Essay on New Insights Into Leprosy: Implications for Treatment and Disease Control

Paper Type:  Essay
Pages:  7
Wordcount:  1715 Words
Date:  2023-04-08

SUMMARY

Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as "leprosy reactions," which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.

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INTRODUCTION

Leprosy, or Hansen's disease (HD), is an ancient bacterial disease that, although curable, continues to be a significant health problem in many parts of the world. HD results from infection with the Mycobacterium leprae bacillus, which produces a chronic infection in humans that affects mainly peripheral nerves and skin but may also affect sites such as the eyes, mucous membranes, bones, and testes and produces a spectrum of clinical phenotypes (1,-3). In the skin, M. leprae has an affinity for keratinocytes, macrophages, and histiocytes (3, 4). In peripheral nerves, M. leprae can be found in Schwann cells (2). Keratinocytes seem to play a key role in the release of the antimicrobial peptide v-defensin in response to M. leprae antigens (4). Once inside the host cell, M. leprae interacts with the host cell lipid metabolism to foster bacterial intracellular survival (5). The predilection for the Schwann cell initiates after its attachment to a2-laminin and adhesins located in the basal lamina and to a-dystroglycan and ErbB2 receptors on its cell surface (6). The entry of M. leprae bacilli into Schwann cells triggers cells to dedifferentiate into immature cells through the activation of signaling of the Erk1/2 pathway. This transformation creates a suitable environment for the bacteria to proliferate (7). More recently, it has been shown that further dedifferentiation leads to the reprogramming the Schwann cell to a "stem cell-like" cell with a plethora of new capabilities, such as redifferentiation into mesenchymal cells with the ability to spread infection or attracting macrophages to develop granulomas that could then serve as a Trojan horse for systemic dissemination of M. leprae (3, 8). The presence of bacilli in the skin produces the dermatological manifestations of the disease, and nerve infection produces axonal dysfunction and demyelination, leading to sensory loss and its consequences of disability and deformity (2, 9). In this sense, the degenerative changes associated with infection of the peripheral sensory nerves are considered a crucial event in the natural history of HD (7, 8). Once the infection is established, the occurrence of leprosy reactions, because of their inflammatory impact on peripheral nerves, remain an important contributor to sensory loss and dysfunction (9,-12).

In the last few decades, particularly with the advent of multidrug therapy (MDT) and the use of anti-inflammatory therapies, there have been substantial improvements in long-term health outcomes for individuals diagnosed with HD. Although the worldwide prevalence of this disease has significantly decreased, HD is still a poorly understood illness, and often, the statistics do not capture the disability and dysfunction that remain after MDT is complete. A 1991 World Health Assembly resolution for HD "elimination" (reducing the prevalence to 1 case of HD per 10,000 people) by the year 2000 was achieved at the global level (13). However, in many regions where HD is endemic, this goal is still far from being met, and the incidence of the disease has not decreased significantly over the past decade. Among the millions of people who have been cured with multidrug therapy, there are a large number who still suffer from long-term complications of the disease, including temporary and permanent disability, deformity, and social stigma.

There were 219,075 new cases of HD reported in 2011, underscoring the persistent transmission of the disease despite an overall decrease in its prevalence (14). Under the current WHO-recommended treatment scheme, many people complete the treatment in less than a year, so the global prevalence of leprosy is often lower than the incidence; the total number of registered cases at the beginning of 2012 was 181,941 (14). India and Brazil account for the majority of these cases. In this article, after a brief discussion of the history of HD and its treatment, we touch on some of the contemporary challenges associated with HD treatment in nations where the disease is and is not endemic as well as some of the more recent findings that may have a positive impact on HD control and patient well-being in the future.

HD PAST AND PRESENT: A BRIEF SUMMARY

Skeletal and genetic evidence of the antiquity of HD provides some clues to understanding the disease in the present context. While there is only speculative evidence that the disease that we understand today to be a result of infection by M. leprae bacilli was among the skin afflictions described in ancient texts from the Old World, concrete skeletal evidence of the disease's existence in the past has been found, including a find dated to 4,000 years ago in India (15). Sequencing of the HD genome and discoveries of genetic material in human skeletal material from previous centuries also give us more information about the movement of the disease as well as about human migration. For example, Schuenemann et al. (16) compared genome sequences of M. leprae from skeletons dated to 1,000 years ago in Europe to contemporary strains, indicating that contemporary M. leprae strains share an ancestor dating back to <4,000 years ago.

