Colorado State University Scientist Unraveling Inner Workings of Leprosy that Still Plagues World

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Next week, Colorado State University researcher John Spencer will travel 1,000 miles by plane and 275 miles by boat up the Amazon River to a little town in Brazil where children are suffering from a disease mostly eradicated from the United States.

Spencer, an assistant professor of Microbiology, Immunology and Pathology at Colorado State, is investigating leprosy in Oriximina, Brazil, and whether a simple blood test can determine if children there are predisposed to leprosy.

Leprosy, caused by Mycobacterium leprae, causes disfiguring lesions on the skin and damages nerves, resulting in disability and deformity if not treated early. Although there are fewer than 200 cases found in the United States each year, about 250,000 cases were diagnosed last year worldwide. Only a few U.S. leprosy research laboratories remain, including at CSU (directed by Patrick J. Brennan, University Distinguished Professor, and Spencer), the National Hansen’s Disease Program (NHDP) in Baton Rouge, La., and the Infectious Disease Research Institute in Seattle. These groups are working together on a diagnostic test for leprosy.

“It would be great to try to figure out why certain people go on to develop disease,” Spencer said. “Detecting antibodies that develop at the very earliest stages of disease is tricky.”

The state of Pará in northeastern Brazil has about 4,000 new cases of leprosy per year, among the highest of any state in Brazil, and many of these cases are in children. In surveys of adolescent children in 10 different cities in this area, 4 percent or more can be diagnosed with clinical symptoms of this disease, which is why it is classified as a hyperendemic area for leprosy.

The average age of diagnosis in surveys of schoolchildren in this area is around 13 years of age. Based on a school population of two million in this state, an estimated 80,000 cases will be diagnosed in the next 20 years. In general, leprosy is still a major health concern in poor parts of the world where unsanitary, crowded living conditions exist.

Spencer recently received a $200,000 grant to spend the next two years working with a Brazilian colleague – Claudio Salgado at the Federal University of Pará in Belem – to develop the blood test. The funding is provided through the Order of Malta (MALTALEP), a lay religious order of the Catholic Church.

Salgado, a dermatologist and immunologist, has been performing surveys of schoolchildren to assess the antibody levels in serum against the leprosy-specific antigen PGL-I for 5 years. In some of the cities he has surveyed, 50 percent or more are positive, indicating that there is a tremendous amount of M. leprae infection in the general population.

“In this area we’re visiting, three-quarters of the children have experienced hunger at some point during the year,” Spencer said. “Claudio was the first doctor some of these kids have ever seen.”

Brazil and India still have the highest number of individuals with leprosy based on the population and the number of cases, but Brazil has the highest number of new cases diagnosed each year – about two per 10,000 people or about 40,000 new cases a year, Spencer said.

Novartis offers the three-drug regimen that treats leprosy to developing countries for free. But Spencer’s goal is to find whether there’s a way to determine first who is predisposed to the disease, particularly in very rural areas where nutrition is lacking and doctors are scarce.

“As is the case with tuberculosis, about 90 percent of people infected with M. leprae will never develop symptoms, while roughly 10 percent will go on to develop leprosy, but it often takes many years for symptoms to develop,” Spencer said. “Are there certain biomarkers of this process of infection and disease progression that we can pinpoint in those individuals that are most at risk? The persons most at risk are those who have lived for an extended period of time, months or years, with a person with untreated disease. The contacts of these untreated people must be more closely monitored and treated at the first signs of disease to break the line of transmission. A simple blood test would facilitate early diagnosis and treatment to prevent the spread of this disease.”

On this next three-week visit to Brazil, the researchers will focus on testing antigens they’ve developed.

“We’re going to test a set of antigens that we think are useful to produce a risk assessment for whether a person is going to come down with leprosy,” Spencer said. “We have examined about 200 different proteins to see if we can see which ones might be good to include in some kind of antibody-mediated test or cell-mediated test for leprosy diagnostics.”