The real war on drugs

Journal name:
Nature Medicine
Volume:
16,
Pages:
948–952
Year published:
DOI:
doi:10.1038/nm0910-948

The murder of ten aid workers, including an optometrist and a surgeon, in Afghanistan last month refocused the world's attention on the difficulties of providing health care in conflict zones. Beyond the dangers of delivering acute care such as surgery, dispensing medicines for chronic illnesses ranging from HIV to diabetes remains a challenge in areas affected by war. Cassandra Willyard looks at the lessons relief agencies have learned in recent years providing care amidst increasingly complex conflicts.

Newscom

On a summer evening early last month, several explosions rocked the southern Iraqi city of Basra. Three bombs erupted near the al-Ashaar market, reportedly killing 43 people and wounding 185 others. Abbas Ali Mansour, a physician, wasn't in the area at the time, but the blast shattered the windows of his private clinic located 100 meters away. “Thank God, only glass destroyed,” he wrote in an email.

Mansour, a diabetes expert and assistant professor of medicine at the Basrah College of Medicine, has been teaching students and treating patients for the past 27 years, bearing witness to the country's deterioration. Iraq's health system was once a source of pride. Then came the Gulf War, followed by 13 years of economic sanctions. “We had no medications; we had no instruments,” Mansour says. According to a report from the Center for Economic and Social Rights, Iraq experienced “one of the most rapid declines in living conditions ever recorded.”

Now that the trade embargo has been lifted, Mansour says it's actually easier to get medicines for his patients than it was before the war. But there are new challenges. Beyond creating new security concerns, the fighting has destroyed or damaged much of Iraq's infrastructure. In Basra, electricity is so spotty that, in June, protesters swarmed the streets to demand that the electricity minister resign. At the hospital, Mansour has a special generator connected to a refrigerator for storing insulin, but many of his patients have to store theirs at room temperature. In the summer, temperatures regularly climb above 43° Celsius. Such intense heat can damage the drug.

Those working to deliver medicines in war-torn regions of the world such as Iraq have learned a lot in the past decade. And, despite the tough conditions, their efforts have become more coordinated and more evidence based. Humanitarian agencies around the world have begun treating diseases once thought too complex to tackle in conflict areas, such as HIV.

DRC: HIV drugs under fire

The humanitarian relief organization Médecins Sans Frontières (MSF) has been working in the Democratic Republic of Congo since 1981, patching wounds and treating malnutrition along with infectious illnesses such as cholera and malaria. In 2001, they decided to tackle a more complex problem: AIDS. Although the prevalence of HIV is lower there than in many other countries in sub-Saharan Africa—around 1.5% of the population, according to UNAIDS estimates—the cases add up.

International Rescue Committee

Caught in the conflict: A child receives care for malaria in North Kivu.

Security remains a concern in some parts of Congo. The country has been embroiled in conflict since the mid-1990s. The most recent war officially ended in 2003, when the national government and rebel groups signed an agreement that brought a transitional government into power. But in mineral-rich Kivu, a province in eastern Congo on the border of Rwanda and Uganda, the fighting continues between the Congolese military and warring rebel groups.

Sumeet Sodhi, a Canadian physician and former MSF volunteer who now works for the Toronto-based humanitarian organization Dignitas International, remembers helping to set up the first AIDS clinic in Bukavu, a city of about 600,000 within Kivu. Just before Sodhi arrived, armed men had gunned down six Red Cross workers. Safety, she says, was on everyone's mind. MSF gave her a curfew and a satellite phone. Every time she changed locations, she had to call in her position using her code name, Sierra Sierra. Sodhi says she had little time to contemplate the dangers she faced. At the time, “I didn't realize how crazy it was,” she says.

Despite the challenges, she and her colleagues got the clinic up and running. They began treating sexually transmitted diseases and providing condoms and HIV counseling. They also tested for HIV, although they lacked the resources to supply antiretroviral medicines.

One day, as Sodhi made her way from her car to the gates of the clinic, a Congolese health worker stopped her. “She was worried about her daughter,” who had been raped by soldiers, she says. The mother explained that the daughter had diarrhea, a fever and was losing weight. The mother suspected HIV, but she wasn't sure. She wanted to arrange for her daughter to get tested, but discreetly.

“Knowing that there was a treatment for this young girl that I couldn't offer, it was extremely frustrating.”

Sodhi ran the test herself. In broken French, she told the daughter that she had HIV and explained what that meant. “She didn't break down and cry. She wasn't indignant,” Sodhi recalls. “She just seemed to accept her diagnosis.” Sodhi says the most difficult part was telling the girl she had a disease with no possibility of treatment. “We didn't have antiretrovirals available,” Sodhi says. “Knowing that there was a treatment for this young girl that I couldn't offer, it was extremely frustrating.”

