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27 January, 2020 00:00 00 AM

Leprosy elimination

WHO Information
Leprosy elimination

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an acid-fast, rod-shaped bacillus. The disease mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract and also the eyes, apart from some other structures. Leprosy has afflicted humanity since time immemorial. It once affected every continent and it has left behind a terrifying image in history and human memory - of mutilation, rejection and exclusion from society.

Leprosy has struck fear into human beings for thousands of years, and was well recognized in the oldest civilizations of China, Egypt and India. A cumulative total of the number of individuals who, over the millennia, have suffered its chronic course of incurable disfigurement and physical disabilities can never be calculated.
Since ancient times, leprosy has been regarded by the community as a contagious, mutilating and incurable disease. There are many countries in Asia, Africa and Latin America with a significant number of leprosy cases. It is estimated that there are between one and two million people visibly and irreversibly disabled due to past and present leprosy who require to be cared for by the community in which they live.

When M.leprae was discovered by G.A. Hansen in 1873, it was the first bacterium to be identified as causing disease in man. However, treatment for leprosy only appeared in the late 1940s with the introduction of dapsone, and its derivatives. Leprosy bacilli resistant to dapsone gradually appeared and became widespread.

Diagnosis of leprosy
Diagnosis of leprosy is most commonly based on the clinical signs and symptoms. These are easy to observe and elicit by any health worker after a short period of training. In practice, most often persons with such complaints report on their own to the health centre. Only in rare instances is there a need to use laboratory and other investigations to confirm a diagnosis of leprosy.

In an endemic country or area, an individual should be regarded as having leprosy if he or she shows ONE of the following cardinal signs:
Skin lesion consistent with leprosy and with definite sensory loss, with or without thickened nerves
Positive skin smears
The skin lesion can be single or multiple, usually less pigmented than the surrounding normal skin. Sometimes the lesion is reddish or copper-coloured. A variety of skin lesions may be seen but macules (flat), papules (raised), or nodules are common. Sensory loss is a typical feature of leprosy. The skin lesion may show loss of sensation to pin pick and/or light touch. Thickened nerves, mainly peripheral nerve trunks constitute another feature of leprosy. A thickened nerve is often accompanied by other signs as a result of damage to the nerve.

These may be loss of sensation in the skin and weakness of muscles supplied by the affected nerve. In the absence of these signs, nerve thickening by itself, without sensory loss and/or muscle weakness is often not a reliable sign of leprosy. Positive skin smears: In a small proportion of cases, rod-shaped, red-stained leprosy bacilli, which are diagnostic of the disease, may be seen in the smears taken from the affected skin when examined under a microscope after appropriate staining.

Classification of leprosy
Leprosy can be classified on the basis of clinical manifestations and skin smear results. In the classification based on skin smears, patients showing negative smears at all sites are grouped as paucibacillary leprosy (PB), while those showing positive smears at any site are grouped as having multibacillary leprosy (MB).

However, in practice, most programmes use clinical criteria for classifying and deciding the appropriate treatment regimen for individual patients, particularly in view of the non-availability or non-dependability of the skin-smear services. The clinical system of classification for the purpose of treatment includes the use of number of skin lesions and nerves involved as the basis for grouping leprosy patients into multibacillary (MB) and paucibacillary (PB) leprosy.
While classifying leprosy, it is particularly important to ensure that patients with multibacillary disease are not treated with the regimen for the paucibacillary form of the disease.

Transmission of leprosy
Leprosy is known to occur at all ages ranging from early infancy to very old age. The youngest age reported for occurrence of leprosy is three weeks in Martinique (Montestruc & Berdonneau, 1954). The youngest case seen by the author was in an infant of two-and-a-half months, where the diagnosis of leprosy was confirmed by histopathology. Occurrence of leprosy, presumably for the first time, is not uncommon even after the age of seventy.

Method of transmission of leprosy
The exact mechanism of transmission of leprosy is not known. At least until recently, the most widely held belief was that the disease was transmitted by contact between cases of leprosy and healthy persons. More recently the possibility of transmission by the respiratory route is gaining ground. There are also other possibilities such as transmission through insects which cannot be completely ruled out.

Sex distribution
Although leprosy affects both sexes, in most parts of the world males are affected more frequently than females often in the ratio of 2:1. This preponderance of males is observed in as diverse geographic situations as India, the Philippines, Hawaii, Venezuela and Cameroon. Doull et al (1942) from their studies in the Philippines have also pointed out that the difference as a true difference due to higher incidence among males, and not due to differing duration of disease for the two sexes. It it were the latter case, the sex-specific prevalence could be different even with the same sex-specific incidence. It should be pointed out that the male preponderance in leprosy is not universal and there are several areas, particularly in Africa, where there is either equal occurrence of leprosy in the two sexes, or occasionally even a higher prevalence among females. Such situations have been observed in Uganda, Nigeria, Malawi, Gambia, Burkina Faso, Zambia, Thailand and Japan.

