Introduction-

Leprosy is a non-fatal, chronic infectious disease caused by a bacteria called Mycobacterium Leprae. It is a disease of peripheral nerves & Skin. It can cause loss of sensation, muscle weakness & paralysis. Sometimes Eyes, Testis, Kidney, Bones & Joints may get involved.

Leprosy is a public health problem because it can cause permanent & progressive physical disability. It is the important reason of social stigma & discrimination associated with leprosy. If Patient is diagnosed & treated early, chances of disability decreases markedly.

One characteristic of leprosy is the Lepra reactions, period of inflammations, which are the main cause of nerve damage and disabilities in leprosy. Reactions if timely diagnosed and managed may prevent disabilities or its further worsening.

EPIDEMIOLOGY OF LEPROSY –

Leprosy is a chronic infectious disease of nerves & skin. It is a dreaded disease because late diagnosis & treatment may cause disabilities & deformities. Leprosy is a neglected tropical disease (NTD) caused by Mycobacterium leprae. Since the introduction of multidrug therapy (MDT), the registered prevalence has decreased substantially, from more than 5 million cases in the 1980s to 133 802 cases in 2021. The overall target for the global elimination of leprosy as a public health problem has been achieved.

The fall in prevalence rate is largely due to an improvement in the management of cases, very low rates of relapse, high cure rates, and absence of drug resistance and shorter duration of treatment with MDT. New cases continued to occur, however, indicating continuing transmission of infection. Screening of contacts and chemoprophylaxis with single-dose rifampicin were recommended as a crucial step to break the chain of transmission. The Global Leprosy Strategy 2021–2030 was developed as constituent of the NTD road map 2021–2030, with the goal of eliminating leprosy (i.e., interruption of transmission).

It is strongly felt that there is need to develop more effective tools and procedures for early recognition and management of leprosy reactions and nerve damage. It is needed to initiate activities to improve quality of life of persons affected by leprosy through prevention of disability (POD) and community based rehabilitation measures.

Magnitude of Problem

In 2021, 143 countries provided statistics, as compared with 127 in 2020: 37 in the African Region (AFR), 27 in the Americas Region (AMR), 21 in the Eastern Mediterranean Region (EMR), 16 in the European Region (EUR), 11 in the South-East Asia Region (SEAR) and 31 in the Western Pacific Region (WPR). Reports were received from all 23 global priority countries. Most countries reported for the calendar year January–December 2021, while a few reported for a different 12-month period (April 2021–March 2022). Rates were calculated per million population according to estimates (medium variant) provided by the United Nations Department of Economic and Social Affairs, World Population Prospects 2022 revision. The population of children (≤15 years) was used as the denominator for calculating child case detection rates.

Globally, the registered prevalence of leprosy (number of cases on treatment at the end of 2021) was 133 802, and the prevalence rate was 16.9 per million population. The number of registered cases at the end of the year was 20 960 (prevalence rate 18.0) in AFR, 25 053 (24.3), in AMR, 4206 (5.5) in EMR, 81 222 (39.4) in SEAR and 2360 (1.2) in WPR.

INDIA –

The prevalence rate of leprosy has come down from 0.69 per 10,000 population in 2014-15 to 0.45 in 2021-22.  Further, annual new case detection rate per 100,000 population has come down from 9.73 in 2014-15 to 5.52 in 2021-22. India has a target of Leprosy Mukt Bharat by 2027. Leprosy is endemic in few states and union territories in India. Except Chattisgarh and Dadar & Nagar haveli, all states/UTs have achieved the level of elimination of leprosy as a public health problem.

Of the new cases detected during 2020-21, 58.1% were multibacillary, 39% were women, 5.8% were children less than 14 years of age and 2.41% had visible deformities. The rate of visible deformities was 1.1 per million population. In March 2021, 79,898 patients were under free MDT treatment for leprosy across the country. Despite COVID 19 disruption of health services during 2020-21, 65,147 new cases of leprosy were identified, diagnosed and provided free treatment

AGENT FACTOR –

Causative agent of leprosy is Mycobacterium Leprae which is a rod shaped, acid fast bacillus having parallel sides and rounded ends. It is found in human host both intracellularly & extracellularly. It has special affinity for neurilemmal cells of peripheral nerves (Schwann’s cells) and cells of reticulo-endothelial system. They occur characteristically in clumps or bundles, called GLOBI inside human host.

