Transcriptomic analysis of resistance and short-term induction response to pyrethroids, in Anopheles coluzzii legs

Abstract Background Insecticide-treated bed nets and indoor residual spraying comprise the major control measures against Anopheles gambiae sl, the dominant vector in sub-Saharan Africa. The primary site of contact with insecticide is through the mosquitoes’ legs, which represents the first barrier insecticides have to bypass to reach their neuronal targets. Proteomic changes and leg cuticle modifications have been associated with insecticide resistance that may reduce the rate of penetration of insecticides. Here, we performed a multiple transcriptomic analyses focusing on An. coluzzii legs. Results Firstly, leg-specific enrichment analysis identified 359 genes including the pyrethroid-binder SAP2 and 2 other chemosensory proteins, along with 4 ABCG transporters previously shown to be leg enriched. Enrichment of gene families included those involved in detecting chemical stimuli, including gustatory and ionotropic receptors and genes implicated in hydrocarbon-synthesis. Subsequently, we compared transcript expression in the legs of a highly resistant strain (VK7-HR) to both a strain with very similar genetic background which has reverted to susceptibility after several generations without insecticide pressure (VK7-LR) and a lab susceptible population (NG). Two hundred thirty-two differentially expressed genes (73 up-regulated and 159 down-regulated) were identified in the resistant strain when compared to the two susceptible counterparts, indicating an over-expression of phase I detoxification enzymes and cuticular proteins, with decrease in hormone-related metabolic processes in legs from the insecticide resistant population. Finally, we analysed the short-term effect of pyrethroid exposure on An. coluzzii legs, comparing legs of 1 h-deltamethrin-exposed An. coluzzii (VK7-IN) to those of unexposed mosquitoes (VK7-HR) and identified 348 up-regulated genes including those encoding for GPCRs, ABC transporters, odorant-binding proteins and members of the divergent salivary gland protein family. Conclusions The data on An. coluzzii leg-specific transcriptome provides valuable insights into the first line of defense in pyrethroid resistant and short-term deltamethrin-exposed mosquitoes. Our results suggest that xenobiotic detoxification is likely occurring in legs, while the enrichment of sensory proteins, ABCG transporters and cuticular genes is also evident. Constitutive resistance is primarily associated with elevated levels of detoxification and cuticular genes, while short-term insecticide-induced tolerance is linked with overexpression of transporters, GPCRs and GPCR-related genes, sensory/binding and salivary gland proteins.

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Transcriptomic analysis of resistance and short-term induction response to pyrethroids, in Anopheles coluzzii legs

10.21203/rs.3.rs-904452/v1 ◽

2021 ◽

Author(s):

Mary Kefi ◽

Jason Charamis ◽

Vasileia Balabanidou ◽

Panagiotis Ioannidis ◽

Hilary Ranson ◽

...

Keyword(s):

Salivary Gland ◽

Resistant Strain ◽

Indoor Residual Spraying ◽

Control Measures ◽

Sub Saharan Africa ◽

Detoxification Enzymes ◽

Bed Nets ◽

Anopheles Coluzzii ◽

Short Term ◽

Susceptible Population

Abstract BackgroundInsecticide-treated bed nets and indoor residual spraying comprise the major control measures against Anopheles gambiae sl, the dominant vector in sub-Saharan Africa. The primary site of contact with insecticide is through the mosquitoes’ legs, which represents the first barrier insecticides have to bypass to reach their neuronal targets. Proteomic changes and leg cuticle modifications have been associated with insecticide resistance that may reduce the rate of penetration of insecticides. Here, we performed a multiple transcriptomic analyses focusing on An. coluzzii legs. ResultsFirstly, leg-specific enrichment analysis identified 359 genes including the pyrethroid-binder SAP2 and 2 other chemosensory proteins, along with 4 ABCG transporters previously shown to be leg enriched. Enrichment gene families included those involved in detecting chemical stimuli including gustatory and ionotropic receptors and genes implicated in hydrocarbon-synthesis. Subsequently, we compared transcript expression in the legs of a highly resistant strain (VK7-HR) to both a strain with very similar genetic background which has reverted to susceptibility after several generations without insecticide pressure (VK7-LR) and a lab susceptible population. 232 differentially expressed genes (73 up-regulated and 159 down-regulated) were identified in the resistant strain when compared to the two susceptible counterparts, indicating an over-expression of phase I detoxification enzymes and cuticular proteins, with decrease in hormone-related metabolic processes in legs from the insecticide resistant population. Finally, we analysed the short-term effect of pyrethroid exposure on An. coluzzii legs, comparing 1hour-deltamethrin-exposed (VK7-IN) to unexposed (VK7-HR) leg transcriptomes and identified 348 up-regulated genes including those encoding for GPCRs, ABC transporters, odorant-binding proteins and members of the divergent salivary gland protein family. ConclusionsThe data on An. coluzzii leg-specific transcriptome provides valuable insights into the first line of defense in pyrethroid resistant and short-term deltamethrin-exposed mosquitoes. Our results suggest that xenobiotic detoxification is likely occurring in legs, while the enrichment of sensory proteins, ABCG transporters and cuticular genes is also evident. Constitutive resistance is primarily associated with elevated levels of detoxification and cuticular genes, while short-term insecticide-induced tolerance is linked with overexpression of transporters, GPCRs and GPCR-related genes, sensory/binding and salivary gland proteins.

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Genetic diversity of Anopheles coustani in high malaria transmission foci in southern and central Africa

10.1101/2020.04.04.020537 ◽

2020 ◽

Author(s):

Ilinca I. Ciubotariu ◽

Christine M. Jones ◽

Tamaki Kobayashi ◽

Thierry Bobanga ◽

Mbanga Muleba ◽

...

Keyword(s):

Genetic Diversity ◽

Malaria Transmission ◽

Malaria Parasite ◽

Indoor Residual Spraying ◽

Control Measures ◽

Sub Saharan Africa ◽

Health Concern ◽

Malaria Vectors ◽

Bed Nets ◽

Internal Transcribed Spacer Region

AbstractDespite ongoing malaria control efforts implemented throughout sub-Saharan Africa, malaria remains an enormous public health concern. Current interventions such as indoor residual spraying with insecticides and use of insecticide-treated bed nets are aimed at targeting the key malaria vectors that are primarily endophagic and endophilic. While these control measures have resulted in a substantial decline in malaria cases and continue to impact indoor transmission, the importance of alternative vectors for malaria transmission has been largely neglected. Anopheles coustani, an understudied vector of malaria, is a species previously thought to exhibit mostly zoophilic behavior. However, recent studies from across Africa bring to light the contribution of this and ecologically similar anopheline species to human malaria transmission. Like many of these understudied species, An. coustani has greater anthropophilic tendencies than previously appreciated, is often both endophagic and exophagic, and carries Plasmodium falciparum sporozoites. These recent developments highlight the need for more studies throughout the geographic range of this species and the potential need to control this vector. The aim of this study was to explore the genetic variation of An. coustani mosquitoes and the potential of this Anopheles species to contribute to malaria parasite transmission in high transmission settings in Nchelenge District, Zambia, and the Kashobwe and Kilwa Health Zones in Haut-Katanga Province, the Democratic Republic of the Congo (DRC). Morphologically identified An. coustani specimens that were trapped outdoors in these study sites were analyzed by PCR and sequencing for species identification and blood meal sources, and malaria parasite infection was determined by ELISA and qPCR. Fifty specimens were confirmed to be An. coustani by the analysis of mitochondrial DNA cytochrome c oxidase subunit I (COI) and ribosomal internal transcribed spacer region 2 (ITS2). Further, maximum likelihood phylogenetic analysis of COI and ITS2 sequences revealed two distinct phylogenetic groups within this relatively small regional collection. Our findings indicate that both An. coustani groups have anthropophilic and exophagic habits and come into frequent contact with P. falciparum, suggesting that this potential alternative malaria vector might elude current vector controls in Northern Zambia and Southern DRC. This study sets the groundwork for more thorough investigations of bionomic characteristics and genetic diversity of An. coustani and its contribution to malaria transmission in these regions.

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Genetic Diversity of Anopheles coustani (Diptera: Culicidae) in Malaria Transmission Foci in Southern and Central Africa

Journal of Medical Entomology ◽

10.1093/jme/tjaa132 ◽

2020 ◽

Vol 57 (6) ◽

pp. 1782-1792

Author(s):

Ilinca I Ciubotariu ◽

Christine M Jones ◽

Tamaki Kobayashi ◽

Thierry Bobanga ◽

Mbanga Muleba ◽

...

