Burkina Faso: article on qualitative monitoring
Publication date: 2000
E S S E N T I A L D R U G S M O N I T O R The Essential Drugs Monitor is produced and distributed by the WHO Department of Essential Drugs and Medicines Policy (EDM). It is published in Chinese, Eng- lish, French, Spanish and Russian, and has a global readership of some 300,000 to whom it is free of charge. The Monitor carries news of developments in national drug policies, therapeutic guidelines, cur- rent pharmaceutical issues, educational strategies and operational research. WHO’s Department of Essential Drugs and Medicines Policy seeks to ensure that all people – wherever they may be – are able to obtain the drugs they need at a price that they and their country can afford; that these drugs are safe, effective and of good quality; and that they are prescribed and used rationally. All correspondence should be addressed to: The Editor Essential Drugs Monitor World Health Organization CH-1211 Geneva 27, Switzerland Fax: +41 22-791-4167 e-mail: email@example.com Essential Drugs Monitor E D I T O R I A L DOUBLE ISSUE – No 28 & 29 (2000) T Newsdesk 2–6 Pregnant women in developing countries face unacceptable health risks New international training course promotes better community drug use Organizations draw up ethical guidelines And much more. Antimicrobial Resistance 7–19 We look at the problem and some possible solutions to one of the world’s greatest health challenges Letters to the Editor 19 National Drugs Policy 20–21 Africa’s essential drug programme managers discuss future WHO’s Director-General speaks out for generics Plus Australia’s National Medicines Policy Access 22–27 Initiatives to create a healthier world NGOs focus on access to drugs Improving drug supply in Dar es Salaam Drug Information 28–31 Pakistan’s Drug Helpline Increasing workload for Tehran’s Drug and Poison Information Centre Research 31 Burkina Faso study shows importance of qualitative monitoring Meetings, Courses & Netscan 32–33 Published Lately 33–34 Traditional Medicine 35 India’s Biodiversity Bill World Trade 35–36 A health-sensitive approach to patent legislation WORLD HEALTH ORGANIZATION I N T H I S I S S U E : SpainUSA Mexico Colombia South Africa South Korea Uruguay Brazil Argentina Chile Hong Kong Thailand Philippines singapore/ Malaysia Taiwan, China Spread of resistant pneumococcus first identified in Spain Antimicrobial resistance: a global threat Source: K. Klugmann, South African Institute of Medical Research wenty years ago physicians in industrialised countries believed that infectious diseases were a scourge of the past. With indus- trialisation came improved sani- tation, housing and nutrition, as well as the revolutionary development of disease- fighting antimicrobials. Populations living in those nations were not only enjoying an unprecedented decrease in mortality and morbidity but a corresponding increase in life expectancy. In the developing world – where poverty and ongoing civil distur- bance offset often modest health gains – people could nevertheless look forward to a time when an increased quality of life might one day lead to a relatively disease free future. The tools were there. Confident in the available pharmacopoeia, the major drug manufacturers turned away from intensive antibacterial research and con- centrated their energies on seeking cures for heart disease and other chronic conditions. Since the l980s significant breakthroughs have been largely confined to the develop- ment of antiviral agents targeting the ever-widening HIV epidemic. But tragically, and even before devel- oping countries were able to fully benefit from medical advances, we face a major risk that diseases considered vanquished in industrialised countries, will once again become killers stalking society, bringing an ever present threat of sudden death and dis- ability. The risk that threatens to turn back the clock to a darker age in industrialised countries and to block health progress in the developing world is antimicrobial resistance. As early as half a century ago – just a few years after penicillin was put on the market – scientists began noticing the emergence of a penicillin/resistant strain of Staphylococcus aureus, a common bacte- rium in the human body’s normal bacterial flora. Resistant strains of gonorrhoea, dys- entery-causing shigella (a major cause of premature death in developing countries) and salmonella rapidly followed. From that first case of resistant staphylococcus, the problem of antimicrobial resistance has snowballed to a serious public health con- cern with economic, social and political implications that are global in scope, and cross all environmental and ethnic boun- daries. Multi-drug resistant tuberculosis (MDR/TB) is no longer confined to any one country or to those co-infected with HIV, but has appeared in locations as diverse as Africa, Asia and Eastern Europe, among health care workers and in the general popu- lation. Penicillin resistant pneumococci are likewise spreading rapidly, while resistant malaria is on the rise, disabling and killing millions of children and adults each year. In 1990 almost all cholera isolates in New Delhi, India, were sensitive to the cheap, first-line drugs furazolidone, ampicillin, co-trimoxazole and nalidixic acid. Now, formerly effective drugs are largely useless in the battle to contain cholera epidemics. Although most drugs are still active, the lengthening shadow of resistance means that many of them may not be for long. In the case of tuberculosis, the emergence of multi-drug resistant bacteria means that medication that once cost US$20 must now be replaced with drugs a hundred times more expensive. Pathogens develop resisistance to anti- microbials through a process known as natural selection. When a microbial popu- lation is exposed to an antibiotic, more susceptible organisms will succumb, leaving behind only those resistant to the antimicrobial onslaught. These organisms can then either pass on their resistance genes to their offspring by replication, or to other related bacteria through “conjuga- tion” whereby plasmids carrying the genes “jump” from one organism to another. This process is a natural, unstoppable phenom- enon exacerbated by the abuse, overuse and misuse of antimicrobials in the treatment of human illness and in animal husbandry, aquaculture and agriculture. Disease – and therefore resistance – also thrives in conditions of civil unrest, poverty, mass migration and environmental degradation where large numbers of people are exposed to infectious diseases, with little in the way of the most basic health care. Our challenge is to slow the rate at which resistance develops and spreads. This Monitor examines the growing spread of antimicrobial resistance and its underlying causes. It reports on the actions of WHO and others to raise awareness of the issue and to counteract this serious menace to public health. And it looks at what you, the reader, whether you are a policy-maker, health care professional, health advocate or member of the public, can do to help tackle the problem. ❏ 2 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 A world of difference: grim statistics on maternal health in developing countries woman living in Africa has a life- time risk of dying from compli- cations related to pregnancy 200 times greater than a woman liv- ing in a wealthy industrialised country, according to research findings reviewed in the WHO Bulletin*. WHO data show that of the more than 500,000 maternal deaths every year, over 99% are in developing countries and less than 1% in the industrialised world. The main causes of these deaths are unsafe abortion, haemorrhage, infections, high blood pressure and obstructed labour. A quarter to a third of all deaths of women and reproductive ill-health because they also suffer discrimination in access to basic needs, health services and the exercise of human rights.” Another Bulletin article reviews data suggesting that making abortion safer could save the lives of many thousands of women a year. ❏ * Bulletin of the World Health Organization, May 2000 (available on the Web at: http:// www.who.int/bulletin/). For subscription details contact: World Health Organization, Marketing and Dissemination, CH 1211 Geneva 27, Switzerland. Doctors revise ethical guidelines on medical research First conference on consumer adverse reaction reporting With so many excellent reasons for direct consumer reporting, why, one might ask, is it not already established? It is because in most countries, consumer reports are simply not eligible for inclu- sion in the existing physician-based systems, and because consumers lack power and knowledge. The Conference recommended that, prior to wide-scale implementation, con- sumer reporting on medicines system/s should be piloted in regions or with patient groups, and handled by an inde- pendent body at arm’s length from government and industry. In aggregated form, reports should be made available to all interested parties, including the mass media. The data would also be related to the current data from the 59 national physician-based schemes in the Uppsala Monitoring Centre (a WHO Col- laborating Centre for International Drug Monitoring). Appropriate arrangements should be made to enable hospitalised patients as well as participants in clinical drug trials to file reports. Expert analysis needed The principle of the subject’s freedom to report should be laid down in Guide- lines for Good Clinical Practice accepted by the European Commission and in clini- cal trial protocols, subject to approval by ethics committees and analogous bodies. Confidentiality agreements concluded between an industrial sponsor and a clini- cal investigator should never be allowed to impede reporting of adverse effects by participants. Provided there is proper feedback and careful expert analysis of reports, it will not necessarily be more difficult to eliminate mischievous, mis- leading or ambiguous reports than has been the case in professional-based systems. A system of consumer reporting on medicines might be supported from pub- lic funds, drug licensing fees or research organizations, including the European Union. Its value will depend to some part on enlisting support from existing sys- tems, allaying unjustified concerns and countering possible misunderstandings. Delegates warned that while develop- ing consumer empowerment, one must also seek to counter potentially harmful influences, such as current efforts to ex- tend Direct-to-Consumer-Advertising of prescription drugs from New Zealand and the USA to the rest of the world. ❏ * David Finer is a medical writer and was Chairperson of the Conference. Further Conference information can be found on the Web at: www.kilen.org N E W S D E S K T A ➢ DAVID FINER* he First International Conference on Consumer Reports on Me- dicines was held in Sigtuna, Sweden, from 29 September– 1 October 2000, with some 70 partici- pants from 35 countries. The Conference sought to call attention to the experiences of consumers as a crucial, untapped force in pharmacovigilance, beneficial for drug safety, but also in terms of consumer empowerment in its own right. Direct consumer reporting of adverse drug events is indeed credible but also controversial in some camps. Yet it is the only system based on the end-users themselves. The Conference was organized by the Swedish organization KILEN (Consumer Institute for Medicines and Health) in cooperation with the Dag Hammarskjöld Foundation, Health Action International, People’s Health Assembly 2000, the Uppsala Monitoring Centre, the Swedish Consumers’ Association, and the Sigtuna Foundation. Participants included experts from the medical and pharmaceutical professions, drug regulatory authorities, the consumer movement and WHO. Presentations of existing consumer reporting systems/initiatives were made by representatives from Australia, the Netherlands, Sweden, Switzerland and the UK. A consensus report from the Con- ference states that general reasons for considering consumer reports on medi- cines relate to the need to promote principles of equity, therapeutic advances, accountability and responsiveness. Also, existing physician-based systems have serious deficiencies, which might to some extent be compensated for by the estab- lishment of consumer reporting. Foremost among these limitations are the small pro- portion of practising physicians (often less than 5%) who contribute data. Input from existing systems relates primarily to new drugs, despite the fact that new prob- lems can emerge with older drugs even after decades of use. Consumers give more complete picture Delegates heard that benefits of con- sumer reporting of adverse drug effects include an earlier accumulation of signals, covering a wider spectrum of organ sys- tems and adverse events. Consumers provide more informative, vivid and com- plete accounts of unwanted experiences and situations, about which physicians are not informed and so cannot report, such as self-treatment with over-the-counter drugs or herbals. he World Medical Association General Assembly has sent a strong signal to all involved in medical research that rich populations should not exploit poor populations by testing on them new treat- ments from which they will never benefit. The Assembly held in Edinburgh, Scot- land, in October 2000, approved a revised Declaration of Helsinki. Initially drawn up in 1964, the Declaration has since be- come the most widely accepted guidance worldwide on medical research involv- ing human participants. Commenting on the changes, Dr Anders Milton, chairman of the Association, said: “Research should not be carried out in countries in devel- opment just because it is cheaper and the laws are more lax. The same ethical rules should apply wherever research is being conducted”. The new Declaration emphasises in much clearer terms than ever before the duty that doctors owe to participants in medical research. It says that freely given informed consent, preferably in writing, should be obtained from all participants. People who cannot give informed consent should be included in research only under exceptional conditions. Strengthening participants’ rights The Declaration specifies that doctors participating in research have an obli- gation to declare any financial or other potential conflict of interest. Research is justified only if the populations to be stud- ied stand to benefit. The Declaration states that every patient entered into a study should have access to the best treat- ment identified by that study once it is completed. Furthermore, testing of any new treatment should be done against the best current method, where that exists, and not against a placebo. This would mean that people in developing countries would at least get access to the best cur- rent treatment if they agree to take part in research into new treatments. The revised Declaration of Helsinki will be distributed to WHO, national bioethics commissions, patients’ repre- sentatives groups and other relevant stakeholders. The full text is on the World Medical Association’s Web site: www.wma.net ❏ Source: BMJ 2000;321:913 T of reproductive age are the result of complica- tions of pregnancy or childbirth. “The poor fare far worse than the rest of so- ciety on all reproductive health outcome indica- tors. But poverty is not an insurmountable bar- rier to health when there is a high level commit- ment to investing in health,” a Bulletin article states. “Gender-based discrimination is an important determinant of poor reproductive health. Women suffer the major burden of sexual Hopefully a trouble-free pregnancy for this woman in Haiti. But women in the developing world have an unacceptably high risk of dying from pregnancy-related complications Ph ot o: W H O / PA H O / A . W aa k 3E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 New course targets better community drug use Welcome new HIV/AIDS resource for francophone Africa new HIV/AIDS information network for Central and West Africa has been launched – the first network of this type in French. Known as SAFCO (SIDA en Afrique du Centre et de l’Ouest), it will encourage discussion and the electronic exchange of information on HIV/AIDS-related issues. The service is particularly welcome because there is a scarcity of such information and technical material in French in Africa, the continent hardest hit by the virus. As well as information exchange, SAFCO aims to: strengthen advocacy efforts; improve information about current projects; promote prevention measures; reinforce access to care and treatment; disseminate the results of international conferences and support their implementation. SAFCO, with over 700 members, is a UNAIDS supported initiative. One of its main strengths is that it is a public cross-sectoral and inter-community information forum. It has input from both the “grassroots” – concerned individuals, government representatives, NGOs, educators, investigators, practitioners and others – and from national and international institutions. ❏ Joining the SAFCO network is free of charge, just send a message to: firstname.lastname@example.org APUA’s small grants programme he Alliance for Prudent Use of Antibiotics (APUA) has initiated a small grants programme, which provides chapters with seed money of US$1,500 for projects designed to curb antibiotic resistance and to promote the rational use of these drugs. APUA’s national chapters form a glo- bal network of health care practitioners and scientific groups working to control antimicrobial resistance. They provide information and tailor the Alliance’s message to local customs and medical practices, and the small grants programme is intended to encourage these efforts. Projects submitted for grants are eva- luated according to their objectives, collaborative components and manage- ment plans. To date grants are helping to support research and education in seven developing and transitional countries. ❏ For further information contact: The Alliance for Prudent Use of Antibiotics, P.O. Box 1372, Boston MA 021171372, USA. E-mail: email@example.com WHO’s Emergency Library Kits ibrary Kits containing essential documents related to public health in emergencies are now available from WHO. Intended to provide technical guidance to field- operating agencies, the Kit includes 120 documents – guidelines and reference manuals produced by WHO, other UN organizations and external publishers. The contents will be updated regularly. Packed in a metal trunk that converts into a bookcase, the Emergency Library Kit costs approximately US$1,320, plus transport charges. ❏ For further information contact: World Health Organization, Department of Emergency and Humanitarian Action, 1211 Geneva 27, Switzerland. WHO list of comparator products ultisource (generic) drugs need to meet the same quality, safety and efficacy standards as the original brand name or innovator product. WHO has now published a list of globally recognised comparator products, to help regulators identify the product against which bioequivalence and interchange- ability of generic versions can be assessed. The list includes 147 drugs from the WHO Model List for which a compara- tor product has already been identified. It names the manufacturer who is the in- novator, and the national market where that manufacturer considers that the prod- uct meets the best safety, quality, efficacy and labelling standards. A second list gives the remaining essential drugs for which a comparator product has yet to be selected. ❏ The information is available in WHO Drug Information Volume 13, No.3, 1999. N E W S D E S K Next Promoting Rational Drug Use in the Community Course If you would like to know more about the course in Entebbe, Uganda, from 11–24 November 2001, please complete and return this form. Alternatively, further details and an application form can be printed out directly from the EDM web-page at: http://www.who.int/medicines/organization/par/secondcourse.html. Course fees are US$2,950, which covers tuition, course materials and accommodation. The deadline for receipt of applications is 1 October 2001. Name Occupation Full postal address Tel Fax E-mail Please return to the address below: University of Amsterdam Faculty of Social and Behavioural Sciences Attn. Dr Ria Reis Oudezijds Achterburgwal 185 1012 DK Amsterdam The Netherlands Tel: +31 20 525 4779 Fax: +31 20 525 3010 E-mail: firstname.lastname@example.org countries, valued the help given to identify clear objec- tives, based on realistic expectations of impact on future work. The skills and experi- ences of everyone on this highly participatory course proved a major resource. Teaching methods were group activities, field work, presentations and discus- sions. Participants spent the final two days preparing a detailed plan of action to tackle an important commu- nity drug use problem in L T A M A Creating a message that counts – participants working on a poster during the course their home country. They also took home a set of session materials and a small core communications library. But from their comments it was evident that course members were leaving Thailand with much more. As one participant put it, “I realise that in my professional life I have only been looking at half of the picture.”