• Diseases are an ever-moving target. Dangerous microbes adapt to survive
• Urgent efforts are under way to develop new drugs

Chart: In the pipeline

Intervention: Providing finance for malarial drugs

In drug development, urgent efforts are under way to develop new drugs to treat diseases like malaria, tuberculosis and pneumonia which are rapidly becoming resistant to first-line drugs. Without a new generation of low-cost drugs, some diseases could become untreatable in countries which cannot afford to buy more expensive second-line drugs. Also being tested are new combination therapies to treat diseases such as lymphatic filariasis, river blindness and malaria - using more than one drug to increase effectiveness and lower the risk of developing drug-resistance. Other priority drugs include a new oral drug which could help reduce deaths from visceral leishmaniasis and a new, non-injectable, quick-acting drug to treat severe cases of malaria.

Top of the global priority wish-list in vaccine development today are vaccines against acute respiratory infections, diarrhoeal diseases, HIV/AIDS, malaria, tuberculosis and dengue.

Of these, a vaccine against HIV/AIDS is arguably the most important since no cure exists and mortality is high. For people living with HIV/AIDS today the disease is still fatal, although some have access to life-prolonging drugs.

Efforts are also under way to reach the one in five children who are still not immunized each year through national immunization programmes. This includes efforts to lower vaccine delivery costs, simplify the administration of vaccines, and reduce the number of immunization contacts needed.

HIV/AIDS vaccine
Until now, efforts to develop a safe and effective vaccine have been hampered by failure to evoke or identify a protective immune response. However, the recent launch of the first-ever large-scale human trials of HIV vaccines in the United States and Thailand represents a major step forward. If these efficacy trials are successful, it is hoped they will pave the way for the development of similar vaccines to protect against HIV/AIDS in Africa. Even if they are not successful, they are expected to provide valuable information for future research efforts. The trials involve 5 000 volunteers in the United States and 2 500 volunteers in Thailand. Results are due in 2001.

Until recently, research has been hampered by the lack of animal models to test vaccines and by the ability of the virus to mutate with every new infection. As most initial vaccine research focused on the type of virus most common in North America and Europe, research must now be intensified on virus types from developing countries, where over 90% of infections occur.

Pneumococcal vaccine
Although low-cost drugs are available to treat pneumonia, many children die because they fail to get treatment in time. And the disease is becoming too expensive to treat in some countries as the available drugs become less effective due to increasing drug-resistance. Although pneumococcal vaccines already exist, they are not effective in children under two - the highest-risk age group.

A new, improved vaccine would be a major breakthrough in preventing pneumococcal pneumonia - the biggest childhood killer.

Four manufacturers are now carrying out clinical trials on new pneumococcal vaccines. The most promising are modelled after the Hib conjugate vaccine which has been highly successful in reducing bacterial meningitis and pneumonia in the industrialized countries.

Malaria vaccine
The need for malaria prevention measures and the spiralling rate of resistance to antimalarial drugs could be reduced by an effective vaccine. But no effective vaccine has yet been developed against a parasite - and the challenges are formidable.

A large number of malaria vaccines are under development. Several of the more advanced are now being tested in Asia, Africa and the United States. The most extensively studied is a vaccine developed in Colombia (SPf66). Although initial promising results have so far not been replicated in other studies, this vaccine has now been modified to increase its potency. And there are hopes that this second-generation vaccine could provide the much-needed breakthrough in malaria prevention. Another advanced-stage vaccine, which might be able to prevent the onset of disease in someone already infected, is now being tested in the Gambia and Kenya. The cost of developing a malaria vaccine has been estimated at $50 million over the next 10 years.

New antimalarial drugs
One promising new product is an oral treatment for cases of uncomplicated malaria in Africa. Development of this new drug (a combination of chlorproguanil and dapsone) is a collaborative effort involving the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), the United Kingdom Department for International Development (DFID), and the pharmaceutical manufacturer SmithKline Beecham.

Another promising new product is a suppository (artesunate) for malaria sufferers who are too sick to take oral medication. It is quick-acting, easy to administer and can "buy time" for people with severe malaria living in remote areas who might not survive the journey to hospital.

Diagnostic tests for sexually transmitted infections (STIs)
New diagnostic tests for sexually transmitted infections (STIs) currently under development could help prevent their spread, ensure prompt and more effective treatment and provide a valuable weapon in the fight against HIV/AIDS. The currently available tests are too expensive for use in developing countries and laboratory analysis is not always available. To make matters worse, syndromic case management - a cost-effective way of treating STIs on the basis of the symptoms alone - is often inadequate for women as they may have no symptoms of infection. Simple diagnostic tests are also required for other diseases including TB and malaria.

Microbicides
Efforts are continuing to develop a vaginal microbicide that could inactivate HIV and other microbes that cause sexually transmitted diseases. This would be a major breakthrough in efforts to protect women who are unable to enforce condom use.

Women are biologically more vulnerable than men to sexual transmission of HIV and account for 75% of all new infections today. Unlike the female condom, which is visible, vaginal microbicides could be used without a male partner's consent.