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

Editors' Summary Background Every year, more than 200 million cases of malaria occur worldwide, and more than 600,000 people, mainly children living in sub-Saharan Africa, die from this parasitic infection. Malaria parasites, which are transmitted to people through the bites of infected night-flying mosquitoes, cause a characteristic fever that needs to be treated promptly with antimalarial drugs to prevent anaemia (a reduction in red blood cell numbers) and organ damage. Prompt treatment also helps to reduce malaria transmission, but the mainstays of global malaria control efforts are the provision of insecticide-treated nets (ITNs) for people to sleep under to avoid mosquito bites, and indoor residual spraying (IRS) of houses with insecticides, which prevents mosquitoes from resting in houses. Both approaches have been scaled up in the past decade. About 54% of households in Africa now own at least one ITN, and 8% of at-risk populations are protected by IRS. As a result of the widespread deployment of these preventative tools and the increased availability of effective antimalarial drugs, malaria-related deaths in Africa fell by 45% between 2000 and 2012. Why Was This Study Done? ? Some countries have chosen to use ITNs and IRS in combination, reasoning that this will increase the proportion of individuals who are protected by at least one intervention and may provide additional protection to people using both interventions rather than one alone. However, providing both interventions is costly, so it is important to know whether this rationale is correct. In this cluster randomised controlled trial (a study that compares outcomes of groups of people randomly assigned to receive different interventions) undertaken in the Muleba District of Tanzania during 2012, the researchers investigate whether ITNs plus IRS provide more protection against malaria than ITNs alone. Malaria transmission occurs throughout the year in Muleba District but peaks after the October-December and March-May rains. Ninety-one percent of the district's households own at least one ITN, and 58% of households own enough ITNs to cover all their sleeping places. Annual rounds of IRS have been conducted in the region since 2007. What Did the Researchers Do and Find? ? The researchers allocated 50 communities to the ITN intervention or to the ITN+IRS intervention. Dwellings allocated to ITN+IRS were sprayed with insecticide just before each of the malaria transmission peaks in 2012. The researchers used household surveys to collect information about ITN coverage in the study population, the proportion of children aged 0.5-14 years infected with the malaria parasite Plasmodium falciparum (the prevalence of infection), and the proportion of children under five years old with anaemia. IRS coverage in the ITN+IRS arm was approximately 90%, and 50% of the children in both intervention arms used ITNs at the start of the trial, declining to 36% at the end of the study. In an intention-to-treat analysis (which assumed that all study participants got the planned intervention), the average prevalence of infection was 13% in the ITN+IRS arm and 26% in the ITN arm. A per-protocol analysis (which considered data only from participants who received their allocated intervention) indicated that the combined intervention had a statistically significant protective effect on the prevalence of infection compared to ITNs alone (an effect that is unlikely to have arisen by chance). Finally, the proportion of young children with anaemia was lower in the ITN+IRS arm than in the ITN arm, but this effect was not statistically significant. What Do These Findings Mean? ? These findings provide evidence that IRS, when used in combination with ITNs, can provide better protection against malaria infection than ITNs used alone. This effect is likely to be the result of IRS providing added protection to ITN users as well as compensating for inadequate ITN use. The findings also suggest that the combination of interventions may reduce the prevalence of anaemia better than ITNs alone, but this result needs to be confirmed. Additional trials are also needed to investigate whether ITN+IRS compared to ITN reduces clinical cases of malaria, and whether similar effects are seen in other settings. Moreover, the cost-effectiveness of ITN+IRS and ITN alone needs to be compared. For now, though, these findings suggest that national malaria control programs should consider implementing IRS in combination with ITNs if local ITN strategies alone are insufficiently effective and cannot be improved. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001630. Information is available from the World Health Organization on malaria (in several languages), including information on insecticide-treated bed nets and indoor residual spraying; the World Malaria Report 2013 provides details of the current global malaria situation The US Centers for Disease Control and Prevention provides information on malaria, on insecticide-treated bed nets, and on indoor residual spraying; it also provides a selection of personal stories about malaria Information is available from the Roll Back Malaria Partnership on the global control of malaria and on the Global Malaria Action Plan (in English and French); its website includes fact sheets about malaria in Africa and about nets and insecticides MedlinePlus provides links to additional information on malaria (in English and Spanish) Background 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. Methods and Findings 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). Conclusions 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. Trial registration www.ClinicalTrials.gov NCT01697852 Please see later in the article for the Editors' Summary