Keyword(s):

Malaria Parasite ◽

Central Africa ◽

Indoor Residual Spraying ◽

Control Measures ◽

Sub Saharan Africa ◽

Health Concern ◽

Malaria Vectors ◽

Bed Nets ◽

Phylogenetic Groups ◽

Internal Transcribed Spacer Region

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The Economics of Malaria Prevention

Oxford Research Encyclopedia of Economics and Finance ◽

10.1093/acrefore/9780190625979.013.252 ◽

2018 ◽

Author(s):

Bénédicte Apouey ◽

Gabriel Picone ◽

Joshua Wilde

Keyword(s):

Financial Constraints ◽

Intermittent Preventive Treatment ◽

Indoor Residual Spraying ◽

Preventive Treatment ◽

Malaria Prevention ◽

Sub Saharan Africa ◽

Bed Nets ◽

Preventive Behaviors ◽

Mosquito Net ◽

Positive Externalities

Malaria is a potentially life-threatening disease transmitted through the bites of female anopheline mosquitos infected with protozoan parasites. Malaria remains one of the major causes of mortality by infectious disease: in 2015, there were an estimated 212 million cases and 429,000 deaths globally, according to the 2016 World Malaria Report. Children under 5 years in sub-Saharan Africa bear the greatest burden of the disease worldwide. However, most of these cases could be prevented or treated. Several methods are highly effective in preventing malaria: in particular, sleeping under an insecticide-treated mosquito net (ITN), indoor residual spraying (IRS), and taking intermittent preventive treatment for pregnant women (IPTp). Regarding treatment, artesiminin-based combination therapy (ACT) is recommended as first-line treatment in many countries. Compared with other actions, malaria prevention behaviors have some specific features. In particular, they produce public health externalities. For example, bed net usage creates positive externalities since bed nets not only directly protect the user, but also reduce transmission probabilities through reduction in the number of disease hosts, and in the case of ITNs, reduction of the vector itself. In contrast, ACT uptake creates both positive externalities when individuals with malaria are treated, and negative externalities in the case of overtreatment that speeds up the spread of long-run parasite resistance. Moreover, ITNs, IPTp, and ACTs are experience goods (meaning individuals only ascertain their benefits upon usage), which implies that current preventive actions are linked to past preventive behaviors. Malaria prevention and eradication produce unambiguous benefits across various domains: economic conditions, educational outcomes, survival, fertility, and health. However, despite the high private returns to prevention, the adoption of antimalarial products and behaviors remains relatively low in malaria-affected areas. A variety of explanations have been proposed for low adoption rates, including financial constraints, high prices, and absence of information. While recent studies highlight that all of these factors play a role, the main barrier to adoption is probably financial constraints. This finding has implications regarding the appropriate pricing policy for these health products. In addition, there is a shortage of causally identified research on the effect of cultural and psychological barriers to the adoption of preventive behaviors. The literature which does exist is from a few randomized control trials of few individuals in very specific geographic and cultural contexts, and may not be generalizable. As a result, there are still ample opportunities for research on applying the insights of behavioral economics to malaria-preventive behavior in particular. Moreover, little research has been done on the supply side, such as whether free or heavily subsidized distribution of prevention technologies is fiscally sustainable; finding effective methods to solve logistical problems which lead to shortages and ineffective alternative treatments to fill the gap; or training sufficient healthcare workers to ensure smooth and effective delivery. Given these gaps in the literature, there are still multiple fruitful avenues for research which may have a first-order effect on reducing the prevalence of malaria in the developing world.

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Reduction of malaria vector mosquitoes in a large-scale intervention trial in rural Burkina Faso using Bti based larval source management

Malaria Journal ◽

10.1186/s12936-019-2951-3 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 8

Author(s):

Peter Dambach ◽

Till Baernighausen ◽

Issouf Traoré ◽

Saidou Ouedraogo ◽

Ali Sié ◽

...

