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Steve M Taylor - One of the best experts on this subject based on the ideXlab platform.

  • rapid diagnostic test performance assessed using latent class analysis for the diagnosis of plasmodium falciparum placental malaria
    American Journal of Tropical Medicine and Hygiene, 2016
    Co-Authors: Yunhao Liu, Carole Khairallah, Steven R Meshnick, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Kyaw L Thwai, Linda Kalilaniphiri
    Abstract:

    Placental malaria causes low birth weight and neonatal mortality in malaria-endemic areas. The diagnosis of placental malaria is important for program evaluation and clinical care, but is compromised by the suboptimal performance of current diagnostics. Using placental and peripheral blood specimens collected from delivering women in Malawi, we compared estimation of the operating characteristics of microscopy, rapid diagnostic test (RDT), polymerase chain reaction, and histopathology using both a traditional contingency table and a latent class analysis (LCA) approach. The prevalence of placental malaria by histopathology was 13.8%; concordance between tests was generally poor. Relative to histopathology, RDT sensitivity was 79.5% in peripheral and 66.2% in placental blood; using LCA, RDT sensitivities increased to 93.7% and 80.2%, respectively. Our results, if replicated in other cohorts, indicate that RDT testing of peripheral or placental blood may be suitable approaches to detect placental malaria for surveillance programs, including areas where Intermittent Preventive Therapy in pregnancy is not used.

  • impact of sulfadoxine pyrimethamine resistance on effectiveness of Intermittent Preventive Therapy for malaria in pregnancy at clearing infections and preventing low birth weight
    Clinical Infectious Diseases, 2016
    Co-Authors: Kassoum Kayentao, Meghna Desai, Julie Gutman, Carole Khairallah, Steve M Taylor, Ryan E Wiegand, Peter Ouma
    Abstract:

    Background: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of Intermittent Preventive Therapy in pregnancy (IPTp) with SP is crucial. Methods: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus–uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. Results: Among 1222 parasitemic pregnant women, overall polymerase chain reaction–uncorrected and –corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69–.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67–.97; P = .02). Conclusions: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

  • antenatal receipt of sulfadoxine pyrimethamine does not exacerbate pregnancy associated malaria despite the expansion of drug resistant plasmodium falciparum clinical outcomes from the queerpam study
    Clinical Infectious Diseases, 2012
    Co-Authors: Gaoqian Feng, Ebbie Chaluluka, Malcolm E Molyneux, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Alejandro L Antonia
    Abstract:

    Pregnancy-associated malaria (PAM) is an important, preventable cause of poor birth outcomes in malaria-endemic areas in sub-Saharan Africa [1]. Intermittent Preventive Therapy with antimalarials during pregnancy (IPTp) is a critical tool for reducing the incidence of PAM-attributable adverse birth outcomes [2]. Sulfadoxine-pyrimethamine (SP) is the most commonly administered drug for IPTp owing to its long half-life, favorable side-effect profile, and safety during pregnancy. However, Plasmodium falciparum strains harboring mutations associated with SP resistance are increasingly prevalent throughout sub-Saharan Africa. The outcome of antimalarial Therapy results from complex interactions between parasite pathogenicity, host immunity, drug characteristics, and parasite susceptibility to drug Therapy. Recent in vitro studies have suggested that the removal of susceptible parasites from heterogeneous parasitemias by antimalarial Therapy may facilitate the relative overgrowth of the remaining resistant parasites and therefore potentiate their pathogenicity [3]. A recent study in Tanzania documented increases in placental inflammation that were associated with SP receipt, suggesting that SP may potentiate placental pathology when applied to partially susceptible infections [4]. However, the effect of these placental findings upon birth outcomes was unclear. Given the prevalence of SP resistance and the current lack of appropriate, safe alternatives for use as IPTp, it is critical to explore the associations between IPTp-SP, SP resistance, and delivery outcomes in further contexts to inform malaria control policies. Malawi adopted a policy of IPTp with SP in 1993, and despite the subsequent development of widespread SP resistance [5], a sustained decline in the prevalence of PAM was observed from 1997 to 2005 [6]. In view of the evidence from Tanzania [4], we hypothesized that the emergence of SP-resistant parasites would modify the effect of IPTp-SP and thereby potentiate placental inflammation and parasite densities and worsen birth outcomes. The Queen Elizabeth Central Hospital Epidemiology of Resistance in Pregnancy-Associated Malaria (QuEERPAM) study [7] was a serial cross-sectional analysis in which we explored the relationships between IPTp-SP, the presence of resistant parasites at delivery, and multiple measures of adverse delivery outcome, including parasite densities, placental histology, maternal hemoglobin concentration, and birth weight.

