By Scott Malone
Reuters

Overdoses of drugs, particularly prescription painkillers and heroin, have overtaken AIDS to become the leading cause of death of homeless adults, according to a study of homeless residents of Boston released on Monday.

The finding came from a five-year study of homeless adults who received treatment from the Boston Health Care for the Homeless Program, though its broad conclusions apply to homeless populations in many urban parts of the United States, the study's author and homeless advocates said.

The tripling in the rate of death by drug overdose reflects an overall rise in pain-killer abuse, said Dr. Travis Baggett of Massachusetts General Hospital, the lead author of the study, to be published next month in the journal JAMA Internal Medicine.

"This trend is happening across the country, in non-homeless populations too," Baggett said. "Homeless people tend to experience in a magnified way the health issues that are going on the general population."

The study, which tracked 28,033 homeless adults from 2003 through 2008, found that of the 17 percent who died during the study period died of drug overdoses while 6 percent died of causes related to HIV, the virus that causes AIDS.

That is a rough reversal of the trend found in a similar study 15 years earlier, when 6 percent of deaths were due to drug overdose and 18 percent due to AIDS.

After the drug overdoses, the second- and third-leading causes of death in the most recent study were cancer, which accounted each for about 16 percent of the deaths.

Homeless people are significantly more likely to die in a given year than their peers in the rest of the population, with those aged 25 to 44 nine times more likely, and those aged 45 to 64 four-and-a-half times more likely to die.

The decline in AIDS-related deaths reflected an overall decline in infection rates, as well as improvement in care and services for patients since the prior study, which was conducted during the peak years of the U.S. AIDS epidemic.

Regional variations
The study looked at a small slice of the roughly 2.3 million to 3.5 million Americans who go through a period of homelessness each year, according to data from the Urban Institute.

While drug abuse is not an uncommon problem among homeless people, the drugs most commonly used vary by region. Heroin and opiate painkillers are the most available and most used drugs along the coasts, while methamphetamine is more common through the middle of the country and prescription painkillers tend to be abused around large military bases, said Neil Donovan, executive director for the National Coalition for the Homeless.

"Fifteen years ago we were talking about homeless people drinking Listerine and that being a leading indicator, and now it's Oxycontin and heroin and it's a very different reality," said Donovan, whose group was not involved in the study.

Prescription painkiller abuse is somewhat more common in Boston than other cities due to the high concentration of hospitals and doctors, which make it easier for users to gain access to the drugs, he said.

Changes in treatment
The rise in deaths related to drug overdoses prompted the Boston Health Care for the Homeless Program to change the way it approaches care, said Dr. Jessie Gaeta, the group's medical director.

"We have to become expert in integrating addiction services into the rest of medical care," Gaeta said. "We have decided to take a very thoughtful and critical look at the way that we prescribe these opiods."

The nonprofit group is considering changes including reducing the overall amount of painkillers it prescribes and providing patients with another drug, naloxone, which can be used as an antidote to overdose, Gaeta said.

Chronic pain, related to causes ranging from cancer to arthritis, is a common problem among the homeless and the groups doctors continue to prescribe painkillers to some of their regular patients, Gaeta said. They have stepped up their efforts to counsel those patients on properly using their drugs and also how to protect them from being stolen.

The relationship between homelessness and drug abuse is a self-reinforcing one, advocates noted. Drug abuse can increase the odds of a person becoming homeless, by making it more likely that they lose a job or fall out with family members, and also makes it harder for the homeless to find shelter as some agencies will not house drug users.

"It's easier to be clean and sober in a bed than on the streets," said Donovan.

MAE SOT, Thailand -- Clipboard in hand, Dr Francois Nosten worked his way down a ward of malaria patients. He stopped in front of five-year-old Ayemyint Than, who sat to attention and smiled. The smile told Nosten as much as his lines of graphs and figures.

Ian Williams / NBC News

Ayemyint Than, 5, is being treated for malaria in northwestern Thailand.

"She's doing well," he said, moving to an older man, whose pale face and dull sunken eyes told a very different story. "Day five, and he's still positive?" he asked another of the doctors. "That's not very good. It means he was very slow to clear the parasite, no?"

To Nosten, it was further evidence of an alarming rise in resistance to artemisinin, currently the front-line drug in the treatment of malaria. He fears it could be the start of a global "nightmare" in which millions of people could lose their lives.

"We have to beat this resistance, win this race and eliminate the parasite before it’s too late. That's our challenge now," he said.

He said that artemisinin should take about 24 hours to deal with the parasite, but it was now taking three or four days in some cases. "We are going to see patients that don't respond to the treatment anymore,” he warned.

Nosten runs the Shoklo Malaria Research Unit, which is part of the Faculty of Tropical Medicine at Thailand's Mahidol University.

The unit has a string of clinics on both sides of the Moi River, which marks the porous border between Thailand and Myanmar.

Ian Williams / NBC News

Migrants cross the Moi River, marking the border between Myanmar and Thailand.

Nosten set up the first one in 1986, since when there has been a steady fall in the total number of cases of malaria, but most recently a worrying emergence of drug resistance.

He first sounded the alarm in research published earlier this year, following the emergence of similar drug resistance along the Thai-Cambodia border.

