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29/04/62
1
Vaccination
Pinyo Rattanaumpawan; MD, MSCE, PhD
Division of Infectious diseases and Tropical Medicine,
Faculty of Medicine Siriraj Hospital, Mahidol University
Outline of Presentation
• Basic concepts of immunization
• Vaccines for all
• Vaccines for young adults
• Vaccines for elderly and persons with co-morbidities
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TYPE OF VACCINE
• Bacteria: – BCG – Typhoid (Ty 21a)
• Virus: – Flu mist – VZV – MMR – OPV – Yellow fever – JE – Dengue
Live Attenuated Inactivated/Killed
• Bacteria: – TT, dT, DTaP, Tdap – Meninogo, Pneumo
• Virus: – Flu shot – VZV (new) – IPV – HAV, HBV – HPV – Typhoid – JE
Recommended Adult Immunization Schedule by Age Group
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2019
Morbidity and Mortality Weekly Report (MMWR) / February 8, 2019 / 68(5);115–118
HPV9
<40 y
<60 y
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Recommended Adult Immunization Schedule by Conditions
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2019
Morbidity and Mortality Weekly Report (MMWR) / February 8, 2019 / 68(5);115–118
Outline of Presentation
• Basic concepts of immunization
• Vaccines for all
• Vaccines for young adults
• Vaccines for elderly and persons with co-morbidities
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Influenza vaccine
• Schedule: Single dose every year
• Influenza Vaccine – Flu Mist (live) or Flu shot (inactivated)
– Trivalent - 2 Flu-A and 1 Flu-B strains
– Quadrivalent – 2 Flu-A and 2-Flu B strains
• Recommendations: – All persons > 6 months
– IM shot: normal hosts, pregnancy, HCW
– ID shot: normal dose in age 18-64,
double dose in age >65
– Flu mist: non-pregnant normal hosts (2-49 years)
Best timing for Flu Vaccination
• Before onset of influenza activity in the community
• Waning effect - Greater in A(H3N2) > A(H1N1) or B1-2
1. Vaccine. 2017 Oct 13;35(43):5799-5807 2. Euro Surveill. 2016 Apr 21;21(16)
Southern hemisphere J F M A M J J A S O N D
Northern hemisphere
Tropical
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Influenza activity in Thailand
WHO 2018. Available at: http://www.who.int/influenza/gisrs_laboratory/flunet/charts/en/. Accessed 9 January 2019.
Recommended composition of Influenza virus vaccines by WHO Global
Influenza Surveillance Network
2017-2018 northern
hemisphere
2018 southern
hemisphere
2018-2019 northern
hemisphere
2019 southern
hemisphere
A/Michigan (H1N1) pdm
A/Michigan (H1N1) pdm
A/Michigan (H1N1) pdm
A/Michigan (H1N1) pdm
A/Hong Kong A/Singapore A/Singapore A/Switzerland
B/Brisbane B/Phuket B/Colorado B/Colorado
B/Phuket B/Brisbane B/Phuket B/Phuket/
http://www.who.int/influenza/vaccines/virus/recommendations/2017_18_north/en/ http://www.who.int/influenza/vaccines/virus/recommendations/2018_south/en/
http://www.who.int/influenza/vaccines/virus/recommendations/2018_19_north/en/
https://www.who.int/influenza/vaccines/virus/recommendations/2019_south/en/
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Comparison of Influenza Vaccines Available in Thailand
Type Composition Immuno-genicity
Reacto- genicity
Brand (available at siriraj)
Split-virion Surface protein + nucleocapsid + matrix prot.
+++ ++ Fluquadri (Sanofi), Vaxigrip (Sanofi), Fluarix (GSK)
Subunit Surface protein ++ + Aggripals (Biogenetech), Influvac (Abbot), GPO Flu (GPO)
Adjuvant Surface protein + adjuvant
++++ ++ Fluad (Biogenetech)
Intradermal Surface protein ++++ ++ Intanza (Sanofi)
Different Types of Flu Vaccines https://www.cdc.gov/flu/vaccines/index.htm, assesed 17 Feb 2019
CDC recommends annual flu vaccine for everyone > 6 mo. with any licensed, age-appropriate flu vaccine (IIV, RIV4, or LAIV4)
with no preference expressed for any one vaccine over another.