Had Sodhi diagnosed the girl later, the conversation might have gone differently. In 2003, MSF became the first organization in Bukavu to hand out antiretrovirals for free (PLoS Med. 4, e129, 2007). At the time, a decade ago, HIV drugs were relatively rare in the developing world. The supplies that did exist went to more stable countries. Treating HIV in areas wracked by violence seemed impossible and possibly even dangerous. Additionally, scientists worried that patients in these conflict zones wouldn't be able to stick to the complicated drug regimen, which could lead to the emergence of drug resistance.

“There was this expectation that if you couldn't provide high-level care, then you may be making the situation worse,” says Edward Mills, a principal investigator at the British Columbia Centre for Excellence in HIV/AIDS in Vancouver. But that logic didn't dissuade MSF. “When you have lots of patients dying of HIV, you want to be able to treat it,” says Daniel O'Brien, an HIV specialist with the Dutch branch of MSF. “You can't just say, 'let's wait until the conflict is over'.”

Since MSF opened that first clinic in Bukavu, it has expanded its HIV program dramatically. The organization now has 24 HIV programs in a dozen conflict or post-conflict countries, including Colombia, Liberia, Ivory Coast, Sudan and Uganda. MSF's team has diagnosed more than 10,500 people with HIV and has started upwards of 4,500 on antiretroviral therapy, including about 350 children (Confl. Health 4, 12, 2010).

O'Brien and his colleagues have shown that people who receive antiretrovirals from these programs have fared just as well as their counterparts in other poor, but stable, areas. To date, the program has experienced only one major interruption, when rebels from the Congolese military invaded Bukavu in 2004. O'Brien and all the other foreigners had to evacuate for a couple of weeks. A Congolese nurse managed to keep the clinic running, but many patients could not reach it. Still, only five of the 66 people taking antiretrovirals ran out of drugs.

Mills says that conflict zones aren't as unstable as they might appear to the outside world. He works just across the border from Kivu in northern Uganda. Although the region has long seen conflict, it's not a battle zone with daily firefights. Most of the time, “it's a setting of tremendous boredom,” he says. In fact, despite the violence, the population is relatively stable. When villagers do have to flee because of attacks, they don't go far, Mills says—typically less than five kilometers. “We actually have suffered larger loss to follow up, where we lose more patients in cities, than we have in northern Uganda,” he says.

Of course, handing out antiretrovirals in unstable areas presents unique challenges. And MSF has learned some valuable lessons. Patients receive an extra three months' supply of drugs—a 'runaway stock'—“so if they have to flee, they have it,” says Paul Spiegel, chief of the public health and HIV section at the UN High Commissioner for Refugees in Geneva. Also, the medication gets divvied up between several locations. “A centralized stock will be pillaged, and then you'll have nothing,” Spiegel says. Many storage facilities allows for easier access too. “If one part is pillaged or if you can't cross a line because of fighting, you have access from another way,” he says.

Contingency planning is a must. MSF also provides what's called a 'washout course'—a week's supply of a different medication. If patients run out of their standard treatment, they know to take these pills, which reduce the risk that they'll develop resistance.

Myanmar: hotbed of resistance

Delivering medicines to populations affected by violence is tough enough. But the task is even more difficult when a country discourages relief organizations from providing aid. The military junta that rules Myanmar (Burma), a country with a civil war that has been raging for 62 years, is notorious for placing travel restrictions on aid workers. One area consistently off limits is the Thai-Myanmar border, where the junta frequently clashes with ethnic groups fighting for autonomy.

In many parts of the country, health care is all but nonexistent. In 2000, the World Health Organization ranked Myanmar's healthcare system the second worst in the world—190 out of 191, followed only by Sierra Leone. According to the World Bank, public and private spending on health in 2007 amounted to just a little more than $7 per person, compared to $136 in neighboring Thailand. One of the biggest killers is malaria. In 2008, Myanmar accounted for 35% of the malaria deaths in Southeast Asia. India, which has 24 times as many people, had fewer confirmed deaths.

If you wanted to find a recipe for how to “cook up a nice batch of drug-resistant malaria,” Myanmar would be a good place to start looking, says Adam Richards, a physician at the University of California–Los Angeles, who works with the Global Health Access Program, which provides technical support to local organizations. He lists the key ingredients: an abundance of fake antimalarials that contain low doses of the real drug, a population on the move and limited access to quality diagnosis and treatment. “Transmission there not only threatens regional control, which it's been doing for a long time,” he says, “but also potentially the global response to malaria.”

