We found that the combination of IRS and ITNs provided significantly greater protection than the protection provided by ITNs alone in preventing malaria P. falciparum infection. Participants who received both interventions experienced a 61% reduction in P. falciparum parasitemia compared with those participants who had ITNs and no IRS, and the benefit extended to all household members, regardless of age. Moreover, those participants in the ITN + IRS group who developed malaria infection had a lower parasite density. The added benefit provided by IRS was observed, despite only 74% of households in the IRS + ITN group having received IRS.
Entomologic data show that IRS was effective in reducing anopheline mosquito numbers within households, and the anopheline mosquitoes remained highly susceptible to the lethal effects of the applied insecticide throughout the study period. Surprisingly, wall bioassays resulted in high mosquito mortality for the full 8 months between the first and second IRS campaigns, considerably longer than the 6-month expected effectiveness of λ-cyhalothrin described by the World Health Organization (WHO),9
suggesting that, with proper timing, a yearly application of this insecticide could be a feasible control strategy.
Despite a significant difference in malaria incidence in the two study groups, we did not find a difference in incidence of moderate anemia, and development of moderate anemia overall was infrequent. This finding likely was because of the study design; hemoglobin was measured monthly and at sick visits, iron supplementation was provided whenever hemoglobin was found to be < 11.0 g/dL, and malaria was detected and treated early.
We observed a reduction in ITN use among participants in the ITN + IRS group, which may have been a consequence of reduced mosquitoes in the house or the perception of reduced malaria risk. Any program that aims to promote the combination of the two strategies will need to include an educational campaign to promote continued ITN use.
Implementation of IRS is not suitable for every setting; it is resource-intensive and requires well-trained, well-coordinated spray teams and homes accessible to those teams. Our data show that a well-planned strategy, implemented under programmatic conditions, can result in reduced P. falciparum
infection even in the setting of high ITN coverage. In fact, the combination of IRS and ITNs may be particularly effective in East Africa and similar areas where the primary malaria vectors include anthropophagic, endophilic vectors, such as An. gambiae
s.s. and An. funestus
, and a more zoophagic, endophilic vector such as An. arabiensis
. High ITN coverage was associated with a dramatic decline of An. gambiae
s.s. and An. funestus
and near replacement by An. arabiensis
in the KEMRI/CDC demographic surveillance area near the study site described in this report.13
Despite an overall decline in vector numbers, malaria transmission has been sustained at relatively high levels; community surveys indicate over 40% of children < 5 years of age have P. falciparum
parasitemia (KEMRI/CDC, unpublished data). The current primary vector, An. arabiensis
, has more varied feeding options and may survive by feeding on alternate hosts when humans are unavailable. IRS reduces the post-feeding resting place options for all anophelines, including An. arabiensis
, which will often rest indoors after feeding outdoors.22
Thus, the combination of IRS and ITNs may work synergistically to eliminate both vector species simultaneously, providing a means to efficiently drive down malaria transmission.
Currently, the Kenyan Malaria Control Program relies on pyrethroid insecticides for both IRS and ITNs, and the development of insecticide resistance is a major concern. Resistance to pyrethroids in An. gambiae
and An. funestus
has been detected in several sites throughout Africa23–26
and has been documented to reduce the effectiveness of IRS in Bioko Island27
and South Africa.28
An advantage of IRS is that four classes of insecticides are available for application on walls; currently, only pyrethroids are considered safe, effective, and long-lasting for use on ITNs. Insecticide resistance management strategies include rotations, where insecticides are switched at regular intervals, and mosaics, where different insecticides are applied in different locations at the same time. The use of non-pyrethroids for IRS in combination with ITNs may represent a form of mosaic application of insecticides, where pyrethroids are on ITNs and non-pyrethroids are on walls, and should be explored as an approach to manage insecticide resistance.
Our study had limitations. First, because of the programmatic nature of the intervention, we were unable to randomize households or blind study staff. We controlled for known confounders, but there is always the risk that unknown confounders exist. We are reassured that the areas are adjacent, with similar population-based parasite prevalence before the introduction of IRS, and the areas have similar access to healthcare. Second, malaria incidence rates varied between study clinics within study areas. Ideally, we would have had pre-intervention incident rates from each study clinic to compare with post-intervention rates, but these rates are not available. Third, because ITNs have proven efficacy in areas of high transmission, we did not include an IRS only group, which could have provided information about whether the effects of ITNs and IRS act synergistically. Without an IRS only treatment arm, we cannot conclude whether the effects of IRS in the context of high ITN ownership would have been observed in the absence of ITNs. If so, the rationale for combining these interventions would be lacking, and vector control in Africa should be directed towards IRS. Given the progress in scaling up ITNs, this question may be difficult to answer definitively. Finally, the follow-up period was limited; over the years, insecticide resistance may develop, resulting in limited use of particular families of insecticide.28
In summary, this study provides the first prospectively collected data on the combined benefit of IRS and ITNs. These findings confirm several observational cross-sectional surveys that indicate an additive benefit from the combination of IRS and ITNs.29
The protective efficacy was substantial, suggesting that the combination of IRS and ITNs could be an effective intervention to further reduce malaria transmission in areas with persistent perennial malaria. These findings should be confirmed through a randomized controlled trial. Additionally, to help determine the best use of finite resources, a cost-effectiveness analysis would be useful and should explore the benefit of providing more protection to a limited number of homes through the combination of IRS and ITNs and less protection with ITNs alone to a larger number of homes. Until those data are available, our data support the deployment of the combination of IRS and ITNs or the introduction of IRS in an area with high ITN coverage where funds permit.