Immunization week one

Goal of immunization

to protect against disease upon subsequent exposure to the infection

Passive immunity

* transfer of immunity produced by one human or animal to another
* implications for immunization - drug interaction with live vaccines

Transplacental transfer

mode of passive immunity

* active transport of IgG during last 1-2 months of gestation (weeks 32-40)
* go across concentration gradient
* baby will get antibodies
* good protection from some diseases - measles, rubella, tetanus
* poor protection from some diseases - polio
* interferes with response to live vaccines as maternal antibodies neutralize vaccine before infant mounts an immune response

active immunity

* stimulate the host to produce a protective response to an antigen
* natural infection
* immunizations
* relies on immunologic memory
* makes its own memory
* makes their own response

vaccine formulations

* live attenuated
* whole inactivated
* polysaccharide
* conjugate
* recombinant DNA
* toxoid
* mRNA

general recommendations for vaccines

* timing of immunization
* childhood and adult immunization schedules updated frequently and published each year

vaccine timing

* any commonly used vaccines can be administered during the same encounter
* inactivated vaccines and inactivated and live vaccines can be administered at intervals without regard to each other
* **live vaccines must be separated by 4 weeks if not administered simultaneously**

live vaccine timing

* on or after the first birthday
* delay following administration of antibody-containing product
* separated by at least 4 weeks
* live vaccine administered second should not be counted
* repeat that vaccine at least four weeks after it was administered as an invalid dose

vaccine dosing intervals

* increasing the interval between doses does **NOT** diminish the effectiveness
* no need to restart ANY vaccine series
* decreasing the interval between doses may interfere with vaccine response

immunization of __immune__ individuals

* no evidence of harm
* MMR, varicella, HiB hepB, polio
* increased incidence and severity of local reactions
* PPSV23 administered

vaccine contraindications (general)

• severe allergy to vaccine component

• for future pertussis containing vaccines: encephalopathy without known cause within seven days of pertussis vaccine

  • very uncommon

temporary contraindications

* pregnancy
* immunosuppression
* decreased response to immunization
* live attenuated vaccines contraindicated
* severe illness (not terrible but worse things to worry about)
* recent receipt of blood and immune globulin products

herd immunity

* community immunity, community protection, indirect protection
* protection conferred to susceptible individuals when sufficient proportion of the population is immune
* depends on reproduction number, Ro
* on how transmissible it is
* number of people to which an infected person transmits the infection
* assumes equal mixing of an entirely susceptible population
* for sars-cov2 estimated Ro=2-3
* measles was Ro=18
* Threshold = 1-1/Ro

approach to herd immunity

* herd immunity describes immunization strategies
* no infection has ever achieved herd immunity
* likely unable to protect the vulnerable
* NEED IMMUNIZATIONS TO GET TO HERD IMMUNITY

immunization to herd immunity

* need community immunity at 60%
* assume
* estimate that 10% has been infected
* vaccine confers 70% protection
* to achieve herd immunity, need vaccine uptake at least 70%

measles

* highly infective viral disease
* most contagious disease known
* transmitted primarily by larger respiratory droplets
* fever, cough, coryza (runny nose), conjunctivitis
* complications include otitis media, pneumonia, encephalitis
* estimated that 10% of cases involve complications
* death rate 1-3/1,000

measles elimination

* goal of healthy people 2010
* WHO, Pan American Health Organization formulated plans for elimination and eradication
* measles eliminated from US
* importations frequent
* threats from vaccine hesitancy and delay
* must keep immunizing

measles outbreaks

* immunization rates sufficient to prevent widespread
* transmission within unimmunized communities
* 85% of cases in unimmunized due to philosophical or religious belief (from 2014 outbreak)
* other 15% were too young

measles vaccine

* live attenuated viral vaccine
* usually administered in combination with mumps and rubella
* combination of measles, mumps, rubella, and varicella available
* vaccine administered at 12-15 months of age with a second dose prior to entering school
* evaluate travelers for immune status

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vaccination strategies for measles