. Another said the course would “help me use scarce resources to implement the most appropriate/feasible and needed in- terventions.” And for a third it was “a great experience, well planned and well organized”. After such initial success the course is set to become a regular event, with the next one being held in Entebbe, Uganda, from 11–24 November 2001. ❏ Reference WHO. Public education in rational drug use: a global survey. EDM Research Series No.24. Geneva: World Health Organization; 1997. WHO/DAP/97.5. Ph ot o: S . S an de rs , M ah id ol U ni ve rs ity , B an gk ok t a time when the majority of medicines are purchased directly by consumers without prescrip- tion, community education is vital, and a new course is setting out to meet the needs of those with a critical role to play in this much neglected area. Just how neglected was shown by a WHO glo- bal survey on public education in rational drug use1, which revealed a shortage of expertise, support and funds for this type of work, in spite of its public health and economic benefits. Developed by WHO’s Department of Essential Drugs and Medicines Policy and the University of Amsterdam, in col- laboration with experts world wide, the course, Promoting Rational Drug Use in the Community, was held for the first time in October 2000 in Bangkok. Enthusias- tic participants learned how to effectively identify and prioritise community drug use problems; choose and develop appropriate intervention strategies and communication channels; pretest materi- als; evaluate impact; and fundraise and network for support and sustainability. Anyone who came looking for “quick fixes” would have been disappointed. Participants learned that interventions must take into account the social and eco- nomic context in which health- and medicine-seeking behaviour take place, and be developed with community input. The course emphasises that change is usually incremental. So programme objectives may start with awareness train- ing, move on to knowledge acquisition, and then finally on to behavioural change. Twenty-five participants, from 14 4 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Leading organizations’ new guidelines on ethics t a time of increased focus on ethical issues in the pharmaceu- tical sector, UNAIDS and the European Medicines Evaluation Agency are among many organizations producing their own guidelines. UNAIDS and vaccine research In the case of the Joint United Nations Programme on HIV/AIDS (UNAIDS) the ethical guidelines cover HIV vaccine research for those giving trial AIDS vaccines. It is widely thought that devel- oping such a vaccine offers the best hope of controlling the AIDS epidemic, espe- cially in developing countries. But experts say it will be a lengthy and complex proc- ess, because of the scientific and ethical challenges involved in clinical trials among human volunteers. The guidance document, which addresses some of these ethical chal- lenges, took over two years to draw up. It was based on a series of consultations or- ganized by UNAIDS and which involved representatives from 33 countries. The meetings took place in Brazil, Thailand and Uganda (countries that are participat- ing in HIV vaccine trials) as well as in Geneva and Washington. They involved lawyers, activists, NGOs, people living with HIV/AIDS, social scientists, ethi- cists, epidemiologists, health policy specialists, and agencies and institutions involved in vaccine development. There was consensus on most, but not all, issues. The most contentious area was the level of treatment that should be of- fered to participants in vaccine trials who become infected with HIV, not through the trials (vaccines cannot cause HIV in- fection) but through eventual behavioural exposure. According to the UNAIDS reflecting a number of issues, including: ➤ international ethical responsibility to support vaccine trials; ➤ the obligation to provide an effective vaccine to populations where trials are conducted and to other populations in need; ➤ the need to strengthen ethical review capacity in developing countries; ➤ the importance of social and behav- ioural aspects of testing, and future use of an HIV vaccine. Collective responsibility The guidelines identify responsibili- ties for the “sponsors” of vaccine trials. In modern vaccine development pro- grammes, sponsors are not usually a single pharmaceutical company. Instead, there tend to be multiple sponsors, with one or more corporations, one or more national governments, and one or more international agencies. The guidelines highlight the impor- tance of involving communities early in the design, development, implementation and distribution of results of HIV vaccine research. They are designed as a frame- work to enable communities to decide what is appropriate for them. Agency acts to ensure integrity, independence, transparency The European Medicines Evaluation Agency is to have a code of conduct giv- ing specific guidance on conflicts of interest, gifts and confidentiality. The Code applies to management board, scientific committee and working party members, European experts listed by the Agency, all Agency staff and by analogy all visiting staff. Three cat- egories of interest are listed: financial interests, work carried out for the phar- maceutical industry in the previous five years, and other links, such as grants for study or research, or fellowships endowed by industry in the previous five years. Anyone with direct interests in the pharmaceutical industry has to end them to remain with the Agency. If there are indirect interests they must be neutralised, for example by preventing someone from taking part in certain tasks. In general staff have to discourage gifts of anything more than token value which can be shared openly with col- leagues. Any gifts of a personal nature must be returned, and staff must not use items with pharmaceutical company logos at work. The Code states that invitations to pre- dominantly leisure events cannot be accepted, and at meetings or on missions staff should normally pay for their own meals. Invitations from individual phar- maceutical companies, suppliers, etc. should not be accepted. In addition no payment may be accepted for speeches, lectures or publications directly related to Agency activities. Permission to speak at conferences will be refused “if network- ing or gaining influence must be assumed to be the major objective of the organ- izer”. Invitations from congresses or meetings organized by pharmaceutical companies are unacceptable. ❏ Africa’s strategy on traditional medicine N E W S D E S K A H T Electronic HAI-Lights AI-Lights has become the first HAI-Europe publication de- signed to be read and used elec- tronically. All of the information included in the newsletter’s August 2000 double issue appears in easy to find links shown on the cover page. HAI-Europe has been working towards a Web-based version of the regional newsletter for some time, due to members’ demand for faster information and more accessible material. It is planned to link the newsletter’s content to a Web site search function so that articles on various issues can be retrieved quickly and easily. Access the August issue of HAI-Lights at: http://www.haiweb.org/pubs/hailights/ aug2000/ The entire newsletter is also available in a downloadable text format. You can choose Word for either PC or Mac to read or print out the issue’s complete contents or a specific section. ❏ document, “Care and treat- ment should be provided, with the ideal being to provide the best proven therapy, and the minimum to provide the highest level of care attainable in the host country” under the circum- stances in which the trial is conducted. With resources in indus- trialised and developing countries so different, how- ever, not every country can expect to provide the same level of care. The document contains 18 “guidance points” The AIDS virus. Development of a vaccine is considered to be the best hope of controlling the AIDS epidemic. Guidelines are now in place to address the complex ethical issues involved in testing such a vaccine Ph ot o: W H O / In sti tu t P as te ur / C . D au ge t he Strategy for Traditional Medi- cine for the African Region (2000–2001) is being developed by the WHO Regional Office for Africa. Its aim is to assist Member States to integrate traditional medicine into health systems and services, and to promote appropriate and rational use. In December 1999, WHO held a consul- tative meeting on the Strategy, which brought together 23 experts from 15 coun- tries for three days of intensive debate in Harare, Zimbabwe. Combatting priority diseases Participants recommended that action plans be developed to implement the Strategy at regional and national levels, so that by 2020 traditional medicine will be an integrated component of the minimum health care package in African countries. Much discussion focused on ensuring the protection of the intel- lectual property rights of indigenous knowledge in traditional medicine, and the cultivation and conservation of native medicinal plants. Delegates asked WHO to provide technical and financial support for developing traditional medicinal prod- ucts to combat priority diseases, such as malaria, hypertension, diabetes and HIV/ AIDS-related conditions. Closing the meeting the WHO Re- gional Director for Africa, Dr Ebrahim Samba, said he wanted to see the contin- ued use of African herbal plants and traditional medicines to treat diseases. He hoped that such traditional medicinal products would eventually be exported, after clinical trials have proved their effi- cacy and safety. Dr Samba stressed the economic importance this could have for Africans. As a follow-up to the December con- sultative meeting, WHO’s Regional Office for Africa organized the African Forum on the role of traditional medi- cine in health systems, in Harare in February 2000. Over 100 participants from throughout the region held wide ranging discussions, reviewed current and needed research on these medicines, and identified local production issues. Recommendations from the meeting included: ensuring adequate legal and regulatory frameworks to promote tra- ditional medicines; establishing or strengthening traditional medicine prac- titioners’ associations; and increasing collaboration among healers, scientists and doctors. ❏ 5E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 A World Health Report with a difference Celebrating the Chinese version of the Monitor French set to curb drug spending Indian training course highlights pharmacists’ evolving role group of community and hospital pharmacists and pharmacy students from the Bengal area benefited from a break in routine when in September 1999 they spent two days looking at broader issues affecting their profession. Twenty- six participants held wide-ranging discussions on subjects including their changing role, the structure of the country’s pharmaceutical industry and the patent situation. Run jointly by the Community Development Medicinal Unit, Cal- cutta, and the Indian Pharmaceutical Association, Bengal Branch, the training course, Good Community Pharmacy Practice, was so successful that it is planned to repeat it every year. Upgrading knowledge and skills In the varied programme, a session on formulations marketed in India although banned by the Government generated animated debate. So too did the topic of clinical waste management – an area new to many of the participants. The second day began with a discussion on how best to respond to symptoms of common ailments, followed by tips on improving drug dispensing, and medical stores management. Although maybe not of immediate relevance to the job description of most participants, two sessions provided plenty of food for thought. One was on the he World Health Report 2000 – Health Systems: Improving Performance1 is an expert analy- sis of the increasingly important influence of health systems in people’s daily lives. In recent decades, health sys- system to carry out four main functions: service provision, resource generation, financing and stewardship. Chapters devoted to each function offer new con- ceptual insights and practical advice on how to assess performance and achieve he French Government has warned that the rate of growth of pharmaceutical spending is still far too high, and that it is decid- ing which products will have price or reimbursement cuts, or be removed from the list of reimbursable products. Speaking at a press conference in May 2000, Labour and Solidarity Minister, Martine Aubry, said that health care expenditure was still rising strongly, par- ticularly in the pharmaceutical sector, which increased by 6.3% in 1999. While projections for 2000 are for a cut of 0.7% this is far higher than the target set by Government of 2%. Addressing the Social Security Accounts Commission shortly before her press conference, Ms Aubry said that it was “absolutely neces- sary” to bring pharmaceutical expenditure into line with Government targets. She singled out “unjustifiable pre- scribing”, saying that some products were quickly capturing a sizeable share of the market more because of what she termed “aggressive commercial policies towards doctors than because they are advances in public health”. “Information arrives in doctors’ surgeries from pharmaceutical companies and only from them” she con- tinued. “ I am not criticising the industry. It does its job, which is to sell and sell even more. But she said that she did not want doctors to be “left alone to face the industry”. The Government intends to supply doctors with independent infor- mation on the correct use of medicines. While encouraged by increasing generic substitution, Ms Aubry said that she wanted to see more generic products on the market soon. The French pharmaceutical industry N E W S D E S K T A T T tems have contributed enor- mously to better health for most of the global population. But they have the potential to achieve further improvements, especially for the poor. As Dr Brundtland, WHO’s Director- General, comments in her introduction to the Report, “The poor are treated with less respect, given less choice of service providers and offered lower-quality amenities. In trying to buy health from their own pockets, they pay and become poorer.” To date very little has been done to unravel the complex factors that explain good or bad performance by individual health systems. Given equal resources, why do some succeed where others fail? Is performance simply driven by the laws of supply and demand, or does another logic apply? Why is dissatisfaction with services so widespread, even in wealthy countries offering the latest interven- tions? If systems need improvement, what tools exist to measure performance and outcomes? These are some of the questions that the Report addresses, as it presents the results of the first ever analysis of the world’s health systems. It provides an index of performance based on three fundamental goals: improving the level and distribution of health, enhancing the responsiveness of the system to the le- gitimate expectations of the population, and assuring fair financial contributions. As the Report argues, good perform- ance depends critically on the delivery of high-quality services. But health sys- tems must also protect citizens from the financial risks of illness and meet their expectations with dignified care. The pub- lication shows how the achievement of these goals depends on the ability of each improvements with available resources. The analysis revealed a number of problems common to many countries. Among them are that: ➤ many health ministries focus on the public sector and often disregard the frequently much larger private sector health care; ➤ in many countries, some if not most physicians work simultane- ously for the public sector and in private practice. This means that the public sector ends up subsidising unofficial private practice; ➤ many governments fail to prevent a “black market” in health, where wide- spread corruption, bribery, “moon- lighting” and other illegal practices flourish. The black markets, which themselves are caused by mal- functioning health systems, and health workers’ low incomes, further undermine those systems; ➤ many health ministries fail to enforce regulations that they themselves have created or are supposed to implement in the public interest. The Report aims to stimulate debate about better ways of measuring health system performance and overcoming such problems. By shedding new light on what makes systems behave in certain ways, WHO also hopes to help policy- makers understand the many complex issues involved, weigh their options and make wise choices. ❏ Reference 1. WHO. The world health report 2000 – health systems: improving performance. Geneva: World Health Organization; 2000. Available from: Marketing and Dis- semination, World Health Organization, 1211 Geneva 27, Switzerland. Price: Sw.fr.15/US$13.50, and in develop- ing countries Sw.fr.10.50. The full report is available on the Web at: http://www.who.int/home/reports.html An elderly patient in France, where the Government is acting to reduce rising pharmaceutical expenditure association, SNIP, has criticised the Government’s target of a 2% increase in pharmaceutical spending in 2000. The Govern- ment cost-containment ini- tiatives (prescribing guidelines, computerization of doctors’ sur- geries, the encouragement of generics and reimbursement review) were necessary, SNIP stated, but had failed to bring spending into line with the 2% limit. ❏ Source: Scrip, No.2543, 26 May 2000. scientific principles of pharmaceutical in- ventory management. The other covered the structure of the pharmaceutical indus- try in India, recent changes in national drug policy and the Indian patents scenario. ❏ For further information contact: Community Development Medicinal Unit, 47/1B Garcha Road, Calcutta-700 019, West Bengal, India, or see: http://education.vsnl.com/ cdmudocu/CDMUHome.htm Participants engrossed by a demonstration of special dosage forms Ph ot o: W H O / E. S ch w ab Ph ot o: C D M U / IPA he Essential Drugs Division of China’s State Drug Adminis- tration has seen its hard work rewarded as the first two issues of the Monitor in Chinese have rolled off the printing presses, to an enthusiastic reception. Ten thousand copies of each issue have been printed and distributed, free of charge, to Government departments, medical institutes and experts in the pharmaceutical sector. While these first issues contain a selection of key articles from recent editions, future copies will reproduce the text of the most recent Monitor. ❏ 6 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Oxfam campaigns to lower drug prices Update on drug donationsDrug donations problem in Venezuela staff and increase working hours simply to classify what has been received. Dr Francisco Griffin, Director- General of the Production Service, said he thought some companies had deliber- ately sent expired products, considered as toxic waste, to evade the cost of having to deal with them themselves. In 1996 WHO published interagency guidelines on drug donations1 in response to increas- ing reports of such problems being caused by inappropriate donations. However, Dr Griffin accepted that the Service had not anticipated such a massive international response to the landslides. When the disorganized nature of the donations and the “titanic work” required to sort through them became clear, advertisements were belatedly posted on the Web sites of international organizations asking only for specifically requested products.* ❏ Source: BMJ 2000;320:1491. ➤ While nurses were the most likely health workers to be in charge of phar- macies and of selecting, prescribing and dispensing drugs, donors usually decided the quantity of each drug to send. Researchers concluded that: ➤ Donated drugs are more appropriate when the recipient, not the donor, decides which drugs are sent. ➤ As nurses play a central role in drug donations they must understand the principles of good donation practices. ➤ There is still a need to promote the essential drugs concept and use of es- sential drugs lists by both donors and recipients. ❏ For further information on the study contact: Dr Eva Ombaka, The Pharmaceutical Pro- gramme, World Council of Churches/ Community Initiatives Support Services Inter- national, P.O. Box 73860, Nairobi, Kenya. Source: Practical Pharmacy, No. 14, 1999. New public health channel piloted in Africa orldSpace Foundation and SATELLIFE have announced a new health service that will pro- vide a steady stream of material to assist medical professionals in Africa in the diagnosis, prevention and treatment of prevalent diseases. The service, called the Public Health Channel, aims to over- come the barriers of poverty, geography and unreliable communications infra- structures, to help stop the rise of diseases such as malaria, tuberculosis and HIV/ AIDS. “The ability to widely disseminate information about the treatment and pre- vention of HIV/AIDS and other diseases is the reason the WorldSpace system was created,” says Gracia Hillman, WorldSpace Foundation President. “The goal of SATELLIFE’s informa- tion services is to connect the health practitioner in the developing world with a range of high-quality information resources in a cost-effective manner, by making use of the most affordable, efficient and appropriate technology”, states SATELLIFE Executive Director, Holly Ladd. “The Public Health Chan- nel will employ the technology of the WorldSpace system to exponentially in- crease the amount of information health practitioners throughout Africa can access – information that most health practitioners in the United States and Europe take for granted.” The Public Health Channel will be launched in four countries: Ethiopia, Kenya, Uganda and Zimbabwe. After an initial test period, the project will expand to other African countries, as funding becomes available. WorldSpace receivers will be placed in hospitals, medical schools, medical libraries, health clinics, health ministries and research settings. WorldSpace receivers provide crystal clear digital audio channels, and can also serve as a modem, downloading text- based material and dynamic images from the AfriStar satellite directly to comput- ers. TheWorldSpace system transcends the difficulties of unreliable telephone systems at a fraction of the cost of most Internet-based projects. N E W S D E S K WorldSpace Foundation works with NGOs and other humanitarian groups to bring life-saving information to people who are disadvantaged by poverty, rural location and the digital divide. ❏ SATELLIFE is an international not-for-profit humanitarian organization. Its mission is to improve health by improving connections between professionals in the field, through electronic communications and information exchange in the areas of public health, medicine and the environment. Particular emphasis is on areas of the world where poor communications, economic conditions or natural disasters limit access. SATELLIFE produces two e-mail publications, HealthNet News and HealthNet News– AIDS, which feature materials from 21 journals, including the British Medical Journal, Lancet and East African Medical Journal. SATELLIFE also operates and maintains several global electronic discussion groups on subjects relevant to developing countries. (See Netscan page 32 for more information on SATELLIFE’s services). WorldSpace Foundation is a non profit organization created in 1997. Based in Washington DC, USA, its work encompasses Africa, Asia-Pacific, Latin America and the Caribbean. It has 5% of the channel capacity of the three WorldSpace Corporation satellites for non commercial social development and distance learning programming. W study carried out by Community Initiatives Support Services Inter- national has investigated the benefits and problems of donated drugs at 24 mission health facilities in Kenya and Tanzania between 1997 and 1998. It found that: ➤ On average health facilities received four deliveries of donated drugs per year. ➤ Approximately a quarter of all do- nated drugs had a shelf-life of less than one year. ➤ A quarter of donated drugs were antibiotics. ➤ Three-quarters of the health facilities had sent a list of drugs required to the donor, but only half received drugs from that list. ➤ When donated drugs were not re- quested by the health facility it was more likely that good drug donation practices were not adhered to. Aonths after devastating floods and landslides left up to 30,000 peo- ple dead or missing and 200,000 homeless, the Bolivarian Repub- lic of Venezuela was being inundated again by a flood of unusable medical aid. Harrowing television pictures of the dis- aster in December 1999 in the coastal states of Vargas and Falcon, near Cara- cas, sparked a massive humanitarian response, and tonnes of medicines arrived from around the world. However, health workers helping the victims say that huge quantities of medi- cal aid remain stockpiled in warehouses, and up to 70% will have to be inciner- ated. A report by the Government’s Pharmacological Production Service says many products cannot be used because they are out of date, unnecessary, have been partially used, or have no Spanish labelling. As a result, the Government has already had to spend at least 10m bolivars (approximately US$16,000) to hire extra M Calm waters on Lake Maracaibo for this auxiliary health worker doing her rounds, but floods in Venezuela in 1999 caused massive devastation * There are signs that coun- tries are beginning to speak out, to avoid receiving un- necessary drugs when faced with disasters. For example, Mozambique required all donations to be consistent with WHO’s Interagency guidelines when areas of the country were flooded in February and March 2000. Reference 1. WHO. Interagency guidelines for drug donations. Geneva: World Health Organization; 1996. (Second edition published 1999). Ph ot o: W H O / P. A lm sa y O xfam, the international development agency, is launching a campaign on access to medicines, with a focus on the issue of affordability. Oxfam has drawn on its programme experience and local research to produce a number of reports looking at the determinants of drug prices, and at policies that can bring them down. It is paying particular attention to the influence of World Trade Organization intellectual property rules and to the policies of the pharmaceutical industry, and makes policy recommendations to the main actors. The British-based organization is seeking to raise public awareness on the issues as part of a broader international campaign to make the world trading system work more to the advantage of poor communities and poor countries. Oxfam has humanitar- ian and development programmes in over 70 low-income countries. It is also a prominent NGO advocate on international economic development issues, including trade and debt. ❏ For more information visit Oxfam’s Web site at: www.oxfam.org.uk or e-mail: <tradecampaign@ oxfam.org.uk>. Alternatively, write to George Tarvit, Campaign Department, Oxfam, 274 Banbury Road, Oxford, OX2 7DZ, UK. 7E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 A N T I M I C R O B I A L R E S I S T A N C E ver the past decade, there has been a dramatic upsurge world wide in the spread of drug-resistant microbes. Major infectious diseases such as tuberculosis, pneumonia and malaria are becoming increas- ingly difficult and expensive to treat, as microbes develop resist- ance to many of the medicines available. How widespread is the problem? How does drug resistance develop? And what is WHO doing to contain this threat? Rosamund Williams, Coordinator, Anti-infective Drug Resistance and Containment at WHO explains. a year in the United States alone, are al- most always caused by drug-resistant microbes. Foodborne infections are also on the increase – promoting growing con- cern about drug resistance in pathogens such as Salmonella and Campylobacter. Meanwhile, tropical diseases, such as leishmaniasis (see box p.8) and African trypanosomiasis, which haunt the poor and marginalised communities of the world, are becoming increasingly diffi- cult to treat among people also infected with HIV. Treatment with the usual (and sometimes only) drug is increasingly ineffective. How widespread is the problem? Drug resistance is a global problem – affecting both developing and developed countries. Its spread is helped by the enor- mous increase in global travel and trade. transmission) or through acquisition from other bacteria of resistance genes (hori- zontal transmission). This dual means of acquiring resistance explains why the resistance trait can spread rapidly and replace a previously drug-susceptible population of bacteria. Are antimicrobial drugs to blame? No. Antimicrobial drugs do not cause resistance. But the process is accelerated when antimicrobials are misused. What be killed and the infection resolved before resistance has time to emerge. However, in the treatment of chronic infections such as TB and HIV/AIDS – especially if treatment compliance is poor – drug-resistant mutants have time to emerge and multiply and replace the drug-susceptible population of microbes. Under these circumstances, it is likely that the treatment outcome will be poor. So why is it that the microbes in- volved in acute infections have also become resistant to many of the first-line Antimicrobial resistance: the facts Antimicrobial resistance is on the in- crease – threatening our ability to treat some of the infectious diseases that cause most deaths. Diseases such as tuberculo- sis (TB), which was once thought to be under control, are becoming increasingly difficult to treat as medicines become less effective – steadily depleting the arsenal of drugs available. Infectious diseases still account for 45% of deaths in low-income countries and for almost one in two premature deaths worldwide. And most of these deaths (about 90%) are due to no more than six diseases: acute respiratory infec- tions (mainly pneumonia), diarrhoeal disease, HIV/AIDS, TB, malaria and measles. Antimicrobial resistance is today challenging our ability to treat effectively at least four of these infec- tions: acute respiratory infections, diarrhoeal disease, malaria and TB. O DECLINING RESPONSE TO ANTIMALARIAL DRUGS 1976 1980 1988 1992 100% 80 60 40 20 0 Mefloquine Quinine Sulfadoxine-Pyrim ethine Chloroquine 1984 Chloroquine, for example – once the first-line treatment for malaria – is no longer effective in 81 of the 92 countries where the disease is a public health prob- lem. In some regions, over half of all cases of streptococcal pneumonia are resis- tant to penicillin. And over 20% of new TB cases are now multidrug-resistant. To make matters worse, resistance is already emerging to anti-HIV drugs. There are reports of resistance to all currently marketed antiretroviral drugs. And resistance is also widespread among sexually-transmitted infections, such as gonorrhoea, that enhance the spread of HIV. But the problem does not end there. Hospital-acquired (nosocomial) infec- tions, which account for 40,000 deaths Documented examples include: ➤ cases of drug-resistant gon- orrhoea acquired by tourists visiting South-East Asia and transmitted among commu- nities in Australia; ➤ outbreaks of multidrug- resistant TB in Western Eu- rope traced back to Eastern European countries where TB control is poor; ➤ two outbreaks of MRSA (methicillin-resistant Sta- phylococcus aureus) hospital infection in Canada involv- ing patients who acquired the strain in India. In addition, cases of drug- resistant malaria occur among travellers returning to developed countries from malaria-endemic drugs available? The problem is that antimicrobial drugs not only kill the microbe being targeted, they also “treat” other normally harmless microbes (“normal flora”) in the body as well. For example, Streptococcus pneumoniae, as well as causing otitis, pneumonia and meningitis, is also carried by many people, especially children, as part of their normal throat flora, without caus- ing any symptoms. So every time they take an antimicrobial – for whatever reason – their streptococci are exposed. If a mutant emerges, it will have a selec- tive advantage and can spread to other people. A similar process occurs when salmonella bacteria are exposed to antimicrobials incorporated into ani- mal feed. While these bacteria may not cause the animal any harm, they can be spread to humans through the food chain. What is multidrug- resistance? There are many different classes of antimicrobials, and microbes have devised ways to resist the action of each and every one. In addition, a single microbial cell can carry resistance genes to a whole series of totally unrelated antimicrobial drugs. Over PENICILLIN-RESISTANT PNEUMOCOCCI IN THE 1990s Israel 80 70 60 50 40 30 20 10 0 % in hospital patients South Korea Saudi Arabia Egypt Bulgaria Kenya Singapore Hong Kong M exico Czech Republic happens is that natural selection – a natural biological process – favours the survival of microbes that develop resistance genes by chance when exposed to antimicrobials. All uses of antimicrobials – both appro- priate and inappropriate – apply a selective pressure on micro- bial populations. However, the more antimicrobials are used, the greater this pressure will be. Thus it is critical to gain maximum benefit from the cura- tive effects of antimicrobials – especially in developing coun- tries, where they are not only misused, but often under-used due to financial constraints. At the same time, it is also essen- tial to minimise the opportunities for resistance to emerge. In practice this means using antimicrobials both widely and wisely – neither too little, nor too much, and never inap- propropiately. Inappropriate prescribing practices – including the wrong choice of drug and incorrect dosage or length of treatment – poor compliance with treatment, and the use of low quality (sometimes counterfeit) drugs all contribute to the emergence of drug-resistant microbes. How does resistance develop? If a person develops an acute infec- tion such as pneumonia with a drug- susceptible strain of Streptococcus pneumoniae, for example, and is treated promptly with penicillin, the bacteria will .cont’d on page 8 ➠ THE PARADOX OF CONTROLLING DRUG RESISTANCE Antibiotics too readily available Undertreatment and inadequate access to antibiotics Encourages resistance Resistant infections not properly treated sistance is high. These drug- resistant infections will not spread in developed countries provided there are no mosquito vectors. But global warming could change all that. What is antimicrobial resistance? When antimicrobial resist- ance occurs, it is the microbe (bacterium, virus, fungus or pro- tozoan) that is resistant; not the drug, nor the patient. Species of bacteria that are normally resist- ant to penicillin, for example, can develop resistance to these drugs either through mutation (vertical Source: The Southeast Journal of Tropical Medicine and Public Health, Mekong Malaria, Volume 30, Supplement 4, p 68, 1999 Source: World Health Organization/CDS countries where re- Source: Collected from published data 8 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 A N T I M I C R O B I A L R E S I S T A N C E The example of leishmaniasis Leishmaniasis is an insect-borne disease that is showing resistance to the highly toxic, heavy metal-based antimonials at rates of 64% in some developing nations. Currently, visceral leishmaniasis – otherwise known as Kala-azar – afflicts 500,000 people each year in 61 countries in East Africa, India and the Mediterranean basin. The sandfly-transmitted parasite attacks the spleen, liver and bone marrow and is characterised by fever, severe weight loss and anaemia. Left untreated, the disease is fatal. Drug-resistant leishmaniasis results when treatment courses are too short, interrupted, or consist of poor-quality or counterfeit drugs. Once infected, victims remain vulnerable to potentially fatal flare-ups throughout their life. As with most infectious diseases, resistant strains flourish in areas where poverty is high, surveil- lance is low and treatment frequently inconsistent due to limited medical access, inadequate diagnosis, the availability of parallel-market drugs, and political discord. Active monitoring procedures that could reveal the true extent of the disease are hindered by lack of available funds and civil unrest. In one study, WHO researchers conducting a house-to-house search discovered that the actual rate of infection was 48 times that which had been initially reported. In the State of Bihar in north-western India, up to 70% of cases are non-responsive to current treatments, while in Bangladesh, Brazil – and particularly Sudan (where 90% of all cases originate), resistance continues to grow. In developed Mediterranean nations, drug-resistant leishmaniasis is spreading as the number of patients co- infected with HIV increases. Those infected with HIV or who are immuno-suppressed in any way (as a result of cancer treatments or organ transplants) are likewise vulnerable. Any kind of immuno-suppression can potentially increase the number of parasites in the blood, thereby giving rise to the likelihood of transmission through the bite of the sandfly. This cycle facilitates a destructive spiral of greater resistance, higher parasitic levels and increased infection-producing potential. War, globalisation, increased travel and climatic change places this parasitic infection solidly in the category of emerging diseases with rapidly-evolving resistance. time, the dysentery-causing bacterium Shigella, for example, has become resistant to each successive class of antimicrobials used in treatment. As a result, it has a string of genes, each Antimicrobial resistance. cont’d from pg. 7 TACKLING THE PROBLEM Can antimicrobial resistance be halted? No. But it can be contained. Antimi- crobial resistance is a natural biological phenomenon – the response of microbes subjected to the selective pressure of an- timicrobial drug use. The main priority RESISTANCE CAN BE EFFECTIVELY TREATED Ideal drug usage involves: • The correct drug • Administered by the best route • In the right amount • At optimum intervals • For the appropriate period • After an accurate diagnosis Problems occur in both developed and developing countries when antimicrobials are: • Not equitably available • Used by too many people • To treat the wrong disease • In the wrong dosage • For the wrong period of time • Not in the correct formulation or strength Antimicrobial resistance is not a new or surprising phenomenon. All micro-organisms have the ability to evolve various ways of protecting themselves from attack BUT over the last decade or so: • Antimicrobial resistance has increased • The pace of development for new and replacement antimicrobials has decreased RESISTANCE MEANS THAT: • People can’t be effectively treated • People are ill for longer • People are at greater risk of dying • Epidemics are prolonged • Others are at greater risk of infection coding for resistance to a different anti- microbial. To make matters worse, this string of genes can be transmitted from one bacterial cell to another. Thus a previously susceptible Shigella can, in one fell swoop, acquire five or six resistance genes. Why is antimicrobial resistance spreading so fast? Although mutations are rare events (about one in a million bacteria may show a mutation which might lead to resistance), microbes multiply very rapidly – thereby enabling a single mutant to rapidly become dominant. Microbes also spread readily from person to person. Thus one patient in- fected with a resistant strain may be an important source of spread, not only of the infection, but of a resistant infec- tion. This is demonstrated in hospitals, where one patient infected with MRSA, for example, is often the source from which many others become infected or colonised. Thus in taking action to contain resistance, both the emergence of resist- ance and the spread of resistant strains need to be considered. should be to prevent infection in the first place. After that, containment of the problem is the best we can aim for. And since it is antimicro- bial use that drives resistance, the focus of any containment strategy should be on minimising any unnecessary, inappropriate or irra- tional use of antimicrobial drugs. Many groups of people play a role in determining how and where antimicrobials are used: ➤ patients and the general public; ➤ all groups of prescribers and dispensers; ➤ hospital managers and health care professionals; ➤ users of antimicrobials in agriculture; ➤ national governments; ➤ pharmaceutical, diagnostic and “surveillance” industries; ➤ international agencies, NGOs, professional societies. Source: World Health Organization/CDS All of these groups need to be engaged in developing and implementing a resistance containment action plan. What is WHO doing? WHO has taken the lead in developing a Global Strategy for the Containment of Antimi- crobial Resistance. The strategy is designed to reduce the emergence of resistance and slow the spread of resistant infections, in an effort to re- duce the mortality, morbidity, and high costs Source: World Health Organization/CDS associated with antimicrobial resistance. The strategy is based on pub- lished evidence, expert opinion, and the deliberations of other expert bodies. It includes a review of the factors responsible for the emergence and spread of resistance and of the interventions that have been tested or proposed to address the problem. The strategy provides a framework of interventions for implementation. It also highlights the gaps in current knowledge and the many outstanding research needs. Foremost among these is the need to develop new drugs to combat drug-resistant infections, and to develop a new environment of incentives and public-private partnerships to address the challenges of antimicrobial resistance. ❏ For further details contact: Dr Rosamund Williams, Communicable Diseases Clus- ter, Anti-infective Drug Resistance and Containment, World Health Organization, 1211 Geneva 27, Switzerland. Source: WHO. Overcoming antimicrobial resistance. Geneva: World Health Organization; 2000. A female patient with Leishmania aethiopica infection Ph ot o: W H O / TD R 9E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Who contributes to misuse of antimicrobials? information, leading to uncertainty about the diagnosis and the most appropriate drug(s), and fear of poor patient outcome ➤ patient demand ➤ earning a living through selling medicines. the time), they are still greatly influenced by pa- tients’ demands. Many tra- ditional practitioners are now prescribing allopathic me- dicines instead of herbal or other kinds of medicines be- cause this is what patients want. In Tanzania 60% of health workers admitted to prescribing inappropriate drugs demanded by socially influential patients, to avoid being labelled “difficult”.6 Many people in India believe in ‘tonics’ and will not return to a doctor unless he or she prescribes according to their wishes. Even though doctors may know that ‘tonics’ are A of antibiotic purchases were for 10 or fewer capsules, which in most circum- stances would be less than a full course. In conclusion, antibiotics are often prescribed irrationally (over-prescription and inappropriate prescription) and this contributes to the development of antimicrobial resistance. However, pre- scribers may have very rational reasons for prescribing irrationally and it is not just a question of lack of knowledge. Only by understanding the reasons underlying inappropriate prescribing can one design effective interventions to change such behaviour. ❏ * Dr Kathleen Holloway is a Medical Of- ficer in the Department of Essential Drugs and Medicines Policy at the World Health Organization. References 1. Gilson L, Jaffar S, Mwankusye S, Teuscher T. Assessing prescribing practice: a Tanzanian example. International Journal of Health Planning and Management 1993;8: 37–58. 2. Uppal R, Sarkar U, Giriyappanavar Cr, Kacker V. Anti- microbial drug use in primary health care. Journal of Clinical Epidemiology 1993;46(7):671–673. 3. Hui L, Li X.S, Zeng X.J, Dai Y.H, Foy H.M. Patterns and determinants of use of antibiotics for acute respira- tory tract infection in children in China. Paediatric Infectious Disease Journal 1997;16(6):560–564. 4. Bosu W.K, Afori-Adjei D. Survey of antibiotic prescrib- ing patterns in government health facilities of the Wassa West District of Ghana. East African Medical Journal 1997;74(3):138–142. 5. Nizami S, Khan I, Bhutta Z. Drug prescribing practices of general practitioners and paediatricians for childhood diarrhoea in Karachi, Pakistan. Social Science and Medicine 1996;42(8):1133–1139. 6. Mnyika K.S, Killewo J.Z.J. Irrational drug use in Tanza- nia. Health Policy and Planning 1991;6(2):180–184. 7. Nichter M, Pharmaceuticals, health commodification and social relations: ramifications for primary health care, Anthropology and International Health, South Asian Case Studies 1989; Section 3, No.9:233–277. (Kluwer Academic Publishers). 8. Branthwaite A, Pechere J-C. Pan-European survey of patients’ attitudes to antibiotics and antibiotic use. Jour- nal of International Medical Research 1996;24(3): 229–238. 9. Britten N, Ukoumunne O. The influence of patients’ hopes of receiving a prescription on doctors’ perceptions and the decision to prescribe: a questionnaire survey. British Medical Journal 1997;315:1506–1510. 10. Paredes P, de la Pena M, Flores-Guerra E, Diaz J, Trostle J. Factors influencing physicians’ prescribing behaviour in the treatment of childhood diarrhoea: knowledge may not be the clue. Social Science and Medicine 1996;42(8):1141–1153. 11. Trap B, Hansen E.H, Hogerzeil H.V. Prescribing by dis- pensing and non-dispensing doctors in Zimbabwe. Copenhagen: Royal Danish School of Pharmacy; 2000. (Unpublished study). 12. Shao-Kang Z, Sheng-Ian T, You-de G, Bloom G. Drug prescribing in rural health facilities in China: implica- tions for service quality and cost. Tropical Doctor 1998;28:42–48. Table 1 Inappropriate use of antibiotics in teaching hospitals Country Inappropriate Type/department use (%) Canada 1977 42% Surgical ward – injections, antibiotics 50% Gynaecology ward 12% Medical ward USA 1978 41% All patients Australia 1979 86–91% Prophylaxis Canada 1980 30% Paediatric medical cases 63% Paediatric surgical cases Australia 1983 48% All departments Kuwait 1988 39% Paediatric inpatients Australia 1990 64% Patients on vancomycin Thailand 1990 91% All departments South Africa 1991 54% Gynaecology inpatients 22–100% Unrestricted antibiotics Thailand 1991 41% All departments 79.7% Surgical prophylaxis 40.2% Documented infection Source: Hogerzeil HV. British Journal of Clinical Pharmacology 1995;39:1–6. Prescribers There is a wide variation in the pre- scribing of antimicrobials and other drugs. In primary health care 30–60% of patients receive antibiotics (see Figure 1), perhaps twice what is clinically needed. Misuse is common and may take the form ➢ KATHLEEN HOLLOWAY* ntimicrobial resistance is a natural consequence of antimicrobial use, which kills the sensitive organisms leaving the resistant ones to survive and multiply (selection of resistance). Overuse and misuse of antimicrobials do not help patients, they merely add to the problem of resistance and waste resources. Figure 1 Percentage of primary health care patients receiving antibiotics of incorrect dosage or inappropriate pre- scription. In Tanzania, 91% of antibiotics were prescribed with incorrect dosage1 and in India over 90% of prescriptions did not have dose specifications.2 Inap- propriate prescription of antibiotics has Many prescribers in de- veloping countries have little access to good quality information about diagnosis and drugs. Standard treat- ment guidelines are often unavailable and health workers are often unsup- ported and unsupervised. Frequently, drug company representatives are doctors’ only source of information. Such information may well be biased, particularly with regard to how effective their company’s drug is com- pared to rival drugs of the same class. Uncertainty of the diagnosis, fear of poor patient outcome, (and in in- dustrialised countries, fear of litigation), lead to over- presciption of antibiotics. In many developing countries, the diagnostic process is often inadequate to arrive at a diagnosis with any certainty (Figure 2). Patient demand or prescriber perception? Even if prescribers are certain of their diagnoses (and none of them will be all Figure 2 Adequacy of diagnostic process Sources: Thaver et al, Social Science and Medicine 1998. Guyon et al, WHO Bulletin 1994. Krause et al, Tropical Medicine and International Health 1998. Bitran, Health Policy and Planning 1995. Bjork et al, Health Policy and Planning 1992, Kanji et al, Health Policy and Planning 1995. ineffective, they prescribe them because they are dependent on the patient return- ing for their livelihood.7 In Europe, over 50% of mothers interviewed in a study expected to receive antibiotics for most respiratory infections.8 Prescribers citing patient demand as a cause of irrational prescribing has been reported in many countries. And patient demand for specific drugs has been widely observed by researchers. How- ever, the degree to which prescribers are influenced by their patients is unknown and probably varies according to the skills and confidence of the prescriber. There is some evidence that it is a prescriber’s perception of patient demand, rather than actual patient demand, during the consultation process that may affect the prescribing decision.9,10 Effects of dispensing doctors Many prescribers, as well as drug retailers, earn their living by selling medicines and not by charging a consul- tation fee. It has been shown in many countries that prescribers who earn money from dispensing medicines consistently prescribe more drugs than those who do not make money from dispensing. In a study in Zimbabwe11 dispensing doctors prescribed antibiotics to 58% of their patients compared to non-dispensing doctors who prescribed antibiotics to 48% of their patients. In China, after the ‘socialist market economy’ reforms of the late 1970s, drug sales became an important source of income for providers, including health worker salary supplements. Once drug sales formed part of health worker sala- ries, greater polypharmacy was observed, and the average prescription was found to cost two to six times the average per capita daily income.12 Selling high cost items, such as antibiotics, may earn dispensing prescribers more profit, but unfortunately many patients cannot afford such drugs and may buy incomplete courses. In a study in the Philippines 90% 0% 10% % of PHC patients receiving antibiotics 20% 30% 40% 50% 60% 70% Sudan Swaziland Cameroon Ghana Tanzania Zimbabwe Indonesia Nepal Bangladesh Eastern Caribbean El Salvador Jamaica Guatemala AFRICA LATIN AMERICA & CARIBBEAN ASIA Pakistan Bangladesh Burkina Faso Senegal Angola Tanzania 0 10 20 30 40 50 60 % observed consultations where the diagnostic process was adequate been reported to occur for vi- ral respiratory tract infections in 97% of cases in China3 and 81% of cases in Ghana.4 In- appropriate prescription of antibiotics for childhood di- arrhoea commonly occurs, as reported in Pakistan. Here pri- vate general practitioners were found to prescribe significantly more antibiotics (41% of pae- diatric cases) than paedia- tricians (36% of paediatric cases) in the public hospitals.5 Hospital prescribers are of- ten the role models for primary health care prescribers. Unfor- tunately, antimicrobials are misused just as much in hospi- tals as in primary health care, as shown in Table 1. Why do providers prescribe antimicrobials too often and unnecessarily? There are many causes including: ➤ lack of knowledge or A N T I M I C R O B I A L R E S I S T A N C E Source: Managing Drug Supply, 2nd ed. Quick JD, Rankin JR, Laing RO, O’Connor RW, Hogerzeil HV, Dukes MN, Garnett A, eds. Hartford CT: Kumarian Press; 1997. 