Many terrifying diseases have long afflicted humans in the warm, wet places of the world. Evidence of some of them is found in mummified Egyptians; others are recorded in the Bible and the Talmud, and the writings of ancient scholars such as Hippocrates. Modern science has established that they are transmitted by parasitic worms, bacteria, viruses, protozoans and fungi.
Some have names that may be unfamiliar. Buruli ulcer, Chagas disease, guinea-worm disease, leishmaniasis, river blindness, trachoma and yaws are some of the 18 now collectively referred to as “neglected tropical diseases” (NTDs). Between them they affect more than a billion people, most of them poor, with blindness, immobility, disfigurement and often great pain. The resulting disabilities keep sufferers mired in poverty; that poverty is also what allows the diseases to thrive.
Medicine is now capable of cutting transmission and driving many NTDs out of existence by 2030. Simple remedies that were already available. In the 1950s and 1960s, China eliminated lymphatic filariasis by adding an anti-parasitic drug to table salt. For sleeping sickness, surveillance and “vector control” (such as spraying with insecticide and setting insect traps) were highly effective. Insecticides were also known to work against other diseases. One of the reasons Japan and South Korea developed so fast after the second world war is that both ran major deworming programmes in schools.
The drug ivermectin was developed by Merck in the 1970s for parasitic infections in animals.
With Lymphatic filariasis, the story begins with a mosquito bite. As the bloodsucker feeds on a human, in some parts of the world there is the chance it will transmit the larvae of worms which cause a disease called lymphatic filariasis (sometimes known as elephantiasis). After many such bites, the larvae develop into thin microscopic worms that invade the host’s lymphatic system, where they grow into adult worms. During their seven-year lives these worms damage the lymphatic system, and cause infections that lead to blockages, swelling and fevers.
Patients have grossly swollen legs that are painful and disabling. Male victims can develop scrotums so large that they can descend to the knees. Their enlarged limbs may smell foul, as they become prone to infections. They may be shunned by their communities and often believe that their sickness is a punishment for some past misdeed.
Globally, about 120m people are infected with lymphatic filariasis, of whom about a third are disfigured or incapacitated.
River blindness, endemic in parts of Africa and Latin America, and in Yemen, in its early stages causes rashes and severe itching; later, it progressively damages the retina. The first human trial of ivermectin for river blindness was in Senegal in 1981, in patients who had the early stages of the disease but no damage to their eyes. Together with several more trials, it showed that ivermectin was safe in humans and highly effective at killing the disease vector in its larval state.
But Merck had a problem: there was no market for it. Those who needed ivermectin were too poor to buy it. So the firm did something remarkable: it made an open-ended commitment to give away as much of the drug as necessary, starting in 1987, with the ultimate goal of eliminating river blindness entirely. In the following decade it donated 100m doses.
Yet a miracle cure was not enough. The biggest obstacle to tackling river blindness, and other NTDs, turned out to be getting the drug to those who needed it. That was too complicated for any one company on its own. Painstaking and costly logistical efforts were required to get treatments to remote areas. Prevalences had to be mapped, and, for some of the diseases, individual patients diagnosed. Since most of the affected areas lacked health-care workers, some had to be trained. The stigma and disability faced by sufferers meant that many were hidden within their communities; they had to be found and persuaded to accept treatment. And after all that, surveillance and follow-ups were required to stop diseases making a comeback.
Troubles shared
Partnerships started to emerge between countries where NTDs were endemic. International institutions such as the World Bank and World Health Organisation (WHO) teamed up with donor governments and charities. By 1999 the Gates Foundation, a charity set up by Bill and Melinda Gates, was funding work in lymphatic filariasis and schistosomiasis, a debilitating ailment caused by a parasitic worm transmitted by freshwater snails.
By then the long-running effort to eradicate guinea worm led by the Carter Centre, a foundation set up by Jimmy Carter in 1982, had gained pace. The worm’s larvae are ingested in dirty water and grow internally to as long as a metre; they emerge, agonisingly, through the skin over several weeks. The only treatment for an established case, even now, is to speed up this expulsion by gradually winding the worm’s emerging body on a stick. But public-information campaigns about the need to filter drinking water and keep sufferers away from water sources, where they might pass on the infection, have brought new cases down from an estimated 3.5m a year globally in 1986, when eradication efforts started, to 25 last year.
