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Article ; Online: Intestinal barrier disruption with Plasmodium falciparum infection in pregnancy and risk of preterm birth: a cohort study.

Wright, Julie K / Weckman, Andrea M / Ngai, Michelle / Stefanova, Veselina / Zhong, Kathleen / McDonald, Chloe R / Elphinstone, Robyn E / Conroy, Andrea L / Coburn, Bryan A / Madanitsa, Mwayi / Taylor, Steve M / Ter Kuile, Feiko O / Kain, Kevin C

EBioMedicine

2023 Volume 97, Page(s) 104808

Abstract: Background: Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and ... ...

Abstract	Background: Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and whether this contributes to systemic inflammation, altered angiogenesis, and preterm birth. Methods: We quantified plasma concentrations of gut leak markers, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) from 1339 HIV-negative pregnant Malawians at <24 weeks gestational age. We assessed the relationship of sCD14 and LBP concentrations with markers of inflammation, angiogenesis, and L-arginine bioavailability and compared them between participants with and without malaria, and with and without preterm birth. Findings: Plasma concentrations of sCD14 and LBP were significantly higher in participants with malaria and were associated with parasite burden (p <0.0001, both analyses and analytes). The odds ratio for preterm birth associated with one log sCD14 was 2.67 (1.33 to 5.35, p = 0.006) and 1.63 (1.07-2.47, p = 0.023) for LBP. Both gut leak analytes were positively associated with increases in proinflammatory cytokines CRP, sTNFR2, IL18-BP, CHI3L1 and Angptl3 (p <0.05, all analytes) and sCD14 was significantly associated with angiogenic proteins Angpt-2, sENG and the sFLT:PlGF ratio (p <0.05, all analytes). sCD14 was negatively associated with L-arginine bioavailability (p <0.001). Interpretation: Malaria in early pregnancy is associated with intestinal barrier dysfunction, which is linked to an increased risk of preterm birth. Funding: Open Philanthropy, Canadian Institutes of Health Research, Canada Research Chair program, European and Developing Countries Clinical Trials Partnership, Bill & Melinda Gates Foundation.
MeSH term(s)	Pregnancy ; Female ; Humans ; Infant, Newborn ; Premature Birth/etiology ; Plasmodium falciparum ; Cohort Studies ; Lipopolysaccharide Receptors ; Canada/epidemiology ; Malaria, Falciparum/complications ; Malaria, Falciparum/epidemiology ; Inflammation/complications ; Malaria/complications ; Arginine ; Biomarkers
Chemical Substances	Lipopolysaccharide Receptors ; Arginine (94ZLA3W45F) ; Biomarkers
Language	English
Publishing date	2023-10-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104808
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Article ; Online: Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis.

Unger, Holger W / Hadiprodjo, Anastasia Jessica / Gutman, Julie R / Briand, Valerie / Fievet, Nadine / Valea, Innocent / Tinto, Halidou / D'Alessandro, Umberto / Landis, Sarah H / Ter Kuile, Feiko / Ouma, Peter / Oneko, Martina / Mwapasa, Victor / Slutsker, Laurence / Terlouw, Dianne J / Kariuki, Simon / Ayisi, John / Nahlen, Bernard / Desai, Meghna /

Madanitsa, Mwayi / Kalilani-Phiri, Linda / Ashorn, Per / Maleta, Kenneth / Tshefu-Kitoto, Antoinette / Mueller, Ivo / Stanisic, Danielle / Cates, Jordan / Van Eijk, Anna Maria / Ome-Kaius, Maria / Aitken, Elizabeth H / Rogerson, Stephen J

Scientific reports

2023 Volume 13, Issue 1, Page(s) 10310

Abstract: In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, ... ...

Abstract	In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.
MeSH term(s)	Infant, Newborn ; Female ; Pregnancy ; Humans ; Plasmodium falciparum ; Placenta ; Malaria/epidemiology ; Malaria/complications ; Infant, Low Birth Weight ; Stillbirth ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/complications
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-37431-3
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Article ; Online: Provider and user acceptability of intermittent screening and treatment for the control of malaria in pregnancy in Malawi.

Almond, Deborah / Madanitsa, Mwayi / Mwapasa, Victor / Kalilani-Phiri, Linda / Webster, Jayne / Ter Kuile, Feiko / Paintain, Lucy

Malaria journal

2016 Volume 15, Issue 1, Page(s) 574

Abstract: Background: Malaria in pregnancy is a major cause of adverse maternal and fetal outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is one of the control strategies promoted by WHO. In response to mounting resistance to ... ...

