Leprosy Perspectives: Past, Present And Future
Wayne M. Meyers, M.D. Ph.D
Member of the Damien-Dutton Board
Leprosy: Patient Care And Research
Introduction And Background
From time immemorial there have been numerous efforts to manage and control leprosy. While these efforts were usually well intentioned, they often went awry. Such were the attempts to halt the leprosy epidemic that began in Hawaii in the early 19th century and rapidly swept through the Islands. King Kamehameha V on January 3, 1865 approved an act to prevent the spread of leprosy, to "secure the isolation and seclusion of such leprous persons as...may be being at large, cause the spread of leprosy." The place chosen to secure the seclusion was on a peninsula of the island of Molokai surrounded on three sides by rough seas and on the fourth by a high pali (cliff). This peninsula was made up of three sections: Kalaupapa, Kalawao and Makanalau. The first patients landed on January 6, 1866. Arthur Mouritz, in his book, The Path of the Destroyer, published in 1916, recounts one consequence of this act in what he called "The Leper War on Kauai." This one-time physician to the "Leper Settlement" on Molokai states that Sheriff Hitchcock of Kauai (known by the sobriquet "The Holy Terror") told him: "If leprosy can be stopped by getting all the lepers to Molokai, I propose to keep going after them until I get them all."
Life as a patient on Molokai in nearly every respect was deplorable, but far from unique. Robert Louis Stevenson, the Scottish novelist, poet and essayist in the latter 19th century, from his own observations wrote, "There are Molokais all over the world." In 1886, Father Damien, undoubtedly the best-known figure in the annals of history of leprosy, sent a poignant report about the leprosy patients on Molokai to Walter Gibson, President of the Board of Health in Honolulu. This document occupies 18 pages of Mouritz' book and is entitled, "A personal Experience: Thirteen Years' Residence and Labor among the Lepers at Kalawao." The social and moral degradation that Damien found in the community of patients and their helpers on his arrival May 10, 1873 is best summarized, as he stated, in Hawaiian, "Aloe kanawai ma kei waki" ("in this place there is no law"). Thirteen years later in his 1886 report, Damien was able to write, "I am happy to say that...my labors here, which seemed to be almost in vain at the beginning, have, thanks to a kind Providence, been greatly crowned with success, as at present, there is very little, if any at all, of the...evils committed."
Those who have had the privilege of visiting Kalaupapa and Kalawao will remember vividly the collection of patent medicine bottles retrieved largely from the lava tube caves by Richard Marks, recipient of the Damien-Dutton Award for 1996 and a long-term resident of Kalaupapa. These bottles originally contained the vain hopes of scores upon scores of patients for a cure. After all, the only treatment they had available were a "few physics and their own native medicines." Damien, however, was a man of vision, and stated, "Perchance, in the near future, through the increasing interest and untiring perseverance in the study of the disease by the most intelligent physicians and scientists, a proper specific for the cure of leprosy may be discovered, which to my knowledge has not yet been found." Damien did not live to see the day he envisaged; however, his life--so deeply devoted to compassionate care, punctuated by acts of political activism--raised the social conscience of the world toward the stigma of leprosy and pleaded for the mitigation of this stigma. Damien's death from complications of leprosy on April 15, 1889 secured his name forever in the chronicles of the struggle against leprosy.
Just before Damien's arrival on Molokai, G. Armauer Hansen in Bergen, Norway, began to pave the way for the modern understanding of leprosy. Hansen was convinced that leprosy was an infectious disease and not, as many of the scientists of the day believed, either hereditary or simply an adverse response to environmental factors. To prove his postulation, Hansen examined numerous specimens of tissue fluid from the skin of leprosy patients, and on February 28, 1873 recorded his belief that the microscopic brownish "sticks" or rods he saw were the cause of leprosy. This landmark in the history of microbiology launched the quest for the scientific understanding of the disease that many years later would lead to the realization of some of Damien's hopes for leprosy sufferers. Hansen's discovery took place nine years before Robert Koch cultivated the tubercle bacillus in Berlin, Germany. The leprosy bacillus (Mycobacterium leprae), thus, was the first germ known to cause chronic disease in humans, and was the first of many findings in leprosy to contribute to biomedical research on other afflictions (e.g. complications of diabetes).
