Man-Eater Overload

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This story ran in Elements, The New Yorker’s science blog in May 2014. I loved reporting it especially because I conducted a lot of the interviews in Kannada, my mother tongue. You can see the original article here.

Last November, a tiger roaming the outskirts of Bandipur National Park, in southern India, mauled and ate a man named Cheluva, who was a member of the Jenu Kuruba tribe. By the following Tuesday, the tiger had killed two others. The Indian media raised the alarm that a “man-eater” was on the prowl. The government ordered that the beast be shot on sight. “Man-eater,” while technically accurate, did not reflect the tiger’s wretched state: old and weak, with porcupine quills embedded deep in its neck, it had most likely been evicted from its territory by a younger, stronger rival. A few days after the attack, a team of veterinarians tranquilized the tiger and carted it away to a zoo.

Four hundred tigers—more than a tenth of the worldwide population—live in India’s parks and in the Western Ghats mountain range, where their habitat spans more than ten thousand square kilometres. Attacks on the thousands of tribal people who live on park land have been escalating.

Free to fight disease

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I wrote this article for Nature Medicine in June 2008, after I had left my job as senior news editor for the magazine. This is a topic I have always found interesting, and there are few publications that would run a long story about it. (You can download a pdf of this article.)

Long ignored by pharmaceutical companies and global health agencies alike, ‘neglected tropical diseases’ devastate people in the poorest parts of the world. But they’re finally getting the attention they deserve, reports Apoorva Mandavilli.

It’s been 20 years since William Campbell visited the small nation of Togo in western Africa. But he still vividly recalls the remote communities he visited, with their tiny mud-thatched huts and trees so large that an entire village of 100 could gather under the leafy canopies.

That was in 1988, barely a year after the pharmaceutical giant Merck had made the unexpected announcement that it would donate its drug ivermectin—the most effective treatment for river blindness—to anyone who needed it for as long as they needed it. The drug, studied by Campbell’s team at Merck and originally used to treat parasitic diseases in animals such as horses, is known commercially as Mectizan. Seven years of trials had shown that a single annual dose of the medication could completely clear the worms that cause river blindness from the human body.

Left untreated, river blindness (known to doctors and researchers as onchocerciasis) can lead to horrible itching and irreversible loss of sight. The disease, caused by the worm Onchocerca volvulus, affects an estimated 18 million people worldwide. Black flies found near river banks transmit the disease to humans when they bite the skin and insert deposits of immature O. volvulus larvae.

Campbell, who led Merck’s parasitology division at the time of his Togo visit, remembers the children he met on his trip—”like kids anywhere, just excited to have their picture taken”—and the sense of humor of the village elders, obvious despite the language barrier. But the images he recalls most vividly are of an elder whose long robe hid the telltale white ‘leopard spots’ of the disease on his legs and of infected young adults who had the inelastic skin of old men. “I was seeing things I’d been teaching but never witnessed first hand,” says Campbell, who had traveled to Togo partly to understand the potential impact of ivermectin.

Since making its drug donation pledge two decades ago, Merck has kept its word, delivering more than 1.8 billion ivermectin tablets at an estimated total value of $2.7 billion and reaching nearly 70 million people a year in 33 countries—making it the longest running donation program by a pharmaceutical company.

These days, Merck’s program is no longer unique: in 2007 alone, Pfizer has donated the antibiotic azithromycin for trachoma, the leading cause of infectious blindness, treating more than 60 million people; Sanofi-Aventis and Bayer gave away medications for sleeping sickness in Africa; and GlaxoSmithKline contributed 150 million tablets of the drug albendazole to eliminate elephantiasis. Meanwhile, Novartis drug donations have helped cure more than 4 million people of leprosy.

