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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

2018 ACIP/MMWR Recommended Adult Immunization Schedule by Age

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2018 ACIP/MMWR Recommended Adult Immunization Schedule by Dis.

Influenza Cases in Rural Thailand, 2009–2010

PLoS One. 2012;7(11):e48609.

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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)

VACCINE STRAINS

• Each year, three strains are chosen for selection in

that year's flu vaccination by the WHO Global

Influenza Surveillance Network.

2018 - Southern Hemisphere/Australia

1. A/Michigan/45/2015 (H1N1)pdm09-like virus

2. A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus

3. B/Phuket/3073/2013-like virus (new, B/Yamagata lineage)

4. B/Brisbane/60/2008-like virus (B/Victoria lineage)

* Different from 2017 southern strain

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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

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.

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CHICKEN POX

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

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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

HEPATITIS B VACCINE

• HIV-patients – Defer until CD4>200 (Better response if CD4>500) – May use high dose HBV (40 mcg) x 3 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 – 75% response after 3 more doses

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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) – FDA-approved in female only – Protect against HPV 16, 18 – Prevent CIN, CA cervix, VIN

• HPV4 (Gardasil): – FDA-approved in female or male – Protect against HPV 6, 11, 16, 18 – Prevent CIN, CA cervix, VIN & condyloma accuminata

• HPV-9 (6, 11, 16, 18, 31, 33, 45, 52, 58)

HPV VACCINES

• Recommendations: • Female: Age 11-26

• Males : 13-21 years (optional in males 22-26 years)

• MSM: 13-26 years

• Pregnancy – should avoid

• HPV testing is not necessary

• Among girls (9-13 y), 2 doses HPV-4 was non-inferiority to conventional 3 doses

JAMA 2013;309(17):1793-1802

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CYD-TDY (Dengvaxia)

• Live-attenuated (recombinant) vaccine

• Uses the yellow fever virus as a backbone, carrying prM and E protein genes of DEN-1, 2, 3, 4

• First licensed dengue vaccine – Mexico (Dec 2015), Thailand (Oct 2016)

• 3-dose series: 0, 6 and 12 months

• Recommended for age 9-45 yrs, in endemic area

CYD-TDY (Dengvaxia): Two Landmark Studies

• 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

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Efficacy and Long term Safety of TDV (CYD-14, CYD-15 and CYD-57)

• During year 3, hospitalization for severe dengue occurred in

– 18 of 22,177 participants in the vaccine group

– 6 of 11,089 participants in the control group

“Although the unexplained higher incidence of

hospitalization for dengue in year-3 among children age <9 years needs to be carefully

monitored during long-term follow-up, the risk among children 2 to 16 years of age was lower in

the vaccine group than in the control group.”

Hadinegoro HR,et al. N Engl J Med. Sep 2015;373:1195-206

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Risk of severe dengue after 5 year of vaccination

• Sero+/Vaccine+ <1.0 per 1000 persons

• Sero+/Vaccine- 4.8 per 1000 persons

• Sero-/Vaccine+ 4.0 per 1000 persons

• Sero-/Vaccine- 1.7 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/

PLoS Med. 2016;13:1–19.

IDAT/PIDST recommendations

• 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

ค ำแนะน ำจำกที่ประชมุผู้ เช่ียวชำญด้ำนวคัซีนไข้เลือดออกซึง่ประกอบด้วยตวัแทนสมำคมโรคติดเชือ้เดก็แห่งประเทศไทย

สมำคมโรคติดเชือ้แหง่ประเทศไทย

กรมควบคมุโรค คณะกรรมกำรอำหำรและยำ ศนูย์วิจยัและพฒันำวคัซีนมหำวิทยำลยัมหิดล ในวนัที่ 7 ธนัวำคม 2560

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Zoster Incidence Among Elderly

http://www.cdc.gov/shingles/surveillance.html

Complications of Zoster

Neurologic

• Postherpetic neuralgia • CN Neuropathies

– Ramsey Hunt – Bell’s palsy

• Encephalitis • Stroke

Cutaneous

• Scarring • Bacterial

superinfection

Visceral (rare)

• Myocarditis • Pericarditis • Arthritis • Hepatitis

Ophthalmic

• Visual loss • Pain • Facial scarring • Keratitis

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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%]

ZVL

• Lived-attenuated vaccine

• Reduced risk of shingle (51%) and PHN (67%)

• Recommendations: – All adults age >60 years regardless of whether they

report a prior episode of herpes zoster

– FDA approve in age > 50 years

– Zoster and PPSV-23 vaccine should not be given concomitantly

• Contraindication: severe immunocompromised hosts and pregnancy

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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: 0, 2 month

• FDA approved in October 2017

ZOE-50

• 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 years

• HZ episode = 0.3 VS. 9.1 cases/1,000 person-years

• Vaccine efficacy for HZ =97.2% [93.7 -99.0]

• ADRs: 17% vs. 3.2%

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ZOE-70

• Phase-3 RCT

• Age ≥ 70 years

• Two doses of HZ/su IM at 0, 2 months VS. Placebo

• Outcomes:

– N=13,900, f/u 3.7 years

– HZ episode = 0.9 VS. 9.2 per 1,000-patient years

– Vaccine efficacy for HZ = 89.8% [84.2-93.7]

– Vaccine efficacy for PHN = 88.8% [98.7-97.1]

– ADRs: 79% VS. 29.5%

Immunogenicity and Safety of ZVL in Adults Previously Vaccinated with ZVL

• Open-label , age-match phase-3 study (n=430)

• Age ≥65 years with previous hx of ZVL (≥ 5 years interval)

• Two doses of HZ/su IM at 0, 2 months

J Infect Dis. 2017;216:1343-1351.

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Summary of MMWR 2018

• Three recommendations

1. Immunocompetent host with age ≥50 years –> RZV

2. Immunocompetent host with previous history of ZVL RZV

3. RZV is preferred over ZVL for the prevention of zoster & zoster related complications

PNEUMOCOCCAL VACCINES

1. Pneumococcal polysaccharide (PPSV23)

• Broader serotype coverage but lower IR

• FDA approved for age > 2 years

• Schedule: 0, 5 yrs (if 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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Recommendation based on Age and Underlying Diseases

Adults age 19-64 years With Medical Conditions

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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

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)

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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!!)

Immunization is Everyone’s Business!!