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Safety, pharmacokinetics, and activity of high-dose ivermectin and chloroquine against the liver-stage of Plasmodium cynomolgi infection in Rhesus Macaques

July 14, 2020 - 15:56 -- Open Access
Vanachayangkul P, Im-Erbsin R, Kobylinski KC, et al.
Antimicrob Agents Chemother. 2020 Jul 13:AAC.00741-20

Previously, ivermectin (1-10 mg/kg) was shown to inhibit liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (IC50 = 10.42 μM) and hypnozoites (IC50 = 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode.

Safety, Pharmacokinetics, and Mosquito-Lethal Effects of Ivermectin in Combination With Dihydroartemisinin-Piperaquine and Primaquine in Healthy Adult Thai Subjects

May 7, 2020 - 13:34 -- Open Access
Kobylinski KC, Jittamala P, Tarning J, et al.
Clin Pharmacol Ther. 2020 May;107(5):1221-1230

Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics, and mosquito‐lethal effects of combinations of ivermectin, dihydroartemisinin‐piperaquine, and primaquine were evaluated. Coadministration of ivermectin and dihydroartemisinin‐piperaquine resulted in increased ivermectin concentrations with corresponding increases in mosquito‐lethal effect across all subjects.

Effects of combined drug treatments on Plasmodium falciparum: In vitro assays with doxycycline, ivermectin and efflux pump inhibitors

April 27, 2020 - 12:53 -- Open Access
Nodari R, Corbett Y, Varotto-Boccazzi I, Porretta D, Taramelli D, Epis S, Bandi C
PLoS ONE 15(4): e0232171

There is great concern regarding the rapid emergence and spread of drug-resistance in Plasmodium falciparum, the parasite responsible for the most severe form of human malaria. Parasite populations resistant to some or all the currently available antimalarial treatments are present in different world regions. Considering the need for novel and integrated approaches to control malaria, combinations of drugs were tested on P. falciparum. The primary focus was on doxycycline, an antibiotic that specifically targets the apicoplast of the parasite.

Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study

April 6, 2020 - 08:30 -- Open Access
Slater HC, Foy BD, Smit MR, et al.
Lancet Infect Dis. 2020 Apr;20(4):498-508

Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use.

NOT Open Access | Ivermectin for causal malaria prophylaxis: a randomised controlled human infection trial

March 9, 2020 - 13:32 -- Kabogo Ndegwa
Metzger WG, Theurer A, Pfleiderer A, Molnar Z, Maihöfer-Braatting D, Bissinger AL, Sulyok Z, Köhler C, Egger-Adam D, Lalremruata A, Esen M, Lee Sim K, Hoffman S, Rabinovich R, Chaccour C, Alonso P, Mordmüller BG, Kremsner PG
Tropical Medicine and International Health Volume 25, Issue 3, March 2020, Pages 380-386

Ivermectin is safe and widely used for treating helminth infections. It also kills arthropods feeding on treated subjects, including malaria vectors. Thus, ivermectin mass drug administration as an additional tool for malaria control is being evaluated by WHO. As in vitro data, animal experiments and epidemiological observations suggest that ivermectin has a direct effect on the liver stages of the malaria parasite, this study was designed to assess the prophylactic effect of ivermectin on Plasmodium falciparum controlled human malaria infection.

Inhibition of Plasmodium sporogonic stages by ivermectin and other avermectins

November 30, 2019 - 12:31 -- Open Access
Azevedo R, Mendes AM, Prudêncio M
Parasit Vectors. 2019 Nov 21;12(1):549

The transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms. Ivermectin is a member of the avermectin family of endectocides, which has been proposed to inhibit malaria transmission due its insecticidal effect. However, it remains unclear whether ivermectin also exerts a direct action on the parasite's blood and transmission stages.

The effect of ivermectin® on fertility, fecundity and mortality of Anopheles arabiensis fed on treated men in Ethiopia

November 11, 2019 - 16:16 -- Open Access
Wondemeneh Mekuriaw, Meshesha Balkew, Louisa A. Messenger, Delenasaw Yewhalaw, Adugna Woyessa and Fekadu Massebo
Malaria Journal 2019 18:357, 8 November 2019

Insecticide resistance is a growing threat to malaria vector control. Ivermectin, either administered to humans or animals, may represent an alternate strategy to reduce resistant mosquito populations. The aim of this study was to assess the residual or delayed effect of administering a single oral dose of ivermectin to humans on the survival, fecundity and fertility of Anopheles arabiensis in Ethiopia.


Not Open Access | Characterization of the target of ivermectin, the glutamate-gated chloride channel, from Anopheles gambiae

May 23, 2015 - 11:05 -- NOT Open Access
Jacob I. Meyers, Meg Gray, Wojtek Kuklinski, Lucas B. Johnson, Christopher D. Snow, William C. Black IV, Kathryn M. Partin and Brian D. Foy
J Exp Biol 218, 1478-1486, May 15, 2015

In summary, we have characterized the first GluCl from a mosquito, A. gambiae, and described its unique activity and expression with respect to it as the target of the insecticide IVM.

Research: Duration of the mosquitocidal effect of ivermectin

October 23, 2012 - 15:43 -- Bart G.J. Knols
Guido J.H. Bastiaens, Geert-Jan van Gemert, Jo Hooghof, Steve W. Lindsay, Chris Drakeley, Thomas S. Churcher, Jan Peter Verhave, Clemens H.M. Kocken, Robert W. Sauerwein, Teun Bousema
MWJ 2012, 3, 10

Ivermectin (IVM) reduces the lifespan of malaria-transmitting mosquitoes after feeding on humans treated with IVM but limited data are available on the exact duration of the mosquitocidal effect of IVM. Daily mosquito feeding assays were conducted to determine this. Mosquito mortality was 70-100% when mosquitoes fed on mice, rats, or cynomolgus monkeys 1-2 days after the last IVM administration. The findings reported here, of a pronounced but short-lived mosquitocidal effect, makes the timing of IVM administration crucial to form a useful addition to anti-malarial drugs.

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