MIP vaccination of contacts of all leprosy patients and their contacts in Haryana and Delhi — An implementation research study in the post-elimination era

**Primary Objective:**To assess the extent of variation in new case detection after implementation of MIP among contacts of leprosy cases and its effect on leprosy patients.

Secondary objectives:1.To conduct a baseline enumeration survey to collect data on leprosy among contacts of leprosy cases.

2.To assess the baseline social acceptance and operational feasibility of the intervention.

3.To assess the difference in critical program parameters — G2D among new cases and new child cases in areas where MIP has been used as a targeted intervention for contacts against that wherein the MIP is not yet implemented.

4.To assess and document the pattern of reactions / neuritis if any, in patients vaccinated with MIP

5.  Cost benefit analysis of the intervention.

6. To assess the impact of community education intervention on acceptance of the intervention.

7. To recommend a model for implementation of intervention which can be scaled up in the national program.

2.     Methodology:a. Study design: Population based non-randomized, implementation study

b. Study sites: Department of Dermatology, Amrita Institute of Medical sciences and Research Centre, Faridabad, Haryana.

Leprosy clinics in selected districts (AIIMS Delhi, UCMS, NDMC and other hospitals and dispensaries where leprosy patients are getting treated for leprosy).

c.  Methods (PICO):

§  Population*: Leprosy patients and their contacts in Faridabad and 3 districts of Delhi*

§  Index patient: Will be defined as per WHO criteria (World Health Organization. (2023). Leprosy. https://www.who.int/news-room/fact-sheets/detail/leprosy). We will recruit newly diagnosed patients with leprosy, those who are already taking treatment and those who have completed treatment in the previous 1 year.

§  Contacts: Will be defined as individuals who have had prolonged regular or interrupted contact with an index case during the last year. The minimum period of contact is 3 months (cumulative) and 20 hours per week. Contact categories are based on physical proximity to the index case (NLEP 2019).

o   Family contacts: All immediate family members, excluding those who have been away for work or education during the last year.

o   Household contacts: People living in the same house as the index case.

o   Neighbour contacts: People living in 3 houses on either side and 3 houses across the street from the index case. For multi-storeyed houses, contacts include people from the same floor.

o   Social contacts: People with whom the index case has been in contact for more than 20 hours per week for a cumulative period of 3 months or more.

·     Intervention:§  MIP vaccine at 0 months and 6 months. In MB index patients, MIP will also be given at 12 months. .

§  Surveys, interviews and    focus group discussions with patients, contacts and healthcare providers about feasibility and acceptance of MIP vaccine.

·     Comparison: NLEP data as of March 31, 2023, for same district for ANCDR, new cases with G2D, and new child cases.

·     Outcome:§  Reduction in ANCDR in Faridabad and 3 districts of Delhi, compared to the baseline data (NLEP, March 31, 2023)

§  Feasibility of administering and social acceptance of MIP vaccine in leprosy patients and their contacts.

d.  Sample size:·     Patients: 600

·     Contacts: ∽ 12,000 contacts of leprosy patients

·     Justification for sample size:§  Number of patients: The study will be conducted in Faridabad and Delhi (3 districts with high burden of leprosy patients — Shahdara, New Delhi, and South Delhi). Based on NLEP data (Faridabad, 31.03.23; Delhi, 31.03.22) the total number of leprosy cases is 657 (Faridabad: 80; Shahdara: 205; South Delhi: 257, New Delhi: 115). However, we expect 10% of patients being migratory or residing outside the study area, the number of leprosy cases we expect to include:

o    657 cases × 90%=591.3 (rounded to 600 cases)

§  Number of contacts: Based on literature, it is estimated that each leprosy case has approximately 20 contacts (Muniyandi M et al., Indian J Med Res, 2021). Therefore, for 600 leprosy cases, the total estimated number of contacts to be included in the study will be:

o 600 cases×20 contacts per case=12,000 contacts

Implementation Strategy: Detailed implementation work flow attached as Annexure 1 The project is a population-based, non-randomized intervention aimed at assessing the impact of implementing MIP vaccination among leprosy patients and their contacts in Faridabad and 3 districts (with high burden of leprosy patients) of Delhi. The study targets 600 index patients with leprosy and their (∽12,000) contacts.

