initially through the drug fund provided by the Nippon Foundation;since 2000, through the MDT donation provided by Novartis and the Novartis Foundation for Sustainable Development.
Leprosy & pregnancy , treatment, control programs
DR Y SRI HARSHA
LEPROSY & PREGNANCY
• It depends upon the changes occurring in a pregnant lady
1. Metabolic changes:
Due to several metabolical changes occurring during pregnancy , there
occurs a state of relative & absolute malnutrition ( deficiency of proteins,
vitamins, iron & other minerals)
Course of leprosy in pregnancy
Cell mediated immunity gets depressed
Worsening of leprosy
2. Altered secretion of steroids:
levels of free cortisol & 17- hydroxycorticosteroid increases during pregnancy
Reduced cell mediated immunity
Exacerbation of leprosy, TB
• 20-30% of female patients develop signs & symptoms of leprosy for the first
time of pregnancy / shortly thereafter due to depressed CMI in pregnancy
• The large no of women who first presented with leprosy lesions in
puerperium could be attributed to the increased visibility of leprosy lesions
due to erythema & edema of reversal reactions (RR) which may occur due to
recovery of CMI in post partum period
First presentation of leprosy in pregnancy
• Leprosy aggravates/downgrades in pregnancy & upgrades during lactation
• There will be an increased bacillary load ( can be attributed to suppressed
CMI & reluctance of women to take medications during pregnancy)
• Due to prolonged immunosuppression in pregnancy , persisters multiply
resulting in relapse ( most of theses cases have been reported in the era of
TYPE 1 REACTIONS:
• Reversal reactions (RR) are frequently encountered ( more during pregnancy than
• Peak incidence of RR occur 3-16 weeks after delivery
• Patients with BL & sub polar LL are at greatest risk of developing RR’s
• In RR’s occurring during pregnancy, cutaneous manifestations are more frequent &
conspicuous than neuritis
• In RR’s occurring during lactation , neuritis & nerve function impairment are seen
Reactions & Pregnancy
TYPE 2 REACTIONS:
• First episodes of type 2 reactions can begin early in pregnancy & peak in the
3rd trimester, the recurrent episodes may continue long into the lactation
• The skin reaction may be severe & recurrent
• Neuritis is present, systemic symptoms are less frequent
• Episodes of ENL in puerperium are often associated with significant motor
&/ sensory deficit involving multiple nerves & frequent involvement of other
systems is seen
• Only few obstetric complications have been consistently reported in women
• Babies born to mothers with LL hansen’s weigh significantly less at birth than
babies born to mothers with tuberculoid leprosy & normal healthy controls
• This may be due to fetoplacental inadequacy in women with LL hansen’s
IMPACT OF LEPROSY
• Though the morphology & immunohistology of placenta is normal, the
placental weight & placental coefficient ( ratio of baby weight to placental
weight) is lower in women with leprosy ( more marked in LL hansen’s )
3. Infants, childhood, adolescence:
• 80% of babies born to LL mothers have been found to be severely
• Infants born to LL mothers have a higher incidence of respiratory problems
• Newborns of mothers on MDT may present with intercurrent disease such as
exfoliative dermatitis in first hours of life (due to dapsone) & brownish
discoloration (due to clofazimine)
• Drugs are best avoided in pregnancy, but the benefits of treating leprosy
during pregnancy far outweighs the risks of the drugs.
• WHO recommends that pregnant women with leprosy should continue to
take the standard MDT
• Drugs which can be administered are dapsone, rifampicin, clofazimine,
corticosteroids, NSAID’S for reactions
• Drugs which are avoided are quinolones, minocycline, thalidomide
Drug Therapy of leprosy during
1. Dapsone - hemolytic anemia, hyperbilirubinemia
2. Rifampicin - hemorrhagic disease of new born ( parenteral vit K)
3. Clofazimine – fetal discoloration, sometimes death ( perinatal center)
4. Quinolones – arthropathies , osteochondrosis
5. Corticosteroids – risk of oral clefts ( avoid in 1st trimester)
6. NSAID’S – premature closure of ductus arteriosus , renal adverse effects,
premature birth ( avoid in 3rd trimester )
7. Thalidomide – phocomelia
Side effects of drugs on fetus
• The patient should be counseled to complete the course of ALT during
pregnancy & emphasize on the safety of these drugs
• She should be counseled about the possibility of reactions during pregnancy
& lactation and advise them to take medical help immediately
• If possible, the patients on ALT during pregnancy should be managed at a
perinatal center with adequate neonatal care facilities
HISTORY OF TREATMENT
In 1941, promin, a sulphone drug, showed efficacy but required many painful
Dapsone pills were found to be effective in the 1950s
But soon (1960s-1970s), M. leprae developed resistance to dapsone.