Full health coverage from NBC News

Nosten’s not sure whether the resistance he's found has spread from the Cambodia border or is home-grown. Either way, he's worried.

"It means that all the progress of the last 10 to 15 years will be lost," he warned. "Now the resistance is here, we worry that we are running out of time."

Ian Williams / NBC News

Staff examine a baby who has been brought to the clinic with a fever, suspected to be malaria.

The malaria parasite -- carried by infected mosquitoes from person to person -- still kills an estimated 655,000 people a year.

That's almost 2,000 a day, mostly in Africa, with children being most at risk.

If the world loses its front-line drug, the impact could be devastating.

"The nightmare scenario is that the resistance will travel," Nosten said.

"We know what will happen in Africa when resistance is bad because we've been there before in the 1990s with chloroquine (another anti-malarial drug) … millions of deaths," he warned.

"We must prevent artemisinin resistance reaching Africa, but we also need to control it for the people in Asia - for their future."

Ian Williams / NBC News

Dr Francois Nosten, right, consults staff as he meets malaria patients at a clinic near Mae Sot, Thailand.

Resistance to just about every major anti-malarial drug has started in the border regions that have been home to Nosten for more than 25 years.

Nobody knows exactly why, but poverty, conflict and large migrant and refugee populations constantly on the move all likely play a part. As do fake drugs or a failure to properly complete a course of treatment.

In the case of chloroquine, once the anti-malarial drug of choice, it took less than 20 years for resistance to spread from the borders of Thailand to Africa.

Study: Mosquitoes change habits to avoid anti-malaria nets

Nosten is worried that artemisinin resistance is growing much faster than he'd anticipated, with the drug failing initially to fully clear the parasite in more than half the cases he now sees.

"It initially goes after a few days, then it comes back. We see that more and more now," he said.

"In 2009, we still had 90 percent of patients cured. In 2010, it dropped to 60 to 70 percent. Now it's about 50 percent," he added.

Ian Williams / NBC News

Migrants from Myanmar wait to be examined at a clinic on the Thai side of the border.

Some scientists claim this is too alarmist, since the parasite does eventually die, with longer treatment and higher drug doses, but Nosten sees no room for complacency.

"We have to respond quickly, not next year or three years' time. It's now or probably it will be too late," he said.

Artemisinin comes from a Chinese plant and is quick, potent and with no side effects. Little wonder it has been hailed as a wonder drug, the golden bullet in the global fight against malaria.

What makes the resistance so worrying is that there is no new drug ready to replace it.

Nosten said that although several drugs are in development, they could be five to 10 years away from deployment "if they make it  … and we haven't got five to 10 years.”

The Shoklo Malaria Research Unit runs its own labs fashioned out of a sprawling old Thai house in the border town of Mae Sot, where teams of research scientists are working to better understand the parasite and the mosquitoes that carry it from person to person.

It is here that Chiara Andolina keeps mosquitoes that are literally hand-reared -- fed from her arm, which she extends through a mesh hole into a container of the hungry creatures every three days.

"Usually I feed around 600 of them in a cage like this," she said.

Of course these are not infected mosquitoes, though watching them settle on her arm for a good lunch is not a sight for the squeamish.

Read more international coverage from NBC News

In another room, Nosten settled over photographs showing the rapid development of the parasite once it has invaded a blood cell.

"If you can kill them very, very young -- like these -- they don't have time to develop into big fatty ones," he said, his pen jabbing at the photo. "These fatty ones are the ones that get stuck in your brain and kill you."

In other rooms, the DNA of parasites was being isolated and sequenced and drugs were being tested as part of Nosten and his team’s efforts to figure out what's behind the emerging resistance.

They are also looking for vulnerabilities and new ways to attack their enemy.

"It's hugely important to understand what's going on and contain it if we can," Nosten said. "We need to try things. We need to explore. It’s like exploring new territories in malaria."

Bazell: Malaria vaccine a half-effective, temporary protection

The French scientist has spent most of his working life in the tropics, initially with the medical humanitarian group Médecins Sans Frontières.

He believes he is engaged in a vital battle -- "a race against malaria" -- as he puts it.

After so many years on the malarial front lines, the battle has become deeply personal.

He dreams of completely eliminating this familiar but wily enemy.

However, he also knows that with the emergence of artemisinin resistance the stakes have never been higher.

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Younger adults who suffered a stroke were often smokers or had abused drugs or alcohol, according to a U.S. study that looked at over 1,000 patients.

Strokes are often thought of as a condition of the elderly, but researchers said long-term changes in the heart, arteries or and blood as a result of drug abuse or heavy drinking may put users at higher-than-average risk earlier in life.

"Substance abuse is common in young adults experiencing a stroke," wrote lead researcher Brett Kissela from the University of Cincinnati in the journal Stroke.

"Patients aged younger than 55 years who experience a stroke should be routinely screened and counseled regarding substance abuse."

It's also possible that some drugs, particularly cocaine and methamphetamines, may trigger a stroke more immediately, according to S. Andrew Josephson, a neurologist from the University of California, San Francisco, who has studied drug use and stroke but was not involved in the study.

"We know that even with vascular risk factors that are prevalent - smoking, high blood pressure... most people still don't have a stroke until they're older," he added.

"When a young person has a stroke, it is probably much more likely that the cause of their stroke is something other than traditional risk factors."

