Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation

Chaccour, Carlos; Ng’habi, Kija; Abizanda, Gloria; Barrio, Ángel Irigoyen; Aldaz, Azucena; Okumu, Fredros O.; Slater, Hannah; Pozo, J.L. del; Killeen, Gerry F.

doi:10.1186/s13071-018-2872-y

Cited by 62 publications

(60 citation statements)

References 40 publications

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“…An alternative to increasing the concentration of the delivered dose, a number of adjuvants have been reported to improve the absorption or extend the half-life of systemic insecticides, such as lipids for lipophilic drugs (48, 49) or efflux pump inhibitors that remove xenobiotics (50–54), respectively. A third promising solution is the development of sustained-release devices, which have been shown to maintain a target concentration for 280 days in livestock (55).…”

Section: Discussionmentioning

confidence: 99%

Optimizing systemic insecticide use to improve malaria control

Meredith

Furuya‐Kanamori

Yakob

2019

Preprint

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9Long lasting insecticidal nets and indoor residual sprays have significantly reduced 10 the burden of malaria. However, several hurdles remain before elimination can be achieved: 11 mosquito vectors have developed resistance to public health insecticides, including 12 pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. 13 Systemic insecticides, drugs applied directly to blood-hosts to kill mosquitoes that take a 14 blood meal, offer a promising vector control option. To date, most studies focus on 15 repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that 16 over-dependence on a single drug will inevitably repeat past experiences with the rapid 17 spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic 18 insecticides used for mass drug administration would improve this strategy's sustainability. 19Here, a review was conducted to identify systemic insecticide candidates and consolidate 20 their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated 21 vector control options and different dosing regimens on malaria transmission reduction are 22 illustrated through a mathematical model simulation. The review identified drugs from four 23 classes commonly used in livestock and companion animals: avermectics, milbemycins, 24 isoxazolines, and spinosyns. Simulations predicted that isoxazoline and spinosyn drugs were 25 promising candidates for mass drug administration, as they were predicted to need less 26 frequent application than avermectins and milbemycins to maintain mosquitocidal blood 27 concentrations. These findings will provide a guide for investigating and applying different 28 systemic insecticides to achieve better mosquito control strategies. 29 30 Significance: 32 The widespread use of long lasting insecticidal nets (LLINs) and indoor residual spray 33 has selected for mosquitoes that are resistant to pyrethroids or avoid exposure by feeding 34 outdoors or on livestock. Systemic insecticides, drugs that render a host's blood toxic to 35 feeding mosquitoes, could be an effective control strategy for mosquitoes with pyrethroid 36 resistance and/or outdoor feeding tendencies. Here, a number of existing systemic insecticide 37 candidates are identified and their pharmacokinetic properties in different drug-host-route 38 scenarios consolidated. These data were used to parameterise a mathematical model that 39 illustrated the projected gains achievable in malaria control programmes already employing 40 LLINs. The findings provide a guide for investigating and applying different systemic 41 insecticides to improve mosquito control strategies and reduce malaria transmission. 42 Introduction: 43 Long lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have played 44 significant roles in reducing the burden of malaria (1, 2). However, several hurdles remain 45 before elimination can be achieved. First, pyrethroids are heavily used in LLINs and, 46 previousl...

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Section: Discussionmentioning

confidence: 99%

Optimizing systemic insecticide use to improve malaria control

Meredith

Furuya‐Kanamori

Yakob

2019

Preprint

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“…This has significant implications for vector control. For example, initial field studies involving endectocidal applications on livestock have shown encouraging results in terms of long-lasting mosquitocidal effects [14, 15]. However, previously this strategy has only been considered for targeting zoophilic malaria vector species (e.g.…”

Section: Discussionmentioning

confidence: 99%

Assessing the blood-host plasticity and dispersal rate of the malaria vector Anopheles coluzzii

Orsborne

Furuya‐Kanamori

Jeffries

et al. 2018

Preprint

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25Difficulties with observing the dispersal of insect vectors in the field have hampered understanding of 26 several aspects of their behaviour linked to disease transmission. Here, a novel method based on 27 detection of blood-meal sources is introduced to inform two critical and understudied mosquito 28 behaviours: plasticity in the malaria vector's blood-host choice and vector dispersal. Strategically 29 located collections of Anopheles coluzzii from a malaria-endemic village of southern Ghana showed 30 statistically significant variation in host species composition of mosquito blood-meals. Trialling a new 31 sampling approach gave the first estimates for the remarkably local spatial scale across which host 32 choice is plastic. Using quantitative PCR, the blood-meal digestion was then quantified for field-caught 33 mosquitoes and calibrated according to timed blood digestion in colony mosquitoes. We demonstrate 34 how this new 'molecular Sella score' approach can be used to estimate the dispersal rate of blood-35 feeding vectors caught in the field. 36 37 Keywords: blood meal analysis, host preference, mosquito, biting preference, blood index 38 39 40 41 42 43 44 45 46

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“…In addition, farm animal ownership has been described as a risk factor for human malaria infection in areas where mosquitoes feed on both animals and humans; thus, the administration of ivermectin to both sources of blood has been proposed. [22][23][24][25] Conveniently, ivermectin is an antiparasitic drug already broadly used in human and veterinary contexts to treat a range of endo-and ectoparasites. 26 Ivermectin MDA would target mosquitoes feeding on treated subjects (humans or animals) regardless of their biting patterns.…”

Section: Product Development Needed To Repurpose Ivermectin To Malariamentioning

confidence: 99%

A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool

Billingsley

Binka

Chaccour

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.

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Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation

Cited by 62 publications

References 40 publications

Optimizing systemic insecticide use to improve malaria control

Optimizing systemic insecticide use to improve malaria control

Assessing the blood-host plasticity and dispersal rate of the malaria vector Anopheles coluzzii

A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool

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