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Background: Malaria in pregnancy can result in placental infection with fetal implications. This study aimed at assessing placental malaria (PM) prevalence and its associated factors in a cohort of pregnant women with peripheral malaria and their offspring., Method: The data were collected in the framework of a clinical trial on treatments for malaria in pregnant women . Placental malaria (PM) was diagnosed by histopathological detection of parasites and/or malaria pigment on placenta biopsies taken at delivery. Factors associated with PM were assessed using logistic regression., Results: Out of 745 biopsies examined, PM was diagnosed in 86.8 % of women. Acute, chronic and past PM were retrieved in 11 (1.5 %), 170 (22.8 %), and 466 (62.6 %) women, respectively. A modifying effect was observed in the association of gravidity or anemia at the study start with pooled PM (presence of parasites and/or malaria pigment). In women under 30, gravidity ≤ 2 was associated with an increased prevalence of pooled PM but in women aged 30 years or more, gravidity was no more associated with pooled PM (OR 6.81, 95 % CI 3.18 - 14.60; and OR 0.52, 95 % CI 0.10 - 2.76, respectively). Anemia was associated with pooled PM in women under 30 (OR 1.96, 95 % CI 1.03 - 3.72) but not in women aged 30 years or more (OR 0.68, 95 % CI 0.31 - 1.49). Similarly, the association of gravidity with past-chronic PM depended also on age. A higher prevalence of active PM was observed in women under 30 presenting with symptomatic malaria (OR 3.79, 95 % CI 1.55 - 9.27), while there was no significant increase in the prevalence of active PM (presence of parasites only) in women with symptomatic malaria when aged 30 years or more (OR 0.42, 95 % CI 0.10 - 1.75). In women with chronic PM, the prevalence of low birth weight or prematurity was the highest (31.2 %) as compared with past PM or no PM., Conclusion: Despite the rapid diagnosis and efficacious treatment of peripheral infection, the prevalence of placental malaria remained high in women with P. falciparum peripheral infection in Nanoro, especially in younger women This underlines the importance of preventive measures in this specific group., (© 2022. The Author(s).)

Background: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage., Methods: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps., Discussion: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels., Trial Registration: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845.

Background: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso., Methods: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex)., Results: Genetic variants in IL-1β (rs1143634) and FcγRIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells., Conclusions: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.

Background: Ultrasound scanning during the 2nd or the 3rd trimester of pregnancy for fetal size disturbances screening is heavily dependent of the choice of the reference chart. This study aimed to assess the agreement of Salomon and the Intergrowth 21st equations in evaluating fetal biometric measurements in a rural area of Burkina Faso, and to measure the effect of changing a reference chart., Methods: Data collected in Nazoanga, Burkina Faso, between October 2010 and October 2012, during a clinical trial evaluating the safety and efficacy of several antimalarial treatments in pregnant women were analyzed. We included singleton pregnancies at 16-36 weeks gestation as determined by ultrasound measurements of fetal bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). Expected mean and standard deviation at a given gestational age was computed using equations from Salomon references and using Intergrowth 21st standard. Then, z-scores were calculated and used subsequently to compare Salomon references with Intergrowth 21st standards., Results: The analysis included 276 singleton pregnancies. Agreement was poor except for HC: mean difference - 0.01, limits of agreement - 0.60 and 0.59. When AC was used as a surrogate of fetal size, switching from the reference of Salomon to the standards of Intergrowth 21st increased ten times the proportion of fetuses above the 90th percentile: 2.9 and 31.2%, respectively. Mean differences were larger in the third trimester than in the second trimester. However, agreement remained good for HC in both trimesters. Difference in the proportion of AC measurements above the 90th percentile using Salomon and Intergrowth 21st equations was greater in the second trimester (2.6 and 36.3%, respectively) than in the third trimester (3.5 and 19.8%, respectively). The greatest difference between the two charts was observed in the number of FL measurements classified as large in the second trimester (6.8 and 54.2%, using Salomon and Intergrowth 21st equations, respectively)., Conclusion: The agreement between Intergrowth 21st and Salomon equations is poor apart from HC. This would imply different clinical decision regarding the management of the pregnancy.

