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VACCINE PREVENTABLE DISEASES AND VACCINATION. Najwa Khuri-Bulos 2012. Jenner. Strong Tools Available/Expected. Comparison of Annual and Current Reported Morbidity, Vaccine-Preventable Diseases and Vaccine Adverse Events, United States.
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VACCINE PREVENTABLE DISEASES AND VACCINATION Najwa Khuri-Bulos 2012
Comparison of Annual and Current Reported Morbidity, Vaccine-Preventable Diseases and Vaccine Adverse Events, United States Total 1,064,845 7,515 -99.29 Vaccine Adverse Events 0 13,497^ +++ Disease 20th Century Annual Morbidity* 2000** % change Diphtheria 175,885 4 -99.99 Measles 503,282 81 -99.98 Mumps 152,209 323 -99.79 Pertussis 147,271 6,755 -95.41 Polio (wild) 16,316 0 -100 Rubella 47,745 152 -99.68 Cong. Rubella Synd. 823 7 -99.15 Tetanus 1,314 26 -98.02 Invasive Hib Disease 20,000 167 -99.16 * Maximum cases reported in pre-vaccine era and year + Estimated because no national reporting existed in the prevaccine era ^ Adverse events after vaccines against diseases shown on Table = 5,296 ** Provisional
Impact of the EPI Case Study, Jordan, a great success story Diphtheria Measles poliomyelitis
outline • Importance of vaccines and vaccinations • Basics of vaccination. • General principles • Routine vaccines in Jordan • Recently introduced vaccines world wide • Important vaccine information sources
Basics of vaccination • Active versus passive immunization • Live versus killed vaccines • Component vaccines, protein versus polysacharide • General rules about minimum age at vaccination • General rules about concommitent use of vaccines • General rules about vaccine interruption • General rules about different vaccine schedules
Principles of Vaccination Active Immunity = Antigen long duration, maybe lifelong Passive Immunity = Antibody limited public health impact, immune compromised hosts, limited duration
Types of vaccine antigens • Live attenuated organisms • Viral • Bacterial • Recently parasitic (Malaria) • Inactivated • Whole organisms • Viral • bacterial • Fractional • Protein • Polysaccharides • Conjugate polysacharide vaccines
Inactivated vaccines general principles Inactivated whole organism and fractional vaccines Safe in immune compromised hosts and pregnancy Protein, better antigens, TH2 response, effective before age two years Polysacharide vaccines, Not effective before 2 years of age, TH1 response In general inactivated by freezing Usually do not interfere with each other Need for booster doses to maintain immunity
Polysaccharide Vaccines: T-cell independent Not effective in children under 2 years and in the immunocompromised Result in a primarily IgM response Do not induce immunological memory and hence cannot be boosted Do not reduce mucosal carriage of pneumococcus1 Pneumococcal Conjugate Vaccines1: T-cell dependent Induce an effective immune response in infants Stimulate an initial response involving both IgM and IgG while subsequent doses stimulate a primarily IgG response Induce immunological memory and can be boosted Polysaccharide versus conjugate vaccines 1Eskola J. PIDJ 2000. 19 (4): 388-93.
