Session 12: Evidence and recommendations for use of ...Moderate icter ic infection Severe icteric...

Session 12: Evidence and recommendations for use of

hepatitis A vaccines Hepatitis A Working Group

Dr. Steven Wiersma

Global Hepatitis Programme

Hepatitis A Working Group—SAGE 2011 2 |

Introduction

l Hepatitis A caused by HAV, hepatovirus of picornaviridae family

l Mostly transmitted through fecal-oral route, either by direct contact or ingestion of contaminated food/water

l Most children experience asymptomatic infections while most adults develop signs and symptoms of acute hepatitis.

l  1992, inactivated hepatitis A vaccines first licensed for use


2000 Position Paper

l  2000 WHO position paper called for epi/economic studies prior to national HepA policy development

l  Also recommended HepA introduction in routine immunization programmes be weighed against competing priorities in terms of BOD and capacity of immunization systems

l  Did not recommend large-scale vaccination in high endemicity settings

l  Recommended vaccination as supplement to health education/improved sanitation in intermediate endemicity settings

l  Recommended vaccine use in low endemicity settings for persons at increased risk


Developments since 2000

l  Changing epidemiology: shift from high to intermediate endemicity

l  Evidence for HepA public health benefit

l  Strengthened immunization systems

l  Evidence for post-exposure efficacy, long-term protection, and population impact

l  Increased supply of HepA with price reduction

l  Mandate for comprehensive hepatitis prevention and control (WHA63.18)

l  Publication of "The immunological basis for immunization series: module 18: hepatitis A" in 2011


Global Prevalence of anti-HAV

l  Systematic review seroprevalence anti-HAV by country/GBD region, age, and sex

l  Kathryn Jacobsen, PhD, Department of Global & Community Health, George Mason U, Fairfax, Virginia

l  Published as WHO/IVB/10.01


Methods

l  Age-specific IgG anti-HAV seroprevalence data

l  2932 papers screened, 637 eligible papers pooled for 21 world regions (as defined by GBD 2005 Study)

l No sample size or quality weighting

l  Scatterplot of seroprevalence rates for each eligible study with ≥2 age groups for each Region (x-axis value = median age of group or midpoint if median not given)

l  Logarithmic or polynomial curve fitted to data


Age-specific Seroprevalence


Summary of Findings

l High-income regions (W Europe, Australia, New Zealand, Canada, US, Japan, ROK, and Singapore) have very low HAV endemicity levels and high proportion of susceptible adults

l  Low-income regions (sub-Saharan Africa and parts of South Asia) have high endemicity levels and almost no susceptible adolescents and adults

l Most middle-income regions have a mix of intermediate and low endemicity levels


*Anti-HAV age 10-14: high > 90%, high-medium 75-89%, medium 60-74%, low-medium 40-59%, low <20%


*Anti-HAV age 35-44: high >40%, medium 20-39%, low-medium 10-19%, low 1-9%, very low =0%


Age Specific Seroprevalence by Region

0

10

20

30

40

50

60

70

80

90

100

Region 1-4 5-9 10-14 15-19 20-24 25-34 35-44 45-54 55-64 65-74 75-84 85+

Series1

Series2

Series3

Series4

Series5

Series6

Series7

Series8

Series9

Series10

Series11

Series12

Series13

Series14

Series15

Series16

Series17

Series18

Series19

Series20

Series21

Series22


Region and Country Specific Data ROK


Region and Country Specific Data India


Region and Country Specific Data New Zealand


Conclusions

l  Anti-HAV prevalence estimates in middle-income regions in Asia, Latin America, Eastern Europe, and the Middle East currently have an intermediate or low level of endemicity

l Countries in these regions may have an increasing burden of disease from hepatitis A

l  Anti-HAV prevalence data is useful for burden modeling


Hepatitis A Model

Incident infection

Anicteric infection

Mild icteric infection

Moderate icteric infection

Severe icteric infection

Fulminant liver failure

Liver transplant

Death

Death Resolved naturally

Recover

Probabilities Incident Infection: Vary by WHO Region. Calculated from age-specific

prevalence as complied by Jacobsen (2009), report. See next slide.