Even though Hansen was unable to grow the leprosy bacillus in test tubes and was not successful in infecting animals experimentally, the scientific community accepted his concepts on leprosy as a contagious disease. The proceedings of the First International Leprosy Congress held in 1897 in Berlin contains reports on the status of leprosy in many endemic countries. By then the widely accepted infectious nature of leprosy reinforced measures for isolation of leprosy patients-- "preferably on an island"--to control the disease, and it was further recommended that "healthy children should be separated from their leprous parents as soon as possible." Lacking effective chemotherapy, these measures may have reduced the prevalence of leprosy in the more affluent countries but had very little, if any, influence on numerous socio-economically deprived countries where leprosy was more highly prevalent.
Modern Era Of Leprosy Control And Research
During 1900-1940, commensurate with the modest technological developments in biomedical research in this period, the control and understanding of leprosy progressed little. The 1940's brought a new exciting era in patient care, ushered in by bold efforts of Guy Faget at Carville, Louisiana, who after careful long-term observations established the efficacy of intravenous sulfone in treating leprosy. By 1947, Cochrane had shown that a more convent oral form of sulfone, called dapsone or DDS, was highly effective. This drug was inexpensive, it withstood harsh tropical climates and was relatively nontoxic. More than a decade would pass before this "miracle drug" was employed widely. Gradually, however, DDS brought revolutionary changes, liberating many patients from both the physical damage and the stigmatizing sequelae of leprosy. Ambulatory treatment programs gradually replaced domiciliary care, markedly diminishing the stigma and the social disruption of the lives of patients and their families. Patients could now live at home and visit the treatment center periodically, or mobile units could go to satellite clinics along roads or paths. One by one leprosaria began to close, but more frequently, the leprosaria became reference centers and provided care for the severely disabled. During this same era, pioneering surgical rehabilitation, coupled with injury-preventive measures for insensitive hands and feet, permitted patients to lead happier, more productive lives. The renowned orthopedic surgeon Paul Brand spearheaded this remarkable effort.
Many proactive groups over the years had called for abolition of the term "leper" to help minimize the stigma of leprosy. Improvements in treatment and management of patients helped their cause. One important outcome in this movement was the following resolution approved by the International Leprosy Association in 1948 in Havana: "That the term 'leper' in designation of the patient with leprosy be abandoned, and the person suffering from the disease be designated ' leprosy patient'".
Others, notably Stanley Stein, Founding Editor of The Star, the patients' publication at Carville, preferred the designation "Hansen's disease" or HD for leprosy. Successive staff members of The Star have remained faithful to Stein's policy. Many authorities, however, retain the word "leprosy" for the disease, and "patient leprosy" for those who have the disease.
Beginning with Hansen in 1873, numerous investigators attempted to grow the leprosy bacillus in the laboratory, without success. John Hanks, for example, spent his long professional career in pursuit of this elusive goal of leprosy research, in laboratories from Culion in the Philippines (1941-1945) to Harvard University and finally Johns Hopkins University.
Failure to achieve cultivation of the bacillus obstructed studies aimed at understanding the organism, and made it all the more important to develop models of the disease in animals. Based on observations by Chapman Binford at the Armed Forces Institute of Pathology, Washington DC, in the late 1950's, leprosy infections were established in experimental animals during the next two decades. Infections in mice became the standard for testing chemotherapeutic agents and revealed the important discovery that leprosy bacilli were becoming resistant to DDS. In the early 1970's, Storrs, Walsh and others at Gulf South Research Institute in Louisiana, found the armadillo to be highly susceptible to leprosy. This salient discovery opened new avenues of leprosy research by providing large numbers of leprosy bacilli for an amazing array of leprosy-related scientific studies in, for example, diagnostic reagents, pathogenesis, epidemiology, chemotherapy, immunology, vaccines, and molecular biology.