In many (but not all) parts of the world, the deformities and disabilities caused by HD, as well as religious and social meanings associated with the disease or the physical changes that might result from it, have resulted in and continue to generate stigmatizing attitudes toward and negative beliefs about people affected by the disease. In 1943, Guy Faget, working at Carville Hospital in Louisiana, demonstrated that sulfone drugs were effective in killing M. leprae bacilli (17), but confinement policies in many countries were in place for many years after this. In Japan, mandatory confinement continued until the mid-1990s. As noted by Sato and Narita, the scientific understanding of HD as a disease with low transmissibility did not always dictate policy decisions, which were more influenced by societal stigma coupled with dilemmas associated with providing services for reintegration of those people who had been isolated (18).

In 1982, multidrug therapy was introduced, which remedied many of the problems associated with monotherapy (17); previously, most patients had to take daily doses of sulfone monotherapy for life, and if there was an interruption in taking the medication, drug resistance could develop. Many patients worldwide complete MDT, which consists of a combination of the medications rifampin, clofazimine, and dapsone, in a year or less. Although patients are considered "cured" after the completion of MDT, many experience complications after MDT is completed, including a lifelong stigma associated with having had the disease, leprosy reactions, permanent disability, and occasional relapse/reinfection. Complications associated with leprosy reactions are significant causes of disability and create particular challenges for patients and physicians over the long term (2).

THE HD BACILLUS AND ITS IMPACT

HD results from infection with Mycobacterium leprae, an intracellular acid-fast bacillus. Most people (an estimated 95% of the world's population) are not genetically susceptible to the disease (11), but there seems to be variation among population groups that may be related to both genetic factors and ancestral exposure to the bacillus. The traditional model of interaction of an infectious agent that includes host, pathogen, and environment is a unique one in the case of HD. Overall, there seems to be little pathogen variability and virulence to explain the different clinical forms, with the possible exception of the recently discovered species Mycobacterium lepromatosis in patients with HD who had diffuse leprosy of Lucio and Latapi (3, 19, 20). Confirmation of this as a new species that could cause HD requires further research, as defined by Gillis et al. (21). However, most of the clinical phenotypes may be due to genetic variability determined by different biological pathways modulated by M. leprae and reprogramming of adult Schwann cells and interactions of innate and adaptive immunity (3, 8).

Some population groups exhibit higher prevalence rates of HD than others. For example, among populations of the Western Pacific, particularly Micronesia, the prevalence (number of cases per 10,000 people) is among the highest in the world (22). This could have to do with greater genetic susceptibility, but it could also be related to the recent introduction of HD to this part of the world. Among susceptible individuals, there is great variety in terms of the individual immune response to the bacilli in the body, such that physicians who work with the disease for many years see the value in looking at each person's disease as unique.

The classification of leprosy should be determined by clinical prognosis and to distinguish which cases may be potentially infectious (1, 23, 24). The World Health Organization suggests a simple scheme for distinguishing different types of HD, which is used as the basis of the current treatment model; in this model, HD is classified based on visible symptoms and (ideally) the presence or absence of bacilli in slit-skin smears from cooler regions of the body (generally from earlobes, elbows, and/or knees) where bacilli proliferate: those patients with just 1 to 5 diagnostic skin patches and no apparent bacilli in slit-skin smears are classified as having "paucibacillary" disease, and those with >5 skin patches and bacilli visible by microscopic analyses of skin smears are classified as having "multibacillary" disease. In areas without access to slit-skin smears, the criterion for diagnosis is the number of visible lesions. Gupta et al. (25) found that this fairly arbitrary model based on the number of lesions that are identifiable can result in both over- and underdiagnosis of HD; they suggested adding additional criteria that take into account the size of the lesions and accompanying nerve enlargement. Prasad and Kaviarisan (26) note that the WHO classification system contains no treatment protocol for cases of neuritic HD in which no skin lesions or changes are present. A more nuanced system of classification recognizes a spectrum of cell-mediated responses to the disease, with five categories of the disease (23, 24); these include, from the least to the most severe (or the greate...

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Essay on New Insights Into Leprosy: Implications for Treatment and Disease Control. (2023, Apr 08). Retrieved from https://proessays.net/essays/essay-on-new-insights-into-leprosy-implications-for-treatment-and-disease-control

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