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Alternative strategy for the prevention of mother-to-child transmission of hepatitis B in Cambodia: the ANRS 12345 TA PROHM study


Author: Segeral, Olivier
Under the direction of: Laurence Meyer
Université Paris-Saclay
Langue française Texte français

Keywords: Epidemiology, Cambodia, Hepatitis B, Pregnant women, Mother-child transmission, Public health, Cambodia, Tenofovir, Health services - Decentralization - Cambodia, Pregnant women - Medical examinations, Rapid diagnostic test, Vaccination schedule, Hepatitis B - Vertical transmission of infectious disease.


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Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection is the cause of most chronic hepatitis B in countries with high HBV endemicity. Prevention is based on early vaccination of newborns at birth and, for HBsAg-positive women, on the administration of antiviral treatment in the third trimester of pregnancy if the HBV DNA viral load is > 5.3 log10 IU/mL and immunoglobulin (HBIg) to the newborn. In Cambodia, the prevalence of HBV infection among pregnant women, children aged 5 to 7 years, and those born to HBsAg-positive mothers was estimated at 4%, 0.6%, and 10%, respectively. The objective of this thesis was to design and evaluate a strategy to reduce HBV MTCT in Cambodia using tools available in the country. This work was structured around the ANRS 12345 TA PROHM study which objective was to evaluate the effectiveness of an HBIg-free alternative strategy to prevent HBV MTCT in Cambodia based on 1/ the use of HBsAg and HBeAg rapid diagnostic tests (RDT) for the screening and management of HBV infection in peripartum 2/ a treatment with tenofovir from 24 weeks of amenorrhea of eligible women 3/ an early vaccination for all infants at birth (< 2 hours of life). The first step was to validate the use of the two RDTs, HBsAg for screening HBV infection and HBeAg for deciding eligibility for TDF. A first evaluation reported the excellent performance of the HBsAg RDT as compared to an enzyme immunoassay technique but an unsatisfactory sensitivity of the HBeAg RDT to identify women with an HBV DNA viral load level > 5.3 log10 IU/mL. A new algorithm selecting HBeAg-positive women and HBeAg-negative women with ALT > 40 U/L increased sensitivity by 17% for this viral load threshold and was used in the study from January 2019.From 2017 to 2020, 21,251 women were screened in antenatal care. Of these, 1194 could be included in the study, of whom 338 (28%) were eligible for TDF. In the absence of HBIg, the rate of HBV MTCT was 1.48% [CI95%, 0.40-3.74] for women eligible for TDF and 0% [CI95%, 0-1.41] for those treated more than one month before delivery. In contrast, the rate of HBV MTCT was 8.33% [CI95%, 1.75-22.5] for those treated less than one month, highlighting the importance of HBV early detection during pregnancy. For women not eligible for TDF, the transmission rate was 1.06% [CI95%, 0.39-2.30], with transmission occurring in highly viremic women not identified by the algorithm. This work shows that an HBIg-free alternative strategy using maternal antiviral prophylaxis with TDF for at least one month before delivery combined with an early infant vaccination at birth can prevent HBV MTCT. This strategy is applicable in decentralized areas, which is essential for countries such as Cambodia where access to technical facilities is limited to the capital or major provincial cities. Such a strategy needs to be implemented in rural settings, including an analysis of the costs and supply chains of drugs and reagents, to initiate the political commitment necessary for a nationwide scaling-up.