. In the early 1960s, Rifampicin and clofazimine, the other two components of
MDT, were discovered.
This multi-drug treatment (MDT) was recommended by the WHO in 1981
and remains, with minor changes, the therapy of choice.
Since 1995, WHO provides free MDT for all patients in the world
NB: MDT, however, does not alter the damage done to an individual by M.
leprae before MDT is started.
• Has been the main drug used against M.leprae since the 60’s
• Weak bactericidal action against M.leprae
• MOA- competitive inhibition of dihydrofolate reductase, involved in the
conversion of PABA to dihydropterate in folic acid synthesis
• Dose: 1-2mg/kg/day (>50kg – 100mg/day, <50kg- 50mg/day)
• Peak levels are reached within 4-6 hrs after complete absorption
• Half life is about 24 hrs
• Occasionally seen in some patients who are on treatment for some months
• Frequency has increased since the introduction of MBMDT
• Has 2 forms
1. Complete form: patient develops fever, skin rash( maculopapular/exfoliative
dermatitis) with lymphadenopathy & hepatitis after 4-6 wks of starting dapsone
2. Incomplete form: one or more manifestations may be missing & recovery is usually
complete on discontinuing dapsone
• Treatment: discontinue dapsone, short course of oral corticosteroids, supportive
DAPSONE HYPERSENSITIVITY SYNDROME
• Became evident in 1964, when petit & Rees showed M.leprae multiplication on foot
pad of mice fed on varying concentrations of dapsone in diet
• Main factors contributing to this problem are:
1. Long practiced monotherapy
2. Irregular intake
3. Suboptimal dose of dapsone used
• Genetic basis of this resistance lies in mutation of fol P gene of M.leprae
• Currently, dapsone is recommended
1. To be used only as a component of MDT,
2. To be given at 50-100mg/day
3. As far as possible without any interruption
• A semi synthetic derivative of rifamycin
• Has a strong bactericidal action against M.leprae
• MOA- selective inhibition of DNA-dependent RNA polymerase of bacterial origin,
thus blocking protein synthesis
• Dose- a monthly once dose of 600mg
• Peak levels are reached within 2-3 hrs after a quick & complete absorption when
taken on an empty stomach
• Half life is about 12 hrs
• Rifampicin monotherapy has resulted in the development of resistant strains (1976)
• synthetic iminophenazine dye
• Mild bactericidal action against M.leprae & additional anti inflammatory properties
• MOA- not exactly known (possibly acts by blocking the template function of DNA)
• Dose-300-350mg/week, preferably taken in a daily dose of 50mg
• Only 30-50% of the drug is absorbed orally, & it passes through several organs &
gets stored as needle like crystals in macrophages, cells of reticulo-endothelial
• Half life is about 2 months
• Bactericidal drugs
• MOA is not exactly not known, possibly by inhibition of mycolic acid,
• dose- 5mg/kg/day (avg adult dose is 375mg/day)
• Effective against dapsone & rifampicin resistant strains
• These drugs are not to be used as monotherapy as several patients have
relapsed following its use
ETHIONAMIDE & PROTHIONAMIDE
• Bacteriostatic drug used in the treatment of leprosy
• Dose- 150mg/day
• It has a short half life ( therefore irregularity in its use can result in resistant
leprosy strains which shows cross resistance to thioamides)
• It is now very rarely used in leprosy because of the availability of more
effective and safer drugs & because of the severity of its side effects
drug Adverse effects
DAPSONE Hemolytic anemia, liver damage, dapsone induced neuropathy, met
hemoglobin formation, skin rash, precipitation of Lepra reactions
RIFAMPICIN Red discoloration of urine, hepatotoxicity, drug rashes, GI symptoms,
thrombocytopenia, psychosis, osteomalacia, flu like syndrome
CLOFAZIMINE Reddish brown pigmentation of skin and conjunctiva, acquired ichthyosis
GI intolerance, anorexia, salivation, metallic taste, hepatotoxicity
THIACETAZONE Nausea, anorexia, skin rash, headache, drowsiness, hemolytic anemia,
agranulocytosis, thrombocytopenia, abnormal liver enzymes
• Nalidixic acid derivatives
• Ofloxacin, moxifloxacin, sparfloxacin
• MOA- by blocking DNA gyrase, thereby inhibiting the coiling & supercoiling of
• Dose- ofloxacin 400mg/day
1. high bioavailability
2. Long half life
3. High urinary excretion
4. Unique MOA
5. Extremely rapid antimicrobial action
• Side effects: abdominal problems, joint pains, pruritus, photosensitivity
• MOA- act by binding to the 30s ribosomal subunits of bacteria, thereby
inhibiting protein synthesis
• Minocycline is lipophilic at neutral pH , easily penetrates the bacterial cell
