Evaluating Immunogenicity of a Birth Dose of HBV Vaccine in the DRC
NCT ID: NCT03897946
Last Updated: 2021-03-03
Study Results
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Basic Information
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COMPLETED
PHASE4
569 participants
INTERVENTIONAL
2019-08-20
2021-02-05
Brief Summary
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Detailed Description
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Pediatric HBV is a substantial problem in the Democratic Republic of the Congo (DRC). Preliminary data from the 2013-2014 Demographic and Health Survey in the DRC revealed that 2.2% of children under the age of five are infected with HBV.
Why is the seroprevalence of HBV so high in children? The three-dose HBV vaccine has been part of the Expanded Program on Immunization (EPI) in the DRC since 2007, with vaccination rates now approaching 80%. However, the EPI vaccination schedule does not begin until six weeks of life. In contrast, in developed countries, infants receive the first dose of HBV vaccine at birth. This birth dose is rarely administered in SSA. Routine birth dose vaccination could be a simple and cost-effective means to reduce the pool of infected and highly infectious children in the DRC.
While the protective efficacy of a three-dose series of HBV vaccine plus immunoglobulin (HBIG) initiated at birth is ≥95%, immunogenicity of HBV vaccine administered according to the EPI schedule (pentavalent vaccine administered at 6,10 and 14 weeks) is only 80-85%. This gap in antibody response leads to a significant population of children who are potentially vulnerable to infection in infancy or later in life. The immunogenicity of a four-dose HBV vaccine series including a monovalent birth dose prior to the EPI schedule has not been fully assessed to date. Furthermore, HBIG is not available in SSA due to prohibitive cost and storage issues, necessitating an evaluation of the effectiveness of the vaccine series alone without HBIG.
In collaboration with the DRC Ministry of Health, Abbott Laboratories and Ohio State University, the investigators are conducting the Arresting Vertical Transmission of HBV (AVERT-HBV) study, which leverages the existing HIV PMTCT framework in the DRC to screen and treat pregnant women and their infants to prevent MTCT of HBV. The investigators will use the AVERT study population to recruit participants (HBV-exposed infants and their mothers) for this study. Women who screen negative for HBV as part of AVERT will be included in this study as the HBV-unexposed cohort.
While HIV PMTCT programs have been successful in reducing the number of HIV-infected infants in the DRC, many infants fall into the HIV-exposed uninfected (HEU) category. These HEU infants are known to have lowered immune responses to vaccines than HIV-unexposed infants, including protective immunity to HBV after the EPI-associated three-dose series. Little is known about the effects of in utero HBV exposure on the immune response to HBV vaccine. The investigators hypothesize that because the immune response of infants exposed to HBV may be blunted, these infants may benefit from an additional dose of HBV vaccine at birth.
Using the AVERT-HBV cohort as a basis, this project will assess the immunogenicity of the birth dose vaccine in HBV-exposed and HBV-unexposed infants. A better understanding of the protection offered by the addition of birth dose vaccine to the EPI schedule is necessary in order to promote universal adoption of a birth dose vaccine in the DRC and throughout SSA.
This prospective cohort study will involve 100 HBV-exposed infants who will receive 4 doses of HBV vaccine starting at birth (Group A), 100 HBV-unexposed infants who receive 3 doses of HBV vaccine according to the EPI schedule (Group B) and 100 HBV-unexposed infants who receive 4 doses of HBV vaccine starting at birth (Group C). The infants will be followed for 12 months, at which time protective immunity against HBV, defined as HBsAb ≥10 milli-international units (mIU)/mL, will be measured.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
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Group A: Hepatitis B exposed, with birth dose
The 100 HBV-exposed (born to HBsAg-positive mothers) infants who are already enrolled in the parent AVERT study will also be enrolled in the current study, as the "HBV-exposed cohort" (Group A). These exposed infants will not receive additional interventions on top of the AVERT study since they will already be receiving a birth dose vaccine through the AVERT study.
