Update on Vaccines - School of Allied Health Professions for CLP… · •Sought remedy to prevent...
Transcript of Update on Vaccines - School of Allied Health Professions for CLP… · •Sought remedy to prevent...
9/28/2017
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Update on Vaccines
Patsy JarreauDepartment of Clinical Laboratory Sciences
LSU Health Sciences Center
New Orleans, LA
Introduction
•Transmission of infectious disease
•History of vaccination•Vaccine preventable diseases•Research for new vaccines
Transmission of InfectionFactors related to emerging
infectious diseases
Interrupting transmissionof infectious diseases
•Hygiene•Sanitation•Environmental modification
•Vector control•Vaccines
How does the immune system work?
• Person is infected• Symptoms arise
• Antigens from invading organism stimulate immune response
• Cytokines and antibodies are produced
• Leads to eventual destruction of the organism
• Memory cells are also produced
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Secondary immune response
• Basis of immunization
• Initial encounter with antigen, immune response evoked
• Memory cells circulate for years
• Upon re‐encounter of invading organism, very quick immune response is generated
• Organism is inactivated and symptoms are prevented
Definition of vaccine
• Agent that resembles a pathogenic microorganism and stimulates the immune system to recognize, destroy, and remember that organism
•May be composed of parts of the organism, weakened or killed forms of the organism, or altered toxins of the microbe
Vaccination in Prevention of Disease
•Herd immunity
• Enough vaccinated individuals and disease does not spread
• Low number of susceptible individuals
• Protects those who cannot be immunized
• Allergic• Immunocompromised
• Unable to make antibodies to vaccine
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How to make a vaccine
• Goal• To induce immune response but not to cause disease
• How to accomplish
• Antigen must be altered
or
• Similar antigen that does not cause disease
Discovery of Vaccines
•Noticed that people who recovered from disease rather than dying from it did not get the disease again
• Chinese attempted to prevent smallpox in 10th century
• Prime minister’s eldest son died of smallpox
• Sought remedy to prevent same from happening to other family members
Variolation
• Exposing people to matter from smallpox lesions
• Removing pus & fluid from lesion & placing under skin of uninfected person
• Drying & grinding scabs into powder for uninfected person to inhale
• Injecting scab powder into vein of uninfected person
• Was not widely practiced until 1500s
Spread of Vaccination for Smallpox
•Practice spread to Turkey in 1600s•Lady Montagu (wife of British ambassador to Turkey) allowed her family to be variolated in 1718
• Practice spread to Europe by 1721
Effects of Variolation
•Mild illness in most individuals
•Death in a few•Mortality and morbidity rates much lower in variolated populations
Edward Jenner
•Was variolated as a small boy
•Became country doctor
•Noticed that on farms where horses with an equine disease similar to smallpox that there were cows with blisters similar to those in smallpox (cowpox) but cows did not die
• Blisters healed leaving small scar
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Jenner• Milkmaid told him that she had cowpox and could not contract smallpox
• 1796 –Conducted experiment
Infected young boy with cowpox
Then intentionally infected boy with smallpox○ Injected pus from lesion under boy’s skin
○Boy did not contract smallpox
• Lead to the production of vaccines for many infectious diseases
• Responsible for marked decrease in deadly diseases
Named “Vaccination”
• “vacca” – Latin for cow• Smallpox has now been eradicated
• Virus is found only in 2 places in the world
• CDC
• Institute of Viral Preparations in Moscow
History of Vaccines
First Vaccine for:1796 small pox1879 cholera1885 rabies1890 tetanus1896 typhoid fever1897 bubonic plague1921 diphtheria1926 pertussis (whooping cough)1927 tuberculosis
and more . . .
