Burden of leprosy in India Multi-drug therapy MDT WHO Diagnostic guidelines Drug resistance Stigma Serological tests Social stigma of leprosy Dapsone resistance Rifampicin resistance Mycobacterium leprae surveillance of AMR in leprosy Adherence to MDT is important Global leprosy strategy

1. Management of Leprosy
Current challenges and the way ahead

2. The burden of leprosy in India
• India has had major advances in battling leprosy
• Successful in bringing down prevalence of leprosy over the last 3
decades
• Internationally, the prevalence rate was brought under one per 10,000
population by 2000
• However, even after the target was achieved, dermatologists
continued to see patients and did not note any great decline in
numbers
Source:http://nlep.nic.in

3. Leprosy Prevalence Rate (per 10000) in India
Source:http://nlep.nic.in

4. The burden of leprosy in India
• Global prevalence estimates by the WHO: 0.23 per 10,000 population
• In 2017, India, Brazil and Indonesia were the only countries where
more than 10,000 new cases were reported per year
• India contributed to a staggering 66% in new cases detected globally
Source:http://nlep.nic.in

5. 2 out of every 3 new global leprosy cases are
detected in India
Source:http://nlep.nic.in
66%India’s
contribution
2,04,686=total new cases detected globally
1,35,485=new cases detected in India

6. Region wise disease contribution: Global
http://www.ilepfederation.org/world-leprosy-day-2016.
74%
14%
9%
2% 1%
Southeast Asia America
Africa Western Pacific
Eastern Mediterranean

7. Multidrug therapy (MDT)
• Reduces treatment costs on the health system
• Over 16 million patients from 138 countries across have been treated with
MDT
• Rapidly reduce the prevalence of the disease to <1 case/10,000 population at
national levels for leprosy to be declared as eliminated in the year 2000
• WHO makes MDT available free of cost in all countries
• MDT was recommended by the WHO in 1981
• In 1982, it was introduced first in two high endemic districts, Wardha in
Maharashtra, and Purulia in West Bengal
http://www.who.int/lep/disease/en/.
JpnJLepr2001;70:25-9

8. Current challenges & future
aspects
1. Diagnostic challenges
2. Stigma about leprosy
3. Drug resistance
4. Non adherence to drugs

9. Diagnostic challenges

10. WHO diagnostic guidelines (2018)
• Based on the presence of at least one of three cardinal signs:
i. Definite loss of sensation in a pale (hypopigmented) or reddish skin patch
ii. Thickened or enlarged peripheral nerve with loss of sensation and/or
weakness of the muscles supplied by that nerve
iii. Presence of acid-fast bacilli in a slit-skin smear
http://www.searo.who.int/entity/global_leprosy_programme/appr
oved-guidelines-leprosy-executives-summary.pdf?ua=1

11. Summary of Evidence-Based WHO Guidelines for
Diagnosis, Treatment, and Prevention of Leprosy, 2018
JAMADermatol.2019;doi:10.1001/jamadermatol.2019.1730

12. Diagnosis of Leprosy
• Diagnosis of leprosy can be made by the clinical signs alone
• In absence of definitive cardinal features, confirmation of
leprosy can be difficult in some patients especially in a non-
endemic country.
• Histopathology is the usual modality for confirmation of a
clinically doubtful case of leprosy.
• Other procedures like skin testing with M. leprae antigen
(lepromin), antibody responses of the host to M. leprae and
molecular techniques to detect the components of M. leprae in
the lesions have also been used for diagnosis of leprosy at early
stage.
IndianDermatolOnlineJ2019;10:106-14

13. Serological tests
• Several serological and nucleic acid amplification diagnostic
tests have been developed
• They are of low sensitivity in difficult-to-diagnose early,
paucibacillary leprosy and/or difficult to perform in the primary
care setting
• No tests are recommended for the identification of infection in
asymptomatic contacts because they have low predictive value.
JAMADermatol.2019;doi:10.1001/jamadermatol.2019.1730

14. Comparative efficacies of immunological and
molecular markers in diagnosis of leprosy
IndianDermatolOnlineJ2019;10:106-14