Even when people escape violence, they cannot escape malaria. During a 2007 trip to the region, Richards met a woman whose heartbreaking story illustrated this reality. When the military burned her village, she fled with her husband and children to the jungle. The family hid there, sleeping on the ground and eating what they could find. After a few weeks, her husband came down with a fever and died.

The woman continued walking—one child trailing behind her, one on her hip and one in her womb. Finally, she arrived at Ei Tu Hta, a camp near the Thai-Myanmar border where displaced people like her congregate. She, too, became feverish, but after receiving malaria drugs she recovered. Her baby—the one she carried inside—did not. When she gave birth, two months too early, the baby was already dead.

It was there, at the clinic in Ei Tu Hta, that Richards met her and learned of her horrific ordeal. Being a physician gives you “a certain toughness,” he says. But this story has stuck with him. “There's a lot of suffering and a lot of challenges to working in Burma,” he says. “But there's an amazing resilience and an increasing capacity to manage their own health.”

Tom Stoddart

Troubled waters: Adam Richards travels on the Salween River to the Ei Tu Hta Clinic.

In 2003, the Karen Department of Health and Welfare (KDHW), a Thailand-based nongovernmental organization aimed at providing healthcare in Karen region of Myanmar, launched a pilot project to see whether it would be possible to control malaria in this area of active conflict. The number of malaria cases in neighboring Vietnam and Cambodia had been falling, and KDHW wanted to see whether they could make a dent in Myanmar's epidemic. At the time, Richards says, “there was no international support for malaria control efforts in eastern Burma.”

Richards helps train KDHW's health workers, but he rarely enters the country. “In eastern Burma, certainly having six-foot, white farong—foreign folks such as myself—tends to endanger local populations.” So he and his colleagues help KDHW train health workers in Thailand to diagnose malaria with a rapid test called the Paracheck. They also teach them to administer combination therapies containing artemisinin, one of the few compounds still effective against malaria in this region. These health workers carry bed nets, rapid malaria tests and antimalarial medication over the border into Myanmar where they train local villagers to diagnose and treat the disease (Glob. Public Health 4, 229241, 2009).

The program started in 2003 with 1,800 participants. It now reaches more than 40,000 people along the Thai-Myanmar border, and Richards and his colleagues have gathered evidence that it works. In one village—Ler Per Her—prevalence fell from 9.4% in 2003 to 0.6% a year later. Overall, prevalence decreased 90% during the two-year pilot study. (Trop. Med. Int. Health 14, 512521, 2009).

Afghanistan: danger zone

Afghanistan has been mired in conflict since the Communist takeover in 1978. Decades of civil war preceded a US-led military invasion in 2001. Basic health services were “extremely disrupted, if not destroyed,” says Akihiro Seita, coordinator of AIDS, malaria and tuberculosis efforts at the World Health Organization's regional office for the eastern Mediterranean, which includes the Middle East.

After the Taliban fell, the new government needed a way to ramp up basic health care, and fast. According to the Afghan Ministry of Public Health, as of 2001 just 9% of the population had access to a health center. With the help of the World Health Organization, leaders identified the most pressing health problems, a so-called “basic package of health services,” and made delivery of essential medicines, including malaria and tuberculosis drugs, a priority.

Rather than providing health care itself, the government in 2003 contracted nongovernmental organizations to provide the care. The Ministry of Public Health coordinates the agencies and ensures that they do what they are supposed to. It has been “a very effective strategy,” says Ronald Waldman, a professor of clinical population and family health at Columbia University in New York who currently lives in India. “Afghanistan made remarkable progress in the health sector.”

According to the Ministry of Public Health, the number of working primary healthcare facilities tripled from 2001 to 2008. Today more than 85% of the population ca nreach a basic healthcare center, although some people have to walk an hour or more. And the country has seen some notable gains in health coverage. In 2003, only 30% of children between the ages of one and two received the polio vaccine. By 2006, that percentage had risen to 70%.

Still, more work remains. Afghanistan is one of only four countries with endemic polio. In 2009, the country reported 38 cases of polio, up from just four in 2004. In July, the country launched a new vaccination campaign, which aims to send 20,000 health workers door to door in 14 of Afghanistan's 34 provinces to give all children under the age of five the oral polio vaccine.

There are places where the basic package of health services doesn't reach, however. “We have armed conflict ongoing in southern provinces,” says Ataulhaq Sanaie, part of the Anti-Tuberculosis Association Afghanistan Program, a Kabul-based nongovernmental organization. The health centers that exist in that region are plagued by staff shortages, and the tuberculosis case detection rate is “very low,” he adds. What's more, Sanaie doesn't trust the data. “It is very difficult to say with confidence that the numbers we have from those provinces are accurate,” he says.

