Study households and participants
The trial was based at the Medical Research Council (MRC) laboratories at Farafenni field station in The Gambia, and carried out in 2006 and 2007. The characteristics of the area have been described in detail elsewhere.16
Briefly, the study area was situated approximately 170 km from the mouth of the Gambia River and covered 70 km2
of the north bank, an area of open Sudan savanna. The climate consists of a single rainy season from June to October followed by a long dry season. There was 808 mm of rain in 2006, and 751 mm in 2007. Malaria cases are almost entirely attributable to Plasmodium falciparum
. Members of the A gambiae
complex are the main vectors and the entomological inoculation rate varies from 0 to 166 infective bites per person per rainy season.17
Combination therapy based on chloroquine and sulfadoxine-pyrimethamine was the first-line treatment for uncomplicated malaria throughout the trial. An effectiveness study that tested artesunate combined with lumefantrine, at the Armed Forces Provisional Ruling Council (AFPRC) General Hospital in Farafenni and at other health centres in the north bank region, started at the end of the trial, in December, 2007. The study area population was composed of 7852 people, with roughly equal numbers of men (n=4162, 53%) and women, and dominated by three ethnic groups: Wolof (n=2984, 38%), Mandinka (n=2199, 28%), and Fula (n=2120, 27%).
MRC Farafenni ran a demographic surveillance system in the study area throughout the study, which included 46 residential blocks in Farafenni town and 23 surrounding villages. Lists of potentially eligible houses, and children sleeping in those houses, were generated from this census and visited to check criteria for recruitment. Houses had to be single-storey buildings, have open eaves, less than five rooms, no existing ceilings, no existing screening, and at least one child aged between 6 months and 10 years sleeping there at night. There were no other exclusion criteria for children. Village and urban block sensitisation meetings were held to explain to the residents the purpose of the study and the benefits from participation in the trial. Subsequently, information sheets were read to individual house owners and to parents or guardians of children. Comprehension was checked before written consent was sought. Participants were invited to sign (or thumbprint if not literate) the consent documents, which were countersigned by the fieldworker present. Separate consent forms were filled in if the house owner was not the parent or guardian of the resident eligible children. Houses were enrolled between December and February before the intervention. Eligible children were enrolled at the same time, and a second round of enrolment of children was done in September of each year to include all children born during the screening installation phase (February to April) who would be eligible for the survey in November. In September, every enrolled child was given a unique study number and individual photographic identification card.
The protocol was approved by the Health Services and Public Health Research Board of the MRC UK and The Gambia Government and MRC Laboratories Joint Ethics Committee, and the Ethics Advisory Committee of Durham University. Two independent panels—a trial steering committee and a data monitoring and ethics committee—reviewed the conduct and results of the trial. The only incentives given to households that participated in the trial were provision of screening, treatment of study children during the clinical survey at the end of the transmission season, and a longlasting insecticide-treated bednet at the end of the trial.
Randomisation and masking
The study was a three-armed randomised controlled trial. Eligible houses were sorted by: (1) rural (village) or urban (Farafenni) location; (2) residential block; and (3) the number of children in each house, to achieve implicit stratification before assigning to the treatment group. The randomisation list was generated by use of Stata version 7 in permuted blocks of five (two houses with full screening, two with screened ceilings, and one control house without screening). PJM generated the allocation sequence and MJK enolled participants and assigned them to trial groups. Clinical assessments were undertaken by a team that was not involved in any other study procedures and that was masked to the intervention status of each child. Investigators who analysed the mosquito trap data were also masked to treatment assignment.
shows the trial design. In each year of the study we aimed to install full screening in 100 houses, and screened ceilings in a further 100 houses. 50 different houses each year served as a control group. A detailed description of the intervention arms is published in the trial protocol.18
In homes with full screening, timber framed doors (figure 2A
) and windows were constructed and covered with PVC-coated fibreglass netting (1·2 m wide for doors, 2·4 m wide for ceilings, and 1·0 m wide for windows), with a mesh size of 42 holes per cm2
(Vestergaard-Frandsen group, Kolding, Denmark). The gap between the top of the wall and roof (eaves) was filled with a mixture of sand, rubble, cement, and water, in accordance with normal local practice (figure 2B
). In homes with screened ceilings, netting was stretched across the room below the eaves, fixed to the walls with wooden battens, and any small holes were filled with mortar (figure 3
). Screening was not treated with insecticide.
*Year 1 cohort. †Year 2 cohort
(A) External view of screened door. (B) Internal view of screened door, showing mortar around door and closing the eaves.
