Interviews of September/October 2019
26 October 2019
Dr. Shripad A. Patil: Director, JALMA Institute for Leprosy (& other mycobacterial diseases), Agra, institute under ICMR. Institute over 50 years old.
* TB biggest health issue in India (among infectious diseases?)
* Joined JALMA in 1983
* Moved to NIMHANS, Bangalore in 1992 - served as professor and head of neuromicrobiology till 2018
* Obtained Masters in microbiology from Karnataka Univ. Dharwad
* PhD in microbacterial immunology from the Agra Univ.
* Worked as a visiting scientist at the Division of infectious diseases, Baylor College of medicine, Houston, and also at Case Western Reserve Univ., Cleveland, Ohio
* Worked extensively in the development of immunodiagnostics for chronic infectious diseases, especially TB, meningitis and neurocysticercosis
* Worked on immunology of autoimmune diseases of central and peripheral nervous system, including leprosy
* Present research interests - CNS infections, especially TB
* Authored over 75 peer-reviewed research publications in national and international scientific journals
* Several awards - National Award for e-governance from GoI in 2018 for targeted intervention to expand and strengthen TB control among tribal populations. Sir CV Raman Award for contribution to medical sciences, from IISc Bangalore in 2003
* When institute was established, incidence of leprosy in India was 10-20 per 1000!
* India still hosts 63% of world's leprosy population
* As per latest survey, incidence of leprosy is 6-7 per 1 lakh
* Dr. TVV: The moment I hear of leprosy, I am repulsed. Let me ask some questions to clear misconceptions. Does one contract leprosy by touching or sitting near a leprosy patient?
* Dr. Patil - It is a common misconception but has no scientific evidence backing it. Experiments with animal models too, to try to spread the disease through contact - it (spreading?) has not happened
* Some animals have reduced immunity (neurmice??) - their thymus has been removed from birth, so they are deficient in T-cell-mediated immunity, the main immunity. When those animals were brough in contact with infected animals, there has been no transmission.
Even when lerosy bacilli were added to their skin, their was no intake of those bacilli to lead to the disease. So no evidence that the disease can spread through contact
* Other myths?
* Leprosy has a big gradation - from a small patch to a serious form where there is breakage or destruction of cartilage, called the leonine phase. It can be a very frightening picture - from zero entity to 100% of the disease. Deformity caused by the disease is the main cause of stigma. Disease also causes skin lesions but those get less noticed and it is disfigurement that is widely noticed. Affected person may hide his deformed fingers to avoid being asked the reason
* Because of the stigma, government has come up with a policy aimed at bringing doen incidence of disfigurement to zero by whatever means - vaccine, treatment or reconstructive surgery
* Next question: Discolouration and sensation changes in skin. Why? Reason: The disease organism has a special affinity to nerves, especially those near skin. A type of cells called Schwann cells related to sensation from skin surface are affected and the infection goes on to affect and even destroy the sensory nerves. Patient may not feel on touching subject - if smoking a cigarette, he may not realize that his fingers are about to burn. If holding a hot vessel, may not feel the heat and therefore has the risk of adding to the damage to the skin. From inside too, bony structure beneath nerves gets impaired
* The disease is very unique. Patient may harbour millions of bacterial cells. Tests such as massilemia used to count the number of organisms in the blood, or a from a gram of tissue ear lobe. Dr. TVV: Why ear lobe? Answer: Ear lobe is one of the cooler parts of the body and leprosy bacteria have a special liking/comfort for cooler parts, so more occurrence likely in cooler parts of idea. Surprising thing is that the patient may have no signs of infection despite the high count of the infectious organism - appear normal, no physical or physiological symptoms - no fever etc. So what must be happening? Perhaps the organism is in the mood of "let us stay as it is now, you (host) stay (seemingly unaffected?), I also stay" like in case of certain other parasites. Even if bacteria does not come out otherwise, nasal secretions turn out to be rich in the bacteria. Scanty in early stages but plenty in severe form of the disease. Hypothesis: Disease spreads through upper respiratory tract. Implication: It is very likely (though unconfirmed) that sneezing could spread the disease.
* TVV: We think leprosy occurs only in poor people? Answer: That belief cannot be ruled out totally. The disease does occur lot more commonly among poor people and there could be several reasons - poor nutrition, poor hygiene, lack of understanding about the disease, so it can be called a poor man's disease.
* With more people having moved above poverty line, prevalence of disease has come down somewhat, but there are several factors behind this. Better hygiene as people become less poor, extra effort from health care workers and better understanding of the treatment, leading to streamlining of health care for this disease. Of course, not everyone is doing their duty to their full extent but at least to a fairly good extent! This has led to some degree of improvement in case detection, proper treatment, educating people about hygiene.
* Third factor - additional efforts from government. In JALMA, patients are given travel passes so that they don't have to be worried about travel expenses for coming to and returning after treatment sessions. If the patient has to be admitted, they/family would be concerned about losing wages. Wages may be around say 500 Rs./day. The institute, through government funding, compensates the patients for the wages lost during the period of admission. This encourages patients to undergo treatment.
