A new study reveals the rapid transmission rate of the Haemophilus influenzae bacterium and the extent of its antibiotic resistance globally. H. influenzae is a major bacterial pathogen that causes meningitis, pneumonia and otitis media, or middle-ear infection, among other diseases.
Globally, an estimated 700 million cases of otitis media occur each year, with roughly a quarter of them caused by H. influenzae. Middle-ear infections are the most common reason for antibiotic prescriptions for small children.
It is the first large-scale genomics-based survey of H. influenzae, advancing considerably epidemiological and evolutionary understanding of the species. H. influenzae was the first bacterium to have its genome fully sequenced from a single isolate, and its publication in 1995 ushered microbiology into a new era. At the time, sequencing just one bacterial genome could take years, but current technology enables sequencing of thousands of genomes in just a few months, resources permitting.
This is the first study to comprehensively investigate H. influenzae in poor and developing countries using accurate mapping of genomic variation.
“We sequenced almost 4,500 bacteria isolated from children in the Mae La refugee camp in north-western Thailand, combining these data with all publicly available H. influenzae genomes for which date and country of isolation was available,” Professor Corander says.
The genomic stage of the study lasted over seven years, starting from when the researchers began preparing frozen bacterial samples for sequencing. The analyses required special expertise in population genomics and bioinformatics, as well as enormous computing and storage capacity.
“Without long-term funding, such extensive basic research would have been impossible,” Corander notes.
The researchers found that multi-drug resistance (MDR) was common in the Mae La samples, and that it has evolved and spread often through recombination, as different bacterial strains exchange genetic material when they end up colonising the same individual.
The strains found to be resistant to antibiotics have spread worldwide and may already be prevalent in areas where diseases caused by this bacterium are common. The researchers also found that what are known as non-typeable (NT) H. influenzae strains were the most prevalent in pneumonia cases among the Mae La population, who nonetheless had not had the Hib vaccination against type b H. influenzae.
No genetic differences in non-typeable H. influenzae bacteria were observed between pneumonia patients and healthy carriers, indicating that all NT strains have the same ability to cause serious diseases, such as pneumonia.
Extensive analyses demonstrated that the rapid inter-regional and -continental spread of this bacterial species is common, and that recombination among these strains is very frequent. This has led to the absence of genetic variation typical of a specific geographic area or period, differing markedly from other bacteria that commonly cause respiratory infections, such as meningococci and pneumococci.
Recommendations for further measures:
- World Health Organisation (WHO) has revised its bacterial pathogens priority list in 2024 and included ampicillin-resistant H. influenzae into the medium priority group. The new study provides support for re-assessing classification into a higher level of priority.
- WHO has additionally revised its GLASS AMR surveillance system, where H. influenzae is now included based on respiratory samples. This is an important step, however, it would be desirable to include the species more broadly also in national surveillance systems since the geographical coverage of GLASS is limited.
- Routine genomic surveillance of healthy colonisation and disease cases would provide the means to better assess the extent and routes of MDR dissemination.
Adopted in the national immunisation programmes of most countries, the Hib vaccine is extremely effective against Hib colonisation and disease, but does not protect against NT strains or other serotypes.
This study provides additional impetus for the development of a universal H. influenzae vaccine to significantly reduce the global burden of disease and the negative health consequences caused by this species. Corander is currently seeking funding for early-stage research on such a vaccine.
Source: Genetic population structure of Haemophilus influenzae at local and global scales, Neil MacAlasdair et al. 2025, Nature Microbiology
Further information:
Jukka Corander,