Alcohol takes its toll on Europe's youth.

News Medicines for all, not just the rich March brought bad news for the HIV virus, but good news for HIV/AIDS patients, particularly those in poor countries. In the second week of the month, Merck and Co., a leading US pharmaceutical manufacturer, announced it would slash the prices of two of its antiretroviral drugs, indivar (Crixivan) and efavirenz (Stocrin), by 90% to US$ 600 and US$ 500, respectively, per patient per year. The price cuts would be extended, Merck said, to all developing countries provided they could guarantee that the low-cost drugs wouldn’t be re-exported. At about the same time, another drug firm, GlaxoSmithKline, which produces 40% of the world’s anti-AIDS drugs, said it would make cut-price AIDS drugs available to any not-for-profit organizations with the capacity to deliver them in developing countries. And the ball kept rolling: yet another US pharmaceutical manufacturer, Pfizer, announced it would distribute the antifungal drug fluconazole (Diflucan) — used to treat AIDS-related meningitis and fungal infections — free of charge in South Africa up till December 2002. Then on 15 March came an offer by the New York-based pharmaceutical company Bristol-Myers Squibb to reduce the prices of two of its antiretroviral drugs, stavudine (Zerit) and didianosine (Videx), to a com- bined price of US $1 per day and to relax its patent protection over Zerit in South Africa. The offer would allow South African-based drug companies to produce and market the drug at low cost. The surprise announcement followed protests from students at Yale University in the United States where stavudine was developed. The university holds the patent for this drug and allows Bristol-Myers Squibb to produce it on licence. What triggered this price avalanche? Certainly, the curtain was raised on this new scenario by the dramatic February offer of the Indian drug company Cipla to sell governments a cocktail of three antiretroviral drugs for US$ 600 a year — a fraction of the US$ 10 000–15 000 price tag for this triple therapy in the United States and other countries in the west. Certainly, Cipla’s offer turned the focus from country-by-country negotiations to across-the-board price reductions aimed at the poorest countries. And for sure, these reductions are part of a broader process which combines pressure from nongovernmental organizations, political will, market forces and close colla- boration between the pharmaceutical indus- try and international organizations to make wider access to AIDS medicines a reality. Meanwhile, another Indian manufacturer of generic drugs is reportedly offering triple antiretroviral therapy for US$ 350 a year. ‘‘This is not about profits and patents. It’s about poverty and a devastating disease,’’ said Mr John L. McGoldrick, executive vice president, Bristol-Myers Squibb. ‘‘We hope our initiatives can be of some help to African AIDS sufferers and may help energize and accelerate world understanding and action.’’ Cipla’s offer catapulted it into the centre of an international squall over the production of low-cost copies of expen- sive AIDS drugs, since it is far from clear which countries can import and sell generic drugs without breaking existing trade agreements granting exclusive rights to patent-holding companies. The squall is fuelled, among other things, by mounting international concern over the high price of many essential drugs — but especially antiretroviral drugs for the treatment ofHIV/AIDS—which puts them beyond the reach of the poorest countries where they are needed most. Of the over 36 million people living with HIV/AIDS, less than 10%have access to lifesaving drugs. Of the 25 million Africans living with HIV, only around 10 000 currently receive proper medical care. Under an international trade agreement known as TRIPS — an acronym for Trade Related Aspects of Intellectual Property Rights — new drugs can be patented for up to 20 years. This gives manufacturers exclusive marketing rights throughout that period at a price set by them.However, under exceptional circumstances — in the event of a national emergency, for example — TRIPS allows signatory states to pass national laws enabling them to bypass patents and to produce or import cheaper versions of a patented drug. Taking advantage of this possibility, the South African government passed a law in 1997 that enables it to import cheaper versions of AIDS drugs for the 4.7 million South Africans now living with HIV/AIDS. The law has never been enacted because in the following year the pharmaceutical in- dustry initiated legal action to overturn it on the grounds that it is too broad and contra- venes international trade agreements. The action has culminated in a high-profile court case due to start in April in the South African capital, Pretoria, with 39 international pharmaceutical companies challenging the South African government. In a press statement, the International Federation of Pharmaceutical Manufac- turers’ Associations (IFPMA) warned that any loss of patent protection would threaten research and that price reductions would do little to improve access to AIDS drugs unless national governments and donors increased funding. The IFPMA’s director general Dr Harvey Bale Jr said: ‘‘The international pharmaceutical industry firmly believes that the weakening or infringement of intellectual property rights as reflected in the inter- national trade agreements amounts to a disincentive for investment and research and development, and that factors other than intellectual property rights are at the root of the problems of access to medicines.’’ The Geneva-based World Trade Organization agrees that ways must be found to improve access to essential drugs in low-income countries but maintains that drug companies must be given incentives to develop new drugs, which can each cost as much as US$ 500 million to produce. ‘‘Were it not for a patent system that rewards companies for risking millions on research,’’ Mr Mike Moore, director-general of the World Trade Organization, wrote in a recent editorial in the International Herald Tribune, ‘‘anti-AIDS drugs would not exist.’’ The British charity Oxfam is cam- paigning for a change in world trade rules to drastically widen access to essential drugs.Mr Kevin Watkins, Oxfam’s senior policy ad- viser, maintains that differential pricing by the pharmaceutical companies on a product-by-product and country-by-country basis is too limited and not the answer. ‘‘What is needed,’’ he told the Bulletin, ‘‘is a system of differentiated patents, with improved safeguards built in to ensure that the public interest comes first and corporate interest second.’’ Oxfam argues that public investment and international cooperation — not extended patents — should be used to finance research. The charity is calling for a US$ 5 billion international fund to be established, under the auspices of WHO, to support a global network of public research institutions dedicated to developing new 377Bulletin of the World Health Organization, 2001, 79 (4) # World Health Organization 2001 medicines and vaccines. Oxfam also wants to see an international fund established to subsidize drug purchases and delivery systems in the poorest countries. In Norway this month (April) about 50 experts from around the world are meeting at a workshop organized by WHO and the WTO to discuss differential pricing as a means to ensure that the poor have access to essential drugs without under- mining the international patents system — a system that gives pharmaceutical manu- facturers an incentive to develop new drugs. However, even at heavily discounted prices, many drugs still remain way beyond the means of low-income countries. WHO’s director-general, Dr GroHarlem Brundtland, says that no matter how low prices go, additional funding — in the form of development assistance and debt relief — will be needed to meet the costs of care for the poorest: ‘‘The private sector is showing it is willing to do its part to fight the HIV/ AIDS epidemic. The onus is now on governments and international organizations to make sure the funds to pay for these drugs are made available and that health systems are strengthened so that they are able to provide the care needed. We are talking about a 500-fold increase in care that could translate to as much as US$ 10 billion per year. This is a great challenge for all of us.’’ n Sheila Davey, Geneva, Switzerland Lifestyle and Alzheimer disease — study strengthens link African-Americans living in an industrialized UScity aremore than twice as likely todevelop Alzheimer disease and other dementias than are Africans living in Nigeria, according to a study published in the 14 February Journal of the American Medical Association. The ten-year study, a collaborative effort of researchers from both countries, compared the incidence rates of Alzheimer disease (AD) and other dementias in people over age 65 in Indianapolis, Indiana, in the US, and in Ibadan, Nigeria. A baseline survey identified 2147 African-Americans in India- napolis and 2459 Yoruba residents of Ibadan who did not have dementia. Follow-up studies at 2 and 5 years found that 2.52% of the African-Americans eventually developed AD, compared to only 1.15% of the Yoruba; overall, 3.24% of the African-Americans developed any form of dementia (including AD), compared to 1.35% of the Yoruba. The rates found among the African-Americans are in the ‘‘higher range of previously published’’ rates, while the rates found in the Yoruba are among the lowest, reported the study’s principal investigators, Dr Hugh C. Hendrie of the University of Indiana School ofMedicine in theUS andDrAdesola Ogunniyi of the University of Ibadan. The researchers did not draw conclu- sions as to why the disease rates varied, but postulated two factors: genetics and lifestyle. They found that a gene (apolipoprotein E), known to raise the risk of Alzheimer disease, occurred with equal frequency in the two groups. However, ‘‘in the African-Americans the gene is definitely increasing the risk for Alzheimer disease, while in the Nigerian group it doesn’t seem to have an effect,’’ Dr Frederick W. Unverzagt, a co-author of the study, told the Bulletin. As for possible lifestyle influences, the study found that the Yoruba have a ‘‘much lower prevalence’’ of vascular risk factors — lower cholesterol levels and fewer cases of diabetes and hypertension— than the African-Americans. ‘‘Maybe the incidence numbers can be explained by a gene–environment inter- action,’’ says Unverzagt. ‘‘It could be that the ApoE gene is just not activated in certain environments.’’ Follow-up studies, he says, will examine diet, activity levels, and social engagedness. ‘‘If factors like diet are found to influence the disease,’’ says Unverzagt, ‘‘the public health implications could be tremendous. If modifying such factors could delay the onset of Alzheimer by 5 to 10 years, you could really forestall some of the looming public health problems posed by the disease.’’ The study is believed to be the first cross-cultural study of dementia to use the same methodology and the same group of researchers at different sites. Previous studies have compared rates from different countries, but drawing conclusions from such comparisons is often difficult because of methodological differences. ‘‘Such cross-cultural studies are extremely difficult to do,’’ Dr Denis Evans, director of the Rush Institute for Healthy Aging, in Chicago, commented to theBulletin. ‘‘They’ve done a magnificent job with that. They carried out the same procedures 4000 miles apart. This is very encouraging for people who have thought about doing this sort of work.’’ In an accompanying editorial, Dr Lindsay Farrer of the Boston University School of Medicine, Massachusetts, says ‘‘preliminary evidence suggests that a high-fat diet may increase the risk of developing’’ Alzheimer disease and ‘‘studies have revealed that [Alzheimer] cases are less active physically than controls in early life.’’ Currently, though, most experts say that the only established risk factors are genetics and increasing age. n Catherine Dold, Boulder, Colorado, USA US health care takes a battering The United States’ health care system fails to deliver consistent, high-quality health care to its citizens, and without a major overhaul the problemwill continue, according to a new report from the Institute of Medicine (IOM) of the US National Academies. The report outlines the problems hobbling the country’s health care system and describes changes necessary to fix it. ‘‘The American health care system offers the sophistication of a space station delivered with the efficiency of a third-world post office,’’ says Dr Lucian L. Leape, a physician at the Harvard School of Public Health and amember of the IOM committee that drafted the report. The report blames ‘‘a highly fragmented delivery system that largely lacks even rudimentary clinical in- formation capabilities’’ for the gap between the calibre of care possible and the quality typically delivered. The committee also criticizes a health care system that ‘‘frequently falls short in its ability to translate knowledge into practice and to apply new technology safely and appropriately.’’ The shortcomings the committee found aren’t unique to theUS.Dr Tessa Tan-Torres Edejer, with WHO’s Global Programme on Evidence for Health Policy, says: ‘‘The few data that we have suggest that the same problems exist in just about every country, with some countries relatively worse, and some better off. Invariably, the countries that look for problems, find them.’’ Australia and Mexico are two countries she recalls that conducted recent studies revealing malfunc- tioning areas of their health care delivery systems. ‘‘There are probably many others but these are not reported in the scientific press because they aremeant for internal use.’’ The problems of the US health care system can’t be resolved without a complete overhaul of the current system, the IOM committee argues. ‘‘The current care system cannot do the job. Trying harder will not work. Changing systems of care will.’’ To this end, the committee established a list of guidelines for improving health care in the US. These include a shift toward patient- focused care. ‘‘Right now the system is designed around what doctors can deliver, rather than on the care that patients need,’’ says Leape. The report says patients must be given greater control over their care, and greater access to current health information. The report also calls for better communication between health care practi- tioners. ‘‘The big secret about the American health care system is that no-one is in charge,’’ Leape told the Bulletin. He says the current system consists of separate care 378 Bulletin of the World Health Organization, 2001, 79 (4) News givers who work as individuals rather than as groups, and this lack of communication means that care is often duplicated or second-rate. The report calls for health care providers to make greater use of information