Birth dose hepatitis B vaccine
Groups A and C will receive a birth dose of hepatitis B vaccine within 24 hours of life.
Group B: Hepatitis B unexposed, no birth dose
For the "HBV-unexposed cohort" in this study, the investigators will enroll 200 infants born to HBsAg-negative mothers. Half (100) of these infants will receive the routine three-dose series of HBV vaccine according to the standard EPI schedule in the DRC with no additional birth dose vaccine (Group B).
No interventions assigned to this group
Group C: Hepatitis B unexposed, with birth dose
Group C will consist of the other half (100) of infants in the "HBV-unexposed cohort" who will receive four doses of HBV vaccine including a birth dose vaccine prior to the routine EPI schedule.
Birth dose hepatitis B vaccine
Groups A and C will receive a birth dose of hepatitis B vaccine within 24 hours of life.
Interventions
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Birth dose hepatitis B vaccine
Groups A and C will receive a birth dose of hepatitis B vaccine within 24 hours of life.
Eligibility Criteria
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Inclusion Criteria
* Infants born to HBsAg-positive and HBsAg-negative women who receive care at Binza and Kingasani maternity centers will be recruited for participation in this study.
Exclusion Criteria
* Women \<18 years of age
INFANTS
* HIV-exposed infants (those born to HIV-positive mothers) will be excluded given an expected difference in immune response in these infants and inability to recruit enough HIV-exposed infants to be able to detect these differences in immune response
* HBV-unexposed infants weighing \<2,000 grams at birth will not be eligible to receive the birth HBV vaccine. (HBV-exposed infants receive the birth dose vaccine regardless of birth weight because the potential benefit of preventing mother-to-child transmission outweighs the potential risk of vaccination in a low birthweight infant. The research team recognizes that Group B may include a disproportionate number of low birthweight infants compared to Group C, but will account for this in post-hoc analyses and if need be, will exclude low birthweight infants from the analysis to account for potential bias).
* Infants born at a facility other than one of the two maternity centers
45 Years
ALL
No
Sponsors
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The American Society of Tropical Medicine and Hygiene
OTHER
Burroughs Wellcome
INDUSTRY
University of North Carolina, Chapel Hill
OTHER
Responsible Party
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Principal Investigators
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Steven R Meshnick, MD, PhD
Role: STUDY_DIRECTOR
UNC-Chapel Hill
Peyton J Thompson, MD
Role: PRINCIPAL_INVESTIGATOR
UNC-Chapel Hill
Locations
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Binza and Kingasani Maternity Centers
Kinshasa, , Democratic Republic of the Congo
Countries
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References
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O'Hara GA, McNaughton AL, Maponga T, Jooste P, Ocama P, Chilengi R, Mokaya J, Liyayi MI, Wachira T, Gikungi DM, Burbridge L, O'Donnell D, Akiror CS, Sloan D, Torimiro J, Yindom LM, Walton R, Andersson M, Marsh K, Newton R, Matthews PC. Hepatitis B virus infection as a neglected tropical disease. PLoS Negl Trop Dis. 2017 Oct 5;11(10):e0005842. doi: 10.1371/journal.pntd.0005842. eCollection 2017 Oct. No abstract available.
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28.
Keane E, Funk AL, Shimakawa Y. Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa. Aliment Pharmacol Ther. 2016 Nov;44(10):1005-1017. doi: 10.1111/apt.13795. Epub 2016 Sep 15.
Edmunds WJ, Medley GF, Nokes DJ, O'Callaghan CJ, Whittle HC, Hall AJ. Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas. Epidemiol Infect. 1996 Oct;117(2):313-25. doi: 10.1017/s0950268800001497.
Breakwell L, Tevi-Benissan C, Childs L, Mihigo R, Tohme R. The status of hepatitis B control in the African region. Pan Afr Med J. 2017 Jun 22;27(Suppl 3):17. doi: 10.11604/pamj.supp.2017.27.3.11981. eCollection 2017.
