Neglected tropical diseases (diseases of poverty) Warwick Grant Department of Animal, Plant and Soil Sciences

What are neglected tropical diseases? These are primarily diseases of poverty They either do not occur at all in developed countries or are rare and of minor importance But they affect tens to hundreds of millions in developing countries, especially in sub-Saharan Africa where the poorest of the poor are concentrated

Parasitic diseases are very common more that two thirds of the world population carry one more more species of parasite the most common are gastrointestinal [soil transmitted] helminths... or gut worms in plain English roundworms such as Ascaris, hookworms and Trichuris and flat worms such as Schistosoma. they rarely kill outright but they cause great morbidity (morbidity vs. mortality... who knows the difference?)

What are the diseases? They are listed at: http://apps.who.int/tdr/svc/diseases This is the website of the branch of the World Health Organisation (WHO) that has special responsibility for these diseases... Tropical Disease Research or TDR There are other links to more Non-Governmental Organisations, or NGO’s: just Google “neglected tropical diseases”

Gut worms (STH) infect ~1.5 - 2 billion people Bethony et al., Lancet 2006

“perfect storm” for >400 million children Middle panel: 21 year old man infected with hookworms next to 10 year old boy. US South circa 1911 Right panel: Two brothers from US South circa 1911. Left17 year old; right 21 year old infected. Numbers below from landmark post hoc analysesby Hoyt Bleakely on impact of hookworms on US South 43%: lower income by people infected with hookworms 22%: Gap in economy in imporverished Southern US states relative to Northern US states attibuted to hookworms 50%: literacy gap South-North attibuted to hookworms 43% 22% 50%

Worms from children in a single Indian village. Couple from UK that dewormed children in a village in India

Soil transmitted (gut) worms Insidious impact on communities, especially on children Chronic anaemia, poor physical and cognitive development, poor nutrition (gut dysfunction), poor response to vaccination and higher susceptibility to secondary infections Higher rates of malaria and TB

River blindness, or onchocerciasis spread by blackflies... called river blindness because the flies must be near a river to breed symptoms are slow to develop but the infection is essentially incurable the symptoms are caused by the baby worms in the skin....

Tanzanian River Blindness Oncho animation Carter Center oncho promo Global Health News videos More information about APOC http://www.ploscollections.org/article/browse/issue/info%3Adoi%2F10.1371%2Fissue.pcol.v08.i11

Where?

The life cycle

http://apps.who.int/tdr/resources/animations/onchocerciasis-life-cycle.swf

Blindness estimates vary, but there are probably around 400,000 people who are blind or sight impaired as a result of infection there are possible 15 million total infections and an “at risk” population in the hundreds of millions no-one dies as a direct result of onchocerciasis but the infection may shorten life expectancy by 15+ years

Severe dermatitis & lymphatic damage

DALYS the WHO love their acronyms but this is a good one Daily Adjusted Life YearS this is a measure of how much quality of life is lost as well as quantity of life for most of the neglected diseases of poverty, the DALYS are the important measure

Lifelong infection, suffering and disability onchocerciasis causes: blindness in severe cases disfigurement of the skin... thickening, scarring, depigmentation intense itchiness, leading to scratching lesions and secondary infections disfiguring nodules where the adult worms live immunological impairment, and disfigurement of the axial and inguinal lymph glands shortening of life expectancy

Treatment & Prevention? Two methods have been used to try to control river blindness. Starting in 1975, the WHO coordinated the spraying of insecticides into the rivers where the blackflies breed. This was effective but VERY expensive. Starting in around 1990, the drug ivermectin has been used instead. This has revolutionised the prevention of river blindness.

Ivermectin This drug does not cure the infection, but can prevent the symptoms from developing (no blindness or skin disease) as long as you keep taking it. This drug now means that river blindness (and some other related diseases) has been controlled in many parts of Africa an acievement that led to the award of this years’ Nobel prize to the two men who discovered it. However, it is not a cure and the disease will likely return if drug treatment fails.

What does my lab do? Onchocerciasis is targeted for elimination by 2025 Elimination is 100% dependent on just one drug…. Ivermectin. If parasites evolve resistance to ivermectin, elimination will fail. So we are developing better tools to monitor ivermectin’s effectiveness.

Other diagnostics? It is also necessary to have very sensitive tools to find the very few parasites that are being transmitted as we approach elimination In other words, knowing when it is safe to stop treatment. So we are also working on better, cheaper, simpler diagnostic tools to detect those last few parasites.

How do we do that? In humans, for example, if you sequence enough of the genome (a person’s DNA) you get enough of a “genetic fingerprint” that you can work out where someone came from. In some circumstances, down to something like a radius of ~80 – 100 km, just using your DNA. We hope to do this for river blindness, so we can track very precisely where the parasites are being transmitted as we get closer to elimination…. Getting the very last worm will require good detective work.

Where does the money for research come from? The TDR (remember that is the branch of the World Health Organisation with special responsibility for these diseases) The TDR has a total budget of $70 million, for ALL of its activities Individual developed countries spend much, much more than this on diseases that cause a tiny fraction of the suffering

In Australia there is some funding (<$10M) for malaria research, largely because it is a “local” problem there is a tiny amount (<$1M) for research on one or two “worm” diseases, but only those that occur close to Australia (eg. in Papua, or in S.E. Asia where tourists go) there is nothing spent on oncho, or many other similarly serious diseases of poverty

The question? in philosophy, there is a school of thought that has been around for a long time called “utilitarianism” utilitarians are do-gooders who think we should try to do things that maximise the good in the society... the ethically right thing to do is the thing that brings most benefit to most people this usually means spending what resources are available on measures that help most people

What should we do? the Australian National Health and Medical Research Council has as one of their most important funding criteria that research must be focused on Australian health issues this all but rules out funding for the most important diseases in the world unless you can find an Australian angle… not a very utilitarian ethical stance most other developed countries are the same and the tiny budgets of our government international aid agencies rarely fund disease research: governments generally see aid as a tool for “international diplomacy” rather than a way to share our wealth with those who are most in need.

Want to know more? even though we officially never recommend Wiki, I suggest: http://en.wikipedia.org/wiki/Onchocerciasis or for a more serious view: http://www.cdc.gov/parasites/onchocerciasis/ and http://apps.who.int/tdr/svc/diseases/helminths or just Google “onchocerciasis” http://www.thiswormyworld.org/about/history for a more general look at information about worm parasite infections globally

Philanthropy websites http://www.thelifeyoucansave.com/ information about the poorest of the poor, and what you can do about it.... founded by the “utilitarian” Melbourne philosopher Peter Singer... read the book with the same title. And this organisation he helped to found https://www.givingwhatwecan.org http://www.givewell.org/ and a bunch of other “effective altruism” sites with similar messages about direct action we can take.