Sam Veasna’s loss is still keenly felt in Cambodia, five years after hisuntimely death. In a desperately poor

country where most people are preoccupiedwith the daily struggle for survival, he was a tenacious field biologist and passionateadvocate for conservation whose workmade a real difference — until he fell preyto malaria.

In November 1999,Veasna ventured to theremote north of the country in search of theelusive kouprey — a wild cow that is Cambo-dia’s national animal, but which may alreadybe extinct. True to form, the kouprey evadedVeasna.But the mosquitoes didn’t.Back homein Siem Reap,where he ran the provincial gov-ernment’s wildlife office,Veasna fell ill.He wastreated with tablets labelled as mefloquine,anantimalarial drug,which should have restoredhim to health.But his fever continued to rage.

“By the time we realized what was goingon,he was slipping into a coma,”recalls ColinPoole, who heads the Asia programme of the

Wildlife Conservation Society, based in NewYork.“We organized a medical evacuation toBangkok.”But it was too late.Veasna was pro-nounced dead on 3 December, shortly beforethe plane that was to whisk him to Thailandtouched down in Siem Reap. He was just 33,and left behind a wife and three children.

Veasna was almost certainly a victim of thetrade in counterfeit drugs — bogus productsthat often contain no active ingredients,or thewrong ones. Cambodia can ill afford to see itsbrightest lights snuffed out in this way,havingalready lost a generation of intellectuals in the1970s to the genocidal Khmer Rouge regime.Yet a criminal investigation into Veasna’sdeath soon collapsed through lack of evidence— the offending tablets had been thrownaway. If he hadn’t been internationallyrenowned, things would probably never evenhave got that far.Many ordinary Cambodiansare thought to suffer a similar fate each year,their deaths gaining scant media attentionand prompting no official response.

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In his office at the Hospital for Tropical Diseasesin Ho Chi Minh City, Vietnam, Jeremy Farrartosses me two blister packs of tablets on which the name ‘Guilin Pharma’ is printed in blue. The company’s factory in Guangxiprovince, southern China, is the leading sourceof artesunate, a highly effective treatmentagainst malaria.

One of the packs doesn’t look quite right.The printing seems slightly washed out. And,tellingly, its security sticker is revealed on close scrutiny not to be a hologram, but a piece of shiny foil with a printed pattern. Afterexamining the two, I’d be fairly confident ofspotting the fake if I was offered it over apharmacy counter.

Unfortunately, the fake artesunate circulatingthroughout southeast Asia today is much harderto detect. Paul Newton, who is studying theproblem of counterfeit drugs in the region from

Across the developing world, people are dying after being peddled fakepharmaceuticals. Peter Aldhous reports from southeast Asia, wherescientists, doctors and regulators battle against organized crime.

Murder by medicine

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Hologram wars

Black market:illicit medicalsupplies for salein Phnom Penh.

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No one knows how many deaths in thedeveloping world can be blamed on fakepharmaceuticals. But thanks to the diligenceof researchers who are monitoring the effec-tiveness of malaria treatments, we now doknow that the trade in counterfeit antimalar-ial drugs is rife across southeast Asia. Scien-tists are battling the menace of fake drugs byraising awareness among doctors and theirpatients, and running lab tests to screen forcounterfeits. But there’s only so much theycan do. Next week in Paris, at the 2nd GlobalForum on Pharmaceutical Anticounterfeit-ing, experts will try to plot the way forward.It’s already clear that this will require morerigorous efforts to crack down on the ruth-less criminals who profit from the trade inbogus drugs.

Innocent victimsThe alarm about fake antimalarials began tosound just months before Veasna’s death. In1999, Jan Rozendaal, who then ran the Euro-pean Union’s Cambodia Malaria ControlProject, began to hear reports of patientswho failed to respond to treatment with arte-sunate. This drug, derived from a Chineseherb, is highly effective against forms of themalaria parasite that resist earlier genera-tions of antimalarials — particularly whenused in combination with mefloquine. So ifthe parasite was evolving resistance to arte-sunate, it would have been a major blow.

But the problem wasn’t drug resistance.Those who failed to respond to artesunate hadbought suspiciously cheap supplies fromsmall commercial pharmacies. So Rozendaalcollected his own samples from similar out-lets, and sent them for analysis to the ThaiMinistry of Public Health1. The drugs weresold in blister packs bearing the name ofGuilin Pharma, a company in China’sGuangxi province. But about half the packs

contained dummy pills withno active ingredient. Closeinspection revealed subtledifferences in the packagingthat distinguished them fromthe genuine Guilin product.It was a similar story for bot-tles of mefloquine tablets,purportedly manufacturedin Australia. In this case, thefakes had carved out a domi-nant market share.

