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Select Committee on Science and Technology Seventh Report

CHAPTER 9 INTERNATIONAL

9.1 Infection is no respecter of nationality or of national frontiers. Many witnesses have warned us that, although in the United Kingdom prudent use, infection control and surveillance are established to high standards, these efforts are constantly being undermined by the arrival of infections from other lands where standards are lower. A frequently-cited example is the introduction and explosive spread of penicillin-resistant pneumococci in Iceland in the early 1990s: rates rose from under one per cent in 1988 to 20-25 per cent in 1993. Subsequent studies of the genetics of the strain showed that it almost certainly came from Spain, where it was common and the usage of oral antibiotics is high (AMM p 12, PHLS p 49).

9.2 The AMM call for more action on an international scale (p 12, QQ 58-60). They call on the Government to take a lead in Europe to "raise the profile" of the resistance problem, to "create a common pool of information" on resistance and on antimicrobial usage, and to control resistant infection. "A serious attempt should be made to control resistance within Europe since it would be difficult to target developing countries before its own house were in order". Then bilaterally and through global agencies, the Government should do what it can for the wider world—though, the AMM admits, "The problems of controlling antibacterial usage in developing countries are almost insuperable".

World Health Organization

9.3 The actions of the World Health Organization (WHO) in this field are described in the evidence provided by Dr Rosamund Williams (p 91). They include assistance to developing countries to develop surveillance, using standard software (WHONET)[72] and feeding into a global "network of networks"; sponsorship of organism-specific resistance surveillance networks for gonorrhoea, TB, leprosy and malaria; education through Model Prescribing Information, a Model Formulary and national policy workshops; guidance to regulators, including Ethical Criteria on Medicinal Drug Promotion; and support for research.

9.4 The WHO Antimicrobial Resistance Monitoring programme (ARM) was set up last year, and has so far been funded largely outside the WHO budget, as is its parent, the Division of Emerging and other Communicable Diseases Surveillance and Control (EMC). The United Kingdom Department for International Development has provided a "large amount" of extrabudgetary funding for EMC, including ARM,[73] for which Dr Williams expressed thanks (Q 111). The ARM budget for 1998 and 1999 is $1.6m (about £1m) (Q 123). The WHO Executive Board has approved a Resolution[74] for the 51st World Health Assembly in May, which would draw attention to the ARM and seek to put it on a firmer financial footing (Q 117). Dr Williams indicated that the ARM would welcome secondment of experts from the United Kingdom; she suggested that this would be mutually beneficial (QQ 113-6).

9.5 Professor Petrie spoke from experience of helping to develop antibiotic policies among some of the world's poorest people (Q 669). He pointed to some of the difficulties: very little money for public health care; and often a private sector with plenty of money, eager to spend it on expensive and possibly inappropriate drugs. He added, "There is evidence in some countries that drugs are purchased for reasons which are not wholly straightforward". In this context, the WHO Essential Drugs List is important, if only as an "Aunt Sally" to begin the process of local discussion and ownership.

Malaria

9.6 Malaria is one of the biggest global killers: it currently kills about two million people every year, and debilitates hundreds of millions more, mostly children in Africa, where the rate of transmission is very high and resources for health care are very sparse. Malaria is caused by a parasite, one of four species of Plasmodium; the parasite is injected by the bite of the Anopheles mosquito, develops in the liver, and then invades the blood to cause fever. The most dangerous type is P. falciparum, the cause of cerebral malaria. Between about 1950 and 1970 attempts were made through the WHO to eradicate malaria by killing the mosquitoes with DDT; this programme succeeded in some areas, but in others, notably Africa and the Far East, it failed. There followed a policy gap, during which malaria increased again. Since 1992 the world has begun again to fight back, but with a new strategy: not eradication of mosquitoes with insecticides, but treatment and prophylaxis with antimalarial drugs.

9.7 Despite climate change, there is no immediate prospect of malaria becoming endemic again in these islands (as it was in the Essex marshes and the fens in the last century) (Q 523). However malaria should be of concern to the United Kingdom for three reasons: exposure of British citizens through travel (each year the United Kingdom currently sees about 2,000 cases and an average of seven deaths); disease in Dependent Territories and the Commonwealth; and general humanitarian concern. The United Kingdom has considerable expertise in the study of malaria (MRC p 430), and a sizeable and increasing investment, notably through the Wellcome Trust (£23m in 1994-95), the MRC (which maintains a laboratory in The Gambia) and the Department for International Development.

