(Lightly edited for readability)
Speakers: Priscilla Rupali, Winsley Rose, Satyabrata Routray, Kavita Singh, Aroma Warsi
00:02 Sponsor announcement: This episode is produced with support from Drugs for Neglected Diseases Initiative.
00:20 Aroma Warsi: In tropical countries, we have a number of unique diseases not found elsewhere in the world. And these diseases are often quite debilitating. Imagine thousands of worms in your intestines sucking away your nutrition, or trachoma, one of the most painful types of blindness in millions of people elephantitis, you've surely seen pictures of those swollen limbs, and know how stigmatizing and painful it can be. And there are many more. These conditions are not just bizarre and life threatening, but have a deeper story to tell. Neglected tropical diseases (NTDs) can often be debilitating, stigmatizing and can cause lifelong disabilities. And they affect more than a billion people globally. However, some are also preventable and treatable. Many organizations around the world are trying to look for solutions.
In this episode of the Nature India podcast, we speak to health professionals on the challenges and way forward for such diseases, especially in the context of India.
Priscilla Rupali, an infectious diseases expert at the Christian Medical College Vellore, specializing in dengue tells us why these diseases are still neglected.
01:41 Priscilla Rupali: Neglected tropical diseases are diseases which occur in the tropics, usually in the low middle income countries settings. And this is basically because of either uncontrolled vector proliferation, and the other one is basically lack of access to safe and clean drinking water. There are about 13 neglected tropical diseases, as they have been designated by the WHO, which cause a fair degree of morbidity and mortality globally.
02:10 Aroma Warsi: The WHO says NTDs affect more than a billion people globally, they are preventable and treatable. However, these diseases and their intricate interrelationships with poverty and ecological systems continue to cause devastating health, social and economic consequences. If you look at India, what are the key reasons for morbidity and mortality here?
02:36 Priscilla Rupali: I think it's dengue and rabies, which actually cause the greatest amount of mortality. Dengue has such a high incidence in the country. And periodically we have outbreaks. And if you look at the National vector borne disease control website, there are about 100,000 cases that have been recorded. But probably the incidence is much larger because of under reporting, as well as the disease itself, which in many cases, people may not really access health care facilities. So the disease is grossly underreported and there's a huge burden in the country. The second one is rabies. And rabies, as you know, actually has 100% mortality at the moment. You get the disease, you actually die from it pretty much, whether it is, you know, within a couple of days or whether it takes two weeks.
03:26 Aroma Warsi: Several conditions disproportionately affect children compared to adults, and children are often simultaneously infected with multiple parasitic NTDs. Despite this, there is limited information on current efforts to increase pediatric therapeutic options. Winsley Rose, a professor and pediatrician at the Christian Medical College Vellore, tells us about NTDs in children and the availability of treatment and vaccines for them.
03:58 Winsley Rose: The most commonly prevalent neglected disease, which also has probably the highest mortality, is dengue. This is more so among children and there are vaccines in development. The earlier vaccine called Dengvaxia, used in many countries did not work very well. And there is a recent vaccine by Takeda, which is actually undergoing trials and we hope they will be available for use in the market in probably a few years time.
04:28 Aroma Warsi: For children under five the most ubiquitous tropical infection is reportedly malaria, followed by the three major soil transmitted helment infections, and dengue.
04:41 Winsley Rose: The main reason why worms have been included in the neglected tropical diseases is that there are a set of like, you know, seven worms, which are all called geohelminths. So these soil transmitted helminths, if you take care of them, are potentially eradicatable. I mean, using certain measures such as masked deworming or building toilets. the other neglected disease, about 20,000 to 30,000 people die in India every year because of this, is rabies. And more than half of these deaths happen among children less than 15. It's got a very effective vaccine, we have a very good strategy to actually prevent somebody from developing rabies. But the gap is in the knowledge that somebody who's been bitten by an animal needs to go to the doctor and get vaccinated against rabies. I think, the key is awareness that if you get bitten by an animal, you need a rabies shot. Vaccinating dogs is another important feature, which is probably the most cost effective strategy in preventing rabies. But we are not there yet.
05:48 Aroma Warsi: Until recently, the Indian subcontinent accounted for 60% of the global burden of kala-azar. Over 40% of the global population requiring mass Drug Administration for Lymphatic Filariasis elimination is in Bangladesh, India and Nepal. Satyabrata Routray, Director for neglected tropical diseases at the global health nonprofit PATH, helps us understand NTDs in India.
06:16 Satyabrata Routray: We have the National Vector Borne Diseases Control Program, based out of the capital here, which is renamed recently as National Center for Vector Borne Disease Control. It includes visceral leishmaniasis, lymphatic filariasis, malaria, Japanese encephalitis, AES, chikungunya, zika. There's an elimination strategy for kala-azar or visceral leishmaniasis, which is prevalent is three or four states primarily U.p., Bihar, Jharkhand and West Bengal. Again for lymphatic filariasis we also have an elimination goal.
06:56 Aroma Warsi: Despite the challenges for the health infrastructure, India has made strides in its quest to beat NTDS. How has the process been so far?
