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MORU/SMRU
Published in Nature Microbiology, the study uncovered extensive antibiotic resistance (AMR), with some strains resistant to most classes of antibiotics, after performing a genomic analysis of new and existing Haemophilus influenzae genomes, from global samples collected between 1962-2023, suggesting to the researchers that there is an urgent need to further increase H. influenzae in global monitoring systems.
“We found a surprising (and worrying) amount of antimicrobial resistance (AMR) in H. influenzae isolates,” said co-senior author Prof Paul Turner, Head of COMRU (Cambodia). “Colonisation with non-typeable H. influenzae was common in both healthy kids and when they also had pneumonia.”
While there is a highly effective vaccine for H. influenzae type b (Hib), which can cause childhood meningitis and other life-threatening infections – but, despite its name, not the flu – this does not work against any other strains in the same species. One of these strains is non-typeable H. influenzae (NTHi), the leading cause of acute ear infections in children, causing an estimated 175m cases per year globally. It can also cause sinusitis and conjunctivitis, and is a frequent cause of pneumonia. Pneumonia is a potentially life-threatening disease that can also cause permanent damage to the lungs and is particularly common among young children in under-resourced countries.
The team found that H. influenzae from around the world show surprisingly little genetic variation, suggesting that a universal vaccine that targets shared features could be developed.
“Genetically the global H. influenzae population is interesting in that there is extremely high levels of recombination, suggesting it should be possible to develop a universal vaccine,” said Prof Turner. “This is important since we are seeing an increase in the incidence of more severe infections caused by non-typeable (NTHi) and non-type b strains not covered by the existing Hib vaccine, and because otitis media (often caused by NTHi) is globally a major reason for antibiotic use in kids, with a clear impact on AMR.
“We have to find new ways to tackle these infections, such as through vaccination, to ensure that everyone is protected from the twin risks of infection and antibiotic resistance," said Prof Turner..
The strain collection that underpins this work was generated from the Maela ARI study conducted at SMRU by Claudia and Paul Turner from. Clare Ling, COMRU Operations Manager, managed the isolates and working with the Sanger team on the genomic data.
The Sanger Institute team conducted the first large-scale genome sequencing study of H. influenzae to comprehensively investigate H. influenzae in high-burden populations, such as those living on the Thailand-Myanmar border. They sequenced nasal swabs from children at the Maela camp for displaced persons in Thailand, giving 4,474 genomes, and combined these with 5,976 available published genomes of H. influenzae to give a global picture of the evolution and epidemiology of this species.
In the Maela camp, over 95 per cent of pneumonia-associated H. influenzae were NTHi strains. This highlights how effective this bacterium is at causing disease and outcompeting both Hib and other strains of the species, even in a population unvaccinated against Hib. The team did not find any genetic variants of NTHi to be more common among pneumonia cases, suggesting they all have the same capacity to cause invasive disease.
Jukka Corander and Paul Turner are continuing to work on samples from Maela and elsewhere to build a strong case for development of an improved Haemophilus influenzae vaccine to target both encapsulated and non-typeable strains, with the aim to reduce both severe disease (ie sepsis, meningitis, and pneumonia) and antibiotic consumption related to less severe infections (ie otitis media).
- Adapted from Sanger Communications team text.
Photo: Courtesy of Paul Turner. © MORU/SMRU.