| Summary: | Introduction and Aims: Invasive disease due to Haemophilus influenzae type-b (Hib) suffered a dramatic reduction in countries that introduced routine immunization of infants with the conjugate vaccine. However, along with the relative increase of H. influenzae non-typeable invasive strains (NTHI), the emergence of non-b serotypes as well as Hib disease due to vaccine failure (VF) have been described.1- 4 The aim of our study is to identify and characterize Hib VF in children living in Portugal. Materials and Methods: From January 2010 to December 2018, 94 invasive H. influenzae strains isolated from paediatric patients in 25 Hospitals were characterized. Serotype was identified by PCR with primers and conditions described in the literature.5 Antibiotic susceptibility was determined by microdilution. Genetic relatedness was examined by MLST as previously described.6 Sequences were analysed and submitted to the MLST website (https://pubmlst.org/hinfluenzae/) for assignment of the sequence type (ST). A case of VF was considered if invasive Hib disease occurred ≥2 weeks after one Hib vaccine dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age.1 Results: Among 94 invasive H. influenzae isolates, 29 (30.8%) were Hib, with half of the cases occurring in the last two years and 72% among pre-school children. Eighteen (62%) cases were considered VF: three infants, seven between 13 and 47 months old and eight ≥4 years old. A risk factor for VF was identified only in one case. The main diagnosis were pneumonia (6), meningitis (5), epiglottitis (3) bacteremia (2), sepsis (1), and arthritis (1). One patient died. All isolates from VF cases were characterized in CC6 (ST6, ST190, ST1231) according to the expected results for Hib. In addition, WGS published data from our laboratory showed that five Hib isolates from VF, segregated together with Hib isolates (37) from both pre and pos-vaccination periods.7 All VF isolates were susceptible to ampicillin. Conclusion: Although the numbers are small, an alert is made by this study, as Hib VF seems to be increasing in previously healthy children with a clinical course that may be as severe as the observed in unvaccinated children. Also 44% of the VF occurred at an age (≥4 years-old) where invasive Hib disease was unusual before Hib-conjugate vaccination. Further analysis should be made considering vaccine formulations used, as no difference in vaccine schedule was made in the NIP, possible decline of protective antibody titers and a correlation with Hib carriage in our population.
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