ORCID Profile
0000-0002-1667-9287
Current Organisations
The University of Tokyo, Institute of Medical Science
,
University of Oxford
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Publisher: BMJ
Date: 05-2019
DOI: 10.1136/BMJOPEN-2018-027503
Abstract: Pregnant women are more vulnerable to malaria leading to adverse impact on both mothers and fetuses. However, knowledge on the efficacy and safety of antimalarials in pregnancy is limited by the paucity of randomised control trials and the lack of standardised protocols in this special subpopulation. Pooling in idual patient data (IPD) for meta-analysis could address in part these limitations to summarise accurately the currently available evidence on treatment efficacy and risk factors for treatment failure. To assess the treatment efficacy of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy, seven databases (Medline, Embase, Global Health, Cochrane Library, Scopus, Web of Science and Literatura Latino Americana em Ciências da Saúde) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrial.gov) were searched. Both interventional and observational cohort studies following up for at least 28 days will be included. IPD of the identified eligible published or unpublished studies will be sought by inviting principal investigators. Raw IPD will be shared through the web-based secure platform developed by the WorldWide Antimalarial Resistance Network using the established methodology. The primary objective is to compare the risk of PCR-corrected treatment failure among different treatments and to find the risk factors. One-stage IPD meta-analysis by Cox model with shared frailty will be conducted. A risk of bias assessment will be conducted to address the impact of unshared potential data and of the quality of in idual studies. Potential limitations include difficulty in acquiring the IPD and heterogeneity of the study designs due to the lack of standard. This IPD meta-analysis consists of secondary analyses of existing anonymous data and meets the criteria for waiver of ethics review by the Oxford Tropical Research Ethics Committee. The results of this IPD meta-analysis will be disseminated through open-access publications at peer-reviewed journals. The study results will lead to a better understanding of malaria treatment in pregnancy, which can be used for clinical decision-making and conducting further studies. CRD42018104013.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2021
DOI: 10.1186/S12916-021-02002-8
Abstract: Artemisinin and artemisinin-based combination therapy (ACT) partner drug resistance in Plasmodium falciparum have spread across the Greater Mekong Subregion compromising antimalarial treatment. The current 3-day artemether-lumefantrine regimen has been associated with high treatment failure rates in pregnant women. Although ACTs are recommended for treating Plasmodium vivax malaria, no clinical trials in pregnancy have been reported. Pregnant women with uncomplicated malaria on the Thailand-Myanmar border participated in an open-label randomized controlled trial comparing dihydroartemisinin-piperaquine (DP), artesunate-mefloquine (ASMQ) and a 4-day artemether-lumefantrine regimen (AL + ). The primary endpoint for P. falciparum infections was the PCR-corrected cure rate and for P. vivax infections was recurrent parasitaemia, before delivery or day 63, whichever was longer, assessed by Kaplan-Meier estimate. Between February 2010 and August 2016, 511 pregnant women with malaria (353 P. vivax , 142 P. falciparum , 15 co-infections, 1 Plasmodium malariae ) were randomized to either DP ( n =170), ASMQ ( n =169) or AL + ( n =172) treatments. Successful malaria elimination efforts in the region resulted in premature termination of the trial. The majority of women had recurrent malaria (mainly P. vivax relapses, which are not prevented by these treatments). Recurrence-free proportions (95% confidence interval [95% CI]) for vivax malaria were 20.6% (5.1–43.4) for DP ( n =125), 46.0% (30.9–60.0) for ASMQ ( n =117) and 28.7% (10.0–50.8) for AL + ( n =126). DP and ASMQ provided longer recurrence-free intervals. PCR-corrected cure rates (95% CI) for falciparum malaria were 93.7% (81.6–97.9) for DP ( n =49), 79.6% (66.1–88.1) for AMSQ ( n =55) and 87.5% (74.3–94.2) for AL + ( n =50). Overall 65% (85/130) of P. falciparum infections had Pfkelch13 propeller mutations which increased over time and recrudescence occurred almost exclusively in them risk ratio 9.42 (95% CI 1.30–68.29). Among the women with falciparum malaria, 24.0% (95% CI 16.8–33.6) had P. vivax parasitaemia within 4 months. Nausea, vomiting, dizziness and sleep disturbance were more frequent with ASMQ. Miscarriage, small-for-gestational-age and preterm birth did not differ significantly among the treatment groups, including first trimester exposures ( n =46). DP was well tolerated and safe, and was the only drug providing satisfactory efficacy for P. falciparum -infected pregnant woman in this area of widespread artemisinin resistance. Vivax malaria recurrences are very common and warrant chloroquine prophylaxis after antimalarial treatment in this area. ClinicalTrials.gov identifier NCT01054248 , registered on 22 January 2010.
Publisher: American Society for Microbiology
Date: 18-03-2021
DOI: 10.1128/AAC.02473-20
Abstract: Quinoline antimalarials cause drug-induced electrocardiograph QT prolongation, a potential risk factor for torsade de pointes. The effects of currently used antimalarials on the electrocardiogram (ECG) were assessed in pregnant women with malaria.
