The Good Medicine
2 November 2002
Imagine a five-year-old girl in a small village in sub-Saharan Africa. A hand on her clammy forehead reveals a fever. Then she begins to shake - and perhaps vomits up her breakfast. The girl's head is hurting, and she is getting weaker. She can't move her small arms. She starts to cough. She can't eat. Her mother takes her to the health post later that day, and the doctor makes a diagnosis: malaria. The parasites are in her. She gets chloroquine to take for three days. This happens to her maybe six times a year. Six times a year! Unfortunately, there is a good chance that the medicine she receives does not even work. Yet drugs do exist that can effectively combat malaria today - the scandal is that, in many places, they are not being used. The most effective malaria treatment today is artemisinin-containing combination therapy (ACT), which MSF has been pushing to introduce in the countries where the old medicines - standard treatments such as chloroquine and sulfadoxine-pyrimethamine (SP) - no longer work. Derived from the sweet wormwood plant, artemisinins have cured fevers in China for two thousand years, and for the last 30 years they have been used to treat malaria, primarily in Asia, where malaria strains have been resistant to standard treatments for many years now. They have proven effective against Plasmodium falciparum, the deadliest of the four malaria parasites, especially when used in combination with another antimalarial (ACT). Artemisinins are five to ten times more effective than other drugs and have very few side-effects. To date, there has been no evidence that resistance has developed to artemisinins. When administered early, they have been shown to substantially reduce the transmission and hence the incidence of malaria, at least in Thailand and South Africa. But, in Africa, ACT is just not being used (apart from in South Africa). Getting ACT to the people who need it most is not merely a question of showing that it works and then offering it to patients. It is a matter of money, policy and protocols. Organizations committed to fighting malaria have failed to advocate effectively; governments faced with policy choices have wavered; and international donors have held back money that could save thousands of lives. Meanwhile, millions of people are still threatened by malaria, a disease that was once the object of global eradication dreams. Malaria is spread by mosquitoes. An insect infected with a malaria parasite bites a human, transferring the parasite to the person's bloodstream, where it multiplies and can cause illness or death. When this person is bitten by another mosquito, the parasite travels from human back to insect, and the cycle continues. To stop this chain, in the 1950s the World Health Organization (WHO) embarked on the ambitious Global Eradication of Malaria Program, seeking to wipe out malaria completely, everywhere. Armies of scientists and others fanned out to countries where the disease was endemic, implementing eradication plans on a grand scale, spraying the chemical DDT to kill hungry hordes of mosquitoes. All this firepower effectively tamed malaria in temperate regions and cowed it into submission in many subtropical areas. Yet by 1967 the WHO realized that eradicating malaria was impossible, and by 1972 the program was declared dead. For people in the United States, Europe and other areas where malaria has been more or less eliminated, the malaria "problem" has been reduced to getting prophylactic pills prior to a vacation in the tropics. But for the 40% of the world's people who live in malaria-endemic areas, the disease remains a daily, deadly threat. It strikes 300 to 500 million people each year, with 90% of cases in sub-Saharan Africa. Since the early 1980s, an estimated 40 million people worldwide, most of them children under five, have died of malaria. Those who survive multiple bouts with malaria can experience retarded physical and mental development, poor educational performance and greater vulnerability to other diseases. After the era of eradication, the focus in malaria-endemic regions turned to treatment, made possible with cheap drugs such as chloroquine and SP. Yet the widespread and indiscriminate use of these treatments eventually fostered the development of strains of the parasite that were resistant to the chemical knockout punch, and in recent years the disease has roared back with a vengeance. The experts were so alarmed that in 1998 the WHO and various other United Nations agencies launched the Roll Back Malaria Campaign, hoping to cut the world's malaria burden in half by 2010. Prevention efforts increased, with campaigns to promote insecticide-impregnated bednets and indoor spraying of DDT. But the recognition that current treatment regimens were failing has lagged behind, and it is here that governments and international actors are at a critical point. Drug resistance - occurring through spontaneous genetic mutations in the parasite which are exacerbated by use and overuse of ineffective drugs - is leading to treatment failure and causing rising rates of mortality, particularly among children. In some MSF projects in Africa, resistance levels show how much standard