Hepatitis B immunisation update - ice-hbv.orgNational policy of infant HB immunisation starting at...

1 |World Health Organization

Western Pacific Region

Hepatitis B immunisationupdate

Tilman RuffNossal Institute, MSPGH, UniMelbWPRO ERP on HB Control Through EliminationICE-HBV World Hepatitis Day Symposium @







Dr Agustinus Sutanto

Dr Didi Sumarsidi

Dr S Soewignyo



Hepatitis B1Hepatitis B1

Estimated 887,000 HBV‐related deaths annually (2015)

Globally, 257 million chronically infected

Chronic infection risk highest early in life; acute disease more likely in adolescence/adulthood

Chronic HB can cause chronic hepatitis, cirrhosis and primary hepatocellular carcinoma

– 15‐25% risk of premature mortality for infection early in life

Accounts for 1/3 of liver cancer

Second only to tobacco as fatal carcinogen

Eventually eradicable

The only infant vaccine where timing of the first dose is critical



Prevalence of HBV infection, by Region, 2015Prevalence of HBV infection, by Region, 2015

WPR: 45% of the global HBV cases and 6.2% prevalence in the general population

Source: Global Hepatitis Report, 2017



0

300,000

600,000

900,000

1,200,000

1,500,000

Global Western Pacific

Tuberculosis

Malaria

HIV/AIDS

Hepatitis related

* Source: GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10;385(9963):117-71.

Comparison of global and Western Pacific mortality by major communicable diseases, 2013

Comparison of global and Western Pacific mortality by major communicable diseases, 2013



Estimated Global Number of Deaths from Hepatitis, HIV, Malaria and TB, 2000‐2015Estimated Global Number of Deaths from Hepatitis, HIV, Malaria and TB, 2000‐2015

Source: Global Burden of Disease and WHO/UNAIDS estimates, seehttp://ihmeuw.org/3pms, http://ihmeuw.org/3pmt (accessed 2 April 2016).



Risk of chronic infectionRisk of chronic infection

Age at infectionAge at infection

00

2020

4040

6060

8080

100100

NeonatesNeonates InfantsInfants ChildrenChildren AdultsAdults

%Risk%

Risk



HB is different from other vaccine‐preventable diseases

HB is different from other vaccine‐preventable diseases

Most infections asymptomatic / unrecognised until a complication develops

Complications usually develop after decades

Causative role of HB may not be recognised

Preventing HB is not so much a ‘child survival’ issue – but primarily an issue of premature adult death

The first vaccine against cancer

The only infant vaccine where timing of first dose is critical







10 mcg rDNA vaccine in Thailand : High‐risk children & infants

10 mcg rDNA vaccine in Thailand : High‐risk children & infants

(Poovorawan 1992)

P 1992


Western Pacific RegionJID 1995;171:290‐6



Lombok experience ‐ HB 1 timingLombok experience ‐ HB 1 timing Baseline carriage rate in children under 5y: 6.2%

N=2548

After 4 y with ~90% coverage:

< 3 doses 3.4%

3 doses

• HB1 > 7d 3.0%• HB1 < 7d 1.4% (p<0.001)

Ruff TA et al JID 1995;171:290-6



Lombok development 2Lombok development 2

Home visits enable broad range other health interventions: Health education

• cord care, exclusive early BF, illness careMicronutrient supplementation

• Vitamin A, iodine, iron Immunisation

• HB1, (OPV, BCG) for infant, TT for mother Identification and special care of LBW infantsMaternal care



HB in Uniject prequalified by WHO, approved by GAVI

UNICEF can procure

Potential for use by non‐professional health staff



Lessons from Lombok and successor projectsLessons from Lombok and successor projects

Immunisation programs can strengthen primary health care

Basis and stimulus for: National policy of infant HB immunisation starting at birth HB in UniJect outside the cold chain for HB1 (also for TT for

mothers) Home visits for ａｌｌｉｎｆａｎｔｓｉｎ first week and again in first month National program of a midwife for every village



