Chonnamet Techasaensiri, MD Division of Infectious Diseases Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Outlines

• General principles for immunization • for health care providers • Other vaccines for adults • Vaccines related complications General Principles for Immunization Type of Immunization

• Passive immunization • Administration of performed antibody that can prevent or treat infectious diseases: • Immune globulin (human origin), antitoxin (animal origin) • Active immunization • Vaccines Immune Globulins Prepared from Human Plasma

Nonproprietary Name Abbreviation For intramuscular administration Immune globulin IG Hepatitis B immune globulin HBIG Tetanus immune globulin TIG Varicella-zoster immune globulin VZIG/VariZIG

For intravenous administration Immune globulin intravenous IGIV Cytomegalovirus immune globulin intravenous CMV-IGIV Botulism immune globulin intravenous BIG-IGIV Vaccinia immune globulin intravenous VIG-IGIV Antibodies of Animal Origin (Animal Antisera)

• Botulism antitoxin • Diphtheria antitoxin • Tetanus antitoxin Type of Vaccines

• Live attenuated vaccines: MMR,varicella, JE, OPV, rotavirus, influenza (intranasal) • vaccines: d/D, T • Component vaccines eg. polysaccharide or polypeptide: Hib, PCV, MPSV • Inactivated (killed) vaccines: rabies, JE, wP, influenza, Ty • Surface Ag (recombinant) vaccines: HBV SARS-CoV-2 Candidates

Vaccine Platforms Vaccine Candidates Viral vector DNA (nonreplicating) Coronavirus Other DNA spike gene Viral vector RNA Virus genes (replicating) (some inactive) 10 Viral vector 12 RNA (+ LNPs) Coronavirus (replicating) 14 spike gene 20 Virus genes Viral vector SARS-CoV-2 (some inactive) (nonreplicating) live 16 3 Virus attenuated (inactivated) 8 Protein based (eg, spike)

Virus 44 SARS-CoV-2 (attenuated) inactivated

Protein based Funk. Frontiers in Pharmacology. 2020; 11:937. Slide credit: clinicaloptions.com Immunization Successes

Vaccine Area Smallpox eradication Worldwide Polio elimination Most of world Measles elimination U.S. Rubella elimination U.S. Expanded Program on Immunization and Pilot Project: Ministry of Public Health, Thailand

Age Vaccines BCG 2013 Live JE Birth HBV1 2 mos DTP-HB-Hib1, OPV1, Rota 2014 HPV 4 mos DTP-HB-Hib2, OPV2, IPV, Rota 2015-2016 IPV, bOPV 6 mos DTP-HB-Hib3, OPV3, Rota 9 mos MMR1

2019 Hib 1 ½ yrs DTP4, OPV4, JE1, MMR2 2 ½ yrs JE2 2020 Rota 4 yrs DTP5, OPV5 11 yrs HPV 12 yrs (gr 6) dT General Recommendation for Immunization • Facilities for immediate allergic reaction, observation 15-20 mins after immunization for syncope and allergic reaction • Multiple vaccines should be given on separate sites, at least 1 inch apart • 28-day minimum interval for >2 live injectable vaccines if not given at the same visit (except OPV, )

CDC. MMWR 2011;60(2):1-61. General Recommendation for Immunization • Minor illness is not a contraindication for immunization • Lapsed immunization • Continue to complete series • No need for re-immunization • Vaccine doses should not be administered at intervals less than minimum intervals or at an age younger than the minimum age suboptimal immune response

CDC. MMWR 2011;60(2):1-61. General Recommendation for Immunization • Vaccine administered <4 d before the minimum interval or age are considered valid except for • Vaccine administered >5 days earlier than the minimum interval or age • Should not be counted as valid doses • Should be repeated as age appropriate

CDC. MMWR 2011;60(2):1-61. Catch-Up Schedule

https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf Catch-Up Schedule

https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf Recommended Intervals Between Receipt of Blood Products and Administration of Live Vaccine

Redbook 2021-2024 32nd Edition Recommended Intervals Between Receipt of Blood Products and Administration of Live Vaccine

Redbook 2021-2024 32nd Edition Live Vaccine During Corticosteroid Treatment

Corticosteroid Therapy Live virus vaccination Topical, aerosol Yes • With evidence of immune No suppression Physiologic maintenance Yes Low or moderate dose Yes High dose* • <14 days Yes after cessation of steroid treatment • >14 days Yes at >1 mo after cessation Immunocompromised host No * High dose: >2 mg/kg/day prednisolone or its equivalent, or >20 mg/day if BW >10 kg Post-exposure Vaccination

• Varicella: <120 hours “may prevent or modify” • Measles: <72 hours “may prevent or modify” • Tetanus: with/without TIG • Rabies: with/without RIG • Hepatitis B: with/without HBIG • Hepatitis A: up to 2 weeks Minimum Intervals for Different Vaccines

• Live-live • 4 weeks if not simultaneous • Live-inactivated • No minimum • Inactivated-inactivated • No minimum Interchangeability of Different Brands of Vaccines • Hib • PRP-T, PRP-OMP, HbOC: Interchangeable if use 4 dose regimen • DTaP • When feasible, same brand • Orginal not available or known – any • 4th and 5th: any product • Hep B: Interchangeable on regular schedule • Hep A: Interchangeable Interchangeability of COVID-19 Vaccines • Inactivated – Viral vector vaccines • Viral vector – mRNA vaccines • mRNA – Viral vector vaccines

Vaccines for Health Care Providers Vaccines for Health Care Providers

• Measles, , • • • Tdap vaccine • : Annually • COVID-19 vaccine MMR For Health Care Providers • Most individuals born prior to 1977 were likely infected naturally and can generally be presumed immune. • However, for unvaccinated health care providers born after 1977 who lack laboratory evidence of measles immunity, vaccination with 2 doses of MMR given at least 28 days apart should be considered. MMR Vaccines in Thailand