According to the U.S. Centers for Disease Control and Prevention, close to 800,000 people in the United States have a stroke every year, and they are the most common cause of serious long-term disability. One study of 2007 data found that almost five percent of people who had a stroke that year were between ages 18 and 44.

The current study involved people from Greater Cincinnati and Northern Kentucky who'd had a stroke before they hit 55.

The researchers reviewed medical charts for blood or urine test results of other records of substance abuse for close to 1,200 stroke patients.

In 2005, the most recent year covered, just over half of young adults who suffered a stroke were smokers at the time, and one in five used illicit drugs, including marijuana and cocaine. Thirteen percent of people had used drugs or alcohol within 24 hours of their stoke.

"The rate of substance abuse, particularly illicit drug abuse, is almost certainly an underestimate because toxicology screens were not obtained on all patients," said Steven Kittner, a professor of neurology at the University of Maryland School of Medicine in Baltimore who also wasn't part of the research.

The rate of smoking, drug use and alcohol abuse - defined as three or more drinks per day - seemed to increase among stroke patients between the mid-1990s and the mid-2000s.

But Kissela and his team said they can't be sure whether more people were actually using those substances or doctors were just getting better at testing for and recording drug abuse.

The study also can't prove that patients' drug or alcohol use directly contributed to their strokes. It's possible, for example, that people who abuse drugs also see their doctors less often or engage in other risky behaviors that increase the chance of strokes, Josephson explained.

He added that the study emphasizes the need to learn and quickly recognizing the signs of strokes, even in young people, since some treatments can only be used in a short window of opportunity after the stroke.

By Linda Thrasybule
MyHealthNewsDaily

Young adults who engage in pre-drinking, also called pre-gaming, are more likely to drink heavily over the course of an evening than those who don't pre-drink, a new study from Switzerland suggests.

Pre-drinking involves drinking alcohol at home or in a public place, such as a park, before going to a party or bar. Drinkers may want to achieve a "buzz" or get drunk before going out, sometimes in an effort to save money by buying less at the bar.

The study also found that those who pre-drank were more likely to suffer risky or unfavorable consequences of drinking, such as blackouts, hangovers, unplanned substance abuse or unprotected sex.

Pre-drinking is a bigger problem in the U.S. because the legal drinking age is higher than in Switzerland, said Dr. Christopher Welsh, an addiction psychiatrist at University of Maryland who was not involved with the study.

"Young adults are drinking a lot more before they go out, knowing they won't be able to drink at the bar, or party or college event," Welsh said.

The study will be published in the February issue of Alcoholism: Clinical and Experimental Research.

Pre-gaming doesn't reduce how much alcohol people drink
Some studies have reported that up to 75 percent of U.S. college students engage in pre-drinking. The studies also found that, on average, young men tend to have three to five drinks, while women have two to four drinks during a pre-drinking session.

The goal of saving money by pre-drinking doesn't usually work, Welsh said.

"People want to lower the cost of buying booze," he said. "But they tend to drink just as much as they would at the bar than if they didn't pre-drink."

So they end up spending even more money on alcohol than they initially intended, when taking into account money spent both at the bar and to drink at home.

"People should drink moderately — anywhere, anytime — and the same applies to pre-drinking," said study researcher, Florian Labhart, a research associate from the Addiction Info Switzerland Research Institute.

"It seems trivial, but having one or two drinks at the beginning of the night will still have an impact on your behavior by the end of the night," Labhart said.

In the study, 183 participants were assessed every Thursday, Friday and Saturday for five weeks. Participants received six text messages per evening, with a link to a brief questionnaire asking how much alcohol they had drunk and where they were drinking.

Researchers found that respondents were more likely to experience risky consequences on evenings when they pre-drank than on evenings when they drank only at a bar or club, or only at home. 

People who pre-drank consumed an average of seven drinks in an evening, while those who didn't pre-drink consumed only four.

Pre-drinking didn't reduce or replace the amount of alcohol people drank later in the evening, but instead increased their risk of suffering negative consequences caused by even more drinking, said Shannon Kenney, a social psychologist at Loyola Marymount University in Los Angeles who was not involved with the study.

Blackouts and hangovers were the most commonly reported consequences in the study. Respondents also engaged in substance abuse and unprotected sex.

Keeping track of your drinking
Kenney said that pre-gaming is such a popular behavior that it's unrealistic to think that young adults would stop.

So people who pre-drink should be "more mindful of pacing drinks, or eating before drinking, so they have food in their stomachs," she said.

She also recommended alternating drinking alcohol with drinking water throughout the evening.

"Early on, be aware of your internal bodily sensations," Kenney said. "You're drinking lots of alcohol, so you don't have time to assess your level of intoxication."

Welsh said parents should keep an eye on how much alcohol they keep at home.

"For high school kids, it's harder for them to get alcohol, so they’re going to drink their parent's stash before they go out," he said.

Follow MyHealthNewsDaily on Twitter @ MyHealth_MHND. We're also on  Facebook  &  Google+.

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AP

Vials of the injectable steroid product made by New England Compounding Center implicated in a fungal meningitis outbreak.

All across the country, doctors, pharmacists and hospital administrators are taking a long, hard look at where they buy drugs. The ongoing outbreak of fungal meningitis, linked to a few batches of contaminated pain injections, has added another reason to worry about the safety of patients.