Carole Khairallah - One of the best experts on this subject based on the ideXlab platform.

  • effect of plasmodium falciparum sulfadoxine pyrimethamine resistance on the effectiveness of Intermittent Preventive Therapy for malaria in pregnancy in africa a systematic review and meta analysis
    Lancet Infectious Diseases, 2019
    Co-Authors: Anna M Van Eijk, David A Larsen, Kassoum Kayentao, Gibby Koshy, Douglas E C Slaughter, Cally Roper, Lucy C Okell, Meghna Desai, Julie Gutman, Carole Khairallah
    Abstract:

    Summary Background Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of Intermittent Preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes. Methods For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540. Findings Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (ptrend=0·0060) but not Ala437Gly (ptrend=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to Interpretation The effectiveness of sulfadoxine-pyrimethamine IPTp is reduced in areas with high resistance to sulfadoxine-pyrimethamine among P falciparum parasites, but remains associated with reductions in low birthweight even in areas where dhps Lys540Glu prevalence exceeds 90% but where the sextuple-mutant parasite (harbouring the additional dhps Ala581Gly mutation) is uncommon. Therapeutic alternatives to sulfadoxine-pyrimethamine IPTp are needed in areas where the prevalence of the sextuple-mutant parasite exceeds 37%. Funding US Centers for Disease Control and Prevention, the Malaria in Pregnancy Consortium (funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine), Worldwide Antimalarial Resistance Network, European and Developing Countries Clinical Trials Partnership.

  • rapid diagnostic test performance assessed using latent class analysis for the diagnosis of plasmodium falciparum placental malaria
    American Journal of Tropical Medicine and Hygiene, 2016
    Co-Authors: Yunhao Liu, Carole Khairallah, Steven R Meshnick, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Kyaw L Thwai, Linda Kalilaniphiri
    Abstract:

    Placental malaria causes low birth weight and neonatal mortality in malaria-endemic areas. The diagnosis of placental malaria is important for program evaluation and clinical care, but is compromised by the suboptimal performance of current diagnostics. Using placental and peripheral blood specimens collected from delivering women in Malawi, we compared estimation of the operating characteristics of microscopy, rapid diagnostic test (RDT), polymerase chain reaction, and histopathology using both a traditional contingency table and a latent class analysis (LCA) approach. The prevalence of placental malaria by histopathology was 13.8%; concordance between tests was generally poor. Relative to histopathology, RDT sensitivity was 79.5% in peripheral and 66.2% in placental blood; using LCA, RDT sensitivities increased to 93.7% and 80.2%, respectively. Our results, if replicated in other cohorts, indicate that RDT testing of peripheral or placental blood may be suitable approaches to detect placental malaria for surveillance programs, including areas where Intermittent Preventive Therapy in pregnancy is not used.

  • scheduled Intermittent screening with rapid diagnostic tests and treatment with dihydroartemisinin piperaquine versus Intermittent Preventive Therapy with sulfadoxine pyrimethamine for malaria in pregnancy in malawi an open label randomized controlled trial
    PLOS Medicine, 2016
    Co-Authors: Carole Khairallah, Victor Mwapasa, Mwayiwawo Madanitsa, Linda Kalilani, Anna M Van Eijk, Cheryl Pace, James Smedley, Kyaw L Thwai, Brandt Levitt
    Abstract:

    Background In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends Intermittent Preventive Therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled Intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP. Methods and Findings This was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the Intermittent screening and treatment in pregnancy with DP (ISTp-DP) arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk]) in paucigravidae (first or second pregnancy) and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher). Analysis was by intention to treat. Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae). The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9%) and IPTp-SP (28.8%) arms (risk difference = 1.08% [95% CI −3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90–1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92–1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71–1.20], p = 0.543). The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference = 7.85%, [95% CI 3.07%–12.63%]; all women: RR = 1.19 [95% CI 1.07–1.33], p = 0.007; paucigravidae: RR = 1.16 [95% CI 1.04–1.31], p = 0.011; multigravidae: RR = 1.29 [95% CI 1.02–1.63], p = 0.037). Fetal loss was more common with ISTp-DP (2.6% versus 1.3%; RR = 2.06 [95% CI 1.01–4.21], p = 0.046) and highest among non-DP-recipients (3.1%) in the ISTp-DP arm. Limitations included the open-label design. Conclusions Scheduled screening for malaria parasites with the current generation of RDTs three to four times during pregnancy as part of focused antenatal care was not superior to IPTp-SP in this area with high malaria transmission and high SP resistance and was associated with higher fetal loss and more malaria at delivery. Trial Registration Pan African Clinical Trials Registry PACTR201103000280319; ISRCTN Registry ISRCTN69800930

