Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania.

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone. In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms. IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08). This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.\ud \u

Malaria risk factors in North West Tanzania: the effect of spraying, nets and wealth.

Malaria prevalence remains high in many African countries despite massive scaling-up of insecticide treated nets (ITN) and indoor residual spraying (IRS). This paper evaluates the protective effect of pyrethroid IRS and ITNs in relation to risk factors for malaria based on a study conducted in North-West Tanzania, where IRS has been conducted since 2007 and universal coverage of ITNs has been carried out recently. In 2011 community-based cross-sectional surveys were conducted in the two main malaria transmission periods that occur after the short and long rainy seasons. These included 5,152 and 4,325 children aged 0.5-14 years, respectively. Data on IRS and ITN coverage, household demographics and socio-economic status were collected using an adapted version of the Malaria Indicator Survey. Children were screened for malaria by rapid diagnostic test. In the second survey, haemoglobin density was measured and filter paper blood spots were collected to determine age-specific sero-prevalence in each community surveyed. Plasmodium falciparum infection prevalence in children 0.5-14 years old was 9.3% (95%CI:5.9-14.5) and 22.8% (95%CI:17.3-29.4) in the two surveys. Risk factors for infection after the short rains included households not being sprayed (OR = 0.39; 95%CI:0.20-0.75); low community net ownership (OR = 0.45; 95%CI:0.21-0.95); and low community SES (least poor vs. poorest tertile: OR = 0.13, 95%CI:0.05-0.34). Risk factors after the long rains included household poverty (per quintile increase: OR = 0.89; 95%CI:0.82-0.97) and community poverty (least poor vs. poorest tertile: OR = 0.26, 95%CI:0.15-0.44); household IRS or high community ITN ownership were not protective. Despite high IRS coverage and equitable LLIN distribution, poverty was an important risk factor for malaria suggesting it could be beneficial to target additional malaria control activities to poor households and communities. High malaria prevalence in some clusters and the limited protection given by pyrethroid IRS and LLINs suggest that it may be necessary to enhance established vector control activities and consider additional interventions

Enhanced protection against malaria by indoor residual spraying in addition to insecticide treated nets: is it dependent on transmission intensity or net usage?

BACKGROUND: Insecticide treated nets (ITNs) and indoor residual spraying (IRS) are effective vector control tools that protect against malaria. There is conflicting evidence regarding whether using ITNs and IRS in combination provides additional benefit over using either of these methods alone. This study investigated factors that may modify the effect of the combined use of IRS and ITNs compared to using ITNs alone on malaria infection prevalence. METHODS: Secondary analysis was carried out on data from a cluster randomised trial in north-west Tanzania. 50 clusters received ITNs from a universal coverage campaign; of these 25 were randomly allocated to additionally receive two rounds of IRS in 2012. In cross-sectional household surveys children 0.5-14 years old were tested for Plasmodium falciparum infections (PfPR) two, six and ten months after the first IRS round. RESULTS: IRS protected those sleeping under nets (OR = 0.38, 95%CI 0.26-0.57) and those who did not (OR = 0.43, 95%CI 0.29-0.63). The protective effect of IRS was not modified by community level ITN use (ITN use = 50%, OR = 0.46, 95%CI 0.28-0.74). The additional protection from IRS was similar in low (<10% PfPR, OR = 0.38, 95%CI 0.19-0.75) and high transmission areas (≥10% PfPR, OR = 0.34, 95%CI 0.18-0.67). ITN use was protective at the individual-level regardless of whether the village had been sprayed (OR = 0.83, 95%CI 0.70-0.98). Living in a sprayed village was protective regardless of whether the individual slept under an ITN last night (OR = 0.41, 95%CI 0.29-0.58). INTERPRETATION: Implementing IRS in addition to ITNs was beneficial for individuals from villages with a wide range of transmission intensities and net utilisation levels. Net users received additional protection from IRS. ITNs were providing some individual protection, even in this area with high levels of pyrethroid insecticide resistance. These results demonstrate that there is a supplementary benefit of IRS even when ITNs are effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT01697852

