As the Ebola epidemic continues to rage in west Africa, with more than 3,000 dead and infections doubling every few weeks, the first confirmed case in the US last week stepped up global fears over the rapid spread of the incurable virus.
But behind the gruesome headlines, the scale of the outbreak has been raising hopes that it could focus minds at the world's biggest pharmaceutical groups, boosting research on other devastating tropical diseases that have been neglected for years by the drugs makers.
There are already an estimated 12 million Americans suffering from life-threatening or debilitating infections such as Chagas disease, dengue fever or West Nile virus. "Ebola helps us realise we are a global planet: the health of one region affects the rest of us," says Julie Jacobson, senior programme officer for infectious diseases at the Bill and Melinda Gates Foundation. Mike Turner, head of infection and immunobiology at the Wellcome Trust, says that "almost certainly, Ebola will increase the visibility" of tropical diseases.
The worst Ebola outbreak in history has infected more than 6,500 people, mainly in Guinea, Liberia and Sierra Leone. The World Health Organisation (WHO) has declared the outbreak an international health emergency, warning that the deadly virus could infect up to 20,000 people by November. When last week a man was hospitalised with the disease in Dallas, Texas, it was the first case diagnosed outside Africa.
GlaxoSmithKline has started making 10,000 doses of its experimental Ebola vaccine – the most advanced product around – and could supply it to the WHO for an emergency vaccination programme early next year, assuming clinical trials go well. The vaccine has been rushed into tests on healthy human volunteers in the UK and US.
Other Ebola vaccines in development, from Johnson & Johnson's Crucell division and NewLink Genetics, are close to entering the laboratory. ZMapp, made by a San Diego-based company, is the most advanced of the experimental treatments and has cured some patients, including the British nurse Will Pooley, but stocks have now run out. ZMapp's development was supported by the US military's main biodefence research facility, amid fears that the virus could be turned into a biological weapon.
But until now Ebola, which had sporadic, smaller outbreaks in the past, was not a priority: it did not feature on the WHO's list of 17 neglected tropical diseases (NTDs) drawn up in 2012. Together those 17, which include tuberculosis, rabies, leprosy, river blindness, sleeping sickness and parasitic worm infections, affect more than 1.4 billion of the world's poorest people across Africa, Asia and Latin America.
The publication of the list in 2012 saw the first concerted effort to tackle those diseases, when 13 pharma companies teamed up with the WHO and the Gates foundation in a pledge known as the London declaration to control or eradicate 10 of the diseases by 2020. The End Neglected Tropical Diseases Act introduced in US Congress this year calls for the United States Agency of International Development to expand its focus on tropical diseases and step up coordinated international efforts.
Research funding for neglected tropical diseases rose 3% to $3.2bn in 2012 after years of decline, according to a survey funded by the Gates foundation. But pharmaceuticals firms contributed just $527m – a fraction of total spending on research and development of $130bn. Most of the money spent on tropical diseases – two-thirds of it – comes from governments.
A study published in the Lancet last year showed that of the 336 new drugs developed between 2000 and 2011, only four were for neglected diseases (three for malaria and one for diarrhoeal diseases), and of 150,000 trials registered in late 2011, only 1% tackled NTDs.
Ebola could change all that. Deutsche Bank analyst Mark Clark says: "Ebola could be the issue that sends the whole thing snowballing. You are going to get more industry engagement. The signs were already positive after the London Declaration on NTDs in 2012."
Jacobson reckons the 2020 goals are "ambitious on all fronts" but "each one is attainable", even though a funding gap of $1.5bn remains. "Unfortunately, it's always a good thing for a disease to make it to an industrialised country," she says. "A lot of tropical diseases have been invisible to the world."
A progress report from signatories of the London declaration earlier this year highlighted early successes: Colombia became the first country to verify the elimination of river blindness (followed by Ecuador); Nigeria, Niger and Ivory Coast were certified as free of Guinea worm; and Morocco has been declared clear of blinding trachoma.
