1

Introduction.

Hansen's disease also known as leprosy is caused by the bacteria named

Mycobacterium leprae sp. which is also a type of obligate acid-fast bacillus. Unlike other

bacteria under the same genus, mycobacteria, this species does not grow in any artificial

media or tissue culture.

Leprosy principally only attacks skin and peripheral nerves in the hands and feet,

upper respiratory tract and mucous membrane which then lead to impairment in sensual and

motor function.

Up till now, the exact mode of transmission of leprosy is still uncertain but according to

Centre of Disease Control (CDC), the bacteria can spread from person to person by air and

direct touch. It might also occur if you are exposed to other nasal fluids (also known as

secretions) that being said, that these secretions contain the bacteria that caused leprosy.

Now, however, the disease is very rare and easily treated with multi-drug therapy

(MDT). Early diagnosis and treatment usually prevent disability related to the disease (WHO,

2014).

The objectives of this assignment are to report and measure leprosy morbidity and

mortality trends: the status of M. leprae detection and treatment outcomes for leprosy.

The objectives that will also cover the aetiology, pathophysiology and

epidemiology of leprosy.

2

History.

In the face of being broadly believed as an historical moment in health, leprosy rests a

surprisingly widespread disease in the 21st century. In 1985, leprosy was still reflected as a

major public health problem in 122 countries.

Hitherto, 2 to 3 million people worldwide are permanently disabled because of leprosy.

Leprosy is a painful condition that can leave its victims deformed and crippled.

Contrary to popular perception, leprosy does not directly cause body parts to fall off of

their own. Instead, they become disfigured as an indirect result of other symptoms. Leprosy is

caused by the bacteria Mycobacterium leprae first identified by Gerhard Hansen in 1873.

Malaysia is not excluded from the pandemic of leprosy. Although the incidence of

leprosy in Malaysia is declining, it is still a public health problem. The disease was probably

introduced into the country in the nineteenth century by Chinese and Indian immigrants

among whom the disease was prevalent.

In 1926, the Leper Enactment Act 1926 was established which required compulsory

notification and isolation of leprosy patients.

As a result, the National Leprosy Control Centre (NLCC) was built in Sungai Buloh,

Selangor. In 1969, the National Leprosy Control programme was launched with the objective

of early case finding and decentralisation of treatment of leprosy. The centre covers an

area of 562 acres of low hilly land and is among the largest in the British Commonwealth. It

has a hospital with 855 beds, an old leprosy settlement of 2000 bed chalets, an administration

block and a research unit.

The National Leprosy Control Programme was launched in 1969 in West Malaysia

and extended into the East Malaysian states of Sarawak and Sabah in 1974 and 1985

respectively. The diagnosis of leprosy is confirmed by skin or nerve biopsy. The treatment of

leprosy patients is fully integrated with basic medical and health services in Malaysia. This has

resulted in 63% decline in the number of patients in the NLCC over a span of 20 years (1970-

1990).

The treatment of leprosy patients is integrated with basic Medical and Health services

in Malaysia. With the implementation of Multiple Drug Therapy in 1985, the National

prevalence rate of leprosy has reduced from 5.7 per 10,000 in 1983 to 1.7 per 10,000 in 1992.

The Research Unit in NLCC was established in 1950, where cultivation of

Mycobacterium leprae using mouse foot-pad technique is done.

3

The mouse foot-pad technique for cultivation of Mycobacterium leprae was started in

the Research Unit of NLCC, Sungai Buloh in the year 1969. Presently this technique is used

for drug susceptibility/ resistancy testing and the drugs tested include Dapsone, Clofazimine

and Rifampicin. .

4

Aetiology

Leprosy is caused by the bacteria Mycobateria leprae sp. It is the first bacterial

pathogen acknowledged affecting human, it rests one of the few that is non-cultivable in vitro.

It is an intracellular, gram-positive, acid-fast bacterium. M. leprae is a rod-shaped aerobic

bacillus.

