Leprosy, Still Claiming Victims By: Natalie Angierjune Throughout his adolescence, José Ramirez Jr., now a clinical social worker in Houston, had a shifting array of bewildering symptoms. Sometimes, he was feverish; at other times, nauseated. He’d find swellings on his hands and his feet, and open sores that wouldn’t heal. He’d grow hypersensitive to touch, unable to bear even the slightest rustle of a bedsheet. Or his forearms would turn numb, a complication he gamely sought to exploit. “I’d insert safety pins into my skin,” he said, “to try to impress girls.” Dermatologists were baffled. Eczema? Lupus? Varicose veins? Spiritualists spoke of demonic possession. Finally, Mr. Ramirez’s sister, who worked at the local hospital, persuaded two doctors there to take on her brother’s medical mystery. They did every possible test. They sent biopsied tissue to federal researchers in Atlanta. “Within 24 hours, the director of the Texas Health Department came to see me,” Mr. Ramirez said. “He told me I had leprosy.” Photo Father Damien with leprosy patients he ministered to in Hawaii during the 1870s; he was later canonized by the Roman Catholic Church. It was 1968, Mr. Ramirez had just turned 20, and he would spend the next seven years at the National Leprosarium in Carville, La. Today, Mr. Ramirez, 66, is considered cured of the disorder, and he has no visible signs of it — no facial scarring or disfigurement, no loss of digits or clawing in of the hands and feet. “I’m very fortunate,” he said, “that the experimental medications they gave me prevented a lot of that.” Emotional scarring is another matter. The “stigma, guilt and shame” that dog the disorder defy belief, Mr. Ramirez said, and public ignorance about it remains profound. That is why he has given talks around the world, with the essential message that everything you think you know about Hansen’s disease, about leprosy, is probably wrong. That message resonates with researchers as well, who say that, for all the antiquity and notoriety of the disease, leprosy continues to surprise and confound them. The illness can now readily be cured through a sustained course of antibiotics, yet the basic nature of the microbial culprit, a waxy, rod-shaped character called Mycobacterium leprae, is still being sketched out. New research suggests that the leprosy parasite is a paradox encapsulated — at once rugged and feeble, exacting and inept. One research group recently proposed that leprosy may be the oldest infectious disease to go specifically for human beings, with origins dating back millions of years, certainly suggesting a pathogen of formidable persistence. A Slow-Growing Pathogen Yet scientists have also found that the leprosy bacillus is remarkably poor at migrating between human hosts. It dies quickly outside the body — a couple of hours on a lab slide, and that’s it — and about 95 percent of people appear immune to it. “I refer to it as a wimp of a pathogen,” said Richard Truman, the chief of the laboratory research branch at the National Hansen’s Disease Program, a federal program dedicated to the treatment and study of leprosy. And it’s a flabby pathogen, too. Whereas the genomes in most bacteria are streamlined sets of chemical instructions for spurring the fastest possible replication, recent studies have found that nearly half the DNA in M. leprae consists of so-called pseudogenes, inert genetic sequences that once encoded proteins but are now so much nucleic dead weight. That proportion of defunct code is among the highest detected in a micro-organism and helps explain why the leprosy pathogen has one of the slowest generation times of its unicellular kind, dividing just once every 12 to 14 days, against 20 minutes for the ubiquitous E. coli. Some researchers attribute the microbe’s decayed genome to its prolonged and virtually exclusive relationship with its human host. “It’s reductive evolution,” said Erwin Schurr, a molecular geneticist at McGill University — a swapping of plasticity in favor of specialization and a degree of complacency. Dr. Xiang Y. Han of the University of Texas M. D. Anderson Cancer Center said the pseudogenes were a result of a “chase-hide” game, with the microbial “mouse” gradually shedding as many surface proteins as possible to elude our prowling cat of an immune system. Slow-growing though the bacteria may be, if left untreated, they will multiply into the many trillions, forming thick, scaly nodules on the face and extremities — “lepra” is the Greek word for scaly — and destroying the Schwann cells that sheathe and protect the nerves of the peripheral nervous system. Reporting recently in the journal PLOS Neglected Tropical Diseases, Dr. Han and Francisco J. Silva of the University of Valencia in Spain sought to trace the antiquity of leprosy by comparing the genomes of M. leprae and a closely related pathogen named Mycobacterium lepromatosis, which Dr. Han recently discovered. The researchers hypothesize that the common ancestor of the two leprosy microbes jumped into our pre-hominid forebears in Africa some 10 million years ago and migrated with us as we colonized the world. Today, Hansen’s is classified as