  • impact of sulfadoxine pyrimethamine resistance on effectiveness of Intermittent Preventive Therapy for malaria in pregnancy at clearing infections and preventing low birth weight
    Clinical Infectious Diseases, 2016
    Co-Authors: Kassoum Kayentao, Meghna Desai, Julie Gutman, Carole Khairallah, Steve M Taylor, Ryan E Wiegand, Peter Ouma
    Abstract:

    Background: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of Intermittent Preventive Therapy in pregnancy (IPTp) with SP is crucial. Methods: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus–uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. Results: Among 1222 parasitemic pregnant women, overall polymerase chain reaction–uncorrected and –corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69–.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67–.97; P = .02). Conclusions: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

  • Secondary newborn outcomes: birth outcomes and neonatal follow-up.
    2016
    Co-Authors: Mwayiwawo Madanitsa, Carole Khairallah, Victor Mwapasa, Linda Kalilani, Cheryl Pace, James Smedley, Anna M. Van Eijk, Doreen Ali, Kyaw-lay Thwai, Brandt Levitt
    Abstract:

    The P-value for the interaction term depicts the p-value for differences in effect size between paucigravidae and multigravidae. IPTp-SP, Intermittent Preventive Therapy in pregnancy with sulfadoxine-pyrimethamine; ISTp-DP, Intermittent screening and treatment in pregnancy with dihydroartemisinin-piperaquine; RR, relative risk.

Feiko O Ter Kuile - One of the best experts on this subject based on the ideXlab platform.

  • rapid diagnostic test performance assessed using latent class analysis for the diagnosis of plasmodium falciparum placental malaria
    American Journal of Tropical Medicine and Hygiene, 2016
    Co-Authors: Yunhao Liu, Carole Khairallah, Steven R Meshnick, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Kyaw L Thwai, Linda Kalilaniphiri
    Abstract:

    Placental malaria causes low birth weight and neonatal mortality in malaria-endemic areas. The diagnosis of placental malaria is important for program evaluation and clinical care, but is compromised by the suboptimal performance of current diagnostics. Using placental and peripheral blood specimens collected from delivering women in Malawi, we compared estimation of the operating characteristics of microscopy, rapid diagnostic test (RDT), polymerase chain reaction, and histopathology using both a traditional contingency table and a latent class analysis (LCA) approach. The prevalence of placental malaria by histopathology was 13.8%; concordance between tests was generally poor. Relative to histopathology, RDT sensitivity was 79.5% in peripheral and 66.2% in placental blood; using LCA, RDT sensitivities increased to 93.7% and 80.2%, respectively. Our results, if replicated in other cohorts, indicate that RDT testing of peripheral or placental blood may be suitable approaches to detect placental malaria for surveillance programs, including areas where Intermittent Preventive Therapy in pregnancy is not used.

  • antenatal receipt of sulfadoxine pyrimethamine does not exacerbate pregnancy associated malaria despite the expansion of drug resistant plasmodium falciparum clinical outcomes from the queerpam study
    Clinical Infectious Diseases, 2012
    Co-Authors: Gaoqian Feng, Ebbie Chaluluka, Malcolm E Molyneux, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Alejandro L Antonia
    Abstract:

    Pregnancy-associated malaria (PAM) is an important, preventable cause of poor birth outcomes in malaria-endemic areas in sub-Saharan Africa [1]. Intermittent Preventive Therapy with antimalarials during pregnancy (IPTp) is a critical tool for reducing the incidence of PAM-attributable adverse birth outcomes [2]. Sulfadoxine-pyrimethamine (SP) is the most commonly administered drug for IPTp owing to its long half-life, favorable side-effect profile, and safety during pregnancy. However, Plasmodium falciparum strains harboring mutations associated with SP resistance are increasingly prevalent throughout sub-Saharan Africa. The outcome of antimalarial Therapy results from complex interactions between parasite pathogenicity, host immunity, drug characteristics, and parasite susceptibility to drug Therapy. Recent in vitro studies have suggested that the removal of susceptible parasites from heterogeneous parasitemias by antimalarial Therapy may facilitate the relative overgrowth of the remaining resistant parasites and therefore potentiate their pathogenicity [3]. A recent study in Tanzania documented increases in placental inflammation that were associated with SP receipt, suggesting that SP may potentiate placental pathology when applied to partially susceptible infections [4]. However, the effect of these placental findings upon birth outcomes was unclear. Given the prevalence of SP resistance and the current lack of appropriate, safe alternatives for use as IPTp, it is critical to explore the associations between IPTp-SP, SP resistance, and delivery outcomes in further contexts to inform malaria control policies. Malawi adopted a policy of IPTp with SP in 1993, and despite the subsequent development of widespread SP resistance [5], a sustained decline in the prevalence of PAM was observed from 1997 to 2005 [6]. In view of the evidence from Tanzania [4], we hypothesized that the emergence of SP-resistant parasites would modify the effect of IPTp-SP and thereby potentiate placental inflammation and parasite densities and worsen birth outcomes. The Queen Elizabeth Central Hospital Epidemiology of Resistance in Pregnancy-Associated Malaria (QuEERPAM) study [7] was a serial cross-sectional analysis in which we explored the relationships between IPTp-SP, the presence of resistant parasites at delivery, and multiple measures of adverse delivery outcome, including parasite densities, placental histology, maternal hemoglobin concentration, and birth weight.

