瘧疾化學預防可有效改善重症貧血患兒出院後的臨床結局
作者：
小柯機器人發布時間：2020/12/4 12:56:11
英國利物浦熱帶醫學院Feiko O. ter Kuile團隊研究了瘧疾化學預防對重症貧血兒童出院後預後的影響。2020年12月2日，該研究發表在《新英格蘭醫學雜誌》上。
在瘧疾流行的非洲地區因嚴重貧血住院的兒童在出院後6個月內有再次入院和死亡的高風險。目前尚沒有專門針對這一階段的預防策略。
為了評估3個月的瘧疾化學預防能否降低5歲以下嚴重貧血兒童出院後的發病率和死亡率，研究組在肯亞和烏幹達的9家醫院進行了一項多中心、兩組、隨機、安慰劑對照試驗，2016年5月到2018年5月，共招募了1049名兒童，所有患兒均接受了嚴重貧血的標準住院治療，出院時接受了3天療程的蒿甲醚-苯芴醇治療。
出院後兩周，將這些患兒隨機分組，其中524例接受雙氫青蒿素-哌喹（化學預防組）治療，525例接受安慰劑治療，分別於出院後2、6和10周進行3天療程的服用。出院後對兒童進行26周的隨訪。主要結局是從分組到出院後6個月的全因死亡或再次入院事件。
從第3周到??第26周，化學預防組共發生184次再入院或死亡事件，安慰劑組共發生316次，風險比為0.65，組間差異顯著。在幹預期（第3周至第14周），化學預防組的再入院或死亡發生率顯著低於安慰劑組，風險比為0.30； 但在那之後（第15周到第26周），兩組間的差異不再顯著，風險比為1.13。使用雙氫青蒿素-哌喹未發生嚴重的不良事件。
總之，在瘧疾傳播嚴重的地區，對最近接受過嚴重貧血治療的兒童，出院後三個月每月服用雙氫青蒿素-哌喹進行化學預防，與安慰劑相比，可有效降低出院後的全因死亡或再入院的風險。
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