15. Clinical diagnosis of early leprosy and PB leprosy
can be a challenge
• A number of serological and other laboratory assays have been developed to
supplement clinical diagnostic methods
• ELISA and lateral flow assays are associated with low diagnostic accuracy
for PB leprosy
• Although some PCR based assays are associated with higher diagnostic
accuracy, they lack standardization, are not commercially available, and would
be difficult to perform in most primary health-care settings
http://www.searo.who.int/entity/global_leprosy_programme/appr
oved-guidelines-leprosy-executives-summary.pdf?ua=1

16. • Due to the broad bioepidemiological aspects, eradication is difficult
• Proper diagnosis and the correct clinical classification are required to ensure
proper treatment

17. Continuous challenges
• Tools and markers for diagnosis and prognosis
• Novel use of nanotechnology
• Strategies for disease control and monitoring populations at higher
risk
• The use of the current diagnostic tools, such as ELISA and PCR has a
very limited approach for leprosy that has been considered as a
marginal disease
• The current diagnostic tools must be applied extensively in the routine
to accumulate clinical experience in order to improve their precise
application, like what has been done in many other infectious diseases
ArchDermatolRes.2008Jul;300(6):269-90.

18. • There are challenges in diagnosing early leprosy
• In spite of intensive efforts by many groups, consensus on a
universal test suitable for endemic areas is awaited.

19. Case detection
• 2 important indicators of the NLE, India, that is, Annual New Case Detection
Rate (ANCDR) and Prevalence Rate (PR) are almost static since 2006–2007
(CLD 2016)
• The trend of the PR and ANCDR per 10,000 population since 2001-02 to
2014-15 is shown
http://nlep.nic.in/pdf/Annual%20report_%202016-17_rev.pdf

20. Early detection & treatment is important
• Nerve damage from leprosy and its complications (leprosy reactions)
can cause disability if not treated early
• It is important therefore that patients are referred early for
appropriate treatment
• Several studies have shown a relationship between high rates of
disability at presentation and late reporting to modern (biomedical)
health facilities

22. Conclusions
• Local practitioners' knowledge of how to diagnose leprosy is poor
• Many of them treat within their own system of medicine; for example,
homeopathy or Ayurveda
• Among the 29 practitioners interviewed in the study, 6 were referring
patients to hospitals and only one was treating with MDT
• This study highlights the need to engage with local practitioners to
promote early referral to specialist centers where patients can be
diagnosed and receive appropriate treatment
https://www.leprosy-ila.org/arquivos/leprosy_congress.pdf

23. • Diagnosis and treatment of leprosy reactions in integrated
services in Nepal was evaluated
• An average delay of 2.9 months between onset of symptoms and
treatment being commenced
• Patients presenting directly to specialist services were 6.6 times
more likely to receive appropriate treatment than those
presenting elsewhere

24. High endemicity
• Pockets of high endemicity still remain in some areas of many
countries
• Even high in countries reporting <1000 new cases
• Some of these areas show very high notification rates for new
cases and may still witness intense transmission

25. Stigma

26. Leprosy: A social stigma
• For thousands of years, leprosy was thought to be a curse of the gods, a
punishment for sin, or a hereditary condition
• Leprosy still remains a public health problem in India
• Stigma and associated psychosocial problems are common in leprosy and may
affect the quality of life (QoL)
• The term has been so heavily stigmatised that it has become synonymous
with abandonment, social isolation, and condemnation to a lifetime at the
margins of society.

27. • xsxs
• This study revealed poor knowledge regarding leprosy and high levels of stigma
and fear and desire to keep social distance towards persons affected by leprosy.
• Community education that takes cultural beliefs, knowledge gaps and fears into
consideration could improve knowledge, reduce misconceptions and positively
influence the perception of leprosy.

28. • Persons affected by leprosy with visible deformity had lower QoL
• Early detection and management would prevent the deformity and
might improve the QoL of persons affected by leprosy.

29. • Women in developing countries seek health care late for any health-related
issues.
• Leprosy, a disease known for its stigma, adds further to these facts.
• Close contact between women and family members, especially children,
increases the chance of transmission to others and thereby increases the
disease burden in the society
• Hence, leprosy in women is an important issue for the affected patient, their
family members, and society as a whole.