More than 200 people have been diagnosed with a never-before-seen type of fungal meningitis, caused by a black mold more commonly blamed for causing sinus infections. Fifteen people are dead, many having suffered from strokes.

“It bothers me as a doctor that I don’t have faith in what I am giving,” said Dr. James Williams, an emergency room physician at St. Joseph’s Medical Center in Baltimore. “I can tell you that hospitals are looking at their stocks.”

Dr. David van Ryn, an emergency physician at Elkhart General Hospital in Indiana, agrees. “It really makes you wonder about the safety of these things, not only from an infectious diseases standpoint but also when you look at the quality control, reliability. Is it the right concentration? Does it contain what it is supposed to?” he asked.

Doctors usually don’t think much about the sourcing of the drugs they prescribe. Office-based doctors generally leave it to patients to fill their prescriptions, often through a large pharmacy benefit managers such as Express Scripts or at retail pharmacies. Hospital-based doctors rely on their hospital’s pharmacy and therapeutics committee to decide what to buy and where for patients.

The outbreak appears to have been caused by three batches of a steroid called methylprednisolone, supplied by the New England Compounding Center in Framingham, Massachusetts. Compounding pharmacies are supposed to mix up drugs to order – a special cream, for instance, or a flavored syrup. NECC, however, had shipped tens of thousands of vials.

The U.S. Food and Drug Administration doesn’t do routine oversight of compounding pharmacies, leaving the responsibility to state boards of pharmacy. Massachusetts officials say they are checking the possibility that NECC had way overstepped its license.

Centers for Disease Control and Prevention

Dr. Benjamin Park, Surveillance Team Lead, updates the Incident Manager and colleagues on CDC activities in response to the 2012 fungal meningitis outbreak.

Bonnie Levin, who heads pharmacy services at Maryland-based MedStar Health, said her not-for-profit, regional healthcare system had sometimes used outside compounding pharmacies on occasion, but has stopped since news of the fungal meningitis outbreak. “This story made us stop,” Levin said in a telephone interview.

“I think it is changing the way people look at the whole industry,” she said.

Sometimes hospitals and clinics turn to compounding pharmacies because of drug shortages. Recent shortages, which have affected cancer drugs, attention deficit hyperactivity disorder drugs and others, are not as bad this year, regulators reported last month.

As of Aug. 31, there were 123 reports of new drug shortages for 2012, about a third lower than those logged for about the same period in 2011. Last year was a record year for drug shortages in the U.S., with 267 drugs in short supply.

The FDA denies that methylprednisolone was in short supply, and says there are plenty of legitimate sources for the drug.

But the source issue may have helped encourage compounders to take on a bigger role than they traditionally filled. “In the last five or 10 years all hospital and outpatient practices have been impacted so severely by drug shortages. I would imagine some of these places will take whatever they can get,” said Van Ryn.

 “There have been times when we couldn’t get a drug from wholesalers or manufacturers,” Levin said. So hospitals bought from repackagers. Now, Levin said, hospitals may look to do more of the repackaging themselves.

“We are concerned about the industry and the regulators,” she said. “I expect these kinds of issues will come to our pharmacy and therapeutics committee.” The committee may look to some creative options for filling gaps in drug supply. “Many drugs have alternatives -- you can use product B instead of product A,” Levin said. “Another is to take product A and re-package it into the dosage form we need.”

Medstar hospitals have sterile rooms for doing this, she said, and will almost certainly start doing more of their own compounding.

And now Williams thinks twice when ordering up a drug for a patient he sees – even in a busy ER.

“It leads us all to wonder about the manufacturing process and the quality control,” he said. He was surprised to learn that compounding pharmacies don’t come under complete FDA regulation, and noted that states have real budget gaps, especially in the current economy. He wonders how they can oversee the compounders – whose role has blossomed in recent years.

Related stories:

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By Genevra Pittman
Reuters

When there was a shortage of a drug used to prevent IV-related infections in kids, the frequency of those infections increased almost ten-fold at one Michigan hospital, a new study shows.

Known as ethanol lock therapy, the preventive drug is given to kids with bowel problems who require an IV feeding line because their intestines don't absorb enough nutrients.

Those children are at higher risk of infection to begin with because their gut bacteria don't have as much practice killing off germs, researchers said.

Luitpold Pharmaceuticals, then the sole supplier of ethanol, or dehydrated alcohol, voluntarily stopped manufacturing the drug between April and September, 2011 after scrutiny of pharmaceutical facilities by the U.S. Food and Drug Administration.

The details of the production halt were not made public.

Up until early 2011, kids being treated at C.S. Mott Children's Hospital in Ann Arbor were given daily ethanol lock therapy in their catheters to prevent infection. But with the shortage, that was cut back to weekly prophylaxis for most young patients.

The new study, published this week in Pediatrics, covers eight children ranging in age from 22 months to 18 years who'd been diagnosed with necrotizing enterocolitis or other intestinal conditions requiring an IV line.

When ethanol was readily available, there was an average of one catheter-related infection per child every four years.

But when the dosing frequency dropped, seven of the eight children developed catheter-related infections in just a few months. Six of them needed to be hospitalized as a result and spent more than two weeks in the hospital, on average. Treating them cost over $100,000 per patient, and two of the youths ended up in the intensive care unit.