wall & inhibits protein synthesis
• Dose- 200mg daily
• Side effects: nausea, vomiting,
• MOA- act by inhibiting protein synthesis by binding to 50s ribosomal
• These drugs tend to get concentrated in the tissues & also in the bacteria
resulting in longer half life
• On using it in leprosy patients, a rapid clinical improvement has been
observed together with a significant decline in MI
• On administering it with minocycline, a synergism of action has been found
against several infections , also in leprosy
• Side effects – gastrointestinal problems
• Highly effective in curing the disease
• Prevents development of drug resistance
• Reduces the period of treatment
• Well accepted by patients
• Easy to apply in the field
• Interrupts transmission of infection
• Reduces risk of relapse
• Prevents disabilities
• Improves community attitude
ADVANTAGES OF MDT
• To interrupt transmission of leprosy in the community by sterilizing
infectious patients as rapidly as possible with bactericidal drugs.
• To ensure early case detection and treatment of cases to prevent deformities.
• To prevent drug resistance.
• All registered and new cases should be started on appropriate MDT regimen
as soon as diagnosis is confirmed.
• The only prerequisite to starting MDT programme is availability of MDT
• Never use single drug to treat leprosy .Use of one drug alone will cause
resistance to that drugs.
• The drugs used in MDT are a combination of Rifampicin, clofazimine, and
dapsone for MB patients.
• A combination of rifampicin and dapsone is used for PB patients.
Monthly treatment : day 1
• Rifampicin 600mg
• Clofazimine 300mg
• Dapsone 100mg
Daily treatment : day 2 to 28
• Clofazimine 50mg
• Dapsone 100mg
Duration of treatment :12 blister packs to be taken monthly within a maximum period
of 18 months
Dosage for children (MBMDT)
Monthly treatment : day 1
• Rifampicin 450mg
• Clofazimine 150mg
• Dapsone 50mg
Daily treatment : days 2 –28
• Clofazimine 50mg every other day
• Dapsone 50mg daily
Monthly treatment :Day 1
• Rifampicin 600mg
• Dapsone 100mg
Daily treatment : Days 2 to 28
• Dapsone 100mg
Duration of treatment : 6 blister packs to be taken monthly within a max
period of 9 months
Dose in relation to adult dose Weight range ( in kg )
One quarter Under 15
One half 15-30
Three quarters 30-45
Adult dose Over 45
Guide for drug dosage in children
NATIONAL LEROSY CONTROL
• Govt of india started national leprosy control programme (NLCP) in 1955, based on
domicillary treatment through vertical units by implementation of survey education &
treatment activities (SET)
• The whole concept of NLCP was based on design of leprosy treatment & care devised by Dr
R V WARDEKAR (a renowned leprologist) and practiced at Gandhi memorial leprosy
foundation at wardha since 1951
NATIONAL LEPROSY ERADICATION
• MDT came into wide use from 1982, following recommendations by WHO study groups &
was successful in significant reduction of the disease burden
• Govt of India established a high power committee under the chairmanship of Dr M S
SWAMINATHAN in 1981 & based on its recommendation, the national leprosy eradication
programme (NLEP) was launched in 1983
• However the coverage remain limited due to organizational issues and fear of the disease
becoming disclosed and the associated stigma
• In view of substantial progress achieved by MDT, in 1991, the world health assembly
resolved to eliminate leprosy at a global scale by the year 2000
• In order to strengthen the process of elimination in the country, the 1st phase of the world
bank supported project was started from 1993-94 and was completed in march 2000.
• To further consolidate the gains , the 2nd phase of world bank project on NLEP was started in
2001 which ended in December 2004 during which decentralization of NLEP to states/UT’s &
integration of leprosy with general health care system (GHS) was carried out
• In 2005, a survey to monitor the performance at close of 2nd NLEP (December 2004) was
carried out during April-may 2005 through an independent agency, the Indian institute of
health management & research, Jaipur
• Leprosy was declared eliminated as a public health problem in India at national level in the
month of December 2005
• From December 2005, the program continues with the support of govt of India
Current status of leprosy in India (as
of march 31st , 2013)
1. A total of 1.35 lakh new cases were detected during the year 2012-13, which gives Annual New Case
Detection Rate (ANCDR) of 10.78 per 100,000 population. This shows increase in ANCDR of 4.15%
from 2011-12 (10.35).