30. • The study was conducted in the Potka Block of East Singhbhum district of the state of
Jharkhand.
• 56% of female and 52% of male respondents are considered untouchable by their natal
families, thus forced to stay in congested leprosy colonies resulting in other social and
health related issues
• Leprosy cured children, and also children of leprosy affected person are being denied
admission iany school, due to the social stigma attached to it.
• Among the, respondents 60% of the females were beggars as compared to 48% of the male
respondents
• Overall this study reflects the poor socio-economic conditions of the leprosy affected
persons.

31. Drug resistance

32. WHO treatment guidelines

33. Drug resistance
• Reduction in effectiveness of a drug such as an antimicrobial or an
antineoplastic (Drug Resistance at the US National Library of
Medicine) in curing a disease or condition.
• When the drug is not intended to kill or inhibit a pathogen, then the
term is equivalent to dosage failure or drug tolerance.
• More commonly, the term is used in the context of resistance that
pathogens have “acquired”, that is, resistance has evolved.
• When an organism is resistant to more than one drug, it is said to be
multidrug-resistant.

34. The emergence of drug resistance
• As treatment of leprosy and tuberculosis, progressed during the 1950s and
1960s, the development of drug resistance was recognized as an obstacle to
case management and control
• Resistance to dapsone, the first effective antileprosy drug, appeared in
parallel with the emergence of resistance to streptomycin, the first
antituberculosis agent
• To prevent further drug-resistance development, the treatment of both
diseases was standardized with a combination of antibiotics
ClinMicrobiolInfect.2018Dec;24(12):1305–1310.

35. The emergence of drug resistance
• As rifampicin is the backbone of the MDT regimen, it is important to monitor
the emergence of rifampicin-resistant strains
• In case of resistance to rifampicin, fluoroquinolones become the preferred
category of second-line drugs
• Quinolone-resistant strains of Mycobacterium leprae have also been reported
in several countries
• This could be due to the extensive use of quinolones for treating several
types of infections.
• Clofazimine resistance is still rare but this antimicrobial cannot be given
alone.

36. Dapsone resistance
• Evident as clinical failure on long-term monotherapy
• Since Mycobacterium leprae cannot be grown on any artificial media, it was
detected through laboratory tests only with the development of the mouse
foot-pad model
• By 1981, dapsone resistance was widespread and rifampicin-resistant cases
had emerged
• Induced WHO to standardize multidrug therapy (MDT) for leprosy by
combining dapsone with rifampicin for all cases, plus clofazimine for multi-
bacillary cases
• MDT remains the recommended regimen for treating leprosy

37. Although relapses in patients treated with MDT are
rare, multiple resistance was eventually reported in
different regions of the world, with the description of
M. leprae strains resistant to dapsone, rifampicin and
ofloxacin concomitant with treatment failure

38. Map of countries reporting rifampicin resistance
in leprosy between 2009 and 2015
Source:Cambau,E.,P.Saunderson,M.Matsuoka,S.T.Cole,M.Kai,P.Suffys,P.S.
Rosaetal.“Antimicrobialresistanceinleprosy:resultsofthefirstprospectiveopen
surveyconductedbyaWHOsurveillancenetworkfortheperiod2009–15.”Clinical
MicrobiologyandInfection(2018)

39. Surveillance of rifampicin resistance and number of rifampicin-resistant
cases reported by country from 2009 to 2015
ClinicalMicrobiologyandInfection24(2018)1305e1310

40. Results of surveillance for dapsone (DDS) and ofloxacin (OFL) resistance (R)
detailed per country for the study period 2009-15
ClinicalMicrobiologyandInfection24(2018)1305e1310

41. Mechanisms of Mycobacterium leprae’s
resistance to antileprosy drugs
• Chromosomal mutations in genes encoding drug targets
• These mutations occur spontaneously as a result of errors in DNA replication
• These mutants are enriched in a population of susceptible M. leprae by
inappropriate drug therapy.
PLoSMed2009;6:e1000146.

