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In 2005, Burkina Faso changed its first-line treatment for uncomplicated malaria from chloroquine to artemisinin-based combination therapies (ACTs). Patient adherence to ACTs regimen is a keystone to achieve the expected therapeutic outcome and prevent the emergence and spread of parasite resistance. Eleven years after the introduction of ACTs in the health system, this study aimed to measure adherence level of patients in rural settlement and investigate the determinants of nonadherence., SCOPUS: ar.j, info:eu-repo/semantics/published

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.

Additional file 1: Supplemental Table 1. Agreement and reliability of fetal biometrics z scores using Intergrowth 21st and Salomon equations.

Adding community-based scheduled malaria screening and treatment to existing intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) strategies did not reduce malaria in pregnancy. Increasing the number of IPTp-SP doses given during pregnancy continues to be a priority., Background We investigated whether adding community scheduled malaria screening and treatment (CSST) with artemether-lumefantrine by community health workers (CHWs) to standard intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) would improve maternal and infant health. Methods In this 2-arm cluster-randomized, controlled trial, villages in Burkina Faso, The Gambia, and Benin were randomized to receive CSST plus IPTp-SP or IPTp-SP alone. CHWs in the intervention arm performed monthly CSST during pregnancy. At each contact, filter paper and blood slides were collected, and at delivery, a placental biopsy was collected. Primary and secondary endpoints were the prevalence of placental malaria, maternal anemia, maternal peripheral infection, low birth weight, antenatal clinic (ANC) attendance, and IPTp-SP coverage. Results Malaria infection was detected at least once for 3.8% women in The Gambia, 16.9% in Benin, and 31.6% in Burkina Faso. There was no difference between study arms in terms of placenta malaria after adjusting for birth season, parity, and IPTp-SP doses (adjusted odds ratio, 1.06 [95% confidence interval, .78–1.44]; P = .72). No difference between the study arms was found for peripheral maternal infection, anemia, and adverse pregnancy outcomes. ANC attendance was significantly higher in the intervention arm in Burkina Faso but not in The Gambia and Benin. Increasing number of IPTp-SP doses was associated with a significantly lower risk of placenta malaria, anemia at delivery, and low birth weight. Conclusions Adding CSST to existing IPTp-SP strategies did not reduce malaria in pregnancy. Increasing the number of IPTp-SP doses given during pregnancy is a priority. Clinical Trials Registration NCT01941264; ISRCTN37259296.

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, 0.55-0.99]; 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.

Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women, resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver enzyme levels (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development, especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008)

Background: Diagnosis of malaria in pregnancy is problematic due to the low sensitivity of conventional diagnostic tests (rapid diagnostic test and microscopy), which is exacerbated due to low peripheral parasite densities, and lack of clinical symptoms. In this study, six potential biomarkers to support malaria diagnosis in pregnancy were evaluated.Methods: Blood samples were collected from pregnant women at antenatal clinic visits and at delivery. Microscopy and real-time PCR were performed for malaria diagnosis and biomarker analyses were performed by ELISA (interleukin 10, IL-10; tumor necrosis factor-α, TNF-α; soluble tumor necrosis factor receptor II, sTNF-RII; soluble fms-like tyrosine kinase 1, sFlt-1; leptin and apolipoprotein B, Apo-B). A placental biopsy was collected at delivery to determine placental malaria.Results: IL-10 and sTNF-RII were significantly higher at all time-points in malaria-infected women (p p p = 0.003 for IL-10 and sTNF-RII respectively). IL-10 levels at delivery, but not during pregnancy, were negatively associated with birth weight. A prediction model was created using IL-10 and sTNF-RII cut-off points. For primigravidae the model had a sensitivity of 88.9% (95%CI 45.7–98.7%) and specificity of 83.3% (95% CI 57.1–94.9%) for diagnosing malaria during pregnancy. For secundi- and multigravidae the sensitivity (81.8% and 56.5% respectively) was lower, while specificity (100.0% and 94.3% respectively) was relatively high. Sub-microscopic infections were detected in 2 out of 3 secundi- and 5 out of 12 multigravidae.Conclusions: The combination of biomarkers IL-10 and sTNF-RII have the potential to support malaria diagnosis in pregnancy. Additional markers may be needed to increase sensitivity and specificity, this is of particular importance in populations with sub-microscopic infections or in whom other inflammatory diseases are prevalent.

