Leprosy, also known as Hansen's disease, is caused by the bacterium Mycobacterium leprae. While it was once considered incurable, effective multidrug therapies (MDTs) containing dapsone, clofazimine, rifampicin and other antibiotics were developed starting in the 1980s. These MDT regimens can cure leprosy within 2 years and also reduce the risk of drug resistance developing. Prior to MDTs, leprosy treatment was often lifelong and relapses were common. The introduction of standardized MDT regimens significantly improved leprosy treatment outcomes.

1. Sandra
Manuel

2.  Leprosy, caused by Mycobacterium leprae ,has been
considered incurable since ages and bears a social
stigma .
 Due to the availability of effective antileprotic drugs
now it is entirely curable, but the deformities/defects
already incurred may not be reversed.
 Use of antileprotic drugs can be dated back to
centuries. Chaulmoogra oil ,with weak antileprotic property
was used in Indian medicine for centuries.

3.  Sulfones- Dapsone
 Phenazine derivatives-Clofazimine
 Antitubercular drugs- Rifampicin, Ethionamide
 Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline,
Clarithromycin

4.  Sulfones-
 Phenazine derivatives-Clofazimine
 Antitubercular drugs- Rifampicin, Ethionamide
 Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline
,Clarithromycin

5.  Sulfones- Dapsone
 Phenazine derivatives-
 Antitubercular drugs- Rifampicin, Ethionamide
 Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline
,Clarithromycin

6.  Sulfones- Dapsone
 Phenazine derivatives-Clofazimine
 Antitubercular drugs- ,Ethionamide
 Other antibiotics- Ofloxacin,Moxifloxacin, Minocycline
,Clarithromycin

7.  Diammino diphenyl sulfone,the oldest,cheapest,most active
member of its class.
 Chemically related to sulfonamides and has the same mechanism
of action-inhibition of PABA incorporation into folic acid by folate
synthesis.
 Specificity for M.leprae - due to the difference in affinity of its folate
synthase.
 But Dapsone resistance among M.leprae, first noted in 1964,has
necessitated the use of multi drug therapy- MDT.
 Dapsone resistant M.leprae have mutated folate synthase which
has lower affinity for dapsone. however the peak serum
concentration of dapsone after 100mg/day dose exceeds the MIC
for M.leprae by nearly 500 times ; it continues to be active against
low to moderately resistant bacilli.
 The risk of relapse due to dapsone resistant bacilli is reported to be
2-3%.

8.  Mild haemolytic aneamia
 Gastric intolerance
 Methaemoglobinaemia
 Paresthesias
 Cutaneous reactions
 Sulfone syndrome – a reaction which develops 4-
6weeks after starting dapsone treatment ; consists of
fever , malaise , lymph node enlargement ,
desquammation of skin , jaundice & anaemia

9.  Mild haemolytic aneamia
 Gastric intolerance
 Methaemoglobinaemia
 Paresthesias
 Cutaneous reactions
 Sulfone syndrome – a reaction which develops 4-
6weeks after starting dapsone treatment ; consists of
fever , malaise , lymph node enlargement ,
desquammation of skin , jaundice & anaemia

10.  Mild haemolytic aneamia
 Gastric intolerance
 Methaemoglobinaemia
 Paresthesias
 Cutaneous reactions
 Sulfone syndrome – a reaction which develops 4-
6weeks after starting dapsone treatment ; consists of
fever , malaise , lymph node enlargement ,
desquammation of skin , jaundice & anaemia

11.  Shouldnot be prescribed to patients with
- severe anaemia (Hb <7g/dL)
- G6PD deficiency
- hypersensitivity reactions

12.  A dye with leprostatic and anti-inflammatory properties
 The putative mechanisms of leprostatic action of
Clofazimine are :-
a. interference with the template function of DNA in M.leprae.
b. alteration of membrane structure and its transport function.
c. disruption of mitochondrial electron transport chain.
 When used alone, the clinical response to Clofazimine is
slower than that to Dapsone and resistance develops in 1-3
years.
 Dapsone –resistant M.leprae respond to Clofazimine, but
apparently after a lag period of about 2 months.

