Scientists fear that diphtheria could soon make a major comeback after a number of worrying trends were spotted in diphtheria's bacterial genomes.
While diphtheria can be easily preventable with vaccines, some samples are showing that the bacteria are evolving to become resistant to a number of classes of antibiotics – and could potentially escape vaccines in the near future. On top of this, the COVID-19 pandemic has disrupted the global vaccine efforts to contain the disease.
Diphtheria is a highly contagious disease caused by toxin-producing strains of the bacterium Corynebacterium diphtheriae. The infection usually affects the mucous membranes of the nose and throat, leading to symptoms including fever and a sore throat. It can lead to a range of nasty complications, including inflammation of the heart muscle, inflammation of nerves, kidney problems, and bleeding problems. Left untreated, it can be fatal.
Modern medicine – namely, widespread vaccines – has helped to quash this disease in recent decades. In 2016, 7,097 cases were officially reported worldwide, reduced dramatically from nearly 100,000 in 1980. However, scientists are starting to worry that this stronghold may be slipping.
Researchers from the University of Cambridge in the UK recently sounded the alarm in the journal Nature Communications. They analyzed the genome of over 500 C. diphtheriae isolates taken from 16 countries and territories over the past 122 years. This included a subset from India, where in 2018, over half of the globally reported cases occurred.
Their analysis revealed some worrying genetic changes. Diphtheria is caused by a toxin produced by C. diphtheriae. This toxin is encoded by the tox gene, and it is this component that’s targeted by vaccines. The study managed to find 18 different variants of the tox gene, many of which could potentially change the structure of the toxin. If these changes continue, the structure of the toxin may change to such an extent that it could potentially evade the vaccine.
“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,” Professor Gordon Dougan, study author from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), said in a statement.
Diphtheria can be treated with a number of different antibiotics. Unfortunately, changes seen in the genome of this bacteria suggest this might also become problematic in the near future. Their analysis showed that antimicrobial resistance genes are becoming increasingly common among C. diphtheriae. Genomes of bacteria isolated from infections in the most recent decade, 2010 to 2019, showed the highest number of antimicrobial resistance genes per genome – an average almost four times higher than in the 1990s, the next highest decade.
“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,” explained Robert Will, first author of the study and PhD student at CITIID.
Along with these two worrying trends, the COVID-19 pandemic may also be fanning the flames, the researchers argue. The World Health Organization estimates that 117 million people worldwide will miss out on vaccinations for preventable diseases like measles due to COVID-19. Considering that levels of diphtheria were already on the rise – 2018 saw the highest incidence in 22 years – disruptions from the pandemic could be yet another blow in the fight to contain the disease.
"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," concludes Dr Ankur Mutreja, lead study author from CITIID.