Diphtheria is resurfacing as a threat worldwide as it evolves antibiotic resistance and could escape vaccine containment, scientists warn.
Diphtheria cases in recent years have doubled what they were in previous decades, to 16 651 cases in 2018. Although babies are vaccinated against it in high-income countries, there is less coverage in middle- and low-income countries.
Diphtheria is mainly caused by Corynebacterium diphtheriae, spread by coughs and sneezes or close contact with the infected. Usually, the bacteria cause acute infections, driven by the diphtheria toxin—the main target of the vaccine. However, non-toxigenic C. diphtheria can also cause disease.
A 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.
Analysing the genomes of 61 bacteria isolated from patients and combining these with 441 publicly available genomes, the researchers were then able to understand how they spread. They also used this information to assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation.
The researchers found clusters to genetically-similar bacteria isolated from different continents, most commonly Asia and Europe. This indicates that C. diphtheriae has been travelling with humans as they spread across the planet.
The diphtheria toxin ch is encoded by the tox gene, for which the researchers found 18 different variations, of which several had the potential to 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.”
First author Robert Will, a PhD student at CITIID, said: “The C. diphtheriae genome is complex and incredibly diverse. It’s acquiring resistance to antibiotics that are not even clinically used in the treatment of diphtheria. There must be other factors at play, such as asymptomatic infection and exposure to a plethora of antibiotics meant for treating other diseases.”
Erythromycin and penicillin are commonly recommended to treat early-stage diphtheria, although there are other classes capable of it. Variants resistant to six of these classes in isolates from the 2010s were identified by the team.
Study leader Dr Ankur Mutreja from CITIID, said: “It’s more important than ever that we understand how diphtheria is evolving and spreading. Genome sequencing gives us a powerful tool for observing this in real time, allowing public health agencies to take action before it’s too late.
“We mustn’t take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form.”
Source: Medical Xpress
Journal information: Will, RC et al. Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheria. Nat Comms; 8 Mar 2021; DOI: 10.1038/s41467-021-21870-5
