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 ≥ 3 ANC visits and ≥ 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 (≥ 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 ≥ 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. © 2008 Gies et al; licensee BioMed Central Ltd. The study was carried out between 2003 and 2006 in Western Burkina Faso, in Boromo Health District (BHD), a rural province with an estimated total population of 204,117 (Figure ​(Figure1).1). There are three seasons: a rainy season (June to October; 20–35°C; mean annual rainfall about 800 mm/year), a cold dry season (November to February, 16–32°C) and a hot dry season (March to May, 25–40°C). Malaria is holo-endemic, with high transmission between July and December. At the time of the study, national guidelines for malaria prevention in pregnant women recommended a full treatment course of CQ (1500 mg over 3 days) at the first antenatal visit followed by 300 mg weekly until 6 weeks post partum. Antenatal care was offered free of charge and included, besides CQ prophylaxis, an ANC card, physical examination, counselling, and haematinic supplementation (200 mg ferrous sulphate and 0.25 mg folic acid). In rural Burkina Faso, antenatal coverage for at least one visit was about 70%, with 22.5% of first visits during the first trimester and 68.5% of deliveries occurring at home [25]. Location of study health centres and dependant villages in Boromo Health District, Burkina Faso. Study interventions were implemented at two different levels: IPTp with SP (two observed doses at the beginning of the second and third trimester) was introduced through antenatal clinics in selected health centres (HC) and promotional activities were conducted at village level. Four out of 26 peripheral HC in BHD were strategically assigned to community promotion in addition to IPTp-SP (Intervention A). Geographically contiguous HC were selected to avoid contamination due to the spread of the promotional campaign across the study arms (Figure ​(Figure1).1). Communities were informed about the dangers of malaria for the pregnant women and their babies and early and regular ANC attendance was promoted to ensure timely IPTp-SP uptake. In 18 villages, female community leaders were trained to promote specifically designed health messages using image boxes for individual and group discussions. These messages were based on a previous socio-anthropological survey investigating local perceptions and beliefs. Eight HC were randomly allocated to either implement IPTp-SP in antenatal clinics without these enhanced promotional activities (Intervention B) or continue with weekly CQ according to the national guidelines (Control). The total study area covered a population of about 75,000 people distributed in 57 villages. Catchment areas of the selected HC varied in number of villages (2–10) and population size (3,500–10,500). In one catchment area (Oury), a new HC (Mou) was opened during the study period, reducing the distance to the nearest HC for two villages. SP was available at ANC from April 2004. The promotional activities in the intervention villages started in May 2004 and continued until June 2006. In August 2004, as part of an additional nutritional study, HC were in a factorial design assigned to one of two forms of micronutrient supplementation: (a) standard haematinics or (b) daily multi-micronutrients [26]. Trained women field assistants (WFA) identified pregnant women by monthly village visits using a screening questionnaire. After obtaining an informed consent, women in their first or second pregnancy were recruited. A questionnaire on demographic and household characteristics, education and socio-economic status, obstetrical history, antenatal visits, illness and treatment during the current pregnancy was administered by the WFA. Uterine fundal height was measured to confirm pregnancy and to estimate the gestational age. If the uterus was non-palpable, a urine pregnancy test was performed. Enrolled women received a card with a unique study number to be shown any time they attended a HC. At around 32 weeks of gestation, WFA visited the enrolled women and administered a questionnaire on antenatal visits, morbidity and treatment received. A capillary blood sample (finger prick) for packed cell volume (PCV) and parasitaemia was collected. At each ANC visit, information on previous illnesses and treatments was collected; fundal height and axillary temperature were measured. Numbers of tablets of directly observed SP treatment and other medicines (CQ, haematinics) handed to mothers were recorded on a study questionnaire. Similar information was collected at unscheduled visits. About half of deliveries were expected to take place at home assisted either by a traditional birth attendant (TBA) or a family member. Around the expected time of delivery, WFA weekly visited women likely to deliver at home. As soon as possible after delivery, babies were weighed using a hanging weighing scale (UNICEF Scale, infant, spring, 5 kg × 25 g) and length was measured to the nearest half centimetre using a transportable measuring board (SECA 210 Measure Mat II). A capillary blood sample for PCV and parasitaemia was collected from the mother. Whenever possible, WFA cut a small piece of tissue from the middle third of the maternal side of the placenta and prepared a smear after swabbing it on blotting paper. Similar samples and information were collected from women delivering at a HC or district hospital in the study area. Women recruited in the study and their offspring were visited by WFA about one year after delivery; if the child had died, the time of the event and its circumstances were recorded. All laboratory tests were performed by three experienced technicians in the laboratory of Boromo District Hospital. Thick films and methanol fixed placental smears were stained with 10% Giemsa for 10 minutes. For peripheral blood, parasite density was determined by counting parasite asexual forms per 200 white blood cells (WBC). The parasite density per μl was estimated assuming 8,000 WBC/μl. A slide was considered negative if no parasite was found after counting 500 WBC. All slides were systematically read by two technicians and for discrepant results a third consensus reading was performed. Parasite density for placental