10 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Problems from antimicrobial use in farming ➢ KLAUS STÖHR* ollowing their success in human medicine, antimicrobials have been increasingly used to treat disease in animals, fish and plants. They also became an important element of intense animal husbandry because of their observed growth enhancing effect, when added in sub-therapeutic doses to animal feed. Some growth promoters belong to groups of antimicrobials (for example, glycopeptides and streptogramins), which are essential drugs in human medicine for the treatment of serious, potentially life-threatening bacterial diseases. These include Staphylococcus or Enterococcus infections. Scale of use The total amount of antimicrobials used in food animals is not precisely known, although it is estimated that about half of the antimicrobials produced glo- bally are used in farming, particularly in pig and poultry production. In Europe, all classes of antimicrobial licensed for disease therapy in humans are also registered for use in animals, a situ- ation comparable with other regions in the world, although comprehensive regis- tration data are much more difficult to obtain. National statistics on the amount and pattern of antimicrobial use, in hu- man medicine or anything else, exist in only a few countries. An average of 100 milligrams of antimicrobials are used in animals in Eu- rope to produce one kilogram of meat for human consumption. Statistics from other regions are scarce, but increased meat production in many developing countries is mainly due to intensified farming, which is often coupled with greater anti- microbial use for both disease therapy and growth promotion. Factors contributing to overuse ➤ Education on antimicrobial resistance and prudent antimicrobial use is lacking amongst dispensers and pre- scribers of antimicrobials, and in many countries, people who are inad- equately trained dispense them. One study reported that more than 90% of the drugs used in animals in the United States in 1987 were administered without professional veterinary con- sultation. Inappropriate doses and combinations of drugs are frequently used in animals. And antimicrobials administered to animal flocks and herds in their feed causes problems of inaccurate dosing, and the inevitable treatment of all animals irrespective of health status. ➤ Empiric treatment predominates because of the widespread lack of diagnostic services, particularly in de- veloping countries. In many places, it is uncommon to submit clinical specimens and samples from sick ani- mals, due to the costs involved, time restrictions and the limited number of laboratories. ➤ Drug sales constitute a significant por- tion of veterinarians’ income in some countries and may lead to unnecessary prescribing. ➤ In many countries, including several developed ones, antimicrobials are available over-the-counter and may be purchased without prescription. ➤ Inefficient regulatory mechanisms or poor enforcement, with lack of quality assurance and marketing of substandard drugs, are important contributory factors. Discrepancies between regulatory requirements and prescribing/dispensing realities are often wider than in human medicine. ➤ Antimicrobial growth promoters are not considered drugs and are licensed, if at all, as feed additives. ➤ As in human medicine, pharma- ceutical industry marketing of antimicrobials influences veteri- narians’ and farmers’ prescribing behaviour and use patterns. There are currently few countries with industry codes or government rules for over- seeing advertising practices for antimicrobials for non human use. ➤ There is a significant increase in intensive animal production, particu- larly in countries with economies in transition where all the factors listed here are present. When animal pro- duction appears to benefit from the use of antimicrobials, economic incen- tives may take precedence over the possible transfer of resistance to hu- mans, and the potential negative impact on human health. Examples of the consequences of overuse ◆ Shortly after the licensing and use of fluoroquinolone, a powerful new class of antimicrobials, in poultry, fluoroquinolone-resistant Salmonella and Campylobacter isolations from animals, and soon afterward from humans, became more common. Community and family outbreaks, as well as individual cases, of Salmonellosis and Campylobacteriosis resistant to treatment with fluoroquinolones have since been reported from several countries. ◆ With the emergence of vancomy- cin-resistant strains of Staphylo- coccus and Enterococcus bacteria in many hospitals around the world, the question arose if the use of those antimicrobial agents in agriculture could have com- pounded the worsening problem. Vancomycin-resistant Enterococci were isolated in animals, food and non-treated volunteers in countries where vancomycins were also used as growth promoters in animals. By 1997 all European countries had banned vancomy- cin, and after this the prevalence of resistant Enterococci in animals and food, particularly in poultry meat, fell sharply. How to tackle the problem WHO, the UN Food and Agriculture Organization, the Office International des Epizooties and 14 other international governmental and nongovernmental or- ganizations and professional societies have developed a framework of recom- mendations to reduce the overuse and misuse of antimicrobials in food animals for the protection of human health. (For further information see: http://www. who.int/emc/diseases/zoo/who_global_ principles.html). What the various stakeholders need to do Responsibilities of regulatory and other relevant authorities All antimicrobials used in food ani- mals should be reassessed in relation to their propensity to cause antimicrobial resistance in bacteria which can be trans- mitted to humans. Priority should be given to those products considered most important in human medicine. After the licensing of veterinary antimicrobials, surveillance of resistance to antimicrobials belonging to classes considered important in human medicine should be conducted. In this way emer- gence of antimicrobial resistance will be detected in time to allow corrective The widespread use of antimicrobials in farming is of serious concern as some of the newly emerging resistant bacteria in animals are transmitted to humans, mainly from food of animal origin or through direct contact with farm animals. Treating disease caused by these resist- ant bacteria in humans is more difficult and costly and, in some cases, available antimicrobials are no longer effective. The best-known examples are diseases caused by the foodborne pathogenic bac- teria Salmonella and Campylobacter and the commensal (harmless in healthy persons and animals) bacteria Enterococ- cus. Research has shown that resistance in these bacteria is often a consequence of using certain antimicrobials in agriculture. More studies are needed, however, as the impact of the widespread distribution of non-metabolised antimicrobials through manure and other effluents into the environment is still unknown. And information is also scarce on the type and amount of antimicrobials used in the ex- panding aquaculture sector. Based on the lessons learned from species living on land, there is an urgent need to review current practices to identify potential haz- ards. This also applies to other uses of antimicrobials, in plant protection and in industry, for example. F A butcher’s stall in the Dominican Republic. There is increasing evidence of the problems caused by feeding antimicrobials to farm animals Ph ot o: W H O / PA H O / A . W aa k A N T I M I C R O B I A L R E S I S T A N C E 11E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Promoting resistance? ➢ JOEL LEXCHIN* he Autumn 1996 issue of Health Horizons, the magazine of the Interna- tional Federation of Pharmaceutical Manufacturers Associations, ran a two-page feature entitled “International Mobilization Against New and Resistant Diseases.” This article highlighted the efforts being made by international organizations and the pharmaceutical industry to deal with the threat of increasing antibiotic resistance. What the article didn’t mention was that some in the industry can also play a role in promoting bacterial resistance to currently available medications. that otitis media, at least in children older than two years, should not be treated with antibiotics unless the child fails to improve after 48 hours. What these advertisements do is to promote, as first line choices, the use of antibiotics that should be kept in reserve, and promote the use of antibiotics for conditions that will probably resolve without any intervention. Both situations represent inappropriate use of antibiotics and clearly have the potential to lead to increased resistance. The other common feature of these advertisements is that they are for new, expensive antibiotics; drugs that can gen- erate large profits for companies, if sales volumes are large. What doctors do not see is advertising for older, less expen- sive antibiotics, even though these drugs are the ones that are the most appropri- ate. When was the last time there was an ad for penicillin for streptococcal phar- yngitis or for trimethoprim for a urinary tract infection? This scenario is not limited to Canada, the situation is, if anything, worse in other parts of the world. The Medical Lobby for Appropriate Marketing (MaLAM) has received a number of examples of inappropriate antibiotic promotion in de- veloping countries. Advertisements in 1994 and 1995 in the Philippines advo- cated the use of lincomycin for tonsillitis/ pharyngitis and clindamycin in upper res- piratory tract infections. The most likely cause of any of these conditions is a viral infection where antibiotics are useless. Once again, antibiotics are being adver- tised for conditions that do not require them. 1997 advertising claims in India for clarithromycin used the words “pae- diatric suspension . . . speed, . . . strength, . . . spectrum, . . . safety” without any qualification. In MaLAM’s opinion it would have been reasonable for readers of this ad to interpret those words to mean that clarithromycin has clinically important advantages over alternative antimicrobials and thus was a first line antibiotic for common childhood in- fections. As MaLAM pointed out, autho- ritative sources did not recommend clarithromycin as the treatment of choice for paediatric otitis media, pharyngitis or sinusitis. The parallels with the Cana- dian example of the advertisement for ciprofloxacin are clear; the advertise- ments are encouraging the overuse of second-line drugs. A couple of American studies, span- ning almost a quarter of a century, make the point that the concern about promo- tion leading to the misuse of antibiotics is more than just a theoretical problem. The first of these, published in the early 1970s, showed that more appropriate use of the antibiotic chloramphenicol was related to infrequent use of journal ads to learn about usefulness of new drugs, and disapproval of detailers as sources of pre- scribing information for new drugs.1 The second study came out in 1996. In this case, researchers presented a group of primary care doctors with three case scenarios, two of which involved infec- tious diseases, and asked them to choose between four treatment options of equal efficacy but with widely varying costs. The more credibility that doctors attached to information coming from sales repre- sentatives the higher the physician’s cost of prescribing.2 In many cases in developing countries doctors lack sources of objective infor- mation about antibiotics. These doctors are totally reliant on promotional mate- rial from companies, with all of the biases that this material entails. In the mid 1980s physicians practicing in a peripheral health centre in Sri Lanka where poly- pharmacy, multiple antibiotic therapy and the use of mixtures of unproven efficacy were common, were totally dependent on, and positive towards, drug information from drug companies.3 Drug companies are now racing to bring out new, more powerful antibiotics to combat drug resistance, and we should welcome these medications. But if the industry is sincere about wanting to do something about resistance then it should start by monitoring its promotional practices more closely. ❏ * Dr Joel Lexchin is an emergency physician in Toronto, Canada, and the Secretary- Treasurer of the Medical Lobby for Appropri- ate Marketing. He is also a co-author of Drugs of Choice: A Formulary for General Practice. References 1. Becker MH, Stolley PD, Lasagna L, McEvilla JD, Sloane LM. Differential education concerning therapeutics and resultant physician prescribing patterns. Journal of Medical Education 1972;47:118–27. 2. Caudill TS, Johnson MS, Rich EC, McKinney WP. Phy- sicians, pharmaceutical sales representatives, and the cost of prescribing. Archives of Family Medicine 1996;5:201–6. 3. Tomson G, Angunawela I. Patients, doctors and their drugs: a study at four levels of health care in an area of Sri Lanka. European Journal of Clinical Pharmacology 1990;39:463–7. According to one company, cipro- floxacin is “an appropriate choice for your [doctors’] patients at risk.” This was the message in an advertisement that ap- peared in the 3rd October 2000 issue of the Canadian Medical Association Jour- nal. “Appropriate” for whom? To answer that question readers had to notice a small asterisk after the word “risk” and then look down to the bottom of the page, where in small print they found the definition. “Appropriate” for what? Once again in small type was the an- swer; ciprofloxacin should be used in “challenging” respiratory tract infections. Challenging was never defined. In the same advertisement the company claimed that it supports the appropriate use of antibiotics. Advertisements that do not give clear information or that give it in print that re- quires the use of a magnifying glass are not supportive of appropriate use of me- dications. The message in the ad for ciprofloxacin is that doctors should feel free to use this medication as a first line agent any time they are worried about their patients, or think that there is some- thing unusual going on. Ciprofloxacin is a good first choice for a limited number of problems but not for most respiratory tract infections. The Australian Schedule of Pharmaceutical Benefits restricts the use of this antibiotic in these situations and the same is true in some Canadian provinces. Another recent Canadian journal ad- vertisement, this time for azithromycin, had a young baseball pitcher, his face determined, ready to release the ball with the message “tough on acute otitis me- dia, easy on kids.” The message in this case was that doctors and their young patients need a powerful medication to deal with otitis media and that azithromycin fits the bill. However, this does not reflect the growing consensus T Farming. cont’d from pg. 10 A N T I M I C R O B I A L R E S I S T A N C E strategies to be implemented as part of an efficient post-licensing review. Authorities should ensure that all antimicrobials for disease control in ani- mals are classified as prescription-only medicines. Distribution/sales/marketing Enforcement policies should be designed to ensure compliance with laws and regulations on the authori- sation, distribution and sale, and use of antimicrobials. They should aim at preventing the illicit manufacture, importation, and sale of antimicro- bials, and at controlling their distribution and use. Special attention should be paid to the distribution and sale of counterfeit, sub-potent and misbranded veterinary antimicrobials. Enforcement action should be taken to stop such distribu- tion and sale by relevant authorities, in coordination with the exporting country, if appropriate. Antimicrobial growth promoters Use of antimicrobial growth promot- ers that belong to classes of antimicrobial agents used (or submitted for approval) in humans and animals should be termi- nated or rapidly phased-out in the absence of risk-based evaluations. Surveillance of antimicrobial resistance Programmes to monitor antimicro- bial resistance in animal pathogens, zoonotic agents (for example, Salmonella spp. and Campylobacter spp.), and bac- teria known to be indicators of anti- microbial resistance (for example, Es- cherichia coli and Enterococcus faecium) should be implemented on bacteria from animals, food of animal origin and humans. Surveillance of antimicrobial use Information on the amounts of anti- microbials given to food animals should be made publicly available at regular intervals, be compared to data from sur- veillance programmes on antimicrobial resistance, and be structured to permit further epidemiological analyses. Prophylactic use of antimicrobials Use of antimicrobials for prevention of disease can only be justified where it can be shown that a particular disease is present or is likely to occur. The routine prophylactic use of antimicrobials should never be a substitute for good animal health management. Prophylactic use of antimicrobials in control programmes should be regularly assessed for effectiveness and whether use can be reduced or stopped. Efforts to prevent disease should continuously be in place, aimed at reducing the need for the prophylactic use of antimicrobials. Education and training Veterinary undergraduate, postgra- duate and continuing education should be evaluated to ensure that preventive medicine, prudent antimicrobial use and antimicrobial resistance are given high priority. The effectiveness of this train- ing should be continuously monitored. Education strategies emphasising the importance and benefits of prudent use principles must be developed and imple- mented to provide relevant information on antimicrobial resistance for producers and stakeholders. Emphasis must also be given to the importance of optimising animal health through implementation of disease prevention programmes and good management practices. The public should be informed of the human health aspects of antimicro- bial use in food animals, so that they can support efforts to control antimicrobial resistance. Research Stakeholders should identify research priorities to address public health issues of antimicrobial resistance from anti- microbial use in farming. Governments, universities, research foundations and industry should give high priority to supporting research in these areas. ❏ * Dr Klaus Stöhr is a Scientist at the World Health Organization, Communicable Dis- eases Cluster, Animal and Food-Related Public Health Risks, Department of Commu- nicable Disease Surveillance and Response. 12 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Antibiotic use and bacterial resistance to antibiotics in children in a Vietnamese community n 1999 a household survey was conducted in one agricultural district in sub-tropical north Viet Nam. This district has 32 community health stations, one district hospital, three licensed private pharmacies, a few private practitioners, about 16 drug outlets and 362 villages. The re- searchers randomly selected 200 children, aged 1–5 years, within 166 households, from the 225 households in five villages (out of 67 villages where there is a surveillance programme). Nasopharygeal and throat specimens were collected from each child, and their carers were interviewed to obtain drug use information. Researchers explained the purpose of the study to each household and obtained permission to collect the specimens. species identification and susceptibility testing. Ignoring treatment guidelines It was found that 82% of the children had at least one symptom of acute respi- ratory infection during the four weeks prior to interview, and that of these children 91% had been treated with antibiotics. Thus, 75% of all the children (both with and without symptoms) had been treated with antibiotics. On average antibiotics were given for 3.9 days and ampicillin was the commonest choice; this is contrary to the national treat- ment guidelines, which recommend cotrimoxazole for acute respiratory infection. When deciding which antibiotic to use, 67% of carers used a pharmacy, 11% decided themselves, and 22% followed a doctor’s prescription. The carers were asked what drug information they paid attention to when treating their children, and replied as below: daily dosage 87% how to take the drug 52% (e.g. with water) total dosage 12% contraindictions 8% expiry date 3% antibiotic resistance 1 person Eighty percent of the antibiotics were purchased from small shops and pedlars, 18% from community health stations and 2% from a national hospital pharmacy. A disturbing level of resistance One hundred and sixty-three isolates from 145 children were susceptibility tested. The carrier rate for S.pneumoniae was 50%, for H.influenzae 39%, and for M.catarrhalis 17%. In 74% of the 145 A standardised questionnaire was developed, piloted and then used by four experienced local interviewers. They asked questions about the types of anti- biotics which had been used, how long for, where they were purchased, and what they knew about them. At the same time, microbiologists from Hanoi Uni- versity collected nasopharygeal (pos- terior nares) and throat (tonsillar) swabs. The swabs were immediately placed in charcoal transport medium, and trans- ported to the laboratory for culture, I Symptom(s) of ARI 4 weeks preceding the study and treated with antibiotics 75% Symptom(s) of ARI 4 weeks preceding the study. Not treated with antibiotics 7% No symptoms/ Not treated with antibiotics 18% Penicillin 12% Amoxicillin 11% Erythromycin 5% Tetracycline 4% Other 3% Don’t know 11% Ampicillin 74% Eighty-two percent of the 200 children had symptoms of ARI four weeks preceding the study (left pie chart) and seventy-five percent of these children had used antibiotics within this four week period (right pie chart). As some antibiotics were used in combination, the percentages total more than 100%. Figure 1 Antibiotic consumption amongst children Table 1 Prevalence of antibiotic resistant (R) and intermediate susceptible (I) strain of H. influenzae, S. pneumoniae and M. catarrhalis H. influenzae S. pneumoniae M. catarrhalis n = 74 n = 62 n = 27 Antibiotics R I R I R I Ampicillin 18% 6% – – 19% 30% Chloramphenicol 24% 0% 25% 3% 15% 4% Ciprofloxacin 6% 6% 0% 80% 0% 19% Erythromycin 4% 49% 23% 3% – – Gentamicin 0% 2% 3% 95% 0% 0% Loracarbef 2% 0% – – 0% 4% Penicillin V 24% 60% 6% 5% 54% 31% Tetracycline 32% 32% 88% 2% 13% 0% Trimethoprim/ 44% 3% 32% 12% 59% 19% Sulphonamide Vancomycin – – 2% 2% – – Number of susceptibility tested strains susceptibility tested (n). Antibiotic not tested (–). children resistant pathogens were found. Resistance to one or more antibiotics was shown in 68% (50/74) of H.influenzae isolates, 90% (56/62) of S.pneumoniae isolates, and 74% (20/27) of M.catarr- halis isolates. The prior consumption of ampicillin or pencillin was associated with a significantly greater ampicillin or penicillin resistance, odds ratio 2.3 (p<0.05). Multi-drug resistance to a com- bination of trimethoprim/sulphonamide, tetracycline, chloramphenicol, penicillin V and ampicillin was found in 26% of H.influenzae isolates. Multi-drug resist- ance was found in 31% of S.pneumoniae isolates. Almost all S.pneumoniae isolates were resistant to both tetracycline and trimethoprim/sulphonamide and about half were resistant to chloramphenicol and/or erythromycin. The authors conclude that there is a serious public health problem in the Vietnamese community. A majority of children will suffer acute respiratory in- fection symptoms within any one month. They will be treated inappropriately with antibiotics, which are contributing to significant levels of resistance. ❏ Source: Larsson M, et al. Antibiotic medica- tion and bacterial resistance to antibiotics: a survey of children in a Vietnamese commu- nity. Tropical Medicine and International Health 2000;5(20):711–721. Working to decrease costs of anti-TB drugs ➢ MARCOS ESPINAL, RAJESH GUPTA, MARIO RAVIGLIONE* mong infectious diseases tuber- culosis (TB) remains a leading cause of adult mortality.1 Over the last decade, the rising spectre of multidrug-resistant TB (MDR-TB) began to threaten global TB control efforts. MDR-TB is defined as disease caused by Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. There is evidence that short-course chemotherapy with first-line anti-TB drugs used to treat drug-susceptible cases is not as effective to cure MDR-TB cases.2 In some areas of the world (especially countries of the former Soviet Union and eastern Europe), rates of MDR-TB among new and pre- viously-treated cases are so high that they are considered “international public health emergencies” given the possibility of international spread.3,4 To respond to the challenge, WHO and several partners have launched pilot projects to manage MDR-TB within pro- gramme conditions in settings of limited resources. However, one of the greatest obstacles to providing treatment to patients infected with MDR-TB has been the high cost of the second-line anti-TB A A N T I M I C R O B I A L R E S I S T A N C E 13E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 drugs needed for the management of MDR-TB.5 Over the last three years, open market prices for these second-line anti-TB drugs have been as high as US$15,000 for an 18-month treatment regimen. In contrast, the first-line anti- TB drugs needed for management of drug-susceptible TB cost as little as US$11 for a six-month treatment regi- men.6 In order to decrease the cost of these drugs, the WHO Working Group (spe- cially created to deal with MDR-TB) has negotiated with both the research-based and generic pharmaceutical industry. Ne- gotiations have resulted in a preferential price decrease in the cost of treatment regimens of up to 90% in comparison to the open market price. These preferential prices were partially achieved through global procurement of drugs. Consolidat- ing the market into a single-demand source not only allowed for some market forces to arise, but also for industry mem- bers to conduct more accurate demand forecasts that, previously, had been very difficult. At the same time, in order to protect against the misuse of drugs and creation of resistance to these drugs (the last line of chemotherapeutic defence against TB), these preferentially priced drugs are only released to those projects adhering to standard scientific guidelines as deter- mined by an independent body called the Green Light Committee.7 This Committee, housed in WHO, is currently com- prised of six institutions: Centres for Disease Control and Prevention, Harvard Medical School, Médecins Sans Frontières, the Na- tional TB Programme – Peru, Royal Netherlands TB Association and WHO (serving as a permanent member and secretariat). Most of the work conducted by the Green Light Com- mittee is performed via videoconference, telecon- ference and e-mail. All decisions are made by consensus.8 Overall, the process has worked well due to the joint efforts of all institutions involved. Pilot projects have benefited from the procurement process and the negotiations, which, by virtue of the mechanism References 1. Raviglione MC, Snider DE Jr, Kochi A. Global epide- miology of tuberculosis. Morbidity and mortality of a worldwide epide- mic. JAMA 1995;273(3): 220–26. 