Keyword(s):

Malaria Vector ◽

Large Scale ◽

Intermittent Preventive Treatment ◽

Indoor Residual Spraying ◽

Control Measures ◽

Sub Saharan Africa ◽

Intervention Period ◽

Selective Treatment ◽

Breeding Sites ◽

The Impact

Abstract Background Malaria remains one of the most important causes of morbidity and death in sub-Saharan Africa. Along with early diagnosis and treatment of malaria cases and intermittent preventive treatment in pregnancy (IPTp), vector control is an important tool in the reduction of new cases. Alongside the use of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), targeting the vector larvae with biological larvicides, such as Bacillus thuringiensis israelensis (Bti) is gaining importance as a means of reducing the number of mosquito larvae before they emerge to their adult stage. This study presents data corroborating the entomological impact of such an intervention in a rural African environment. Methods The study extended over 2 years and researched the impact of biological larviciding with Bti on malaria mosquitoes that were caught indoors and outdoors of houses using light traps. The achieved reductions in female Anopheles mosquitoes were calculated for two different larviciding choices using a regression model. Results In villages that received selective treatment of the most productive breeding sites, the number of female Anopheles spp. dropped by 61% (95% CI 54–66%) compared to the pre-intervention period. In villages in which all breeding sites were treated, the number of female Anopheles spp. was reduced by 70% (95% CI 64–74%) compared to the pre-intervention period. Conclusion It was shown that malaria vector abundance can be dramatically reduced through larviciding of breeding habitats and that, in many geographical settings, they are a viable addition to current malaria control measures.

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Analysis of Control Interventions against Malaria in communities with Limited Resources

Analele Universitatii Ovidius Constanta - Seria Matematica ◽

10.2478/auom-2021-0019 ◽

2021 ◽

Vol 29 (2) ◽

pp. 71-91

Author(s):

E.A. Bakare ◽

B.O. Onasanya ◽

S. Hoskova-Mayerova ◽

O. Olubosede

Keyword(s):

Optimal Control ◽

Malaria Transmission ◽

Control Strategies ◽

Indoor Residual Spraying ◽

Control Measures ◽

Limited Resources ◽

Effective Control ◽

Bed Nets ◽

Multiple Control ◽

Potential Impact

Abstract The aim of this paper is to analyse the potential impact of multiple current interventions in communities with limited resources in order to obtain optimal control strategies and provide a basis for future predictions of the most effective control measures against the spread of malaria. We developed a population-based model of malaria transmission dynamics to investigate the effectiveness of five different interventions. The model captured both the human and the mosquito compartments. The control interventions considered were: educational campaigns to mobilise people for diagnostic test and treatment and to sleep under bed nets; treatment through mass drug administration; indoor residual spraying(IRS) with insecticide to reduce malaria transmission; insecticide treated net (ITN) to reduce morbidity; and regular destruction of mosquito breeding sites to reduce the number of new mosquito and bites/contact at dusks and dawn. Analysis of the potential impact of the multiple control interventions were carried out and the optimal control strategies that minimized the number of infected human and mosquito and the cost of applying the various control interventions were determined.

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Accounting for regional transmission variability and the impact of malaria control interventions in Ghana: A population level mathematical modelling approach.

10.21203/rs.2.22332/v1 ◽

2020 ◽

Author(s):

Timothy Awine ◽

Sheetal P Silal

Keyword(s):

Malaria Control ◽

Malaria Incidence ◽

Protective Efficacy ◽

Indoor Residual Spraying ◽

Information Management System ◽

Control Measures ◽

Bed Nets ◽

Model Parameters ◽

Insecticide Treated Bed Nets ◽

The Impact

Abstract Background Assessing the effectiveness of malaria control measures in Ghana will require taking transmission dynamics of the disease into account given the influence of climate variability in the region of interest. The impact of preventative interventions on malaria incidence and the prospects of meeting program timelines in Ghana have been investigated using mathematical models based on regionally diverse climatic zones. Methods An ordinary non-linear differential equation model with its associated rate parameters was developed incorporating the transitions between various disease compartments for three ecological zones in Ghana. Model parameters were estimated using data captured on the District Health Information Management System in Ghana from 2008 to 2017.The impact of insecticide treated bed nets and indoor residual spraying on the incidence of malaria were simulated at various levels of coverage and protective effectiveness in each ecological zone. To fit the model, Approximate Bayesian Computational sampling approach was adopted. Results Increasing the coverage levels of both long lasting insecticide treated bed nets or indoor residual spraying activities without a corresponding increase in their proper use or patronage does not impact highly on averting predicted incidence of malaria in Ghana. Improving on the protective efficacy of long lasting insecticide treated bed nets through proper usage could lead to substantial reductions in the predicted incidence of malaria. Similar results were obtained with indoor residual spraying across all zones. Conclusions Projected goals set in the National Strategic plan for malaria control 2014-2020 as well as WHO targets for malaria pre-elimination by 2030 are only likely be achieved if a substantial improvement in treated bed net usage is achieved coupled with targeted deployment of indoor residual spraying with high efficacy.