Name (Company) Measles Rubella Mumps MMR (Masu) Edmonston- Wistar RA L-Zagreb Zagreb 27/3M strain Priorix (GSK) Schwarz Wistar RA Modified Jeryl 27/3M strain Lynn MMR II (MSD) Ender’s Wistar RA Jeryl Lynn 27/3M strain MMR Efficacy

• Seroconversion after MMR vaccination • Measles: 95% after 1 dose, >99% after 2 doses • Rubella >95%, confer long-term immunity, probably lifelong • Mumps • Jeryl-Lynn 61.6-80.7% • Urabe 54.4-73.1% • Rubini 55.3%

Ong G, et al. J Infect. 2005;51(4):294-8. Bonnet MC, et al. Vaccine. 2006;24:7037-45. Richard JL, et al. Eur J Epidemiol. 2003;18(6):569-77. Mumps Vaccines: Adverse events

Strain Aseptic meningitis Parotitis

Jeryl Lynn 0/1,800,000 - 1/950,000 0.5%

L-Zagreb 1/55,000 - 1/3,300 3.1%

Urabe 1/69,000 – 1/400 1.3%

A Review for the Global Advisory Committee on Vaccine Safety. W.H.O. June, 2003 MMR: Contraindications

• Previous anaphylactic reaction to MMR or its components • Pregnancy or possibility of pregnancy within 4 wks • Severe immunodeficiency

Patient with egg allergy can receive MMR vaccine Varicella Vaccine for health Care Providers

• Positive history of varicella: No need for varicella vaccine • Negative history of varicella vaccine and disease: Check varicella IgG • If negative varicella IgG: Varicella vaccine 2 doses, 4-8 weeks apart Product VarilrixTM VarivaxTM Varicella GCCTM Vaccine OKA/ GSK OKA/ Merck MAV/06 strain Indication >12 months of age Schedule 2 doses 1-12 yrs: First dose at 12-15 months Second dose at 2.5-6 years >13 yrs: 4 wks apart Formulation Licensed 19844 Licensed 19955 Refrigerator Form

Refrigerator Form Refrigerator Form Since 1994 since 2000 Minimum Expire 2,000 PFU 1,350 PFU 1,400 PFU Date of PFU Thermostability 90 min at 25◦C 30 minutes post 30 minutes post (post 8 hrs at 2-8◦C reconstitution reconstitution reconstitution)

1. VarilrixTM Prescribing Information 2.VarilvaxTM Prescribing Information 3.Varicella GCC TM Prescribing Information 4. Kreth HW, Lee BW, Kosuwon P, Salazar J, Barzaga NG, Bock HL, et al. Sixteen Years of Global Experience with the First Refrigerator-Stable Varicella Vaccine (VarilrixTM). BioDrugs 2008;22:387-402. 5. Marin M, Guris D, Chaves SS, Schmid S, Seward JF, MBBS CDC. Prevention of Varicella Recommendation of the Advisory Committee on Immunization Practice (ACIP), MMWR 2007;56:1-37 6. VarilvaxTM Summary of Product Characteristics 2014 32 Random effects model of 1-dose varicella VE for prevention of all varicella, by vaccine

Marin M, et al. Pediatrics. 2016;137(3):e20153741. Random effects model of 1-dose varicella VE for prevention of combined moderate and severe varicella, by vaccine

Marin M, et al. Pediatrics. 2016;137(3):e20153741. Marin M, et al. Pediatrics. 2016;137(3):e20153741. In Korea, more than half of all vaccinees were immunized with vaccine A, derived from an MAV/06 strain of varicella isolated from a 33-month-old Korean boy in 1989 Lee YH. J Korean Med Sci 2016; 31: 1897-1901 HBV for Health Care Providers

• Prevaccination serology (with anti-HBs, anti-HBcAb, and HBsAg) is indicated in previously non-immunized health care providers born before 1992 • Anti-HBs level is ≥10 mIU/mL: Immunity to Hepatitis B • Anti-HBs titer is <10 mIU/ML: Should receive a dose of HBV and have anti-HBs titers repeated in 1-2 months. • Anti-HBs titer is <10 mIU/ML: Should receive 2 more doses of HBV and have anti-HBs titers repeated in 1-2 months. Follow-Up Testing After Immunization • Anti-HBs in 1-2 months after receiving their final dose of vaccine • Anti-HBs level is ≥10 mIU/mL: Vaccine responder • Anti-HBs titer is <10 mIU/ML: Should receive a course of HBV and have anti-HBs titers repeated in 1-2 months. • If the anti-HBs is still <10mIU/mL, the HCP is considered a vaccine nonresponder and should receive HBIG if postexposure prophylaxis is required. Testing for Anti-HBs 1-2 Months After Vaccination

• Routine: not indicated • Recommended for • Infants: HBsAg +mothers • Hemodialysis patients • HIV-infected persons • People at occupational risk of exposure from needlestick injuries • Immunocompromised patients at risk of exposure to HBV Repeat a series of vaccination in non-responders DTP

• Diphtheria outbreak in Southern and Northeast Thailand in 2012 • In Thailand pertussis is still present esp. in adolescents and adults, but hard to make diagnosis • Tetanus have been rare in Thailand • TT should have been replaced by dT (10-25% of Thai adolescents and adults are susceptible to diphtheria) • DTwP-HB-Hib has been used widely in EPI • Still found problems of adverse events following immunization (AEFI) >> rationale for widely use of DTaP Pertussis in Thai Adults

