Evidence from archaeological sites in the medieval English city of Winchester shows that English red squirrels once served as an important host for Mycobacterium leprae strains that caused leprosy in people according to a study published in the journal Current Biology.

Leprosy is one of the oldest recorded diseases in human history and is still prevalent to this day in Asia, Africa, and South America. “For thousands of years, humans were thought to be the only natural host of M. leprae until the discovery of M. leprae in several wild animals in recent decades, such as armadillos and, more recently, red squirrels and chimpanzees,” the authors write. While scientists have traced the evolutionary history of the mycobacterium that causes it, how it may have spread to people from animals in the past was not known beyond some hints that red squirrels in England may have served as a host.

In the new study, the researchers studied 25 human and 12 squirrel samples to look for M. leprae at two archaeological sites in Winchester. The city was well known for its leprosarium (a hospital for people with leprosy) and connections to the fur trade. In the Middle Ages, squirrel fur was widely used to trim and line garments. Many people also raised them as pets.

The researchers sequenced and reconstructed four genomes representing medieval strains of M. leprae, including one from a red squirrel. An analysis to understand their relationships found that all of them belonged to a single branch on the M. leprae family tree. They also showed a close relationship between the squirrel strain and a newly constructed one isolated from the remains of a medieval person, says a release. The study found that the medieval squirrel strain is more closely related to human strains from medieval Winchester than to modern squirrel strains from England, indicating that the infection was circulating between people and animals in the Middle Ages in a way that hadn’t been detected before.

“These findings on the natural reservoir of M. leprae indicated that M. laprae circulates in more wild animals than we suspected, and zoonotic infection may contribute to the epidemic of leprosy. Therefore, it is inevitable that leprosy epidemics can persist for a long time in the future, and we should remain vigilant against the spread of M. leprae between humans and wildlife,” they write. 

The low incidence rate of leprosy (0.45 per 10,000 population) in India makes it a rare disease.
| Photo Credit: Getty Images

Much of our conversation about health leads to the talk of a few common ailments that afflict several of our acquaintances — diabetes probably tops this list. Yet, for each of the few ailments that preoccupy us, there are many that occur only rarely, but whose effects can be devastating to the sufferers and their families.

The most common definition of a rare disease is a prevalence rate of one case in a population of 10,000 people. The term orphan disease is apt for many reasons. Rarity made them difficult to diagnose, because young medical practitioners may not have seen even one case. For the same reason, not much research was carried out in these areas, because of which treatments often did not exist.

This situation has undergone a change as awareness of the diseases, and genomic technologies to diagnose them, has spread. In many countries, regulatory bodies offer incentives to promote investments in the development of pharmaceuticals for neglected illnesses. Expectedly, such moves have heightened interest in “orphan drugs”. Between 2009 and 2014, half of all approvals made by the FDA were for rare ailments and cancers. However, the costs of these therapies are prohibitive, especially from an Indian viewpoint. Estimates put these costs between Rs.1 million and Rs.20 million per year.

Initiatives by patient groups

Global numbers indicate that there are around 7,000 rare diseases affecting 300 million people. By extrapolation, India should have 70 million cases. Yet hospitals in India have so far reported less than 500 of these diseases. There is not enough epidemiological data on the communities in which these rare diseases occur. Sophisticated clinical genomics tools are often needed to confirm these disorders. The Government’s National Policy for Treatment of Rare Diseases has only recently started making its mark. Diseases prevailing in our countries include cystic fibrosis, hemophilia, lysosomal storage disorders, sickle-cell anemia, etc.

Citizen’s initiatives are another highlight of India’s progress regarding orphan diseases. A good example is DART, the Dystrophy Annihilation Research Trust, a body formed by parents of patients suffering from Duchenne’s muscular dystrophy. In this condition, muscles in the pelvis begin to waste away from the age of three. In partnership with the IIT and AIIMS located in Jodhpur, the Trust has begun a clinical trial of an efficient and personalised antisense oligonucleotide-based therapeutic regimen for this dystrophy.

Leprosy-free India

With an incidence rate of 0.45 per 10,000 population, leprosy is now considered a rare disease in India. But much remains to be done to restrict the spread of this disease. Leprosy is a good example of how research on orphan diseases can have societal benefits. Recent research on the synthetic antibiotic rifapentine, which is widely used against tuberculosis, has shown that a single dose of this drug, when administered to household relatives of a leprosy patient, significantly curtailed the spread of leprosy to them over a four-year study period (New England Journal of Medicine, 2023; 388:1843-1852). Such findings may help fulfil our government’s aim of a leprosy-free India by 2027.

(The article was written in collaboration with Sushil Chandani, who works in molecular modelling)