Epidemiology of Hepatitis B and Evaluation of Vaccine Efficacy in a Census-Based Community Serosurvey of Ndirande Township in Blantyre, Malawi

Epidemiology of hepatitis B and evaluation of vaccine efficacy in a census-based community serosurvey of Ndirande township in Blantyre, Malawi

Dr Alexander Stockdale Wellcome Trust Clinical PhD Fellow Malawi-Liverpool-Wellcome Trust Clinical Research Programme Blantyre, Malawi Background: Malawi

• Pop 18m • 85% rural • 70% <$1.90/day1 • Strong track record of health sciences research & innovation

1 World Bank 2018 HBV prevalence, Malawi

Pooled proportion 8.1% (95% CI 6.1, 10.3) Hepatitis B in Malawi

• HBV vaccine introduced in January 2002: >80% coverage since 2003 • WHO: call for HBV vaccine efficacy assessment in 5-year olds (2017) • No data on children post vaccine introduction

Research Questions

What is the epidemiology of hepatitis B in an urban township in Malawi?

What is the efficacy of the HBV vaccine introduced in 2002? Methods

• Laboratory ELISA: HBsAg Monolisa Ultra (Bio-rad, France) • Indeterminate results: (optical ratio 0.9-4.0) – retested in duplicate Serosurvey • STRATAA (The Strategic Typhoid alliance across Africa and Asia study) serosurvey n=6076 • Ndirande census, 2016: n=97,411 • Participants randomly selected from census : oversampling children, older adults

Age distribution of serosurvey vs census

HBV prevalence by gender

HBsAg positive % 95% CI Male 74/2618 2.8 2.3- 3.5 Female 95/3455 2.8 2.3- 3.3 Total 169/6073 2.8 2.4- 3.2

Odds ratio (adjusted for age) for HBV infection: • Female = 0.9 (95% CI: 0.7, 1.2, p=0.53) HBV prevalence by age

Age HBsAg % 95% CI

0-3 0/299 0 0.0 – 1.3 Post- 4-9 10/1575 0.6 0.3 – 1.2 vaccine introduction 10-13 3/ 663 0.5 0.2 – 1.3 14-19 14/ 695 2.0 1.2 – 3.4 20-29 35/ 698 5.0 3.6 – 6.9 Pre- 30-39 63/ 911 6.9 5.4 – 8.8 vaccine introduction 40-49 24/ 501 4.8 3.2 – 7.0 50-59 11/ 389 2.8 1.6 – 5.0 60+ 9/ 342 2.6 1.4 – 4.9 HBSAg Prevalence, by Age and Sex n=6073

Born post- Born before vaccine vaccine introduction introduction Vaccination status

• Vaccine status ascertained for 262/509 (51%) of under 5s • (Health record 40%, parent/guardian report 60%)

Of those whose vaccination status ascertained: • Completed HepB3: 261/262 (99.6%) Vaccine impact

Age-sex standardised HBV prevalence: • Pre-vaccine introduction: 5.0% (95% CI 4.1, 5.9) • Post-vaccine introduction: 0.5% (95% CI 0.2, 0.8)

• Odds ratio= 0.1, 95% CI (0.1, 0.2, P<0.0001) Wealth, education, ethnicity

• Principle component analysis of 12 household variables to generate socioeconomic score for area – based on 617 randomly selected houses • OR for HBV infection per decrease in wealth quintile = 0.85 (95% CI 0.67, 1.08, p=0.18)

• No association observed with ethnic group (p=0.26) or educational level (p=0.65) Conclusions

• Low rate of HBV transmission to children (0.5%) with no birth dose, maternal tenofovir or immunoglobulin • Very high rates of vaccination observed • HBV intermediate prevalence (5%) in individuals born prior to vaccine introduction • No HBV infections identified in under 4s Acknowledgements

Malawi Liverpool Wellcome Trust Clinical Research Programme Dr Isaac Shawa Prof Dean Everett Prof Melita Gordon

University of Liverpool Prof Anna Maria Geretti

Malawi Ministry of Health Dr Leo Masamba Dr Collins Mitambo