History of Vaccines
• First Vaccine for:
• 1932 yellow fever
• 1937 typhus
• 1945 influenza
• 1952 polio
• 1954 Japanese encephalitis
• 1954 anthrax
• 1957 adenovirus 4 and 7
• 1962 oral polio vaccine
History of VaccinesFirst Vaccine for:
1963measles
1967 mumps
1970 rubella
1974 chicken pox
1977 pneumonia (Streptococcus pneumoniae)
1978 meningitis
1981 hepatitis B
1985Haemophilus influenzae type b (HiB)
1992hepatitis A
1998Lyme disease
1998rotavirus
Types of vaccines
•Attenuated vaccines•Killed vaccines•Acellular vaccines•Toxoids•Subunit vaccines
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Attenuated vaccine
• Often referred to as live, attenuated vaccine
• Live microbe that has been altered or weakened so that it can enhance immunity but not cause disease
• Very effective in producing immunity
• Example: Sabin vaccine for polio (oral vaccine)
Live, attenuated (weakened) vaccines
• Usually the most effective vaccines
• Organism is multiplying
• Therefore, large immune response
• Usually results in lifelong immunity
• Boosters usually not necessary
• Disadvantage• May mutate and cause disease
• Not recommended in immunocompromised patients
Methods used to attenuate microbe
•Aging•Changing its growth conditions
Killed Vaccines
• Prepared from dead but antigenically active microorganisms
• Organism killed with formalin
• Used when microorganism is too virulent to attenuate
• Immune system responds in same manner as it does to the live microorganism but not as effective as live, attenuated vaccine
• Examples
• Salk polio vaccine (parenteral vaccine)
• Typhoid vaccine
Acellular vaccines
• Uses one part of the organism• Capsule• Flagella• Cell wall
• Do not produce strongest immune responses
• May require booster(s)
• Safe for immunocompromised patients
Recombinant (subunit) vaccines
• Isolate gene from organism that codes for subunit
•Use bacteria or yeast to produce large quantities of subunit molecules
•Cannot cause disease•Used in immunocompromised patients
• Example
• Hepatitis B vaccine
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Toxoids
•Made from toxin produced by microbe
• Toxin is chemically treated with aluminum or other agent to decrease harmful effects
•Adjuvant usually added to enhance immune response
•Boosters required every 10 years• Examples
• Diphtheria• Tetanus
Exposure to similar organism
•Using an organism similar to the one that causes serious disease
• Coxpox for smallpox
• BCG for tuberculosis (attenuated Mycobacterium bovis to protect from Mycobacterium tuberculosis)
Conjugate vaccine
•A poor antigen (polysaccharide) is attached to a carrier protein
• Increases antigenicity• Induces stronger immune response
•Requires boosters• Examples
• H. influenzae vaccine• N. meningitidis vaccine
• S. pneumoniae vaccine
Delivery of vaccines
•Parenteral•Needle
•Needleless – Jet Injected
•Oral
• Inhaled
HPV
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Human Papillomavirus (HPV)
• Most common sexually transmitted disease
• 14 million new infections per year
• 9 of 10 people infected sometime in their lives
• Associated with cervical, vaginal, anal, penile, throat cancers and genital warts
• 120 genotypes• 30 genotypes affecting ½ of sexually active individuals
• 12 cause cervical cancer
Transmission
• Intimate skin to skin contact
• Vaginal, anal, or oral sex• Can be transmitted by someone who has no signs or symptoms
Symptoms
•Most are asymptomatic
•Papilloma (genital warts) may occur
•Usually resolves on its own and does not cause health problems
•Persistent infections can lead to cancer
HPV vaccine
• Gardisil: protects against 4 genotypes
• Gardisil‐9: protects against 9 genotypes
• Cervarix: protects against 2 other genotypes
• Recommended for preteen boys and girls aged 10‐12 years
• Higher immune response in preteens than older adolescents
• 2 injections 6 months apart
• Older adolescents require 3 injections
HPV Vaccination –Adolescent Females (2016) > 1 dose
HPV Vaccination –Adolescent Males (2016) > 1 dose
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HPV16/18 vaccine doses(Study Sept 2017)
• Fewer does may provide protection
•Women studied
• 2043 – 3 doses• 79 – 2 doses 6 months apart
• 193 – 2 doses 1 month apart
• 134 – 1 dose• 2382 – unvaccinated controls
HPV16/18 vaccine doses(Study Sept 2017)
•All vaccinated women still seropositive at year 7 regardless of # of doses
•Antibody levels constant between years 4 and 7
•Prevalence of HPV 31/33/45 lower in all vaccine groups
Reasons for low vaccination rates
• Safety of vaccine• No serious safety concerns linked to vaccine
•Mandated HPV vaccination for school‐aged girls?
• Parents argue it should be individual choice• Thought to promote early initiation of sexual activity & increase promiscuity
Case Study
Case Study ‐Colin
October – Healthy newborn – 7 lbs
Early December
Parents detected something definitely wrong
Took to pediatrician
Referred to emergency room
Diagnosed with stomach virus and discharged
2 nights later
Severe vomiting
Returned to hospital
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Case Study ‐Colin
• Hospitalization• Numerous respiratory tests
• CSF tests
• Chest x‐rays
• Admitted for pneumonia
• Over next 24 hours
• Breathing more and more labored
• Gagging cough
What is the diagnosis?
