Fetal biometry assessment with Intergrowth 21st's and Salomon's equations in rural Burkina Faso.

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

Age-modified factors associated with placental malaria in rural Burkina Faso.

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

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life

Background: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. Methods: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. Results: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/ 8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. Conclusions: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of lif

Additional Screening and Treatment of Malaria During Pregnancy Provides Further Protection Against Malaria and Nonmalarial Fevers During the First Year of Life.

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

Research Article (New England Journal of Medicine) Four artemisinin-based treatments in African pregnant women with malaria

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.

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life

Spectrophotometric determination of antiplasmodial cochloxanthins from roots of Cochlospermum planchonii Hook.f. (Bixaceae)

The roots and leaves of Cochlospermum planchonii and C. tinctorium are widely used in Burkina Faso as medication for malaria treatment. The cochloxanthins, carotenoids, are - at least partially - responsible for the antimalarial activity of Cochlospermum spp.. Because of large variation of cochloxanthin contents in rhizomes and leaves of Cochlospermum spp., the available products are not always reliable. The gold standard method for the quantification of cochloxanthins is HPLC. However, HPLC is expensive, time consuming, and needs experienced personnel. Therefore, for quick analysis of Cochlospermum roots in local pharmacies and companies, we developed a spectrophotometric method that is inexpensive, fast, simple and robust. In our study, we produced ethanolic extracts of market samples of roots of Cochlospermum sp. from Burkina Faso and analysed them in parallel by HPLC and spectrophotometry. The two methods correlated well with an R2  > 0.95 (P < 0.001). However, spectrophotometry overestimated the samples by 10% compared to HPLC analyses. For the spectrophotometric method, the coefficients of variation inter day and intra days were 9% and 12.8%, respectively with a limit of detection (LOD) of 0.65 µg/g. A parallel test of the spectrophotometric assay in a 96 well microplate format showed a good correlation (R2 = 0.96) with conventional spectrophotometry. Variation of sample volumes in the wells did not influence the results, but extreme values were not correctly measured in the microplate reader. The new spectrophotometric method is well suitable for the analysis of cochloxanthins in Cochlospermum spp. roots; however, due to interfering absorbance, plant material containing chlorophyll cannot be analysed. Keywords: Carotenoids, Cochlospermum planchonii, Cochlospermum tinctorium, Cochloxanthins, HPLC, Spectrophotometr

Prevalence and factors associated with carriage of Pfmdr1 polymorphisms among pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and artemether-lumefantrine for malaria treatment in Burkina Faso.

Single nucleotide polymorphisms occurring in the Plasmodium falciparum multidrug resistant gene 1 (pfmdr1) are known to be associated with aminoquinoline resistance and, therefore, represent key P. falciparum markers for monitoring resistance both in susceptible groups (children under 5 years old and pregnant women) and in the general population. This study aimed to determine prevalence and factors associated with the carriage of pfmdr1 N86Y, Y184F and D1246Y polymorphisms among pregnant women in a setting of high malaria transmission in Burkina Faso.info:eu-repo/semantics/publishe

Presence of quintuple dhfr N51, C59, S108-dhps A437, K540 mutations in Plasmodium falciparum isolates from pregnant women and the general population in Nanoro, Burkina Faso

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 warrante

Plants against Malaria and Mosquitoes in Sahel region of Burkina Faso: An Ethno-botanical survey

International audienceArtemisinin-based Combination Therapy is recommended for the treatment of malaria in Burkina Faso but, most people in this country prefer to use herbal medicine because of its low cost and high availability. The aim of the study was to identify plants used by traditional healers from Sahel region of Burkina Faso in the prevention and the treatment of malaria. An ethno-botanical survey was carried out among traditional healers in the Sahel region of Burkina Faso. Questionnaires were administrated to people willing to participate in the survey and the plants used for prevention and treatment of malaria were recorded. A total of 80 traditional healers were interviewed. Forty two plants were identified as being commonly used in the treatment of malaria and 16 in repelling mosquitoes. The use of plants in the treatment and protection against malaria is widespread in the Sahel region of Burkina Faso