CHENNAI: Over a decade ago, in 2005, India almost declared the end of the leprosy elimination programme, assuming that the disease had been eradicated. But two years ago, experts realised they had made a great mistake. For, leprosy cases had started to relapse with increasing frequency. That was when a comprehensive Leprosy Elimination Programme, involving screening and early detection, was introduced. The challenge of relapse as well as family members and others in contact with the patient contracting the infection remained, since the multi-drug regimen failed to control it.
This was the problem Dr G P Talwar, founder director of the National Institute of Immunology, and his team sought the address. Their efforts yielded results, as they developed the first-ever exclusive vaccine for leprosy. Dr Talwar shares his journey, in an interview with Sunday Express. Excerpts:
The beginning
In 1970, when we decided to undertake the task, India had the world’s largest number of lepers. A multi-drug regimen was given for treatment. But the course was long-duration — two-three years for multibacillary (multi-lesion) leprosy. And relapse infection to family contacts was a challenge. The drugs acted on the causative bacteria, but in no way improved the immunity of the patients to resist infection. So, we began research to address that problem. Thereafter, arose the issue of developing a product with the potential of resolving that problem.
The challenge
Almost 99 per cent of humans resist Mycobacterium Leprae, (the bacteria that cause leprosy). The few who get it develop leprosy, of which there are different types, with varying immunity: Tuberculoid leprosy (TT), Borderline Tuberculoid leprosy (BT), Borderline Borderline leprosy (BB), Borderline Lepromatous leprosy (BL) and Lepromatous Leprosy (LL). Leprosy primarily affects the skin, mucous membranes, peripheral nervous system (nerve function), eyes and testes. Extensive investigations showed that the immunity deficit in LL Patients was their inability to recognise and respond to some key antigens of M Leprae. Their white blood cells that fight infection cultured with M Leprae extracts showed they don’t produce a response to a white blood cell (macrophages) that protects the body.
The patients also give a negative result to lepromine, a skin test to see what type of leprosy a person has. As M Leprae compulsorily requires a cell to grow, we developed a method for cultivation of the white blood cell in test tubes.
Development of vaccine
Normally, vaccines kill or weaken the bacteria or virus that causes the disease to induce immunity. In this case, M Leprae was not logical to employ, as the very defect in LL patients is their inability to respond to M Leprae. Hence a different approach was adopted.
We collected 16 cultivable mycobacteria, many known, but some uncharacterised atypical mycobacteria. We investigated the ability of each one of these to induce blast transformation of leukocytes (a type of white cell) from TT and LL patients. Five of these mycobacteria were shortlisted for their desirable properties — M Vaccae, M Phlei, M Gordonae, ICRC bacillus and an atypical Mycobacteria coded as Mycobacterium W.
After test tube and animal studies, the potential of lepromin-like preparations made from these mycobacteria and also lepromin from M Leprae were investigated for evoking delayed hypersensitivity skin response in patients of TT and LL patients.
We were looking for those strains of Mycobacteria which evoke response not only in TT patients, but also those which evoke positive lerpomin response in LL patients on whom M Leprae lepromin gives a consistently negative response.
On the basis of studies conducted in two centres in South India, (Dichpalli, Hyderabad and Polambakkam, Vellore) and three centres in North India (Maulana Azad Medical College Delhi, Institute of Medical Sciences, Varanasi and the AIIMS Delhi) in 39 TT and BT and 52 borderline lerpomatous leprosy (BL)-LL patients, we were able to single out an atypical mycobacteria fulfilling the requisites searched for. Now, it is named as Mycobacterium Indicus Pranii (MiP).
Efficacy of this vaccine
MiP, is a non-disease causing, cultivable mycobacteria. It evoked positive lepromin response not only in TT, BL patients but also in several BL and LL patients. We also carried out similar studies in Kolkata. It was observed that 20 out of 32 BL-LL cases persistently negative to lepromin were converted to lepromin positivity after a single injection of autoclaved MiP.
The conversion was also lasting over time. On reinvestigation of the converted cases after 6-7 months, these were found to remain positive to lepromin.
After conducting requisite toxicology studies and after obtaining permission
from the Ethics Committee and Drugs Controller General of India, Phase I, Phase II and Phase III studies were carried out in leprosy patients at the AlIMS, Safdurjung Hospital and Ram Manohar Lohia Hospital in Delhi.
One group of patients were given multi drugs regime (MDT) and the vaccine. The other group received MDT plus 10 times diluted tetanus Toxoid (TT). Combined MDT and vaccine resulted in faster bacterial clearance and shortened recovery time. It also cleared lesions. The lesions disappeared in almost all cases, restoring the patients to normal appearance. Another remarkable feature of the vaccine was, it cleared of M Leprae resident in peripheral nerves.
Field trials
Field trials were carried out in Kanpur Dehat in collaboration with JALMA Institute of Leprosy Agra, which showed the feasibility of using this vaccine in rural areas.
In fact, it converted lepromin negative healthy contacts of patients to lepromin positivity status, reducing their chances of becoming leprosy patients. On the basis of the results from these trails, the vaccine received the approval of the Drugs Controller General of India (DCGI) and also of USFDA. It is at present the only vaccine of its type in the world.
Licence
The vaccine also licensed to M/s Cadilla Pharma, Ahmedabad and is available to the public in the market.
Other efficacy of the vaccine
It even worked well in patients not responding to multi-drug therapy. To one group, the vaccine was given in addition to the drugs, the other continued to receive the drugs and placebo injections. The people received vaccine for treatment had a noticeable effect on decline of bacterial index, whereas the group given placebo injection had hardly any effect on the bacterial index.
In tuberculosis patients
The vaccine based on MiP also found utility in treatment of tuberculosis patients, who were otherwise difficult to treat. As many as 48 out of 49 patients given MiP in addition to drugs were cured (cure rate was 97.96 per cent), whereas only 21 out of 27 (77.77 percent) of those who received only drugs were cured. The relapse rate as observed 24 months later showed a significant difference. Only two out of 46 patients who received MiP in addition to drugs relapsed, whereas 11 out of 20 patients relapsed in the group treated with drugs alone.
Anogenital warts cure
AIIMS has treated ugly-looking warts on penis and anus of patients. Findings are reported in Journal of European Academy of Dermatology and Venereology.