Utilising a Cohort Study of Hepatitis B Virus (HBV) Vaccine-Mediated Immunity in South African Children to Model Infection Dynamics: Can We Meet Global Targets for Elimination by 2030?

Background: Sustainable Development Goals and the World Health Organisation (WHO) Global health sector strategy on viral hepatitis have set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Based on current estimates of 250 million individuals with chronic infection, an intensive scale-up of preventive interventions will be required to achieve this goal, alongside enhanced diagnosis and treatment. Although a safe, effective HBV vaccine has been part of the Expanded Programme on Immunisation since the mid-1990s, the extent to which enhanced immunization can contribute to these elimination targets is currently uncertain. We set out to characterise the epidemiology of HBV infection and the prevalence of vaccine-mediated protection in a cohort of South African children in order to inform a model of HBV transmission and prevention. This has allowed us to develop robust, evidence-based insights into the extent to which scaling up vaccination and prevention of mother-to-child transmission (PMTCT) might ultimately contribute to HBV elimination, and to assess the extent to which the targets for 2030 are realistic. Methods and findings: We studied a cohort of 310 children (136 HIV-positive; 174 HIV-negative) aged 6-60 months in Kimberley, South Africa. We screened for HBV infection (HBsAg) and exposure (anti-HBc); these were each present in 3 children ( 60 months), we demonstrated significantly higher antibody titres in the younger group (p

[1]  Susan A. Doyle,et al.  The effect of timing of influenza vaccination and sample collection on antibody titers and responses in the aged. , 2017, Vaccine.

[2]  T. Ndung’u,et al.  PARV4 prevalence, phylogeny, immunology and coinfection with HIV, HBV and HCV in a multicentre African cohort , 2017, Wellcome open research.

[3]  L. Piroth,et al.  Hepatitis B virus vaccination in HIV-infected people: A review , 2017, Human vaccines & immunotherapeutics.

[4]  J. Beghin,et al.  Effectiveness of the South African expanded program of immunization against hepatitis B in children infected with human immunodeficiency virus‐1 living in a resource‐limited setting of Kwazulu‐Natal , 2017, Journal of medical virology.

[5]  K. Jeffery,et al.  Screening, characterisation and prevention of Hepatitis B virus (HBV) co-infection in HIV-positive children in South Africa , 2016, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[6]  T. Hallett,et al.  Requirements for global elimination of hepatitis B: a modelling study. , 2016, The Lancet. Infectious diseases.

[7]  Gérard Krause,et al.  Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013 , 2015, The Lancet.

[8]  M. Cotton,et al.  Hepatitis B virus infection in HIV-exposed infants in the Western Cape, South Africa. , 2015, Vaccine.

[9]  T. Ndung’u,et al.  Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana , 2015, PloS one.

[10]  B. Walker,et al.  Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection , 2015, PloS one.

[11]  N. Crowcroft,et al.  How and why researchers use the number needed to vaccinate to inform decision making--a systematic review. , 2015, Vaccine.

[12]  D. Corley,et al.  Vertical Transmission of Hepatitis B Virus , 2014, Annals of Internal Medicine.

[13]  P. Klenerman,et al.  Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa. , 2014, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[14]  D. Reynders,et al.  Investigating hepatitis B immunity in patients presenting to a paediatric haematology and oncology unit in South Africa. , 2014, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[15]  G. Borgia,et al.  Vertical transmission of hepatitis B virus: challenges and solutions , 2014, International journal of women's health.

[16]  R. Burnett,et al.  Evidence for a change in the epidemiology of hepatitis B virus infection after nearly two decades of universal hepatitis B vaccination in South Africa , 2014, Journal of medical virology.

[17]  H. Whittle,et al.  Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986–90) and in the nationwide immunisation program , 2014, BMC Infectious Diseases.

[18]  R. Tedder,et al.  The epidemiology of hepatitis B virus infection in HIV-infected and HIV-uninfected pregnant women in the Western Cape, South Africa☆ , 2013, Vaccine.

