2 weeks to confer immunity
millions in US are exposed each year before vaccines are available
purified subunit vaccine in US
grown in chick eggs
virions lysed with detergent, lysate purified, adjuvant and preservative added
aluminum used, MF59 being investigated
thimerosal (contains mercury)

SWINE FLU PREVENTION
current flu is type A H1N1
spread by cough and sneeze
consider if pt has fever, URI
do nasal swab if suspect flu, refrigerate (don't freeze) and report to public health
swab only useful for about 7 days
pts should be considered contagious for up to 7 days
virus resistant to antiviral meds amantadine and rimantadine
but sensitive to oseltamivir and zanamivir (tamiflu and )
this year was light flu season
this year's swine flu has definitely been hyped
wearing face mask not a bad idea, stops resp droplets
change gloves, sterile facilities
70% alcohol is effective, 100% not effective at killing virus
100% evaporates too quickly, slower evap gives time to work on viral membrane

PROS
hopefully prevent or at least reduce incidence of:
transmission of flu by healthcare worker
outbreaks of flu in care facilities
exposures of infants

CONS
CI: egg allergies, may have surprise rxns
must be repeated every year
vaccines often totally miss (effectiveness is worse than CDC admits)
not as strong an immune building response as actually getting sick

TREATMENT: DRUG THERAPY
expect concurrent circulation of multiple influenza strains with different susceptibility
recommended prophylactic and treatment use of antivirals is more complex than prev yrs
treatment options include amantadine, rimantadine, oseltamivir, and zanamivir
two main classes:
adamantanes (amantadine and rimantadine) and
neuraminidase inhibitors (oseltamivir/Tamiflu; and zanamivir/Relenza)
ADAMANTANES
only active against A strains of influenza, and not B strains
resistant strains emerge rapidly in epidemics where the drug is used
up to 30% of patients treated with amantadine shed resistant viruses 2-3 days after tx
resistant viruses are transmissible
most N. American strains already resistant
NEURAMINIDASE INHIBITORS
proposed as best tx for future pandemic
active against seasonal strains of either A or B influenza viruses
Tamiflu reduces the severity of influenza in trials
drug must be given early in the course of infection (within 48-60 hours)
recent review: Tamiflu is much less effective for H5N1 influenza (Crusat and deJong)
Tamiflu rapidly promotes development of viral resistance
(25% of patients in one small study)(de Jong et al.)
future strains will probably become resistant quickly
RESISTANCES
Seasonal influenza A (H1N1) virus (A/Brisbane/59/2007) is resistant to oseltamivir, susceptible to the rest
Pandemic influenza A (H1N1) virus, seasonal influenza A (H3N2) virus, and seasonal influenza B (B/Brisbane 60/2008, Victoria lineage) virus are resistant to amantadine and rimantadine and susceptible to oseltamivir and zanamivir

PREVENTION BY INCREASING HOST RESISTANCE
dietary changes, nutritional supplementation, and herbal medicines.
saunas, sweat lodges, heating of body and mucous membranes
influenza virus dies above 96 degrees thus stays on surface
nutrition

NUTRITION
nutrients increasing host resistance: zinc, vitamins A, C, E, D, selenium, iron, and EFAs
ZACES formula = zinc, A, C, E, selenium, formula developed in S Africa as AIDS Tx
whole foods diet also used for AIDS Tx
ZACES FORMULAs vary, this is the generic formula:
Zinc 20mg
beta carotene 25000 iu per day
vitamin C 2 gram twice a day
vitamin E 200 IU per day
selenium 100mcg twice a day
also recommended:
3-5 cloves of garlic per day
multiple vitamin containing B-complex
local herbs
vitamin C is highly protective at onset, reduces sx over 80% relative to control
control group txd with pain killers and decongestants

COMMON NUTRITIONAL DEFICIENCIES
selenium (~50%, no official serum optimums)
zinc (~50%)
vitamin A (1% in US adults, 30% in kids)
iron (205% of males, 9-22% of females)
vitamin C (~66%)
vitamin E (suboptimal take almost universal, 90% don't get RDA)
EFAs (no RDA, deficiencies in US deepening since 1900 (Hibbein)(cod liver oil used elsewhere)
cholecalciferol = vit D, a steroid hormone

