DR Y SRI HARSHA

LEPROSY & PREGNANCY

• It depends upon the changes occurring in a pregnant lady1. 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

3. Altered immunological response:

Humoral immunity Cell mediated immunity

Pregnancy increased depressed

Post Partum depressed Increased

• 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 dapsone monotherapy)

TYPE 1 REACTIONS:• Reversal reactions (RR) are frequently encountered ( more during

pregnancy than lactation)• 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 more frequently

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 periods

• 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

1. Fetus:• Only few obstetric complications have been consistently reported

in women with leprosy• 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

2. placenta:• 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

underweighted• 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 pregnancy

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 , osteochondrosis5. 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

MANAGEMENT

TREATMENT OF LEPROSY

HISTORY OF TREATMENT In 1941, promin, a sulphone drug, showed efficacy but required many

painful injections.

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

DAPSONE

• 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 therapy

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 monotherapy2. Irregular intake3. Suboptimal dose of dapsone used• Genetic basis of this resistance lies in mutation of fol P gene of M.leprae• Currently, dapsone is recommended1. To be used only as a component of MDT, 2. To be given at 50-100mg/day3. As far as possible without any interruption

DAPSONE RESISTANCE

• 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)

RIFAMPICIN

• 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 system

• Half life is about 2 months

CLOFAZIMINE

• Bactericidal drugs • MOA is not exactly not known, possibly by inhibition of mycolic

acid, protein synthesis• 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

THIACETAZONE

ADVERSE 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

ETHIONAMIDE & PROTHIONAMIDE

GI intolerance, anorexia, salivation, metallic taste, hepatotoxicity

THIACETAZONE Nausea, anorexia, skin rash, headache, drowsiness, hemolytic anemia, agranulocytosis, thrombocytopenia, abnormal liver enzymes

1. Fluoroquinolones (ofloxacin, pefloxacin, moxifloxacin)2. Minocycline3. Clarithromycin4. Ansamycins ( rifabutin, rifapentine)5. Dihydrofolate reductase inhibitors (brodimoprim, K-130)6. Fusidic acid7. Beta lactamase resistant antibiotics

NEWER DRUGS FOR LEPROSY

• Nalidixic acid derivatives• Ofloxacin, moxifloxacin, sparfloxacin• MOA- by blocking DNA gyrase, thereby inhibiting the coiling & supercoiling of

DNA• Dose- ofloxacin 400mg/day• Advantages:1. high bioavailability2. Long half life3. High urinary excretion4. Unique MOA 5. Extremely rapid antimicrobial action• Side effects: abdominal problems, joint pains, pruritus, photosensitivity

FLUOROQUINOLONES

• 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,

MINOCYCLINE

• MOA- act by inhibiting protein synthesis by binding to 50s ribosomal subunits

• 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

CLARITHROMYCIN

• 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.

OBJECTIVES

• 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 drugs.

• 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.

MDT DRUGS

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

MB-MDT regimen

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

PB-MDT regimen 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

Control programs in leprosy

NATIONAL LEROSY CONTROL PROGRAMME

• 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 PROGRAMME

• 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 10,000 population.

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 (18.49%).

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 local community.

• 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 medical colleges.

• 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 DISABILITIES:• 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

sensation.• 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

appropriate action.• Accredited Social Health Activists(ASHA):• Rogi-kalyan samities:Authorized to procure drugs at local level in emergency.

• REHABILITATION:• 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 surgeries.

• Social and economic rehabilitation aims at social integration,equal oppurtunities and economic development.

• 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.