[19]  G. Mieli-Vergani,et al.  Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. , 2013, Journal of hepatology.

[20]  S. Healy,et al.  HIV/HBV coinfection in children and antiviral therapy , 2013, Expert review of anti-infective therapy.

[21]  C. Klingler,et al.  Cost-effectiveness analysis of an additional birth dose of Hepatitis B vaccine to prevent perinatal transmission in a medical setting in Mozambique. , 2012, Vaccine.

[22]  R. Burnett,et al.  An update after 16 years of hepatitis B vaccination in South Africa. , 2012, Vaccine.

[23]  Desmond J. Martin,et al.  HBV/HIV co-infection: the dynamics of HBV in South African patients with AIDS. , 2012, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[24]  L. Aurpibul,et al.  Prevalence of protective level of hepatitis B antibody 3 years after revaccination in HIV-infected children on antiretroviral therapy. , 2011, Vaccine.

[25]  T. Bärnighausen,et al.  Levels of childhood vaccination coverage and the impact of maternal HIV status on child vaccination status in rural KwaZulu-Natal, South Africa* , 2009, Tropical medicine & international health : TM & IH.

[26]  W. Borkowsky,et al.  Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy. , 2009, The Journal of infectious diseases.

[27]  Ryan T Novak,et al.  Persistence of Protection Against Hepatitis B Virus Infection Among Adolescents Vaccinated With Recombinant Hepatitis B Vaccine Beginning at Birth: A 15-Year Follow-Up Study , 2008, The Pediatric infectious disease journal.

[28]  R. Harrington,et al.  Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons , 2008, International journal of STD & AIDS.

[29]  A. De Luca,et al.  Serological response to hepatitis B virus vaccine in HIV‐infected children in Tanzania , 2008, HIV medicine.

[30]  L. Aurpibul,et al.  Antibody response to hepatitis B re-vaccination in HIV-infected children with immune recovery on highly active antiretroviral therapy. , 2007, Vaccine.

[31]  J. Brok,et al.  Hepatitis B immunisation for newborn infants of hepatitis B surface antigen‐positive mothers , 2006 .

[32]  T. Puthanakit,et al.  Prevalence of protective antibody against hepatitis B virus in HIV-infected children with immune recovery after highly active antiretroviral therapy. , 2006, Vaccine.

[33]  G. Leroux-Roels,et al.  Hepatitis B virus and human immunodeficiency virus co‐infection in sub‐Saharan Africa: a call for further investigation , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[34]  H. Kelly,et al.  The number needed to vaccinate (NNV) and population extensions of the NNV: comparison of influenza and pneumococcal vaccine programmes for people aged 65 years and over. , 2004, Vaccine.

[35]  Graham F. Medley,et al.  Hepatitis-B virus endemicity: heterogeneity, catastrophic dynamics and control , 2001, Nature Medicine.

[36]  P. van Damme,et al.  Lifelong protection against hepatitis B: the role of vaccine immunogenicity in immune memory. , 2000, Vaccine.

[37]  H. Whittle,et al.  What level of hepatitis B antibody is protective? , 1999, The Journal of infectious diseases.

[38]  P. van Damme,et al.  Integration of hepatitis B vaccination into national immunisation programmes , 1997, BMJ.

[39]  B. McMahon,et al.  Frequency of adverse reactions to hepatitis B vaccine in 43,618 persons. , 1992, The American journal of medicine.

[40]  S. Hadler,et al.  Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. , 1986, The New England journal of medicine.

[41]  A. Dibisceglie,et al.  Prevalence of hepatitis B virus infection among black children in Soweto. , 1986, British medical journal.

[42]  R. Mikolajczyk,et al.  Time trends of chronic HBV infection over prior decades - A global analysis. , 2017, Journal of hepatology.

[43]  A. Floreani,et al.  Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers. , 2004, Vaccine.