• Thai adults >18 years with prolonged cough >2 weeks • 18.4% (14 of 76 patients) with the mean age of 59 years, had laboratory evidence of acute pertussis • One patient was diagnosed by the PCR method, while the rest had serological diagnosis

Siriyakorn N, et al. BMC Infect Dis. 2016;16:25-30. Tdap Vaccination in Adults

• Administer one dose of Tdap vaccine to pregnant women during each pregnancy (preferred during 27–36 weeks’ gestation), regardless of number of years since prior Td or Tdap vaccination. • Administer Tdap to all other adults who have not previously received Tdap or for whom vaccine status is unknown. • Tdap can be administered regardless of interval since the most recent tetanus or diphtheria-toxoid containing vaccine. • Tdap should be offered to all adolescent and adults every 10 years

MMWR 2013;62(Suppl 1) Diphtheria – Tetanus - Pertussis

Vaccine Age Recommended DTwP 2 mos – 6 yrs DTaP 2 mos – 6 yrs DT 2 mos – 6 yrs Tdap >7 yrs dT >7 yrs Influenza Vaccine

• Trivalent inactivated influenza vaccine • Split virion: FluarixTM, VaxigripTM • : Agrippal S1TM, InfluvacTM, InflexalTM • Quadrivalent inactivated influenza vaccine • Split virion: FluquadriTM, Fluarix tetraTM, Vaxigrip tetraTM • Cell based: SKYCellfluTM Recommended composition of influenza virus egg-based vaccines

Type 2020-2021 Northern 2021 Southern 2021-2022 Northern

A/H1N1 A/Guangdong- A/Victoria/2570/2019 A/Victoria/2570/2019 Maonan/SWL1536/2019

A/H3N2 A/Hong Kong/2671/A2019 A/Hong Kong/2671/2019 A/Cambodia/e0826360/2020

B/Victoria B/Washington/02/2019 B/Washington/02/2019 B/Washington/02/2019

B/Yamagata B/Phuket/3073/2013 B/Phuket/3073/2013 B/Phuket/3073/2013

https://www.who.int/influenza/vaccines/virus/recommendations/2021-22_north/en/ Recommended composition of influenza virus cell- or recombinant-based vaccines

Type 2020-2021 Northern 2021 Southern 2021-2022 Northern

A/H1N1 A/Hawaii/70/2019 A/Wisonsin/588/2019 A/Wisonsin/588/2019

A/H3N2 A/Hong Kong/2671/A2019 A/Hong Kong/2671/2019 A/Cambodia/e0826360/2020

B/Victoria B/Washington/02/2019 B/Washington/02/2019 B/Washington/02/2019

B/Yamagata B/Phuket/3073/2013 B/Phuket/3073/2013 B/Phuket/3073/2013

https://www.who.int/influenza/vaccines/virus/recommendations/2021-22_north/en/ Influenza Vaccine: Recommendation

• Persons at high risk for influenza complications • Aged 6 mos – 4 yrs, >65 yrs • Person with medical conditions, immunosuppression, conditions that compromise respiratory function • Residents of chronic-care facilities • Receiving long term aspirin therapy • Pregnant women • Obesity • Health care personnel • House hold contacts of high risk persons Influenza Vaccine

• Influenza vaccine can be successfully administered to egg allergic individuals • There is no evidence that egg ovalbumin is the antigen responsible for adverse reactions to TIV in egg allergic individuals • Most manufacturers use the lowest ovalbumin content

Only anaphylaxis type of egg hypersensitivity that vaccine should be held

Greenhawt MJ, Li JT. AAAAI. October 2010. Other Vaccines for Adults Japanese Encephalitis Vaccines

Characteristics CD-JEVAX® IMOJEV® JEVAC®

Live/inactivated Live-attenuated Live-attenuated Inactivated

Vaccine strain SA14-14-2 SA14-14-2 Beijing P-3

Cell growth PHK Vero cells Vero cells

Dosing primary Single dose Single dose 2 doses D0,D28

Booster schedule Booster after 3-12 Booster after 12 to Booster after 1 year months 24 months*

* Adults: no need for a booster dose Pediatrics (>9 months): a booster dose should be given in order to confer long term protection Hepatitis A Vaccines

Characteristics HavrixTM AvaximTM VaqtaTM HealiveTM Mevac-ATM

Live/inactivated Inactivated Inactivated Inactivated Inactivated Live- attenuated

Vaccine strain HM175 GBM CR326 TZ84 H2

Dose in 0.5 ml 0.5 ml 0.5 ml 0.5 ml 0.5 ml children (1-18 yrs) (1-15 yrs) (1-17 yrs) (1-16 yrs)

Dose in adults 1 ml 1 ml 1 ml 1 ml 0.5 ml (>19 yrs) (>16 yrs) (>18 yrs) (>16 yrs)

Dosing 2 doses D0, 2 doses D0, 2 doses D0, 2 doses D0, Single dose schedule M6-12 M6-12 M6-12 M6-12 Comparison of Anti-HAV IgG Positivity From 1971 to 2014

Sa-nguanmoo P, et al. PLoS One. 2016;11(3):e0151304. Pneumococcal Conjugate (PCV) and Polysaccharide (PPSV) Vaccines

Pneumococcal conjugate vaccines

Protein Carriers:  Protein D SynflorixTM 4 6B 9V 14 18C‡ 19F† 23F 1 5 7F  †Diphtheria toxoid  ‡Tetanus toxoid

Protein Carrier: Prevnar13TM 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A CRM197

Pneumococcal polysaccharide vaccine

2 9N 11A 15B 20 4 6B 9V 1 3 Pneumov 33F 14 5 ax 23TM 8 10A 12F 17F 22F 18C 19F 23F 7F 19A