* two dose strategy implemented in early 1990s
* second dose is *not* a “booster”
* second chance to get immune
* two doses recommended for healthcare workers and college students
* can consider those before 1957 immune

mumps

* acute self-limited parotitis
* transmitted by large respiratory droplets
* complications include gastritis, meningoencephalitis, orchitis, mastitis, and oophoritis
* death 1-3.4/10,000 (much smaller)

mumps immunization

* live attenuated viral vaccine
* administered with measles and rubella (MMR)
* combination of measles, mumps, rubella, and varicella available
* recommended for 12-15 months olds, susceptible adolescents and adults
* can consider immune if born before 1957
* two doses for school aged children and high risk adults
* healthcare workers
* international travelers
* students at post-high school educational institutions
* third dose recommended for outbreak response

rubella

* mild exanthematous (rash) viral infection
* transmitted via respiratory route
* congenital rubella syndrome if infection during pregnancy
* deafness, cataracts, heart defects, intellectual disabilities, liver and spleen damage, low birth weight

rubella elimination

* rubella and congenital rubella syndrome eliminated from Western Hemisphere
* immunization continues to be required because threat of transportation

rubella immunization

* live attenuated viral vaccine
* administered with measles and mumps (MMR) or varicella (MMRV)
* recommended for 12-15 months, susceptible adolescents and adults

rubella vaccine cautions

* do not immunize pregnant individuals
* no evidence for congenital rubella syndrome from vaccine
* avoid pregnancy for 28 days
* routine pregnancy screening not recommended
* don’t need a pregnancy test

vaccinations of adults who may become pregnant for rubella

* vaccination of susceptible people of childbearing age
* routine general medical and gynecologic outpatient care
* all family planning settings
* before discharge from hospital, birthing center, or other medical facility
* prenatal assessment and post partum immunization
* will be screened for rubella immunity
* pregnant people should not get live vaccines

Viral hepatitis - overview

Hepatitis A infection

* viral disease caused by hepA virus
* transmitted by fecal-oral route
* immune mediated liver injury
* relatively mild illness in children
* more serious illness in adults
* elevated LFT (live function test)
* jaundice
* rare fulminant hepatitis (makes you so sick you end up in ICU)
* no chronic carrier state
* no specific treatment; supportive care

Hepatitis A outbreak

as of 2023 61% of people had hospitilizations

* this is really high
* if you get it as a child you may be asymptomatic and won’t be as sick

Hepatitis A Vaccine Indications

* travelers to countries with high or intermediate endemicity
* men who have sex with men
* people who use drugs
* persons with occupational risk
* perons with chronic liver disease
* if they do get it, their liver may fail
* experiencing unstable housing or homelessness aged 1 and older
* currently or recently incarcerated
* all children 12 months of age and catch up for unimmunized 18 years and younger

Haemophilus influenzae type b

* small gram negative organism causing infections ranging from colonization to meningitis
* meningitis has 10% mortality rate and 40% have neurological deficits

Haemophilus influenzae type b vaccine

* conjugate vaccines
* recommended at 2,4, (6), and 12-15 months of age
* recommended for those >5 years if immunocompromised
* sickle cell, splenectomy, HSCT (hematopoietic stem cell transplantation)

hepatitis b virus

* affects liver
* viral disease caused by hepb virus
* transmitted by parenteral routes (injected/not oral)
* blood transfusion
* sharing of needels
* sexual contact
* mother to neonate
* must have chronic infection at the time of pregnancy

hepatitis b infection in US

the groups from 0-19 and 20-29 are very low numbers for infections since they were immunized as babies

similarly, ages 60+ have a low rise

reported risks for hepatitis B infections

* injection drug use most commonly reported rise
* note that no risk identified/reported in about 2/3 of cases

hepatitis b immunization of adults

* routine immunizations for all adults aged

hepB vaccines

* recombinant hepatitis b surface angtigen with aluminum adjuvant
* energix (pediatric or adult)
* recombivax (pediatric or adult)
* both require 3 doses for immunity: 0, 1, and 6 months
* recombinant hepatitis b surface antigen with CpG 1018 adjuvant
* cool new adjuvant
* heplisav-b (ages 18 and older)
* two doses separated by one month
* recombinant vaccine with multiple surface antigens with aluminum adjuvant
* prehevbrio (ages 18 and older)
* three dose series: 0, 1, and 6 months

post vaccination testing for hepb

• post vaccine antibody testing in healthcare workers at risk for sharp injury

  • measure antiHBs (antibody to hepatitis B surface antigen)

