THE MICROBIOLOGY OF LEPROSY (Hansen's Disease)
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These notes are designed to stimulate an awareness of the problem that Leprosy (Hansen's Disease or H.D.) still presents in many countries around the world. Also, they are meant to provide information to medical personnel in areas soon (after the year 2000) to have leprosy cases treated in general public health clinics where the prevalence rate of the disease falls below one case per 10,000 population, as per W.H.O. criteria. Those who have not received specific training in the diagnosis and treatment of H.D. are advised to contact the W.H.O., visit our Forum on Leprosy or email us at skillicorn@ozemail.com.au Another way of sharing in discussion is through our Usenet Group "alt.support.leprosy" which may be accessed via YAHOO.
Mycobacterium leprae or M.leprae, is a rod-like bacillus measuring 2-7 um (1 um=1/1000 of a mm) in length and 0.3-0.4 um in width . It was first discovered in 1873, in Norway, by G. Armauer Hansen. The organism is sometimes known, therefore, as “Hansen’s bacillus”. It is both Acid-Fast and Alcohol-Fast and can only be seen under the microscope if it is stained and that is done using the “Zeihl-Neelsen” Staining Method.
Its morphology is somewhat similar to that of Mycobacterium Tuberculosis. To this point in time (1999) the M.leprae bacillus has not been cultured in artificial laboratory material. Many attempts have been made but without success. In a limited way, it has been made to grow in the (cool) foot pads of mice (first undertaken by Shepherd in 1960) and also in the 9-banded Armadillo (Dasypus novemcintus linn). These techniques have been helpful in testing for drug-resistance (Sulphone Drugs) of the organisms.
The majority of pathogenic mycobacteria may be grown in a variety of laboratory culture media, with the help of various nutrients, however, M.leprae still cannot be cultivated artificially in laboratory media and this has caused much frustration and delay in finding an effective anti-leprosy vaccine. There is a very real challenge for microbiologists to continue this vital research and this brief text is designed simply to stimulate an awareness of this unfinished task.
MYCOBACTERIUM LEPRAE - Its Structure. :- This is best studied under an electron microscope. The most natural and congenial environment for M.leprae is a eucaryotic cell, in most cases human but occasionally that of the Nine-Banded Armadillo, the mouse foot-pad and, to a lesser degree, the monkey.
M. leprae has four main components - The Capsule, the Wall, the Membrane and the Contents of the Cell and these are dealt with in detail by (1) P.Draper in “Leprosy Review”, Vol.57, Supplement 2. In the same publication, (2) P.R. Wheeler discusses “Enzymes and Other Biochemically Active Components of Mycobacteria”, (3) P.J. Brennan discusses “The Carbohydrate-containing Antigens of Mycobacterium leprae, and (4) M.Harboe and H.G.Wiker deal with “Immunological and Biochemical Characterisation and Classification of Mycobacterial Antigens”. In a “Leprosy Forum” such as this, it is impossible to make a more in-depth study of M.leprae but we direct you to information on M.leprae in the :-
WORLD HEALTH ORGANISATION'S LEPROSY SITE - CLICK HERE.
Please go to the CONTENTS / INDEX on the left of the page. Click on ITEM 7 - "The Disease and its Treatment". Then a few lines down, click on "mycobacterium leprae" where you'll also see a photo of the bacillus under the microscope. That will give you access to the World Health Organisation’s information on M.leprae under the “Microbiology of M.leprae”
In patients with a lack of cell-mediated immunity against leprosy, M.leprae may be found in large numbers in the skin, especially in the nasal mucosa, ear-lobes, face, buttocks and the larynx -- all of which are COOLER areas. In lepromatous leprosy, numerous M.leprae may be found in the lymph nodes, male testes, spleen, liver and bone marrow. It is thought that those patients with lepromatous (LL) or Multibacilliary (MB) forms, pass on the bacilli mainly in nasal droplets discharged from untreated patients. Discharges from the infected throat may also contain bacilli in LL cases.