a rare disease, yet it still strikes some 200,000 people a year, most of them in Brazil, India and other developing nations. Dr. Schurr and other investigators have identified a handful of leprosy susceptibility genes, variants of human genes that for still mysterious reasons appear to enhance the likelihood that exposure to the pathogen will result in the disease. The susceptibility genes also seem to play a role in other, relatively common immune syndromes like Crohn’s disease, a bowel inflammation. “I’m absolutely convinced that leprosy must be thought of as a genetic disease as well as an infectious one,” Dr. Schurr said. In the end, he added wryly, “understanding it may help cure diseases of rich people, too.” Medical historians likewise are overhauling leprosy tropes, questioning the assumption that people with leprosy have always and everywhere been shunned and reviled. Through new scrutiny of documents, art and skeletal remains from the medieval era, when fear of “the leper” was supposedly at its height, scholars are piecing together a more nuanced portrait of how the afflicted were viewed. “There was a spectrum of attitudes, practices and emotional reactions,” said Monica Green, a medical historian at Arizona State University, “which ranged from repulsion and rejection to sympathy and care and even nonchalance.” Reassessing History Scholars long cited the frenzied construction of monasterylike leprosariums in towns across Europe from the 11th through the 14th centuries as evidence that the leprous were considered so dangerous they had to be isolated from society. But more recent historians have argued that the era’s leprosy mania was as much about fund-raising as anything else, a way for villages to attract wealthy donors. “If you look at where leprosaria were located, they were often at major crossroads, where it was easy to conduct business,” Dr. Green said. Studying 733 skeletons from four medieval cemeteries in the Danish town of Odense, one of them the burial ground for the local leprosarium, Jesper L. Boldsen and Lene Mollerup of the University of Southern Denmark found leprotic lesions on a number of the bones from all four locations, suggesting that any segregation was informal at best. As for the notion that medieval “leper bells” were used to to warn healthy citizens of a pariah’s approach — a cliché so enduring it was mentioned on a June episode of the HBO comedy “Veep” — historians now say they believe the real purpose of the noisemaker was to attract rather than repel; people with leprosy often had extreme hoarseness and needed the bells to beg for alms. Carole Rawcliffe, a professor of medieval history at the University of East Anglia and the author of “Leprosy in Medieval England,” has proposed that the real link between leprosy and pariah status dates to the 19th century, when promoters of the new germ theory of disease sought to bolster their case for the rigid isolation of leprosy patients by citing medieval leprosariums as a precedent. And the new generation of leprosariums in the 19th and early 20th centuries were indeed isolation colonies, built on islands like Molokai, in Hawaii, or remote outposts like Carville. The Victorian fear of contagion arose even though Gerhard Armauer Hansen, the Norwegian doctor who discovered M. leprae in 1874 (and after whom the disease was later renamed), ultimately failed to offer gold-standard proof of his organism’s pathogenicity. Nothing Hansen injected with samples, including himself, ended up with leprosy. Even today, researchers remain hampered by M. leprae’s balkiness, its refusal to grow in cell culture or nearly any nonhuman animal. The one puzzling exception is the nine-banded armadillo, which, if anything, the microbe prefers over people. Researchers say they believe wild armadillos — insectivorous, plated mammals native to the Western Hemisphere and now found throughout much of Latin America and the southern United States — first contracted the infection from European settlers a couple of centuries ago, and the resulting disease looks a lot like human leprosy. “You get nerve involvement, systemic infection, issues with the eyes,” Dr. Truman said. Armadillos are now a reservoir for the disease, and in coastal marsh habitats where population densities of the animal can be high, 20 percent or more of the armadillos are thought to be infected with M. leprae and capable of passing it on to susceptible people. Of the 200 cases of leprosy diagnosed annually in the United States, most are thought to stem from contact with armadillos, although the precise route of transmission remains unclear. José Ramirez Jr. suspected he contracted Hansen’s during childhood stints with his migrant worker grandfather in the field, where armadillos were a common sight. Dr. Truman advises people who spot a wild armadillo to steer clear, but please leave the hunting rifle behind. “I can’t think of any way of exposing yourself to greater risk than trying to shoot armadillos,” he said. “They’re living in our environment, and they’re wonderful for taking out fire ants.” Whose sting, after all, is truly medieval.
Posted on: Wed, 02 Jul 2014 15:53:17 +0000