  • antiHBS > 10 mlUml protective

• 100% effective in those who develop an antibody response

• older individuals (age >40 years), chronic conditions, immunosuppression at risk for nonresponse

  • repeat series

  • choose hepB with CPG

    • heplisav b or prehevbrio

polio

* acute viral illness which in its serious form affects the central nervous system
* fecal-oral transmission
* complications include flaccid paralysis
* death rate as high as 10%

polio vaccines

* live attenuated vaccine - no longer used (hasn’t been for 23 years)
* OPV (stockpile with CDC for public health emergency)
* enhanced-potency inactivated vaccine
* IPV
* No wild type polio cases in the western hemisphere since 1991
* Vaccine associated poliomyelitis occurs in approximately 1 in 2.4 million doses
* become infectious after receiving the vaccine

polio case in NY

* unvaccinated young adult developed symptoms in June 2022
* caused by VDPV2
* vaccine deprived
* wastewater monitoring shows vaccine virus present in April 2022
* low immunization rates in Rockland County
* high vaccine coverage rates absolutely needed

polio vaccine scheduling

* polio vaccine recommended at 2, 4, 6-18 months and again at 4-6 years
* any immunized adult; however if person received any childhood vaccines, almost certainly vaccinated for polio

varicella

* highly contagious disease due to varicella zoster virus
* spread by directed contact or the respiratory route
* characteristic pruritic vesicular rash with fever
* complications include bacterial infection of lesion, pneumonia, encephalitis, and cellulitis

varicella epidemiology

* children
* 3.5 to 4 million cases each year
* generally mild disease with rare complications
* adults
* 5% of all cases occur in those >15 years
* complications much more common

varicella vaccine

* varivax licensed april 1995
* a live attenuated viral vaccine
* contraindicated in these situations:
* immunosuppression
* pregnancy
* receipt of blood products - dose dependent
* active and untreated TB

evidence of varicella immunity

* born in US before 1980
* physician documented clinical history of chicken pox or zoster
* laboratory evidence of immunity
* two doses of varicella vaccine after first birthday separated by at least 4 weeks

evidence of varicella immunity for healthcare worker

* physician documented clinical history of chicken pox or zoster
* laboratory evidence of immunity
* two doses of varicella vaccine after first birthday separated by at least 4 weeks

@@**birth before 1980 doesn’t count*\*@@

varicella vaccine indications

* all infants at age 12 months with second dose prior to entering school
* minimum 3 month interval between doses
* second dose recommended for anyone who has received only one dose
* when first licensed, it was only one dose
* children entering child care facilities or schools (or evidence of immunity)
* assume immune in US before 1980 unless healthcare worker, pregnant woman, or immunocompromised

varicella vaccine indications

* routine immunization of all adolescents and adults without evidence of immunity
* prenatal assessment + postpartum immunization

varicella vaccine adverse effects

* fever
* rash
* at injection site: median number of lesions = 2
* generalized: median number of lesions = 5

rotavirus infection

* half million childhood deaths worldwide
* serious infection
* one third of hospitalizations for diarrhea
* w/o immunization
* incidence **similar** in developing AND developed countries

rotavirus vaccines

* live oral vaccine stores refrigerated
* two preparations
* rotateq (merck)
* pentavalent bovine reassortment viruses
* must be reconstituted with supplied diluent
* three oral doses
* rotarix (GSK)
* attenuated human rotavirus
* liquid preparation
* two oral doses
* recommended at 2, 4, and (6 if merck used) months

vaccine schedule for rotavirus

* first dose between 6 and 14 weeks of age
* if inadvertently started, complete series
* second and third doses spaced by 4 to 10 weeks
* series must be completed by 8 months of age
* DON’T FINISH IF IT’S PAST EIGHT MONTHS
* initiate or complete series for infant who have had rotavirus infection

