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From informed consent to adherence: factors influencing involvement in mass drug administration with ivermectin for malaria elimination in The Gambia

April 28, 2021 - 15:47 -- Open Access
Alexandra Fehr, Claudia Nieto-Sanchez, Koen Peeters Grietens, et al.
Malaria Journal 2021 20:198, 26 April 2021

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 Treatment for Cattle Reduced the Survival of Two Malaria Vectors, Anopheles dirus and Anopheles epiroticus, Under Laboratory Conditions in Central Vietnam

April 28, 2021 - 13:51 -- Open Access
Cramer EY, Quang NX, Hertz JC, Van Nguyen D, Quang HH, Mendenhall I, Lover AA
Am J Trop Med Hyg. 2021 Apr 26:tpmd201239

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.

Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study

March 23, 2021 - 14:39 -- Open Access
Nicolas P, Kiuru C, Wagah MG, Muturi M, Duthaler U, Hammann F, Maia M, Chaccour C
Parasit Vectors. 2021 Mar 20;14(1):172

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.

Endectocides as a complementary intervention in the malaria control program: a systematic review

January 20, 2021 - 07:25 -- Open Access
Khaligh FG, Jafari A, Silivanova E, Levchenko M, Rahimi B, Gholizadeh S
Syst Rev. 2021 Jan 18;10(1):30

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.

Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial

November 25, 2020 - 12:10 -- Open Access
Dabira ED, Soumare HM, D'Alessandro U, et al.
JMIR Res Protoc. 2020 Nov 19;9(11):e20904

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.

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.


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