Ivermectin to reduce malaria transmission III. Considerations regarding regulatory and policy pathways

Chaccour, Carlos; Rabinovich, N. Regina

doi:10.1186/s12936-017-1803-2

Cited by 23 publications

(21 citation statements)

References 46 publications

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“…Currently, ivermectin is used to treat other tropical diseases, such as onchocerciasis, lymphatic filariasis, and strongyloidiasis (2), and it is also active against scabies and lice (6,7). Recently, ivermectin has been under investigation as a complementary tool for blocking and controlling malaria transmission (8,9).…”

mentioning

confidence: 99%

Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro

Carvalho

Sandri

Melo

et al. 2019

Antimicrob Agents Chemother

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Ivermectin is the drug of choice for many parasitic infections, with more than one billion doses being distributed in onchocerciasis programs. The drug has been put into focus recently by the malaria community because of its potential to kill blood-sucking mosquitoes, thereby reducing malaria transmission. However, the activity of ivermectin against the malaria parasite itself has been only partly investigated. This study aimed to investigate the in vitro activity of ivermectin against asexual and sexual stages of Plasmodium falciparum. Both asexual and late-stage gametocytes were incubated with ivermectin and control drugs in vitro. The growthinhibiting effects were assessed for asexual stages of different Plasmodium falciparum laboratory strains and culture-adapted clinical isolates using the histidine-rich protein 2 enzyme-linked immunosorbent assay technique. The effect against stage IV/V gametocytes was evaluated based on ATP quantification. Ivermectin showed activities at nanomolar concentrations against asexual stages (50% inhibitory concentration of ϳ100 nM) and stage IV/V gametocytes (500 nM) of P. falciparum. Stagespecific assays suggested that ivermectin arrests the parasite cycle at the trophozoite stage. Ivermectin might add a feature to its "wonder drug" properties with activity against asexual stages of the malaria parasite Plasmodium falciparum. The observed activities might be difficult to reach with current regimens but will be more relevant with future high-dose regimens under investigation. Further studies should be performed to confirm these results in vitro and in vivo.

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confidence: 99%

Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro

Carvalho

Sandri

Melo

et al. 2019

Antimicrob Agents Chemother

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“…In addition, there are several manufacturers of active pharmaceutical ingredients (APIs) with self-reported productions above 50 tons per year. 18 Most of the global manufacturing of APIs is of veterinary grade, whereas the process for human APIs requires additional quality controls and documentation. As guidance, only around 2.5 tons of APIs per year are needed to treat 180 million people with the current single-dose onchocerciasis regimen, and thus, the pathway to increased supply can be managed if the increase in demand is communicated, planned, and phased.…”

Section: Transition and Implementation At Scalementioning

confidence: 99%

“…15,16 More recently, the results of several modeling, pharmacological, and insectary-based research studies, as well as several clinical and field MDA trials, have positioned ivermectin as a first-inclass tool to enhance malaria control. [17][18][19] After recognizing the potential for endectocides to tackle the issue of residual transmission, the WHO held a technical consultation on ivermectin in 2016. Subsequently, preferred product characteristics (PPCs) for endectocides against malaria were published with ivermectin as a reference product.…”

Section: Introductionmentioning

confidence: 99%

“…A launch meeting took place at the 2017 Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) in Baltimore (US). The multidisciplinary team included global health experts whose backgrounds encompassed entomology, infectious diseases, vaccines, veterinary, environmental sciences, ethics, financing systems, clinical trials, supply chain management, and scaling-up of interventions, among others (see full list of contributors on pages [18][19].…”

Section: Introductionmentioning

confidence: 99%

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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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“…Another approach for controlling mosquitoes is based on endectocide ivermectin, a molecule that has been used for more than 30 years to control lymphatic filariasis. This molecule remains in the human bloodstream following a standard oral dose and can kill Anopheles mosquitoes that feed on the blood of medicated persons [76][77][78][79]. Controlling vector mosquito populations is a difficult task and so the addition of new technologies to be considered for IVM will help improve the effectiveness of vector-borne disease transmission [80][81][82][83].…”

Section: New Tools To Fight Malaria Vectors In An Ivm Perspectivementioning

confidence: 99%

Newer Approaches for Malaria Vector Control and Challenges of Outdoor Transmission

Beier¹,

Wilke²,

Benelli³

2018

Towards Malaria Elimination - A Leap Forward

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The effective and reliable management of malaria vectors is still a global challenge. Recently, it has been noted that the first vaccine against Plasmodium falciparum malaria, RTS,S/AS01 showed only transient protection, particularly in infants, and rapid resistance has been developing to artemisinin-based drugs. Therefore, the control of malaria mosquito vectors according to strategies of integrated vector management (IVM) is receiving emphasis. A rather wide number of novel mosquito control tools have been tested, including attractive toxic sugar baits, eave tubes, nano-synthesized pesticides loaded with microbial-and plant-borne compounds, biocontrol agents with little nontarget effects, new adult repellents, oviposition deterrents, and even acoustic larvicides. However, their real-world applications remain limited. Most National Malaria Control Programs in Africa still rely on indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) to reduce malaria incidence but generally have insufficient impact on malaria prevalence. Here, we focus on facts, trends, and current challenges in the employment of the above-mentioned vector control tools in the fight against malaria. We emphasize the needs for better vector control tools used in IVM to overcome the challenges posed by outdoor transmission and growing levels of insecticide resistance, which are threatening the efficacy of LLINs and IRS.

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Ivermectin to reduce malaria transmission III. Considerations regarding regulatory and policy pathways

Cited by 23 publications

References 46 publications

Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro

Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro

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

Newer Approaches for Malaria Vector Control and Challenges of Outdoor Transmission

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