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.

Molecular epidemiology of respiratory syncytial virus in children in sub-Saharan Africa.

OBJECTIVES: This study investigated the molecular epidemiology of respiratory syncytial virus (RSV) among febrile children with acute respiratory tract infection in Ghana, Gabon, Tanzania and Burkina Faso between 2014 and 2017 as well as the evolution and diversification of RSV strains from other sub-Saharan countries. METHODS: Pharyngeal swabs were collected at four study sites (Agogo, Ghana: n = 490; Lambaréné, Gabon: n = 182; Mbeya, Tanzania: n = 293; Nouna, Burkina Faso: n = 115) and analysed for RSV and other respiratory viruses using rtPCR. For RSV-positive samples, sequence analysis of the second hypervariable region of the G gene was performed. A dataset of RSV strains from sub-Saharan Africa (2011-2017) currently available in GenBank was compiled. Phylogenetic analysis was conducted to identify the diversity of circulating RSV genotypes. RESULTS: In total, 46 samples were tested RSV positive (Ghana n = 31 (6.3%), Gabon n = 4 (2.2%), Tanzania n = 9 (3.1%) and Burkina Faso n = 2 (1.7%)). The most common RSV co-infection was with rhinovirus. All RSV A strains clustered with genotype ON1 strains with a 72-nucleotide duplication and all RSV B strains belonged to genotype BAIX. Phylogenetic analysis of amino acid sequences from sub-Saharan Africa revealed the diversification into 11 different ON1 and 22 different BAIX lineages and differentiation of ON1 and BAIX strains into potential new sub-genotypes, provisionally named ON1-NGR, BAIX-KEN1, BAIX-KEN2 and BAIX-KEN3. CONCLUSION: The study contributes to an improved understanding of the molecular epidemiology of RSV infection in sub-Saharan Africa. It provides the first phylogenetic data for RSV from Tanzania, Gabon and Burkina Faso and combines it with RSV strains from all other sub-Saharan countries currently available in GenBank.

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.

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.

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.

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.

Influence of iron status on risk of maternal or neonatal infection and on neonatal mortality with an emphasis on developing countries.

Infection is a major cause of neonatal death in developing countries. This review investigates whether host iron status affects the risk of maternal and/or neonatal infection, potentially contributing to neonatal death, and summarizes the iron acquisition mechanisms described for pathogens causing stillbirth, preterm birth, and congenital infection. In vitro evidence shows that iron availability influences the severity and chronicity of infections that cause these negative outcomes of pregnancy. In vivo evidence is lacking, as relevant studies of maternal iron supplementation have not assessed the effect of iron status on the risk of maternal and/or neonatal infection. Reducing iron-deficiency anemia among women is beneficial and should improve the iron stores of babies; moreover, there is evidence that iron status in young children predicts the risk of malaria and, possibly, the risk of invasive bacterial diseases. Caution with maternal iron supplementation is indicated in iron-replete women who may be at high risk of exposure to infection, although distinguishing between iron-replete and iron-deficient women is currently difficult in developing countries, where a point-of-care test is needed. Further research is indicated to investigate the risk of infection relative to iron status in mothers and babies in order to avoid iron intervention strategies that may result in detrimental birth outcomes in some groups of women.

Bottlenecks for high coverage of intermittent preventive treatment in pregnancy: the case of adolescent pregnancies in rural Burkina Faso.

BACKGROUND: While IPTp-SP is currently being scaled up in sub-Saharan Africa (SSA), the coverage with the required>or=2 doses of SP remains considerably short of the Roll Back Malaria (RBM) goal of 80%, not to mention of the recently advocated universal coverage. METHODS: The study triangulates quantitative data from a health center randomized community-based trial on IPTp-SP effectiveness and the additional benefit of a promotional campaign with qualitative data from focused ethnography. FINDINGS: In rural Burkina Faso, despite the significantly higher risk of malaria infection among adolescent primigravidae (PG) (OR 2.44 95%CI 1.81-3.28, p<0.001), making them primary target beneficiaries of IPTp-SP, adolescents adhered to the required three or more ANC visits significantly less (PG: 46.6%; SG 43.7%) than adults (PG: 61.9%; SG 54.9%) and had lower SP uptake during the malaria transmission season, further showing the difficulty of reaching this age group. Adolescents' structural constraints (such as their social position and household labor requirements) and needs (such as anonymity in the health encounter) leave them highly vulnerable during their pregnancies and, especially, during the high malaria transmission season. CONCLUSION: Our study shows that adolescents need to be targeted specifically, prior to their first pregnancy and with measures adapted to their social context, addressing their structural constraints and needs and going beyond standard health promotion campaigns. Unless such specific measures are taken, adolescents' social vulnerability will present a serious bottleneck for the effectiveness of IPTi-SP.

Trends in pregnancy outcomes in Malawian adolescents receiving antimalarial and hematinic supplements.

