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- Saito, Makoto, et al.
(författare)
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Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
- 2023
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 401:10371, s. 118-130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. Methods: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. Findings: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49–1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47–1·17), stillbirth (aHR=0·71, 0·32–1·57), and major congenital anomalies (aHR=0·60, 0·13–2·87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92). Interpretation: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.
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| 2. |
- Wynberg, Elke, et al.
(författare)
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Variability in white blood cell count during uncomplicated malaria and implications for parasite density estimation : a WorldWide Antimalarial Resistance Network individual patient data meta-analysis
- 2023
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Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875 .- 1475-2875. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.Methods: Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/mu L and age-stratified values) using estimates derived from the measured WBC value as reference.Results: Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (x 1000 cells/mu L) in age groups < 1, 1-4, 5-14 and >= 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/mu L resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged = 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients.Conclusions: Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.
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