known to make a toxin (poison which is encoded by the tox gene), affecting the nose, throat, and seldom the skin. It is known to spread by coughs and sneezes, or through close contact with someone infected. It is characterized by
Globally the infection witnesses an increasing number of cases. There were 16,651 reported cases In 2018 – more than double the yearly average for 1996-2017 (8,105 cases).
Generally, the babies are vaccinated against infection in the UK and other high-income countries. But, the disease can still cause sporadic infections or outbreaks in unvaccinated and partially-vaccinated communities in low- and middle-income countries.
Genomics of Diphtheria
The study team applied genomics to analyze the genomes of 61 bacteria isolated from patients (including a subset from India, where over half of the globally reported cases occurred in 2018) and combining these with 441 publicly available genomes to map the spread of infections by building a phylogenetic tree – a genetic ‘family tree. The presence of antimicrobial resistance (AMR) genes and toxin variation was also assessed using the obtained data.
It was found that clusters of genetically-similar bacteria were isolated from multiple continents, most commonly Asia and Europe, thereby intimating that C. diphtheriae has been set in the human population for at least over a century, and disperses across the globe as populations migrate.
Also, the team found 18 different variants of the tox gene (that is targeted by vaccines to neutralize them), of which several had the potential to change the structure of the toxin. Thus an ever-increasing diversity of tox variants mandates the need for modification of the vaccine, and treatments that target the toxin.
Antimicrobial Resistance and Treatment of Diphtheria
The average number of AMR genes per genome was found to be increasing by each decade, almost four times as many on average in 2010-19 than in the 1990s.
“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”, says Robert Will, a Ph.D. student at CITIID and the study’s first author.
The study states that COVID-19 has had a negative consequence on childhood vaccination schedules worldwide and begins at a time when reported case numbers are surging, with 2018 showing the largest incidence in 22 years.
“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”, says Dr. Ankur Mutreja from CITIID, who led the study.
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