Matthew J. Kirby

Effect of two different house screening interventions on exposure to malaria vectors and on anaemia in children in The Gambia: a randomised controlled trial.

BACKGROUND House screening should protect people against malaria. We assessed whether two types of house screening--full screening of windows, doors, and closing eaves, or installation of screened ceilings--could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission. METHODS During 2006 and 2007, 500 occupied houses in and near Farafenni town in The Gambia, an area with low use of insecticide-treated bednets, were randomly assigned to receive full screening, screened ceilings, or no screening (control). Randomisation was done by computer-generated list, in permuted blocks of five houses in the ratio 2:2:1. Screening was not treated with insecticide. Exposure to mosquitoes indoors was assessed by fortnightly light trap collections during the transmission season. Primary endpoints included the number of female Anopheles gambiae sensu lato mosquitoes collected per trap per night. Secondary endpoints included frequency of anaemia (haemoglobin concentration <80 g/L) and parasitaemia at the end of the transmission season in children (aged 6 months to 10 years) who were living in the study houses. Analysis was by modified intention to treat (ITT), including all randomised houses for which there were some outcome data and all children from those houses who were sampled for haemoglobin and parasitaemia. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN51184253. FINDINGS 462 houses were included in the modified ITT analysis (full screening, n=188; screened ceilings, n=178; control, n=96). The mean number of A gambiae caught in houses without screening was 37.5 per trap per night (95% CI 31.6-43.3), compared with 15.2 (12.9-17.4) in houses with full screening (ratio of means 0.41, 95% CI 0.31-0.54; p<0.0001) and 19.1 (16.1-22.1) in houses with screened ceilings (ratio 0.53, 0.40-0.70; p<0.0001). 755 children completed the study, of whom 731 had complete clinical and covariate data and were used in the analysis of clinical outcomes. 30 (19%) of 158 children from control houses had anaemia, compared with 38 (12%) of 309 from houses with full screening (adjusted odds ratio [OR] 0.53, 95% CI 0.29-0.97; p=0.04), and 31 (12%) of 264 from houses with screened ceilings (OR 0.51, 0.27-0.96; p=0.04). Frequency of parasitaemia did not differ between intervention and control groups. INTERPRETATION House screening substantially reduced the number of mosquitoes inside houses and could contribute to prevention of anaemia in children. FUNDING Medical Research Council.

ArticlesEffect of two different house screening interventions on exposure to malaria vectors and on anaemia in children in The Gambia: a randomised controlled trial

BACKGROUND House screening should protect people against malaria. We assessed whether two types of house screening--full screening of windows, doors, and closing eaves, or installation of screened ceilings--could reduce house entry of malaria vectors and frequency of anaemia in children in an area of seasonal malaria transmission. METHODS During 2006 and 2007, 500 occupied houses in and near Farafenni town in The Gambia, an area with low use of insecticide-treated bednets, were randomly assigned to receive full screening, screened ceilings, or no screening (control). Randomisation was done by computer-generated list, in permuted blocks of five houses in the ratio 2:2:1. Screening was not treated with insecticide. Exposure to mosquitoes indoors was assessed by fortnightly light trap collections during the transmission season. Primary endpoints included the number of female Anopheles gambiae sensu lato mosquitoes collected per trap per night. Secondary endpoints included frequency of anaemia (haemoglobin concentration <80 g/L) and parasitaemia at the end of the transmission season in children (aged 6 months to 10 years) who were living in the study houses. Analysis was by modified intention to treat (ITT), including all randomised houses for which there were some outcome data and all children from those houses who were sampled for haemoglobin and parasitaemia. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN51184253. FINDINGS 462 houses were included in the modified ITT analysis (full screening, n=188; screened ceilings, n=178; control, n=96). The mean number of A gambiae caught in houses without screening was 37.5 per trap per night (95% CI 31.6-43.3), compared with 15.2 (12.9-17.4) in houses with full screening (ratio of means 0.41, 95% CI 0.31-0.54; p<0.0001) and 19.1 (16.1-22.1) in houses with screened ceilings (ratio 0.53, 0.40-0.70; p<0.0001). 755 children completed the study, of whom 731 had complete clinical and covariate data and were used in the analysis of clinical outcomes. 30 (19%) of 158 children from control houses had anaemia, compared with 38 (12%) of 309 from houses with full screening (adjusted odds ratio [OR] 0.53, 95% CI 0.29-0.97; p=0.04), and 31 (12%) of 264 from houses with screened ceilings (OR 0.51, 0.27-0.96; p=0.04). Frequency of parasitaemia did not differ between intervention and control groups. INTERPRETATION House screening substantially reduced the number of mosquitoes inside houses and could contribute to prevention of anaemia in children. FUNDING Medical Research Council.