Diphtheria, tetanus & pertussis vaccines
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Re-emergence of Pertussis
• 18% of Thai adults with chronic cough (>1 mo.) had acute Pertussis infection
BMC Infect Dis. 2016 Jan 25;16:25
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Tetanus, diphtheria & acellular pertussis vaccine
• Recommendations: – 1 Tdap to all pregnant women (GA 27-36 wk) regardless
of vaccine history
– 1 Tdap to all adults who have not previously received Tdap or for whom vaccine status is unknown
– Adults with an unknown or incomplete Hx of 3-dose Td • Unvaccinated or unknown: 2 doses Td + 1 Tdap at 0,
4-6 weeks, 6-12 months • Incomplete: administer remaining doses.
Chicken pox
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Varicella vaccine
• 2 doses: 0, 1-2 mo.
•Recommendations: – Anyone without evidence of varicella immunity: • Hx of doctor dx of chicken pox and zoster,
• Complete vaccination or VZV Ab +
• Birthdate before 1980
– Special settings (At least 1 month before): • Close contact with immunocompromised patients • Pregnancy
Hepatitis B vaccine
• Schedule: 0, 1-2 mo, 6 mo
• Serologic test should be done before vaccination
• Recommendations:
– High-risk sexual behavior i.e. multiple partners, MSM
– DM (frequent DTX monitoring)
– ESRD, HIV, Chronic liver disease
– HCW
– Household members with HBsAg+ve patients
– International travelers to countries with high or intermediate prevalence of chronic HBV infection including Thailand
• Free for all children born after 1992
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Hepatitis B vaccine
• HIV-patients – Defer until CD4>200 (Better response if CD4>500) – May use high dose HBV (40 mcg) x 3-4 doses
• Hemodialysis or immunocompromised pts – 1 dose of 40 mcg/mL at 0,1, 6 mo. – 2 doses of 20 mcg/mL at 0, 1, 2, and 6 mo.
• Non-responder after 3-dose HBV vaccination – 50% response after 1 booster dose (amnestic response) – 75% response after 3 more doses
Outline of Presentation
• Basic concepts of immunization
• Vaccines for all
• Vaccines for young adults
• Vaccines for elderly and persons with co-morbidities
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MMR VACCINES
• Schedule: 0, +/-4 weeks
• Recommendations:
1. All without evidence of immunity of MMR
2. Second dose is required in
– Students in post secondary educational institutes
–HCW
– Plan to travel internationally (including Thailand)
HPV Infection & Cervical Cancer
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HPV vaccines
• Schedule: 0, 1-2 mo., 6 mo.
• HPV2 (Cervarix, HPV-16,18) – not approved in male • HPV4 (Gardasil, HPV-6, 11, 16, 18 ) • HPV-9 (Gardasil, HPV-6, 11, 16, 18, 31, 33, 45, 52, 58)
• USA data • HPV 6, 11: 90% condylomata & recurrent resp. papilloma • HPV 16 or 18: 80% CA cervix • HPV 31, 33, 45, 52, and 58: 12% CA cervix
• HPV testing is not necessary
HPV vaccines
• ACIP recommendations: • Female: 11-26 year
• Males : 13-21 years (optional in males 22-26 years)
• MSM: 13-26 years
• Pregnancy – should avoid
• Among girls (9-13 y), 2 doses HPV-4 was non-inferiority to conventional 3 doses1
• Persons who previously received 3-dose HPV 2
• ACIP did not routinely recommend HPV-9 revaccination
• Data indicated that revaccination with 9vHPV is safe • Cost/benefit should be discussed
1. JAMA 2013;309(17):1793-1802 2. http://www.immunize.org/askexperts/experts_hpv.asp
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CYD-TDY
• Age 2-14 years
• N= 10,275
• Asia countries (+Thailand)
• Efficacy against
• Symp. dengue = 56.5%
• Reduced hosp. = 67.2%
• Severe dengue = 80.0%
CYD-141 CYD-152
• Age 9-16 years
• N= 20,869