Afghanistan is a prime example of another disturbing trend: deliberate attacks on aid workers. There is a long tradition of warring parties putting down their guns to allow aid workers to provide medical care. In 1995, for example, Jimmy Carter negotiated a cease-fire in southern Sudan so that health workers could give civilians living in the region cloth filters to protect them from Guinea worm, medication for river blindness and vaccines against polio and measles. The peaceful interlude lasted four months.

But now that's changing, Spiegel says. “Humanitarian space is not respected as it was in the past,” he says. The Humanitarian Policy Group reports that attacks against aid workers have increased dramatically in recent years. Between 2003 and 2005, 440 aid workers were kidnapped, injured or killed. That number jumped to 705 during 2006–2008. According to the report, Sudan is the most dangerous place to work, but Afghanistan is not far behind.

Alarmingly, the organizations offering humanitarian aid are often the targets of the attacks. Last month, Taliban gunmen shot ten aid workers from the Christian organization International Assistance Mission in a remote northeastern corner of Afghanistan. UN Secretary General Ban Ki Moon condemned the killings at a press conference in New York, saying that “health workers must have access to treat those in need and must be able to do so without fear. Under international law, health workers must be protected while they carry out their lifesaving work.”

Iraq: chronic concerns

In August, the same month bombs exploded in Basra, the military scheduled some fifteen thousand US troops to leave Iraq. As of September, only non-combat troops—some 50,000 soldiers—will remain. The war there may be slowly winding down, but the battles have taken their toll. Estimates of the number of Iraqi dead vary wildly from 100,000 to more than 600,000 (see: Counting the dead). Furthermore, the 2003 US invasion left the already precarious health system in shambles. According to the research branch of the US Library of Congress, the 2003 attacks destroyed an estimated 12% of hospitals, as well as Iraq's two main public health laboratories. Looters ransacked health facilities in the chaos that followed.

In the years after the attacks, the country saw outbreaks of cholera, hepatitis and measles, as well as increases in typhoid fever and childhood diarrhea. But chronic diseases such as heart disease and cancer have long been among the biggest killers in Iraq.

Treating these diseases, which often require extended therapy, is more complicated than curing many infectious diseases. An individual with diarrhea might need a dose or two of medication, but people with diabetes or hypertension need drugs for the rest of their lives.

According to Mansour, chronic diseases are becoming even more prevalent in Iraq. “Unfortunately, diabetes and hypertension are increased nowadays after the war,” he says. Since the embargo ended, he says, Iraqis have adopted the Western lifestyle. Food is more readily available and people are getting less exercise and watching more television. This is driving up rates of chronic illness, he says. A 2006 survey found that 40% of adults have high blood pressure. The results also showed that a third of adults are obese, and another third can be classified as overweight. A new survey, planned for 2011, should give researchers a sense of whether Mansour's prediction is coming true.

Spiegel says that, in the context of war, communicable diseases historically have had a much bigger impact, at least in refugee camps and low-income countries. Now, relief agencies, which have long focused on preventing outbreaks of infectious diseases, are increasingly finding themselves working in more developed countries such as Iraq and, therefore, treating chronic diseases in conflict zones. “In the past, we didn't really deal with these diseases,” Spiegel says. In medicine, just as in affairs of state, new battles emerge just when victory seems within reach.

Soldiers benefit from medical innovation

More than 5,500 US troops have died as a result of the wars in Iraq and Afghanistan. That number is grim, but experts note that better armor and improved medical care have increased soldiers' chances of surviving battle injuries compared with previous conflicts. According to information from the US Department of Defense's Directorate for Information Operations and Reports, only 70% of soldiers survived battle injuries during World War II. That has increased to a 90% chance of survival for soldiers in the Iraq war.

Better survival, however, means more ongoing treatment of serious wounds. “The injuries that they sustain are very complicated,” says Barbara Boyan, director of the new Center for Advanced Bioengineering for Soldier Survivability at the Georgia Institute of Technology in Atlanta. “They involve multiple tissues, and oftentimes there's infection involved.” Boyan and her colleagues are using Department of Defense funding to investigate the potential of using stem cells to heal complex wounds.

One of the most pressing issues on the front lines is staunching blood flow. Blood loss accounts for 40% of all combat deaths. Companies have already developed several bandages that help blood clot, such as the HemCon and the QuikClot, both already on the market. One unconventional approach comes from Rutledge Ellis-Behnke, a researcher at the Massachusetts Institute of Technology in Cambridge, Massachusetts. Ellis-Behnke developed an amino acid mixture that forms a nanomesh when it encounters a salty solution, such as blood. When applied to a wound, the mesh stops the bleeding instantaneously without causing a clot to form—at least in animal trials (Nanomedicine 2, 207215, 2006). “You could lay this on and the bleeding would stop,” he says.