07:07 Satyabrata Routray: As far as visceral leishmaniasis is concerned, we are very close to elimination. So elimination is measured in terms of reduced transmission. That primarily involves early diagnosis, early detection through active cases in the community and giving appropriate treatments for visceral leishmaniasis and PKDL, another variant. Indoor residual spray, which happens in the endemic high risk villages, where two rounds of insecticides are sprayed inside those houses and villages which are endemic to sand fly, which is the main vector for visceral leishmaniasis. For lymphatic filariasis, we have this mass drug administration, which happens, where everybody in the endemic districts across India, gets the three drugs now — albendazole, DEC (diethylcarbamazine citrate) and ivermectin.
08:11 Aroma Warsi: Right. The number of people affected by snakebites is also highest in India and Bangladesh. Winsley rose talks about snake anti-venom availability.
08:22 Winsley Rose: Poly venom, which is actually targeting the four common poisonous snakes in India, is quite effective in preventing deaths due to snake bite. After a snake bite, it's very important to actually get to a hospital as quickly as possible. Often supply is the problem. There are places where you don't get snake antivenom. And because of that, treatment desk gets delayed, and that leads on to mortality.
08:52 Aroma Warsi: We asked Priscilla Rupali about the research and development needed to control or eliminate NTDs.
08:59 Priscilla Rupali: The research has majorly focused on diseases which affect both the temperate and the tropical countries. So the rich and poor countries, so a lot of the research actually gets neglected. But if you look at the WHO website, you will actually find that they have implemented various cross cutting programs, and they hope to basically control the diseases by 2030. So they've actually enabled governments in the low middle income countries to be able to integrate programs for control of the various neglected tropical diseases into their existing program. So yes, there is a research imbalance but I think the world realizes that we are a global village now.
09:45 Aroma Warsi: Right. The task can be daunting. Winsley Rose tells us about the gap between research and development and availability of treatment.
09:55 Winsley Rose: See, we've had dengue epidemics going on now for the past 30-40 years. In fact, there has been a eight fold increase in the last 20 years. But have we developed one drug for dengue? We have not. Is there any particular drug that can actually deal with the effects of dengue? We do not have one. Do we have a vaccine which is available for anybody to use? We do not have one. Mainly because it actually affects the most populous regions of the world which also may not be the most affluent regions of the world.
10:30 Aroma Warsi: We asked Kavita Singh, Director, Drugs for Neglected Diseases Initiative, South Asia, about the efforts her organization is making in this area.
10:40 Kavita Singh: Short term, midterm and long term strategies. The short term would ideally mean making available a drug. One of the short term strategies is if there are 2-3 treatments available, can we choose the most ideal one with efficacy, the least side effects, is affordable and available? And that's how we did a lot of work on visceral leishmaniasis — compared three existing treatment modalities four kala-azar and identified that a single dose of liposomal amphotericin B is most ideally suited. And we see such excellent results when the program integrated the results of those clinical trials into the control strategy that went on towards elimination.
We have a medium term strategy in which we look at: can we change the formulation of the drug so that you need less dosage, maybe the formulation becomes more stable so it's easy to transport?
And the the long term strategy which we have, also the riskiest most, is to discover new drugs. We all know technologies have changed and we have much deeper biological ways of studying new drugs and the targets. So things we could not have done in the previos era are now possible, and COVID made us aware of many of these. We have been very successful in working with pharma partners and very recently we have worked a lot in sleeping sickness, which is of course not seen in India. We are doing drug development of a new molecule, an oral molecule, for visceral leishmaniasis in a phase two clinical trial in Bihar. When we develop drugs for such diseases, usually we do not get pharma companies and partners. So our efforts have been towards open science, partnering with research institutes and at times, also taking support of pharma companies in kind. So it's a very unique model of doing drug discovery.
12:33 Aroma Warsi: And what does it look like on the ground for elimination of these diseases, specifically in India?
12:38 Kavita Singh: India has about 12 or 13 of them, some couple of them we have eliminated. The National Center for Vector Borne Diseases Control Program includes some of these diseases which are caused by mosquitoes or sandfly, while the Ministry of Health has another program which is focused on leprosy. There's another program which is focused on soil transmitted helminthiasis. As a strategy roadmap for NTDs for India, maybe it could be an ask from the government. The National Center for Vector Borne Diseases has a very focused program on two major diseases of India that is kala-azar (visceral leishmaniasis — VL) and lymphatic filariasis (LF). Both these programs are on the elimination radar of the government, with VL being 2023 and LF being 2030. So there's a lot of implementation. There's a lot of international support. There's a lot of donation which the government programs are getting. What perhaps could have been done a little more is research and development. But when any disease goes through a different phase of coming under control or going under elimination, the requirement of the tools, whether it's a diagnostic tool or treatment tool, keeps changing. So that's perhaps in the wish list of people who work in the space.
13:56 Aroma Warsi: Neglected tropical diseases continue to pose significant health burdens on some of the most disadvantaged communities in developing countries. The ask is to have a unifying theme of innovation in diagnostics, treatment, and prevention of NTDs to create solutions that are effective, relevant, locally feasible, and sustainable. Neglected Diseases are the missing piece to improving global health.
14:29 Sponsor announcement: This episode was produced with support from Drugs for Neglected Diseases Initiative.
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