HB birth dose timing – Micronesia, 1990‐6HB birth dose timing – Micronesia, 1990‐6

Palau 12-14 mo N HBsAg+ %

95%CI

Birth dose

No 30 6.7 1.1 - 121

Yes 323 0.6Pohnpei 3-4 y

Birth dose

No 78 2.6 0.8 -

Yes 217 0

Birth dose within first 3 days, all children received 3 vaccine dosesMahoney FJ et al. Pacific Health Dialog 1996;3(2):140-6



WHO ResolutionsWHO Resolutions

WPR Regional Committee

2003 Measles and hepatitis B as pillars of EPI.

2005 Reduce HBsAg prevalence to <2% by 2012.

2013 Reduce HBsAg prevalence to <1% by 2017

World Health Assembly

2010 World Hepatitis Day, …

2014 Develop and implement coordinated multisectoral national strategies, …



Global Targets and Guidance for Hep B ControlGlobal Targets and Guidance for Hep B ControlSDG 3 Good Health & Well Being• Target: By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected

tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases; it is proposed the INDICATOR of the target be Prevalence of HBsAg among children

WHA-Adopted GVAP • Performance: 90% National coverage HepB-BD & HepB3 by 2020• Performance: 80% District coverage HepB-BD & HepB3 by 2020

WHA-Adopted GHSS• Target: <1% HBsAg in children by 2020; <0.1% by 2030• Performance: 90% HepB3 by 2020; 50% HepB-BD by 2020 & 90% by 2030

SAGE Oct 2016• Target: Disease Burden Estimates• Strategy: Update the Vaccine Position Paper (BD, CTC, OCC)

WHO/HQ/IVB/EPI• Performance: New 2017 Birth Dose Monitoring Standards (JRF Amendment)• Strategy: New HepB-BD Introduction Guidelines



Medium Term Regional Targets(GHSS target of 0.1% by 2030)Medium Term Regional Targets(GHSS target of 0.1% by 2030)

WHO Region

Prevalence Target

Age Range

By when

Endorsement Notes

AFR < 2% <5 Yrs 2020 Regional Committee (RC)

Resolution

Specifies to be reached in all Member States

WPR < 1% >5 Yrs 2017 RC Resolution Specifies ≥95% HepB3 & BD coverage

SEAR < 1% 5 Yrs 2020 Technical Advisory Group

EMR < 1% <5 Yrs 2015 RC Resolution

EUR ≤ 0.5% 5‐10 Yrs 2020 RC Resolution

AMR ≤ 0.1% 5 Yrs 2020 RC Resolution 2 step approach



Regional Committee ResolutionsRegional Committee Resolutions

2003 201520132005

WPR/RC54.R3: Hepatitis B set as an EPI pillar

WPR/RC56.R8: Reduce HBsAg prevalence to <2% by 2012

2012

WPR/RC64.R5: Reduce HBsAg prevalence to <1% by 2017

30 out of 36 countries reach <2% goal

2016

WPR/RC66.R1: Endorse Regional Action Plan forViral Hepatitis 2016‐2020

Publication showing 2017 1% Regional goal was met

Global Health Sector Strategy for Viral Hepatitis establishes 0.1% goal by 2030

2016



Three global health sector strategies 2016‐2021End viral hepatitis, HIV and STI epidemics

as public health threats by 2030

Three global health sector strategies 2016‐2021End viral hepatitis, HIV and STI epidemics

as public health threats by 2030

Zero new HIV infections among infants by 2020

≤50 cases congenital syphilis per 100,000 live births in 80% of countries by 2030

0.1% prevalence of HBsAg among children by 2030



Hepatitis B Third Dose Coverage:84% globally in 2015

0

10

20

30

40

50

60

70

80

90

100

1990 1995 2000 2005 2010 2015

Coverage (%

)