VIT D
Cholecalciferol promotes immune competence specifically in the respiratory tract by assisting in the production of immune-peptides in the white blood cells there. The hormone also has anti-inflammatory effects, and specifically has a moderating influence on the production of pro-inflammatory cytokines. Part of the pathology of highly virulent influenza strains is the overproduction of such cytokines, which, in excess, may cause more damage to the system than the virus itself. Cholecalciferol may thus prevent influenza infection or moderate its severity. Supplementation with Vitamin D3 in a dose of 4000 IU per day will restore near-normal serum levels over a period of months. Higher doses to more rapidly achieve optimal serum levels may be warranted in the face of a spreading pandemic. Although the official upper safe limit of vitamin D is 2000 IU/day, this is been revised upward by leading vitamin D researchers in the last twelve months. Hathcock et al provided evidence in January of 2007 that the safe limit should be raised to 10000 IU/day. In a study published in September 2007, researchers gave doses greatly in excess of 10000 IU/day for many months, and found no evidence of vitamin D toxicity (Kimball et al.) In order to rapidly raise serum levels toward normal, up to 40,000 IU/day might be safely given for a period of six weeks, followed by daily doses of 4000-10000 IU. Increased calcium in the serum and/or urine are the defining symptoms of vitamin D toxicity. An individual taking supplements in excess of the official upper safe limit of 2000 IU might out of prudence have serum and urine calcium measured periodically. Because vitamin D production in the skin is moderated by serum levels, Hathcock et al suggest that serum levels cannot be raised above the normal upper limit with doses of 10,000 IU/day. Except in certain uncommon genetic conditions, that dose should never produce serum levels sufficient to produce toxicity. --Paul Berger

BERGER'S SUPPLEMENTATION RECOMMENDATIONS
Vitamin D 4,000 to 10,000 IU vitamin D3
Zinc 40 mg
Vitamin C 1000-2000 mg
Vitamin E 100-200 IU
Selenium 200 mcg
Cod Liver Oil 1 teaspoon
Vitamin A (if not taking cod liver oil) 25,000 IU as beta-carotene
Iron 10 mg/day, but only when a diagnosed deficiency is present.

HERBS TO INCREASE RESISTANCE TO VIRUS
echinacea
garlic
boneset (Eupatorium perfoliatum)
American ginseng (Panax quinquefolium)
osha (ligusticum porteri)
red root (ceanothus americanus)
licorice (glycyrrhiza spp.)
ginger (zingiber off.)
Oregon grape (mahonia spp.)
western red cedar (thuja plicata)
wild indigo (baptisia tinctoria)
elderberry (samubcol tm)
astragalus and codonopsis
artemisia, salvia, frankincense, myrrh (smudges)

AAP NOTES
recommendations revised 9/09, link at bottom of page
according to American Acad of Pediatrics, B vaccine strain changed in trivalent vaccine
target kids at high risk for influenza complic (chronic med condition, immunosuppression)
school aged kids have the highest risk of needing flu-related medical care
protect school aged kids with vaccines-->protect all their contacts
also vaccinate household members and out-of-home care providers of kids thru adolescence
vaccine not approved for kids under 6 mos
effort to vaccinate those at risk to continue throughout flu season
offering second dose of vaccine to children "needing" 2 doses
kids under 9 given flu vaccine first time get second dose in same season after 4+ weeks
kids 9 and over w/o prior flu vaccinations should only get 1 dose in 1st season of vacc

CHANGES TO CDC RECOMMENDATIONS SINCE MAY
priority for use of antiviral drugs is still for flu pts who are hospitalized or at high risk for complications
clinicians should consider providing prescriptions for antiviral medications ahead of time to high risk pts so pt can fill scrip if suspect infx
new guidance as to situations in which antiviral medications used for chemoprophylaxis
do not use for prevention in healthy persons based on community exposures
not necessary to tx all who are at high risk of exposure
watch and wait, give antiviral if sx develop
don't give to asx pts
rationale: lower development of resistance
same as before CDC says all hospitalized pts with flu sx get oseltamivir or zanamivir
also give to those with high risk of complications
high risk = kids under 5, adults over 65, pregnant, chronic med, immunosuppressed, under 19 on longterm aspirin therapy

SOURCES
http://www.cdc.gov/vaccines/recs/schedules/adult-schedule.htm
my notes from Heather Zwickey lectures
http://medherb.com/influenza-references.pdf

on 2009 swine flu vaccine:
http://www.cdc.gov/h1n1flu/vaccination/public/vaccination_qa_pub.htm

strep superinfection in 1918:
http://www.reuters.com/article/scienceNews/idUSTRE5146PD20090205?feedType=RSS&feedName=scienceNews&sp=true

On FLU prevention, by Paul Berger (ZACES formula, herbs)
Dec. 4th, 2008 Medical Herbalism Eletter
http://medherb.com or http://naimh.com

American Pediatric Assoc revised recommendations for trivalent vaccine 9/8/09
http://www.medscape.com/viewarticle/708499?src=mpnews&spon=34&uac=89474MT
CDC revised recommendations for H1N1 vaccine
http://www.medscape.com/viewarticle/708580?src=mpnews&spon=34&uac=89474MT

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