International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2025
Hepatitis A breakthrough infections despite vaccination: A systematic review and meta-analysis.
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Schnyder Jenny L, Hutten David, Bache Bache E, Spijker René, Welkers Matthijs R A, de Jong Hanna K, Grobusch Martin P, Goorhuis Abraham
Аннотация
OBJECTIVES: This systematic review and meta-analysis summarized documented breakthrough hepatitis A (HepA) infections and assessed whether they occur more frequently in immunocompromised populations (ICPs).
METHODS: We searched Medline, Embase, and Global Index Medicus for records on HepA breakthrough infections, defined as symptomatic HepA among previously vaccinated individuals, published 1991-2024 (PROSPERO: CRD42023450205). Risk of bias was assessed with an adapted Newcastle-Ottawa Scale. Moderate and good-quality studies were analyzed using random-effects and Bayesian hierarchical meta-analyses. The primary outcome compared the proportion of ICPs among fully vaccinated (≥50 days before symptoms) confirmed breakthrough cases to that among all virologically confirmed HepA cases. Meta-analyses assessed the proportion of breakthrough infections among confirmed cases.
RESULTS: Of 3345 reports screened, 90 were included, reporting 43,861 HepA cases, including 832 (partially) vaccinated. We identified six confirmed breakthrough infections with proof of complete vaccination (6.4%; 95% confidence interval 2.6-14.3%), including four ICPs (67%). Post-vaccination serology was available in 3/6 cases: two HIV-positive patients were seronegative, and one neutropenic leukemia patient was seropositive but pauci-symptomatic. The pooled proportion of ICPs among confirmed HepA cases was 17.8% (95% confidence interval 7.7-35.9%).
CONCLUSIONS: HepA breakthrough infections are rare, but appear more common among ICPs who fail to seroconvert post-vaccination.
METHODS: We searched Medline, Embase, and Global Index Medicus for records on HepA breakthrough infections, defined as symptomatic HepA among previously vaccinated individuals, published 1991-2024 (PROSPERO: CRD42023450205). Risk of bias was assessed with an adapted Newcastle-Ottawa Scale. Moderate and good-quality studies were analyzed using random-effects and Bayesian hierarchical meta-analyses. The primary outcome compared the proportion of ICPs among fully vaccinated (≥50 days before symptoms) confirmed breakthrough cases to that among all virologically confirmed HepA cases. Meta-analyses assessed the proportion of breakthrough infections among confirmed cases.
RESULTS: Of 3345 reports screened, 90 were included, reporting 43,861 HepA cases, including 832 (partially) vaccinated. We identified six confirmed breakthrough infections with proof of complete vaccination (6.4%; 95% confidence interval 2.6-14.3%), including four ICPs (67%). Post-vaccination serology was available in 3/6 cases: two HIV-positive patients were seronegative, and one neutropenic leukemia patient was seropositive but pauci-symptomatic. The pooled proportion of ICPs among confirmed HepA cases was 17.8% (95% confidence interval 7.7-35.9%).
CONCLUSIONS: HepA breakthrough infections are rare, but appear more common among ICPs who fail to seroconvert post-vaccination.