1. leprae cannot grow in artificial medium. However it is reported that they can grow in foot pad of mice & Armadillo.

It resembles tubercle bacilli in appearance and is morphologically indistinguishable from other mycobacterias. A large no. of antigens have been identified in M. Leprae.

HOST FACTOR –

Leprosy can affect any age, but maximum incidence is observed between 10 & 20 years of life, the peak being near about 15 years.

As far as Sex is concerned, males show a higher prevalence than females, the differential is more striking in adults than in children. This may be due to greater exposure in males.

SOCIAL FACTORS –

Among Social factors, poverty, poor housing, overcrowding & mobility facilitate transmission of leprosy. Conversely Socio-economic development & improved standard of living, predispose to natural decline in the incidence of leprosy.

ENVIRONMENTAL FACTORS –

Hot & humid climate is favourable for growth of leprosy bacilli.

RESERVOIR & SOURCE OF INFECTION –

Both human & non-human reservoirs have been described, but MAN remains the most important reservoir, one who may be suffering from apparent or inapparent disease and may be harboring bacilli in various tissues of the body. Non-human reservoirs implicated are MANGABEY MONKEYS, RHESUS MONKEYS, AFRICAN GREEN MONKEYS & CHIMPANZEES.

On epidemiological grounds, man is the only source of infection of Leprosy. MULTI BACILLARY CASES being the most important source.

MODE OF TRANSMISSION –

Predominant mode of transmission is by DROPLET INFECTION. Prolonged close contact may also facilitate the spread.

INCUBATION PERIOD –

Incubation period varies from 6 months to 40 years. Average Incubation period being 2 to 5 years.

DIAGNOSIS OF LEPROSY –

Diagnosis of leprosy depends upon presence of clinical signs. At least one of the following cardinal signs must be there to diagnose a case, a case of leprosy.

• Hypo-pigmented or erythematous skin lesion with definite sensory loss.
• Thickening of peripheral nerves with loss of functions
• Positive skin smear for M. Leprae.

CLINICAL EXAMINATION –

A patient presenting with a hypo-pigmented or erythematous skin lesion must undergo through following steps of clinical examination –

• History Taking
• Examination of Skin
• Sensory testing in the skin lesion
• Nerve Examination

In National Leprosy Eradication Program skin smear for M. Leprae is indicated only in doubtful cases.

History Taking –

• Ask about patient particulars (Name, age, sex, address, occupation, marital status etc.)
• Presenting complaints & duration – In leprosy, skin lesions appear slowly.

Skin lesions present since birth cannot be a leprosy lesion.

• History of itching or pain in skin lesion – Itching & pain is not found usually in leprosy lesion.
• History of recurrence – Recurrent skin lesions are not found in leprosy.
• History of Unusual feelings (Tingling & numbness) – may be present in leprosy.
• History of weakness in hands & feet – May be a feature of leprosy.
• History of Deformity, its onset & Progress – Deformity is generally present in late neglected leprosy with progressive course in absence of treatment.
• History of previous treatment – May prevent re – registration or re- cycling of patients.
• History of other associated diseases – Jaundice, Anaemia, Cough, allergy to sulpha drugs.
• Family History – Helps in detection of new cases & counseling.

Examination of Skin –

For proper examination of skin following pre-requisites should be fulfilled –

• Place of examination should have sufficient light for proper visualization.
• Place should be such that privacy of patients can be maintained.
• Order of examination should be from head to toe. No body part should be left.
• Ask patients to completely undress, if necessary, in presence of an attendant.

If a skin lesion is found, following points should be noted –

• SITE – It helps in follow up of cases.
• NUMBER- It helps in grouping of cases, treatment options & follow up of cases. The number of lesions tells about severity of disease.
• COLOUR – may be hypo-pigmented or erythematous. In leprosy, erythematous colour of skin lesion indicates activity of disease or reaction. In leprosy, skin lesion is never depigmented.
• SENSORY LOSS – It is invariably found in leprosy. Helps in diagnosis of leprosy.
• EDGE – Edge of skin lesion may be flat or raised. Raised edges indicate activity of the disease.
• SHAPE/SIZE – Leprosy lesions are found in different shapes & sizes.
• PRESENCE OF INFILTRATION – Indicate severe form of Leprosy (MB Leprosy). Infiltration is seen in skin as thickened, red, shiny & dry area. Leprosy in such cases should be diagnosed by examining the nerves.
• NODULES/LUMPS IN THE SKIN – If found indicate severe form of leprosy. A skin smear if taken from a nodule will show a large no. of leprosy bacilli.

