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Influence of sublethal exposure to abamectin on the biological performance of Neoseiulus longispinosus (Acari: Phytoseiidae)

Ibrahim YB, Yee TS

J Econ Entomol, 2000 Aug;93(4):1085-9.
PMID: 10985016

Effects of sublethal exposure to abamectin on the biological performance of Neoseiulus longispinosus (Evans) were studied under ambient laboratory conditions of 28 +/- 2 degrees C and 80 +/- 15% RH with 24 h light. The red form of the twospotted spider mite, Tetranychus urticae Koch, complex (Acari: Tetranychidae), was offered as prey. The LC50 obtained from the contact bioassay at 48 h after treatment was 0.015 ppm (AI). A big change in kill for a given variation in dosage for the regression slope probably indicated that abamectin was unlikely selective. Sublethal exposure to abamectin caused a reduction in survival with the female reaching 50% mortality by the sixth day and the male 4 d later. The mean preoviposition period was extended by almost 1 d, whereas the mean oviposition period was shortened by almost 5 d causing a reduction in the mean fecundity female-1 to almost half that of the untreated females. The net reproductive rate (Ro), the intrinsic rate of increase (rm), and the finite rate of increase (lambda) of the treated females were markedly inferior. Treated males were seriously affected; the mean life span was almost half that of the untreated.

Matched MeSH terms: Ivermectin/analogs & derivatives*; Ivermectin/pharmacology
Fulltext The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis

Kow CS, Merchant HA, Mustafa ZU, Hasan SS

Pharmacol Rep, 2021 Oct;73(5):1473-1479.
PMID: 33779964 DOI: 10.1007/s43440-021-00245-z

OBJECTIVE: The effect of ivermectin on mortality in patients with novel coronavirus disease 2019 (COVID-19) has been investigated in many studies. We aimed to perform a meta-analysis of randomized controlled trials to investigate the overall effect of ivermectin on the risk of mortality in patients with COVID-19.
METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and preprint repository databases (up to February 28, 2021). Random-effects and inverse variance heterogeneity meta-analysis were used to pool the odds ratio of individual trials. The risk of bias was appraised using Version 2 of the Cochrane risk-of-bias tool for randomized trials.
RESULTS: Six randomized controlled trials were included in this analysis with a total of 658 patients who were randomized to receive ivermectin and 597 patients randomized in the control group who did not receive ivermectin. Of six trials, four had an overall high risk of bias. The estimated effect of ivermectin indicated mortality benefits (pooled odds ratio = 0.21; 95% confidence interval 0.11-0.42, n = 1255), with some evidence against the hypothesis of 'no significant difference' at the current sample size.
CONCLUSION: We observed a preliminary beneficial effect on mortality associated with ivermectin use in patients with COVID-19 that warrants further clinical evidence in appropriately designed large-scale randomized controlled trials.

Matched MeSH terms: Ivermectin/adverse effects*
Fulltext Pitfalls in Reporting Sample Size Calculation Across Randomized Controlled Trials Involving Ivermectin for the treatment of COVID-19

Kow CS, Hasan SS

Am J Ther, 2021 Aug 06;28(5):e616-e619.
PMID: 34387564 DOI: 10.1097/MJT.0000000000001441
Matched MeSH terms: Ivermectin/therapeutic use*
Chemoprophylactic studies with ivermectin against subperiodic Brugia malayi infection in the leaf monkey, Presbytis cristata

Mak JW, Lam PL, Rain AN, Suresh K

J Helminthol, 1987 Dec;61(4):311-4.
PMID: 3437112

Four Presbytis cristata were treated with oral ivermectin at the same time as the subcutaneous inoculation of 100 infective larvae monthly for three months. Two animals given 0.2 mg/kg monthly and two others given 0.3 mg/kg monthly as well as three control animals became patent for microfilaraemia. However, only 1% of the infective dose was recovered as adult worms from animals in the higher drug dosage group compared to 8.2% and 6.2% in the lower dosage and control groups respectively.

Matched MeSH terms: Ivermectin/therapeutic use*
Fulltext Antifilarial compounds in the treatment and control of lymphatic filariasis

Mak JW

Trop Biomed, 2004 Dec;21(2):27-38.
PMID: 16493396

Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.

Matched MeSH terms: Ivermectin
Effect of ivermectin against subperiodic Brugia malayi infection in the leaf monkey, Presbytis cristata

Mak JW, Lam PL, Rain AN, Suresh K

Parasitol Res, 1988;74(4):383-5.
PMID: 3387410

Ivermectin at single doses of 0.2-1.0 mg/kg body weight reduced the microfilarial counts of subperiodic Brugia malayi in Presbytis cristata by 59.9%-89.6% of initial counts, 4 weeks after treatment. Adult filaricidal activity was poor, live adult worms being recovered from all animals at autopsy. There was no serious side effect at these doses.