Year

AfricanAmericanEastern MediterraneanEuropeanSouth East AsiaWestern PacificGlobal

Source: WHO AND UNICEF



10

72

83

39

0

10

20

30

40

50

60

70

80

90

2000 2005 2010 2015

Coverage (%

)

Year

African

AmericanWestern Pacific

Global

Source: WHO AND UNICEF

Hepatitis B Birth Dose Coverage:39% global coverage in 2015



0

10

20

30

40

50

60

70

80

90

100

Immun

ization coverage (%

)

Timely birth dose coverage (≤ 24 hrs)3‐dose hepatitis B coverage

Reported Hepatitis B Birth Dose and HepB3 CoverageWestern Pacific Region, 1990–2016

Reported Hepatitis B Birth Dose and HepB3 CoverageWestern Pacific Region, 1990–2016

Source: WHO/UNICEF Joint Reporting Form (JRF) on Immunization. Regional coverage is based on weighted average among all countries, regardless if they reported coverage or not.



WPRO Hep B Control TimelineWPRO Hep B Control TimelineYear targetestablished

Target threshold

Targeted Year Outcome

2005 (RC) <2% 2012 30 of 36 countries reached

2013 (RC) <1% 2017 Regionally met + 18 countries verified (as of June 2017)

Proposed by ERP for post 2017

<1% among all countries

2025 TBD

Proposed by ERP for post 2017

<0.5%(regional)

2025 TBD

2016 <0.1% 2030 (GHSS) TBD



Verification Status of 2017 <1% Target as of June 2017

Verified (18)Serosurvey planned or ongoing (7)Programme improvements required (5)Serosurvey completed and awaiting results (3)Ready for verification (2)Universal HepB3 vaccination started in 2016 (1)



HBsAg Prevalence by SerosurveysHBsAg Prevalence by Serosurveys

0.00%

0.50%

1.00%

1.50%

2.00%

2.50%

3.00%

3.50%

For <1% target (by 2017):18 have been verified and22 with evidence of <1%

For <0.5% ERP-proposed target (by 2025):19 with evidence of <1%

No serosurveys since 2012: Federal State of Micronesia, Fiji, Nauru, New Caledonia, Philippines, Republic of the MarshallIslands, Tonga, Tuvalu and Vanuatu.

(preliminary)



Source: Eric Wiesen, Sergey Diorditsa & Xi Li, Progress towards hepatitis B prevention through vaccination in the Western Pacific, 1990–2014, Vaccine, May 2016. 27;34(25):2855-62.

The 2017 regional goal of <1% seroprevalence among 5 year olds was achieved.

As a result of immunization programmes, over 7 million deaths (and 37 million chronic infections) have been averted among children born from 1990 to 2014.

Impact of Vaccination Programs in the Western Pacific

Impact of Vaccination Programs in the Western Pacific



China alone accounts for 55% of hepatocellular carcinoma (HCC) cases worldwide

China alone accounts for 55% of hepatocellular carcinoma (HCC) cases worldwide

Estimated incidence of liver cancer 33.7/100,000 for men and 10.5/100,000 for women

Estimated numbers of 5‐year prevalence of HCC is 2,201,000 men and 708,000 women.

2nd leading cause of cancer‐related deaths in males and the 3rd in females, with a total mortality rate of 23.76/100,000

In China, approximately 85% of Chinese HCC cases are HBV‐related, 10% of cases are HCV‐related.

Despite the 97% reduction in vertical transmission, a 0.32% HBsAg prevalence among young children implies that 50,000 newborns are annually infected

Source: Shin HR et al. Prevention of infection-related cancers in theWHO Western Pacific Region. Jpn J Clin Oncol. 2016; 46:13-22.