• Latin America & Caribbean
• Efficacy against
• Symp. dengue = 60.8%
• Reduced hosp. = 80.3%
• Severe dengue = 95.0%
Lancet. 2014 Oct 11;384(9951):1358-65 N Engl J Med. 2015 Jan 8;372(2):113-23
• Live-attenuated (recombinant) vaccine
• 3-dose series: 0, 6 and 12 months
• Recommended for age 9-45 yrs, in endemic area
Long term impact of CYD-TDY
• Sero+/Vaccine- 4.8 per 1000 persons
• Sero+/Vaccine+ <1.0 per 1000 persons
• Sero-/Vaccine- 1.7 per 1000 persons
• Sero-/Vaccine+ 4.0 per 1000 persons
Updated Questions and Answers related to the dengue vaccine Dengvaxia® and its use. Available from: http://www.who.int/immunization/diseases/dengue/q_and_a_dengue_vaccine_dengvaxia_use/en/
• ELISA Dengue IgG/IgM: underestimate dengue immunity
• PRNT-50 : more sensitive in immune pts. (vaccine/natural infection) • Anti-NS1: +ve only in natural infection
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Current recommendation
• WHO positioning paper 20161
• Use of Dengue vaccine in the highly endemic area
• Possibility of low efficacy and an elevated risk of severe dengue in vaccinated seronegative individuals
• IDAT recommendation 20172
• Recommend dengue vaccine in previously infected case
• Live in area with high seroprevalence
• Study among Thais (21-30 years) – PRNT50 + 50%
• Incomplete vaccination – discuss risk/benefit
1. Dengue vaccine: WHO position paper – July 2016 Available from: http://www.who.int/wer/2016/wer9130.pdf?ua=1
2. นะน ำจำกที่ประชุมผู้เช่ียวชำญด้ำนวัคซนีไข้เลือดออกซ฿งประกอบด้วยตวัแทนสมำคมโรคติดเช้ือเด็กแห่งประเทศไทย สมำคมโรคติดเช้ือแห่งประเทศไทย
กรมควบคุมโรค คณะกรรมกำรอำหำรและยำ ศูนย์วิจัยและพัฒนำวัคซีนมหำวิทยำลัยมหิดล ในวันที่ 7 ธันวำคม 2560
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Outline of Presentation
• Basic concepts of immunization
• Vaccines for all
• Vaccines for young adults
• Vaccines for elderly and persons with co-morbidities
Pneumococcal Vaccines
1. Pneumococcal polysaccharide (PPSV23)
• Broader serotype coverage but lower IR
• FDA approved for age > 2 years
• Schedule: 0, 5 yrs (if poor IR) and another dose after 65
2. Pneumococcal conjugate 13 valent (PCV13)
• Narrower serotype coverage but better IR
• FDA-approved for children 6 weeks or older
• Schedule: single dose
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Adults age 19-64 years with medical conditions
+ elderly > 65 y ✓ ✓
Recommendation based on Age and Underlying Diseases
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Zoster Incidence Among Elderly
http://www.cdc.gov/shingles/surveillance.html
Shingles Prevention Study (SPS) Efficacy of Zoster Vaccine
• 38,546 Adults (>60 y) with Hx of VZV +ve, HZ -ve
RR = 66.5% [47.5% – 79.2%]
Zoster RR = 51.3% [44.2%–57.6%]
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ZVL
• Lived-attenuated vaccine
• Reduced risk of shingle (51%) and PHN (67%)1
• FDA approve in age > 50 years (in 2006)
• CI: severe immunocom. hosts & pregnancy
ZVL efficacy wanes to zero 4–12 y after vaccination2
RZV
• Inactivated recombinant subunit vaccine (HZ/su)
• VZV glycoprotein E • New adjuvant AS01 • MPL (2 immunostimulants: 3-O-desacyl-4′-
monophosphoryl lipid A) • QS-21 (purified extract from the bark of the Quillaja
saponaria tree) • Higher gE-specific cell-mediated and HMIR
• Schedule: 2 doses - 0, 2 months (or 6 months)
• FDA approved in October 2017
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Immunogenicity and Safety of RZV in Adults Previously Vaccinated with ZVL
• Open-label , age-match phase-3 study (n=430)
• Age ≥65 years with previous hx of ZVL (≥ 5 y interval)
• Two doses of RZV IM at 0, 2 months
J Infect Dis. 2017;216:1343-1351.