Abstract	Background: Malaria in pregnancy is a major cause of adverse maternal and fetal outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is one of the control strategies promoted by WHO. In response to mounting resistance to SP, intermittent screening and treatment (ISTp) has been proposed as an alternative. The objective of this study was to explore the acceptability of ISTp for health workers and pregnant women. Methods: Semi-structured interviews of ten health workers and five focus group discussions of 38 women enrolled in an ongoing trial comparing IPTp-SP and ISTp with dihydroartemisinin-piperaquine (DP) were conducted at two antenatal clinics in rural Malawi. All transcripts were coded and themes were identified using a content analysis approach. Results: Amongst health workers, there were contrasting opinions on the preference of blood sampling methods, and the influence of method on reliability of diagnosis. The perceived greater effectiveness of DP compared to SP was appreciated, however concerns of user compliance with the full dose of DP in non-trial settings were raised. Despite the discomfort of repeated finger pricks, pregnant women were generally accepting of ISTp, particularly the chance for regular blood tests to check for infections and the perceived greater effectiveness with fewer side effects of DP compared to SP. Conclusion: In the trial context, pregnant women tended to prefer ISTp-DP over IPTp-SP. Health workers were also accepting of ISTp-DP as an alternative to IPTp-SP in light of increasing SP resistance. However, reliability of stock, adherence to malaria test results and user adherence to the full course of DP may present barriers to successful routine implementation. Effective communication with health workers and between health workers, pregnant women and their communities will be essential for the acceptability of focused antenatal care, including the best malaria control measures available.
MeSH term(s)	Adolescent ; Adult ; Antimalarials/therapeutic use ; Female ; Health Personnel ; Humans ; Infant, Newborn ; Interviews as Topic ; Malaria/diagnosis ; Malaria/drug therapy ; Malawi ; Mass Screening/methods ; Patient Acceptance of Health Care ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis ; Pregnancy Complications, Infectious/drug therapy ; Pregnant Women ; Young Adult
Chemical Substances	Antimalarials
Language	English
Publishing date	2016-11-28
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Observational Study
ISSN	1475-2875
ISSN (online)	1475-2875
DOI	10.1186/s12936-016-1627-5
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Article ; Online: Modelling the incremental benefit of introducing malaria screening strategies to antenatal care in Africa.

Nature communications

2020 Volume 11, Issue 1, Page(s) 3799

Abstract: Plasmodium falciparum in pregnancy is a major cause of adverse pregnancy outcomes. We combine performance estimates of standard rapid diagnostic tests (RDT) from trials of intermittent screening and treatment in pregnancy (ISTp) with modelling to assess ... ...

Abstract	Plasmodium falciparum in pregnancy is a major cause of adverse pregnancy outcomes. We combine performance estimates of standard rapid diagnostic tests (RDT) from trials of intermittent screening and treatment in pregnancy (ISTp) with modelling to assess whether screening at antenatal visits improves upon current intermittent preventative therapy with sulphadoxine-pyrimethamine (IPTp-SP). We estimate that RDTs in primigravidae at first antenatal visit are substantially more sensitive than in non-pregnant adults (OR = 17.2, 95% Cr.I. 13.8-21.6), and that sensitivity declines in subsequent visits and with gravidity, likely driven by declining susceptibility to placental infection. Monthly ISTp with standard RDTs, even with highly effective drugs, is not superior to monthly IPTp-SP. However, a hybrid strategy, recently adopted in Tanzania, combining testing and treatment at first visit with IPTp-SP may offer benefit, especially in areas with high-grade SP resistance. Screening and treatment in the first trimester, when IPTp-SP is contraindicated, could substantially improve pregnancy outcomes.
MeSH term(s)	Antimalarials/therapeutic use ; Drug Combinations ; Female ; Health Policy ; Humans ; Malaria, Falciparum/diagnosis ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/prevention & control ; Mass Screening/methods ; Parasitic Sensitivity Tests ; Plasmodium falciparum/drug effects ; Pregnancy ; Pregnancy Complications, Parasitic/drug therapy ; Pregnancy Complications, Parasitic/prevention & control ; Pregnancy Trimester, First ; Prenatal Care/methods ; Pyrimethamine/therapeutic use ; Sulfadoxine/therapeutic use ; Tanzania ; World Health Organization
Chemical Substances	Antimalarials ; Drug Combinations ; fanasil, pyrimethamine drug combination (37338-39-9) ; Sulfadoxine (88463U4SM5) ; Pyrimethamine (Z3614QOX8W)
Language	English
Publishing date	2020-07-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-17528-3
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Article ; Online: Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data.