RV and intussusception

with the old vaccine there was an increase in intussusception (bowel obstruction)

pain, inflammation, sometime surgery needed

no evidence that risk is different between vaccines

about 45-213 cases per birth cohort

prevents 53,000 hospitalizations and 170,000 ED visits per birth cohort

risk is worth the benefit

RV vaccine impact

* dramatic reductions in disease
* decreased hospitalization by 42-63%
* decreased lost workdays by 87%

tetanus diptheria pertussis abbreviation

upper case means higher doses

bigger dose for smaller people

pertussis

* whooping cough
* bacterial respiratory infection caused by bordetella pertussis
* direct transmission from close contact
* major manifestation is severe paroxysms of cough
* severe complications include pneumonia, encephalopathy, malnutrition

pertussis vaccine

* administered in combination with diptheria and tetanus
* recommended at 2, 4, 6, and 15-18 months with boosters at 4-6 years
* routine Tdap for 11-12 years
* use for 7-10 year olds with incomplete childhood series
* Tdap for next dose of adults

pertussis vaccine scheduling

* adacel license for booster after 8 years
* Td or Tdap can be administered every 10 years
* late 2nd or 3rd trimester of each pregnancy
* transfer immunity to baby

vaccine products for TDAP

DTaP for children

cocooning

* strategy from protecting very young infants from pertussis
* Tdap recommended for pregnant females in late 2nd or 3rd trimester
* immunization of parents, siblings, grandparents, out of state home care providers
* Tdap immunization at hospital discharge for mother
* Key role for pharmacy based immunization services

diptheria

• Bacterial infection caused by Corynebacterium diphtheriae

• Person to person transmission through direct contact

  • Must be pretty close

• Major manifestation is membranous inflammation of respiratory tract

• May damage myocardium, nervous system, and kidney

diptheria vaccine

• Toxoid, adsorbed inducing immunity to the bacterial exotoxin

• Administered in combination with tetanus and pertussis

• Recommended at 2, 4, 6, 16-18 months and at 4-6 years

• Routine boosters (Td or Tdap) every 10 years

tetanus

• All muscles are in contracted state

• Acquired through environmental exposure

• Mediated via bacterial toxin

• Not contagious

• Get from environment

• Worse for diabetics since they can get bad wounds

Clinical presentation / clinical syndroms tetanus

• Clinical syndromes

  • Localized: painful contractions, generally mild

  • Generalized: spasm of facial muscles, hyperreflexia, opisthotonos, tonic tetanic seizure-like activity

  • Cephalic: atonic cranial nerve palsies, may progress to generalized

  • Muscle constraints so strong you may break bones

Tetanus vaccine

• Toxid, adsorbed from Clostridium tetani

• Administered in combination with diphtheria and pertussis

• Recommended at 2, 4, 6, and 15-18 months and 4-6 years

• Routine boosters (Td or Tdap) every 10 years

Wound management

• If wound and its been >5 years immunize

• If wound and it’s been <5 years no need to immunize

pneumococcal disease

Infection caused by the bacteria Streptococcus pneumonia 

* Otitis media
* 20 million office visits (28-55% strep)
* Pneumonia
* 175,000 cases annually
* Meningitis
* Leading cause 3,000-6,000 cases annually
* Bacteremia
* 50,000 cases annually

invasive pneumococcal disease

* Defined as S. pneumoniae in normally sterile body site


* Incidence >65 years 24 cases/100,000 population
* Pneumococcal pneumonia
* * **> 65 years: 847-3365 per 100,000**
* **Much larger**

pneumococcal vaccines

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* Pneumococcal conjugate 15 valent (vaxneuvance)
* Pneumococcal conjugate 20 valent (prevnar 20)
* Pneumococcal polysaccharide 23 valent (pneumovax23)
* When we vaccinate kids we see way decrease because herd immunity