For what many view as unfortunate missed opportunities, research on the pathogenesis and treatment of experimental leprosy in the armadillo was never sufficiently funded to reach its enormous research potential. Nevertheless, as a spin-off, the armadillo opened new vistas in the epidemiology of leprosy: newly captured animals often already had leprosy, indicating that there were nonhuman sources from which humans could contract the disease, discussed more fully later in this chapter.
Present Status Of Leprosy, And Prospects For The Future
With the above background we will proceed to several topics of current interest in the battle to control leprosy. Some of these subjects are controversial. While the views expressed here are often shared by others, unless otherwise indicated any opinion that appears polemic is the author's responsibility.
Chemotherapy with multi-drug regimens
The report of sulfone-resistant leprosy in 1964, and the subsequent discovery that such resistance was virtually universal, made therapeutic alternatives imperative and urgent. While several other antileprosy drugs were already in use, combined regimens were not employed. The pioneer multi-drug therapeutic trial was undertaken in 1973, by Depasquale and Freerksen in Malta. Their regimen contained dapsone, prothionamide, isoniazid and rifampin, and proved to be effective.
In 1982, the World Health Organization (WHO) issued their recommendations for Multi-drug Therapy (MDT). These recommendations were based on carefully considered but empirical judgments of efficacy, applicability in field programs, and cost. Goals were to, 1) treat patients, 2) prevent bacterial resistance and 3) interrupt transmission. The primary drugs employed were dapsone, clofazimine and rifampin, administered for fixed periods of six or 24 months depending on the form of leprosy. Treatment would then be stopped and the patient removed from official registries as a leprosy patient, whether or not there were sequelae such as deformity and/or disability.
Cooperation between WHO, voluntary agencies, and the governments of endemic countries was excellent. Based on the above criteria, in 1991 WHO reported that the number of leprosy patients worldwide had dropped from a previously estimated 10-20 million to 5.5 million, a remarkable achievement in any light. These statistics prompted WHO to approve a resolution in May 1991 to "...attain the global elimination of leprosy as a public health problem by the year 2000." Elimination as a public health problem was arbitrarily set at one patient or less per 10,000 population, by country. WHO data in 2002 indicated that, compared to 1981, the prevalence of leprosy was reduced by more that 90%. Currently the global prevalence of leprosy is slightly less than 1 per 10,000 population and 83% of the patients live in 6 major endemic countries-India, Brazil, Myanmar (Burma), Indonesia, Madagascar and Nepal. WHO sets the total global number of leprosy patients today at approximately 800,000. Many authorities, however, estimate that the total number is 2-3 times higher.
WHO's goal of elimination of leprosy as a public health problem by the year 2000 was not achieved. However, special strategies were established to aim to achieve this goal by the year 2005: 1) elimination campaigns to reach hidden cases, 2) action programs to reach patients in all readily accessible areas, and 3) provision of MDT to every general health facility. At the same time there are attempts to reduce the maximum duration of treatment to 1 year, and even to 1 month or less. If such reduced duration treatment programs become acceptable and present WHO guidelines for patients with active leprosy are maintained, prevalence rates will approach the number of new patients "successfully" treated per year. Potentially, this could lead to the somewhat absurd interpretation that leprosy had been conquered.
The stated accomplishments to date of the WHO's program of the "elimination of leprosy as a public health problem," unfortunately, has had certain results that have negatively impacted leprosy programs: for example, leprosy research today is meagerly funded, if at all, in most research institutes; treatment programs are now being increasingly integrated into general health services that do not possess the special expertise in diagnosis and treatment required for leprosy, and both the public and the medical community are beginning to view leprosy as a solved problem.
