A Qualitative Study of the Experience of COVID-19 Patients in Burkina Faso.

In Burkina Faso, the health system is characterized by systemic insufficient and antiquated health-care infrastructures. Consequently, few health-care establishments have the required resources to diagnose and manage patients with COVID-19, and fewer still have intensive care facilities for severely ill patients with COVID. Furthermore, there is a widespread scarcity of qualified health-care staff. The aim of this study was to explore the experiences of patients with COVID-19 who recovered after being cared for in Bobo Dioulasso and Ouagadougou. Using individual semistructured interviews, we performed a cross-sectional qualitative, descriptive study from June 12 to 30, 2020 with the aid of 13 well-educated patients who had survived COVID-19. The results reveal that prior to hospital admission, the main reason that prompted patients to seek care was onset of symptoms of COVID-19, regardless of whether they had been in contact with suspected or confirmed cases. Transmission was mainly believed to have occurred in the community, in the hospital, and during travel. Patient management was punctuated by frequent self-medication with medicinal plants or pharmaceutical drugs. The participants reported a negative perception of hospitalization or home-based management, with several forms of stigmatization, but a positive perception influenced by the satisfactory quality of management in health-care centers. This report of patient experiences could be helpful in improving the management of COVID-19 in Burkina Faso, both in the health-care setting and in home-based care.

Enhanced effect of seasonal malaria chemoprevention when coupled with nutrients supplementation for preventing malaria in children under 5 years old in Burkina Faso: a randomized open label trial.

BACKGROUND: In rural African settings, most of the children under the coverage of Seasonal Malaria Chemoprevention (SMC) are also undernourished at the time of SMC delivery, justifying the need for packaging malarial and nutritional interventions. This study aimed at assessing the impact of SMC by coupling the intervention with nutrients supplementation for preventing malaria in children less than 5 years old in Burkina Faso. METHODS: A randomized trial was carried out between July 2020 and June 2021 in the health district of Nanoro, Burkina Faso. Children (n = 1059) under SMC coverage were randomly assigned to one of the three study arms SMC + Vitamin A (SMC-A, n = 353) or SMC + Vitamin A + Zinc (SMC-AZc, n = 353) or SMC + Vitamin A + PlumpyDoz(tm) (SMC-APd, n = 353)-a medium quantity-lipid-based nutrient supplement (MQ-LNS). Children were followed up for one year that included an active follow-up period of 6 months with scheduled monthly home visits followed by 6 months passive follow-up. At each visit, capillary blood sample was collected for malaria diagnosis by rapid diagnosis test (RDT). RESULTS: Adding nutritional supplements to SMC had an effect on the incidence of malaria. A reduction of 23% (adjusted IRR = 0.77 (95%CI 0.61-0.97) in the odds of having uncomplicated malaria in SMC-APd arm but not with SMC-AZc arm adjusted IRR = 0.82 (95%CI 0.65-1.04) compare to control arm was observed. A reduction of 52%, adjusted IRR = 0.48 (95%CI 0.23-0.98) in the odds of having severe malaria was observed in SMC-APd arm compared to control arm. Besides the effect on malaria, this combined strategy had an effect on all-cause morbidity. More specifically, a reduction of morbidity odds of 24%, adjusted IRR = 0.76 (95%CI 0.60-0.94) in SMC-APd arm compared to control arm was observed. Unlike clinical episodes, no effect of nutrient supplementation on cross sectional asymptomatic infections was observed. CONCLUSION: Adding nutritional supplements to SMC significantly increases the impact of this intervention for preventing children from malaria and other childhood infections. TRIAL REGISTRATION: NCT04238845.

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.

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 a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy'Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT).

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.

Risk of malaria in young children after periconceptional iron supplementation.