  • Intermittent Preventive Therapy for malaria with monthly artemether lumefantrine for the post discharge management of severe anaemia in children aged 4 59 months in southern malawi a multicentre randomised placebo controlled trial
    Lancet Infectious Diseases, 2012
    Co-Authors: Kamija S Phiri, Carole Khairallah, Michael Boele Van Hensbroek, Michael O Esan, Brian Faragher, Feiko O Ter Kuile
    Abstract:

    Summary Background Young children with severe malarial anaemia in Africa are at high risk of readmittance to hospital or death within 6 months of discharge. We aimed to assess whether 3 months of chemoprevention with artemether–lumefantrine reduced this risk. Methods We did a randomised, placebo-controlled, multicentre trial in four hospitals in Malawi testing the efficacy and safety of Intermittent Preventive Therapy post-discharge (IPTpd) in children aged 4–59 months admitted for severe malarial anaemia. All convalescent children who had completed a blood transfusion received artemether–lumefantrine at discharge and were randomly assigned by a computer-generated sequence to receive placebo or artemether–lumefantrine at 1 month and 2 months after discharge, providing about 1 month and 3 months of protection, respectively. Patients and study staff were masked throughout the study. The primary endpoint was a composite of all-cause mortality or hospital readmittance because of all-cause severe anaemia or severe malaria between 1 and 6 months after enrolment. This trial is registered, number ISRCTN89727873. Results Of 1414 children enrolled, 708 were assigned to receive placebo and 706 the intervention. By 6 months, 192 children (14%) had died or were readmitted with severe malaria or severe anaemia. 1–6 months after randomisation, 109 primary events occurred in 85 children in the placebo group and 86 in 74 children in the intervention group (adjusted protective efficacy [PE] 31%, 95% CI 5–50; absolute rate reduction 11·7 per 100 children years, 95% CI 1·8–18·9; p=0·024). The protective effect was greatest during the IPTpd period (1–3 months), when 58 primary events occurred in 49 children in the placebo group and 37 in 34 children in the intervention group (PE 41%, 10–62; p=0·01), but was not sustained after the third month (4–6 months, PE 17%, −27 to 45; p=0·395). When episodes in the first month were included—ie, before the first dose of IPTpd, when both groups benefited from the post-treatment prophylactic effect of artemether–lumefantrine provided at discharge—the overall cumulative PE by 6 months was 26% (−2 to 46; p=0·06). Interpretation In areas with intense malaria transmission, chemoprevention with IPTpd given to children with severe malarial anaemia might reduce rates of readmittance to hospital for severe anaemia or malaria. Studies to confirm these findings and to investigate different delivery mechanisms and cost-effectiveness are needed. Funding The Netherlands African Partnership for Capacity Development and Clinical Interventions Against Poverty Related Diseases, the UBS-Optimus Foundation, and the Gates Malaria Partnership.

  • pharmacokinetics of sulfadoxine pyrimethamine in hiv infected and uninfected pregnant women in western kenya
    The Journal of Infectious Diseases, 2007
    Co-Authors: Michael D Green, Anna M Van Eijk, Richard W. Steketee, Feiko O Ter Kuile, John G Ayisi, Monica E Parise, Piet A Kager, Bernard L Nahlen, Henry Nettey
    Abstract:

    Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV+) women require more frequent doses of Intermittent Preventive Therapy with SP than do HIV-uninfected (HIV-) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP. Seventeen pregnant HIV- women and 16 pregnant HIV+ women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV- and 6 HIV+ postpartum women returned 2-3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups. HIV status did not affect the area under the curve (AUC/or8) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P < .001) and the median AUC/or8 was ~40% lower (22816 vs 40106 microg/mL/h P < .001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics. Pregnancy significantly modifies the disposition of SP whereas HIV status has little influence on pharmacokinetic parameters in pregnant women. (authors)

Victor Mwapasa - One of the best experts on this subject based on the ideXlab platform.