2. A total of 0.92 lakh cases are on record as on 1st April 2013, giving a Prevalence rate (PR) of 0.73 per
3. Detailed information on new leprosy cases detected during 2012-13 indicates the proportion of MB
(49.92%), Female (37.72%), Child (9.93%), Visible Deformity (3.45%), ST cases (17.01%) and SC cases
4. A total of 4650 Gr. II disability detected amongst the New Leprosy Cases during 2012-13, indicating the
Gr. II Disability Rate of 3.72 / million population (Annexure-II). In addition 5175 Gr. I cases were recorded
which indicates the rate of 4.14/million population.
5. A total of 13387 child cases were recorded, which shows the Child Case rate of 1.07/100,000 population
NEW PARADIGMS IN NLEP
BURDEN OF LEPROSY:
• Firstly, the most relevant epidemiological measure of the burden of leprosy is
the incidence(no.of new cases during a set period of time)of the disease.
• Secondly, the burden may be related to the registered prevalence of disease,
which is the number of people on treatment at a certain point of time.
• Thirdly, burden can be viewed through the affected people themselves
IMPROVING THE QUALITY OF SERVICES:
• MDT treatment should be provided at all health units, should be patient centered and
recognize the patient’s rights, including the rights to appropriate and timely treatment
and to privacy and confidentiality.
• Diagnosis is to be carried out accurately.
• Supportive counselling.
• Timely free treatment with MDT.
• Should also incorporate appropriate disability prevention interventions.
INTEGRATION OF LEPROSY SERVICES WITH PRIMARY
HEALTH CARE SYSTEM FOR SUSTAINABILITY:
• General health services are widely distributed ,have close and frequent contact with
• There involvement in leprosy control will improve case finding case holding and
awareness of the local community about the disease.
• Integration will improve the efficiency and effectiveness, provide greater
equity,reduce stigma and discrimintaion and ensure long term sustainability.
• REFERRAL SERVICES AND LONG TERM CARE:
• The referral network, which provides referral services for other diseases and
conditions in the area must be part of the integrated system .e.g. District hospitals or
• CHCs with adequate infrastructure including trained manpower and equipment may
serve as the first referral unit in the referral network.
The different indications for referring the patients are:
• For significant Eye pathology.
• Dermatology clinic for diagnosing, treating the disease and its reactions.
• Laboratory for skin smears and H/P.
• Physiotherapy: for assessment and management of disability.
• Podiatrist or chiropodist for feet and footwear.
• Plastic and reconstructive surgery: skin grafting for nonhealing ulcers.
• Orthopedic surgeon for reconstructive surgery, wound debridement, arthritis.
PREVENTION AND MANAGEMENT OF IMPAIRMENTS AND
• Interventions include Early detection,
• Effective management of leprosy related reactions and nerve damage
• proper counselling on self care,
• participation of household members in home-based care development.
• use of esthetically acceptable footwear and other appliances.
IMPROVING COMMUNITY AWARENESS AND INVOLVEMENT:
• The Information Education Communication(IEC) efforts should be to encourage self
reporting of new cases and to reduce stigma and discrimination.
• Four key messages for general public health:
• 1.curable:leprosy can be cured with drugs that are widely available.
• 2.Early signs of leprosy: pale or reddish skin patches with loss or impairment of
• 3.No need to fear: The disease can be managed just like any other disease.
• 4.Support and encouragement of the family and community.
• SUPPORT OF NATURAL RURAL HEALTH MISSION:
• Village health and sanitation committee:To decide health priorities and to take
• Accredited Social Health Activists(ASHA):
• Rogi-kalyan samities:Authorized to procure drugs at local level in emergency.
• Leprosy may lead to physical,functional,social and economic problems.
• Physical rehabilitation includes physiotherapy,and occupational therapy,orthotics and
prosthetic services,assistive and protective devices and sometimes corrective
• Social and economic rehabilitation aims at social integration,equal oppurtunities and
• INDICATORS FOR MONITORING AND EVALUATION:
• 1.Number of new cases detected in a given area each year.
• 2.Treatment completion/cure rate.
• 3.Registered prevalence
• 4.Additional indicators like proportion of new child cases.new female cases,cases
presenting with disabilities.