Baseline characteristics of individuals and households by study arm, Muleba District, 2011.

a<p>Calculated from individual-level data.</p>b<p><i>Pf</i>PR from RDTs.</p>c<p>Recorded in baseline survey 1 (February–March 2011).</p>d<p>Baseline survey 2 (June–July 2011) after the UCC.</p>e<p>Haemoglobin <8 g/dl.</p>f<p>Reported sleeping under an ITN the night previous to the survey.</p>g<p>Calculated from household-level data.</p>h<p>At least one ITN per sleeping place.</p>i<p>Approximately 1 mo after spraying.</p>j<p>Arithmetic mean.</p>k<p>Proportion of mosquitoes positive for <i>P. falciparum</i> sporozoites.</p>l<p>Number of infective bites per month.</p

<i>Pf</i>PR in children 0.5–14 y old in the ITN only and ITN+IRS arms (intention to treat) in survey A, B, and C, Muleba District, Tanzania, 2012.

<p>Survey A = 2 mo after first intervention spray. Survey B = 6 mo after first intervention spray and 2 mo after second intervention spray. Survey C = 10 mo after first intervention spray and 6 mo after second intervention spray.</p>a<p><i>Pf</i>PR from RDTs.</p>b<p>Adjusted for survey.</p

Study timetable.

<p>Surveys 1 and 2 are baseline surveys. Surveys A, B, and C are post-intervention.</p

Per-protocol analysis of <i>Pf</i>PR in children 0.5–14 y old and anaemia in children under 5 y old in surveys A, B, and C.

<p>Muleba, Tanzania, 2012; analysis restricted to ITN users in both study arms. Survey A = 2 mo after first intervention spray. Survey B = 6 mo after first intervention spray and 2 mo after second intervention spray. Survey C = 10 mo after first intervention spray and 6 mo after second intervention spray.</p>a<p><i>Pf</i>PR from RDTs.</p>b<p>ITN used by the individual the night preceding the survey in the ITN only arm.</p>c<p>ITN used by the individual the night preceding the survey, and household with IRS in the ITN+IRS arm. One cluster that was allocated to be in the ITN only arm but received IRS in the second spray round was excluded from this analysis.</p>d<p>Prevalence of moderate/severe anaemia (haemoglobin <8 g/dl).</p

Mean number of <i>An. gambiae</i> mosquitoes per household, sporozoite rate, and EIR in the ITN only and ITN+IRS arms during the post-intervention period, Muleba District, Tanzania, 2011–2012.

a<p>Data are mean [95% CI] (number of houses) for mean <i>An. gambiae</i> per house per night and percent [95% CI] (number of <i>An. gambiae</i>) for sporozoite rate.</p>b<p>Arithmetic mean.</p>c<p>Proportion of mosquitoes positive for <i>P. falciparum</i> sporozoites.</p>d<p>Number of infective bites per month.</p

Trial profile for study households and children in the ITN only and ITN+IRS study arms.

<p>Note: Survey A = 2 months after first intervention spray. Survey B = 6 months after first intervention spray and 2 months after second intervention spray. Survey C = 10 months after first intervention spray and 6 months after second intervention spray. *No children 0.5–14 y old. ¹Dwelling vacant for survey duration. ²Includes not found (91.0%), not visited (2.4%), and missing data (6.6%). ³Households (HH) that were included and where children attended for testing.</p

Model 2: Household and community level effect of IRS, and individual net use on <i>Pf</i>PR (as per protocol analysis), Muleba 2012.

<p>Note: ¹<i>Pf</i>PR = <i>Plasmodium falciparum</i> infection prevalence from RDTs. ²Unadjusted odds ratios are only adjusted for survey. ³Adjusted for all other factors in the table and: household SES, individual age, baseline malaria prevalence and survey. ⁴HH = Household. CI = Confidence interval. N = Number tested.</p><p>Model 2: Household and community level effect of IRS, and individual net use on <i>Pf</i>PR (as per protocol analysis), Muleba 2012.</p