Risk factors for house-entry by malaria vectors in a rural town and satellite villages in The Gambia

BackgroundIn the pre-intervention year of a randomized controlled trial investigating the protective effects of house screening against malaria-transmitting vectors, a multi-factorial risk factor analysis study was used to identify factors that influence mosquito house entry.MethodsMosquitoes were sampled using CDC light traps in 976 houses, each on one night, in Farafenni town and surrounding villages during the malaria-transmission season in The Gambia. Catches from individual houses were both (a) left unadjusted and (b) adjusted relative to the number of mosquitoes caught in four sentinel houses that were operated nightly throughout the period, to allow for night-to-night variation. Houses were characterized by location, architecture, human occupancy and their mosquito control activities, and the number and type of domestic animals within the compound.Results106,536 mosquitoes were caught, of which 55% were Anopheles gambiae sensu lato, the major malaria vectors in the region. There were seven fold higher numbers of An. gambiae s.l. in the villages (geometric mean per trap night = 43.7, 95% confidence intervals, CIs = 39.5–48.4) than in Farafenni town (6.3, 5.7–7.2) and significant variation between residential blocks (p < 0.001). A negative binomial multivariate model performed equally well using unadjusted or adjusted trap data. Using the unadjusted data the presence of nuisance mosquitoes was reduced if the house was located in the town (odds ratio, OR = 0.11, 95% CIs = 0.09–0.13), the eaves were closed (OR = 0.71, 0.60–0.85), a horse was tethered near the house (OR = 0.77, 0.73–0.82), and churai, a local incense, was burned in the room at night (OR = 0.56, 0.47–0.66). Mosquito numbers increased per additional person in the house (OR = 1.04, 1.02–1.06) or trapping room (OR = 1.19, 1.13–1.25) and when the walls were made of mud blocks compared with concrete (OR = 1.44, 1.10–1.87).ConclusionThis study demonstrates that the risk of malaria transmission is greatest in rural areas, where large numbers of people sleep in houses made of mud blocks, where the eaves are open, horses are not tethered nearby and where churai is not burnt at night. These factors need to be considered in the design and analysis of intervention studies designed to reduce malaria transmission in The Gambia and other parts of sub-Saharan Africa.

Effect of temperature and inter-specific competition on the development and survival of Anopheles gambiae sensu stricto and An. arabiensis larvae

The two major African malaria vectors Anopheles gambiae sensu stricto and An. arabiensis are sibling species that occupy different climatic niches but are frequently found in the same larval habitats. Differences in survival and development of the aquatic larval stages of these species at different temperatures may help explain adult distribution. The development time from first instar larva to adult at constant water temperatures (25, 30 and 35 degrees C) was measured in these two species when reared together in the same container (ratio 1:1) and separately. Survival to adult was highest in both species reared at 25 degrees C and decreased with increasing temperature. More adult An. gambiae s.s. were produced at 25 degrees C than An. arabiensis (80% interquartile range (78-88) versus 68% (63-78)) but this situation was reversed at 35 degrees C (7% (3-17) versus 33% (27-32)). The survival of An. gambiae s.s. when reared alone was similar to that when reared in the presence of An. arabiensis. In marked contrast An. arabiensis suffered reduced survival when raised with An. gambiae s.s. at 30 degrees C (20% (7-57)) than when reared independently (57% (45-72)). Mean age at eclosion and adult size decreased for both species with increasing water temperature, however An. arabiensis larvae developed at a slower rate and resulted in larger adults than An. gambiae s.s. throughout. The apparent greater production of An. arabiensis at high water temperatures and An. gambiae s.s. at lower water temperatures may in part explain the spatial and temporal distribution of the two species.

