Contact centred strategies to reduce transmission of M. leprae

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1 Contact centred strategies to reduce transmission of M. leprae Jan Hendrik Richardus, MD, PhD Department of Public Health Erasmus MC, University Medical Center Rotterdam The Netherlands

2 Outline lecture 1. Leprosy new case detection and trends over time 2. Past and current leprosy control strategies 3. Introducing a new leprosy control strategy 4. Risk groups for leprosy 5. Interventions targeting contacts 6. Introducing the concept of contact management 7. A future triple-legged approach to leprosy control

3 Newly detected leprosy cases 2012

4 New case detection

5 Global leprosy control strategy Up to : Elimination of leprosy as public health problem (reduction of leprosy prevalence below 1:10,000 population) Active case detection through population surveys Free provision of multidrug therapy (MDT) to all patients Simplified and standardized treatment regimens Control usually through vertical (disease specific) programs Strong support for national governments by WHO and others

6 Global leprosy control strategy From 2006 to 2015: Further reduction of disease burden (reduction by 35% of new cases with grade 2 disability) (Passive) detection of all cases in a community Completion of prescribed treatment using MDT Integration into general health services Sustaining expertise and increase number of skilled leprosy staff Improving participation of leprosy affected persons and reduce stigma

7 Conclusion: Global leprosy control strategy Early detection and treatment with MDT has remained the key strategy in leprosy control over the past 30 years Global new case detection rates have remained stable, indicating ongoing transmission of M. leprae Our leprosy control strategy needs to be revisited and innovation is unavoidable to achieve lasting results

8 A new leprosy control strategy We cannot go back to the situation before 2000: Leprosy has become a rare disease in many countries Leprosy is now fully integrated into general health services Leprosy is not a priority disease (neglected tropical disease) Financial crisis causes limited funds, also for leprosy Expertise in leprosy is disappearing A new control strategy should achieve optimal results with limited activity and resources

9 A new leprosy control strategy Contacts are key to a future leprosy control strategy: Population-based approaches are no longer cost-effective Risk of exposure in the general community is very low The main risk of exposure is in contacts of new, untreated cases An increasing proportion of new cases will be from household contacts A new control strategy should aim at reducing transmission to exposed contacts of new cases

10 cases/10,000 Risk groups for leprosy Contacts of leprosy patients have a higher risk of leprosy Three levels: 1. Physical distance New case detection in contact groups general population household contacts neighbour contacts social contacts

11 cases/10,000 Risk groups for leprosy Contacts of leprosy patients have a higher risk of leprosy Three levels: 1. Physical distance New case detection in relatives 2. Genetic distance general population Blood related Not blood related

12 cases/10,000 Risk groups for leprosy Contacts of leprosy patients have a higher risk of leprosy Three levels: 1. Physical distance New case detection classification index case 2. Genetic distance Leprosy classification index patient 20 0 general population MB PB 2-5 lesions PB 1 lesion

13 Interventions at contact level Contact survey and treatment of newly found cases Chemoprophylaxis (e.g. single dose Rifampicin) Immunoprophylaxis (e.g. BCG vaccination of contacts) Early diagnosis of sub-clinical infections

14 Contact survey Contact tracing after finding new leprosy case Comparable to TB, Hepatitis B, meningitis Contact survey (after 4-6 weeks) and treatment of new cases among contacts A contact survey is an effective intervention in itself! Important part of early detection Close contacts are at increased risk Identifying close contacts Examination at home or clinic Opportunity for health education when receptive

15 Chemoprophylaxis Evidence: Chemoprophylaxis with Rifampicin Bangladesh, (COLEP study) Randomized Controlled Trial with >21,000 participants contacts of 1037 PB and MB patients Single dose rifampicin (SDR) Given after the second MDT dose of index patient (6 weeks) mg based on age and weight Overall reduction of leprosy 57% (overall NNT: 265) Result after 2 years, no further reduction after 4 and 6 years

