More Thoughts On Neglected Tropical Diseases

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The 'big three' infectious diseases in global health are the all too familiar HIV/AIDS, malaria and tuberculosis. Less well known are a series of other infections endemic across the world.

Caused by a motley variety of parasites, viruses and bacteria, these diseases represent a serious problem in low-and middle-income countries, causing deaths, long-term disability and disadvantage. They are diseases of poverty, mostly affecting the world's poorest nations and trapping their people in a round of economic stagnation, but they don't receive anything like the attention or funding given to work on the general three.

But What About This??

In the past five years or so, wider attention has started to fall on these other diseases, thanks largely to a campaign led predominantly by scientists and centred on a new name: 'neglected tropical diseases ', or NTDs.

Hotez's research is on vaccines for human hookworm infection and other parasitic worms. As with many NTDs, they're not lethal in themselves but infections can last for decades, impairing children's growth, development and physical fitness and causing severe anaemia during pregnancy. This leads to low birth weight and increased infant and maternal mortality.

In other cases, neglect is from richer nations, where diseases such as schistosomiasis and dracunculiasis are unfamiliar and infections such as cholera and leprosy are chapters from history rather than pressing medical problems.

It does not help that the available information about how many people are infected or dying from these diseases isn't always reliable. NTDs are more common in areas of extreme poverty or conflict-not situations that lend themselves to effective epidemiological monitoring.

Research into NTDs may have been neglected too. The Wellcome Trust has consistently funded research on tropical diseases and currently spends a significant part of its funding on global health research. The World Health Organization (WHO) established its Special Program for Research and Training in Tropical Diseases (TDR) in 1975.

Other major health challenges were competing for attention in the second half of the 20th century, however-including emerging infections and the increase in the incidence of cancer and cardiovascular disease. Meanwhile, the pharmaceutical industry cut programmes on parasitic infections, for example, because there was not a profitable market to invest in.

Effective drugs were already available for a handful of them but weren't being widely used frustratingly for those scientists who were researching NTDs. Even when drug companies began donating these drugs or supplying them at very low cost for use in lower-income countries, simple cost-effective programs to implement mass drug administration often struggled to find sustained funding.

Professor Alan Fenwick, Director of the Schistosomiasis Control Initiative (SCI) at Imperial College London, worked in Egypt for 15 years. In that time, the prevalence of schistosomiasis there fell from 20 per cent to under 5 per cent. He knew it was possible to reduce the weight of the disease until it was not enough a public health issue; his problem was in finding the support to implement this knowledge in other countries.

In 2002, he approached the Bill & Melinda Gates Foundation and suggested they buy and distribute praziquantel, an effective schistosomiasis drug treatment, in countries where the disease was endemic.

Fenwick was awarded $30m to work with African countries to introduce national programmes to control schistosomiasis. The first treatment began in Uganda in 2003 and after one year, the intensity of schistosome infection had fallen by 70 per cent. Disease control is an ongoing challenge, however :' If we stop treating,' he says,' I fear that within five years it'll come back again. '

The SCI has supported or is presently working in 12 African countries and is still expanding coverage. More than 100 million people have been addressed at least once. Moreover, it treated people for three parasitic worm infections at the same time, effectively tackling four NTDs with one integrated programme.

Programmes such as the SCI are successful not only for the drugs are donated or provided at low cost but also because the drugs are safe and effective and can be given orally in one dose every six or 12 months.

The drugs available for many other NTDs aren't so practical. There is a desperate need to discover new treatments. Wellcome Trust funding continues to contribute to each step of this process.

Professor Alan Fairlamb, Co-Director of the Wellcome Trust-funded Drug Discovery Unit at the University of Dundee, agrees that only a small number of current NTD drugs are truly fit for purpose :' Many compounds were developed with a different indication in mind, perhaps from cancer research or antifungal drug discovery programs. The target product profile for these original indications doesn't take into consideration the association with poverty and the rural setting where most NTD drugs are needed.

The Dundee Unit works on the best potential targets wherever they come from, making concepts viable for further development in animal models. Fairlamb says they're always looking for scientists with a promising target but who do not have either the know-how or the facility to do drug discovery. ' Our vision is to take excellent basic science and transform it into useful medical products,' he says.

Their most successful project to date is founded on an enzyme called N-myristoyltransferase (NMT). This was conceived as a target at Imperial College London by Professor Deborah Smith, now at the University of York. The enzyme has been found in several parasites: the Dundee Unit is working on the elaboration of a drug for human African trypanosomiasis (sleeping sickness) while Smith, also with funding from the Wellcome Trust, is leading on developing drugs and vaccines for leishmaniasis. NMT may even be a target for new malaria drugs.

Some NTDs have no effective drugs or vaccines. Dengue virus, for example, causes fluid to leak from blood vessels into surrounding tissues, leading to severe shock in some cases. The only available treatment is to replace the fluid in hospital. This puts a huge burden on health systems during outbreaks.

It's a point that applies to NTDs as a whole: each presents specific challenges, but they all require continuing research on the entire range from basic to applied and will need a variety of strategies to control, eliminate or even eradicate them.

Grouping these diseases together under a collective name does not necessarily help the research effort, but it has been successful in drawing more attention to the enormous problem they continue to present as well as the need for sustained, coordinated action. Hotez highlights some of the gains made since 2005, when the first paper to employ the term 'neglected tropical diseases' was published: they include major initiatives from the US Agency for International Development and the UK Department for International Development; a new Department of Control of Neglected Tropical Diseases at the WHO; and PLoS NTDs. These launched in 2007.

Ultimately, says Fenwick, it will not be possible to achieve any of the Millennium Development Goals without tackling NTDs. ' How can you break the poverty cycle? ' He demands. ' How can you achieve primary education for all if the kids are full of worms? If they have no energy so that even though they go to school they fall asleep? '

11/16/2014 05:22:04
harold
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