M. leprae prefer to grow in cooler regions of the body. The bacillus is dependent on

the metabolic products of the host, which explain its long incubation period and incapability to

grow in vitro. Since the bacteria does not grow in vitro, understanding its biology is a challenge

that takes time and money.

The bacteria was first discovered by Norwegian physician, Gerhard Armauer Hansen

thus named in honour of him (Hansens disease) who first identified the causative organism

in 1873.

There are three (3) types of leprosy characterised by its severity:

1. Tuberculoid (paucibacillary).

2. Lepromatous (multibacillary).

3. Borderline or dimorphous (intermediate-certain)

The category is based on the number of bacteria present: paucibacillary (small) and

multibacillary (many) and by the number of poorly pigmented numb skin patches present, with

paucibacillary (5).

5

Pathophysiology.

The pathophysiology of leprosy can be easily guessed with the known aetiology. Once

M. leprae entered a host, it needed more time to replicate and grow including people with

immunodeficiency.

The route of entry is thru respiratory tract by direct contact or air droplets that

contained the bacteria. Prone to replicate around wet/ damp areas; skin and nerves, Schwann

cell.

Can withhold its life outside human body up to a week. Incubation is long and

asymptomatic ranging from 4 to 8 years.

Leprosy is harmful to the body by disabling the function of sensory and motor

(peripheral neuritis). Furthermore, the injury of the 7th and 5th cranial nerves exposed patients

to trauma, sepsis and possible blindness.

6

Clinical Manifestations.

Leprosy attacks skin, nerves and eyes thus causing systemic failure. Patients

generally present with skin lesions, weakness or numbness caused by a peripheral-nerve

lesion or a burn.

Patients with dimorphous leprosy may develop nerve pain, sudden palsy, eye pain or

a systemic febrile illness.

The signs and symptoms of leprosy are:

1. Skin lesions.

2. Thickened peripheral nerves.

3. Acid-fast bacilli on skin smears or biopsy.

The nerves most often involved are the

1. Ulnar (elbow),

2. Median (wrist),

3. Radial (wrist),

4. Peroneal (knee),

5. Posterior tibial and sural (ankle),

6. Facial and great auricular (posterior triangle of the neck).

7. Affected nerves may be enlarged and tender.

Blindness is a devastating complication of leprosy in patients with anaesthetic hands and

feet. Eyelid closure is impaired when the facial nerve is affected. Damage to the trigeminal

(5th) nerve causes anaesthesia of the conjunctiva and the cornea, which is then susceptible

to trauma and ulceration.

Tuberculoid leprosy has a good prognosis. It may self-heal, and peripheral nerve

damage is limited.

Borderline tuberculoid is when the skin lesions are similar to those in tuberculoid leprosy,

but more numerous. Peripheral nerve damage may be widespread and severe. Borderline

leprosy is unstable; patients have numerous skin lesions varying in size, shape and

distribution. Annular lesions with a broad, irregular edge and a sharply defined, punched-out

centre are characteristic. Nerve damage is variable.

Borderline lepromatous leprosy is characterized by widespread of small macules.

Patients may experience type 1 and type 2 reactions. Peripheral nerve involvement is

widespread.

7

Lepromatous leprosy patients with untreated polar lepromatous leprosy may be

carrying 1011 M. leprae. The earliest lesions are ill-defined.

Clinical Characteristics Lepromatous Tuberculoid

Skin and nerves

-Number and distribution

Widely disseminated One or few sites, asymmetrical.

Skin lesions

Definition: i. Clarity of margin ii. Elevation of margin

Color i. Dark skin ii. Light skin

Surface

Central healing

I. Poor II. Never

III. Slight hypopigmentation IV. Slight erythema

Smooth, shin.

None.

I. Good II. Common

III. Hypopigmentation IV. Coppery or red

Dry, scaly.

Common

Sweat and hair growth

Loss of sensation

Impaired late

Late

Impaired early

Early and marked

Nerve enlargement and

damage

Late Early and marked

Bacilli (Bacterial Index) Many (5 or 6+) Absent (0)

Natural outcome Progression Healing

Other tissues Upper respiratory mucosa,

eye, testes, bones, muscle

None

Reactions Immune complexes Cell-mediated

Gradually, the skin becomes infiltrated and thickened. Dermal nerves are destroyed,

sweating is lost and glove-and-stocking neuropathy is common. Nerve damage to large

peripheral nerves occurs late in the disease.