Klugman K, et al. Vaccine 2011;295:C43-48. Comparison of Polysaccharide & Conjugate Vaccines

Property Conjugate Polysaccharide

T-cell dependent immune response Yes No (response by children <2 yo) Immune memory Yes No

Lack of hyporesponsiveness Yes No

Booster effect Yes No

Persistence of protection Yes No

Herd immunity Yes No

Reduction of nasopharyngeal carriage yes No of bacteria Pichichero M. Consultant for Pediatricians 2005;June:263-7. Indications for PCV13 and PPSV23 Administration and Revaccination for Children 6–18 years

** Including chronic obstructive pulmonary disease, emphysema, and asthma CDC. MMWR 2013;62 (25):521-4. Common Medical Conditions Increase Pneumococcal Pneumonia Risk in Adults

Data from a retrospective cohort study from 3 large, longitudinal, US health care databases of medical and outpatient pharmacy claims from 2007–2010* 600 7.7x

18–49 years 516 500 50–64 years Risk vs healthy 5.9x ≥65 years population) 4.9x 398 400 4.6x

,000 ,000 4.3x 4.0x 330 Incidence 3.8x 3.9x 305 287 100 300 264 266

2.8x 254 248 (n per per (n 200 1.9x 187 148 136 128 124 126 106 111 108 116 90 76 81 100 67 72 63 61 51 52 39 44 42 25 14 0 None Chronic Diabetes Chronic Smokers Rheumatoid Chronic Alcoholism Neuro- Asthma Chronic use of oral heart arthritis/ liver muscular/ lung steroids disease Crohn’s/ disease seizure disease Comorbidity risk group lupus disorders *Persons aged 18–49 years, 50–64 years, and ≥65 years contributed a total of 49.3 million, 30.6 million, and 11.7 million person-years of observation, respectively.

1. Shea KM, et al. Open Forum Infect Dis. Published online May 8, 2014. doi:10.1093/ofid/ofu024. ซีโรทัยป์ที่พบบ่อยที่เป็นสาเหตุของการเกิดไอพีดี ในประเทศไทย (ทุกอายุ) ปีค.ศ.1998-2008

PPV23 ร้อยละ70

PCV13 ร้อยละ 68 จานวนสายพันธุ์

ซีโรทัยป์ จากเช้ ือท้งั หมด 598 สายพันธุ์ Adapted from Dejsirilert S, et al. Poster presentation 7th ISPPD, 2010, Tel aviv, Israel ACIP Recommended pneumococcal and intervals, by age, health condition, and other risks

No health Immuno- Anatomical or CSF leak or condition compromising functional cochlear implant or other risk condition asplenia

Chronic Smoker or health resident of PCV13 condition long-term PCV13 Adults care facility aged > 8 weeks 19-64 > 8 weeks years PPSV23 PPSV23 > 5 years

> 1year > 5 years PPSV23

> 5 years Adults PCV13 aged When both PCV13 and PPSV23 are >65 > 1year indicated, administer PCV13 first (PCV13 years and PPSV23 should not be administered PPSV23 during the same visit)

*Advisory Committee on Immunization Practice https://www.cdc.gov/vaccines/schedules/downloads/adult/adult-combined-schedule.pdf Adapted from Kim DK, et al. Ann Intern Med 2015;162:214-233. Adults Immunization Schedule, IDAT

http://www.idthai.org http://www.idthai.org60 HPV Vaccines

Petrosky E, et al. MMWR Morb Mortal Wkly Rep. 2015;64:300-4. THE 9 HPV TYPES CAUSE THE MAJORITY OF HPV-RELATED CANCERS AND DISEASES

a a a a a aValues are approximate. Not all cervical precancers and lesions, vulvar, vaginal, and anal cancer cases are caused by HPV. 1. de Sanjosé S et al. Lancet Oncol. 2010;11:1048–1056. 2. de Sanjosé S et al. Eur J Cancer. 2013;49:3450–3461. 3. Alemany L et al. Eur J Cancer. 2014;50:2846‒2854. 4. Alemany L et al. Int J Cancer. 2015;136:98–107. 5. Joura EA et al. Cancer Epidemiol Biomarkers Prev. 2014;23:1997−2008. 6. Garland SM et al. J Infect Dis. 2009;199:805–814. 9v-HPV: Efficacy

Petrosky E, et al. MMWR Morb Mortal Wkly Rep. 2015;64:300-4. TETRAVALENT * CONSTRUCT

• There are 4 genetic constructs, 1 for each serotype • The envelope (E) and precursor membrane (prM) genes from each serotype were combined with the genes encoding the capsid and nonstructural proteins from the yellow fever (YFV 17D) vaccine strain • The 4 recombinant, live, attenuated dengue viruses are combined into a single vaccine which is freeze-dried and contains no adjuvant or preservatives Guirakhoo, 2001, J Virol. Guirakhoo, 2000, J Virol. *Vaccine referred to in the literature as Chimeric Yellow Fever 17D-Tetravalent Dengue Vaccine (CYD-TDV). Guy, 2011, Vaccine. CONSISTENT EFFICACY PROFILE OF CYD 14 & CYD 15 STUDIES IN SUBJECTS 9–16 YEARS OF AGE DURING ACTIVE PHASE Key Efficacy Results 25-month active phase* Pooled efficacy analyses‡1

Reduction in Reduction in Reduction in symptomatic dengue hospitalized dengue severe dengue † 65.6% 80.8% 93.2% (95% CI: 60.7–69.9) (95% CI: 70.1–87.7) (95% CI: 77.3–98.0)

For each serotype:

. DENV-1: 58.4% (95% CI: 47.7–66.9)

. DENV-2: 47.1% (95% CI: 31.3–59.2) . DENV-3: 73.6% (95% CI: 64.4–80.4) . DENV-4: 83.2% (95% CI: 76.2–88.2) By dengue serostatus: . Seropositive: 81.9% (95% CI: 67.2–90.0) . Seronegative: 52.5% (95% CI: 5.9–76.1)

*Data come from the 2 pivotal, phase III, large-scale efficacy trials CYD14 and CYD15, which were designed to fully assess efficacy; postdose 1; 1Full Analysis Set for Efficacy (FASE): all subjects who received at least one injection. †dengue hemorrhagic fever, World Health Organization 1997 criteria. CI=confidence interval; DENV=dengue virus.