technologies, such as the internet, to better coordinate patient care and increase effi- ciency. Other priorities include keeping providers informed about current scientific knowledge and providing health care for the nation’s 40 million uninsured citizens. In addition, the committee urges US government agencies to identify at least 15 of the most common chronic conditions and develop strategies for managing them over the long term. ‘‘We need to shift the focus to managing chronic disease instead of merely treating single episodes in isolation,’’ Leape says. ‘‘The obvious question now is: Who is going to make this happen? We’ve asked for the allocation of funds to begin making these changes. But whether that happens or not is a political decision. It’s unclear what will happen in the current political climate.’’ WHO’s Tan-Torres Edejer adds that all countries would like to have a health system that provides seamless top-quality service wherever the patient accesses the system, from the family physician to the high-tech hospital. ‘‘However, I don’t know of any country that has reached that ideal. Perhaps the US, with its capability and penchant to use management models from other sectors, like the error reporting system in the aviation sector, and to take advantage of the latest technology, has the potential to get close to that ideal. But as the IOM reports, even the US system has still a long way to go.’’ n Christie Aschwanden, Nederland, Colorado, USA In Brief New partnership boosts work on malaria vaccine for children The pharmaceutical giant GlaxoSmithKline (GSK) has teamed up with the US-based Program for Appropriate Technology in Health (PATH) to develop a malaria vaccine for use in children. PATH will inject US$ 6.7 million into the partnership’s work on the vaccine, which GSK initiated in 1983. The vaccine consists of a malaria parasite protein fused to a fragment of the hepatitis B virus. In a field trial in 1998–99 in West Africa, it conferred short-term protection on adults: about two-thirds of the vaccinated volunteers were protected for up to 8 weeks after vaccination. n Further information from Anne P. Walsh, GSK, Rixensart, Belgium: tel +32 (2) 656 9831; PATH Malaria Vaccine Initiative, Rockville, MD, USA: tel: +1 (301) 770 5377, fax: (301) 770-5322, email: <info@malariavaccine.org>, web site: www.MalariaVaccine.org Update on depleted uranium tests A group of experts reported in March to the European Commission that exposure to depleted uranium could not result in detect- able damage to human health. Another report, however, issued in the same month by the UN Environment Programme (UNEP), said that although tests had shown ‘‘no significant risks... of contamination to air or plants’’, depleted uranium ammunition buried in the soil could produce a 10- to 100-fold increase in uranium levels in drinking water that might exceed WHO health standards. n Further information from Melinda Henry, WHO: tel: +41 (22) 791 2535; fax: +41 (22) 791 4858; email <henrym@who.int>; web site: <www.who.int> Multiple sclerosis and hepatitis B vaccine — no evidence of link Two large US studies that since 1976 and 1989, respectively, have monitored health-related events in a total of about 140 000 nurses, have found no association between hepatitis B vaccination and the development of multiple sclerosis. Rumours of such a link were mooted several years ago in France andmore recently in theUS. n Further information from <http://www.nejm.org/ content/2001/0344/0005/0327.asp> 379Bulletin of the World Health Organization, 2001, 79 (4) News WHO News Alcohol takes its toll on Europe’s youth Whether it is drinks or drugs — getting high seems to be increasingly popular among European teenagers. In most European countries, today’s 16-year-olds consume more alcohol, cannabis and other drugs than ever. And they’re paying a price. Alcohol is to blame for one in four deaths of young European men aged 15 to 29. These bleak findings were presented in late February at the European Ministerial Conference on Young People and Alcohol in Stockholm, where WHO and the Swedish government had convened European health ministers, other high-ranking decision-makers and young citizens from 51 European countries to discuss the impact of alcohol and drugs on the health of Europe’s coming generations — and to sketch out a region-wide action plan to keep them ‘‘safe and dry.’’ Concerted measures are necessary, says Dr Cees Goos, the coordinator of WHO’s Alcohol, Drugs and Tobacco Unit in Copenhagen, because ‘‘the alcohol industry is out to aggressively infiltrate their future market. They’re sponsoring fun events, they put their banners on web pages, they’re trying everything to get at young people.’’ And they seem to be getting results, if the findings of the 1999 European School Survey Project on Alcohol and other Drugs (ESPAD), which were presented in Stock- holm, are anything to go by. Conducted by the Swedish Council for Information on Alcohol and Other Drugs (CAN), the ESPAD project collects data by question- naire survey on alcohol, tobacco and drug use among 15–16-year-old high school students in 30 European countries. Altogether, nearly 100 000 students participated in the 1999 survey. According to the report, binge drinking, that is, having five or more drinks in a row, has increased by 21% to 55% in almost half of the countries; heading the list is Slovenia, where the number of binge drinkers has more than tripled. As in 1995, when the first ESPAD was conducted, alcohol use among youngsters is still most prevalent in Denmark, Ireland and the United Kingdom, where between 36% and 51% of the teenagers had imbibed alcohol 20 times or more within the last 12 months. Not surprisingly the frequency of drunkenness has also increased. Among the countries with the highest alcohol intoxication rates, the proportion of 16-year-olds who were drunk three times or more within the last 30 days rose from 21% to 30% in Denmark and from 15% to 24% in Ireland, while rates in Finland and the United Kingdom remained largely unchanged at about 18% and 24%. What’s more, illicit drug use also rose by 20–400% in the 30 countries as a whole. The largest increases occurred in central and eastern Europe, such as in Lithuania, where illicit drug use rose about fivefold. But the highest prevalence rate, more than 30%, is still found in western European countries, such as the UK and Ireland. With respect to cannabis, for instance — by far the commonest illicit drug consumed — the Czech Republic is now on a par with as the UK’s and France’s 35% of lifetime users, closely followed by Ireland, with 32%. For Dr Bjo¨rn Hibell, CAN director and coordinator of the survey, the numbers indicate that the situation has deteriorated since 1995. ‘‘Overall, young people simply consume more drugs today,’’ he says. And WHO’s Goos adds, ‘‘There seems to be a change in the way young people drink. Binge drinking is becoming more and more popular. And that’s not particularly good for public health, to put it mildly, because there are strong links between high-risk drinking like binge drinking, violence, unsafe sexual behaviour, and traffic and other accidents.’’ Data also presented at the meeting from the ongoing Global Burden of Disease 2000 Study by Ju¨rgenRehmof theAddiction Research Institute in Zu¨rich, Switzerland, illustrate just how strong the links really are. Altogether, more than 57 000, or one in four, Europeans between the ages of 15 to 29 died in 1999 from causes related to alcohol use, such as transport accidents, poisonings, self-inflicted injuries and homicide In parts of eastern Europe the figure is even as high as one in three young men. (A similar study in the US, published in the March issue of Alcoholism: Clinical and Experimental Research, foundmotor vehicle crashes to be the leading cause of death for 15 to 20-year old Americans — and more than a quarter of them had been drinking beforehand.) Yet another study, the European Comparative Alcohol Study (ECAS), found that ‘‘more is worse,’’ that is, the higher a country’s per capita alcohol consumption, the higher its alcohol-related mortality rate. And in a further blow to alcohol’s already tainted reputation the ECAS study could not find any evidence that moderate alcohol consumption protects from heart disease. ‘‘There are a lot of myths about the positive effects of wine drinking,’’ says Goos. ‘‘But based on these data there’s no way that you could recommend drinking even low amounts of alcohol to prevent heart disease.’’ n Michael Hagmann, Zurich, Switzerland In Brief WHO airline meeting sparks deep thrombosis research A mid-March meeting of experts and airline representatives convened by the WHO concluded that ‘‘a link probably exists between air travel and deep vein thrombosis’’ but that evidence is lacking to determine the magnitude of the problem. The meeting participants decided to launch three large- scale studies to quantify the link, to identify precipitating factors and to examine possible preventive measures. The studies will be coordinated by the WHO and the International Civil AviationOrganization. n Further information from Mr Gregory Hartl, WHO, email: hartlg@who.int; fax: (+41 22) 791 4858 New anti-malarial drug should outsmart parasite resistance The WHO and the pharmaceutical firm GlaxoSmithKline (GSK) announced in March that they had linked up to develop a new antimalarial combination drug, called LAPDAP. The drug, which is given orally, combines two existing antimalarial com- pounds, chlorproguanil and dapsone, and will be offered to public health programmes at a preferential price. Clinical trials in Africa have shown the drug to be effective in uncomplicated malaria resistant to other standard antimalarials. To further protect the new combination drug from parasite resistance, the partnership plans eventually to equip it with a third antimalarial drug, artemisinin. n Further information from Mr Gregory Hartl, WHO, email: hartlg@who.int; fax: (+41 22) 791 4858 380 Bulletin of the World Health Organization, 2001, 79 (4)