Pre-study Training:

Before the study begins, workshops at district hospitals will be conducted to train healthcare workers (HCWs), medical officers (MOs), and other staff involved in care of leprosy patients in the program These workshops will focus on:

·      Identifying leprosy cases, with help of program staff

·      Screening for contacts based on the predefined contact definitions

·      Conducting awareness activities for patients and their contacts

·      Proper administration of the MIP vaccine and follow-up protocols

Advocacy, Communication, and Social Mobilization Activities (ACSM):·      Contact screening: During the contact screening phase, awareness campaigns will educate the community about leprosy symptoms, the importance of early detection, and the role of contacts in transmission. Pamphlets, posters, and community sessions will be used to encourage participation and reduce stigma.

·      Vaccination phase: Focus will shift to sensitizing contacts of benefits and side effects of MIP vaccination, explaining how it prevents leprosy in contacts and reduces transmission. Outreach through meetings and informational materials will clarify the vaccination process, side effects, and follow-up.

Index Case Identification: Newly diagnosed patients with leprosy, those who are already taking treatment and those who have completed treatment in the previous 1 year will be identified in collaboration with State Leprosy Officers (SLO), District Leprosy Officers (DLO), and Medical Officers (MO) in Faridabad and 3 districts of Delhi (Shahdara, New Delhi, and South Delhi).

Contact Tracing and Screening:·      Awareness campaign in the area of index patient will be conducted to educate community about symptoms and features of leprosy, the importance of early detection, and the role of contacts in transmission with help of pamphlets, posters, and community sessions. This will encourage participation and reduce stigma.

·      Health Care Workers (HCWs), under supervision of a designated Doctor (Project scientist), will enumerate and identify contacts (according to the definition) of the index patients.

·      HCWs will visit the households and immediate neighbourhood of the index cases (without revealing the identity of the index patient, if required) to screen contacts for leprosy. Suspected cases identified during these screenings will be evaluated by

designated medical officer for confirmation. If confirmed to have leprosy will be referred to nearby medical facilities for appropriate treatment.

·      During the contact screening phase, in addition to identifying contacts, healthcare workers will assess the acceptance using surveys and interview of MIP vaccination among contacts. Educational materials will be distributed to inform contacts about the benefits of the vaccine, and any concerns or hesitations will be addressed during the screening process. This will ensure that contacts are well informed and more likely to accept the vaccination when offered.

Inclusion criteria:1. Index patient of leprosy: Newly diagnosed patients with leprosy (both paucibacillary, PB, and multibacillary, MB), those who are already taking treatment and those who have completed treatment in the previous 1 year.

2. Contacts of index patient of leprosy**:**

§  Definitions of contact: Someone who has had prolonged regular or interrupted contact with an index case during the last one year. The minimum time period of contact will be 3 months (cumulative) and 20 hrs wk.

§  Contact categories: This is based on physical proximity to the index case. The categories are family contacts, household contacts, neighbor contacts and social contacts.

1. Family contacts: Comprise of all family members. However, if a family member has been away due to reasons eg work or education during the last 1 year, then he will not be included among contacts.

2. Household contacts: People living in the same house as the index case.

3. Neighbour contacts: All people living in 3 houses on either side and 3 houses across street from the index case. In multi-storeyed houses, same floors of the house will be considered among contacts.

4.Social contacts: All people with whom the index case is in contact for > 20 hrs per week for a cumulative of 3 months or more.

Exclusion criteria:1. Infants < 1 year age and geriatric people >65 years of age.

2.     Contacts having clinically active signs of leprosy. They will be counselled and referred to a medical facility for treatment

3.  Pregnant women, and subjects who are HIV positive

4. Subjects with CNS-TB, any serious ailment and malignancy

5. Patients or contacts not willing to participate/provide informed consent (however, at least three attempts would be made to convince the contact to participate before exclusion).

6. Refusal of disclosure by index case. Though we would counsel him, and can even vaccinate contacts without disclosing the patient’s identity.