Matched MeSH terms: Ivermectin/administration & dosage; Ivermectin/therapeutic use*
Status of Onchocerca volvulus infection and transmission by blackflies after 15 years of ivermectin distribution at Adani, Nigeria

Onah IE, Ubachukwu PO, Eyo JE

Trop Biomed, 2020 Mar 01;37(1):174-185.
PMID: 33612728

The nuisance bites of blackflies and transmission of Onchocerca volvulus, which causes onchocerciasis, constitutes a threat to public health and an impediment to food production in rural and riverine communities in Nigeria. The entomological profile of onchocerciasis at Adani, Nigeria, was investigated from August 2010 to January 2011 to determine the transmission of O. volvulus after 15 years of ivermectin distribution in the area. A total of 548 adult female blackflies of the Simulium damnosum complex were caught using human baits and dissected. Of this number, 248 flies were caught in the wet season (August to October), while 300 flies were caught in the dry season (November to January). The relative abundance of flies at Adani varied from 21 in December to 243 in January. The monthly catches between September and October and between December and January were significantly different. The monthly population density of the flies ranged from 0.5Flies/Man/Hour (FMH) in December to 5.5FMH in January. The diurnal biting pattern of the S. damnosum complex at the site showed a bimodal peak of activity with the evening peak being higher than the morning peak except in October when the morning peak was higher than the evening peak. The morning peaks were observed between 7.00 am and 10.00 am, whereas the evening peaks occurred between 4.00 pm and 6.00 pm. The morning and evening biting peaks in all the months were not significantly different. Nulliparous flies accounted for 75.7% of the total catch, whereas 24.3% of the flies caught were parous. The infection, infective bites and transmission of O. volvulus during the study period were zero. This study suggests that transmission of O. volvulus has been halted and the flies are presently more nuisance biters than disease vectors since no stage of O. volvulus was found in the flies dissected.

Matched MeSH terms: Ivermectin/administration & dosage*; Ivermectin/therapeutic use
Fulltext Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication

Low ZY, Yip AJW, Lal SK

Biochim Biophys Acta Mol Basis Dis, 2022 Feb 01;1868(2):166294.
PMID: 34687900 DOI: 10.1016/j.bbadis.2021.166294

Ivermectin (IVM) is an FDA approved macrocyclic lactone compound traditionally used to treat parasitic infestations and has shown to have antiviral potential from previous in-vitro studies. Currently, IVM is commercially available as a veterinary drug but have also been applied in humans to treat onchocerciasis (river blindness - a parasitic worm infection) and strongyloidiasis (a roundworm/nematode infection). In light of the recent pandemic, the repurposing of IVM to combat SARS-CoV-2 has acquired significant attention. Recently, IVM has been proven effective in numerous in-silico and molecular biology experiments against the infection in mammalian cells and human cohort studies. One promising study had reported a marked reduction of 93% of released virion and 99.98% unreleased virion levels upon administration of IVM to Vero-hSLAM cells. IVM's mode of action centres around the inhibition of the cytoplasmic-nuclear shuttling of viral proteins by disrupting the Importin heterodimer complex (IMPα/β1) and downregulating STAT3, thereby effectively reducing the cytokine storm. Furthermore, the ability of IVM to block the active sites of viral 3CLpro and S protein, disrupts important machinery such as viral replication and attachment. This review compiles all the molecular evidence to date, in review of the antiviral characteristics exhibited by IVM. Thereafter, we discuss IVM's mechanism and highlight the clinical advantages that could potentially contribute towards disabling the viral replication of SARS-CoV-2. In summary, the collective review of recent efforts suggests that IVM has a prophylactic effect and would be a strong candidate for clinical trials to treat SARS-CoV-2.

Matched MeSH terms: Ivermectin/pharmacology; Ivermectin/therapeutic use*
Treatment of subperiodic Brugia malayi infection with a single dose of ivermectin