2. Espinal MA, et al. Standard short-course chemotherapy for drug-resistant tuberculo- sis: treatment outcome in six countries. JAMA 2000;283 (19):2537–2545. 3. WHO, International Union Against Tuberculosis and Lung Disease. Anti-tuber- culosis drug resistance in the world: the WHO/ IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance, Report No. 2. Geneva: World Health Organiza- tion; 2000. WHO/TB/2000. 278. 4. Harvard Medical School and Open Society Institute. The global impact of drug-resistant tuberculosis. Programme in Infectious Disease and Social Change. 1999. 5. WHO. Procurement of sec- ond-line anti-tuberculosis drugs for DOTS-Plus Pilot Projects. Proceedings of a described, guarantee that high-quality anti-TB drugs provided at preferential prices are used in the best possible, controlled manner. This method of procurement helps to ensure the scientific integrity of the pilot projects and should be explored for use in other infectious diseases, including HIV/AIDS. ❏ * The authors work for the World Health Organization, Communicable Diseases Cluster, in Strategy Development and Monitoring for Endemic Bacterial and Viral Diseases, Communi- cable Disease Control, Prevention and Eradication. meeting. Gupta R, Brenner JG, Henry CL, et al, eds. Geneva: World Health Organization; 2000. WHO/CDS/ TB/2000.276. 6. Khatri. Personal Communication. 2000. 7. WHO. Guidelines for establishing DOTS-Plus Pilot Projects for the management of multi-drug-resistant tu- berculosis. Geneva: World Health Organization; 2000. WHO/CDS/TB/2000.279. 8. WHO. DOTS-Plus and the Green Light Committee. Ge- neva: World Health Organization, 2000. WHO/CDS/TB/ 2000.283. A patient in Tanzania suffering from TB, a disease which is becoming increasingly common and increasingly resistant to drug treatments Ph ot o: W H O / O . H ar re r How Chile tackled overuse of antimicrobials I Committee on Health of the National Congress. Professional organizations of physicians and chemists, and the National Department of Consumer Affairs were also consulted, with a view to informing the general public before adopting any potentially unpopular measures. This was necessary because people were accustomed to purchasing anti- biotics without a prescription, and even individual tablets in Chile’s pharmacies. Hitting the headlines At the end of September 1999, after this consultative process, the Ministry of Health acted to control antibiotics, by making them available only through chemists and on prescription. Compliance with the measure was encouraged by dis- tributing leaflets in private chemists, displaying posters and by extensive coverage on radio and television news programmes. In addition, the attention of the pharmaceutical chemists respon- sible for the technical management of pharmacists was drawn to the increase in antibiotic consumption over the previous 10 years. Table 1 Percentage increases in consumption of selected antibiotics and groups of antibiotics, 1988–1997 Antimicrobial 1988 1997 Variation DDD/1000 DDD/1000 % increase pop. per day* pop. per day cloxacillin 0.39 0.417 7 ampicillin 0.54 0.613 14 amoxicillin 0.87 5.204 498 clavul. amoxicillin 0.0025 0.414 16460 cotrimoxazole 0.965 1.163 20 cephalosporins 0.064 0.262 309 fluoroquinolones 0.049 0.281 473 * Defined Daily Dose per 1,000 population per day These children playing happily in Chile stand to benefit from the country’s actions to minimise antimicrobial resistance Ph ot o: W H O / PA H O / C . G ag ge ro A N T I M I C R O B I A L R E S I S T A N C E Anti-TB drugs. cont’d from pg. 12 ➢ LUIS BAVESTRELLO AND ANGELA CABELLO* n 1998, the Pan American Infec- tious Diseases Society and the Pan-American Health Organiza- tion carried out a study in Chile on trends in antimicrobials use during the previous 10 years.1 The study revealed a significant increase in antibiotic con- sumption, expressed in terms of DDD (defined daily dose) per 1,000 population per day over the 10 years, based on an- nual sales data for antibiotics in terms of both grams consumed and units of sale.2 Noteworthy findings included increases in sales of amoxicillin (+ 498%), oral cephalosporins (+ 309%) and oral fluoro- quinolones (+ 473%) between 1988 and 1997. The only antibiotic with declining consumption was chloramphenicol (-18%). See Tables 1 and 2. These findings were submitted to the Chilean Ministry of Health, and meetings arranged to study what to do about the problem. Health Ministry staff met with scientific associations, the body regulat- ing drug manufacture and prescribing, the Institute of Public Health and the .cont’d on page 14 ➠ 14 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Nepal: an economic strategy to improve prescribing pre-post with control study was conducted in 33 health facilities (10–12 per district) in three dis- tricts in Eastern Nepal1. In 1992 all three districts charged the same flat fee per prescription, covering all drugs in whatever amounts. In 1995 the control district charged the same fee, but the other two districts had instituted new fee sys- tems. One district charged a single fee per drug item (1-band item fee), whatever the drug, but covering a full course of the drug. A second district charged a higher fee per expensive item (e.g. antibiotics and injections) and a lower fee per cheap item (e.g. vitamins), each fee covering a full course of the drug. All the fees were priced so as to cost patients about 25% of average daily household income for two drug items. Prescribing was monitored in all health facilities before and after the fee systems were changed. Table 1 shows that both item fees were associated with significantly better pre- scribing quality than the prescription fee. The percentage of patients receiving an- tibiotics decreased and the proportion of prescriptions conforming to standard treatment guidelines increased in both item fee districts as compared to the pre- scription fee district. The 1-band fee was associated with a greater reduction in cheap vitamins and tonics, and the 2-band fee with a greater reduction in expensive injections. ❏ Reference 1. Holloway KA, Gautam BR. The effects of different charging mechanisms on rational drug use in eastern ru- ral Nepal. Paper presented at the First International Conference on Improving Use of Medicines; 1997 April 1 to 4; Chiang Mai, Thailand. Available on the Web at: www.who.int/dap-icium/posters/4e2_Text.html A Table 1 The effects of different kinds of user fee on prescribing quality in Nepal Fees system Control flat fee / Px 1-band fee / drug item 2-band fee / drug item n=12 n=10 n=11 Av. no. 2.9 ➜ 2.9 (0%) 2.9 ➜ 2.0 (-31%) 2.8 ➜ 2.2 (-21%) items/Px % Px with 66.7➜ 67.5 (+0.8%) 63.5➜ 54.8 (-8.7%) 60.7➜ 54.3 (-6.4%) antibiotics % Px with 23.4➜ 20.0 (-3.4%) 19.8➜ 16.1 (-3.7%) 21.8➜ 14.9 (-6.9%) injections % Px with 27.0➜ 22.1 (-4.9%) 26.5➜ 8.4 (-18.1%) 23.5➜ 15.8 (-7.8%) vitamins or tonics % Px conforming 23.5➜ 26.3 (+2.8%) 31.5➜ 45.0 (+13.5%) 31.2➜ 47.7 (+16.5%) to STGs Av. cost / 24.3➜ 33.0 (+35.8%) 27.7➜ 28.0 (+1.1%) 25.6➜ 24.0 (-6.3%) Px (NRs) Px = prescription Table 2 Annual sales of packs of antimicrobials in private pharmacies in Chile, by antimicrobial group, 1988–1997 Year Macrolides Penicillin: broad Penicillin: Cephalo- Cotrimox- Tetra- Chloram- Fluoro- spectrum M-R Spectrum sporin azole cycline phenicol quinolone 1988 765,800 3,199,000 3,488,600 . 1,409,800 836,500 392,600 . 1989 798,400 3,373,700 3,797,800 185,200 1,457,000 851,400 457,100 . 1990 989,235 3,633,271 3,379,425 214,084 1,478,396 870,288 398,428 . 1991 1,053,390 4,104,949 3,354,194 221,457 1,717,625 1,028,031 402,170 . 1992 1,118,807 4,368,913 3,240,031 247,261 1,578,412 914,297 278,566 . 1993 1,435,275 5,151,850 3,289,910 322,135 1,752,653 883,301 298,809 240,167 1994 1,400,078 5,090,712 3,250,074 367,539 1,543,922 844,178 276,392 269,452 1995 1,615,879 6,213,139 3,548,893 505,036 1,532,223 1,016,890 320,594 307,376 1996 1,818,824 6,858,590 3,676,448 537,154 1,550,226 979,917 341,639 335,728 1997 2,076,073 7,799,949 4,035,888 563,902 1,692,889 1,055,055 330,348 414,625 … = No data available Source: International Marketing System Table 4 Dollar sales of groups of antimicrobials by private pharmacies in Chile, 1998–1999 Group of 1998 1999 Difference(US$) antimicrobials macrolides 14,763,740 12,448,627 2,315,113 broad spectrum penicillins 13,747,242 11,227,954 2,519,288 oral cephalosporin 4,488,543 4,193,849 294,694 fluoroquinolone 4,075,818 4,115,261 -39,443 med.-nar. spect. penicillin 4,121,100 3,275,517 845,583 cotrimoxazole 2,316,260 1,767,612 548,648 Total 43,512,703 37,028,820 6,483,883 Source: International Marketing System Table 3 Changes in consumption by DDD/1000 pop./per day between the last quarter of 1998 and the same quarter of 1999 (immediately after the introduction of the Ministry of Health regulation) Antimicrobials 4th quarter 1998 4th quarter 1999 Variation (%) clarithromycin 0.366 0.446 21.8 azithromycin 0.342 0.353 3.2 erythromycin 0.536 0.370 -30.9 amoxicillin 4.639 2.943 -36.5 ampicillin 0.391 0.182 -53.4 clavulanic amoxicillin 0.459 0.443 -3.5 cloxacillin 0.424 0.338 -20.3 phenoxymethylpenicillin 0.184 0.111 -39.7 cotrimoxazol 0.913 0.633 -30.7 tetracycline 0.499 0.340 -31.8 ciprofloxacin 0.317 0.386 21.8 A N T I M I C R O B I A L R E S I S T A N C E Three months after the Ministry’s action an evaluation study showed a downturn in consumption. This further study, entitled “Preliminary evaluation of the impact of the measures to regulate out- patient consumption of antimicrobials in Chile”, involved a comparison between the same two quarters of two years, one immediately before the introduction of the measure, the other immediately after. The study showed a decline in consumption of 36% in amoxicillin, 56% in ampicillin and 30% in erythromycin between the last quarter of 1998 and the same quarter of 1999. Expenditure dropped by US$6,483,883 between 1998 and 1999, representing a saving for the population as shown in Table 4. Studies reveal that the Ministry of Health’s control measures introduced after consultation with scientific, profes- sional and consumer associations, and with Parliament, had a clear impact on the sale and consumption of antibiotics in Chile. As a result, in Chile antibiotics may now only be purchased by prescrip- tion. This has reduced self-medication and the concomitant threat of microbial resistance. This Chilean example shows that given political will, determination, con- sultation and public education, effective measures that save lives – by promoting rational use of antibiotics – and money are possible. ❏ * Dr Luis Bavestrello is a clinical pharma- cologist and Head of the Infectious Diseases Department, Dr Gustavo Fricke Hospital, and Angela Cabello is a pharmaceutical chemist in the Pharmaceutical Unit, Dr Gustavo Fricke Hospital, Alvarez 1532, Viña del Mar, Chile. Tel/fax: + 56 32 652450. References 1. PAHO. Resistencia antimicrobiana en las Américas: Magnitud del problema y su contención. Editores Salavtierra-González R, Benguigui Y. OPS/HCP/HCT/ 163/2000 pp.234–240. 2. Bavestrello L, Cabello A. Estudio del consumo de antimicrobianos en la comunidad. Chile, diez años después. Rev Chil Infect (1999);16(3):185–190. Chile. cont’d from pg. 13 15E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Containing drug resistance through hospital infection control ➢ NIZAM DAMANI* ospitals are a crucial component of the antimicrobial resistance problem world wide, because highly vulnerable patients often require prolonged antibiotic therapy, and the problem of cross infection arises. Every hospital should make con- tainment and control of multi-resistant micro-organisms a high priority, and it re- quires a team approach. The first step is to establish an active and effective infec- tion control committee with responsibility for formulating, implementing and audit- ing an infection control programme throughout the hospital. The microbiology laboratory’s role A good diagnostic microbiology labo- ratory service is essential. Laboratories should use internationally recognised protocols to identify organisms and antibiotic sensitivity, and their range of diagnostic facilities should cover non bacterial and unusual infections. Close liaison with clinicians, the infection control team and the drug and therapeu- tics committee is essential. Laboratories should serve as an important source of local surveillance data both for the hospital and the community. Antibiotic prescribing: a crucial element Hospital drug and therapeutics committees should be responsible for the promotion of rational prescribing, drug use monitoring and cost con- tainment. They must regularly review antibiotic use, conduct audits and give doctors feedback to influence prescribing habits. Committees should also approve the use of newer antimicrobial agents, which should be restricted to agreed clinical conditions. Doctors must be trained to take re- sponsibility for rational prescribing and to justify their antimicrobial use. Their prescribing policy must be evidence- based and should reflect local antibiotic resistance surveillance data. This can be achieved by having a written hospital for- mulary, and an antibiotic policy that is regularly updated and has broad input and consensus among all involved. Infection control measures Barrier precautions are vital to pre- vent the spread of multi-resistant micro- organisms in hospitals. These include isolating patients with multi-resistant organisms, and ensuring that staff ad- heres to hand hygiene procedures and use of appropriate personal protective equipment. It is important for infection control measures to be based on the local epidemiology and be tailored to suit individual needs. Hospitals should have a written dis- infectant policy with procedures to ensure adequate decontamination of equipment and the environment. Internationally recommended sterility checks must be carried out on a regular basis. As multi- resistant organisms can survive in the environment for prolonged periods, and may act as a reservoir for infection, the hospital environment should be kept clean, dry and dust free. Therapeutic devices, such as urinary and intravenous catheters, are not only responsible for the majority of hospital- acquired (nosocomial) bacteraemias, but also for cross infection/outbreaks of catheter-associated and intravenous line infection is not recommended. A universal challenge The control and containment of multi- resistant micro-organisms represents a universal challenge requiring national and international efforts, as ease of long distance travel no longer limits spread. Every hospital should devote ade- quate resources to an infection control programme or health and health care resources could suffer. ❏ * Dr Nizam Damani is Clinical Director and Consultant Microbiologist, Craigavon Area H Hospital, 68 Lurgan Road, Portadown, Co. Armagh BT63 5QQ, Northern Ireland, UK. Tel: + 44 128 38 33 4444 ext. 2654, fax: + 44 128 38 33 4582. References 1. WHO. Recommendations for the control of meticillin- resistant Staphylococcus aureus (MRSA). Geneva: World Health Organization; 1996. WHO/EMC/LTS/96.1. 2. The Hospital Infection Control Practices Advisory Com- mittee. Recommendations for preventing the spread of Vancomycin resistance. Morbidity and Mortality Weekly Report 1995;44:1–13. 3. Global consensus conference on infection control issues related to antimicrobial resistance: Final recommenda- tions. American Journal of Infection Control 1999; 27:503–513. Changing prescriber behaviour TRAINING AND TREATMENT GUIDELINES IMPROVE PRESCRIBING IN UGANDA randomised controlled trial to test the impact of standard treatment guidelines (STGs) plus training and supervision on rational pre- scribing was carried out in 127 health units in Uganda. Prescribing was moni- tored in all facilities both before and after the interventions. In a control group of 42 health units, no intervention was in- troduced. In a second group of 42 health units, the national standard treatment guidelines were disseminated but no training or supervision was conducted. In a third group of 29 health units, the national standard treatment guidelines were introduced and on-site training on therapeutic problems conducted. In a fourth group of 14 health units, the same was done as for the third group but, in addition, four supervisory visits were conducted over a six-month period. Table 1 shows how prescribing changed in the different groups. Prescrib- ing quality, (as judged by the percentage of prescriptions conforming to standard treatment guidelines) did not improve when only guidelines were disseminated, but greatly improved if dissemination was accompanied by training and supervision. The intervention used was not only di- rected at antibiotic prescribing, but other aspects of prescribing also. This may account for why the changes in prescrib- ing quality (percentage of prescriptions conforming to treatment guidelines) were much greater than for antibiotic use alone (percentage of prescriptions containing antibiotics). ❏ Reference Kafuko J.M, Zirabumuzaale C, Bagenda D. Rational drug use in rural health units of Uganda: effect of national standard treatment guidelines on rational drug use. Final report. Kampala: UNICEF, Uganda; 1996. Table 1 Randomised controlled trial in Uganda Randomised group n % prescriptions % prescriptions containing antibiotics conforming to STG Control group 42 53.0 ➜ 58.0% +5.0% 24.8 ➜ 29.9% +5.1% Dissemination of STG 42 51.6 ➜ 57.8% +6.2% 24.8 ➜ 32.3% +7.5% STG + on-site training 29 51.7 ➜ 50.7% -1% 24.0 ➜ 52.0% +28.0% in therapeutic problems STG + on-site training 14 54.3 ➜ 54.3% 0% 21.4 ➜ 55.2% +33.8% in therapeutic problems + 4 supervisory visits in 6 months A No one is more vulnerable to multi-drug resistance than people admitted to hospital wards 4. The Hospital Infection Control Practices Ad- visory Committee. Guidelines for isolation precautions in hospitals. American Journal of Infection Control 1996;24:24–52. 5. Shlaes DM, Gerding DN, John JF, et al. Soci- ety of Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimi- crobial Resistance: Guidelines for prevention of antimicrobial resistance in hospitals. Infec- tion Control and Hospital Epidemiology 1997;18:279–291. 6. Goldman DA, et al. Strategies to prevent and control the emergence and spread of antimi- crobial-resistant micro-organisms in hospitals. Journal of American Medical Association 1996; 275:234–240. ■ ■ ■ multi-resistant organisms. Urinary catheters should be inserted only when necessary and removed when no longer required. All hygiene precautions must be followed. The use of antibiotics should be restricted to patients who show clinical signs of infection. The majority of primary blood stream infections are associated with the use of intravascular de- vices. Again the best prevention is to insert an intravascular line only if necessary and to keep it in place for a minimum period. The rou- tine use of antibiotics to prevent Ph ot o: W H O / PA H O / A . W aa k A N T I M I C R O B I A L R E S I S T A N C E 16 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Prioritising interventions to contain antimicrobial resistance ➢ KATHLEEN HOLLOWAY* ust as there are many actors and activities that contribute towards anti- microbial resistance, so there are many potential strategies to contain the growth and spread of resistance. The WHO Global Strategy to con- tain resistance, (which will be published in 2001 and will be available on the Web via http://www.who.int/emc/amr), identifies 64 interventions in total. Of these, 44 interventions are aimed at improving the use of antimicrobial drugs in humans at the national level or below, (i.e. excluding interventions concerning animal use, new vaccine and drug development and international measures). described. The first method was used in two WHO Regional Offices and one country, whilst the Global Strategy was being developed. From the problems en- countered using the first method, a second method was developed and used at WHO Headquarters in finalising the present draft of the Global Strategy. THE REGIONS’ PRIORITISATION PROCESS Step one: deciding who participates in the process A list of participants was agreed lo- cally. In the Regional Office for the Eastern Mediterranean (EMRO) and the Regional Office for South-East Asia (SEARO), participants were WHO staff members. In Nepal they were from the Ministry of Health, academic institutions and local NGOs. All health disciplines concerned with antimicrobial use and/or resistance were invited, including all those concerned with communicable dis- eases, health systems, essential drugs and primary health care. Step two: developing a list of interventions EMRO participants developed a list of interventions starting from those recommended in the WHO draft Global Strategy. SEARO and Nepali parti- cipants also agreed to use this list (see Table 1). Step three: voting on the proposed interventions Each intervention was scored accord- ing to: (1) the importance or relevance of any impact it might have, and (2) the feasibility of implementation. It was agreed that “relevance” would take into account whether an intervention would impact on the diseases of particu- lar concern locally, and that “feasibility” would take into consideration both cost of implementation and the political con- text. The scoring was as follows: 0 = not feasible or no relevant impact 1 = medium feasibility or medium relevant effect 2 = good feasibility or very relevant effect Step four: collating the voting data All the participants’ scores for likely relevant impact and feasibility for each intervention were added up and then plot- ted on a matrix. Interventions that were likely to have the greatest impact and be feasible appeared in the top right-hand corner of the chart and were judged to be of highest priority. Those interventions that appeared in the bottom left-hand corner of the chart were judged less fea- sible and relevant. For example, in a group of 11 people, the maximum score an intervention could receive for either importance or feasibility was 22 (11 par- ticipants awarding a maximum of two points). The points plotted on the matrix would therefore be 22 for importance and 22 for feasibility. Diverse