The collapse of the bridge of the nose results from bacillary destruction of the bony

nasal spine. Testicular atrophy is caused by diffuse infiltration and the acute orchitis that

occurs with type 2 reactions. This results in azoospermia and gynaecomastia.

8

Type 1 reaction. This man developed erythematous, oedematous lesions on his face and trunk 6 weeks after starting

treatment.

Type 1 reaction. This woman developed acute ulnar nerve neuritis as part of the reversal reaction, leading to overnight loss

of function. Early clawing and swelling of the hand is visible.

9

Epidemiology.

Leprosy still remains as main global concern to date. There are about 650,000 new

cases per year, 70% of which are in India. In all new cases seen in the UK, infection was

acquired overseas. HIV infection is not a risk factor for the development of leprosy, but may

worsen leprous neuritis.

Infected individuals discharge bacilli from their nose. Infection occurs through the nose

followed by haematogenous spread to skin and nerve. The incubation period of M. leprae is 2

to 5 years in tuberculoid disease and 812 years in lepromatous disease.

In 2001, registered cases of leprosy in Sabah were 206 and the rate of prevalence

was less than one per 10,000 population (0.7/10,000 population). However, five districts with

prevalence rate of more than one in every 10,000 population are from districts of Kota

Kinabalu, Kudat, Semporna, Tawau and Lahad Datu.

Notification on leprosy in year 2000 was 61 cases whereas in 2001 it was 72 new

cases. Amongst these cases, 44 (61%) are immigrants and 28 (39%) cases were Malaysian.

In this analysis, all patients diagnosed were treated with MDT regime since year 1999. Total

number of defaulters were less than 22%.

Year Case

analysed

Completed

treatment (%)

Abandoned

treatment (%) Death (%) Others (%)

1994 2024 83.6 12.2 4.2 0

1995 1924 82.1 9.2 5.04 3.7

1996 2028 86.7 6.1 5.03 2.2

1997 1876 82.46 10.02 3.46 4.05

1998 2035 79.4 10.8 3.5 6.3

1999 2048 83.1 8.3 3.4 5.2

Table 1. Cohort analysis Sabah, 1994-1996

10

Year Malaysian Immigrants

Total

population

Notified

new cases

Rate per

100k

population

Total

population

Notified

new cases

Rate per

100k

population

1996 1775500 28 1.58 747100 39 5.22

1997 1879700 32 1.70 748200 37 4.72

1998 1989800 33 1.66 823100 51 6.19

1999 2106400 24 1.14 864000 38 4.39

2000 2229800 21 0.94 906900 40 4.41

2001 1952300 28 1.43 764500 44 5.76

Table 2. Notification rate of new cases of leprosy amongst immigrants and Malaysians, Sabah 1996-2001.

Year Total cases

registered

Regular with treatment follow-

up (number and percentage).

Treatment defaulters

(number and percentage).

1999 221 173 (78%) 48 (22%)

2000 215 171 (80%) 44 (20%)

2001 206 178 (86%) 28 (14%)

Table 3. Registered leprosy cases on Multiple Drug Therapy (MDT), Sabah 1999-2001.

Prevalence rate of leprosy in Sabah.

11

Investigations.

Tuberculoid leprosy in these patients, lymphocytes respond to M. leprae antigens

in vitro. Skin tests with lepromin (a soluble M. leprae sonicate preparation) elicit strongly

positive responses. This strong cell-mediated response clears antigen, but with concomitant

local tissue destruction.

Lepromatous leprosy these patients have specific cell mediated anergy (a state of

immune unresponsiveness) to M. leprae and their lymphocytes do not respond to M. leprae

antigens in vitro. They are unresponsive to intradermal challenge with lepromin. Lepromatous

patients exhibit specific T cell failure and macrophage dysfunction. Immune-mediated

reactions: acute immune-mediated reactions are a serious complication of leprosy.

