Investing in neglected diseases
You may not realise this, but over 1.4 billion people have diseases known collectively as neglected tropical diseases (NTDs). That’s roughly one in five of the global population. The world is getting richer, meaning modern medicine is reaching out ever further – often to communities previously untouched by organised healthcare.
There are investment opportunities in addressing these new healthcare demands. Funding for research and treatment comes from governments and charities – but also from investors looking to profit. As billions of people around the world pull themselves out of poverty, they’re willing to spend more on healthcare. That’s a virtuous circle, as better health means more earning potential and then more income to spend.
Today, I’ll be interviewing Dr Anouk Gouvras, postdoctoral researcher on parasites and neglected tropical disease at the Natural History Museum. Together, we’ll look at exactly how this often-forgotten biotech market is set to change the world.
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AL: What are neglected tropical diseases?
AG: “Neglected tropical diseases” is a term given to a diverse group of 18 infectious diseases. These are highly prevalent in tropical and subtropical countries. They particularly thrive in poverty stricken areas, with low sanitation and clean water infrastructure. They also cause huge damage to public health and socio-economic development – and yet still receive little global attention. Together they infect over 1.4 billion people worldwide. The majority are caused by protozoan or parasitic worm infections. They are the diseases of neglected people of low income countries. However, they also affect the poor living in richer countries. For example, it is estimated that 1.2 million people are infected with at least one NTD in the US.
AL: What is being done about them?
AG: On 30 January 2012, charities, pharmaceutical companies, NGOs, government bodies and academics came together. They declared their commitment to the WHO [World Health Organisation] roadmap to control NTDs by 2020. This declaration, now known as the London Declaration on NTDs, was the first of its kind, with 13 pharmaceutical companies pledging to donate millions of dollars’ worth of drugs to NTD control programmes in endemic countries and charities, government departments and academic institutes also pledging to work together to help deliver the objectives of the WHO roadmap. Progress made towards these objectives is assessed each year. There’s an annual progress report, released on the Uniting to Combat NTDs website.
AL: You mentioned that most of these diseases are caused by parasites. Can you please explain exactly what you mean by this?
AG: A parasite is an organism that lives in (or on) a host organism, and takes nutrients from its host. It often causes damage to the host, which may or may not be fatal. Parasitism is more of a life strategy rather than a type of animal. And it is arguably one of the most successful life forms on Earth. Plants have parasites, mammals have parasites, fish have parasites, insects have parasites, even parasites can have parasites!
AL: Impressive, how are parasites found in nature?
AG: Parasites come in many different shapes and sizes; they can be tiny cellular organisms living inside host cells like blood cells or they can be big worms living in a host’s gut. Some animals have parasitic “stages” in their life cycle. For example, some mussel species live as parasites on fish when they are juveniles. Later, they becoming free-living adult mussels attached to rocks. Some insects lay their offspring on or in a host, which the offspring consume when the hatch. These are called parasitoids.
AL: Why have parasites been neglected?
AG: There are “famous” parasites and there are “neglected” parasites. For example, the organism that causes malaria is a famous parasite. It is a single-celled parasite, from the Plasmodium genus. The WHO and CDC [Centers for Disease Control and Prevention] estimated that there were over 214 million cases of malaria in 2015. These caused 438,000 deaths – most of which were children. This parasite can kill people rapidly, particularly children. After diarrhoea, pneumonia and difficult births, malaria is one of the leading causes of mortality in under-fives. Child mortality is a key indicator of development. Not only was child mortality a Millennium Development Goal (MDG 4), but there was a separate millennium development goal (MDG 6) called “Combating HIV/AIDS, malaria and other diseases”. Governments, NGOs, research institutes and private companies work hard to bring down global and national child mortality and malaria. In 2000, annual deaths due to malaria were estimated at 653,000 to 1.1 million a year; the global effort to combat malaria has led to a 48% decline in deaths.
