LEPROSY
Leprosy (Hansen disease) is a chronic infectious disease, caused by Mycobacterium leprae. It mainly affects the peripheral nerves and skin, though upper respiratory tract, eyes, testes and other organs may also be involved.
While India achieved the target of leprosy elimination at National level in Dec 2005 with prevalence rate of lt; 1/10000 population, it still accounts for over half of the new leprosy cases in the world. About 7% of them are children lt;15 years of age. While there have been few reports of some resurgence in selected regions during 2021-22, National Health Mission aims to eradicate leprosy from India by 2027.
Epidemiology: M. leprae is an intracellular as well as extracellular acid-fast bacillus, present predominantly inhuman host.
Source of infection is usually a multibacillary open case, harbouring millions of organisms in nasal mucosa. Paucibacillary cases are intermittently infectious during exacerbations.
Mode of infection: Organisms are usually transmitted to susceptible host as droplet infection. Other modes of transmission, e.g. direct skin-to-skin contact, contaminated fomites, breast milk and via insect vectors, are extremely rare.
High-riskfactors: Prolonged close contact with an index case is necessary for transmission. Infection in children is usually acquired from a family contact. Other risk factors include overcrowding, high humidity, social stigma preventing early diagnosis and immune status of the child.
Etiopathogenesis: All infected cases do not develop the disease and cell-mediated immunity (CMI) plays an important role in course of the disease. While in persons with high CMI, organisms are destroyed immediately on entry; progressive disease is produced in hosts with no or a little CMI. Most cases with moderate immunity develop a localized disease, e.g. tuberculoid or indeterminate leprosy, with acute exacerbations during periods of immunosuppression.
M. leprae multiplies very slowly, with long incubation period of ~ 3-5 years for Iepromatous leprosy, though it is shorter in tuberculoid form.
Clinical spectrum spans from mildest indeterminate disease to most severe Iepromatous leprosy (see classification below), with one or more of following cardinal features:
• Skin lesions, i.e. hypopigmented patches with/without loss of sensations. Loss of normal histamine induced flare response over hypopigmented patch is an early indicator of peripheral nerve damage, before detectable anesthesia.
• Neurological lesions, i.e. tender thickening of peripheral nerve trunks on palpation or nerve abscess formations with secondary anesthesia or parasthesia (tingling, crawling or pricking sensations). These lesions are best palpable over ulnar nerve behind the greater epicondyle or lateral popliteal nerve behind the lateral malleolus.
• Secondary trophic changes, e.g. neuropathic ulcers and deformities rarely appear in childhood and include facial deformities (nasal septal perforation, ear-lobule deformities, corneal ulcers) or limb deformities (wrist-drop, foot-drop, acral-ulcers, absorption of digits). Typical leonine facies with loss of eyebrows is uncommon in childhood.
Classification: According to Indian classification, leprosy is classified into five major types: (i) indeterminate, (ii) tuberculoid, (iii) borderline, (iv) lepromatous, and (v) neuritic disease. WHO classify leprosy as: (a) paucibacillary, single lesion, (b) paucibacillary (2-5 patches) and (c) multibacillary (6 patches).
• Indeterminate type is the earliest and least severe form, characterized by: (a) one or two flat hypopigmented macules, measuring 2-4 cm in size, with ill-defined margins, (b) nil or minimal loss of sensations over lesions, (c) negative smear and lepromin test. Most of these cases heal spontaneously, though 25-50% may progress to more severe forms.
• Tuberculoid leprosy is the commonest (50-60%) type in children, characterized by: (a) one or two large, raised erythematous papules or plaques (gt;10 cm) with well- defined margins, (b) definite loss of sensations over skin lesions, (c) thickening of regional nerve trunk, with/without formation of tender nerve abscesses,
(d) negative smear but positive lepromin test and
(e) granulomatous lesions (tuberculoid foci) on skin biopsy.
Untreated cases remain stable for long time with intermittent exacerbations and increasing size.• Borderline leprosy is a relatively ill-defined and unstable state, with frequent changes between tuberculoid (after treatment) or lepromatous (during immunosuppression) forms. Clinical features vary between two extremes of spectrum.
• Lepromatous leprosy, is most severe but rarest (lt;10%) type, with: (a) innumerable, confluent and symmetrical skin lesions, which begin as vague macules but turn papulo-nodular in late stages, (b) nil or minimal loss of sensations over lesions, (c) diffuse and often symmetrical sensory polyneuropathy, (d) positive smear but negative lepromin test, and (e) presence of vacuolated macrophages filled with M. leprae (foam cells) on skin/nerve biopsy.
Untreated lepromatous cases may progress to develop trophic ulcers and deformities over years, while treated cases respond very slowly over 2-5 years with frequent recurrences. A combination of skin lesions (diffuse thickening of skin) and neuritic lesions (with loss of eyebrows and distortion of ear lobes) is responsible for typical Leonine facies in adults.
• Pure neuritic leprosy is very rare, characterized by tender thickening of multiple nerve trunks with sensory, motor and trophic changes in supplied area, leading to deformities and neuropathic ulcers, without skin lesions.
