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Chapter 15 of 16

The need for intensified research

• Infectious diseases are low on the global health agenda but research needs are vast

Graphs:

• Health research budgets
• Vaccines licensed since 1900

Initative: Setting disease priorities

The combined investment in research and development into ARI, diarrhoeal diseases and TB - which kill over 7 million people a year - was $133 million( about 0.2% of global spending on health research and development). Yet these three diseases together account for almost one-fifth of the global disease burden. Malaria, which accounts for 3% of the disease burden globally and almost 10% in sub-Saharan Africa, fared as poorly - attracting about 0.1% of research funds.

In contrast to the limited funds available, the research needs for infectious diseases are vast. Some of the research needed involves cutting-edge science - sequencing the genome of the major disease-causing microbes, for example, or discovering ways of slowing the spread of antimicrobial drug resistance. Other critical research needs include the discovery of new affordable drugs, vaccines and diagnostic tests. In some cases, these are needed to lower costs, improve compliance and replace drugs that have been compromised by antimicrobial resistance.

Equally important is the need for research to find ways of making more widespread and better use of existing cost-effective tools such as vaccines, multidrug therapy, bednets and an integrated approach to childhood illness. Meanwhile, research is also needed to establish the disease burden in individual countries, so that health systems can respond effectively to today's and future health needs in the most cost-effective way.

A top priority today is the urgent need to develop new low-cost antimicrobial drugs to replace drugs that have become ineffective due to antimicrobial resistance. Without this ongoing research and development, diseases such as TB, malaria, pneumonia and dysentery could become untreatable in countries which cannot afford available second- or third-line drugs. To help accelerate the discovery of new drugs to treat malaria, a new joint initiative has been launched involving both the private and public sector. The New Medicines for Malaria Venture (MMV) aims to develop one new affordable antimalarial drug every five years.

Elsewhere, research is under way to develop new low-cost drugs that could improve compliance with drug therapy by shortening the course or simplifying the treatment. The drop-out rates for DOTS therapy for TB, for example, could be greatly improved if the multidrug therapy could be combined in a single tablet and the length of treatment reduced from the minimum 24 weeks now required. For leprosy, efforts are being made to develop new drugs which could both increase the effectiveness and shorten the duration of multidrug therapy.

A new generation of vaccines is under development which could save millions of lives. Dramatic advances in genetic engineering have produced a raft of vaccine contenders that will simplify immunization, boost the performance of existing vaccines and protect children against diseases which are not yet vaccine-preventable. In addition, new vaccines against diseases such as TB, malaria and acute respiratory infections could provide the first line of defence against drug-resistant microbes. Vaccines under development to address rotavirus, cholera, typhoid and shigella will help reduce the burden of disease caused by diarrhoeal disease.

The successful sequencing of the genome of the tuberculosis-causing microbe in 1998 was a major breakthrough that is expected to shed more light on which genes cause TB and to speed up the development of a more effective vaccine. Meanwhile progress in microbial genetics is also driving the development of new, improved vaccines against meningococcal meningitis, dengue fever and Japanese encephalitis.

In addition to the need to develop new or improved vaccines, research is also under way to simplify the administration of existing vaccines, reduce delivery costs, and boost immunization coverage. This includes research into ways of reducing the number of immunization contacts that are needed through combining several vaccines in a single dose and combining several booster doses in a single slow-release dose. Another priority is the development of new, safer ways of delivering vaccines - orally or nasally - that minimize the risk of injection hazards.

Research is also needed to develop low-cost rapid diagnostic tests to improve the accuracy of diagnosis and accelerate the start of appropriate treatment. Although rapid diagnostic dipstick tests for malaria are in the final stages of development, they are currently too expensive for widespread use in developing countries. Tests are also needed for TB, gonorrhoea and sleeping sickness for use in developing countries.

However, in the short term a great deal could be achieved through research into ways of improving the use of existing tools - one of the most neglected areas of research. A 1997 study by WHO on TB research funding, involving 17 public and non-profit research funders, found that most of the $92 million they spent in 1995 was to extend the knowledge base and develop new tools. They spent least on research to improve the use of existing tools such as DOTS.

A number of initiatives have been launched to help improve the use of existing tools. They include efforts to improve the home management of malaria and other childhood diseases and provide clear information about the need for prompt referral for severely ill children.

Studies are being carried out to improve the follow-up by parents of health care advice from health workers and studies are under way to determine why some parents fail to seek care for sick children before it is too late.Similarly, research is also critically needed to find ways of ensuring that newer, more expensive vaccines such as Hib and hepatitis B - which have proved so successful in the industrialized countries - can now be introduced into developing countries.