Monthly sulfadoxine/pyrimethamine-amodiaquine or dihydroartemisinin-piperaquine as malaria chemoprevention in young Kenyan children with sickle cell anemia: A randomized controlled trial.
Monthly sulfadoxine/pyrimethamine-amodiaquine or dihydroartemisinin-piperaquine as malaria chemoprevention in young Kenyan children with sickle cell anemia: A randomized controlled trial.
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DOI：
10.1371/journal.pmed.1004104
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发表时间：
2022-10
期刊：
影响因子：
15.8
通讯作者：
Njuguna, Festus M.
中科院分区：
文献类型：
--
作者：
Taylor, Steve M.;Korwa, Sarah;Wu, Angie;Green, Cynthia L.;Freedman, Betsy;Clapp, Sheila;Kirui, Joseph Kipkoech;O'Meara, Wendy P.;Njuguna, Festus M.
Children with sickle cell anemia (SCA) in areas of Africa with endemic malaria transmission are commonly prescribed malaria chemoprevention. Chemoprevention regimens vary between countries, and the comparative efficacy of prevention regimens is largely unknown. We enrolled Kenyan children aged 1 to 10 years with homozygous hemoglobin S (HbSS) in a randomized, open-label trial conducted between January 23, 2018, and December 15, 2020, in Homa Bay, Kenya. Children were assigned 1:1:1 to daily Proguanil (the standard of care), monthly sulfadoxine/pyrimethamine-amodiaquine (SP-AQ), or monthly dihydroartemisinin-piperaquine (DP) and followed monthly for 12 months. The primary outcome was the cumulative incidence of clinical malaria at 12 months, and the main secondary outcome was the cumulative incidence of painful events by self-report. Secondary outcomes included other parasitologic, hematologic, and general events. Negative binomial models were used to estimate incidence rate ratios (IRRs) per patient-year (PPY) at risk relative to Proguanil. The primary analytic population was the As-Treated population. A total of 246 children were randomized to daily Proguanil (n = 81), monthly SP-AQ (n = 83), or monthly DP (n = 82). Overall, 53.3% (n = 131) were boys and the mean age was 4.6 ± 2.5 years. The clinical malaria incidence was 0.04 episodes/PPY; relative to the daily Proguanil group, incidence rates were not significantly different in the monthly SP-AQ (IRR: 3.05, 95% confidence interval [CI]: 0.36 to 26.14; p = 0.39) and DP (IRR: 1.36, 95% CI: 0.21 to 8.85; p = 0.90) groups. Among secondary outcomes, relative to the daily Proguanil group, the incidence of painful events was not significantly different in the monthly SP-AQ and DP groups, while monthly DP was associated with a reduced rate of dactylitis (IRR: 0.47; 95% CI: 0.23 to 0.96; p = 0.038). The incidence of Plasmodium falciparum infection relative to daily Proguanil was similar in the monthly SP-AQ group (IRR 0.46; 95% CI: 0.17 to 1.20; p = 0.13) but reduced with monthly DP (IRR 0.21; 95% CI: 0.08 to 0.56; p = 0.002). Serious adverse events were common and distributed between groups, although compared to daily Proguanil (n = 2), more children died receiving monthly SP-AQ (n = 7; hazard ratio [HR] 5.44; 95% CI: 0.92 to 32.11; p = 0.064) but not DP (n = 1; HR 0.61; 95% CI 0.04 to 9.22; p = 0.89), although differences did not reach statistical significance for either SP-AQ or DP. Study limitations include the unexpectedly limited transmission of P. falciparum in the study setting, the high use of hydroxyurea, and the enhanced supportive care for trial participants, which may limit generalizability to higher-transmission settings where routine sickle cell care is more limited. In this study with limited malaria transmission, malaria chemoprevention in Kenyan children with SCA with monthly SP-AQ or DP did not reduce clinical malaria, but DP was associated with reduced dactylitis and P. falciparum parasitization. Pragmatic studies of chemoprevention in higher malaria transmission settings are warranted. clinicaltrials.gov (NCT03178643). Pan-African Clinical Trials Registry: PACTR201707002371165. In a randomized trial, Steve M Taylor and colleagues study the effects of 3 malaria chemoprevention regimens on clinical malaria incidence, P. falciparum infection, and dactylitis among children with sickle cell anemia in Kenya. Sickle cell anemia (SCA) is a very common condition among children born in malaria-endemic areas of sub-Saharan Africa, but their supportive care regimens are poorly tailored to African settings. Among the complications that children with SCA suffer are more severe outcomes owing to malaria, and, therefore, many African countries recommend various malaria preventive regimens for children with SCA. It is important to compare the efficacy and safety of these regimens in order to enhance the supportive care of African children with SCA. In this study, 3 malaria chemoprevention regimens were compared among children under 10 years old with SCA at a single site in Homa Bay, Kenya. Children were randomly assigned to take daily Proguanil (which is the standard of care in Kenya), a monthly combination of sulfadoxine-pyrimethamine with amodiaquine (SP-AQ), or a monthly combination of dihydroartemisinin-piperaquine (DP), and then followed monthly for 12 months. Cases of malaria were very low among all 3 groups, but the combination of DP reduced the risk of being infected by Plasmodium falciparum parasites and of dactylitis, which is a common complication of SCA. DP was not associated with a higher rate of serious adverse events, but SP-AQ was associated with an unexpectedly higher rate of deaths that did not achieve statistical significance. Monthly DP may be an alternative to existing chemoprevention regimens for children with SCA owing to its safety, acceptability, and efficacy on hematologic events. SP-AQ-associated mortality among children with SCA was unexpected and though it did not achieve statistical significance merits further evaluation. Further studies are needed to compare chemoprevention regimens on parasitologic and hematologic outcomes in areas of high P. falciparum transmission and delivered through routine SCA providers.
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DOI：
10.1016/s0140-6736(20)32227-3
发表时间：
2020-12-05
期刊：
Lancet (London, England)
影响因子：
--
作者：
ACCESS-SMC Partnership
通讯作者：
ACCESS-SMC Partnership
影响因子：
3.7
作者：
Gupta H;Galatas B;Chidimatembue A;Huijben S;Cisteró P;Matambisso G;Nhamussua L;Simone W;Bassat Q;Ménard D;Ringwald P;Rabinovich NR;Alonso PL;Saúte F;Aide P;Mayor A
通讯作者：
Mayor A
影响因子：
3
作者：
Gansané A;Moriarty LF;Ménard D;Yerbanga I;Ouedraogo E;Sondo P;Kinda R;Tarama C;Soulama E;Tapsoba M;Kangoye D;Compaore CS;Badolo O;Dao B;Tchwenko S;Tinto H;Valea I
通讯作者：
Valea I
影响因子：
3
作者：
Marwa KJ;Schmidt T;Sjögren M;Minzi OM;Kamugisha E;Swedberg G
通讯作者：
Swedberg G
影响因子：
3.7
作者：
Poirot, Eugenie;Vittinghoff, Eric;Gosling, Roland
通讯作者：
Gosling, Roland