Other wild ideas in the pipeline include a tourniquet that stops bleeding using ultrasonic waves rather than pressure, inflatable balloons to fill wounds and nanocapsules that leak antibiotics in the presence of disease-causing bacteria.

These and dozens of other products are still being tested in the laboratory, and many will never make it into or out of clinical trials. Those that do will require even more research. “There are lots of new technologies,” says Andrew Pollak, chief of orthopedic traumatology at the University of Maryland Medical Center in Baltimore. “[Determining] which ones are efficacious and which ones are not is going to require comparative effectiveness studies.”

Advances don't have to be high tech to have a big impact, Pollak says. Emergency medics used to forgo tourniquets for fear of damaging nerves or killing the wounded limb. They now know, however, that tourniquets are safe. “By applying them earlier rather than later, you'll still save a lot of lives,” he says. With new one-handed tourniquet models available, soldiers even have a shot at saving themselves. — CW

Counting the dead

Research isn't easy under the best of circumstances. But in a conflict zone, it can be downright hazardous.

In 2004, epidemiologist Les Roberts decided to figure out how many people had died in Iraq since the US-led attacks. He had no trouble finding a partner at a local university, but getting into the country to conduct the investigation was a bit trickier. First, he flew to Amman, Jordan. Then, he found a driver willing to take him to Baghdad. He crossed the Iraqi border lying on the floor in the backseat of an SUV.

Roberts, an associate professor of population and family health at Columbia University in New York, and his colleagues began surveying randomly selected neighborhoods throughout Iraq. Eventually the security situation deteriorated to the point where he wasn't comfortable going outside. “I actually spent the last two weeks of that five-week period in my hotel room with the furniture barricaded against the door,” Roberts says.

Based on responses from 988 Iraq households, they estimated that 100,000 people died as a result of the invasion (Lancet 364, 18571864, 2004). Roberts followed that study with a second one based on a survey of even more people. His team reported that the annual mortality rate had jumped from 5.5 deaths per 1,000 people before the invasion to 13.3 deaths per 1,000 in the three years following the 2003 invasion. They attributed an estimated 654,965 deaths to the war (Lancet 368, 14211428, 2006). The results were met with widespread skepticism and accusations of bias.

Earlier this year, another survey from a group Roberts has collaborated with came under fire. The International Rescue Committee (IRC) 'Measuring Mortality in Congo' report, estimated that, for example, between 2001 and 2007 violence in the Democratic Republic of Congo resulted in 2.8 million deaths. In contrast, the Human Security Report, produced by a Canadian group that tracks the causes and consequences of global violence, charged that the actual number was closer to 860,000.

Mortality estimates are important, because they can affect humanitarian relief funding. But counting the dead is difficult. Countries such as the US use official death certificates and coroners' reports to track mortality within their borders. That's the gold standard, says Roberts. But in areas of conflict, such systems are almost always broken, if they even exist. “All the methods we have [for estimating mortality] are poor,” Roberts says.

Francesco Checchi, a lecturer at the London School of Hygiene and Tropical Medicine in London who also conducts mortality estimates, says the controversy has been less about the science and more about politics. Still, he acknowledges that methods do need improvement. He and others in the field are working to come up with better surveying methods.

Nathan Ford, who heads a section of Médecins Sans Frontières (MSF) that provides medical support to the organization's field programs, is also working on techniques to facilitate research in regions affected by conflict. A decade ago, humanitarian agencies didn't regularly conduct research. But, over that past six years or so, that has changed. MSF now regularly conducts studies to determine whether its programs are effective. That kind of research, Ford says, is essential to “providing effective care and doing better.”

Not every war-torn country is as dangerous as Iraq was in 2004, but researchers still face many logistical challenges, such as interruptions due to fighting and people on the move. Shifting populations can make it difficult for researchers to count cases of malaria or pneumonia, or even to determine the denominator, says Paul Spiegel, chief of the public health and HIV section at the UN High Commissioner for Refugees in Geneva. “It's very challenging,” he adds, “but it is doable.”

Ford agrees. In fact, he says, much of the research, including study design and analysis, can be done from a distance. Ford notes that MSF is thinking about rolling out comparative study designs in the field—for example, implementing a new intervention in only half the clinics in a given area so that they have a comparison group. The idea that conflict zones are too dangerous or too sensitive for research is just a “failure of imagination,” he says. — CW

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