Mak JW, Navaratnam V, Grewel JS, Mansor SM, Ambu S

Am J Trop Med Hyg, 1993 Apr;48(4):591-6.
PMID: 8480868

A clinical trial on the efficacy of a single oral dose of ivermectin at 20, 50, 100, and 200 micrograms/kg was carried out in 40 subjects with subperiodic Brugia malayi microfilaremia. There was no significant difference in the clearance of microfilaremia in the four treatment groups, and the lowest geometric mean microfilarial count (GMC) achieved in the 40 subjects was 8.8/ml or 8.3% of the initial count (106.1/ml), at two weeks post-treatment. The GMC started to increase at one month post-treatment and by six months was 22.2% of the initial GMC. Only 27.5%, 23.1%, 15.0%, and 18.9% of subjects were amicrofilaremic at two, four, 12, and 24 weeks post-treatment, respectively. Mild fever in 35% of the subjects was the primary side reaction and was more common in those with microfilarial counts > or = 500/ml (85.7%) than in those with counts < 500/ml (32%). The clearance of B. malayi microfilaremia by ivermectin was less rapid than that reported for Wuchereria bancrofti. The smaller number of side reactions encountered in the present study compared with those reported for bancroftian filariasis is probably related to the lower microfilarial density in the present subjects. Since ivermectin at a single oral dose of 20-200 micrograms/kg can reduce the GMC to less than 10% at two weeks and maintain it below 25% of the initial level even at six months post-treatment, it is recommended that the drug be seriously evaluated for use in the control of brugian filariasis.

Matched MeSH terms: Ivermectin/administration & dosage; Ivermectin/therapeutic use*
Isolation of an ivermectin-resistant strain of Haemonchus contortus from sheep in Malaysia

Sivaraj S, Pandey VS

Vet Rec, 1994 Sep 24;135(13):307-8.
PMID: 7817517
Matched MeSH terms: Ivermectin/pharmacology*; Ivermectin/therapeutic use
Fulltext The effect of macrocyclic lactones-ivermectin exposure on egg hatching and larval development of Caenorhabditis elegans

Mariani Mohd Zain, Zary Shariman Yahaya, Nik Ahmad Irwan Izzauddin Nik Him

Trop Life Sci Res, 2016;27(11):3-8.
MyJurnal

To date, the ivermectin resistance in nematode parasites has been reported
and many studies are carried out to determine the causes of this problem. A free-living
Caenorhabditis elegans is used as a model system for this study to investigate the
response of C. elegans to ivermectin exposure by using larval development assay. Worms
were exposed to ivermectin at concentration from 1 ng/mL to 10 ng/mL and dimethyl
sulphoxide (DMSO) as a control. The developments of the worms were monitored for 24,
48, 72, and 96 hours until the worms become adults. Results indicated that worms’ growth
began to be affected by ivermectin at a concentration of 5 ng/mL, while at the
concentration of 6, 7, 8, 9, and 10 ng/mL, the growth of worms were inhibited compared to
control worms. Further study of the protein expression in C. elegans should be done to
investigate the up-regulated and down-regulated proteins involve in ivermectin resistance.

Matched MeSH terms: Ivermectin
The Repurposing of Ivermectin for Malaria: A Prospective Pharmacokinetics-Based Virtual Clinical Trials Assessment of Dosing Regimen Options

Badhan R, Zakaria Z, Olafuyi O

J Pharm Sci, 2018 08;107(8):2236-2250.
PMID: 29626533 DOI: 10.1016/j.xphs.2018.03.026

Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance, attention has turned toward ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiology-based pharmacokinetic model in healthy adults (20-50 years), pediatric (3-5 years/15-25 kg) subjects, and a representative adult malaria population group (Thailand). Dosing optimization demonstrating a twice-daily dose for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and pediatric subjects. Furthermore, to address the occurrence of CYP450 induction that is often encountered with antiretroviral agents, simulated drug-drug interaction studies with efavirenz highlighted that a 1-mg/kg once-daily dose for 5 days would counteract the increased ivermectin hepatic clearance and enable a time above LC50 of 138.8 h in adults and 141.2 h in pediatric subjects. It was also demonstrated that dosage regimen design would require consideration of the age-weight geographical relationship of the subjects, with a dosage regimen for a representative Thailand population group requiring at least a single daily dose for 5 days to maintain ivermectin plasma concentrations and a time above LC50 similar to that in healthy adults.

Matched MeSH terms: Ivermectin/administration & dosage*; Ivermectin/pharmacokinetics*; Ivermectin/therapeutic use
15 years of APOC--a lifetime of public health evidence

Allotey P, Amazigo U, Adjei S, Seddoh A, Lusamba-Dikassa PS

Lancet, 2012 Oct 20;380(9851):1361-3.
PMID: 23084441 DOI: 10.1016/S0140-6736(12)60723-5
Matched MeSH terms: Ivermectin/therapeutic use
Fulltext In vitro drug susceptibility of Acanthamoeba castellani to chloroquine, ivermectin and fungizon

Rain AN, Radzan T, Sajiri S, Mak JW

Southeast Asian J. Trop. Med. Public Health, 1996 Jun;27(2):319-24.
PMID: 9279996

In vitro sensitivity of Acanthamoeba castellani was tested to three drugs: Chloroquine, ivermectin and fungizone (amphotericin B). Sensitivity was demonstrated to the latter two compounds but not to chloroquine. Thus ivermectin and amphotericin B show promise as therapeutic agents against this parasite.