Western Pacific Region33

Population and child health care in China, 2015Population and child health care in China, 2015

• Population 1.36 billion• CBR 12.08 ‰ • MMR 21.7/100,000 livebirths• IMR 8.9/1,000 livebirths• ANC (≥1 visit) coverage 95.6%• Hospital delivery rate 99.6%

Data sources: * Chinese Health Statistical Digest, 2014

3



Prevalence of HBsAg (3 curves, 1 for each survey) and HepB coverage (bars) by year of birth for individuals born between 1992 and 2013

Prevalence of HBsAg (3 curves, 1 for each survey) and HepB coverage (bars) by year of birth for individuals born between 1992 and 2013

4



HB control in ChinaHB control in China Progressive decline in HBsAg prevalence 1992, 2006, 2014

among 1‐4yo: 9.9 to 1.0 to 0.32%

5‐15yo: 10.6 to 2.4 to 0.9%

N=31,713

Cui F EID 2017;23(5):765‐72



Rate of Hepatitis B Virus (HBV) Infection among InfantsRate of Hepatitis B Virus (HBV) Infection among Infants

Pan C Q, Duan Z, Dai E, et al. NEMJ, 2016, 374(24):2324-2334.

In a cohort of HBeAg-positive mothers withan HBV DNA level ofmore than 200,000 IUper milliliter during thethird trimester, the rateof mother-to-childtransmission waslower among those whoreceived TDF therapythan among those whoreceived usualcare without antiviraltherapy.

23



• DHS 2014:

83% HepBBD

• Source HIS, MoH

Cambodia – increase in facility births and effective engagement with private sector



October 2016 SAGE meeting – Hepatitis B vaccination Cold ChainOctober 2016 SAGE meeting – Hepatitis B vaccination Cold Chain

• All producers of prequalified hepatitis B vaccine provided information on their vaccine’s thermostability. The data suggest that the reviewed hepatitis B vaccines are thermostable.

• SAGE strongly urges all the pre-qualified vaccine manufacturers of monovalent hepatitis B vaccine to pursue regulatory approval for Controlled Temperature Chain (CTC) as soon as possible, given the available evidence of compatibility with CTC requirements.

• SAGE supports countries that choose to pursue an out of cold chain policy for a given monovalent hepatitis B vaccine and strongly recommends that when doing so they should follow the current IPAC recommendations for out of cold chain and CTC use of vaccines.*

“WHO could support an off-label recommendation for an OCC approach consistent with CTC programmatic requirements. Where appropriate, such a recommendation would help support a country’s decision to use the CTC approach to improve birth dose HBV coverage and timeliness”

*http://www.who.int/immunization/programmes_systems/policies_strategies/ipac/en/



Laos OCC pilot study 2016 ‐ Birth Dose coverage in comparison and intervention arm

Laos OCC pilot study 2016 ‐ Birth Dose coverage in comparison and intervention arm



Solomon Islands outside cold chain pilot 3 provinces 2015‐6Cumulative HepB‐BD and BCG Coverage by Age and Project

Period

Solomon Islands outside cold chain pilot 3 provinces 2015‐6Cumulative HepB‐BD and BCG Coverage by Age and Project

Period

0

10

20

30

40

50

60

70

80

90

100

0 14 28 42 56 70 84 98 112 126 140 154 168 182 196 210 224 238 252 266 280

Cumulative Pe

rcen

t (%)

Vaccine administration day post birth

Pre‐project period HepB‐BD Project period HepB‐BD

Pre‐project period BCG Project period BCG

24 Hr HepB‐ BD increased by 156% (23% to 59%)

24‐Hr BCG increased by 85% (13% to 24%)



Global modelling of hep B eradicationGlobal modelling of hep B eradication

S Nayagam, Thursz M, Sicuri E, Conteh L, Wiktor S, Low-Beer D, Hallett TB. Requirements for global elimination of hepatitis B: a modelling study. Lancet Infect Dis. 2016 Dec;16(12):1399-1408. doi: 10.1016/S1473-3099(16)30204-3.