16 Chemoprophylaxis Variable Placebo Rifampicin Protective effect p Blood related 18/ / % 0.49 Not blood related 49/ / % < Index patient MB 21/ / % 0.12 Index patient PB2-5 22/3133 9/ % Index patient PB1 24/ / % Household contact 13/912 6/924 54% 0.17 Neighbour 17/2770 8/ % 0.12 Social 32/5559 8/ %

17 Immunoprophylaxis Vaccine trials with BCG, often in combination with M. leprae or related mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, showed protective effect and that BCG vaccination alone gives the best results Meta-analysis shows that the protective effect of BCG vaccination is higher among contacts of leprosy patients than among the general population: 68% vs. 53%

18 Immunoprophylaxis Protective effect of infant BCG vaccination and SDR for leprosy: Intervention Leprosy No Leprosy Multivariate* Protective OR 95% CI effect None Rifampicin only % BCG only % Rifampicin and BCG % * Adjusted for age, sex, physical distance to and classification of index patient

19 Diagnosis of sub-clinical infections Diagnosis of leprosy is based on disease signs and symptoms Antibody response based tests (PGL-1) are only effective for detecting infection in MB patients, and do not predict the development of disease in subclinical cases accurately Currently specific T cell diagnostic tests are developed and examined on their validity and applicability in the field Results of such test or combination of tests could determine the choice of intervention given to the contact (e.g. MDT, chemoprophylaxis and/or immunoprophylaxis)

20 Modeling impact contact interventions Predicted effect of interventions targeted at household contacts on the new case detection rate in the population No infant BCG vaccination Present program (contact survey) Chemoprofylaxis (SDR) Early diagnosis and treatment Assumptions: Chemoprophylaxis: 0.5 protective effect among contacts developing leprosy BCG Vaccination: protective effect of 0.5 Early diagnosis of subclinical infections Probability of test of 0.7 to detect a sub-clinical case

21 Conclusions contact interventions Contact survey and treatment of newly found cases is an effective intervention to reduce the incidence of leprosy The infant BCG vaccination program has a substantial effect on the reduction of the leprosy incidence in the population SDR chemoprophylaxis for household contacts gives added reduction of the leprosy incidence in the population BCG immunoprophylaxis for household contacts is also likely to give added reduction to the leprosy incidence in the population Diagnosis of pre-clinical infection and treatment will have substantial impact on the leprosy incidence in the population

22 A new leprosy control strategy Contact management This strategy will help interrupt transmission of M. leprae in the community and reduce the incidence of leprosy!

23 Steps to be taken: Contact management Diagnose new leprosy cases and start on MDT Identify close contacts (house, family, others) Confirm acceptability to index case to perform contact survey Examine contacts (at home or at clinic) on leprosy Treat newly found leprosy cases among contacts Provide chemoprophylaxis and/or immunoprophylaxis to eligible contacts

24 Contact management Advantages: Feasible (it is not a complicated intervention) Cheap (it is not an expensive intervention) Cost-effective (small investment to reduce disease burden over time) Contacts are likely to accept intervention Drug resistance with single dose rifampicin negligible Useful in every endemic situation

25 To be considered: Contact management How far should contact level be extended? (still effect of intervention in neighbours and social contacts) How to deal with acceptability, which may differ per country? (privacy, especially among neighbours en social contacts) How to deal with close household members? (highest risk, lowest effect SDR: observation?; test for infection?; full treatment?)

26 A new leprosy control strategy A new three-legged (tripod) and triple focus leprosy control strategy for the future: 1. Case identification 2. Case management 3. Contact management

27 A new leprosy control strategy This strategy combines classical elements of leprosy control (diagnosis, MDT, and POD) with a third stabilizing leg of contact management This strategy includes innovative tools focusing on prevention through reducing transmission of M. leprae in the population This strategy can be implemented in various integrated health care settings

28 I gratefully acknowledge the dedicated work of the staff of the Rural Health Program of The Leprosy Mission Bangladesh, who have for many years pioneered the concepts of contact centred management

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