Diagnosis of leprosy in children depends on:
• Pathognomonic signs, i.e. (a) hypopigmented lesion with loss of sensation, and (b) neural thickening and tenderness. Diagnosis of paucibacillary disease usually rests on clinical grounds only.
• Bacteriological confirmation ons Ziehl-Neelson staining of smears from skin lesions (slit and scrape smear) and nasopharynx. At least 6 slides should be prepared from each site and at least 200 fields should be examined before declaring the smear as negative.
Bacterial index is calculated to assess the response to therapy after examining 7 smears-4 from skin lesions, one from nasal swab and 2 from ear lobes.
Each smear is graded as per WHO criteria as negative, 1+, 2+ and 3+, followed by averaging of results to calculate bacterial index. Cases with bacterial index lt;2 are designated as paucibacillary while others as multibacillary lesions.• Histopathological confirmation by skin or nerve biopsy to demonstrate granulomatous lesions is rarely required.
• Lepromin test measures the presence of CMI against M. leprae, using a refined antigen preparation, i.e. Lepromin. After intradermal injection of 0.1 ml of lepromin on forearm, reaction is read after 48 hours and after 21 days. Early (Fernandez) reaction, i.e. redness and induration of gt;10 mm after 48 hours, indicates previous infection by lepra bacilli. Late (classical mitsuda) reaction is taken as positive in presence of a nodule of gt; 5 mm on 21st day. Lepromin test is not diagnostic for leprosy but helps to classify the disease- strongly positive in tuberculoid leprosy and strongly negative in lepromatous variety.
• Serological tests, e.g. fluorescent leprosy antibody absorption tests (FLA-ABS test), RIA and ELISA are useful to detect subclinical infections, with high sensitivity and specificity.
TABLE 10.25: Anti-Ieprosy therapy in children (National Leprosy Eradication Programme)
| Age | gt; 10 years | lt; 10 years |
| Multibacillary disease (3 drugs for 12 months) | ||
| Rifampicin (monthly) | 450 mg | 10 mg/kg |
| Dapsone (daily) | 50 mg | 2 m#8800;g |
| Clofazimine (monthly) | 150 mg | 6 mg/kg |
| Clofazimine (alternate day) | 50 mg | 1 m#8800;g |
| Paucibacillary disease (2 drugs for 6 months) | ||
| Rifampicin (monthly) | 450 mg | 10 mg/kg |
| Dapsone (daily) | 50 mg | 2 m#8800;g |
*Based on WHO schedules, which also includes single-dose therapy for single-lesion disease (Rifampcin 600 mg, Ofloxacin 400 mg and Minocycline 100 mg).
However, it may be less effective than 6 months regimen.
• Molecular diagnosis with PCR testing is possible but rarely needed.
Management of leprosy includes:
• Specific antimicrobial therapy: Due to emergence of drug-resistance, current anti-leprosy therapy is essentially a multi-drug therapy, using three drugs- bacteriostatic dapsone and clofazimine and bacteriocidal rifampicin, in different regimens according to bacillary load (Table 10.25). Therapy should continue for minimum 12 months in multibacillary and 6 months in paucibacillary disease or till smears are negative.
• Post-treatment surveillance: All cases should be followed clinically and bacteriologically, every year for minimum 2 years (paucibacillary) or 5 years (multibacillary disease), for relapses.
• Supportive therapy with: (a) prevention and treatment of trophic ulcers and deformities including reconstructive surgery, (b) vocational and social rehabilitation, (c) psychological support and (d) control of lepra reactions, discussed later.
Prevention: Reduction of infectious population by complete treatment is the mainstay of leprosy prevention in children. In an individual child with close family contact, following measures may be useful:
• Chemoprophylaxis with Dapsone (PO 1-4 mg/kg/ week) for minimum 3 years or till index cases turns bacteriologically negative, has shown ~35-53% protection rate. Recently, long-acting acedapsone given intramuscularly every 10 weeks for 210 days, has shown ~ 78% protection.
• Vaccine is not available, though BCG is expected to provide ~30% protection against leprosy.
Lepra reactions, i.e. acute clinical exacerbation, usually after initiation of therapy are common (50%), and reflect sudden change in host's parasite immunological balance. Mainly two types of reactions are seen:
• Type I (Reversal) reactions are common in borderline leprosy, with acute swelling and tenderness over existing cutaneous and neural lesions, often leading to irreversible nerve injury with foot-drop, claw-hand, etc. These may be treated with PO prednisolone 1 mg/ kg/d till response, followed by alternate day therapy to prevent relapse.
• Type II (Erythema nodosum leprosum) reactions occur in lepromatous leprosy, presenting with high fever, migratory polyarthralgia and tender erythema nodosum. These reactions may be treated with steroids, thalidomide or clofazimine.
National Leprosy Eradication Programme
National Leprosy Eradication Programme (1983) is the revised version of previous National Leprosy Control Programme (1955) that aims to eradicate leprosy from India by early case detection, multidrug chemotherapy, and disability prevention. Leprosy screening has been now integrated with Rashtriya Bal Swasthya Karyakram (RBSK) and Rashtriya Kishor Swasthya Karyakram (RKSK) for screening of children. National Health Mission aims to eradicate leprosy by 2027.
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