Prevalence estimates of chronic hepatitis B virus infection
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1 Conference on Liver Disease in Africa September 13-15, 2018 Prevalence estimates of chronic hepatitis B virus infection A comparative study of four sources and implications for burden assessment in sub-saharan Africa Nora Schmit, Shevanthi Nayagam, Mark Thursz, Tim Hallett Imperial College London
2 Background Chronic hepatitis B virus (HBV) prevalence estimation Systematic review + modelling of empirical seroprevalence data 4 recent sources of country-level, regional and global estimates of chronic HBV prevalence Prevalence in the general population Prevalence in children 5 years of age Testing and treatment New infections, vaccination impact
3 Background 4 sources of HBV prevalence estimates different methods Schweitzer et al IHME 2016 (Global Burden of Disease Study) WHO 2015 (modelling by LSHTM) CDA 2016
4 Background 4 sources of HBV prevalence estimates different methods Schweitzer et al WHO 2015 (modelling by LSHTM) IHME 2016 (Global Burden of Disease Study) CDA 2016 Meta-analysis of all available data using different regression models Single highest-quality prevalence estimate in a country used as input for dynamic transmission model
5 Background 4 sources of HBV prevalence estimates different methods Schweitzer et al WHO 2015 (modelling by LSHTM) IHME 2016 (Global Burden of Disease Study) CDA 2016 WHO data is based on updated Schweitzer systematic review
6 Background 4 sources of HBV prevalence estimates different methods Schweitzer et al WHO 2015 (modelling by LSHTM) IHME 2016 (Global Burden of Disease Study) CDA 2016 WHO Geospatial data is extrapolation, based on updated including to Schweitzer countries with systematic no empirical review seroprevalence data
7 Published estimates of global HBV prevalence Background Nearly identical global estimates from WHO, CDA and Schweitzer Higher estimates from IHME
8 Published estimates of global HBV prevalence Background Nearly identical global estimates from WHO, CDA and Schweitzer Higher estimates from IHME
9 Aim Compare the most recent country-level HBV prevalence estimates generated by 4 data sources: analyse the magnitude and direction of differences between estimates in the general population and in children under 5 years of age assess implications of differences for HBV burden estimation in sub- Saharan Africa Are similarities in global estimates reflected on the country level in sub-saharan Africa?
10 Are similarities in global estimates reflected on the country level in sub-saharan Africa? Results Differences between prevalence estimates from any 2 sources in a country range from 0.03 to 16.9 percentage points. WHO/CDA in The Gambia WHO/Schweitzer in Swaziland Median difference between estimates from different sources: General population: 3.0% [IQR ] Children under 5 years of age: 4.0% [IQR ]
11 Results Where do estimates differ the most across sources? Relative to the median prevalence, estimates are among the most variable across sources in: Countries with no empirical seroprevalence data Children <5 years compared to general population estimates (p=0.001) Relative variability Mean absolute deviation around the median prevalence median prevalence No empirical seroprevalence data in WHO estimate of estimates
12 Results Which sources have generated the most similar prevalence estimates? Higher estimates from IHME and Schweitzer: older seroprevalence data and no vaccination covariate Most similar estimates between WHO and CDA despite different methods CDA covers fewer countries than the other sources: 25 vs
13 Results Comparing CDA and WHO general population estimates Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
14 Results Comparing CDA and WHO general population estimates Nearly identical estimates in Tanzania, Mozambique, Senegal Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
15 Results Comparing CDA and WHO general population estimates CDA > WHO Nearly identical estimates in Tanzania, Mozambique, Senegal WHO > CDA in 15/25 countries CDA > WHO in 10/25 countries WHO > CDA Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
16 Results Comparing CDA and WHO general population estimates Large differences in some countries despite overall similarity: Estimates in less than half of countries within 25% of each other, and 6/25 countries with relative differences >50% Largest absolute differences (>3.9 percentage points) in Nigeria, Chad, Burkina Faso and Gabon Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
17 Results Comparing CDA and WHO general population estimates Relative estimate discrepancy not correlated with relative uncertainty in the WHO estimate after excluding Chad (p = 0.66) suggests that larger differences between WHO and CDA point estimates do not reflect lack of seroprevalence studies in a country Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