AL: Can you tell us about some neglected parasites?
AG: Unlike malaria, schistosomiasis is a neglected parasitic disease. It’s caused by a complex parasitic blood fluke. It does not kill quickly, and the severity of the damage it can cause is only felt years after infection. This parasite is estimated to infect over 250 million people worldwide with over 90% of infection occurring in sub-Saharan Africa – particularly in the rural poor. Infants and children are especially prone to infection. The damage caused by schistosomes can lead to painful chronic cramps, anaemia, lethargy, damage to the urinary and intestinal tract, genital lesions and severe damage to internal organs – particularly the kidneys, bladder and liver.
AL: It seems that the parasite is as dangerous as the one that causes malaria. Why then the neglect?
AG: Measuring the mortality rate caused by schistosomiasis is not straightforward. This is because infections happen in childhood, and the damage builds up with time. The link between severe organ damage and cancer can be missed and is difficult to measure. Currently estimates of mortality rate due to schistosomiasis range from 20,000 to 200,000 per year. The estimated chronic “everyday” illness it causes has a huge impact on child development, quality of life, productivity and social mobility.
One tool we can use to assess the impact is disability-adjusted life years (DALYs). This metric combines years of life lost due to premature death and years of “healthy” life lost due to disability. When measured in this way, schistosomiasis is estimated to cause a whopping 1.7 million to 56 million DALYs! Yet unlike malaria, schistosomiasis was not explicitly part of the Millennium Development Goals.
AL: Is the recent “three disease drug” funded by the Wellcome Trust as big as it’s cracked up to be?
AG: The “three disease drug” discovery GNF6702, targets the waste disposal system of the protozoan parasites that cause three key diseases. These are African sleeping sickness (aka Human African trypanosomiasis), Chagas diseases and leishmaniasis. These three diseases affect 20 million people worldwide and lead to more than 50,000 deaths annually. Current drug treatments are not ideal, with long courses needed. This results in high costs, not to mention numerous side-effects. New therapies are needed. These must be more effective and better tolerated. This discovery is therefore very good news indeed!
AL: Can you share some insight into the development process that led to the creation of this drug?
AG: GNF6702 was identified by researchers testing a huge collection of over three million compounds to identify which ones would kill these protozoan parasites grown in lab cultures. Ones that killed the parasites in lab cultures were then tested on infected rodents without harming the hosts.
However, this compound still needs to be tested on humans – and it is still a long way from being ready. [Shilpi] Khare, and the study’s coauthors, called for more research. They also pointed out that a single drug for all three diseases may not necessarily be an advantage. This is because these parasites live in different niches in the body. Therefore, each disease may need different formulations and concentrations, in order to target a specific species of parasite.
AL: A South American study shows that the fertility rate can be positively affected by parasitic infestation. Are we taking a risk by trying to “cure” such “diseases”?
AG: Blackwell’s South American study looked at Tsimane women in Bolivia. The researchers investigated women infected with different parasitic worms. These were: Ascaris lumbricoides, aka the roundworm; and Necator americanus, the hookworm. The researchers looked at the number of pregnancies over time – ie, fecundity; and the age of first pregnancies. The authors found that women infected with Ascaris roundworms had their first pregnancy at a much younger age and had less time between pregnancies than uninfected women. But with hookworms the opposite was true. Women with hookworm infections had their first pregnancy at an older age and their pregnancies were more spaced out than uninfected women. They also had lower body mass index (BMI) and were more anaemic than uninfected women. One worm species appeared to increase the occurrence of pregnancy whereas the other appeared to hinder it and negatively affect the woman’s health.
AL: It was an interesting study. Can you explain the conclusions?
AG: The authors suggested that the increase in fecundity seen in Ascaris roundworm-infected women may be due to the parasites’ amazing ability of controlling the host’s immune system. Ascaris roundworms are known to dampen inflammatory responses of the immune system. This increases the parasites’ survival and reproductive success. The authors suggest that this roundworm control of the immune system suppresses the immune responses that would normally decrease fecundity – which is a reduction in the number of successful pregnancies.