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Mosquitoes and Malaria Control – A Complex Problem for Entomologists to Unravel

Outlooks on Pest Management ◽

10.1564/v30_oct_07 ◽

2019 ◽

Vol 30 (5) ◽

pp. 213-216

Author(s):

Basil Brooke

Keyword(s):

Vector Control ◽

Malaria Vector ◽

Malaria Control ◽

Life Stage ◽

Indoor Residual Spraying ◽

Transmission Intensity ◽

Sub Saharan Africa ◽

Malaria Vectors ◽

Bed Nets ◽

Vector Species

The control of malaria transmitting mosquitoes hinges on accurate species identification. This enables assessments of insecticide susceptibilities and important behavioural characteristics (such as feeding and resting behaviours) by species, leading to the design of coherent insecticide-based control strategies that can be enhanced by additional methodologies for malaria elimination. Malaria is a mosquito-borne parasitic disease that affects many vertebrates including humans. Prior to the 20th century the human malarias (Plasmodium falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi) occurred in tropical and temperate regions but their distribution has since reduced to the tropical belt with by far the highest incidence in sub-Saharan Africa. Global incidence for 2017 was estimated by the WHO at 219 million cases corresponding to 435 000 deaths. It is also estimated that investment in malaria control and elimination amounted to $3.1 billion in 2017. The control (and elimination) of malaria largely hinges on the suppression of mosquito vectors, accurate diagnosis and case detection, and case management using appropriate antimalarial drug regimens. Controlling malaria vector mosquitoes (and of course other mosquito-borne diseases) means being able to identify that which needs to be controlled. This is not unlike the maxim of knowing one's enemy, and disease vector control is often phrased in militaristic terms. The arsenal of tools in the war against malaria vectors includes insecticides, bed nets, repellents, larvicides, endectocides, toxic baits and even modified genes. This call to arms against the transmitters of a deadly disease presupposes that the enemy can be identified, which, unfortunately, is not as easy as it sounds. Identifying malaria vectors to species has posed a significant challenge ever since Ronald Ross and Giovanni Grassi implicated dappled-winged Anopheles mosquitoes in malaria transmission. They could not have known the Pandora's Box they had opened, because several Anopheles species are cryptic. Many hide in cryptic species complexes and groups that confound straightforward morphological methods of identifying them. A species complex is a group of morphologically identical species that are very closely related, but nevertheless vary significantly in their feeding and resting behaviours, and mate assortatively (i.e. they recognise and tend only to mate with conspecific partners) enough that hybridisations between them are rare. Many member species of these complexes are sufficiently diverged that cross-mating between them yields infertile or non-viable offspring, but not in all cases. A species group is a looser assortment of related species whose morphological features match to a point where they are very nearly identical, often requiring specimens from more than one life stage to identify them. They also mate assortatively, and hybrids are rarer or simply never occur. The problem for malaria control is that several vector species, including many primary vectors, are members of cryptic complexes or groups. These invariably contain vector and non-vector species, requiring a complex and laborious system to unravel them and ascribe unambiguous genetic methods for their identification. Added to this complexity is the possibility that any Anopheles. species that takes human blood is a potential vector of the human malarias, with the added caveat that not all populations within a species are vectors. Some member species, and even populations within a species, feed either exclusively on humans (anthropophagy) and are potentially high transmission intensity vectors, or exclusively on livestock animals (zoophagy) making them non-vectors, or take blood from a range of sources including humans, becoming potential vectors of low to medium transmission intensity. An added layer of complexity is genetic heterogeneity between populations within a species. It can be argued that this complexity is not necessarily a problem for malaria control. After all, the aim of suppressing or even eliminating vector populations is the interruption of transmission, regardless of what species they are. But mosquito adaptability dictates otherwise. This is because the primary method of malaria vector control is deployment of specially formulated insecticides against adult mosquitoes, either by indoor residual spraying (IRS) or the treatment of bed nets. Mosquito adaptability has enabled a powerful response to these interventions, with resistance to insecticides becoming so widespread that fully insecticide susceptible malaria vector populations are now quite rare.

