Invasive Haemophilus influenzae Serotype A in the Post-Hib Vaccine Era: A Systematic Review and Meta-analysis

The introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine have led to the reduction of Hib infection and emergence of non-b serotypes. We aimed to investigate the prevalence, clinical features, antimicrobial susceptibility, and molecular lineages of Hia disease in the post-Hib vaccine era. A total of 29 eligible studies published up to December 2025 were included. The pooled prevalence of invasive Hia infection was 15.12% (95% CI: 7.81–24.18%), with substantial geographic variation. Prevalence was highest in North America (28.57%) and lowest in Europe (2.16%). Reported incidence ranged from 0.01 to 20.2 cases per 100,000 population, with the greatest burden observed among infants, young children, and Indigenous populations. Meningitis and pneumonia were the most common clinical presentations, and case-fatality rates ranged from 1.9% to 20%. Most isolates remained susceptible to commonly used antibiotics, with β-lactamase–mediated ampicillin resistance less reported (2%). Molecular typing identified 17 sequence types, with ST23 and related lineages predominating across regions. These findings indicate that Hia disease shows heterogeneous geographic distribution, primarily affecting young children, and is characterised by low antimicrobial resistance and a predominance of the ST23 lineage.