Disturbed by his find-ings, Rozendaal contactedNick White, a leadingmalaria researcher at theUK Wellcome Trust’s unit at Mahidol University inBangkok. The trust has units and collabora-tors across southeast Asia,so White was able toextend Rozendaal’s investigation to cover theentire region. Over a year, ending in August2000, volunteers purchased artesunate inCambodia, Laos, Myanmar, Thailand andVietnam. Of a total of 104 samples boughtmore or less at random,38% were found to befakes containing no active ingredient2.

The researchers hoped their survey wouldraise awareness of the problem,and they sub-sequently called for international action toclamp down on the counterfeiters3. But a fol-low-up study, which concluded in February2003, revealed that the situation had actuallyworsened. This time, 53% of 188 artesunatesamples were useless fakes4.Worse, the coun-terfeiters had upped their game, improvingtheir mimicry of the Guilin packaging to thepoint that the fake packs were virtually indis-tinguishable (see ‘Hologram wars’,below).

Back in 2000, many pharmacists proba-bly knew they were selling knock-offs, saysArjen Dondorp, a clinician at the WellcomeTrust’s Bangkok unit, who coordinated

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the second survey.“They’dsay: ‘This is a little bit less effective, but it’scheaper.’” In Cambodia,where the average annualincome is about US$300and a course of arte-sunate sells for aboutUS$1.50, that was anespecially compellingsales pitch. Today,Dondorp suspects thatsome pharmacists arebeing duped as well,and the price differ-ence between genuineand fake artesunatehas all but disap-

peared. “It’s clearly organized crime, andhighly sophisticated,”says Dondorp.Sophis-ticated, maybe, but callous in the extreme.“You can think of it as attempted murder,”he adds.

StreetlifeIn December, I visit the Cambodian capital,Phnom Penh, to get a feel for the environ-ment in which this trade flourishes. Thereare many reminders that this is one of Asia’spoorest countries: at one junction, peopleare picking through piles of garbage for any-thing that might be reused. I wander thestreets, searching out the city’s small phar-macies. Most consist of a single open-fronted room, separated from the street by a simple counter. Packages of drugs line thewalls inside. At each, I turn up with a scrapof paper on which I’ve written “artesunateor mefloquine” or “tetracycline”. The last ofthese drugs is an antibiotic deployed againsta variety of bacterial infections; it is alsoused, together with quinine, to treat malaria.

For someone used to the controlled

his base at the Mahosot Hospital in Vientiane,Laos, has documented seven distinct types offake ‘Guilin’ artesunate. The counterfeiters soonbegan to incorporate security stickers bearing a real hologram, albeit a crude example. And the holographic stickers on the latest fakes, ifanything, look more professional than the genuine version. Only an expert could reliably tell the two apart.

Yet it doesn’t have to be that way, according to David Pizzanelli, sales and marketing manager

with Light Impressions, a holography firm inLeatherhead, near London. “The main problem is that the genuine hologram is terrible,” he says.Depicting the limestone hills that surround the cityof Guilin, plus a few Chinese characters, it haslittle three-dimensional relief. A passable imitationcould be knocked up by more than 200workshops worldwide, says Pizzanelli. And at lessthan 15 millimetres across, the sticker is way toosmall. Surveys for credit-card companies haveshown that security holograms need to be at least

twice this size if people are not to be fooled bycrude imitations.

The answer, argues Pizzanelli, is to incorporatea more complex, repeating hologram into the foilof the blister pack itself. There are fewer than adozen companies worldwide who could supplysuch a security feature, making life extremelydifficult for the counterfeiters. But this couldrequire an investment running to millions ofdollars. And without clear evidence of how muchrevenue is lost as a result of counterfeiting, it’shard for cautious drug-company executives tojustify spending such sums.

Lucy Jiang, who is responsible for internationalaffairs at Guilin, says the company is talking tothe World Health Organization and other expertsabout ways to protect its product fromcounterfeiting. But it has no plans to introduce a much more sophisticated hologram. “The costis so high that we cannot bear it,” says Jiang. P.A.

Cambodia’s health agencies are runningawareness campaigns on fake drugs.

