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Efforts hope to eliminate ancient disease
Far from Dr. Varalakshmi Vissa’s office at Colorado State University, a young girl is examined for possible nerve damage and skin lesions at the Eversley Childs Sanitaria on the tiny island of Cebu in the Philippines. Though worlds apart, Dr. Vissa and the girl are linked together by an ancient mycobacterium that causes a disease once so feared its victims were banished from family, friends, and communities.
Known more commonly in world health circles as Hansen’s disease, leprosy still evokes a strong reaction and continues to challenge scientists and physicians who had hopes of eliminating the affliction globally by the year 2000, later revised to 2005. With the introduction of a highly effective multi drug-treatment program in the early 1980s, an incurable disease became curable. The goal of elimination was achieved worldwide (with global rates of 1 case per 10,000 inhabitants), but at a national level there remain 12 endemic countries where leprosy rates are four times higher than the World Health Organization’s standard for elimination. In 2004, the global incidence of new cases of leprosy was estimated to be just over 400,000 (two to three million people are estimated to be permanently disabled because of the disease).
Mycobacterium leprae, the causative agent of leprosy, is proving to be tenacious as are the medical limitations, geographic inaccessibility, and social stigmas which help maintain leprosy’s status as a public health threat. Despite advances in treatment, early diagnosis remains problematic (when the disease is treated subclinically the risk of long-term disfigurement or disability drops dramatically). A multi-national approach, incorporating laboratories from around the world including the Mycobacteria Research Laboratories at CSU, might just be the golden arrow that finally takes down the disease some medieval societies considered a Purgatory on Earth.
“We are collaborating with laboratories all over the world studying disease transmission modalities, epidemiology, drug resistance, incorporating molecular tools such as DNA fingerprinting, and more,” said Dr. Vissa, an Assistant Professor in the Department of Microbiology, Immunology and Pathology and member of the Mycobacteria Research Laboratories (MRL) since 1994. Dr. Vissa is originally from India where leprosy is endemic and still above WHO elimination levels. “We are looking at M. leprae not only from a molecular level, but also from population studies that examine leprosy rates within families and villages, the incidence of relapse and re-infection, and most likely forms of transmission. Despite the fact that leprosy has been with us for centuries, there is still much we don’t understand. I feel my work with leprosy is not only a challenge, but an obligation.
”In 2001, the M. leprae genome was sequenced and researchers had a new tool with which to work. New drug targets, diagnostic antigens, and in vitro manipulations offered novel areas for research breakthroughs, as did the investigation into genomic markers that distinguish one bacterium from another. But researchers also realized that in order to advance the understanding of M. leprae and leprosy, laboratories needed to be connected and communicating. From her office, Dr. Vissa is at the center of a global virtual leprosy research community. A grant from the National Institutes of Health is enabling her to establish a formal communications network, as well as provide seed money for collaborative experiments. She also is a member of an international consortium known as “Initiative for Diagnostic and Epidemiological Assays for Leprosy” (IDEAL) that was awarded funds by the Heiser Program for Research in Leprosy and Tuberculosis for developing and testing molecular and immunology reagents.
“One of our small pilot projects is looking at prevalence and new case detection in villages and family groups on Cebu Island,” said Dr. Vissa. “We are trying to design more controlled experiments that look at epidemiology and transmission. For example, we know prolonged and high frequency contact increases the risk of infection, but what about the workplace, water, the respiratory route? We know that M. leprae is not a highly contagious bacterium, and needs a susceptible host, but we still don’t know exactly how it is transmitted or what all the reservoirs of infection may be. Part of what we are trying to do is track the disease to see if we can determine the most likely route of transmission.”
Among the laboratories and organizations collaborating with the MRL are Beijing Tropical Medicine Research Institute in China, Instituto Colombiano de Medicina Tropical, Thai National Institutes of Health, Blue Peter Research Center and Stanley Brown Laboratories in India, Leonard Wood Memorial in the Philippines, Oswaldo Cruz Institute (IOC) – Oswaldo Cruz Foundation (Fiocruz) in Brazil, Yonsei University in Korea, and the National Hansen’s Disease Program in Baton Rouge. In addition to collaborative research projects, Dr. Vissa coordinates campus visits for other leprosy researchers to assist them in learning how to work through and set up experiments, do DNA testing, collect samples, and other practical skills. Dr. Vissa continues to learn new skills to share with her colleagues, including tutoring from Dr. William Black, also with MIP, on how to manage and interpret multilocus variable number tandem repeats (VNTRs). Dr. Vissa’s mentor, and longtime founder/director of the Leprosy Resource Service at CSU, is Dr. Patrick Brennan, who continues to provide leadership and direction to the group’s leprosy research programs.
“There are so many new tools we can incorporate into our research that a major part of our efforts is to teach others how to use and gain maximum benefit from these tools,” Dr. Vissa said. “We don’t have formal meetings, other than when we see each other at conferences, but provide a lot of support and information via e-mails and the Web, as well as bringing our expertise to colleagues in other parts of the world. We are trying to make this as interactive as possible, given the diversity of cultures and time zones.”
Dr. Vissa spends time visiting other laboratories including travel to India for the recent International Leprosy Congress and, last year, a trip to China to explore the challenges of biomedical research and refining plans of how she can help. Growing up in India, witnessing the devastation of leprosy firsthand, for Dr. Vissa it’s not only what she wants to do, it’s what she has to do.