The decision made by these companies to take action against neglected tropical diseases (NTDs) seems to be part of a larger movement. In February, the US government announced that, beginning in 2009, it would spend $350 million over the following five years to treat seven neglected tropical diseases, including trachoma, river blindness and another parasitic worm disease called schistosomiasis. The heads of the World Health Organization (WHO) and the United Nations have both designated neglected tropical diseases as a top priority. At the same time, several advocacy groups are pushing to include these ailments on the agenda of the annual meeting of G8 industrialized nations in July, and they are challenging donors to provide another $650 million to tackle these illnesses.

“Suddenly there is quite a lot of fervor around neglected tropical diseases,” says Christy Hanson, senior public health advisor at the US Agency for International Development based in Washington, DC. “They really aren’t neglected anymore; we’ll have to change the name.”

Neglected no longer?

A dose of hope: (This page) Malian doctor Alpha Mamadou Bah, who worked with William Campbell to treat river blindness in Togo, smiles while seated next to a village elder; A technician prepares ivermectin tablets for distribution; (Opposite page) Former US President Jimmy Carter helps administer praziquantel, a drug used to fight Schistosomiasis

Until recently, much of the world’s attention was focused on the big three—AIDS, tuberculosis and malaria—which together kill up to 6 million people each year. Calling the remaining tropical diseases ‘neglected’ may suggest that they are trivial, but these diseases collectively infect about a billion people, most of them in the poorest parts of the world, and claim up to a million lives. “More and more groups and agencies and institutions are realizing that it’s horrible to die from HIV/AIDS, but it’s also horrible to die from sleeping sickness,” says Jean Jannin, coordinator of the Innovative and Intensified Disease Management Unit at the WHO in Geneva.

Not all neglected tropical diseases are fatal, but they often blind, maim or deform their victims. And the consequences—school dropouts and loss of wages, for instance—keep affected commun

ities trapped in a vicious spiral of illness and poverty.

Crucially, most NTDs are easy to treat. In many cases, a single dose of a drug delivered once a year to a large number of people can control and even eliminate the disease from a country.

For example, Merck reported in November 2007 that an eradication campaign had succeeded in eliminating river blindness from Colombia and in halting transmission in certain areas within Ecuador and Guatemala. The number of people infected with guinea worm has also dropped from 3 million cases worldwide in 1986 to just 25,000 in 2007, thanks in part to a 20-year campaign led by former US President Jimmy Carter.

Donation programs have historically targeted a single disease at a time, but the new US program set to start in 2009 aims to deliver treatments for each of the seven NTDs. The $350 million initiative builds on a congressional scheme that began in 2006 with $15 million per year and expands the number of countries targeted from 10 to about 30 by 2013. “Where [the countries] had staff planning for one disease, now they’re able to do it for seven diseases together,” says Hanson.

Because companies such as Merck and GlaxoSmithKline together donate about $400 million worth of drugs each year, only 25% of the US funds will be used to buy drugs. The rest will cover drug distribution and community training, together estimated at an annual cost of less than 40 cents per person receiving treatment in sub-Saharan Africa.

Intelligent investments

Why would a pharmaceutical company, whose main aim (like that of any commercial enterprise) is profit, donate drugs for free? “We do it because—and people don’t like to believe this—it’s the right thing to do,” says Ken Gustavsen, director of Merck’s product donation program headquartered in New Jersey.

That may be so, but other people note that there are more prosaic reasons: companies that donate drugs can claim tax deductions of up to twice the cost of the product. The programs also improve the morale of employees. What’s more, pharmaceutical companies can use donation programs to establish a presence in new countries. “The market tomorrow will be developing countries,” notes Ulrich Madeja, head of Bayer-Schering’s social healthcare program.

Last, and perhaps more immediate, is the public relations impact. According to Carl Nathan, chair of microbiology and immunology at Weill Cornell Medical College in New York, drug companies are among the most consistently profitable enterprises in the world and, perhaps as a result, the most scrutinized by the public and the press. Their image took a severe drubbing in the late 1990s, when the world’s attention was focused on the untenable prices of AIDS drugs.