OBJECTIVE: To describe pregnancy outcomes of adolescent and adult primigravidae receiving antimalarials and hematinic supplementation and compare findings with a survey in this area a decade earlier. DESIGN: Cross-sectional surveys in intervention and control sites. SETTING: Community, antenatal and delivery facilities in Chikwawa, Malawi. A rural area with year round malaria transmission. METHODS: Data on antenatal attendance, uptake of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP), birthweight, malaria, anaemia, for 2,152 primigravidae. OUTCOME MEASURES: Place of delivery, anaemia, malaria, birthweight. RESULTS: Fewer adolescent than adult primigravidae received >or=2 IPTp-SP doses (66 vs. 77.2%, p < 0.001), although more attended for two or more antenatal visits (92.0 vs. 76.7%, p < 0.001). Only 24.1% of adolescent primigravidae attended for hospital delivery. Women resident in intervention sites receiving IPTp-SP community distribution were more likely to choose a community delivery (p < 0.01), and have higher uptake of IPTp-SP (p = 0.036) than women not resident in these villages. Postnatal malaria prevalence was low and did not differ by age or place of delivery. Postnatal anaemia and low birthweight prevalence were higher in adolescents with community deliveries. Maternal anaemia and low birthweight prevalence were lower amongst adolescents in this study compared to estimates from the same population a decade previously. CONCLUSIONS: Adolescents had higher anaemia risk, lower IPTp-SP uptake than adults and under a quarter had a hospital delivery. Pregnancy outcomes improved compared to the survey a decade earlier. Monitoring and surveillance is required to reinforce to policy makers the need to improve adolescent coverage for available interventions.

Community-based promotional campaign to improve uptake of intermittent preventive antimalarial treatment in pregnancy in Burkina Faso.

Malaria preventive strategies in pregnancy were assessed in a health center randomized trial comparing intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) with and without community based promotional activities in rural Burkina Faso. The study involved 2,240 secundigravidae and secundigravidae and evaluated factors associated with antenatal clinic (ANC) attendance and uptake of IPTp-SP. With promotion, 64.2% completed > or = 3 ANC visits compared with 44.7% without (P = 0.05). Complete uptake of IPTp-SP was 71.8% with and 49.1% without promotion (P = 0.008). The IPTp-SP uptake was lowest in adolescents delivering during high malaria transmission with (29%) or without promotion (30%). Uptake of SP was higher during the low transmission season than in the high transmission season (adjusted odds ratio = 2.17, 95% confidence interval = 1.59-3.03). Community sensitization increased ANC attendance and IPTp-SP uptake. Adolescents were the most difficult to reach, particularly during the high malaria transmission period. The impact of IPTp-SP will be limited unless this high risk group is protected.

Individual efficacy of intermittent preventive treatment with sulfadoxine-pyrimethamine in primi- and secundigravidae in rural Burkina Faso: impact on parasitaemia, anaemia and birth weight.

OBJECTIVE: To assess the efficacy at individual level of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) in primi- and secundigravidae in rural Burkina Faso. METHODS: Data of 1441 women enrolled in a health centre randomized trial and delivering a live-singleton between September 2004 and October 2006 were analysed at individual level. Prevalence of peripheral and placental parasitaemia, anaemia (PCV <33%), low-birth weight (<2500 g; LBW), mean packed cell volume (PCV) and birth weight were compared in relation to the number of directly observed SP doses. RESULTS: Two or more doses of SP significantly reduced the risk of placental parasitaemia [adjusted odds ratio (AOR) = 0.04, 95%CI = 0.003-0.60, P = 0.023] and anaemia at delivery (AOR = 0.31, 95%CI = 0.18-0.52, P < 0.001). IPTp was associated with reduced risk of LBW in primigravidae (AOR = 0.11, 95%CI = 0.07-0.17, P < 0.001) but not secundigravidae (AOR = 0.70, 95%CI = 0.26-1.91, P = 0.452). For each increment in number of SP doses mean PCV increased by 1.0% (95%CI = 0.4-1.7, P = 0.005) at 32 weeks gestation, by 1.2% (95%CI = 0.2-2.2, P = 0.025) at delivery and mean birth weight by 220 g (95%CI = 134-306 P < 0.001) in primigravidae and by 102 g (95%CI = 55-148, P = 0.001) in secundigravidae. CONCLUSION: The risk of malaria infection was significantly reduced by IPTp with SP in primi- and secundigravidae in rural Burkina Faso. The impact on clinical outcomes is lower and mainly limited to primigravidae for LBW. Incomplete uptake of IPTp-SP and limited effect in low risk groups together may substantially dilute the measurable impact of effective interventions. This needs to be taken into account when evaluating interventions at community level.

Monitoring and evaluation of malaria in pregnancy - developing a rational basis for control.