"We definitely had concerns that rationing (ethanol) or decreasing the amount of time we used it could lead to an increase in infection," said lead author Dr. Matthew Ralls, from Mott and the University of Michigan Medical School.

But the researchers said the spike in infections was far greater than what they'd expected.

"We had basically a complete failure in prophylaxis," Ralls told Reuters Health. "We reverted back to the numbers from before we even used ethanol."

He said he and his colleagues hope that in the future, the FDA can come to an agreement with companies that are the sole producers of important drugs to only shut down some of their production facilities at any given time, for example.

"This had a profound effect on these kids," Ralls said. "Some of the complications were pretty devastating for some of these children."

A press officer at the FDA said the agency hadn't reviewed the new study.

But, Sarah Clark-Lynn told Reuters Health in an email, "the FDA is working hard with pharmaceutical companies to prevent and resolve drug shortages. Drug shortages (are) a top priority issue for the FDA and we are working hard to help assure that patients in the United States have access to the high quality medications they need."

She added that another company, Akorn Pharmaceuticals, is now manufacturing ethanol lock therapy. "We do not anticipate any further shortage issues at this time for this drug," she said.

Luitpold did not respond to a request for comment.

Con artists posing as U.S. Food and Drug Administration agents are trying to extort money from people who buy medications online and over the telephone, the agency warned on Tuesday.

The FDA, which is charged with protecting consumers, says these fake government officials gather people's personal information from online transactions, questionnaires and consumer lists and then call them demanding fines.

The scammers tell victims that buying drugs over the Internet or telephone is illegal and threaten them with prosecution unless a fine or fee ranging from $100 to $250,000 is paid, the agency said in a statement.

"If you refuse to pay up, the caller threatens to search your properties, arrest or deport you, put you in jail, and even physically harm you," the FDA said.

The problem is being investigated by FDA agents with help from other federal agencies, including the Drug Enforcement Administration, Immigration and Customs Enforcement and the Department of Homeland Security.

Authorities acknowledge that scams of this kind are hard to trace. The crooks can sound convincing if they're armed with your address, phone number, Social Security number, date of birth, purchase history and credit card account number.

"The best thing they can do is ignore the caller and hang up," said Philip Walsky, special agent in charge at FDA's Office of Criminal Investigations. He stressed that true FDA agents do not call up consumers to demand payment.

The good news for frightened consumers is that no one is known to have been approached in person, so there is little danger of a physical threat. In fact, most of the fraudulent callers are overseas.

Nor is buying drugs online illegal, though the FDA has warned consumers that some websites peddle unsafe medicines and offered advice on how to identify trustworthy Internet pharmacies. 

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SHANGHAI/LONDON — Philippe Andre, a detective in the murky world of Chinese pharmaceuticals, has some alarming tales to tell.

Keith Bedford / Reuters

U.S. Customs and Border Protection officer Boris Sapozhnikov looks at counterfeit drugs seized by the agency on Aug. 15 at its offices at John F. Kennedy Airport in New York.

In May last year, he visited a factory an hour outside Shanghai that supposedly produced a pharmaceutical ingredient. While shown around by men wearing protective clothing and spotless hard hats, Andre noticed oddities: the floor was immaculately clean and some workers sat around idle.

The factory had an inspection log that spanned eight years with perfect record-keeping, but the handwriting was the same for all those years and not a single page was dog-eared. What's more, while the factory had equipment to dry its product, there were no connecting pipes to funnel steam or waste gases out of the plant.

"Obviously the product was not made there," said Andre, a Belgian who runs a pharmaceutical auditing firm in the eastern Chinese city of Tianjin that advises foreign drug companies buying ingredients in China. The building, he says, was just one of the "showroom" factories intended to disguise China's thriving industry in substandard and counterfeit drugs.

Four years ago, Beijing promised to clean up its act following the deaths of at least 149 Americans who received contaminated Chinese supplies of the blood-thinner heparin. But an examination by Reuters has found that unregulated Chinese chemical companies making active pharmaceutical ingredients (API) are still selling their products on the open market with few or no checks.

Interviews with more than a dozen API producers and brokers indicate drug ingredients are entering the global supply chain after being made with no oversight from China's State Food and Drug Administration (SFDA), and with no Good Manufacturing Practice (GMP) certification, an internationally recognized standard of quality assurance.

"There is falsification of APIs going on, we know it," said Lembit Rago, coordinator for Quality Assurance and Safety in Medicines with the World Health Organisation (WHO). "The regulated markets like Europe and the United States are relatively safe because they have well-resourced regulatory authorities. But the situation is different in places like Africa, where there are a lot of local medicine manufacturers who all use APIs from China."

The export of unregulated drug ingredients may be putting lives at risk, particularly in poor countries where local pharmaceutical controls are minimal. Medicines containing faulty active ingredients or the wrong dose do not work properly and can contribute to the emergence of drug-resistant strains of dangerous diseases, such as malaria.

'Crime against public health'
"We see this as a global crime against public health," said Edward Sagebiel, a spokesman for Eli Lilly and Co., a multinational pharmaceutical company that says it imposes high standards on its own products, but has seen the unauthorized production of the active ingredients for its drugs by unsupervised Chinese firms. "Because these bulk chemicals are unregulated, they are inherently unsafe."