Most (average of around 75 % world-wide) leprosy sufferers have the Paucibacillary forms of the disease and in those with Tuberculoid leprosy it may not be possible to find even one bacillus in the skin by ordinary light microscopic examination methods. In such cases, it sometimes is necessary to take a biopsy by which it can be seen whether or not M.leprae has been at work. In Paucibacillary types, even in skin biopsies it may not be possible to find even one M.leprae bacillus, in which case, if you still have doubts about the diagnosis, it may be necessary to take a nerve biopsy.
Following is a list of the various inflammatory cells in leprosy Granulomas, the presence of which can reveal the prognosis of a patient invaded by M.leprae:-
1. Lymphocytes:- these are formed in bone marrow, lymph nodes and spleen and circulating in the blood stream. They are small cells with dark staining nucleii and very little cytoplasm. Their task is to produce Cell-Mediated-Immunity (CMI). In Indeterminate and Tuberculoid forms of the disease they are found in large numbers.
2. Plasma Cells:- Like lymphocytes, they, too, are small but they have no cytoplasm. Usually, they are found in lepromatous granulomas, in patients with CMI deficit and they produce antibodies which also circulate in the blood stream.
3. Macrophages:- Produced in the bone marrow, they are found in the blood-stream as monocytes. In the tissue, they are known as Histiocytes and Reticulo-enothelial cells . The task of these large defence cells is to engulf (phagocytosis) foreign substances such as M.leprae. In lepromatous leprosy (the infectious form of the disease) , Macrophages become “Foam Cells” and in Tuberculoid patients, they become “Epitheliod Cells”. Without the assistance of “T” - type lymphocytes, macrophages cannot digest M.leprae but only ingest them.
4. Foam Cells:- While the macrophage has the double duty of both ingesting and digesting M.leprae, in the lepromatous form of leprosy, the cell ingests but cannot digest in which case it becomes a “Foam Cell” in which M.leprae continue to grow and multiply and are transported to all parts of the body in the blood stream. This makes lepromatous leprosy a form of the disease which is found in all parts of the body. As the organisms multiply in number, fat accumulates in the cell cytoplasm forming vacuoles.. The existence of large intracellular vacuoles gives the body tissue a definite “foamy” appearance. Over a period of time, the cell deteriorates, leaving behind only vacuoles.
5. Epithelioid Cells:- In patients with a good Cell-Mediated-Immunity, the macrophages can both ingest and digest the leprosy bacilli and, when they have digested their bacterial meal, they become “Epithelioid Cells. They are found in large numbers in Tuberculoid leprosy and, within these cells it is not possible to find acid-fast M.leprae.
6. Giant Cells:- Also called “Langhan’s Giant Cells”, they are produced by a fusion of Epithelioid Cells of varying shapes and sizes with many nucleii. These cells are present in the lesions of Tuberculoid or “TT” patients.
Because living M.leprae produce no toxins and have no motile power, it is thought that they cannot enter unbroken skin or intact mucous membrane. There is still debate over this. Most leprologists believe that M.leprae can only enter through a break in the skin and the mucous membrane of the nose, in particular.
Firstly, after M.leprae gain entry to the body, they can provoke one of three possible, responses, contingent upon the measure of Cell-Mediated-Immunity(CMI) in the host. To begin with, they could be ingested by the macrophages and completely digested, if CMI is present. This action can take place at the point of entry or at the lymph nodes to where they may be transported inside the large defence cells (macrophages). This type of action is believed to take place in most people infected by M.leprae, many of whom may never have known that they had been invaded by the leprosy bacilli.. Approx 90 to 95% of people exposed to leprosy experience this defensive action of the body.
Secondly, in persons with no resistance (lack of CMI), M.leprae freely multipy even within the very cells (macrophage) which are meant to destroy them. It has been known for up to 300 approx. M.leprae to prolferate inside these large defence cells which later, transport the multiplying and dying (dying of old age) bacilli from the site of entry to many different parts of the body. This multiplication of the bacilli, even in the defence cells, is the most serious form of leprosy, which is contagious and known as “lepromatous” or “multibacilliary” (MB) leprosy.