Copycats:(from left) thehologram on agenuine pack ofGuilin Pharmadrugs, a silverfoil copy, and aconvincing fake.

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environment of a typical Western pharmacy,this shopping trip is an eye-opening experi-ence. Over two days, I visit a total of 27 outlets. Only once am I asked about the con-dition the drugs are supposed to treat. “It’sfor a friend with a fever,”I say, before enquir-ing about the dose. The pharmacist says thatmy friend should take three tablets of tetra-cycline each day. But for how long? She scru-tinizes the Khmer language informationsheet supplied with the antibiotic, whichdoesn’t seem to help.“As long as you like,”sheeventually suggests — vague advice thatcould place patients at risk, and promote thespread of drug resistance.

Faking itAs I pocket the packages, I contemplate theodds of them being genuine. Two officialsurveys conducted by the Cambodian Min-istry of Health, with the backing of theWorld Health Organization, have shed somelight on this question. National drug-testinglabs in Phnom Penh and Bangkok looked at 230 samples of 24 pharmaceuticals pur-chased on the Cambodian market in 2000,including antibiotics and painkillers. Theyfound about 3.5% of them contained lessthan 60% of the labelled quantity of activeingredient5. When the survey was repeatedfor a wider range of drugs purchased in2003, 11% of the samples fell into this cate-gory6. Both surveys also turned up a smallnumber of products that contained thewrong ingredient.

Some of these problems may representshoddy manufacturing,rather than conscious

criminality.But ominously,the team that ranthe second survey was unable to find any offi-cial record of the existence of five of the com-panies whose drugs they found on sale inCambodia. ‘Brainy Pharmaceutical’, forinstance, is supposedly based in Thailand,but is not registered with the appropriateauthority in Bangkok. Its tested productsincluded fake antibiotics with no activeingredients.

Chroeng Sokhan, vice-director of theCambodian health ministry’s Department ofDrugs and Food, is trying to prevent bogusmanufacturers from operating quite sobrazenly in his country. His department,based in a run-down building in a shabbyside street of Phnom Penh, hasheld workshops to educateretailers, and distributedposters warning of thedangers posed by counter-feit drugs — includingsome with photographs ofknown fakes. “Those prod-ucts are harder to find on themarket now,”says Sokhan. Inrecent weeks, the anti-coun-terfeiting campaign hasextended to broadcast-ing adverts on state-run television.

These activi-ties have relied

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heavily on foreign aid, as do most efforts tocombat drug counterfeiting in Cambodia.The US Pharmacopeia, a non-governmentalbody that develops standards to ensure drugquality, is working in the country with fund-ing from the US Agency for InternationalDevelopment. Focusing on malaria drugs, ithas already turned up samples of Brainy-branded quinine that — like the bogus com-pany’s antibiotics — don’t contain any of thecorrect active ingredient.

Part of the strategy has been to involveprovincial officials in testing drug samples,sothat they take ownership of the problem.

“They were very surprised whenthey found fake drugs in theirprovinces,” says Lon Chantap, aresearcher at the National Cen-

ter for Parasitology,Entomol-ogy and Malaria Control inPhnom Penh, who works on

the project.Testing the quality ofdrugs is usually the

preserve of large, well-funded nationallaboratories. Butthe US Pharma-

copeia’s project isalso using a ‘minilab’

developed by the GermanPharma Health Fund, acharity financed by thatcountry’s drug industry.

This portable kit allows localtechnicians to analyse pharmaceutical

ingredients using simplified versions of

Mean streets: the impoverished population of Phnom Penh makes an easy target for criminals selling fake pharmaceuticals.

This ‘minilab’ allowsusers to check whetherdrugs are genuine.

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techniques such as chromatography7. At the US Centers for Disease Control and Prevention in Atlanta, Georgia, analyticalchemist Michael Green is similarly workingon cheap drug-testing methods, including ared dye that turns yellow in the presence ofartesunate8.

But in Cambodia,problems thrown up bygrinding poverty run deeper than the abilityto afford good drug-quality tests. Qualifiedstaff are few in number and poorly paid.Sokhan can call upon just 13 national inspec-tors to police the country’s entire drug sup-ply. As the sun sets, he takes me for a drivethrough the streets that surround PhnomPenh’s Olympic Market, which are packedwith small pharmacies and wholesalers thatsell drugs on to retailers in the provinces.Many, says Sokhan, are unlicensed outlets,and their continued existence is obviously a major source of frustration for him.“Unbelievable,” Sokhan mutters, as we turnback towards the main road.