  • rapid diagnostic test performance assessed using latent class analysis for the diagnosis of plasmodium falciparum placental malaria
    American Journal of Tropical Medicine and Hygiene, 2016
    Co-Authors: Yunhao Liu, Carole Khairallah, Steven R Meshnick, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Kyaw L Thwai, Linda Kalilaniphiri
    Abstract:

    Placental malaria causes low birth weight and neonatal mortality in malaria-endemic areas. The diagnosis of placental malaria is important for program evaluation and clinical care, but is compromised by the suboptimal performance of current diagnostics. Using placental and peripheral blood specimens collected from delivering women in Malawi, we compared estimation of the operating characteristics of microscopy, rapid diagnostic test (RDT), polymerase chain reaction, and histopathology using both a traditional contingency table and a latent class analysis (LCA) approach. The prevalence of placental malaria by histopathology was 13.8%; concordance between tests was generally poor. Relative to histopathology, RDT sensitivity was 79.5% in peripheral and 66.2% in placental blood; using LCA, RDT sensitivities increased to 93.7% and 80.2%, respectively. Our results, if replicated in other cohorts, indicate that RDT testing of peripheral or placental blood may be suitable approaches to detect placental malaria for surveillance programs, including areas where Intermittent Preventive Therapy in pregnancy is not used.

  • scheduled Intermittent screening with rapid diagnostic tests and treatment with dihydroartemisinin piperaquine versus Intermittent Preventive Therapy with sulfadoxine pyrimethamine for malaria in pregnancy in malawi an open label randomized controlled trial
    PLOS Medicine, 2016
    Co-Authors: Carole Khairallah, Victor Mwapasa, Mwayiwawo Madanitsa, Linda Kalilani, Anna M Van Eijk, Cheryl Pace, James Smedley, Kyaw L Thwai, Brandt Levitt
    Abstract:

    Background In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends Intermittent Preventive Therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled Intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP. Methods and Findings This was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the Intermittent screening and treatment in pregnancy with DP (ISTp-DP) arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk]) in paucigravidae (first or second pregnancy) and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher). Analysis was by intention to treat. Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae). The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9%) and IPTp-SP (28.8%) arms (risk difference = 1.08% [95% CI −3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90–1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92–1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71–1.20], p = 0.543). The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference = 7.85%, [95% CI 3.07%–12.63%]; all women: RR = 1.19 [95% CI 1.07–1.33], p = 0.007; paucigravidae: RR = 1.16 [95% CI 1.04–1.31], p = 0.011; multigravidae: RR = 1.29 [95% CI 1.02–1.63], p = 0.037). Fetal loss was more common with ISTp-DP (2.6% versus 1.3%; RR = 2.06 [95% CI 1.01–4.21], p = 0.046) and highest among non-DP-recipients (3.1%) in the ISTp-DP arm. Limitations included the open-label design. Conclusions Scheduled screening for malaria parasites with the current generation of RDTs three to four times during pregnancy as part of focused antenatal care was not superior to IPTp-SP in this area with high malaria transmission and high SP resistance and was associated with higher fetal loss and more malaria at delivery. Trial Registration Pan African Clinical Trials Registry PACTR201103000280319; ISRCTN Registry ISRCTN69800930

  • Secondary newborn outcomes: birth outcomes and neonatal follow-up.
    2016
    Co-Authors: Mwayiwawo Madanitsa, Carole Khairallah, Victor Mwapasa, Linda Kalilani, Cheryl Pace, James Smedley, Anna M. Van Eijk, Doreen Ali, Kyaw-lay Thwai, Brandt Levitt
    Abstract:

    The P-value for the interaction term depicts the p-value for differences in effect size between paucigravidae and multigravidae. IPTp-SP, Intermittent Preventive Therapy in pregnancy with sulfadoxine-pyrimethamine; ISTp-DP, Intermittent screening and treatment in pregnancy with dihydroartemisinin-piperaquine; RR, relative risk.

  • Flow chart.
    2016
    Co-Authors: Mwayiwawo Madanitsa, Carole Khairallah, Victor Mwapasa, Linda Kalilani, Cheryl Pace, James Smedley, Anna M. Van Eijk, Doreen Ali, Kyaw-lay Thwai, Brandt Levitt
    Abstract:

    aOne woman randomized to IPTp-SP was erroneously recorded as being in the ISTp-DP arm on her antenatal care card and as a result received ISTp-DP. She was included in the ITT population under the IPTp-SP arm. bScreening failures were not followed to delivery and were excluded from the modified ITT population. cWomen lost to follow-up prior to delivery and women who withdrew consent were included in the ITT population and contributed to the antenatal follow-up analyses (e.g., incidence of malaria). IPTp-SP, Intermittent Preventive Therapy in pregnancy with sulfadoxine-pyrimethamine; ISTp-DP, Intermittent screening and treatment in pregnancy with dihydroartemisinin-piperaquine; ITT, intention to treat; SGA/LBW/PT, small for gestational age or low birthweight or preterm.

