Scientists Warn Diphtheria Is on the Rise, Could Become Major Global Threat Again

A nearly vanquished infectious disease looks to be making a comeback. In a new paper this week, scientists warn that cases of diphtheria have gradually increased in recent years, while there are signs that antibiotics and vaccines against the bacteria could be in danger of losing their potency as the germ continues to evolve.

Diphtheria is caused by certain strains of the bacteria Corynebacterium diphtheriae. It’s primarily spread through respiratory droplets and, more rarely, through skin contact with infected wounds. The harm these bacteria cause doesn’t usually come from the infection itself but from the toxin they can produce. Early symptoms include a sore throat and mild fever. Within days, the toxin can kill off enough cells along the throat that it causes a telltale grayish build-up of dead debris that makes it hard for victims to breathe. Sufferers can also develop a swollen “bull neck,” caused by enlarged lymph nodes. If left untreated, the toxin can seep into the bloodstream and other organs, causing massive internal damage that kills about half of its victims.

Though diphtheria has been killing people for centuries, the emergence of antitoxins, antibiotics, and a highly effective vaccine in the first half of the 20th century greatly neutered it. From 1980 to 2000, following the World Health Organization’s push for universal childhood vaccination in the 1970s, the incidence of annual new diphtheria cases dropped by over 90%. Today, around 85% of the world’s population is vaccinated against diphtheria, and the disease is virtually extinct in many countries, including the U.S.

There are still pockets of the world where access to effective treatments and vaccines is more limited, however. The incidence of diphtheria has also gradually started to climb recently. In a new study published Monday in Nature Communications, scientists say there’s evidence that diphtheria bacteria are at risk of changing enough genetically to weaken the effectiveness of antibiotics and vaccines used against them.

The study, which involved researchers from the UK, India, and the World Health Organization, looked at the genetic diversity of these bacteria (both toxin and non-toxin producing strains) over the past century, by studying samples collected from patients in 16 countries. This included India, where a majority of the world’s annual cases of diphtheria now happen. They used this data to chart the evolution of these bacteria over time.

There are signals that the bacteria are starting to adapt to our weapons, the researchers found. They found a substantial increase in the average number of antimicrobial resistance genes carried by diphtheria bacteria in the past decade, compared to earlier decades. The diversity of their “tox” gene, responsible for producing the deadly toxin, has also increased recently. They identified 18 different variants of the tox gene, some of which could conceivably change the basic structure of the toxin, which could make existing treatments less effective.

Antibiotic-resistant strains of diphtheria bacteria could also make it harder for doctors to treat infections. Meanwhile, the diphtheria vaccine works by training the body to recognize the toxin specifically. Any meaningful change in its structure could weaken how well our immune system will fend it off, as well as the strength of antitoxin drugs. That said, these findings don’t show that diphtheria is now impervious to antibiotics or vaccines. The mutations found in its tox gene don’t seem to impact the effectiveness of our current vaccine, while there was no evidence of substantial resistance to the most common antibiotics used to treat infection.

The growing diversity of these bacteria do suggest that it could one day “learn” how to better evade our vaccines, antitoxins, and antibiotics, though. And against the backdrop of current trends, that’s definitely concerning. In 2018, there were more than 16,000 cases of diphtheria reported worldwide—the single highest annual toll seen in 22 years—and 2019 was even worse. And in the past year, the covid-19 pandemic has disrupted vaccination efforts for diseases like diphtheria.

Even in the worst-case scenario, vaccines and antitoxins can be modified if needed, and there are other antibiotics doctors can use if the front-line drugs for these still-rare infections start to fail as well. But the researchers warn that we have to keep studying and start preparing for these possibilities now, before it’s too late and diphtheria follows in the footsteps of other vaccine-preventable diseases like measles that have made a frightening resurgence lately.

“[I]t is more important than ever to understand this historically important disease, to prevent it from becoming a major global threat ever again in its original or a modified, better adapted, form,” the authors wrote.