Inactivation of disease
Where leprosy treatment facilities exist, inactivation or cure due to specific treatment is an important mode of elimination of cases from the prevalence pool. Even in the absence of specific treatment, a majority of patients, particularly of the tuberculoid and indeterminate types, tend to get cured spontaneously. An earlier study in India had shown that over a period of 20 years, the extent of spontaneous regression among children with tuberculoid leprosy was about 90%. A study in Culion Island in the Philippines showed that among children self-healing occurred in 77.7% of cases (Lara & Nolasco, 1956). A later study in South India involving long-term follow-up of a high endemic population showed that among newly detected tuberculoid cases of all ages and both sexes, the rate of inactivation was 10.9% per year, the bulk of inactivation in the study being spontaneous (Noordeen, 1975).

Reservoir of infection
The human being is the only known reservoir of infection in leprosy except for the fact that naturally occurring disease with organisms indistinguishable from M.leprae has also been detected among wild armadillos in parts of the southern United States (Walsh et al, 1981). Up to 5% of armadillos in Louisiana have been found to have clinical disease with about 20% having serological evidence of M.leprae infection (Truman et al, 1986). The epidemiological significance of the armadillo is generlly considered to be negligible in spite of occasional cases reported among individuals giving history of handling armadillos (Lumpkin et al, 1983). Among human beings it is the lepromatous cases that carry the largest load of organisms, the maximum load reaching over seven billion organisms per gram of tissue.

Patients with non-lepromatous cases carry a very much smaller bacillary load, probably not exceeding one million organisms in total. In additon to clinically identified cases, the occurrence of acid-fast bacilli (AFB) in the skin (Figueredo & Desai, 1949; Chatterjee, 1976) and nasal mucosa of healthy subjects (Chacko et al, 1979) have also been reported. The evidence that the AFB found on such 'carriers' is M.leprae is not conclusive, although there is some evidence that persons who carry such AFB have a higher chance of developing the disease as found during their follow-up (Chatterjee, 1976).

Portal of exit of M.leprae
The two portals of exit of M.leprae often described are the skin and the nasal mucosa. However, the relative importance of these two portals is not clear. It is true that the lepromatous cases show large numbers of organisms deep down in the dermis. However, whether they reach the skin surface in sufficient numbers is doubtful. Although there are reports of AFB being found in the desquamating epithelium of the skin, Weddell et al (1963) have reported that they could not find any AFB in the epidermis even after examining a very large number of specimens from patients and contacts. Regarding the nasal mucosa, its importance has been recognized as early as 1898 by Schaeffer (1898), particularly tht of the ulcerated mucosa. The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy has been demonstrated by Shepard (1960) as large, with counts ranging from 10 000 to 10 000 000.

Pedley (1973) has reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through nose blows. Davey & Rees (1974) have indicated that nasal secretions from lepromatous patients can yield as much as 1 million viable organisms per day.

Viability of M.leprae outside the human host
The possiblity of discharge of M.leprae from the nasal mucosa raises the question of survival of the discharged organisms outside the human host. Davey & Rees (1974) have reported that M.leprae from the nasal secretions can survive up to 36 hours or more. Desikan (1977) has reported on the survival of M.leprae in nasal secretions under tropical conditions for up to nine days. Such survival of the organisms suggests the possibility of contaminated clothing and other fomites acting as sources of infection.

Portal of entry of M.leprae
The portal of entry of M.leprae into the human body is not definitely known. However, the two portals of entry seriously considered are the skin and the upper respiratory tract. With regard to the respiratory route of entry of M.leprae, the evidence in its favour is on the increase in spite of the long-held belief that the skin was the exclusive portal of entry. Rees & McDougall (1977) have succeeded in the experimental transmission of leprosy through aerosols containing M.leprae in immune-suppressed mice, suggesting a similar possibility in humans. Successful results have also been reported on experiments with nude mice when M.leprae were introduced into the nasal cavity through topical application (Chehl et al, 1985). In summary, although no firm conclusions can be reached with regard to the portal of entry, entry through the respiratory route appears most probable, although other routes, particularly broken skin, cannot be ruled out.