Screened ceilings fixed, below open eaves, with wooden battens and mortar
The primary objectives were to estimate the efficacy of the house screening interventions against A gambiae
house entry, and to assess whether these interventions were comfortable, durable, and acceptable to local communities. The primary endpoints were number of female A gambiae
caught per light trap per night, proportion of residents willing to continue use of the intervention, and number of screens showing damage at 6 months and 12 months after installation. Secondary endpoints were sporozoite rate estimations in trapped mosquitoes and estimated entomological inoculation rate (ie, mean number of infective mosquitoes per person per season). The trial was also designed to examine the efficacy of house screening in preventing anaemia and reducing malaria infection at the end of the transmission season in November each year. The clinical endpoints were haemoglobin concentration, frequency of anaemia (defined as haemoglobin <80 g/L) and severe anaemia (haemoglobin <50 g/L), presence of malaria parasites, parasite density, and frequency of high parasitaemia (≥5000 parasites per μL). Children were selected for investigation because they are most at risk from anaemia in this population.19
Guidelines for recommending either type of intervention were established before the trial began. Full screening or screened ceilings would be recommended if they reduced house entry by malaria mosquitoes by 50% and were considered acceptable by more than 67% of householders. If both interventions satisfied those criteria, the intervention that was statistically more protective, or, if there was no difference, the cheapest, would be recommended.
Exposure to mosquitoes was measured by routine surveillance with US Centers for Disease Control and Prevention (CDC) light traps (one per house; model 512; John Hock Company, Gainsville, FL, USA) positioned 1 m above the ground, 1—2 m from the foot end of a bed protected with an untreated net used on that night only. Each study house was sampled every 2 weeks during this surveillance period (June 26—Nov 2, 2006, or July 16—Nov 5, 2007). Sub-samples of A gambiae
mosquitoes from each trial group and each month of the surveillance period were taken for species identification by PCR.20
To identify infective mosquitoes, heads and thoraces of mosquitoes were homogenised in pools of ten individuals and the presence of sporozoites identified by ELISA.21
A clinical cross-sectional survey of children was done at the end of each transmission season, at least 6 months after the screening was installed. Axillary temperature was measured and a rapid diagnostic test (ICT malaria Pf Cassette Test, ICT Diagnostics, South Africa) undertaken in children with temperature 37·5°C or more or history of fever in the preceding 48 h, to allow on-the-spot treatment of unwell children with detectable malaria. A finger-prick blood sample was taken from each child to measure haemoglobin concentration by use of a portable haemoglobin photometer (Hemocue, Ängelholm, Sweden), and to make thin and thick films for detection and quantification of malaria parasites. To establish parasite presence and density (asexual stages per μL, assuming a blood volume of 0·002 μL per high-power field), Giemsa-stained blood slides were examined (magnification ×1000). 200 fields were examined before a slide was declared negative.
Children with haemoglobin concentration less than 80 g/L were classified as anaemic and given iron supplementation. Chloroquine and sulfadoxine-pyrimethamine (Fansidar, Roche, Basel, Switzerland) were given to any child who had a positive ICT test result, and to children who had a negative ICT result or who were not tested but found to be positive on subsequent blood-slide examination. The parents of any child treated for malaria were asked to take their child to the nearest maternal and child health clinic if he or she did not recover from the symptoms of malaria within 48 h. Children with haemoglobin concentration less than 50 g/L were taken to the AFPRC General Hospital at Farafenni for blood transfusion and treatment of any underlying illnesses. They were followed up at MRC Farafenni for repeat haemoglobin measurement and general clinical review 2 weeks after discharge from hospital. Socioeconomic status was based on nine household characteristics, including household commodities, livestock, and house structure.22
After the end of the survey, house owners were given the choice of keeping the screening they had been given or having it removed, with the option of having the other screening type installed. Those in the control group were given the choice of having either screening type installed. The relative acceptability of each intervention was measured as the proportion of residents that continued the use of each intervention after they had been given the choice of the alternative or of having no screening. Two durability surveys, carried out at 6 months and 12 months after the screening was installed, recorded data specific to each type of screening.
Two costings incorporating materials and labour were calculated for both interventions on a per-person basis: the cost incurred during the trial, and a cost incorporating locally available netting. Each costing was based on the average study house of 22·2 m2, with 2·6 doors and 0·3 windows, with four residents.
The trial had in excess of 90% power to detect a 50% reduction or more in the number of mosquitoes collected per trap per night in either intervention group compared with the control group. We also designed the trial to compare the two types of screening. We based our sample size calculations on discriminating between a mean of 7·5 (50% reduction) and 5·0 (67% reduction) mosquitoes per trap per night in the two intervention groups. On the assumption of an SD of log(e) catch of 1·2, 181 houses per intervention group would be needed for a two-group one-sided t test to have 90% power to reject the null hypothesis that the difference between the group means is 2·5 or more, with an alpha level of 0·025 and assuming the expected difference between the means is zero. We considered that a smaller difference would make little, if any, appreciable change to the clinical pattern of malaria in the study area. Thus, in a three-armed trial we needed 200 houses in each intervention group and 100 in the control arm, allowing for 10% of houses to be excluded from the analysis because of withdrawal or non-adherence to protocol. The study was designed to have 90% power to detect a difference of 5 g/L or more in the mean haemoglobin concentration of children in the intervention groups compared with the control group, assuming a standard deviation of 17 g/L, an average of 2·5 children per house, and an intraclass correlation of between 0·04 to 0·08 from earlier studies (Milligan PJ, unpublished data and Cisse B, London School of Hygiene and Tropical Medicine, London, UK, personal communication).