One little known risk of a summary approach to the management of leprosy is the potential for misdiagnosis. To economize resources and personnel, clinicians are not being encouraged to take skin smears or biopsy specimens to help establish diagnosis or to guide clinical treatment. Our files in the Leprosy Registry of the Armed Forces Institute of Pathology contain many specimens that represent recent misdiagnoses by clinicians. A cavalier approach to the diagnosis of leprosy is never good medical practice. There is little question that there are fewer leprosy patients now than several decades ago, and that for most patients the quality of life is significantly improved. Much of this can be attributed to concerted efforts to reach more patients with effective drugs. This is most laudable. In view of our present knowledge, however, are we yet in possession of sufficient data to suppose that by 2005 A.D. the goal set by WHO can be reached? Many individuals and some agencies deeply involved in the care of people affected by leprosy believe this possibility is remote. For example, do the reported national prevalence's of leprosy represent the real prevalence's? Valid data on this question are difficult for many endemic countries to generate. The number of new patients each year (incidence) has declined very little, even in regions where MDT has been rigidly applied for many years, and remains at about 600,000-800,000 new cases each year worldwide. Thus, the goal of the interruption of transmission of leprosy is not being realized. Also, there is insufficient data to assume that there will not be a significant number of relapses following MDT treatment, especially if the period of therapy is reduced to 1 year or less.
Given the relative vacuum of hard data that would withstand rigorous critical analysis, those who proclaim the "elimination of leprosy as a public health problem" must consider their decision very carefully. When "success" is finally announced, will support for leprosy related programs then be withdrawn by WHO? Will national programs be diminished? Will voluntary agencies experience still further reductions in resources to support care of leprosy--both active patients and the millions of individuals who remain disabled by the disease? Are those in authority to do so willing to take this step as soon as the year 2005? I hope not, or only if they possess compelling hard data to answer the questions that more and more critics are raising on this issue. Premature reductions in the struggle against leprosy for the sake of a calendar deadline may well spell disaster, and leave our posterity with an enormous health problem, as similar concepts did for tuberculosis.
Eradication of Leprosy
The motto of the XV International Leprosy Congress in Beijing in 1998 was wisely phrased, "Toward the Eradication of Leprosy." This wording was chosen with the belief that eradication is probably a long way off. There are many unknowns. For example, are there significant nonhuman sources of leprosy? What are the most important modes of transmission? Is a vaccine feasible? Can the presumed current trend of reduction of patients be sustained with diminishing resources? Are there modes of control of leprosy other than chemotherapy?
In consideration of this latter question there are two significant historic correlatives: 1) endemic leprosy disappeared from northern Europe long before specific chemotherapeutic agents became available, and 2) no infectious disease so far has been eradicated by chemotherapy. The beginning of the disappearance of leprosy in northern Europe coincided with quantum improvement in housing and other socioeconomic factors in the Renaissance period. Today, socioeconomic status and prevalence of leprosy in most regions are inversely proportional, suggesting that improved housing and other living conditions will reduce or even eradicate leprosy. Further, if the most important route of transmission is the nasorespirtory passages, as most authorities believe, then more spacious dwellings would reduce contagion.
We now know that there are nonhuman sources of leprosy bacilli. A high percentage of armadillos in the southern United States are naturally infected with leprosy bacilli. Some wild nonhuman primates (monkeys, chimpanzees and possibly baboons) in West Africa and the Philippines have naturally-acquired leprosy. These animals may serve as reservoirs that could perpetuate endemic leprosy in spite of all efforts to eradicate the disease in humans. Some investigators believe that the leprosy bacillus may survive in soil, although this is not widely accepted. At any rate, the role that nonhuman sources of leprosy may play in efforts to eradicate leprosy in humans has been investigated only superficially.
Candidate vaccines for leprosy have long been tested in large field trials, and found wanting. Nevertheless, there is currently a renewed interest in vaccines for leprosy, stimulated by recent developments in the immunology and molecular biology of leprosy and the bacillus that causes the disease. Repeated BCG vaccination confers significant protection against leprosy and may have use in high-risk individuals. The effect, however, seems insufficient to consider BCG as part of a leprosy eradication program.
In conclusion, the struggle against leprosy must go until all people affected by the disease can live happy and productive lives. Currently there are approximately 3 million people with leprosy-related disabilities, in addition to those with active disease. Today specific national programs for leprosy control management have been largely dismantled. Many believe that this step is premature, but this is the "real world" of leprosy care. Measures must be undertaken to train all relevant medical and paramedical personnel in the diagnosis and management of leprosy. I do not believe that this is being achieved at an acceptable level, and may be the greatest need in leprosy related activities today. There is still much to do.