Malaria: Unconvincing arguments

"In poor countries like ours, children have only one chance. They struggle just to visit a health service, and if they get the wrong drug the first time, they are then found dead." Dr. Fred Binka, professor of epidemiology, University of Ghana
The cost of ACT as well as the limits of existing supplies are key areas where donors, agencies and governments could potentially make a real difference. Unfortunately, until now, in terms of articulated policy the donors have fallen into two camps. The US and the UK, the "go slow" countries, which have spent considerable energy chronicling the barriers to ACT introduction, suggest "leaving alone" current protocols whenever possible;1 and the rest of the donor community, which has "no opinion." In other words, most countries have not actively supported the World Health Organization's recommendations to implement ACT now. They have been conspicuously silent on the issue. The "go slow" camp has argued: >> We must not rush because ACT has not been proven safe and effective at the village or national level in Africa << In fact, artemisinins have been studied more extensively than many other antimalarials,2 and it is estimated that about two million people have so far been treated with ACT, with little report of gross toxicity.3 Not only have these drugs been used for more than ten years in Asia but there is also extensive safety as well as efficacy data from studies conducted both in Asia and Africa.4 In a recently completed meta-analysis of artesunate-based combinations versus the standard antimalarial drug alone, which included 5,194 patients and took place in sites in eight African countries, the combination showed a clear benefit in terms of reduction of risk of treatment failure, superior pharmacodynamic action (parasite clearance and fever clearance), and reduction in gametocyte carriage.5 The total number of serious adverse events was small [n=65] and was similar in both groups. Implementation of Coartem&##8482; along with enhanced prevention measures in KwaZulu Natal has resulted in remarkable improvements in malaria control and public health.6 Unconvincing arguments ACT is "not ready for prime time." Dennis Carroll, USAID14 "State of the art is fine, but poor people tend not to be able to afford it..." US official, Nairobi, Kenya15
>>ACT shouldn't yet come into widespread use because its use has not been adequately studied in pregnancy << Although there need to be additional studies in pregnant women of the risks of using these drugs in pregnancies, even inadvertently, their use needs to be weighed against the risks of using older treatments or nothing at all. Plasmodium falciparum malaria can be particularly dangerous to mother and foetus during pregnancy,7 so it is important that work continue toward offering expectant mothers the best possible option. There is a particular paucity of clinical data on the effects of artemisinin derivatives on women who are in the first trimester of pregnancy, but unfortunately the same problem plagues the use of older treatments such as SP. However, based on animal studies and on the clinical data that does exist (including controlled trials in Asia and Africa which included hundreds of pregnant women among 15,000 participants8), the World Health Organization has already given the green light for use of artemisinin and its derivatives in the second and third trimesters.9 Considering the available data, WHO experts have wisely recommended that artemisinin derivatives not be used during the first trimester of pregnancy, if there is an effective alternative. The same recommendation exists for SP.10 Other current options include chloroquine in the few places where resistance is not a problem, and quinine, which is effective but difficult to use and has significant side-effects. The bottom line is that there is no reason to withhold ACT from the general population because of concerns about use in pregnancy. >>It is better to use a less effective treatment that can be given in one dose than to expect people to comply with three days of ACT<< In a presentation at a Roll Back Malaria partners meeting in February 2002, the US Centers for Disease Control (CDC) urged African governments to be conservative when considering changing their malaria policy - whenever possible, to "leave it alone."11 The CDC presented a schema indicating that malaria programme effectiveness would be higher with a single-dose drug that was only 50% effective rather than a three-day treatment that was 100% effective, essentially promoting SP monotherapy in areas where resistance had already developed. The CDC based its argument on an assumption that about 70% of people would not complete a multi-day treatment course. Simply put, the argument states that, since people will not take a three-day course, lives can be saved by offering a less effective one-time treatment. As health professionals, MSF teams agree with CDC that compliance is a real challenge. For this reason we call on the international community to support endemic countries to improve compliance. But let's not use this as an alibi to continue giving older, less expensive, less effective medicines. In KwaZulu Natal, South Africa, an ongoing evaluation of the combination ACT/DDT project in place since February 2001 has already suggested that compliance to the three-day ACT regimen has had reasonable success and can, with continued support, be sustained.12 In a survey conducted in 2001 of about 2,500 households in KwaZulu Natal, 95% of recent cases self-reported completing their treatment.13 (See page 15 for more on the KwaZulu Natal program.) The important issue is maximizing compliance to ACT treatment. This means, among other things, training health workers, improving packaging of medicines and offering them for free or at affordable prices, and improving patient education and information. In the long term, it also means developing fixed-dose combinations to facilitate ease of use.