Publisher: Public Library of Science (PLoS)
Date: 12-08-2021
DOI: 10.1371/JOURNAL.PONE.0255902
Abstract: Four in five neonatal deaths of preterm births occur in low and middle income countries and placental histopathology examination can help clarify the pathogenesis. Infection is known to play a significant role in preterm birth. The aim of this systematic review is to explore the association between placental histopathological abnormality and preterm birth in the presence of confirmed infection. PubMed/Medline, Scopus, Web of Science and Embase were searched using the keywords related to preterm birth, placental histopathology and infection. Titles and abstracts were screened and the full texts of eligible articles were reviewed to extract and summarise data. Of 1529 articles, only 23 studies (13 bacterial, 6 viral and 4 parasitic) were included, and they used 7 different gestational age windows, and 20 different histopathological classification systems, precluding data pooling. Despite this, histopathological chorioamnionitis, and funisitis (when examined) were commonly observed in preterm birth complicated by confirmed bacterial or viral, but not parasitic, infection. The presence of malaria parasites but not pigment in placenta was reported to increase the risk of PTB, but this finding was inconclusive. One in three studies were conducted in low and middle income countries. An array of: definitions of preterm birth subgroups, histological classification systems, histopathologic abnormalities and diagnostic methods to identify infections were reported in this systematic review. Commitment to using standardised terminology and classification of histopathological abnormalities associated with infections is needed to identify causality and potential treatment of preterm birth. Studies on preterm birth needs to occur in high burden countries and control for clinical characteristics (maternal, fetal, labor, and placental) that may have an impact on placental histopathological abnormalities.
Publisher: Oxford University Press (OUP)
Date: 31-05-2019
DOI: 10.1093/OFID/OFZ264
Abstract: Follow-up for 28–42 days is recommended by the World Health Organization to assess antimalarial drug efficacy for nonpregnant populations. This study aimed to determine the optimal duration for pregnant women, as no specific guidance currently exists. The distributions of time to recrudescence (treatment failure), confirmed by polymerase chain reaction genotyping for different antimalarial drugs in pregnancy, were analyzed by accelerated failure time models using secondary data on microscopically confirmed recurrent falciparum malaria collected in prospective studies on the Thailand–Myanmar border between 1994 and 2010. Of 946 paired isolates from 703 women, the median duration of follow-up for each genotyped recurrence (interquartile range) was 129 (83–174) days, with 429 polymerase chain reaction–confirmed recrudescent. Five different treatments were evaluated, and 382 Plasmodium falciparum recrudescences were identified as eligible. With log-logistic models adjusted for baseline parasitemia, the predicted cumulative proportions of all the recrudescences that were detected by 28 days were 70% (95% confidence interval [CI], 65%–74%) for quinine monotherapy (n = 295), 66% (95% CI, 53%–76%) for artesunate monotherapy (n = 43), 62% (95% CI, 42%–79%) for artemether–lumefantrine (AL n = 19), 46% (95% CI, 26%–67%) for artesunate with clindamycin (n = 19), and 34% (95% CI, 11%–67%) for dihydroartemisinin–piperaquine (DP n = 6). Corresponding figures by day 42 were 89% (95% CI, 77%–95%) for AL and 71% (95% CI, 38%–91%) for DP. Follow-up for 63 days was predicted to detect ≥95% of all recrudescence, except for DP. In low-transmission settings, antimalarial drug efficacy assessments in pregnancy require longer follow-up than for nonpregnant populations.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 02-06-2020
DOI: 10.1186/S12916-020-01592-Z
Abstract: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. In idual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and 37.0 weeks), small for gestational age (SGA, birthweight of 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. Of the 22 eligible studies ( n = 5015), IPD from16 studies were shared, representing 95.0% ( n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine ( n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine ( n = 1087), artesunate-amodiaquine ( n = 775), artesunate-mefloquine ( n = 965), and dihydroartemisinin-piperaquine ( n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p 0.001). The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Informa UK Limited
Date: 23-10-2018
DOI: 10.1080/14740338.2018.1535593
Abstract: Malaria in pregnancy and postpartum cause maternal mortality and adverse fetal outcomes. Efficacious and safe antimalarials are needed to treat and prevent such serious consequences. However, because of the lack of evidence on fetal safety, quinine, an old and less efficacious drug has long been recommended for pregnant women. Uncertainty about safety in relation to breastfeeding leads to withholding of efficacious treatments postpartum or cessation of breastfeeding. Areas covered: A search identified literature on humans in three databases (MEDLINE, Embase and Global health) using pregnancy or lactation, and the names of antimalarial drugs as search terms. Adverse reactions to the mother, fetus or breastfed infant were summarized together with efficacies. Expert opinion: Artemisinins are more efficacious and well-tolerated than quinine in pregnancy. Furthermore, the risks of miscarriage, stillbirth or congenital abnormality were not higher in pregnancies exposed to artemisinin derivatives for treatment of malaria than in pregnancies exposed to quinine or in the comparable background population unexposed to any antimalarials, and this was true for treatment in any trimester. Assessment of safety and efficacy of antimalarials including dose optimization for pregnant women is incomplete. Resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum and long unprotected intervals between intermittent treatment doses begs reconsideration of current preventative recommendations in pregnancy. Data remain limited on antimalarials during breastfeeding while most first-line drugs appear safe, further research is needed.
Location: Japan
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Makoto Saito.