1.Hadinegoro, 2015, N Engl J Med. คำแนะน ำเพื่อเป็นแนวทำงในเวชปฏิบัติกำรใช้วัคซีนไข้ เลือดออก (Denvaxia)โดยสมำคมโรคติดเชื้อในเด็กแห่งประเทศไทยและ สมำคมโรคติดเชื้อแห่งประเทศไทย วันที่ 26 ธันวำคม 2560 คำแนะน ำเพื่อเป็นแนวทำงในเวชปฏิบัติกำรใช้วัคซีน ไข้เลือดออก (Denvaxia)

• ในผู้ที่เคยติดเชื้อมำก่อน (seropositive) 1,000 คน เมื่อฉีดวัคซีนจะป้องกันกำรนอน โรงพยำบำลจำกไข้เลือดออกได้ 15 คนและป้องกันไข้เลือดออกรุนแรง (ซึ่งหมำยรวมถึง DHF grade I, II, III, IV, และ severe dengue อื่นๆ) ได้ 4 คน ในเวลำ 5 ปี • ในผู้ที่ไม่เคยติดเชื้อมำก่อน (seronegative) 1,000 คน เมื่อฉีดวัคซีนจะทำให้ มีโอกำสเพิ่มกำร นอนโรงพยำบำลจำกไข้เลือดออก 5 คนและเพิ่มกำรเป็นไข้เลือดออกรุนแรง (ซึ่งหมำยรวมถึง DHF grade I, II, III, IV, และ severe dengue อื่นๆ) 2 คน ในเวลำ 5 ปี คำแนะน ำเพื่อเป็นแนวทำงในเวชปฏิบัติกำร ใช้ วัคซีนไข้เลือดออก (Denvaxia) สำมำรถประมำณควำมเสี่ยงของกำรจะเกิดไข้เลือดออกรุนแรง (severe dengue) ในเวลำ 5 ปี ได้ดังนี้ • ผู้ที่ seropositive และได้รับวัคซีน โอกำสเกิด น้อยกว่ำ 1 ต่อ 1,000 คนที่ฉีดวัคซีน • ผู้ที่ seropositive และไม่ได้รับวัคซีน โอกำสเกิด เท่ำกับ 4.8 ต่อ 1,000 คนที่ไม่ได้ฉีดวัคซีน • ผู้ที่ seronegative และได้รับวัคซีน โอกำสเกิด เท่ำกับ 4 ต่อ 1,000 คนที่ฉีดวัคซีน • ผู้ที่ seronegative และไม่ได้รับวัคซีน โอกำสเกิดเท่ำกับ 1.7 ต่อ 1,000 คนที่ไม่ได้ฉีดวัคซีน ZOSTAVAX™ [ Live (Oka/Merck)] Indications and Contraindications

• ZOSTAVAX is indicated for vaccination of adults aged 50 years and older for Indications* • Prevention of herpes zoster (HZ) • Prevention of postherpetic neuralgia (PHN) • Reduction of acute and chronic HZ-associated pain

• History of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine Contra- • Immunosuppression or immunodeficiency indications • Active untreated tuberculosis • Pregnancy ZOSTAVAX™ [Zoster Vaccine Live (Oka/Merck)] Reduced HZ Incidence in Adults Aged ≥60 Years in SPS

Efficacy 51.3% 63.9% 37.6% (95% CI) (44.2%–57.6%) (55.5%–70.9%) (25.0%–48.1%)

700 642 Placebo 600 ZOSTAVAX

500

400 334 315 308

300 Number of HZcases of Number 193 200 122 100

0 (n=19,247) (n=19,254) (n=10,356) (n=10,370) (n=8,891) (n=8,884) All Subjects1 Aged 60–69 Years1,2 Aged ≥70 Years 1,2

• CI=confidence interval; HZ=herpes zoster. • 1. Oxman MN et al. N Engl J Med. 2005;352:2271–2284. 2. Oxman MN et al. J Infect Dis. 2008;197(Suppl 2):S228–S236. ZOSTAVAX™ [Zoster Vaccine Live (Oka/Merck)] Reduced PHN Incidence in Adults Aged ≥60 Years in SPS1,a

Efficacy 66.5% 65.7% 66.8% (95% CI) (47.5%–79.2%) (20.4%–86.7%) (43.3%–81.3%)

100 Placebo ZOSTAVAX 80 80

60 57

40 27 23 Number of HZ cases with PHN with cases HZ of Number 19 20 8

0 (n=19,247) (n=19,254) (n=10,356) (n=10,370) (n=8,891) (n=8,884) All Subjects Aged 60–69 Years Aged ≥70 Years