You need to be cautious, when interpreting these results. The authors themselves state that there was no measurement of the participant’s immune system. This means they cannot prove that the effects were due to parasite-immune modulation. They also didn’t consider factors such as worm burden, which has a huge effect on the host. Nor did they look at other infections, which may decrease fecundity. It was certainly an interesting bit of research – but much more work is needed before scientists can confirm this is a real effect.
AL: What’s the importance of such studies?
AG: Such studies are crucial to understand the mechanisms and impact of parasitic worm modulation on the host. Some of these mechanisms can be used to develop new drug treatments for autoimmune disease. But parasitic worm infections are not benign “natural” cures to autoimmune diseases. They are linked to underdevelopment and sickness and can be very dangerous. In fact, hookworms are dangerous for pregnant women. In this study the authors noted the lower BMI and higher anaemia in those women infected with hookworms. With high worm burdens, these disease symptoms can be far more severe – and they can lead to poor birth outcomes. These problems include low infant birth weight, miscarriages and stillbirths – or an increased risk of maternal mortality. There is a significant impact of heavy parasitic worm loads on child development. That then hinders an individual’s opportunity to better their lot. And even worms that appear to be more “mild” than others can lead to complications – including fatal ones, such as obstructed colons.
Ultimately what is it we are trying to achieve? Are we trying to maintain the potential of high fecundity, for people living in poverty? Or is our aim to improve the health and quality of life of millions, if not billions, of people living in poverty-stricken conditions?
AL: Please explain your personal background, motivation.
AG: I have always been fascinated by the enormous capacity and diversity of life – so biology and zoology was a natural field of study for me to pursue. My initial interest was in conservation. At university, I attended a few lectures on parasites and I loved it. I am amazed at the ability of these parasites to hijack bodies and brains; manipulate immune systems or behaviour; to evolve incredible life cycles; and adapt to changing environments. Also parasites have such a huge impact on their hosts that parasite research is directly applicable to human and animal health. It is science research with direct and clear benefits to society. That greatly appeals to me.
AL: Can you tell me more about your day-to-day work?
AG: Currently I work as a postdoctoral researcher in the Parasites and Vectors division of the Natural History Museum in London. The NHM is a WHO Collaborating Centre on schistosomiasis. This is in recognition of its expertise in identifying the parasites that cause the disease, and the aquatic intermediate host snails responsible for its transmission. We help national schistosomiasis control and elimination programmes in affected countries. We do this by finding better diagnostics, and interventions to reduce the impact and prevalence of the disease. In addition, we support researchers from affected countries, through training and capacity building.
People are often surprised to hear that I research a neglected tropical disease at the NHM – but the museum has a long and prestigious reputation in biological research. Using and adding to the 80 million specimens already in our collections, we study, analyse and document life and evolution. That includes parasites.
Unbeknownst to most visitors the museum has state-of-the-art molecular and imaging laboratories – and over 300 researchers. In our group we use cutting-edge molecular approaches to research the parasites in our collections. We provide new insights into the biology and interactions of parasites and their hosts. Such information is vital for accurate disease mapping, monitoring and control. We also support external researchers and international collaborations. We do this by providing field-collected schistosome genetic material, from our rapidly expanding schistosome and snail collection called SCAN (the Schistosomiasis Collection at the NHM). This can be used to identify new targets for parasite or host control; and for monitoring risks to disease control programmes, such as the emergence of drug resistance.
Apart from research we are also very committed to engaging the public on parasites, their life cycles and the diseases they cause – particularly neglected tropical diseases. Through the museum’s excellent public engagement group, and through external events and online media, we love to show off our extensive parasite collection. We can show how current scientific research is helping combat the diseases they cause.
Please do send your thoughts, symptoms and samples to firstname.lastname@example.org.