Editor—The paper by Plowe et al entitled “Sustained clinical efficacy of sulfadoxine-pyrimethamine for uncomplicated falciparum malaria” might be better titled “Sustained lack of efficacy of sulfadoxine-pyrimethamine....”1 By the start of the study period five years ago, molecular genotyping showed that Plasmodium falciparum in Malawi had already acquired significant resistance to the combination.1,2 This explains the sustained lack of efficacy; 28 day cure rates in children with acute falciparum malaria remained steadily less than 40% over the five year study period. This is confirmed by the Malawi component of recent WHO-Special Programme for Research and Training in Tropical Diseases (TDR) multicentre trials; the 28 day cure rate with sulfadoxine-pyrimethamine in children with acute falciparum malaria was only 23%,3 and this for a major killing disease of childhood. A 77% failure rate is among the worst responses ever documented. Only 7% (5/71) of reported trials on sulfadoxine-pyrimethamine have had worse failure rates.4
Before sulfadoxine-pyrimethamine was introduced widely it was very effective in Malawi, but, since then, efficacy has fallen dramatically (table). The front page of the BMJ was wrong: sulfadoxine-pyrimethamine is not “still working.” A drug giving a cure rate of consistently less than 40% for a potentially life threatening infection cannot be described as having “good efficacy,” particularly when highly effective alternatives exist.
Table 1.
Therapeutic responses (percentages) to sulfadoxine-pyrimethamine in Malawian children with acute falciparum malaria, 1987-2003
| Reference* | Day 7 | Day 14 | Day 21 or 28 |
|---|---|---|---|
| Heymann et al 19876 | 100 | 100 (day 21) | |
| Nwanyanwu et al 19967 | 98 | 98 | |
| Verhoeff et al 19978 | 98 | 90.5 | |
| Nwanyanwu et al 20009 | 89 | 81-93 | |
| MacArthur et al 200010 | 80 | ||
| WHO-TDR study 2000-23 | 53 | 23† (day 28) | |
| Plowe et al 20041 | 78-88 | 61-73 | 27-39 (day 28) |
Full details of references 6-10 are available on bmj.com
True success rate, excluding reinfections, 32% (36/113) confirmed by polymerase chain reaction genotyping.
Can you imagine endorsing an antibiotic with a more than 60% failure rate for use in European or American children with those words? Demographic surveillance system data from eastern and southern Africa show that mortality attributable to malaria in children almost doubled between 1990 and 1998, whereas by contrast non-malaria related mortality fell. The use of ineffective drugs, such as sulfadoxine-pyrimethamine in Malawi, may well be to blame.5
Supplementary Material
Extra references in table are available on bmj.com
Competing interests: None declared.
References
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