Sensory Testing –

• Assure the Patient.
• Tell the patient what you are going to do.
• Take a ball point pen.
• With patient’s eyes open, start sensory testing. With tip of ball point pen, first touch the normal skin and ask patient to indicate, with the index finger of other hand, to the point where skin was touched. Then proceed towards affected skin lesion again asking patient to indicate.
• Repeat this procedure with patient’s eyes closed.
• In affected skin lesion, patient will be not able to point the exact or nearby spot where skin was touched.
• While sensory testing, just touch the skin with tip of ball point pen so that a dimple appears in skin. Don’t press.
• Pen should be kept perpendicular to skin.
• Don’t Stroke.
• Time interval between the points touched should vary. Don’t follow a rhythm.
• Don’t ask patients to count or say yes or no. As it may create confusion. Only in inaccessible parts ask patients to count when the skin is touched.

Examination of Nerves – 

Thickened & enlarged peripheral nerves may indicate leprosy. Nerves which are commonly enlarged & can be palpated easily in leprosy are as follows.

• Ulnar Nerve
• Lateral Popliteal nerve
• Posterior tibial nerve

Other nerves which can get enlarged in leprosy but cannot be palpated easily are as follows.

• Facial Nerve
• Trigeminal Nerve
• Radial Nerve
• Median nerve

While palpating nerves, thickness & tenderness should be noticed. In leprosy, nerve will be thickened with or without tenderness. Tenderness of nerves while palpation indicate inflammation or neuritis.

ULNAR NERVE is the most commonly involved nerve in leprosy. It should be felt in the groove above & behind medial epicondyle of the elbow. Ideally both arms should be examined for ulnar nerve thickening.

LATERAL POPLITEAL NERVE can be palpated at the back & lateral side of knee, behind the head of fibula. POSTERIOR TIBIAL NERVE can be palpated below & behind the medial malleolus at the mid-point between medial malleolus & heel.

While palpating a nerve –

• Patient should be properly positioned.
• Always palpate with pulp of fingers not with the tip.
• Always palpate across the nerve & along the course of nerve.
• Watch final expressions for signs of tenderness.

REMEMBER –

• A skin lesion with intact sensations cannot be leprosy.
• A skin with Itching cannot be leprosy.
• A skin lesion with pain cannot be leprosy.
• A completely white/ depigmented lesion cannot be leprosy.
• A recurrent skin lesion cannot be leprosy.
• A completely Black skin lesion cannot be leprosy.
• A skin lesion present since birth cannot be leprosy.

A skin lesion of leprosy may have loss of sweating & loss of hair in the affected part along with sensory loss.

CLASSIFICATION OF LEPROSY –

There are many classifications e.g. Reidley – Jopling Classification, Madrid Classification, Indian classification etc. But for operational uniformity & simplicity, CLINICAL CLASSIFICATION was proposed which is as follows –

Paucibacillary (PB) Case –

A case of leprosy with 1-5 skin lesions, without demonstrated presence of bacilli in a skin smear.

Multibacillary (MB) Case –

A case of leprosy with more than 5 skin lesions; or with nerve involvement (pure neuritis, or any no. of skin lesions and neuritis); or with the demonstrated presence of bacilli in a slit skin smear, irrespective of the no. of skin lesions.

All the cases with infiltration of skin should be treated as MB case. All the relapse cases should be treated as MB case.

This classification not only indicate severity of disease but also help in planning of treatment of cases.

TREATMENT OF LEPROSY –

Leprosy is curable with treatment. Treatment of Leprosy is MULTI DRUG THERAPY (MDT).  MDT was developed because of growing resistance to dapsone. It is based on 3 anti-leprosy drugs (rifampicin, Clofazimine & Dapsone) in combination to prevent the development of resistance. Leprosy should not be treated with any single anti-leprosy drug.

Since its introduction in treatment of leprosy, MDT has remained highly effective in widely varying field conditions. MDT is provided in Blister Calender Packs (BCPs). Each blister pack contains 28 days treatment. Separate blister packs are available for MB & PB variety as well as for adults & children i.e. MB-A, MB-C, PB-A, PB-C blister calendar packs. So, in total 4 types of BCPs are available in MDT for treatment of leprosy. Children more than 14 years of age will be considered adult.