China's dominant position in the global market for pharmaceutical ingredients makes the issue both pressing and hard to tackle.

"Illegal ingredients in bulk are a big problem, but nobody talks about it," said Guy Villax, chief executive of Hovione, an API supplier based in Portugal with factories there and in China, the United States and Ireland.

About 70 to 80 percent of all active drug ingredients — the biologically active component in medicines — originate in China and India, estimate industry experts, with China accounting for the lion's share. Its export market in these products is worth $22 billion in annual sales, according to the China Chamber of Commerce for Import and Export of Medicines and Health Products.

"If China for some reason decided to stop exporting APIs, within three months all our pharmacies would be empty," said Villax.

The risks go beyond approved drugs. Unlicensed Chinese chemical firms advertise substances that have been pulled from western markets on safety grounds, such as the weight-loss treatment rimonabant, once sold by French firm Sanofi SA as Acomplia.

Rimonabant was withdrawn in Europe in 2008 after being linked with users having suicidal thoughts, and it was never approved in the United States. Yet in August, Chinese suppliers were advertising the chemical compound online as available for export. Other unlicensed Chinese manufacturers offer active ingredients still protected by patent in western markets.

Meanwhile China's SFDA — the equivalent of the U.S. Food and Drug Administration — says foreign companies should take responsibility for standards by buying products only from properly certified exporters.

A spokesman for the SFDA told Reuters: "We hope drug watchdogs from importing countries give similar suggestions."

After the heparin scandal of 2008, Beijing issued a white paper stating that pharmaceutical companies making any APIs, not just those manufacturing APIs for a designated final product, must have a license from the SFDA. The authorities have also introduced more stringent manufacturing standards.

However, loopholes remain and legal experts say the tougher framework is not strictly enforced.

This year fake versions of Roche's injectable cancer drug Avastin appeared in the United States after transiting Europe. At the time, Roche said it was aware of many cases where counterfeiters had tried to fake other drugs in its portfolio and it was working with law enforcement agencies to stop the trade.

The precise origin of the fake Avastin remains unknown, but in June last year a Shanghai court sentenced 11 people to jail in connection with another case involving bogus Avastin.

A key regulatory weakness in China is the distinction between pharmaceutical and chemical companies. While the former are regulated by the SFDA, the latter, making everything from sweeteners to solvents, are not. Yet many chemical companies also churn out drug ingredients, exploiting a loophole by describing the products as chemicals, which they are, rather than the more specific designation of APIs.

Unregulated trade
The company New-Sensation Chemical, based in Zhengzhou, the capital of China's Henan province, is one chemical company involved in the unregulated trade. It specializes in producing peptides, a relatively complex class of compounds used in a range of drugs.

Grace Xi, a sales representative, said the company does its own manufacturing, quality control and export. While there is no suggestion its products are substandard, the firm is not GMP-certified or registered with the SFDA.

A New-Sensation product list reviewed by Reuters showed the chemical names of APIs used to treat prostate cancer, bone disease and abnormally low blood pressure, alongside growth hormones used by bodybuilders to build muscle.

The list also showed bremelanotide, touted as a female version of Viagra, which is still under testing by the U.S. company Palatin Technologies Inc. Though the drug is not yet approved for use in western markets, the product list of New-Sensation Chemical offered the active ingredient for $13 a vial.

When asked about bremelanotide, Xi said the chemical, though on the product list, was not really for sale. She said the company sold only chemical compounds, "not APIs".

Another chemical company, Jinan Hongfangde Pharmatech (JHP), of Jinan city in Shandong province, had a product list showing at least five patented products for sale. They included tiotropium bromide, a blockbuster lung drug co-promoted by Boehringer-Ingelheim and Pfizer Inc. and sold under the name Spiriva, and Eli Lilly's chemotherapy drug pemetrexed, sold under the name Alimta.

A spokeswoman for Boehringer-Ingelheim said the German group was aware there were problems with unlicensed suppliers, adding that it only bought ingredients to make its branded products from trusted sources and was rigorous on quality controls.

Pfizer and other multinational drug manufacturers, some of which have long-standing deals with respected Chinese companies, also said they were confident in their supplies and only bought from GMP-certified firms.

Allen Li, a sales representative of JHP, said his firm, which has no GMP certification and is not registered with the SFDA, was doing nothing wrong. "We do not infringe on patents, we respect the original manufacturer's research," he said.

When pressed about the production of APIs still under patent, Li said those substances were not for sale despite being advertised. He declined to answer further questions. "I'm tired of the criticism. Internet, print media, newspapers are keen to criticize," he said.

No senior executive from JHP or New-Sensation Chemical was available for comment.

Fatal consequences
The rise of the Internet has facilitated exports of drug ingredients. An online search brings up websites offering hundreds of Chinese API sellers. Those not GMP-certified or SFDA-registered are not necessarily substandard, but buyers lack independent quality assurance.

The pervasive presence of brokers in the supply line is another risk. Pharmaceutical companies looking to source APIs in China typically hire middlemen to help them navigate the language, red tape and protocol. That system helps Chinese companies making substandard APIs avoid detection.

Robert Walsh, managing director of biotech advisers Samsara Biopharma Consulting, which has offices in the United States and China, believes big-name multinational drug companies typically select Chinese suppliers on the basis of quality and core manufacturing competence, but says not all buyers are so picky, particularly low-cost generic drugmakers.