Analysis of this trial adhered, as far as possible, to a detailed analytical plan established before the investigators had access to the finalised data. We used a modified intention-to-treat (ITT) approach to compare each intervention group with the control group. The modified ITT population for the analysis of the entomological endpoint included all randomised houses for which there were some outcome data (excluding collections when the light trap was not working, houses that were vacated by residents or destroyed, and houses for which the occupier withdrew consent). When comparing the two intervention groups, it was also useful to make a comparison by use of a per-protocol analysis, which excluded all houses from either intervention group with screening that had scored as badly damaged in the durability study done 6 months after installation. The definition of badly damaged screens differed between treatment groups. In houses with full screening, badly damaged screening was defined as doors not closing tightly or five or more holes in the netting. This number of holes was selected because in a study of untreated bednets in The Gambia, more than five small holes reduced greatly the protective efficacy of untreated bednets against parasite infection.23
In houses with screened ceilings, screening was defined as badly damaged if there were five or more holes in the netting or if netting had come away from the battens that secured it to the walls.
We estimated the relative reduction in mean mosquito count for each intervention group compared with the control group by use of Poisson regression models. Additionally, we incorporated a variable for household in these models as a gamma-distributed random effect; this incorporation provided a means of accounting for dependence among counts made at the same house, and was also a way of modelling overdispersion in the distribution of mosquito counts. To estimate the effect of the screened ceilings intervention, data from this intervention group and the control group were selected and the outcome was regressed on an indicator for the ceiling intervention. We report the exponentiated coefficient, which is interpreted as the ratio of the mean mosquito count for the group receiving the ceiling intervention relative to the mean count of the control group. The statistical significance of the effect was tested with the p value obtained from this regression. To adjust for multiple comparisons, a significance level of α=0·025 was used. Poisson regression was also used to determine the efficacy of full screening, and to compare the relative efficacies of screened ceilings versus full screening. For the latter comparison, a non-inferiority analysis was undertaken in which we considered the two treatments to be equivalent if the lower bound of the CI for the ratio of full screening/screened ceilings exceeded 2/3.
In a further analysis of the entomological data, efficacy was estimated by use of negative binomial regression models for the number of A gambiae
and number of culicine mosquitoes caught per house. Multiple imputation was used to reduce bias due to missing mosquito counts and missing covariate data. Ratios of the mean mosquito count (screened ceiling/control and full screening/control) were adjusted for covariates specified in the analysis plan that were shown to be associated with mosquito catch size in this area:16
(1) presence of horse(s) tethered near the house at night; (2) number of people sleeping in the trapping room; (3) wall material (mud brick or concrete); and (4) household socioeconomic status. Where variables were recorded at each visit (ie, covariates 1—2), the mean value was used. Socioeconomic status scores were computed with the first component of a principal components analysis of nine household characteristics (wall material, roof material, radio, iron or carved wooden bed, cart, bicycle, car or motorbike, livestock, literacy of mother).22
The modified ITT population for the analysis of clinical data included all children (from the houses included in the modified ITT analysis) recruited before the clinical survey who were sampled for haemoglobin and parasitaemia at that survey. We report mean haemoglobin concentration for each of the trial groups. Differences between trial groups were estimated from a regression model that included household as a random effect.
A further analysis of clinical data was based on a complete case analysis (ie, only individuals with complete outcome and covariate data were included). Differences in mean haemoglobin densities between trial groups were estimated by use of a normal model in which household was included as a random effect. Adjusted estimates of mean difference were based on a model that incorporated the full set of covariates used for the analysis of the entomological outcome, plus age of study participant. Unadjusted and adjusted odds ratios (ORs) were estimated for anaemia, severe anaemia, the presence of malaria parasites, and high parasitaemia. In each case, a logistic regression was used in which the household was modelled as a random effect. Adjusted ORs were obtained by including the covariates used in the model for haemoglobin concentration previously described.
For all adjusted analyses, we explored the effect on estimates of the inclusion of variables that represented other methods of mosquito control that might be affected by the intervention—namely, churai (local incense) burnt at night, bednet use, and bednet condition. By including these mediator variables in the regression models, the direct effect of the intervention could be estimated—ie, the effect in households where these characteristics were the same.
Contingency tables were used to compare the durability between years, sporozoite rates between years and trial groups, and the relative acceptability of each type of screening. Analyses were done with SPSS version 15.0, EpiInfo version 6, and Stata version 10.1. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN51184253.
Role of the funding source
The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. MJK and SWL had full access to all the data in the study and had final responsibility for the decision to submit for publication.