Wilson P, Parr JB, Jhaveri R, Meshnick SR. Call to Action: Prevention of Mother-to-Child Transmission of Hepatitis B in Africa. J Infect Dis. 2018 Mar 28;217(8):1180-1183. doi: 10.1093/infdis/jiy028.
Andersson MI, Rajbhandari R, Kew MC, Vento S, Preiser W, Hoepelman AI, Theron G, Cotton M, Cohn J, Glebe D, Lesi O, Thursz M, Peters M, Chung R, Wiysonge C. Mother-to-child transmission of hepatitis B virus in sub-Saharan Africa: time to act. Lancet Glob Health. 2015 Jul;3(7):e358-9. doi: 10.1016/S2214-109X(15)00056-X. No abstract available.
Klingler C, Thoumi AI, Mrithinjayam VS. Cost-effectiveness analysis of an additional birth dose of Hepatitis B vaccine to prevent perinatal transmission in a medical setting in Mozambique. Vaccine. 2012 Dec 17;31(1):252-9. doi: 10.1016/j.vaccine.2012.08.007. Epub 2012 Aug 15.
Poovorawan Y, Sanpavat S, Pongpunlert W, Chumdermpadetsuk S, Sentrakul P, Safary A. Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers. JAMA. 1989 Jun 9;261(22):3278-81.
Wong VC, Ip HM, Reesink HW, Lelie PN, Reerink-Brongers EE, Yeung CY, Ma HK. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Lancet. 1984 Apr 28;1(8383):921-6. doi: 10.1016/s0140-6736(84)92388-2.
Tsega E, Tafesse B, Nordenfelt E, Wolde-Hawariat G, Hansson BG, Lindberg J. Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI). J Med Virol. 1990 Dec;32(4):232-5. doi: 10.1002/jmv.1890320407.
Apiung T, Ndanu TA, Mingle JA, Sagoe KW. Hepatitis B virus surface antigen and antibody markers in children at a major paediatric hospital after the pentavalent DTP-HBV-Hib vaccination. Ghana Med J. 2017 Mar;51(1):13-19. doi: 10.4314/gmj.v51i1.3.
Abu-Raya B, Kollmann TR, Marchant A, MacGillivray DM. The Immune System of HIV-Exposed Uninfected Infants. Front Immunol. 2016 Sep 28;7:383. doi: 10.3389/fimmu.2016.00383. eCollection 2016.
Njom Nlend AE, Nguwoh PS, Ngounouh CT, Tchidjou HK, Pieme CA, Otele JM, Penlap V, Colizzi V, Moyou RS, Fokam J. HIV-Infected or -Exposed Children Exhibit Lower Immunogenicity to Hepatitis B Vaccine in Yaounde, Cameroon: An Appeal for Revised Policies in Tropical Settings? PLoS One. 2016 Sep 22;11(9):e0161714. doi: 10.1371/journal.pone.0161714. eCollection 2016.
Tulenko SE, Ngimbi P, Mwandagalirwa K, Tabala M, Matondo J, Ntambua S, Mbonze N, Mbendi C, Luhata C, Jhaveri R, Edwards JK, Becker-Dreps S, Moormann AM, Kaba D, Yotebieng M, Parr JB, Gower EW, Thompson P. Immunogenicity of a Birth Dose of Hepatitis B Vaccine in Kinshasa, Democratic Republic of Congo: A Randomised, Controlled Trial. J Viral Hepat. 2024 Dec;31(12):795-807. doi: 10.1111/jvh.14003. Epub 2024 Sep 24.
Related Links
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World Health Organization Global Hepatitis Report, 2017
Congo Democratic Republic: Demographic and Health Survey, 2013-2014 - Final Report
Other Identifiers
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18-2793
Identifier Type: -
Identifier Source: org_study_id
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