Matched MeSH terms: Ivermectin/pharmacology*
Recent advances in the chemotherapy of lymphatic filariasis

Navaratnam V

Southeast Asian J. Trop. Med. Public Health, 1993;24 Suppl 2:51-4.
PMID: 7973948

Lymphatic filariasis is the most widespread of human filarial infections, a group of vector-borne infestations. After the discovery of diethylcarbamazine (DEC), little advance was made in the development of new chemotherapeutic agents for the treatment of lymphatic filariasis until 1985. Since then, several new initiatives have occurred as the result of a global effort by the World Bank/UNDP/WHO Special Programme on Tropical Diseases and the Onchocerciasis Control Programme. Some of these global research initiatives are reviewed in this paper. Recent observations throw a new light on the rational use of DEC including its deployment as a medicated salt. Ivermectin, an established drug for the treatment of river-blindness is examined for its potential use in the treatment of lymphatic filariasis. Experimental results from two novel compounds out of several being developed by the WHO/OCP Macrofil project are considered in respect to their potential macrofilaricidal activity, particularly in relation to lymphatic filarial infections.

Matched MeSH terms: Ivermectin/therapeutic use
Effect of ivermectin on sarcoptic mange lesions of goats

Zamri-Saad M, Kamal Hizat A, Kamil WM

Trop Anim Health Prod, 1990 May;22(2):144-5.
PMID: 2371754
Matched MeSH terms: Ivermectin/therapeutic use*
Experimental chemotherapy of lymphatic filariasis. A review

Mak JW, Navaratnam V, Ramachandran CP

Ann Trop Med Parasitol, 1991 Feb;85(1):131-7.
PMID: 1888210

An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2-carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Matched MeSH terms: Ivermectin/therapeutic use
Heterogeneous response of Wuchereria bancrofti-infected persons to diethylcarbamazine (DEC) and its implications for the Global Programme to Eliminate Lymphatic Filariasis (GPELF)

Sankari T, Subramanian S, Hoti SL, Pani SP, Jambulingam P, Das PK

Parasitol Res, 2021 Jan;120(1):311-319.
PMID: 33146778 DOI: 10.1007/s00436-020-06950-7

DEC or ivermectin (IVM) in combination with albendazole (ALB) has been the recommended strategy of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) since 2000. Despite effective population coverage (> 65%) with several rounds of MDA with DEC or combination of DEC plus ALB, microfilariae persist in few individuals and they continue to be the source of infection for transmitting LF. We report an individual's variability in response to DEC by defining the response as complete absence of microfilaria (mf) (post-treatment mf count = 0) and non-response as presence of mf (post-treatment mf count ≥ 1). We analyzed follow-up data on individual's response to treatment from two randomized clinical trials in which 46 microfilaremic individuals were treated with single-dose DEC (6 mg/kg body weight). They were classified into low, medium, and high mf density categories based on their pre-treatment mf counts. Of the 46 individuals, 65.2% have not responded throughout the 12-month post-treatment period. Application of a logistic regression model with fixed (age, gender, mf density, post-treatment time, and their interactions) and random (individual's response over time) effects indicated that treatment response is independent of age, gender, and time. The overall treatment response increases in low and decreases in high mf density categories. Furthermore, the estimates for the random coefficients model showed that there is a greater variability in response between individuals over post-treatment time. The results substantiate that individual variation in response to DEC exists which indicate the importance of studying the parasite as well as host genetic factors associated with DEC action.

Matched MeSH terms: Ivermectin/therapeutic use
Fulltext Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Cromwell EA, Osborne JCP, Unnasch TR, Basáñez MG, Gass KM, Barbre KA, et al.

PLoS Negl Trop Dis, 2021 07;15(7):e0008824.
PMID: 34319976 DOI: 10.1371/journal.pntd.0008824

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

Matched MeSH terms: Ivermectin/administration & dosage
Efficacy of ivermectin against Parastrongylus malaysiensis infection in rats

Ambu S, Mak JW, Ng CS

J Helminthol, 1992 Dec;66(4):293-6.
PMID: 1293196

The efficacy of ivermectin on experimental infections of P. malaysiensis in rats was determined. Ivermectin was 99.4% and 97.9% effective at a dosage of 400 meg and 800 meg respectively at seven days post-infection. The same two dosages of ivermectin when given at 14 days post infection had an efficacy of 100%. However, as an adulticide it had only 40.7% efficacy. Ivermectin may therefore be useful for the treatment of parastrongyliasis due to the larval stages of the worm which can cause significant pathology in man and animals.

Matched MeSH terms: Ivermectin/therapeutic use*

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