Case Study ‐Colin
• Transferred to Children’s Hospital• Put on life support• 2nd day – diagnosed with pertussis
•Died at 7 weeks of age
• Probably contracted disease from older unimmunized child
Whooping cough (pertussis)
•Caused by Bordetella pertussis•Prior to 1940 hundreds of thousands of children infected annually
•Thousands of infants died•Dramatically reduced infection rate after vaccination introduced
Danger level of infection
• Infection rate• 90% within the household
• 10% death rate in infants
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Pertussis remains endemic in U.S.
•Reasons:• Less reactogenic acellular vaccine• Modest efficacy (70‐90%)
• Increase in vaccine refusals• Increasing pool of susceptible adults• Immunity waned over time
Concerns about pertussis vaccine
Published study suggesting neurological complications (1974)Vaccination rate decreases○UK – from 70% to 30%
○Japan & Sweden – lifted mandates
○Widespread epidemics occurred
Results refuted by several well‐designed studies Show no evidence of association between
whole‐cell DPT vaccine and encephalopathy
Whooping cough
• Immunization wanes after 10 years
•Adolescents and adults up to age 64 should be immunized with one time dose of Tdap
•Herd immunity does not seem to protect children from pertussis
•Vaccine is acellular. Unlike live vaccines, multiple boosters
Pertussis
•Severe respiratory infection• Called the hundred day cough•Highly communicable
• 80%‐90% infection rates within household
Early Symptoms
•Lasts 1‐2 weeks
•Similar to common cold
• Runny nose• Low‐grade fever• Mild cough
• Apnea•Often goes undiagnosed
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Later stage symptoms
• Fits of violent and rapid coughs followed by high‐pitched “whoop” sound
• Vomiting during or after coughing
• Exhaustion after coughing fit• Coughing occurs more often and severe as disease worsens
•May last 10 weeks or more
Pertussis
•Caused by Bordetella pertussis•Gram negative coccobacillus• Attaches to cilia that line part of upper respiratory system
• Releases toxins that damage epithelium of lungs and causes lymphocytosis and swelling of airways
Pertussis in infants
• 10% mortality rate• 50% require hospitalization• Most deaths occur in unimmunized
children or children too young to be immunized
• Infant usually contracts disease from family member
• Important that teens and adults receive booster immunization (Tdap)
Incidence of Disease
• WHO estimates 200,000 – 400,000 deaths/year from pertussis
• Average of 7,000 – 9,000 cases/year in U.S.• Epidemics occur every 3‐5 years• In 2005, U.S. had 25,616 reported cases• Increase thought to be due to waning antibody
levels in adults
• Only vaccine preventable disease on the rise• Infant cases tripled in last 2 decades
Complications – Babies & Children
•50% under 1 y.o. require hospitalization•1.1% ‐ convulsions•61% ‐ apnea•0.3% ‐ encephalopathy•1% ‐ death
Complications – teens and adults
•Less serious due to vaccination•Fainting – 6%•Rib fracture during coughing – 4%•Pneumonia – 2%
•<5% require hospitalization
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Diagnosis
•History and symptoms
•Physical examination
•Laboratory testing
Laboratory testing
•Mucus from back of throat
• Culture –first 2 weeks of coughing
•Gold standard • PCR – up to 4 weeks after onset of cough
Laboratory testing
•Serological testing•Used to confirm diagnosis•More useful in later phases of disease
•Optimal timing: 2‐ 8 weeks after onset of coughing
•May perform up to 12 weeks after onset of coughing
Vaccine for pertussis
•Acellular vaccine• Uses parts of the bacteria (capsule, flagella, or cell wall)
• Not as effective as attenuated, live vaccines
• Requires several immunizations
• 2 months, 4 months, 6 months, 15‐18 months, 4 – 6 years
• Booster needed > 11 years of age
Prevention
•Vaccination with DTaP(babies/children) or Tdap (preteens, teens, adults)
• Tdap for pregnant women in 3rd trimester each pregnancy
•Post‐exposure antimicrobial prophylaxis
Prevalence
•World‐wide
• 24.1 million cases annually
• 167,000 deaths•Most recent peak year in U.S.: 2012
• 48,277 cases• Largest number reported since 1955
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Last outbreak of pertussis
•2013 & 2014: Dropped to 29,000•Between 1965 and 2005
•No more than 10,000 cases / year
Theories on increase in cases
• Increased awareness
•Better diagnostic techniques•Vaccine ingredients less effective
Study shows best theory
•Change in composition of vaccine
•Original vaccine (194o’s)
•Used dead bacteria (whole cell vaccine)
• Side effects: fever, convulsions
New vaccine (1990s)
•Acellular• Far fewer components of the bacteria
• Less side effects• Less effective• Prevents 80% of cases• Old vaccine – prevents 90% of cases
Acellular vaccine
•2010 outbreak•Many cases in 7 – 13 year olds
•Due to weaker vaccine received by them in 1990s
• Antibody levels waned
• Booster required•Need vaccine with broader protection
DTP, DTaP, Tdap
•DTP•Older vaccine; no longer used in U.S.
