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  • Writer's pictureP.K. Peterson

Rifapentine: a “Potential Game Changer” for Leprosy Control

“[A] selective approach to postexposure prophylaxis is desirable because alerting social contacts and neighbors about a nearby case of leprosy arouses concerns about confidentiality, stigma, and discrimination.”

- David Scollard, MD, PhD, former director, National Hansen’s Disease (Leprosy) Programs, Baton Rouge, Louisiana

“The biggest disease today is not leprosy or tuberculosis, but rather the feeling of being unwanted.”

Although rarely fatal, leprosy is one of the most ancient and stigmatized of all human infections. During the Middle Ages it was referred to as the “living death.” Its victims often were treated as if they had already died, and “leper masses” were conducted to declare those living with the disease “dead” to society. Leprosy still occurs in more than 120 countries with over 200,000 new cases reported every year, but it is now considered a “neglected tropical infection.”

Last month the New England Journal of Medicine (NEJM) published the results of a randomized clinical trial showing an 84% reduction of cumulative leprosy cases in household exposures after just a single dose of the antibiotic rifapentine.This is a “game changer” for leprosy prevention. In today’s post, I provide a brief review of this enigmatic disease, including the substantial progress made in the recent past in its treatment and prevention.

What is leprosy? Leprosy is a chronic bacterial infection caused by Mycobacterium leprae or M. lepromatosis that results in progressive damage to nerves, skin, and eyes. It is also known as “Hansen’s disease.”

In 1873 in Bergen, Norway, Dr. Gerhard Hansen was the first person to identify the causative agent of leprosy. His detection of the M. leprae bacillus in a patient’s nasal biopsy specimen marked the very first time that a pathogen was identified as causing a disease in humans. (Earlier this year, the 150th Anniversary of Dr. Hansen’s discovery was celebrated around the world.)

The diagnosis of leprosy is confirmed by finding the bacilli in a skin biopsy. The two main types of the disease—paucibacillary and multibacillary—differ in the number of bacteria present in the skin. Multibacillary disease is most severe. If left untreated, the nerve damage can result in crippling of the hands and feet, paralysis, and blindness.

To this day, M. leprae has never been grown in artificial media. It can be propagated, however, in the mouse footpad and in the nine-banded armadillo. Natural infection of armadillos by M. leprae was observed before they became an animal model for human leprosy, and contact with armadillos is considered a risk factor for leprosy. Although exceedingly rare, this animal-to-human transmission classifies leprosy as a zoonotic infection.

How is leprosy transmitted? One of the biggest mysteries of leprosy is its mode of human-to-human transmission. Bacilli are thought to be transmitted via droplets from the nose and mouth. Its transmission requires continuous and close contact of susceptible people with those infected by M. leprae.

Overall, the risk of contracting leprosy is very low. More than 95% of all people have natural immunity to the disease. Those who develop leprosy, however, may have genes that make them susceptible to clinical disease. Because the disease isn’t highly contagious, people with leprosy can live with their families and go to school and work.

In the 1980s, there were more than 5 million cases of leprosy globally. Due to treatment and prevention measures, by 2020 that number had fallen to 200,000 cases. Most new cases occur in 14 countries, with India accounting for more than half. About 200 new cases are reported per year in the U.S., all in immigrants already infected with the disease.

Leprosoria. Because of ignorance and the exaggerated fear of acquiring leprosy from infected people, leprosoria (leper colonies) sprang up around the world to shield uninfected people from lepers. About 750 such colonies still exist in India.

In the U.S., the remote Kalaupapa peninsula on the Hawaiian island of Molokai housed a settlement for leprosy patients from 1866 to 1969. (When it was closed, many residents chose to remain.) From 1894 to 2005, Carville, Louisiana was home to the only national leprosarium in the continental U.S. Its medical, cultural, and architectural legacy lives on as the National Hansen’s Disease Museum in Baton Rouge.

Treatment. Due to the advent of antibiotics, leprosy has been considered curable since the mid-20th century. Nonetheless, in the 1960s, tens of millions of leprosy cases were recorded worldwide when M. leprae started developing resistance to dapsone, the most common treatment option at the time. The World Health Organization, the International Federation of Anti-Leprosy Associations, and other nonprofit organizations, responded by initiating major campaigns against leprosy. These resulted in finding a highly effective three-drug regimen (rifampin, dapsone, and clofazimine) to treat the disease. This treatment showed a steady improvement of outcomes, including a decline in new cases.

Prevention. In 2017, researchers initiated clinical trials of a novel leprosy vaccine (LepVax); preliminary results are encouraging. But while we await the outcome of these trials, prophylactic administration of antibiotics to exposed individuals is the cornerstone of prevention. This is why the results of the study of rifapentine mentioned at the beginning of this Germ Gems post were met with much enthusiasm.

Hongsheng Wang and his colleagues of the National Center for Leprosy Control at the Chinese Center for Disease Control and Prevention in Beijing carried out the study “Single-Dose Rifapentine in Household Contacts of Patients with Leprosy” reported in the NEJM on May 17, 2023. After over four years of follow-up, they found that the subjects who received a single dose of rifapentine had an 84% lower risk of developing leprosy than the no-intervention control group. In addition, they found that rifapentine outperformed a group given rifampin, another antibiotic used in prophylaxis.

In an accompanying NEJM editorial, “A New Step in Postexposure Prophylaxis for Leprosy,” Dr. David Scollard, the former director of the National Hansen’s Disease (Leprosy) Programs in Louisiana, stated, “[T]hese new findings with rifapentine provide additional energy in the implementation of postexposure prophylaxis for leprosy.” Scollard also commented that the study design, which provided confidentiality so social contacts and neighbors were unaware of nearby leprosy, was desirable to avoid stigma and discrimination.

Stigmatization of leprosy. Sadly, the stigmatization of lepers as “unclean” is as ancient as the disease—a disease with clinical descriptions dating to 1400 BC in India. Fortunately, there are some very notable exceptions to this social ostracization. For example, the embrace of a leper by Francis of Assisi in 1205 is said to be the origin of his conversion. And in modern times, Mother Teresa, upon recognizing that stigmatization is a human rights issue, initiated a fund to support educational efforts, establish housing and vocational support and create clinics to provide medication and wound care of infected individuals. (In 2008, the United Nations Human Rights Council adopted a resolution on “Elimination of discrimination against persons affected by leprosy and their family members.”)

With continued advances in its prevention with measures, such as rifapentine prophylaxis (and hopefully, an effective vaccine), leprosoria are likely to become increasingly obsolete. And along with improvements in clinical outcomes, it is hoped the social stigmatization of leprosy will become ancient history.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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