This study in Burkina Faso investigated whether offspring of young mothers who had received weekly periconceptional iron supplementation in a randomised controlled trial were at increased risk of malaria. A child safety survey was undertaken in the peak month of malaria transmission towards the end of the trial to assess child iron biomarkers, nutritional status, anaemia and malaria outcomes. Antenatal iron biomarkers, preterm birth, fetal growth restriction and placental pathology for malaria and chorioamnionitis were assessed. Data were available for 180 babies surviving to the time of the survey when their median age was 9 months. Prevalence of maternal iron deficiency in the last trimester based on low body iron stores was 16%. Prevalence of active placental malaria infection was 24.8%, past infection 59% and chorioamnionitis 55.6%. Babies of iron supplemented women had lower median gestational age. Four out of five children ≥ 6 months were iron deficient, and 98% were anaemic. At 4 months malaria prevalence was 45%. Child iron biomarkers, anaemia and malaria outcomes did not differ by trial arm. Factors associated with childhood parasitaemia were third trimester C-reactive protein level (OR 2.1; 95% CI 1.1-3.9), active placental malaria (OR 5.8; 1.0-32.5, P = 0.042) and child body iron stores (OR 1.13; 1.04-1.23, P = 0.002). Chorioamnionitis was associated with reduced risk of child parasitaemia (OR 0.4; 0.1-1.0, P = 0.038). Periconceptional iron supplementation of young women did not alter body iron stores of their children. Higher child body iron stores and placental malaria increased risk of childhood parasitaemia.

Iron Status of Burkinabé Adolescent Girls Predicts Malaria Risk in the Following Rainy Season.

High levels of storage iron may increase malaria susceptibility. This risk has not been investigated in semi-immune adolescents. We investigated whether baseline iron status of non-pregnant adolescent girls living in a high malaria transmission area in Burkina Faso affected malaria risk during the following rainy season. For this prospective study, we analysed data from an interim safety survey, conducted six months into a randomised iron supplementation trial. We used logistic regression to model the risk of P. falciparum infection prevalence by microscopy, the pre-specified interim safety outcome, in relation to iron status, nutritional indicators and menarche assessed at recruitment. The interim survey was attended by 1223 (82%) of 1486 eligible participants, 1084 (89%) of whom were <20 years at baseline and 242 (22%) were pre-menarcheal. At baseline, prevalence of low body iron stores was 10%. At follow-up, 38% of adolescents had predominantly asymptomatic malaria parasitaemias, with no difference by menarcheal status. Higher body iron stores at baseline predicted an increased malaria risk in the following rainy season (OR 1.18 (95% CI 1.05, 1.34, p = 0.007) after adjusting for bed net use, age, menarche, and body mass index. We conclude that routine iron supplementation should not be recommended without prior effective malaria control.

Effect of adding azithromycin to the antimalarials used for seasonal malaria chemoprevention on the nutritional status of African children.

OBJECTIVES: Mass administration of azithromycin has reduced mortality in children in sub-Saharan Africa but its mode of action is not well characterised. A recent trial found that azithromycin given alongside seasonal malaria chemoprevention was not associated with a reduction in mortality or hospital admissions in young children. We investigated the effect of azithromycin on the nutritional status of children enrolled in this study. METHODS: A total of 19 578 children in Burkina Faso and Mali were randomised to receive either azithromycin or placebo alongside seasonal malaria chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine monthly for three malaria transmission seasons (2014-2016). After each transmission season, anthropometric measurements were collected from approximately 4000 randomly selected children (2000 per country) at a cross-sectional survey and used to derive nutritional status indicators. Binary and continuous outcomes between treatment arms were compared by Poisson and linear regression. RESULTS: Nutritional status among children was poor in both countries with evidence of acute and chronic malnutrition (24.9-33.3% stunted, 15.8-32.0% underweight, 7.2-26.4% wasted). There was a suggestion of improvement in nutritional status in Burkina Faso and deterioration in Mali over the study period. At the end of each malaria transmission season, nutritional status of children did not differ between treatment arms (seasonal malaria chemoprevention plus azithromycin or placebo) in either the intention-to-treat or per-protocol analyses (only children with at least three cycles of SMC in the current intervention year). CONCLUSIONS: The addition of azithromycin to seasonal malaria chemoprevention did not result in an improvement of nutritional outcomes in children in Burkina Faso and Mali.

