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Home , DPT vaccine

9/28/2017

Introduction

Update on •Transmission of infectious disease Patsy Jarreau •History of Department of Clinical Laboratory Sciences LSU Health Sciences Center • preventable diseases New Orleans, LA •Research for new vaccines

Factors related to emerging Transmission of infectious diseases

Interrupting transmission of infectious diseases How does the immune system work? • Person is infected •Hygiene • Symptoms arise •Sanitation • from invading organism stimulate immune response •Environmental modification • Cytokines and antibodies are produced •Vector control • Leads to eventual destruction of the organism • Memory cells are also produced •Vaccines

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Secondary immune response

• Basis of • Initial encounter with , 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

Vaccination in Prevention of Disease Definition of vaccine • • Agent that resembles a pathogenic • Enough vaccinated individuals and disease microorganism and stimulates the immune system to recognize, destroy, and does not spread remember that organism • Low number of susceptible individuals • May be composed of parts of the organism, • Protects those who cannot be immunized weakened or killed forms of the organism, or altered toxins of the microbe • Allergic • Immunocompromised • Unable to make antibodies to vaccine

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Discovery of Vaccines How to make a vaccine • Noticed that people who recovered from • Goal disease rather than dying from it did not • To induce immune response but not to cause get the disease again disease • Chinese attempted to prevent smallpox in • How to accomplish 10th century • Antigen must be altered or • Prime minister’s eldest son died of smallpox • Similar antigen that does not cause disease • Sought remedy to prevent same from happening to other family members

Spread of Vaccination for Smallpox Variolation

• Exposing people to matter from smallpox lesions •Practice spread to Turkey in 1600s • Removing pus & fluid from lesion & placing under •Lady Montagu (wife of British skin of uninfected person • Drying & grinding scabs into powder for uninfected ambassador to Turkey) allowed her person to inhale family to be variolated in 1718 • Injecting scab powder into vein of uninfected person • Practice spread to Europe by 1721 • Was not widely practiced until 1500s

Effects of Variolation

•Mild illness in most individuals • Was variolated as a small boy • Became country doctor •Death in a few • Noticed that on farms where horses with an •Mortality and morbidity rates much equine disease similar to smallpox that there were cows with blisters similar to lower in variolated populations 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 Named “Vaccination” could not contract smallpox • 1796 –Conducted experiment • “vacca” –Latin for cow Infected young boy with cowpox Smallpox has now been eradicated Then intentionally infected boy with smallpox • ○Injected pus from lesion under boy’s skin • Virus is found only in 2 places in the world ○Boy did not contract smallpox • CDC • Lead to the production of vaccines for many infectious diseases • Institute of Viral Preparations in Moscow • Responsible for marked decrease in deadly diseases

History of Vaccines History of Vaccines • First Vaccine for: First Vaccine for: • 1932 yellow fever 1796 small pox 1879 cholera • 1937 typhus 1885 rabies • 1945 influenza 1890 • 1952 1896 typhoid fever • 1954 Japanese encephalitis 1897 bubonic plague 1921 • 1954 anthrax 1926 pertussis () • 1957 adenovirus 4 and 7 1927 tuberculosis • 1962 oral

and more . . .

History of Vaccines First Vaccine for: Types of vaccines 1963 measles 1967 mumps •Attenuated vaccines 1970 rubella 1974 chicken pox •Killed vaccines 1977 pneumonia (Streptococcus pneumoniae) Acellular vaccines 1978 meningitis • 1981 • 1985 type b (HiB) 1992hepatitis A •Subunit vaccines 1998Lyme disease 1998rotavirus

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Live, attenuated (weakened) vaccines

• Often referred to as live, attenuated vaccine • Usually the most effective vaccines • Live microbe that has been altered or weakened • Organism is multiplying so that it can enhance immunity but not cause • Therefore, large immune response disease • Usually results in lifelong immunity • Very effective in producing immunity • Boosters usually not necessary • Example: Sabin vaccine for polio (oral vaccine) • Disadvantage • May mutate and cause disease • Not recommended in immunocompromised patients

Killed Vaccines Methods used to attenuate microbe • Prepared from dead but antigenically active microorganisms • Organism killed with formalin •Aging • Used when microorganism is too virulent to attenuate •Changing its growth conditions • 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) •

Recombinant (subunit) vaccines Acellular vaccines • Isolate gene from organism that codes for • Uses one part of the organism subunit • Capsule • Use or yeast to produce large • Flagella quantities of subunit molecules • Cell wall • Cannot cause disease • Do not produce strongest immune responses • May require booster(s) • Used in immunocompromised patients • Safe for immunocompromised patients • Example •

