Active substances: Ivermectin
Innovation is required to reach the ambitious goals proposed by the Global Technical Strategy for Malaria —2030.
Ivermectin is a mixture of two semi-synthetic analogs of the fermentation products of Sterptomyces avermitilis. It belongs to the macrocyclic lactone complex; its chemical structure has been reviewed elsewhere.
Ivermectin is an anti-parasitic medicine approved for the treatment and control of human onchocerciasis, lymphatic filariasis LF, strongyloidiasis and scabies.
It is also an endectocide, a drug capable of killing arthropods that feed on a treated individual, including Anopheles mosquitoes. Such an intervention has the potential to reach malaria vectors that feed on the temporal and spatial gaps left by core vector control interventions long-lasting insecticidal nets LLINs and indoor residual spraying IRS.They contain ivermectin and you can considered the gold standard for diagnosing stromectol uk phd, ricercatore principale. Stato senior houtan noushmehr, buy stromectol uk phd, ricercatore principale.
This paper reviews the pharmacokinetic and pharmacodynamic properties of ivermectin that can affect the efficacy and safety of MDA campaigns for malaria transmission reduction.
Essential pharmacology Mechanism of action Ivermectin blocks synaptic transmission in invertebrates by binding to glutamate-gated chlorine channels in nerve and muscle, leading to hyperpolarization, paralysis and death of the invertebrate, including mosquitoes.
These channels are part of the Cys-loop family of ligand-gated ion channels and ivermectin has consequently been shown to have additional effects on other members, for instance the gamma-aminobutyric acid GABA, histamine, and pH-sensitive chloride channels.
In mammals, ivermectin acts as an allosteric agonist of GABAA receptor, another member of the Cys-loop family of ligand-gated ion channels.
These receptors are located on neurons in many central nervous system regions incl. In vertebrates, GABA is a major inhibitory transmitter.
The net effect of GABAA receptor stimulation is central nervous depression, which defines the syndrome of ivermectin toxicity in vertebrates. The glutamate-gated chlorine channel in Anopheles gambiae The glutamate-gated chlorine channel GluCl from Anopheles gambiae has recently been characterized.
These channels are predominantly expressed in some of the organs involved in motor and sensory systems, which explains the paralytic and other effects of the drug on mosquitoes, even at sub-lethal concentrations.
Little is known about the expression of these channels in wild mosquito populations. Mosquito resistance to ivermectin has not been reported, but theoretically selective over-expression of the ivermectin-insensitive isoform could develop as a resistance mechanism.
However, the reduced fertility seen in mosquitoes taking sub-lethal doses of the drug could help delay this possibility. Pharmacokinetics The following discussion refers to pharmacokinetics of ivermectin in humans. Veterinary references are explicitly mentioned as such.