Terlouw Dianne J, Nahlen Bernard L, Courval Jeanne M, Kariuki Simon K, Rosenberg Oren S, Oloo Aggrey J, Kolczak Margarette S, Hawley William A, Lal Altaf A, Kuile Feiko O ter
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Antimicrob Agents Chemother. 2003 Sep;47(9):2929-32. doi: 10.1128/AAC.47.9.2929-2932.2003.
Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onward.
1993年至1999年期间，我们在肯尼亚西部对1175名24个月以下儿童使用广泛采用的按年龄划分的剂量方案监测了磺胺多辛-乙胺嘧啶治疗恶性疟原虫疟疾的疗效：婴儿，125毫克加6.25毫克（磺胺多辛加乙胺嘧啶）；12至23个月的儿童，250毫克加12.5毫克。第7天的累积治疗失败率定义为第3天出现早期临床失败或第7天存在寄生虫血症，从1993年至1994年的18%增至1997年至1998年的22%（P趋势检验=0.20）。根据体重，接受的中位剂量为20毫克加1.00毫克/千克，73%的治疗剂量低于推荐的目标剂量25毫克加1.25毫克/千克。剂量不足占累积治疗失败的26%。1998年剂量增加后（中位剂量，36毫克加1.8毫克/千克），只有4.2%的患者接受的剂量低于25毫克加1.25毫克/千克，且与治疗失败无关。然而，累积治疗失败率到1999年继续增至27%（P趋势检验=0.03）。这些结果引发了对磺胺多辛-乙胺嘧啶在这些环境中使用寿命的担忧。剂量不足可能促成了该地区磺胺多辛-乙胺嘧啶耐药性的产生速度。治疗指南应确保从最初使用抗疟药开始就给予足够的剂量。
