Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial.
Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial.
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DOI：
10.1016/s1473-3099(18)30415-8
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Laufer MK
中科院分区：
文献类型：
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作者：
Divala TH;Mungwira RG;Mawindo PM;Nyirenda OM;Kanjala M;Ndaferankhande M;Tsirizani LE;Masonga R;Muwalo F;Boudová S;Potter GE;Kennedy J;Goswami J;Wylie BJ;Muehlenbachs A;Ndovie L;Mvula P;Mbilizi Y;Tomoka T;Laufer MK
Sulfadoxine-pyrimethamine (SP) resistance threatens efficacy of intermittent preventive treatment during pregnancy (IPTp) and there is an urgent need to identify alternative regimens. With the return of chloroquine efficacy in Southern Africa, we hypothesized that chloroquine either as IPTp or as chemoprophylaxis would be more efficacious than SP-IPTp for prevention of pregnancy malaria and associated maternal and newborn adverse outcomes. We conducted an open label, single-centre randomized clinical trial of chloroquine prophylaxis (600mg day-1, 300mg weekly), chloroquine-IPTp (2 doses of 600mg day-1, 600mg day-2, 300mg day-3) or SP-IPTp (2 doses), to HIV negative first and second gravid women at 20 to 28 weeks gestation, in Malawi. Participants were randomly assigned to receive SP-IPTp, chloroquine-IPTp, and chloroquine-prophylaxis in a 1:1:1 ratio. We used a computer-generated randomization list. Our primary endpoint was placental malaria in participants in the modified intent-to-treat population, comprised of those who were randomized and contributed histopathology data at birth. ClinicalTrials.gov registration: NCT01443130. From 2012–2014 we randomized 900 women, 765(85%) contributed histopathology data and were included in the analysis. 14% (108/765) experienced placental malaria, which was lower than the anticipated rate of placental malaria infection. Our primary analysis did not find improved protection from placental malaria by chloroquine as prophylaxis (relative risk (RR) 0.75 [95% confidence interval (CI): 0.48, 1.17]), or as IPTp (RR 1.00 [95% CI: 0.67, 1.50]) compared to SP-IPTp. However, our protocol specified adjusted analysis of the primary outcome found that, women taking chloroquine-prophylaxis experienced 36% lower placental infections than those in SP-IPTp arm (RR 0.64 [95% CI: 0.44, 0.93]). Incidence of clinical malaria, maternal anaemia and low birth weight was not improved by the interventions. There were nine cases of clinical malaria in the SP-IPTp group, four in the chloroquine IPTp group (p = 0.26) and two in the weekly chloroquine group (p = 0.06). There were five cases of maternal anaemia in the SP-IPTp group, fifteen in the chloroquine IPTp group (p = 0.04) and six in the weekly chloroquine group (p = 1.00). There were 31 cases of low birth weight in the SP-IPTp group, 29 in the chloroquine IPTp group (p = 0.78) and 41 in the weekly chloroquine group (p = 0.28). Compared to SP-IPTp both chloroquine arms had more related adverse events overall, but there was no difference in severe or life-threatening events. Adverse events possibly related to study product were experienced by four maternal subjects in the SP-IPTp group, 94 in the chloroquine IPTp group (p < 0.001) and 26 in the weekly chloroquine group (p < 0.001). There were three maternal subjects who experienced severe or life threatening adverse events related to study product. These were all in the chloroquine IPTp group (p = 0.25). Chloroquine administered as IPTp did not provide better protection from malaria and related adverse effects than SP-IPTp in this setting of high SP-resistance. Protocol-specified adjusted analyses suggest that chloroquine chemoprophylaxis may provide benefit in protecting against malaria during pregnancy.