Sub-clinical infection in leprosy
In spite of the fact that as yet there is no simple immunological test to identify sub-clinical infection with sufficient specificity and sensitivity, evidence accumulated in the past few years clearly indicate that sub-clinical infection does occur in leprosy as in many other communicable diseases. This evidence has mainly come from limited studies with in vitro tests for cell-mediated immunity (CMI) such as the lymphocyte transformation test (LTT) and serological tests for detecting humoral antibodies such as phenolic glycolipid I-based ELISA. In addition to the above, skin tests with various preparations of lepromin, and more recently with soluble antigens from M.leprae, have also provided useful information on the occurrence of sub-clinical infection, although the specificity of these tests, particularly of integral lepromin, has been rather questionable. Zuniga et al (1982), using a soluble skin test antigen prepared by the Convit method, have found that skin test positivity in a part of Venezuela was 19% among the general population (non-contacts), 36% among contacts outside the household and 48% among household contacts. The gradation of reactivity clearly suggests the correlation between exposure and possible sub-clinical infection. However, in India (Gupte et al, 1990) no difference was seen in the distribution of skin test reactions to soluble antigens among cases, contacts and general population.

Transmission by contact
The term 'contact' in leprosy is generally not clearly defined. All that we know at present is that individuals who are in close association or proximity with leprosy patients have a greater chance of acquiring the disease. It is with reference to this observation that the early workers appear to have used the term 'contact' as method of transmission. However, it is the definition of contact by later workers with qualifications such as 'skin to skin', 'intimate', 'repeated', etc. that has made it appear as if the disease could be acquired only under such conditions, and that the transmission involved some kind of 'inunction' or rubbing in of the organisms from the skin of affected persons into the skin of healthy subjects. Certainly, there is no proof that transmission takes place only through such inunction. In general, closeness of contact is related to the dose of infection which in turn is related to the occurrence of disease.
Of the various situations that promote close contact, contact within the household is the only one that is easily identified. In that area the relative risk for contacts was about four times that of non-contacts. The actual incidence among contacts and the relative risk for them appear to vary considerably in different studies. Attack rates for contacts of lepromatous leprosy have varied from 6.2 per 1000 per year in Cebu (Doull et al, 1942) to 55.8 per 1000 per year in a part of South India (Noordeen & Neelan, 1978).
Tranmission by contact
The possibility of transmission of leprosy through the respiratory route is gaining increasing attention in recent years. It is interesting to note that as early as 1898 this possibility has also been discussed at some length by Schiffer (Schiffer, 1898). The possibility of transmission through the respiratory route is based on (a) the inability of the organisms to be found on the surface of the skin, (b) the demonstration of a large number of organisms in the nasal discharge, (c) the high proportion of morphologically intact bacilli in the nasal secretions, and (d) the evidence that M.leprae could survive outside the human host for several hours or days.

Transmission through insects
With the available evidence on intracutaneous inoculation as a successful method of transmission of M.leprae in the mouse footpad model and a similar situation possibly existing in human beings, the question arises whether insects could play any role in natural infection. Although a large number of experiments had been conducted in the past demonstrating AFB in biting insects, the question whether insects actually transmitted infection had remained unanswered.

Microbiology of M.leprae
The aetiological agent of leprosy is Mycobacterium leprae. It is a strongly acid-fast rod-shaped organism with parallel sides and rounded ends. In size and shape it closely resembles the tubercle bacillus. It occurs in large numbers in the lesions of lepromatous leprosy, chiefly in masses within the lepra cells, often grouped together like bundles of cigars or arranged in a palisade. Chains are never seen. Most striking are the intracellular and extra-cellular masses, known as globi, which consist of clumps of bacilli in capsular material. Under the electron microscope the bacillus appears to have a great variety of forms. The commonest is a slightly curved filament 3-10 m in length containing irregular arrangements of dense material sometimes in the shape of rods. Short rod-shaped structures can also be seen (identical with the rod-shaped inclusions within the filaments) and also dense spherical forms. Some of the groups of bacilli can be seen to have a limiting membrane.

It is believed that only leprosy bacilli which stain with carbol-fuchsin as solid acid-fast rods are viable and that bacilli which stain irregularly are probably dead and degenerating. The differences are valuable pointers in biopsy specimens to the effects of treatment. In patients receiving standard multidrug therapy (MDT), a very high proportion of bacilli are killed within days, which suggests that many of the manifestations of leprosy, including reactions of the erythema nodosum type, which follow initial treatment, must be due in part to antigens from dead organisms rather than living bacilli. We therefore need drugs which will help the body to dispose of dead but still intact leprosy bacilli.