* To address the problem of stigma-invoking disfigurement, if patient has to undergo reconstructive surgery and stay at the institute's hospital for 10 days, an amount of Rs.7000 is given, in addition to the compensation for lost wages! So the problem of "economic impairment" is taken care of so that patients feel comfortable about coming to the institute and staying there to complete the treatment
* Dr. Patil believes that the stigma around the disease has come down. More (former) patients now tell that they have/had the disease
* TVV: Can leprosy be detected through blood tests just like most other bacterial infections whose telltale signs are often found in blood tests? Dr. Patil says that this is a question that he too had as a student when he entered this field. When pathogens are present in large numbers, they secrete chemicals or yoke an immune response and they may lead to formation of complexes and so on. So if millions of organisms are present, it shiould be possible to find "the criteria for diagnosis", i.e. presence of antigens. But after doing some assays, like antigen-capture assays, found that there was no evidence of antigens. So hypothesized that there may be a high antibody response and the antigens may be interacting with the antibodies to form complexes which cannot be detected. Parallely, looked at other tests like PAGE (poly acclomite?? gel electrophoresis). SDS (sodium dodecyl sulphate) PAGE which can break down protein complexes into individual polypeptides. Performed small experiments like taking immune complex from serum, putting it into tube and adding SDS, shaking it before putting it into incubator at 37 degrees centigrade, and then looking for the presence of the antigen. Then by performing one of the simple tests, gel diffusion test, against hyperimmune sera from rabbit, was surprised to find a clear band (meaning the antigen was detected?). Was very surprised that this simple test could detect the antigen, submitted the findings to an international journal that immediately accepted it for publication and the study was widely discussed.
* TVV: Was this the 1st test that could detect the antigen? Answer: There was a published study (in an international journal) even earlier that showed that leprosy antigen could be detected but it involved a very cumbersome process and interpretation of the test process's results was not very clear. But Dr. Patil's method was a simple one and one could easily see this is the antigen, this is the antibody and this is the reaction. And the process's simplicity allowed for 64 samples or more to be tested in a slide. Leave the sample in the evening and by morning everything is ready to be read and result could be interpreted as positive or negative. Says he was very elated, a eureka moment according to TVV
* TVV: There is a presumption that patients with leprosy don't have normal mental functions. If it is true, are there tests that can be performed on brain fluid?
Answer: After reading literature about reduced IQ in leprosy patients, team performed tests on cerebrospinal fluids from patients. Highly sensitive and basic mononucleotide tests, (yet) was surprised to find that all 3 types of antigens - the highly specific one, to a cross-domain (??) but highly reactive variant.
* TVV: When India became independent, China and Japan too had a high incidence of leprosy. But when we look at the graph since then, we find that those countries have eradicated the disease. Why does India still have prevalence of the disease - it has decreased sharply since the time independence but remained at the same level during the past 1 decade. There are even claims by some that leprosy is on the rise.
* Dr. Patil: The disease is chronic and treatment goes for a long period. WHO criteria - 6 months of treatment for early leprosy, 1 year for late leprosy. If patients complete the treatment for this period, they are considered cured. But we have observed that this is not exactly correct. Patients, even after completing year of treatment, come back with "viable" bacilli - so treatment must go continue since viable bacilli are gone. China had controlled this disease even before rifampicin came into picture. On discussing this with delegates from China in international conferences, we were told that China was using the only drug for leprosy available back then, DDS (diamino dipheny sulphur). It came as a small 100mg white tablets and patient had to take it almost lifelong. But this drug has a major side-effect, loss of appetite and loss of taste for food. So some individuals would discontinue the medication, leading to disease prevalence not going. But since China has had a communist rule, people cannot afford to violate government's guidelines. So patients there did not discontinue the medication, therefore prevalence there came down drastically from 20-50 per 1000 to a very small number with just DDS. So if people follow medication religiously, the disease can be eradicated. TVV: "Should not discontinue drug just because of hearsay about some drug not being good/effective"
* TVV: What about vaccine for leprosy? It is a terrible disease - it may not take away life, but it takes away living.
Answer: You put it very rightly ("does not take away life, but takes away the living"). 2-3 decades ago, incidence was 15-20 per 1000, now it is 6 per lakh. Field surveys using house-to-house screening done in places around JALMA revealed that the disease still occurs. Lesson - should not rely on just patients coming for treatment to estimate the prevalence but should do a thorough screening at a rural area. Highlights one interesting survey case - a rural area near Kanpur that is known to harbour many diseases. Water samples shows sequence/signal indicative of leprosy. To further surprise, this finding was confirmed by other labs too. We now need to study the village population to find whether there is endemicity of this disease and why it has come up.
(On vaccine, on being asked again by TVV) Vaccine was in talk when the disease was very common, now due to much lower incidence and people even believing that the disease is almost gone, focus on vaccine was lost. Now with recent surveys showing prevalence is no longer decreasing steadily but is going up and down, we are giving a rethought about the vaccine. Vaccines for leprosy have been developed (synthesized??) by Indian C Research Centre, Bombay National Institute of Immunology, Delhi and had been tried but had not been put to use thereafter. Since those readymade vaccines had been approved, the MW vaccine, now renamed as MIB (Mycobacterium indicus pranii, named after the discoverer of the organism?) now the leprosy eradication programme has started clinical trials of the MIP vaccine in a few states - Gujarat, Chattisgarh, Bihar. To be monitored by state-level and district-level leprosy officers. 5000 people have been administered the vaccine so far as a part of these trials in Gujarat - we now need to monitor the response in these patients and the incidence among them. The study will need to cover the other states - if the vaccine works out, then there is an end in sight for the disease and it will then be completely eradicated.