OBJECTIFS: L'administration massive d'azithromycine a réduit la mortalité infantile en Afrique subsaharienne mais son mode d'action n'est pas bien caractérisé. Un essai récent a révélé que l'azithromycine administrée parallèlement à la chimioprévention du paludisme saisonnier n'était pas associée à une réduction de la mortalité ou des hospitalisations chez les jeunes enfants. Nous avons étudié l'effet de l'azithromycine sur l'état nutritionnel des enfants inscrits à cette étude. MÉTHODES: 19.578 enfants au Burkina Faso et au Mali ont été randomisés pour recevoir soit de l'azithromycine soit un placebo parallèlement à une chimioprévention du paludisme saisonnier avec du sulfadoxine-pyriméthamine plus de l'amodiaquine par mois pendant trois saisons de transmission du paludisme (2014-2016). Après chaque saison de transmission, des mesures anthropométriques ont été recueillies auprès d'environ 4.000 enfants sélectionnés au hasard (2.000 par pays) lors d'une enquête transversale et utilisées pour dériver des indicateurs de l'état nutritionnel. Les résultats binaires et continus entre les bras de traitement ont été comparés par la régression linéaire et de Poisson. RÉSULTATS: L'état nutritionnel des enfants était médiocre dans les deux pays avec des signes de malnutrition aiguë et chronique (24,9 à 33,3% de retard de croissance, 15,8 à 32,0% d'insuffisance pondérale, 7,2 à 26,4% d'émaciation). Il a été suggéré une amélioration de l'état nutritionnel au Burkina Faso et une détérioration au Mali au cours de la période d'étude. A la fin de chaque saison de transmission du paludisme, l'état nutritionnel des enfants ne différait pas entre les bras de traitement (chimioprévention contre le paludisme saisonnier plus azithromycine ou placebo) dans les analyses en intention de traiter ou selon le protocole (seulement les enfants avec au moins trois cycles de chimioprévention dans l'année d'intervention en cours). CONCLUSIONS: L'ajout d'azithromycine à la chimioprévention du paludisme saisonnier n'a pas entraîné d'amélioration des résultats nutritionnels chez les enfants au Burkina Faso et au Mali.

Malaria early in the first pregnancy: Potential impact of iron status.

BACKGROUND & AIMS: Low iron stores may protect from malaria infection, therefore improving iron stores in early pregnancy in line with current recommendations could increase malaria susceptibility. To test this hypothesis we compared iron biomarkers and red cell indices in nulliparae and primigravidae who participated in a randomized controlled trial of long-term weekly iron supplementation. METHODS: Cross-sectional and longitudinal data analysis from a randomized controlled trial of long-term weekly iron supplementation in rural Burkina Faso. Malaria parasitaemia was monitored and biomarkers and red cell indices measured at study end-points: plasma ferritin, transferrin receptor (sTfR), zinc protoporphyrin, hepcidin, sTfR/log10 ferritin ratio, body iron, haemoglobin, red cell distribution width; mean corpuscular haemoglobin concentration/volume, and C-reactive protein. Correlation coefficients between biomarkers and red cell indices were determined. A regression correction approach based on ferritin was used to estimate iron body stores, allowing for inflammation. Body iron differences were compared between nulliparae and primigravidae, and the association determined of iron biomarkers and body iron stores with malaria. RESULTS: Iron and haematological indices of 972 nulliparae (mean age 16.5 years) and 314 primigravidae (median gestation 18 weeks) were available. Malaria prevalence was 54.0% in primigravidae and 41.8% in nulliparae (relative risk 1.28, 95% CI 1.13-1.45, P < 0.001), anaemia prevalence 69.7% and 43.4% (P < 0.001), and iron deficient erythropoiesis (low body iron) 8.0% and 11.7% (P = 0.088) respectively. Unlike other biomarkers the sTfR/log10 ferritin ratio showed no correlation with inflammation as measured by CRP. Most biomarkers indicated reduced iron deficiency in early pregnancy, with the exception of haemoglobin. Body iron increased by 0.6-1.2 mg/kg in early gestation, did not differ by malaria status in nulliparae, but was higher in primigravidae with malaria (6.5 mg/kg versus 5.0 mg/kg; relative risk 1.53, 95% CI 0.67-2.38, P < 0.001). CONCLUSION: In primigravidae, early pregnancy haemoglobin was not a good indicator of requirement for iron supplementation, which could be detrimental given the association of better iron status with increased malaria infection. TRIAL REGISTRATION: clinicaltrials.gov:NCT01210040. Until placed in a public repository, data relating to the current study can be requested from the corresponding author and will be made available following an end user data agreement and sponsor approval.

Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area.

BACKGROUND: In view of recent evidence from a randomized trial in Burkina Faso that periconceptional iron supplementation substantially increases risk of spontaneous preterm birth (< 37 weeks) in first pregnancies (adjusted relative risk = 2.22; 95% CI 1.39-3.61), explanation is required to understand potential mechanisms, including progesterone mediated responses, linking long-term iron supplementation, malaria and gestational age. METHODS: The analysis developed a model based on a dual hit inflammatory mechanism arising from simultaneous malaria and gut infections, supported in part by published trial results. This model is developed to understand mechanisms linking iron supplementation, malaria and gestational age. Background literature substantiates synergistic inflammatory effects of these infections where trial data is unavailable. A path modelling exercise assessed direct and indirect paths influencing preterm birth and gestation length. RESULTS: A dual hit hypothesis incorporates two main pathways for pro-inflammatory mechanisms, which in this model, interact to increase hepcidin expression. Trial data showed preterm birth was positively associated with C-reactive protein (P = 0.0038) an inflammatory biomarker. The malaria pathway upregulates C-reactive protein and serum hepcidin, thereby reducing iron absorption. The enteric pathway results from unabsorbed gut iron, which induces microbiome changes and pathogenic gut infections, initiating pro-inflammatory events with lipopolysaccharide expression. Data from the trial suggest that raised hepcidin concentration is a mediating catalyst, being inversely associated with shorter gestational age at delivery (P = 0.002) and positively with preterm incidence (P = 0.007). A segmented regression model identified a change-point consisting of two segments before and after a sharp rise in hepcidin concentration. This showed a post change hepcidin elevation in women with increasing C-reactive protein values in late gestation (post-change slope 0.55. 95% CI 0.39-0.92, P < 0.001). Path modelling confirmed seasonal malaria effects on preterm birth, with mediation through C-reactive protein and (non-linear) hepcidin induction. CONCLUSIONS: Following long-term iron supplementation, dual inflammatory pathways that mediate hepcidin expression and culminate in progesterone withdrawal may account for the reduction in gestational age observed in first pregnancies in this area of high malaria exposure. If correct, this model strongly suggests that in such areas, effective infection control is required prior to iron supplementation to avoid increasing preterm births. Trial registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.

Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso.

BACKGROUND: Iron supplementation before a first pregnancy may improve the future health of mother and baby by reducing maternal anaemia. Iron supplementation could, however, increase malaria infections, notably in primigravidae who are most susceptible. The pathogenicity of other iron-utilizing pathogens could also increase, causing inflammation leading to increased risk of adverse birth outcomes. This paper reports pre-specified secondary birth outcomes from a safety trial in Burkina Faso in an area of high malaria endemicity. Primary outcomes from that trial had investigated effects of long-term weekly iron supplementation on malaria and genital tract infections in non-pregnant and pregnant women. METHODS: A double-blind, randomized controlled trial. Nulliparous, mainly adolescent women, were individually randomized periconceptionally to receive weekly either 60 mg elemental iron and 2.8 mg folic acid, or 2.8 mg folic acid alone, continuing up to the first antenatal visit for those becoming pregnant. Secondary outcomes were ultrasound-dated gestational age, fetal growth, placental malaria, chorioamnionitis and iron biomarkers. Seasonal effects were assessed. Analysis was by intention to treat. RESULTS: 478 pregnancies occurred to 1959 women: 258/980 women assigned iron and folic acid and 220/979 women assigned folic acid alone. Malaria prevalence at the first antenatal visit was 53% (iron) and 55% (controls). Mean birthweight was 111 g lower in the iron group (95% CI 9:213 g, P = 0.033). Mean gestational ages were 264 days (iron) and 269 days (controls) (P = 0.012), with 27.5% under 37 weeks compared to 13.9% in controls (adjRR = 2.22; 95% CI 1.39-3.61) P < 0.001). One-third of babies were growth restricted, but incidence did not differ by trial arm. Half of placentae had evidence of past malaria infection. C-reactive protein > 5 mg/l was more common prior to births < 37 weeks (adjRR = 2.06, 95% CI 1.04-4.10, P = 0.034). Preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001). Chorioamnionitis prevalence peaked in the dry season (P = 0.046), with no difference by trial arm (P = 0.14). CONCLUSION: Long-term weekly iron supplementation given to nulliparous women in a malaria endemic area was associated with higher risk of preterm birth in their first pregnancy. Trial Registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.