• CI=confidence interval; HZ=herpes zoster; PHN=postherpetic neuralgia. • aPHN was defined as HZ-associated pain rated as ≥3 on a 10-point scale and persisting or appearing at least 90 days after rash onset. • 1. Oxman MN et al. N Engl J Med. 2005;352:2271–2284. Adults Immunization Schedule, IDAT

http://www.idthai.org Guideline for Rabies Exposure Prophylaxis

2018 2018 2018

73 Guideline for Rabies Exposure Prophylaxis

2018 2018 2018 Pre Exposure Prophylaxis (PREP) IM 1-1 IM 1-1 IM 1-1 Day 0-7 Day 0-7 Day 0-7 ID 2-2 ID 2-2 ID 2-2 Day 0-7/21 Day 0-7 Day 0-7 **For special risk person **For special risk person IM 1-1-1 IM 1-1-1 ID 1-1-1 Day 0-7-21/28 Day 0-7-21/28

Source: แนวทางการดูแลรักษาผู้สัมผัสโรคพิษสุนัขบ้า, สถานเสาวภา สภากาชาดไทย พ.ศ.2561 และคาถามที่พบบ่อย , แนวทางเวชปฏิบัติโรคพิษสุนัขบ้า และคาถามที่พบบ่ อย พิมพ์ครั้งที่ 6, 2561, สานักโรคติดต่อทั่วไป กรมควบคุมโรค กระทรวงสาธารณสุข, WHO Expert Consultation on Rabies, 2018, WHO TRS 1012 Categories of exposure and post exposure prophylaxis

WHO Type of contract with a suspect or confirmed rabid animal Recommended Category treatment

. Touching or feeding animals, . Touching or feeding animals, . Touching or feeding animals, No treatment . licks on intact skin, contact of . licks on intact skin, contact of . licks on intact skin I intact skin with secretions or intact skin with secretions or excretions of a rabid animal or excretions of a rabid animal or human human . Nibbling of uncovered skin . Nibbling of uncovered skin . Nibbling of uncovered skin Vaccine should be . Minor sickness or abrasions . Minor sickness or abrasions . Minor scratches or abrasions injected as soon as without bleeding without bleeding without bleeding possible II . Eats raw products from rabid animal

. Single or multiple transdermal . Single or multiple transdermal . Single or multiple transdermal Vaccine and RIG bites or scratches, Lick on bites or scratches, Lick on broken bites or scratches should be broken skin. skin. . Contamination of mucous administered as . Contamination of mucous . Contamination of mucous membrane with saliva from soon as possible III membrane with saline membrane with saline (i.e. licks, licks . Exposure to bat eats raw products from rabid . Licks in broken skin animal) . Exposure to bat . Exposure to bat

แนวทางการดูแลรักษาผู้สัมผัสโรคพิษสุนัขบ้า, สถานเสาวภา สภากาชาดไทย พ.ศ.2561 และคาถามที่พบบ่อย , แนวทางเวชปฏิบัติโรคพิษสุนัขบ้า และคาถามที่ พบบ่อย พิมพ์ ครั้งที่ 6, 2561, สานักโรคติดต่อทั่วไป กรมควบคุมโรค กระทรวงสาธารณสุข, WHO Expert Consultation on Rabies, 2018, WHO TRS 1012 Guideline for Rabies Exposure Prophylaxis

2018 2018 2018 Post Exposure Prophylaxis (PEP) IM 1-1-1-1-1 (Essen) IM 1-1-1-1-1 (Essen) IM 1-1-1-1 Day 0-3-7-14-28 Day 0-3-7-14-30 Day 0-3-7-14to28 IM 2-1-1 X X Day 0-7-21/28 ID 2-2-2-0-2 (Modified TRC-ID) ID 2-2-2-0-2 (Modified TRC-ID) ID 2-2-2-0-0 Day 0-3-7-(14)-28 Day 0-3-7-(14)-30 Day 0-3-7-(14)-(28)

Source: แนวทางการดูแลรักษาผู้สัมผัสโรคพิษสุนัขบ้า, สถานเสาวภา สภากาชาดไทย พ.ศ.2561 และคาถามที่พบบ่อย , แนวทางเวชปฏิบัติโรคพิษสุนัขบ้า และคาถา มที่พบบ่อย พิมพ์ ครั้งที่ 6, 2561, สานักโรคติดต่อทั่วไป กรมควบคุมโรค กระทรวงสาธารณสุข, WHO Expert Consultation on Rabies, 2018, WHO TRS 1012 Guideline for Rabies Exposure Prophylaxis

2018 2018 2018 Short post exposure prophylaxis regimen for previous vaccinate person / Booster regimen

Within 6 months of completion Within 6 months of completion Within 3 months of completion PEP/PREP PEP/PREP PEP/PREP IM 1 IM 1 No PEP is recommend ID 1 ID 1 Day 0 Day 0 Over 6 months of completion Over 6 months of completion Over 3 months of completion PEP/PREP PEP/PREP PEP/PREP IM 1-1 IM 1-1 IM 1-1 ID 1-1 ID 1-1 ID 1-1 Day 0-3 Day 0-3 Day 0-3

ID 4 ID 4 Day 0 Day 0 แนวทางการดูแลรักษาผู้สัมผัสโรคพิษสุนัขบ้า, สถานเสาวภา สภากาชาดไทย พ.ศ.2561 และค าถามที่พบบ่อย, แนวทางเวชปฏิบัติโรคพิษสุนัขบ้า และค าถามที่พบบ่อย พิมพ์ครั้งที่ 6, 2561, ส านัก โรคติดต่อทั่วไป กรมควบคุมโรค กระทรวงสาธารณสุข, WHO Expert Consultation on Rabies, 2018, WHO TRS 1012 COVID-19 Vaccines PFIZER ประสิทธิภำพจำกกำรศึกษำระยะที่ 3 MODERNA mRNA BNT162b2 Efficacy of Phase 3 ในกำรป้องกนั ป่วย mRNA-1273 EFFICACY: 95% EFFICACY: 94% DOSE: 2 doses, 3 weeks DOSE: 2 doses, 4 weeks apart Johnson&Johnson apart Ad26.COV2.S AstraZeneca EFFICACY: 72% (US), 68% GAMALEYA (SputnikV) ChAdOx AZD1222 (Brazil) and 64%(SA) Ad26 + Ad5V EFFICACY: 79% DOSE: 1 dose EFFICACY: 91.6% DOSE: 2 doses DOSE: 2 doses, 3 weeks apart