Live vaccines general considerations Live vaccines can be frozen induce longer lasting immunity SHOULD NOT be given to immune compromised and to pregnant women maternal antibody may neutralize the vaccine and make it less effective in early life
Common Live vaccines • BCG • OPV • MMR • Rotavirus • Chickenpox • Intranasal influenza vaccine • Live typhoid vaccines
Killed or fractional vaccines • IPV • Hepatitis a vaccine • DTP • DTaP • IPV • HB • HIB • Pneumoccal vaccine • Meningococcal vaccines • Injectable influenza • HPV
Vaccines in use for children in Jordan and worldwide Vaccines in use in Jordan • Diptheria • Tetanus • Pertussis • Polio both IPV and OPV • Measles, • Mumps • Rubella • Hemophilus influenza b • Hepatitis b • BCG Vaccines not yet introduced in Jordan • Chickenpox • Pneumococcus ( recent donation) • Chickenpox/VZV vaccine • Rotavirus • Hepatitis a • Influenza vaccine • Acellular pertussis vaccine for adolescents and adults • Meningococcal vaccine • HPV vaccine
History of Expanded program on Immunization (EPI) – Jordan • 1979 National Program on Immunization was established Diphtheria, Pertussis, Tetanus, Polio, BCG • 1982 First dose Measles • 1982 Tetanus toxoid for women in child bearing age • 1993 4th dose of polio • 1995 Hepatitis “B” and second dose Measles • 2000 MMR replaced 2nd dose of Measles • 2001 HIB introduced • 2003 IPV first dose instead of OPV • 2006 IPV second dose Plus OPV
Vaccination schedule Jordan 2008 Age Vaccine BCG 1st contact DTP + HepB1 +Hib1 + IPV 2 months2 3 months DTP+HepB2+Hib2+ IPV,OPV 4 months DTP+HepB3+Hib3 + OPV 9 months 18 Months Measles + OPV MMR +DTP booster1+OPV booster1 Td (OPV for 1st class) 1st & 10th class
Vaccination to school age children • 1st elementary class Td +OPVbooster2 Validation of measles and MMR • 10th class Td Second dose of MMR
Vaccine to be discussed • Diphtheria • Tetanus • Pertussis • Polio • Measles • Mumps • Rubella • HIB • HB • Hep A • Chickenpox • Pneumococcal • Rotavirus • HPV • Influenza
Diphtheria Greek diphtheria (leather hide) Gram positive rod, a human pathogen that is transmitted by droplets, both asymptomatic and symptomatic individuals may transmit infection There are four biotypes mitis, intermedius,belfanti, and gravis). All biotypes of C diphtheriae may beeither toxigenic or nontoxigenic. Diphtheria is caused by toxigenic strains of Corynebacteriumdiphtheriae.
Epidemiology of diphtheria • Only human pathogen • Can be carried in the nasopharynx • Bacteriophage induces toxin production • Transmitted by droplet • Vaccinated individuals can carry the organism but do not get sick
Diphtheria pathogenesis • Toxigenic strains expressan exotoxin that consists of an enzymatically active A domainand a binding B domain, which promotes the entry of A into thecell. • The toxin gene, tox, is carried by a family of relatedcorynebacteria bacteriophages. • The toxin inhibits protein synthesisin all cells, including myocardial, renal, and peripheral nervecells, resulting in myocarditis, acute tubular necrosis, anddelayed peripheral nerve conduction. Nontoxigenic strains ofC diphtheriae can cause sore throat and other invasive infections.
Diptheria clinical considerations • Usually sick looking and tonsils have a membrane which is grayish and difficult to remove • Membrane may involve more than the tonsils • Toxin production most important and initially may have difficulty in breathing • Arrhythmia with cardiac toxicity occurs in the second week • Most common cause of death is cardiac toxicity • Neurologic complications occur after three to four weeks • Antitoxin should be given before four days
Diphtheria vaccine, toxin only • Formalin-inactivated diphtheria toxin • Protein antigen • Must administer by deep IM • Do not freeze • Efficacy Approximately 95% • Duration Approximately 10 years • Amount of antigen higher in children • Should be administered with tetanus toxoid as DTP. DTaP, DT, Td, or Tdap