•DTaP• Replaced DTP; safer; less side effects•Given to children 6 weeks to 6 years of age
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DTP, DTaP, Tdap
•Tdap• Lower concentration of diphtheria and pertussis toxoids than DTaP
•Given to 10 – 64 year olds
Annually since 2010Pertussis
Influenza
Influenza
• Contagious respiratory illness•Mild to severe
•May require hospitalization
•May cause death
•High risk for complications
• Elderly• Young children• Other health conditions
Types of flu virus
• Influenza Type A• Sub‐types depending on genes that make up the surface proteins
• Influenza Type B•Both types circulate in a season and cause illness
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Flu virus can change
• Antigenic drift• Small genetic changes that occur as virus replicates
• Cross protection• Immune system still able to respond
•Over time small genetic changes accumulate
• Antibodies ineffective against newer virus
• Individual can get flu again
Antigenic shift
• Abrupt, major change in virus
• Results in a new influenza A subtype that has emerged from an animal population so different from the same subtype in humans that most people have no immunity
• Results in pandemic
• Type B changes only by drift•Drift happens often, shift only occasionally
Transmission
•Person to person through droplets when infected person sneezes, coughs, or talks
•Up to 6 feet away
•Less often by touching contaminated surfaces
Transmission
• Infectious 1 day before symptoms appear
• 5 – 7 days after•Children transmit the virus for longer
•Some cases subclinical, but still infectious
Flu season
•Fall and winter
•Peaks from November to March
Symptoms
• Fever• Sore throat• Cough• Runny or stuffy nose
• Body aches•Headache• Chills• Fatigue
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Laboratory testingon nasal or throat swab
• Rapid influenza tests • Sensitivity less than perfect
• Rapid molecular assay
• Direct or indirect immunofluorescence
• RT‐PCR• Rapid cell culture• Viral tissue culture
Testing Algorithm
Annual flu vaccine
•Mixture of 3 most common strains circulating in the world
New for 2017‐2018
•No use of nasal spray vaccine
•Updated to better match circulating viruses
• Trivalent vaccine • 2 new quadrivalent vaccines licensed• One inactivated –Afluria Quadrivalent (IIV)
• One recombinant ‐ Flublok Quadrivalent (RIV)
• Not propagated in eggs
•New trivalent vaccine with adjuvant
How effective is flu vaccine?
•Depends on age and health status• Immune status of individual
•Match of vaccine to circulating viruses
Vaccine effectiveness
•Overall vaccine effectiveness against influenza‐associated pediatric death in children: 65%
•Vaccine effectiveness in children with high‐risk medical conditions: 51%
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CDC study
•Published August 2016•Study participants: >50 y.o.•Vaccination reduced risk of flu‐related hospitalization by 50%
Statistics
•U.S. prior to 2010‐2011 flu season•3 flu seasons• 115,000 to 630,000 hospitalizations• 5,000 to 27,000 deaths• People over 65 • 54% ‐ 71% of hospitalizations• 71% ‐ 85% deaths
Research – influenza fusion protein
• To increase protection of standard flu vaccine by providing broader cross‐protection and long‐term immunity
• Boosting skin vaccination • Delivered by microneedle skin patch
• Uses a fusion protein (4 sequences of M2e from 4 different influenza subtypes and flagellin)
• M2e: a peptide found in all influenza strains
• Flaggelin: peptide found in bacterial flagella (acts as adjuvant)
CDC recommendations
• Children & adults receive vaccination by October if possible (continue through flu season)
•Use injectable vaccine• Not live‐attenuated nasal spray vaccine
• 2 doses for previously unvaccinated children 6 months to 9 years old
Flu vaccine saves kid’s lives
•CDC:4 year study (2010‐2014)• Influenza‐associated pediatric deaths less likely in those vaccinated (291 of 358)
Case Study
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Case Study
•52 year old woman
•Presented with flu‐like symptoms
• Fatigue, fever, chills, headaches•Burning‐tingling pain on face•Painful to touch
24 hours later
•Rash with few blisters on upper left side of face
What is the Diagnosis?