Importance of Eaves to House Entry by Anopheline, But Not Culicine, Mosquitoes

ABSTRACT Screening homes is an effective way of reducing house entry by mosquitoes. Here, we assess how important blocking the eaves is for reducing house entry by anopheline and culicine mosquitoes for houses that have screened doors and no windows. Twelve houses, with two screened doors and no windows, in which a single adult male slept, were included in a simple crossover design. In the first period, six houses were randomly selected and had the eaves blocked using a mixture of rubble and mortar; the other six were left with open eaves. Mosquitoes were sampled using CDC light traps from each house twice a week for 4 wk. Mosquito control activities and the number and type of domestic animals within the compound was recorded on each sampling occasion. Before beginning the second sampling period, homes with blocked eaves had them opened, and those with open eaves had them closed. Mosquitoes were then sampled from each house for a further 4 wk. When houses had their eaves closed, a three-fold reduction in Anopheles gambiae s.l. Giles caught indoors was observed. However, there was no reduction in total culicine numbers observed. This study demonstrates that the eaves are the major route by which An. gambiae enters houses. By contrast, culicine mosquitoes enter largely through doors and windows. Sealing the eave gap is an important method for reducing malaria transmission in homes where doors and windows are screened.

Malaria risk factors in north-east Tanzania

BackgroundUnderstanding the factors which determine a households or individuals risk of malaria infection is important for targeting control interventions at all intensities of transmission. Malaria ecology in Tanzania appears to have reduced over recent years. This study investigated potential risk factors and clustering in face of changing infection dynamics.MethodsHousehold survey data were collected in villages of rural Muheza district. Children aged between six months and thirteen years were tested for presence of malaria parasites using microscopy. A multivariable logistic regression model was constructed to identify significant risk factors for children. Geographical information systems combined with global positioning data and spatial scan statistic analysis were used to identify clusters of malaria.ResultsUsing an insecticide-treated mosquito net of any type proved to be highly protective against malaria (OR 0.75, 95% CI 0.59-0.96). Children aged five to thirteen years were at higher risk of having malaria than those aged under five years (OR 1.71, 95% CI 1.01-2.91). The odds of malaria were less for females when compared to males (OR 0.62, 95% CI 0.39-0.98). Two spatial clusters of significantly increased malaria risk were identified in two out of five villages.ConclusionsThis study provides evidence that recent declines in malaria transmission and prevalence may shift the age groups at risk of malaria infection to older children. Risk factor analysis provides support for universal coverage and targeting of long-lasting insecticide-treated nets (LLINs) to all age groups. Clustering of cases indicates heterogeneity of risk. Improved targeting of LLINs or additional supplementary control interventions to high risk clusters may improve outcomes and efficiency as malaria transmission continues to fall under intensified control.

Infection of the malaria mosquito, Anopheles gambiae, with two species of entomopathogenic fungi: effects of concentration, co-formulation, exposure time and persistence.

BackgroundEntomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana isolates have been shown to infect and reduce the survival of mosquito vectors.MethodsHere four different bioassays were conducted to study the effect of conidia concentration, co-formulation, exposure time and persistence of the isolates M. anisopliae ICIPE-30 and B. bassiana I93-925 on infection and survival rates of female Anopheles gambiae sensu stricto. Test concentrations and exposure times ranged between 1 × 107 - 4 × 1010 conidia m-2 and 15 min - 6 h. In co-formulations, 2 × 1010 conidia m-2 of both fungus isolates were mixed at ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence, mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with conidia concentrations of 2 × 109, 2 × 1010 or 4 × 1010.ResultsMosquito survival varied with conidia concentration; 2 × 1010 conidia m-2 was the concentration above which no further reductions in survival were detectable for both isolates of fungus. The survival of mosquitoes exposed to single and co-formulated treatments was similar and no synergistic or additive effects were observed. Mosquitoes were infected within 30 min and longer exposure times did not result in a more rapid killing effect. Fifteen min exposure still achieved considerable mortality rates (100% mortality by 14 d) of mosquitoes, but at lower speed than with 30 min exposure (100% mortality by 9 d). Conidia remained infective up to 28 d post-application but higher concentrations did not increase persistence.ConclusionBoth fungus isolates are effective and persistent at low concentrations and short exposure times.