Fernandes, Silke / Sicuri, Elisa / Kayentao, Kassoum / van Eijk, Anne Maria / Hill, Jenny / Webster, Jayne / Were, Vincent / Akazili, James / Madanitsa, Mwayi / ter Kuile, Feiko O / Hanson, Kara

The Lancet. Global health

2015 Volume 3, Issue 3, Page(s) e143–53

Abstract: Background: In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of ...

Abstract	Background: In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2). Methods: For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted. Findings: The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67 producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7·7 per DALY averted for moderate risk of low birthweight, $19·4 per DALY averted for low risk, and $4·0 per DALY averted for high risk. The ICER for HIV-negative women was $6·2 per DALY averted. Interpretation: Our findings lend strong support to the WHO guidelines that recommend a monthly dose of IPTp-SP from the second trimester onwards. Funding: Malaria in Pregnancy Consortium and the Bill & Melinda Gates Foundation.
MeSH term(s)	Africa South of the Sahara ; Anemia/prevention & control ; Antimalarials/administration & dosage ; Antimalarials/economics ; Antimalarials/therapeutic use ; Cost-Benefit Analysis ; Drug Combinations ; Female ; Humans ; Infant, Low Birth Weight ; Malaria/complications ; Malaria/economics ; Malaria/prevention & control ; Pregnancy ; Pregnancy Complications, Parasitic/economics ; Pregnancy Complications, Parasitic/prevention & control ; Pyrimethamine/administration & dosage ; Pyrimethamine/economics ; Pyrimethamine/therapeutic use ; Quality-Adjusted Life Years ; Sulfadoxine/administration & dosage ; Sulfadoxine/economics ; Sulfadoxine/therapeutic use
Chemical Substances	Antimalarials ; Drug Combinations ; fanasil, pyrimethamine drug combination (37338-39-9) ; Sulfadoxine (88463U4SM5) ; Pyrimethamine (Z3614QOX8W)
Language	English
Publishing date	2015-03
Publishing country	England
Document type	Comparative Study ; Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	2723488-5
ISSN	2214-109X ; 2214-109X
ISSN (online)	2214-109X
ISSN	2214-109X
DOI	10.1016/S2214-109X(14)70385-7
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Article ; Online: The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women.

Gutman, Julie / Kalilani, Linda / Taylor, Steve / Zhou, Zhiyong / Wiegand, Ryan E / Thwai, Kyaw L / Mwandama, Dyson / Khairallah, Carole / Madanitsa, Mwayi / Chaluluka, Ebbie / Dzinjalamala, Fraction / Ali, Doreen / Mathanga, Don P / Skarbinski, Jacek / Shi, Ya Ping / Meshnick, Steve / ter Kuile, Feiko O

The Journal of infectious diseases

2015 Volume 211, Issue 12, Page(s) 1997–2005

Abstract: Background: The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called ... ...

Abstract	Background: The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy. Methods: Between 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant. Results: Samples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: . Conclusions: IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.
MeSH term(s)	DNA, Protozoan/chemistry ; DNA, Protozoan/genetics ; Dihydropteroate Synthase/genetics ; Drug Combinations ; Drug Resistance ; Female ; Genotype ; Humans ; Infant, Newborn ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/prevention & control ; Malawi ; Mutation, Missense ; Plasmodium falciparum/enzymology ; Plasmodium falciparum/genetics ; Plasmodium falciparum/isolation & purification ; Point Mutation ; Polymerase Chain Reaction ; Pregnancy ; Pyrimethamine/pharmacology ; Pyrimethamine/therapeutic use ; Sequence Analysis, DNA ; Sulfadoxine/pharmacology ; Sulfadoxine/therapeutic use ; Tetrahydrofolate Dehydrogenase/genetics ; Treatment Outcome
Chemical Substances	DNA, Protozoan ; Drug Combinations ; fanasil, pyrimethamine drug combination (37338-39-9) ; Sulfadoxine (88463U4SM5) ; Tetrahydrofolate Dehydrogenase (EC 1.5.1.3) ; Dihydropteroate Synthase (EC 2.5.1.15) ; Pyrimethamine (Z3614QOX8W)
Language	English
Publishing date	2015-01-06
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiu836
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Article ; Online: Gestational age assessment in malaria pregnancy cohorts: a prospective ultrasound demonstration project in Malawi.

