Update on Vaccines. Interrupting transmission of infectious diseases 9/28/2017. Introduction. Factors related to emerging infectious diseases

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1 Introduction Update on Vaccines Patsy Jarreau Department of Clinical Laboratory Sciences LSU Health Sciences Center New Orleans, LA Transmission of infectious disease History of vaccination Vaccine preventable diseases Research for new vaccines Transmission of Infection Factors related to emerging infectious diseases Interrupting transmission of 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 1

2 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 2

3 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 10 th 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 3

4 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 pox 1879 cholera 1885 rabies 1890 tetanus 1896 typhoid fever 1897 bubonic plague 1921 diphtheria 1926 pertussis (whooping cough) 1927 tuberculosis History of Vaccines First Vaccine for: 1932 yellow fever 1937 typhus 1945 influenza 1952 polio 1954 Japanese encephalitis 1954 anthrax 1957 adenovirus 4 and oral polio vaccine and more... History of Vaccines First Vaccine for: 1963 measles 1967 mumps 1970 rubella 1974 chicken pox 1977 pneumonia (Streptococcus pneumoniae) 1978 meningitis 1981 hepatitis B 1985 Haemophilus influenzae type b (HiB) 1992hepatitis A 1998Lyme disease 1998rotavirus Types of vaccines Attenuated vaccines Killed vaccines Acellular vaccines Toxoids Subunit vaccines 4

5 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 5

6 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 6

7 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 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 7

8 HPV16/18 vaccine doses (Study Sept 2017) Fewer does may provide protection Women studied doses 79 2 doses 6 months apart doses 1 month apart 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 Colin Case Study 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 8

9 Case Study Colin Hospitalization Numerous respiratory tests CSF tests Chest x rays Admitted for pneumonia What is the diagnosis? Over next 24 hours Breathing more and more labored Gagging cough Case Study Colin Transferred to Children s Hospital Put on life support 2 nd 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 9

10 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 10

11 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 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 11

12 Diagnosis Laboratory testing History and symptoms Physical examination 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, 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 3 rd 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.: ,277 cases Largest number reported since

13 Last outbreak of pertussis Theories on increase in cases 2013 & 2014: Dropped to 29,000 Between 1965 and 2005 No more than 10,000 cases / year 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 13

14 DTP, DTaP, Tdap Annually since 2010 Pertussis Tdap Lower concentration of diphtheria and pertussis toxoids than DTaP Given to year olds 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 14

15 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 Symptoms Fall and winter Peaks from November to March Fever Sore throat Cough Runny or stuffy nose Body aches Headache Chills Fatigue 15

16 Laboratory testing on nasal or throat swab Testing Algorithm Rapid influenza tests Sensitivity less than perfect Rapid molecular assay Direct or indirect immunofluorescence RT PCR Rapid cell culture Viral tissue culture Annual flu vaccine Mixture of 3 most common strains circulating in the world New for 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% 16

17 CDC study Published August 2016 Study participants: >50 y.o. Vaccination reduced risk of flu related hospitalization by 50% Statistics U.S. prior to 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 crossprotection 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 ( ) Influenza associated pediatric deaths less likely in those vaccinated (291 of 358) Case Study 17

18 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 18

19 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 blisterphase 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 19

20 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 cellmediated immunity declines Due to increasing age, certain medical conditions, immunocompromising drugs 20

21 Potential risk factors Shingles Women at greater risk Less common in African Americans than Caucasians (50% less) 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 21

22 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? 22

23 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 23

24 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 posttraumatic anxiety through immunization Group B Strep Prion disea se 24