One of the current strategies to prevent malaria in pregnancy is intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). However, in order for pregnant women to receive an adequate number of SP doses, they should attend a health facility on a regular basis. In addition, SP resistance may decrease IPTp-SP efficacy. New or additional interventions for preventing malaria during pregnancy are therefore warranted. Because it is known that community health workers (CHWs) can diagnose and treat malaria in children, in this study screening and treatment of malaria in pregnancy by CHWs was evaluated as an addition to the regular IPTp-SP program. CHWs used rapid diagnostic tests (RDTs) for screening and artemether-lumefantrine was given in case of a positive RDT. Overall, CHWs were able to conduct RDTs with a sensitivity of 81.5% (95% confidence interval [CI] 67.9-90.2) and high specificity of 92.1% (95% CI 89.9-93.9) compared with microscopy. After a positive RDT, 79.1% of women received artemether-lumefantrine. When treatment was not given, this was largely due to the woman being already under treatment. Almost all treated women finished the full course of artemether-lumefantrine (96.4%). In conclusion, CHWs are capable of performing RDTs with high specificity and acceptable sensitivity, the latter being dependent on the limit of detection of RDTs. Furthermore, CHWs showed excellent adherence to test results and treatment guidelines, suggesting they can be deployed for screen and treat approaches of malaria in pregnancy.

Background: Adolescence is associated with adverse fetal outcome, particularly in resources limited settings. We assessed the association between mother’s age and low birth weight or prematurity in Nanoro, a rural health district of Burkina Faso. Methods: We collected data on mothers and their newborns in the framework of the “Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women with Malaria” clinical trial. Low birth weight or prematurity was defined as adverse fetal outcome. Logistic regression was used to compare its occurrence in teenagers and in women aged ≥ 20 years. Results: From June 2010 to November 2013, 870 pregnant women enrolled in the PREGACT study were treated for a Plasmodium falciparum infection and followed up until delivery. Of the 823 women with singleton live-borns, 205 (24.9%) were teenagers of whom 44 (5.3%) were minors (15-17 years). Up to 91.7% of adolescents presented with anemia at entry. The incidence of adverse fetal outcome in teenagers was 39.8%, increasing to 50.0% in minors. Anemic adolescents were significantly at higher risk of delivering low birth weight or preterm babies compared to their older counterparts. In multivariate analysis, teenagers with both anemia and fever presented the highest and significant odds ratios of adverse fetal outcome, whatever was their BMI: Teenagers with anemia, fever and high BMI at entry, AOR=3.46, 95% CI: (1.40, 8.58), teenagers with anemia, fever and low BMI at entry, AOR=2.86, 95% CI: (1.14, 7.13). Conclusion: Teenager’s pregnancy is associated with adverse fetal outcome in the rural health district of Nanoro, mainly when teenagers experiment anemia and fever. In low resources setting, multidisciplinary approach including education and setting up favorable socio-economic environment are needed to prevent early motherhood.

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.

Background: Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy (IPTp-SP) is widely implemented to prevent these negative effects of malaria. However, resistance against SP by P. falciparum may decrease efficacy of IPTp-SP. Combinations of point mutations in the dhps (codons A437, K540) and dhfr genes (codons N51, C59, S108) of P. falciparum are associated with SP resistance. In this study the prevalence of SP resistance mutations was determined among P. falciparum found in pregnant women and the general population (GP) from Nanoro, Burkina Faso and the association of IPTp-SP dosing and other variables with mutations was studied.Methods: Blood spots on filter papers were collected from pregnant women at their first antenatal care visit (ANC booking) and at delivery, from an ongoing trial and from the GP in a cross-sectional survey. The dhps and dhfr genes were amplified by nested PCR and products were sequenced to identify mutations conferring resistance (ANC booking, n = 400; delivery, n = 223; GP, n = 400). Prevalence was estimated with generalized estimating equations and for multivariate analyses mixed effects logistic regression was used.Results: The prevalence of the triple dhfr mutation was high, and significantly higher in the GP and at delivery than at ANC booking, but it did not affect birth weight. Furthermore, quintuple mutations (triple dhfr and double dhps mutations) were found for the first time in Burkina Faso. IPTp-SP did not significantly affect the occurrence of any of the mutations, but high transmission season was associated with increased mutation prevalence in delivery samples. It is unclear why the prevalence of mutations was higher in the GP than in pregnant women at ANC booking.Conclusion: The high number of mutants and the presence of quintuple mutants in Burkina Faso confirm concerns about the efficacy of IPTp-SP in the near future. Other drug combinations to tackle malaria in pregnancy should, therefore, be explored. An increase in mutation prevalence due to IPTp-SP dosing could not be confirmed.

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

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

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

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To evaluate persistence of several Plasmodium antigens in pregnant women after treatment and compare diagnostics during treatment follow-up.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.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) (P0.05), 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 (P0.05).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.

Additional file 1: Table S1. Genotypic-based association analysis for malaria infection using co-dominant models.

Additional file 2: Table S2. Genotypic-based association analysis for clinical malaria using co-dominant models.

Additional file 2: Table S2. Genotypic-based association analysis for clinical malaria using co-dominant models.