PCV15 or PCV20 recommendations for children

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* Universal immunization for infants
* 2, 4, 6, and 12-15 month schedule
* Immunocompromised children aged 6-18 years
* Single dose of PCV15 or PCV20 if no history of previous conjugate vaccine
* If at least one PCV20, no additional doses
* If PCV13 or PCV15 administer either PCV20 or PPSV23
* So must have 20 at some point

pneumococcal vaccines for immunosupressed

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* Congenital or acquired immunodeficiency
* HIV
* Chronic renal failure
* Nephrotic syndrome
* Leukemia
* Lymphoma
* Hodgkin disease
* Generalized malignancy
* Iatrogenic immunosuppression
* Solid organ transplant
* Multiple myeloma 

other conditions that are indications

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* Chronic heart disease (REAL not hypertension)
* Chronic lung disease (asthma >19)
* Diabetes
* Cerebrospinal fluid leak
* Cochlear implant
* Sickle cell disease other hemoglobinopathy
* Alcoholism
* Cigarette smoking (>19 year)
* **All adults aged 65 years and older**

for those aged 65 and older

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* PCV20 or PCV15 + PPSV23 later (PCV20 can be substituted for PPSV23)
* If adults received PCV13 and/or PPSV23 prior, PCV20 may be considered

for those 19-64 years old

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* PCV15 or PCV20
* If PCV15 used this should be followed up with PPSV23
* Chronic conditions, immunocompromised

patient has PCV13 history

* Used for adults who were immunocompromised
* Used by shared clinical decision making for those aged 65 years and older who were NOT immunocompromised
* Followed by PPSV23
* Additional dose of conjugate vaccine not routinely recommended
* Healthcare professionals may recommend PCV20 for those 65+ years of age who were previous immunized (PCV13 +- PPSV23)

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Pneumococcal polysaccharide vaccine (PPSV23)

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* Vaccine composition
* Capsular polysaccharide inducing type-specific antibodies
* Used for those who receive PCV15
* Immunocompromised: 8 weeks after PCV15
* Chronic conditions: >1 year after PCV15
* Aged 65 years and older: >1 year after PCV15
* 65+ years who received PPSV23 only, PCV15 or PCV20 recommended >1 year later

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Using ACIP pneumococcal vaccine recommendations

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* Infants and immunocompromised children straightforward
* Adults
* Use the table posted on canvas
* Do the problems posted on canvas

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Human papillomavirus infection

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* Most common sexually transmitted infection
* Highest rates among sexually active young adults
* Nearly everyone will get HPV at some point
* Spread through intimate skin to skin contact
* Infection often asymptomatic; clincial pathology diagnosed by Pap test
* Screening tests not available for other cancers caused by HPV

HPV infection

* Oncogenic viruses associated with cervical, vulvar, vaginal, anal, oropharyngeal, penile cancer
* Types 6 and 11 are associated with anogenital warts and respiratory papillomatosis  (wart like growth on vocal cords)
* Besides cervical we don’t have screening

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Low HPV immunizations

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* Very low numbers although Tdap and meningitis are much higher
* They should be given at the same time

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HPV vaccine

* 9vHPV containing VLP 6, 11, 16, 18, 31, 33, 45, 52, 58
* If age 9-14 years, **two doses** 0, 6-12 months
* i f age 15-26 years, **three doses** 0, 1-2, 6 months
* Recently expanded licensure for 27-45 years old

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ACIP HPV vaccine recommendations

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* Recommended for all adolescents aged 11-12 years
* Also recommended for all aged 13-26 years
* Immunization prior to sexual debut preferred
* Can initiate series in individuals as young as 9 years if clinician deems appropriate

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HPV vaccine for 27-45 year olds

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* Acip recommended vaccine for use in 27-45 years by shared clinical decision making
* New partner, immunosuppression

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HPV vaccine limitations

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* Duration of protection unknown, but more than a decade of follow-up shows little indication of waning
* No change in recommendations for pap test frequency

opportunities for pharmacists and HPV

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* Unacceptably low rates of series completion
* Partner with clinic
* Series initiated at annual visits
* Finish series at pharmacies
* Communication
* Between clinicians
* Personal immunization record
* Immunization registry

Meningococcal disease

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* Five major serogroups A, B, C, Y, and W - 135
* Transmission via direct contact with respiratory secretions of a nasopharyngeal carrier
* Most common cause of bacterial meningitis in individuals 2-18 years
* Mortality rates 10-13%
* 10% of survivors with severe morbidity
* Mental retardation
* Hearing loss
* Loss of limbs

