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Diphtheria could become a 'major global threat'

Tuesday March 9th 2021

Diphtheria could become a global threat again because it is evolving and becoming resistant to a number of classes of antibiotics, scientists have warned.

The researchers, led by the University of Cambridge, UK, say the impact of Covid-19 on diphtheria vaccination schedules, coupled with a rise in the number of infections, risk the disease becoming a major threat again.

While babies are vaccinated against the infection in the UK and other high-income countries, the disease can still cause sporadic infections or outbreaks in unvaccinated and partially vaccinated communities in low- and middle-income countries.

The number of diphtheria cases reported globally is growing, with 16,651 reported cases in 2018 compared with the yearly average of 8,105 cases between 1996 and 2017.

In a study published in Nature Communications, an international team of researchers from the UK and India used genomics to map infections, including a subset from India, where more than half of the globally reported cases occurred in 2018.

They analysed the genomes of 61 bacteria isolated from patients and combined them with 441 publicly available genomes to build a phylogenetic tree.

They found clusters to genetically similar bacteria isolated from multiple continents, most commonly Asia and Europe, which suggests that C. diphtheriae has been established in the human population for at least more than a century.

The main disease-causing component of C. diphtheriae is the diphtheria toxin, which is targeted by vaccines, and the researchers found 18 different variants of the tox gene, several of which could potentially change the structure of the toxin.

Professor Gordon Dougan from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) said: “The diphtheria vaccine is designed to neutralise the toxin, so any genetic variants that change the toxin’s structure could have an impact on how effective the vaccine is.

“While our data doesn’t suggest the currently used vaccine will be ineffective, the fact that we are seeing an ever-increasing diversity of tox variants suggests that the vaccine, and treatments that target the toxin, need to be appraised on a regular basis.”

When the researchers looked for genes that might provide some resistance to antimicrobials, they found the average number of AMR genes per genome was increasing each decade, with genomes of bacteria isolated from infections from 2010-19 showing almost four times as many on average AMR genes per genome compared to the 1990s.

Dr Pankaj Bhatnagar from the World Health Organization country office for India said: “AMR has rarely been considered as a major problem in the treatment of diphtheria, but in some parts of the world, the bacterial genomes are acquiring resistance to numerous classes of antibiotics. There are likely to be a number of reasons to this, including exposure of the bacteria to antibiotics in their environment or in asymptomatic patients being treated against other infections.”

Will, RC et al. Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheria. Nat Comms 8 March 2021; doi: 10.1038/s41467-021-21870-5.

Tags: Asia | Gastroenterology | UK News

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