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Updated: Jul 14, 2026

Assessing Respiratory Immune Responses to Haemophilus Influenzae
Published on: June 29, 2021
Nontypeable Haemophilus influenzae meningitis in children: phenotypic and genotypic characterization of isolates
Rita Cardines1, Maria Giufrè, Paola Mastrantonio
1Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Background:
With the decline in the incidence of invasive Haemophilus influenzae type b disease as result of routine immunization of infants, the potential emergence of nontypeable H. influenzae (NTHi) strains as important pathogens has been suggested.
Methods:
From June 1997 to July 2006, 9 cases of NTHi meningitis in children aged < or =60 months were detected. The 9 NTHi isolates were characterized. Antimicrobial susceptibility patterns were determined by E-test. The transpeptidase domain of penicillin binding protein 3 of a beta-lactamase negative ampicillin-resistant strain was sequenced. Genetic relatedness among isolates was assessed by pulsed field gel electrophoresis and by multilocus sequence typing. The presence of HMW and Hia adhesins and hemagglutinating fimbriae was investigated by PCR and Western Blotting.
Results:
The 9 cases of NTHi meningitis did not occur in specific risk groups, except for one patient. Of the 9 NTHi isolates, 2 were beta-lactamase producers and 1 showed the beta-lactamase negative ampicillin-resistant phenotype. Sequencing of the penicillin binding protein 3 revealed novel amino acid substitutions. A high degree of genetic diversity among isolates was demonstrated by pulsed field gel electrophoresis. Multilocus sequence genotyping confirmed that the 9 NTHi isolates did not belong to related phylogenetic clusters. HMW adhesins were found in 2 isolates, and 5 strains possessed Hia. No hemagglutinating fimbriae were detected, even though 2 isolates contained hifA gene sequences.
Conclusion:
NTHi isolates from cases of meningitis in children are genetically diverse. Distribution of adhesins among the isolates we examined is unusual: most strains express Hia that generally occurs in a minority of strains in NTHi, suggesting that this adhesin may play a role in virulence mechanisms of NTHi causing meningitis.
Insights
Nontypeable Haemophilus influenzae (NTHi) meningitis in children shows genetic diversity. The Hia adhesin was unusually prevalent, suggesting a role in NTHi virulence for meningitis.
Area of Science:
- Pediatric infectious diseases
- Bacterial pathogenesis
- Molecular microbiology
Background:
- Routine infant immunization has decreased invasive Haemophilus influenzae type b disease.
- Nontypeable H. influenzae (NTHi) strains are emerging as significant pathogens.
- Understanding NTHi virulence factors is crucial for managing pediatric meningitis.
Purpose of the Study:
- To investigate the genetic diversity and virulence factors of NTHi isolates causing meningitis in children.
- To characterize antimicrobial resistance patterns and adhesin expression in NTHi meningitis cases.
Main Methods:
- Analysis of 9 NTHi meningitis cases in children under 60 months.
- Antimicrobial susceptibility testing (E-test).
- Genetic characterization using pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST).
- Detection of adhesins (HMW, Hia) and fimbriae via PCR and Western Blotting.
Main Results:
- NTHi meningitis cases occurred sporadically without specific risk groups.
- Genetic diversity was high among NTHi isolates, with no clear phylogenetic clustering.
- The Hia adhesin was present in 5 out of 9 isolates, an unusual distribution for NTHi meningitis strains.
Conclusions:
- NTHi meningitis in children is caused by genetically diverse strains.
- The high prevalence of the Hia adhesin suggests its potential role in NTHi meningitis pathogenesis.
- Further research into NTHi virulence factors is warranted.
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