•Shingles
•Prescribed high dose of acyclovir
Shingles
•Cause• Reactivation of chicken pox virus (Herpes zoster)
•Treatment
•High dose of antiviral drug• Reduces pain• Reduces chance of complications
• Shortens course of disease
Shingles
•Almost 1 in 3 people in the U.S. will develop shingles in their lifetime
•1 million cases each year
•At risk: anyone who has had chickenpox
Disease occurrence
•Annual occurrence• 4 cases per 1000 U.S. population• 10 cases per 1000 U.S. population in those over age 60
• 1,000,000 cases in U.S. annually• Incidence of recurrence unknown
• 96 deaths/year
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Shingles
•Can occur at any age•Most common in elderly
• Half of all cases occur over age 60•Usually only occurs once in lifetime
Increased risk for shingles
•Medical conditions that cause immunodeficiency
•HIV• Leukemia
• Lymphoma
• Immunosuppressive drugs
Symptoms
• Pain, itching, or tingling in area where rash will develop
• 1 – 5 days prior to rash• Painful rash that develops on one side of face or body
• Small blisters
• Scab over in 7‐10 days• Clears up in 2 to 4 weeks
Other symptoms
•Fever•Headache•Chills•Upset stomach
Transmission
•Cannot be spread from one person to another
•Contact with blisters can spread virus to someone who has not had chickenpox
•Not infectious before or after blister‐phase
Complications of shingles
• Permanent nerve damage
• Post‐herpetic neuralgia
• Another attack of shingles
• Bacterial skin infections
• Blindness• Deafness• Encephalitis• Sepsis• Ramsay Hunt syndrome
• Facial paralysis
• Hearing loss
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Post‐herpetic neuralgia (PHN)
• Severe pain persisting after rash clears•May be debilitating
• Lasts from few weeks or months to years
• Risk increases with age
• Rare in persons under 40 y.o. •Occurs in 1/3 of untreated aged 60 or older
Prevention
•Vaccination• CDC recommends 1 dose for those aged 60 and older
• Vaccine efficacy wanes 5 years after vaccination
• Protection beyond 5 years is uncertain
Treatment• Antiviral drugs• Acyclovir• Valacyclovir• Famciclovir
• Shorten duration and severity of disease•Must be initiated as soon as possible after appearance of rash
Treatment
•Analgesics to relieve pain•Wet compresses
•Calamine lotion
•Colloidal oatmeal baths
At risk for shingles
•Only those naturally infected with wild‐type VZV or varicella vaccination
•Vaccinated individuals risk is lower than naturally infected individuals
•99.5% of people in U.S. over age 40 have been infected with wild‐type VZV
Reasons VZV reactivates
•Not well understood
•Risk increases as VZV‐specific cell‐mediated immunity declines
•Due to increasing age, certain medical conditions, immunocompromising drugs
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Potential risk factors
•Women at greater risk
•Less common in African Americans than Caucasians (50% less)
Shingles
•500,000 cases annually•Vaccine approved February, 2006• Estimated 250,ooo cases prevented and 250,000 cases with reduced severity & complications
•Get the vaccination!
CDC Recommended Vaccination Protocols
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Adult Immunization Schedule by Health Condition
Vaccinate or Not??
• Are sequelae of preventable diseases dangerous?
• Do you believe the risk of infection still exists?
• Is the risk serious enough that it should be prevented?
• Do vaccinations cause autism and/or SIDS?• If the general population refuses
vaccinations, what would happen?• Will we need vaccinations to protect us from
biological warfare?
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Vaccine Safety: Controversies
•Because of vaccines, parents have no experience with devastating diseases
•Fear of disease replaced with fear of vaccines
•Vaccines are victims of their own success
Religious & moral issues
•Object to acquisition of initial cell lines for vaccines from voluntarily aborted fetuses
•Catholic church• Suggested that children be immunized
• Do not refuse vaccination because of church’s opposition to abortion
• Issued statement that parent was not responsible for the aborted fetuses
Overwhelmed immune system
•Number of childhood vaccines skyrocketed in last 50 years
•By 2 y.o. child has received 14 vaccines and 26 injections
•Modern vaccines have drastically reduced the number of antigens
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Conclusion
• Schedule of vaccines has increased• Fear of disease replaced by fear of vaccines
•High community vaccination rate necessary to protect those who cannot be vaccinated
Role of health care provider
•Keep current on scientific research•Recognize parent’s fears•Dedicate time to discuss with parents
More research for new and better vaccines
• Malaria• Dengue fever• Cholera• Influenza• Tuberculosis• HSV2• EBV• West Nile encephalitis• Hepatitis E• Many others
Research on Vaccines
• HIV• Alzheimers
• Drugs of abuse• Nicotine
• DNA vaccines ‐Developing New Strategies to Enhance Immune Responses
• Adjuvants
• Reducing post‐traumatic anxiety through immunization
• Group B Strep
• Prion disea se