DTP, DTaP, DT, and Td Diphtheria 7-8 Lf units 2-2.5 Lf units Tetanus 5-12.5 Lf units 5 Lf units DTP,DTaP, DT Td, Tdap (adult) DTP, DTaP and pediatric DT used through age 6 years. Adult Td for persons 7 years and older. Tdap for persons 10-18 years (Boostrix) or 11-64 years (Adacel)
Diphtheria vaccine, schedule, same as Tetanus and pertussis • Three doses before the age of one year starting at the age of 2 months • Each to be given one to two months apart • Repeat booster dose at 18 months • Repeat booster dose at 4-6 years • Every ten years thereafter • Give only small d after the age of 6 years of life
Diphtheria and Tetanus ToxoidsAdverse Reactions and contraindications Reactions • Local reactions (erythema, induration) • Exaggerated local reactions (Arthus-type) • Fever and systemic symptoms not common Contraindications Severe allergic reaction to vaccine component or following a prior dose Moderate or severe acute illness
Tetanus • First described by Hippocrates • Cl tetani Anaerobic gram-positive, spore-forming bacteria, Spores found in the environment, soil, animal feces; may persist for months to years • Multiple toxins produced with growth of bacteria • Tetanospasmin estimated human lethal dose = 2.5 ng/kg • It is not contagious to others • Clostridium tetani is present in the environment
Pathogenesis of tetanus • Anaerobic conditions allow germination of spores but there is little inflammation at the site of infection • The vegetative formof C tetani produces a potent plasmid-encoded exotoxin (tetanospasmin) • This binds to gangliosides at the myoneural junction of skeletalmuscle and on neuronal membranes in the spinal cord, blockinginhibitory impulses to motor neurons. • This Leads to unopposed muscle contraction and spasm. The movements mimic seizures
Tetanus Clinical Features • Incubation period; 8 days (range, 3-21 days) • The shorter the incubation period the more severe is the disease • Three clinical forms: local (uncommon), cephalic (rare), generalized (most common) • Generalized tetanus: descending symptoms of trismus (lockjaw), difficulty swallowing, muscle rigidity, spasms • Spasms continue for 3-4 weeks; complete recovery may take months • In the newborn only generalized tetanus occurs • Maternal vaccination during pregnancy provides maternal antibodies that cross the placenta and help provide antitoxin antibodies to the new born infant
Tetanus Complications • The disease lasts for weeks • Must be treated with antitoxin and antibiotics but contractions continue • Laryngospasm Fractures Hypertension • Nosocomial infections • Pulmonary embolism, Aspiration pneumonia • In the newborn often times the infants become malnourished and wasted
Tetanus vaccine (Tetanus Toxoid) • Formalin-inactivated tetanus toxin , Protein antigen • Schedule Initially Three or four doses + booster Booster every 10 years • Efficacy Approximately 100% • Duration Approximately 10 years • Vaccine content same for children and adults • Preferable administered with diphtheria toxoid as DTP, DTaP, DT, Td, or Tdap
Clean, minor wounds All other wounds Vaccination History Unknown or <3 doses 3+ doses Td TIG Yes No No* No Td TIG Yes Yes No** No post exposure wound prophylaxisTetanus Wound Management * Yes, if >10 years since last dose ** Yes, if >5 years since last dose Dose of TIG is 250 units regardless of age and weight
Pertussis • Highly contagious respiratory infection caused by Bordetella pertussis a fastidious gram negative bacterium, only humans • Outbreaks first described in 16th century • Bordetella pertussis isolated in 1906 • Estimated 285,000 deaths worldwide in 2001 • Recently increased in some parts • Transmission Respiratory droplets • Communicability Maximum in catarrhal stage Secondary attack rate up to 80%
Pertussis Pathogenesis • Attachment to cilia in respiratory tract leading to Local tissue damage in respiratory tract, Systemic disease may be toxin mediated, no bacteremia • Antigenic and biologically active components: • pertussis toxin (PT) • filamentous hemagglutinin (FHA) • agglutinogens • adenylate cyclase • pertactin • tracheal cytotoxin • NO Bacteremia