smears was expressed as the percentage of parasitized red blood cells (RBC) over the total number of RBC after counting at least 1,000 RBC. Heparinized capillary tubes containing whole blood were centrifuged within 48 hours after collection and PCV read. To minimize losses during the transport two capillaries were collected from the same finger prick. If two results were available the mean value was computed. Asexual P. falciparum parasites of any density, in a thick film of peripheral blood (peripheral parasitaemia) or a placental smear (placental parasitaemia). PCV < 33%; women were further divided according to the degree of anaemia, i.e. moderate to severe anaemia PCV < 30%; severe anaemia PCV < 24%. For the analysis of the haematological status at delivery, only blood samples collected at the day of delivery were considered. Weight values obtained within 24 hours of delivery were analysed as such. Weights obtained between day 1–8 post-delivery were corrected for the physiological fall (D1 4%, D2 3%, D3 3%, D4 1%) and increase (D5 0%, D6 1%, D7 2%, D8 4%) in weight occurring during the first week after delivery. The correction factor was estimated by weighing 132 newborns with known birth weight every two days up to 8 days after delivery. The birth weight analysis includes only singleton live births. Low birth weight (LBW) is defined as a corrected birth weight < 2,500 grams. Fundal height measurements, when compared with delivery dates, were shown to be inaccurate for estimating the gestational age. Thus, gestational age at first antenatal visit was estimated using the time between first ANC visit and delivery [27], assuming delivery occurred after 40 weeks gestation. Women were considered in the first trimester when their first antenatal visit was 25 to 40 weeks before delivery, in the second if between 13 to 24 weeks and in the third if between 0 and 12 weeks. Analyses including gestational age were restricted to normal deliveries of singleton live-births. Due to the uncertainty of gestational age, no attempt to define preterm delivery and to distinguish between miscarriages and stillbirths was done. Low transmission from January through June and high transmission from July through December, based on locally obtained rainfall and malaria prevalence, and taking into account the delay between onset of rains and onset of malaria transmission. All deliveries and blood samples were thus assigned to a period of either "low" or "high" transmission. In addition, for birth weight analysis the low transmission period was sub-divided into "early" (January to March) and "late" (April to June) low transmission. A relative index of socio-economic status based on the construction material of the house and roof and household assets (bicycle, motorbike, cart, car, television, radio, cell phone) was constructed using principal component analysis [28,29]. Classes were derived by dividing the index into quartiles graded as most poor, poor, less poor and least poor. Mean distances between villages and the nearest HC are those used by BHD for the vaccination program and are consistent with our own GPS derived data. Assuming a mean birth weight of 2,600 grams with no intervention and accounting for the cluster (village) effect with a small coefficient of variation between clusters in each group, the study was designed to detect, at the 5% level and with 80% power, a difference in mean birth weight of 200 grams between study arms. With 50 expected pregnancies per 1,000 inhabitants per year, one third first or second pregnancies, and allowing for 20% loss to follow-up, a total population of 70,000 was needed for including and following up 2,000 primi- and secundigravidae in two years. Access 2003 was used for double data entry and validation and EpiInfo 2000 (version 3.2.2; Centers for Disease Control and Prevention, Atlanta) and STATA (Intercooled version 10; Stata Corp., College Station, TX) software packages were used for analysis. Initially villages were intended to be considered as the sampling unit. However, as HC were the units of randomization, it was decided to account for the cluster design using linearized variance estimations with HC as the primary sampling unit (svyset HC, vce (linearized) in STATA 10). Baseline characteristics were compared between study arms using a design-based Pearson χ2-test (svy linearized: tabulate in STATA 10). Linear regression models (svy linearized: regress) were used to compare means of birth weight and PCV and logistic regression models (svy linearized: logistic) to compare proportions of ANC and IPTp-SP coverage, parasitaemia, anaemia and LBW and to determine odds ratios with corresponding 95% confidence intervals (CI). The criterion for statistical significance was set at alpha = 0.05. Variables tested as possible confounders were age (dichotomized ≤ 19/> 19 years), parity, education, marital status, wealth index, bed net ownership, season, distance (dichotomized ≤ 5/> 5 km) and, for birth weight analyses, sex of the baby. Variables associated with outcomes at a significance level with p < 0.1 in univariate analysis were entered in multiple logistic regression models. Intervention arm was kept as a variable in all models. Women enrolled during the first months of the study were likely to have started antenatal clinics before the interventions were implemented and have already received CQ chemoprophylaxis instead of IPTp-SP. The intervention A arm would not have been exposed to promotional activities. Therefore, women in their 4th or later month of pregnancy at the time the study started (delivery date prior to September 1st 2004) were excluded a priori from the analysis. The study was approved by the Burkina Faso Ministry of Health and the Ethical Committee at ITM, Antwerp. Local health authorities and community leaders were informed about the study objectives and procedures for data collection. All study participants gave informed consent after explanation of the procedures in the local language and were free to remove consent at any time of the study without influencing their access to health services. Women found to be parasitaemic or anaemic at 32 weeks or at delivery were offered antimalarial treatment (either quinine in the intervention arms or CQ in the control arm) and extra haematinics according to national guidelines.