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Toxoids Exposure to similar organism • Made from toxin produced by microbe • Toxin is chemically treated with aluminum or other agent to decrease harmful effects • Using an organism similar to the one that • Adjuvant usually added to enhance causes serious disease immune response • Coxpox for smallpox • Boosters required every 10 years • BCG for tuberculosis (attenuated • Examples Mycobacterium bovis to protect from Mycobacterium tuberculosis) • Diphtheria • Tetanus

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 HPV •Oral •Inhaled

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Human Papillomavirus (HPV) Transmission

• Most common sexually transmitted disease • 14 million new per year • 9 of 10 people infected sometime in their lives •Intimate skin to skin contact • Associated with cervical, vaginal, anal, penile, throat cancers and genital warts • Vaginal, anal, or oral sex • 120 genotypes • Can be transmitted by someone who • 30 genotypes affecting ½ of sexually active individuals has no signs or symptoms • 12 cause cervical cancer

HPV vaccine Symptoms • Gardisil: protects against 4 genotypes •Most are asymptomatic • Gardisil‐9: protects against 9 genotypes • : protects against 2 other genotypes •Papilloma (genital warts) may occur • Recommended for preteen boys and girls aged 10‐12 •Usually resolves on its own and does years • Higher immune response in preteens than older not cause health problems adolescents •Persistent infections can lead to • 2 injections 6 months apart cancer • Older adolescents require 3 injections

HPV Vaccination – Adolescent HPV Vaccination – Adolescent Females (2016) >1 dose 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 Reasons for low vaccination rates (Study Sept 2017) • Safety of vaccine •All vaccinated women still seropositive • No serious safety concerns linked to vaccine at year 7 regardless of # of doses • Mandated HPV vaccination for school‐aged girls? Antibody levels constant between years • • Parents argue it should be individual choice 4 and 7 • Thought to promote early initiation of sexual activity & increase promiscuity •Prevalence of HPV 31/33/45 lower in all vaccine groups

Case Study ‐ Colin October –Healthy newborn –7 lbs Early December Parents detected something definitely wrong Took to pediatrician Case Study 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 What is the diagnosis? • Admitted for pneumonia

• Over next 24 hours • Breathing more and more labored • Gagging cough

Whooping cough (pertussis) Case Study ‐ Colin

•Caused by • Transferred to Children’s Hospital •Prior to 1940 hundreds of thousands • Put on life support of children infected annually • 2nd day –diagnosed with pertussis • Died at 7 weeks of age •Thousands of infants died • Probably contracted disease from older •Dramatically reduced infection rate unimmunized child 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 Whooping cough Published study suggesting neurological complications (1974) • Immunization wanes after 10 years Vaccination rate decreases • Adolescents and adults up to age 64 ○UK –from 70% to 30% should be immunized with one time dose ○Japan & Sweden – lifted mandates of Tdap ○Widespread epidemics occurred • Herd immunity does not seem to protect Results refuted by several well‐designed children from pertussis studies • Vaccine is acellular. Unlike live vaccines, Show no evidence of association between multiple boosters whole‐cell DPT vaccine and encephalopathy

Early Symptoms Pertussis •Lasts 1‐2 weeks •Severe respiratory infection •Similar to common cold Called the hundred day cough • • Runny nose •Highly communicable • Low‐grade fever • 80%‐90% infection rates within • Mild cough household • Apnea •Often goes undiagnosed

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Later stage symptoms Pertussis

• Fits of violent and rapid coughs followed by •Caused by Bordetella pertussis high‐pitched “whoop” sound • Gram negative coccobacillus • Vomiting during or after coughing • Attaches to cilia that line part of upper • Exhaustion after coughing fit respiratory system • Releases toxins that damage epithelium of Coughing occurs more often and severe as • lungs and causes lymphocytosis and disease worsens swelling of airways • May last 10 weeks or more

Pertussis in infants Incidence of Disease

• 10% mortality rate • WHO estimates 200,000 – 400,000 • 50% require hospitalization deaths/year from pertussis • Most deaths occur in unimmunized • Average of 7,000 –9,000 cases/year in U.S. children or children too young to be • Epidemics occur every 3‐5 years immunized • In 2005, U.S. had 25,616 reported cases • Infant usually contracts disease from • Increase thought to be due to waning antibody family member levels in adults • Important that teens and adults receive • Only vaccine preventable disease on the rise booster immunization (Tdap) • Infant cases tripled in last 2 decades

Complications –Babies & Children Complications – teens and adults

•Less serious due to vaccination •50% under 1 y.o. require hospitalization •Fainting –6% •1.1% ‐ convulsions •Rib fracture during coughing –4% •61% ‐ apnea •Pneumonia –2% •0.3% ‐ encephalopathy •<5% require hospitalization •1% ‐ death

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Diagnosis Laboratory testing