treatments are failing. In Bandundu, Democratic Republic of Congo, resistance to chloroquine is 78-85%; in Maheba, Zambia, it is 50%; in Mbarara, Uganda, it is 87%; and the list goes on. Nowhere has the problem of resistance been more evident than in Burundi, seized in 2000-2001 by an unrelenting malaria epidemic that produced around 3 million cases among the country's 6.5 million people. MSF treated over a million cases during the epidemic, often having to use drugs that did not work. As realization set in that chloroquine - then the country's protocol (standard for treatment) for first-line treatment of simple malaria - was not working (in areas where MSF was active, resistance to chloroquine ranged from 63-87%; resistance to SP, the second-line drug, was 32-56%), MSF tried to change to ACT. With neither the funds nor the political will to make the change, the Burundi government resisted, opting instead for an interim protocol, chloroquine and SP combination therapy, and later SP monotherapy. MSF, prevented from using ACT, introduced it illegally (though publicly). The government then suspended MSF's malaria-related programs, and as of September 2002 MSF was still not able to use ACT in Burundi, though other work continued. In July 2002, an expert panel recommended changing the national protocol to ACT, and the government agreed to begin implementing it by July 2003. Ironically, artemisinin derivatives have been and remain available in private pharmacies in Burundi for people who can pay. Money, policy and protocols In addition to trying to introduce ACT into all its projects where people are sick with malaria, MSF is also fighting to make better malaria treatments a priority at the international level, by advocating policy and protocol changes and pushing for funding. Yet, despite evidence of its effectiveness, and the many lives at stake, implementation of ACT has been delayed by meager health budgets, lack of international support and lack of political will. ACT is much more expensive than chloroquine or SP. Combinations that do not contain artemisinin derivatives cost about US$0.25 for each adult dose; those with the potent remedy cost US$1.30, while the brand-name ACT, CoartemÃ?®, is about US$2.40 per dose. In a report released in February 2002 ("Changing National Malaria Treatment Protocols in Africa: What is the Cost and Who Will Pay?"), MSF showed that for Burundi, Kenya, Rwanda, Tanzania and Uganda - countries where resistance to chloroquine and SP is particularly high - the extra cost of changing to ACT instead of to a non-ACT combination would be US$19 million in total. This is just not affordable for these countries. To make the switch, they need international help. The money must come from somewhere The funding for effective treatment for the hundreds of millions of people with malaria in sub-Saharan Africa must come from international donors. However, although malaria has recently been highlighted internationally as one of three priority diseases that need to be tackled, the cash and concrete action needed to reduce malaria deaths have not materialized and public initiatives (eg, the Global Fund to Fight AIDS, Tuberculosis and Malaria) have failed to secure the required funds. Despite the growing consensus among experts that ACT is the malaria treatment of choice, and the WHO's recent acknowledgement that ACT is the most effective malaria treatment in many places, the United States Agency for International Development and the British Department for International Development, influential international donors, have failed to support quick implementation of ACT in Africa. These agencies have remained silent in the face of direct pleas from African countries for financial assistance to implement ACT and are supporting continued use of ineffective medicines. US officials have said that the drugs have not been sufficiently tested on babies, and that in any case at least one of the first-line drugs, SP, could still be used for several years. MSF has demanded that the US offer evidence to support its strategy of SP monotherapy even in cases of known resistance to the drug. Cost is also cited as a problem. It is true that ACT costs more than current malaria treatments. But ACT works where the others do not. Another argument put forth against ACT is that the treatment is too long and complex to ensure patient compliance. SP is a one-dose treatment but chloroquine, the standard for more than 40 years, is taken for three days - and so is ACT. There is currently no evidence that malaria patients in Africa will not comply with ACT treatment regimens. Prospects MSF is ramping up use of ACT in field projects where it is appropriate, with ACT offered in 12 countries as of September 2002. MSF is also continuing to pressure governments and international bodies to do the right thing. But once ACT is more firmly established, there will still be much work to do - making treatments easier to administer and take, developing appropriate drugs for very young infants, and getting new drugs into the development pipeline. The clock is ticking on all these fronts. In the meantime, people who should - and could - be receiving good treatment are slipping away, one fever at a time.