Other drug firms, including GSK, Pfizer and Novartis, started to donate medicines on a large scale for other conditions. These included albendazole, another anti-parasitic for lymphatic filariasis; azithromycin, an antibiotic that works against trachoma (a bacterial infection that can cause blindness); and a combination of drugs for leprosy (another bacterial infection, which leads to skin lesions and nerve damage). Yet these disjointed initiatives added up to less than what was needed. In an article in 2004 in the Lancet, a medical journal, Dr Molyneux argued that these diseases were unfairly neglected in comparison with tuberculosis, malaria and HIV/AIDS, which were the subject of well-funded global programmes. Experience in a range of countries showed that these diseases could be controlled, he reminded his readers—and doing so brought dividends besides the relief of great suffering.
For example, the control of river blindness in west Africa has been described by the World Bank as one of the most cost-effective ways to reduce premature death and disability in poor countries. Each dollar spent on the control of lymphatic filariasis in China, or Chagas disease in Brazil, has been estimated to produce benefits of $15 and $17 respectively, by reducing spending on treatment and cutting the number of prematurely curtailed working lives. Some disease-control programmes had built logistics for distributing drugs from scratch, which could be used for other public-health efforts, and had strengthened national health systems more broadly.
By the turn of the millennium the common features of a group of tropical diseases were increasingly recognised by public-health experts, donors and the WHO. They were diseases of poverty but also causes of poverty. They caused disability and made it harder to absorb nutrients in food; reduced school attendance, thus condemning children to a life of grunt work; and trapped families in poverty when breadwinners were too sick to work or farm. Though prevention and treatment methods varied, there was clear potential for combining attempts to control or even eradicate them. Some required the suppression of vectors such as flies and mosquitoes, for example by spraying insecticides or distributing bednets. Some could be tackled by dosing entire communities with cheap, safe drugs; others by identifying and managing individual cases over extended periods. And most could be greatly reduced by providing safe drinking water, sanitation and information about hygiene.
Gateway to success
The Gates Foundation has helped a lot. In 2010 Mr Gates and Tachi Yamada, who led the foundation’s global health programme at the time, invited the bosses of a group of drug companies to tell them what could be done to tackle the field’s greatest challenges. The firms said that they wanted help to deliver the free drugs that they were offering. At around the same time the WHO created a detailed plan for controlling each of the NTDs.
Finally, the stage was set for an ambitious global coalition. Margaret Chan, the director-general of the WHO, and Mr Gates were able to rally charities, NGOs, big donors (such as the governments of America, Britain and the United Arab Emirates) and, crucially, 13 drug firms. Many, including Merck KGaA, Johnson & Johnson and Gilead, had been donating treatments for years. Others, including Eisai, a Japanese firm, were new to the fight. Together, they declared themselves ready to give away drugs worth billions of dollars each year. In 2012 the group signed the “London Declaration” which promised to control, eliminate or eradicate ten NTDs by the end of the decade.
Five would be controlled with mass drug administration: lymphatic filariasis, river blindness, schistosomiasis, trachoma and diseases caused by helminths (parasitic worms such as hookworm and roundworm) that spend part of their lifecycles in soil. Tackling the rest, including sleeping sickness and Chagas disease—both parasitic diseases transmitted by insect bites—would require the identification and treatment of infected individuals.
Since the signing of the London declaration, the alliance against NTDs has developed into the largest and most successful public-health initiative in history. The number of people at risk globally from NTDs has fallen by 20%. Most of Latin America has eliminated river blindness. The number of new cases of leprosy has declined in eight of the past nine years. In the past year eight countries eliminated lymphatic filariasis. The number of cases of sleeping sickness is at its lowest in 75 years, and eradication is now thought possible. In 2015, 1.5bn treatment doses were donated by drug firms, and almost a billion people received them—an increase of more than a third since 2012.
Critics of foreign aid often charge that it weakens the countries that receive it, by undermining their economies and governance. But support for tackling NTDs, and other health problems, has shown quite the opposite effect. It removes an obstacle that stops abjectly poor people bettering themselves. And, like efforts to control malaria, tuberculosis and HIV/AIDS, it improves public-health systems and disease surveillance. As countries become more organised they can often combine their programmes. The excellent results are persuading some recipient countries to chip in: a quarter of programmes on NTDs in the Democratic Republic of Congo, for example, are now locally funded, up from none in 2011. Aid given to set up the infrastructure needed to tackle polio in Nigeria meant that the country was better placed to fight Ebola when that disease emerged.