Wylie, Blair J / Kalilani-Phiri, Linda / Madanitsa, Mwayi / Membe, Gladys / Nyirenda, Osward / Mawindo, Patricia / Kuyenda, Redson / Malenga, Albert / Masonbrink, Abbey / Makanani, Bonus / Thesing, Phillip / Laufer, Miriam K

Malaria journal

2013 Volume 12, Page(s) 183

Abstract: Background: Malaria during pregnancy is associated with an increased risk for low birth weight (<2500 grams). Distinguishing infants that are born premature (< 37 weeks) from those that are growth-restricted (less than the 10th percentile at birth) ... ...

Abstract	Background: Malaria during pregnancy is associated with an increased risk for low birth weight (<2500 grams). Distinguishing infants that are born premature (< 37 weeks) from those that are growth-restricted (less than the 10th percentile at birth) requires accurate assessment of gestational age. Where ultrasound is accessible, sonographic confirmation of gestational age is more accurate than menstrual dating. The goal was to pilot the feasibility and utility of adding ultrasound to an observational pregnancy malaria cohort. Methods: In July 2009, research staff (three mid-level clinical providers, one nurse) from The Blantyre Malaria Project underwent an intensive one-week ultrasound training to perform foetal biometry. Following an additional four months of practice and remote image review, subjects from an ongoing cohort were recruited for ultrasound to determine gestational age. Gestational age at delivery established by ultrasound was compared with postnatal gestational age assessment (Ballard examination). Results: One hundred and seventy-eight women were enrolled. The majority of images were of good quality (94.3%, 509/540) although a learning curve was apparent with 17.5% (24/135) images of unacceptable quality in the first 25% of scans. Ultrasound was used to date 13% of the pregnancies when menstrual dates were unknown and changed the estimated gestational age for an additional 25%. There was poor agreement between the gestational age at delivery as established by the ultrasound protocol compared to that determined by the Ballard examination (bias 0.8 weeks, limits of agreement -3.5 weeks to 5.1 weeks). The distribution of gestational ages by Ballard suggested a clustering of gestational age around the mean with 87% of the values falling between 39 and 41 weeks. The distribution of gestational age by ultrasound confirmed menstrual dates was more typical. Using ultrasound confirmed dates as the gold standard, 78.5% of preterm infants were misclassified as term and 26.8% of small-for gestational age infants misclassified as appropriately grown by Ballard. Conclusion: Ultrasound should be strongly considered in prospective malaria studies with obstetric endpoints to confirm gestational age and avoid misclassification of infants as premature or growth-restricted. The use of ultrasound does require a significant investment of time to maintain quality image acquisition.
MeSH term(s)	Anthropometry/methods ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Malaria/pathology ; Malawi ; Pregnancy ; Pregnancy Complications/pathology ; Prospective Studies ; Ultrasonography/methods
Language	English
Publishing date	2013-06-04
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1475-2875
ISSN (online)	1475-2875
DOI	10.1186/1475-2875-12-183
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Article ; Online: Timing of malaria infection during pregnancy has characteristic maternal, infant and placental outcomes.

Kalilani-Phiri, Linda / Thesing, Phillip C / Nyirenda, Osward M / Mawindo, Patricia / Madanitsa, Mwayi / Membe, Gladys / Wylie, Blair / Masonbrink, Abbey / Makwakwa, Kingsley / Kamiza, Steve / Muehlenbachs, Atis / Taylor, Terrie E / Laufer, Miriam K

PloS one

2013 Volume 8, Issue 9, Page(s) e74643

Abstract: We conducted a clinical study of pregnant women in Blantyre, Malawi to determine the effect of the timing of malaria infection during pregnancy on maternal, infant and placental outcomes. Women were enrolled in their first or second trimester of their ... ...

