projects 2008-2012

Occurrence of drug resistance among relapse cases poor responders and new cases of leprosy - amulti-centric study of ICMR task force on leprosy

Principal Investigator Dr. Vanaja P Shetty

Participating centers National Institute of Epidemiology (NIE) Chennai, Lepra India- Blue Peter Public Health and Research Center, Hyderabad and Father Muller Medical College, Department of Dermatology, Venereology and Leprosy, Mangalore

Collaborators with FMR Bombay Leprosy Project, Mumbai (Dr. VV. Pai) and Kusthrog Nivaran Samiti, Panvel (Mr. Uday Thakar)

Project team Dr. Shubhada Pandya, Ms. Swaran Kamble, Ms. Anju Dighe

Funder Indian Council of Medical Research (ICMR)

Duration July 2011 to June 2014

Budget Rs.63.69 Lakhs


This is a multi-centric study being coordinated by FMR at 4 sites in India.

Rifampicin is an important key component of the MDT regimen and resistance to rifampicin as evidenced through MFP test was recorded in an earlier study at this centre and elsewhere. This would create great difficulties for treatment of individual patients and its widespread dissemination would pose a serious threat to reaching the leprosy elimination target. To effectively meet the challenge of containing the disease, it is essential to keep a vigil on the secondary and primary drug resistance scenario at many vulnerable settings.

More over very little emphasis on follow up and surveillance makes it difficult to know the exact incidence of relapse or problem of recurrence of lesions following the release from multi-drug treatment in leprosy. It is easy to lose track because of the long incubation time between the release from treatment (RFT) and reappearance of clinical symptoms suggestive of relapse that prompts the patients to seek medical attention. In most MB cases it is more than 10 years indicate delay in identifying the relapse symptoms. We note that relapse is on increase in this metropolis city. Over 60 referral relapse cases were recorded during the year 2005 -2009.


General objective To study the occurrence of drug resistance in relapse cases poor responders and new cases of leprosy and to investigate the clinico-pathological features of these cases, using a prospective study design.

Specific objectives

  • To determine the extent and to describe the clinico-pathological features of post MDT relapse and recurrence of lesions in a cohort of leprosy patients who were released from treatment (RFT) between April 2005and March 2010, based on the records at the primary health centres (Cohort 1)
  • To determine the frequency of drug resistance in Cohort 1 using molecular and mouse foot pad methods
  • To describe the clinico-pathological features of new cases detected in the study area during the study period July 2011-June 2014 (Cohort 2)
  • To determine the frequency of primary drug resistance in Cohort2 using molecular and mouse foot pad methods
  • Probability of detection of relapses and drug resistance to be increased by yearly examination of Cohort 1 and 2 cases till end of June 2014.

Some notable findings

In Cohort 1,three periodic active tracing and examinationswere done over a period of 30 months,among 577 eligible RFT cases-a sizable number i.e. 92 (15.9%)patients were detected with ‘problem’ including 65 during the recruitment, 19 during 1st follow up and 8 during 2nd follow up. Majority had more than 1 problem of which neuritis topped the list (~60%) demanding medical attention.It was noted that active screening approach facilitated early detection and intervention of events that would have otherwise remained undetected and unattended.

Drug resistance/ Mutation noted in the DRDR region in cohort 1 and 2

In Cohort 1, 59 specimens collected from 59 patients, 56were PCR amplified. 28 PCRproducts were successfully sequenced for rpoB gene (Rifampicin) of which 3(3/28=10.7%) showed mutation. Of the 21PCR products sequenced for gyrA gene (Ofloxacin), 1 (1/21) showed mutation and of the 9 PCR products sequenced for the folP gene (Dapsone), no mutations were observed.

In Cohort-2 (New cases), out of the 87 specimens collected, 60 were PCR amplified. Among them, 27 PCR products were successfully sequenced for rpoB gene, wherein mutations were observed in 2 cases (2/27= 7.4%);26 PCR products were sequenced for gyrA gene of which 1 showed mutation (1/26) and for the folP gene, 17 samples were sequenced and no mutations were detected.Some of the mutations noted were synonymous and some non-synonymous.

Work is in progress to discern further.

Mouse foot pad (MFP) test: In Cohort 1, of the 29 samples tested only 2 showed growth in the MFP, and both tested sensitive to Dapsone (DDS) and Rifampicin (RFP).

In Cohort 2,6/17 samples tested showed growth,only 2 were tested for drugssensitivity,both tested sensitive to both the drugs.

Discordance noted between genotypic and phenotypic resistance

Forty seven referral relapse cases were received at FMR from in and around Mumbai, were also tested for drug resistance. All 47 cases were subjected to molecular testing and 20 among them were also tested using MFP.

Notably in the MFP assay resistance to both DDS and RFP were detected in 3 cases but mutations were not detected in the specific codons of all three genes by sequencing except in one case that showed mutation for gyrA gene. In one case resistance to only DDS was detected in MFP assay that also showed mutation in folP gene. All the remaining patients tested sensitive in either one or both methods.

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