Evaluation of a national universal coverage campaign of long-lasting insecticidal nets in a rural district in north-west Tanzania

BackgroundInsecticide-treated nets (ITN) are one of the most effective measures for preventing malaria. Mass distribution campaigns are being used to rapidly increase net coverage in at-risk populations. This study had two purposes: to evaluate the impact of a universal coverage campaign (UCC) of long-lasting insecticidal nets (LLINs) on LLIN ownership and usage, and to identify factors that may be associated with inadequate coverage.MethodsIn 2011 two cross-sectional household surveys were conducted in 50 clusters in Muleba district, north-west Tanzania. Prior to the UCC 3,246 households were surveyed and 2,499 afterwards. Data on bed net ownership and usage, demographics of household members and household characteristics including factors related to socio-economic status were gathered, using an adapted version of the standard Malaria Indicator Survey. Specific questions relating to the UCC process were asked.ResultsThe proportion of households with at least one ITN increased from 62.6% (95% Confidence Interval (CI) = 60.9-64.2) before the UCC to 90.8% (95% CI = 89.0-92.3) afterwards. ITN usage in all residents rose from 40.8% to 55.7%. After the UCC 58.4% (95% CI = 54.7-62.1) of households had sufficient ITNs to cover all their sleeping places. Households with children under five years (OR = 2.4, 95% CI = 1.9-2.9) and small households (OR = 1.9, 95% CI = 1.5-2.4) were most likely to reach universal coverage. Poverty was not associated with net coverage. Eighty percent of households surveyed received LLINs from the campaign.ConclusionsThe UCC in Muleba district of Tanzania was equitable, greatly improving LLIN ownership and, more moderately, usage. However, the goal of universal coverage in terms of the adequate provision of nets was not achieved. Multiple, continuous delivery systems and education activities are required to maintain and improve bed net ownership and usage.

Exploiting the behaviour of wild malaria vectors to achieve high infection with fungal biocontrol agents

BackgroundControl of mosquitoes that transmit malaria has been the mainstay in the fight against the disease, but alternative methods are required in view of emerging insecticide resistance. Entomopathogenic fungi are candidate alternatives, but to date, few trials have translated the use of these agents to field-based evaluations of their actual impact on mosquito survival and malaria risk. Mineral oil-formulations of the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were applied using five different techniques that each exploited the behaviour of malaria mosquitoes when entering, host-seeking or resting in experimental huts in a malaria endemic area of rural Tanzania.ResultsSurvival of mosquitoes was reduced by 39-57% relative to controls after forcing upward house-entry of mosquitoes through fungus treated baffles attached to the eaves or after application of fungus-treated surfaces around an occupied bed net (bed net strip design). Moreover, 68 to 76% of the treatment mosquitoes showed fungal growth and thus had sufficient contact with fungus treated surfaces. A population dynamic model of malaria-mosquito interactions shows that these infection rates reduce malaria transmission by 75-80% due to the effect of fungal infection on adult mortality alone. The model also demonstrated that even if a high proportion of the mosquitoes exhibits outdoor biting behaviour, malaria transmission was still significantly reduced.ConclusionsEntomopathogenic fungi strongly affect mosquito survival and have a high predicted impact on malaria transmission. These entomopathogens represent a viable alternative for malaria control, especially if they are used as part of an integrated vector management strategy.

First report of Metarhizium anisopliae IP 46 pathogenicity in adult Anopheles gambiae s.s. and An. arabiensis (Diptera; Culicidae)

The entomopathogenic fungus Metarhizium anisopliae isolate IP 46, originating from a soil sample collected in 2001 in the Cerrado of Central Brazil, was tested for its ability to reduce the survival of adult male and female Anopheles gambiae s.s. and An. arabiensis mosquitoes. A 6-h exposure to the fungus coated on test paper at a concentration of 3.3 × 106 conidia cm-2 reduced the daily survival of both mosquito species (HR = 3.14, p < 0.001), with higher risk of dying in An. gambiae s.s relative to An. arabiensis (HR = 1.38, p < 0.001). Fungal sporulation was observed in >95% of mosquito cadavers in the treatment groups. The results indicate that M. anisopliae IP 46 has the potential to be a bio-control agent for African malaria vector species, and is a suitable candidate for further research and development.