It is tempting to extrapolate, and predict that all 18 NTDs will be consigned to history. Progress might even speed up: new diagnostic tools and treatments are on their way. The Gates Foundation is paying for final trials of a triple-drug therapy for lymphatic filariasis that clears the parasite from infected people’s bodies far more effectively than current treatments. When they are completed later this year, India might be able to get rid of the disease in just a couple of years, and other countries could quickly follow.
Mr Gates thinks that it should also be possible to get visceral leishmaniasis, a parasitic disease that destroys the internal organs, down to tiny numbers of new infections in Asia. (To public-health aficionados, “eliminating” a disease means making it rare, rather than completely eradicating it.) By 2030 he hopes to see just 170m people globally at risk of NTDs, down from 1.7bn now. For that to happen drug companies will need to remain strongly committed; that means making sure they receive “well-deserved” credit, he says.
But what worries some, including the authors of the WHO’s latest report on NTDs, published on April 19th at a summit in Geneva to evaluate progress and gather new donations, is the endgame. “Sometimes the last mile is the hardest,” says Ken Gustavsen, who runs corporate responsibility for Merck. As efforts to control a disease are successful, the sense of urgency fades, making it hard to maintain the political momentum. Tackling some of the NTDs requires long-term commitment. Chagas will have to be tracked into the remote reaches of the Amazon basin; diminished concern about canine rabies is already weakening attempts to eradicate it in Latin America. A campaign in 1952-64 against yaws, a bacterial infection that attacks skin, bone and cartilage, provides an object lesson. As cases became fewer, funding and attention shifted away, and in the 1970s the disease rebounded.
There are fears that something similar could happen with guinea-worm disease. Its imminent demise has been declared prematurely several times in recent years. Last year’s tally of 25 reported cases was slightly higher than the figure for 2015. Fortunately, it can be transmitted only if an infected person enters drinking water around the time when a worm is leaving the body, meaning the disease would be slow to bounce back, unlike, say, polio, which is passed on through fecal matter and could quickly return from near-extinction if eradication efforts were to slacken.
But wiping out guinea-worm disease, as the London declaration envisages, and controlling or eliminating the other NTDs, will take continued focus—and plenty more money. A big worry is whether the governments that fund much drug distribution, chief among them America’s and Britain’s, will continue to do so. This week the British government said it would double spending on NTDs over the next five years, to £360m ($460m). But the department responsible for aid was reluctant to provide a spokesman to discuss the programme. And a turn to insularity in many rich countries means foreign aid is increasingly criticised. British newspapers have become strikingly hostile towards it, arguing that most is squandered, and that even if it were not, the money is needed to cut poverty at home. The Daily Mail, one of the most splenetic, frequently splashes stories of wasted aid on its front page (often blaming the European Union). It is campaigning for Britain’s government to abandon a pledge, passed into law in 2015, to earmark 0.7% of GDP for foreign aid.
In America Donald Trump’s administration has said it wants to slash the budget of the state department, the part of government responsible for most foreign-aid spending. Mr Gates, who recently met Mr Trump, remarks that it is unlikely Congress will allow drastic cuts. But even a modest trimming of American spending on NTDs would be worrisome, if it discouraged spending by other governments.
Private donors could fill part of the gap, but not all. Plenty find the cause appealing, says Ellen Agler of the END Fund, which co-ordinates philanthropy for NTDs with those of governments and international organisations: “The clear return on investment is so powerful, and the timeline is so short.” Since the fund was set up in 2012 it has treated more than 140m people at risk in 26 countries, and raised more than $75m from individuals, corporate foundations and philanthropic groups. Its donors bring more than their money, says Ms Agler: they strengthen oversight, and provide private-sector problem-solving skills—and sometimes local contacts and logistical support.
The effort to defeat NTDs produces plenty of heart-warming stories. In Tanzania Ms Mwingira talks about men with lymphatic filariasis who have received surgery to reduce the size of their genitals and can return to normal life, marry and have children. Kofi Nyarko, a former leprosy patient who lives in Ghana, says he would be dead without treatment. It came too late to save his hands from deformity; they are twisted and rigid. But he has been able to achieve his dream of becoming a special-needs teacher.
Where charity begins
It is worth recalling the motivation for Merck’s original decision, back in 1987, to donate ivermectin for river blindness, says Mr Gustavsen. There was no economic rationale: the firm’s scientists simply felt it was the right thing to do. Having discovered the drug, and established that it worked against a disease that caused awful suffering, neglecting to use it would have been “incredibly demoralising”, he says. That sense of moral purpose must not weaken if the global coalition against NTDs is finally to prevail.