Within the industry, GlaxoSmithKline, Britain's biggest drugmaker, and France's Sanofi are investing the most, each putting more than $100m a year into tropical disease research, according to Deutsche Bank. They are followed by Switzerland's Novartis, which plays a key role in the supply of antimalarial drugs in Africa, its Swiss rival Roche and Germany's Bayer. By contrast, most US pharmaceuticals firms regard tropical diseases as a philanthropic venture and restrict themselves to donating off-patent drugs such as anti-worm tablets, Clark says.
He added: "To the extent that these diseases are starting to appear in the US, this will put the issue much more firmly on [US companies'] radar."
Chikungunya has recently joined a growing list of mostly hidden diseases that have taken up residence in the US (mainly on the Gulf coast), according to a study in the Lancet published last month. There is no cure for the mosquito-borne virus, which causes fever and severe joint pain. Once it is established, says Turner, it is extremely difficult to eradicate.
Manhattan is now regularly sprayed from the air with pesticide to counter another mosquito-borne disease, West Nile virus, which is potentially fatal. Chagas, which can cause heart damage and can be cured in its early stages, affects an estimated 300,000 Americans. Two parasitic worm infections found widely in the US affect the brain: cysticercosis, which has emerged as a significant cause of epilepsy, and toxocariasis.
Peter Hotez of the Baylor College of Medicine in Houston, Texas, refers to these illnesses as the "diseases of extreme poverty and of conflict or post-conflict settings". Their rapid spread can be partly attributed to lack of sanitation, health infrastructure and clean drinking water.
"While there won't be an Ebola epidemic in the US, I am very concerned about the neglected tropical diseases now affecting the US Gulf coast," Hotez says. "They're widespread, but because they occur predominantly among Americans who live in extreme poverty, very few people know about them."
Andrew Hollingsworth, policy manager of the Association of the British Pharmaceutical Industry, says: "Unfortunately, the standard economic model for drug development, in which industry takes all of the risk in R&D and gets a return on investment from successful products, does not work for diseases that primarily impact low-income countries and developing healthcare systems."
As a result, collaborations with academia and government now account for the bulk (86%) of research efforts. Many companies have formed partnerships with the Gates foundation, which has supported infectious disease research worth tens of billions of dollars and recently pledged $50m to fight Ebola, its largest emergency donation so far.
Turner says two commissions are looking at alternative financial models, one created by Chatham House and a commission on antimicrobial resistance which looks at the growing problem of drug-resistant infections and is led by economist Jim O'Neill (and backed by the Department of Health, HM Treasury and the Wellcome Trust). One idea is that governments could underpin the economic cost of drug development by committing early to buy the first 2m doses of a new vaccine, for example.
But most drugs for tropical diseases are either donated by pharma firms or sold at not-for-profit prices. The Deutsche Bank analysts highlight the resurgence of the industry's engagement through WHO donations, flexible pricing and patent policies, collaborative R&D and investments in healthcare infrastructure.
"We see this as both 'doing the right thing' and a strategic investment in the customers of tomorrow, given that the tropics are home to over 40% of the world's population," they write. "Economic growth in the decades ahead will inevitably see many of these nations becoming increasingly important commercially to the pharma industry."
One is three people globally are at risk of malaria and there are 3,000 malaria cases in the UK every year, all imported. GSK is developing a malaria vaccine that could be ready late next year and is expected to be sold on a not-for-profit basis. Its success rate was only about 30% in infants but better in toddlers, although final clinical results and data on the effect of a booster are still due.
But other tropical diseases are much less well known. Dengue fever (also known as breakbone fever), which kills an estimated 20,000 people each year, including many children, has become the fastest-growing tropical disease globally. French drugmaker Sanofi has developed a vaccine with a 60% success rate that will be on the market next year after two decades of research. Mexico, Brazil and Colombia could be the first to market the vaccine.
Unlike treatments for many other tropical diseases it is expected to become a commercial blockbuster, with annual sales of more than €1bn.
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