Two indices which depend on observation of M. leprae in smears from skin or nasal smears are useful in assessing the amount of infection, and the viability of the organisms and also the progress of the patient under treatment. They are the morphological index and the bacteriological index.

The bacteriological index (BI)
This is an expression of the extent of bacterial loads. It is calculated by counting six to eight stained smears under the 100 x oil immersion lens. in a smear made by nicking the skin with a sharp scalpel and scraping it; the fluid and tissue obtained are spread fairly thickly on a slide and stained by the Ziehl-Neelsen method and decolorized (but not completely) which 1% acid alcohol.
 The results are expressed on a logarithmic scale.
1+ At least 1 bacillus in every 100 fields.
2+ At least 1 bacillus in every 10 fields.
3+ At least 1 bacillus in every field.
4+ At least 10 bacilli in every field.
5+ At least 100 bacilli in every field.
6+ At least 1000 bacilli in every field.
The bacteriological index is valuable because it is simple and is representative of many lesions but is affected by the depth of the skin incision, the thoroughness of the scrape and the thickness of the film.

A more accurate and reliable index of the bacillary content of a lesion is given by the logarithmic index of biopsies (LIB. These indices help to assess the state of patients at the beginning of treatment and to assess progress.

The morphological index (MI)
This is calculated by counting the numbers of solid-staining acid-fast rods. Only the solid-staining bacilli are viable. It is not unusual for solid-staining M. leprae to reappear for short periods in patients being successfully treated with drugs. It is important to recognize that measurement of MI is liable for observer variations and therefore not always reliable.

Leprosy Today
Today, the diagnosis and treatment of leprosy is easy and most endemic countries are striving to fully integrate leprosy services into existing general health services. This is especially important for those under-served and marginalised communities most at risk from leprosy, often the poorest of the poor.

Access to information, diagnosis and treatment with multidrug therapy (MDT) remain key elements in the strategy to eliminate the disease as a public health problem, defined as reaching a prevalence of less than 1 leprosy case per 10,000 population. MDT treatment has been made available by WHO free of charge to all patients worldwide since 1995, and provides a simple yet highly effective cure for all types of leprosy.

According to official reports received during 2011 from 130 countries and territories, the global registered prevalence of leprosy at the beginning of 2011 stood at 192,246 cases, while the number of new cases detected during 2010 was 228,474 (excluding the small number of cases in Europe).

The "Final Push" strategy for elimination
The main thrust of the leprosy elimination strategy is to:
Expand Multi Drug Therapy (MDT) services to all health facilities
Ensure that all existing and new cases are given appropriate MDT regimens
Encourage all patients take treatment regularly and completely
Promote awareness in the community on leprosy so that individuals with suspicious lesions will report voluntarily for diagnosis and treatment
Set targets and time table for activities and make all efforts to achieve them
Keep good records of all activities in order to monitor the progress towards elimination.
The global strategy builds on the geographic stratification of the problem, based on epidemiological and operational factors. High priority countries or areas are then identified and targeted.

Intensive and flexible deployment of MDT services to every village is being actively promoted by intensive leprosy elimination campaigns. Targets are being closely monitored by WHO and by individual countries, as they progress along the road to elimination.

WHO Multidrug therapy (MDT)
Since 1995, WHO has supplied MDT free of cost to leprosy patients in all endemic countries.

The drugs used in WHO-MDT are a combination of rifampicin, clofazimine and dapsone for MB leprosy patients and rifampicin and dapsone for PB leprosy patients. Among these rifampicin is the most important antileprosy drug and therefore is included in the treatment of both types of leprosy. Treatment of leprosy with only one antileprosy drug will always result in development of drug resistance to that drug. Treatment with dapsone or any other antileprosy drug used as monotherapy should be considered as unethical practice.

Monitoring and evaluation
This component ensures a continuous exchange of epidemiological information between all endemic countries and WHO, organizes evaluation meetings with the programme managers from endemic countries and assists in independent evaluations of programmes in endemic countries.
The implementation of elimination plans in the most endemic countries is closely monitored so as to detect potential problems that might impede its progress and to identify rapid, yet feasible solutions.



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Editor : M. Shamsur Rahman

Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

Editor : M. Shamsur Rahman
Published by the Editor on behalf of Independent Publications Limited at Media Printers, 446/H, Tejgaon I/A, Dhaka-1215.
Editorial, News & Commercial Offices : Beximco Media Complex, 149-150 Tejgaon I/A, Dhaka-1208, Bangladesh. GPO Box No. 934, Dhaka-1000.

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