Disease outcomes vary by age category (0 to 4, 5 to 14, 15+) Anicteric infection: 0.15 to 0.93 (Armstrong and Bell, 2002) Mild icteric infection: 0.55 to 0.65 (Armstrong and Bell, 2002) Moderate icteric infection: 0.017 to 0.157 (Armstrong and Bell, 2002;

CDC surveillance) Severe icteric, non-fulminant: .001 to .032 (Armstrong and Bell, 2002;

CDC surveillance) Fulminant, death, and transplant states: <.001 to .008 (Armstrong and Bell, 2002;

CDC surveillance; U.S. United Network for Organ Sharing 1990 -2003)


Burden of HAV-related Disease 1990 and 2005

l  Annual incidence declined from 2.1%/year in 1990 to 1.9%/year in 2005

l HAV infected 115 million people in 1990 and 119 million in 2005

l Resulted in 24.7M symptomatic illnesses and 29,000 deaths in 1990 and 31M symptomatic illnesses and 34,000 deaths in 2005


Countries Using HepA Vaccine in National Immunization Schedule, 2010

Source: WHO/IVB database, 193 WHO Member States. 27 October 2011

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2011. All rights reserved

No (182 countries or 94%)

Yes (11 countries or 6%)


Universal childhood HepA introduction

2002 2003 2004 2005 2006 2007 2008 2009 2010 HepA in EPI per JRF

1 1 2 3 5 7 9 10 11

WHO Member State

Israel Bahrain Argen-tina

Panama, USA

China, Greece

Saudi Arabia, Uruguay

Kazakh-stan

Qatar


Global Introduction of Childhood HepA

0.0%2.0%4.0%6.0%8.0%

10.0%12.0%14.0%16.0%18.0%20.0%

2002 2004 2006 2008 2010

Proportion ofCountries with HepAin Schedule (%)Proportion of Infantsin Countries withHepA in Schedule (%)


Process of evidence review

Questions Process The efficacy and safety of available hepatitis A vaccines, i.e. Does hepatitis A vaccine prevent HAV-related disease?

Systematic review and meta-analysis conducted by Cochrane Gastrointestinal and Liver Disease group. Evidence review using GRADE by WHO

The use of hepatitis A vaccines in post-exposure prophylaxis and outbreak control, i.e. Does hepatitis A vaccine prevent HAV-related disease when given post-exposure?

Systematic review and meta-analysis conducted by Cochrane Gastrointestinal and Liver Disease group, supplemented by additional review. Evidence review using GRADE by WHO

Experience regarding the public health impact of the use of hepatitis A vaccine in mass immunization programs, i.e. Does universal hepatitis A vaccination reduce the disease burden of hepatitis A in the population?

Systematic review conducted by WHO, evidence review using GRADE by WHO

Evidence on the duration of protection achieved by hepatitis A vaccine, i.e. Do hepatitis A vaccines provide long-term protection?

Systematic review conducted by WHO, evidence review using GRADE by WHO


Acknowledgments

l  SAGE HepA Working Group Members

–  Art Reingold (Chair) –  Liang Xiaofeng –  Jeffrey Mphahlele, South Africa –  Marta Vacchino, Argentina –  Daniel Shouval, Israel –  Andrew Hall, UK –  John Ward, USA

l  Secretariat Members –  Jördis Ott –  Yvan Hutin

l  External Experts –  Greg Irving –  John Holden –  David Rein –  Carla Vizzotti –  Maximo Diosque –  Margarita Ramonet –  Angela Gentile –  Jorge Gonzalez –  Analia Rearte –  Christian Herzog –  Marie Claude Bonnet –  Alejandro Lepetic –  Reinaldo de Menezes Martins

Thanks


Countries Using HepA Vaccine in National Immunization Schedule, 2010

Source: WHO/IVB database, 193 WHO Member States. 27 October 2011

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2011. All rights reserved

No (170 countries or 88%)

Yes (11 countries or 6%)

Yes (Risk groups) (12 countries or 6%)


Co-administration of HepA

l Concurrent administration of many vaccines with HepA does not lead to significant interference in the immunogenicity, reactogenicity and safety of the individual vaccines.

l  Studies 12–15 mo infants, children <18 years and adults, inactivated HepA can be administered simultaneously with:

–  diphtheria, tetanus, acellular pertussis (DTaP), polio (oral and inactivated), Haemophilus influenzae (Hib), MMR typhoid (oral and intramuscular), hepatitis B, cholera, Japanese encephalitis, rabies and yellow fever vaccines

l  Injections should be given at different sites.

Session 12: Evidence and recommendations for use of ...Moderate icter ic infection Severe icteric...

Documents

Transcript of Session 12: Evidence and recommendations for use of ...Moderate icter ic infection Severe icteric...