Background: Although consensus exists that malaria in pregnancy (MiP) increases the risk of malaria in infancy, and eventually nonmalarial fevers (NMFs), there is a lack of conclusive evidence of benefits of MiP preventive strategies in infants., Methods: In Burkina Faso, a birth cohort study was nested to a clinical trial assessing the effectiveness of a community-based scheduled screening and treatment of malaria in combination with intermittent preventive treatment with sulfadoxine-pyrimethamine (CSST/IPTp-SP) to prevent placental malaria. Clinical episodes and asymptomatic infections were monitored over 1 year of follow-up to compare the effect of CSST/IPTp-SP and standard IPTp-SP on malaria and NMFs., Results: Infants born during low-transmission season from mothers receiving CSST/IPTp-SP had a 26% decreased risk of experiencing a first clinical episode (hazard ratio, 0.74 [95% confidence interval, .55-0.99]; P = .047). CSST/IPTp-SP interacted with birth season and gravidity to reduce the incidence of NMFs. No significant effects of CSST/IPTp-SP on the incidence of clinical episodes, parasite density, and Plasmodium falciparum infections were observed., Conclusions: Our findings indicate that CSST/IPTp-SP strategy may provide additional protection against both malaria and NMFs in infants during the first year of life, and suggest that malaria control interventions during pregnancy could have long-term benefits in infants.

Sulphadoxine-pyrimethamine (SP) is only used for intermittent preventive treatment during pregnancy (IPTp) in most Sub-Saharan African countries. However, there are concerns about the efficacy of IPTp-SP because of increasing resistance. Combinations of point mutations in the dhps and dhfr genes of Plasmodium falciparum are associated with SP resistance, in particular the quintuple dhfr (N51, C59, S108) - dhps (codons A437, K540) mutant. In Nanoro, Burkina Faso, filter paper samples from pregnant women at first antenatal care visit and at delivery plus samples from the general population (GP) were studied for dhfr and dhps mutations by sequencing. Quintuple mutants were present in 2 delivery and 4 GP samples. This is the first time the quintuple mutation is found in Burkina Faso and although the prevalence is still very low, emergence of the quintuple mutation could highly diminish the efficacy of IPTp-SP. Close surveillance of SP resistance mutations is therefore warranted., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa., Methods: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chain-reaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes., Results: The PCR-adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin-piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-adjusted cure rates in the intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin-piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine-artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups)., Conclusions: Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest posttreatment prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.).

Rapid diagnostics tests (RDTs) detect malaria specific antigen(s) in the circulation, even when parasites are sequestered in the placenta and not visible by microscopy. However, research on their diagnostic accuracy during pregnancy is limited. Pregnant women (n = 418) were screened for malaria during routine antenatal care by using two RDTs that detect histidine-rich protein 2 (HRP2) or Plasmodium lactate dehydrogenase, and enzyme-linked immunosorbent assays with antibodies that detect dihydrofolate reductase-thymidylate synthase or heme-detoxification protein, and compared with real-time polymerase chain reaction (RT-PCR) and microscopy for evaluation of their diagnostic accuracy. Prevalence of malaria infection was high (53% by PCR). The RT-PCR and the HRP2 RDT detected most cases of malaria during pregnancy, whereas microscopy, the Plasmodium lactate dehydrogenase RDT, and enzyme-linked immunosorbent assays for dihydrofolate reductase-thymidylate synthase and heme-detoxification protein antibodies did not detect several low-density infections. Therefore, the HRP2 RDT could be a useful tool in high-transmission areas for diagnosis of malaria in asymptomatic pregnant women.

Objectives: To evaluate persistence of several Plasmodium antigens in pregnant women after treatment and compare diagnostics during treatment follow-up., Methods: Thirty-two pregnant women (N = 32) with confirmed malaria infection by a histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) and microscopy were followed for 28 days after artemisinin-based combination therapy (ACT). A Plasmodium lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on the detection of dihydrofolate reductase-thymidylate synthase (DHFR-TS) and haeme detoxification protein (HDP) were compared with each other and to RT-PCR at each visit., Results: The mean visit number (95% confidence interval) on which the HRP2-based RDT was still positive after treatment was 3.4 (2.7-4.1) visits with some patients still positive at day 28. This is significantly later than the pLDH-based RDT [0.84 (0.55-1.1)], microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7 (1.1-2.3)] and RT-PCR (median 2, range 1-5) (P < 0.05), but not significantly later than HDP-ELISA [2.1 (1.6-2.7)]. Lower gravidity and higher parasite density at day 0 resulted in significantly longer positive results with most tests (P < 0.05)., Conclusions: HRP2 can persist up to 28 days after ACT treatment; therefore, this test is not suitable for treatment follow-up in pregnant women and can generate problems when using this test during intermittent preventive treatment (IPTp). DHFR-TS is less persistent than HRP2, making it a potentially interesting target for diagnosis., (© 2012 Blackwell Publishing Ltd.)

A bioactivity guided fractionation of roots of Canthium multiflorum led to the isolation of the new ursenoic acid derivative 19alpha-hydroxy-3-oxo-ursa-1,12-dien-28-oic acid (1), which showed antiplasmodial effect without inducing change of the shape of membranes of erythrocytes.