DURATION OF TREATMENT is 12 months (12 BCPs) for MB Leprosy and 6 months (6BCPs) for PB leprosy.

For MB & PB leprosy, a three drug combination (Rifampicin, Clofazimine & Dapsone) is used in MDT.

Standard treatment regimen –

For Adult leprosy-

• Rifampicin – 600 mg once a month
• Clofazimine – 300 mg once a month & 50 mg daily
• Dapsone –      100 mg daily

For Child Leprosy-

• Rifampicin – 450 mg once a month
• Clofazimine – 150 mg once a month & 50 mg on alternate day
• Dapsone – 50 mg daily

For >10 years of cases, Child pack is used. For children below 10 years of age, adjusted dose of above drugs should be given. For example –

For Leprosy in 6-9 years child-

• Rifampicin – 300 mg once a month
• Clofazimine – 100 mg once a month & 50 mg twice weekly
• Dapsone – 25 mg daily

No separate BCPs are provided for children 6-9 years of age in MDT in NLEP. Doses adjustment is the only option for them. Even in children < 6 years of age with leprosy (a rare phenomenon), doses should be adjusted accordingly using same combinations of drugs for MB or PB leprosy.

After completion of treatment, patients should be released from treatment. Recent guideline of WHO/GOI suggest release of patients from treatment on the day of giving/ receiving last dose of treatment i.e. 12^th dose for MB & 6^th dose for PB leprosy.  

Supervised doses in Leprosy –

In MDT, whether for PB or MB, once a month drugs described above in different regimen plus Dapsone one tablet is generally given as supervised dose on day one of each month for duration of treatment. i.e. 600mg/450 mg rifampicin plus 300 mg/150 mg clofazimine plus dapsone one tablet for MB BCPs or 600 mg/450 mg rifampicin plus dapsone one tablet for PB BCPs.

Ideally supervised dose should be given to patient and asked to consume in front of MDT providers. As rifampicin is the only bactericidal drug in combination, its consumption must be ensured. Patient should be told to consume medicine regularly & to collect next BCPs from the nearest health institutions.

ADVANTAGES OF MDT –

• Highly effective.
• Low relapse rate
• Almost no resistance
• Cost effective
• Minimal side effects
• Reduce frequency of lepra reaction
• Easy to administer
• Safe in pregnancy & lactation
• Prevention of disabilities through early treatment
• Can be stored under normal storage condition
• Cures leprosy & stops transmission of leprosy
• Takes care of resisters & persisters (bacilli).

SIDE EFFECTS OF MDT –

Rifampicin – Reddish discoloration of urine, saliva & sweats, allergy, Hepatitis, Flu like illness.

Clofazimine – Brownish black discoloration of body, Ichthyosis, conjunctival Xerosis, Abdominal symptoms.

DAPSONE – Anaemia, Exfoliative dermatitis, Hepatitis, Abdominal Symptoms.

DRUG RESISTANT LEPROSY TREATMENT –

For rifampicin-resistant leprosy, guidelines recommend treatment with at least 2 second line drugs (Clarithromycin, minocycline or a quinolone) plus clofazimine daily for 6 months, followed by clofazimine plus one of these drugs for an additional 18 months.

When ofloxacin resistance is also present, a fluoroquinolone should not be used as part of second line treatment. The regimen of choice in such cases shall consist of 6 months of clarithromycin, minocycline or clofazimine followed by clarithromycin or minocycline plus clofazimine for an additional 18 months.

Recommended regimens for drug resistant leprosy are as follows –

PREVENTIVE TREATMENT –

Guidelines recommend the use of single dose RIFAMPICIN (SDR) as preventive treatment of adults & children (equal to or more than 2 years) contacts of leprosy patients, after excluding Leprosy & TB disease and in the absence of other contraindications.

SDR should be implemented only if program ensures 1) adequate management of contacts & 2) consent of the index case to disclose his/her disease.

Rifampicin dose for single dose rifampicin (SDR) is as follows –

BCG at birth is effective in reducing the risk of leprosy, therefore, its use should be maintained at least in all leprosy high burden countries. BCG at birth appears to potentiate the protective effect of SDR in contacts from 57% to 80%.