Abstract	We conducted a clinical study of pregnant women in Blantyre, Malawi to determine the effect of the timing of malaria infection during pregnancy on maternal, infant and placental outcomes. Women were enrolled in their first or second trimester of their first or second pregnancy and followed every four weeks until delivery. Three doses of sulfadoxine-pyrimethamine were given for intermittent preventive treatment for malaria, and all episodes of parasitemia were treated according to the national guidelines. Placentas were collected at delivery and examined for malaria parasites and pigment by histology. Pregnant women had 0.6 episodes of malaria per person year of follow up. Almost all episodes of malaria were detected at enrollment and malaria infection during the follow up period was rare. Malaria and anemia at the first antenatal visit were independently associated with an increased risk of placental malaria detected at delivery. When all episodes of malaria were treated with effective antimalarial medication, only peripheral malaria infection at the time of delivery was associated with adverse maternal and infant outcomes. One quarter of the analyzed placentas had evidence of malaria infection. Placental histology was 78% sensitive and 89% specific for peripheral malaria infection during pregnancy. This study suggests that in this setting of high antifolate drug resistance, three doses of sulfadoxine-pyrimethamine maintain some efficacy in suppressing microscopically detectable parasitemia, although placental infection remains frequent. Even in this urban setting, a large proportion of women have malaria infection at the time of their first antenatal care visit. Interventions to control malaria early and aggressive case detection are required to limit the detrimental effects of pregnancy-associated malaria.
MeSH term(s)	Cost of Illness ; Female ; Humans ; Infant ; Malaria/complications ; Malaria/parasitology ; Malaria/pathology ; Malawi ; Placenta/parasitology ; Placenta/pathology ; Pregnancy ; Pregnancy Complications, Parasitic/pathology ; Pregnancy Outcome ; Risk Factors ; Time Factors ; Young Adult
Language	English
Publishing date	2013-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0074643
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Article ; Online: Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa.

Taylor, Steve M / Antonia, Alejandro L / Harrington, Whitney E / Goheen, Morgan M / Mwapasa, Victor / Chaluluka, Ebbie / Fried, Michal / Kabyemela, Edward / Madanitsa, Mwayi / Khairallah, Carole / Kalilani-Phiri, Linda / Tshefu, Antoinette K / Rogerson, Stephen J / Ter Kuile, Feiko O / Duffy, Patrick E / Meshnick, Steven R

Emerging infectious diseases

2014 Volume 20, Issue 7, Page(s) 1140–1148

Abstract: Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive ... ...

Abstract	Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance.
MeSH term(s)	Africa, Eastern ; Antimalarials/therapeutic use ; Cross-Sectional Studies ; Dihydropteroate Synthase/genetics ; Drug Resistance/genetics ; Female ; Haplotypes/genetics ; Humans ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Malawi ; Microsatellite Repeats/genetics ; Mutation/genetics ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/genetics ; Pregnancy ; Sulfadoxine/therapeutic use
Chemical Substances	Antimalarials ; Sulfadoxine (88463U4SM5) ; Dihydropteroate Synthase (EC 2.5.1.15)
Language	English
Publishing date	2014-06-19
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Intramural
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2007.131720
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Article ; Online: Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific.

Unger, Holger W / Cates, Jordan E / Gutman, Julie / Briand, Valerie / Fievet, Nadine / Valea, Innocent / Tinto, Halidou / d'Alessandro, Umberto / Landis, Sarah H / Adu-Afarwuah, Seth / Dewey, Kathryn G / Ter Kuile, Feiko / Dellicour, Stephanie / Ouma, Peter / Slutsker, Laurence / Terlouw, Dianne J / Kariuki, Simon / Ayisi, John / Nahlen, Bernard /

Desai, Meghna / Madanitsa, Mwayi / Kalilani-Phiri, Linda / Ashorn, Per / Maleta, Kenneth / Mueller, Ivo / Stanisic, Danielle / Schmiegelow, Christentze / Lusingu, John / Westreich, Daniel / van Eijk, Anna Maria / Meshnick, Steven / Rogerson, Stephen

BMJ open

2016 Volume 6, Issue 12, Page(s) e012697

Abstract: Purpose: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and ... ...

Abstract	Purpose: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. Participants: Data were pooled on 14 635 singleton, live birth pregnancies from women who had participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015. Findings to date: Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort. Future plans: This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria-nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective.
MeSH term(s)	Adult ; Africa ; Cohort Studies ; Datasets as Topic ; Female ; Fetal Development ; Gestational Age ; Humans ; Infant, Newborn ; Malaria/complications ; Male ; Malnutrition/complications ; Nutritional Status ; Papua New Guinea ; Pregnancy ; Pregnancy Complications ; Prenatal Care
Language	English
Publishing date	2016-12-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2016-012697
Database	MEDical Literature Analysis and Retrieval System OnLINE

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