views The graphs below (figures 1–3) in- dicate the priority given to different interventions. Comparison shows how the various regions agreed and disagreed on which interventions should have highest priority. The reasons for differences in the priorities between these three groups may have been due to different priorities in different areas, but were also in large part due to the different expertise of partici- pants in the different groups. For example, in SEARO there was no one specialising in health systems or drug regulation, in Nepal microbiologists were poorly rep- resented, as were agriculturalists in both EMRO and SEARO. The most feasible and important inter- ventions agreed by everyone included: ➤ training of prescribers and dispensers, and the use of guidelines and formu- laries; ➤ establishing infection control commit- tees, guidelines for antimicrobial use, and surveillance of antimicrobial use in hospitals; ➤ developing national drug policies, essential drugs lists and standard treatment guidelines; ➤ ensuring undergraduate and post- graduate training on antimicrobial resistance; Critical decisions No country in the world is imple- menting all of these recommended interventions and most would find it im- possible to do so. Therefore, all countries will need to prioritise the interventions and choose which ones to implement first and which to implement later. Develop- ing countries in particular will need to prioritise and choose only those interven- tions that, in their local contexts, are both feasible and likely to have the greatest impact. This article discusses the prob- lem of how to choose which interventions will be both feasible and have a signifi- cantly large impact. Two methods are J Table 1 Agreed list of interventions to contain antimicrobial resistance Target group Recommended interventions A 1. Education on appropriate use Patients and 2. Education on hygiene the public 3. Discourage self-medication B 1. Training Prescribers and 2. Guidelines and formularies dispensers 3. Monitoring and supervision 4. Regulation of professionals 5. Educate prescribers about promotion C 1. Therapeutic committees Health systems 2. Infection control committees 3. Guidelines for antimicrobial use 4. Antimicrobial use surveillance 5. Laboratory network and epidemiological resistance surveillance D 1. National AMR task force with budget Government 2. Drug policies e.g. essential drugs list, standard policies, strategies treatment guidelines and regulations 3. Registration of all drug outlets 4. Antimicrobials by prescription-only 5. Dispensing of antimiocrobials by licensed staff only 6. Quality assurance system 7. Drug licensing to include resistance data 8. Undergraduate and postgraduate training on AMR 9. Access to evidence-based drug information 10. Cut perverse rational drug use economic incentives 11. Monitor and supervise drug promotion 12. Monitor and link AMR and drug use data E 1. Incentives for industry to do research and development Pharmaceutical 2. Monitor and supervise drug promotion industry 3. Production according to Good Manufacturing Practice standards F 1. Surveillance of resistance and use Non-human 2. Phase-out growth promoters antimicrobial use 3. Educate farmers and vets A N T I M I C R O B I A L R E S I S T A N C E A pharmacy in Colombia. Ensuring good dispensing practices is seen as a high priority in the fight against antimicrobial resistance Ph ot o: W H O / PA H O / A .W aa k 17E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Figure 1 Prioritisation of interventions by the 11 members of EMRO antimicrobial resistance task force Figure 2 Prioritisation of interventions by 15 health officials in Nepal Figure 3 Prioritisation of interventions by 7 staff members of SEARO Priorities in the WHO Global Strategy for Containment of Antimicrobial Resistance Although all interventions were classi- fied into fundamental, high, medium and low, only the first two categories are shown below. Within the two priority groupings shown here, interventions are not ranked. Fundamental interventions Make containment of antimicrobial resistance a national priority including: ◆ creating a national task force; ◆ allocating resources to implement interventions to contain antimicrobial resistance; ◆ developing indicators to monitor and evaluate the impact of an antimicrobial resistance strategy; ◆ designating or developing reference microbiology laboratory facilities. These would coordinate effective, epidemiologically-sound, surveillance of antimicrobial resistance among common pathogens in the community, hospitals and other health care facilities. High priority interventions 1. Patient education on: ◆ the importance of measures to prevent infection such as immuniza- tion, vector control, use of bed-nets; ◆ simple measures that may reduce transmission of infection in the household and community, such as hand washing, food hygiene. 2. Prescriber and dispenser (including drug seller) education on: ◆ the importance of appropriate antimicrobial use and containment of antimicrobial resistance; ◆ disease prevention (including immunization) and infection control issues. 3. Targeted undergraduate and post- graduate education programmes for all prescribers, dispensers and other health care workers, and veterinarians, on accurate diagnosis and management of common infections. 4. Development, updating and use of standard treatment guidelines and treatment algorithms to foster appropriate use of antimicrobials. 5. Infection control programmes with responsibility for effective manage- ment of antimicrobial resistance in hospitals. 6. Diagnostic laboratories that provide: ◆ microbiology laboratory services which are appropriately matched to the level of the hospital (e.g. secondary, tertiary); ◆ appropriate diagnostic tests, bacte- rial identification, antimicrobial susceptibility tests of key pathogens, with adequate quality assurance, and timely, relevant reporting of results. 7. Limiting the availability of antimicrobials to prescription-only status, except in special circum- stances where they may be dispensed on the advice of a trained health care professional. 8. Ensuring that only antimicrobials meeting international standards of quality, safety and efficacy are granted marketing authorisation. The figures should be viewed in conjunction with Table 1, as the different shapes and colours on the three graphs each represent one of the six target groups (A–F) listed in the Table. For example, a green circle signifies D – interventions involving government policies, strategies and regulations. The numbers within each shape correspond to the different recommended interventions in each of the target groups. So there are 12 green circles on the map numbered 1 to 12, corresponding to the numbered list of interventions under D in Table 1. Their position on the graph is dependent on the scores participants awarded them. For example, D10 – cutting perverse rational drug use economic incentives – appears in the bottom left-hand corner of the graph, showing that it received the lowest scores for both importance and feasibility. The dotted green cross lines signify where the average score (1 point for both importance and feasibility awarded by each person in the group) would appear. 4 Im po rta nc e 25 20 15 10 5 0 5 10 15 20 25 Feasibility Not feasible or relevant Feasible and relevant interventions targeting patients, families, communities interventions targeting prescribers and dispensers interventions targeting health systems interventions involving government policies, strategies, regulations interventions targeting the pharmaceutical industry interventions targeting non-human antimicrobial use 1 2 1 3 3 2 5 1 3 3 5 2 1 1 2 0 F E C B A D 8 2 39 2 3 6 5 4 12 7 11 10 1 4 1 1 Im po rta nc e 25 20 15 0 10 15 20 25 Feasibility Not feasible or relevant Feasible and relevant 0 interventions targeting patients, families, communities interventions targeting prescribers and dispensers interventions targeting health systems interventions involving government policies, strategies, regulations interventions targeting the pharmaceutical industry interventions targeting non-human antimicrobial use 1 2 3 3 2 5 1 4 3 2 3 3 5 2 1 2 4 5 4 10 12 7 1 6 11 13 9 3 2 8 F E C B A D Im po rta nc e 15 10 5 0 0 5 10 15 Feasibility Not feasible or relevant Feasible and relevant F E C B A D 4 1 2 1 3 3 2 5 1 3 3 5 21 1 2 8 23 9 23 6 5 4 12 7 11 10 4 interventions targeting patients, families, communities interventions targeting prescribers and dispensers interventions targeting health systems interventions involving government policies, strategies, regulations interventions targeting the pharmaceutical industry interventions targeting non-human antimicrobial use 1 A N T I M I C R O B I A L R E S I S T A N C E ➤ ensuring drugs are produced accord- ing to Good Manufacturing Practice standards. The least feasible and important inter- ventions agreed by everyone included: ➤ ensuring that antimicrobials are dis- pensed by licensed staff and only with a prescription; ➤ cutting perverse economic incentives to prescribe antibiotics – for example the problem of dispensing prescribers earning more money from selling antibiotics than from other drugs; ➤ monitoring and linking data concern- ing antimicrobial resistance and antimicrobial use; ➤ monitoring and supervising drug pro- motion both for human and animal use; ➤ phasing out growth promoters in animal use. PRIORITISING INTERVENTIONS FOR THE WHO GLOBAL STRATEGY As a result of the diverse views ob- tained from the regions, a different process of prioritisation was conducted for the draft Global Strategy, in order to produce some concrete practical advice for Member States. Experts in the fields of drug use, clinical microbiology and other related disciplines from all over the world were invited to a workshop in Geneva. Parti- cipants were divided into three working groups, with each considering inter- ventions aimed at a particular target audience: Group 1: Prescribers and dispensers Group 2: Hospitals Group 3: Health systems For each target audience, the interven- tions were prioritised according to their relative merits and ranked according to sequence and importance of implemen- tation. This complex task required consideration of multiple factors relating to each intervention including: ➤ overall importance of the interven- tion to improving the appropriate use of antimicrobials and containing antimicrobial resistance; ➤ likely impact, allowing for the ex- pected cost of implementation; ➤ complexity of implementation, con- sidering the capacity of various health care systems and political realities; ➤ time required for implementation and the expected lag period before outcomes could be expected; ➤ the accuracy with which most health care systems could assess the efficacy of each intervention; .cont’d on page 18 ➠ ➤ the interrelationship between various interventions, including the need to undertake some interventions in a logical sequence. As a result of this process, interven- tions were ranked as high, medium and low, and consideration was given to whether the ranking would vary accord- ing to a national health system’s level of development. Once interventions for each target 18 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Useful websites on antimicrobial resistance A N T I M I C R O B I A L R E S I S T A N C E audience were ranked, the interventions were then ranked according to their over- all importance and timing (sequence) of implementation, without consideration of their target audience. This was done by all the participants in a plenary session (see box). It was recognised that some priorities might vary depending on the health care system in which they would be implemented. However, this did not impact to any significant extent on the priority given to the majority of very high priority interventions. Although it was not planned to address issues relating to consumers and drug promotion at this workshop, in fact they were also considered. This was because participants, particularly in Group 1, felt that prescribers and dispensers could not be considered separately from consumers. INTERVENTIONS FOR MAXIMUM IMPACT Comparison of the priorities identified at country, regional and international levels shows many similarities. The in- terventions agreed by everyone to be both high priority and feasible are: 1. training prescribers and dispensers, and using guidelines and formularies; 2. establishing infection control commit- tees and guidelines for antimicrobial use; 3. developing national drug policies, essential drugs lists and standard treat- ment guidelines; 4. ensuring undergraduate and post- graduate training on antimicrobial resistance; 5. ensuring that drugs are produced ac- cording to good manufacturing practice standards and are of adequate quality. D ep ar tm en t o f H ea lth , U K A leaflet from the UK’s public education campaign on the correct use of antibiotics APUA-Alliance for the Prudent Use of Antibiotics http://www.antibiotic.org (see also EDM No.24 p.20) AR InfoBank-WHO Antimicrobial Resistance Information Bank http://oms2.b3e.jussieu.fr/arinfobank BUBL Catalogue of Internet Resources – Infectious Diseases http://bubl.ac.uk/link/i/infectiousdiseases.htm Center for Adaptation Genetics and Drug Resistance http://www.healthsci.tufts.edu/labs/Sblevy/home.html Center for Complex Infectious Diseases http://www.ccid.org/ Centers for Disease Control, Drug Resistance Homepage http://www.cdc.gov/drugresistance/ CIA. The global infectious disease threat and its implications for the United States. 1999 http://www.odci.gov/cia/publications/nie/report/nie99-17d.html EARSS-European antimicrobial resistance surveillance system http://EARSS.rivm.nl Eurosurveillance http://eurosurv.org/ Global Polio Eradication Initiative http://www.polioeradication.org Infectious Disease News http://www.slackinc.com/general/idn/idnhome.htm International Society for Infectious Diseases http://isid.organize-it.com/ Johns Hopkins University – Infectious Diseases http://www.hopkins-id.edu/index_id_links.html Karolinska Institute, Sweden http://micf.mic.ki.se/Diseases/ National Foundation for Infectious Diseases, USA http://www.nfid.org/ Project Icare: Intensive Care Antimicrobial Resistance Epidemiology http://www.sph.emory.edu/ICARE/ Roll Back Malaria http://www.rbm.who.int/ Stop TB Initiative http://www.stoptb.org The Hot Zone: Emerging Infectious Diseases Reports and Web Sites http://www.qis.net/~edwardmc/eid.htm UK Public Health Laboratory http://www.phls.co.uk/ US National Center for Infectious Diseases http://www.cdc.gov/ncidod/eidtopics.htm Washington University Infectious Disease Division, USA http://www.id.wustl.edu/ WHO Communicable Diseases Home Page http://www.who.int/health-topics/idindex.htm WHO/TDR (Special Programme for Tropical Disease and Research) http://www.who.int/tdr Selected references Coast J, Smith RD, Millar MR. An economic perspective on policy to reduce antimicrobial resistance. Soc Sci Med 1998;46:29–38. Fidler DP. Legal issues associated with antimicrobial drug resistance. Emerg Infect Dis 1998;4:169–77. Finch RG, Williams RJ. Eds. Antibiotic resistance. Clin Infect Dis 1999;5(2). Goldmann DA, Huskins WC. Control of nosocomial anti- microbial-resistant bacteria: a strategic priority for hospitals worldwide. Clin Infect Dis 1997;24 (Supplement 1):S139–45. Hart CA, Kariuki S. Antimicrobial resistance in developing countries. BMJ 1998;317:647–650. Institute of Medicine. Antimicrobial resistance: issues and options. Workshop report. Washington D.C.: National Academy Press; 1998. http://books.nap.edu/books/0309060842/html/ R1.html#pagetop Pittet D et al. Effectiveness of a hospital-wide programme to improve compliance with hand hygiene. Lancet 2000;356: 1307–1312. Polk HC Jr, Christmas AB. Prophylactic antibiotics in surgery and surgical wound infections. Am Surg 2000;66:105–11. UK Standing Medical Advisory Committee Sub-Group on Antimicrobial Resistance. The path of least resistance. London: Department of Health; 1998. http://www.open.gov.uk/doh/smac.htm WHO. World Health Assembly 1998. Emerging and other communicable diseases: antimicrobial resistance. WHA51.17, agenda item 21.3. http://www.who.int/emc/ WHO. Anti-tuberculosis drug resistance in the world. The WHO/International Union Against Tuberculosis and Lung Disease global report on anti-tuberculosis drug resistance surveillance 1994–97. Geneva: World Health Organization; 1997. WHO/TB/97.229. WHO. Guidelines for the management of drug-resistant tuberculosis. Geneva: World Health Organization; 1997. WHO/ TB/96.210. WHO. Integrated management of childhood illnesses: A WHO/ UNICEF initiative. WHO Bulletin 1997;75 (Supplement 1). WHO. The medical impact of the use of antimicrobials in food animals: Report and proceedings of a WHO meeting, Berlin, Germany, 13–17 October 1997. Geneva: World Health Organization; 1997. WHO/EMC/ZOO/97.4. WHO. Treatment of tuberculosis: guidelines for national programmes; 2nd ed. Geneva: World Health Organization; 1997. WHO/TB/97.220. WHO. Use of quinolones in food animals and potential impact on human health. Report and proceedings of a WHO meeting, Geneva, Switzerland, 2–5 June 1998. Geneva: World Health Organization; 1998. WHO/EMC/ZDI/98.12. WHO. Basis for the development of an evidence-based case-management strategy for MDR-TB within the WHO’s DOTS Strategy. Geneva: World Health Organization; 1999. WHO/TB/99.269. WHO. Containing antimicrobial resistance. Review of the literature and report of a WHO workshop on the development of a global strategy for the containment of antimicrobial resistance. Geneva, Switzerland, 4–5 February 1999. Geneva: World Health Organization; 1999. WHO/CDS/CSR/DRS/99.2. www.who.int/emc/WHO_docs/general.htm WHO. WHO report on infectious diseases. Removing obstacles to healthy development. Geneva: World Health Organization; 1999. WHO/CDS/99.1. http://www.who.int/infectious-disease-report/ WHO. Anti-tuberculosis drug resistance in the world. Report no. 2. Prevalence and trends. The WHO/International Union Against Tuberculosis and Lung Disease global report on anti- tuberculosis drug resistance surveillance. Geneva: World Health Organization; 2000. WHO/CDS/TB/2000.278. WHO. Global tuberculosis control: WHO Report 2000. Geneva: World Health Organization; 2000. WHO/CDS/TB/2000.275. WHO. Guidelines for establishing DOTS-Plus pilot projects for the management of multidrug-resistant tuberculosis (MDR-TB). Geneva: World Health Organization; 2000. WHO/CDS/TB/ 2000.279. WHO. Management of the child with a serious infection or severe malnutrition: guidelines for care at the first-referral level in developing countries. Geneva: World Health Organization; 2000. WHO/FCH/00.1. WHO. World Health Organization report on infectious diseases 2000. Overcoming antimicrobial resistance. Geneva: World Health Organization; 2000. WHO/CDS/2000.2. http://www.who.int/infectious-disease-report-2000 WHO. Surveillance standards for antimicrobial resistance. Geneva: World Health Organization; 2000. CDS/CSR/DRS 2000.2 (in preparation). Interestingly, regional staff felt that surveillance of antimicrobial use in hos- pitals was feasible and important, and gave it higher priority than the experts invited to Geneva did. On the other hand, while the Geneva group felt that restrict- ing antimicrobials to prescription-only status was very important, regional staff felt that it was not feasible. There is no hard evidence as to which interventions are most important and have the greatest impact, and expert opinion varies. Nevertheless the two different processes of prioritisation identified the five interventions listed above. Everyone agreed that these interventions were fea- sible and would have the greatest impact on antimicrobial resistance if adequately implemented. ❏ * Dr Kathleen Holloway is a Medical Of- ficer in the Department of Essential Drugs and Medicines Policy at the World Health Organization. Prioritising interventions. cont’d from pg. 17 19E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Private sector prescribing Editor, When I worked as a pharmacist in the public sector I found it relatively easy to promote rational use of drugs through adherence to the essential drugs list, standard treatment guidelines and formu- laries. However, now employed in the private sector, I find these tools difficult to use because of prescribers’ resistance to what they see as restrictions upon them. Obviously the forces driving the pri- vate sector are unlike those in the public sector. For example, cost containment is not a priority, as the consumer (generally those dissatisfied with the public health care system) pays for services, mainly through some form of health insurance. My question is, in the private sector is it really possible to rationalise medicines’ use and still have a good income? I would be interested to hear readers’ views. —Dr Atieno Ojoo, P.O. Box 13576, Nairobi, Kenya. ✍ ✍ ✍ A simple solution to outpatient record keeping? Editor, In developing countries the idea of keeping medical records in hospital offices is impractical, and often impossi- ble to implement. Here in Tanzania’s Dodoma region the Out Patient Service has adopted my suggestion of patients keeping a “health booklet”. The booklet is in fact a primary school exercise book, widely available and priced at around US$0.06. As the booklet is the patient’s property, a sense of ownership means it is usually well kept and made available whenever requested. The system’s advantages are that it can provide a full patient history, particularly useful in cases such as hypertension, dia- betes, asthma or allergy. Also data are recorded chronologically, whereas before we often had to sort through numerous pieces of paper and put them in date or- der. When there is a shortage of hospital cards and files, the booklet can also be used as an in patient file or as a growth chart for the under-fives. As senior doc- tors can comment on and change previous diagnoses and treatments, the system can help in improving junior colleagues’ skills and prescribing practices. Lack of supplies and of motivated staff should convince hospital managements to rely more on user commitment, and let patients document their own medical histories. —Dr Massimo Serventi, Paediatrician, Dodoma General Hospital, Box 1498, Dodoma, Tanzania. ✍ ✍ ✍ L E T T E R S T O T H E E D I T O R Substandard chloroquine in Ghana Editor, Countries in tropical Africa account for more than 90% of total malaria inci- dence and the great majority of malaria deaths, with children the most vulnerable to the disease. Cloroquine is one of the most frequently used drugs in prevention and treatment. But in recent years in some endemic areas certain strains of plasmo- dium falciparum, one of the parasites responsible for malaria, has become re- sistant to chloroquine. Among the reasons cited for this is the manufacture, sale and use of substandard chloroquine formula- tions. In Ghana we have completed an eight-year study to discover the scale of the problem, and it has reinforced con- cerns about the quality of chloroquine available here. Thirty-eight samples of chloroquine phosphate tablets and 57 samples of syr- ups, manufactured locally by different firms, were tested in the Ghana Standards Board’s laboratories between 1992 and 1999. All the samples were analysed ac- cording to British Pharmacopoiea assay methods. The Pharmacopoiea’s specifi- cation for the content of chloroquine phosphate in tablets ranges between 92.5% and 107% of the label claim. In Ghanaian produced tablets 250 mg of chloroquine is the norm and for syrup the Paul Ehrlich, 1854–1915 A German medical scientist renowned for his pioneering work in haematol- ogy, immunology and chemotherapy, Ehrlich won the 1908 Nobel Prize for his discovery of the first effective treatment for syphilis. As well as his research into early chemotherapy, Ehrlich also developed “side chain theory” a hypothesis that provided the first plausible description of the body’s own immunological response to destructive pathogens. Louis Pasteur, 1822–1895 Considered one of the greatest French biologists of the nineteenth century, Pasteur devoted his life to solving practical problems in industry, agri- culture and medicine. Pasteur was the first to discover that fermentation and putrefaction only took place in the presence of living organisms. With further research he developed the technique of pasteuri- zation that not only revolutionized the dairy industry, but food processing as well. A N T I M I C R O B I A L R E S I S T A N C E Pioneers of antimicrobial resistance acceptable level is between 118.75 and 131.25 per 5ml. Of the 38 tablet samples analysed, four contained levels of chloroquine phosphate below the minimum requirement, with one sample at 38.9%. Of the 57 samples of syrup 10 contained levels of active in- gredient below the minimum required. We conclude that during the eight-year study period some malaria sufferers were exposed to significant amounts of sub- standard chloroquine phosphate in both tablets and syrups. However, lessons have been learned, and steps taken to improve matters. One local manufacturer had to withdraw affected batches of drugs and had his factory closed until an effective quality assurance scheme was in place. Local manufacturers supplying the Min- istry of Health must now have their products tested and certified by the na- tional quality control laboratory. The Food and Drugs Board is implementing measures to assure drug quality in manu- facture, supply and distribution. And during 1999 an association of drug manu- facturers was formed, pledging to comply with WHO Good Manufacturing Practices. —Charlotte Ohene-Manu and Jonathan Martey, Ghana Standards Board, Drugs and Cosmetics Department, P.O. Box MB, 245, Accra, Ghana. ✍ ✍ ✍ Selman Waksman, 1888–1973 A Ukrainian-born biochemist, Selman Waksman played a major role in initi- ating a calculated, systematic search for antibiotics among microbes. His dis- covery of streptomycin – effective in the treatment of tuberculosis – garnered him the Nobel Prize in 1952. Sir Alexander Fleming, 1881–1955 Honoured with a Nobel Prize for his discovery of penicillin, Fleming transformed medical science with the development of the world’s first antibiotic. While working with Sta- phylococcus bacteria in 1928, the Scottish bacteriologist noticed a bacteria-free circle around a mould growth contaminating a culture of staphylococci. Upon further investigation he discovered a substance that prevented bacterial replication even when diluted 800 times. In 1943 he was elected fellow of the Royal Society and knighted in 1944. Robert Koch, 1843–1910 A 1905 Nobel Prize honoree, Koch was the first scientist to identify the organ- ism that causes tuberculosis, Koch is considered the founder of modern bacteriology because he successfully isolated several disease-causing bacte- ria and discovered the animal vectors of a number of major diseases includ- ing anthrax. Through his many experiments, Koch discovered how to obtain microorganisms from animals, and how to culture those same samples. It was Koch who discovered that cholera is primarily a water-borne disease. John Enders, 1897–1985 American microbiologist and Nobel laureate John Enders led a research team which developed a technique for growing viruses in cultured cells. He showed that poliomyelitis viruses grew in both brain and cultured tissues and in this way caused cell destruction. John Enders went on to demonstrate the safety of cul- tured viruses in producing immunity, and proved that measles could be prevented through vaccination.