Class 6- Vaccine Preventable Diseases- Measles, GIS, & R0 Flashcards
First documented account of vaccination
1000AD A Buddhist nun described how smallpox scabs were dried, ground, and blown into the nostrils of susceptible persons
Edward Jenner
In the late 1700s Noted that milkmaids rarely became infected with smallpox-and postulated that contact with cowpox puss protected them 1796 inoculated James Phipps, the son of his gardener, with cowpox. Scrapped pus from a cowpox blister
Inoculation vs Vaccination
Inoculation: Administration of pathogen to induce infection and immunity.
- Historical method for the prevention of smallpox by deliberate introduction into the skin of material from smallpox pustules
- Brought on less-severe symptoms
- 2% mortality in healthy individuals
- Valley forge inoculation- revolutionary war
Vaccination: Administration of antigenic material, that stimulates adaptive immunity (antibody production)
Passive Immunization
Refers to the protection conferred by the transfer of animal or human antibody
Route- injection, in utero, breast feeding Is typically short lived
- maternal antibodies protect newborns for up to 6 months
Active Immunization
Refers to protection produced by the host’s own immune system and relies on the host to generate an immune response
- Longer lasting
Types of Vaccines
Live
- Live organism has been attenuated (weakened)
Inactivated (Killed) vaccine
- Organism is killed by heat, chemicals or radiation
Recombinant
- Created through genetic manipulation of organisms genomic material
- Can be live or inactivated
Vaccines that minimize consequences of infection
Where as some vaccines are imagined as being able to prevent infection, many others prevent or minimize the consequences of infection
- Examples:
- Inactivated polio does not prevent wild-type poliovius from multiplying in the intestinal tract
- Immunity prevents the virus from causing cNS damage
- Toxoid vaccine
- Prevent tissue damage from bacterial toxins
- Inactivated polio does not prevent wild-type poliovius from multiplying in the intestinal tract
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Vaccine development phases<!--EndFragment-->
Licensure of any new vaccine requires that efficacy be demonstrated from preclinical studies
- Investigational new drug filed with the FDA
- Preclinical studies (animal studies)
- Phase 1: Dose Finding and Safety (small number of volunteers 5-10 people)
- Phase 2: Safety and Immunogenicity trials (post-vaccination serology)
- Phase 3: Comparative Efficacy trials (RCT)
Takes a long time and can be stopped at any of the phases – expensive
Characteristics of an Ideal Vaccine
- Produces a good immune response, similar to natural infection, in a single dose
- Protects against disease
- Provides protection for years/lifetime
- Minimal adverse effects
- Induced immunity confers protections to multiple strains of organisms
- Easy to administer
- Don’t require special handling (e.g. cold chain)
- Doesn’t interfere with other immune responses or vaccines
- Cheap
Contradiction for Vaccination
- Severe allergy to any vaccine component
- Severe illness
- Immunosuppression
- HIV infection
- Pregnancy
- Encephalopathy
- Recent receipt of blood products
List of available vaccines
- HPV
- HBV (hepatitus B)
- TDAP (Tetanus, Diphtheria, Pertussis)
- HIB (Haemophilus Influenzae Type b)
- HAV (hepatitus A)
- MMR
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Childhood Vaccines in the US<!--EndFragment-->
As of 2009:
- Prevent 42,000 deaths a year and as many as 20 million cases
Costs savings
- $13.5 Billion dollars
- Excludes influenza
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Vaccines and Autism<!--EndFragment-->
Andrew Wakefield
- Published paper on 28 February 1998 linking the MMR vaccine to autism
- Study suggested that gastrointestinal inflammation, brought on by the MMR vaccine is responsible for autism.
- Published in The Lancet
- Included twelve other authors about twelve autistic children
- Resulted in the creation of the VAERS -Vaccine Adverse Event Reporting System
Shoddy science and multiple accusations of fraudulent billing
- Lead to a decrease in vaccination rates and an increase in preventable diseases in the UK and US.
- Since that time, 200,000 reports have shown there is no link
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R0<!--EndFragment-->
R0 is the reproductive number of an infectious disease
Immunization rates influence R0 rates
- Fewer susceptible individuals = fewer potential cases (concept of herd immunity)
- R0<1 disease is dying out
- R0=1 endemic stable transmission
- R0>1 epidemic transmission
- Herd immunity threshold = 1- (1/r0)
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Poliovirus<!--EndFragment-->
Reservoir- Humans- most frequently asymptomatic carriers
- No long term carriers of wild-type polio have been detected (2008)
Route- person to person, fecal-oral, contaminated water
- Virus is more detectable in feces than throat swabs
Incubation- 7 to 14 days for paralytic cases
Symptoms- non specific fever, acute flaccid paralysis (1% of cases)
- Maximum extent of paralysis is usually reached in 3-4 days
Communicability- not well defined, virus persist in throat for 1 week and for 3-6 weeks in feces
Polio vaccine history
Salk vaccine
- Inactivated polio vaccine (IPV) introduced in 1955
- A 90% reduction in poliomyelitis cases attributed to the vaccine alone.
Fear of vaccine-associated paralytic poliomyelitis (VAPP)
- Oral polio vaccine only
- Incidence Is 0.34 per 1 million polio vaccinations
- Response- in 1999 US switched to two dose IPV
Toward global Eradication of Polio
1988 the world health assembly set a target to eradicate polio by 2000
- Between 1988 and 2003 global cases decreased by 99%
Two remaining barriers to polio eradication
- Failure to vaccinate and vaccine failures (wild type polio outbreaks)
- Fear of outbreaks in conflict zones due to failure of health systems
- Syria, crimea, etc.
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Measles virus
Reservoir- Humans
Route- airborne droplet, direct contact with nasal secretions of infected individual.
Incubation- 7-18 days, usually 14 days until rash appears (median 12.5 days)
Symptoms- red blotchy rash, Prodromal fever, conjunctivitis, cough,
- Case fatality rate in developing countries is 3-5% but can be s high as 10-30% in severely impoverished areas
Communicability- 1 day before onset of fever (4 days before the rash) till 4 days after rash appears
- One of the most highly communicable infectious diseases
- Outbreaks can occur in populations in which fewer than 10% of all persons are susceptible
High level Measles
Highly contagious disease from single strand RNA virus
- Caused by paramyxovirus; genus Morbillivirus
- Affect mostly children
Transmitted through droplets from nose, mouth, throat
Causes blindness, encephalitis, severe diarrhea, ear infection, and pneumonia
Malnourished and immune compromised most susceptible
Preventable by vaccination
Measles Globally
Between 2000 and 2013 the measles vaccination has prevented an estimated 15.6 million deaths
- There has been a 75% reduction in deaths between 2000 and 2013 due to vaccination
- In 2013, 84% of the world’s children received one dose of measles vaccine
- up from 73% in 2000
- In 2013, 84% of the world’s children received one dose of measles vaccine
In 2013 there were 145,7000 measles deaths globally
Modified SEIR Model Assumptions
St= susceptible
Et = exposed
It = infectious individuals
t = time
b = constant transmission parameter (R0 or force of infection)
M = migration
γ (gamma) = the mean recovery/death rate
1/γ (gamma) = the mean infective period
Infectious individuals have 3 stages in exposed class and 4 stages in infectious class
φ (phi) and γ (gamma) =1/2 correspond to duration of class, 6 days in exposed and 8 days in infectious
MS,t and ME,t represent susceptible and exposed individuals migrating
