Diphtheria is developing to get antibiotic-resistant safe and could prompt vaccine escape

Diphtheria is developing to get antibiotic-resistant safe and could prompt vaccine escape


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  • Source: University of Cambridge

  • Date: 08 Mar,2021

Diphtheria – a comparatively easily-preventable infection – is evolving to become immune to a range of types of antibiotics and in the future could lead to vaccine escape, warn an international group of researchers in the UK and India.

The researchers, led by scientists at the University of Cambridge, say that the impact of COVID-19 on diphtheria vaccination schedules, coupled with a rise in the amount of diseases, risk the disorder once more becoming a major global threat.

Diphtheria is a highly infectious disease that may affect the nose and throat, and sometimes the skin. If left untreated it may prove fatal. However, in low- and middle-income nations, the disease can still cause sporadic infections or outbreaks in unvaccinated and partially-vaccinated communities.

The number of diphtheria cases reported globally has been increasing slowly. In 2018, there were 16,651 reported instances, more than double the annual average for 1996-2017 (8,105 instances ).

Diphtheria is mostly caused by the bacterium Corynebacterium diphtheriae and is mainly spread by coughs and sneezes, or through close contact with a person who is infected. In most cases, the bacteria cause acute infections, driven by the diphtheria toxin – the important target of this vaccine. But, non-toxigenic C. diphtheria may also lead to disease, often in the form of systemic infections.

In a study published today in Nature Communications, an international group of researchers from the UK and India used genomics to map ailments, such as a subset from India, where more than half of those internationally reported cases occurred in 2018.

They also used this information to estimate the presence of antimicrobial resistance (AMR) genes and evaluate toxin variation.

This implies that C. diphtheriae has been established in the human population for over a century, spreading across the globe as populations migrated.

The major disease-causing part of C. diphtheriae is the diphtheria toxin, which can be encoded by the tox gene. It is this component that’s targeted by vaccines. In total, the researchers found 18 different variations of the tox gene, of which several had the potential to alter the structure of the poison.

Professor Gordon Dougan from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) said:””The diphtheria vaccine is designed to neutralize the toxin, so any genetic variations that change the poison’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.”

Diphtheria infections can usually be treated with a number of classes of antibiotics. While C. diphtheriae resistance to antibiotics have been reported, the extent of such resistance remains largely unknown.

When the team looked for genes which may confer some level of resistance to antimicrobials, they discovered that the average number of AMR genes per genome was growing each decade.

Genomes of bacteria isolated from infections from the most recent decade (2010-19) showed the greatest average number of AMR genes per genome, almost four times as many on average than at the next highest decade, the 1990s.

It’s acquiring resistance to antibiotics which are not even clinically utilized 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 different diseases.”

Erythromycin and penicillin are the traditionally recommended antibiotics of choice for treating confirmed cases of early-stage diphtheria, though there are lots of diverse classes of antibiotics available to treat the infection.

The team identified variants resistant to six of these classes in isolates from the 2010s, greater than in any other decades.

Dr Pankaj Bhatnagar in the World Health Organization state office for India said:”AMR has seldom been regarded 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 will likely be quite a few reasons to this, including exposure of the bacteria to antibiotics in their environment or in asymptomatic patients being treated against other infections.”

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.”

Dr. Ankur Mutreja, Study Lead, Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)

The researchers say that COVID-19 has had a negative effect on childhood vaccination schedules worldwide and comes at a time when reported case numbers are rising, with 2018 demonstrating the maximum prevalence in 22 years.

Journal reference:

Will, R. C., et al. (2021) Spatiotemporal persistence of multiple, diverse clades and toxins of Corynebacterium diphtheriae. Nature Communicationsdoi.org/10.1038/s41467-021-21870-5.


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