13. 

Reddish black discolouration of exposed parts
Discolouration of hair and body secretions
Dryness of skin and itching
Acneform eruptions
Phototoxicity
Conjunctival pigmentation
Nausea, Anorexia
Abdominal pain
Weight loss
Enteritis with intermittent loose stools

14. To be avoided during
 early pregnancy.
 In patients with renal or hepatic damage.

15.  This important tuberculocidal drug is also the most
potent cidal drug for M.leprae : rapidly renders leprosy
patients noncontagious.
 Up to 99.9% M.leprae are killed in 3-7 days by
600mg/day dose.
 Clinical effects of Rifampicin are rapid.
 However the nerve damage already incurred is little
benefited.
 It is not satisfactory ,if used alone- persisters are found
even after prolonged treatment and resistance
develops.

16.  Hepatitis
 Cutaneous syndrome-flushing, pruritus,rash
 Flu syndrome- with chills,fever, headache,malaise and watering of
eyes
 Abdominal syndrome- nausea ,vomting,abdominal
crampswith/without diarrhoea.

17.  Hepatitis
 Cutaneous syndrome-flushing, pruritus,rash
 Flu syndrome- with chills,fever, headache,malaise and watering of
eyes
 Abdominal syndrome- nausea ,vomting,abdominal
crampswith/without diarrhoea.
Urine and secretions may become orange-red but this is harmless.
 However ,it should not be given to patients with hepatic or renal
dysfunction , as well as during Erythema nodosum leprosum and
Reversal reactions in leprosy patients , because it can release large
quantities of mycobacterial antigens by inducing rapid bacillary
killing.

18.  To deal with dapsone resistant strains of M.leprae and to
shorten the duration of treatment,multidrug therapy
with Rifampicin,Clofazimine and Dapsone was
introduced by the WHO in 1981.
 Following the initiative under WHO Action Programme
for Elimination of Leprosy, India introduced MDT for
Leprosy through NLEP-National Leprosy Eradication
Programme in 1982
 Conventionally,all forms of leprosy had been treated
with dapsone alone-monotherapy.(100-200mg,daily-5
days a week.duration od treatment depening upon
type: TT- 4to 5 years,LL-8 to 12 years or lifelong.

19.  The MDT is the regimen of choice for all cases of leprosy.
 Initially under standard MDT,the PBL cases were treated
with Dapsone +Rifampicin for 6 months, while MBL cases
were treated with Dapsone+Rifampicin+ Clofazimine for a
minimum of 2 years or till disease inactivity/skin smear
negativity was achieved.
 Due to operational reasons ,NLEP in India experimented
with ‘fixed duration therapy of 24 month’(FDT-24) for MBL
cases found that the relapse rates were similar to that in
standard protocol.
 Later,FDT-24 was recommended by WHO in 1994 for all
MBL cases whether disease inactivity/skin smear negativity
was achieved or not.
 The 6 months FDT continues for PBL cases.

20. MDT
leprosy
Reduced risk
of
develpmnt
of resistance
Shortens
duration of
treatment
Quick relief &
safe even
during
pregnancy
Renders MBL
cases
noninfectious

22.  Many alternative regimens incorporating newer
antileprotic drugs have been investigated. However,
these are used only in case of Rifampicin - resistance
or when it is impossible/inadvisable to employ the
standard MDT regimen
 Intermittent ROM-rifampicin 600mg+ ofloxacin
400mg+ minocycline 100mg are given once a month
for PBL and 12-24 month for MBL cases.
 Single dose ROM-a single dose of rifampicin +
ofloxacin+ minocycline was given for single lesion
PBL.
 Four drug regimen of rifampicin 600mg+sparfloxacin
200mg+clarithromycin 500mg+minocycline 100mg
daily for 12 weeks.