Tropical Parasitology

: 2015  |  Volume : 5  |  Issue : 1  |  Page : 71--74

An E-mail interview with Prof. John Horton


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Prof. John Horton is a medical practitioner with 30 years experience in drug development in industry. For the last 25 years he has worked exclusively in Developing World Medicine - malaria, helminths, leishmaniasis, diarrhoea, and TB, and was the moving force and 'father figure' of the tropical disease initiatives in GlaxoSmithKline. He was closely involved in the establishment of the Medicines for Malaria Venture and the Global Alliance for TB Drug Development, and was a member of GATB scientific advisory committee. As an industry member of the WHO/IFPMA working party, he was instrumental in elevating 'Neglected Diseases' into the public arena. At the same time, in GSK, he ensured involvement of the company in Public Private Partnerships with the WHO to develop drugs for tropical diseases and in developing concepts for access to modern pharmaceutical products in public health in developing countries. He was intimately involved in the establishment of the Helminth Control Initiatives that culminated in the WHO call for elimination, supervising the original studies and subsequent rollout of school based interventions. He was also deeply involved in the Global Programme to Eliminate Lymphatic Filariasis (GPELF), having initiated both the original studies that formed the basis of the programme, and the concepts behind the global programme, and continues scientific involvement in the area. Over the years he has acted as an advisor in a number of WHO programme initiatives (e.g. global helminth elimination).

Although now retired from GlaxoSmithKline, he continues to work part time as an advisor to private and public drug development organizations. He has been Chair of the Military Infectious Disease Research Programme review panel for parasitic diseases since 2004 and has served on several US government review panels since retiring. He has over 120 publications, and continues to support new public health initiatives and specifically drug development for neglected diseases. He was Editor in Chief of Experimental Parasitology between 2004 and 2012, and was a founding trustee of the Malaria Consortium, a UK NGO. He is an Honorary Fellow of the Royal Society of Tropical Medicine and Hygiene (and was Vice President during their Centenary celebrations), and an Honorary Member of the American Society of Tropical Medicine. He was the Honorary General Secretary of the British Society for Parasitology for 5 years and shortly after ICOPA XII, he joined the Board of Trustees of the Royal Society of Tropical Medicine and Hygiene. John is married with 5 children and lives in Hertfordshire in the UK.

Tropical Parasitology (TP): As an eminent expert member of various prestigious organizations, please share your views and research experiences in parasitology.

Prof. John Horton: Much of my career has been spent developing drugs and solutions for global health problems, focusing principally on neglected tropical diseases (NTDs) and more specifically on helminths and malaria. For nearly 25 years I worked in the pharmaceutical industry, but for the last 12, I have been advising academic, industrial and international groups on drug development and global health programs. One thing I have learned is that even with the increased focus on NTDs, finding new tools and solutions is far from easy. Despite increased funding and effort, we are still struggling to develop new drugs for some of the commonest parasitic diseases on the planet.

TP: Parasitic diseases are still a major cause of morbidity and mortality in developing countries. What is the scenario in the developed nations? Is it re-emerging or a forgotten disease?

Prof. John Horton: I agree that the major problem lies in the less developed countries, and as such is a significant brake on economic development of communities, especially rural ones and indeed whole countries and regions. In the past many developed countries were endemic for what are now thought of purely as problems of countries in the "tropics," and their disappearance has probably resulted from improvements in hygiene in its broadest sense, rather than from active efforts to eliminate them. Of course there are exceptions such as the hookworm eradication program in the USA (The Rockefeller Sanitation Program) during the early part of the last century. Today most developed countries are free from these problems, but that does not mean that they are never seen. Most are imported by immigrants (e.g., cysticercosis to the USA from Latin America, malaria in returning visitors to Africa and Asia), but the average doctor does not see them very often and hence knowledge is poor. In that sense, they are neglected. With increased immigration, awareness has increased, but still many infections go undiagnosed, ultimately ending up in specialist clinics as cases of interest. In the current situation, with good community services, it seems unlikely that many diseases could re-emerge, but changing climates might permit vectors, especially mosquitoes, to spread, perhaps establishing local transmission of diseases such as malaria and dengue.

TP: Why is drug research in parasitology lagging when compared to development of antiviral or antibacterial agents?