Pertussis Clinical Features • Incubation period 7-10 days (range 4-21 days) • Catarrhal stage 1-2 weeks • Paroxysmalcough stage 1-6 weeks • Convalescence Weeks to months • Fever usually minimal throughout course of illness unless complicated by superinfection • In adults and older children Infection may be asymptomatic, or may present as classic pertussis, these serve as sources of infection to children
Pertussis Complications* Condition Pneumonia SeizuresEncephalopathy Hospitalization Death Percent reported 5.2 0.8 0.1 20 0.2 *Cases reported to CDC 1997-2000 (N=28,187)
Pertussis Complications by Age *Cases reported to CDC 1997-2000 (N=28,187)
Pertussis vaccines • Both are inactivated vaccines • Whole cell (WC) or acellular pertussis (aP) • WC contraindicated after 6 years of age • Immunity decreases with time and hence re vaccination in older individuals is needed but with acellular smaller doses only • ONLY acellular P are allowed for use in adolescents and older individuals
Whole-Cell Pertussis Vaccine • Developed in mid-1930s and combined as DTP in mid-1940s • 70%-90% efficacy after 3 doses • Protection for 5-10 years • Fever 40% • Local reactions 35% • Seizures 1/1750 • HHE 1/1750 • Encephalopathy 1/110,000
Acellular Pertussis Vaccines • Local reactions (pain, redness, or swelling at the site of injection) • Local reactions more common following 4th and 5th doses • Reports of swelling of entire limb • Extensive swelling after 4th dose NOT a contraindication to 5th dose • Low-grade fever
Composition* of Acellular Pertussis Vaccines PT 10 25 23 8 2.5 FHA 5 25 23 8 5 PERT 3 8 -- 2.5 3 FIM 5 -- -- -- 5 ProductDaptacel Infanrix Tripedia Boostrix Adacel *mcg per dose
DTP/DTaP Contraindications • Severe allergic reaction to vaccine component or following a prior dose • Encephalopathy not due to another identifiable cause occurring within 7 days after vaccination • Progressive CNS disease
DTP/DTaP Precautions* • Moderate or severe acute illness • Temperature >105°F (40.5°C) or higher within 48 hours with no other identifiable cause • Collapse or shock-like state (hypotonic hyporesponsive episode) within 48 hours • Persistent, inconsolable crying lasting >3 hours, occurring within 48 hours • Convulsions with or without fever occurring within 3 days *may consider use in outbreaks
Poliomyelitis • First described by Michael Underwood in 1789 • Enterovirus, Strict human pathogen • Three serotypes: 1, 2, 3 • Minimal heterotypic immunity between serotypes • Rapidly inactivated by heat, formaldehyde, chlorine, ultraviolet light • Entry into mouth/ Replication in pharynx, GI tract, local lymphatics • Hematologic spread to lymphatics and central nervous system/Viral spread along nerve fibers • Destruction of anterior horn cell (motor neurons) with resultant paralysis
POLIOMYELITIS IN JORDAN 1978-2001 140 120 100 No. of Cases 80 60 40 20 0 1978 1979 1980 1981 1982 1983 1984 1985 1988 1989 1990 1991 1992 1993 1994 2001 Years Khuri-Bulos (bull WHO 1984)
History of Poliovirus Vaccine • 1955 Inactivated vaccine • 1961 Types 1 and 2 monovalent OPV • 1962 Type 3 monovalent OPV • 1963 Trivalent OPV • 1987 Enhanced-potency IPV (IPV)
Oral Polio Vaccine (Sabin) • Types 1,2,3 live vaccine • Shed in stool for up to 6 weeks • Shed for prolonged periods in immunecompromised individuals • Highly effective in producing immunity to poliovirus • 50% immune after 1 dose • >95% immune after 3 doses • Immunity probably lifelong • Immunity less in developing countries?? Other enteroviruses interfere with immunity • Induces both local and systemic immunity
Inactivated Polio Vaccine • Contains 3 serotypes of vaccine virus • Grown on monkey kidney (Vero) cells • Inactivated with formaldehyde • Highly effective in producing immunity to poliovirus • >90% immune after 2 doses • >99% immune after 3 doses • Duration of immunity not known with certainty • Does not induce high local intestinal immunity and allows for replication in the gut • Immune individuals can transmit the virus to others but are themselves immune and not sick