In Vivo Antiplasmodial Activity of Two Sahelian Plant Extracts on Plasmodium berghei ANKA Infected NMRI Mice.

Up to now, the control of malaria remains a challenge. The World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs) for uncomplicated malaria treatment. Despite this guideline, many people in Burkina Faso use herbal medicine as primary treatment against malaria. The aim of this study was to assess the in vivo activity of Guiera senegalensis J. F. Gmel and Bauhinia rufescens Lam. leaves extracts against Plasmodium berghei ANKA. A four-day treatment of leaves decoction of each plant was administrated orally to 7 groups of six NMRI (Naval Medical Research Institute) mice infected with Plasmodium berghei ANKA strain. The control group received distilled water as treatment while the treated groups each received daily 100, 250, and 500 mg extract/kg body weight. Thin blood smears were performed on day five and the percentage of reduction of parasitaemia was determined compared to the control. The percentages of reduction of the parasitaemia at the doses of 100, 250, and 500 mg extract/kg body weight were, respectively, 57.5%, 35.9%, and 44.9% for Guiera senegalensis and 50.6%, 22.2%, and 25.7% for Bauhinia rufescens. Our findings on antiplasmodial activity of these two plants justify the traditional use by local populations against malaria. Thus, the isolation of the active compounds from these two plants is suggested for possible antimalarial candidate drugs.

Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial.

Background: The safety of iron supplementation for young women is uncertain in malaria-endemic settings. Methods: This was a double-blind, randomized controlled noninferiority trial in rural Burkina Faso. Results: A total of 1959 nulliparae were assigned to weekly supplementation (60 mg iron and 2.8 mg folic acid) (n = 980) or 2.8 mg folic acid (n = 979) until first antenatal visit (ANC1), or 18 months if remaining nonpregnant. Three hundred fifteen women attended ANC1, and 916 remained nonpregnant. There was no difference at ANC1 in parasitemia prevalence (iron, 53.4% [95% confidence interval {CI}, 45.7%-61.0%]; control, 55.3% [95% CI, 47.3%-62.9%]; prevalence ratio, 0.97 [95% CI, .79-1.18]; P = .82), anemia (adjusted effect, 0.96 [95% CI, .83-1.10]; P = .52), iron deficiency (adjusted risk ratio [aRR], 0.84 [95% CI, .46-1.54]; P = .58), or plasma iron biomarkers. Outcomes in nonpregnant women were parasitemia (iron, 42.9% [95% CI, 38.3%-47.5%]; control, 39.2% [95% CI, 34.9%-43.7%]; prevalence ratio, 1.09 [95% CI, .93-1.28]; P = .282); anemia (aRR, 0.90 [95% CI, .78-1.05]; P = .17), and iron deficiency (aRR, 0.99 [95% CI, .77-1.28]; P = .96), with no iron biomarker differences. Conclusions: Weekly iron supplementation did not increase malaria risk, improve iron status, or reduce anemia in young, mostly adolescent menstruating women, nor in early pregnancy. World Health Organization Guidelines for universal supplementation for young nulliparous women may need reassessment. Clinical Trials Registration: NCT01210040.

Community approval required for periconceptional adolescent adherence to weekly iron and/or folic acid supplementation: a qualitative study in rural Burkina Faso.