Monitoring and evaluation of malaria control in pregnancy is essential for assessing the efficacy and effectiveness of health interventions aimed at reducing the major burden of this disease on women living in endemic areas. Yet there is no currently integrated strategic approach on how this should be achieved. Malaria control in pregnancy is formulated in relation to epidemiological patterns of exposure. Current emphasis is on intermittent preventive treatment (IPTp) during pregnancy with sulphadoxine-pyrimethamine in higher transmission areas, combined with insecticide treated bed nets (ITNs) and case management. Emphasis in lower transmission areas is primarily on case management. This paper discusses a rational basis for monitoring and evaluation based on: assessments of therapeutic and prophylactic drug efficacy; proportional reductions in parasite prevalence; seasonal effects; rapid assessment methodologies; birthweight and/or anaemia nomograms; case-coverage methods; maternal mortality indices; operational and programmatic indicators; and safety and pharmacovigilance of antimalarials in pregnancy. These approaches should be incorporated more effectively within National Programmes in order to facilitate surveillance and improve identification of high-risk women. Systems for utilizing routinely collected data should be strengthened, with greater attention to safety and pharmacovigilance with the advent of artemisinin combination therapies, and prospects of inadvertent exposures to artemisinins in the first trimester. Integrating monitoring activities within malaria control, reproductive health and adolescent-friendly services will be critical for implementation. Large-scale operational research is required to further evaluate the validity of currently proposed indicators, and in order to clarify the breadth and scale of implementation to be deployed.

A community effectiveness trial of strategies promoting intermittent preventive treatment with sulphadoxine-pyrimethamine in pregnant women in rural Burkina Faso.

BACKGROUND: Intermittent preventive treatment with sulphadoxine-pyrimethamine for pregnant women (IPTp-SP) is currently being scaled up in many countries in sub-Saharan Africa. Despite high antenatal clinic (ANC) attendance, coverage with the required two doses of SP remains low. The study investigated whether a targeted community-based promotion campaign to increase ANC attendance and SP uptake could effectively improve pregnancy outcomes in the community. METHODS: Between 2004 and 2006 twelve health centres in Boromo Health District, Burkina Faso were involved in this study. Four were strategically assigned to community promotion in addition to IPTp-SP (Intervention A) and eight were randomly allocated to either IPTp-SP (Intervention B) or weekly chloroquine (Control). Primi- and secundigravidae were enrolled at village level and thick films and packed cell volume (PCV) taken at 32 weeks gestation and at delivery. Placental smears were prepared and newborns weighed. Primary outcomes were peripheral parasitaemia during pregnancy and at delivery, placental malaria, maternal anaemia, mean and low birth weight. Secondary outcomes were the proportion of women with > or = 3 ANC visits and > or = 2 doses of SP. Intervention groups were compared using logistic and linear regression with linearized variance estimations to correct for the cluster-randomized design. RESULTS: SP uptake (> or = 2 doses) was higher with (Intervention A: 70%) than without promotion (Intervention B: 49%) (OR 2.45 95%CI 1.25-4.82 p = 0.014). Peripheral (33.3%) and placental (30.3%) parasite rates were significantly higher in the control arm compared to Intervention B (peripheral: 20.1% OR 0.50 95%CI 0.37-0.69 p = 0.001; placental: 20.5% OR 0.59 95%CI 0.44-0.78 p = 0.002) but did not differ between Intervention A (17.4%; 18.1%) and Intervention B (20.1; 20.5%) (peripheral: OR 0.84 95%CI 0.60-1.18 p = 0.280; placental: OR 0.86 95%CI 0.58-1.29 p = 0.430). Mean PCV and birth weight and prevalence of anaemia and low birth weight did not differ between study arms. CONCLUSION: The promotional campaign resulted in a major increase in IPTp-coverage, with two thirds of women at delivery having received > or = 2 SP. Despite lower prevalence of malaria infection this did not translate into a significant difference in maternal anaemia or birth weight. This data provides evidence that, as with immunization programmes, extremely high coverage is essential for effectiveness. This critical threshold of coverage needs to be defined, possibly on a regional basis.

Malaria burden among pregnant women living in the rural district of Boromo, Burkina Faso.

In two cross-sectional surveys carried out in the rural health district of Boromo, Burkina Faso, malaria infection was evaluated in 295 pregnant women in May 2003 and 288 pregnant women in December 2003. Malaria prevalence, all P. falciparum infection, was higher in December (32.2%) than in May (11.9%) (P < 0.0001). In both surveys primigravidae had a significantly higher risk of infection than multigravidae (P < 0.0001). Such risk decreased significantly and progressively with gestational age, the highest risk being during the first trimester. Women who had not attended the antenatal clinic had also a significantly higher risk of malaria infection. Despite the high antenatal clinic attendance and the use (or misuse) of chloroquine chemoprophylaxis, malaria remains an important problem for pregnant women living in the rural district of Boromo. This requires a major effort by the health authorities to guarantee all pregnant women have access to and use preventive measures.