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      Most outdoor malaria transmission by behaviourally-resistant Anopheles arabiensis is mediated by mosquitoes that have previously been inside houses

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          Abstract

          Background

          Anopheles arabiensis is stereotypical of diverse vectors that mediate residual malaria transmission globally, because it can feed outdoors upon humans or cattle, or enter but then rapidly exit houses without fatal exposure to insecticidal nets or sprays.

          Methods

          Life histories of a well-characterized An. arabiensis population were simulated with a simple but process-explicit deterministic model and relevance to other vectors examined through sensitivity analysis.

          Results

          Where most humans use bed nets, two thirds of An. arabiensis blood feeds and half of malaria transmission events were estimated to occur outdoors. However, it was also estimated that most successful feeds and almost all (>98 %) transmission events are preceded by unsuccessful attempts to attack humans indoors. The estimated proportion of vector blood meals ultimately obtained from humans indoors is dramatically attenuated by availability of alternative hosts, or partial ability to attack humans outdoors. However, the estimated proportion of mosquitoes old enough to transmit malaria, and which have previously entered a house at least once, is far less sensitive to both variables. For vectors with similarly modest preference for cattle over humans and similar ability to evade fatal indoor insecticide exposure once indoors, >80 % of predicted feeding events by mosquitoes old enough to transmit malaria are preceded by at least one house entry event, so long as ≥40 % of attempts to attack humans occur indoors and humans outnumber cattle ≥4-fold.

          Conclusions

          While the exact numerical results predicted by such a simple deterministic model should be considered only approximate and illustrative, the derived conclusions are remarkably insensitive to substantive deviations from the input parameter values measured for this particular An. arabiensis population. This life-history analysis, therefore, identifies a clear, broadly-important opportunity for more effective suppression of residual malaria transmission by An. arabiensis in Africa and other important vectors of residual transmission across the tropics. Improved control of predominantly outdoor residual transmission by An. arabiensis, and other modestly zoophagic vectors like Anopheles darlingi, which frequently enter but then rapidly exit from houses, may be readily achieved by improving existing technology for killing mosquitoes indoors.

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          Most cited references44

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          Increased proportions of outdoor feeding among residual malaria vector populations following increased use of insecticide-treated nets in rural Tanzania

          Background Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) represent the front-line tools for malaria vector control globally, but are optimally effective where the majority of baseline transmission occurs indoors. In the surveyed area of rural southern Tanzania, bed net use steadily increased over the last decade, reducing malaria transmission intensity by 94%. Methods Starting before bed nets were introduced (1997), and then after two milestones of net use had been reached-75% community-wide use of untreated nets (2004) and then 47% use of ITNs (2009)-hourly biting rates of malaria vectors from the Anopheles gambiae complex and Anopheles funestus group were surveyed. Results In 1997, An. gambiae s.l. and An. funestus mosquitoes exhibited a tendency to bite humans inside houses late at night. For An. gambiae s.l., by 2009, nocturnal activity was less (p = 0.0018). At this time, the sibling species composition of the complex had shifted from predominantly An. gambiae s.s. to predominantly An. arabiensis. For An. funestus, by 2009, nocturnal activity was less (p = 0.0054) as well as the proportion biting indoors (p < 0.0001). At this time, An. funestus s.s. remained the predominant species within this group. As a consequence of these altered feeding patterns, the proportion (mean ± standard error) of human contact with mosquitoes (bites per person per night) occurring indoors dropped from 0.99 ± 0.002 in 1997 to 0.82 ± 0.008 in 2009 for the An. gambiae complex (p = 0.0143) and from 1.00 ± <0.001 to only 0.50 ± 0.048 for the An. funestus complex (p = 0.0004) over the same time period. Conclusions High usage of ITNs can dramatically alter African vector populations so that intense, predominantly indoor transmission is replaced by greatly lowered residual transmission, a greater proportion of which occurs outdoors. Regardless of the underlying mechanism, the residual, self-sustaining transmission will respond poorly to further insecticidal measures within houses. Additional vector control tools which target outdoor biting mosquitoes at the adult or immature stages are required to complement ITNs and IRS.
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            Characterizing, controlling and eliminating residual malaria transmission

            Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) interventions can reduce malaria transmission by targeting mosquitoes when they feed upon sleeping humans and/or rest inside houses, livestock shelters or other man-made structures. However, many malaria vector species can maintain robust transmission, despite high coverage of LLINs/IRS containing insecticides to which they are physiologically fully susceptible, because they exhibit one or more behaviours that define the biological limits of achievable impact with these interventions: (1) Natural or insecticide-induced avoidance of contact with treated surfaces within houses and early exit from them, thus minimizing exposure hazard of vectors which feed indoors upon humans; (2) Feeding upon humans when they are active and unprotected outdoors, thereby attenuating personal protection and any consequent community-wide suppression of transmission; (3) Feeding upon animals, thus minimizing contact with insecticides targeted at humans or houses; (4) Resting outdoors, away from insecticide-treated surfaces of nets, walls and roofs. Residual malaria transmission is, therefore, defined as all forms of transmission that can persist after achieving full universal coverage with effective LLINs and/or IRS containing active ingredients to which local vector populations are fully susceptible. Residual transmission is sufficiently intense across most of the tropics to render malaria elimination infeasible without new or improved vector control methods. Many novel or improved vector control strategies to address residual transmission are emerging that either: (1) Enhance control of adult vectors that enter houses to feed and/or rest by killing, repelling or excluding them; (2) Kill or repel adult mosquitoes when they attack people outdoors; (3) Kill adult mosquitoes when they attack livestock; (4) Kill adult mosquitoes when they feed upon sugar or; (5) Kill immature mosquitoes in aquatic habitats. To date, none of these options has sufficient supporting evidence to justify full-scale programmatic implementation. Concerted investment in their rigorous selection, development and evaluation is required over the coming decade to enable control and, ultimately, elimination of residual malaria transmission. In the meantime, national programmes may assess options for addressing residual transmission under programmatic conditions through pilot studies with strong monitoring, evaluation and operational research components, similar to the Onchocerciasis Control Programme.
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              A global index representing the stability of malaria transmission.

              To relate stability of malaria transmission to biologic characteristics of vector mosquitoes throughout the world, we derived an index representing the contribution of regionally dominant vector mosquitoes to the force of transmission. This construct incorporated published estimates describing the proportion of blood meals taken from human hosts, daily survival of the vector, and duration of the transmission season and of extrinsic incubation. The result of the calculation was displayed globally on a 0.5 degrees grid. We found that these biologic characteristics of diverse vector mosquitoes interact with climate to explain much of the regional variation in the intensity of transmission. Due to the superior capacity of many tropical mosquitoes as vectors of malaria, particularly those in sub-Saharan Africa, antimalaria interventions conducted in the tropics face greater challenges than were faced by formerly endemic nations in more temperate climes.
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                Author and article information

                Contributors
                gkilleen@ihi.or.tz
                govella@ihi.or.tz
                dwilson@ihi.or.tz
                fredros@ihi.or.tz
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                19 April 2016
                19 April 2016
                2016
                : 15
                : 225
                Affiliations
                [ ]Environmental Health and Ecological Sciences Thematic Group, Ifakara Health Institute, Ifakara, Kilombero, Morogoro, United Republic of Tanzania
                [ ]Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK
                [ ]School of Public Health, University of the Witwatersrand, Johannesburg, Republic of South Africa
                Article
                1280
                10.1186/s12936-016-1280-z
                4837512
                27093890
                01531cda-c15e-4c78-a606-35cb273ef426
                © Killeen et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 December 2015
                : 12 April 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 102350/Z/13/Z
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP52644
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004963, Seventh Framework Programme (BE);
                Award ID: 265660
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Infectious disease & Microbiology
                plasmodium,malaria,anopheles,mosquito,vector control,residual transmission

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