◆ ◆ ◆ 20 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Brazil: WHO’s Director-General speaks out for generics r Gro Harlem Brundtland, WHO’s Director-General, has made a major speech in Brazil strongly supportive of generic drug strategies. Testifying before the country’s Parliamentary Commission on Investigation of Medicines in April 2000, she discussed national drug policies, essential drugs and the importance of generics in promoting affordability of medicines. Saying that there are no “simplistic solutions and no magic bullets”, Dr Brundtland explored how people living in poverty might get sustainable access to drugs at affordable prices. She spoke of pharmaceutical companies’ moral ob- ligation to contribute to the solution, but also said that protective tariff barriers and distribution margins for drugs should come down. Dr Brundtland highlighted the need for political acceptance of the concept of “equity pricing”, especially for newer essential drugs of vital public health importance. Equity pricing means that the poor would not have to pay the same price for life-saving drugs as those who are better off. She urged govern- ments of industrialised countries to lead in its establishment. While developing country governments must facilitate access by “improving financing, impor- cost, increasing choice and helping to rationalise both the selection and use of pharmaceuticals. Relevance for the private sector Dr Brundtland told Commission members that policies advocating gener- ics – which are frequently only associated with the public sector – can be just as beneficial in the private sector, because they promote efficiency within pharma- ceutical markets. She stressed the importance of this in developing coun- tries, where up to 90% of drug con- sumption is through the private sector. She added that generic strategies in- volve much more than legal mandates; “they need support and enforcement, must respond to the concerns of involved par- ties and provide adequate economic incentives”. More countries adopt the strategy Dr Brundtland spoke of the progress made to date. In Latin America, several countries have already enacted legislation relevant to generic strategies, but in most cases implementation is limited. Overall, however, the results indicate that lower prices have resulted where solid and transparent legislation exists. The Direc- tor-General pointed out that in the USA generic drugs represent half of the mar- ket in volume. One of the European Union’s three major policy regulations on pharmaceutical pricing and reimburse- ment is to enhance competition by making the market more transparent and encour- aging generics. And many hospitals in developed countries have lists of ap- proved drugs which identify products by generic name. In conclusion, Dr Brundtland said that WHO has, for a long time, been en- couraging drug policies based on the promotion of generic drugs of assured quality – a cost-effective strategy in containing drug expenditure. She told Commission Members that WHO is, therefore, in favour of so called “early workings” of patented drugs for generic manufacturers, to encourage competition and give impetus to research for improved products. This includes the use of pat- ented drugs for research and testing, which necessitates prompt registration and early production of generic drugs, the Director-General said. Countries with variations of early workings provisions include Argentina, Australia, Canada, Hungary, Israel and the USA. ❏ ■ ■ ■ A young patient in Brazil, where generic drugs are rapidly increasing their share of the pharmaceutical market tation, purchasing and distribution systems for medicines, vaccines and medical equipment”, Dr Brundtland continued. Brazil’s National Drug Policy highlights generic drug prescribing and use, and stipulates mandatory adoption of generic names in all public purchases. The Director-General said that promoting generics can help meet the ob- jectives of health sector reforms by improving affordability, reducing D Ph ot o: W H O / PA H O / C . G ag ge ro Meetings give impetus to Africa’s essential drugs programmes ssential drugs programme manag- ers in Africa have met to debate a range of pharmaceutical issues and move forward their agenda to ensure access to essential medicines. At two critical meetings they endorsed the Intensified Essential Drugs Programme for the African Region, and made numerous policy recommendations. The first meeting, in South Africa in March 2000, brought together managers from 16 anglophone countries. They called on health authorities to adopt good procurement practices for essential drugs. Authorities should capitalise on economies of scale, and make pricing information available to prescribers, dispensers, consumers and health insur- ance companies, to enable them to make informed decisions. Participants also pro- posed that governments should encourage local production of essential drugs, and remove taxes on both the drugs and their raw materials. The managers endorsed the idea of joint bulk purchasing of drugs for prior- ity health problems, and urged WHO to provide more information to Member States on the benefits and limitations of such schemes. However, they insisted that local industries should not be put at an undue disadvantage in the bidding process. Delegates emphasised that easy access to reliable information on pharmaceu- tical suppliers and pricing was vital to achieve optimal quality at affordable prices. A Web site should be established, coordinated by WHO, to make such in- formation freely available and keep it updated. Participants also wanted information disseminated on the concept and benefits and efficiency. Rational use of drugs was high on the agenda. Participants recommended that Member States develop strategies and incorporate rational use principles in health workers’ training curricula. Phar- macotherapeutics committees were seen as a way to improve rational use by pre- scribers and dispensers, and should be introduced at all levels of care. Acknowledging the role of traditional medicines in African health care, pro- gramme managers urged WHO to N A T I O N A L D R U G P O L I C Y inspection services; and the legislation and regulations necessary to ensure drug quality. As in South Africa there was much discussion on improved pricing policy. Participants called for com- plementarity between the public and private sectors, the creation of autono- mous central medical stores, promotion of local production, and state and com- munity co-financing to improve drug supply and access. They also discussed integrating drug policy programmes in health development plans, creating ra- tional drug use strategies, and improving staff training. At both meetings WHO requested countries to specify the activities they would carry out to implement the Inten- sified Essential Drugs Programme, so that the Organization can make detailed plans for supporting them. But important work is already underway. The WHO Regional Office for Africa is running training in good manufacturing practices, and the AFRO Essential Drugs Price Indicator has been launched. Countries continue to receive support in implementing national drug policies, assessing drug regula- tory capacity in Member States and reviewing pharmaceutical legislation. ❏ E of harmonisation of drug regulatory activities, and the promotion of common minimum standards. This would generate confi- dence in the quality of services. Public health needs rather than commer- cial interests should drive the harmonisation pro- cess, delegates stressed. In addition, Member States should strengthen the ca- pacity of drug regulatory agencies and grant them some degree of autonomy, to ensure effectiveness The AFRO Essential Drugs Price Indicator – one of the welcome initiatives introduced by the AFRO Intensified Essential Drugs Programme give support to countries in deciding how best to use them within health systems. In August 2000 it was the turn of 38 essential drugs programme manag- ers from 20 francophone countries to spend time reflecting on their work and planning ahead. Meet- ing in Lomé, Togo, they recommended: the crea- tion of Directorates of Pharmacy and Medicines; quality control labora- tories; pharmaceutical 21E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Progress on drug policy in FYR Macedonia he Former Yugoslav Republic of Macedonia launched its National Drug Policy development process in February 2000, with the support of WHO/EURO and WHO Humanitarian Assistance Office, Skopje. Five working groups were created to develop different elements of policy: legislation and regulations; drug selection; drug information; rational drug use; supply and economic strategies; and human resource development. By October the groups were ready to move to the next phase of the process – combining the different drafts to produce one comprehensive document. Macedonia is now deciding on future activities and a time frame for policy implementation. ❏ Launch of the Australian National Medicines Policy ➢ ANTHONY SMITH* ustralia has gained a reputation as an innovative country for its work on the quality of use of medicines, and for its recently established National Prescribing Service. It may therefore come as a surprise to learn that, until recently, Australia had no formal, comprehensive, endorsed National Me- dicines Policy. The reasons are historic rather than political. For more than 50 years, acceptable quality, safety and efficacy of medicines have been assured through the work of the Therapeutic Goods Administration. Equity of access to medicines is pro- vided through the Pharmaceutical Benefits Scheme which, by a system of graduated co-payments, allows access to medicines for all including the poorest members of society – in the extreme at no cost to the consumer. This Scheme has operated for half a century. While the pharmaceutical industry may have some ambivalence about its re- lationships with government, financial incentives have been provided to enhance industry’s viability, both in Australia and as a presence in the South-East Asia/Western Pacific region. In line with the prototype policy elaborated by WHO, rational use (or qual- ity use, as we chose to call it) of medicines became the fourth component of Austra- lian policy in 1992. Therefore, our Medicines Policy evolved over a long period in contrast to that of many coun- tries who have devised theirs over a period as short as a few months. At last, and primarily through the work of the Australian Pharmaceutical Advisory Council (APAC), all this activ- ity has come together in the National Medicines Policy which was formally launched by the Joint Parliamentary Secretary for Health, Senator Grant Tambling, on 10 December 1999. APAC was a good vehicle for the de- velopment of the Policy document as its membership reflects the partnership ap- proach which has become central, particularly, to the Quality Use of Me- dicines Programme in Australia. Con- sumers, the pharmaceutical industry, government and health professionals are all represented on APAC. The document reflects all of their views including, most recently, those relating to the community role of complementary medicines (Aus- tralia has a Federal Government Office for Complementary Medicines and a World Health Assembly 2000: drug debates focus on HIV/AIDS comprehensive resolution on HIV/AIDS was among the high- lights of the World Health Assem- bly, held in Geneva in May 2000. Ninety-five percent of the 34 million people living with HIV/AIDS are in developing countries. And it was these countries’ representatives who success- fully campaigned for WHO to increase its role in advising on the best treatment options, and how to overcome drug pricing and access problems. During discussions on the Revised Drug Strat- egy delegates also stressed the need for WHO to support broader approaches to drug financing, and to address the grow- ing dangers of unregulated sale of medicines on the Internet and counterfeit drugs. Among its provisions resolution WHA53.14 on confronting the HIV/ AIDS epidemic requests the Director- General to: support the implementation of drug price monitoring systems in Mem- ber States, to promote equitable access to care, including essential drugs; promote rational use of drugs by strengthening Member States’ capacity to implement drug monitoring systems; and continue to develop methods and support for moni- toring the pharmaceutical and public health implications of trade agreements. Numerous delegates stressed the need for WHO to retain its independent voice when advising countries on the com- plex subject of health-related aspects of trade. At one of the many side meetings dur- ing the Assembly, public health advocates from Health Action International, Mé- decins Sans Frontières and Consumer Project on Technology held a joint brief- ing for Member States on improving access to essential drugs. And they added their voices to support for WHO’s role in providing global pricing information on quality medicines for people living with HIV/AIDS. Tackling counterfeit drugs A well-attended technical briefing on drug quality at the Assembly focused on counterfeits. The presence of senior health officials, and representatives from Inter- pol, the pharmaceutical industry and NGOs reflected the multi-faceted nature N A T I O N A L D R U G P O L I C Y N E W S D E S K A A separate evaluation committee for these products). As a country we have been very fortunate that several of the essential ingredients of a National Medicines Policy have been in existence for so long. Bridging the digital divide Nevertheless, our comprehensive policy has finally won the endorsement of Gov- ernment and with this endorsement goes the expectation that continuing resources will be made available to ensure that we can implement strategies in the many ar- eas which are currently less than ideal. It would have been good to have had this policy and its endorsement a long while ago! The Australian Medicines Policy document may be accessed and down- loaded from: http://www.health.gov. au:80/haf/docs/nmp2000.htm ❏ * Anthony Smith is Professor of Clinical Phar- macology, Newcastle University Mater Misericordiae Hospital, Waratah NSW 2298, Australia. of the problem. The audience was told of highly sophisticated operations in which criminals take advantage of cross-border loopholes. Supplies, production, shipping re-labelling, financing and distribution of these drugs are often handled in different countries. The meeting called for closer coop- eration between law-enforcing agencies, legislative bodies and the pharmaceuti- cal industry. Saying that there was “an urgent need for action”, Dr Yasuhiro Suzuki, Executive Director of WHO’s Health Technology and Pharmaceuticals Cluster, referred to the “deadly combina- tion of demand for cheap drugs and fat profit margins” that makes counterfeiting drugs so attractive to criminals and such a threat to society. ❏ T Aborigines in Kalgoorlie, Australia. Adoption of the National Drug Policy has formalised the country’s efforts to provide quality medicines for all nly a small fraction of global health research expenditure goes to research into diseases and health issues that affect the poor, such as malaria, killer childhood diseases and nutrition. One step towards changing this is to facilitate research in the countries that have first-hand experience of these problems. Now WHO and the Open Society Institute (part of the Soros Foundation network) have teamed up with information provid- ers ISIO and SilverPlatter, and other partners to do just that. They will provide medical and health research institutions in Africa, Central Asia and Eastern Eu- rope with Internet access to quality scientific information from around the world. The project’s first year pilot phase will enable scientists at leading research institutions in Armenia, Ghana, Mali, Mozambique, Mongolia, Uganda, Tanza- nia and Uzbekistan to access information in digital format. In this way integration of the world scientific community through electronic communication will advance. WHO will be among those negotiating with service providers in the eight initial countries to provide high- speed connection to the Internet. Research staff in the countries will receive com- prehensive training to ensure maximum benefit from the project. It is anticipated that by the end of its second year between 30 and 40 countries will have joined the project, which is part of the wider United Nations programme “Health InterNetwork”. This aims to improve pub- lic health world wide by facilitating the flow of health information using Internet technologies. ❏ O Ph ot o: W H O : H . A ne nd en 22 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 WHO and partners – taking the initiative to make a healthier world Opening a meeting of 200 health and advocacy experts from 70 countries in Winterthur, Switzerland, Dr Brundtland said that although the world had long known that illness and poverty are closely linked, recent data show a much more devastating economic impact on devel- oping country economies by a few infectious diseases, particularly malaria, HIV/AIDS and tuberculosis. But a number of effective health interventions exist that dramatically reduce mortality of these killers, she emphasised. “Quite simply, if we can take these interven- tions to scale – and by that I mean to a global scale – we have in our hands a concrete, result-oriented and measurable way of starting to reduce poverty.” Dr Brundtland said that a concerted global effort was needed that would involve a process, a road to follow, a framework for thinking and a set of values to underpin it all. The forum followed recent announce- ments by the G8 leading industrial nations of targets to reduce the burden of malaria and tuberculosis by 50% within 10 years, and to reduce the spread of HIV/AIDS by 25% within the same time period. It also comes after the creation of a new policy framework by the European Com- mission intended to focus the European Union’s aid effort on reaching those targets. ACCESSING VACCINES Every year, nearly three million chil- dren die from diseases that could be prevented with currently available vaccines. The Global Alliance for Vaccines and Immunization (GAVI), formed in 1999, is a coalition of interna- tional organizations, with a mission to ensure that every child is protected against vaccine-preventable diseases. It wants to close the growing gap in the number of vaccines available to children in industrialised and developing countries. GAVI is working to: ➤ improve access to sustainable immu- nization services; ➤ expand the use of all existing cost- effective vaccines; ➤ accelerate the development and intro- duction of new vaccines; ➤ accelerate research and development efforts for vaccines and related prod- ucts specifically needed by developing countries; ➤ make immunization coverage an integral part of the design and assessment of health systems and international development efforts. Since its inception the Alliance has received a great deal of interest from de- veloping countries wanting to benefit from its work. On 20th September 2000 the Global Vaccine Fund, one of the financial tools used by the initiative, an- nounced that it will be giving more than US$150 million worth of vaccines and funding over five years to improve im- munization rates in Africa, Asia and Latin America. According to estimates more than 100,000 lives will be saved every year due to initial grants to 13 countries. For further information check: www.who.int/vaccines/aboutus/gavi.htm ROLLING BACK MALARIA When she became WHO’s Director- General in 1998, Dr Gro Harlem Brundtland decided that malaria would be one of the Organization’s top priori- ties. She instigated Roll Back Malaria, a partnership involving a wide range of organizations at country, regional and global levels. The initiative’s goals include: ➤ support to endemic countries in devel- oping their national health systems as a major strategy for controlling malaria; ➤ efforts to develop the broader health sector – all providers of health care to the community. This includes the pub- intensive final phase in order to mop up the final pockets of the virus. In September 2000, a broad spectrum of leaders from business, governments, UN agencies and humanitarian groups, met at the United Nations in New York to galvanise the necessary financial re- sources and political will for the Initiative to ensure it meets the 2005 deadline. Over 250 participants pledged to help over- come the challenges: poliovirus was still circulating in up to 20 countries at the end of 2000, and US$450 million in new fund- ing is needed to conquer the disease in those places. The 20 high-risk countries also present some of the most difficult logistical challenges to polio eradication, including populations that are geogra- phically isolated and, in a handful of countries, living in the midst of severe civil conflict. Emphasising the urgency of the task, UN Secretary-General, Kofi Annan, said that “our race to reach the last child is a race against time. If we do not seize the chance now, the virus will regain its grip and the opportunity will elude us forever”. A recent milestone The WHO Western Pacific Region was certified polio-free on 29 October 2000 by an independent panel of interna- tional public health experts. The Region includes 37 countries and areas ranging from tiny islands to China with a popula- tion of 1.2 billion people. The Regional Certification Commission on Poliomyeli- tis Eradication confirmed that no new cases of