"Any number of foreign pharmaceutical companies go no further than looking for API suppliers at CPhI (an international pharmaceutical fair) based only on price," Walsh said.

Reuters spoke to brokers who said an API made by an unregulated chemical company would cost less than one from a company that had a GMP certificate.

"Different (API) grades have different prices. Sometimes we accept an order sheet and we happen to find a factory that can do it cheaper than our factory, we will outsource to them and make a bigger margin," said one broker based in China who sources for a South African outsourcing firm.

In China there are few legal repercussions for broker firms who relabel or misrepresent products, and tracing counterfeit and substandard APIs is extremely difficult.

"There are a lot of brokers who are relabeling (APIs) which means you can't trace where the API comes from and that adds to the risk," said the WHO's quality assurance expert Rago.

Andre, the Belgian drug detective, estimates he has uncovered fraud or misrepresentations in as many as 25 percent of cases where he has been hired to audit factories all over China. "If you can substitute an API that is expensive to make and manufactured at a high level with something that costs much less, then that can happen," Andre said. "It's impossible to give an exact number, but it's not rare. It's a minority, but not tiny minority."

The human cost can be high. Low-quality and fake anti-malarial drugs accounted for more than a third of samples recently analyzed in sub-Saharan Africa, according to a study in the Lancet Infectious Diseases journal in May. Separate research in the journal Research and Reports in Tropical Medicine found Chinese-made drugs to treat malaria and other common tropical infections performed particularly poorly in tests.

"I think Chinese exporters to Africa know that bad products will be less likely spotted there," said Roger Bate, resident scholar at the American Enterprise Institute, who led the second study.

Sometimes the effects of substandard medicines can be fatal: in 2006 about 100 people died in Panama after taking cough syrups containing a Chinese-made sweetener tainted with diethylene glycol, an industrial chemical used in antifreeze. Other cases, though not immediately lethal, pose long-term health threats. Earlier this year, Chinese authorities announced they had discovered millions of medicine capsules made with industrial gel containing chromium, a carcinogenic heavy metal.

Tougher enforcement
In August, Chinese authorities arrested nearly 2,000 people in a nationwide crackdown on counterfeit drugs, seizing more than $180 million worth of fake products purporting to treat illnesses ranging from diabetes to high blood pressure and rabies.

Officials are also deploying more technology. By 2015, China hopes to be able to electronically track different types of drugs from their production to end-market to prevent counterfeit and inferior drugs from being distributed, although this will only apply to products traded inside the country.

Despite these advances, legal experts and international officials still think China is not doing enough. Eli Lilly says it is unfortunate that the crackdown does not specifically target bulk pharmaceutical ingredients.

At the U.S. FDA, Commissioner Margaret Hamburg said her agency now had three offices in China and had identified a number of other products, in addition to heparin, where there could be particular "vulnerabilities".

She declined to give details, but brokers said any API with a potentially lucrative return was at risk if it could be made more cheaply by unregulated companies. Hamburg said: "We do think there's more work to be done in this area and we're very interested in working closely with China."

The United States and Europe both plan to tighten regulations to control API quality better. Washington recently approved the Generic Drug User Fee Amendments, which require inspections of foreign and domestic generic drug manufacturing facilities once every two years.

From next year the European Union will implement a Falsified Medicines Directive, putting the onus on drug companies to prove the purity of the ingredients they use, whether they are produced in Europe or imported.

These new measures will further protect western markets, where the risk of dangerous or counterfeit medicines entering the legitimate supply chain is already low. But developing countries with weak domestic regulations remain vulnerable.

Melanie Lee reported from Shanghai and Ben Hirschler from London; Additional reporting by Anna Yukhananov in Washington and Bill Berkrot in New York.

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Drugs used to control the AIDS virus can also be used to protect uninfected people, researchers concluded on Tuesday in a “last-word” review of the data.

Their report, released in the Cochrane Library, bolsters calls for policies backing distribution of the drugs to people most at risk from the virus -- including gay and bisexual men, drug users, and women in some African-American communities as well as across the developing world.

The findings also underscore the debate over how best to use scarce resources to fight the pandemic of human immunodeficiency virus or HIV, which infects 33 million people globally, including more than a million in the United States. It has killed 25 million people. There is no cure and no vaccine.

But studies are showing hope on several fronts.

“We think we are at the beginning of the end of the AIDS epidemic,” Dr. Diane Havlir, an AIDS specialist at the University of California, San Francisco, and one of the organizers of a giant, international AIDS conference being held in Washington, D.C. later this month, told reporters on Tuesday. “Over the past three years, there has been a series of breakthroughs in interventions that can dramatically curb the rate of infections with HIV.”

Work on a vaccine is promising, it’s been shown clearly that circumcising men protects them from infection, and it’s also obvious that treating infected people not only keeps them alive and healthy, but it helps prevent them from infecting others. Work is also progressing on a microbicide -- a gel that women could use to protect themselves from infected husbands and partners. And now research is also showing that giving people a once-a-day dose of the pills used to treat HIV can keep them from becoming infected in the first place.

The studies on this last approach, called pre-exposure prophylaxis or PrEP, have been mixed. So Charles Okwundu of Stellenbosch University in South Africa and colleagues studied the studies.