SINOVAC SINOPHARM BHARAT EFFICACY: 51% (>mild), BBIBP-CorV 84% (>moderate) EFFICACY: 79.34% EFFICACY: 78% DOSE: 2 doses, 2-4 weeks DOSE: 2 doses, 3 weeks DOSE: 2 doses, 4 apart apart weeks apart NOVAVAX Anhui Zhifei Protein NVX-CoV2373 Protein ZF2001 EFFICACY: 96% (original), 86% EFFICACY: Unknown (B.1.1.7), 49% (B.1.351) DOSE: 3 doses, 4 weeks DOSE: 2 doses, 3 weeks apart apart สรุปเปรียบเทียบวัคซีนโควิด-19

วัคซีน ชนิด ป้องกันป่วย (มี VOC) ป้องกันป่วย ป้องกันการ เก็บ (oC) หนัก แพร่เชือ้ Pfizer mRNA 95% 100% 60% -20 Moderna mRNA 94% 100% ไม่มีข้อมูล -20 Astra Zeneca Adenovirus 79% 100% 50% 3-5 Johnson Adenovirus 64-72% (B1.351) 77% ไม่มีข้อมูล 3-5 Sputnik Adenovirus 92% 100% ไม่มีข้อมูล 3-5 Sinovac Inactivated 51% (เบำ-กลำง-หนัก) 100% ไม่มีข้อมูล 3-5 84% (กลำง-หนัก) (P1) Sinopharm Inactivated 73%-78% ไม่มีข้อมูล ไม่มีข้อมูล 3-5 Vaccines Related Complications Trivalent oral or Sabin vaccine

• Disadvantages

• Approx. 1 in every 2.7 million first doses of the vaccine can cause paralysis (VAPP).

• Virus in the vaccine may genetically change and start to circulate among a population. These viruses are known as circulating vaccine-derived polioviruses (cVDPV).

http://www.polioeradication.org/Polioandprevention/Thevaccines/Oralpoliovaccine(OPV).aspx#sthash.1BTkBIsC.dpuf- Polio Vaccine

OPV IPV Cost Low High Route of administration Oral SC or IM Intestinal immunity Yes No Control outbreak after the 1st dose Yes No

Immunocompromised host Contraindicated Safe Vaccine-associated paralytic Possible No poliomyelitis (VAPP) Interfere with enteroviral infection Yes No Incidence of Intussusception after RV Implementation

• Australia (HRV, RV5) 1 : 18,000 • US (HRV, RV5) 1-5 : 100,000 • Mexico (HRV) 1 : 51,000 • Brazil (HRV) 1 : 68,000

Carlin JB et al. Clin Infect Dis 2013;57:1427–34; Glass R. New Engl J Med 2014;370;6:568–570; Wkly Epidemiol Rec 2013;88:49–64; Murphy et al. New Engl J Med 2001; 344: 564–72 Risk of Intussusceptions during 7 Days after First Dose of RV1 and RV5

Rosillon D, et al. Pediatr Infect Dis J. 2015;34:763-8 Risk of Intussusceptions during 7 Days after Second Dose of RV1 and RV5

Rosillon D, et al. Pediatr Infect Dis J. 2015;34:763-8 MMRV vaccines: risk of febrile convulsions

First dose ProQuad™ Priorix-Tetra™ of MMRV 1 additional case in 2,300 1 additional case in 5,882 or doses 2,747 subjects Children 1 (One additional case of febrile convulsion (An additional case of febrile convulsion per 12–23 months 7–10 days post-vaccination for every 2,300 5,882 or 2,747 subjects post-vaccination or doses of MMRV administered, in with MMRV compared with matched 9–30 months2 comparison with controls who received MMR, or MMR + V at separate injection sites1) simultaneous MMR + V vaccinations2)

Second dose of MMRV No such link found to date3 Children 2–6 years

1Klein et al. Pediatrics 2010; 126: e1–8; 2GlaxoSmithKline. Priorix-Tetra™ European SmPC 2013; 3Klein et al. Pediatrics 2012; 129: 809–14 วัคซีนอะดีโนไวรัสเวคเตอร์ ใช้ไวรัสอะดีโนก่อโรคหวัด มาดัดแปลงพันธุกรรม สอด Adnovirus vector ใส่สารพนั ธุกรรมทกี่ า กับการสร้างโปรตนี สไปค์ ของโค วิด-19 เมอื่ ฉีดเข้าสู่ร่างกาย เซลลส์ ร้างภมู คิ มกันจะุ้ สร้างภมู ติ ่อโปรตนี สไปค์ Known AEFI:

• Frequent reactogenicity • VITT

อะดีโนไวรัสมนุษย์ชนิด5

อะดีโนไวรัสมนุษย์ชนิด26 อะดีโนไวรัสมนุษย์ชนิด5+26 อัตราการเคยตดิ เชอื้ มาก่อนในคนจนี AdHu5=73.1% (844/1,154) AdHu26 = 35.3% (407/1,154) อะดีโนไวรัสชิมแพนซี AdC68= 12.7% (147/1,154) Zhang S. J Med Virology 15 Apr 2013 Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study อาการข้างเคยี งทพี่ บในชวี ิตจริง พบอาการ systemic 30-40% Systemic Local