42. Types of resistance
• Drug-resistant M. leprae mutants can be acquired:
 During the initial infection from an infection source containing
drug-resistant leprosy (primary drug resistance)
 From inadequate treatment (secondary drug resistance).
ClinMicrobiolRev1995;8:496-514.

43. Frequency of mutants
• Frequency of dapsone-resistant mutants in a population of M. leprae is
estimated to be 106
• Frequency for rifampicin and ofloxacin resistance is estimated to be 10 and
10 respectively
• Rates of clofazimine resistance in M. leprae are unknown but appear to be
extremely low
IntJLeprOtherMycobactDis1995;63:195-201.

44. WHO approach
• The present WHO approach for eliminating leprosy is based on
case detection and antimicrobial chemotherapy
• The practice of unsupervised chemotherapy with attendant
potential noncompliance, and unavailability of a test for
drug-resistant M. leprae on a routine basis, can cause incomplete
chemotherapy
• This could lead to relapse, reinfection, and natural selection of
drug-resistant strains of M. leprae

45. Drug resistance in new cases
• Drug resistance among new cases appears to be rare
• Reports of single and multidrug-resistant M. leprae among
relapse patients continue to appear in the literature
• Since the magnitude of resistance at the global level remains
unclear, monitoring of drug resistance in leprosy is especially
important
• The understanding of drug resistance in M. leprae has led to the
development of many different assays for its detection
LeprRev2012;83:269-81

46. Relapse
• Drug-resistant leprosy, including dapsone- and
rifampin-resistant and MDR leprosy, has been reported in other
parts of the world, usually in association with relapse after
insufficient therapy
• Relapses in leprosy are not usually seen until many years after
completion of treatment.
ClinMicrobiolRev2006;19:338-81,http://www.who.int/wer/2011/wer8623.pdf?ua=1.,
IntJLeprOtherMycobactDis2004;72:1-7

47. Scheme for
surveillance of AMR in
leprosy
Source:TabledevelopedbyProfessorE.Cambau,DrM.MatsuokaandDrL.Gillini

48. Non adherence to drugs

49. Adherence to MDT is important
• MDT has proven to be a powerful tool in the control of leprosy,
especially when patients report early and start prompt treatment
• Adherence to and its successful completion is equally important
• Due to a number of personal, psychosocial, economic, medical, and
health service factors, a significant number of patients become
irregular and default from MDT.

50. Defaulting patients
• Extent of such defaulting, its correlates and reasons are described,
based on a study of six leprosy mission hospitals.
• Nearly 50% of patients closer to the hospitals as compared to 60%
beyond have defaulted.
• Patients from outside the district had significantly higher default
rate for all types of leprosy cases as compared to patients living close
by to the centers.

51. Defaulting patients
• Defaulter rate was quite high and did not differ by males and females.
• The MB defaulter rates were higher as compared to PB excluding the
first dose, but the difference was not statistically significant
• The main reasons for defaulting were psychosocial and health related

52. Corrective measures
• Health education decreases the stigma of leprosy
• Early signs and curability should be emphasized as self-referred
patients are more likely to adhere.
• Advertising leprosy as disfiguring and disabling merely enhances
stigma.
• Advertising should be tailored to populations using locally revered
members of the community, politicians, and actors.
• Targeting young adults who are more literate and amenable to change
can influence their elders to seek treatment.

53. Corrective measures
• Changes to medication to increase adherence include sustained release
drugs, more convenient doses, blister packs, and regimens tailored to
individuals.
• Monetary incentives to improve adherence are controversial.
• They were successful in anti-TB programs among homeless populations.
http://www.ijmyco.org/temp/IntJMycobacteriol63222-
2105754_055057.pdf

54. The way ahead
Meaningful engagement of stakeholders

55. https://www.who.int/lep/resources/9789290226192/en/

56. Strengthen government ownership, coordination
and partnership
• Ensuring political commitment and adequate resources for leprosy programs.
• Contributing to universal health coverage with a special focus on children,
women and underserved populations including migrants and displaced people.
• Promoting partnerships with state and non-state actors and promote
intersectoral collaboration and partnerships at the international level and
within countries.
• Facilitating and conducting basic and operational research in all aspects of
leprosy and maximize the evidence base to inform policies, strategies and
activities.
• Strengthening surveillance and health information systems for program
monitoring and evaluation (including geographical information systems)
https://www.who.int/lep/resources/9789290226192/en/