Thirdly, there are those patients who have some resistance to the infecting bacilli but not enough immunity to completely destroy the organisms. Their defence system allows a limited but a variable multiplication of the bacilli, contingent upon the degree of CMI. In some patients - those with the ”Tuberculoid” form of the disease - many of the bacilli are killed off by the body’s defences which keep the infection localised to a small area of the body. In others, with a lesser degree of immunity the disease may be somewhat generalised with leprosy lesions scattered in different places. This type is in the “borderline” category.
These groups constitute what is called the “Immunological Spectrum” , ranging from those with a strong CMI at the Tuberculoid end to the more serious types with a CMI deficit at the lepromatous or infectious end. There is another group which is not considered as part of the spectrum because, in its early stage, it is not known whether it will progress into the spectrum to become Tuberculoid or Lepromatous and this is called the “Indeterminate” type.
INDETERMINATE TYPE:- It is of great importance that we be able to properly diagnose this group which may be identified by a rather vague, hypopigmented patch on the skin. In examining a population, this type is the one generally found to be the earliest manifestation of the disease. Because there may NOT be any loss of sensations in the patch, diagnosis may sometimes be difficult. In the facial areas (mainly cheeks) of many malnourished children in some of the poorer countries, such hypopigmented patches are really those due to protein and vitamin deficiency and it may be wise to wait a few months to make a full diagnosis while the child is given a nourishing diet. Sometimes, biopsies are necessary to determine if it is a case of leprosy. There are actual cases of leprosy (Indeterminate) which, because of the body’s good defences, resolve spontaneously.
When a biopsy is taken of such doubtful patches, histopathological examination reveals a definite infiltration of the skin by lymphocytes which collect around the hair follicles, sweat and sebaceous glands, blood vessels, nerves and arrector pili muscle cells. This is generally enough to confirm a case of Indeterminate leprosy, whether or not M.leprae may be present. If a large number of sections are pathologically examined for acid fast bacilli, only very rarely is the odd bacillus found, perhaps in a nerve bundle or arrector pili muscle cell.
In Indeterminate leprosy, there may be no involvement of the peripheral nerves but only the cutaneous nerves supplying that particular patch. The nerves are seen to be surrounded by lymphocytes but, because they very seldom are actually infiltrated by these inflammatory cells, there is no loss of sensations. Anaesthesia is minimal, if at all present but, if the disease persists for many years as Indeterminate, there is a possibility of a slow destruction of the nerves, leading to loss of sensation.
It is of extreme importance that no patient suffering from malnutrition, tinea, worm infiltration, leukaderma (vitiligo) etc., with such doubtful hypopigmented skin patches, be diagnosed as having Indeterminate leprosy, especially where stigma against Hansen’s Disease prevails. Such a false diagnosis is a “crime” which virtually condemns the sufferer to a death sentence! As the WHO hopes to gradually merge treatment of leprosy patients into the general health programmes, it is a matter of VERY GREAT URGENCY that all medical personnel engaged in public health, be skilled in the “Differential Diagnosis” of leprosy (Hansen’s Disease)
Please read “The Challenge of Leprosy” which is Chapter ten of our book, "AN IMPOSSIBLE DREAM"
It also will be helpful to access the Homepage of INTERNATIONAL FEDERATION OF ANTI-LEPROSY ORGANISATIONS (ILEP) which represent about 20 different agencies involved in caring for leprosy sufferers. ILEP has a lot of documentary material under "Information"
TECHNICAL BOOKS ON LEPROSY ARE AVAILABLE "ON-LINE" THROUGH OUR INTERNET AMAZON.COM AGENCYSimply type in the word "Leprosy" and hit the search button. By purchasing your books on leprosy or on any other subject (also music CD's), we earn commission which we have dedicated to caring for leprosy sufferers.
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