Remark*: Tuberculosis, Co-existent conditions of diabetes and any immune-compromised state (if evidence available readily) including malnutrition are not being considered for exclusion since the vaccine is a killed vaccine and as per data available there is no indication of these conditions being a contraindication for the vaccine. Furthermore the vaccine has found utility in TB.*

Vaccination Protocol:·    Vaccine administration: MIP vaccine (0.5×10⁹ heat-killed bacilli) will be administered intradermally at the point of insertion of deltoid on arms with:

§  1st dose: Being 2 separate injections of 0.5 × 10⁹ each on same day, with each arm receiving one injection

§  2nd (and 3rd dose as in some MB index patients) dose: 6 (and 12) months later, single injection, on 1 arm.

·

Vaccine schedule:

·       Contacts: Contacts will receive MIP vaccine as follows:

§  1st dose: On the day they join study

§  2nd dose: 6 months later, single

Feasibility and social acceptance: Feasibility and social acceptance will be assessed using surveys, interviews and focus group discussions with patients, contacts and healthcare providers

Follow-up: HCWs will conduct follow-ups every 6 months for up to 3 years after vaccination to monitor outcome indicators and report any adverse events. This approach ensures comprehensive coverage and consistent monitoring of the vaccine’s impact.

Data Collection and Analysis: Data on vaccine administration, follow-up outcomes, and adverse events will be systematically collected. Statistical analysis will compare pre- and post- intervention incidence rates of leprosy among contacts and evaluate the intervention’s cost- effectiveness.

Procurement, storage and transportation of Vaccines:·       Procurement: Vaccines will be procured based on the anticipated needs of the study, ensuring sufficient supply for both the initial and booster doses. Initial procurement will account for all participants—covering both contacts and leprosy cases (PB and MB)—with the first dose to be administered within the first six months of the study. An additional procurement will be planned to cater to the booster doses; for contacts and PB cases at 6 months, and for MB cases at 6 and 12 months. This calculation will include a buffer stock of 20% above the estimated need to account for any potential wastage and to ensure availability in case of increased demand or logistical delays.

·       **Storage:**Vaccines will be stored at Amrita Hospital in specially designated vaccine storage refrigerators. These refrigerators are designed to maintain optimal conditions essential for preserving vaccine efficacy and are compliant with the standards required for medical storage

·       Transportation: During vaccination drives, vaccines will be transported from storage to various vaccination sites using insulated vaccine carriers to maintain the cold chain as per the requirements mentioned by the manufacturer.

Indicators to measure the impact of the effects of MIP vaccination:1. Reduction in ANCDR vis a vis historical ANCDR of same district in 2023,

2. Reduction in new cases with Grade II disability as compared new cases with grade II disability in  same district in 2023.

3. Reduction in detection of new child cases as compared new child cases in same district in 2023.

It may be noted herewith that as mentioned above, the real impact of the interventions can only be seen by reduction in the prevalence which will be available after a few years of implementation.

Design of Statistical Analysis·        Data will be used to compare the key program indicators (ANCDR, new cases with G2D, new child cases) 3 years after MIP vaccination of leprosy patients and their contacts with historical ANCDR of 2023 (without a contemporary control group) of the same district (as available from NLEP data). Descriptive statistics will summarize demographic and baseline characteristics. The impact of the vaccination will be assessed using incidence rate ratios, with 95% confidence intervals to determine statistical significance.

·       The operational feasibility and social acceptance will be analyzed through qualitative feedback from participants and health workers, coded and thematically analysed.

·       Cost-effectiveness will be evaluated by comparing the costs of vaccination implementation against the estimated healthcare savings from prevented leprosy cases.

·       Longitudinal follow-up data will be analysed using survival analysis techniques to assess the long-term efficacy of the vaccine and the need for booster doses. This comprehensive will ensure a robust evaluation of MIP vaccine’s potential to reduce leprosy transmission.

 9.     Expected outcome/ Deliverables aligned with research question:·      Reduction of ANCDR at 3-years of MIP vaccination of leprosy patients and their contacts  in Faridabad and the 3 districts of Delhi compared to historical ANCDR of 2023 of the same district (as available from NLEP data).

·      Reduction in other key program indicators (G2D among new cases and new child cases) in areas where MIP has been used as a targeted intervention for leprosy patients and their contacts.

·      Improvement in social acceptance over baseline acceptance as an impact of community awareness intervention.

·      MIP as a cost-effective intervention to control of leprosy.