Why Use of Interventions Targeting Outdoor Biting Mosquitoes will be Necessary to Achieve Malaria Elimination

of 20–120 infectious mosquito bites per person per year). During the elimination program which ran from 1972 to 1973, near complete coverage of all households (97–99%) with propoxur-based IRS combined with mass drug administration of the anti-malarials sulfalene and pyrimethamine (73–92% coverage) was attained throughout the study area. Although these intense efforts led to a drastic reduction in malaria prevalence within the region from 70 to 1%, the threshold for local elimination was not even approached (Molineaux and Gramiccia, 1980). A critical factor in the failure of elimination was incomplete suppression of vector populations due to the existence of low level outdoor-feeding (exophagy) and resting (exophily) behaviors within a small proportion of locally important vector populations (Molineaux and Gramiccia, 1980). This small proportion of mosquitoes with atypical behaviors was sufficient to prevent elimination even across a short period of time in which the potential for insecticide resistance was not recorded. Furthermore, by preventing the rapid achievement of elimination, the existence of these vectors may enhance the likelihood and spread of Insecticide Resistance by necessitating the continued application of high dose formulations over longer periods of time. While historically transmission in much of Africa has been dominated by vector species that primarily feed and rest indoors where they can be efficiently targeted with domestic insecticides (Gillies and DeMeillon, 1968; White, 1974; Gillies and Coetzee, 1987), there is growing evidence from across the continent that the widespread use of LLINs and IRS is driving vector species composition toward those with more flexible behaviors (Braimah et al., 2005; Pates and Curtis, 2005; Tirados et al., 2005; Antonio-Nkondjio et al., 2006; Oyewole and Awolola, 2006; Geissbühler et al., 2007; Bayoh et al., 2010; Reddy outside, their existence could be enough to prevent the transition from very low to zero transmission. The World Health Organization (WHO) defines malaria elimination as meaning the permanent reduction “to zero incidence of locally contracted cases, although imported cases will continue to occur and continued interventions measures are required” (WHO, 2008b). Achieving this goal will require full understanding of where and when persons are most exposed to the bites of mosquito vectors in order to target interventions where they can achieve maximum impact. While elimination is possible in some settings with low malaria transmission intensity (WHO, 2009; Griffin et al., 2010), and where the dominant vectors exhibit the stereotypical behaviors of biting indoors and late at night where they can be targeted by LLIN and/or IRS (Mabaso et al., 2004; Sharp et al., 2007b; John et al., 2009; WHO, 2009), it is unlikely that these methods will be sufficient to push prevalence below the WHO-defined pre-elimination threshold (<1 case/1000 population/year) in areas of high transmission (Molineaux and Gramiccia, 1980; Kleinschmeidt et al., 2009; Russell et al., 2010) and where the majority of human exposure to transmitting mosquitoes occurs outside human dwellings to which most current interventions are restricted (Taylor, 1975; Pates and Curtis, 2005; Tirados et al., 2005; Oyewole and Awolola, 2006; Geissbühler et al., 2007; Griffin et al., 2010; Van Bortel et al., 2010; Bugoro et al., 2011a; Yohannes and Boelee, 2012). To date, probably the most comprehensive attempt to achieve local elimination within an endemic region of Africa was made in the Garki region of northern Nigeria in the 1970’s (Molineaux and Gramiccia, 1980; WHO, 2008b). Before initiating this campaign, malaria transmission within this region was extremely high (example as indexed by an estimated annual entomologic inoculation rate, EIR Existing malaria vector control measures such as Long Lasting Insecticidal Nets (LLIN) and Indoor Residual Spraying (IRS) combined with Artemisinin Based Combination Therapy (ACT) drugs have significantly reduced the malaria burden in many parts of Africa (Battarai et al., 2007; Sharp et al., 2007a; Ceesay et al., 2008; O’Meara et al., 2008; WHO, 2009; Chizema-Kawesha et al., 2010; Ngomane and de Jager, 2012). The benefit of these interventions extends beyond the personal protection of the households that use them to protect entire communities by reducing either the infectiousness of blood stage parasites in human populations (Killeen et al., 2006a), or the abundance and survival of mosquito vectors (Killeen et al., 2007). It has been shown both theoretically (Killeen and Smith, 2007; Killeen et al., 2007) and in the course of operational control (Hawley et al., 2003; Klinkenberg et al., 2010) that significant community-wide reductions in transmission can be obtained even when intervention coverage levels are modest (35–75%). However, it is unlikely that these packages of interventions of their own will be sufficient to achieve malaria elimination in the most endemic settings where transmission rates are extremely high (Gillies and Smith, 1960; White, 1969; Oyewole and Awolola, 2006; Bayoh et al., 2010; Van Bortel et al., 2010; Bugoro et al., 2011a; Reddy et al., 2011; Russell et al., 2011). Even should the considerable financial, logistic, and behavioral obstacles that currently limit attainment of 100% coverage be overcome (Vanden et al., 2010; Larson et al., 2012), the combined use of effective anti-malarial drugs and these vector control interventions are not predicted to be sufficient for elimination in these settings (Killeen et al., 2000; Griffin et al., 2010) Because they do not cover the full spectrum of all locations where mosquito exposure occurs, and even if only a small percentage of mosquitoes remain and bite