Prof. John Horton: Parasitic diseases when viewed globally are incredibly important, but as already noted they are not seen as a problem in developed countries. As a result, there has been little interest from most pharmaceutical companies in undertaking drug research and development. Furthermore, if products were developed, they are not seen as commercially viable, since those who need them most are least able to afford them. Interestingly, the reverse is true for academia, where huge amounts of research is undertaken for its intellectual and scientific benefits. Advances are being made with the increased awareness of the global community of the NTDs, together with a massive (compared to 20 years ago) increase in funding from the Bill and Melinda Gates Foundation and the Welcome Foundation often into public/private research partnerships such as the Medicines for Malaria Venture, The Global Alliance for Tuberculosis Drug Development and the Drugs for Neglected Diseases initiative. For the most part, developed country government funding is targeted on the implementation of control programs rather than on developing new tools. Thus, while progress is being made, it is still grossly underfunded compared to that for other infectious disease agents, which affect both developed and developing countries alike.

TP: Drug resistance in Plasmodium has been a global threat for decades. As you have contributed immensely for the development of newer drugs in malaria, can you shed light on the prospects of antimalarial drug research?

Prof. John Horton: Malaria drug research and development has moved very slowly despite it being the most heavily funded of all the NTDs both in academia and industry. Despite decades of research, the elucidation of the malaria parasites genomes, advances in proteomics and metabolomics, we still do not know an awful lot about the basic biology of malaria, and where are the weak points in its biology. As a result, the modern approach to drug development, target identification, is not really effective. For the most part, and this applies to both drug and vaccine development, we have almost totally failed to identify any weak spots in the parasite. Most of the drugs we use today target, in one way or another, the haem detoxification pathway. Thus, we have advanced little from the development of chloroquine over 50 years ago! To make matters worse, the malaria parasites seem to be able, in a short time, to find ways round whatever we throw at them. I always feel that they are far more intelligent than we are, although it is, in reality, only a function of the enormous number of parasites out there being exposed to drugs (many orders of magnitude greater than the numbers of humans exposed, and their high reproduction rate, which makes mutational change inevitable. Thus, probably we will always face an uphill struggle.

Is there a solution? Clearly we need more, and importantly, novel drugs. Since high throughput screening huge libraries of chemicals has turned up few scaffolds of interest that would permit structure diversification to increase potency, should we perhaps look elsewhere? It may be no accident that almost all our current antimalarials (e.g., quinine, 4-aminoquinolines, artemisinins) have their origins in plants. Since plants have evolved multiple strategies to deal with parasites, it is highly likely that some compounds could be useful as starting points, although identifying them, developing methods of synthesis of extremely complex molecules, and dealing with metabolic instability are all significant challenges. Clearly we have to use what we have more wisely, ensuring not only that combinations of drugs are always deployed, but they are used at fully effective doses, and ensuring that antivector measures (insecticide-treated bebnets, household spraying and larviciding) are also used.

TP: The context of the emergence of drug resistance has always been centered on malaria. What is the current status of this phenomenon in other antiparasitic agents? Has it been well studied or are we seeing only the tip of the iceberg?

Prof. John Horton: There is no doubt that we are now facing the prospect of resistance in a number of parasites other than malaria because of the massive increase in the use of antiparasitic drugs that are being used for the control and hopefully the elimination of a number of NTDs. While there is no firm data to suggest that there is a problem at present, there are hints that reducing sensitivity is occurring through the use of drugs that are not fully effective. For example, efficacy of mebendazole against hookworm in Pemba Island, Tanzania, has been falling as a result of years of treatment of school-age children, and there are repeated reports of poor efficacy of praziquantel against schistosomes. However, all these programs fail to treat a significant portion of the population, and so there are large numbers of wild-type parasites out there as well. This will tend to blunt the development of resistance. In the long term we do have to face the probability of resistance to some of our very limited armamentarium of drugs for NTDs, and therefore we need to learn from the experience of malaria and consider the use of combinations to further slow resistance, and also work hard to identify new drugs that can be used more effectively.

TP: How has been the involvement of the World Health Organization (WHO) in helping the developing countries to control parasitic diseases over the past few decades?