  • antenatal receipt of sulfadoxine pyrimethamine does not exacerbate pregnancy associated malaria despite the expansion of drug resistant plasmodium falciparum clinical outcomes from the queerpam study
    Clinical Infectious Diseases, 2012
    Co-Authors: Gaoqian Feng, Ebbie Chaluluka, Malcolm E Molyneux, Steve M Taylor, Victor Mwapasa, Feiko O Ter Kuile, Alejandro L Antonia
    Abstract:

    Pregnancy-associated malaria (PAM) is an important, preventable cause of poor birth outcomes in malaria-endemic areas in sub-Saharan Africa [1]. Intermittent Preventive Therapy with antimalarials during pregnancy (IPTp) is a critical tool for reducing the incidence of PAM-attributable adverse birth outcomes [2]. Sulfadoxine-pyrimethamine (SP) is the most commonly administered drug for IPTp owing to its long half-life, favorable side-effect profile, and safety during pregnancy. However, Plasmodium falciparum strains harboring mutations associated with SP resistance are increasingly prevalent throughout sub-Saharan Africa. The outcome of antimalarial Therapy results from complex interactions between parasite pathogenicity, host immunity, drug characteristics, and parasite susceptibility to drug Therapy. Recent in vitro studies have suggested that the removal of susceptible parasites from heterogeneous parasitemias by antimalarial Therapy may facilitate the relative overgrowth of the remaining resistant parasites and therefore potentiate their pathogenicity [3]. A recent study in Tanzania documented increases in placental inflammation that were associated with SP receipt, suggesting that SP may potentiate placental pathology when applied to partially susceptible infections [4]. However, the effect of these placental findings upon birth outcomes was unclear. Given the prevalence of SP resistance and the current lack of appropriate, safe alternatives for use as IPTp, it is critical to explore the associations between IPTp-SP, SP resistance, and delivery outcomes in further contexts to inform malaria control policies. Malawi adopted a policy of IPTp with SP in 1993, and despite the subsequent development of widespread SP resistance [5], a sustained decline in the prevalence of PAM was observed from 1997 to 2005 [6]. In view of the evidence from Tanzania [4], we hypothesized that the emergence of SP-resistant parasites would modify the effect of IPTp-SP and thereby potentiate placental inflammation and parasite densities and worsen birth outcomes. The Queen Elizabeth Central Hospital Epidemiology of Resistance in Pregnancy-Associated Malaria (QuEERPAM) study [7] was a serial cross-sectional analysis in which we explored the relationships between IPTp-SP, the presence of resistant parasites at delivery, and multiple measures of adverse delivery outcome, including parasite densities, placental histology, maternal hemoglobin concentration, and birth weight.

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  • effect of plasmodium falciparum sulfadoxine pyrimethamine resistance on the effectiveness of Intermittent Preventive Therapy for malaria in pregnancy in africa a systematic review and meta analysis
    Lancet Infectious Diseases, 2019
    Co-Authors: Anna M Van Eijk, David A Larsen, Kassoum Kayentao, Gibby Koshy, Douglas E C Slaughter, Cally Roper, Lucy C Okell, Meghna Desai, Julie Gutman, Carole Khairallah
    Abstract:

    Summary Background Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of Intermittent Preventive treatment during pregnancy (IPTp) in sub-Saharan Africa. We aimed to assess the associations between markers of sulfadoxine-pyrimethamine resistance in P falciparum and the effectiveness of sulfadoxine-pyrimethamine IPTp for malaria-associated outcomes. Methods For this systematic review and meta-analysis, we searched databases (from Jan 1, 1990 to March 1, 2018) for clinical studies (aggregated data) or surveys (individual participant data) that reported data on low birthweight (primary outcome) and malaria by sulfadoxine-pyrimethamine IPTp dose, and for studies that reported on molecular markers of sulfadoxine-pyrimethamine resistance. Studies that involved only HIV-infected women or combined interventions were excluded. We did a random-effects meta-analysis (clinical studies) or multivariate log-binomial regression (surveys) to obtain summarised dose-response data (relative risk reduction [RRR]) and multivariate meta-regression to explore the modifying effects of sulfadoxine-pyrimethamine resistance (as indicated by Ala437Gly, Lys540Glu, and Ala581Gly substitutions in the dhps gene). This study is registered with PROSPERO, number 42016035540. Findings Of 1097 records screened, 57 studies were included in the aggregated-data meta-analysis (including 59 457 births). The RRR for low birthweight declined with increasing prevalence of dhps Lys540Glu (ptrend=0·0060) but not Ala437Gly (ptrend=0·35). The RRR was 7% (95% CI 0 to 13) in areas of high resistance to sulfadoxine-pyrimethamine (Lys540Glu ≥90% in east and southern Africa; n=11), 21% (14 to 29) in moderate-resistance areas (Ala437Gly ≥90% [central and west Africa], or Lys540Glu ≥30% to Interpretation The effectiveness of sulfadoxine-pyrimethamine IPTp is reduced in areas with high resistance to sulfadoxine-pyrimethamine among P falciparum parasites, but remains associated with reductions in low birthweight even in areas where dhps Lys540Glu prevalence exceeds 90% but where the sextuple-mutant parasite (harbouring the additional dhps Ala581Gly mutation) is uncommon. Therapeutic alternatives to sulfadoxine-pyrimethamine IPTp are needed in areas where the prevalence of the sextuple-mutant parasite exceeds 37%. Funding US Centers for Disease Control and Prevention, the Malaria in Pregnancy Consortium (funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine), Worldwide Antimalarial Resistance Network, European and Developing Countries Clinical Trials Partnership.

  • impact of sulfadoxine pyrimethamine resistance on effectiveness of Intermittent Preventive Therapy for malaria in pregnancy at clearing infections and preventing low birth weight
    Clinical Infectious Diseases, 2016
    Co-Authors: Kassoum Kayentao, Meghna Desai, Julie Gutman, Carole Khairallah, Steve M Taylor, Ryan E Wiegand, Peter Ouma
    Abstract:

    Background: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of Intermittent Preventive Therapy in pregnancy (IPTp) with SP is crucial. Methods: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus–uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. Results: Among 1222 parasitemic pregnant women, overall polymerase chain reaction–uncorrected and –corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69–.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67–.97; P = .02). Conclusions: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

  • drugs for preventing malaria in pregnant women in endemic areas any drug regimen versus placebo or no treatment
    Cochrane Database of Systematic Reviews, 2014
    Co-Authors: Denitsa Radevapetrova, Feiko O Ter Kuile, Kassoum Kayentao, David A Sinclair, Paul Garner
    Abstract:

    Background Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. Objectives To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of Intermittent Preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and Preventive regimens for Plasmodium vivax. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Selection criteria Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Data collection and analysis Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. Main results Seventeen trials enrolling 14,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine-dapsone (weekly or fortnightly), and mefloquine (weekly), or Intermittent Preventive Therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment. For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence), and two trials reported a reduction in febrile illness (low quality evidence). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality (very low quality evidence). For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence), and reduces placental parasitaemia by around 46% (RR 0.54, 95% CI 0.43 to 0.69; seven trials, 2830 participants, high quality evidence). Fewer trials evaluated spontaneous abortions, still births, perinatal deaths, or neonatal deaths, and these analyses were underpowered to detect clinically important differences. In multigravid women, chemoprevention has similar effects on antenatal parasitaemia (RR 0.38, 95% CI 0.28 to 0.50; three trials, 977 participants, high quality evidence)but there are too few trials to evaluate effects on other outcomes. In trials giving chemoprevention to all pregnant women irrespective of parity, the average effects of chemoprevention measured in all women indicated it may prevent severe anaemia (defined by authors, but at least < 8 g/L: RR 0.19, 95% CI 0.05 to 0.75; two trials, 1327 participants, low quality evidence), but consistent benefits have not been shown for other outcomes. In an analysis confined only to Intermittent Preventive Therapy with SP, the estimates of effect and the quality of the evidence were similar. A summary of a single trial in Thailand of prophylaxis against P. vivax showed chloroquine prevented vivax infection (RR 0.01, 95% CI 0.00 to 0.20; one trial, 942 participants). Authors' conclusions Routine chemoprevention to prevent malaria and its consequences has been extensively tested in RCTs, with clinically important benefits on anaemia and parasitaemia in the mother, and on birthweight in infants.

