Leprosy Recognizing Hansen's disease today -- the bell tolls quietly BY Mariam Abdurrahman and Jay Keystone, MD

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Leprosy remains an important global health problem. Also known as Hansen's disease, it's a chronic granulomatous infection caused by the obligate intracellular bacterium, Mycobacterium leprae, that proliferates in cool locations such as the skin and peripheral nerves. Clinical manifestations range from tuberculoid to lepromatous disease, reflecting the variation in cellular immune response to the bacteria. Untreated leprosy can result in permanent, irreversible neurologic deficits and secondary transmission to close contacts. As such, early diagnosis and management are essential to minimize the individual and public health impacts of the disease. Multidrug therapy (MDT) is a highly effective cure.

From antiquity to the present, Hansen's disease remains a socially and physically devastating illness. Historically, leprosy was permanent and disfiguring. It invoked such fear that those afflicted with it carried a clapper and bell to warn of their approach. Today, the disease is curable but more silent, i.e. less recognized, in non-endemic countries like Canada. Rising levels of immigration, however, from countries such as India, Myanmar, Vietnam and the Philippines, where the disease is endemic, underscore the need for improved vigilance and prevention of irreversible nerve damage.

A disfiguring disease
Leprosy is rare in North America. Although most cases occur in immigrants, there are still small endemic pockets in Texas, Hawaii and Louisiana. Currently, there are no such regions known in Canada and transmission within Canadian borders has not been documented. The prevalence here is estimated to be 0.6 cases per 100,000 population. About 5-10 new cases are reported annually.

Globally, at the beginning of 2006, figures indicated 219,826 cases. The incidence in 2005 was 296,499 new cases -- 111,000 less than in 2004. Angola, Brazil, Central African Republic, Democratic Republic of Congo, India, Madagascar, Mozambique, Nepal and the United Republic of Tanzania accounted for about 84% of the new cases detected that year.

Leper colonies
The first reported case of leprosy in Canada occurred in New Brunswick in 1815. Years later, the first Canadian leprosarium, or leper colony, was established in 1891 when five symptomatic Chinese immigrants were forcibly removed from Victoria and transported to Bentinck Island, British Columbia. The institution operated from 1924-1957. It was one of three Canadian leprosaria; the other two were located on D'Arcy Island, BC (1894-1924) and Tracadie, NB (1868-1964).

Insidious onset
Between 1979 and 2002, 184 patients presented to the Tropical Disease Unit of the Toronto General Hospital. Of these, 79% immigrated from the Indian subcontinent, the Philippines and Vietnam. The two documented North American-born individuals contracted the disease while studying or carrying out long-term missionary work in India.

Canadian physicians have the expertise and resources to treat leprosy, but recognition of the disease can be challenging in the face of more common ailments with similar neurologic and dermatologic manifestations. Leprosy can have a protracted, insidious onset -- 3 months to 40 years, with a mean of 2-4 years. Most new immigrants with leprosy manifest within one year of residence, even though the diagnosis is often delayed for several years.

Humans are the chief reservoir of M. leprae, though a few other animal species can also be infected, including the nine-banded armadillo found in thr southern U.S. Aerosol spread of nasal secretions from lepromatous patients and uptake through nasal or respiratory mucosa is thought to be the primary mode of transmission of M. leprae. Direct skin contact is not a common mode of transmission as M. leprae can't traverse intact skin in either direction.

Contagiousness
Those at greatest risk of contracting leprosy are individuals in close, frequent contact with patients who have active, predominantly multibacillary disease. Long-term travellers to endemic regions, particularly those who return home to visit friends and relatives, may also be at increased risk. Most cases, however, have no identifiable contacts.

Ninety-five percent of the world's population is not susceptible to leprosy (see Fig.1), although familial clustering has been demonstrated. Like tuberculosis, most infected individuals don't develop clinical disease. Host loci coding for leprosy susceptibility have been identified on chromosomes within the major histocompatibility complex. The HLA locus tends to also affect the clinical spectrum of the disease. Polymorphisms in the natural-resistance-associated macrophage protein 1 gene (NRAMP1) are associated with multibacillary leprosy in African patients.

Immunity to M. leprae is largely a T-cell mediated event. Unlike tuberculosis, however, infection with HIV-1 does not yet appear to be a risk factor for leprosy, although recent evidence may change this observation.