9.8 According to Professor David Bradley and Dr David Warhurst, of the London School of Hygiene and Tropical Medicine, co-directors of the PHLS Malaria Reference Laboratory, "The spread of resistance to the common and inexpensive antimalarial drugs...is the leading cause for concern in the fight against malaria" (p 235). The leading first-line drug is chloroquine, which is cheap, easy to take and fast to act. Resistance appears to arise by a rare mutation, which may have occurred only twice, in Colombia and Vietnam; but by selection and transmission chloroquine-resistant P. falciparum is now encountered in all the main malaria areas (except central America, Haiti and parts of the Middle East). The other cheap first-line drug is Fansidar (pyrimethamine-sulphadoxine); resistance to this in P. falciparum is found at low levels even without selective pressure, and is now widespread in Africa, South America and the Far East. Newer and more expensive drugs are also encountering resistance. Resistance spreads at different rates in different places, but its rise and spread are, according to Bradley and Warhurst, "inexorable...a losing battle".

New drugs

9.9 According to Bradley and Warhurst, there is a great need for new antimalarial drugs: preferably drugs which are cheap, and chemically novel so as to reduce the chances of cross-resistance. However, "the pharmaceutical industry...is not strongly motivated to produce more medicines for impoverished people". Whereas the pharmaceutical industry looks for a market of $300m to justify the cost of developing a new drug, the world market for antimalarials is only about $100m (Warhurst Q 487), making any antimalarial an "orphan drug". According to SmithKline Beecham, industry is in fact putting "significant R&D effort" into anti-malarials, though not into other anti-parasitics of great importance to the developing world. They told us that five new anti-malarial compounds are currently under development; but each has drawbacks, and all are "likely to be much more expensive" than current drugs (p 480).

9.10 Bradley and Warhurst believe that the United Kingdom should encourage industry to develop antimalarials, by "the climate of opinion, appropriate tax relief, and support of the collaborating international agencies", perhaps by extending patent life (Q 492), and possibly in very poor countries by sharing the cost of actually buying the drugs. The WHO is already active in this area (Q 482; WHO p 93, Q 128); Professor Bradley gave us examples of two expensive new drugs which are being supplied in Africa at no cost to the users (Q 488), and mentioned a project to enable the pharmaceutical majors to collaborate on antimalarials through a "virtual company" (Q 482). He acknowledged that new drugs will in time encounter resistance as the old ones have; "Therefore it is a matter of trying to ensure a steady stream of drug availability over time" (Q 478).

9.11 One new antimalarial much talked about at the moment is artemisinin (qinghaosu). Artemisinin is derived from a Chinese medicinal plant; but its natural origins offer no special protection against resistance. Artemisinin is effective against resistant P. falciparum by blocking transmission of the parasite; but it is expensive, it is not suitable for prophylaxis, and in Professor Bradley's view it has been released in Africa sooner than was necessary, giving rise to a risk that resistance will develop prematurely. (See Q 479 and p 241, and MRC p 431.) SmithKline Beecham consider that the transmission-blocking action of artemisinin is promising, but "requires considerable commitment to achieve scientifically valid data with which to build drug control strategies" (p 480).

Prudent use of drugs

9.12 According to Bradley and Warhurst, "Adequate control of the drug supply is a key aspect of preventing the emergence of resistance, or at any rate of delaying it. Medicines are available in an uncontrolled way in many developing countries. High-cost unnecessary drugs are often aggressively marketed in the private sector when they are not yet needed for case management. Consequently, resistance to them may be established by the time that they are really needed. It is difficult to develop an effective licensing policy and to enforce it. United Kingdom companies are not blameless in these matters". Bradley and Warhurst call on the British Government to influence this situation in several ways: by supporting developing countries in their efforts to regulate the availability of medicines, regardless of any general preference for free trade (Bradley Q 480); by applying "appropriate pressure" to British pharmaceutical companies; and by supporting poor countries in developing drug formularies and policies.

Infection control and vaccination

9.13 With malaria as with other infections, reducing transmission of the disease reduces the need for drugs and the selective pressure towards resistance—though transmission of malaria is not person-to-person but mosquito-to-person. According to Bradley and Warhurst, there is a place for old-fashioned insecticide sprays, and for the new approach of impregnating bed-nets with insecticides (QQ 499-504; MRC p 432); and research is being carried out into genetic engineering of mosquitoes and ways to interfere with the mechanisms of pathogenicity, while work is under way to sequence the Plasmodium genome (Q 507; MRC p 430). The "best long-term hope" is a vaccine; researchers have sought for years for an effective malaria vaccine without success, but recent advances in molecular biology and increases in funding (see below) have speeded up the search (Q 506; MRC p 430).[75] Bradley and Warhurst call for increased support for research in these areas "both from and by the United Kingdom".