RZV induces a strong immune response irrespective of prior ZVL vaccination
Landmark trials of RZV
• Phase-3 RCT
• Age ≥ 50 years
• Two doses of HZ/su IM at 0, 2 months VS. Placebo
• Results: • N=15,411, mean f/u 3.2 y
• HZ episode = 0.3 VS. 9.1/1,000 py
• VE for HZ = 97.2% [93.7 -99.0]
• ADRs: 17% vs. 3.2%
ZOE-50 ZOE-70
• Phase-3 RCT
• Age ≥ 70 years
• Two doses of HZ/su IM at 0, 2 months VS. Placebo
• Results:
• N=13,900, mean f/u 3.7 y
• HZ episode = 0.9 VS. 9.2/1,000 py
• VE for HZ = 89.8% [84.2-93.7]
• VE for PHN = 88.8% [98.7-97.1]
• ADRs: 79% VS. 29.5%
N Engl J Med. 2016;375:1019-1032. N Engl J Med. 2015;372:2087-2096.
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MMWR 2019 recommendation
• Age ≥ 50 years:
– 2-dose RZV (2–6 mo. apart, minimum 4 wk, at least 2 mo. after ZVL)
• Age ≥ 60 years:
– 2-dose RZV (2–6 mo. apart, minimum 4 wk, at least 2 mo. after ZVL)
– 1 dose ZVL
– RZV preferred over ZVL
• Severe immunocompromised hosts: ZVL is contraindicated
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2019
Morbidity and Mortality Weekly Report (MMWR) / February 8, 2019 / 68(5);115–118
Meningococcal Vaccines
1. Meningococcal polysaccharide quadrivalent (MPSV4)
A,C,Y,W-135 FDA-approved age: 11- 55 y Booster q 5 y if high risk Need 2 doses (0, 2 mo.) if IR
2. Meningococcal conjugate quadrivalent (MCV4)
A,C,Y,W-135 FDA-approved age: > 2 y Single dose
Serogroups Locations
B Thailand
B and C Europe and USA
A and C Asia and Africa
W-135 Meningitis Belt
Y Israel and Sweden
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Haemophilus influenzae type B (HIB) vaccine
• Recommendations: – Single dose:
• Surgical or functional asplenia
• Sickle cell anemia
• Elective splenectomy (4 weeks prior)
– 3- doses (0, 2, 4 months)
• Post stem cell transplantation (6 mo. After)
Hepatitis A Vaccine
• Serology should be done prior to vaccination
• Schedules: two doses (0, 6-12 months)
• Recommendations: 1. MSM
2.IVDU
3.Contact to HAV (i.e. in lab)
4.Chronic liver disease
5.Persons who receive clotting factor concentrates
6.Persons who travel to an endemic area (i.e. Thailand!!)
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IDAT 2018 Recommendation
IDAT 2018 Recommendation
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IDAT 2018 Recommendation
Siriraj price list- 2019
Recommended vaccines
THB Optional Vaccines THB
Flu shot (trivalent) 184 Dengue 3,055
Flu shot (quadrivalent) 292 Lived JE 439
dT 34 Killed JE 430
Tdap 580 HPV2 2,166
MMR 338 HPV4 2,171
HAV 1,096 MCV4 2,550
HBV 197 PPSV23 1,134
HBV/HAV 929 PCV13 2,466
Varicella 880 ZVL 5,119
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Rabies Prophylaxis
Cat-1: PrEP
Cat-2: PEP
Cat-3: PEP+RIG
• Cat-1: touching or feeding animals, licks on intact skin
• Cat-2: minor scratches or abrasions without bleeding
• Category III: transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal
Rabies vaccines and immunoglobulins: WHO position summary of 2017 updates
Conventional regimen New WHO regimen
• 1-IM on D0, 7, 21/28 • 1-IM on D0, 7 • 2-ID on D0, 7
Pre-exposure prophylaxis (PrEP)
PEP after PrEP • 1-IM on D0, 3 • 1-ID on D0, 3 • 4-ID on D0 • RIG is not required • No need for additional dose
for repeated exposure <3 mo.
Rabies vaccines and immunoglobulins: WHO position summary of 2017 updates
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Conventional regimen New WHO regimen
• 1-IM on D0, 3, 7, 14, 28 • 2-IM on D0 +
1-IM on D7, 21
• 2-ID on D0, 3, 7
Note: • ERIG 40 IU/Kg (1000 IU/vial) • HRIG 20 IU/Kg (300 IU/vial) • Within 7 days after 1st dose of vaccine
Post-exposure prophylaxis (PEP)
Rabies vaccines and immunoglobulins: WHO position summary of 2017 updates
Contact: [email protected]
FB page: Siriraj Infectious Disease Conference