Since then, pharmaceutical companies have become more aware that the public expects them to be socially responsible—to go beyond merely donating drugs and help build health infrastructure. In an attempt to present themselves as responsible partners in public health, many are creating entire divisions dedicated to issues of access to medicines. For example, the Access to Medicines department at Sanofi-Aventis was launched in 2006 and now employs 35 people.

Profit versus philanthropy

Although pharmaceutical giants proudly tout what they call their new commitment toward access to medicines, their motives are met with a healthy dose of skepticism from some quarters. An Oxfam report released in November 2007, titled ‘Investing for Life’, concluded that companies are more interested in setting up these programs to boost their reputations than in establishing tiered-pricing systems, which could serve as a more sustainable way to make medications affordable to all who need them.

“[The companies] decide whom to give it to, for how long and at what price,” adds Beverley Snell, an essential drugs specialist at the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia. “There are always conditions, limitations, et cetera.” Snell notes that ivermectin, for example, is useful against other crippling parasitic diseases such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis. But Merck donates the drug only for river blindness.

According to some experts, it’s unrealistic to expect companies to be philanthropic at the expense of their bottom line: “It’s a misunderstanding that companies exist to provide drugs,” says Nathan. “In fact they exist to make money for their shareholders.”

Nathan says it is instead up to individual governments to create a ‘medicine fund’ that would provide incentives for companies to make certain drugs. A 2002 study from Médecins Sans Frontières (Doctors without Borders) found that of 1,393 new drugs marketed between 1975 and 1999, only 13 were for tropical diseases (Lancet 359, 2188–2194; 2002). But as incentives appear—such as a $19 million cash influx from the Bill & Melinda Gates Foundation to find a drug for sleeping sickness—companies are returning to research on these diseases.

For their part, the companies have their own complaints about the way in which many countries operate. They note, for example, that African nations each have their own complex rules for drug importation and don’t make special allowances, such as waiving customs duties, for donation programs. “It’s problematic when you’re trying to get the product in, and you wind up paying a huge amount of money [in customs],” says Heather Lauver, assistant director for Pfizer’s Global Operations of International Philanthropy Programs. “It’s kind of an insult when you’re donating out of good will.”

Troubled partnerships

When Merck’s researchers first stumbled on to ivermectin’s potential in the late 1970s, they encountered skepticism from experts at the WHO. “The [WHO] sent these very imperious, wonderfully clad officials to visit us,” recalls Roy Vagelos, who served as Merck’s CEO at the time. “They looked at our data, and they were rather negative about our results. They said we had probably not done the experiment very well.”

In 1974, the WHO had launched its own river blindness program, which employed a small fleet of planes to spray insecticides on black fly breeding areas. “They were very protective of their program,” Vagelos says. Instead of working through the WHO, Merck—and later Pfizer—set up independent expert committees to approve applications from countries for their drugs. Finally, though, the WHO began providing technical advice to Merck’s program and now helps train community-based workers to organize ivermectin’s distribution.

Similar turf battles doomed the Children’s Vaccine Initiative, the forerunner to the Global Alliance for Vaccines and Immunization, and a public-private partnership intended to deliver the drug praziquantel for schistosomiasis, a disease that can cause symptoms such as abdominal pain and liver lesions.

In the past few years, drug makers have formed coalitions such as the Partnership for Quality Medical Donations and, more recently, the Partnership for Disease Control Initiatives. These organizations bring together donors who are grappling with similar logistical challenges linked to delivering free medications, such as dealing with many different government regulations.

Things are better now, all parties insist. “The relationship between us and the pharma companies has changed a lot in the past ten years,” says the WHO’s Jannin. This past November, the agency moved its neglected diseases division from communicable diseases into the same cluster as AIDS, tuberculosis and malaria. “It’s a small signal” of the WHO’s increased focus on neglected diseases, says Jannin, “but it’s an important one.”