Prof. John Horton: Twenty years ago, the WHO was mostly concerned in providing advice and support for the use of drugs and other approaches to treating disease and at best reduce morbidity and mortality. More recently there has been a clear move toward disease control and even elimination or eradication. This has required a sea change in approach, with the deployment of huge amounts of drugs (almost one billion doses of albendazole annually for example) as well as vast quantities of insecticide-treated bed nets. The WHO has been key in this effort by providing guidance to individual countries on the methods to be used for mapping of disease, mass treatment, monitoring of the impact and eventually the documentation of the transmission elimination. Without the WHO providing the central policy-making role as well as coordination, many of the current programs would never have happened.

TP: How successful has been the achievement of goals by the global programs in elimination of parasitic diseases?

Prof. John Horton: There are 17 diseases that are listed by WHO as being neglected (there are many more, but one has to be realistic), and many of these are susceptible to intervention and control. Among these are lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and guinea worm disease. Great strides have been made against guinea worm, and it is likely that this will be completely eliminated in the next few years; we now only have a few tens of cases reported a year from 5 countries. There have been great advances in the move toward a global elimination of the others, with many countries already in the surveillance stage before being certified as disease eliminated. Within the WHO Road Map all the above are targeted for elimination by 2020. This was a highly ambitious target in the first place, and while many will reach this goal, the job may not be completed for at least another decade. That said, the benefits of these global programs is enormous and is freeing many millions from infection, disease and morbidity. The biggest problem is perhaps not in starting the effort, but bringing it to a satisfactory conclusion

TP: In your opinion, what newer perspectives can be addressed in global programs in elimination of parasitic diseases?

Prof. John Horton: As we move towards elimination, the problem lies not in how to deliver mass treatment to billions of people, but how to monitor and evaluate the progress towards elimination. When the programs started, we had the tools to map the distribution of infection and to mass treat, which was all that was needed in the early days. However, as you moves to the "end game," you need different tools. Even within apparently effectively treated areas, there often remains a few people who were consistently noncompliant, "hot spots" of infection are identified, or simply a country has been slow in activating mass treatment. These challenges require new responses in treatment, and better and more sensitive tools to identify the problems. Currently there is a huge effort ongoing to develop these tools, especially biomarkers and diagnostics, and to work out how best to use them.

Another approach, largely aimed at improving the use of very limited resources, is the integration of the various programs aiming for the simplest delivery paradigm. We are now moving toward the integration of bet net programs as being an efficient process for delivery of many interventions, as well as gaining benefit that they supply in the control of vectors of diseases other than malaria.

TP: What measures do you suggest to improve the quality of parasitology research in the developing countries to make it in par with the developed nations?

Prof. John Horton: It is an historical anomaly that much of the research into parasitic diseases is conducted in countries where the diseases do not occur or just imported curiosities. The major schools of tropical medicine are situated in developed countries, and for many years many of the researchers had never seen a case of the disease they were researching. That is changing, and it is recognized that both training of endemic country researchers and field work by those working in developed isolation is essential. Developing countries have the research material, and indeed some brilliant researchers, and this must be an advantage. Initially, the way forward is to establish "north-south" collaborations in specific areas of interest, whereas at the same time ensuring that the capacity (laboratory and clinical expertise, facilities etc.) are developed locally and most importantly are sustainable. There is no reason why high-quality research units could not be established, and there are actually many examples around the world where scientists from developed countries desire to visit and work. The key is collaboration - ensuring that the facilities are such that material does not have to be exported to be investigated, but can be researched in country.

TP: Please share few valuable suggestions for the budding scientists in the field of parasitology.

Prof. John Horton: Parasites are fascinating, whether they are human, animal or even plant parasites. Unlike almost any other area of science or medicine, there are discoveries to be made and new ideas to be developed. The number of scientists working in parasitology is tiny compared with those working on cardiovascular disease or cancer (and unfortunately less well funded).

Find your parasite: look for an area that really interests you so that you can be enthusiasticThink outside the box: See how you can import ideas from other areas that will benefit your area of researchExpand your horizons: Talk to others, especially those who are engaged in other areas of research: when I go to meetings, I rarely listen to lectures on my topics, but go to talks on fish parasites or ecologyRealize that what you are doing is unique: in all probability no-one has ever thought the way you doAbove all, enjoy what you are doing. If it is getting boring, then it is time to seek new pastures.