indigenous polio have been de- tected in the Western Pacific in the last three years, despite excellent surveillance for the virus – the major benchmark for certification. For more news on the Polio Eradi- cation Initiative check: www.who.int/ vaccines-polio/ STOPPING TB Tuberculosis (TB) remains the larg- est killer of young people and adults in the world, and the problem is growing with the spread of HIV/AIDS and drug resistant strains of the disease. Stop TB is a global movement to accelerate social and political action to stop the unneces- sary spread of TB around the world. Its mission is to ensure that every person with TB has all the necessary information and access to treatment and cure. Stop TB is a partnership working with public and private organizations from the local to the global level. Donors, research in- stitutions, industry, international agencies, governments and NGOs are all playing a role in: ➤ linking TB control to health sector development; ➤ linking TB control to poverty allevia- tion; ➤ linking TB control to relevant aspects of socioeconomic development; ➤ promoting a more client-centered approach for wider coverage and compliance by partnering with community-based groups and others. For further information check: www.stoptb.org/stop.tb.initiative/index. html#StopTB One of Stop TB’s partners is the Glo- bal Alliance for TB Drug Development, a not-for-profit venture that is accelerat- ing the discovery and development of new drugs to fight the disease by drawing upon best practice and resources from the pub- lic and private sectors (see page 19). The Alliance aims to fill a gap in TB drug development by using a lean research and development operating model that outsources projects to public or private partners. It will survey all TB drug de- velopment and selectively intervene when its actions will help move a drug candi- date towards registration and use in therapy. In this way the Global Alliance will build a portfolio of projects with varying levels of funding, management and ownership. Further information is available at: www.tballiance.org/home.cfm IMPROVING INJECTION PRACTICES Injections are predominantly needed for the treatment of severe diseases, mostly in hospital settings. Nevertheless, they are overused to administer medica- tions in many countries because of an ingrained preference for injections among health workers and patients. In develop- ing countries up to 50% of injections are administered with re-used syringes and needles. Such unsafe practices have been linked to the transmission of many A C C E S S T A sight that will soon disappear? A polio victim learns to walk with callipers Ph ot o: W H O / PA H O / C . G ag ge ro here are several important and new international health initiatives involv- ing WHO in global partnerships that are addressing some of the most pressing health problems of our time. Here we focus on some of them, beginning with WHO Director-General Gro Harlem Brundtland’s call for a concerted global effort to tackle diseases of poverty, made in October 2000. lic sector health system, civil so- ciety, NGOs and private health providers (including drug ven- dors and traditional healers) and others; ➤ encouragement to obtain the necessary human and financial investments for health system development. In recent months Roll Back Ma- laria has received a major boost from the African summit meeting, which set the agenda for the continent’s efforts to beat the disease (see report on page 23). Find out more at: www.rbm. who.int ERADICATING POLIO The Polio Eradication Initiative is on track to certify global eradica- tion of the disease in 2005, with more than 190 countries and territories which will have interrupted polio- virus transmission by the end of the year 2000. This is an initiative that began in 1988, but it is entering an 23E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 pathogens between patients, including the hepatitis, HIV, Ebola and dengue fever viruses, and the malaria parasite. The Safe Injection Global Network (SIGN) is a coalition of several public and private partners, including WHO, UNICEF, UNAIDS, NGOs, govern- ments, universities, health workers and industry. Formed in Geneva in October 1999, it aims to unite the partners’ strengths and skills to work together on injection safety. Because there have been few integrated programmes that link com- munity and health systems to promote safe injection use, SIGN is coordinating the launch of pilot projects in five coun- tries. Results of the pilot projects’ evaluation should be available by 2002, and will enable the Network to identify and adopt successful strategies to counter unsafe injections. Positive developments SIGN’s annual meeting, held in Cairo in October 2000, showed that there has already been progress. For example, Pa- kistan has set up a national “SIGN” group, Tanzania has launched an education cam- paign for the public and health workers, and Burkina Faso has made significant improvements in injection safety recently. Participants reviewed the previous year’s activities, exchanged information and coordinated their advocacy and public awareness activities. New technical guidelines on prevent- ing infection from injections are being prepared, and a provisional document open for comments from the public will be available on the SIGN Web site: www.injectionsafety.org ❏ New drugs needed to fight TB alaria, a disease that is prevent- able, treatable and curable, kills one million people a year in Africa, with nine out of 10 cases occurring in the sub-Saharan region. Now, the first summit of African heads of state to focus on the disease has com- mitted to intensive efforts to halve malaria mortality by 2010. Held in Abuja, Nigeria, in May 2000, the summit was attended by representatives of forty-four of the fifty malaria-affected countries in Africa. Also present were officials from United Na- tions agencies and major international donors. The meeting culminated in the signing of the Abuja Declaration and the Plan of Action in which the leaders re- solved to initiate sustainable actions to strengthen health systems, so that by 2005: ➤ at least 60% of those suffering from malaria have prompt access to, and are able to correctly use, affordable and appropriate treatment within 24 hours of the onset of symptoms; ➤ at least 60% of those at risk of ma- laria, particularly children under five years of age and pregnant women, benefit from the most suitable combi- nation of personal and community protective measures. These include in- secticide treated mosquito nets and other accessible and affordable inter- ventions, to prevent infection and suffering; ➤ at least 60% of all pregnant women who are at risk of malaria, especially those in their first pregnancies, have access to chemoprophylaxis or pre- sumptive intermittent treatment. Commitment, targets and resources The Heads of State called upon all countries to undertake and continue health systems reforms that will promote com- munity participation in rolling back malaria, and so increase sustainability. Diagnosis and treatment of malaria should be available as peripherally as possible (including home treatment), and accessible to the poorest. Amongst other things the signatories to the Declaration pledged to: prevent re-emergence of malaria; provide reliable information on the disease to decision- makers at all levels; and to reduce or waive taxes and tariffs for mosquito nets, insecticides, anti-malarial drugs, and other goods and services needed for malaria control strategies. Hidden costs reinforce urgency The summit’s impor- tance was reinforced by simultaneous publication of a report showing that the cost of malaria is substan- A C C E S S M M The world’s biggest bednet was erected at Abuja as a symbol of the 225 African children who die every two and a half hours from malaria tially greater than economists previously estimated. According to the report,1 the disease results in a loss of economic growth of more than one percentage point per year. Previous estimates have looked only at immediate short-term financial implications, such as the loss of labour and the costs of treatment and prevention. Beating malaria: leaders pledge action at historic summit Ph ot o: W H O / RB M But the longer-term costs are even more devastating to the country, the report argues. ❏ Reference 1. Gallup JL, Sachs JD. Economics of malaria. Centre for International Development, Harvard University and the London School of Hygiene and Tropical Medicine. (Forthcoming). Executive summary available on the Web at: http://www.malaria.org/jdsachseconomic.html C re di t: W H O ore than 120 tuberculosis (TB) and public health experts, govern- ment and industry representa- tives, researchers and donors discussed TB drug development at a two- day workshop in Cape Town, South Africa, in February 2000. They met be- cause of the urgent need for new drugs to ensure shorter TB treatments and to fight the increasing resistance to existing drugs. Basic TB drugs are already 20–30 years old, and few new drugs have been marketed in recent years. TB experts, including WHO repre- sentatives, described the need for new TB drugs, researchers presented promising state-of-the-art research methods and findings, and drug companies explained the difficulties of drug development. Mixed panels discussed the pharmaco- economics of the TB drug market, which is predicted to be US$700 million for treating 10,000,000 TB patients world- wide by 2008. The general opinion was that the size of this market should enable the development of at least one or two new drugs. But some participants argued that there was a reluctance to develop drugs for a market where most of the people are poor, and where developing countries, institutional buyers and agencies work- ing on TB demand low prices. A guaranteed off-take or market would be a strong incentive for manufacturers. There was a view that “corporate aware- ness” of the problem is increasing. Some companies have specific TB projects, oth- ers are considering “donating” the licensing rights of economically less viable second-line TB drugs to public bodies. Not only money… Many participants warned that low cost drugs or even donations are no guarantee of solving the TB problem, as managerial problems in many countries with mid level economies have meant that they have only achieved 50–60% cure rates. Poor patient adherence after the first two months of a six- month treatment period increases the risk of drug resistance. The meeting discussed accelerating the development of new TB drugs to im- prove prevention and treatment of the disease. It also decided to develop a de- dicated Global Alliance for TB Drug Development, with partners from aca- demia, industry, major agencies, NGOs and donors worldwide. From vision to fruition… By October 2000 the participants’ push for a Global Alliance for TB Drug Development became a reality with its launch by WHO’s Director-General, Dr Gro Harlem Brundtland, at a meeting in Bangkok. And in February 2001 the Alli- ance opened its head office in Cape Town, South Africa, to coordinate and fund research in tuberculosis in developing countries. The main aim is to find a major new treatment for TB by 2010, specifically a drug that is more effective so that it needs to be used for a shorter time, reducing the treatment period by at least 50 per cent, and so increasing adherence. The Alliance will not to set up its own research institutions but will support ex- isting projects, particularly in developing countries, and coordinate their findings. The first funding allocations will be made in April 2001. ❏ For further information on the Global Alliance for TB Drug Development see page 22. 24 E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 NGO meetings on drug access ollowing their successful confer- ence on compulsory licensing held in Geneva in March 1999 (see EDM-27), Médecins Sans Frontières, Health Action International and the Consumer Project on Technology have organized two more meetings on one of today’s most topical issues. A con- ference entitled Increasing Access to Essential Drugs in a Globalised Economy – Working Towards Solutions, brought together 350 people from 50 countries in Amsterdam in November 1999. Health advocates and public health profes- sionals from developing countries, The presentation of a new study show- ing that East Africans pay more than Europeans for life-saving drugs1 was one of the conference highlights. Among the many examples cited in the study is that of the antibiotic, ciprofloxacin, which was found to be twice as expen- sive in Uganda as in Norway. Another example is fluconazole, a treatment for AIDS-related meningitis. In Thailand, where generic competition has lowered prices, fluconazole costs only US$0.30. However, the same drug costs US$18.00 in Kenya, where it is patent protected. Participants argued that the reasons Trade and access: Ugandan groups push for progress A C C E S S F he title of a workshop held in Kampala, Uganda, in February 2000, certainly conveyed the spirit of the event and the breadth of subjects addressed. “Advocacy and Campaign for Better Trade, Access to Essential Medicine and Promoting Rational Drug Use in Uganda ” was the result of collaboration between Uganda’s Consumers Protection Association, Action Aid Uganda, Health Action International and Médecins Sans Frontières. Participants left this lively meeting in February 2000 determined to push for better trade policy, improved health serv- ices and increased consumer awareness of pharmaceutical issues. They agreed that access to drugs is a crosscutting is- sue, and that to be more effective they need to network and to create awareness of key issues using various media. Discus- sions also highlighted the importance of involvement in legislation review and formulation (particularly the draft bill on intellectual property rights), and participa- This ambulance may be stuck in the mud in Uganda, but the description could not apply to campaigners pushing for improvements in the pharmaceutical sector Ph ot o: E . P at er so n tion in Uganda’s National Drug Policy review. Delegates were urged to campaign for improved infrastructure. Only when this is in place can important develop- ments get underway, such as offering incentives to open drug outlets in poor rural areas. ❏ For further information contact: R. Mutambi, Health and Gender Officer, Uganda Consumers Protection Association, Desai House, Plot 4, Parliament Avenue, PO Box 23783, Kampala, Uganda. Tel: + 256 41 234 002, Fax: + 234003, e-mail: ucpa@ imul.com T Five key messages from WHO on trade agreements and pharmaceuticals ◆ ◆ ◆ “First, patent protection is a necessary and effective incentive for research and development for needed new drugs. Essential drugs are a public good and not simply just another commodity. Patents must therefore be managed in an impartial way to benefit both the patent holders and the public. Protectionism has never benefited public health. WHO supports governments to enact national legislation which can draw advantage from more open trade and a better regulated international system. And we support governments in incorporating the safeguards that have been built into the WTO TRIPS Agreement to protect the rights of the public. Second, priority-setting for research and development in the pharmaceutical market is imperfect. There are also striking market failures when there is such desperate demand for products that are available – but not within reach of those in need. WHO has initiated, with other partners, innovative mechanisms to stimulate research and development in areas of high public health need, such as malaria and tuber- culosis. Through its Medicines for Malaria Venture (MMV), the Global Alliance for Vaccines and Immunization (GAVI) and other initiatives, WHO is actively encourag- ing public sector financing for critical public health problems and neglected tropical diseases. Third, WHO strongly supports development of mechanisms for preferential low prices for essential drugs in lower-income countries. Lower-income countries simply cannot be expected to pay the same price for essential drugs as the wealthier countries. For governments, industry, and other stakeholders, there is a range of measures which might be used to achieve preferential pricing. But where there is an abuse of patent rights, where patented essential drugs are unavailable or where a national emergency exists, recourse to compulsory licensing is a legitimate measure consistent with the TRIPS Agreement. Fourth, WHO supports implementation of the TRIPS Agreement to ensure prompt availability of generic drugs upon patent expiration. WHO has long promoted use of generic drugs of assured quality. Experience from countries with “generic-friendly” policies clearly demonstrates that the market competition created by these policies increases affordability of medicines, stimulates true innovation within the research- based industry, and encourages increased production efficiency by the generic industry. Finally, trade agreements should not create barriers to trade. An important WTO principle is that technical regulations, standards and assessment procedures should be based on international standards, guides and recommendations. In the area of pharmaceuticals, WHO norms, standards and guidelines represent such international consensus. So we will actively promote these guidelines”. representatives from domestic and inter- national NGOs, the pharmaceutical industry, international organizations, na- tional governments and academics all contributed their ideas on how to achieve access to essential medicines. After two days intensive work, the Conference cul- minated in the drawing up of the Amsterdam Statement, which includes a recommendation for the World Trade Organization to create a Standing Work- ing Group on Access to Medicines. The Group would work within the WTO to consider the impact of trade policies on people in developing and least developed countries. It would provide a public health framework for the interpretation of key features of WTO agreements, and WHO and other international organiza- tions would support the activities of the Working Group. Among the many thought-provoking speeches, Dr Gro Harlem Brundtland, WHO’s Director-General, told delegates that “Making a difference requires the often painful work to build consensus among stakeholders that can move things in the right direction. Health products and health services are tradable. Health products such as pharmaceuticals are pro- duced, marketed and sold across the globe – benefiting some but failing to reach too many. So the rules that regulate this trade are key”, she told delegates. The Director-General listed WHO’s five key public health messages on international trade agreements and pharmaceuticals (see box). Moving on to Africa The NGO campaign on access to es- sential drugs gathered further momentum in Nairobi in June 2000. The Kenyan capital was the venue for the East Africa Access to Drugs Conference, where rep- resentatives from 21 countries met to devise a regional strategy. medicines are expensive in East Africa include high tariffs, taxes and lack of generic competition as well as strong patent protection. Discus- sion focused on strategies to enact legal safeguards to remedy the cur- rent situation. Delegates heard that, within existing international trade rules, such safeguards include par- allel importing (the right to shop around for the best prices of branded products) and compulsory licensing (granting limited production rights to generic producers). Another report presented at the meet- ing on patent protection and medicines in Kenya and Uganda2, calls on govern- ments to ensure these safeguards, and to include Ministry of Health representatives and health professionals when negotiat- ing and adopting trade agreements. ❏ References 1. Myhr K. Pharmaceutical pricing: law of the jungle. Amsterdam: Health Action International; 2000. 2. Boulet P. Patent protection of medicines in Kenya and Uganda. Geneva: Médecins Sans Frontières; 2000. Further information on this series of meetings on access to essential drugs can be found at: www.haiweb.org Intense concentration on the faces of delegates at the Nairobi meeting, which tackled complex and controversial issues Ph ot o: M éd ec in s Sa ns F ro nt iè re s 25E S S E N T I A L D R U G S M O N I T O R Issue No. 28 & 29, 2000 Transforming drug supply in Dar es Salaam ➢ KARIN WIEDENMAYER, DEO MTASIWA* n 1990 the inadequacy of the pharmaceutical supply system in Dar es Salaam, commercial capital of the United Republic of Tanzania, was evident. There was chronic shortage of drugs at health facilities, supply was erratic as was Government funding, drug supply management was poor and use of drugs irrational. Despite a national policy to provide drugs free of charge, unofficially patients often had to pay for them. Drugs were purchased from the national Central Medical Stores, which was seen as inefficient, unreli- able and poorly stocked. Drug quality was questionable and pharmacy premises were often unsuitable – hot, humid and cluttered with piles of drugs, some of them expired. Pharmacists tended to have low professional visibility and not to be involved in hospital committees. At a time when studies showed that patients equated availability of drugs with good quality of care1, a survey of user pat- terns in Dar es Salaam in 1990 reported that “the majority of patients complained that usually health facilities do not have drugs at all”. as well as irrational use. In 1984, the Government created the Essential Drugs Programme to provide essential drugs to health facilities. The Programme introduced a prepacked drug kit system, which partially improved the situation for health centres and dispensa- ries, but not for the hospital sector. And the foreign financed and operated (by WHO, the Danish International Develop- ment Agency and the United Nations Children’s Fund) drug kit system did not help to improve management of the drug sector’s infrastructure. In the early 1990s, when the Dar es Salaam Urban Health Project began, Tan- zania started to restructure the economy towards a market-oriented environment. In the health sector this translated into the appearance of the private profit oriented sector and the introduction of user fees. In 1991, Tanzania formulated the National Drug Policy, which aimed to improve the whole pharmaceutical sector, and ensure a regular supply and rational use of essential drugs through- out the country. Later, the Health Sector Reform Action Plan 1996–1999 covered decentralised district-based drug supply and management, liberalised drug procurement, quality assurance, and eq- uitable access and affordability of drugs. Here we highlight the main elements of the Health Project’s work and how against this background, it has transformed drug supply in the region. BUYING DRUGS: WHICH, HOW MUCH AND WHERE? Drug need quantification was initially done by morbidity and later by the con- sumption method. Drug selection was based on the National Essential Drug List. Drug kits for the Dar es Salaam Health Project were procured through restricted international tender. The kit system was centrally and externally organized, donor funded, supplied and imported from overseas, with little or no involvement or commitment from the recipient side. The project bypassed the national procure- ment system, the former Central Medical Stores being unreliable and inefficient. Later the organization was restructured and became an autonomous department within the Ministry of Health, under the responsibility of an external management team. In 1996, the new Medical Stores Department was operating efficiently, and it was considered appropriate to start us- ing the existing local drug procurement infrastructure. The Department’s per- formance has been good overall, with an adequate product range, appropriate pricing, good quality and service, and sufficient provision for emergency situa- tions. The Medical Stores Department has become the backbone of the Project’s supply system. Drug kits are a good but not optimal solution. Because of their predetermined contents (selection and quantity) certain items were regularly out of stock, others were piling up and some even expired before redistribution. Quantification was therefore introduced at the health facilities and ordering is now done by decentralised requisition, i.e. the indent system has gradually replaced the push system with prepacked kits. A recent study o
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