Getting personal

Making the connection: The leg of a villager in Togo bears the telltale ‘leopard spots’ indicative of river blindness infection; William Campbell (seated second from the left) and his colleagues speak with locals in 1988 about delivering ivermectin to an additional town

Ultimately, behind the massive drug donation plans stand individuals who had the vision and determination to see the programs through many hurdles. In the case of the Merck ivermectin program for river blindness, it took at least three such people: Campbell, whose team discovered that a horse medicine effectively kills the parasite behind river blindness; Mohammed Azeez, a physician from Bangladesh who had seen the disease’s devastating effects in Africa and who foresaw ivermectin’s potential; and, perhaps most important, CEO Vagelos, who was so sure that donating was the right thing to do that he made the decision without consulting the company’s board of directors.

Campbell remembers one particular day in Togo when residents from a nearby village had gathered where ivermectin was being distributed. Their village was so remote that they had built a section of road for the doctors to reach them—but they had still not been added on the list to receive ivermectin.

Because of ethical and safety considerations, the doctors couldn’t just add a village without authorization, Campbell says. But that afternoon, another remarkable individual—Alpha Mamadou Bah, the Malian doctor who led the treatment in Togo—sent a telex to the program’s headquarters in Wagadugu, Burkina Faso, asking them to include the village. If necessary, Bah said, the cost should be deducted from his salary. Bah later received the approval to treat the village, but his dedication left a lasting impression on Campbell, who now teaches at Drew University in Madison, New Jersey.

“To me it’s striking that so many people got involved in it; it became huge and had this ripple effect,” Campbell says. “It was all a very emotional experience.”

Health agency backs use of DDT against malaria

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(Nature asked me to write this article after the editor saw my feature in Nature Medicine on DDT’s return. The feature came two months ahead of the announcement that the WHO would back DDT. This article appeared the week after the announcement, in the 21 September 2006 issue.)

After decades of being shunned 
as an environmentally damaging chemical, the pesticide DDT is once again being touted as the most effective way to fight malaria.

The World Health Organization (WHO) announced on
15 September that it will support the indoor spraying of pesticides generally, and DDT specifically, to control mosquitoes in countries with high rates of malaria. The US Agency for International Development signalled a similar shift in policy back in May.

Although these agencies never formally opposed DDT, they did not fund countries to purchase it, and instead actively promoted the use of insecticide-treated bednets. Malaria rates have continued to rise in the meantime, claiming more than a million lives a year, mostly in sub-Saharan Africa. The agencies now advocate combining the two approaches.

“I have to pinch myself a little to believe that they’ve done this, but I’m really, really happy they have,” says Amir Attaran, professor of law and medicine at the University of Ottawa, Canada, who has long criticized the agencies for their malaria policies.

In sharp contrast to its previous stance, the WHO also admitted for the first time that it stopped supporting DDT despite evidence of its effectiveness. “There are 
lots of data there, but people are 
so emotional about the issues,” says Arata Kochi, director of the WHO’s Global Malaria Programme. “Science comes first and we must take a position based on the science and the data.”

DDT, or dichlorodiphenyl-trichloroethane, is an organochlorine that is more effective, cheaper and longer-lasting than the alternatives. Fears about its use date back to the 1960s when Rachel Carson’s book, Silent Spring, famously chronicled its devastating effects on the environment. In the years that followed, the United States and many European countries banned DDT.

These countries once used thousands of tonnes of the pesticide for agricultural purposes. But the use of DDT for malaria control is very different: small quantities are sprayed once or twice a year on the inside walls and ceilings of houses.

Following widely publicized success with DDT in some countries such as India and South Africa, others began clamouring for the pesticide. “A lot of countries, especially in southern Africa, have become bullish about the use of DDT,” says Richard Tren of the non-profit group Africa Fighting Malaria.

PDF: Health agency backs use of DDT against malaria

Heroin boom fuels AIDS epidemic

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(I wrote this article for Nature from the XVI International AIDS Conference in Toronto. It appeared on Nature’s site on August 15, 2006.)

Sharing of needles accounts for a large amount of HIV transmission outside of Africa.