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MALARIA IN CHILDREN

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2012.073 ◽

2012 ◽

Vol 4 (1) ◽

pp. e2012073 ◽

Cited By ~ 31

Author(s):

Richard-Fabian Schumacher ◽

Elena Spinelli

Keyword(s):

Malaria Control ◽

Child Death ◽

Severe Anaemia ◽

Control Measures ◽

Childhood Mortality ◽

Sub Saharan Africa ◽

Bed Nets ◽

Resistance Patterns ◽

Sub Saharan ◽

Long Acting

This review is focused on childhood specific aspects of malaria, especially in resource-poor settings. We summarise the actual knowledge in the field of epidemiology, clinical presentation, diagnosis, management and prevention.These aspects are important as malaria is responsible for almost a quarter of all child death in sub-Saharan Africa. Malaria control is thus one key intervention to reduce childhood mortality, especially as malaria is also an important risk factor for other severe infections, namely bacteraemia.In children symptoms are more varied and often mimic other common childhood illness, particularly gastroenteritis, meningitis/encephalitis, or pneumonia. Fever is the key symptom, but the characteristic regular tertian and quartan patterns are rarely observed. There are no pathognomonic features for severe malaria in this age group. The well known clinical (fever, impaired consciousness, seizures, vomiting, respiratory distress) and laboratory (severe anaemia, thrombocytopenia, hypoglycaemia, metabolic acidosis, and hyperlactataemia) features of severe falciparum malaria in children, are equally typical for severe sepsis.Appropriate therapy (considering species, resistance patterns and individual patient factors) – possibly a drug combination of an artemisinin derivative with a long-acting antimalarial drug - reduces treatment duration to only three days and should be urgently started.While waiting for the results of ongoing vaccine trials, all effort should be made to better implement other malaria-control measures like the use of treated bed-nets and new chemoprophylaxis regimens.

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Accounting for regional transmission variability and the impact of malaria control interventions in Ghana: A population level mathematical modelling approach.

10.21203/rs.2.22332/v2 ◽

2020 ◽

Author(s):

Timothy Awine ◽

Sheetal P Silal

Keyword(s):

Malaria Control ◽

Malaria Incidence ◽

Protective Efficacy ◽

Indoor Residual Spraying ◽

Information Management System ◽

Control Measures ◽

Bed Nets ◽

Model Parameters ◽

Insecticide Treated Bed Nets ◽

The Impact

Abstract Background Assessing the effectiveness of malaria control measures in Ghana will require taking transmission dynamics of the disease into account given the influence of climate variability in the region of interest. The impact of preventative interventions on malaria incidence and the prospects of meeting program timelines in Ghana were investigated using mathematical models based on regionally diverse climatic zones. Methods An ordinary non-linear differential equation models with their associated rate parameters were developed incorporating the transitions between various disease compartments for three ecological zones in Ghana. Models were fitted using data from the District Health Information Management System in Ghana from 2008 to 2017 and historical intervention coverage levels. To calibrate the models, Approximate Bayesian Computational sampling approach with a distance based rejection criteria was adopted. A leave-one-out approach was used to validate model parameters and the most sensitive evaluated using a multivariate regression sensitivity analysis. The impact of insecticide treated bed nets and their usage and indoor residual spraying as well as their protective efficacy on the incidence of malaria were simulated at various levels of coverage and protective effectiveness in each ecological zone to investigate the prospects of achieving goals of the malaria control strategy for 2014-2020. Results Increasing the coverage levels of both long lasting insecticide treated bed nets and indoor residual spraying activities without a corresponding increase in their recommended usage does not impact highly on averting predicted incidence of malaria. Improving upon the protective efficacy of long lasting insecticide treated bed nets through proper usage could lead to substantial reductions in the predicted incidence of malaria. Similar results were obtained with indoor residual spraying across all zones.Conclusions Projected goals set in the national strategic plan for malaria control 2014-2020 as well as WHO targets for malaria pre-elimination by 2030 are only likely to be achieved if a substantial improvement in treated bed net usage is achieved coupled with targeted deployment of indoor residual spraying with high community acceptability and efficacy. Key words: model, malaria, interventions, long lasting insecticide bednets, indoor residual spraying

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