Both T cells and macrophages are involved when there is a M. leprae infection.

Type 1 reactions are episodes of delayed hypersensitivity occurring at sites of localization

of M. leprae antigens.

Type 2 reactions acute, nodular, erythematous eruption that usually is limited to the extensor

aspects of the lower legs (erythema nodosum leprosum) results from immune complex

deposition.

Diagnosis is clinical, by the finding of a cardinal sign of leprosy, and is supported by

acid-fast bacilli in slit-skin smears or typical histology on skin biopsy. Skin biopsy reviewed

by an experienced health practitioner is invaluable in classifying the patient and to rule out

other diseases.

Skin lesions should be tested for anaesthesia. The peripheral nerves should be

palpated for thickening and tenderness. There are no serological tests that detect leprosy

across the spectrum. Polymerase chain reaction analysis for M. leprae DNA has not been

developed as a diagnostic tool.

Differential diagnosis of leprosy is the most common cause of peripheral nerve

thickening. Uncommon conditions such as CharcotMarieTooth disease and amyloid are

differentiated from leprosy by the absence of skin lesions and acid-fast bacilli. The anaesthesia

of tuberculoid and borderline tuberculoid lesions differentiates them from other conditions

resembling leprosy like in vitiligo and mycotic skin infections.

12

Management.

WHO recommendations for chemotherapy of leprosy are listed in table below. First-

line antileprotic drugs are Rifampicin, Dapsone and Clofazimine.

Type of leprosy Regimen Duration of

treatment

Paucibacillary Monthly supervised

Rifampicin, 600 mg

Daily self-administered

Dapsone, 100 mg

6 months

Multibacillary Rifamcipin, 600 mg

Chlofaziminem, 300 mg

Rifamcipin, 50 mg

Dapsone, 100 mg

12 months

Any patient with acid-fast bacilli on skin smear or biopsy should be treated for

multibacillary disease. Patients with high bacterial loads (on skin biopsy or slit-skin smear)

need treatment with multi-drug therapy for at least 24 months. Clinical improvement is rapid

and toxicity is uncommon.

New nerve damage that occurred to any patient with motor or sensory loss of less

than 6 months duration should receive a 6-month course of oral corticosteroids as for the

treatment of type 1 reactions.

Patient education is vital. Patients must be reassured that, within a few days of

chemotherapy, they will no longer be infectious and can lead a normal social life. It should be

emphasized that care and awareness of their limbs is as important as chemotherapy.

Preventing disability nerve damage produces anaesthesia, dryness and muscle

weakness, which lead to misuse of the affected limb and resultant ulceration, infection and,

ultimately, severe deformity. Dryness predisposes to cracking of the skin and secondary

infection; it can be alleviated by soaking the feet and applying oil-based creams.

Physiotherapy can prevent contractures, muscle atrophy and over-stretching of

paralysed muscles.

13

Principles of management of leprosy reactions are:

1. Control the acute inflammation and ease the pain.

2. Treat the neuritis.

3. Halt eye damage.

Type 1 reactions should be treated using Prednisolone, 40 mg/day PO. initially reduced

by 5 mg/day each month.

Vaccines there is no specific vaccine against leprosy, but several trials have shown

BCG to be protective.

14

Conclusion.

In todays world, thousands of people across the globe will stop to remember those

who suffer this horrendous effects of leprosy.

World Leprosy Day helps to focus on the needs of the very poorest of people and

with leprosy. It helps to tell story to people who simply dont know that leprosy still exists and

most importantly, that it can be cured.

Discussion.

With the resurgence of TB as a global concern, immediate attention has to be given

to this disease in all sectors of health systems and community.

Although a Plan of Action in prevention and control of TB at the national level is

available, every district needs to develop its own specific action plan, because, to be

effective, action plans must address local issues such as disease patterns and resource

availability.

Although the prevalence rate of leprosy is less than 1 case per 10,000 population,

new cases continue to be detected. Total commitment of everyone will make a difference in

the prevention and control of tuberculosis and leprosy in Malaysia.

15

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