The flourishing drug trade in Afghanistan is fuelling the AIDS epidemic in that country and its neighbours in Asia, warns a World Bank report released at the International AIDS Conference in Toronto, Canada, this week.

More than 7.4 million people in South and Southeast Asia are infected with HIV, but the epidemic is vastly variable across the region. In many parts of India — which, with 5.7 million cases has more people living with HIV than any other country in the world — infections are driven by commercial sex work.

But in the predominantly Muslim countries of Afghanistan, Pakistan and Bangladesh, limited data suggest that HIV is primarily a problem among injecting drug users. More widely, drug users sharing infected needles is now thought to be responsible for nearly one in three new cases outside Africa.

Drug-injecting commercial sex workers could spread the epidemic into
 the general population, warns Julian Schweitzer, director for human
 development in the World Bank’s South Asia regional team. “This should be a cause of great concern for all the countries in that region,” he says.

Heroin capital

Afghanistan had negligible rates of HIV/AIDS until 2000. But since then, prolonged war and civil unrest have boosted drug use, says David Wilson, co-author of the report. The country has reclaimed its historical role as the world’s largest producer and exporter of heroin.

Afghanistan is estimated to have more than 900,000 illicit drug users, including 120,000 women and 60,000 children. Afghanis have traditionally smoked opium, but refugees living in Pakistan and Iran began injecting heroin. Of some 50,000 heroin users in Afghanistan, a negligible number of women but about 15% of male users are thought to inject the drug.

As a result, the prevalence of HIV/AIDS among injecting drug users in Afghanistan is now 4%.

The increased drug traffic from Afghanistan is likely to have an impact on nearby countries already struggling with HIV. In Pakistan, about 25% of injecting drug users are thought to be infected.

The Afghan government is negotiating with the World Bank to fund programmes for injecting drug users, to help people come off the drug or to use clean needles. The World Bank is also conducting a larger surveillance study, results of which are expected in 6 months.

References:

World Bank report- AIDS in South Asia: understanding and responding. (2006).

 

The epicentre

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(This is a sidebar to The coming epidemic, an article about the AIDS epidemic in India, and part of a special package on Indian science called Nature Outlook: India.)

In Bangalore, the bustling capital of the southern state of Karnataka, people drive shiny new cars, work in gleaming new buildings and carry mobile phones. Just a few hundred kilometres north, the residents are poorer than many in sub-Saharan Africa. In Bangalore, dubbed India’s Silicon Valley, the land is green, but here it is brown and dry. This is the home of one of India’s two AIDS hotspots.

“Someone’s got to wake up to the fact that there are two Karnatakas,” says Ashok Alexander, director of Avahan, the Bill & Melinda Gates Foundation’s AIDS programme in India.

Driven by poverty and unemployment, women from northern towns such as Bijapur and Belgaum travel across the border to work as prostitutes in the richer cities in the adjoining Maharashtra state. When they return home, they bring the money they’ve earned — and HIV. On a map (right), the districts along this ‘AIDS corridor’ are immediately visible. “This is the epicentre of the whole Indian AIDS epidemic,” Alexander says.

He has discussed his theory with several people in the government. “We entirely agree with him because those pockets are surely high-prevalence,” says S. Y. Quraishi, director-general of the National AIDS Control Organization.

Yet until Avahan — meaning ‘call to action’ in Sanskrit — was launched in April 2003, Karnataka was largely ignored by AIDS groups. Most donor agencies ‘adopted’ other high-prevalence states: the US Agency for International Development earmarks its money for Tamil Nadu and Maharashtra, for instance, and Britain’s Department for International Development champions states such as Andhra Pradesh.

Avahan has already spent more than US$17 million working with sex workers, truck drivers and drug users. It is also backing research on migration patterns in the corridor, large-scale surveys to measure behavioural changes and mathematical models that chart the epidemic’s course. “We’re going to be here as long as it takes to make an impact,” says Alexander.