Fighting diphtheria: This old disease needs a new treatment

It’s a tragedy whenever a child dies needlessly of a disease that is both preventable and treatable. Sadly, that happens daily around the globe, due mainly to a raft of infectious diseases. One of these is diphtheria. It is still a killer mainly because the treatment for it is no longer made and stockpiles of it are aging and dwindling.

Highly contagious and particularly deadly among children under age 5, the name of the disease comes from the Greek word for “leather hide,” a reference to the gray, leather-like coating that the toxin generated by the diphtheria bacterium leaves behind in the nose and throat. Within a few days, the disease can suffocate a child. In the United States, diphtheria was once a leading cause of childhood deaths. The discovery of an antitoxin derived from horse serum at the end of the 19th century, followed by the widespread vaccination of infants against diphtheria in the 20th century, helped to erase it as a common disease here and in other developed countries.

But diphtheria hasn’t been defeated. In 2015, more than 4,500 cases of it were reported to the World Health Organization. The bacterium continues to circulate even among immunized populations. Most diphtheria outbreaks occur in poor countries in Africa, the Middle East, and Asia where vaccination is not universal or complete. But cases can, and do, occur anywhere public health is disrupted by natural disasters or conflicts, as has happened recently in Haiti, Syria, and the Ukraine. European doctors have been shocked to see cases of diphtheria among migrants from African and Middle Eastern countries.

They have been even more shocked to learn that the antitoxin is no longer manufactured, that the stockpile of it is shrinking, and that it often can’t be delivered in time to save a sick child. International health leaders, monitoring the upheavals occurring around the globe, say that the need for a reliable supply of the diphtheria antitoxin is dire. Some have compared the world’s lack of preparedness for diphtheria outbreaks to walking into a storm.

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MassBiologics, a nonprofit unit of the University of Massachusetts Medical School that I lead, has been at the forefront of diphtheria treatment since 1894, when the organization was created specifically to produce the newly-discovered diphtheria antitoxin, which saved the lives of thousands of children in Massachusetts and beyond. The antitoxin was made by extracting blood from horses exposed to small amounts of diphtheria toxin. Once vaccination helped prevent the disease, demand for the equine antitoxin began falling steadily. The number of companies willing to make the antitoxin dwindled; today, none distribute it internationally.

Research teams at MassBiologics have identified a much safer human antibody to diphtheria toxin. Instead of making it by bleeding horses kept in stables, we use cell cultures to produce this antibody consistently

and cleanly in sterilized steel tanks. Preclinical testing has proven that our antibody neutralizes the diphtheria toxin.

Our next step is to generate enough of it for a Phase 1 clinical trial in humans that will validate its dosage and safety. This week, officials from the WHO and the Centers for Disease Control and Prevention will report on this potential advance at a strategic advisory meeting in Geneva.

Public health ministers in places like the Dominican Republic, where spillover cases from Haiti have been threatening public health, have been pleading for diphtheria antitoxin. The unnecessary shortage of this treatment exposes a widespread and troubling gap in the global public health community: the lack of a coordinated, strategic, and modern approach to address diseases that lack commercial incentives for production.

Of course, even promising vaccines and preventive therapies such as a diphtheria antitoxin face innumerable challenges during the years it takes to move from the lab to patients, often because their potential markets are too small to encourage private investment and the countries where they are needed don’t have resources to fund research or buy the necessary doses. Clearly, the world needs new vehicles to develop drugs for infectious diseases. The recently launched Coalition for Epidemic Preparedness Innovations — a partnership among governments, foundations, pharmaceutical companies, and academic research centers — may be one solution. Although it will initially focus on developing vaccines for the most urgent epidemic threats, its model could eventually encompass other medical interventions.

Diphtheria is an old disease, a terrible disease, and one for which we believe there’s an effective new treatment at hand — if only we can liberate it from our freezer and put it into the hands of doctors around the world.

Mark S. Klempner, MD, is the executive vice chancellor for MassBiologics, part of the University of Massachusetts Medical School.