Combination of Insecticide Treated Nets and Indoor Residual Spraying in Northern Tanzania Provides Additional Reduction in Vector Population Density and Malaria Transmission Rates Compared to Insecticide Treated Nets Alone: A Randomised Control Trial.

Indoor residual spraying (IRS) combined with insecticide treated nets (ITN) has been implemented together in several sub-Saharan countries with inconclusive evidence that the combined intervention provides added benefit. The impact on malaria transmission was evaluated in a cluster randomised trial comparing two rounds of IRS with bendiocarb plus universal coverage ITNs, with ITNs alone in northern Tanzania. From April 2011 to December 2012, eight houses in 20 clusters per study arm were sampled monthly for one night with CDC light trap collections. Anopheles gambiae s.l. were identified to species using real time PCR Taq Man and tested for the presence of Plasmodium falciparum circumsporozoite protein. ITN and IRS coverage was estimated from household surveys. IRS coverage was more than 85% in two rounds of spraying in January and April 2012. Household coverage with at least one ITN per house was 94.7% after the universal coverage net campaign in the baseline year and the proportion of household with all sleeping places covered by LLIN was 50.1% decreasing to 39.1% by the end of the intervention year. An.gambiae s.s. comprised 80% and An.arabiensis 18.3% of the anopheline collection in the baseline year. Mean An.gambiae s.l. density in the ITN+IRS arm was reduced by 84% (95%CI: 56%-94%, p = 0.001) relative to the ITN arm. In the stratum of clusters categorised as high anopheline density at baseline EIR was lower in the ITN+IRS arm compared to the ITN arm (0.5 versus 5.4 per house per month, Incidence Rate Ratio: 0.10, 95%CI: 0.01-0.66, p-value for interaction <0.001). This trial provides conclusive evidence that combining carbamate IRS and ITNs produces major reduction in Anopheles density and entomological inoculation rate compared to ITN alone in an area of moderate coverage of LLIN and high pyrethroid resistance in An.gambiae s.s

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

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

Post intervention entomological outcomes by study arm and by low and high density <i>An</i>.<i>gambiae</i> s.l. density stratum at baseline.

<p>¹Odd Ratio (OR), Density Ration (DR) and Incidence Rate Ration (IRR) are adjusted for baseline mean cluster An. gambiae s.l. as categorical with < = 1 An. gambiae s.l./household/night and clusters>1</p><p>²N = Total Anopheles for Sporozoite rates and</p><p>³N total of houses for An. gambiae s.l. density and EIR</p><p>⁴ Interaction p value = p-value for difference between strata</p><p>Post intervention entomological outcomes by study arm and by low and high density <i>An</i>.<i>gambiae</i> s.l. density stratum at baseline.</p

Adjusted incidence rate ratio for mean <i>An</i>.<i>gambiae</i> s.l. density per household between ITN arm (reference IRR = 1) and ITN+ IRS arm per light trap collection round.

<p>Adjusted incidence rate ratio for mean <i>An</i>.<i>gambiae</i> s.l. density per household between ITN arm (reference IRR = 1) and ITN+ IRS arm per light trap collection round.</p

Monthly mean <i>Anopheles</i> density per house in the two arms and rainfall during baseline and post intervention period.

<p>Monthly mean <i>Anopheles</i> density per house in the two arms and rainfall during baseline and post intervention period.</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

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

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

<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