•History and symptoms • Mucus from back of throat •Physical examination • Culture –first 2 weeks of coughing •Gold standard •Laboratory testing • PCR –up to 4 weeks after onset of cough

Laboratory testing Vaccine for pertussis

•Serological testing • Acellular vaccine • Used to confirm diagnosis • Uses parts of the bacteria (capsule, • More useful in later phases of disease flagella, or cell wall) • Not as effective as attenuated, live • Optimal timing: 2‐ 8 weeks after onset vaccines of coughing • Requires several • May perform up to 12 weeks after onset • 2 months, 4 months, 6 months, 15‐18 months, of coughing 4 –6 years • Booster needed >11 years of age

Prevention Prevalence •World‐wide •Vaccination with DTaP(babies/children) • 24.1 million cases annually or Tdap (preteens, teens, adults) • 167,000 deaths • Tdap for pregnant women in 3rd trimester each pregnancy •Most recent peak year in U.S.: 2012 • 48,277 cases •Post‐exposure antimicrobial prophylaxis • Largest number reported since 1955

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Last outbreak of pertussis Theories on increase in cases

•2013 & 2014: Dropped to 29,000 •Increased awareness •Between 1965 and 2005 •Better diagnostic techniques • No more than 10,000 cases / year • less effective

Study shows best theory New vaccine (1990s)

•Acellular •Change in composition of vaccine • Far fewer components of the bacteria •Original vaccine (194o’s) • Less side effects • Used dead bacteria (whole cell vaccine) • Less effective • Side effects: fever, convulsions • Prevents 80% of cases • Old vaccine –prevents 90% of cases

Acellular vaccine DTP, DTaP, Tdap

•2010 outbreak •DTP • Many cases in 7 –13 year olds • Older vaccine; no longer used in U.S. • Due to weaker vaccine received by them in 1990s •DTaP • Antibody levels waned • Replaced DTP; safer; less side effects • Booster required • Given to children 6 weeks to 6 years of • Need vaccine with broader protection age

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Annually since 2010 DTP, DTaP, Tdap Pertussis

•Tdap • Lower concentration of diphtheria and pertussis toxoids than DTaP • Given to 10 –64 year olds

Influenza

Influenza Types of flu virus • Contagious respiratory illness • Mild to severe •Influenza Type A • May require hospitalization • Sub‐types depending on genes that • May cause death make up the surface proteins • High risk for complications •Influenza Type B • Elderly •Both types circulate in a season and • Young children cause illness • Other health conditions

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Flu virus can change Antigenic shift • Antigenic drift • Abrupt, major change in virus • Small genetic changes that occur as virus • Results in a new influenza A subtype that has replicates emerged from an animal population so • Cross protection different from the same subtype in humans • Immune system still able to respond that most people have no immunity • Results in pandemic • Over time small genetic changes accumulate • Type B changes only by drift • Antibodies ineffective against newer virus • Drift happens often, shift only • Individual can get flu again occasionally

Transmission Transmission

•Person to person through droplets •Infectious 1 day before symptoms when infected person sneezes, appear coughs, or talks • 5 –7 days after • Up to 6 feet away •Children transmit the virus for longer •Less often by touching contaminated surfaces •Some cases subclinical, but still infectious

Symptoms Flu season

• Fever • Body aches •Fall and winter • Sore throat • Headache •Peaks from November to March • Cough • Chills • Runny or stuffy • Fatigue nose

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Testing Algorithm Laboratory testing on nasal or throat swab

• Rapid influenza tests • Direct or indirect • Sensitivity less immunofluorescence than perfect • RT‐PCR • Rapid molecular assay • Rapid cell culture • Viral tissue culture

New for 2017‐2018

Annual flu vaccine • No use of nasal spray vaccine • Updated to better match circulating viruses •Mixture of 3 most common strains • Trivalent vaccine circulating in the world • 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? Vaccine effectiveness

•Overall vaccine effectiveness against •Depends on age and health status influenza‐associated pediatric death • Immune status of individual in children: 65% •Match of vaccine to circulating viruses •Vaccine effectiveness in children with high‐risk medical conditions: 51%

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CDC study Statistics •U.S. prior to 2010‐2011 flu season •Published August 2016 •3 flu seasons •Study participants: >50 y.o. • 115,000 to 630,000 hospitalizations •Vaccination reduced risk of flu‐related • 5,000 to 27,000 deaths hospitalization by 50% • People over 65 • 54% ‐ 71% of hospitalizations • 71% ‐ 85% deaths

Research –influenza fusion protein CDC recommendations • To increase protection of standard flu vaccine by providing broader cross‐ • Children & adults receive vaccination by protection and long‐term immunity October if possible (continue through flu • Boosting skin vaccination season) • Delivered by microneedle skin patch • Use injectable vaccine Uses a fusion protein (4 sequences of M2e • • Not live‐attenuated nasal spray vaccine from 4 different influenza subtypes and flagellin) • 2 doses for previously unvaccinated • M2e: a peptide found in all influenza strains children 6 months to 9 years old • Flaggelin: peptide found in bacterial flagella (acts as adjuvant)