57. Stop leprosy and its complications
• Strengthening patient and community awareness on leprosy.
• Promoting early case detection through active case-finding (e.g. campaigns) in
areas of higher endemicity and contact management.
• Ensuring prompt start and adherence to treatment, including working towards
improved treatment regimens.
• Improving prevention and management of disabilities.
• Strengthening surveillance for antimicrobial resistance including laboratory
network.
• Promoting innovative approaches for training, referrals and sustaining
expertise in leprosy such as eHealth.
• Promoting interventions for the prevention of infection and disease.
https://www.who.int/lep/resources/9789290226192/en/

58. Stop discrimination and promote inclusion
• Promoting societal inclusion through addressing all forms of discrimination and stigma.
• Empowering persons affected by leprosy and strengthen their capacity to participate
actively in leprosy services.
• Involving communities in actions for improvement of leprosy services.
• Promoting coalition-building among persons affected by leprosy and encourage the
integration of these coalitions and or their members with other community-based
organizations.
• Promoting access to social and financial support services, e.g. to facilitate income
generation, for persons affected by leprosy and their families.
• Supporting community-based rehabilitation for people with leprosy-related disabilities.
• Working towards abolishing discriminatory laws and promote policies facilitating
inclusion of persons affected by leprosy.
https://www.who.int/lep/resources/9789290226192/en/

59. Reducing the disease and disability burden in
the community
• Early case detection
• Regular and complete treatment
• Early detection of impairment and disability
• Tackle the research gaps through novel collaborations, to
improve operational aspects
IntJMycobacteriol2017;6:222-8.

60. Social marketing & awareness
• Positive health messages should be designed
• Innovative use of media to appeal to and reach target groups to motivate
leprosy patients to seek early treatment and the community to accept
leprosy patients
• Treatment services should focus on leprosy patients’ needs and satisfaction
• Enhancing training of health-care providers in communication and behavior
change skills
• Improving the patients’ access to quality care and friendly services
IntJMycobacteriol2017;6:222-8.

61. Tackling drug resistance
• Monitoring of drug resistance in leprosy is extremely important
• The understanding of drug resistance in M. leprae has led to the development
of many different assays for its detection
• The PCR/direct DNA sequencing assay is currently the choice of laboratories
around the world for detecting drug-resistant strains of M. leprae
• Other molecular assays, not requiring DNA sequencing, have been developed
and show promise for laboratories unable to perform DNA sequencing
• It is anticipated that these new assays may evolve into much needed low cost,
point-of-care diagnostic tools for monitoring drug resistance in leprosy
IntJMycobacteriol2017;6:222-8.

62. Interventions to increase adherence
• Adherence to MDT is essential to ensure adequate treatment and
potential elimination of leprosy
• Adherence can be improved by multiple initiatives that target the
views and actions of patients, health-care workers, and society
• Beneficial strategies include reminder letters, peer assistance,
monetary incentives, patient education, and increased attention from
health-care workers
IntJMycobacteriol2017;6:222-8.

63. Eliminating stigma
• The stigma of leprosy has a large impact on many people’s lives
• It affects their physical, psychological, social, and economic well-being
• Stigma has multiple causes; these should be addressed in partnership
with communities and persons affected
• Stigma reduction activities and socioeconomic rehabilitation are
urgently needed in addition to strategies to reduce the development
of further disabilities after release from treatment.
IntJMycobacteriol2017;6:222-8.

64. Multi-level stakeholder engagement
• Collaborations with multiple players in all neglected tropical diseases
• Incorporate new approaches in community engagement that would
enhance public health at the community level
• The leprosy world, including WHO, national governments, NGOs, the
research community, and industry, together with people affected by
leprosy, must respond to this situation
IntJMycobacteriol2017;6:222-8.