+ ++



Targets Interventions 2020 target 2030 target

1. Service coverage

1. 3‐ dose hepatitis B vaccine 90% 90%

2. HBV PMTCT 50% 90%

3. Blood and injection safety 95 % screened donations 100 % screened donations

50% RUP devices 90% RUP devices

4. Harm reduction 200 injection sets / PWID 300 injection sets / PWID

5. Treatment 30% diagnosed 90% diagnosed

5M and 3M treated for HBV and HCV

80% eligible treated

2. Impact A. Incidence ‐30%(About 1% HBsAg in children )

‐90%(0.1% HBsAg in children)

B. Mortality ‐10% ‐65%

GLOBAL HEALTH SECTOR STRATEGY (GHSS) ON VIRAL HEPATITIS

PMTCT: Prevention of mother to child transmission (universal birth dose or other approaches)PWID: Person who injects drugs

WPR 201693%83%

0.93%



Verification Status of 2017 <1% Targetby World Bank Income Classification

Verification Status of 2017 <1% Targetby World Bank Income Classification

AustraliaBrunei DarussalamFrench Polynesia

GuamHong Kong SAR

JapanRepublic of Korea

Macao SARNew CaledoniaNew Zealand

Northern Mariana IslandsNauru

Singapore

CambodiaKiribatiLao PDR

Federated States of MicronesiaMongoliaPhilippines

Papua New GuineaSamoa

Solomon IslandsTonga

VanuatuViet Nam

American SamoaPalauChinaFiji

MalaysiaMarshall Islands

Tuvalu

High Lower MiddleUpper Middle

N/ACook Islands

NiueTokelau

Wallis and Futuna Islands

=> Verified countries and areas

World Bank list of economies: The World Bank; 2016 [updated December 2016]. Available from: https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups



HepB birth dose coverage in Vietnam, 2003-2016HepB birth dose coverage in Vietnam, 2003-2016

54.4 55.262.2 63.2

28.1 25.5

40.3

21.4

55

75.6

56 55

69.8 69

0

20

40

60

80

100

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Hep

B BD

Cov

erage (%

)

<3 days <24 hrs

AEFIs

Stock out

AEFIs



ChallengesChallengesPersisting low coverage of HepB BD in

Mountainous areas: Difficulty in accessing service Daily vaccine supply High rate of birth delivery at home

Several urban areas effected by AEFIs Health workers: false contraindication,

provide vaccine to “pristine” newborns and to HBsAg (+) mothers.

Several hospitals irregularly implement timely birth dose.

HBsAg (-) mothers refuse vaccinating HepB BD for their neonates. Timely Birth Dose, 2016



Viet Nam Birth Dose AssessmentViet Nam Birth

Dose Assessment

Temperature 35.5 – 37.5

No heart irregularities

Normal breathing

Normal activity

>2000 g

No other contraindications



Recommendations from 2016 Viet Nam BD AssessmentRecommendations from 2016 Viet Nam BD Assessment

Prioritize BD expansion to polyclinics and commune health clinics

Antenatal HBsAg screening not nationally implemented Standardize antenatal care by including antenatal screening

recommendations and prophylaxis of newborns from HBsAg+ mothers

HCW education Revise screening guidelines and develop standing order for timely BD High refusal rates suggest continued HCW vaccine hesitancy Risk communication: BD as a standard of care and transmission risk

Lack of VVMs for nationally produced hep B vaccine Reverse Circular 21 to allow home outreach Include VVMs in tender requirements





S escape variants …. so far so good …..

Thank you!



Hepatitis Heroes (2016 WHD)

Hepatitis Heroes (2016 WHD)



Costed and funded.

Clear targets.

Dedicated and sustainable domestic funding.

In place by 2020.5 countries have National Action Plans• Australia, Mongolia, New Zealand, Japan and Viet

Nam4 countries are developing National Action Plans• Fiji, Kiribati, Malaysia and Philippines

National Policy Driving National Action National Policy Driving National Action



Key 2017 ERP Recommendations (1 of 2)Key 2017 ERP Recommendations (1 of 2)1. All countries reduce HBsAg prevalence to less than 1% among children at least 5

years of age by 2025.