The next morning I continue my shoppingtrip.My final haul consists of five blister packsof Guilin-branded artesunate, some loosecapsules of mefloquine, and five samples oftetracycline.In addition,I havethree packets of a productcalled Malarine, whichincludes both artesunateand mefloquine pills and is distributed byPopulation ServicesInternational. Thisnonprofit body inWashington DCtackles problemswith health and fam-ily planning in the devel-oping world by placingaffordable products into thecommercial sector. At leastthese should be OK, I muse, before sendingthe samples to Green for testing.

Clean sweepAll of my drugs turn out to contain roughlythe right quantities of active ingredients,and so seem to be genuine. Given that someof the pharmacies I visited carried Sokhan’sposters, perhaps the campaign is havingsome effect. But Sokhan and other expertswarn against reading too much into theseresults. As a wealthy Westerner, my sourcessuggest, I am more likely to be sold genuinedrugs than a typical Cambodian customer.Perhaps if Veasna had been one of the manytourists who flock to Siem Reap to visit theancient temples of Angkor, he would still bealive today.

For anyone familiar with Western prac-tices of drug regulation,the solutions to Cam-bodia’s problems with fake drugs seem clear:get police and customs officials to crack downon the distribution chain, allow only licensedpharmacists to continue operating, and close

any pharmacy caughtselling counterfeit prod-

ucts.But Sokhan says thathis department doesn’t

have the power toenforce such mea-

sures. “We can dothings only step

by step,”he says.“It’s not easy.”

Sokhanwon’t be pressed

into further explanation, butRozendaal is frank about the

obstacles to progress. Corruption isendemic in Cambodia,he says,and the

distributors of counterfeit drugs are pro-tected by powerful figures in the govern-ment. Now working as a consultant inIndonesia,Rozendaal is free to speak out.Butwhen he raised the alarm about fake drugs inCambodia while running the EuropeanUnion’s malaria project, Rozendaal felt hisjob was threatened as spurious complaintsabout his competency reached his bosses inBrussels. For local officials, the stakes couldbe even higher.“You really take a big personalrisk,”says Rozendaal.

In some neighbouring countries, lawenforcement is more rigorous. In Laos, forexample, some pharmacies have been closed down. And as an example of what’spossible, experts point to Nigeria, where one influential woman has made a coura-geous and effective stand against pharma-ceutical counterfeiting (see ‘In the line offire’,page 134).

But counterfeit drugs will continue toplague southeast Asia until the problem isdefeated at its source. That means targetingthe factories that are producing the fakes,which are mostly thought to be in China.This, in turn, will require pharmaceuticalfirms and governments to exert pressure onthe Chinese authorities. Some progress isbeing made, says Joe Damond, deputy vice-president for international affairs withPhRMA, the trade body that represents theUS drug industry. Regulations designed tocombat drug counterfeiting have recentlybeen strengthened,he says.

The acid test will be how these are implemented. So far, Chinese drug counter-feiters have mostly been handed modestfines that they can write off as a cost ofdoing business. As a result, some organizedcriminals are believed to have shifted theiractivities from narcotics, where sentences are severe and include the death penalty, tofake pharmaceuticals. Those who mournVeasna’s death can confirm that this newtrade is equally murderous. And they are still waiting for his killers to be brought to justice. ■

Peter Aldhous is Nature’s chief news & features editor.1. Rozendaal, J. A. Lancet 357, 890 (2001).2. Newton, P. et al. Lancet 357, 1948–1950 (2001).3. Newton, P. N., White, N. J., Rozendaal, J. A. & Green, M. D.

Br. Med. J. 324, 800–801 (2002).4. Dondorp, A. M. et al. Trop. Med. Int. Health 9, 1241–1246 (2004).5. Study Report on Counterfeit and Substandard Drugs in Cambodia

(Cambodian Ministry of Health, Phnom Penh, 2001).6. Second Study Report on Counterfeit and Substandard Drugs in

Cambodia (Cambodian Ministry of Health, Phnom Penh, 2004).7. Jähnke, R. W. O. Pharm. Ind. 66, 1187–1193 (2004).8. Green, M. D., Mount, D. L., Wirtz, R. A. & White, N. J. J. Pharm.

Biomed. Anal. 24, 65–70 (2000).

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Life or death? A selection of drugs (below) bought from street pharmacies in Phnom Penh.

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