Leprosy Chemotherapy

Chemotherapy of Leprosy

( Hansen’s Disease)

Leprosy is caused by acid-fast bacteria Mycobacterium leprae an acid-fast bacteria.  Gregor Hansen discovered causative microorganism of leprosy in 1873, thus it is also called Hansen's disease.  It mainly affects skin, nerve and mucous membrane.Sign and symptoms of leprosy are the presence of patches on the skin. These patches have following characteristics

• Loss of sensation
• No pain sensation
• No itching
• Hypopigmentation: reddish or copper-red color patches
• Patches may be flat or elevated. (Flat Patch is called Macule and raised patch is called Papules)                                                                                                                          

Mycobacterium leprae grow very slowly. Its incubation period may be up to 5 years. It does not grow in artificial media. Animal-like some species of monkey, rat, rabbit and etc are used to grow M. leprae. It develops resistance to the drug very rapidly.

There are two types of leprosy

•   Infectious leprosy or Multibacillary leprosy
• Non-infectious leprosy  or Paucibacillary leprosy

National leprosy eradication program divides leprosy into following five types.

·         Lepromatous Leprosy LL

·         Tuberculoid Leprosy TL

·         Borderline lepromatous leprosy BL

·         Indeterminate Leprosy IL

LL and BL are multibacillary leprosies

TL and BT are Paucibacillary leprosies

IL is the initial stage of leprosy. It cannot be determined, whether it is multibacillary leprosy or paucibacillary leprosy.

Indian leprosy association classified leprosy into following five classes

·         Indeterminate: It is an early stage of leprosy. Only one or more macules with hypopigmentation appear. Macules are bacteriologically negative. But there will be sensory impairment.

·         Tuberculoid: One or two hypopigmented flat or raised lesions with sensory impairment. But lesions are bacteriologically negative.

·         Borderline: Four or more hypopigmented or erythematous flat or raised lesion with sensory impairment. Lesions are bacteriologically positive.

·         Lepromatous type: Various flat or raised, shiny smooth lesions. They are bacteriologically positive.

·         Pure Neuritic Type: It affects nerve with a lesion on the skin. They are bacteriologically negative.

Antileprotic drug classification

•        SULFONES

•      Dapsone
•      Salapsone
•       Acedapsone

•        Phenazines
•      Clofazimine

•        Thiosemicarbazones
•      Amithiazone

•        Antitubercular drugs
•      Rifampicine
•      Pyrazinamide
•      Ethionamide

•         Antibiotics
•      Minocycline
•      Ofloxacin
•       Clarithromycin

•          Natural Drugs
•       Chaulmoogra oil.

Drugs to treat leprosy

Dapsone: It is diamine diphenyl sulfones. i.e. structurally related to sulphonamides. Thus it inhibits biosynthesis of folic acid from PABA inside bacterial cells. It mainly antagonizes PABA to produce bacteriostatic effects. M. leprae develops resistance to dapsone. It may be primary resistance or secondary resistance. Thus, dapsone is always used with other antibacterial drugs to prevent the development of resistance in M. leprae.

It is slowly and completely absorbed from GIT, well distributed in body tissues especially skin, muscle liver, and kidney. It is metabolized by acetylation. Bith active drug and metabolites are excreted in urine.

Adverse effect: Sulfones are not very toxic. GIT disturbance, fever, and pruritis may occur. Haemolysis in a patient suffering from glucose-6-phosphate dehydrogenase, methemoglobinemia.

Sulfoxone Sodium:  It is used in a patient suffering from GIT disturbance due to dapsone.

Rifampicin: It acts as a bacteriocidal agent to M. leprae. It kills all most all M. leprae in three to seven days. Rifampicin is essential to the drug to treat leprosy. A single dose of 600 to 1500 mg of rifampicin reduces the number of leprae to an undetectable level. Even single dose 600 to 900 is very effective.

Clofazimine: It has both antileprotic and anti-inflammatory effect. It binds to DNA template. This produces bactericidal effect against M. leprae. It changes resistant M.leprae to dapsone sensitive. M.leprae cannot develop resistance to clofazimine. Thus, it is very useful to treat leprosy.

Leprosy treatment: M. leprae is an acid-fast bacteria. It is difficult to treat leprosy because M. leprae can survive for years in an unfavorable condition. It remains as an inactive form in unfavorable condition is called persistor.

M. leprae can also develop resistance to an antileprotic agent. Thus leprosy treatment requires multi antibacterial agents to prevent the development of resistance to M. leprae and rapid cure.

WHO Recommendations for multibacillary leprosy.

Dapsone       100 mg daily, Self Administration

Rifampicin   600 mg once in a month, under the supervision of a medical practitioner. 

Clofazimine  300 mg once in a month, under the supervision of a medical practitioner. Or 50 mg daily self-administration.

Ethionamide or prothionamide is also recommended in place of clofazimine if clofazimine is not tolerated by the patient. In India recommended a dose of dapsone is 50 mg daily.

WHO Recommendations for Paucibacillary leprosy

Dapsone: 100 mg for 6 months

Rifampicin 600 mg once in a month.

Govt of India recommendation

Multibacillary smear negative

Dapsone 100 mg daily

Rifampicin 600 mg once in a month under supervision of medical practitioner for  6 months.

Then dapsone is continued till cure of disease

Multibacillary smear positive

Dapsone 100 mg daily for 2 years

Rifampicin 600 mg daily for 2 weeks

Followed by 600 mg once in a month under supervision of medical practitioner

Clofazimine 100 mg on an alternate day

Or

50 mg daily for 2 years.

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