2. Countries that have reduced HBsAg prevalence to less than 1% among 5 year old children further reduce HBsAg seroprevalence to less than 0.5% by 2025.

3. For countries that still implement selective birth dose [New Zealand and Japan], evaluate and assess whether all pregnant women are screened for HBsAg and whether all newborns of HBsAg‐positive mothers are vaccinated with timely HepB‐BD.

4. While awaiting manufacturers to incorporate controlled temperature chain thermostability data on their labels, the ERP reaffirms using vaccines outside the old chain in remote and hard‐to‐reach areas; in regions where inadequate CCE exists; among countries with a high proportion of home deliveries; and for vaccinating babies born at home, preferably within 24 hours of birth.



5. Countries mitigate negative perceptions of hepatitis B immunization through proactive risk communication planning and health education outreach.

6. WPR gain experience in using new methods to measure low HBsAg prevalence targets, including classification serosurveys; a two‐step risk assessment; and incorporating hepatitis B serosurveys into other national coverage surveys.

7. Conduct cost‐effectiveness analyses and incremental cost‐effectiveness ratios to help countries and areas ascertain which potential hepatitis B interventions, including multiple interventions, are programmatically and financially feasible.

Key 2017 ERP Recommendations (2 of 2)Key 2017 ERP Recommendations (2 of 2)



For Member States

1. The TAG reaffirms the long‐standing WHO guidance that all countries should universally administer hepB‐BD, as soon as possible after birth and preferably within 24 hours, even in countries with low hepatitis B endemicity.

2. The TAG reiterates its support for the use of hepatitis B vaccine outside the cold chain to facilitate delivery of hepB‐BD. The TAG endorses SAGE’s October 2016 recommendation to support countries that choose to pursue an out‐of‐cold‐chain policy and follow the current IPAC recommendations for out‐of‐cold‐chain and controlled‐temperature‐chain use of vaccines.

Key Recommendations for 26th TAG MeetingKey Recommendations for 26th TAG Meeting



Key Recommendations for 26th TAG MeetingFor WHO Secretariat

Key Recommendations for 26th TAG MeetingFor WHO Secretariat

:

1. The TAG recommends adoption of ERP’s proposed post‐2017 control goals:‐ All Member States reduce prevalence among 5+ y/o to <1%.‐ Countries that met the <1% goal reduce to <0.5% by 2025.

2. The TAG requests that the ERP develop and prioritize recommendations for additional interventions to be incorporated into perinatal programmes, considering cost and cost‐effectiveness along with other attributes, to achieve the post‐2017 hepatitis B goals.

3. The TAG endorses the ERP's 2017 vaccine‐related recommendations.



Birth Dose Coverage Improvement StrategiesBirth Dose Coverage Improvement Strategies Increase health facility deliveries

Conduct national birth dose assessment to identify main barriers to BD vaccination (Cambodia, Lao PDR, Philippines and Viet Nam)

Increase hepatitis B education during antenatal care Kiribati: Healthcare workers hep B education during ANC

Increase links with communities and outreach vaccination Kiribati: Village health workers coordination Lao PDR: Compared health facilities with high & low hep B prevalence Viet Nam: Rapid qualitative behavioral assessment for vaccine hesitancy

Use hepatitis B outside the cold chain where needed Lao PDR and Papua New Guinea expansion and training projects



Continue ERP collaboration

Directly support countries with low vaccination coverage

Share successful birth dose improvement experience, including OCC

Promote outside cold chain work (where applicable) while awaiting CTC endorsement

Promote healthcare worker vaccination and education

Strengthen and further viral hepatitis lab network for the WPR

Submit reviewed framework for triple elimination for mother‐to‐child transmission of HIV, hepatitis B and syphilis to 2017 RCM

The Way ForwardThe Way Forward

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