AE มากกว่าใน: - ผู้หญิง - <55 ปี - เคยเป็น COVID-19 มาก่อน

Menni C, et al. Lancet ID April 27, 2021DOI:https://doi.org/10.1016/S1473-3099(21)00224-3 อาการอันไม่พึงประสงค์ของวัคซีน จอห์นสัน (N=19,514 vs 19,544) พบปัญหาลิม่ เลือด 11 รายในกลุ่มวัคซีน และ 3 ราย ในกลุ่มยาหลอก Sadoff J, et al. NEJM April 21, 2021 • There were 11 thromboembolic events in vaccine group vs 3 in placebo group. DOI: 10.1056/NEJMoa2101544 • Imbalances were also observed with regard to seizure (which occurred in 4 participants in the vaccine group vs. 1 in the placebo group) and tinnitus (in 6 vs. 0).

อาการเฉพาะที่ฉีด อาการระบบร่างกาย ภาวะลิม่ เลือดทมี่ ีเกร็ดเลือดต่า เกิดหลังการฉีด วัคซีน AZ 1 :100,000 -1:1,000,000

The MHRA recently confirmed that the evidence to date does not suggest that the COVID-19 Vaccine AstraZeneca causes venous thromboembolism without a low platelet count.

It is important to note that this type of blood clot together with lowered platelets can rarely occur naturally in unvaccinated people as well as in people with COVID-19 disease.

VITT เกิด 4/ล้าน แต่ไม่เกีย่ วกับ thrombosis without • By 31 March 20.2 million doses of the COVID-19 Vaccine AstraZeneca had been given in the UK, risk of Likely cause CVST and SVT thrombocytopenia these blood clots is approximately 4/ Individuals who experience any severe symptoms…… million. shortness of breath, chest pain, leg swelling, persistent • Anyone who did not have these side effects should abdominal pain, neurological symptoms, such as severe come forward for their second dose when invited. and persistent headaches or blurred vision, tiny blood • shortness of breath, chest or persistent spots under the skin beyond the site of the injection - abdominal pain, leg swelling • from around 4-20 days following vaccination, should HLA-DRB1*03:01blurred and vision, HLA-DQB confusion1*02:01 or seizures is genetic •riskunexplained for PF4 antibody pin-prickคนไทยพบ rash or bruisingHeparin beyond-induced Thrombocytopenia seek urgent medical attention. The Journal for Nurse Practitioners 0.12% (อังกฤษ พบthe 12.7 injection%) site Volume 14, Issue 5, May 2018, Pages 402-408.e3 พบว่า วัคซนี ของจอหน์ สัน กเ็ กดิ เช่นกัน เกดิ ในผู้หญิงทงั้ หมด อัตรา 7/ล้านในผู้ทอี่ ายุ 18-49 ปี

Slide from Sara Oliver MD, MSPH, US ACIP Meeting, April 23, 2021 Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine: ข้อมูลจาก e-health network พบโอกาสเป็น CVT หลังโควิด = 39/m หลังได้ mRNA vaccine = 4.1/m (หลังได้ AZ Vaccine =5/m ข้อมูลจาก EMA)

The incidence of CVT after COVID-19 diagnosis was 39.0 per million people (95% CI, 25.2–60.2). This was higher than after influenza (0.0 per million people, 95% CI 0.0–22.2, adjusted RR=6.73, P=.003) or after receiving BNT162b2 or mRNA-1273 vaccine (4.1 per million people, 95% CI 1.1–14.9, adjusted RR=6.36, P<.001). From the European Medicines Agency for the incidence associated withChAdOx1 nCoV-19 vaccine (5.0 per million people, 95% CI 4.3–5.8)

Taquet M, et al. https://osf.io/a9jdq/ วัคซนี ชนิดเชือ้ ตาย ผลติ โดยนา เชอื้ ไวรัสมาเพาะเลยี้ ง แล้วทา ให้เชอื้ Inactivated ตายด้วยฟอรม์ ัลดฮี ายด ์ หรือความร้อน เมอนื่ ามา ฉีด ร่างกายจะตอบสนองเหมอื นตดิ เชอื้ ตาม ธรรมชาตแิ ละสร้างภูมคิ ุ้มกัน Known AEFI

• ISRR การเลีย้ งเชือ้ ต้องทา ให้ห้อง แลป BSL3 มันคือปฏิกิริยาของร่างกายต่อความเครียดของร่างกายและจิตใจ เกดิ มากในผู้หญิง>ผู้ชาย อายุน้อย>อายุมาก และเมือ่ ร่างกายและจติ ใจไม่พร้อม

Serious adverse events after COVID-19 vaccination: US

• Anaphylaxis: 2-5 people per million vaccinated in the US • Thrombosis with thrombocytopenia syndrome (TTS) after Johnson & Johnson’s Janssen (J&J/Janssen) COVID-19 vaccination: • >13 million doses of the J&J/Janssen COVID-19 Vaccine have been given in the US: 39 confirmed TTS, women <50 years old • >324 million doses of mRNA COVID-19 vaccines have used in the US: 2 confirmed cases of TTS following mRNA COVID-19 vaccination (Moderna) • Guillain-Barré Syndrome (GBS): • After 12.8 million J&J/Janssen COVID-19 Vaccine doses administered: Around 100 preliminary reports of GBS, mostly in men, >50 years • Myocarditis and pericarditis: • 1,148 reports of myocarditis or pericarditis among people ages <30 years who received COVID-19 vaccine: Most after mRNA COVID-19 vaccination (Pfizer-BioNTech or Moderna), particularly in male adolescents and young adults. ขอบคุณครับ