Perspectives on the design and methodology of periconceptional nutrient supplementation trials.

Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved, but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also because they generate subsidiary information on participants who remain non-pregnant. The methodological challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the periconceptional trial design--two of which are non-pregnant and two are pregnant--and this structure provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the initial decision for single or micronutrient intervention is central--as is the choice of dosage and content--in order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial

Traitement préventif intermittent à la sulfadoxine – pyriméthamine du paludisme chez les femmes enceintes: efficacité et observance dans deux hôpitaux urbains du Burkina Faso

Introduction: La présente étude prospective se propose dévaluer l’efficacité thérapeutique du traitement préventif intermittent à la sulfadoxine - pyriméthamine et son observance chez la femme enceinte dans deux hôpitaux urbains au Burkina Faso. Méthodes: Chaque femme répondant aux critères d’inclusion a été soumise à un questionnaire pour la collecte des données socio - démographiques et des renseignements sur la grossesse. A l’accouchement, une apposition placentaire a été réalisée systématiquement. La lecture a été faite au microscope à lobjectif 100 à immersion. Résultats: Au total, 542 femmes ont été incluses avec un âge moyen de 26,0 ± 6,45 ans (extrêmes 13- 43 ans). Le taux de couverture du TPI à la sulfadoxine- pyriméthamine a été de 80%. Le taux d’infestation placentaire a été de 4,7 %. Il a diminué avec le nombre de dose de traitement préventif intermittent. Il a augmenté cependant de juillet à octobre. De 42,9% en octobre, il a diminué significativement à 9,5% en novembre (p<0,05). Le taux global de bonne d'observance a été de 55%. Il a augmenté avec l'âge (p<0,05). Conclusion: Le taux de couverture de la sulfadoxine - pyriméthamine a été de 80%. Ce résultat est en conformité avec les objectifs du plan stratégique 2006-2010 de lutte contre le paludisme au Burkina Faso, qui préconisait un taux de couverture en sulfadoxine - pyriméthamine de 80% pour 2010. L’augmentation de la fréquence d’infestation de juillet à octobre, serait liée à la recrudescence de la transmission palustre pendant la saison des pluies (mai-octobre).Pan African Medical Journal 2013; 14: 10

Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data

From Springer Nature via Jisc Publications RouterHistory: received 2021-02-20, accepted 2021-09-16, registration 2021-09-21, pub-electronic 2021-09-27, online 2021-09-27, collection 2021-12Publication status: PublishedAbstract: Background: Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions. Methods: Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (< 0 mg/kg). Continuous outcomes were fitted to a mixed-effects linear model with month, age and pregnancy status as fixed effect covariates and woman as a random effect. Dichotomous infection outcomes were fitted with analogous logistic regression models. Results: Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P < 0.001), peaking at 81% in those who became pregnant. Seasonal variation occurred in antibiotic prescription rates (0.7–1.8 prescriptions/100 weekly visits, P < 0.001) and chorioamnionitis prevalence (range 15–68%, P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2–22 μg/ml, P < 0.016), when chorioamnionitis was least frequent. BIS fluctuated annually by up to 53.2% per year around the mean BIS (5.1 mg/kg2, range 4.1–6.8 mg/kg), with low BIS (< 0 mg/kg) of 8.7% in the dry and 9.8% in the wet seasons (P = 0.36). Median serum transferrin receptor increased during the wet season (P < 0.001). Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in BIS. Mean Body Mass Index and Mid-Upper-Arm-Circumference values peaked mid-dry season (both P < 0.001). Conclusions: Our analysis supports preventive treatment of malaria among adolescents 15–19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated

Assessment of the performance of malaria rapid diagnostic test in acutely malnourished children under five years of age in Nanoro - Burkina Faso

The interaction of malaria with malnutrition is complex. In areas where malnutrition among children is prevalent, management of malaria is not standardized. In Burkina Faso, malaria treatment is prescribed after positive malaria rapid diagnostic test (RDT) or thick blood smears confirmation regardless of the nutritional status of the child. The study aims to assess the performance of malaria RDT in acute malnourished children under five years of age. A descriptive cross-sectional study was carried out from June 1st to August 31th 2014 in the health district of Nanoro in Burkina Faso. The study involved the children less than 5 years of age who were admitted for acute malnutrition and tested for malaria using RDT. The diagnostic values were then assessed for their agreement with the gold standard of the World Health Organization (thick blood smears) using Cohen-Kappa coefficient. In total, RDT and thick blood smear results were obtained from 131 children (aged 1-59 months). RDT was positive in 87 tested children (66.4%), while the thick smear indicated that only 47 were infected by malaria (35.9%) and Cohen kappa coefficient was 0.44. The sensitivity, specificity, positive predictive value and negative predictive value of RDT for malaria compared to microscopy were respectively 100% (95% CI: 92.5 - 100), 52.4% (95% CI: 51.1 - 52.9), 54% (95% CI: 43 - 64.8), 100% (95% CI: 92.5 - 100). Their timeliness was 8 min (± 3.47 min). Using malaria RDT in acutely malnourished children results in high number of false positive

Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data.

BackgroundAdolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions.MethodsData collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (ResultsSeasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P 2, range 4.1-6.8 mg/kg), with low BIS (ConclusionsOur analysis supports preventive treatment of malaria among adolescents 15-19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated

Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence.

BACKGROUND: Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite susceptibility to ACT in Africa have now been well documented. Strategies that retain current ACT as efficacious treatments are urgently needed. METHODS: We present an open-label, randomised three-arm clinical trial protocol in three African settings representative of varying malaria epidemiology to investigate whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites. The protocol investigates whether a sequential course of two licensed ACT in 1080 children aged 6-120 months exhibits superior efficacy against acute P. falciparum malaria and non-inferior safety compared with standard single-course ACT given to 540 children. The primary endpoint is PCR-corrected clinical and parasitological response at day 42 or day 63 of follow-up. Persistence of PCR-detectable parasitaemia at day 3 is analysed as a key covariate. Secondary endpoints include gametocytaemia, occurrence of treatment-related adverse events in the double-ACT versus single-ACT arms, carriage of molecular markers of drug resistance, drug kinetics and patient adherence to treatment. DISCUSSION: This protocol addresses efficacy and safety of sequential ACT regimens in P. falciparum malaria in Africa. The approach is designed to extend the useful life of this class of antimalarials with maximal impact and minimal delay, by deploying licensed medicines that could be swiftly implemented as sequential double ACT by National Malaria Control Programmes, before emerging drug resistance in Africa becomes a major threat to public health

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

Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year