MacAlasdair N.Pöntinen A.K.Ling C.Mallawaarachchi S.Thaipadungpanit J.Nosten F.H.Turner C.Bentley S.D.Croucher N.J.Turner P.Corander J.Mahidol University2025-11-062025-11-062025-01-01Nature Microbiology (2025)https://repository.li.mahidol.ac.th/handle/123456789/112924Haemophilus influenzae is an opportunistic bacterial pathogen that causes both non-invasive and invasive disease in humans. Although the H. influenzae type b vaccine can reduce invasive disease, it is not effective against non-b serotypes or unencapsulated non-typeable H. influenzae (NTHi). The genetic population structure of H. influenzae, especially NTHi, which is typically prevalent in lower- and middle-income countries, is unclear. Here we whole-genome sequenced 4,474 isolates of H. influenzae from an unvaccinated paediatric carriage and pneumonia cohort from the Maela camp for displaced persons in northwestern Thailand. Despite no H. influenzae type b immunization, serotype b was uncommon, whereas 92.4% of the isolates were NTHi. Most multidrug-resistant lineages were NTHi, and there were no lineages enriched among disease samples. Incorporating 5,976 published genomes revealed a highly admixed population structure, low core genome nucleotide diversity and evidence of pervasive negative selection. Our findings expand our understanding of this major pathogen in lower- and middle-income countries and at a global scale.Biochemistry, Genetics and Molecular BiologyMedicineImmunology and MicrobiologyArticleSCOPUS10.1038/s41564-025-02171-92-s2.0-10502028899720585276