RECOGNITION & MANAGEMENT OF LEPROSY REACTION –

Reactions are the main cause of nerve damage and impairment in leprosy. It must be promptly diagnosed and treated to prevent any disability. It is an acute inflammatory response, caused by the body’s immune system attacking the leprosy bacilli.

Leprosy reactions cause inflammation in skin & the nerves because leprosy bacilli principally affect nerves & skin. Inflammation in a skin lesion is never serious while inflammation in a nerve can cause serious damage, with loss of function caused by swelling & pressure in the nerve. Some patients even with nerve involvement are asymptomatic. So, one must examine carefully for detecting early nerve damage.

DIAGNOSIS OF LEPRA REACTION –

SIGNS – In the skin ——————————— Inflamed skin lesions

• In the Nerves ——————————Pain or tenderness in the nerve, new loss of function,

                                                                New muscular weakness.

• In the eye ———————————- Pain & redness in the eye, New loss of vision, New

                                                                  Weakness in eye closure.

TYPES OF LEPRA REACTION –

Two types of Lepra Reaction occur – TYPE 1 & TYPE 2.

Diagnosis of lepra reaction is much more important than classification as treatment is more or less same.

A person with leprosy can have lepra reaction at almost any time during the course of the disease i.e. before treatment, at diagnosis, during treatment & after the treatment had completed.

Most reactions occur during the first year after diagnosis. MDT should not be stopped during the treatment of lepra reaction.

Some patients are more likely to develop lepra reaction –

• Those with multiple lesions.
• Those with lesions close to the nerve.
• Those with skin lesions on face.
• Those with pregnancy.
• Those with early nerve involvement.

These patients should be monitored regularly by doing VMT & ST (Voluntary Muscle & Sensory Testing) for early detection of reaction & its proper management.

Early detection & treatment of leprosy is the best way to prevent disability. Unfortunately many patients are diagnosed & treated late and are at great risk of developing the reaction or neuritis. If these reactions are managed effectively, early nerve damage can be reversed & disability can still be prevented.

Mild reaction is one that occurs in –

• Skin only ( except on face & over major nerve trunk)
• Have mild fever
• Slight swelling of the limbs

Severe Reaction is one that

• Affects the nerves or eyes
• Affects Skin of face
• Affects skin over major nerve trunks
• With other nerve involvement.

Signs of Severe Reaction are –

• Pain or tenderness in the nerves
• New loss of sensation
• New areas of weakness of muscles.
• Inflammation in the eyes
• Severe oedema of limbs
• Involvement of other organs such as testes, lymph nodes or joints
• Ulceration of skin lesions.

Every times a leprosy patient turns up, he should be examined for signs of reaction in skin, nerves & eyes. For loss of early nerve function, VMT (Voluntary muscle testing) & ST (sensory Testing) should be done and patient managed properly.

MANAGEMENT –

Irrespective of the type of lepra reaction,

• Rest to the affected nerve
• Analgesics
• Prednisolone- 1mg/KBW single dose and then gradually tapered fortnightly and lastly stopped after 12 weeks.

Schedule recommended is as follows –

40 mg OD for first 2 weeks followed by

30 mg OD for 3^rd & 4^th weeks

20 mg OD for 5^th & 6^th weeks

15 mg OD for 7^th & 8^th weeks

10 mg OD for 9^th & 10^Th weeks

5 mg OD for 11^th & 12^th Weeks & then stopped.

• Continue MDT, if patient is under treatment.
• CLOFAZIMINE – The drug is also effective in ENL for its anti inflammatory properties, but not as effective as prednisolone. It can be used in cases where corticosteroids are contraindicated.

Dose Schedule – 100 mg thrice daily in 1^st month

• 100 mg twice daily in 2^nd month
• 100mg once daily in 3^rd month and continue in same dose till reaction subsides.

The total dose of Clofazimine should not be more than 12 months.

• In Iridocyclitis,

Mild cases – Atropine & steroid eye drops

Severe cases –  refer to ophthalmologist.

NOTE – Leprosy was eliminated from INDIA as PUBLIC HEALTH PROBLEM in 2005 when at national level Prevalence of leprosy < 1 case per 10,000 population was achieved. Now India aims for LEPROSY MUKT BHARAT by 2027 which is 3 years earlier than SDG. Aim is to interrupt the transmission of leprosy.