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Meningococcal vaccines

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* Meningococcal conjugate vaccine covering serogroups A, C, Y, and W-135
* Repeat doses for high risk
* License for use in individuals aged 9 months to 55 years (Menactra) and 2 months - 55 years (menveo)
* Recommended for routine use in 11-12 year olds and repeat dose at age 16

Meningococcal vaccine also recommended for

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* Individuals with complement deficiency or receiving complement inhibitor
* Eculizumab or ravulizumab
* Those with HIV infection
* Individuals with asplenia
* Travelers to endemic areas
* Microbiologists with occupational exposure 
* Those who live in residence halls or military recruits if incompletely immunized

Revaccination with MenACWY

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* Revaccinate individuals at prolonged risk of invasive disease
* Complement deficiencies
* Anatomic or functional splenectomy
* Prolong exposure (microbiologist, travelers, resident of epidemic areas)

Revaccination schedule for meningococcal ACWY

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* Revaccinate adolescent at 16 years of age
* Revaccinate after 5 years if age >7 years
* Revaccinate after 3 years of age 2-6 years
* Continue to revaccinate at 5 year intervals if remain in high risk group 

Meningococcal immunization for infants

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* MeACWY recommended for infants at high risk of invasive meningococcal disease
* Four dose series in infant immunization schedule
* Use age-appropriate vaccine product

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Meningococcal serogroup B vaccine

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* Trumenba: recombinant serogroup B fHBP protein 
* H binding protein
* Induces complement dependent antibody responses
* 2 dose series at 0 and 6 months for 16-23 year olds under shared clinical decision-making
* 3 dose series 0, 2, 6 months for high risk and outbreaks
* Bexsero: multicomponent; recombinant
* Big increases in antibody concentrations
* 2 dose series at least one month apart for 10-25 year olds

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ACIP recommendations for meningococcal b

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* Either vaccine for individuals at high risk for invasive meningococcal disease starting at age 10 years
* No upper age limit
* Complement deficiency or inhibitor
* Asplenia
* Microbiologists with occupational exposure
* Either vaccine may be used in an outbreak
* 16-23 year olds may be vaccinated to provide short-term production

Influenza

• Acute febrile illness caused by varying strains of influenza virus

• Transmitted by respiratory droplets

  • Rarely by contact with contaminated objects

• characterized by headache, fever, myalgia, dry cough, pharyngitis

• Complications due to secondary bacterial infection or involvement of the myocardium or central nervous system

• It can be the tipping point for chronic conditions

• Super onset (know exactly when it happened)

influenza vaccine

• Influenza viruses representing circulating viral strains

  • All vaccines are quadrivalent (2A strains and 2B strains)

• Vaccine formulation strategies

  • Grown in eggs

    • Live (flumist) (LAIV4)

    • Inactivated split or subunit (various)

    • Everything else is eggs

  • Grown in MDCK cells (Flucelvax) (ccIIV4)

    • Mammalian cells

  • Recombinant DNA grown in transfected insect cells (Flublok) (RIV)

  • Contains strains that experts think will arise)

influenza vaccine preparations abbreviations

• IIV4: quadrivalent inactivated influenza vaccine

• LAIV4: quadrivalent live attenuated influenza vaccine

  • Nasal spray

• ccIIV4: quadrivalent cell culture based inactivated influenza vaccine

• RIV4: quadrivalent recombinant influenza vaccine

enhanced influenza vaccines

• High dose

  • 4x more antigen

• Adjuvantated

  • Makes vaccine work better

• Recombinant 

  • RIV4

• No standard definition of enhanced influenza vaccine 

• Preferentially recommended for those aged >65 years

high dose inactivated influenza vaccine

• Licensed for individuals >65 years of age

• More antigen than regular influenza vaccine

  • 60 mcg HA vs. 15 mcg HA

  • Vaccine volume is 0.7 mL (higher)

• Higher antibody concentrations

  • Clinical trials endpoint higher Ab titers to two vaccine viruses

  • Higher antibody responses in nursing home residents

• Higher rate of injection side reactions

  • More antigen duh

  • Not really a deferent for people

• Older people make poorer responses to vaccines and they are at higher risk for complications from influenza