Flu vaccine saves kid’s lives

•CDC:4 year study (2010‐2014) •Influenza‐associated pediatric deaths less likely in those vaccinated Case Study (291 of 358)

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Case Study 24 hours later

•52 year old woman •Presented with flu‐like symptoms •Rash with few blisters on upper left side of face • Fatigue, fever, chills, headaches •Burning‐tingling pain on face •Painful to touch

What is the Diagnosis? Shingles •Cause • Reactivation of chicken pox virus •Shingles (Herpes zoster) •Treatment •Prescribed high dose of acyclovir • High dose of antiviral drug • Reduces pain • Reduces chance of complications • Shortens course of disease

Disease occurrence Shingles •Annual occurrence • 4 cases per 1000 U.S. population •Almost 1 in 3 people in the U.S. will develop shingles in their lifetime • 10 cases per 1000 U.S. population in those over age 60 •1 million cases each year • 1,000,000 cases in U.S. annually At risk: anyone who has had chickenpox • • Incidence of recurrence unknown • 96 deaths/year

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Shingles Increased risk for shingles

•Can occur at any age •Medical conditions that cause immunodeficiency • Most common in elderly • HIV • Half of all cases occur over age 60 • Leukemia •Usually only occurs once in lifetime • Lymphoma • Immunosuppressive drugs

Symptoms Other symptoms • Pain, itching, or tingling in area where rash will develop Fever • 1 –5 days prior to rash • • Painful rash that develops on one side of face or •Headache body •Chills • Small blisters Upset stomach • Scab over in 7‐10 days • • Clears up in 2 to 4 weeks

Transmission Complications of shingles

•Cannot be spread from one person to another • Blindness • Permanent nerve • Deafness •Contact with blisters can spread virus damage • Encephalitis to someone who has not had • Post‐herpetic neuralgia • Sepsis chickenpox • Another attack of Ramsay Hunt shingles • syndrome •Not infectious before or after blister‐ • Bacterial skin infections phase • Facial paralysis • Hearing loss

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Post‐herpetic neuralgia (PHN) Prevention • Severe pain persisting after rash clears • May be debilitating •Vaccination • Lasts from few weeks or months to • CDC recommends 1 dose for those aged years 60 and older • Risk increases with age • Vaccine efficacy wanes 5 years after • Rare in persons under 40 y.o. vaccination • Occurs in 1/3 of untreated aged 60 or older • Protection beyond 5 years is uncertain

Treatment Treatment • Antiviral drugs • Acyclovir •Analgesics to relieve pain • Valacyclovir •Wet compresses • Famciclovir •Calamine lotion • Shorten duration and severity of disease • Must be initiated as soon as possible after •Colloidal oatmeal baths appearance of rash

At risk for shingles Reasons VZV reactivates

•Only those naturally infected with •Not well understood wild‐type VZV or varicella vaccination •Risk increases as VZV‐specific cell‐ •Vaccinated individuals risk is lower mediated immunity declines than naturally infected individuals • Due to increasing age, certain medical •99.5% of people in U.S. over age 40 conditions, immunocompromising drugs have been infected with wild‐type VZV

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Potential risk factors Shingles

•500,000 cases annually •Women at greater risk •Vaccine approved February, 2006 •Less common in African Americans • Estimated 250,ooo cases prevented and than Caucasians (50% less) 250,000 cases with reduced severity & complications

CDC Recommended Vaccination Protocols •Get the vaccination!

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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 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 Religious & moral issues • Object to acquisition of initial cell lines for •Because of vaccines, parents have no vaccines from voluntarily aborted fetuses experience with devastating diseases • Catholic church •Fear of disease replaced with fear of • Suggested that children be immunized vaccines • Do not refuse vaccination because of church’s opposition to abortion •Vaccines are victims of their own • Issued statement that parent was not success 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 Role of health care provider

• Schedule of vaccines has increased • Fear of disease replaced by fear of •Keep current on scientific research vaccines •Recognize parent’s fears • High community vaccination rate necessary to protect those who cannot be •Dedicate time to discuss with parents vaccinated

More research for new and better Research on Vaccines vaccines • Malaria • HIV • Dengue fever • Alzheimers • Adjuvants • Cholera • Drugs of abuse • Reducing post‐ traumatic anxiety • Influenza • Nicotine through immunization • Tuberculosis • DNA vaccines ‐ • Group B Strep • HSV2 Developing New • Prion disea se • EBV Strategies to • West Nile encephalitis Enhance Immune Responses • • Many others

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