They looked at experiments involving more than 9,800 people around the world at high risk of becoming infected with HIV, including gay or bisexual men and sex workers. The drug tenofovir alone -- sold under the brand name Truvada by Gilead Sciences -- cut the risk of HIV infection by nearly two-thirds, while trials using Truvada with a second drug called emtricitabine, brand name Emtriva, cut the risk by 49 percent, they reported in the Cochrane Library, a journal that seeks to find the “last word” on studies.

It’s not clear why using two drugs seemed to be less effective than using just one, but the trials were done very differently and using different groups of people.

"Our findings suggest that antiretroviral drugs can reduce the risk of HIV infection for people in high risk groups," Okwundu said in a statement. "However, in the search for highly reliable HIV prevention strategies, it is important to determine how pre-exposure prophylaxis can best be combined with existing programs, as no strategy is likely to be 100 percent effective."

Okwundu’s team noted controversy over using PrEP.

“One concern is the long-term side effects of antiretroviral drugs used over many years by uninfected individuals,” they noted.

These include possible kidney damage and bone loss. In addition, if people don’t take the drugs consistently, they could develop what is known as resistant virus -- infections that defy the use of drugs. This can hurt the patients themselves, and they can also pass this resistant and hard-to-treat virus to others.

“There also are concerns that PrEP will lead to an increase in high-risk behavior,” Okwundu’s team adds. “If PrEP is not completely effective, even a partial reduction in use of safer sex could lead to an increased rate of HIV transmission.”

And the drugs are expensive -- Truvada costs more than $1,000 a month in the United States, although Gilead allows for much cheaper generic versions to be made and distributed in the developing world.

Despite the concerns, in May a panel of Food and Drug Administration advisers recommended that the FDA approve the pills for this use. Already, doctors can and often do prescribe the pills as they like, but FDA approval would clear the way for U.S. insurance companies to pay for it and for the company to promote the drug for this use.

Related stories on Vitals: 

• FDA approves first rapid, at-home HIV test
• Experimental AIDS therapy may be the beginning of the end
• Study: 1 in 900 sex acts spreads HIV

By Christina Caron
NBC News

KEY WEST -- The kaleidoscope of life in the coral reefs under the turquoise waters of the Florida Keys is a magnet for tourists, but it’s not just a pretty view.

The same chemistry that helps corals and sponges survive is also helping people fight cancer.

“What we’re doing is taking advantage of that chemistry and turning those chemicals into drugs to save lives,” said Stephanie Wear, director of coral reef conservation at the Nature Conservancy.

Wear describes the reefs as the "New York City" of the oceans, “where everything is happening,” because it is 400 to 600 times more likely to find a source for a drug in the ocean than on land -- and the densely packed coral reefs are an even more plentiful source.

But climate change and waterway pollution threaten the sea life that house these healing properties.

“The [coral reef] population is diminished by about 90 percent across the Caribbean,” said James Byrne, the marine science program manager at the Nature Conservancy.

With corals under siege, scientists at the Nature Conservancy have created coral farms --- currently supporting more than 30,000 corals across Florida and the U.S. Virgin Islands -- to sustainably harvest the life-saving properties of the reef.

“We’re taking these corals and growing them out in nurseries just like a tree farm would and replanting them back on the reef and doing it in a way that we’re really maximizing that potential for reproduction in the future,” said Byrne.

In the clear waters of the Florida Keys, scientists glue some of the corals to cinder blocks on the ocean floor, and hang others from a rope resembling a laundry line, allowing them to float in the water.  Eventually, they hope to put out up to 4,000 corals a year – all to battle some of the worst diseases known to humankind: cancer, leukemia, AIDS -- and perhaps even Lupus, Alzheimer’s, and Parkinson’s.

Arden O'Connor, a 34-year-old who lives in Boston, Mass., beat leukemia with help from Ara-C, a chemotherapy drug originally derived from sea sponges that thrive in the coral reefs.

Without it, O'Connor said, she could have died at age 26. 

“I’ve spent most of my life swimming in the ocean but absolutely didn’t assume it would have anything to do with my cancer,” said O’Connor, who has been cancer-free for seven years.  

Halaven, another drug also derived from a sea sponge, came on the market in Nov. 2010, and has improved survival among women who have metastatic breast cancer.

“Without the reefs and without doing that biodiversity conservation, we have no starting points,” said Dr. Edward Suh, who develops new drugs at Japanese pharmaceutical company Eisai, the lab that produces Halaven.

Using the chemicals present in the sea sponge saves time during the drug production process, he added. 

“In order to make this natural product a drug by synthesis, we would require over 60 steps,” he said. “And the typical drug is about 10 steps or less.”

For many doctors, the drug has proven to be an exciting option for their patients.

“Sometimes patients are interested in where the drugs come from … and it’s interesting because when you mention to them that it’s derived from a natural product they seem to be a little bit better with the concept of getting these types of therapies,” said Dr. Linda Vahdat, the director of the breast cancer research program at Weill Cornell Medical College. “For millennia there have been natural products used to treat tumors and we know it from the ancient Egyptian writings -- and certainly moving into contemporary space we use a lot of natural products to treat our patients with breast cancer.”

NBC's Mario Garcia contributed to this report.