  • burden of malaria in pregnancy in mali and impact of dosing frequency and antimalarial drug resistance on the effectiveness of Intermittent Preventive Therapy in pregnancy in africa
    2014
    Co-Authors: Kassoum Kayentao
    Abstract:

    For many centuries, malaria has remained the most common parasitic disease in sub-Saharan Africa potentially placing 32 million pregnancies at risk each year. Malaria in pregnancy (MiP) in malaria endemic Africa is mostly asymptomatic or paucisymptomatic, yet associated with maternal anaemia and intra-uterine growth retardation resulting in low birth weight (LBW) which is an important risk factor for infant mortality (chapter 1). In Mali, several observational studies have determined the risk and consequences of malaria in pregnancy. However, national estimates of the burden of MiP and its potential impact are lacking. This thesis describes the results of a series of surveys conducted in different malaria transmission settings countrywide from 2005 to 2010, to quantify the burden and consequences of MiP in Mali (chapter 2). Results demonstrate that the risk of malaria infection at delivery was generally high ([average prevalence 11.6%]) and showed marked diversity between regions and transmission settings. Coverage of Intermittent Preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) and impregnated treated bednets (ITNs) was low (30.4% and 60.7%) and indicated important miss opportunities for the control of PAM. To prevent the disease and its consequences in pregnancy, the World Health Organization recommends IPTp using SP and use of an ITN. For IPTp, the recommended regimen consists of at least 2 doses of SP given during the second and third trimesters for HIV negative women and at least 3 doses for HIV-positive women not receiving cotrimoxazole. However, there are concerns that the 2-dose regimen, which provides at most 12 weeks of prophylaxis, leaves many women unprotected for as much as half of the 20-26 pregnancy weeks after quickening. Re-infection with the 2-dose regimen is common, especially during the transmission seasons and amongst women who complete their last dose early in the third trimester. A trial was therefore conducted to compare the standard 2-dose regimen versus 3 doses using SP, hypothesizing that the third dose may add significant benefit over the 2-dose regimen in preventing placental malaria and other birth outcomes (chapter 3). The study concluded that IPTp-SP with 3-doses was superior to the standard 2-dose regimen and resulted in better birth outcomes. The results of this trial were then combined with 6 similar trials as part of a meta-analysis assessing if 3 or more doses of IPTp-SP are more effective than the current standard 2-dose regimen. The pooled results suggested a marked benefit of adding extra SP doses over the standard 2-dose regimen in both regions of high and low SP resistance as measured by the prevalence of dihydropteroate synthase K540E mutations (chapter 4). Although studies from western Africa favour the use of IPTp-SP, SP resistance is now a serious threat to the longevity of IPTp with SP in parts of eastern and southern Africa where the quintuple dihydofolate reductase (N51I, C59L, S108N) /dhps (A437G, K540E) mutation is saturated in many places. In order to get a better understanding of the impact of SP resistance on IPTp effectiveness, this thesis also determined the in vivo response of parasites in asymptomatic parasitaemic pregnant women who received IPTp-SP and the effectiveness of IPTp-SP on birth parameters in West-Africa (chapter 5 & 6) Overall, the study concluded that SP resistance in Mali and Burkina Faso is low and that the IPT-SP is associated with clinically relevant improvements in birth outcomes in Mali.

  • Intermittent Preventive Therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine pyrimethamine and risk of low birth weight in africa systematic review and meta analysis
    JAMA, 2013
    Co-Authors: Kassoum Kayentao, Anna M Van Eijk, Cally Roper, Paul Garner, Inbarani Naidoo, Abdunoor Mulokozi, John R Macarthur, Mari Luntamo, Per Ashorn, Ogobara K Doumbo
    Abstract:

    Importance Intermittent Preventive Therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. Objective To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for Intermittent Preventive Therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) ( Data Sources and Study Selection ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of Intermittent Preventive Therapy during pregnancy with sulfadoxine-pyrimethamine monoTherapy. Data Extraction Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. Results Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722-3239 g) and on average 56 g higher (95% CI, 29-83 g; I2 = 0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR, 0.80; 95% CI, 0.69-0.94; I 2 = 0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10-52]; number needed to treat = 31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had less placental malaria (RR, 0.51; 95% CI, 0.38-0.68; I 2 = 0%, in 6 trials, 63 vs 32 per 1000; absolute risk reduction, 31 per 1000 [95% CI, 20-39]). In primigravid plus secundigravid women, the risk of moderate to severe maternal anemia was lower in the ≥3-dose group (RR, 0.60; 95% CI, 0.36-0.99; I2 = 20%; in 6 trials, 36 vs 22 per 1000; absolute risk reduction, 14 per 1000 [95% CI, 0.4-23]). There were no differences in rates of serious adverse events. Conclusions and Relevance Among pregnant women in sub-Saharan Africa, Intermittent Preventive Therapy with 3 or more doses of sulfadoxine-pyrimethamine was associated with a higher birth weight and lower risk of LBW than the standard 2-dose regimens. These data provide support for the new WHO recommendations to provide at least 3 doses of Intermittent Preventive Therapy during pregnancy at each scheduled antenatal care visit in the second and third trimester.