疟疾化学预防可有效改善重症贫血患儿出院后的临床结局
疟疾化学预防可有效改善重症贫血患儿出院后的临床结局
作者： 小柯机器人 发布时间：2020/12/4 12:56:11
本期文章：《新英格兰医学杂志》：Vol.383 No.23
英国利物浦热带医学院Feiko O. ter Kuile团队研究了疟疾化学预防对重症贫血儿童出院后预后的影响。2020年12月2日，该研究发表在《新英格兰医学杂志》上。
在疟疾流行的非洲地区因严重贫血住院的儿童在出院后6个月内有再次入院和死亡的高风险。目前尚没有专门针对这一阶段的预防策略。
为了评估3个月的疟疾化学预防能否降低5岁以下严重贫血儿童出院后的发病率和死亡率，研究组在肯尼亚和乌干达的9家医院进行了一项多中心、两组、随机、安慰剂对照试验，2016年5月到2018年5月，共招募了1049名儿童，所有患儿均接受了严重贫血的标准住院治疗，出院时接受了3天疗程的蒿甲醚-苯芴醇治疗。
出院后两周，将这些患儿随机分组，其中524例接受双氢青蒿素-哌喹（化学预防组）治疗，525例接受安慰剂治疗，分别于出院后2、6和10周进行3天疗程的服用。出院后对儿童进行26周的随访。主要结局是从分组到出院后6个月的全因死亡或再次入院事件。
从第3周到??第26周，化学预防组共发生184次再入院或死亡事件，安慰剂组共发生316次，风险比为0.65，组间差异显著。在干预期（第3周至第14周），化学预防组的再入院或死亡发生率显著低于安慰剂组，风险比为0.30； 但在那之后（第15周到第26周），两组间的差异不再显著，风险比为1.13。使用双氢青蒿素-哌喹未发生严重的不良事件。
总之，在疟疾传播严重的地区，对最近接受过严重贫血治疗的儿童，出院后三个月每月服用双氢青蒿素-哌喹进行化学预防，与安慰剂相比，可有效降低出院后的全因死亡或再入院的风险。
附：英文原文
Title: Malaria Chemoprevention in the Postdischarge Management of Severe Anemia
Author: Titus K. Kwambai, M.D., Ph.D.,, Aggrey Dhabangi, M.D., Ph.D.,, Richard Idro, M.D., Ph.D.,, Robert Opoka, M.D.,, Victoria Watson, B.Sc.,, Simon Kariuki, Ph.D.,, Nickline A. Kuya, Dip.Clin.Med.,, Eric D. Onyango, B.Sc.,, Kephas Otieno, M.P.H.,, Aaron M. Samuels, M.D., M.H.S.,, Meghna R. Desai, Ph.D.,, Michael Boele van Hensbroek, M.D., Ph.D.,, Duolao Wang, Ph.D.,, Chandy C. John, M.D.,, Bjarne Robberstad, Ph.D.,, Kamija S. Phiri, M.D., Ph.D.,, and Feiko O. ter Kuile, M.D., Ph.D.
Issue&Volume: 2020-12-02
Abstract:
BACKGROUND
Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period.
METHODS
We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether–lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin–piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice–Williams–Peterson total-time approach.
RESULTS
From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin–piperaquine.
CONCLUSIONS
In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin–piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo.
DOI: 10.1056/NEJMoa2002820
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2002820