18 Results Comparing CDA and WHO general population estimates Relative estimate discrepancy not correlated with relative uncertainty in the WHO estimate after excluding Chad suggests that larger differences between WHO and CDA point estimates do not reflect lack of seroprevalence studies in a country Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
19 Results Case study: Nigeria most data-rich country in sub-saharan Africa WHO Prevalence in % (95% CI ) 9.9 million infected people CDA Prevalence in % (95% CI ) 20.8 million infected people
20 Results Case study: Nigeria most data-rich country in sub-saharan Africa WHO Prevalence in % (95% CI ) 9.9 million infected people CDA Prevalence in % (95% CI ) 20.8 million infected people 78 primary studies included 1 primary study included
21 Results Case study: Nigeria most data-rich country in sub-saharan Africa WHO Prevalence in % (95% CI ) 9.9 million infected people CDA Prevalence in % (95% CI ) 20.8 million infected people 78 primary studies included Nearly all conducted on a subnational level and many in special population groups (e.g. pregnant women in antenatal care) Recent (2016) national serosurvey among the general population employing multistage household sampling and covering the six geopolitical zones of Nigeria Confirmed by national expert feedback
22 Results WHO and CDA take different perspectives on the available data Countries with differences > 2.5 percentage points: CDA quality scoring prioritises generalisable (geographic scope, population, study design) and more recent studies with larger sample size (Nigeria, Burundi, Burkina Faso, Madagascar) BUT: many countries do not have one particularly high-quality serosurvey (Chad, Malawi, Ivory Coast, Gabon, Mali) in 6/9 countries the included studies do not overlap between WHO and CDA different identification process/inclusion criteria?
23 Results Comparing CDA and WHO estimates in children < 5 years of age Large relative differences overall (majority of estimates differ by over 50%) Countries with largest absolute differences largely the same as those with most discrepant general population estimates Trend towards a higher WHO estimate Absolute difference between estimates > 2.5 percentage points > 5 percentage points Relative difference between estimates < 25% of average prevalence < 50% of average prevalence
24 Estimate ratio: General population / children <5 years Results Comparing CDA and WHO estimates in children < 5 years of age Ratio of estimates in general population to children <5 years: lower and less variable in WHO estimates CDA WHO suggests a lack of primary data and a systematic difference in modelling strategy of age-specific prevalence patterns (statistical vs. dynamic model)
25 Conclusions & recommendations Large differences in country-level estimates in sub-saharan Africa, particularly in children under 5 years of age: - IHME: consistently higher - WHO and CDA: lower and most similar estimates based on more recent data Differences between estimates arise from: - differences in the choice of primary data (currency and quality) - differences in modelling strategy (covariates, statistical vs. dynamic models)
26 Conclusions & recommendations Need for seroprevalence data in sub-saharan African countries with and without previous serosurveys: - up-to-date - high quality (generalisable) - age-specific including young children Regular refinement of modelled estimates with new data Model comparison could improve understanding of how different assumptions and covariates affect the estimates
27 Thank you! Acknowledgements Funding: Medical Research Council DTP Research studentship Participants of Technical Consultation on Modelling of Hepatitis B (London, May 2018): - CDA: Devin Razavi-Shearer - IHME: Nick Kassebaum & Kathryn Lau - Schweitzer: Jördis Ott & Johannes Horn - WHO: Yvan Hutin
28 References Prevalence estimates and methods: Institute for Health Metrics and Evaluation (IHME), GBD Results Tool. Seattle, WA: IHME, University of Washington. Available from [Accessed Oct 2017] Razavi-Shearer, D., Gamkrelidze, I., Nguyen, M.H., Chen, D.S., Van Damme, P., Abbas, Z., Abdulla, M., Rached, A.A., Adda, D., Aho, I. and Akarca, U., Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. The Lancet Gastroenterology & Hepatology, 3(6), pp Schweitzer, A., Horn, J., Mikolajczyk, R.T., Krause, G. and Ott, J.J., Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and The Lancet, 386(10003), pp Vos, T., Abajobir, A.A., Abate, K.H., Abbafati, C., Abbas, K.M., Abd-Allah, F., Abdulkader, R.S., Abdulle, A.M., Abebo, T.A., Abera, S.F. and Aboyans, V., Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, : a systematic analysis for the Global Burden of Disease Study The Lancet, 390(10100), pp World Health Organization, Global and Country Estimates of immunization coverage and chronic HBV infection. Available from [Accessed Nov 2017] Other: World Health Organization, Global Hepatitis Report World Health Organization. United Nations, Department of Economic and Social Affairs, Population Division, World Population Prospects Available from [Accessed April 2018]
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