BACKGROUND: Iron deficiency remains a prevalent adolescent health problem in low income countries. Iron supplementation is recommended but improvement of iron status requires good adherence. OBJECTIVES: We explored factors affecting adolescent adherence to weekly iron and/or folic acid supplements in a setting of low secondary school attendance. METHODS: Taped in-depth interviews were conducted with participants in a randomised, controlled, periconceptional iron supplementation trial for young nulliparous women living in a rural, malaria endemic region of Burkina Faso. Participants with good, medium or poor adherence were selected. Interviews were transcribed and analysed thematically. RESULTS: Thirty-nine interviews were conducted. The community initially thought supplements were contraceptives. The potential benefits of giving iron supplementation to unmarried "girls" ahead of pregnancy were not recognised. Trial participation, which required parental consent, remained high but was not openly admitted because iron supplements were thought to be contraceptives. Unmarried non-school attenders, being mobile, were often sent to provide domestic labour in varied locations. This interrupted adherence - as did movement of school girls during vacations and at marriage. Field workers tracked participants and trial provision of free treatment encouraged adherence. Most interviewees did not identify health benefits from taking supplements. CONCLUSIONS: For success, communities must be convinced of the value of an adolescent intervention. During this safety trial, benefits not routinely available in iron supplementation programmes were important to this low income community, ensuring adolescent participation. Nevertheless, adolescents were obliged to fulfil cultural duties and roles that interfered with regular adherence to the iron supplementation regime. TRIAL REGISTRATION: Trial Registration at clinicaltrials.gov : NCT01210040.

Effects of long-term weekly iron and folic acid supplementation on lower genital tract infection - a double blind, randomised controlled trial in Burkina Faso.

BACKGROUND: Provision of routine iron supplements to prevent anaemia could increase the risk for lower genital tract infections as virulence of some pathogens depends on iron availability. This trial in Burkina Faso assessed whether weekly periconceptional iron supplementation increased the risk of lower genital tract infection in young non-pregnant and pregnant women. METHODS: Genital tract infections were assessed within a double blind, controlled, non-inferiority trial of malaria risk among nulliparous women, randomised to receive either iron and folic acid or folic acid alone, weekly, under direct observation for 18 months. Women conceiving during this period entered the pregnancy cohort. End assessment (FIN) for women remaining non-pregnant was at 18 months. For the pregnancy cohort, end assessment was at the first scheduled antenatal visit (ANC1). Infection markers included Nugent scores for abnormal flora and bacterial vaginosis (BV), T. vaginalis PCR, vaginal microbiota, reported signs and symptoms, and antibiotic and anti-fungal prescriptions. Iron biomarkers were assessed at baseline, FIN and ANC1. Analysis compared outcomes by intention to treat and in iron replete/deficient categories. RESULTS: A total of 1954 women (mean 16.8 years) were followed and 478 (24.5%) became pregnant. Median supplement adherence was 79% (IQR 59-90%). Baseline BV prevalence was 12.3%. At FIN and ANC1 prevalence was 12.8% and 7.0%, respectively (P < 0.011). T. vaginalis prevalence was 4.9% at FIN and 12.9% at ANC1 (P < 0.001). BV and T. vaginalis prevalence and microbiota profiles did not differ at trial end-points. Iron-supplemented non-pregnant women received more antibiotic treatments for non-genital infections (P = 0.014; mainly gastrointestinal infections (P = 0.005), anti-fungal treatments for genital infections (P = 0.014) and analgesics (P = 0.008). Weekly iron did not significantly reduce iron deficiency prevalence. At baseline, iron-deficient women were more likely to have normal vaginal flora (P = 0.016). CONCLUSIONS: Periconceptional weekly iron supplementation of young women did not increase the risk of lower genital tract infections but did increase general morbidity in the non-pregnant cohort. Unabsorbed gut iron due to malaria could induce enteric infections, accounting for the increased administration of antibiotics and antifungals in the iron-supplemented arm. This finding reinforces concerns about routine iron supplementation in highly malarious areas. TRIAL REGISTRATION: Trial registration number NCT01210040 . Registered with Clinicaltrials.gov on 27 September 2010.

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.

Antiplasmodial compounds from Cochlospermum tinctorium.

Fractionation of an ethanol extract of roots of Cochlospermum tinctorium afforded five compounds: 3-O-E-p-coumaroylalphitolic acid (1), cochloxanthin (2), dihydrocochloxanthin (3), alphitolic acid (4), and 1-hydroxytetradecan-3-one (5). This is the first example of a 1-hydroxyalkan-3-one obtained from plant material after gentle workup. The antiplasmodial activities of the compounds were determined, and the IC(50) value of 3-O-E-p-coumaroylalphitolic acid was 2.3 microM.