Ivermectin is a broad-spectrum antiparasitic agent that interferes with glutamate-gated chloride channels found in invertebrates but not in vertebrate species. Mass drug administration (MDA) with ivermectin-based regimes has been a mainstay of elimination efforts targeting onchocerciasis and lymphatic filariasis for more than 3 decades. More recently, interest in the use of ivermectin to control other neglected tropical diseases (NTDs) such as soil-transmitted helminths and scabies has grown.
Finding new chemotherapeutic interventions to treat malaria through repurposing of time-tested drugs and rigorous design of new drugs using tools of rational drug design remains one of the most sought strategies at the disposal of medicinal chemists.
Malaria control primarily depends on two vector control strategies: indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs). Both IRS and LLIN target indoor-biting mosquitoes. However, some of the most important malaria vectors have developed resistance against the chemical compounds used in IRS and LLINs. Insecticide-induced behavioural changes in vectors, such as increased outdoor feeding on cattle and other animals, also limit the effectiveness of these strategies. Novel vector control strategies must therefore be found to complement IRS and LLINs. A promising tool is the use of cattle-applied endectocides. Endectocides are broad-spectrum systemic drugs that are effective against a range of internal nematodes parasites and blood-feeding arthropods. The aim of this study was to investigate the effect of two endectocide drugs, injectable ivermectin and topical fipronil, on the survival and fecundity of zoophilic Anopheles arabiensis.
Cluster-randomized trials allow for the evaluation of a community-level or group-/cluster-level intervention. For studies that require a cluster-randomized trial design to evaluate cluster-level interventions aimed at controlling vector-borne diseases, it may be difficult to assess a large number of clusters while performing the additional work needed to monitor participants, vectors, and environmental factors associated with the disease. One such example of a cluster-randomized trial with few clusters was the “efficacy and risk of harms of repeated ivermectin mass drug administrations for control of malaria” trial. Although previous work has provided recommendations for analyzing trials like repeated ivermectin mass drug administrations for control of malaria, additional evaluation of the multiple approaches for analysis is needed for study designs with count outcomes.
Malaria is transmitted through the bite of Plasmodium‐infected adult female Anopheles mosquitoes. Ivermectin, an anti‐parasitic drug, acts by killing mosquitoes that are exposed to the drug while feeding on the blood of people (known as blood feeds) who have ingested the drug. This effect on mosquitoes has been demonstrated by individual randomized trials. This effect has generated interest in using ivermectin as a tool for malaria control.
The World Health Organization (WHO) recommends consideration of mass drug administration (MDA) for malaria control in low-endemic settings approaching elimination. However, MDA remains a controversial strategy, as multiple individual, social, and operational factors have shown to affect its acceptability at local levels. This is further complicated by inconsistent definitions of key indicators derived from individual and community involvement—coverage, adherence, and compliance—that cast doubts about the actual and potential epidemiological impact of MDA on disease control and elimination. This study aimed to identify limitations and enabling factors impacting involvement at different stages of a large cluster-randomized trial assessing the effect of combining dihydroartemisinin-piperaquine (DP) and ivermectin (IVM) in malaria transmission in The Gambia.
Ivermectin is a low-cost and nontoxic mosquitocide that may have a role in malaria elimination. However, the extent to which this drug impacts the mortality of Anopheles dirus and Anopheles epiroticus, two important malaria vectors in Southeast Asia, is unknown. This study compared quantified anopheline mortality after feeding on ivermectin-treated cattle and control cattle in Vietnam.
Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively.
Malaria is the most common vector-borne disease transmitted to humans by Anopheles mosquitoes. Endectocides and especially ivermectin will be available as a vector control tool soon. The current review could be valuable for trial design and clinical studies to control malaria transmission.
With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission.