21 CFR 520.1193 - Ivermectin tablets and chewables.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin tablets and chewables. 520.1193 Section 520.1193 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1193 Ivermectin...

Oral ivermectin for the treatment of head lice infestation.

PubMed

Sanchezruiz, Wendy L; Nuzum, Donald S; Kouzi, Samir A

2018-05-22

Published literature describing the use of oral ivermectin for the treatment of head lice infestation is reviewed. In the United States and globally, head lice infestation, or pediculosis capitis, remains a public health issue with both social and medical implications. Treatment with oral or topical medications is typically required for head lice eradication. Resistance to traditional topical therapies for head lice infestation is increasing, creating a need for consideration of additional treatment options. A growing body of data describing the potential role of oral ivermectin for the treatment or prevention of head lice infestation is available. A literature search identified 5 clinical trials that evaluated safety and/or effectiveness outcomes of oral ivermectin use as an alternative to malathion, other topical prescription medications, and traditional, nonprescription remedies; those studies were conducted in various parts of the world (e.g., Australia, Brazil, Mexico, Egypt) and likely involved varying types and degrees of lice resistance. Clinical research findings to date, while not consistently robust, suggest that oral ivermectin is comparable or superior in effectiveness to other topical treatment options for head lice infestation while being well tolerated and favorably perceived by patients and caretakers. Oral ivermectin is an option for the treatment of head lice infestation, especially in individuals who have experienced a treatment failure. Published evidence from clinical trials indicates that oral ivermectin is as effective as currently available topical treatments. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

In Vivo Protection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

PubMed Central

Radwan, Rasha

2014-01-01

The inhibitory glycine receptor, a ligand-gated ion channel that mediates fast synaptic inhibition in mammalian spinal cord and brainstem, is potently and selectively inhibited by the alkaloid strychnine. The anthelminthic and anticonvulsant ivermectin is a strychnine-independent agonist of spinal glycine receptors. Here we show that ivermectin is an effective antidote of strychnine toxicity in vivo and determine time course and extent of ivermectin protection. Mice received doses of 1 mg/kg and 5 mg/kg ivermectin orally or intraperitoneally, followed by an intraperitoneal strychnine challenge (2 mg/kg). Ivermectin, through both routes of application, protected mice against strychnine toxicity. Maximum protection was observed 14 hours after ivermectin administration. Combining intraperitoneal and oral dosage of ivermectin further improved protection, resulting in survival rates of up to 80% of animals and a significant delay of strychnine effects in up to 100% of tested animals. Strychnine action developed within minutes, much faster than ivermectin, which acted on a time scale of hours. The data agree with a two-compartment distribution of ivermectin, with fat deposits acting as storage compartment. The data demonstrate that toxic effects of strychnine in mice can be prevented if a basal level of glycinergic signalling is maintained through receptor activation by ivermectin. PMID:25317421

Ivermectin toxicosis in a dog.

PubMed

Hopkins, K D; Marcella, K L; Strecker, A E

1990-07-01

A 5-year-old male Doberman Pinscher was examined after ingesting an equine paste dewormer containing approximately 115 mg of ivermectin. Clinical signs consisted of profound hypothermia, mild dehydration, dilated unresponsive pupils, localized muscle group fasciculations around the face and hind limbs, and no response to any external stimuli. Twelve days after parenteral administration of isotonic fluids and IV administration of dexamethasone and dimethyl sulfoxide, the dog returned to a clinically normal neurologic state. Ivermectin toxicosis has been reported frequently in Collies; however, other breeds may have idiosyncratic reactions to low doses. Patients with severe toxicosis should eventually recover completely if given appropriate intensive care.

Ivermectin: a complimentary weapon against the spread of malaria?

PubMed Central

Alout, Haoues; Foy, Brian

2017-01-01

Introduction Ivermectin has transformed the treatment of parasitic diseases and led to incommensurable benefits to humans and animals. Ivermectin is effective in treating several neglected infectious diseases and recently it has been shown to reduce malaria parasite transmission. Areas covered Malaria control strategies could benefit from the addition of ivermectin to interrupt the transmission cycle if it is a long lasting formulation or repeatedly administered. In turn, this will help also to control neglected infectious diseases where the elimination goal has been slower to achieve. Despite the relevance of using ivermectin for integrated and sustained disease control, there are still essential questions that remain to be addressed about safety and practicality. The efficacy in various malaria ecologies and the interaction between control tools, either drugs or insecticides, are also important to assess. Expert commentary Overlapping distribution of several infectious diseases reveals the benefit of integrating control programs against several infectious diseases into one strategy for cost effectiveness and to reach the elimination goals. The use of ivermectin to control malaria transmission will necessitate development and testing of long-lasting formulations or repeated treatments, and implementation of these treatments with other disease control tools may increase the chance of successful and sustained control. PMID:27960597

Oral ivermectin in the treatment of scabies.

PubMed

Elmogy, M; Fayed, H; Marzok, H; Rashad, A

1999-12-01

One hundred and twenty scabietic patients attending the outpatient clinic of the Department of Dermatology, Mansoura University Hospital, voluntarily participated in this uncontrolled, open label study to evaluate ivermectin 20 microg/kg as a scabietic after they had given their consent. The scabietic subjects included in this study were otherwise healthy, mentally competent, aged more than 18 years, and used no topical antiscabietic treatment in the week before ivermectin treatment, or during the 4-week study period. Patients were also required to show clinical evidence of scabies, and the microscopically demonstrated presence of Sarcoptes scabiei, their eggs, or their fecal pellets (scybala). A thorough history was taken, and a physical examination was conducted that included measurement of the pulse, blood pressure, temperature, and weight. For each participant, the distribution of scabies lesions was plotted on a body diagram, and the severity of disease was recorded as mild (10 or fewer lesions), moderate (11-49 lesions), or severe (50 or more lesions). Skin scrapings were examined for mites, eggs, or scybala. Urinalysis, stool analysis, a complete blood count, prothrombin time, and serum chemistry studies (serum creatinine, alanine aminotransferase (ALT), and total bilirubin) were performed before treatment, and 2 and 4 weeks after the drug was given. Ivermectin was administered as scored 6-mg tablets with water, and the dose was designed to provide 200 micrograms/kg (ivermectin was provided by Delta Pharma, Tenth of Ramadan City, Egypt). The patients were instructed to have recently worn clothing, sheets, and towels washed in a hot cycle the day after treatment. The patients were interviewed 3 days after treatment about any symptoms or subjective evidence of adverse reactions. Follow-up examinations were carried out 2 and 4 weeks after intake of ivermectin, and all examination procedures and laboratory investigations were repeated. Cure criteria included

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin, pyrantel, and praziquantel tablets... Ivermectin, pyrantel, and praziquantel tablets. (a) Specifications. Each chewable tablet contains: (1) 34...) Amount. Administer monthly according to body weight as follows: (i) 6 to 12 lb: one tablet as described...

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin, fenbendazole, and praziquantel tablets... Ivermectin, fenbendazole, and praziquantel tablets. (a) Specifications. Each chewable tablet contains either... § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer tablets to provide 6...

Occurrence of ivermectin in bovine milk from the Brazilian retail market.

PubMed

Lobato, V; Rath, S; Reyes, F G R

2006-07-01

High-performance liquid chromatography (HPLC) with fluorescence detection was used for the quantification of ivermectin residues in bovine milk intended for human consumption. After liquid-liquid extraction of ivermectin and purification of the extract, the compound was derivatized with 1-methylimidazol in N,N-dimethyl formamide to form a fluorescent derivative, which was separated by HPLC, using reversed-phase C18, with methanol : water (96 : 4 v/v) mobile phase at a flow rate 0.7 ml min-1. The excitation and emission wavelengths of the fluorescence detector were adjusted at 360 and 470 nm, respectively. The linearity of the method was in the range 10-100 ng ivermectin ml-1. Based on a sample of 5.0 ml, the limit of detection and the limit of quantification for ivermectin in milk were 0.6 and 2 ng ml-1, respectively. The recovery rate varied from 76.4 to 87.2%, with an average of 77.9 +/- 3.2%, at four fortification levels. The inter-day precision of the method was 13% (n = 5). Of 168 samples analysed, 17.8% contained ivermectin above the limit of quantification. Nevertheless, none of the samples contained ivermectin above the maximum residue limit (10 ng ml-1) established by the Brazilian Ministry of Agriculture.

Ivermectin cream for rosacea.

PubMed

2015-11-01

Rosacea is a chronic facial skin disease that mainly occurs in people aged over 30 years. It is common, with an estimated incidence of 1·7 per 1,000 person-years in general practice in the UK.(1,2) Rosacea can cause embarrassment, anxiety, low self-esteem and lack of confidence.(3) A new topical treatment has become available for the treatment of one of the clinical subtypes of rosacea. Ivermectin 10mg/g (1%) cream (Soolantra-Galderma) has received marketing authorisation for the treatment of inflammatory lesions of papulopustular rosacea in adults.(4) Here we review the safety and effectiveness of ivermectin cream in the treatment of rosacea and assess how it compares with standard therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Pharmacokinetics of ivermectin in llamas (Lama glama).

PubMed

Jarvinen, J A; Miller, J A; Oehler, D D

2002-03-16

The pharmacokinetic behaviour of ivermectin was investigated in adult llamas (Lama glama) by using high performance liquid chromatography with a lower limit of quantification of 2 ng/ml to measure its concentration in serum. Llamas were treated with one of three commercial formulations (injectable, pour-on or oral paste) at dosages recommended by the manufacturer, or with an experimental injectable sustained-release formulation. In five llamas given 1 per cent ivermectin subcutaneously at 200 microg/kg, the median peak serum concentration (Cmax) was 3 ng/ml and the area under the serum concentration-time curve (AUC) was 13.5 ng x day/ml. In six llamas treated topically with 0.5 per cent ivermedin pour-on at 500 microg/kg, Cmax was 2.5 ng/ml or less and the AUC was 7.75 ng x day/ml or less. In seven llamas with measurable concentrations of ivermedin, the median times to peak serum concentration (tmax) were six days after subcutaneous injection and seven days after treatment with the pour-on formulation. In six llamas, the serum concentration of ivermectin remained less than 2 ng/ml for 124 hours after treatment with a 1.87 per cent oral paste at 200 microg/kg. In five llamas treated subcutaneously with 25 per cent ivermectin sustained-release microspheres at 1500 microg/kg, the median Cmax was 5 ng/ml and the median AUC was 224 ng x day/ml.

Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yingying; Fang, Shanshan; Sun, Qiushi

Glioblastoma is one of the most vascular brain tumour and highly resistant to current therapy. Targeting both glioblastoma cells and angiogenesis may present an effective therapeutic strategy for glioblastoma. In our work, we show that an anthelmintic drug, ivermectin, is active against glioblastoma cells in vitro and in vivo, and also targets angiogenesis. Ivermectin significantly inhibits growth and anchorage-independent colony formation in U87 and T98G glioblastoma cells. It induces apoptosis in these cells through a caspase-dependent manner. Ivermectin significantly suppresses the growth of two independent glioblastoma xenograft mouse models. In addition, ivermectin effectively targets angiogenesis through inhibiting capillary network formation, proliferation andmore » survival in human brain microvascular endothelial cell (HBMEC). Mechanistically, ivermectin decreases mitochondrial respiration, membrane potential, ATP levels and increases mitochondrial superoxide in U87, T98G and HBMEC cells exposed to ivermectin. The inhibitory effects of ivermectin are significantly reversed in mitochondria-deficient cells or cells treated with antioxidants, further confirming that ivermectin acts through mitochondrial respiration inhibition and induction of oxidative stress. Importantly, we show that ivermectin suppresses phosphorylation of Akt, mTOR and ribosomal S6 in glioblastoma and HBMEC cells, suggesting its inhibitory role in deactivating Akt/mTOR pathway. Altogether, our work demonstrates that ivermectin is a useful addition to the treatment armamentarium for glioblastoma. Our work also highlights the therapeutic value of targeting mitochondrial metabolism in glioblastoma. - Highlights: • Ivermectin is effective in glioblastoma cells in vitro and in vivo. • Ivermectin inhibits angiogenesis. • Ivermectin induces mitochondrial dysfunction and oxidative stress. • Ivermectin deactivates Akt/mTOR signaling pathway.« less

21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin and pyrantel pamoate chewable tablets. 520.1196 Section 520.1196 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Ivermectin and pyrantel pamoate chewable tablets. (a) Specifications. Each chewable tablet contains either 68...

Post-ivermectin encephalopathy in Senegal: a case report.

PubMed

Massi, Daniel Gams; Mansare, Mohamed Lelouma; Traoré, Mariétou; Ndiaye, Moustapha; Diop, Amadou Gallo; Ndiaye, Mouhamadou Mansour

2017-01-01

Ivermectin is an ant parasitic drug used for combating onchocerciasis and lymphatic filariasis. It works by inhibiting the function of neurons and muscles, thus causing paralysis of microfilariae. Side effects of this drug have been reported including post-ivermectin encephalopathy requiring emergency care in hospital. We report the case of a 35 years old patient living in rural areas of Senegal who presented two days after a mistake in administration of a second dose of ivermectin, headaches, altered consciousness and bilateral blindness. The workup revealed brain white matter lesions, abnormal liver function tests and biological inflammation without evidence of Loa loa microfilariae in blood and cerebrospinal fluid. Corticosteroid treatment was administered in emergency and patient recovered despite the persistence of bilateral blindness. Inflammatory process seems to have an important role in the pathophysiology of this encephalopathy. We should therefore carefully control the administration of this drugs.

Crusted scabies in an immunocompetent child: treatment with ivermectin.

PubMed

Gladstone, H B; Darmstadt, G L

2000-01-01

An 11-year-old girl presented to our clinic with recalcitrant crusted scabies despite repeated applications of topical scabicides. She had no history of corticosteroid use prior to onset of the eruption and no evidence of immunodeficiency. A combination of oral ivermectin, topical lindane, and keratolytics cleared the infestation. Our patient is exceptional in that she had no risk factors commonly associated with a propensity to develop crusted scabies. While topical therapy remains the first-line treatment for children with classic scabies, in the unusual instance of a child with recalcitrant, crusted scabies, ivermectin may offer an efficacious alternative, although it should be used with caution. We discuss the use of oral ivermectin for treatment of crusted scabies and the challenging comprehensive management needed for this socially stigmatizing condition.

Low doses of ivermectin cause sensory and locomotor disorders in dung beetles

NASA Astrophysics Data System (ADS)

Verdú, José R.; Cortez, Vieyle; Ortiz, Antonio J.; González-Rodríguez, Estela; Martinez-Pinna, Juan; Lumaret, Jean-Pierre; Lobo, Jorge M.; Numa, Catherine; Sánchez-Piñero, Francisco

2015-09-01

Ivermectin is a veterinary pharmaceutical generally used to control the ecto- and endoparasites of livestock, but its use has resulted in adverse effects on coprophilous insects, causing population decline and biodiversity loss. There is currently no information regarding the direct effects of ivermectin on dung beetle physiology and behaviour. Here, based on electroantennography and spontaneous muscle force tests, we show sub-lethal disorders caused by ivermectin in sensory and locomotor systems of Scarabaeus cicatricosus, a key dung beetle species in Mediterranean ecosystems. Our findings show that ivermectin decreases the olfactory and locomotor capacity of dung beetles, preventing them from performing basic biological activities. These effects are observed at concentrations lower than those usually measured in the dung of treated livestock. Taking into account that ivermectin acts on both glutamate-gated and GABA-gated chloride ion channels of nerve and muscle cells, we predict that ivermectin’s effects at the physiological level could influence many members of the dung pat community. The results indicate that the decline of dung beetle populations could be related to the harmful effects of chemical contamination in the dung.

Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study.

PubMed

Mellgren, Marianne; Bergvall, Kerstin

2008-01-02

A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice. Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200-476 microg kg-1 subcutaneously 2-3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618-2185 microgkg-1) and oral ivermectin (range 616-2732 microgkg-1) administered by the owners, 3-6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2-20,0 mgkg-1, 1-3 times with an interval of 2-4 weeks. Follow-up time was 4 months-4.5 years. Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively. All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols.

Synergistic activity of antibiotics combined with ivermectin to kill body lice.

PubMed

Sangaré, Abdoul Karim; Rolain, Jean Marc; Gaudart, Jean; Weber, Pascal; Raoult, Didier

2016-03-01

Ivermectin and doxycycline have been found to be independently effective in killing body lice. In this study, 450 body lice were artificially fed on a Parafilm™ membrane with human blood associated with antibiotics (doxycycline, erythromycin, rifampicin and azithromycin) alone and in combination with ivermectin. Fluorescence in situ hybridisation and spectral deconvolution were performed to evaluate bacterial transcriptional activity following antibiotic intake by the lice. In the first series, a lethal effect of antibiotics on lice was observed compared with the control group at 18 days (log-rank test, P≤10(-3)), with a significant difference between groups in the production of nits (P=0.019, Kruskal-Wallis test). A high lethal effect of ivermectin alone (50ng/mL) was observed compared with the control group (log-rank test, P≤10(-3)). Fluorescence of bacteriocytes in lice treated with 20μg/mL doxycycline was lower than in untreated lice (P<0.0001, Kruskal-Wallis test). In the second series with antibiotic-ivermectin combinations, a synergistic lethal effect on treated lice (log-rank test, P<10(-6)) was observed compared with the control group at 18 days, associated with a significant decrease in the production of nits (P≤0.001, Kruskal-Wallis test). Additionally, survival of lice in the combination treatment groups compared with ivermectin alone was significant (log-rank test, P=0.0008). These data demonstrate that the synergistic effect of combinations of antibiotics and ivermectin could be used to achieve complete eradication of lice and to avoid selection of a resistant louse population. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study

PubMed Central

Mellgren, Marianne; Bergvall, Kerstin

2008-01-01

Background A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice. Methods Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200–476 μg kg-1 subcutaneously 2–3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618–2185 μgkg-1) and oral ivermectin (range 616–2732 μgkg-1) administered by the owners, 3–6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2–20,0 mgkg-1, 1–3 times with an interval of 2–4 weeks. Follow-up time was 4 months–4.5 years. Results Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively. Conclusion All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols. PMID:18171479

Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda.

PubMed

Chaccour, Carlos J; Rabinovich, N Regina; Slater, Hannah; Canavati, Sara E; Bousema, Teun; Lacerda, Marcus; Ter Kuile, Feiko; Drakeley, Chris; Bassat, Quique; Foy, Brian D; Kobylinski, Kevin

2015-06-11

The potential use of ivermectin as an additional vector control tool is receiving increased attention from the malaria elimination community, driven by the increased importance of outdoor/residual malaria transmission and the threat of insecticide resistance where vector tools have been scaled-up. This report summarizes the emerging evidence presented at a side meeting on "Ivermectin for malaria elimination: current status and future directions" at the annual meeting of the American Society of Tropical Medicine and Hygiene in New Orleans on November 4, 2014. One outcome was the creation of the "Ivermectin Research for Malaria Elimination Network" whose main goal is to establish a common research agenda to generate the evidence base on whether ivermectin-based strategies should be added to the emerging arsenal to interrupt malaria transmission.

21 CFR 556.344 - Ivermectin.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.344 Ivermectin. (a) Acceptable daily intake (ADI). The ADI for total... tolerance is established for 22,23-dihydroavermectin B1a (marker residue) in liver (target tissue) as...

21 CFR 556.344 - Ivermectin.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.344 Ivermectin. (a) Acceptable daily intake (ADI). The ADI for total... tolerance is established for 22,23-dihydroavermectin B1a (marker residue) in liver (target tissue) as...

21 CFR 556.344 - Ivermectin.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.344 Ivermectin. (a) Acceptable daily intake (ADI). The ADI for total... tolerance is established for 22,23-dihydroavermectin B1a (marker residue) in liver (target tissue) as...

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie.

PubMed

Han, Jae-Ik; Son, Hyoung-Won; Park, Seung-Cheol; Na, Ki-Jeong

2010-12-01

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance.

Novel insertion mutation of ABCB1 gene in an ivermectin-sensitive Border Collie

PubMed Central

Han, Jae-Ik; Son, Hyoung-Won; Park, Seung-Cheol

2010-01-01

P-glycoprotein (P-gp) is encoded by the ABCB1 gene and acts as an efflux pump for xenobiotics. In the Border Collie, a nonsense mutation caused by a 4-base pair deletion in the ABCB1 gene is associated with a premature stop to P-gp synthesis. In this study, we examined the full-length coding sequence of the ABCB1 gene in an ivermectin-sensitive Border Collie that lacked the aforementioned deletion mutation. The sequence was compared to the corresponding sequences of a wild-type Beagle and seven ivermectin-tolerant family members of the Border Collie. When compared to the wild-type Beagle sequence, that of the ivermectin-sensitive Border Collie was found to have one insertion mutation and eight single nucleotide polymorphisms (SNPs) in the coding sequence of the ABCB1 gene. While the eight SNPs were also found in the family members' sequences, the insertion mutation was found only in the ivermectin-sensitive dog. These results suggest the possibility that the SNPs are species-specific features of the ABCB1 gene in Border Collies, and that the insertion mutation may be related to ivermectin intolerance. PMID:21113104

21 CFR 558.300 - Ivermectin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin. 558.300 Section 558.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS Specific New Animal Drugs for Use in...

21 CFR 558.300 - Ivermectin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ivermectin. 558.300 Section 558.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS Specific New Animal Drugs for Use in...

Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial

PubMed Central

Mandro, Michel; Mukendi, Deby; Dolo, Housseini; Suykerbuyk, Patrick; Van Oijen, Marieke

2017-01-01

Background Many studies have reported an association between epilepsy, nodding syndrome (NS), and onchocerciasis (river blindness). A high prevalence of epilepsy has been noted particularly in onchocerciasis hyperendemic areas where onchocerciasis is not or insufficiently controlled with mass ivermectin distribution. There is evidence that increasing the coverage of ivermectin reduces the incidence of epilepsy, and anecdotal evidence suggests a reduction in seizure frequency in onchocerciasis-associated epilepsy (OAE) patients who receive ivermectin. Finding an alternative treatment for epilepsy in these patients will have major consequences. Objective The goal of the study is to assess whether ivermectin treatment decreases the frequency of seizures and leads to seizure freedom in OAE patients, including patients with NS. If we are able to demonstrate such an effect, this would strengthen the argument that onchocerciasis is causing epilepsy and therefore we should increase our efforts to eliminate onchocerciasis. Methods We will conduct a randomized clinical trial in the Democratic Republic of Congo to compare seizure freedom in onchocerciasis-infested epilepsy patients who receive immediate ivermectin treatment with delayed (after 4 months) ivermectin treatment. All participants will simultaneously receive antiepilepsy drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the 4 month of follow-up. Secondary endpoint is significant (>50%) seizure reduction compared to baseline seizure frequency. Reduction of seizures will be compared between ivermectin and nonivermectin arms. Results Start of enrollment is planned for August 2017, and we expect to have enrolled all 110 participants by December 2017. Results are expected in June 2018. Conclusions If ivermectin treatment in addition to AEDs is able to lead to seizure freedom or significantly reduces seizure frequency in OAE patients

The lack of influence of food and local alcoholic brew on the blood level of Mectizan(®) (ivermectin).

PubMed

Homeida, Mamoun M; Malcolm, Stephen B; ElTayeb, A Z; Eversole, Rob R; Elassad, Asma S; Geary, Timothy G; Ali, Magdi M; Mackenzie, Charles D

2013-08-01

There is concern that extraneous factors, such as food and drink, may alter the pharmacodynamics of Mectizan(®) (ivermectin) in patients receiving this important anti-parasitic drug, and thus might put such individuals in danger of serious adverse events. The effects of a common local alcohol-containing beverage and a local food on plasma levels of ivermectin were studied in Sudanese volunteers after administration of the standard dose used in mass drug administration programs for onchocerciasis and filariasis. Plasma levels of ivermectin at various time points (0-48h) after administration of ivermectin were ascertained by HPLC assay in ten volunteers given 150μgkg(-1) ivermectin together with either a local sorghum-based food ('assida'), or a locally brewed alcoholic beverage ('arangi' made from sorghum grain) or in those who were fasting. Maximum mean (±SD) plasma levels of ivermectin (67±49ngml(-1)) were reached within 2h in fasting patients, and had dropped to 26±20ngml(-1) after 30h. The coadministration of local food or alcoholic beverage did not cause an increase in ivermectin plasma levels above those observed in people who were fasting. However, at 2h after ivermectin administration, patients given alcohol had significantly lower plasma ivermectin levels than fed patients or fasting patients. There were no significant differences among treatments for AUC0-30, Cmax, or tmax, and so the coadministration of local food or alcoholic beverage did not cause any change in pharmacokinetic parameters of ivermectin in the plasma in comparison with fasting. None of the measured levels of plasma ivermectin were greater than those reported in previous studies with this compound. These findings do not support the hypothesis that acute intake of alcohol is an important factor in the development of the serious adverse reactions that can occur during the treatment of loaisis patients with ivermectin (Mectizan(®)). Copyright © 2013 Elsevier B.V. All rights reserved.

Ivermectin susceptibility, sporontocidal effect, and inhibition of time to re-feed in the Amazonian malaria vector Anopheles darlingi.

PubMed

Kobylinski, Kevin C; Escobedo-Vargas, Karín S; López-Sifuentes, Victor M; Durand, Salomón; Smith, Edward S; Baldeviano, G Christian; Gerbasi, Robert V; Ballard, Sara-Blythe; Stoops, Craig A; Vásquez, Gissella M

2017-11-21

Outdoor malaria transmission hinders malaria elimination efforts in the Amazon region and novel vector control tools are needed. Ivermectin mass drug administration (MDA) to humans kills wild Anopheles, targets outdoor-feeding vectors, and can suppress malaria parasite transmission. Laboratory investigations were performed to determine ivermectin susceptibility, sporontocidal effect and inhibition of time to re-feed for the primary Amazonian malaria vector, Anopheles darlingi. To assess ivermectin susceptibility, various concentrations of ivermectin were mixed in human blood and fed to An. darlingi. Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with Probit analysis was used to calculate lethal concentrations of ivermectin that killed 50% (LC 50 ), 25% (LC 25 ) and 5% (LC 5 ) of mosquitoes. To examine ivermectin sporonticidal effect, Plasmodium vivax blood samples were collected from malaria patients and offered to mosquitoes without or with ivermectin at the LC 50 , LC 25 or LC 5 . To assess ivermectin inhibition of mosquito time to re-feed, concentrations of ivermectin predicted to occur after a single oral dose of 200 μg/kg ivermectin were fed to An. darlingi. Every day for 12 days thereafter, individual mosquitoes were given the opportunity to re-feed on a volunteer. Any mosquitoes that re-blood fed or died were removed from the study. Ivermectin significantly reduced An. darlingi survivorship: 7-day-LC 50  = 43.2 ng/ml [37.5, 48.6], -LC 25  = 27.8 ng/ml [20.4, 32.9] and -LC 5  = 14.8 ng/ml [7.9, 20.2]. Ivermectin compound was sporontocidal to P. vivax in An. darlingi at the LC 50 and LC 25 concentrations reducing prevalence by 22.6 and 17.1%, respectively, but not at the LC 5 . Oocyst intensity was not altered at any concentration. Ivermectin significantly delayed time to re-feed at the 4-h (48.7 ng/ml) and 12-h (26.9 ng/ml) concentrations but not 36-h (10.6 ng/ml) or 60-h (6.3 ng/ml). Ivermectin is

Comparison of oral ivermectin versus crotamiton 10% cream in the treatment of scabies.

PubMed

Goldust, Mohamad; Rezaee, Elham; Raghifar, Ramin

2014-12-01

Scabies is a relatively contagious infection caused by a tiny mite (Sarcoptes scabiei). Products used to treat scabies are called scabicides because they kill scabies mites; some also kill mite eggs. The aim of this study was to compare the efficacy and safety of oral ivermectin versus crotamiton 10% cream for the treatment of scabies. In total, 320 patients with scabies were enrolled, and were randomized into two groups: the first group received a single dose of oral ivermectin 200 µg/kg body weight, and the second group were treated with crotamiton 10% cream and were told to apply this twice daily for five consecutive days. Treatment was evaluated at intervals of two and four weeks, and if there was treatment failure at the two-week follow-up, the treatment was repeated. A single dose of ivermectin provided a cure rate of 62.5% at the two-week follow-up, which increased to 87.5% at the four-week follow-up after repeating the treatment. Treatment with crotamiton 10% cream was effective in 46.8% of patients at the two-week follow-up, which increased to 62.5% at the four-week follow-up after this treatment was repeated. A single dose of ivermectin was as effective as one application of crotamiton 10% cream at the two-week follow-up. After repeat treatment, ivermectin was superior to crotamiton 10% cream at the four-week follow up. The delay in clinical response with ivermectin suggests that it may not be effective against all the stages in the life cycle of the parasite.

Endectocide activity of a pour-on formulation containing 1.5 per cent ivermectin +0.5 per cent abamectin in cattle.

PubMed

Silva, Heloisa Cristina; Prette, Nancy; Lopes, Welber Daniel Zanetti; Sakamoto, Cláudio Alessandro M; Buzzulini, Carolina; Dos Santos, Thais Rabelo; Cruz, Breno Cayeiro; Teixeira, Weslen F Pires; Felippelli, Gustavo; Carvalho, Rafael Silveira; Maciel, Willian Giquelin; Soares, Vando Edésio; da Costa, Alvimar José

2015-01-01

The present work aimed to evaluate, through ten different studies, the therapeutic efficacy of a new pour-on formulation, containing 1.5 per cent ivermectin +0.5 per cent abamectin, against parasites of cattle. Results obtained on trials against Rhipicephalus (Boophilus) microplus showed that the pour-on combination of 1.5 per cent ivermectin +0.5 per cent abamectin obtained superior efficacy indexes against this ectoparasite, when compared with formulations containing 0.5 per cent ivermectin, 1 per cent ivermectin and the combination of 1 per cent abamectin +20 per cent levamisole. The results of efficacy of the ivermectin+abamectin and the 0.5 per cent ivermectin against Haematobia irritans were similar. Against Cochliomyia hominivorax larvae, all pour-on formulations tested (1.5 per cent ivermectin +0.5 per cent abamectin, 0.5 per cent ivermectin and 0.5 per cent abamectin), as well as 1 per cent doramectin administered subcutaneously, were considered ineffective. Cattle medicated with 1.5 per cent ivermectin +0.5 per cent abamectin, pour-on, remained free from parasitism by Dermatobia hominis larvae during 42 days (96 per cent efficacy), while values superior to 90 per cent were obtained by 0.5 per cent ivermectin (92 per cent) and 0.5 per cent abamectin (93 per cent) until the 42nd and 35th days post treatment, respectively. Against Haemonchus placei and Oesophagostomum radiatum, the pour-on of ivermectin+abamectin showed better efficacy than the 0.5 per cent ivermectin and 0.5 per cent abamectin. As to Cooperia punctata, there was no difference regarding efficacy results obtained by the avermectins combination and abamectin. The pour-on combination of 1.5 per cent ivermectin +0.5 per cent abamectin obtained high efficacy against R. (B.) microplus, D. hominis and some species of cattle gastrointestinal helminths when compared with formulations of 0.5 per cent ivermectin and 0.5 per cent abamectin administered through the same route.

21 CFR 520.1192 - Ivermectin paste.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1192 Ivermectin paste. (a...): Trichostrongylus axei; Large mouth Stomach Worms (adults): Habronema muscae; Bots (oral and gastric stages...

21 CFR 520.1194 - Ivermectin meal.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1194 Ivermectin meal. (a...; Large Mouth Stomach Worms (adults): Habronema muscae; Bots (oral and gastric stages): Gasterophilus spp...

[Ivermectin as an adjunct in the treatment of refractory epilepsy].

PubMed

Diazgranados-Sanchez, J A; Mejia-Fernandez, J L; Chan-Guevara, L S; Valencia-Artunduaga, M H; Costa, J L

2017-10-01

Ivermectin, a 22'23 dihydro derivative of avermectins beta-1a, is a highly effective veterinary and human anti parasitic, used to treat endoparasites of difficult control such as filariasis and onchocerciasis, with a median plasma life of at least of 16 hours. The recommended therapeutic doses range from 0.05 to 0.40 mg/kg, without undesirable effects or risk to human life. It went from being a great success in animal health to its application in humans, where it has had great impact. Studies in basic sciences have shown that ivermectin has anticonvulsive effects in different epileptic animal models, where five different mechanisms of action have been described. Descriptive, prospective observational study, performed between 2013 and 2015, with 32 refractory epileptic patients, who received ivermectin as an a dose of adjunctive treatment of 10 mg/day three or seven times a week, controlled every three months, followed by 12-24 months, without withdrawal of anticonvulsant medications that they received previously. Progressively, patients entered into crisis control, at the end of the programmed follow-up period, the total percentage of crisis reduction was 97%, of which 57% did not return to crisis from the beginning of treatment, all patients being free of crisis according to International League Against Epilepsy criteria. Ivermectin has been useful as an adjuvant, achieving a significant decrease in seizures in this group of drug resistant patients.

Rhipicephalus (Boophilus) microplus resistant to acaricides and ivermectin in cattle farms of Mexico.

PubMed

Rodríguez-Vivas, Róger Iván; Pérez-Cogollo, Luis Carlos; Rosado-Aguilar, José Alberto; Ojeda-Chi, Melina Maribel; Trinidad-Martinez, Iris; Miller, Robert John; Li, Andrew Yongsheng; de León, Adalberto Pérez; Guerrero, Félix; Klafke, Guilherme

2014-01-01

Ticks and the diseases they transmit cause great economic losses to livestock in tropical countries. Non-chemical control alternatives include the use of resistant cattle breeds, biological control and vaccines. However, the most widely used method is the application of different chemical classes of acaricides and macrocyclic lactones. Populations of the cattle tick, Rhipicephalus (Boophilus) microplus, resistant to organophosphates (OP), synthetic pyrethroids (SP), amitraz and fipronil have been reported in Mexico. Macrocyclic lactones are the most sold antiparasitic drug in the Mexican veterinary market. Ivermectin-resistant populations of R. (B.) microplus have been reported in Brazil, Uruguay and especially in Mexico (Veracruz and Yucatan). Although ivermectin resistance levels in R. (B.) microplus from Mexico were generally low in most cases, some field populations of R. (B.) microplus exhibited high levels of ivermectin resistance. The CHPAT population showed a resistance ratio of 10.23 and 79.6 at lethal concentration of 50% and 99%, respectively. Many field populations of R. (B.) microplus are resistant to multiple classes of antiparasitic drugs, including organophosphates (chlorpyrifos, coumaphos and diazinon), pyrethroids (flumethrin, deltamethrin and cypermethrin), amitraz and ivermectin. This paper reports the current status of the resistance of R. (B.) microplus to acaricides, especially ivermectin, in Mexican cattle.

Ivermectin alters reproductive success, body condition and sexual trait expression in dung beetles.

PubMed

González-Tokman, Daniel; Martínez M, Imelda; Villalobos-Ávalos, Yesenia; Munguía-Steyer, Roberto; Ortiz-Zayas, María Del Rosario; Cruz-Rosales, Magdalena; Lumaret, Jean-Pierre

2017-07-01

Ivermectin is a very common parasiticide used in livestock. It is excreted in the dung and has negative effects on survival and reproduction of dung-degrading organisms, including dung beetles. Here we exposed the dung beetle Euoniticellus intermedius to different concentrations of ivermectin in the food and evaluated reproductive success and the expression of traits associated with survival and reproduction under laboratory conditions. It is the first time the effects of ivermectin were evaluated on offspring physiological condition and the expression of a secondary sexual trait. We also registered the number of emerged beetles, sex ratio and body size of emerged adult beetles. Besides reducing the number of emerged beetles and body size, as found in the same and other insects, ivermectin at high doses reduced muscle mass while at intermediate doses it increased lipid mass. Ivermectin changed offspring sex ratio and at high doses increased the size of male horn, which is an important trait defining the male mating success. Our results highlight the importance of regulating parasiticide usage in livestock in order to maintain ecosystem services provided by dung beetles and confirm that contaminants impose new environmental conditions that not only impact on wild animal survival, but also on evolutionary processes such as sexual selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

The efficacy of topical and oral ivermectin in the treatment of human scabies.

PubMed

Panahi, Yunes; Poursaleh, Zohreh; Goldust, Mohamad

2015-01-01

Scabies is an itchy skin condition caused by the microscopic mite Sarcoptes scabei. The itching is caused by an allergic reaction to the mites. The treatment of choice is still controversial. It is commonly treated with topical insecticides. The aim of this study was to assess the efficacy of topical and oral ivermectin in the treatment of human scabies. We searched electronic databases (Cochrane Occupational Safety and Health Review Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (Ovid), Pubmed, EMBASE, LILACS, CINAHL, Open Grey and WHO ICTRP) up to September 2014. Randomized controlled trials (RCTs) or cluster RCTs which compared the efficacy of ivermectin with other medications in the treatment of scabies. Interventions could be compared to each other, or to placebo or to no treatment. The author intended to extract dichotomous data (developed infection or did not develop infection) for the effects of interventions. We intended to report any adverse outcomes similarly. It has been sated that ivermectin was as effective as permethrin in the treatment of scabies. In comparison to other medications such as lindane, benzyl benzoate, crotamiton and malathion, ivermectin was more effective in the treatment of scabies. Ivermectin is an effective and cost-comparable alternative to topical agents in the treatment of scabies infection.

21 CFR 520.1195 - Ivermectin liquid.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1195 Ivermectin liquid. (a... oral drench. (ii) Indications for use. For treatment and control of: (A) Large Strongyles (adults...

Failure of Ivermectin per Rectum to Achieve Clinically Meaningful Serum Levels in Two Cases of Strongyloides Hyperinfection

PubMed Central

Bogoch, Isaac I.; Khan, Kamran; Abrams, Howard; Nott, Caroline; Leung, Elizabeth; Fleckenstein, Lawrence; Keystone, Jay S.

2015-01-01

Two cases of Strongyloides hyperinfection are presented. Ivermectin was initially administered orally and per rectum pending the availability of subcutaneous (SC) preparations. In neither case did rectal suppositories of ivermectin achieve clinically meaningful serum values. Clinicians should use SC preparations of ivermectin as early as possible in Strongyloides hyperinfection and dissemination. PMID:25918215

Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection.

PubMed

Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea

2007-05-23

Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Over the period 1990-2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries.

The Effect of Macrocyclic Lactones-Ivermectin Exposure on Egg Hatching and Larval Development of Caenorhabditis elegans

PubMed Central

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

2016-01-01

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. PMID:27965734

The Effect of Macrocyclic Lactones-Ivermectin Exposure on Egg Hatching and Larval Development of Caenorhabditis elegans.

PubMed

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

2016-11-01

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.

Differential modulation of FXR activity by chlorophacinone and ivermectin analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsu, Chia-Wen

Chemicals that alter normal function of farnesoid X receptor (FXR) have been shown to affect the homeostasis of bile acids, glucose, and lipids. Several structural classes of environmental chemicals and drugs that modulated FXR transactivation were previously identified by quantitative high-throughput screening (qHTS) of the Tox21 10 K chemical collection. In the present study, we validated the FXR antagonist activity of selected structural classes, including avermectin anthelmintics, dihydropyridine calcium channel blockers, 1,3-indandione rodenticides, and pyrethroid pesticides, using in vitro assay and quantitative structural-activity relationship (QSAR) analysis approaches. (Z)-Guggulsterone, chlorophacinone, ivermectin, and their analogs were profiled for their ability to altermore » CDCA-mediated FXR binding using a panel of 154 coregulator motifs and to induce or inhibit transactivation and coactivator recruitment activities of constitutive androstane receptor (CAR), liver X receptor alpha (LXRα), or pregnane X receptor (PXR). Our results showed that chlorophacinone and ivermectin had distinct modes of action (MOA) in modulating FXR-coregulator interactions and compound selectivity against the four aforementioned functionally-relevant nuclear receptors. These findings collectively provide mechanistic insights regarding compound activities against FXR and possible explanations for in vivo toxicological observations of chlorophacinone, ivermectin, and their analogs. - Highlights: • A subset of Tox21 chemicals was investigated for FXR antagonism. • In vitro and computational approaches were used to evaluate FXR antagonists. • Chlorophacinone and ivermectin had distinct patterns in modulating FXR activity.« less

The efficacy of oral ivermectin vs. sulfur 10% ointment for the treatment of scabies.

PubMed

Alipour, Human; Goldust, Mohamad

2015-01-01

Human scabies is caused by an infection of the skin by the human itch mite (Sarcoptes scabiei var. hominis). There are different medications for the treatment of scabies. This study aimed at comparing the efficacy and safety of oral ivermectin vs. sulfur 10% ointment for the treatment of scabies. In total, 420 patients with scabies were enrolled, and randomized into two groups: the first group received a single dose of oral ivermectin 200 μg/kg body weight, and the second group received sulfur 10% ointment and were told to apply this for three successive days. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated. A single dose of ivermectin provided a cure rate of 61.9% at the 2-week follow-up, which increased to 78.5% at the 4-week follow-up after repeating the treatment. Treatment with single applications of sulfur 10% ointment was effective in 45.2% of patients at the 2-week follow-up, which increased to 59.5% at the 4-week follow-up after this treatment was repeated. A single dose of ivermectin was as effective as single applications of sulfur 10% ointment at the 2-week follow-up. After repeating the treatment, ivermectin was superior to sulfur 10% ointment at the 4-week follow up. The delay in clinical response with ivermectin suggests that it may not be effective against all the stages in the life cycle of the parasite. .

The curative and antioxidative efficiency of ivermectin and ivermectin + vitamin E-selenium treatment on canine Sarcoptes scabiei infestation.

PubMed

Behera, Suvendu Kumar; Dimri, Umesh; Singh, Shanker Kumar; Mohanta, Ranjan Kumar

2011-04-01

The objective of the present study was to investigate the curative and antioxidative efficacy of ivermectin and ivermectin + vitamin E-selenium, and the influence of these agents on oxidative stress parameters in canines infested by Sarcoptes scabiei. Twenty two sarcoptic mites infested dogs and nine healthy dogs of 6 months to 2 years of age were divided into three groups. Group I comprised of healthy dogs (n=9) whereas animals in group II (n=11) and III (n=11) were positive for scabies. Group II animals were treated with only 1% ivermectin @ 0.2 mg/kg SC whereas group III were additionally treated with Vitamin E and selenium (tocopherol 50 mg + Se 1.5 mg/ml) @ 0.5 ml/20 kg IM at weekly intervals for three times. Blood samples were collected on day 0 and 28 post therapy. The values for hemato-biochemical parameters and activities of antioxidant enzymes were significantly decreased (P<0.05) whereas level of lipid peroxidation was significantly increased in all the infested dogs in comparison to the healthy dogs on day 0 which approached normalcy by day 28 post therapy. The dogs of group III showed better clinical recovery in comparison to group II at the end of therapy. Thus, administration of vitamin E and selenium in addition to standard therapy can alleviate these alterations hastening the clinical recovery of diseased dogs and can be recommended as an adjunct therapy with miticides for canine sarcoptic mange. © Springer Science+Business Media B.V. 2011

Clinical efficacy and safety of topical versus oral ivermectin in treatment of uncomplicated scabies.

PubMed

Ahmad, Hesham M; Abdel-Azim, Eman S; Abdel-Aziz, Rasha T

2016-01-01

Many medications are available for scabies treatment including oral and topical ivermectin. However, studies comparing these two forms as a scabies treatment are few. This study compares efficacy and safety of topical versus oral ivermectin as scabies treatment. The study included 62 confirmed uncomplicated scabies patients, divided into: Group I (32 patients, received topical ivermectin) and Group II (30 patients, received oral ivermectin). Patients were assessed, clinically and by KOH smear at 1, 2 and 4 weeks. Treatment was repeated after one week in patients with persistent infection. Adverse events were recorded. Most patients (87.5% and 73.5% in group I and group II respectively) were symptom free after a single treatment. A second treatment was required in 4 patients of group I and 8 patients of group II. However, 2 weeks after treatment symptoms and signs completely resolved in all cases with no recurrence at 4 weeks. This study suggests that both topical and oral ivermectin are safe and equally effective in treatment of uncomplicated scabies. Single treatment, whether topical or oral, is associated with high cure rate in a week post treatment. However, repeating treatment after one week may be required to achieve 100% cure. © 2015 Wiley Periodicals, Inc.

Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection

PubMed Central

Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea

2007-01-01

Background Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. Methods A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Results Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. Conclusion The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries. PMID:17521449

Assessment of oral ivermectin versus shampoo in the treatment of pediculosis (head lice infestation) in rural areas of Sine-Saloum, Senegal.

PubMed

Leulmi, Hamza; Diatta, Georges; Sokhna, Cheikh; Rolain, Jean-Marc; Raoult, Didier

2016-12-01

Reports of treatment failure and the emergence of resistance to topical head lice treatments have become increasingly common, driving the need for continued development of new therapeutic options for pediculosis. Ivermectin has been proposed as a potential alternative for the treatment of pediculosis but has not been sufficiently evaluated. In this study, the effectiveness of oral ivermectin versus shampoo in the treatment of pediculosis in Senegal was compared. The study was conducted in two neighbouring villages of Sine-Saloum, Senegal: Dielmo (ivermectin trial group; 201 female participants) and Ndiop (shampoo trial group; 239 female participants). In the ivermectin group, patients received two doses of oral ivermectin (400 µg/kg body weight; Mectizan ® ) 7 days apart. In contrast, the shampoo group received a shampoo treatment based on d-phenothrin (0.23%; Hégor ® ). At the beginning of the study, 70 (34.8%) of 201 participants in the ivermectin group were infested by head lice versus 145 (60.7%) of 239 participants in the shampoo group. At Day 15 post-treatment, the efficacy of the treatment against head lice reached 41/53 (77.4%) in the ivermectin group (53 patients were tested in this group) versus 42/130 (32.3%) in the shampoo group (130 patients were tested in this group) (P <10 -7 ). However, 4 (7.5%) of the 53 females in the ivermectin group exhibited probable ivermectin treatment failure, suggesting the emergence of ivermectin-resistant lice. This study demonstrates that oral ivermectin is highly effective for the treatment of pediculosis compared with shampoo, but also suggests that ivermectin resistance may emerge during treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals.

PubMed

Seaman, Jonathan A; Alout, Haoues; Meyers, Jacob I; Stenglein, Mark D; Dabiré, Roch K; Lozano-Fuentes, Saul; Burton, Timothy A; Kuklinski, Wojtek S; Black, William C; Foy, Brian D

2015-10-15

Ivermectin has been proposed as a novel malaria transmission control tool based on its insecticidal properties and unique route of acquisition through human blood. To maximize ivermectin's effect and identify potential resistance/tolerance mechanisms, it is important to understand its effect on mosquito physiology and potential to shift mosquito population age-structure. We therefore investigated ivermectin susceptibility and gene expression changes in several age groups of female Anopheles gambiae mosquitoes. The effect of aging on ivermectin susceptibility was analyzed in three age groups (2, 6, and 14-days) of colonized female Anopheles gambiaemosquitoes using standard survivorship assays. Gene expression patterns were then analyzed by transcriptome sequencing on an Illumina HiSeq 2500 platform. RT-qPCR was used to validate transcriptional changes and also to examine expression in a different, colonized strain and in wild mosquitoes, both of which blood fed naturally on an ivermectin-treated person. Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and

Effect of the antiparasitic drugs fenbendazole and ivermectin on the soil nematode Pristionchus maupasi.

PubMed

Grønvold, Jørn; Svendsen, Tina Stendal; Kraglund, Hans-Ole; Bresciani, José; Monrad, Jesper

2004-09-20

Pristionchus maupasi, a soil nematode, was used to elucidate the potential ecotoxic effect of the two anthelmintics fenbendazole and ivermectin in cattle dung. The population growth of P. maupasi was greater in faeces from cattle harbouring active Panacur- or Ivomec-boli, which are releasing fenbendazole and ivermectin to the rumen, respectively, compared to the growth in control faeces. In dose-response experiments it could be shown that the pure chemical compound of fenbendazole was increasingly nematocidal to P. maupasi in concentrations from 10 to 20 microg/g faeces (ww, i.e. wet weight) and the pure compound of ivermectin was effective above 3 microg/g faeces (ww). The results indicate that neither fenbendazole nor ivermectin have any acute toxic effect on P. maupasi in naturally excreted concentrations of the pure drugs, together with their metabolites in faeces from bolus-treated cattle. Both drugs are excreted in concentrations that are non-toxic to P. maupasi.

Tolerance and efficacy of emamectin benzoate and ivermectin for the treatment of Pseudocapillaria tomentosa in laboratory zebrafish (Danio rerio).

PubMed

Collymore, Chereen; Watral, Virginia; White, Julie R; Colvin, Michael E; Rasmussen, Skye; Tolwani, Ravi J; Kent, Michael L

2014-10-01

Tolerance of adult zebrafish and efficacy of emamectin benzoate and ivermectin in eliminating Pseudocapillaria tomentosa infection were evaluated. In the tolerance study, behavioral changes, fecundity, histopathology, and mortality were evaluated for in-feed administration of emamectin (0.05, 0.10, and 0.25 mg/kg) and ivermectin (0.05 and 0.10 mg/kg). All doses of emamectin were well tolerated. Ivermectin 0.05 mg/kg administration resulted in mild behavioral changes and a transient decrease in fecundity. Ivermectin 0.10 mg/kg administration resulted in severe behavioral changes and some mortality. In the efficacy study, emamectin (0.05 and 0.25 mg/kg) and ivermectin (0.05 mg/kg) were evaluated for their efficacy in eliminating P. tomentosa infection. Emamectin reduced parasite burden in infected zebrafish, and ivermectin eliminated intestinal nematode infections. Despite a small margin of safety, ivermectin 0.05 mg/kg was effective at eliminating P. tomentosa infection in adult zebrafish. Higher doses or a longer course of treatment may be needed for complete elimination of P. tomentosa infection using emamectin. In this study, we propose two possible treatments for intestinal nematode infections in zebrafish.

Tolerance and Efficacy of Emamectin Benzoate and Ivermectin for the Treatment of Pseudocapillaria tomentosa in Laboratory Zebrafish (Danio rerio)

PubMed Central

Collymore, Chereen; Watral, Virginia; White, Julie R.; Colvin, Michael E.; Rasmussen, Skye; Tolwani, Ravi J.

2014-01-01

Abstract Tolerance of adult zebrafish and efficacy of emamectin benzoate and ivermectin in eliminating Pseudocapillaria tomentosa infection were evaluated. In the tolerance study, behavioral changes, fecundity, histopathology, and mortality were evaluated for in-feed administration of emamectin (0.05, 0.10, and 0.25 mg/kg) and ivermectin (0.05 and 0.10 mg/kg). All doses of emamectin were well tolerated. Ivermectin 0.05 mg/kg administration resulted in mild behavioral changes and a transient decrease in fecundity. Ivermectin 0.10 mg/kg administration resulted in severe behavioral changes and some mortality. In the efficacy study, emamectin (0.05 and 0.25 mg/kg) and ivermectin (0.05 mg/kg) were evaluated for their efficacy in eliminating P. tomentosa infection. Emamectin reduced parasite burden in infected zebrafish, and ivermectin eliminated intestinal nematode infections. Despite a small margin of safety, ivermectin 0.05 mg/kg was effective at eliminating P. tomentosa infection in adult zebrafish. Higher doses or a longer course of treatment may be needed for complete elimination of P. tomentosa infection using emamectin. In this study, we propose two possible treatments for intestinal nematode infections in zebrafish. PMID:25237985

Successful management of ivermectin-induced blindness in an African lion (Panthera leo) by intravenous administration of a lipid emulsion.

PubMed

Saqib, Muhammad; Abbas, Ghazanfar; Mughal, Mudassar Niaz

2015-11-26

Ivermectin is widely used in veterinary practice for the treatment of ecto- and endo-parasites. In wildlife, an extra-label use this parasiticide is sometimes associated with toxicity. Different treatment regimens have been used in ivermectin toxicosis. The present report describes a successful reversal of ivermectin toxicity by intravenous administration of a commercially available lipid emulsion in a captive African lion (Panthera leo). A 2-year old captive African lion (Panthera leo) weighing ~130 kg was presented with acute neurological impairment and bilateral blindness that had developed 24 h after ivermectin exposure. The animal was treated with a commercially available lipid emulsion along with supportive therapy and experienced complete recovery. To our knowledge, this is the first case report of the use of lipid emulsion in the management of ivermectin induced blindness in an African lion and it appears that intravenous lipid emulsion may be an effective therapy in ivermectin toxicity in lions. Further testing in expanded clinical trials is clearly warranted.

The Effect of Ivermectin in Seven Strains of Aedes aegypti (Diptera: Culicidae) Including a Genetically Diverse Laboratory Strain and Three Permethrin Resistant Strains

PubMed Central

Deus, K. M.; Saavedra-rodriguez, K.; Butters, M. P.; Black, W. C.; Foy, B. D.

2014-01-01

Seven different strains of Aedes aegypti (L.), including a genetically diverse laboratory strain, three laboratory-selected permethrin-resistant strains, a standard reference strain, and two recently colonized strains were fed on human blood containing various concentrations of ivermectin. Ivermectin reduced adult survival, fecundity, and hatch rate of eggs laid by ivermectin-treated adults in all seven strains. The LC50 of ivermectin for adults and the concentration that prevented 50% of eggs from hatching was calculated for all strains. Considerable variation in adult survival after an ivermectin-bloodmeal occurred among strains, and all three permethrin-resistant strains were significantly less susceptible to ivermectin than the standard reference strain. The hatch rate after an ivermectin bloodmeal was less variable among strains, and only one of the permethrin-resistant strains differed significantly from the standard reference strain. Our studies suggest that ivermectin induces adult mortality and decreases the hatch rate of eggs through different mechanisms. A correlation analysis of log-transformed LC50 among strains suggests that permethrin and ivermectin cross-resistance may occur. PMID:22493855

Antiparasitic efficacy of ivermectin in naturally parasitized sheep.

PubMed

Yazwinski, T A; Greenway, T; Presson, B L; Pote, L M; Featherstone, H; Williams, M

1983-11-01

Sixteen sheep harboring naturally acquired parasitisms were allocated to 1 of 2 treatment groups: (i) sheep given ivermectin in an oral solution at the dosage rate of 200 micrograms/kg of body weight, and (ii) those given the vehicle at a dosage rate of 0.25 ml/kg. All animals were necropsied at 2 weeks after treatment. Parasites and percentages of parasitic reductions, as demonstrated in this trial, were: Dictyocaulus filaria (99.4%), Oestrus ovis first stage instars (100%), Trichuris ovis (98.9%), Strongyloides papillosus (99.8%), Nematodirus spathiger (100%), arrested 4th stage Nematodirus spp (96.2%), Trichostrongylus colubriformis (100%), T axei (100%), Oster tagia circumcincta (100%), Haemonchus contortus (100%), and arrested Haemonchus spp 4th stage larvae (99.9%). The sheep showed no adverse effects due to ivermectin or vehicle administration.

Treatment of Human Scabies with Oral Ivermectin. Eczematous Eruptions as a New Non-Reported Adverse Event.

PubMed

Sanz-Navarro, J; Feal, C; Dauden, E

2017-09-01

Oral ivermectin is an alternative therapy for human scabies infection due to its ease of administration and good safety profile. However, there is no definitive consensus on the optimal dosing regimen. To describe the treatment of human scabies with different dosages of oral ivermectin and the possible adverse events. 23 patients with human scabies were treated with oral ivermectin: 10 patients received a single oral dose of 200μg/kg and 13 a dose of 400μg/kg. A second, or even a third dose, was administered in cases of treatment failure. A complete clinical response was achieved by all of the patients. The first ten patients required at least two (80%) or three (20%) doses of ivermectin for complete resolution of the infection. The remaining cases resolved with a single 400μg/kg oral dose. Within the first 72h after the administration of oral ivermectin, new cutaneous lesions were observed in eleven patients (47.8%). Cutaneous biopsies showed signs of subacute eczema. The eruption was treated with topical corticosteroids and emollient therapy. There was no other new drug administration or a history of irritants. There was no history of atopic diathesis except for one patient. Oral ivermectin is an effective therapy for the treatment of human scabies. A single 400μg/kg oral dose demonstrated high efficacy and good tolerance. However, the appearance of eczematous cutaneous lesions induced by oral ivermectin has not previously been reported in the literature. Dermatologists should be aware of this possible adverse event. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States.

PubMed

Taieb, Alain; Stein Gold, Linda; Feldman, Steven R; Dansk, Viktor; Bertranou, Evelina

2016-06-01

Papulopustular rosacea is a chronic skin disease involving central facial erythema in combination with papules and pustules. Papulopustular rosacea is treated with topical, systemic, or a combination of topical and systemic therapies. Currently approved topical therapies include azelaic acid gel/cream/foam twice daily (BID) and metronidazole cream/gel/lotion BID. Ivermectin 1% cream once daily (QD) is a new topical agent for the treatment of papulopustular rosacea that has been approved for the management of inflammatory lesions of rosacea and offers an alternative to current treatments. To evaluate the cost-effectiveness of ivermectin 1% cream QD compared with current topical treatments in order to understand the cost of adding ivermectin as a treatment option that would bring additional clinical benefit for adults with papulopustular rosacea in the United States. The cost-effectiveness of ivermectin 1% cream QD was compared with metronidazole 0.75% cream BID and azelaic acid 15% gel BID for adults in the United States with moderate-to-severe papulopustular rosacea using a Markov cohort state transition structure with 2 mutually exclusive health states (rosacea and no rosacea) and 5 phases. Patients could succeed or fail to respond to treatment and experience a relapse after treatment success. The model took a health care payer perspective (direct medical costs of topical and/or systemic therapy plus health care costs for physician and specialist visits) and used a 3-year time horizon. The model was run for a cohort of 1,000 patients. Costs (2014 U.S. dollars) and benefits (disease-free days and quality-adjusted life-years [QALYs]) were discounted at a rate of 3% per annum. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) and measured in terms of incremental cost per QALY gained (estimated from health state utilities for patients with and without rosacea). Univariate and probabilistic sensitivity analyses (PSA) were conducted to

Interferences on microbial inhibitor tests related to ivermectin treatment in lactating dairy goats.

PubMed

Romero, Tamara; Moya, Vicente Javier; Fernández, Nemesio; Althaus, Rafael; Reybroeck, Wim; Molina, María Pilar

2016-08-01

This Research Communication reports interferences related to the administration of ivermectin in lactating dairy goats on the response of microbial tests for screening antibiotics in milk. Twenty-eight Murciano-Granadina goats, naturally infested with Sarcoptes scabiei var. caprae, were treated with a subcutaneous injection of ivermectin (200 µg/kg b.w.). To prevent re-infestation, a second dose was applied 7 d later. Individual milk samples were collected, daily, up to 15 d post-treatment. Milk samples were analysed by microbial inhibitor tests (BRT MRL, Delvotest SP-NT MCS and Eclipse 100) and ivermectin residues were quantified by HPLC. A large number of positive results were obtained for all microbial tests, especially on the first day after treatment (BRT MRL = 46·4%; Delvotest SP-NT MCS = 14·3%; and Eclipse 100 = 17·8%). However, the highest concentration of drug residues in milk (24·3 ng/ml) was detected on the tenth day after treatment, when positive outcomes were relatively lower (BRT MRL = 17·8%; Delvotest SP-NT MCS = 10·7%; and Eclipse 100 = 7·4%). Results herein suggest that factors related to the ivermectin treatment other than drug residues in milk, or alterations produced by the parasitic disease itself affecting the immune response of animals, could be the cause of false-positive results in microbial tests. It can be concluded that the application of ivermectin in dairy goats infested with sarcoptes mange during lactation produces persistent drug residues in milk, and could also cause false-positive results in microbial inhibitor tests for screening antibiotics.

Dominance of P-glycoprotein 12 in phenotypic resistance conversion against ivermectin in Caenorhabditis elegans

PubMed Central

Figueiredo, Luiza Almeida; Rebouças, Thais Fuscaldi; Ferreira, Sebastião Rodrigo; Rodrigues-Luiz, Gabriela Flavia; Miranda, Rodrigo Cambraia; Araujo, Ricardo Nascimento

2018-01-01

While diseases caused by nematodes remains a considerable drawback for the livestock, agriculture and public health, anthelmintics drug resistance has been observed over the past years and is a major concern for parasite control. Ivermectin, initially considered as a highly potent drug, currently presents a reduced anti-helminthic efficacy, which is influenced by expression of several ATP-binding cassette transporters (ABC), among them the P-glycoproteins (Pgps). Here we present some evidences of Pgps dominance during Ivermectin resistance/susceptibility using Pgps double silencing in C. elegans and the phylogenetic relationship of Pgps among nematodes, which strengthen the use of this model for study of drug resistance in nematodes. Firstly, we evaluated the quantitative gene expression of 12 out the 15 known Pgps from resistant and WT strains of C. elegans, we demonstrated the upregulation of Pgps 12 and 13 and downregulation of all remaining Pgps in ivermectin resistant strain. By using an RNAi loss-of-function approach we observed that Pgp 12 gene silencing reverts the resistance phenotype to ivermectin, while Pgp 4 gene silencing does not alter the resistance phenotype but induces a resistance in wild type strain. Interestingly, the dual silencing of Pgp 12 and Pgp 4 expression demonstrates the dominance of phenotype promoted by Pgp 12 silencing. Finally, in silico analysis reveals a close relationship between Pgps from C. elegans and several nematodes parasites. Taken together, our results indicate that Pgp 12 is crucial for the resistance to ivermectin and thus a good candidate for further studies aiming to develop specific inhibitors to this transporter, allowing the continuous use of ivermectin to control the burden on animal and human health inflicted by nematode parasites globally. PMID:29474375

Effectiveness of ivermectin against later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P W; Vasey, J

1982-09-01

Twelve pony foals were reared worm-free and inoculated with Strongylus vulgaris. Approximately 8 weeks after they were inoculated, 6 foals were given ivermectin IM at a dosage rate of 200 micrograms/kg of body weight and 6 were given a placebo. All foals were necropsied 35 days after treatment. Ivermectin was 98.9% effective in eliminating later 4th-stage S vulgaris larvae located near the origin of major intestinal arteries and in reducing clinical signs and permitting resolution of lesions associated with verminous arteritis. One pony foal reared on pasture and with evidence of arteritis of the cranial mesenteric and ileocolic arteries on arteriography was treated with ivermectin at a dosage rate of 200 micrograms/kg of body weight. On arteriographs taken subsequently, there was evidence of regression of the lesion, and at necropsy 9 weeks after treatment, there was no arteritis or larvae in those arteries.

Treatment for crusted scabies: limitations and side effects of treatment with ivermectin.

PubMed

Fujimoto, Kazuhisa; Kawasaki, Yushi; Morimoto, Kensuke; Kikuchi, Izumi; Kawana, Seiji

2014-01-01

Skin eruption with mild itching of the hands and feet developed in a man in his 90s 1 month after he was hospitalized following a traffic accident. Scabies was diagnosed in an attending nurse 3 months after the patient's hospitalization, and infection from the patient was suspected. Cornification of the patient's soles and marked hypertrophy of the nails of both feet were observed. After a large number of scabies mites were detected on microscopic examination, crusted scabies was diagnosed. The patient was given oral ivermectin, 6 mg, once per week for 3 weeks, and crotamiton topical ointment containing 30% benzyl benzoate was applied on the body from the neck down. However, because a large number of scabies mites were detected again on microscopic examination, the dose of ivermectin was increased to 12 mg and administered 3 times. One week after the sixth dose of ivermectin was administered, hemorrhagic scabs around the mouth and erosion of the tongue developed. Mucosal drug eruption was suspected, and eruptions around the mouth and on the tongue resolved within 1 week after ivermectin being discontinued. 1% gamma-benzene hexachloride ointment was applied topically on the body from the neck down once a week, crotamiton ointment containing benzyl benzoate was applied daily, and the hypertrophic parts of the nails were removed. The patient subsequently achieved a full recovery.

Construction of ivermectin producer by domain swaps of avermectin polyketide synthase in Streptomyces avermitilis.

PubMed

Zhang, Xiaolin; Chen, Zhi; Li, Meng; Wen, Ying; Song, Yuan; Li, Jilun

2006-10-01

Ivermectin, 22, 23-dihydroavermectin B1, is commercially important in human, veterinary medicine, and pesticides. It is currently synthesized by chemical reduction of the double bond between C22 and C23 of avermectins B1, which are a mixture of B1a (>80%) and B1b (<20%) produced by fermentation of Streptomyces avermitilis. The cost of ivermectin is much higher than that of avermectins B1 owing to the necessity of region-specific hydrogenation at C22-C23 of avermectins B1 with rhodium chloride as the catalyst for producing ivermectin. Here we report that ivermectin can be produced directly by fermentation of recombinant strains constructed through targeted genetic engineering of the avermectin polyketide synthase (PKS) in S. avermitilis Olm73-12, which produces only avermectins B and not avermectins A and oligomycin. The DNA region encoding the dehydratase (DH) and ketoreductase (KR) domains of module 2 from the avermectin PKS in S. avermitilis Olm73-12 was replaced by the DNA fragment encoding the DH, enoylreductase, and KR domains from module 4 of the pikromycin PKS of Streptomyces venezuelae ATCC 15439 using a gene replacement vector pXL211. Twenty-seven of mutants were found to produce a small amount of 22, 23-dihydroavermectin B1a and avermectin B1a and B2a by high performance liquid chromatography and liquid chromatography mass spectrometry analysis. This study might provide a route to the low-cost production of ivermectin by fermentation.

An Improved Ivermectin-activated Chloride Channel Receptor for Inhibiting Electrical Activity in Defined Neuronal Populations*

PubMed Central

Lynagh, Timothy; Lynch, Joseph W.

2010-01-01

The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial light-activated halorhodopsin and the invertebrate allatostatin-activated G protein-coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human α1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G α1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity. PMID:20308070

21 CFR 524.1140 - Imidacloprid and ivermectin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Imidacloprid and ivermectin. (a) Specifications. The product is available in unit applicator tubes containing 0.4, 1.0, 2.5, or 4.0 milliliters (mL). Each mL of solution contains 100 milligrams (mg) imidacloprid....1140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 524.1140 - Imidacloprid and ivermectin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Imidacloprid and ivermectin. (a) Specifications. The product is available in unit applicator tubes containing 0.4, 1.0, 2.5, or 4.0 milliliters (mL). Each mL of solution contains 100 milligrams (mg) imidacloprid....1140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

Effects of repeated Strongylus vulgaris inoculations and concurrent ivermectin treatments on mesenteric arterial lesions in pony foals.

PubMed

Klei, T R; Turk, M A; McClure, J R; Holmes, R A; Dennis, V A; Chapman, M R

1990-04-01

Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin-treated foals had fewer days (12 +/- 2.9) with rectal temperatures greater than 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

21 CFR 522.1193 - Ivermectin and clorsulon.

Code of Federal Regulations, 2011 CFR

2011-04-01

... female dairy cattle of breeding age. Do not use in other animal species because severe adverse reactions... chapter. (e) Conditions of use in cattle—(1) Amount. Administer 1 mL (10 mg ivermectin and 100 mg...) Limitations. For subcutaneous use only. Not for intravenous or intramuscular use. Do not treat cattle within...

21 CFR 522.1193 - Ivermectin and clorsulon.

Code of Federal Regulations, 2012 CFR

2012-04-01

... female dairy cattle of breeding age. Do not use in other animal species because severe adverse reactions... chapter. (e) Conditions of use in cattle—(1) Amount. Administer 1 mL (10 mg ivermectin and 100 mg...) Limitations. For subcutaneous use only. Not for intravenous or intramuscular use. Do not treat cattle within...

21 CFR 522.1193 - Ivermectin and clorsulon.

Code of Federal Regulations, 2010 CFR

2010-04-01

... female dairy cattle of breeding age. Do not use in other animal species because severe adverse reactions... chapter. (e) Conditions of use in cattle—(1) Amount. Administer 1 mL (10 mg ivermectin and 100 mg...) Limitations. For subcutaneous use only. Not for intravenous or intramuscular use. Do not treat cattle within...

21 CFR 524.1195 - Ivermectin otic suspension.

Code of Federal Regulations, 2011 CFR

2011-04-01

....1195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Ivermectin otic suspension. (a) Specifications. Each tube contains 0.5 milliliter (mL) of a 0.01 percent...—(1) Amount. Administer the contents of one 0.5-mL tube topically into each external ear canal. (2...

21 CFR 524.1195 - Ivermectin otic suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

....1195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Ivermectin otic suspension. (a) Specifications. Each tube contains 0.5 milliliter (mL) of a 0.01 percent...—(1) Amount. Administer the contents of one 0.5-mL tube topically into each external ear canal. (2...

Anthelmintic Resistance of Strongyle Nematodes to Ivermectin and Fenbendazole on Cart Horses in Gondar, Northwest Ethiopia.

PubMed

Seyoum, Zewdu; Zewdu, Alemu; Dagnachew, Shimelis; Bogale, Basazinew

2017-01-01

A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group). Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites.

Anthelmintic Resistance of Strongyle Nematodes to Ivermectin and Fenbendazole on Cart Horses in Gondar, Northwest Ethiopia

PubMed Central

Zewdu, Alemu; Dagnachew, Shimelis; Bogale, Basazinew

2017-01-01

A study was conducted from November 2015 to April 2016 to determine fenbendazole and ivermectin resistance status of intestinal nematodes of cart horses in Gondar, Northwest Ethiopia. Forty-five strongyle infected animals were used for this study. The animals were randomly allocated into three groups (15 horses per group). Group I was treated with fenbendazole and Group II with ivermectin and Group III was left untreated. Faecal samples were collected from each cart horse before and after treatment. Accordingly, the reduction in the mean fecal egg count at fourteen days of treatment for ivermectin and fenbendazole was 97.25% and 79.4%, respectively. It was significantly different in net egg count between treatment and control groups after treatment. From the study, resistance level was determined for fenbendazole and suspected for ivermectin. In addition, a questionnaire survey was also conducted on 90 selected cart owners to assess their perception on anthelmintics. In the survey, the most available drugs in the study area used by the owners were fenbendazole and ivermectin. Most respondents have no knowledge about drug management techniques. Hence, animal health extension services to create awareness regarding anthelmintic management that plays a key role in reducing the anthelmintic resistance parasites. PMID:28265572

Strongylus vulgaris in the tunica media of arteries of ponies and treatment with ivermectin.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P W; Ducharme, N; Baird, J D

1987-04-01

A preliminary investigation was made into the effect of fourth-stage Strongylus vulgaris larvae sequestered in the tunica media of ileocolic arteries of pony foals treated with ivermectin. The foals had been reared parasite-free, inoculated with infective larvae and given orally a placebo or ivermectin paste. Two foals received subsequently one or two further inoculations with larvae and treatment with ivermectin. Arteriography was used to identify the lesions in the ileocolic artery following inoculation and their regression following treatment. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was highly effective against fourth-stage larvae and those present in the media appeared not to unduly affect the integrity of the ileocolic artery. Increased numbers of larvae were not found in the media of foals receiving repeat inoculations and repeat treatments. Larvae were not found in the media of foals treated with a placebo. The major pathological changes in the arterial wall of all foals were attributed to infection with S. vulgaris and there was no strong tendency for the damaged arteries to return to normal after the S. vulgaris were removed.

Strongylus vulgaris in the tunica media of arteries of ponies and treatment with ivermectin.

PubMed Central

Slocombe, J O; McCraw, B M; Pennock, P W; Ducharme, N; Baird, J D

1987-01-01

A preliminary investigation was made into the effect of fourth-stage Strongylus vulgaris larvae sequestered in the tunica media of ileocolic arteries of pony foals treated with ivermectin. The foals had been reared parasite-free, inoculated with infective larvae and given orally a placebo or ivermectin paste. Two foals received subsequently one or two further inoculations with larvae and treatment with ivermectin. Arteriography was used to identify the lesions in the ileocolic artery following inoculation and their regression following treatment. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was highly effective against fourth-stage larvae and those present in the media appeared not to unduly affect the integrity of the ileocolic artery. Increased numbers of larvae were not found in the media of foals receiving repeat inoculations and repeat treatments. Larvae were not found in the media of foals treated with a placebo. The major pathological changes in the arterial wall of all foals were attributed to infection with S. vulgaris and there was no strong tendency for the damaged arteries to return to normal after the S. vulgaris were removed. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:3607653

The varied beneficial effects of ivermectin (Mectizan) treatment, as observed within onchocerciasis foci in south-eastern Nigeria.

PubMed

Anosike, J C; Dozie, I N S; Ameh, G I; Ukaga, C N; Nwoke, B E B; Nzechukwu, C T; Udujih, O S; Nwosu, D C

2007-10-01

In the treatment of humans, ivermectin (Mectizan((R))), a semi-synthetic macrocyclic lactone, is now primarily used as a rapid microfilaricide. The drug has several other benefits, however, and these have recently been investigated in five states in south-eastern Nigeria, where there have been mass treatments with ivermectin, for the control of Onchocerca volvulus, for more than 10 years. Between the January and December of 2005, 3125 adult onchocerciasis patients (each aged >/=20 years and known to have at least one clinical sign of onchocerciasis) were enlisted, clinically examined and interviewed. Relevant data were collected in the interviews, using a structured, pre-tested questionnaire, and in personal and focus-group discussions. Overall, 612 (19.6%) of the subjects reported that they had had nodules that had disappeared following repeated doses of ivermectin, although only 83.8% of the 612 attributed their nodule clearance to ivermectin (the other 16.2% being unsure of the cause). A larger percentage of the subjects (24.6%) reported that they had expelled intestinal helminths following the last round of ivermectin treatment (i.e. been dewormed). Other side-benefits reported in the study were improved vision (11.7% of subjects), reversal of secondary amenorrhea (4.5%), increased appetite (22.3%), reduction in arthritic or other musculo-skeletal pain (7.9%), reductions in the severity of body itching (18.5%) and skin rash (17.3%), darkening of leopard skin (6.6%), improved libido in men (6.6%), and clearance of head lice (4.5%). If, via health education, the local communities could be made more aware of the side-benefits of ivermectin treatment, the sustainability of the on-going programme of community-directed treatment with ivermectin (CDTI) in south-eastern Nigeria would probably be improved.

Neurotoxic effects of ivermectin administration in genetically engineered mice with targeted insertion of the mutated canine ABCB1 gene.

PubMed

Orzechowski, Krystyna L; Swain, Marla D; Robl, Martin G; Tinaza, Constante A; Swaim, Heidi L; Jones, Yolanda L; Myers, Michael J; Yancy, Haile F

2012-09-01

To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. 14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1-1Δ mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.

Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie.

PubMed

Clarke, Dana L; Lee, Justine A; Murphy, Lisa A; Reineke, Erica L

2011-11-15

A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination. On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits. The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism. Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is

21 CFR 520.1198 - Ivermectin and praziquantel paste.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Section 520.1198 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1198 Ivermectin...; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral and gastric stages)—Gasterophilus spp...

The effectiveness of a single treatment with doramectin or ivermectin in the control of gastrointestinal nematodes in grazing yearling stocker cattle.

PubMed

Ballweber, L R; Smith, L L; Stuedemann, J A; Yazwinski, T A; Skogerboe, T L

1997-09-01

Four studies were conducted to a similar experimental design in the U.S. to evaluate the effectiveness of doramectin injectable administered to yearling stocker cattle in the control of gastrointestinal nematodiasis over the subsequent grazing period. Studies were conducted in Wisconsin (WI) and Arkansas (AR) during the summer season. The other two studies were conducted in Georgia (GA) and Mississippi (MS) during the winter/spring season. Doramectin was compared with both ivermectin injectable and ivermectin pour-on in the WI study, with ivermectin injectable alone in the GA study and with ivermectin pour-on alone in the other two studies. At each study site, an area of permanent pasture previously grazed by parasitized animals was subdivided by fencing into equal pasture units each with its own water supply. A treatment designation (non-medicated control, doramectin injectable, ivermectin injectable or ivermectin pour-on) was randomly assigned to each pasture unit. Weaned beef calves with confirmed gastrointestinal nematode infections were randomly allotted to a pasture unit and corresponding treatment group. Each treatment group consisted of three replicates of seven animals per pasture unit (total 21 animals) in the WI study, three replicates of four or six animals per pasture unit (total 16 animals) in the AR study, five replicates of six animals per pasture unit (total 30 animals) in the GA study and three replicates of 12 animals per pasture unit (total 36 animals) in the MS study. Treatments were 1% doramectin injectable solution, 1% ivermectin injectable solution, 0.5% ivermectin pour-on solution or non-medicated controls. The injectables were administered at a dose of 1 ml/50 kg body weight (200 micrograms doramectin or ivermectin/kg) by subcutaneous injection in the neck. Ivermectin pour-on solution was administered topically at a dose of 1 ml/10 kg body weight (500 micrograms ivermectin/kg). After receiving their prescribed treatment, animals were

Use of a molasses–based liquid feed supplement to deliver Ivermectin to cattle to control ectoparasites

USDA-ARS?s Scientific Manuscript database

Two different dosages of ivermectin were used to medicate a liquid molasses feed supplement for free-choice consumption by cattle. Calves that fed on supplement medicated at 25 ppm with ivermectin had a 14 day mean consumption of 0.62 ± 0.07 kg supplement/animal/day producing an average dose of 15....

Brief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance.

PubMed

Yoon, K S; Strycharz, J P; Baek, J H; Sun, W; Kim, J H; Kang, J S; Pittendrigh, B R; Lee, S H; Clark, J M

2011-12-01

Transcriptional profiling results, using our non-invasive induction assay {short exposure intervals (2-5 h) to sublethal amounts of insecticides [< lethal concentration 3% (LC(3)) at 24 h] administered by stress-reducing means (contact vs. immersion screen) and with induction assessed in a time frame when tolerance is still present [~lethal concentration 90% (LC(90)) in 2-4 h]}, showed that ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses. Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin. Injection of double-stranded RNAs (dsRNAs) against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increased sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.

Ivermectin: activity against larval Strongylus vulgaris and adult Trichostrongylus axei in experimental infections in ponies.

PubMed

Lyons, E T; Drudge, J H; Tolliver, S C

1982-08-01

Activity of ivermectin, administered IM at the dosage rate of 200 micrograms/kg of body weight, was evaluated in controlled tests against migrating larvae of Strongylus vulgaris and adult Trichostrongylus axei in experimental infections in 6 ponies raised worm-free. Ponies were given 2,190 or 2,400 infective 3rd-stage larvae of S vulgaris at 7 days before treatment and 22,000 or 22,750 infective 3rd-stage larvae of T axei at 42 or 45 days before treatment. Three ponies were given ivermectin plus vehicle, and 3 ponies were given the vehicle only; the ponies were euthanatized 7 or 9 days after treatment. At necropsy, 4th-stage S vulgaris larvae were not recovered from visceral arteries of the 3 ivermectin plus vehicle-treated ponies, but 21 to 40 larvae were recovered from each of the 3 vehicle-treated ponies. Also at necropsy, adult T axei (140 specimens) were recovered from only 1 ot the 3 ivermectin plus vehicle-treated ponies, but 4,610 to 6,410 specimens were found in each of the 3 vehicle-treated ponies. Toxicosis was not observed after treatment.

Brief exposures of human body lice to sub-lethal amounts of ivermectin over transcribes detoxification genes involved in tolerance

PubMed Central

Yoon, K. S.; Strycharz, J. P.; Baek, J. H.; Sun, W.; Kim, J.H.; Kang, J.S.; Pittendrigh, B. R.; Lee, S. H.; Clark, J. M.

2011-01-01

Transcriptional profiling results, using our non-invasive induction assay [short exposure intervals (2–5 h) to sub-lethal amounts of insecticides (ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses. Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin. Injection of dsRNAs against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increase sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance. PMID:21895817

21 CFR 520.1193 - Ivermectin tablets and chewables.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ivermectin tablets and chewables. 520.1193 Section... tablets and chewables. (a) Specifications. (1) Each tablet or chewable contains 68, 136, or 272 micrograms... tablets or chewables described in paragraph (a)(1) as in paragraph (d)(1) and chewables described in...

RETROSPECTIVE EVALUATION OF A NOVEL SUSTAINED-RELEASE IVERMECTIN VARNISH FOR TREATMENT OF WOUND MYIASIS IN ZOO-HOUSED ANIMALS.

PubMed

Avni-Magen, Nili; Eshar, David; Friedman, Michael; Kirmayer, David; Letschert, Lital; Gati, Irith; Kaufman, Elizabeth; Paz, Avital; Lavy, Eran

2018-03-01

Myiasis is a major disease condition in human and veterinary medicine. Domestic, free-ranging, and zoo-housed animals can be severely affected by myiasis. Depending on case severity, multiple treatment episodes may be indicated and can lead to recurrent capturing, handling stress, and anesthetics, all of which increase the risk of adverse responses (including death) individually and also in the herd. As an insecticide, ivermectin is often used for larval control. A total of 28 individual myiasis cases were retrospectively evaluated, out of which 11 cases were also treated using an ivermectin sustained-release varnish (SRV). The clinical outcome of all cases was assessed and the results suggest that the use of a topical ivermectin SRV (with or without concurrent injectable ivermectin) can reduce handling and treatments, has no adverse effects, and has minimal recurrence of the disease when compared with cases treated without it.

A Knowledge, Attitudes and Practices Survey Conducted Three Years after Halting Ivermectin Mass Treatment for Onchocerciasis in Guatemala

PubMed Central

Richards, Frank O.; Klein, Robert E.; de León, Oscar; Mendizábal-Cabrera, Renata; Morales, Alba Lucía; Cama, Vitaliano; Crovella, Carol G.; Díaz Espinoza, Carlos E.; Morales, Zoraida; Sauerbrey, Mauricio; Rizzo, Nidia

2016-01-01

Background Mass drug administration (MDA) with ivermectin for onchocerciasis was provided in Guatemala’s Central Endemic Zone (CEZ) over a 24 year period (1988–2011). Elimination of Onchocerca volvulus transmission was declared in 2015 after a three year post MDA surveillance period (2012–2014) showed no evidence of recrudescence. The purpose of the present study was to evaluate the knowledge, attitudes and practices (KAP) towards onchocerciasis and ivermectin among residents in the post endemic CEZ. A major interest in this study was to determine what community residents thought about the end of the ivermectin MDA program. Methodology/Principal Findings A total of 148 interviews were conducted in November 2014 in four formerly hyperendemic communities using a standard questionnaire on smart phones. The majority (69%) of respondents knew that the MDA program had ended because the disease was no longer present in their communities, but a slight majority (53%) was personally unsure that onchocerciasis had really been eliminated. Sixty-three percent wanted to continue to receive ivermectin because of this uncertainty, or because ivermectin is effective against intestinal worms. Eighty-nine percent of respondents said that they would seek medical attention immediately if a family member had symptoms of onchocerciasis (especially the presence of a nodule), which is a finding very important for ongoing surveillance. Conclusions/Significance Many respondents wanted to continue receive ivermectin and more than half did not believe onchocerciasis had been eliminated. The ministry of health outreach services should be prepared to address ongoing concerns about onchocerciasis in the post endemic CEZ. PMID:27341104

Efficacy of ivermectin, closantel and fenbendazole against gastrointestinal nematodes of sheep in Kashmir valley.

PubMed

Tramboo, S R; Shahardar, R A; Allaie, I M; Wani, Z A; Abbas, Maria

2017-06-01

The present work was undertaken to evaluate the therapeutic efficacy of ivermectin, closantel and fenbendazole under field conditions against Gastrointestinal Nematodes (GIN) of cross bred merino sheep in Budgam area of Kashmir Valley. A total of 115 sheep having Egg per gram of faeces (EPG) greater than or equal to 150 (mean EPG 258.89) were selected. The animals were randomly divided into four groups comprising of 30 animals each in three treatment groups (ivermectin, closantel and fenbendazole) and twenty-five in fourth untreated infected control group. Faecal samples from the selected animals were collected on day '0' pre treatment and on days 8th and 14th post treatment. Based on Faecal Egg Count Reduction Test (FECRT), ivermectin was found to be 98.80 % effective against strongyles on 8th day post treatment, however an efficacy of 100 % was seen against strongyle worms on 14th day post treatment. 98.80 and 100 % efficacy was observed on day 8th post treatment against strongyles in case of closantel and fenbendazole respectively, however efficacy decreased to 97.60 and 98.8 % respectively on 14th day post treatment. There was no evidence of development of resistance by GIN of cross bred merino sheep in District Budgam of Kashmir Valley to ivermectin, closantel and fenbendazole.

Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

PubMed Central

Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

2011-01-01

Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

Effect of ivermectin treatment on eosinophilic pneumonia and other extravascular lesions of late Strongylus vulgaris larval migration in foals.

PubMed

Turk, M A; Klei, T R

1984-01-01

Eighteen parasite-free pony foals were infected orally with 500 third stage larvae of Strongylus vulgaris. At 56 days after infection, six ponies were treated with intramuscular ivermectin (22, 23-dihydroavermectin B1); six were treated with oral ivermectin; and six were not treated. Necropsy was done 91 days after infection to study the pathologic effects of migrating S. vulgaris larvae and to determine the efficacy of ivermectin in attenuation of S. vulgaris-induced lesions. Larval migration induced eosinophilic inflammation of the liver, spleen, mesenteric, colic and cecal lymph nodes, and small and large intestine. Previously unreported parasitic lesions included eosinophilic pneumonia with eosinophilic granulomas and pulmonary lymphoid nodules. S. vulgaris larvae were observed in eosinophilic granulomas in the lung, epicardium, liver, and intestinal serosa. Injectable and oral ivermectin formulations were equally effective in reduction of these lesions.

Interruption of infection transmission in the onchocerciasis focus of Ecuador leading to the cessation of ivermectin distribution.

PubMed

Lovato, Raquel; Guevara, Angel; Guderian, Ronald; Proaño, Roberto; Unnasch, Thomas; Criollo, Hipatia; Hassan, Hassan K; Mackenzie, Charles D

2014-05-01

A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. Thirty-five rounds of ivermectin treatment occurred between 1991-2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39-101) and 72.7 (CI 42-116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1-15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption.

Interruption of Infection Transmission in the Onchocerciasis Focus of Ecuador Leading to the Cessation of Ivermectin Distribution

PubMed Central

Lovato, Raquel; Guevara, Angel; Guderian, Ronald; Proaño, Roberto; Unnasch, Thomas; Criollo, Hipatia; Hassan, Hassan K.; Mackenzie, Charles D.

2014-01-01

Introduction: A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. Methodology and Principle Findings: Thirty-five rounds of ivermectin treatment occurred between 1991–2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39–101) and 72.7 (CI 42–116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1–15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. Significance: This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption. PMID:24853587

TREATMENT OF PULMONICOLA COCHLEOTREMA INFECTION WITH IVERMECTIN-PRAZIQUANTEL COMBINATION IN AN ANTILLEAN MANATEE (TRICHECHUS MANATUS MANATUS).

PubMed

Borges, João Carlos Gomes; Jung, Larissa Molinari; Santos, Sebastião Silva Dos; Carvalho, Vitor Luz; Ramos, Rafael Antonio Nascimento; Alves, Leucio Câmara

2017-03-01

The aim of this study was to report the use of an oral combination of ivermectin plus praziquantel in the treatment of a Pulmonicola cochleotrema in an Antillean manatee ( Trichechus manatus manatus). A female manatee was found exhibiting respiratory changes and the presence of parasites in the nares. Based on clinical manifestations presented by the manatee, a symptomatic therapeutic protocol was employed, which included an anthelmintic treatment using a combination of ivermectin plus praziquantel. The parasites retrieved were identified as P. cochleotrema. The fourth day after the onset of the therapeutic protocol, the clinical signs declined and on the seventh day posttreatment no clinical signs were observed. This is the first time a therapeutic protocol of ivermectin plus praziquantel has been used in the treatment of P. cochleotrema in manatees.

Rationale for the Coadministration of Albendazole and Ivermectin to Humans for Malaria Parasite Transmission Control

PubMed Central

Kobylinski, Kevin C.; Alout, Haoues; Foy, Brian D.; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E.; Richardson, Jason H.

2014-01-01

Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin, pyrantel, and praziquantel tablets. 520.1199 Section 520.1199 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1199...

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin, fenbendazole, and praziquantel tablets. 520.1200 Section 520.1200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1200...

Efficacy of ivermectin pour-on against Ostertagia ostertagi infection and residues in the American bison, Bison bison.

PubMed

Marley, S E; Knapp, S E; Rognlie, M C; Thompson, J R; Stoppa, T M; Button, S M; Wetzlich, S; Arndt, T; Craigmill, A

1995-01-01

Sixteen American bison, Bison bison, were artificially infected with 10(5) infective stage larvae of Ostertagia ostertagi on 21 April 1993. At 42 days post-infection eight bison were treated with 0.5% ivermectin pour-on (500 micrograms/kg bodyweight) and eight treated with the carrier only. Bison were necropsied 17 and 18 days post-treatment (21 and 22 June 1993, respectively). Mean (+/- SE) of 5,413 (+/- 1,716) adults and 565 (+/- 305) immature O. ostertagi were recovered at necropsy from bison treated with the carrier. No O. ostertagi were detected in bison treated with ivermectin pour-on. Based on the levels of the ivermectin marker metabolite in liver and adipose tissue 18 days post-treatment, the established bovine withdrawal time of 48 days appears adequate to insure that violative residues do not occur.

Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation.

PubMed

Chaccour, Carlos J; Ngha'bi, Kija; Abizanda, Gloria; Irigoyen Barrio, Angel; Aldaz, Azucena; Okumu, Fredros; Slater, Hannah; Del Pozo, Jose Luis; Killeen, Gerry

2018-05-04

Mosquitoes that feed on animals can survive and mediate residual transmission of malaria even after most humans have been protected with insecticidal bednets or indoor residual sprays. Ivermectin is a widely-used drug for treating parasites of humans and animals that is also insecticidal, killing mosquitoes that feed on treated subjects. Mass administration of ivermectin to livestock could be particularly useful for tackling residual malaria transmission by zoophagic vectors that evade human-centred approaches. Ivermectin comes from a different chemical class to active ingredients currently used to treat bednets or spray houses, so it also has potential for mitigating against emergence of insecticide resistance. However, the duration of insecticidal activity obtained with ivermectin is critical to its effectiveness and affordability. A slow-release formulation for ivermectin was implanted into cattle, causing 40 weeks of increased mortality among Anopheles arabiensis that fed on them. For this zoophagic vector of residual malaria transmission across much of Africa, the proportion surviving three days after feeding (typical mean duration of a gonotrophic cycle in field populations) was approximately halved for 25 weeks. This implantable ivermectin formulation delivers stable and sustained insecticidal activity for approximately 6 months. Residual malaria transmission by zoophagic vectors could be suppressed by targeting livestock with this long-lasting formulation, which would be impractical or unacceptable for mass treatment of human populations.

Oral, Slow-Release Ivermectin: Biting Back at Malaria Vectors.

PubMed

Chaccour, Carlos J; Rabinovich, N Regina

2017-03-01

Bellinger and colleagues offer an elegant twist for a promising new tool against malaria. This formulation is designed to release ivermectin, a mosquito-killing drug for 10 days after a single oral dose. This could reduce the vector population and serve as a complementary tool for malaria elimination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Willingness to pay for community-based ivermectin distribution: a study of three onchocerciasis-endemic communities in Nigeria.

PubMed

Onwujekwe, O E; Shu, E N; Nwagbo, D; Akpala, C O; Okonkwo, P O

1998-10-01

To determine the willingness to pay (WTP) for local ivermectin distribution in a community financing framework. Contingent valuation in three communities in Nigeria, using randomly selected household heads. WTP was elicited using a bidding game, and for collecting information on the households' socio-economic status, level of knowledge, priority ranking and perception of risk of contracting the disease, structured questionnaires were used. Ordinary least squares (OLS) multiple regression analysis was used to analyse factors associated with WTP. Between 92.1% and 93.3 % of respondents were willing to pay amounts ranging from 5 Naira (US$ 0.06) to 100 Naira (US$ 1.25) (median: 20 Naira, US$ 0.25) in the three communities, more than three times the modelled unit direct cost of distributing ivermectin by the communities themselves. Occupation of the respondent, marital status, average monthly expenditure on health care, manifestations of onchocerciasis, the type of savings scheme embarked on by the respondent, age-group, level of education and type of property were statistically significant (P < 0.05) variables affecting WTP. This study shows that there is WTP for local ivermectin distribution in the three study communities, and that it should be assessed before instituting community-directed treatment with ivermectin.

Assessment of the safety and efficacy of three concentrations of topical ivermectin lotion as a treatment for head lice infestation.

PubMed

Meinking, Terri L; Mertz-Rivera, Kamara; Villar, Maria Elena; Bell, Margie

2013-01-01

Ivermectin is a broad-spectrum parasiticide in widespread systemic use, including as an off-label treatment for head lice infestation. The potential of the topical use of ivermectin as a treatment for head lice infestation was suggested by an in vitro report of a novel lotion formulation. This study investigated the relative effectiveness of three ivermectin lotion concentrations (0.15, 0.25, and 0.5%) compared with vehicle placebo in eliminating head lice infestation. In this randomized, blinded study, 78 head lice-infested subjects, aged 2-62 years, received a single, 10-minute application of product on day 1. Evaluations were completed at two and six hours post-application, and on days 2, 8 (±1), and 15 (+2). Safety was assessed according to the evaluations of trained observers and adverse event (AE) reports. Efficacy was assessed according to scalp and hair examinations. Compared with placebo, all ivermectin concentrations resulted in the statistically significant (P ≤ 0.003) eradication of head lice through to day 15, with the highest level of eradication (73.7%) in subjects who received the 0.5% concentration. The severity of pruritus decreased from baseline in all treatment groups, including the placebo group, from six hours post-treatment to day 15, with the greatest reduction in the 0.5% concentration group. No ocular irritation was observed. All three ivermectin treatment strengths and vehicle were well tolerated. A single application of a 0.5% concentration of this ivermectin lotion formulation shows promise as a safe and effective treatment for head lice infestation and the associated signs of pruritus. © 2013 The International Society of Dermatology.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

PubMed

Muñoz, Jose; Ballester, Maria Rosa; Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia; Krolewiecki, Alejandro J

2018-01-01

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers

PubMed Central

Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia

2018-01-01

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI

Anthelmintic efficacy of ivermectin and abamectin, administered orally for seven consecutive days (100 µg/kg/day), against nematodes in naturally infected pigs.

PubMed

Lopes, Welber Daniel Zanetti; Teixeira, Weslen Fabricio Pires; Felippelli, Gustavo; Cruz, Breno Cayeiro; Buzulini, Carolina; Maciel, Willian Giquelin; Fávero, Flávia Carolina; Gomes, Lucas Vinicius Costa; Prando, Luciana; Bichuette, Murilo A; Dos Santos, Thais Rabelo; da Costa, Alvimar José

2014-12-01

The present study aimed to evaluate ivermectin and abamectin, both administered orally in naturally infected domestic swine, as well as analysing if the EPG (eggs per gram of faeces) values were equivalent with the ivermectin and abamectin efficacy obtained by parasitological necropsies. The animals were randomly selected based on the average of three consecutive EPG counts of Strongylida, Ascaris suum and Trichuris for experiment I, and of Strongylida and Trichuris for experiment II. After the random draw, eight animals were treated, orally, during seven consecutive days with 100 µg/kg/day ivermectin (Ivermectina® premix, Ouro Fino Agronegócios), eight other animals were treated, orally, during seven consecutive days with 100 µg/kg/day abamectin (Virbamax® premix - Virbac do Brasil Indústria e Comércio Ltda.), and eight pigs were kept as controls. EPG counts were performed for each individual animal at 14th day post-treatment (DPT). All animals (control and treatment) were necropsied at the 14th DPT. The results from both experiments demonstrate that both ivermectin and abamectin, administered orally for a continuous period of seven days, at a daily dosage of 100 µg/kg, were highly effective (>95%) against Hyostrongylus rubidus, Strongyloides ransomi, Ascaris suum and Metastrongylus salmi. Against Oesophagostomum dentatum, abamectin presented over 95% efficacy against both evaluated strains, while ivermectin reached other strain as resistant. Regarding T. suis, both ivermectin and abamectin were effective (efficacies >90%) against one of the tested strains, while the other one was classified as resistant. Furthermore, the EPG values were equivalent with the ivermectin and abamectin efficacy obtained by parasitological necropsies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

PubMed Central

Nana-Djeunga, Hugues C.; Kengne-Ouafo, Jonas A.; Pion, Sébastien D. S.; Bopda, Jean; Kamgno, Joseph; Wanji, Samuel; Che, Hua; Kuesel, Annette C.; Walker, Martin; Basáñez, Maria-Gloria; Boakye, Daniel A.; Osei-Atweneboana, Mike Y.; Boussinesq, Michel; Prichard, Roger K.; Grant, Warwick N.

2017-01-01

Background Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Methodology/Principal findings Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. Conclusions/Significance This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different

Demonstration of the sustained anthelmintic efficacy of a controlled-release capsule formulation of ivermectin in weaner lambs under field conditions in New Zealand.

PubMed

Gogolewski, R P; Allerton, G R; Rugg, D; Kawhia, D; Barrick, R A; Eagleson, J S

1997-08-01

Ten field trials were conducted in the North and South Islands of New Zealand to evaluate the anthelmintic efficacy and production responses attributable to treatment of weaner lambs with an intra-ruminal controlled-release capsule formulation of ivermectin. A total of 800 Coopworth, Perendale and Romney lambs weighing on average 20.8-34.8 kg were used. Lambs were either untreated or treated shortly after weaning with an ivermectin controlled-release capsule which delivers ivermectin at 0.8 mg per day for 100 days (minimum dose rate 20 microg/kg/day). Bodyweights, faecal nematode egg counts and dag scores (assessment of faecal soiling in the breech area) were determined before treatment and at about 4,8, 12, 14 and 16 weeks after treatment. Sheep treated with the Ivermectin capsule gained significantly more weight (11.6 kg) over the 16 weeks of the trials compared to untreated sheep (7.3 kg) (p < 0.01). Before treatment, faecal strongylid and Nematodirus spp. egg counts were equivalent (p > 0.10) but, at each time point thereafter, egg counts in ivermectin capsule-treated sheep were significantly lower (p < 0.01 or p < 0.05). Dag scores were not different at the start of the trial (p > 0.10), but at the end of the trial control sheep had significantly greater dags (p < 0.05) than sheep treated with the ivermectin capsule. These findings indicate that treated animals contributed significantly fewer nematode eggs to the contamination of pasture and therefore pasture contamination should be significantly reduced for at least 112 days. The productivity of the ivermectin capsule-treated sheep over the I6 weeks of the trials was also significantly increased compared to salvage-treated controls. Furthermore, the presence of dags, which predispose sheep to blowfly strike in the breech area and result in production losses due to the costs of dagging and downgrading of breech wool, were also significantly (p < 0.05) reduced in the ivermectin capsule-treated sheep.

21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... this chapter. (c) Conditions of use—(1) Dogs—(i) Amount. A minimum of 6 µg of ivermectin and 5 mg of... for use. To prevent canine heartworm disease by eliminating the tissue larval stages of Dirofilaria... stenocephala. (iii) Limitations. Use monthly. Recommended for dogs 6 weeks of age and older. Federal law...

21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... this chapter. (c) Conditions of use—(1) Dogs—(i) Amount. A minimum of 6 µg of ivermectin and 5 mg of... for use. To prevent canine heartworm disease by eliminating the tissue larval stages of Dirofilaria... stenocephala. (iii) Limitations. Use monthly. Recommended for dogs 6 weeks of age and older. Federal law...

21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... this chapter. (c) Conditions of use—(1) Dogs—(i) Amount. A minimum of 6 µg of ivermectin and 5 mg of... for use. To prevent canine heartworm disease by eliminating the tissue larval stages of Dirofilaria... stenocephala. (iii) Limitations. Use monthly. Recommended for dogs 6 weeks of age and older. Federal law...

21 CFR 520.1196 - Ivermectin and pyrantel pamoate chewable tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ivermectin and pyrantel pamoate chewable tablets. 520.1196 Section 520.1196 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1196...

Topical (pour-on) ivermectin in the treatment of canine scabies.

PubMed Central

Paradis, M; de Jaham, C; Pagé, N

1997-01-01

The efficacy of a pour-on formulation of ivermectin at 500 micrograms/kg body weight applied on the dorsum on days 1 and 15 was evaluated in 90 dogs from a shelter, naturally infested with Sarcoptes scabiei. This very practical form of treatment was successful in eradicating scabies from this shelter. PMID:9187806

Efficacy of two anthelmintic treatments, spinosad/milbemycin oxime and ivermectin/praziquantel in dogs with natural Toxocara spp. infection.

PubMed

Heredia Cardenas, Rafael; Romero Núñez, Camilo; Miranda Contreras, Laura

2017-11-30

Toxocara canis is one of the most important zoonotic parasites of dogs. The aim of the present study was to compare the efficacy of spinosad/milbemycin oxime and ivermectin/praziquantel in dogs naturally infected with Toxocara spp. We studied 200 dogs with a positive diagnosis of Toxocara spp. Through coproparasitoscopic analysis, two study groups of 100 dogs each were assigned: spinosad/milbemycin oxime at a dose of 30-60mg/kg and 0.75-1.0mg/kg, respectively, or ivermectin/praziquantel administered at a dose of 0.2mg/kg and 5mg/kg, respectively. Both groups received a single dose. Three stool samples, one at day 0 before treatment, and at 14 and 28days post-treatment were examined using concentration-flotation techniques. In both treatments, the number of Toxocara spp. eggs decreased; with spinosad/milbemycin oxime treatment, eggs decreased by 87% at 14days (P=0.008) and 94% at 28days after treatment, compared with 71% at day 14 and 88% at day 28 in dogs medicated with ivermectin/praziquantel. The spinosad/milbemycin oxime treated group showed a greater decrease in the number of Toxocara spp. positive dogs compared to the group receiving ivermectin/praziquantel. Copyright © 2017 Elsevier B.V. All rights reserved.

Ivermectin lipid-based nanocarriers as novel formulations against head lice.

PubMed

Ullio-Gamboa, Gabriela; Palma, Santiago; Benoit, Jean Pierre; Allemandi, Daniel; Picollo, María Inés; Toloza, Ariel Ceferino

2017-08-01

The use of pyrethroids to control the human head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), has suffered considerable loss of efficacy due to the evolution of resistance. Thus, the development of efficiently insecticide delivery systems is imperative for the control of head lice. We studied the insecticidal activity of ivermectin-loaded lipid nanocapsules (IVM-LNC) against permethrin-resistant head lice from Argentina. The LNC, prepared by a phase inversion procedure, were characterized in terms of size, surface potential, and physical stability. These nanoparticles were nearly spherical with mean diameters of 55 nm and narrow size distribution (PI ≤ 0.2). The KT 50 mortality values of head lice after exposure to two IVM-LNC formulations (0.11 and 0.28%) were significantly smaller (5 and 3 h, respectively) compared to those exposed only to LNC control group (8 h). This investigation showed the effectiveness in the encapsulation of ivermectin (IVM) into stable LNC dispersion with a potential clinical activity against head lice.

Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea.

PubMed

Schaller, M; Gonser, L; Belge, K; Braunsdorf, C; Nordin, R; Scheu, A; Borelli, C

2017-11-01

Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo. To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea. A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score ≥3) and a Demodex density ≥15/cm 2 . Patients were treated with topical ivermectin 1% cream once daily (Soolantra ® ) for ≥12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining. The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-α were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-α at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score ≤1. Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin. © 2017 European Academy of Dermatology and Venereology.

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment.

PubMed

Wanji, Samuel; Eyong, Ebanga-Echi J; Tendongfor, Nicholas; Ngwa, Che J; Esuka, Elive N; Kengne-Ouafo, Arnaud J; Datchoua-Poutcheu, Fabrice R; Enyong, Peter; Agnew, Dalen; Eversole, Rob R; Hopkins, Adrian; Mackenzie, Charles D

2017-07-01

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM

Efficacy of an ivermectin controlled-release capsule against nematode and arthropod endoparasites in sheep.

PubMed

Rehbein, S; Batty, A F; Barth, D; Visser, M; Timms, B J; Barrick, R A; Eagleson, J S

1998-03-28

Five controlled trials were conducted in Germany or in the United Kingdom, using 74 female sheep of merino or Dorset horn breeds, to evaluate the efficacy of an ivermectin controlled-release capsule against naturally acquired or induced infections of gastrointestinal nematodes, lungworms and nasal bot larvae and against incoming infections with gastrointestinal and pulmonary nematodes. Half of the animals were treated with one ivermectin controlled-release capsule that delivered ivermectin at the rate of 1.6 mg per day for 100 days while the other half remained untreated. Parasites were counted 21, 28, 35 or 56 days after administration of the capsule. The treatment was highly effective (> or = 99 per cent) against established parasites of the following species: Haemonchus contortus (adults and fourth-stage larvae), Ostertagia circumcincta, O pinnata, O trifurcata, Ostertagia species fourth-stage larvae, Trichostrongylus axei, T colubriformis, T vitrinus, Cooperia curticei, Nematodirus battus, N filicollis, Strongyloides papillosus, Chabertia ovina, Oesophagostomum venulosum, Trichuris ovis, Tr skrjabini, Dictyocaulus filaria, Protostrongylus rufescens and Oestrus ovis (larvae). The treatment prevented the establishment of the gastrointestinal nematodes H contortus, O circumcincta, T axei, T colubriformis, C curticei, N battus, N filicollis, Ch ovina, Oe vennulosum and the establishment of the lungworm D filaria by > 99 per cent compared with untreated controls (P < or = 0.01).

Sequential mesenteric arteriography in pony foals during repeated inoculations of Strongylus vulgaris and treatments with ivermectin.

PubMed

Holmes, R A; Klei, T R; McClure, J R; Turk, M A; Watters, J W; Chapman, M R

1990-04-01

Semiselective mesenteric arteriography was performed at regular intervals (inoculation weeks [IW] 0, 11, 18, and 24) in 9 of 10 pony foals raised to be free of parasites. Fifty infective larvae (L3) of Strongylus vulgaris were administered weekly for 4 weeks, then every 2 weeks through the 20th week. Three ponies were given ivermectin (oral paste, 0.2 mg/kg of body weight) treatment at IW 8, 16 and 24. Four ponies were inoculated, but did not receive ivermectin, and a third group of 2 ponies acted as uninoculated controls. Control ponies did not have gross or arteriographic lesions, whereas the inoculated untreated ponies had gross and progressive arteriographic lesions typical of verminous arteritis. Arteriographic lesions in the ivermectin-treated inoculated ponies were not as severe those in the untreated inoculated group, and there was either a partial resolution or a lack of progression of arteriographic lesions in all treated ponies. One untreated inoculated pony did not have progressive arterial lesions as did the 3 others in the group, and may develop resistance to the parasite.

Evaluation of ivermectin against later fourth-stage Strongylus vulgaris in ponies at two and five weeks after treatment.

PubMed

Slocombe, J O; McCraw, B M

1984-10-01

The efficacy of ivermectin against later fourth-stage Strongylus vulgaris larvae was studied in pony foals at 14 and 35 days after treatment. These foals had been reared parasite-free, inoculated with 500 infective larvae and 56 days later given either ivermectin at 200 micrograms/kg or a placebo intramuscularly. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was found to be highly effective (98.6%) against later fourth-stage larvae in five foals which were examined at 35 days after treatment, but not in five others examined at 14 days (72.5%). In some foals larvae were found in the tunica media of the ileocolic arteries. The conformation of these larvae appeared normal, but there were degenerative changes which suggested that they were dying or dead. Questions as to how the larvae attained that site and the consequences of their presence there were raised.

Impact of Long-Term Treatment with Ivermectin on the Prevalence and Intensity of Soil-Transmitted Helminth Infections

PubMed Central

Moncayo, Ana Lucia; Vaca, Maritza; Amorim, Leila; Rodriguez, Alejandro; Erazo, Silvia; Oviedo, Gisela; Quinzo, Isabel; Padilla, Margarita; Chico, Martha; Lovato, Raquel; Gomez, Eduardo; Barreto, Mauricio L.; Cooper, Philip J.

2008-01-01

Background Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children. Methods and Findings A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6–16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0–5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR =  0.06, 95% CI 0.03–0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11–0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments. Conclusion Annual and twice

The prevalences of Wuchereria bancrofti antigenaemia in communities given six rounds of treatment with diethylcarbamazine, ivermectin or placebo tablets.

PubMed

Ramaiah, K D; Vanamail, P; Pani, S P; Das, P K

2003-10-01

The ICT filariasis card test was used to determine the prevalences of Wuchereria bancrofti antigenaemia among villagers in India. Prior to the tests, those living in the 15 study villages had been treated six times, in six rounds of mass treatment (with 54%-75% coverage) spread over 6 years, with single doses of diethylcarbamazine (five villages), ivermectin (five villages) or placebo (five villages). The corresponding overall prevalences (and ranges) of filarial antigenaemia were 20.2% (13.7%-28.6%), 22.6% (15.3%-34.3%) and 25.9% (22.6%-29.3%), respectively. The overall prevalence of antigenaemia in the villages where diethylcarbamazine (DEC) had been distributed (but not that in the 'ivermectin' villages) was significantly lower than that recorded in the 'placebo' villages (z =2.56; P <0.05). The prevalences of antigenaemia among the villagers aged 1-5 years (18.9%, 15.6% and 22.4% in the DEC, ivermectin and placebo villages, respectively) did not differ significantly with treatment (P >0.05). The results indicate that annual mass treatments based on DEC or ivermectin, with 54%-75% treatment coverage, may have only a limited effect on the prevalence of infection with adult W. bancrofti. The possible reasons for the antigenaemias observed are discussed.

A pilot study of the use of oral ivermectin to treat head lice in primary school students in Australia.

PubMed

Currie, Marian J; Reynolds, Graham J; Glasgow, Nicholas J; Bowden, Francis J

2010-01-01

Head lice are a common, costly public health problem worldwide. We aimed to determine the feasibility of an ivermectin intervention program. Consenting students in two schools were screened for head lice. Infested students and siblings at one school were offered a head lice fact sheet and two doses of oral ivermectin, 7 days apart. Parents of infested students in the other school were given the same fact sheet and asked to treat the child and siblings using their preferred topical treatment. Seven hundred two of 754 (93.1%) students enrolled in the two schools were screened; 40 (5.3%; 95% CI 3.7-6.9) had head lice; 31 (9.4%; 95% CI 6.1-12.2) in the intervention school and nine (2.5%; 95% CI 1.1-3.8) in the control school. Subsequently 93.6% of children in the intervention school were treated with oral ivermectin. No adverse events were reported. At 6 months the reduction in the head lice infestation rates for the intervention and control schools were 87% and 56%, respectively. This pilot study suggests that school wide screening for head lice and the administration of oral ivermectin is feasible and acceptable. A randomized controlled trial at 20 schools is planned. © 2010 Wiley Periodicals, Inc.

Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus.

PubMed

Kim, J H; Gellatly, K J; Lueke, B; Kohler, M; Nauen, R; Murenzi, E; Yoon, K S; Clark, J M

2018-02-01

We previously observed that ivermectin-induced detoxification genes, including ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) were identified from body lice following a brief exposure to a sublethal dose of ivermectin using a non-invasive induction assay. In this current study, the functional properties of PhABCC4 and CYP6CJ1 were investigated after expression in either X. laevis oocytes or using a baculovirus expression system, respectively. Efflux of [ 3 H]-9-(2-phosphonomethoxyethyl) adenine ([ 3 H]-PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA-injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors. Efflux was also determined to be ATP-dependent. Using a variety of insecticides in a competition assay, only co-injection of ivermectin and dichlorodiphenyltrichloroethane led to decreased efflux of [ 3 H]-PMEA. PhABCC4-expressing oocytes also directly effluxed [ 3 H]-ivermectin, which increased over time. In addition, ivermectin appeared to be oxidatively metabolized and/or sequestered, although at low levels, following functional expression of CYP6CJ1 along with cytochrome P450 reductase in Sf9 cells. Our study suggests that PhABCC4 and perhaps CYP6CJ1 are involved in the Phase III and Phase I xenobiotic metabolism of ivermectin, respectively, and may play an important role in the evolution of ivermectin resistance in lice and other insects as field selection occurs. © 2017 The Royal Entomological Society.

76 FR 57905 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... solution for treatment and control of various internal and external parasites in cattle, swine, reindeer...: John K. Harshman, Center for Veterinary Medicine (HFV-170), Food and Drug Administration, 7500 Standish... of BIMECTIN (ivermectin) Injection for Cattle and Swine for treatment and control of various internal...

Toxicity and potential utility of ivermectin and moxidectin as xenointoxicants against the common bed bug, Cimex lectularius L.

PubMed

Sheele, Johnathan M; Ridge, Gale E

2016-08-01

The recent resurgence of the common bed bug Cimex lectularius L. throughout western industrialized nations has been facilitated in part by the insect becoming pesticide-resistant. Novel control strategies, including xenointoxication, should be considered to combat C. lectularius. Ivermectin, a U.S. Food and Drug Administration (FDA)-approved treatment for several human parasites, and the antiparasitic drug moxidectin, currently being explored in human clinical trials, were evaluated for efficacy against C. lectularius. Results showed that C. lectularius fed on ivermectin or moxidectin blood concentrations of >25 ng/mL and had significantly higher mortality (50-100 %) than controls (0-6 %) by day 13. Bed bugs that survived a blood meal containing >2.5 ng/mL of ivermectin suffered long-term sequelae including reduced fecundity, feeding difficulty, and incomplete ecdysis. Some insects that survived a blood meal containing ≤75 ng/mL moxidectin were able to feed and reproduce.

Evaluation of ivermectin against later fourth-stage Strongylus vulgaris in ponies at two and five weeks after treatment.

PubMed Central

Slocombe, J O; McCraw, B M

1984-01-01

The efficacy of ivermectin against later fourth-stage Strongylus vulgaris larvae was studied in pony foals at 14 and 35 days after treatment. These foals had been reared parasite-free, inoculated with 500 infective larvae and 56 days later given either ivermectin at 200 micrograms/kg or a placebo intramuscularly. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was found to be highly effective (98.6%) against later fourth-stage larvae in five foals which were examined at 35 days after treatment, but not in five others examined at 14 days (72.5%). In some foals larvae were found in the tunica media of the ileocolic arteries. The conformation of these larvae appeared normal, but there were degenerative changes which suggested that they were dying or dead. Questions as to how the larvae attained that site and the consequences of their presence there were raised. Images Fig. 1.,Fig. 2.,Fig. 3.,Fig. 4.,Fig. 5.,Fig. 6. PMID:6391639

Ivermectin treatment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect on hookworm and lice infection status, haematological parameters, growth, and survival.

PubMed

Marcus, Alan D; Higgins, Damien P; Gray, Rachael

2015-07-01

A placebo-controlled study was used to investigate the effectiveness of ivermectin to treat hookworm (Uncinaria sanguinis) and lice (Antarctophthirus microchir) infections in free-ranging Australian sea lion (Neophoca cinerea) pups and to test the hypotheses that these parasitic infections cause anaemia, systemic inflammatory responses, and reduced growth, and contribute towards decreased pup survival. Ivermectin was identified as an effective and safe anthelmintic in this species. Pups administered ivermectin had significantly higher erythrocyte counts and significantly lower eosinophil counts compared to controls at 1-2 months post-treatment, confirming that U. sanguinis and/or A. microchir are causatively associated with disease and demonstrating the positive effect of ivermectin treatment on clinical health parameters. Higher growth rates were not seen in ivermectin-treated pups and, unexpectedly, relatively older pups treated with ivermectin demonstrated significantly reduced growth rates when compared to matched saline-control pups. Differences in survival were not identified between treatment groups; however, this was attributed to the unexpectedly low mortality rate of recruited pups, likely due to the unintended recruitment bias towards pups >1-2 months of age for which mortality due to hookworm infection is less likely. This finding highlights the logistical and practical challenges associated with treating pups of this species shortly after birth at a remote colony. This study informs the assessment of the use of anthelmintics as a tool for the conservation management of free-ranging wildlife and outlines essential steps to further the development of strategies to ensure the effective conservation of the Australian sea lion and its parasitic fauna.

A field test of the effect of spiked ivermectin concentrations on the biodiversity of coprophagous dung insects in Switzerland.

PubMed

Jochmann, Ralf; Lipkow, Erhard; Blanckenhorn, Wolf U

2016-08-01

Veterinary medical product residues can cause severe damage in the dung ecosystem. Depending on the manner of application and the time after treatment, the excreted concentration of a given pharmaceutical varies. The popular anthelmintic drug ivermectin can be applied to livestock in several different ways and is fecally excreted over a period of days to months after application. In a field experiment replicated in summer and autumn, the authors mixed 6 ivermectin concentrations plus a null control into fresh cow dung to assess the reaction of the dung insect community. Taxon richness of the insect dung fauna emerging from the dung, but not Hill diversity ((1) D) or the total number of individuals (abundance), decreased as ivermectin concentration increased. Corresponding declines in the number of emerging insects were found for most larger brachyceran flies and hymenopteran parasitoids, but not for most smaller nematoceran flies or beetles (except Hydrophilidae). Parallel pitfall traps recovered all major dung organism groups that emerged from the experimental dung, although at times in vastly different numbers. Ivermectin generally did not change the attractiveness of dung: differences in emergence therefore reflect differences in survival of coprophagous offspring of colonizing insects. Because sample size was limited to 6 replicates, the authors generally recommend more than 10 (seasonal) replicates and also testing higher concentrations than used in the present study as positive controls in future studies. Results accord with parallel experiments in which the substance was applied and passed through the cow's digestive system. In principle, therefore, the authors' experimental design is suitable for such higher-tier field tests of the response of the entire dung community to pharmaceutical residues, at least for ivermectin. Environ Toxicol Chem 2016;35:1947-1952. © 2015 SETAC. © 2015 SETAC.

Can ivermectin mass treatments eliminate onchocerciasis in Africa?

PubMed Central

Winnen, M.; Plaisier, A. P.; Alley, E. S.; Nagelkerke, N. J. D.; van Oortmarssen, G.; Boatin, B. A.; Habbema, J. D. F.

2002-01-01

OBJECTIVE: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS: ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS: Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION: Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas. PMID:12077614

Functional properties of internalization-deficient P2X4 receptors reveal a novel mechanism of ligand-gated channel facilitation by ivermectin.

PubMed

Toulmé, Estelle; Soto, Florentina; Garret, Maurice; Boué-Grabot, Eric

2006-02-01

Although P2X receptors within the central nervous system mediate excitatory ATP synaptic transmission, the identity of central ATP-gated channels has not yet been elucidated. P2X(4), the most widely expressed subunit in the brain, was previously shown to undergo clathrin-dependent constitutive internalization by direct interaction between activator protein (AP)2 adaptors and a tyrosine-based sorting signal specifically present in the cytosolic C-terminal tail of mammalian P2X(4) sequences. In this study, we first used internalization-deficient P2X(4) receptor mutants to show that suppression of the endocytosis motif significantly increased the apparent sensitivity to ATP and the ionic permeability of P2X(4) channels. These unique properties, observed at low channel density, suggest that interactions with AP2 complexes may modulate the function of P2X(4) receptors. In addition, ivermectin, an allosteric modulator of several receptor channels, including mammalian P2X(4), did not potentiate the maximal current of internalization-deficient rat or human P2X(4) receptors. We demonstrated that binding of ivermectin onto wild-type P2X(4) channels increased the fraction of plasma membrane P2X(4) receptors, whereas surface expression of internalization-deficient P2X(4) receptors remained unchanged. Disruption of the clathrin-mediated endocytosis with the dominant-negative mutants Eps15 or AP-50 abolished the ivermectin potentiation of wild-type P2X(4) channel currents. Likewise, ivermectin increased the membrane fraction of nicotinic alpha7 acetylcholine (nalpha7ACh) receptors and the potentiation of acetylcholine current by ivermectin was suppressed when the same dominant-negative mutants were expressed. These data showed that potentiation by ivermectin of both P2X(4) and nalpha7ACh receptors was primarily caused by an increase in the number of cell surface receptors resulting from a mechanism dependent on clathrin/AP2-mediated endocytosis.

Strategic use of ivermectin during pregnancy to control toxocara canis in greyhound puppies.

PubMed

Payne, P A; Ridley, R K

1999-09-01

Twenty-one greyhound bitches were bred (Day 0) and housed throughout their pregnancies on three greyhound breeding farms in Kansas. These dogs were assigned randomly to one of four treatment groups. Group A dogs (6) were given ivermectin subcutaneously (300 microg/kg) on Day 0 (the first day the dogs were bred), and Days 30 and 60 of gestation. Group B dogs (6) were given ivermectin (300 microg/kg SQ) on Day 42. Group C dogs (3) were given ivermectin (300 microg/kg SQ) on Days 0, 30, and 60 plus 10 days after whelping. Group D dogs (6) served as controls and received no anthelmintic. Bitches and puppies were moved to the university on the day after birth and were maintained inside for 28 days. Weekly quantitative fecal exams were done on the bitches during this time. The puppies were euthanized humanely at 28 days of age. Intestinal parasites were recovered, identified, counted, sexed, and preserved in either 10% formalin or frozen at -70 degrees C. The geometric mean numbers of adult Toxocara canis in the small intestines for Group A puppies (n = 40) were 2.8, 8.5 for Group B puppies (n = 39), and 29.7 for Group D puppies (n = 28). No adults were found in the Group C puppies (n = 15). The geometric mean eggs per gram of feces from the pups in group A, B, and D were 1.3, 704, and 27, 134, respectively. No eggs were recovered from the Group C pups. The strategic use of ivermectin at 300 microg/kg in greyhound bitches on Days 0, 30, and 60 of gestation reduced the worm burden carried by the puppies by 90% and the actual number of eggs passed into the environment by 99.8%. The same dose on day 42 reduced the worm burden by 71.4% and the number of eggs passed into the environment by 97.4%. This dose given on days 0, 30, and 60 plus 10 days postwhelping, reduced the worm burden by 100%, and no eggs were passed into the environment.

A clinical trial to evaluate the effects of flumethrin or ivermectin treatment on hemoparasites, gastrointestinal parasites, conception and daily weight gain in a dairy farm in Japan.

PubMed

Yamane, I; Arai, S; Nakamura, Y; Hisashi, M; Fukazawa, Y; Onuki, T

2000-02-01

A clinical trial was performed to compare the effects of flumethrin and ivermectin treatments of grazing heifers at one farm in central Japan. 64 heifers were randomly allocated into two groups. Flumethrin (1 mg/kg pour on) was applied approximately once every 3 weeks to heifers in one group and heifers in the second group were injected approximately once every month with ivermectin (200 microg/kg; id). Between groups, no significant differences were detected in the proportions of animals that showed parasitemia of Theileria sergenti and conception risks. Significantly lower average log-transformed nematode-egg counts and higher average daily weight gain were observed in the ivermectin-treated group. Animals with higher body weight at the start of grazing and lower log-transformed total nematode-egg and coccidia-oocyst counts had higher odds of conceiving. Animals with ivermectin treatment, lower body weight at the start of grazing and lower log-transformed coccidia-oocyst count had higher daily weight gain. Ivermectin may be more useful in this farm because of the higher productivity for cattle and lower cost for its usage.

Drawing and interpreting data: Children's impressions of onchocerciasis and community-directed treatment with ivermectin (CDTI) in four onchocerciasis endemic countries in Africa

PubMed Central

Amuyunzu-Nyamongo, Mary; Tchounkeu, Yolande Flore Longang; Oyugi, Rahel Akumu; Kabali, Asaph Turinde; Okeibunor, Joseph C.; Manianga, Cele; Amazigo, Uche V.

2011-01-01

Although the depiction of a child leading a blind man is the most enduring image of onchocerciasis in Africa, research activities have hardly involved children. This paper aims at giving voice to children through drawings and their interpretation. The study was conducted in 2009 in Cameroon, Democratic Republic of Congo (DRC), Nigeria and Uganda. Children aged 6–16 years were asked to draw their perceptions of onchocerciasis and community-directed treatment with ivermectin (CDTI) in their communities. A total of 50 drawings were generated. The drawings depicted four main aspects of onchocerciasis: (1) the disease symptoms, (2) the negative consequences of onchocerciasis among children and in the community generally, (3) the ivermectin distribution process, and (4) the benefits or effects of taking ivermectin. Out of the 50 drawings, 30 were on symptoms, 7 on effects of the disease on children, 8 on distribution process, and 5 represented multiple perceptions on symptoms, drug distribution processes, benefits, and effects of treatment. The lack of clarity when treatment with ivermectin can be stopped in endemic areas requires working with children to ensure continued compliance with treatment into the future. Children's drawings should be incorporated into health education interventions. PMID:21637349

Development and validation of a new HPLC-UV method for the simultaneous determination of triclabendazole and ivermectin B1a in a pharmaceutical formulation.

PubMed

Shurbaji, Maher; Abu Al Rub, Mohamad H; Saket, Munib M; Qaisi, Ali M; Salim, Maher L; Abu-Nameh, Eyad S M

2010-01-01

A rapid, simple, and sensitive RP-HPLC analytical method was developed for the simultaneous determination of triclabendazole and ivermectin in combination using a C18 RP column. The mobile phase was acetonitrile-methanol-water-acetic acid (56 + 36 + 7.5 + 0.5, v/v/v/v) at a pH of 4.35 and flow rate of 1.0 mL/min. A 245 nm UV detection wavelength was used. Complete validation, including linearity, accuracy, recovery, LOD, LOQ, precision, robustness, stability, and peak purity, was performed. The calibration curve was linear over the range 50.09-150.26 microg/mL for triclabendazole with r = 0.9999 and 27.01-81.02 microg/mL for ivermectin with r = 0.9999. Calculated LOD and LOQ for triclabendazole were 0.03 and 0.08 microg/mL, respectively, and for ivermectin 0.07 and 0.20 microg/mL, respectively. The intraday precision obtained was 98.71% with RSD of 0.87% for triclabendazole and 100.79% with RSD 0.73% for ivermectin. The interday precision obtained was 99.51% with RSD of 0.35% for triclabendazole and 100.55% with RSD of 0.59% for ivermectin. Robustness was also studied, and there was no significant variation of the system suitability of the analytical method with small changes in experimental parameters.

Encephalopathy after ivermectin treatment in a patient infected with Loa loa and Plasmodium spp.

PubMed

Kamgno, Joseph; Boussinesq, Michel; Labrousse, François; Nkegoum, Blaise; Thylefors, Björn I; Mackenzie, Charles D

2008-04-01

Despite over 350 million people being safely treated with ivermectin, there have been rare cases of death post-treatment; these events are most often associated with high Loa loa microfilaremia. This first autopsy description of an encephalopathy case following the administration of ivermectin involves a 45-year-old male who became comatose 3 days after treatment. He slowly deteriorated over 5 weeks and died at 54 days after the anthelminthic treatment, probably as a result of a secondary skin or pulmonary infection exacerbated by malnutrition. The major pre- and post-autopsy findings included the presence of high loads of Loa loa, positivity for Plasmodium, the presence of a longstanding respiratory condition, and vascular pathology in the brain. The central nervous system lesions have similarities with those described in previously reported cases of Loa loa-associated death following diethylcarbamazine treatment.

The development of an ivermectin-based attractive toxic sugar bait (ATSB) to target Anopheles arabiensis.

PubMed

Tenywa, Frank Chelestino; Kambagha, Athumani; Saddler, Adam; Maia, Marta Ferreira

2017-08-15

An increasing number of countries in sub-Saharan Africa are moving towards malaria-elimination, mostly thanks to successful vector control campaigns. However, elimination has proven challenging, resulting in the persistence of malaria transmission. It is now accepted that in order to eliminate malaria, new complementary vector control approaches must be developed. This study describes the development of a sugar-baited resting place containing a toxic dose of ivermectin for the control of Anopheles arabiensis. Dose response experiments were performed in insectary conditions to determine the LD90 of ivermectin against An. arabiensis. Over 95% of An. arabiensis were knocked down 48 h post-sugar feeding on 10% sucrose solutions containing 0.01% ivermectin. When investigating different juices as attractants, it was observed that An. arabiensis preferred orange, watermelon and commercial guava juice over pawpaw, tomato, mango or banana, but were most likely to feed on simple 10% sugar solution. Using recycled materials, different bait prototypes were tested to determine the best design to maximize sugar feeding. Baits that offered a resting place for the mosquito rather than just a surface to sugar feed were more likely to attract An. arabiensis to sugar feed. The optimized prototype was then placed in different locations within a screen-house, colour-coded with different food dyes, containing competing vegetation (Ricinus communis) and experimental huts where humans slept under bed nets. Around half of all the released An. arabiensis sugar fed on the sugar baits, and approximately 50% of all sugar fed mosquitoes chose the baits close to outdoor vegetation before entering the huts. Ivermectin is an effective insecticide for use in sugar baits. The design of the sugar bait can influence feeding rates and, therefore, efficacy. Sugar baits that offer a resting surface are more efficient and sugar feeding on the baits is maximized when these are placed close to peri

Impact of 3 years ivermectin treatment on onchocerciasis in Yanomami communities in the Brazilian Amazon.

PubMed

Banic, Dalma M; Calvão-Brito, Regina H S; Marchon-Silva, Verônica; Schuertez, Joana C; de Lima Pinheiro, Luís Renerys; da Costa Alves, Marilene; Têva, Antônio; Maia-Herzog, Marilza

2009-11-01

In the current study, it was assessed, for the first time, the effect of ivermectin treatment administered twice a year on the prevalence and morbidity of onchocerciasis in the hyperendemic Yanomami communities of the Roraima State (Brazil). Physical and parasitological examinations were carried out every 6 months until six drug rounds of treatment were completed. The coverage during the six rounds of ivermectin treatment ranged from 89% to 92% of the eligible Yanomami population. Overall, comparison of results at pre-treatment with results after six rounds of treatment, the prevalence of infection had declined from 87% to 42% (P<0.0001, CI 95%=0.05-0.22); the community microfilarial load (CMFL) fell from 1.17 to 0.53Mf/mg of skin; and the crude intensity of infection (MFL-Total) decreased from 18.95 to 1.96Mf/mg of skin during the same period (P<0.0001, for both microfilarial loads). Although no significant difference was observed between microfilarial densities in skin snips from iliac crest and scapula after the 6th round of ivermectin treatment it was observed that the prevalence of positive skin snips was significantly higher when skin snips were taken from iliac crest (42%) than from scapula (8%) (P=0.001, CI 95%=3.41-22.67). After six rounds of ivermectin treatments, no significant differences were observed in the prevalences of palpable nodules and of onchodermatitis in relation to pre-treatment prevalences, from 45% to 41% and from 17% to 20% (P>0.05, for both). These findings suggest that mass population treatment should continue without interruption and achieve higher levels of drug coverage in order to alleviate disease manifestations and interrupt infection transmission to hasten the elimination of onchocerciasis in Yanomami communities. In addition, the sensitivity of iliac crest snips for parasitological assessment in epidemiological surveillance of Yanomami communities may increase the acceptance of the population in biopsy sampling and seems to be

Suspected ivermectin toxicosis in a miniature mule foal causing blindness.

PubMed

Plummer, Caryn E; Kallberg, Maria E; Ollivier, Franck J; Brooks, Dennis E; Gelatt, Kirk N

2006-01-01

A 9-week-old miniature mule foal presented to the Veterinary Medical Teaching Hospital for acute blindness, ataxia, and depression following an overdose of an over-the-counter ivermectin-based de-worming medication. Ophthalmic examination and electrodiagnostic evaluation eliminated outer retinal abnormalities as the primary cause of the bilateral blindness, implicating instead a central neurologic effect of the drug. With symptomatic and supportive care, the foal recovered fully and regained its vision.

Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis.

PubMed

Palmeirim, Marta S; Hürlimann, Eveline; Knopp, Stefanie; Speich, Benjamin; Belizario, Vicente; Joseph, Serene A; Vaillant, Michel; Olliaro, Piero; Keiser, Jennifer

2018-04-01

The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31-0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87-1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin

Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis

PubMed Central

Palmeirim, Marta S.; Hürlimann, Eveline; Knopp, Stefanie; Belizario, Vicente; Joseph, Serene A.; Olliaro, Piero

2018-01-01

Background The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. Methods and findings We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis

[Outbreaks of Scabies in Schools and Use of Ivermectin].

PubMed

Weigl, Josef A I

2018-04-01

At Pentecost 2017 outbreaks of scabies occurred in three schools in Ploen County. Several classes were supposed to go on an excursion or had returned from an excursion with symptomatic kids. Rapid investigation, on site outbreak confirmation, home visits of the environment of the index cases, simultaneous mass treatment and post exposure prophylaxis (PEP) with Ivermectin according to the outbreak characteristics were applied. The index case of school A was ill since 5 months, but was misdiagnosed as eczema. Not all cases were linked to this index case. The entire school was treated in three steps within a 10-day period: step 1 began 48 h after notification. The attack rate was 6.4% (19 out of 298 pupils). A total of 93% of the kids and 100% of the teaching staff were treated. For school B with two sporadic and independent cases, an alert warning was issued. In school C, the two classes with cases were treated and according to the contact pattern two further classes were physically examined: 7 out of 39 (18%) of the kids were symptomatic, but none in the contact classes. The endemicity of scabies appears to be much higher than previously assumed. With the use of Ivermectin, the local public health department could act quickly and demonstrate that interventional public health is possible. However, several obstacles had to be overcome, but parents and teachers were cooperative and thankful. © Georg Thieme Verlag KG Stuttgart · New York.

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

PubMed Central

2010-01-01

Background Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies. Methods Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients. Results We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). CYP3A4*1B, CYP3A5*3 and CYP3A5*6 alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. CYP3A5*1/CYP3A5*1 and CYP3A5*1/CYP3A5*3 genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin. Conclusion A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders. PMID:20630055

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

PubMed

Kudzi, William; Dodoo, Alexander N O; Mills, Jeremy J

2010-07-14

Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies. Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients. We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). CYP3A4*1B, CYP3A5*3 and CYP3A5*6 alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. CYP3A5*1/CYP3A5*1 and CYP3A5*1/CYP3A5*3 genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin. A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.

Predictors of compliance with community-directed treatment with ivermectin for onchocerciasis control in Kabo area, southwestern Ethiopia.

PubMed

Endale, Adugna; Erko, Berhanu; Weldegebreal, Fitsum; Legesse, Mengistu

2015-02-15

Compliance with annual ivermectin treatment is a major challenge in community-directed treatment with ivermectin (CDTI) implementation. There are individuals who do not comply with the annual mass treatment, which contributes to the continuity for disease transmission. Hence, ensuring high treatment coverage and sustained compliance should be given due emphasis in the control of onchocerciasis. The aim of this study was to determine CDTI compliance rate and predictors of compliance where the CDTI was in its 9(th) round in Kabo area, southwestern Ethiopia. Community-based cross-sectional study was conducted in Kabo area, three weeks after the 9th round of annual ivermectin distribution. Systematic random sampling was used to select head of households and structured, pre-tested questionnaire was used to interview the study participants. Data was analyzed using SPSS version 16. Descriptive statistics was used to compute mean and standard deviation of continuous variables and frequency for categorical variables, while bivariate and multivariate logistic regressions were used to assess the effects of independent variables on the outcome variable. Variables which showed association in multivariate analysis were considered as final predictors of compliance and strength of association was measured through adjusted odds ratio (AOR). A total of 308 respondents (age range 18-70, mean age ± SD, 32.21 ± 9.64) participated in the study. Of these, 249 (80.8%) reported that they took ivermectin during the 9th round annual treatment. Significantly higher rate of treatment compliance was reported by participants age ≥35 years (AOR = 5.48, 95% CI; 1.97 - 15.23), participants who stayed in the area for more than ten years (AOR = 3.86, 95% CI; 1.83- 8.11), participants who perceive that they are at risk of contracting the disease(AOR = 7.05, 2.70- 18.43), participants who perceive community drug distributors (CDDs) are doing their work well (AOR = 2.35 95% CI; 1

Factors affecting the attrition of community-directed distributors of ivermectin, in an onchocerciasis-control programme in the Imo and Abia states of south-eastern Nigeria.

PubMed

Emukah, E C; Enyinnaya, U; Olaniran, N S; Akpan, E A; Hopkins, D R; Miri, E S; Amazigo, U; Okoronkwo, C; Stanley, A; Rakers, L; Richards, F O; Katabarwa, M N

2008-01-01

In areas of Nigeria where onchocerciasis is endemic, community-directed distributors (CDD) distribute ivermectin annually, as part of the effort to control the disease. Unfortunately, it has been reported that at least 35% of the distributors who have been trained in Nigeria are unwilling to participate further as CDD. The selection and training of new CDD, to replace those unwilling to continue, leads to annual expense that the national onchocerciasis-programme is finding difficult to meet, given other programme priorities and the limited resources. If the reported levels of attrition are true, they seriously threaten the sustainability of community-directed treatment with ivermectin (CDTI) in Nigeria. In 2002, interviews were held with 101 people who had been trained as CDD, including those who had stopped serving their communities, from 12 communities in south-eastern Nigeria that had high rates of CDD attrition. The results showed that, although the overall reported CDD attrition was 40.6%, the actual rate was only 10.9%. The CDD who had ceased participating in the annual rounds of ivermectin blamed a lack of incentives (65.9%), the demands of other employment (14.6%), the long distances involved in the house-to-house distribution (12.2%) or marital duties (7.3%). Analysis of the data obtained from all the interviewed CDD showed that inadequate supplies of ivermectin (P<0.01), lack of supervision (P<0.05) and a lack of monetary incentives (P<0.001) led to significant increases in attrition. Conversely, CDD retention was significantly enhanced when the distributors were selected by their community members (P<0.001), supervised (P<0.001), supplied with adequate ivermectin tablets (P<0.05), involved in educating their community members (P<0.05), and/or involved in other health programmes (P<0.001). Although CDD who were involved in other health programmes were relatively unlikely to cease participating in the distributions, they were more likely to take longer

Observations on topical ivermectin in the treatment of otoacariosis, cheyletiellosis, and toxocariosis in cats.

PubMed Central

Pagé, N; de Jaham, C; Paradis, M

2000-01-01

The purpose of this study was to observe the efficacy of a topical pour-on formulation of ivermectin in the treatment of otoacariosis, cheyletiellosis, and toxocariosis in cats. Forty-five cats were treated. All cats received 2 to 4 topical applications of ivermectin on the skin between the shoulder blades in a narrow strip, 14 days apart. This practical treatment was effective in 96% (23/24) of cases of feline otoacariosis and in 100% (20/20) of cats with toxocariosis. All cats with cheyletiellosis (16/16) received 4 treatments and had resolution of clinical signs, but one Cheyletiella egg could still be found 45 days after the last treatment. The viability of this egg could not be evaluated, but the cats were still free of clinical signs on follow-up 6 months later. The treatment was well tolerated in all the animals. A few cats developed a transient small alopecic area and mild scaling at the site of application of the drug. PMID:11062834

Coherent anti-Stokes Raman scattering (CARS) spectroscopy in Caenorhabditis elegans and Globodera pallida: evidence for an ivermectin-activated decrease in lipid stores.

PubMed

Smus, Justyna P; Ludlow, Elizabeth; Dallière, Nicolas; Luedtke, Sarah; Monfort, Tual; Lilley, Catherine; Urwin, Peter; Walker, Robert J; O'Connor, Vincent; Holden-Dye, Lindy; Mahajan, Sumeet

2017-12-01

Macrocyclic lactones are arguably the most successful chemical class with efficacy against parasitic nematodes. Here we investigated the effect of the macrocyclic lactone ivermectin on lipid homeostasis in the plant parasitic nematode Globodera pallida and provide new insight into its mode of action. A non-invasive, non-destructive, label-free and chemically selective technique called Coherent anti-Stokes Raman scattering (CARS) spectroscopy was used to study lipid stores in G. pallida. We optimised the protocol using the free-living nematode Caenorhabditis elegans and then used CARS to quantify lipid stores in the pre-parasitic, non-feeding J2 stage of G. pallida. This revealed a concentration of lipid stores in the posterior region of J2 s within 24 h of hatching which decreased to undetectable levels over the course of 28 days. We tested the effect of ivermectin on J2 viability and lipid stores. Within 24 h, ivermectin paralysed J2 s. Counterintuitively, over the same time-course ivermectin increased the rate of depletion of J2 lipid, suggesting that in ivermectin-treated J2 s there is a disconnection between the energy requirements for motility and metabolic rate. This decrease in lipid stores would be predicted to negatively impact on J2 infective potential. These data suggest that the benefit of macrocyclic lactones as seed treatments may be underpinned by a multilevel effect involving both neuromuscular inhibition and acceleration of lipid metabolism. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug.

PubMed

Mastrangelo, Eloise; Pezzullo, Margherita; De Burghgraeve, Tine; Kaptein, Suzanne; Pastorino, Boris; Dallmeier, Kai; de Lamballerie, Xavier; Neyts, Johan; Hanson, Alicia M; Frick, David N; Bolognesi, Martino; Milani, Mario

2012-08-01

Infection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgently needed. Starting from the crystal structure of the NS3 helicase from Kunjin virus (an Australian variant of West Nile virus), we identified a novel, unexploited protein site that might be involved in the helicase catalytic cycle and could thus in principle be targeted for enzyme inhibition. In silico docking of a library of small molecules allowed us to identify a few selected compounds with high predicted affinity for the new site. Their activity against helicases from several flaviviruses was confirmed in in vitro helicase/enzymatic assays. The effect on the in vitro replication of flaviviruses was then evaluated. Ivermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication (EC₅₀ values in the sub-nanomolar range). Moreover, ivermectin inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalitis viruses. Ivermectin exerts its effect at a timepoint that coincides with the onset of intracellular viral RNA synthesis, as expected for a molecule that specifically targets the viral helicase. The well-tolerated drug ivermectin may hold great potential for treatment of YFV infections. Furthermore, structure-based optimization may result in analogues exerting potent activity against flaviviruses other than YFV.

Community-directed treatment with ivermectin in two Nigerian communities: an analysis of first year start-up processes, costs and consequences.

PubMed

Onwujekwe, Obinna; Chima, Reginald; Shu, Elvis; Okonkwo, Paul

2002-10-01

To determine the start-up processes, costs and consequences of community-directed treatment with ivermectin (CDTI) in two onchocerciasis endemic rural towns of Southeast Nigeria; namely Achi and Nike. The other objectives were to discover the community-financing mechanisms, local ivermectin distribution strategies and communities' organisational capacity to handle the programme. Structured questionnaires, informal interviews, observations, discussions with community members at general village assemblies and community outreach lectures were used at different stages of the study. The towns had the organisational capacity to implement the programme. Coverage with ivermectin was between 31-73% in Achi (mean = 58.6%), and 36.6-72% in Nike (mean = 61.95%). The unit financial costs were $0.17 in Nike and $0.13 in Achi, but the unit aggregate cost was $0.37 in Nike and $0.39 in Achi. When research costs were removed, the unit aggregate cost was $0.22 in Achi and $0.20 in Nike. Provider's financial costs and communities' non-financial costs were the biggest contributors to the aggregate cost. The cost would decrease in subsequent years since the research cost and parts of the mobilisation and training costs would not be incurred after the first year. Governments and sponsors of CDTI should find means of continuously strengthening the programme and providing technical support to the communities. As both CDTI and communities are dynamic entities, continuous health education campaigns are needed to keep reminding the people of the benefit of long-term ivermectin distribution, together with the need for community ownership of the programme.

Onchocerciasis control in Nigeria: will households be able to afford community-directed treatment with ivermectin?

PubMed

Onwujekwe, O; Shu, E; Onwuameze, O; Ndum, C; Okonkwo, P

2001-12-21

To determine the level of affordability of community-directed treatment with ivermectin (CDTI) to households living in two onchocerciasis endemic Nigerian communities namely Toro in the north and Nike in the south. The proportion of the cost of treating people with ivermectin will deplete in average monthly/projected annual household expenditure on food and health care, and on average monthly and projected annual household income were respectively calculated and used to determine the level of affordability of CDTI. Questionnaires administered to heads of households or their representatives were used to collect information on the household expenditures and income. The suggested unit CDTI cost of $0.20 was used. However, as a test of sensitivity, we also used the unit cost of $0.056 which some community based distributors are charging per treatment. Using $0.20 as the unit treatment cost, this will consume less than 0.05% of average annual household income in both communities. It will equally deplete 0.05% of combined annual household expenditures on food and health care in both communities. However, using $0.056 as the unit treatment cost, then 0.02% of average annual household expenditure on health care, 0.01% average annual expenditure on combined health care and food, and 0.01% of average annual household income will be depleted. The households living in both communities may be able to afford CDTI schemes. However, the final decision on levels of affordability lies with the households. They will decide whether they can afford to trade-off some household income for ivermectin distribution.

[The effect of ivermectin on geohelminth frequency (i.e. as used in the onchocerciasis control program in Colombia)].

PubMed

Knudson, Angélica; Ariza, Yoseth; López, Myriam C; Fajardo, Oscar S; Reyes, Patricia; Moncada, Ligia I; Duque, Sofía; Álvarez, Carlos A; Nicholls, Rubén S

2012-08-01

Evaluating the effect of ivermectin on soil-transmitted helminthes (STH) infection frequency in a Colombian population included in the Onchocerciasis Elimination Program for the Americas (OEPA). This was an impact evaluation study which adopted a longitudinal approach using the population of Naicioná (1996) as baseline for comparison to people from the same population as controls (2008). The cross-sectional approach involved comparing the reference population of Naicioná (2008) to the population of Dos Quebradas (2008) used as controls. Fecal samples were processed by a modified Ritchie-Frick method. Ascaris lumbricoides was the most frequently found parasite in Naicioná (60/121; 49.6 %: 37.8-63.895%CI) and in Dos Quebradas (36/76; 47.4 %: 33.2-65.6 95 % CI). Ivermectin's main effect on the population aged over 5 years was a decreased risk of Trichiuris trichiura infection in both longitudinal assessment (86 % reduction: 74-93 95 % CI) and cross-sectional assessment (63 %:24-82 95 % CI). A 93 % reduction (45-99 95 % CI) in Strongyloides stercoralis frequency was found in longitudinal assessment, compared to 85 % in cross-sectional assessment (-031-99 95 % CI). Ivermectin use in the OEPA is not sufficient for STH morbidity control. Integrated programs including education and basic sanitation are required.

Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.

PubMed

Gardon, J; Gardon-Wendel, N; Demanga-Ngangue; Kamgno, J; Chippaux, J P; Boussinesq, M

1997-07-05

In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. Ivermectin (at 150 micrograms/kg) was given to 17877 people living in the Lékié area of Cameroon. 50 microL samples of capillary blood were taken during the daytime before treatment from all adults (aged > or = 15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. 20 patients (0-11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2-3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio > 1000) for loads above 50000 microfilariae/mL. Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for

Integrated control of Strongylus vulgaris infection in horses using ivermectin.

PubMed

Dunsmore, J D

1985-05-01

An attempt was made to control or eliminate Strongylus vulgaris from a closed group of three horses at pasture near Perth, Western Australia, by dosing with ivermectin on four occasions during the time of year when it was believed that environmental conditions would eliminate all the non-parasitic stages of that species. At necropsy, five months after the last dose of anthelmintic and after continually grazing the same pastures, no S vulgaris or arterial lesions were found in those horses and S edentatus, Draschia megastoma and Habronema species were also almost completely eliminated.

Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug

PubMed Central

Mastrangelo, Eloise; Pezzullo, Margherita; De Burghgraeve, Tine; Kaptein, Suzanne; Pastorino, Boris; Dallmeier, Kai; de Lamballerie, Xavier; Neyts, Johan; Hanson, Alicia M.; Frick, David N.; Bolognesi, Martino; Milani, Mario

2012-01-01

Objectives Infection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgently needed. Methods Starting from the crystal structure of the NS3 helicase from Kunjin virus (an Australian variant of West Nile virus), we identified a novel, unexploited protein site that might be involved in the helicase catalytic cycle and could thus in principle be targeted for enzyme inhibition. In silico docking of a library of small molecules allowed us to identify a few selected compounds with high predicted affinity for the new site. Their activity against helicases from several flaviviruses was confirmed in in vitro helicase/enzymatic assays. The effect on the in vitro replication of flaviviruses was then evaluated. Results Ivermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication (EC50 values in the sub-nanomolar range). Moreover, ivermectin inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalitis viruses. Ivermectin exerts its effect at a timepoint that coincides with the onset of intracellular viral RNA synthesis, as expected for a molecule that specifically targets the viral helicase. Conclusions The well-tolerated drug ivermectin may hold great potential for treatment of YFV infections. Furthermore, structure-based optimization may result in analogues exerting potent activity against flaviviruses other than YFV. PMID:22535622

Community financing of local ivermectin distribution in Nigeria: potential payment and cost-recovery outlook.

PubMed

Onwujekwe, O E; Shu, E N; Okonkwo, P O

2000-04-01

The preferred payment mechanism in a community financing scheme for local ivermectin distribution was elicited from randomly selected household heads from three communities in Nigeria using interviewer-administered structured questionnaires. The majority of the respondents in the three communities were prepared to pay for local ivermectin distribution. Additionally, the average amounts the respondents were prepared to pay per person treated ($0.28, $0.30 and $0.38 in Nike, Achi and Toro, respectively) were all more than the $0.20 ceiling recommended by the partners of the African Programme on Onchocerciasis Control (APOC). Thus, the cost-recovery outlook is bright in these communities. However, the preferred payment modality varied. Fee-for-service was the predominant payment modality in the Achi and Nike communities, while the Toro community preferred pre-payment. This study demonstrates that many communities have different payment preferences for endemic disease control efforts. This knowledge will help in developing acceptable and sustainable schemes. The imposition of unacceptable payment mechanisms will lead to an unwillingness to pay.

Household-wide ivermectin treatment for head lice in an impoverished community: randomized observer-blinded controlled trial

PubMed Central

Pilger, Daniel; Heukelbach, Jorg; Khakban, Adak; Oliveira, Fabiola Araujo; Fengler, Gernot

2010-01-01

Abstract Objective To generate evidence on the effectiveness of household-wide treatment for preventing the transmission of pediculosis capitis (head lice) in resource-poor communities. Methods We studied 132 children without head lice who lived in a slum in north-eastern Brazil. We randomized the households of the study participants into an intervention and a control group and prospectively calculated the incidence of infestation with head lice among the children in each group. In the intervention group, all of the children’s family members who lived in the household were treated with ivermectin; in the control group, no family member was treated. We used the χ² test with continuity correction or Fisher’s exact test to compare proportions. We performed survival analysis using Kaplan–Meier estimates with log rank testing and the Mann–Whitney U test to analyse the length of lice-free periods among sentinel children, and we used Cox regression to analyse survival data on a multivariate level. We also carried out a subgroup analysis based on gender. Findings Children in the intervention group remained free from infestation with head lice significantly longer than children in the control group. The median infestation-free period in the intervention group was 24 days (interquartile range, IQR: 11–45), as compared to 14 days (IQR: 11–25) in the control group (P = 0.01). Household-wide treatment with ivermectin proved significantly more effective among boys than among girls (P = 0.005). After treatment with ivermectin, the estimated number of annual episodes of head lice infestation was reduced from 19 to 14 in girls and from 15 to 5 in boys. Female sex and extreme poverty were independent risk factors associated with a shortened disease-free period. Conclusion In an impoverished community, girls and the poorest of the poor are the population groups that are most vulnerable for head lice infestation. To decrease the number of head lice episodes per unit of

Household-wide ivermectin treatment for head lice in an impoverished community: randomized observer-blinded controlled trial.

PubMed

Pilger, Daniel; Heukelbach, Jorg; Khakban, Adak; Oliveira, Fabiola Araujo; Fengler, Gernot; Feldmeier, Hermann

2010-02-01

To generate evidence on the effectiveness of household-wide treatment for preventing the transmission of pediculosis capitis (head lice) in resource-poor communities. We studied 132 children without head lice who lived in a slum in north-eastern Brazil. We randomized the households of the study participants into an intervention and a control group and prospectively calculated the incidence of infestation with head lice among the children in each group. In the intervention group, all of the children's family members who lived in the household were treated with ivermectin; in the control group, no family member was treated. We used the chi(2) test with continuity correction or Fisher's exact test to compare proportions. We performed survival analysis using Kaplan-Meier estimates with log rank testing and the Mann-Whitney U test to analyse the length of lice-free periods among sentinel children, and we used Cox regression to analyse survival data on a multivariate level. We also carried out a subgroup analysis based on gender. Children in the intervention group remained free from infestation with head lice significantly longer than children in the control group. The median infestation-free period in the intervention group was 24 days (interquartile range, IQR: 11-45), as compared to 14 days (IQR: 11-25) in the control group (P = 0.01). Household-wide treatment with ivermectin proved significantly more effective among boys than among girls (P = 0.005). After treatment with ivermectin, the estimated number of annual episodes of head lice infestation was reduced from 19 to 14 in girls and from 15 to 5 in boys. Female sex and extreme poverty were independent risk factors associated with a shortened disease-free period. In an impoverished community, girls and the poorest of the poor are the population groups that are most vulnerable for head lice infestation. To decrease the number of head lice episodes per unit of time, control measures should include the treatment of all

Comparison of a combination of oxfendazole and fenthion versus ivermectin in feedlot calves

PubMed Central

Jim, G. Kee; Booker, Calvin W.; Guichon, P. Timothy

1992-01-01

A trial involving 6,169 feedlot calves was conducted under commercial feedlot conditions in western Canada to compare the relative efficacy of treatment with a combination of oxfendazole and fenthion (O/F) versus ivermectin (I) with respect to the outcome variables, final weight, gain, days on feed (DOF), dry matter intake (DMI), average daily gain (ADG), dry matter intake to gain ratio (DM:G), and morbidity, mortality, and carcass grade parameters. There were no significant differences (p ≥ 0.05) between the treatment groups for final weight, gain, DOF, DMI, ADG and DM:G. In addition, there were no significant differences (p ≥ 0.05) in the carcass grading parameters between the treatment groups. The bovine respiratory disease (BRD) relapse rates, the overall mortality rates, and the cause specific mortality rates were not significantly different (p ≥ 0.05) between the treatment groups. The BRD treatment rate in the O/F group was significantly lower (p ≤ 0.05) than in the I group, but this difference was not economically important. These data indicate that a combination of oxfendazole and fenthion is comparable to ivermectin with respect to performance, animal health, and carcass grade parameters. PMID:17424076

Topical ivermectin improves allergic skin inflammation.

PubMed

Ventre, E; Rozières, A; Lenief, V; Albert, F; Rossio, P; Laoubi, L; Dombrowicz, D; Staels, B; Ulmann, L; Julia, V; Vial, E; Jomard, A; Hacini-Rachinel, F; Nicolas, J-F; Vocanson, M

2017-08-01

Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transport of oxytetracycline, chlortetracycline, and ivermectin in surface runoff from irrigated pasture.

PubMed

Bair, Daniel A; Popova, Ina E; Tate, Kenneth W; Parikh, Sanjai J

2017-09-02

The transport of oxytetracycline, chlortetracycline, and ivermectin from manure was assessed via surface runoff on irrigated pasture. Surface runoff plots in the Sierra Foothills of Northern California were used to evaluate the effects of irrigation water application rates, pharmaceutical application conditions, vegetative cover, and vegetative filter strip length on the pharmaceutical discharge in surface runoff. Experiments were designed to permit the maximum potential transport of pharmaceuticals to surface runoff water, which included pre-irrigation to saturate soil, trimming grass where manure was applied, and laying a continuous manure strip perpendicular to the flow of water. However, due to high sorption of the pharmaceuticals to manure and soil, less than 0.1% of applied pharmaceuticals were detected in runoff water. Results demonstrated an increase of pharmaceutical transport in surface runoff with increased pharmaceutical concentration in manure, the concentration of pharmaceuticals in runoff water remained constant with increased irrigation flow rate, and no appreciable decrease in pharmaceutical runoff was produced with the vegetative filter strip length increased from 30.5 to 91.5 cm. Most of the applied pharmaceuticals were retained in the manure or within the upper 5 cm of soil directly beneath the manure application sites. As this study evaluated conditions for high transport potential, the data suggest that the risk for significant chlortetracycline, oxytetracycline, and ivermectin transport to surface water from cattle manure on irrigated pasture is low.

Disposition of 3H-selamectin and 3H-ivermectin in the brain of the cat flea Ctenocephalides felis felis using micro-image analysis.

PubMed

Phipps, A N; Martin-Short, M R; Littlewood, L; Blanchflower, S E; Gration, K A F

2005-07-15

In addition to intrinsic potency and metabolic stability, the disposition of an antiparasitic drug within the target parasite plays a major role in determining drug activity. A novel technique that allows the disposition of radiolabelled drugs to be visualised within the body of the cat flea (Ctenocephalides felis felis) is described. The concentrations of two macrocyclic lactones, (3)H-selamectin and (3)H-ivermectin, within the supra- and sub-oesophageal ganglia of the flea brain following in vitro feeding of fleas on different doses of drug solubilised in calf blood have been measured. Drug disposition was visualised in cryostat sections of fleas using a micro-image analysis (MIA). A relationship between the concentration of radioactivity in the ganglia and the dose of drug in the blood meal was obtained. The concentration of selamectin in the ganglia was significantly higher than ivermectin at all doses investigated. The enhanced concentration of selamectin, at a site rich in glutamate-gated chloride channels may, in part, explain the higher potency of selamectin against fleas compared to ivermectin.

Standardized laboratory tests with 21 species of temperate and tropical sepsid flies confirm their suitability as bioassays of pharmaceutical residues (ivermectin) in cattle dung.

PubMed

Blanckenhorn, Wolf U; Puniamoorthy, Nalini; Schäfer, Martin A; Scheffczyk, Adam; Römbke, Jörg

2013-03-01

Veterinary pharmaceuticals excreted in the dung of treated livestock can have strong non-target effects on the dung organism community. We report results of ecotoxicological tests with ivermectin for 21 species of temperate (Europe, North America) and tropical (Asia, Central America) black scavenger flies (Diptera: Sepsidae), using standardized methods developed previously for the yellow dung fly and the face fly. Our study documents great variation in ivermectin sensitivity of more than two orders of magnitude among species and even populations within species: estimated lethal effect concentrations LC(50) (at which 50% of the flies died) ranged from 0.05 to 18.55 μg/kg dung fresh weight (equivalent to 0.33-132.22 μg/kg dung dry weight). We also show that controlled laboratory tests can--within reasonable limits-be extended to the field or to laboratory settings without climate control, as obtained LC(50) were roughly similar. In addition to lethal effects, our study revealed relevant sub-lethal effects at lower ivermectin concentrations in terms of prolonged development, smaller body size and reduced juvenile growth rate. Finally, oviposition choice experiments showed that females generally do not discriminate against dung containing ivermectin residues. We conclude that sepsid flies are well suited test organisms for pharmaceutical residues in the dung of livestock due to their ease and speed of rearing and handling, particularly in the tropics, where high-tech laboratory equipment is often not available. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficacy of closantel against ivermectin- and fenbendazole-resistant Haemonchus sp. in sheep in Ontario, Canada.

PubMed

Westers, T; Jones-Bitton, A; Menzies, P; Van Leeuwen, J; Poljak, Z; Peregrine, A S

2016-09-15

In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the only readily available ovine anthelmintics, has been documented, primarily in Haemonchus sp. In other parts of the world, closantel has been used to control such infections; however, the drug was not currently licensed for use in Canada and the USA. A randomized controlled trial was conducted on six client-owned farms in Ontario in 2013 and 2014 to determine the efficacy of closantel (Flukiver ® 5% Oral Suspension, Elanco Animal Health, 10mg/kg bodyweight) against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in periparturient ewes and grazing lambs. Three farms were randomly assigned to treat all ewes, and three farms were randomly assigned to selectively treat individual ewes at lambing, using predetermined criteria. Fecal samples were collected from a minimum of 15 randomly selected ewes and 13 lambs per group on each farm at the time of treatment and approximately 14days later. Trichostrongyle-type fecal egg counts (FEC) were performed using a modified McMaster technique with a lower detection limit of 8.3 eggs per gram of feces (epg). Haemonchus-specific FECs were determined by multiplying FECs by the proportion of Haemonchus sp. identified from coproculture for each farm; Haemonchus-specific FEC reductions were calculated for each farm. Twenty grazing lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg, all lambs were randomly allocated to either closantel, positive control (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre-treatment Haemonchus-specific mean FECs ranged from 27 to 3359 epg in ewes and 0-5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99% (95% CI: 97%-99%) to 100% in recently lambed ewes on all farms in both years (total n=274 ewes), and from 99% (95% CI: 98%-99%) to 100% in grazing lambs in both years on all but one farm (total n=171 lambs). On the latter farm, a whole

The efficacy of avermectins (ivermectin, doramectin and abamectin) as treatments for infestation with the tick Haemaphysalis longicornis on rabbits in Korea.

PubMed

Doan, Huong Thi Thanh; Noh, Jin Hyeong; Kim, Young Ha; Yoo, Mi Sun; Reddy, Kondreddy Eswar; Jung, Suk Chan; Kang, Seung Won

2013-12-06

The efficacy of a single subcutaneous injection of an avermectin (ivermectin, doramectin, or abamectin) as a treatment for infestation with nymphal and adult Haemaphysalis longicornis was evaluated in 24 New Zealand White rabbits. Two days after artificial infestation with nymphs or adult ticks, the rabbits were randomly allocated to three treatment groups (to be treated with ivermectin, doramectin, and abamectin) and a control group. The animals in the treatment groups were injected with commercial injectable formulations of each avermectins at a dose of 200 μg/kg live weight. The results showed that on rabbits treated with these avermectins, nymphs and female ticks had significantly reduced weight, nymphs had reduced moulting success rates, and females had inhibited ovary development. Among the treatments, doramectin was most effective in reducing the weight of nymphs (weight was reduced by 80%) and females (by 97.3%); ivermectin was most effective in reducing the moulting success rate in nymphs (by 55%); and both doramectin and abamectin were effective in inhibiting the development of female ticks' ovaries (by 46%). Data from this investigation show that avermectins are suitable for the control of H. longicornis on rabbits in Korea. Copyright © 2013 Elsevier B.V. All rights reserved.

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon.

PubMed

Kouam, Marc K; Tchatchueng-Mbougua, Jules B; Demanou, Maurice; Boussinesq, Michel; Pion, Sébastien D S; Kamgno, Joseph

2013-09-27

Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999-2000. There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999-2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon

PubMed Central

2013-01-01

Background Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. Methods A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999–2000. Results There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999–2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. Conclusion The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is

Effects of Ivermectin on the Susceptibility of Culicoides Sonorensis (Diptera: Ceratopogonidae) to Bluetongue and Epizootic Hemorrhagic Disease Viruses

USDA-ARS?s Scientific Manuscript database

Ivermectin is one of the most frequently used antiparasitic drugs in the livestock industry. It is toxic to insects, because it can hyperpolarize their nerve and muscle cells and increases cellular membrane permeability to chloride ions, which leads to muscular paralysis. The mortality of Culicoides...

The current status of resistance to alpha-cypermethrin, ivermectin, and amitraz of the cattle tick (Rhipicephalus microplus) in Ecuador.

PubMed

Rodríguez-Hidalgo, Richar; Pérez-Otáñez, Ximena; Garcés-Carrera, Sandra; Vanwambeke, Sophie O; Madder, Maxime; Benítez-Ortiz, Washington

2017-01-01

Rhipicephalus microplus is widely distributed in tropical and subtropical areas of the world where livestock is a principal activity with great veterinary and economic importance. In Ecuador, this hematophagous ectoparasite has been observed between 0 and 2600 masl. One of the main tick control measures is the use of acaricides, which have been indiscriminately used worldwide and in Ecuador. In this country, no studies on acaricide resistance in Rhipicephalus microplus have been published. The current study aims to characterise the level of resistance of R. microplus against three main acaricides commonly used in Ecuador i.e. amitraz, alpha-cypermethrin and ivermectin to determine the level and pattern of dose-responses for R. microplus in 12 field populations (farms). The level of acaricide resistance was evaluated using three different bioassays: adult immersion test (AIT), larval package test (LPT) and larval immersion test (LIT), as recommended by the FAO. The predictive dose-responses were analysed by binomial logistics regression of the larval survival rate (resistance). In general, we found resistance of 67% for amitraz; 50% for alpha-cypermethrin and from 25 to 42% for ivermectin in the twelve field populations analysed. Resistance levels were studied in larval and adult bioassays, respectively, which were slightly modified for this study. For larval bioassays based on corrected mortality i.e. high (above 51%), medium (21-50%) and low (11-20%) resistance, percentages less than 10% were considered as susceptible. For the adult test, two resistance levels were used i.e. high (more than 76%) and medium (51 to 75%) resistance. Percentages lower than 50% were considered as susceptible. In this context, for larval bioassays, amitraz showed 21%, 38% and 8% for high, medium and low resistance, respectively. Alpha-cypermethrin presented 8%, 4 and 38% for high, medium and low resistance, respectively. Ivermectin presented 8%, 25% and 8% for high, medium and low

The current status of resistance to alpha-cypermethrin, ivermectin, and amitraz of the cattle tick (Rhipicephalus microplus) in Ecuador

PubMed Central

Garcés-Carrera, Sandra; Vanwambeke, Sophie O.; Madder, Maxime; Benítez-Ortiz, Washington

2017-01-01

Rhipicephalus microplus is widely distributed in tropical and subtropical areas of the world where livestock is a principal activity with great veterinary and economic importance. In Ecuador, this hematophagous ectoparasite has been observed between 0 and 2600 masl. One of the main tick control measures is the use of acaricides, which have been indiscriminately used worldwide and in Ecuador. In this country, no studies on acaricide resistance in Rhipicephalus microplus have been published. The current study aims to characterise the level of resistance of R. microplus against three main acaricides commonly used in Ecuador i.e. amitraz, alpha-cypermethrin and ivermectin to determine the level and pattern of dose-responses for R. microplus in 12 field populations (farms). The level of acaricide resistance was evaluated using three different bioassays: adult immersion test (AIT), larval package test (LPT) and larval immersion test (LIT), as recommended by the FAO. The predictive dose-responses were analysed by binomial logistics regression of the larval survival rate (resistance). In general, we found resistance of 67% for amitraz; 50% for alpha-cypermethrin and from 25 to 42% for ivermectin in the twelve field populations analysed. Resistance levels were studied in larval and adult bioassays, respectively, which were slightly modified for this study. For larval bioassays based on corrected mortality i.e. high (above 51%), medium (21–50%) and low (11–20%) resistance, percentages less than 10% were considered as susceptible. For the adult test, two resistance levels were used i.e. high (more than 76%) and medium (51 to 75%) resistance. Percentages lower than 50% were considered as susceptible. In this context, for larval bioassays, amitraz showed 21%, 38% and 8% for high, medium and low resistance, respectively. Alpha-cypermethrin presented 8%, 4 and 38% for high, medium and low resistance, respectively. Ivermectin presented 8%, 25% and 8% for high, medium and low

Adaptation of in vitro bioassays for the diagnosis of resistance to Fipronil and Ivermectin in R. (B.) microplus

USDA-ARS?s Scientific Manuscript database

R. microplus represents the most important pathological constraint to livestock production in Brazil and Uruguay. The infestation of cattle by ticks is controlled by chemical applications on a regular basis. Fipronil and ivermectin have been widely used in recent years to the benefit of cattle produ...

Crusted ("Norwegian") scabies in a specialist HIV unit: successful use of ivermectin and failure to prevent nosocomial transmission.

PubMed Central

Corbett, E L; Crossley, I; Holton, J; Levell, N; Miller, R; De Cock, K M

1996-01-01

A nosocomial outbreak of scabies in a specialist inpatient HIV unit resulted from a patient admitted with crusted scabies. Treatment of his infestation with topical scabicides alone failed and he remained infectious for several weeks. His infestation was then eradicated with combined topical treatment and oral ivermectin. In total, 14 (88%) out of 19 ward staff became symptomatic, and 4 (21%) had evidence of scabies on potassium hydroxide examination of skin scrapings. The ward infection control policy was changed to distinguish patients with crusted scabies from those with ordinary scabies. A second patient with crusted scabies was treated with combined oral and topical therapy early in his admission and nursed with more stringent isolation procedures. No nosocomial transmission occurred and his infestation responded rapidly to treatment. Patients with crusted scabies require strict barrier nursing if nosocomial transmission is to be avoided. Ivermectin combined with topical scabicides may be a more efficacious treatment than topical scabicides alone in such patients. Images PMID:8698358

Ivermectin dissipation and movement from feces to soil under field conditions.

PubMed

Iglesias, Lucía Emilia; Saumell, Carlos; Sagüés, Federica; Sallovitz, Juan Manuel; Lifschitz, Adrián Luis

2018-01-02

The aim of this work was to evaluate the fate of ivermectin (IVM) at two concentrations in cattle feces and its movement to the nearby soil and plants. Feces were spiked with IVM at two levels: 3000 ng g -1 (high group, HG) and 300 ng g -1 (low group, LG). Artificial dung pats were prepared and deposited in an experimental field area. Feces and underlying soil were sampled up to 60 days post-deposition (dpd). As an additional analysis, grasses growing around the pats were sampled at 30 and 60 dpd. Ivermectin concentrations in all matrices were determined by HPLC. Mean IVM fecal concentrations were in the range between 3901.9 ng g -1 and 2419.2 ng g -1 (high group) and 375.3 ng g -1 and 177.49 ng g -1 (low group). Mean times for 50% and 90% dissipation were 88.23 and 293.03 days (HG) and 39.1 and 129.9 days (LG). Soil concentrations ranged from 26.1 ng g -1 to 71.1 ng g -1 (HG) and 3.4 to 5.9 ng g -1 (LG); in plants, concentrations were between 71.4 and 380.8 ng g -1 and 5.40 and 51.8 ng g -1 in HG and LG, respectively. These results confirm that IVM moves from feces to the underlying soil as well as to nearby plants. The potential risk of detrimental effects on soil organisms and the impact on herbivorous animals should be further evaluated.

Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study

PubMed Central

Mohammed, Khalfan A.; Haji, Hamad J.; Gabrielli, Albis-Francesco; Mubila, Likezo; Biswas, Gautam; Chitsulo, Lester; Bradley, Mark H.; Engels, Dirk; Savioli, Lorenzo; Molyneux, David H.

2008-01-01

Background Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention. Methodology/Principal Findings Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events. Conclusions/Significance Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs. PMID:18235853

Canine generalized demodicosis treated with varying doses of a 2.5% moxidectin+10% imidacloprid spot-on and oral ivermectin: parasiticidal effects and long-term treatment outcomes.

PubMed

Paterson, Tara E; Halliwell, Richard E; Fields, Paul J; Louw, Marta Lanza; Ball, Geoff; Louw, Jakobus; Pinckney, Rhonda

2014-10-15

Advocate(®) (2.5% moxidectin+10% imidacloprid) (Bayer HealthCare, Leverkusen, Germany) is a multiparasiticidal spot-on authorized for treating canine demodicosis in many countries. This blinded, randomized three-phase clinical trial compared its efficacy employing different dosing regimens with that of ivermectin. In the blinded first phase, 58 dogs suffering from generalized demodicosis were randomly assigned to one of four groups and treated with monthly, biweekly or weekly applications of Advocate(®), or with oral ivermectin (IVR) at 500 μg/kg daily. Dogs were evaluated clinically and multiple skin scrapings undertaken every 4 weeks until parasitological cure was achieved (defined as two consecutive series of deep skin scrapings at monthly intervals negative for all life forms). Forty dogs completed the 16-week initial blinded phase, with 5 cases achieving parasitological cure. Five dogs were deemed treatment failures and subsequently treated with ivermectin. The treatment protocol was then changed for the remaining 35 dogs and this cross-over phase (Phase 2) was maintained for a further 8 weeks with an additional 9 dogs achieving parasitological cure. Thereafter, all remaining animals were treated with IVR until cured (Phase 3). Overall, 26 dogs achieved parasitological cure during the clinical investigation. Of these, 23 remained disease-free for at least 12 months while two were lost to follow up and one died of unrelated causes. A total of 32 (55.2%) dogs were withdrawn at various stages of the investigation including the 5 dogs that were judged treatment failures. Other reasons for withdrawal included: non-compliance, lost to follow-up, ivermectin toxicity or reasons unrelated to the investigation. No adverse effects were attributable to the use of Advocate(®). Parasiticidal efficacy was assessed by changes in mite counts (live adult, juvenile and egg) and skin lesion extent & severity scores. Statistical significance was assessed using ANCOVA with

Onchocerciasis in the Amazonian focus of southern Venezuela: altitude and blackfly species composition as predictors of endemicity to select communities for ivermectin control programmes.

PubMed

Vivas-Martinez, S; Basáñez, M G; Grillet, M E; Weiss, H; Botto, C; García, M; Villamizar, N J; Chavasse, D C

1998-01-01

In preparation for an ivermectin distribution programme, the prevalence and intensity of infection due to Onchocerca volvulus as well as the species composition and abundance of Simulium vectors were investigated in 22 Yanomami communities situated along 2 altitudinal transects in the southern Venezuelan onchocerciasis focus. These transects corresponded to the Ocamo-Putaco and Orinoco-Orinoquito river systems, covering a range of elevation between 50 m and 740 m above sea level (asl). A total of 831 people underwent parasitological examination in this survey and an additional 196 patients from a previous study, at an altitude of 950 m, were included in the analysis. A total of 92,659 man-biting blackflies were collected and identified to morphospecies. S. oyapockense s.l. was the predominant simuliid up to 150 m asl, whereas S. guianense s.l. and S. incrustatum s.l. prevailed above 150 m. Communities located below 150 m were found to range from hypo- to mesoendemic; all villages above 150 m proved to be hyperendemic (> 60% microfilarial prevalence) and mass ivermectin treatment should be implemented. Age above 10-14 years, altitude of the village and biting rate of S. guianense s.l. up to 200 m asl were found to be statistically significant independent predictors of infection by multivariate logistic regression using a spline model. There were no differences in infection status according to sex. Above 200 m, microfilarial rate and density remained approximately constant, prevalence averaging 79% regardless of blackfly abundance. For the implementation of ivermectin-based onchocerciasis control programmes in the Amazonian focus, altitude and species composition of the blackfly population might be adopted as useful indicators aiding selection of the most affected communities. However, below 200 m additional parasitological indicators may also be necessary. As a direct result of this study, regular mass-ivermectin delivery to meso- and hyperendemic communities is now

Randomised controlled clinical trial of increased dose and frequency of albendazole and ivermectin on Wuchereria bancrofti microfilarial clearance in northern Malawi.

PubMed

Tafatatha, Terence T; Ngwira, Bagrey M; Taegtmeyer, Miriam; Phiri, Amos J; Wilson, Trevor P; Banda, Louis G; Piston, Wilson N; Koole, Olivier; Horton, John; French, Neil

2015-06-01

In Africa, albendazole and ivermectin are currently used in combination for annual mass drug administration (MDA) for lymphatic filariasis (LF) elimination. Rapid and sustained clearance is desirable for public health impact and elimination of LF. Increasing the dose and/or frequency of albendazole and ivermectin treatment may be more effective in clearing microfilariae than standard MDA. We conducted a randomised controlled open label trial in northern Malawi comparing three modified treatment groups to standard dosage of ivermectin and albendazole in adults with confirmed circulating LF antigen and microfilaria. Participants were followed-up every 6 months for 2 years for repeat microfilarial counts and safety assessments. A total of 1851 adults were screened and 70 with microfilarial counts >80 microfilariae/ml were randomised. All treatment groups achieved a significant reduction of microfilariae levels by 12- and 24-months of follow-up. Doubling the standard dose and administering it twice yearly showed a non-significant tendency towards faster and more complete clearance. There were no serious adverse reactions. In this small study, all regimens effectively cleared microfilaria. Standard treatment may be adequate in settings like Malawi but not in all endemic settings and larger studies are required to demonstrate benefit of higher dosages. [ClinicalTrials.gov identifier: NCT01213576]. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Immune responses of pony foals during repeated infections of Strongylus vulgaris and regular ivermectin treatments.

PubMed

Dennis, V A; Klei, T R; Miller, M A; Chapman, M R; McClure, J R

1992-04-01

Ten helminth-free pony foals divided into three groups were used in this study. Eight foals were each experimentally infected per os with 50 Strongylus vulgaris infective larvae weekly for 4 weeks, at which time one foal died of acute verminous arteritis. The remaining seven foals subsequently received 50 S. vulgaris infective larvae every 2 weeks for an additional 20 weeks. Four of the infected foals remained untreated (Group 1) and three of the infected foals were given ivermectin at 8, 16 and 24 weeks post initial infection (Group 2). Two foals served as controls (Group 3). Foals in Group 1 developed eosinophilia, which was sustained throughout the course of infection. A mild eosinophilia also developed in Group 2 foals; however, the eosinophil numbers were markedly reduced for 3 weeks after each ivermectin treatment. Only foals in Group 1 developed significant (P less than 0.05) hyperproteinemia, hyperbetaglobulinemia and a reversal of the albumin/globulin (A/G) ratio 4 weeks after initial infection. Significant (P less than 0.05) IgG anti-S. vulgaris ELISA titers developed in foals in Groups 1 and 2 3 weeks after infection and were sustained for the duration of the experiment. Western blot analysis of soluble somatic antigens of S. vulgaris adult female and male worms probed with sera from foals in Groups 1 and 2 revealed only subtle differences between these animals. The blastogenic reactivity of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin and concanavalin A was not significantly different between groups. Peripheral blood mononuclear cells from foals in Groups 1 and 2 developed significant (P less than 0.05) blastogenic reactivity to S. vulgaris soluble adult somatic antigen when examined at 25 weeks after infection. Mesenteric lymph node cells from foals in Group 2, although not statistically significant, were more reactive to antigen than were the mesenteric lymph node cells from foals in Group 1 when examined at 27 weeks after infection

Lessons from the History of Ivermectin and Other Antiparasitic Agents.

PubMed

Campbell, William C

2016-01-01

The twentieth century's arsenal of chemical anthelmintics brought manifold improvement in human health and, more abundantly, in animal health. The benefits were not only in health per se but also in agricultural economics, livestock management, and the overall production of food and fiber to support expanding human populations. Nevertheless, there remains (due in large part to drug resistance and paucity of available vaccines) a great need for new means of controlling disease caused by parasitic worms. Prudence should persuade us to look to our past for lessons that might help in our quest for new drugs. The lessons suggested here derive from the history of ivermectin and other anthelmintics. They deal with the means of finding substances with useful antiparasitic activity and with alternative approaches to drug discovery.

An evaluation of ivermectin in the treatment of sarcoptic mange in dogs.

PubMed

Scheidt, V J; Medleau, L; Seward, R L; Schwartzman, R M

1984-06-01

A colony of mixed-breed dogs (n = 298) naturally infested with Sarcoptes scabiei was treated, twice, with 200 micrograms of ivermectin/kg of body weight subcutaneously at 14-day intervals. After the initial injection, positive skin scrapings from 20 treated dogs decreased from 7 to 1 and the degree of pruritus decreased. In contrast, positive skin scrapings from 22 nontreated dogs increased from 10 to 14, and there was an additional deterioration in the condition of the skin and an increase in the degree of pruritus. Complete control was noticed in all treated dogs by posttreatment day 28 (14 days after a 2nd injection) based on negative skin scrapings.

Isolation and determination of ivermectin in post-mortem and in vivo tissues of dung beetles using a continuous solid phase extraction method followed by LC-ESI+-MS/MS

PubMed Central

Ortiz, Antonio J.; Cortez, Vieyle; Azzouz, Abdelmonaim

2017-01-01

A new analytical method based on solvent extraction, followed by continuous solid-phase extraction (SPE) clean-up using a polymeric sorbent, was demonstrated to be applicable for the detection of ivermectin in complex biological matrices of dung beetles (hemolymph, excreta or dry tissues) using liquid chromatography combined with positive electrospray ionization tandem mass spectrometry (LC/ESI+–MS/MS). Using a signal-to-noise ratio of 3:1, the limit of detection (LOD) in the insect matrices at trace levels was 0.01 ng g–1 and the limit of quantification (LOQ) was 0.1 ng g–1. The proposed method was successfully used to quantitatively determine the levels of ivermectin in the analysis of small samples in in vivo and post mortem samples, demonstrating the usefulness for quantitative analyses that are focused on future pharmacokinetic and bioavailability studies in insects and the establishment of a new protocol to study the impact of ivermectin on non-target arthropods such as dung beetles and other insects that are related with the “dung community”. Because satisfactory precision and accuracy values were obtained in both in vivo matrices, we suggest that the method can be consistently used for quantitative determinations that are focused on future pharmacokinetic and bioavailability studies in insects. Furthermore, this new analytical method was successfully applied to biological samples of dead dung beetles from the field suggesting that the method can be used to establish a new routine analysis of ivermectin residues in insect carcasses that is applied to complement typical mortality tests. PMID:28207908

The efficacy of ivermectin, pyrantel and fenbendazole against Parascaris equorum infection in foals on farms in Australia.

PubMed

Armstrong, S K; Woodgate, R G; Gough, S; Heller, J; Sangster, N C; Hughes, K J

2014-10-15

This study was performed to estimate the prevalence of patent Parascaris equorum infections and determine the efficacy of ivermectin, pyrantel and fenbendazole against P. equorum infection in foals on farms in southern Australia. Foals aged >3 months on five farms in the south-western slopes region of New South Wales were used. Faeces were collected from each foal and foals with a P. equorum faecal egg count (FEC) of >100 eggs per gram (EPG) were used to measure anthelmintic efficacy using the FEC reduction (FECR) test, after random allocation to a control group or an ivermectin, pyrantel embonate or fenbendazole treatment group. Treatment was administered on day 0 and faeces were collected on day 14 and a FEC was performed. For determination of anthelmintic efficacy, FECRs and lower 95% confidence intervals (LCL) were calculated using previously described methods, based on individual or group FECRs. P. equorum populations were considered susceptible when FECR was >90% and LCL >90%, suspected resistant when FECR was FECR was 80-90% and LCL <90% and resistant when FECR was <80% and LCL <90%. A Poisson distribution quality control method was applied to the data to remove suspected erroneous FECR results. Prevalence of patent P. equorum infection was 58.3% (147/252 foals) and 89 foals on 5 farms were included in the FECR study. Resistance of P. equorum to ≥ 1 anthelmintic was present on all five farms prior to and on four farms after application of the quality control method. Two farms had evidence of multiple drug resistance. Ivermectin was effective and ineffective on two and three farms, respectively. Fenbendazole was effective on two farms, equivocal on one farm and ineffective on one farm. Pyrantel embonate was effective on three farms and ineffective on one farm. These data indicate that anthelmintic-resistant P. equorum populations are present on farms in Australia and multiple drug resistance may occur on individual farms. Copyright © 2014 Elsevier B.V. All

An attempt to replace an ivermectin-resistant Cooperia spp. population by a susceptible one on grazing pastures based on epidemiological principles and refugia management.

PubMed

Fiel, C A; Steffan, P E; Muchiut, S M; Fernández, A S; Bernat, G; Riva, E; Lloberas, M M; Almada, A; Homer, D

2017-11-15

The maintenance of anthelmintic-susceptible parasite refugia to delay the onset of anthelmintic resistance is an almost impossible effort in many grazing livestock production countries given that current refugia consist of already resistant parasites. Rather, efforts could be focused on replacing the resistant parasite refugia by susceptible parasite ones and implementing sustainable parasite control measures from then on. To this purpose, a trial was conducted to attempt to establish a new population of ivermectin-susceptible Cooperia sp. on a beef cattle farm with proven problems of ivermectin-resistant Cooperia. During two consecutive years, 82 (Year 1) and 100 (Year 2) recently weaned and parasite-free heifers were inoculated with 40,000 or 30,000 susceptible Cooperia L3, respectively, at a time when levels of resistant parasite refugia were normally low. The animals were subsequently allowed to graze on the problem pastures during autumn until the end of spring. Levels of parasitism in the animals and on pasture were monitored monthly and animals were treated with levamisole when needed. The combination of parasitological monitoring and local epidemiological knowledge was essential to determine when treatments were to be administered. No clinical signs of gastrointestinal parasitosis in the herd were observed throughout the study and unnecessary treatments were avoided. Faecal egg counts reduction tests (FECRT) and controlled efficacy tests (CET) employing worm counts were carried out at different times throughout the study to determine the clinical efficacy (FECRT) and the absolute efficacy (CET) of ivermectin, respectively. The clinical efficacy of ivermectin increased from an initial 73% to 99.4%, while the absolute efficacy increased from 54.1% to 87.5% after just two animal production cycles. The switch from a resistant parasite population to a susceptible one requires knowledge of parasitological epidemiology, especially in relation to seasonal

Strongyloides seroprevalence before and after an ivermectin mass drug administration in a remote Australian Aboriginal community

PubMed Central

Currie, Bart J.; Cheng, Allen C.; McCarthy, James; Carapetis, Jonathan R.; Holt, Deborah C.; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Mulholland, Eddie; Ward, Linda; Andrews, Ross M.

2017-01-01

Background Strongyloides seroprevalence is hyper-endemic in many Australian Aboriginal and Torres Strait Islander communities, ranging from 35–60%. We report the impact on Strongyloides seroprevalence after two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Methods Utilizing a before and after study design, we measured Strongyloides seroprevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined changes in serostatus. Serodiagnosis was undertaken by ELISA that used sonicated Strongyloides ratti antigen to detect anti-Strongyloides IgG. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 10–42 days if Strongyloides and/or scabies was diagnosed; others followed a standard alternative algorithm. A questionnaire on clinical symptoms was administered to identify adverse events from treatment and self-reported symptoms associated with serostatus. Findings We surveyed 1013 participants at the baseline population census and 1060 (n = 700 from baseline cohort and 360 new entrants) at month 12. Strongyloides seroprevalence fell from 21% (175/818) at baseline to 5% at month 6. For participants from the baseline cohort this reduction was sustained at month 12 (34/618, 6%), falling to 2% at month 18 after the second MDA. For new entrants to the cohort at month 12, seroprevalence reduced from 25% (75/297) to 7% at month 18. Strongyloides positive seroconversions for the baseline cohort six months after each MDA were 2.5% (4/157) at month 6 and 1% at month 18, whilst failure to serorevert remained unchanged at 18%. At 12 months, eosinophilia was identified in 59% of baseline seropositive participants and 89% of seropositive new entrants, compared with 47%baseline seronegative participants and 51% seronegative new entrants. Seropositivity was not correlated with haemoglobin or any

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone.

PubMed

Koroma, Joseph B; Sesay, Santigie; Conteh, Abdul; Koudou, Benjamin; Paye, Jusufu; Bah, Mohamed; Sonnie, Mustapha; Hodges, Mary H; Zhang, Yaobi; Bockarie, Moses J

2018-04-06

Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone. Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict. Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution. In total, 39 sentinel villages from hyper- and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010. Results were analyzed and compared with the baseline data from the same 39 villages. The average microfilaridermia (MF) prevalence across 39 sentinel villages was 53.10% at baseline. The MF prevalence was higher in older age groups, with the lowest in the age group of 1-9 years (11.00%) and the highest in the age group of 40-49 years (82.31%). Overall mean MF density among the positives was 28.87 microfilariae (mf)/snip, increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years. Males had higher MF prevalence and density than females. In 2010 after five rounds of mass drug administration, the overall MF prevalence decreased by 60.26% from 53.10% to 21.10%; the overall mean MF density among the positives decreased by 71.29% from 28.87 mf/snip to 8.29 mf/snip; and the overall mean MF density among all persons examined decreased by 88.58% from 15.33 mf/snip to 1.75 mf/snip. Ten of 12 endemic districts had > 50% reduction in MF prevalence. Eleven of 12 districts had ≥50% reduction in mean MF density among the positives. A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage. The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025. Annual MDA with ivermectin should continue in all 12 districts and

P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of Ivermectin and Zinc Allosteric Modulation

PubMed Central

Latapiat, Verónica; Rodríguez, Felipe E.; Godoy, Francisca; Montenegro, Felipe A.; Barrera, Nelson P.; Huidobro-Toro, Juan P.

2017-01-01

Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) and ivermectin, an antiparasite drug currently used in veterinary medicine. To this aim, docking studies, molecular dynamics simulations and non-bonded energy calculations for the P2X4R in the apo and holo states or in the presence of ivermectin and/or Zn(II) were accomplished. Based on the crystallized Danio rerio P2X4R, the rat P2X4R, P2X2R, and P2X7R structures were modeled, to determine ivermectin binding localization. Calculations revealed that its allosteric site is restricted to transmembrane domains of the P2X4R; the role of Y42 and W46 plus S341 and non-polar residues were revealed as essential, and are not present in the homologous P2X2R or P2X7R transmembrane domains. This finding was confirmed by preferential binding conformations and electrophysiological data, revealing P2X4R modulator specificity. Zn(II) acts in the P2X4R extracellular domain neighboring the SS3 bridge. Molecular dynamics in the different P2X4R states revealed allosterism-induced stability. Pore and lateral fenestration measurements of the P2X4R showed conformational changes in the presence of both modulators compatible with a larger opening of the extracellular vestibule. Electrophysiological studies demonstrated additive effects in the ATP-gated currents by joint applications of ivermectin plus Zn(II). The C132A P2X4R mutant was insensitive to Zn(II); but IVM caused a 4.9 ± 0.7-fold increase in the ATP-evoked currents. Likewise, the simultaneous application of both modulators elicited a 7.1 ± 1.7-fold increase in the ATP-gated current. Moreover, the C126A P2X4R mutant evoked similar ATP

Residue depletion of ivermectin in broiler poultry.

PubMed

Mestorino, Nora; Buldain, Daniel; Buchamer, Andrea; Gortari, Lihuel; Daniele, Martín; Marchetti, María Laura

2017-04-01

Helminth infections are widespread in the poultry industry. There is evidence of extra-label use of some drugs, such as ivermectin (IVM), in broiler poultry. Pharmacokinetic and residual studies of IVM in poultry, however, are rather scarce. Our aim was to determine time restrictions for broiler chickens fed with balanced feed mixed with IVM for 21 days, and thus achieve acceptable residual levels for consumption as established by the European Union. Sixty 1-day-old chicks were fed with food supplemented with IVM at 5 mg kg -1 feed for 21 days. Groups of six treated animals were sacrificed at 0, 1, 2, 4, 8, 10, 15, 20 and 28 days after treatment. Liver, skin/fat, kidney and muscle samples were obtained. IVM were determined by liquid chromatography with fluorescence detection after automatic solid-phase extraction with SPE C 18 cartridges. The highest concentrations were measured in the liver, which is logical given that IVM is a drug that undergoes extensive hepatic metabolism. The optimal withdrawal time for edible tissues of these animals to stay within the permitted residual levels were: 12 days for liver, 8 days for skin/fat, 0 days for muscle and 10 days for kidney.

Proof-of-principle of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: final results of a study in Mali and Senegal.

PubMed

Traore, Mamadou O; Sarr, Moussa D; Badji, Alioune; Bissan, Yiriba; Diawara, Lamine; Doumbia, Konimba; Goita, Soula F; Konate, Lassana; Mounkoro, Kalifa; Seck, Amadou F; Toe, Laurent; Toure, Seyni; Remme, Jan H F

2012-01-01

Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment. Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination. The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.

Determination of Ivermectin in Medicated Feeds by Liquid Chromatography with Fluorescence Detection

PubMed Central

2013-01-01

A labour- and time-effective analytical procedure for determination of ivermectin in medicated feed at recommended level of 2.0 mg kg−1 has been developed and validated. The analyte was extracted from grinded feed samples with acetonitrile and derivatisated with N-methylimidazole and trifluoracetic anhydride. The fluorescent derivatives were analysed by liquid chromatography method using C8 column. The isocratic conditions using acetonitrile, methanol, water, and tetrahydrofuran were applied. Fluorescence detection was performed at 365 nm (excitation) and 475 nm (emission) wavelengths. The total analysis time was 10 min. The validation results of the method (within-laboratory reproducibility 4.0% CV, mean recovery 100.1%) confirm the appropriate precision and accuracy of the developed method. PMID:24453835

Willingness to pay for the maintenance of equity in a local ivermectin distribution scheme in Toro, Northern Nigeria.

PubMed

Onwujekwe, O E; Shu, E N; Okonkwo, P O

1999-07-01

The willingness to pay (WTP) for the maintenance of equity in a local ivermectin distribution scheme in the context of a community financing framework was determined in Toro, Northern Nigeria, using 214 randomly selected heads of households, or their representatives. Though WTP of the respondents for their own households was elicited, the focus of this paper is on WTP to maintain equity in a community financing scheme. Contingent valuation was used for the exercise, and WTP was elicited using an open-ended question. 97.2% of the respondents were in favour of allowing those that lack the ability to pay, to benefit from the scheme and the maximum WTP amounts they were willing to contribute annually so that those who lack the ability to pay could benefit from the scheme ranged from 5 Naira ($0. 06) to 100 Naira ($1.25). The mean WTP to maintain equity was 29.00 Naira ($0.36) while the median was 20.00 Naira ($0.25). This study shows that a community financing scheme for local ivermectin distribution will not be inequitable, since enough funds will be realised from well-to-do community members to cover the costs for those who are unable to pay.

Structure of the microfilarial reservoir of Loa loa in the human host and its implications for monitoring the progr,ammes of Community-Directed Treatment with Ivermectin carried out in Africa.

PubMed

Pion, D S S; Gardon, J; Kamgno, J; Gardon-Wendel, N; Chippaux, J P; Boussinesq, M

2004-11-01

This paper describes the structure of the microfilarial reservoir of Loa loa in an endemic population of central Cameroon. The possible effects of age and sex on the prevalence and intensity of microfilaraemia have been explored. Logistic analysis showed that the prevalence of microfilaraemia increased significantly with age, reaching 60 % in the oldest males. This result suggests that the figure commonly reported, according to which only one third of the infected individuals were microfilaraemic, should be reconsidered; in addition, as part of surveys of loiasis, crude microfilaraemia prevalence values should be replaced by adjusted ones. The intensity of infection did not show any age-specific change. As a result, even if the oldest members of the male population are clearly the most at risk of developing post-ivermectin serious adverse reactions, especially Loa-encephalopathy, the other members of the population are not risk-free. Therefore, in those areas where the African Programme for Onchocerciasis Control is undertaking regular mass distributions of ivermectin for onchocerciasis control, and where loiasis is co-endemic, no subpopulation should be excluded from surveillance and monitoring during community directed treatments with ivermectin.

Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

PubMed

Coffeng, Luc E; Stolk, Wilma A; Hoerauf, Achim; Habbema, Dik; Bakker, Roel; Hopkins, Adrian D; de Vlas, Sake J

2014-01-01

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.

Ongoing Transmission of Onchocerca volvulus after 25 Years of Annual Ivermectin Mass Treatments in the Vina du Nord River Valley, in North Cameroon

PubMed Central

Eisenbarth, Albert; Achukwi, Mbunkah Daniel; Renz, Alfons

2016-01-01

Background Recent reports of transmission interruption of Onchocerca volvulus, the causing agent of river blindness, in former endemic foci in the Americas, and more recently in West and East Africa, raise the question whether elimination of this debilitating disease is underway after long-term treatment of the population at risk with ivermectin. The situation in Central Africa has not yet been clearly assessed. Methods and findings Entomologic data from two former endemic river basins in North Cameroon were generated over a period of 43 and 48 months to follow-up transmission levels in areas under prolonged ivermectin control. Moreover, epidemiologic parameters of animal-borne Onchocerca spp. transmitted by the same local black fly vectors of the Simulium damnosum complex were recorded and their impact on O. volvulus transmission success evaluated. With mitochondrial DNA markers we unambiguously confirmed the presence of infective O. volvulus larvae in vectors from the Sudan savannah region (mean Annual Transmission Potential 2009–2012: 98, range 47–221), but not from the Adamawa highland region. Transmission rates of O. ochengi, a parasite of Zebu cattle, were high in both foci. Conclusions/significance The high cattle livestock density in conjunction with the high transmission rates of the bovine filaria O. ochengi prevents the transmission of O. volvulus on the Adamawa plateau, whereas transmission in a former hyperendemic focus was markedly reduced, but not completely interrupted after 25 years of ivermectin control. This study may be helpful to gauge the impact of the presence of animal-filariae for O. volvulus transmission in terms of the growing human and livestock populations in sub-Saharan countries. PMID:26926855

A model for evaluating the sustainability of community-directed treatment with ivermectin in the African Program for Onchocerciasis Control.

PubMed

Okeibunor, Joseph; Bump, Jesse; Zouré, Honorat G M; Sékétéli, Azodoga; Godin, Christine; Amazigo, Uche V

2012-01-01

Onchocerciasis is controlled by mass treatment of at-risk populations with ivermectin. Ivermectin is delivered through community-directed treatment (CDTI) approach. A model has been developed to evaluate the sustainability of the approach and has been tested at 35 projects in 10 countries of the African Program for Onchocerciasis Control (APOC). It incorporates quantitative and qualitative data collection and analysis, taking account of two factors identified as crucial to project sustainability. These are (i) the provision of project performance information to partners, and (ii) evidence-based support for project implementation. The model is designed to provide critical indicators of project performance of the model to implementing, coordinating, and funding partners. The model's participatory and flexible nature makes it culturally sensitive and usable by project management. This model is able to analyze the different levels involved in project implementation and arrive at a judgment for the whole project. It has inbuilt mechanisms for ensuring data reliability and validity. The model addresses the complex issue of sustainability with a cross-sectional design focusing on how and at which operational level of implementation to strengthen a CDTI project. The unique attributes and limitations of the model for evaluating the sustainability of projects were described. Copyright © 2012 John Wiley & Sons, Ltd.

The In Vitro Effect of Ivermectin on the Activity of Trehalose Synthesis Pathway Enzymes and Their mRNA Expression in the Muscle of Adult Female Ascaris suum (Nematoda)

PubMed Central

Łopieńska-Biernat, Elżbieta; Zaobidna, Ewa Anna

2014-01-01

The in vitro effect of ivermectin lethal dose on the activity of trehalose-6-phosphate synthase (TPS) and phosphatase (TPP) and the expression of their mRNA (tps1, tps2, and tpp genes) in the muscle of adult female Ascaris suum was investigated. The presence of ivermectin in the medium caused a decrease in TPS and TPP activities during the experiment compared with the start and control groups. The exception was the group of worms grown for 8 hours in a IVM solution, in which there was a little higher TPS activity than in the control. Real-time qPCR analysis showed reduced expression of tps1 and tps2, and unchanged tpp expression after 20 hours of incubation relative to the expression at time zero. Relative to the appropriate control groups, the expression of tps2 gene was slight increased but the other two genes were reduced after 8-hours of IVM-treatment. Then the expression of all three genes was lower at the end of cultivation. The level of gene expression was positively correlated with the activity of specific enzymes. In the case of tpp gene there was only a weak correlation. Prolonged exposure to ivermectin was effective in lowering TPS and TPP activity and their mRNA expression. However, the drug did not block the pathway. PMID:25405239

The in vitro effect of ivermectin on the activity of trehalose synthesis pathway enzymes and their mRNA expression in the muscle of adult female Ascaris suum (Nematoda).

PubMed

Dmitryjuk, Małgorzata; Łopieńska-Biernat, Elżbieta; Zaobidna, Ewa Anna

2014-01-01

The in vitro effect of ivermectin lethal dose on the activity of trehalose-6-phosphate synthase (TPS) and phosphatase (TPP) and the expression of their mRNA (tps1, tps2, and tpp genes) in the muscle of adult female Ascaris suum was investigated. The presence of ivermectin in the medium caused a decrease in TPS and TPP activities during the experiment compared with the start and control groups. The exception was the group of worms grown for 8 hours in a IVM solution, in which there was a little higher TPS activity than in the control. Real-time qPCR analysis showed reduced expression of tps1 and tps2, and unchanged tpp expression after 20 hours of incubation relative to the expression at time zero. Relative to the appropriate control groups, the expression of tps2 gene was slight increased but the other two genes were reduced after 8-hours of IVM-treatment. Then the expression of all three genes was lower at the end of cultivation. The level of gene expression was positively correlated with the activity of specific enzymes. In the case of tpp gene there was only a weak correlation. Prolonged exposure to ivermectin was effective in lowering TPS and TPP activity and their mRNA expression. However, the drug did not block the pathway.

Control of scabies, skin sores and haematuria in children in the Solomon Islands: another role for ivermectin.

PubMed Central

Lawrence, Gregor; Leafasia, Judson; Sheridan, John; Hills, Susan; Wate, Janet; Wate, Christine; Montgomery, Janet; Pandeya, Nirmala; Purdie, David

2005-01-01

OBJECTIVE: To assess the effects of a 3-year programme aimed at controlling scabies on five small lagoon islands in the Solomon Islands by monitoring scabies, skin sores, streptococcal skin contamination, serology and haematuria in the island children. METHODS: Control was achieved by treating almost all residents of each island once or twice within 2 weeks with ivermectin (160-250 microg/kg), except for children who weighed less than 15 kg and pregnant women, for whom 5% permethrin cream was used. Reintroduction of scabies was controlled by treating returning residents and visitors, whether or not they had evident scabies. FINDINGS: Prevalence of scabies dropped from 25% to less than 1% (P < 0.001); prevalence of sores from 40% to 21% (P < 0.001); streptococcal contamination of the fingers in those with and without sores decreased significantly (P = 0.02 and 0.047, respectively) and anti-DNase B levels decreased (P = 0.002). Both the proportion of children with haematuria and its mean level fell (P = 0.002 and P < 0.001, respectively). No adverse effects of the treatments were seen. CONCLUSION: The results show that ivermectin is an effective and practical agent in the control of scabies and that control reduces the occurrence of streptococcal skin disease and possible signs of renal damage in children. Integrating community-based control of scabies and streptococcal skin disease with planned programmes for controlling filariasis and intestinal nematodes could be both practical and produce great health benefits. PMID:15682247

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community.

PubMed

Kearns, Thérèse M; Speare, Richard; Cheng, Allen C; McCarthy, James; Carapetis, Jonathan R; Holt, Deborah C; Currie, Bart J; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Bundhala, Leanne; Mulholland, Eddie; Chatfield, Mark; Andrews, Ross M

2015-10-01

Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2-3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1-2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. Australian New Zealand Clinical Trial Register (ACTRN-12609000654257).

Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

PubMed Central

2010-01-01

Background In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. Methods In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Results Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Conclusions Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of

Fifteen Years of Annual Mass Treatment of Onchocerciasis with Ivermectin Have Not Interrupted Transmission in the West Region of Cameroon

PubMed Central

Katabarwa, Moses N.; Eyamba, Albert; Nwane, Philippe; Enyong, Peter; Kamgno, Joseph; Kueté, Thomas; Yaya, Souleymanou; Aboutou, Rosalie; Mukenge, Léonard; Kafando, Claude; Siaka, Coulibaly; Mkpouwoueiko, Salifou; Ngangue, Demanga; Biholong, Benjamin Didier; Andze, Gervais Ondobo

2013-01-01

We followed up the 1996 baseline parasitological and entomological studies on onchocerciasis transmission in eleven health districts in West Region, Cameroon. Annual mass ivermectin treatment had been provided for 15 years. Follow-up assessments which took place in 2005, 2006, and 2011 consisted of skin snips for microfilariae (mf) and palpation examinations for nodules. Follow-up Simulium vector dissections for larval infection rates were done from 2011 to 2012. mf prevalence in adults dropped from 68.7% to 11.4%, and nodule prevalence dropped from 65.9% to 12.1%. The decrease of mf prevalence in children from 29.2% to 8.9% was evidence that transmission was still continuing. mf rates in the follow-up assessments among adults and in children levelled out after a sharp reduction from baseline levels. Only three health districts out of 11 were close to interruption of transmission. Evidence of continuing transmission was also observed in two out of three fly collection sites that had infective rates of 0.19% and 0.18% and ATP of 70 (Foumbot) and 300 (Massangam), respectively. Therefore, halting of annual mass treatment with ivermectin cannot be done after 15 years as it might escalate the risk of transmission recrudescence. PMID:23691275

Ivermectin reduces alcohol intake and preference in mice

PubMed Central

Yardley, Megan; Wyatt, Letisha; Khoja, Sheraz; Asatryan, Liana; Ramaker, Marcia J.; Finn, Deborah A.; Alkana, Ronald L.; Huynh, Nhat; Louie, Stan G.; Petasis, Nicos A.; Bortolato, Marco; Davies, Daryl L.

2012-01-01

The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice. Overall, IVM (1.25–10 mg/kg, intraperitoneal) significantly reduced 24-h alcohol consumption and intermittent limited access (4-h) binge drinking, and operant alcohol self-administration (1-h). The effects on alcohol intake were dose-dependent with the significant reduction in intake at 9 h after administration corresponding to peak IVM concentrations (Cmax) in the brain. IVM also produced a significant reduction in 24-h saccharin consumption, but did not alter operant sucrose self-administration. Taken together, the findings indicate that IVM reduces alcohol intake across several different models of self-administration and suggest that IVM may be useful in the treatment of AUDs. PMID:22465817

Transmission of Onchocerca volvulus Continues in Nyagak-Bondo Focus of Northwestern Uganda after 18 Years of a Single Dose of Annual Treatment with Ivermectin

PubMed Central

Katabarwa, Moses N.; Lakwo, Tom; Habomugisha, Peace; Agunyo, Stella; Byamukama, Edson; Oguttu, David; Tukesiga, Ephraim; Unoba, Dickson; Dramuke, Patrick; Onapa, Ambrose; Tukahebwa, Edridah M.; Lwamafa, Dennis; Walsh, Frank; Unnasch, Thomas R.

2013-01-01

The objective of the study was to determine whether annual ivermectin treatment in the Nyagak-Bondo onchocerciasis focus could safely be withdrawn. Baseline skin snip microfilariae (mf) and nodule prevalence data from six communities were compared with data collected in the 2011 follow-up in seven communities. Follow-up mf data in 607 adults and 145 children were compared with baseline (300 adults and 58 children). Flies collected in 2011were dissected, and poolscreen analysis was applied to ascertain transmission. Nodule prevalence in adults dropped from 81.7% to 11.0% (P < 0.0001), and mf prevalence dropped from 97.0% to 23.2% (P < 0.0001). In children, mf prevalence decreased from 79.3% to 14.1% (P < 0.0001). Parous and infection rates of 401 flies that were dissected were 52.9% and 1.5%, respectively, whereas the infective rate on flies examination by polymerase chain reaction (PCR) was 1.92% and annual transmission potential was 26.9. Stopping ivermectin treatment may result in onchocerciasis recrudescence. PMID:23690555

Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community

PubMed Central

Kearns, Thérèse M.; Speare, Richard; Cheng, Allen C.; McCarthy, James; Carapetis, Jonathan R.; Holt, Deborah C.; Currie, Bart J.; Page, Wendy; Shield, Jennifer; Gundjirryirr, Roslyn; Bundhala, Leanne; Mulholland, Eddie; Chatfield, Mark; Andrews, Ross M.

2015-01-01

Background Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drug administrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Methods Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2–3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. Principal Findings We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. Conclusion Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1–2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. Clinical Trial Registration Australian New Zealand Clinical Trial Register (ACTRN—12609000654257). PMID:26516764

A fenbendazole oral drench in addition to an ivermectin pour-on reduces parasite burden and improves feedlot and carcass performance of finishing heifers compared with endectocides alone.

PubMed

Reinhardt, C D; Hutcheson, J P; Nichols, W T

2006-08-01

Two studies utilizing 1,862 yearling heifers were conducted to determine the effects of a fenbendazole oral drench in addition to an ivermectin pour-on (SG+IVPO), compared with an ivermectin pour-on (IVPO) or a doramectin injectable (DMX) alone, on parasite burden, feedlot performance, and carcass merit of feedlot cattle. In the first study, heifers receiving the SG+IVPO had fewer (P = 0.02) cattle retreated for disease and 73% fewer (P = 0.06) worm eggs per fecal sample 98 d after treatment than heifers treated with IVPO. Heifers treated with SG+IVPO consumed more DM, had greater ADG, were heavier at slaughter, and had heavier carcasses than IVPO-treated heifers (P < 0.05). Heifers treated with SG+IVPO also had more (P = 0.07) carcasses grading USDA Prime or Choice than IVPO-treated heifers. In the second study, heifers treated with SG+IVPO had fewer (P < 0.01) worm eggs per fecal sample 35 d after treatment and had fewer numbers of adult and larval Cooperia and Trichostrongylus spp. in the small intestine at slaughter (P < 0.10) compared with heifers treated with DMX. Heifers treated with SG+IVPO consumed more DM, were heavier at slaughter, and had heavier carcasses than DMX-treated heifers (P < 0.01). The SG+IVPO-treated heifers also had greater ADG (P < 0.10). The broad-spectrum effectiveness of a combination of a fenbendazole oral drench and an ivermectin pour-on reduced parasite burden and increased feed intake, ADG, and carcass weight in feedlot heifers compared with treatment with an endectocide alone.

Causal Interrogation of Neuronal Networks and Behavior through Virally Transduced Ivermectin Receptors.

PubMed

Obenhaus, Horst A; Rozov, Andrei; Bertocchi, Ilaria; Tang, Wannan; Kirsch, Joachim; Betz, Heinrich; Sprengel, Rolf

2016-01-01

The causal interrogation of neuronal networks involved in specific behaviors requires the spatially and temporally controlled modulation of neuronal activity. For long-term manipulation of neuronal activity, chemogenetic tools provide a reasonable alternative to short-term optogenetic approaches. Here we show that virus mediated gene transfer of the ivermectin (IVM) activated glycine receptor mutant GlyRα1 (AG) can be used for the selective and reversible silencing of specific neuronal networks in mice. In the striatum, dorsal hippocampus, and olfactory bulb, GlyRα1 (AG) promoted IVM dependent effects in representative behavioral assays. Moreover, GlyRα1 (AG) mediated silencing had a strong and reversible impact on neuronal ensemble activity and c-Fos activation in the olfactory bulb. Together our results demonstrate that long-term, reversible and re-inducible neuronal silencing via GlyRα1 (AG) is a promising tool for the interrogation of network mechanisms underlying the control of behavior and memory formation.

Efficacy of ivermectin in injectable and oral paste formulations against eight-week-old Strongylus vulgaris larvae in ponies.

PubMed

Klei, T R; Torbert, B J; Chapman, M R; Turk, M A

1984-01-01

A controlled test method was used to evaluate the efficacy of injectable micelle and oral paste formulations of ivermectin (22,23-dihydroavermectin B1) against 8-week-old Strongylus vulgaris larvae in experimentally infected pony foals. The dosage level of the drug in both formulations tested was 0.2 mg/kg. Ponies were euthanatized and necropsied 5 weeks after treatment. Based on the recovery of live vs dead S vulgaris from mesenteric arteries, both formulations were greater than 99% effective. Increased weight gains and marked reductions in the severity of arterial lesions were observed in treated ponies.

DISTRIBUTION AND UTILISATION OF IVERMECTIN (MECTIZAN): A CHEMOTHERAPEUTIC APPROACH TO THE CONTROL OF ONCHOCERCIASIS IN OLD OHAOZARA LGA, EBONYI STATE, EASTERN NIGERIA.

PubMed

Okpara, Elom Michael; Mnaemeka, Alo Moses; Iyioku, Ugah Uchenna; Udoh, Usanga Victor

2015-12-01

Onchocerciasis (river blindness) is a devastating, debilitating Stigmatising and incapacitating parasitic disease that is endemic in tropical and subtropical regions of the world, including Nigeria. Mass distribution of ivermectin (Mectizan) to the endemic parts of the world was initiated by the Onchocerciasis Control Programmes (OCPs). Absolute compliance to the regimen for up to 15 years has been reported to be effective in the control of the disease. The study was carried out in Ohaozara LGA, Onicha LGA and Ivo LGA. The three (3) LGAs made up the defunct Old Ohaozara LGA. A structured questionnaire was used to generate information on knowledge of Onchocerciasis and on the use of ivermectin by the inhabitants of the communities of the study areas. The distribution coverage of ivermectin in the study areas dating from 2010 to 2014 was ascertained with drug distribution charts obtained from Ebonyi State Health Management Board (ESHMB), Abakaliki (the point source of distribution in the state), and from the health centres in communities of old Ohaozara LGA (the service delivery points (SDPs) to inhabitants of the communities. Data was analysed using descriptive statistics. Utilization of the regimen was ascertained by determining the actual number of tablets of mectizan that was administered to the patients at the various health cenrtes (service delivery points (SDPs) in the communities. The percentage utilization of the regimen was determined by dividing the number of mectizan tablets administered to the patients at SDPs with the number of mectizan tablets supplied from state point source of distribution and multiplying by 100. A total of 347, 299 out of 1, 919135 tablets of mectizan supplied to the study areas from 2010 to 2014 were actually utilized, forming an overall percentage utilization of 18.10%. There was adequate supply but very poor utilization of the regimen. The poor utilization resulted from factors including locating of health centres very far from

Efficacy and security of ivermectin given orally to rats naturally infected with Syphacia spp., Giardia spp. and Hymenolepis nana.

PubMed

Foletto, V R S; Vanz, F; Gazarini, L; Stern, C A J; Tonussi, C R

2015-07-01

The results of this study show that the oral administration of ivermectin (48 mg/L) repeatedly for 72 h used in accordance with the present protocol is a safe and highly effective treatment for Giardia spp. and Hymenolepis nana in laboratory rat colonies. The drug can be easily and safely administered using drinking water. This simple regimen should control pinworm infection (Syphacia muris), a problem that can be endemic in laboratory colonies. Experiments using healthy animals are likely to generate more consistent results, thereby requiring a reduced number of animals per group. © The Author(s) 2014.

Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of Strongyloides stercoralis and hookworm in northwestern Argentina: A community-based pragmatic study.

PubMed

Echazú, Adriana; Juarez, Marisa; Vargas, Paola A; Cajal, Silvana P; Cimino, Ruben O; Heredia, Viviana; Caropresi, Silvia; Paredes, Gladys; Arias, Luis M; Abril, Marcelo; Gold, Silvia; Lammie, Patrick; Krolewiecki, Alejandro J

2017-10-01

Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm. Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed. STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009). Hookworm' infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control.

PubMed

Verver, Suzanne; Walker, Martin; Kim, Young Eun; Fobi, Grace; Tekle, Afework H; Zouré, Honorat G M; Wanji, Samuel; Boakye, Daniel A; Kuesel, Annette C; de Vlas, Sake J; Boussinesq, Michel; Basáñez, Maria-Gloria; Stolk, Wilma A

2018-06-01

Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Prevalence of strongyles and efficacy of fenbendazole and ivermectin in working horses in El Sauce, Nicaragua.

PubMed

Kyvsgaard, Niels C; Lindbom, Jenny; Andreasen, Line Lundberg; Luna-Olivares, Luz Adilia; Nielsen, Martin Krarup; Monrad, Jesper

2011-09-27

Horses, mules and donkeys are indispensable farming and working animals in many developing countries, and their health status is important to the farmers. Strongyle parasites are ubiquitous in grazing horses world-wide and are known to constitute a threat to equine health. This study determined the prevalence of strongyle infection, the efficacy of ivermectin and fenbendazole treatment, and strongyle re-infection rates of working horses during the dry months in Nicaragua. One hundred and five horses used by farmers for transport of people and goods were randomly allocated into three treatment groups, i.e., the IVM group treated with ivermectin, the FBZ group treated with fenbendazole and the control group treated with placebo. Determined by pre-treatment faecal egg counts (FECs), horses showed a high prevalence (94%) of strongyle parasites with high intensities of infection (mean FEC of 1117 eggs per gram (EPG) with an SD of 860 EPG, n=102). Body condition scores of all horses ranged from 1.5 to 3.5 with a mean of 2.4 (scales 1-5). Fourteen days after treatment faecal egg count reductions (FECRs) were 100% and 94% in the IVM and the FBZ groups, respectively. The egg reappearance period (ERP) defined as the time until the mean FEC reached 20% of the pre-treatment level, was estimated as 42 days for the FBZ group and 60 days for the IVM group. Individual faecal cultures were set up and the larval differentiation revealed a 36% prevalence of Strongylus vulgaris before treatment (n=45). In the FBZ group, 25% of the horses were S. vulgaris-positive 70 days post treatment compared to 11% in the IVM group. Our results indicate that strongyle infection intensities in Nicaragua are high and that S. vulgaris is endemic in the area. Furthermore, efficacies and ERPs of IVM and FBZ were within the expected range with no signs of anthelmintic resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

The Cost of Annual versus Biannual Community-Directed Treatment of Onchocerciasis with Ivermectin: Ghana as a Case Study

PubMed Central

Turner, Hugo C.; Osei-Atweneboana, Mike Y.; Walker, Martin; Tettevi, Edward J.; Churcher, Thomas S.; Asiedu, Odame; Biritwum, Nana-Kwadwo; Basáñez, María-Gloria

2013-01-01

Background It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. Methodology The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. Principal Findings The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50–60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. Conclusions/Significance This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control

Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of Strongyloides stercoralis and hookworm in northwestern Argentina: A community-based pragmatic study

PubMed Central

Juarez, Marisa; Vargas, Paola A.; Cajal, Silvana P.; Cimino, Ruben O.; Heredia, Viviana; Caropresi, Silvia; Paredes, Gladys; Arias, Luis M.; Abril, Marcelo; Gold, Silvia; Lammie, Patrick; Krolewiecki, Alejandro J.

2017-01-01

Background Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm. Methodology Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed. Principal findings STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009). Conclusions Hookworm’ infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis. PMID:28991899

Treatment and prevention of natural heartworm (Dirofilaria immitis) infections in red pandas (Ailurus fulgens) with selamectin and ivermectin.

PubMed

Lan, Jingchao; Fu, Yan; Yang, Zhi; Zhang, Zhihe; Wang, Chengdong; Luo, Li; Liu, Li; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

2012-06-01

Ten of the 48 red pandas in the Chengdu Research Base of Giant Panda Breeding, Sichuan province, China, died in 2006 after prolonged periods of depression, weight loss, and mucocutaneous membrane xanthochromia. During postmortem examination, live heartworms were found in the right cardiac ventricles and pulmonary arteries of all 10 animals. Selamectin and ivermectin were used for clinical prophylaxis in the remaining red pandas between December 2006 and November 2010. We observed a gradual decrease in morbidity and mortality during this period. As a consequence of our prophylaxis program, dirofilariosis did not occur in the remaining red pandas at Chengdu Research Base during 2010. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon

PubMed Central

Boussinesq, Michel; Gardon, Jacques; Gardon-Wendel, Nathalie; Chippaux, Jean-Philippe

2003-01-01

In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events were reported after ivermectin treatment. The first signs, occurring within the 12–24 hours following treatment, included fatigue, generalized arthralgia, and sometimes agitation, mutism, and incontinence. Disorders of consciousness, including coma, generally appeared between 24 and 72 hours, and showed a rapid variation with time. The most frequent objective neurological signs were extrapyramidal. The patients presented with haemorrhages of the conjunctiva and of the retina. Biological examinations showed a massive Loa microfilaruria, the passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an increase in the C-reactive protein, all of which have been correlated with the high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased dramatically within the first 24 hours, and then rose again rapidly. Electroencephalograms suggested the existence of a diffuse pathological process within the first weeks; the abnormalities disappearing after 3–6 months. Death may occur when patients are not properly managed, i.e. in the absence of good nursing. However, some patients who recovered showed sequelae such as aphasia, episodic amnesia, or extrapyramidal signs. The main risk factor for these encephalopathies is the intensity of the initial Loa microfilaraemia. The disorders of consciousness may occur when there are >50,000 Loa microfilariae per ml. The possible roles of co-factors, such as Loa strains, genetic predisposition of individuals, co-infestations with other parasites, or alcohol consumption, seem to be minor but they should be considered. The mechanisms of the post-ivermectin Loa-related encephalopathies should be investigated to improve the management of patients developing the condition. PMID:14975061

Reproductive Status of Onchocerca volvulus after Ivermectin Treatment in an Ivermectin-Naïve and a Frequently Treated Population from Cameroon

PubMed Central

Bopda, Jean; Kengne-Ouafo, Jonas A.; Njiokou, Flobert; Prichard, Roger K.; Wanji, Samuel; Kamgno, Joseph; Boussinesq, Michel

2014-01-01

Background For two decades, onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). In some Ghanaian communities, the long-term use of IVM was associated with a more rapid than expected skin repopulation by mf after treatment. Here, we assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients. Methodology Onchocercal nodules were surgically removed just before (D0) and 80 days (D80) after a standard dose of IVM in two cohorts with different treatment histories: a group who had received repeated doses of IVM over 13 years, and a control group with no history of large-scale treatments. Excised nodules were digested with collagenase to isolate adult worms. Embryograms were prepared with females for the evaluation of their reproductive capacities. Principal Findings Oocyte production was not affected by IVM. The mean number of intermediate embryos (morulae and coiled mf) decreased similarly in the two groups between D0 and D80. In contrast, an accumulation of stretched mf, either viable or degenerating, was observed at D80. However, it was observed that the increase in number of degenerating mf between D0 and D80 was much lower in the frequently treated group than in the control one (Incidence Rate Ratio: 0.25; 95% CI: 0.10–0.63; p = 0.003), which may indicate a reduced sequestration of mf in the worms from the frequently treated group. Conclusion/Significance IVM still had an embryostatic effect on O. volvulus, but the effect was reduced in the frequently treated cohort compared with the control population. PMID:24762816

Ivermectin treatment of bovine psoroptic mange: effects on serum chemistry, hematology, organ weights, and leather quality.

PubMed

Rehbein, S; Visser, M; Meyer, M; Lindner, T

2016-04-01

Psoroptic mange is a skin disease which may result in serious health and welfare problems and important economic losses. Apart from the effect on weight gain, little information is available concerning other responses of the organism consequent to the successful therapy of bovine psoroptic mange. Accordingly, serum chemistry, hematology, organ weights, and leather quality of young bulls with experimentally induced clinical Psoroptes ovis mange and treated with either ivermectin long-acting injection (IVM LAI; IVOMEC(®) GOLD, Merial) or saline (n = 16 each) were examined 8 weeks after treatment when all IVM LAI-treated bulls were free of live P. ovis mites while the saline-treated bulls maintained clinical mange. IVM LAI-treated bulls had higher (p < 0.05) alkaline phosphatase, creatinine, cholesterol, glucose, and albumin levels and lower (p < 0.01) total protein and β- and γ-globulin levels than the saline-treated bulls. Complete blood counts revealed higher leukocyte counts associated with higher eosinophil counts and higher platelet counts in the saline-treated compared to the IVM LAI-treated bulls (p < 0.01). Correlating with body weight, the warm carcass weight of the saline-treated bulls was lower than that of the IVM LAI-treated bulls (p < 0.05). Absolute and relative (organ weight divided by body weight) weights of the spleen, thymus, omental fat, and perirenal fat were higher (p < 0.01) for the IVM LAI-treated bulls than for the saline-treated bulls, while the IVM LAI-treated bulls had lower (p < 0.05) absolute and relative weights of the liver, adrenal glands, and selected lymph nodes than the saline-treated bulls. The leathers produced from the IVM LAI-treated bulls showed significantly (p < 0.001) less severe gouging or etching than leathers from the saline-treated bulls, and significantly (p < 0.05) more leather from the IVM LAI-treated bulls was of usable quality than the size of leather from the saline

Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin

PubMed Central

Harischandra, Hiruni; Yuan, Wang; Zamanian, Mostafa

2018-01-01

The filarial nematode Brugia malayi is an etiological agent of Lymphatic Filariasis. The capability of B. malayi and other parasitic nematodes to modulate host biology is recognized but the mechanisms by which such manipulation occurs are obscure. An emerging paradigm is the release of parasite-derived extracellular vesicles (EV) containing bioactive proteins and small RNA species that allow secretion of parasite effector molecules and their potential trafficking to host tissues. We have previously described EV release from the infectious L3 stage B. malayi and here we profile vesicle release across all intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female worms). Nanoparticle Tracking Analysis was used to quantify and size EVs revealing discrete vesicle populations and indicating a secretory process that is conserved across the life cycle. Brugia EVs are internalized by murine macrophages with no preference for life stage suggesting a uniform mechanism for effector molecule trafficking. Further, the use of chemical uptake inhibitors suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling of adult male and female EVs using nano-scale LC-MS/MS described quantitative and qualitative differences in the adult EV proteome, helping define the biogenesis of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia life stages. Further this drug effect was also observed in the related filarial nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin-unresponsive field isolate of that parasite, highlighting a potential mechanism of action for this drug and suggesting new screening platforms for anti-filarial drug development. PMID:29659599

Use of a reverse line blot assay to survey small strongyle (Strongylida: Cyathostominae) populations in horses before and after treatment with ivermectin.

PubMed

Ionita, Mariana; Howe, Daniel K; Lyons, Eugene T; Tolliver, Sharon C; Kaplan, Ray M; Mitrea, Ioan Liviu; Yeargan, Michelle

2010-03-25

A sensitive and specific PCR hybridization assay was applied for species-specific monitoring of the small strongyle (Strongylida: Cyathostominae) populations in horses in a herd before and after treatment with the anthelmintic drug ivermectin. Fecal samples were collected pre- and post-treatment weekly from eight individual horses (four foals and four yearlings) for 6 weeks to determine counts of strongyle eggs per gram of feces (EPGs). Additionally, one foal and one yearling were nontreated controls. Also, one horse, from another herd known to be infected with Strongylus spp., was a positive control for these parasites. Genomic DNA was obtained from eggs in groups of approximately 6000-7000 eggs except for two samples containing low EPGs in which 450 eggs were used. Amplification of the intergenic spacers (IGSs) of ribosomal DNA (rDNA) of small and large strongyles followed by reverse line blot (RLB) assay were performed to identify the presence of the 12 most common equine small strongyle species and to discriminate them from Strongylus spp. Overall, 11 small strongyle species were identified in pretreatment samples. In the samples collected at 4 weeks after ivermectin treatment, eight small strongyle species were identified and four of them were predominant (Cylicocyclus nassatus, Cylicostephanus longibursatus, Cylicostephanus calicatus and Cylicostephanus minutus). At 5 and 6 weeks post-treatment, the RLB assay analysis showed almost the same composition in the small strongyle population as before treatment. Strongylus spp. were identified only in samples collected from the positive control horse for these parasites. These data confirm the ability of the PCR-RLB technique for simultaneous species-specific differentiation of equine strongyle eggs, indicating a valuable way of furthering drug-resistance studies.

Simplified RP-HPLC method for multi-residue analysis of abamectin, emamectin benzoate and ivermectin in rice.

PubMed

Xie, Xianchuan; Gong, Shu; Wang, Xiaorong; Wu, Yinxing; Zhao, Li

2011-01-01

A rapid, reliable and sensitive reverse-phase high-performance liquid chromatography method with fluorescence detection (RP-FLD-HPLC) was developed and validated for simultaneous analysis of the abamectin (ABA), emamectin (EMA) benzoate and ivermectin (IVM) residues in rice. After extraction with acetonitrile/water (2 : 1) with sonication, the avermectin (AVMs) residues were directly derivatised by N-methylimidazole (N-NMIM) and trifluoroacetic anhydride (TFAA) and then analysed on RP-FLD-HPLC. A good linear relationship (r(2 )> 0.99) was obtained for three AVMs ranging from 0.01 to 5 microg ml(-1), i.e. 0.01-5.0 microg g(-1) in rice matrix. The limit of detection (LOD) and the limit of quantification (LOQ) were between 0.001 and 0.002 microg g(-1) and between 0.004 and 0.006 microg g(-1), respectively. Recoveries were from 81.9% to 105.4% and precision less than 12.4%. The proposed method was successfully applied to routine analysis of the AVMs residues in rice.

Positive and negative electrospray LC-MS-MS methods for quantitation of the antiparasitic endectocide drugs, abamectin, doramectin, emamectin, eprinomectin, ivermectin, moxidectin and selamectin in milk.

PubMed

Durden, David A

2007-05-01

Avermectin endectocides are used for the treatment of cattle against a variety of nematode and arthropod parasites, and consequently may appear in milk after normal or off-label use. The compounds abamectin, doramectin, and ivermectin, contain only C, H and O and may be expected to be detected by LC-MS in negative ion mode. The others contain nitrogen in addition and would be expected to be preferentially ionized in positive mode. The use of positive ion and negative ion methods with electrospray LC-MS-MS were compared. Using negative ion the compounds abamectin, doramectin, ivermectin, emamectin, eprinomectin, and moxidectin gave a curvilinear response and were quantified in raw milk by LC-MS-MS with a triethylamine-acetonitrile buffer over the concentration range 1-60 ppb (microg/kg) using selamectin as the internal standard. The limits of detection (LOD) were between 0.19 ppb (doramectin) and 0.38 ppb (emamectin). The compounds gave maximum sensitivity with positive ionisation from a formic acid-ammonium formate-acetonitrile buffer and were detected in milk (LC-MS-MS) also with a curvilinear response over the range 0.5-60 ppb. Although the positive ion signals were larger, with somewhat lower limits of detection (LOD between 0.06 ppb (doramectin) and 0.32 ppb (moxidectin) the negative ion procedure gave a more linear response and more consistent results. Comparison of spiked samples in the range 2-50 ppb showed a high degree of correlation between the two methods.

Pilot Study to Assess the Efficacy of Ivermectin and Fenbendazole for Treating Captive-Born Olive Baboons (Papio anubis) Coinfected with Strongyloides fülleborni and Trichuris trichiura.

PubMed

Reichard, Mason V; Thomas, Jennifer E; Chavez-Suarez, Maria; Cullin, Cassandra O; White, Gary L; Wydysh, Emily C; Wolf, Roman F

2017-01-01

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM-FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 μg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM-FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM-FBZ. All baboons treated with IVM-FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM-FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura.

Pilot Study to Assess the Efficacy of Ivermectin and Fenbendazole for Treating Captive-Born Olive Baboons (Papio anubis) Coinfected with Strongyloides fülleborni and Trichuris trichiura

PubMed Central

Reichard, Mason V; Thomas, Jennifer E; Chavez-Suarez, Maria; Cullin, Cassandra O; White, Gary L; Wydysh, Emily C; Wolf, Roman F

2017-01-01

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM–FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 μg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM–FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM–FBZ. All baboons treated with IVM–FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM–FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura. PMID:28905715

[Experiences with ivermectin in exotic animals: scabies in camelids (Camelus bactrianus, Lama guanicoe, L. glama) and scabies and roundworms in bears (Thalarctos maritimus and Ursus arctos)].

PubMed

Kuntze, A; Kuntze, O

1991-02-01

For the control of scabies in tylopodes (L. bactrianus, L. guanicoe, L. glama) and brown bears 0.2 mg/kg body weight (1 ml/50 kg body weight) of Ivermectin subcutaneously injected proved to be remedy of choice. In Kodiak-bears the oral application of Ivomec-solution was effective against ascariasis, not, however, in polar bears. Sufficient effect was reached only once, whereas Equalan-paste proved to be highly effective. Despite of strong hygienic measures continous follow-up treatment for the prevention of re-invasion is indispensible.

Actions of Agonists, Fipronil and Ivermectin on the Predominant In Vivo Splice and Edit Variant (RDLbd, I/V) of the Drosophila GABA Receptor Expressed in Xenopus laevis Oocytes

PubMed Central

Suwanmanee, Siros; Buckingham, Steven David; Biggin, Philip; Sattelle, David

2014-01-01

Ionotropic GABA receptors are the targets for several classes of insecticides. One of the most widely-studied insect GABA receptors is RDL (resistance to dieldrin), originally isolated from Drosophila melanogaster. RDL undergoes alternative splicing and RNA editing, which influence the potency of GABA. Most work has focussed on minority isoforms. Here, we report the first characterisation of the predominant native splice variant and RNA edit, combining functional characterisation with molecular modelling of the agonist-binding region. The relative order of agonist potency is GABA> muscimol> TACA> β-alanine. The I/V edit does not alter the potency of GABA compared to RDLbd. Docking calculations suggest that these agonists bind and activate RDLbdI/V through a similar binding mode. TACA and β-alanine are predicted to bind with lower affinity than GABA, potentially explaining their lower potency, whereas the lower potency of muscimol and isoguvacine cannot be explained structurally from the docking calculations. The A301S (resistance to dieldrin) mutation reduced the potency of antagonists picrotoxin, fipronil and pyrafluprole but the I/V edit had no measurable effect. Ivermectin suppressed responses to GABA of RDLbdI/V, RDLbd and RDLbdI/VA301S. The dieldrin resistant variant also showed reduced sensitivity to Ivermectin. This study of a highly abundant insect GABA receptor isoform will help the design of new insecticides. PMID:24823815

Update on the distribution of Mansonella perstans in the southern part of Cameroon: influence of ecological factors and mass drug administration with ivermectin.

PubMed

Wanji, Samuel; Tayong, Dizzle Bita; Layland, Laura E; Datchoua Poutcheu, Fabrice R; Ndongmo, Winston Patrick Chounna; Kengne-Ouafo, Jonas Arnaud; Ritter, Manuel; Amvongo-Adjia, Nathalie; Fombad, Fanny Fri; Njeshi, Charity Nya; Nkwescheu, Armand Seraphin; Enyong, Peter A; Hoerauf, Achim

2016-05-31

Mansonellosis remains one of the most neglected of tropical diseases and its current distribution in the entire forest block of southern Cameroon is unknown. In order to address this issue, we have surveyed the distribution of Mansonella perstans in different bioecological zones and in addition, elucidated the influence of multiple rounds of ivermectin (IVM) based mass drug administration (MDA). A mixed design was used. Between 2000 and 2014, both cross-sectional and longitudinal surveys were carried out in 137 communities selected from 12 health districts belonging to five main bioecological zones of the southern part of Cameroon. The zones comprised of grassland savanna (GS), mosaic forest savanna (MFS), forested savanna (FS), deciduous equatorial rainforest (DERF) and the dense humid equatorial rainforest (DHERF). The survey was carried out in some areas with no treatment history as well as those currently under IVM MDA. Individuals within the participatory communities were screened for the presence of M. perstans microfilariae (mf) in peripheral blood by the calibrated thick film method to determine both prevalence and geometric mean intensities at the community level. Apart from sporadic cases in savanna areas, distribution of M. perstans was strongly linked to the equatorial rainforest zones. Before CDTI, the highest mean prevalence (70.0 %) and intensity (17,382.2 mf/ml) were obtained in communities in Mamfes' DHERF areas followed by communities in the DHERF zone of Lolodorf (53.8 % and 7,814.8 mf/ml, respectively). A longitudinal survey in Mamfe further showed that M. perstans infections had reduced by 34.5 % in DERF (P < 0.001) but not DHERF zones after ten years of IVM MDA. Further data from the cross-sectional study revealed that there was a decrease in prevalence in DHERF zones only after ten years of MDA. In DERF zones however, the infection was relatively lower after four years of MDA. The distribution of M. perstans in the southern part of

Contribution of migrant coffee labourers infected with Onchocerca volvulus to the maintenance of the microfilarial reservoir in an ivermectin-treated area of Mexico

PubMed Central

Rodríguez-Pérez, Mario A; Cabrera, Aldo Segura; Ortega, Cristian Lizarazo; Basáñez, María-Gloria; Davies, John B

2007-01-01

Background Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination of the disease. Methods The prevalence and intensity of Onchocerca volvulus microfilariae (mf), as well as their transmission from humans to vectors, were assessed during the coffee planting-clearing and harvesting seasons of 1997–1998, and 1998–1999 in two localities (I and II) of Southern Chiapas, Mexico, which regularly receive an influx of untreated migrant coffee labourers. Results Localities I and II had, respectively, an average of 391 (± 32) and 358 (± 14) resident inhabitants, and 70 (± 52) and 498 (± 289) temporary labourers. The ratio of migrants to residents ranged from 0.1:1 in locality I to 2.4:1 in locality II. The proportion of infected Simulium ochraceum s.l. parous flies was significantly lower in locality I than in locality II, and significantly higher during the stay of the migrants than before their arrival or after their departure. Parity and infection were higher in May-July than in November-February (in contrast with the latter being typically considered as the peak onchocerciasis transmission season by S. ochraceum s.l.). Conclusion The presence of significant numbers of untreated and potentially infected migrants may contribute to ongoing transmission, and their incorporation into ivermectin programmes should be beneficial for the attainment of the elimination goals of the regional initiative. However, the possibility that the results also reflect transmission patterns for the area cannot be excluded and these should be analyzed further. PMID:18088423

Fate of ivermectin residues in ewes' milk and derived products.

PubMed

Cerkvenik, Vesna; Perko, Bogdan; Rogelj, Irena; Doganoc, Darinka Z; Skubic, Valentin; Beek, Wim M J; Keukens, Henk J

2004-02-01

The fate of ivermectin (IVM) residues was studied throughout the processing of daily bulk milk from 30 ewes (taken up to 33 d following subcutaneous administration of 0.2 mg IVM/kg b.w.) in the following milk products: yoghurt made from raw and pasteurized milk; cheese after pressing; 30- and 60-day ripened cheese; and whey, secondary whey and whey proteins obtained after cheese-making (albumin cheese). The concentration of the H2B1a component of IVM was analysed in these dairy products using an HPLC method with fluorescence detection. The mean recovery of the method was, depending on the matrix, between 87 and 100%. Limits of detection in the order of only 0.1 microg H2B1a/kg of product were achieved. Maximum concentrations of IVM were detected mostly at 2 d after drug administration to the ewes. The highest concentration of IVM was found on day 2 in 60-day ripened cheese (96 microg H2B1a/kg cheese). Secondary whey was the matrix with the lowest concentration of IVM (<0.6 microg H2B1a/ kg). Residue levels fell below the limits of detection between day 5 (for secondary whey) and day 25 (for all cheese samples). In the matrices investigated, linear correlations between daily concentrations of IVM, milk fat and solid content were evident. During yoghurt production, fermentation and thermal stability of IVM was observed. During cheese production, approximately 35% of the IVM, present in the raw (bulk) milk samples, was lost. From the results it was concluded that the processing of ewes' milk did not eliminate the drug residues under investigation. The consequences of IVM in the human diet were discussed. Milk from treated animals should be excluded from production of fat products like cheese for longer after treatment with IVM than for lower fat products.

Aquatic toxicity of ivermectin in cattle dung assessed using microcosms.

PubMed

Mesa, Leticia M; Lindt, I; Negro, L; Gutierrez, M F; Mayora, G; Montalto, L; Ballent, M; Lifschitz, A

2017-10-01

Ivermectin (IVM) is a parasiticide widely used for livestock. It is a semisynthetic derivative of avermectin, a macrocyclic lactone produced by Streptomyces avermitilis. This drug is only partly metabolized by livestock; considerable amounts of parent drug are excreted mostly via feces. To simulate exposure of aquatic invertebrates and macrophytes to direct excretion of cattle dung into surface waters, a microcosm experiment with IVM spiked in cattle dung was conducted. The objectives of this study were to characterize accumulation of IVM in water, sediment+dung, roots of the floating fern Salvinia and the zooplankton Ceriodaphnia dubia, the amphipod Hyalella and the apple snail Pomacea; to determine the effect of this drug spiked in cattle dung on life-history traits of these invertebrates; and to evaluate the influence of IVM on aquatic nutrient cycling. Dung was spiked with IVM to attain concentrations of 1150, 458, 50 and 22µgkg -1 dung fresh weight, approximating those found in cattle dung at days 3, 7, 16 and 29 following subcutaneous injection. Concentrations found in dung during the first week of excretion were lethally toxic to Ceriodaphnia dubia and Hyalella, whereas no mortality was observed in Pomacea. Concentrations of IVM in roots, sediment + dung and Pomacea increased significantly from the lowest to the highest treatment level. The effect of this drug on decomposition and release of nutrients from dung would have negative consequences for nutrient cycling in water. Increasing concentrations in sediment + dung with days of the experiment suggested that toxic concentrations would persist for an extended period in the water-sediment system. IVM represents an ecological risk for aquatic ecosystems, underscoring the need for livestock management strategies to limit its entry into water bodies. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of parasiticidal activity of fenbendazole, ivermectin, oxibendazole, and pyrantel pamoate in horse foals with emphasis on ascarids (Parascaris equorum) in field studies on five farms in Central Kentucky in 2007.

PubMed

Lyons, E T; Tolliver, S C; Ionita, M; Collins, S S

2008-07-01

Horse foals on five farms in Central Kentucky were used in field studies in 2007 evaluating activity of paste formulations of four compounds (fenbendazole-FBZ, ivermectin-IVM, oxibendazole-OBZ, and pyrantel pamoate-PRT) against internal parasites with emphasis on ascarids (Parascaris equorum). It has been well established the last few years that there is widespread resistance of P. equorum to ivermectin. The main purpose of the present research was to obtain current data on ascaridicidal activity of FBZ, OBZ, and PRT; also, to acquire further information on ascarid resistance to ivermectin. Additionally, data were documented on drug activity on small strongyles. Detection of ascarid and strongyle eggs in feces of foals was by a qualitative method (presence or absence) or a quantitative method (eggs per gram of feces). Strongyle eggs all were assumed to be from small strongyles. This is based on fecal cultures from horses on one farm and historic records from horses in this area on excellent deworming programs. A girth tape was used to estimate the body weight of each foal so that the appropriate dose rate of each drug could be given. Many of the foals were used in more than one cycle of treatments. Efficacy of the drugs, administered intraorally, was determined by calculating the average percentage reduction (% red.) of the number of foals passing eggs after vs. before treatment: (1) FBZ at 10 mg/kg was tested on four farms; 76 foals were examined, 50 with ascarid eggs (84% red.) and 62 with strongyle eggs (0% red.); (2) IVM at 200 microg/kg was tested on three farms; 58 foals were examined, 18 with ascarid eggs (0% red.) and 48 with strongyle eggs (100% red.); (3) OBZ at 10 mg/kg was tested on three farms; 181 foals were examined, 78 with ascarid eggs (94% red.) and 79 with strongyle eggs (0% red.); (4) PRT was tested on two farms, one farm at 1x (6.6 mg base/kg); 42 were foals examined, 16 with ascarid eggs (0% red.) and 33 with strongyle eggs (12% red.) and one

Validation of a simple liquid chromatographic method for determination and quantitation of residual ivermectin and doramectin in pig liver.

PubMed

Knold, Lone; Reitov, Marianne; Mortensen, Anna Birthe; Hansen-Møller, Jens

2002-01-01

A rapid and quantitative method for the extraction, derivatization, and liquid chromatography with fluorescence detection of ivermectin (IVM) and doramectin (DOM) residues in porcine liver was developed and validated. IVM and DOM were extracted from the liver samples with acetonitrile, the supernatant was evaporated to dryness at 37 degrees C under nitrogen, and the residue was reconstituted in 1-methylimidazole solution. After 2 min at room temperature, IVM and DOM were converted to a fluorescent derivative and then separated on a Hypersil ODS column. The derivatives of IVM and DOM were detected and quantitated with high specificity by fluorescence (excitation: 365 nm, emission: 475 nm). Abamectin was used as an internal standard. The mean extraction efficiencies from fortified samples (15 ng/g) were 75% for IVM and 70% for DOM. The limit of detection was 0.8 ng/g for both IVM and DOM.

Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole, albendazole plus oxantel pamoate, and mebendazole alone against Trichuris trichiura and concomitant soil-transmitted helminth infections: a four-arm, randomised controlled trial.

PubMed

Speich, Benjamin; Ali, Said M; Ame, Shaali M; Bogoch, Isaac I; Alles, Rainer; Huwyler, Jörg; Albonico, Marco; Hattendorf, Jan; Utzinger, Jürg; Keiser, Jennifer

2015-03-01

Existing anthelmintic drugs (eg, albendazole and mebendazole) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted. We aimed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened. In this randomised controlled trial, we compared three drug combinations and one standard drug alone in children aged 6-14 years in two schools on Pemba Island, Tanzania infected with T trichiura and concomitant intestinal nematodes. We assigned children, via a randomisation list with block sizes of either four or eight, to orally receive albendazole (400 mg) plus ivermectin (200 μg/kg); albendazole (400 mg) plus mebendazole (500 mg); albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg) alone. The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means, both analysed by available case. This study is registered with ISRCTN, number ISRCTN80245406. We randomly assigned 440 eligible children infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four treatment groups (110 children per group). Data for 431 children were included in the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of 108 children cured [68·5%, 95% CI 59·6-77·4]; egg reduction 99·2%, 98·7-99·6) and albendazole plus ivermectin (30 of 109 cured [27·5%, 19·0-36·0]; egg reduction 94·5%, 91·7-96·3) were significantly more effective against T trichiura than mebendazole alone (nine of 107 cured [8·4%, 3·1-13·8]; egg reduction 58·5%, 45·2-70·9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured [8·4%, 3·1-13·8; egg reduction 51·6%, 35·0-65·3) to mebendazole alone. About a fifth of the children reported adverse events, which were mainly mild. Abdominal cramps and headache were

Ivermectin reduces motor coordination, serum testosterone, and central neurotransmitter levels but does not affect sexual motivation in male rats.

PubMed

Moreira, N; Sandini, T M; Reis-Silva, T M; Navas-Suáresz, P; Auada, A V V; Lebrun, I; Flório, J C; Bernardi, M M; Spinosa, H S

2017-12-01

Ivermectin (IVM) is a macrocyclic lactone used for the treatment of parasitic infections and widely used in veterinary medicine as endectocide. In mammals, evidence indicates that IVM interacts with γ-aminobutyric acid (GABA)-mediated chloride channels. GABAergic system is involved in the manifestation of sexual behavior. We previously found that IVM at therapeutic doses did not alter sexual behavior in male rats, but at a higher dose, the appetitive phase of sexual behavior was impaired. Thus, we investigated whether the reduction of sexual behavior that was previously observed was a consequence of motor or motivational deficits that are induced by IVM. Data showed significant decrease in striatal dopaminergic system activity and lower testosterone levels but no effects on sexual motivation or penile erection. These findings suggest IVM may activate the GABAergic system and reduce testosterone levels, resulting in a reduction of motor coordination as consequence of the inhibition of striatal dopamine release. Copyright © 2017 Elsevier Inc. All rights reserved.

Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia.

PubMed

Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

2016-02-01

Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone.

Determination of abamectin, doramectin, emamectin, eprinomectin, ivermectin, and moxidectin in milk by liquid chromatography electrospray tandem mass specrometry.

PubMed

Sheridan, Robert; Desjardins, Lucille

2006-01-01

The avermectin and milbemycin families of compounds are derived from naturally occurring yeasts. They have proven to be potent preventatives against a variety of pests such as insects and parasites. Only eprinomectin and moxidectin are currently approved for use on lactating cattle with tolerances in milk of 12 microg/kg for eprinomectin and 40 microg/kg for moxidectin. Detection of misuse or inadvertent contamination in milk requires a sensitive and definitive analytical method. A method has been developed for the determination of 5 avermectins and 1 milbemycin in milk using a simple liquid-liquid extraction and liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. Ivermectin (IVR), doramectin (DOR), abamectin (ABA), eprinomectin (EPR), emamectin (EMA), and moxidectin (MOX) were extracted from whole milk by partitioning into acetonitrile with a subsequent solvent exchange into methanol-water. Simultaneous confirmation and quantification were achieved with LC separation, positive electrospray ionization (ESI+), and MS/MS. The limits of detection ranged from 16 pg/g (ppt) for EMA to 1.7 microg/g (ppb) for MOX.

Variations in gut microbiota and fecal metabolic phenotype associated with Fenbendazole and Ivermectin Tablets by 16S rRNA gene sequencing and LC/MS-based metabolomics in Amur tiger.

PubMed

He, Fengping; Zhai, Jiancheng; Zhang, Le; Liu, Dan; Ma, Yue; Rong, Ke; Xu, Yanchun; Ma, Jianzhang

2018-05-15

The Amur tiger is one of the most endangered species in the world, and the healthy population of captive Amur tigers assists the recovery of the wild population. Gut microbes have been shown to be important for human disease and health, but little research exists regarding the microbiome of Amur tigers in captivity. In this study, we used an integrated approach of 16S rRNA gene sequencing combined with ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics to analyze the effects of Fenbendazole and Ivermectin Tablets on the gut microbiota and fecal metabolic phenotype of the Amur tiger. The relative abundances of the bacterial genera Collinsella, Clostridium XI and Megamonas were decreased, whereas those of Escherichia and Clostridium sensu stricto were increased in experimental Amur tigers compared with those in normal controls. Meanwhile, distinct changes in the fecal metabolic phenotype of the experimental Amur tigers were also found, including lower levels of acrylic acid, acetoacetate and catechol and higher amounts of 5,6-dihydrouracil, adenine hydrochloride hydrate and galactitol. Moreover, the differentially abundant gut microbes were substantially associated with the altered fecal metabolites, especially the bacteria in the Firmicutes and Actinomycetes, which were involved in the metabolism of 5,6-dihydrouracil, 6-phospho-d-gluconate and 1-methylnicotinamide. Our results indicate for the first time that Fenbendazole and Ivermectin Tablets not only disturb the gut microbiota at the abundance level but also alter the metabolic homeostasis of the Amur tiger. Copyright © 2018 Elsevier Inc. All rights reserved.

Simultaneous determination of emamectin and ivermectin residues in Atlantic salmon muscle by liquid chromatography with fluorescence detection.

PubMed

van de Riet, J M; Brothers, N N; Pearce, J N; Burns, B G

2001-01-01

A liquid chromatographic (LC) method for determining residues of the antiparasitic drugs emamectin (EMA) and ivermectin (IVR) in fish tissues has been developed. EMA and IVR residues are extracted with acetonitrile and cleaned up on a C18 solid-phase extraction column. Extracts are derivatized with 1-methylimidazole and trifluoroacetic anhydride and the components are determined by LC on a C18 reversed-phase column with fluorescence detection (excitation: 365 nm, emission: 470 nm). The mobile phase is 94% acetonitrile-water run isocratically. Calibration curves were linear between 1 and 32 ng injected for both EMA and IVR. The limit of detection for both analytes was 0.5 ng/g, with a limit of quantitation of 1.5 ng/g. Recoveries of EMA and IVR added to salmon muscle averaged 96 +/- 9% and 86 +/- 6%, respectively, at levels between 5 and 80 ng/g. The percent relative standard deviation for the described method was less than 7% over the range of concentrations studied. The operational errors, interferences, and recoveries for fortified samples compare favorably with an established IVR method. The recommended method is simple, rapid, and specific for monitoring residues of EMA and IVR in Atlantic salmon muscle.

Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia

PubMed Central

Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

2016-01-01

Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from −1900% to 100%, 99% to 100%, −167% to 100%, −467% to 89%, and −200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone. PMID:27019686

Still mesoendemic onchocerciasis in two Cameroonian community-directed treatment with ivermectin projects despite more than 15 years of mass treatment.

PubMed

Kamga, Guy-Roger; Dissak-Delon, Fanny N; Nana-Djeunga, Hugues C; Biholong, Benjamin D; Mbigha-Ghogomu, Stephen; Souopgui, Jacob; Zoure, Honorat G M; Boussinesq, Michel; Kamgno, Joseph; Robert, Annie

2016-11-14

After more than a decade of community-directed treatment with ivermectin (CDTI) in Centre and Littoral Regions of Cameroon, onchocerciasis endemicity was still high in some communities according to the 2011 epidemiological evaluations. Some corrective measures were undertaken to improve the CDTI process and therefore reduce the burden of the disease. The objective of the present study was to assess the progress made towards the elimination of onchocerciasis in the Centre 1 and Littoral 2 CDTI projects where the worst performances were found in 2011. To this end, a cross-sectional survey was conducted in April 2015 in eight communities in two health districts (HD), Bafia in Centre 1 and Yabassi in Littoral 2, chosen because assessed at baseline and in 2011. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual compliance to ivermectin treatment was also assessed. Analyses of data were weighted proportionally to age and gender distribution in the population. In the Bafia and Yabassi HD, 514 and 242 individuals were examined with a mean age of 35.1 (standard deviation, SD: 20.7) and 44.6 (SD: 16.3) years, respectively. In the Bafia HD, the weighted prevalences varied from 24.4 to 57.0 % for microfilaridermia and from 3.6 to 37.4 % for nodule presence across the surveyed communities. The community microfilarial load (CMFL), expressed in microfilariae/skin snip (mf/ss), significantly dropped from 20.84-114.50 mf/ss in 1991 to 0.31-1.62 mf/ss in 2015 in all the surveyed communities. In the Yabassi HD, the weighted prevalences varied from 12.3 to 59.3 % for microfilaridermia and from 1.5 to 3.7 % for nodule presence across the surveyed communities, while a significant drop was observed in CMFL, from 20.40-28.50 mf/ss in 1999 to 0.48-1.74 mf/ss in 2015. The 2014 weighted therapeutic coverage of participants varied from 65.8 % (95 % CI: 58.4-73.2) in Yabassi HD, to 68.0 % (95

Interruption of the transmission of Onchocerca volvulus in the Kashoya-Kitomi focus, western Uganda by long-term ivermectin treatment and elimination of the vector Simulium neavei by larviciding.

PubMed

Lakwo, T; Garms, R; Wamani, J; Tukahebwa, E M; Byamukama, E; Onapa, A W; Tukesiga, E; Katamanywa, J; Begumisa, S; Habomugisha, P; Oguttu, D; Byamukama, E; Richards, F; Unnasch, T R; Katabarwa, M

2017-03-01

Uganda is the only country in sub-Saharan Africa whose onchocerciasis elimination programme extensively uses vector control and biannual treatment with ivermectin. The purpose of this study was to assess the impact of combined strategies on interrupting onchocerciasis transmission in the Kashoya-Kitomi focus. Mass Drug Administration annually (13 years) followed by biannual treatments (6 years) and ground larviciding (36 cycles in 3 years) with temephos (Abate ® , EC500) against Simulium neavei were conducted. Routine fly catches were conducted for over seven years in six catching sites and freshwater crabs Potamonautes aloysiisabaudiae were examined for immature stages of Simulium neavei. Epidemiological assessments by skin snip were performed in 2004 and 2013. Collection of dry blood spots (DBS) from children <10 years for IgG4 antibodies analysis were done in 2010 and 2013. Treatment coverage with ivermectin improved with introduction of biannual treatment strategy. Microfilaria prevalence reduced from 85% in 1991 to 62% in 2004; and to only 0.5% in 2013. Crab infestation reduced from 59% in 2007 to 0% in 2013 following ground larviciding. Comparison of total fly catches before and after ground larviciding revealed a drop from 5334 flies in 2007 to 0 flies in 2009. Serological assays conducted among 1,362 children in 2010 revealed 11 positive cases (0.8%; 95% CI: 0.4%-1.2%). However, assessment conducted on 3246 children in 2013 revealed five positives, giving point prevalence of 0.15%; 95% CI: 0.02%-0.28%. Four of the five children subjected to O-150 PCR proved negative. The data show that transmission of onchocerciasis has been interrupted based on national and WHO Guidelines of 2012 and 2016, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Relative bioavailability and comparative clinical efficacy of different ivermectin oral formulations in lambs

PubMed Central

2013-01-01

Background Several oral ivermectin (IVM) formulations for use in sheep are available in the pharmaceutical veterinary market in different countries. All of them are indicated at the same dose rate to treat the gastrointestinal nematodes. However, there is a lack of information on the relative systemic exposure (plasma bioavailability) and clinical efficacy among oral formulations routinely used in sheep. The main goal of the work reported here was to perform a pharmaco-parasitological assessment of three different IVM oral formulations in lambs infected with multiple resistant gastrointestinal nematodes. The comparative drug systemic exposure (IVM plasma concentrations) and nematodicidal efficacies (clinical efficacy) in lambs were determined for a reference (RF) and two different test (T1, T2) IVM oral formulations. One hundred and fifty six (n= 156) healthy Corriedale lambs, naturally infected with multiple resistant gastrointestinal nematodes were allocated into four experimental groups (n=39). Animals in each group received treatment (200 μg/kg) with either the RF, one of the test IVM formulations or were kept as untreated control. Blood samples were collected over 15 days post-treatment (n=8). The IVM plasma concentrations were measured by high performance liquid chromatography with fluorescence detection. The faecal nematode egg count reduction test (FECRT) (n=39) and evaluation of the clinical efficacy were performed at day 14 post-treatment (n=6), where a predominance of IVM highly resistant nematodes was observed. Results and conclusions Neither the overall kinetic behaviour nor the IVM systemic exposure differed among all the tested oral formulations. Equivalent efficacy results were obtained for the different preparations, with an evident therapeutic failure to control Haemonchus spp. and Teladorsagia circumcincta, which correlates with a high degree of nematode resistance to IVM. PMID:23398629

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Xin; Chen, Hao; Shaffer, Paul L.

Ivermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), γ-aminobutyric acid receptors (GABA ARs), glycine receptors (GlyRs), and neuronal α7-nicotinic receptors (α7 nAChRs). The crystal structure of Caenorhabditis elegans GluCl complexed with ivermectin revealed the details of its ivermectin binding site. Although the electron microscopy structure of zebrafish GlyRα1 complexed with ivermectin demonstrated a similar binding orientation, detailed structural information on the ivermectin binding and pore opening for Cys-loop receptors in vertebrates has been elusive. Here we present the crystal structures of human GlyRα3 in complex with ivermectin at 2.85 and 3.08more » Å resolution. Our structures allow us to explore in detail the molecular recognition of ivermectin by GlyRs, GABA ARs, and α7 nAChRs. Comparisons with previous structures reveal how the ivermectin binding expands the ion channel pore. Our results hold promise in structure-based design of GlyR modulators for the treatment of neuropathic pain.« less

Interactions of L-3,5,3'-Triiodothyronine, Allopregnanolone, and Ivermectin with the GABAA Receptor: Evidence for Overlapping Intersubunit Binding Modes

PubMed Central

Westergard, Thomas; Salari, Reza; Martin, Joseph V.; Brannigan, Grace

2015-01-01

Structural mechanisms of modulation of γ-aminobutyric acid (GABA) type A receptors by neurosteroids and hormones remain unclear. The thyroid hormone L-3,5,3’-triiodothyronine (T3) inhibits GABAA receptors at micromolar concentrations and has common features with neurosteroids such as allopregnanolone (ALLOP). Here we use functional experiments on α2β1γ2 GABAA receptors expressed in Xenopus oocytes to detect competitive interactions between T3 and an agonist (ivermectin, IVM) with a crystallographically determined binding site at subunit interfaces in the transmembrane domain of a homologous receptor (glutamate-gated chloride channel, GluCl). T3 and ALLOP also show competitive effects, supporting the presence of both a T3 and ALLOP binding site at one or more subunit interfaces. Molecular dynamics (MD) simulations over 200 ns are used to investigate the dynamics and energetics of T3 in the identified intersubunit sites. In these simulations, T3 molecules occupying all intersubunit sites (with the exception of the α-β interface) display numerous energetically favorable conformations with multiple hydrogen bonding partners, including previously implicated polar/acidic sidechains and a structurally conserved deformation in the M1 backbone. PMID:26421724

Analysis of the mdr-1 Gene in Patients Co-Infected with Onchocerca volvulus and Loa loa Who Experienced a Post-Ivermectin Serious Adverse Event

PubMed Central

Bourguinat, Catherine; Kamgno, Joseph; Boussinesq, Michel; Mackenzie, Charles D.; Prichard, Roger K.; Geary, Timothy G.

2010-01-01

Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs. PMID:20595473

Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle.

PubMed

Lifschitz, A; Virkel, G; Pis, A; Imperiale, F; Sanchez, S; Alvarez, L; Kujanek, R; Lanusse, C

1999-10-01

Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p < 0.05) and delayed peak plasma concentration (p < 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p < 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.

Anthelmintic efficacies of a tablet formula of ivermectin-praziquantel on horses experimentally infected with three Strongylus species.

PubMed

Bonneau, Stephane; Maynard, Laurence; Tomczuk, Krzysztof; Kok, Dawid; Eun, Hyone-Myong

2009-09-01

In this blinded randomized and controlled study, the anthelmintic efficacy of a tablet formula of ivermectin-praziquantel was evaluated in horses experimentally infected with three species of Strongylus larvae. Eighteen previously dewormed horses were inoculated on study day 0 with third-stage larvae of Strongylus vulgaris, Strongylus equinus, and Strongylus edentatus. The horses were randomly allocated to three groups (n = 6): test-drug (tablet formula), positive-control (reference gel), and negative-control (placebo tablet). On day 56, the horses were treated once with the respective drugs. On day 95, the horses were sacrificed, and necropsy examinations were performed to assess the status of the parasite burden (L4 and immature L5) and pathological lesions on selected organs and tissues. By the criteria of worm counts, the test-drug and positive-control showed, respectively, 100% and 97.3% anthelmintic efficacies on S. vulgaris, 100% and 81.4% on S. equinus, and equally 100% on S. edentatus. However, the efficacies on S. equinus and S. edentatus should be taken only as face values considering their respective low worm counts in the placebo group. The S. vulgaris-induced arterial lesions were also reduced in the test-drug and positive-control groups with efficacies of 73.9% and 62.9%, respectively. No adverse reactions were observed with either of the drugs. Our data demonstrate that the Equimax tablet formula was as safe and efficacious as the gel formula anthelmintic on large strongyles in horses.

Interactions of L-3,5,3'-Triiodothyronine [corrected], Allopregnanolone, and Ivermectin with the GABAA Receptor: Evidence for Overlapping Intersubunit Binding Modes.

PubMed

Westergard, Thomas; Salari, Reza; Martin, Joseph V; Brannigan, Grace

2015-01-01

Structural mechanisms of modulation of γ-aminobutyric acid (GABA) type A receptors by neurosteroids and hormones remain unclear. The thyroid hormone L-3,5,3'-triiodothyronine (T3) inhibits GABAA receptors at micromolar concentrations and has common features with neurosteroids such as allopregnanolone (ALLOP). Here we use functional experiments on α2β1γ2 GABAA receptors expressed in Xenopus oocytes to detect competitive interactions between T3 and an agonist (ivermectin, IVM) with a crystallographically determined binding site at subunit interfaces in the transmembrane domain of a homologous receptor (glutamate-gated chloride channel, GluCl). T3 and ALLOP also show competitive effects, supporting the presence of both a T3 and ALLOP binding site at one or more subunit interfaces. Molecular dynamics (MD) simulations over 200 ns are used to investigate the dynamics and energetics of T3 in the identified intersubunit sites. In these simulations, T3 molecules occupying all intersubunit sites (with the exception of the α-β interface) display numerous energetically favorable conformations with multiple hydrogen bonding partners, including previously implicated polar/acidic sidechains and a structurally conserved deformation in the M1 backbone.

Field tests demonstrating reduced activity of ivermectin and moxidectin against small strongyles in horses on 14 farms in Central Kentucky in 2007-2009.

PubMed

Lyons, Eugene T; Tolliver, Sharon C; Collins, Sandra S; Ionita, Mariana; Kuzmina, Tetiana A; Rossano, Mary

2011-02-01

Efficacy of ivermectin (IVM) and moxidectin (MOX) against small strongyles was evaluated in horses (n=363) in field tests on 14 farms in Central Kentucky between 2007 and 2009. Most of the horses were yearlings but a few were weanlings and mares. The number of horses treated with IVM was 255 and those treated with MOX was 108. Horses on six farms were allotted into two groups. One group was treated with each of the two drugs, whereas horses on the other eight farms were treated with only one of the two drugs--IVM on six farms and MOX on two farms. Strongyle eggs per gram of feces (EPGs) compared to initial use of IVM and MOX returned almost twice as quickly after treatment of horses on all of the farms. IVM has been used much more extensively in this geographical area than MOX. Reduced activity of MOX was evident even on farms with rare or no apparent previous use of MOX but with probable extensive use of IVM.

Effects of ivermectin on Danio rerio: a multiple endpoint approach: behaviour, weight and subcellular markers.

PubMed

Domingues, I; Oliveira, R; Soares, A M V M; Amorim, M J B

2016-04-01

Ivermectin (IVM) is a broad acting antihelmintic used in various veterinary pharmaceuticals. It has been shown that IVM enters the aquatic compartment and adversely affects organisms including fish. This study is based on the hypothesis that long term exposure to IVM affects fish and thus, the main objective was to assess the chronic effects of 0.25 and 25 µg IVM/L to zebrafish using multiple endpoints representative of several levels of biological organization: weight, behaviour (swimming and feeding) and subcellular markers including biomarkers for oestrogenicity (vitellogenin-VTG), oxidative stress (catalase-CAT and glutathione-S-transferase-GST) and neurotransmission (cholinesterase-ChE). Concentrations as low as 0.25 µg IVM/L disrupted the swimming behaviour, causing fish to spend more time at the bottom of aquaria. Such reduction of the swimming performance affected the feeding ability which is likely responsible for the weight loss. The effects on weight were gender differentiated, being more pronounced in males (0.25 µg IVM/L) than in females (25 µg IVM/L). Fish exposed to 25 µg/L exhibited darker coloration and mild curvature of the spine. No effects on VTG and AChE were observed, but a reduction on CAT and GST levels was observed in fish exposed to 25 µg IVM/L, although these alterations probably only reflect the general condition of the fish which was significantly compromised at this concentration. Despite that predicted environmental concentrations of IVM are below 0.25 µg/L, the behavioural effects may be translated into important ecological impacts, e.g. at predator-prey interactions where fish competitive advantage can be decreased. Future work should address the link between behaviour disruption and population fitness. The current study was based on a one experiment and multiple endpoint (anchored) approach, allowing the results to be integrated and linked towards a mechanistic understanding.

Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis.

PubMed

Thomsen, Edward K; Sanuku, Nelly; Baea, Manasseh; Satofan, Samson; Maki, Elit; Lombore, Bart; Schmidt, Mark S; Siba, Peter M; Weil, Gary J; Kazura, James W; Fleckenstein, Lawrence L; King, Christopher L

2016-02-01

Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown. We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels. Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels. Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis. NCT01975441. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens.

PubMed

Cirak, V Y; Aksit, D; Cihan, H; Gokbulut, C

2018-05-01

To determine the plasma disposition and concentrations of ivermectin (IVM) in eggs produced by laying hens following S/C, oral and I/V administration. Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg were allocated to three groups of eight birds. The injectable formulation of IVM was administered either orally, S/C, or I/V, at a dose of 0.2 mg/kg liveweight, following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples were collected at various times between 0.25 hours and 20 days after drug administration. Eggs produced by hens were also collected daily throughout the study period. Samples of plasma and homogenised egg were analysed using HPLC. Maximum concentrations of IVM in plasma and mean residence time of IVM were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively) than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively) administration (p<0.01). The time to maximum concentration and elimination half-life were shorter following oral (0.14 (SD 0.04) and 0.23 (SD 0.11) days, respectively) than S/C (0.25 (SD 0.00) and 1.45 (SD 0.45) days, respectively) administration (p<0.01). IVM was first detected in eggs 2 days after treatment in all groups and was detected until 8 days after oral and I/V administration, and until 15 days after S/C administration. Peak concentrations of IVM were 15.7, 23.3 and 1.9 µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively. The low plasma bioavailability of IVM observed after oral administration in laying hens could result in lower efficacy or subtherapeutic plasma concentrations, which may promote the development of parasitic drug resistance. Due to high IVM residues in eggs compared to the maximum residue limits for other food-producing animal species, a withdrawal period should be necessary for eggs after IVM treatment in laying hens.

The route of administration drastically affects ivermectin activity against small strongyles in horses.

PubMed

Saumell, Carlos; Lifschitz, Adrián; Baroni, Renato; Fusé, Luis; Bistoletti, Mariana; Sagües, Federica; Bruno, Santiago; Alvarez, Gustavo; Lanusse, Carlos; Alvarez, Luis

2017-03-15

The goal of the current study was to evaluate the comparative efficacy of ivermectin (IVM) against small strongyles (cyathostomins) following its oral and intramuscular (IM) administration, in naturally parasitized horses. The parasitological data were complemented with the assessment of the plasma disposition kinetics of IVM. The trial included two different experiments. In experiment I, 40 horses naturally infected with small strongyles were randomly allocated into four experimental groups (n=10) and treated with IVM (0.2mg/kg) as follows: IVM oral paste, animals were orally treated with Eqvalan ® (IVM 1.87% paste, as the reference formulation) by the oral route; IVM oral solution, animals were orally treated with Remonta ® (IVM 2% solution, as a test formulation); IVM IM solution, animals were IM treated with the test product (Remonta ® IVM 2% solution); and control, animals were kept without treatment as untreated controls. In experiment II, 24 horses naturally parasitized with small strongyles were randomly allocated into the same four experimental groups (n=6) described for experiment I. Faecal samples were individually collected directly from the rectum of each horse prior (day -1) and at 7 and 15 (Experiment I) or 7, 15 and 21 (Experiment II) days after-treatment, to assess the eggs per gram (epg) counts and estimate the efficacy of the treatments. Additionally, the comparative plasma disposition kinetics of IVM in treated animals was assessed in experiment II. In both experiments, an excellent (100%) IVM efficacy was observed after its oral administration (test and reference formulations). However, the IM administration of IVM resulted in a low efficacy (36-64%). Similar IVM plasma concentration was observed after its oral administration as a paste or as a solution. The higher IVM plasma profiles observed after the IM administration accounted for an enhanced systemic availability. The improved IVM efficacy observed against adult cyathostomins after its

Twelve-month longitudinal parasitological assessment of lymphatic filariasis-positive individuals: impact of a biannual treatment with ivermectin and albendazole.

PubMed

Kanamitie, John N; Ahorlu, Collins S; Otchere, Joseph; Aboagye-Antwi, Fred; Kwansa-Bentum, Bethel; Boakye, Daniel A; Biritwum, Nana-Kwadwo; Wilson, Michael D; de Souza, Dziedzom K

2017-11-01

Mass drug administration (MDA) for the control of lymphatic filariasis (LF), in Ghana, started in the year 2000. While this had great success in many implementation units, there remain areas with persistent transmission, after more than 10 years of treatment. A closer examination of the parasite populations could help understand the reasons for persistent infections and formulate appropriate strategies to control LF in these areas of persistent transmission. In a longitudinal study, we assessed the prevalence of microfilaraemia (mf) in two communities with 12 years of MDA in Ghana. In baseline surveys 6 months after the National MDA in 2014, 370 consenting individuals were tested for antigenaemia using immunochromatographic test (ICT) cards and had their mf count determined through night blood surveys. 48 ICT positives, of whom, 17 were positive for mf, were treated with 400 μg/kg ivermectin + 400 mg albendazole and subsequently followed for parasitological assessment at 3-month intervals for 1 year. This overlapped with the National MDA in 2015. There was a 68% parasite clearance 3 months after treatment. The pre-treatment mf count differed significantly from the post-treatment mf counts at 3 months (P = 0.0023), 6 months (P = 0.0051), 9 months (P = 0.0113) and 12 months (P = 0.0008). In these settings with persistent LF transmission, twice-yearly treatment may help accelerate LF elimination. Further large-scale evaluations are required to ascertain these findings. © 2017 John Wiley & Sons Ltd.

Field trial assessment of ivermectin pharmacokinetics and efficacy against susceptible and resistant nematode populations in cattle.

PubMed

Canton, Candela; Canton, Lucila; Domínguez, María Paula; Moreno, Laura; Lanusse, Carlos; Alvarez, Luis; Ceballos, Laura

2018-05-30

The study compared the pharmacokinetic (PK) behaviour and anthelmintic efficacy against susceptible and resistant nematodes following subcutaneous (SC) and oral administration of ivermectin (IVM) to cattle. Six commercial farms were involved: Farms 1 and 2 (IVM-susceptible nematode population) and Farms 3, 4, 5 and 6 (IVM-resistant nematode population). On each farm, forty-five calves naturally infected with gastrointestinal (GI) nematodes were randomly allocated into three groups (n = 15): untreated control, IVM SC administration, and IVM oral administration (both at 0.2 mg/kg). PK assessment (plasma and faeces) was performed on Farm 1. Efficacy was determined by Faecal Egg Count Reduction Test. IVM systemic availability upon SC administration (421 ± 70.3 ng·d/mL) was higher (P < 0.05) compared to the oral treatment (132 ± 31.3 ng·d/mL). However, higher (P < 0.05) faecal IVM concentrations were observed following oral treatment (9896 ± 1931 ng·d/mL) compared to SC administration (4760 ± 924 ng·d/mL). Similar (91-93%) IVM efficacy was observed on Farms 1 and 2 by both routes. Efficacy against resistant nematodes was slightly higher on Farms 3 and 4 after the oral (63 and 82%, respectively) compared to the SC (36 and 68%, respectively) treatment. However, there was complete therapeutic failure (0% efficacy) on Farm 5 and a very low response on Farm 6 (40 and 41% for SC and oral administration, respectively). Although larger faecal concentrations following IVM oral administration may increase drug exposure of GI adult worms, this does not always improve efficacy against resistant nematodes. The potential therapeutic advantages of oral treatments should be cautiously assessed, especially in presence of anthelmintic resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

“Test and not treat” for onchocerciasis control in a Loa loa endemic area

PubMed Central

Kamgno, Joseph; Pion, Sébastien D.; Chesnais, Cédric B.; Bakalar, Matthew H.; D'Ambrosio, Michael V.; Mackenzie, Charles D.; Nana-Djeunga, Hugues C.; Gounoue-Kamkumo, Raceline; Njitchouang, Guy-Roger; Nwane, Philippe; Tchatchueng-Mbouga, Jules B.; Wanji, Samuel; Stolk, Wilma A.; Fletcher, Daniel A.; Klion, Amy D.; Nutman, Thomas B.; Boussinesq, Michel

2017-01-01

Background Implementation of ivermectin-based community treatment for onchocerciasis or lymphatic filariasis elimination has been delayed in Central Africa because of severe adverse events (SAEs), including death, in people with high levels of circulating Loa loa microfilariae (mf). LoaScope, a rapid field-friendly diagnostic tool to quantify L. loa mf in peripheral blood, permits point-of-care identification of individuals “at risk” for SAEs. Methods A “Test and not Treat” (TaNT) strategy was used to implement ivermectin treatment in the Okola health district in Cameroon, where ivermectin distribution was halted in 1999 after the occurrence of fatal Loa-related SAEs. The LoaScope was used to identify and exclude individuals with >20,000 mf per milliliter of blood (at-risk for SAEs) from ivermectin treatment. Active surveillance for post-treatment adverse events (AEs) was conducted daily for 7 days. Results Between August and October 2015, 16,259 (71.1%) individuals >=5 years of age were tested out of a target population of ~22,800. Among the ivermectin-eligible population, 15,522 (95.5%) received ivermectin; 340 (2.1%) were excluded from ivermectin treatment because of a L. loa density above the risk-threshold and 397 (2.4%) were excluded for pregnancy or illness. No SAEs were observed. Non-severe AEs were recorded in 934 individuals, most (67%) of whom had no detectable L. loa mf. Conclusions The LoaScope-based TaNT strategy permitted safe re-implementation of community-wide ivermectin distribution in a heretofore ‘off limits’ health district in Cameroon and is an extremely promising and practical approach for large-scale ivermectin treatment for lymphatic filariasis and onchocerciasis elimination in Loa loa-endemic areas. PMID:29116890

Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

PubMed

Miyajima, Atsushi; Hirota, Takashi; Sugioka, Akihito; Fukuzawa, Masao; Sekine, Mari; Yamamoto, Yosuke; Yoshimasu, Takashi; Kigure, Akira; Anata, Taichi; Noguchi, Wataru; Akagi, Keita; Komoda, Masayo

2016-09-01

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM. © 2016 Japanese Dermatological Association.

Effects of ivermectin application on the diversity and function of dung and soil fauna: Regulatory and scientific background information.

PubMed

Adler, Nicole; Bachmann, Jean; Blanckenhorn, Wolf U; Floate, Kevin D; Jensen, John; Römbke, Jörg

2016-08-01

The application of veterinary medical products to livestock can impact soil organisms in manure-amended fields or adversely affect organisms that colonize dung pats of treated animals and potentially retard the degradation of dung on pastures. For this reason, the authorization process for veterinary medicinal products in the European Union includes a requirement for higher-tier tests when adverse effects on dung organisms are observed in single-species toxicity tests. However, no guidance documents for the performance of higher-tier tests are available. Hence, an international research project was undertaken to develop and validate a proposed test method under varying field conditions of climate, soil, and endemic coprophilous fauna at Lethbridge (Canada), Montpellier (France), Zurich (Switzerland), and Wageningen (The Netherlands). The specific objectives were to determine if fecal residues of an anthelmintic with known insecticidal activity (ivermectin) showed similar effects across sites on 1) insects breeding in dung of treated animals, 2) coprophilous organisms in the soil beneath the dung, and 3) rates of dung degradation. By evaluating the effects of parasiticides on communities of dung-breeding insects and soil fauna under field conditions, the test method meets the requirements of a higher-tier test as mandated by the European Union. The present study provides contextual information on authorization requirements for veterinary medicinal products and on the structure and function of dung and soil organism communities. It also provides a summary of the main findings. Subsequent studies on this issue provide detailed information on different aspects of this overall project. Environ Toxicol Chem 2016;35:1914-1923. © 2015 SETAC. © 2015 SETAC.

Impact of Eighteen-Year Varied Compliance to Onchocerciasis Treatment with Ivermectin in Sentinel Savannah Agrarian Communities in Kaduna State of Nigeria.

PubMed

Osue, Hudu O; Inabo, Helen I; Yakubu, Sabo E; Audu, Patrick A; Galadima, Musa; Odama, Lillian E; Musa, Danjuma; Ado, Saleh A; Mamman, Mohammed

2013-01-01

Baseline and impact assessment data were generated in 1994 (n = 532) and 2011 (n = 593) from 6 sentinel villages with generalized onchocerciasis. Only volunteers and a cohort (n = 445, 75%) were screened at both visits. Each village had received 11 (64.7%) annual treatments and 92.6%, range 88.7-100%, treatment compliance. Overall mean number of treatment was 2.9 ± 1.6 with a range 2.0 ± 1.2-3.3 ± 0.6. Significant decreases in skin microfilaria prevalence from 201 (38%) to 0 (0%), palpable nodule from 77 (15%) to 4 (0.7%), dermal changes from 51 (9.6%) to 2 (0.04%), optic nerve disease from 24 (4.5%) to 4 (2.0%), and onchocercal inducible ocular lesions from 31 (5.8%) to 12 (2.0%) were recorded, P < 0.05, (t-test of unpaired data). Cases of glaucoma, 8 (1.4%), and blindness, 6 (1.05%), remained unchanged. Visual acuity ≥6/24 in one or both eyes, 198 (33.45%); cataract, 169 (28.5%); pterygium 157 (26.5%); and acute senilis, 165 (27.9%), were significantly increased and positively correlated with increase in age (R (2) = 0.898 - 0.949). Dissected parous Simulium damnosum caught (n = 222) were without infective third stage larva. Active onchocerciasis transmission seems halted despite varied compliance to long-term ivermectin treatment. We recommend continued surveillance and targeted treatment of controlled and hypoendemic areas.

Impact of Six Years Community Directed Treatment with Ivermectin in the Control of Onchocerciasis, Western Ethiopia

PubMed Central

Samuel, Abdi; Belay, Tariku; Yehalaw, Delenasaw; Taha, Mohammed; Zemene, Endalew; Zeynudin, Ahmed

2016-01-01

Background The African Program for Onchocerciais Control (APOC) with a main strategy of community directed treatment with ivermectin (CDTI) was established with the aim of eliminating Onchocerciasis as a disease of public health and socio-economic importance. The study area was a hyper endemic area just before the implementation of CDTI. It has been implemented for six years in this district but yet not been evaluated. So, the objective of this study was to evaluate the impact of six years CDTI on parasitological and clinical indices of Onchocerciasis Methods This study employed a pre-post impact evaluation design. The minimum sample size for this study was 1318; the respondents were selected by multi-stage sampling technique. Data on socio-demographic characteristics using a semi-structured questionnaire, clinical examination for skin signs and symptoms of Onchocerciasis and two bloodless skin snips from each side of the gluteal fold were taken from the entire study participants. SPSS version 16.0 and Medcalc version 12.2.1.0 were used for analysis. Result The microfilaridermia reduced from the pre-intervention value of 74.8% to 40.7%, indicating a 45.6% reduction, mean intensity from 32.1(SD = 61.5) mf/mg skin snip to 18.7(SD = 28.7)indicating 41.75% reduction, CMFL from 19.6 mf/mg skin snip to 4.7 indicating 76% reduction. The result also showed that microfilaridermia and mean intensity decreased as the number of treatment taken increased. Pruritis, leopard skin, onchocercomata and hanging groin reduced by 54.4%, 61.3%, 77.7% and 88.5% respectively. Conclusions The implementation of CDTI significantly reduced the parasitological and clinical indices of Onchocerciasis, so, efforts should be made to improve the annual treatment coverage and sustainability of CDTI to drastically reduce the micro filarial load to the level the disease would no longer be a public health problem. PMID:26942910

Status of forest onchocerciasis in the Lower Cross River basin, Nigeria: entomologic profile after five years of ivermectin intervention.

PubMed

Opara, Kenneth N; Fagbemi, Olakunle B; Ekwe, Asuquo; Okenu, Daniel M N

2005-08-01

In the Lower Cross River basin in Nigeria, no pre-control entomologic profile of Onchocerca volvulus infection in the local Simulium damnosum population was available prior to the initiation of an ivermectin control program in 1995. A longitudinal entomologic study was therefore carried out over a 12-month period (January-December 2001) at the Agbokim waterfalls and Afi River, which are breeding sites of S. damnosum in the river basin. A total of 9,287 adult S. damnosum were caught on human bait; 9,048 (97.43%) were dissected, of which 313 (3.46%) were infected. Annual biting rates (ABRs) of 42,419 and 28,346 bites per persons per year were recorded at the Agbokim Waterfalls and Afi River, respectively. The annual transmission potential (ATP) was 419 infective larvae per person per year at the Agbokim Waterfalls and 427 at the Afi River. Monthly biting rate and monthly transmission potential varied significantly (P < 0.05) at the two sites. Transmission was highly seasonal from April to September, corresponding to the peak biting period of the vector. The high ATP and ABR values are a measure of the mesoendemicity of onchocerciasis in the river basin. There was a significant F(0).05 (1, 10) (P < 0.05) variation in the relative fly abundance from both sites. It was observed that human activities such as farming, fishing, timber cutting, and hunting are done in the early morning and late afternoon, which corresponds to the peak diurnal biting period of the vector. Changes in these practices and attitudes may markedly affect the disease intensity and transmission.

Mass Drug Administration for Scabies Control in a Population with Endemic Disease.

PubMed

Romani, Lucia; Whitfeld, Margot J; Koroivueta, Josefa; Kama, Mike; Wand, Handan; Tikoduadua, Lisi; Tuicakau, Meciusela; Koroi, Aminiasi; Andrews, Ross; Kaldor, John M; Steer, Andrew C

2015-12-10

Scabies is an underrecognized cause of illness in many developing countries. It is associated with impetigo, which can lead to serious systemic complications. We conducted a trial of mass drug administration for scabies control in Fiji. We randomly assigned three island communities to one of three different interventions for scabies control: standard care involving the administration of permethrin to affected persons and their contacts (standard-care group), mass administration of permethrin (permethrin group), or mass administration of ivermectin (ivermectin group). The primary outcome was the change in the prevalence of scabies and of impetigo from baseline to 12 months. A total of 2051 participants were enrolled; 803 were in the standard-care group, 532 in the permethrin group, and 716 in the ivermectin group. From baseline to 12 months, the prevalence of scabies declined significantly in all groups, with the greatest reduction seen in the ivermectin group. The prevalence declined from 36.6% to 18.8% in the standard-care group (relative reduction in prevalence, 49%; 95% confidence interval [CI], 37 to 60), from 41.7% to 15.8% in the permethrin group (relative reduction, 62%; 95% CI, 49 to 75), and from 32.1% to 1.9% in the ivermectin group (relative reduction, 94%; 95% CI, 83 to 100). The prevalence of impetigo also declined in all groups, with the greatest reduction seen in the ivermectin group. The prevalence declined from 21.4% to 14.6% in the standard-care group (relative reduction, 32%; 95% CI, 14 to 50), from 24.6% to 11.4% in the permethrin group (relative reduction, 54%; 95% CI, 35 to 73), and from 24.6% to 8.0% in the ivermectin group (relative reduction, 67%; 95% CI, 52 to 83). Adverse events were mild and were reported more frequently in the ivermectin group than in the permethrin group (15.6% vs. 6.8%). Mass drug administration, particularly the administration of ivermectin, was efficacious for the control of scabies and impetigo. (Funded by the

The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats.

PubMed

Gokbulut, C; Karademir, U; Boyacioglu, M; McKellar, Q A

2008-10-01

The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 microg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two-phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4-week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half-lives and resultant longer mean resident time were observed after s.c. administration of the both

Simultaneous determination of residues of emamectin and its metabolites, and milbemectin, ivermectin, and abamectin in crops by liquid chromatography with fluorescence detection.

PubMed

Yoshii, K; Kaihara, A; Tsumura, Y; Ishimitsu, S; Tonogai, Y

2001-01-01

A liquid chromatographic (LC) method was developed for the determination of emamectin and its metabolites (8,9-Z-isomer, N-demethylated, N-formylated, and N-methylformylated emamectin) in various crops. The analytes were extracted with acetone, cleaned up on cartridge columns (C18 and NH2), derivatized with trifluoroacetic anhydride and 1-methylimidazole, and determined by LC with fluorescence detection. Because radish inhibited the formation of the fluorescent derivatives, an additional Bond Elut PRS cartridge was used in the cleanup of Japanese radish samples. During sample preparation, N-formylated emamectin partially degraded to emamectin B1b and emamectin B1a, and the 8,9-Z-isomer partially degraded to N-demethylated emamectin. Therefore, emamectin and its metabolites were determined as total emamectin, i.e., their sum was estimated as emamectin benzoate. Their recoveries from most crops were approximately 80-110% with the developed method. The detection limits for the analytes in vegetables were 0.1-0.3 parts per trillion (ppt). The results for these compounds were confirmed by LC/mass spectrometry (LC/MS; electrospray ionization mode). Because the fluorescent derivative of emamectin was undetectable by LC/MS, the results for the analyte were confirmed by using a sample solution without derivatization. Limits of detection by LC/MS were similar to the fluorescence detection limits, 0.1-0.3 ppt in vegetables. In addition to the emamectins, milbemectin, ivermectin, and abamectin were also determined by the developed method.

Multi-year and short-term responses of soil ammonia-oxidizing prokaryotes to zinc bacitracin, monensin, and ivermectin, singly or in combination.

PubMed

Magda, Konopka; Hugh A L, Henry; Romain, Marti; Edward, Topp

2015-03-01

A field experiment was initiated whereby a series of replicated plots received annual applications of ivermectin, monensin, and zinc bacitracin, either singly or in a mixture. Pharmaceuticals were added at concentrations of 0.1 mg/kg soil or 10 mg/kg soil. The authors collected soil samples in 2013, before and after the fourth annual application of pharmaceuticals. In addition, a 30-d laboratory experiment was undertaken with the same soil and same pharmaceuticals, but at concentrations of 100 mg/kg soil. The impact of the pharmaceuticals on nitrification rates, on the abundance of ammonia-oxidizing bacteria (AOB), and on the abundance of ammonia-oxidizing archaea (AOA) was assessed. None of the pharmaceuticals at 0.1 mg/kg had any effect on nitrification. Referenced to control soil, nitrification was accelerated in soil exposed to 100 mg/kg zinc bacitracin or 10 mg/kg of the pharmaceutical mixture, but none of the treatments inhibited nitrification. Neither AOB abundance nor AOA abundance was affected by the pharmaceuticals at 0.1 mg/kg. At 10 mg/kg, monensin, zinc bacitracin, and a mixture of all 3 pharmaceuticals suppressed the abundance of AOB, and zinc bacitracin and the mixture increased AOA abundance. The decrease in AOB abundance and increase in AOA abundance when exposed to 10 mg/kg soil suggests that AOB are more sensitive to these chemicals and that AOA populations can expand to occupy the partially vacated niche. Published 2014 SETAC.

Resistant nematodes in cattle: Pharmaco-therapeutic assessment of the ivermectin- ricobendazole combination.

PubMed

Canton, Candela; Ceballos, Laura; Fiel, César; Moreno, Laura; Domingo Yagüez, Pablo; Bernat, Gisele; Lanusse, Carlos; Alvarez, Luis

2017-01-30

Nematodicidal combinations have been proposed as a valid strategy to achieve effective nematode control in the presence of drug resistance. The goals of this study were: (1) to compare the clinical efficacy (therapeutic response) of ivermectin (IVM) and ricobendazole (RBZ) given subcutaneously either by separate or combined administration to calves naturally infected with gastrointestinal nematodes resistant to IVM, and (2) to evaluate the potential pharmacokinetic (PK) and/or pharmacodynamic (PD) interactions occurring after the co-administration of both anthelmintics. Sixty male calves naturally infected with gastrointestinal nematodes resistant to IVM were randomly allocated into four groups (n=15). Untreated control: animals not receiving anthelmintic treatment; IVM alone: animals treated with IVM by subcutaneous (SC) injection (0.2mg/kg); RBZ alone: animals received RBZ by the SC route (3.75mg/kg); IVM+RBZ: animals treated with IVM and RBZ (0.2 and 3.75mg/kg, respectively), by SC injection in two separates sites. Eight animals of each treated group were randomly selected to perform the PK study. Plasma samples were taken from those animals up to 28days post-treatment. IVM and RBZ plasma concentrations were quantified by HPLC. The therapeutic response was determined by faecal egg count reduction test (FECRT). The proportions of third-stage larvae (L3) recovered from coprocultures were used to calculate the efficacy against the main parasite genera. The daily total egg deposition for each experimental group was estimated. Similar pharmacokinetic trends were obtained for both IVM and RBZ allying the single-drug and the combined treatments, which indicates the absence of PK interactions between both anthelmintics. The observed overall clinical drug efficacies were 48% (IVM alone), 94% (RBZ alone) and 98% (IVM+RBZ). Haemonchus spp. and Cooperia spp. were recovered in the coproculture after IVM treatment, suggesting that resistance to IVM includes both genera. In

Ivermectin

MedlinePlus

... sometimes used to treat certain other roundworm infections, head or pubic lice infestation, and scabies (itchy skin condition caused by infestation with small mites that live under the skin). Talk to your doctor about ... for other uses; ask your doctor or pharmacist for more information.

Parasitological indicators of onchocerciasis relevant to ivermectin control programmes in the Amazonian focus of Southern Venezuela.

PubMed

Vivas-Martínez, S; Basáñez, M G; Botto, C; Villegas, L; García, M; Curtis, C F

2000-11-01

In the previous paper it was concluded that those aged > or = 15 years of both sexes could comprise the indicator group for rapid epidemiological assessment (REA) of onchocerciasis in the Amazonian focus. This paper explores relationships between community microfilarial (mf) prevalence, intensity, and nodule prevalence in 20 Yanomami communities, that would allow identification of REA methods in the region. The mean nodule ratio (prevalence of nodules/prevalence of mf) was 0.54 when onchocercomata in the indicator group were considered. The Spearman correlation coefficient between mf and nodule prevalence was 0.686 (P = 0.001). Palpation of nodules had 92 % specificity and 32 % sensitivity when compared to skin-snipping for the diagnosis of onchocerciasis. The predictive value positive increased from 75 % to 81 % when the indicator group was used. A microfilarial prevalence > 75 % in this group would be indicative of hyperendemic status in the village, between 30 and 75 % of mesoendemicity, and < 30 % of hypoendemicity. For the assessment of infection intensity, biopsies may be taken from the iliac crest for all endemicity levels. Five of the hyperendemic villages surveyed in this work had a community microfilarial load (CMFL) greater than 10 mf/skin snip; the remaining 5 had a CMFL between 5 and 9. These levels of infection merit high priority ivermectin treatment. In Latin America, communities at both moderate and severe risk are included in mass chemotherapy programmes (i.e. when mf prevalence is over 20 %). Roughly, a nodule prevalence in the indicator group > 10 % would suggest a community mf prevalence > 20 % with a sensitivity of 85 % and a specificity of 71 %. A multiple linear regression model of the arc-sine transformed mf prevalence in the village (all ages) on nodule prevalence in those aged > or = 15 years and altitude of the village explained 72 % of the variance. The model combining nodule and altitudinal information had a sensitivity of 92 % and a

Efficacy of different treatment regimes against setariosis (Setaria tundra, Nematoda: Filarioidea) and associated peritonitis in reindeer

PubMed Central

Laaksonen, Sauli; Oksanen, Antti; Orro, Toomas; Norberg, Harri; Nieminen, Mauri; Sukura, Antti

2008-01-01

Background When a severe peritonitis outbreak in semi-domesticated reindeer was noticed in 2003 in Finland, the concerned industry urged immediate preventive actions in order to avoid detrimental effects of S. tundra and further economical losses. A research programme was swiftly initiated to study S. tundra and its impact on the health and wellbeing of reindeer. Methods The ultimate aim of this study was to test the efficacy of different treatment regimes against S. tundra and associated peritonitis in reindeer. The timing of the trials was planned to be compatible with the annual rhythm of the reindeer management; (1) the treatment of calves in midsummer, during routine calf ear marking, with ivermectin injection prophylaxis and deltamethrin pour-on solution as a repellent against insect vectors, (2) the treatment of infected calves in early autumn with ivermectin injection, and (3) ivermectin treatment of breeding reindeer in winter. The results were assessed using the post mortem inspection data and S. tundra detection. Finally, to evaluate on the population level the influence of the annual (late autumn-winter) ivermectin treatment of breeding reindeer on the transmission dynamics of S. tundra, a questionnaire survey was conducted. Results In autumn, ivermectin treatment was efficient against peritonitis and in midsummer had a slight negative impact on the degree of peritonitis and positive on the fat layer, but deltamethrin had none. Ivermectin was efficient against adult S. tundra and its smf. All the reindeer herding cooperatives answered the questionnaire and it appeared that antiparasitic treatment of reindeer population was intense during the study period, when 64–90% of the animals were treated. In the southern part of the Finnish reindeer husbandry area, oral administration of ivermectin was commonly used. Conclusion Autumn, and to a lesser degree summer, treatment of reindeer calves with injectable ivermectin resulted in decreased severity of

Absence of Loa loa Microfilaremia among Newly Arrived Congolese Refugees in Texas.

PubMed

Montour, Jessica; Lee, Deborah; Snider, Cathy; Jentes, Emily S; Stauffer, William

2017-12-01

The Centers for Disease Control and Prevention recommends that refugees at risk of Loa loa infection be tested for microfilaria before treatment with ivermectin. We report observational results of this approach in African refugees in Texas. Daytime blood smears were performed for microfilaria on at-risk African refugees who arrived in Texas from July 1, 2014 through December 30, 2016. Clinics were asked if there were any adverse events reported among those who received ivermectin. Of the 422 persons screened, 346 (82%) were born in L. loa -endemic countries, with 332 (96%) of these being born in the Democratic Republic of Congo. No smears detected microfilaria, and all received presumptive ivermectin with no reports of significant adverse events. In this investigation, the prevalence of significant microfilarial load in sub-Saharan African refugees appeared to be low, and ivermectin treatment was safe and well tolerated.

Serum Strongylus vulgaris-specific antibody responses to anthelmintic treatment in naturally infected horses.

PubMed

Nielsen, Martin K; Vidyashankar, Anand N; Bellaw, Jennifer; Gravatte, Holli S; Cao, Xin; Rubinson, Emily F; Reinemeyer, Craig R

2015-02-01

Strongylus vulgaris is the most pathogenic helminth parasite of horses, causing verminous endarteritis with thromboembolism and infarction. A serum enzyme-linked immunosorbent assay (ELISA) has been validated for detection of antibodies to an antigen produced by migrating larvae of this parasite. The aim was to evaluate ELISA responses to anthelmintic treatment in cohorts of naturally infected horses. Fifteen healthy horses harboring patent S. vulgaris infections were turned out for communal grazing in May 2013 (day 0). On day 55, horses were ranked according to ELISA titers and randomly allocated to the following three groups: no treatment followed by placebo pellets daily; ivermectin on day 60 followed by placebo pellets daily; or ivermectin on day 60 followed by daily pyrantel tartrate. Fecal and serum samples were collected at ∼28-day intervals until study termination on day 231. Increased ELISA values were observed for the first 53 days following ivermectin treatment. Titers were significantly reduced 80 days after ivermectin treatment. Horses receiving daily pyrantel tartrate maintained lower ELISA values from 137 days post ivermectin treatment until trial termination. These results illustrate that a positive ELISA result is indicative of either current or prior exposure to larval S. vulgaris infection within the previous 5 months.

Doxycycline as an inhibitor of p-glycoprotein in the alpaca for the purpose of maintaining avermectins in the CNS during treatment for parelaphostrongylosis.

PubMed

Agbedanu, Prince N; Anderson, Kristi L; Brewer, Matthew T; Carlson, Steve A

2015-09-15

Meningeal worms (Parelaphostrongylus tenuis) are a common malady of alpacas, often refractory to conventional treatments. Ivermectin is a very effective anthelmintic used against a variety of parasites but this drug is not consistently effective against alpaca meningeal worms once the parasite has gained access to the CNS, even if used in a protracted treatment protocol. Ivermectin is not effective against clinical cases of P. tenuis, raising the possibility that the drug is not sustained at therapeutic concentrations in the central nervous system (CNS). A specific protein (designated as p-glycoprotein (PGP)) effluxes ivermectin from the brain at the blood-brain barrier, thus hampering the maintenance of therapeutic concentrations of the drug in the CNS. Minocycline is a synthetic tetracycline antibiotic with an excellent safety profile in all animals tested to date. Minocycline has three unique characteristics that could be useful for treating meningeal worms in conjunction with ivermectin. First, minocycline is an inhibitor of PGP at the blood-brain barrier and this inhibition could maintain effective concentrations of ivermectin in the brain and meninges. Second, minocycline protects neurons in vivo through a number of different mechanisms and this neuroprotection could alleviate the potential untoward neurologic effects of meningeal worms. Third, minocycline is a highly lipid-soluble drug, thus facilitating efficient brain penetration. We thus hypothesized that minocycline will maintain ivermectin, or a related avermectin approved in ruminants (abamectin, doramectin, or eprinomectin), in the alpaca CNS. To test this hypothesis, we cloned the gene encoding the alpaca PGP, expressed the alpaca PGP in a heterologous expression system involving MDCK cells, and measured the ability of minocycline to inhibit the efflux of avermectins from the MDCK cells; doxycycline was used as a putative negative control (based on studies in other species). Our in vitro studies

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

PubMed

Bernigaud, Charlotte; Fang, Fang; Fischer, Katja; Lespine, Anne; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

2016-10-01

Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

The Treatment of Scabies.

PubMed

Dressler, Corinna; Rosumeck, Stefanie; Sunderkötter, Cord; Werner, Ricardo Niklas; Nast, Alexander

2016-11-14

Scabies is a contagious infestation transmitted by skin-to-skin contact and sometimes by contact with contaminated material. The scabies mite burrows into the skin, producing a papular rash and severe itch at typical sites of predilection. We systematically reviewed the literature to compare the efficacy of various anti-scabies agents, including a calculation of relative risks and confidence intervals. A literature search yielded 596 initial hits; after screening in accor-dance with the defined inclusion and exclusion criteria, 16 studies were selected for this review. Among topical treatments for scabies, permethrin was equally effective or more effective than crotamiton or benzyl benzoate. In a comparison of topical versus systemic treatment, topical permethrin and systemic ivermectin did not differ substantially in efficacy (7 comparative studies revealed no difference; one revealed a difference in favor of permethrin). Comparative trials of topical benzyl benzoate versus systemic ivermectin yielded inconsistent findings. Single and double administrations of ivermectin were similarly effective. In trials involving entire populations with a high prevalence of scabies, systemic ivermectin was found to be superior to topical permethrin. There are hardly any differences in efficacy between the available treatments for scabies. Single administrations of permethrin 5%, crotamiton 10%, and systemic ivermectin are all comparably effective. There are differences in the frequeny and ease of application as well as when eradicating scabies in populations with a high prevalence.

Changes in Serum Strongylus Vulgaris-Specific Antibody Concentrations in Response to Anthelmintic Treatment of Experimentally Infected Foals.

PubMed

Nielsen, Martin Krarup; Scare, Jessica; Gravatte, Holli Sullivan; Bellaw, Jennifer Lynn; Prado, Julio C; Reinemeyer, Craig Robert

2015-01-01

Strongylus vulgaris is the most pathogenic nematode parasite of horses. Its extensive migration in the mesenteric blood vessels can lead to life-threatening intestinal infarctions. Recent work has shown that this parasite is still identified among managed horse populations. A serum enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of migrating larvae of S. vulgaris. Previous work has documented an increase in ELISA values following larvicidal treatment with ivermectin and suggested that the target parasite antigen is primarily produced by the later larval stages. The aim of this study was to experimentally inoculate cohorts of foals with S. vulgaris, and then compare ELISA responses to early or later ivermectin treatments. Fifteen foals were held in confinement and infected orally with ~25 S. vulgaris third-stage larvae on Days 0, 7, 14, and 21. Foals were weaned on Day 43 and turned out to a pasture not previously grazed by horses. Foals remained at pasture continuously until the study was terminated on Day 196. On Day 55, foals were randomly allocated to three treatment groups of five each. Group 1 received ivermectin on Day 56, Group 2 received ivermectin on Day 112, and Group 3 foals served as untreated controls. Serum and fecal samples were collected at 28-day intervals throughout the study. Serum samples were analyzed with the S. vulgaris-specific ELISA and fecal samples were processed for fecal egg counting. The ELISA values of Group 1 foals were significantly lower than Groups 2 or 3 on Days 140-196. Both treated groups exhibited increased ELISA values following ivermectin treatment. Results indicate that the target diagnostic antigen is produced throughout the course of arterial infection with S. vulgaris, but that an early ivermectin treatment can reduce the cumulative antigen produced over the course of an infection.

Changes in Serum Strongylus Vulgaris-Specific Antibody Concentrations in Response to Anthelmintic Treatment of Experimentally Infected Foals

PubMed Central

Nielsen, Martin Krarup; Scare, Jessica; Gravatte, Holli Sullivan; Bellaw, Jennifer Lynn; Prado, Julio C.; Reinemeyer, Craig Robert

2015-01-01

Strongylus vulgaris is the most pathogenic nematode parasite of horses. Its extensive migration in the mesenteric blood vessels can lead to life-threatening intestinal infarctions. Recent work has shown that this parasite is still identified among managed horse populations. A serum enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of migrating larvae of S. vulgaris. Previous work has documented an increase in ELISA values following larvicidal treatment with ivermectin and suggested that the target parasite antigen is primarily produced by the later larval stages. The aim of this study was to experimentally inoculate cohorts of foals with S. vulgaris, and then compare ELISA responses to early or later ivermectin treatments. Fifteen foals were held in confinement and infected orally with ~25 S. vulgaris third-stage larvae on Days 0, 7, 14, and 21. Foals were weaned on Day 43 and turned out to a pasture not previously grazed by horses. Foals remained at pasture continuously until the study was terminated on Day 196. On Day 55, foals were randomly allocated to three treatment groups of five each. Group 1 received ivermectin on Day 56, Group 2 received ivermectin on Day 112, and Group 3 foals served as untreated controls. Serum and fecal samples were collected at 28-day intervals throughout the study. Serum samples were analyzed with the S. vulgaris-specific ELISA and fecal samples were processed for fecal egg counting. The ELISA values of Group 1 foals were significantly lower than Groups 2 or 3 on Days 140–196. Both treated groups exhibited increased ELISA values following ivermectin treatment. Results indicate that the target diagnostic antigen is produced throughout the course of arterial infection with S. vulgaris, but that an early ivermectin treatment can reduce the cumulative antigen produced over the course of an infection. PMID:26664946

Systemic activity of the avermectins against the cat flea (Siphonaptera: Pulicidae).

PubMed

Zakson-Aiken, M; Gregory, L M; Meinke, P T; Shoop, W L

2001-07-01

Ivermectin has potent systemic activity against numerous species of nematodes and arthropods, but there are some important species in these two groups, such as the cat flea, Ctenocephalides felis (Bouché), that appear to be refractory to it. In an effort to determine if the lack of systemic activity against C. felis is specific to ivermectin, or if it is a class-wide phenomenon, 20 avermectin derivatives were tested in an artificial membrane flea feeding system at concentrations of 20, 10, and 1 microg/ml. Results showed that ivermectin had LC90 and LC50 values against fleas of 19.1 and 9.9 microg/ml, respectively. Only four of the other 19 compounds evaluated possessed both LC90 and LC50 values more potent than ivermectin and even then the advantage was modest. Among those four compounds was a two-fold increase in potency relative to ivermectin when the LC90 values were considered (range, 9.2-10.3 microg/ml) and a two- to eight-fold increase when the LC50 values were examined (range, 1.23-5.26 microg/ml). Neither the possession nor the number of oleandrosyl sugars on the macrocyclic backbone were relevant for additional flea activity because among these four compounds were two disaccharides, a monosaccharide and an aglycone. Also, bond disposition between C-22 and 23 did not contribute to increase in activity because these molecules comprise members with either single or double bonds. One of these avermectin analogs was scaled-up and tested subcutaneously in a dog at >100 times the commercial ivermectin dosage and zero efficacy was observed against the flea. We conclude that even the best in vitro avermectin does not have the in vivo potential to become a commercial oral or subcutaneous flea treatment for companion animals.

Knowledge, attitude and practice of community drug distributors' about onchocerciasis and community directed treatment with ivermectin in Quara district, North Western Ethiopia.

PubMed

Weldegebreal, Fitsum; Medhin, Girmay; Weldegebriel, Zemichael; Legesse, Mengistu

2016-04-06

Onchocerciasis is one of the most important public health problems over large areas of tropical Africa countries including Ethiopia. The African Program for Onchocerciasis Control (APOC) has been working with ultimate goal of reducing the public health and socio-economic problems of onchocerciasis through administration of the tablet for continuous 12-15 years using the strategy of yearly community-directed treatment with ivermectin (CDTI) in endemic areas of Africa to kill the microfilariae that invade the eyes and are present in the skin to be transported to another victim by the black fly. The objective of this study was to assess knowledge, attitude and practice of community drug distributors (CDDs) towards onchocerciasis and CDTI in Quara district. Of all the study participating CDD 11.4% (9/79) said that they knew about the etiology of the disease, 35.4% (28/79) had good level of knowledge, 19 (24.1%) had good level of positive attitude and 18 (22.8%) had good level of positive practice about onchocerciasis. Similarly, 45.6% (36/79), 81.0% (64/79) and 29.1% (23/79) had good level of knowledge, attitude and practice about CDTIP, respectively. Being a female CDD (adjusted OR 7.246, P = 0.035, 95% CI 1.147, 45.455) and being older than 35 years (adjusted OR 8.435, P = 0.001, 95% CI 4.53, 9.003) were significantly associated with the likelihood of having good level of knowledge about the disease. Although onchocerciasis is endemic in Quara district, large proportion of the CDDs had misconceptions about its causation, transmission and prevention. Therefore, CDTIP for onchocerciasis control need to be supported by proper and continuous training, and health education about different aspects of the disease.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

PubMed Central

Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

2016-01-01

Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

Ivermectin Topical

MedlinePlus

... the application and rinsing steps. Use a fine-tooth comb or lice comb to remove the dead lice and nits (empty egg shells) after this treatment. Discard any unused portion of the tube once you finish this treatment. Do not use ...

Protection of yearling ponies against Strongylus vulgaris by foalhood vaccination.

PubMed

Klei, T R; French, D D; Chapman, M R; McClure, J R; Dennis, V A; Taylor, H W; Hutchinson, G W

1989-06-01

The long-term efficacy of an irradiation attenuated larval (L3) vaccine against Strongylus vulgaris was tested in ponies which were reared on pasture. Prior to foaling, mares were divided into two groups. One group of mares and foals received regular (eight weekly) treatment with ivermectin and the second group remained untreated. Half the foals in each pasture group were vaccinated at eight to ten weeks of age. Foals were weaned at three to four months of age and maintained on separate pastures. At eight to ten months of age, ponies were placed in box stalls and half of each treatment group were challenged with S. vulgaris (5 x 1000 L3). Clinical signs and lesions typical of acute verminous arteritis were found at necropsy in the ivermectin treated non-vaccinated challenged yearlings. Ivermectin treated vaccinated challenged yearlings did not show these clinical signs, had markedly reduced to absent arterial lesions and showed an 89 per cent reduction in arterial larval burdens post mortem. Significant differences in clinical signs, arterial lesions or arterial larval burdens were not seen between vaccinated and non-vaccinated foals reared without benefit of ivermectin treatment.

Ocular onchocerciasis: current management and future prospects

PubMed Central

Babalola, Olufemi Emmanuel

2011-01-01

This paper reviews the current management of onchocerciasis and its future prospects. Onchocerciasis is a disease affecting millions of people in Africa, South and Central America, and Yemen. It is spread by the blackfly as a vector and caused by the filarial nematode, Onchocerca volvulus. A serious attempt was made by the Onchocerciasis Control Program between 1975 and 2002 to eliminate the vector in eleven of the endemic countries in West Africa, and with remarkable success. Formerly, the treatment was with diethyl carbamazine for the microfilaria and suramin for the adult worm. These drugs are now known to be toxic and unsuitable for mass distribution. In particular, they precipitate optic nerve disease. With the discovery of ivermectin, a much safer microfilaricide, and the decision of Merck to distribute the drug free of charge for as long as needed, the strategy of control switched to mass drug administration through community-directed treatment with ivermectin. So far, millions have received this annual or biannual treatment through the African Program for Onchocerciasis Control and the Onchocerciasis Elimination Program for the Americas. However, the problem with ivermectin is that it is a monotherapy microfilaricide which has limited effect on the adult worm, and thus will need to be continued for the life span of the adult worm, which may last up to 15 years. There are also early reports of resistance. Serious encephalopathy and death may occur when ivermectin is used in subjects heavily infested with loiasis. It seems unlikely that a break in transmission will occur with community-directed treatment with ivermectin in Africa because of population migrations and the highly efficient vector, but in the Americas some countries such as Columbia and the Oaxaca focus in Mexico have reported eradication. Vector control is only now applicable in selected situations, and particularly to control the nuisance value of the blackfly. Trials are ongoing for

Treatment and control of Trixacarus caviae infestation in a conventional guinea pig (Cavia porcellus) breeding colony.

PubMed

Nath, Anjan Jyoti

2016-12-01

A case of sarcoptic mange caused by Trixacarus caviae in a conventional guinea pig breeding colony is reported. The infestation was reported in a large colony of guinea pigs during the month of July, 2013 affecting 30 breeder guinea pigs. Severely infested animals were treated individually with subcutaneous injection of ivermectin 1 % w/v (Neomec ® ) at the rate of 400 µg/kg body weight 10 days apart. Three doses of ivermectin were sufficient to eliminate the parasite which tested negative after 30 days of the first treatment. The entire colony was given preventive dose of ivermectin spray (2 mg/ml solution) following the same schedule. Strict hygienic measures were followed. New hair growth in the severely affected animals was evidenced on 30th day of treatment.

Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials.

PubMed

Stein Gold, Linda; Kircik, Leon; Fowler, Joseph; Jackson, J Mark; Tan, Jerry; Draelos, Zoe; Fleischer, Alan; Appell, Melanie; Steinhoff, Martin; Lynde, Charles; Sugarman, Jeffrey; Liu, Hong; Jacovella, Jean

2014-11-01

Papulopustular rosacea (PPR) is characterized by facial erythema and inflammatory lesions believed to be primarily caused by dysregulation of the innate immune system. More recent evidence also suggests that Demodex folliculorum mites may contribute to the etiology of PPR. Ivermectin (IVM) 1% cream is a novel topical treatment developed to treat PPR. Two phase 3 trials have demonstrated that IVM 1% cream was significantly better than vehicle at investigator global assessment (IGA) success rate and lesion reductions and that it was safe and well tolerated. Two 40-week extension studies of those trials were conducted to assess the long-term safety of IVM 1% cream vs azelaic acid (AzA) 15% gel. Subjects originally treated with IVM 1% continued on IVM 1% and those originally treated with vehicle switched to AzA 15% gel. IVM 1% cream was safe throughout the study with a lower incidence of related adverse events (AEs) compared to AzA 15% gel. No subjects in the IVM 1% cream group discontinued either study due to a related AE. IVM 1% also continued to be efficacious during the 40-week extension studies as the percentage of subjects with IGA scores of clear or almost clear was higher at the end of the study compared to baseline. The results of these 40-week extension studies support the use of IVM 1% cream as a long-term therapy for PPR as IVM 1% cream was shown to be safe and effective for up to 52 weeks of total treatment.

The Effect of Oral Anthelmintics on the Survivorship and Re-feeding Frequency of Anthropophilic Mosquito Disease Vectors

PubMed Central

Kobylinski, Kevin C.; Deus, Kelsey M.; Butters, Matt T.; Hongyu, Tan; Gray, Meg; Silva, Ines Marques da; Sylla, Massamba; Foy, Brian D.

2010-01-01

In the Tropics, there is substantial temporal and spatial overlap of diseases propagated by anthropophilic mosquito vectors (such as malaria and dengue) and human helminth diseases (such as onchocerciasis and lymphatic filariasis) that are treated though mass drug administrations (MDA). This overlap will result in mosquito vectors imbibing significant quantities of these drugs when they blood feed on humans. Since many anthelmintic drugs have broad anti-invertebrate effects, the possibility of combined helminth control and mosquito-borne disease control through MDA is apparent. It has been previously shown that ivermectin can reduce mosquito survivorship when administered in a blood meal, but more detailed examinations are needed if MDA is to ever be developed into a tool for malaria or dengue control. We examined concentrations of drugs that follow human pharmacokinetics after MDA and that matched with mosquito feeding times, for effects against the anthropophilic mosquito vectors Anopheles gambiae s.s. and Aedes aegypti. Ivermectin was the only human-approved MDA drug we tested that affected mosquito survivorship, and only An. gambiae s.s. were affected at concentrations respecting human pharmacokinetics at indicated doses. Ivermectin also delayed An. gambiae s.s. re-feeding frequency and defecation rates, and two successive ivermectin-spiked blood meals following human pharmacokinetic concentrations compounded mortality effects compared to controls. These findings suggest that ivermectin MDA in Africa may be used to decrease malaria transmission if MDAs were administered more frequently. Such a strategy would broaden the current scope of polyparasitism control already afforded by MDAs, and which is needed in many African villages simultaneously burdened by many parasitic diseases. PMID:20540931

[Crusted scabies in HIV/AIDS infected patients. Report of 15 cases].

PubMed

Tirado-Sánchez, Andrés; Bonifaz, Alexandro; Montes de Oca-Sánchez, Griselda; Araiza-Santibañez, Javier; Ponce-Olivera, Rosa María

2016-01-01

Crusted (Norwegian) scabies is a rare disease that occurs in patients with compromised immune system like patients with HIV/AIDS. We report 15 cases of crusted scabies in patients with HIV/AIDS successfully treated with oral ivermectin. The mean age of the patients was 43.7±8.06 and the diagnosis was made at a median of 5 months. All patients were diagnosed with HIV/AIDS treatment with antiretroviral therapy. Patients were treated with repeated doses of oral ivermectin with different schemes with good tolerance and efficacy with full resolution and without recurrence. Ivermectin is the treatment of choice for crusted scabies; it is tolerable and accessible to the patient. Immunosuppressed patients are those with the highest risk of acquiring that disease; we highlight the importance of lesion scraping to perform a correct and early diagnosis.

Eliminating female Anopheles arabiensis by spiking blood meals with toxicants as a sex separation method in the context of the sterile insect technique

PubMed Central

2013-01-01

Background Ivermectin has longevity reducing effects in several insect species, including disease transmitting mosquitoes after feeding on hosts that have received ivermectin treatment. This has important implications in mosquito population control and thus the reduction of disease transmission. In addition, ivermectin could play an enormous role in mosquito control operations by its use in the female elimination process during mass-rearing, enabling the release of only sterile males in the context of the sterile insect technique (SIT). Methods Blood meals were spiked with various toxicants and were then offered to adult Anopheles arabiensis and killing effects were observed. Varying concentrations of the most effective substance were then tested in subsequent trials to obtain an optimal dose for quick and total female elimination. The remaining males were mated with untreated virgin females to assess whether their mating efficiency had been compromised. The most promising substance at the optimal concentration was further tested on a larger number of adults, after they had been irradiated and partially sterilised as pupae with 70 Gy to evaluate the feasibility of the method in a mass-rearing, and SIT context. The males resulting from the latter trial were also checked for mating efficiency post treatments. Results Ivermectin (Virbamec®) at a concentration of 7.5 ppm was chosen from the toxicants tested as sufficiently effective in eliminating all female An. arabiensis in 4 days, the shortest time required for female elimination of all chemicals tested. Mating efficiency of the non-blood feeding male mosquitoes was not compromised significantly compared to controls even when they were kept for a total of 4 days (from emergence) before theoretical release. The irradiation treatment did not affect overall female feeding behaviour in this setting, nor were the sterile males less competitive for mating with virgin females after the treatments than virgin sterile

A field study on the effect of some anthelmintics on cyathostomins of horses in sweden.

PubMed

Lind, E Osterman; Kuzmina, T; Uggla, A; Waller, P J; Höglund, J

2007-01-01

The objective of the study was to investigate different aspects on the efficacy of three anthelmintics on cyathostomin nematodes of Swedish horses. A faecal egg count reduction (FECR) test was performed on 26 farms. Horses were treated orally with recommended doses of ivermectin, pyrantel pamoate or fenbendazole. Faecal samples were collected on the day of deworming and 7, 14 and 21 days later. No resistance was shown against ivermectin; the FECR was constantly >99%. The effect of pyrantel was assessed as equivocal in 6 farms 14 days after treatment; the mean FECR was 99%. As many as 72% of the fenbendazole-treated groups met the criteria for resistance; the mean FECR was 86%, ranging from 56% to 100%. A re-investigation of two farms where pyrantel resistance had been suspected clearly revealed unsatisfactory efficacy of pyrantel on one of these farms; the FECR varied from 72% to 89%. Twenty-six of the horses previously dosed with pyrantel or fenbendazole, and which still excreted >/=150 eggs per gram of faeces 14 days after treatment, were dewormed with ivermectin and fenbendazole or pyrantel in order to eliminate the remaining cyathostomins. A total of 13 cyathostomin species were identified from horses that initially received fenbendazole and seven species were identified from pyrantel-treated individuals. The egg reappearance period (ERP) following treatment with ivermectin and pyrantel was investigated on two farms. The shortest ERP after ivermectin treatment was 8 weeks and after pyrantel was 5 weeks. We conclude that no substantial reversion to benzimidazole susceptibility had taken place, although these drugs have scarcely been used (<5%) in horses for the last 10 years. Pyrantel-resistant populations of cyathostomins are present on Swedish horse farms, but the overall efficacy of pyrantel is still acceptable.

Relative Neurotoxicity of Ivermectin and Moxidectin in Mdr1ab (−/−) Mice and Effects on Mammalian GABA(A) Channel Activity

PubMed Central

Ménez, Cécile; Sutra, Jean-François; Prichard, Roger; Lespine, Anne

2012-01-01

The anthelmintics ivermectin (IVM) and moxidectin (MOX) display differences in toxicity in several host species. Entrance into the brain is restricted by the P-glycoprotein (P-gp) efflux transporter, while toxicity is mediated through the brain GABA(A) receptors. This study compared the toxicity of IVM and MOX in vivo and their interaction with GABA(A) receptors in vitro. Drug toxicity was assessed in Mdr1ab(−/−) mice P-gp-deficient after subcutaneous administration of increasing doses (0.11–2.0 and 0.23–12.9 µmol/kg for IVM and MOX in P-gp-deficient mice and half lethal doses (LD50) in wild-type mice). Survival was evaluated over 14-days. In Mdr1ab(−/−) mice, LD50 was 0.46 and 2.3 µmol/kg for IVM and MOX, respectively, demonstrating that MOX was less toxic than IVM. In P-gp-deficient mice, MOX had a lower brain-to-plasma concentration ratio and entered into the brain more slowly than IVM. The brain sublethal drug concentrations determined after administration of doses close to LD50 were, in Mdr1ab(−/−) and wild-type mice, respectively, 270 and 210 pmol/g for IVM and 830 and 740–1380 pmol/g for MOX, indicating that higher brain concentrations are required for MOX toxicity than IVM. In rat α1β2γ2 GABA channels expressed in Xenopus oocytes, IVM and MOX were both allosteric activators of the GABA-induced response. The Hill coefficient was 1.52±0.45 for IVM and 0.34±0.56 for MOX (p<0.001), while the maximum potentiation caused by IVM and MOX relative to GABA alone was 413.7±66.1 and 257.4±40.6%, respectively (p<0.05), showing that IVM causes a greater potentiation of GABA action on this receptor. Differences in the accumulation of IVM and MOX in the brain and in the interaction of IVM and MOX with GABA(A) receptors account for differences in neurotoxicity seen in intact and Mdr1-deficient animals. These differences in neurotoxicity of IVM and MOX are important in considering their use in humans. PMID:23133688

Persistent strongyloidiasis complicated by recurrent meningitis in an HTLV seropositive Peruvian migrant resettled in Italy.

PubMed

Zammarchi, Lorenzo; Montagnani, Francesca; Tordini, Giacinta; Gotuzzo, Eduardo; Bisoffi, Zeno; Bartoloni, Alessandro; De Luca, Andrea

2015-06-01

We describe a case of persistent strongyloidiasis complicated by recurrent meningitis, in a human T cell lymphotropic virus type 1 (HTLV-1) seropositive Peruvian migrant adult resettled in Italy. He was admitted with signs and symptoms of acute bacterial meningitis, reporting four other meningitis episodes in the past 6 years, with an etiological diagnosis of Escherichia coli and Enterococcus faecium in two cases. He had been previously treated with several antihelmintic regimens not including ivermectin, without eradication of strongyloidiasis, and he had never been tested for HTLV before. During the described episode, the patient was treated for meningitis with broad-spectrum antibiotic therapy and 200 μg/kg/dose oral ivermectin once daily on day 1, 2, 15 and 16 with full recovery and no further episodes of meningitis. The presented case underlines several critical points concerning the management of poorly known neglected diseases such as strongyloidiasis and HTLV infection in low-endemic areas. Despite several admissions for meningitis and strongyloidiasis, the parasitic infection was not adequately treated and the patient was not previously tested for HTLV. The supply of ivermectin and the choice of treatment scheme was challenging since ivermectin is not approved in Italy and there are no standardized guidelines for the treatment of severe strongyloidiasis in HTLV seropositive subjects. © The American Society of Tropical Medicine and Hygiene.

Comparative efficacy of different anthelmintics against fenbendazole-resistant nematodes of pashmina goats.

PubMed

Ram, H; Rasool, T J; Sharma, A K; Meena, H R; Singh, S K

2007-08-01

A trial using albendazole, albendazole plus rafoxanide combination, ivermectin and doramectin was conducted in Pashmina goats having history of fenbendazole resistance to Haemonchus spp. and maintained at high altitude (>2350 m above sea level). Day 0 infection level was variable in different groups of animals and their larval cultures indicated Haemonchus, Trichostrongylus, Ostertagia and Oesophagostomum spp. infection, in addition to Nematodirus spp. as observed in egg counts. Efficacy of drugs was calculated on day 14 post treatment by faecal egg count reduction test (FECRT). Albendazole was least effective (14%) followed by its combination with rafoxanide (54%). However, ivermectin and doramectin were 96% and 94% effective against gastrointestinal nematodes of Pashmina goats. It was concluded that use of albendazole and its combination with rafoxanide are ineffective in controlling the nematodes of goats at this farm; hence, future use must be avoided. However, regular monitoring of the efficacy of ivermectin and doramectin is needed.

Reduced Efficacy of Commercial Acaricides Against Populations of Resistant Cattle Tick Rhipicephalus microplus from Two Municipalities of Antioquia, Colombia

PubMed Central

Lopez-Arias, Anderson; Villar-Argaiz, David; Chaparro-Gutierrez, Jenny J; Miller, Robert J; Perez de Leon, Adalberto A

2014-01-01

Two distant Antioquian cattle farms where systemic and topical acaricides had previously failed to control infestations by Rhipicephalus (Boophilus) microplus were studied. An initial in vivo study was conducted using single subcutaneous injections with a long-acting formulation of ivermectin (630 μg/kg). Injections were made at 3-month intervals on animals at each farm to evaluate the therapeutic and persistent efficacy of ivermectin against R. microplus. Body tick counts and reproductive parameters of semi- or fully engorged females (≥5 mm) were assessed at 10-day intervals, and since no negative control group could be included, values were compared against those for day 0. Although there was an overall reduction of 50%–75% in tick numbers that persisted for 30–40 days, it was not significantly different at one of the farms and not enough to afford protection from severe infestations. The engorgement weight and egg mass weight of ticks from treated animals were significantly lower throughout the 50-day posttreatment period. Egg hatch was not significantly reduced posttreatment and remained at levels of 80%–90%. A random selection of 9 out of 28 commercial formulations of ivermectin sold in Colombia were analyzed by High Performance Liquid Chromatography (HPLC). All were within the expected labeled concentration (±15% deviation) of 1% and 3.15% ivermectin except for one. A popular unregistered injectable widely used in both farms and labeled as “natural pyrethrin”, was found to contain 10.5% ivermectin. An adult immersion test was conducted to evaluate the efficacy of topical acaricides to recommended concentrations of five commercial products and/or their combinations. Efficacy was determined by comparing the reproductive index of each treated group to that of the control group. Cypermethrin (150 ppm) was completely ineffective at both farms. Amitraz (208 ppm) exhibited low and intermediate efficacies of 14% and 56%. The combination of amitraz (100

[Evaluation of practices in the management of scabies in children].

PubMed

Lê, M-S; Richard, M-A; Baumstarck, K; Hesse, S; Gaudy-Marqueste, C; Grob, J-J; Mallet, S

2017-05-01

Scabies has been on the rise in France in recent years and has posed therapeutic problems, mainly due to the withdrawal of benzyl benzoate. The objective of this study was to describe prescribing practices for scabies in children. A national survey was conducted by means of a standardized questionnaire covering various clinical situations of scabies and the drugs used preferentially according to age, which was sent out between December 2014 and March 2015 to members of the clinical research group of the French Society of Paediatric Dermatology. Of the 38 experts contacted, 20 replied. For a typical case of scabies, 55% of the experts initially prescribed oral ivermectin for children aged 6 years, 15% prescribed ivermectin in children aged 2 years, and 5% in infants aged 3 months. Ivermectin was more widely prescribed after failure of prior treatment or recurrence of scabies, on skin lesions or impetigo, if precarious, especially for profuse hyperkeratotic scabies. A total of 35% of the experts reported no prescribing restrictions with regard to patient age or weight. Discrepancies were observed concerning the mode of administration and the time between consecutive doses. Esdepallethrin remained the preferred local treatment among the experts (38% of all topical prescriptions) except in asthmatic children, while permethrin was the least-prescribed topical agent. This study confirms the heterogeneity of our practices. Formal expert recommendations are awaited, particularly concerning the use of ivermectin in infants. Copyright © 2017. Published by Elsevier Masson SAS.

Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial

PubMed Central

Debrah, Alexander Yaw; Specht, Sabine; Klarmann-Schulz, Ute; Batsa, Linda; Mand, Sabine; Marfo-Debrekyei, Yeboah; Fimmers, Rolf; Dubben, Bettina; Kwarteng, Alexander; Osei-Atweneboana, Mike; Boakye, Daniel; Ricchiuto, Arcangelo; Büttner, Marcelle; Adjei, Ohene; Mackenzie, Charles D.; Hoerauf, Achim

2015-01-01

Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839. PMID:25948064

Influence of sustained deworming pressure on the anthelmintic resistance status in strongyles of sheep under field conditions.

PubMed

Vijayasarathi, M K; Sreekumar, C; Venkataramanan, R; Raman, M

2016-10-01

Anthelmintic resistance (AR) status in Madras Red sheep from selected field flocks of a government funded scheme, covered by regular, sustained anthelmintic treatment for more than 10 years was determined. Parameters such as fecal egg count reduction test (FECRT), larval paralysis assay (LPA), and allele-specific-PCR (AS-PCR) were used to test the efficacy of fenbendazole, tetramisole, and ivermectin at recommended doses, in two seasons. Sheep belonging to non-beneficiary farmers were used as controls. Mean FECRT values of beneficiary group during winter and summer seasons were 77.77 and 76.04, 93.65 and 92.12, and 95.37 and 98.06 %, respectively, for fenbendazole, tetramisole, and ivermectin. In the non-beneficiary groups, the corresponding values were 74.82 and 81.09 %, 96.05 and 97.40 %, and 97.26 and 98.23 %, respectively. The results revealed resistance to fenbendazole, suspect resistance to tetramisole and susceptibility to ivermectin in beneficiary flock. In non-beneficiary flock, while resistance was noticed against fenbendazole, both tetramisole and ivermectin were effective. FECR values were found to be significantly different between beneficiary and non-beneficiary groups against tetramisole. The results of LPA confirmed this finding, as 50 % of the Haemonchus contortus larvae were paralyzed at the concentration of 0.0156 μg/ml in the beneficiary group, while those of non-beneficiary groups required lower concentrations of 0.0078 μg/ml. AS-PCR revealed the predominance of heterozygous susceptible population of H. contortus in the beneficiary group. In this study, resistance to fenbendazole was confirmed in both the beneficiary and non-beneficiary groups and this could be attributed to frequent use of benzimidazoles as seen from the deworming records. Emergence of tetramisole resistance was detected in the beneficiary group, where the drug was used continuously for 4 years. Ivermectin was found to be effective in all the flocks. It is

Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity

PubMed Central

Endara, P; Vaca, M; Chico, M E; Erazo, S; Oviedo, G; Quinzo, I; Rodriguez, A; Lovato, R; Moncayo, A-L; Barreto, M L; Rodrigues, L C; Cooper, P J

2010-01-01

Background The low prevalence of allergic disease in the rural tropics has been attributed to the protective effects of chronic helminth infections. There is concern that treatment-based control programmes for these parasites may lead to an increase in the prevalence of allergic diseases. Objective We measured the impact of 15–17 years of anthelmintic treatment with ivermectin on the prevalence of allergen skin test reactivity and allergic symptoms in school-age children. Methods The prevalence of allergen skin test reactivity, exercise-induced bronchospasm and allergic symptoms was compared between school-age children living in communities that had received community-based treatments with ivermectin (for onchocerciasis control) for a period of 15–17 years with those living in geographically adjacent communities that had received no ivermectin. Results The prevalence of allergen skin test reactivity was double in children living in treated communities compared with those in untreated communities (16.7% vs. 8.7%, adjusted OR 2.10, 95% CI 1.50–2.94, P<0.0001), and the effect was mediated partly by a reduced prevalence of Trichuris trichiura among treated children. Ivermectin treatments were associated with an increased prevalence of recent eczema symptoms (adjusted OR 2.24, 95% CI 1.05–4.78, P=0.04) but not symptoms of asthma or rhino-conjunctivitis. The effect on eczema symptoms was not associated with reductions in geohelminth infections. Conclusion Long-term periodic treatments with ivermectin were associated with an increased prevalence of allergen skin test reactivity. There was some evidence that treatment was associated with an increased prevalence of recent eczema symptoms but not those of asthma or rhino-conjunctivitis. Cite this as: P. Endara, M. Vaca, M. E. Chico, S. Erazo, G. Oviedo, I. Quinzo, A. Rodriguez R. Lovato, A.-L. Moncayo, M. L. Barreto, L. C. Rodrigues and P. J. Cooper, Clinical & Experimental Allergy, 2010 (40) 1669–1677. PMID

Glycine receptor mechanism elucidated by electron cryo-microscopy.

PubMed

Du, Juan; Lü, Wei; Wu, Shenping; Cheng, Yifan; Gouaux, Eric

2015-10-08

The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders, including autism and hyperekplexia. Understanding of molecular mechanisms and pharmacology of glycine receptors has been hindered by a lack of high-resolution structures. Here we report electron cryo-microscopy structures of the zebrafish α1 GlyR with strychnine, glycine, or glycine and ivermectin (glycine/ivermectin). Strychnine arrests the receptor in an antagonist-bound closed ion channel state, glycine stabilizes the receptor in an agonist-bound open channel state, and the glycine/ivermectin complex adopts a potentially desensitized or partially open state. Relative to the glycine-bound state, strychnine expands the agonist-binding pocket via outward movement of the C loop, promotes rearrangement of the extracellular and transmembrane domain 'wrist' interface, and leads to rotation of the transmembrane domain towards the pore axis, occluding the ion conduction pathway. These structures illuminate the GlyR mechanism and define a rubric to interpret structures of Cys-loop receptors.

First Report of Anthelmintic Resistance in Gastrointestinal Nematodes of Sheep from Costa Rica

PubMed Central

Maroto, R.; Jiménez, A. E.; Romero, J. J.; Alvarez, V.; De Oliveira, J. B.; Hernández, J.

2011-01-01

As the prevalence and severity of anthelmintic resistance continue to rise, nematode infections in sheep correspondingly reduce the profitability of the sheep industry. In Costa Rica, sheep production systems are increasing in both number and importance. A field trial study was carried out to detect the level of anthelmintic resistance to albendazole and ivermectin in gastrointestinal nematodes (GIN) of sheep from seven farms in Costa Rica. Resistance was determined using the fecal egg count reduction test (FECRT). Three treatment groups were assessed on each farm: control, albendazole, and ivermectin. Haemonchus spp. (71%), Strongyloides sp. (57%), and Trichostrongylus spp. (43%) presented resistance levels to albendazole, whereas Strongyloides sp. (43%), Haemonchus spp. (29%), and Trichostrongylus spp. (29%) were resistant to ivermectin. Haemonchus spp., Strongyloides sp., and Trichostrongylus spp. were the most resistant GIN to both products. This study suggests that frequency of treatment, exclusive chemical control, and visual estimation of animal weight to calculate dosage may contribute to the high levels of anthelmintic resistance that were observed on the farms analyzed herein. PMID:21772962

Macrocyclic lactone-resistant Parascaris equorum on stud farms in Canada and effectiveness of fenbendazole and pyrantel pamoate.

PubMed

Slocombe, J Owen D; de Gannes, Rolph V G; Lake, Mary C

2007-04-30

The aims of studies in 2002 and 2003 on three farms with 76 foals naturally infected with Parascaris equorum were to (i) identify if the nematode was resistant to ivermectin and moxidectin, and (ii) confirm the effectiveness of fenbendazole and pyrantel pamoate for the parasite. Twelve clinical trials, each with a Fecal Egg Count Reduction Test, were conducted on two Thoroughbred and one Standardbred farms in southwestern Ontario, Canada. In each trial, Parascaris eggs/g feces were estimated for each foal pre- and post-treatment using the Cornell-Wisconsin double flotation and Cornell-McMaster dilution techniques. On each farm and for each trial, foals were randomized into treatment groups. Treatments were ivermectin, moxidectin, fenbendazole, pyrantel pamoate administered at the manufacturers' recommended dosages, and some foals were untreated. The overall efficacy for ivermectin was 33.5% (19 foals) and for moxidectin 47.2% (28 foals). Fenbendazole (16 foals) and pyrantel pamoate (21 foals) were highly effective for P. equorum each at 97.6%. For fenbendazole, 15 foals had 100% and for pyrantel pamoate 17 foals had >97% with 14 at 100%.

Interruption of Transmission of Onchocerca volvulus in the Southern Chiapas Focus, México

PubMed Central

Rodríguez-Pérez, Mario A.; Domínguez-Vázquez, Alfredo; Unnasch, Thomas R.; Hassan, Hassan K.; Arredondo-Jiménez, Juan I.; Orozco-Algarra, María Eugenia; Rodríguez-Morales, Kristel B.; Rodríguez-Luna, Isabel C.; Prado-Velasco, Francisco Gibert

2013-01-01

Background The Southern Chiapas focus of onchocerciasis in Southern Mexico represents one of the major onchocerciasis foci in Latin America. All 559 endemic communities of this focus have undergone semi-annual mass treatment with ivermectin since 1998. In 50 communities of this focus, ivermectin frequency shifted from twice to four times a year in 2003; an additional 113 communities were added to the quarterly treatment regimen in 2009 to achieve a rapid suppression of transmission. Methodology/Principal findings In-depth epidemiologic and entomologic assessments were performed in six sentinel communities (which had undergone 2 rounds of ivermectin treatment per year) and three extra-sentinel communities (which had undergone 4 rounds of ivermectin treatment per year). None of the 67,924 Simulium ochraceum s.l. collected from this focus during the dry season of 2011 were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.06/2,000 flies examined. Serological assays testing for Onchocerca volvulus exposure conducted on 4,230 children 5 years of age and under (of a total population of 10,280 in this age group) revealed that 2/4,230 individuals were exposed to O. volvulus (0.05%; one sided 95% confidence interval = 0.08%). Conclusions/Significance The in-depth epidemiological and entomological findings from the Southern Chiapas focus meet the criteria for interruption of transmission developed by the international community. PMID:23556018

Doing well while fighting river blindness: the alignment of a corporate drug donation programme with responsibilities to shareholders.

PubMed

Hernando, Yolanda; Colwell, Kaela; Wright, Brian D

2016-10-01

Using the example of Merck's donations of ivermectin, to show how tax incentives and non-profit collaborators can make corporate largesse consistent with obligations to maximise returns to shareholders. We obtained information from publicly available data and estimated Merck's tax deductions according to the US Internal Revenue Code. Reviews of Merck-Kitasato contracts and personal interviews provided additional information regarding key lessons from this collaboration. Our best estimate of the direct cost to Merck of the ivermectin tablets donated during 2005-2011 is around US$ 600 million, well below the stated value of US$ 3.8 billion. Our calculation of tax write-offs reduces the net cost to around US$ 180 million in that period. Indirect market benefits and effects on goodwill further enhanced the compatibility of Merck's donation programme with the company's profit-maximising objective. The case offers lessons for effective management of collaborations with public and non-profit organisations. Merck's role in the donation of ivermectin for the treatment of onchocerciasis is widely and justly acknowledged as a prime example of corporate largesse in the public interest. It is nevertheless important to note that several public and non-profit collaborators, and United States taxpayers, played significant roles in increasing Merck's incentives, and indeed ability, to conduct the donation programme that changed so many lives in poor countries, while meeting its responsibilities to shareholders. Overall, the record indicates responsible corporate management of Merck's ivermectin programme and demonstrates the feasibility of socially responsible policies in a manner compatible with obligations to shareholders. © 2016 John Wiley & Sons Ltd.

High prevalence of epilepsy in onchocerciasis endemic regions in the Democratic Republic of the Congo

PubMed Central

Tepage, Floribert; Ensoy-Musoro, Chellafe; Mandro, Michel; Bonareri Osoro, Caroline; Suykerbuyk, Patrick; Kashama, Jean Marie; Komba, Michel; Tagoto, Alliance; Falay, Dadi; Begon, Michael

2017-01-01

Background An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. The objective of this study was to determine the prevalence of epilepsy in onchocerciasis endemic areas in the Democratic Republic of the Congo (DRC) and investigate whether a higher annual intake of Ivermectin was associated with a lower prevalence of epilepsy. Methodology/Principle findings Between July 2014 and February 2016, house-to-house epilepsy prevalence surveys were carried out in areas with a high level of onchocerciasis endemicity: 3 localities in the Bas-Uele, 24 in the Tshopo and 21 in the Ituri province. Ivermectin uptake was recorded for every household member. This database allowed a matched case-control pair subset to be created that enabled putative risk factors for epilepsy to be tested using univariate logistic regression models. Risk factors relating to onchocerciasis were tested using a multivariate random effects model. To identify presence of clusters of epilepsy cases, the Kulldorff's scan statistic was used. Of 12, 408 people examined in the different health areas 407 (3.3%) were found to have a history of epilepsy. A high prevalence of epilepsy was observed in health areas in the 3 provinces: 6.8–8.5% in Bas-Uele, 0.8–7.4% in Tshopo and 3.6–6.2% in Ituri. Median age of epilepsy onset was 9 years, and the modal age 12 years. The case control analysis demonstrated that before the appearance of epilepsy, compared to the same life period in controls, persons with epilepsy were around two times less likely (OR: 0.52; 95%CI: (0.28, 0.98)) to have taken Ivermectin than controls. After the appearance of epilepsy, there was no difference of Ivermectin intake between cases and controls. Only in Ituri, a significant cluster (p-value = 0.0001) was identified located around the Draju sample site area. Conclusions The prevalence of epilepsy in health areas in onchocerciasis endemic regions in the DRC was 2–10 times higher than in non

Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees

PubMed Central

Guseman, Alex J.; Miller, Kaliah; Kunkle, Grace; Dively, Galen P.; Pettis, Jeffrey S.; Evans, Jay D.; vanEngelsdorp, Dennis; Hawthorne, David J.

2016-01-01

Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

Coherent anti‐Stokes Raman scattering (CARS) spectroscopy in Caenorhabditis elegans and Globodera pallida: evidence for an ivermectin‐activated decrease in lipid stores

PubMed Central

Smus, Justyna P; Ludlow, Elizabeth; Dallière, Nicolas; Luedtke, Sarah; Monfort, Tual; Lilley, Catherine; Urwin, Peter; Walker, Robert J; O'Connor, Vincent

2017-01-01

Abstract BACKGROUND Macrocyclic lactones are arguably the most successful chemical class with efficacy against parasitic nematodes. Here we investigated the effect of the macrocyclic lactone ivermectin on lipid homeostasis in the plant parasitic nematode Globodera pallida and provide new insight into its mode of action. RESULTS A non‐invasive, non‐destructive, label‐free and chemically selective technique called Coherent anti‐Stokes Raman scattering (CARS) spectroscopy was used to study lipid stores in G. pallida. We optimised the protocol using the free‐living nematode Caenorhabditis elegans and then used CARS to quantify lipid stores in the pre‐parasitic, non‐feeding J2 stage of G. pallida. This revealed a concentration of lipid stores in the posterior region of J2 s within 24 h of hatching which decreased to undetectable levels over the course of 28 days. We tested the effect of ivermectin on J2 viability and lipid stores. Within 24 h, ivermectin paralysed J2 s. Counterintuitively, over the same time‐course ivermectin increased the rate of depletion of J2 lipid, suggesting that in ivermectin‐treated J2 s there is a disconnection between the energy requirements for motility and metabolic rate. This decrease in lipid stores would be predicted to negatively impact on J2 infective potential. CONCLUSION These data suggest that the benefit of macrocyclic lactones as seed treatments may be underpinned by a multilevel effect involving both neuromuscular inhibition and acceleration of lipid metabolism. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:28834172

Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees.

PubMed

Guseman, Alex J; Miller, Kaliah; Kunkle, Grace; Dively, Galen P; Pettis, Jeffrey S; Evans, Jay D; vanEngelsdorp, Dennis; Hawthorne, David J

2016-01-01

Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species.

Psoroptes cuniculi induced oxidative imbalance in rabbits and its alleviation by using vitamins A, D3, E, and H as adjunctive remedial.

PubMed

Singh, Shanker Kumar; Dimri, Umesh; Sharma, Mahesh Chandra; Swarup, Devendra; Kumar, Mritunjay; Tiwary, Ramesh

2012-01-01

The oxidant/antioxidant balance of rabbits naturally infected with Psoroptes cuniculi and treated with ivermectin +/- vitamins A, D(3), E, and H supplementation was investigated. Two groups of seven mixed ♂ and ♀, 6-to-8 month-old New Zealand White rabbits, diagnosed Psoroptes mites-positive by skin scraping examination and seven clinically healthy control rabbits were examined. Blood samples were obtained on day 0 and at 28 days post-therapy to determine oxidative stress indices. On day 0, the levels of lipid peroxides were significantly higher (P ≤ 0.01) in the Psoroptes-infected rabbits compared with the healthy controls while those of reduced glutathione and the activities of the antioxidant enzymes glutathione peroxidase, glutathione-S-transferase, catalase, and superoxide dismutase were significantly lower (P ≤ 0.01). Vitamin supplementation of the ivermectin-treated rabbits revealed both faster clinical (14 days) and parasitological (10 days) recovery. It was concluded that significant alteration of oxidant/antioxidant balance is a factor in the pathogenesis of P. cuniculi infestation of rabbits, and recovery can be enhanced by combining ivermectin treatment with vitamin A, D(3,) E, and H supplementation.

The elimination of scabies: a task for our generation.

PubMed

McLean, Florence E

2013-10-01

Scabies prevalence remains unacceptably high in many regions throughout the world. Infestation with scabies significantly impacts quality of life and is linked to pyoderma and consequently to severe long-term sequelae such as post-streptococcal glomerulonephritis. In the past, control programs using topical treatments have met with poor compliance; however, the highly effective oral agent ivermectin may offer a new paradigm in scabies management. Problems still exist with insensitive diagnostic tests, questions concerning mite reservoirs, and restrictions on who can receive ivermectin. Despite these difficulties, the elimination of scabies in communities worst affected may soon be possible. © 2013 The International Society of Dermatology.

The acaricidal efficacy of aqueous neem extract and ivermectin against Sarcoptes scabiei var. cuniculi in experimentally infested rabbits.

PubMed

Seddiek, Shaker A; Khater, Hanem F; El-Shorbagy, Mohamed M; Ali, Ali M

2013-06-01

Sarcoptes scabiei var. cuniculi is one of the most important veterinary ectoparasites in rabbits and results in considerable loss of weight, productivity, and wool quality. The acaricidal activity of aqueous leaf extract of neem (CAN) and ivermectin (IVR) were evaluated in vitro and in vivo against S. scabiei var. cuniculi. Rabbits were classified into four groups (ten rabbits each). The first group (group 1) was designated as the negative control group. Each rabbit of the other groups was experimentally infested with 50 mites. One month post-infestation, the second group (group 2) was not treated and taken into account as the positive control group. The third group (group 3) was subcutaneously injected with 1 % IVR (200 μg/kg body weight, three times within a week interval). The fourth group (group 4) was treated topically with CAN (25 %) every 3 days for three consecutive weeks. Index scoring of lesions was described weekly. The number of live mites (larvae, nymphs, and adults) on each rabbit was counted on the 14th, 28th, and 42th day post-treatment (PT). Blood samples were taken 28 and 42 days PT for estimation of some chemical parameters. The body weight and cumulative body weight gain were recoded 14, 28, and 42 days PT. CAN (40 %) was highly efficacious against larvae of S. scabiei var. cuniculi as 100 % mortality was reached 24 h PT. On the other hand, all treated mites with CAN (20 %) and IVR died 48 h PT. The lethal values of CAN (LC50, LC90, LC95, and LC99) were 7.496, 14.67, 17.75, and 25.37 %, respectively, 48 h PT. Lesion scoring in groups 3 and 4 were significantly decreased (P ≤ 0.05), reaching 0.20 and 0.40, respectively, when compared with that of group 2 (4.00), 42 days PT. Twenty-eight days PT, the reduction percentages of mites infesting rabbits were 93.38 and 93.09 % for IVR and CAN, respectively. However, complete mite reduction was reached 42 days PT. Rabbits treated with CAN did not show signs of restlessness or

Progress toward elimination of onchocerciasis in the Americas.

PubMed

Sauerbrey, Mauricio; Rakers, Lindsay J; Richards, Frank O

2018-03-01

The Onchocerciasis Elimination Program for the Americas (OEPA) is a regional initiative and international partnership that has made considerable progress toward its goal since it was launched in 1993. Its strategy is based on mass drug administration of ivermectin (Mectizan, donated by MSD, also known as Merck & Co., Inc., Kenilworth, NJ, USA), twice or four times per year, with at least 85% coverage of eligible populations. From 1989 to 2016, 11 741 276 ivermectin treatments have been given in the Americas, eliminating transmission in 11 of 13 foci. The OEPA's success has had a great influence on programs in Africa, especially Sudan and Uganda, which moved from a control to an elimination strategy in 2006 and 2007, respectively. The successes in the Americas have also greatly influenced WHO guidelines for onchocerciasis transmission elimination. With four of the six originally endemic American countries now WHO verified as having eliminated onchocerciasis transmission, and 95% of ivermectin treatments in the region halted, the regional focus is now on the remaining active transmission zone, called the Yanomami Area, on the border between Venezuela and Brazil. Both countries have difficult political climates that hinder the elimination task in this remote and relatively neglected region. As with other elimination efforts, 'the final inch' is often the most difficult task of all.

Anthelmintic resistance impact on tropical beef cattle productivity: effect on weight gain of weaned calves.

PubMed

Borges, Fernando A; Almeida, Gabriel D; Heckler, Rafael P; Lemes, Raul T; Onizuka, Marcel K V; Borges, Dyego G L

2013-03-01

The performance of grazing cattle in tropical areas is deeply influenced by parasitism, and the increasing reports of resistance are a threat to effective nematode control. The present study aimed to evaluate the effect of avermectins on the performance of weaned calves naturally infected by ivermectin-resistant gastrointestinal nematodes. The effect of four commercial endectocides (ivermectin 2.25 % + abamectin 1.25 %, ivermectin 3.15 %, doramectin 3.15 %, and doramectin 1 %) on parasitism and performance of a hundred weaned Nellore calves were evaluated during 112 days. The most effective anthelmintic showed efficacy of 84 % and resulted in an increase (P < 0.05) of live weight gain of 11.85 kg, compared to untreated group, 9.05 and 9.41 kg compared to those treated with more ineffective avermectins which showed efficacy of 0 and 48.2 %, respectively. A significant (P < 0.05) and weak negative correlation (r = -0.22) between the eggs per gram (EPG) and body weight was observed, indicating that even the low mean EPG (175 ± 150) observed at day 0 in the control group, with predominance of Haemonchus sp., was responsible for production losses. These results indicate that control of nematode parasites in beef cattle in the weaning phase may not result in increased productivity when carried out without technical criteria.

[Determination of tick species and treatment of cows, sheep and goats in the Sivas-Zara region].

PubMed

Mamak, Nuri; Gençer, Lütfiye; Ozkanlar, Yunus Emre; Ozçelik, Semra

2006-01-01

The purpose of this study was to examine tick infestation in cattle, sheep and goats in the Zara-Sivas region for one year and to determine the epizootiology of the tick species as well as to investigate treatment of the infested animals. Tick infestation was detected in 71 (29.6%) out of 240 cattle, 66 (24.0%) out of 275 sheep and 50 (19.9%) out of 252 goats in the Zara region. It has been shown that the tick infestation on cattle included Haemaphysalis parva (33.8%), Dermacentor marginatus (2.8%), Boophilus annulatus (21.1%), Haemaphysalis concinna (15.5%), Hyalomma marginatum (19.7%) and Rhipicephalus bursa (7%). Those on sheep included Dermacentor niveus (18.2%), Dermacentor marginatus (31.8%), Haemaphysalis parva (13.6%), Haemaphysalis concinna (4.5%), Hyalomma marginatum (4.5%) and Rhipicephalus bursa (27.3%). Those on goats included Dermacentor niveus (4%), Dermacentor marginatus (12%), Haemaphysalis parva (40%), Haemaphysalis concinna (2%), Boophilus annulatum (4%), Hyalomma marginatum (6%) and Rhipicephalus bursa (32%). Ivermectin was administered to the infested animals in a dose of 200 microg/kg subcutaneously. The administration of the ivermectin was effective. As a result, it has been shown that the tick infestation is present in cattle, sheep and goats in Zara region, the tick species differ according to the season and administration of ivermectin was an effective treatment.

Toxicity of four veterinary pharmaceuticals on the survival and reproduction of Folsomia candida in tropical soils.

PubMed

Zortéa, Talyta; Segat, Julia C; Maccari, Ana Paula; Sousa, José Paulo; Da Silva, Aleksandro S; Baretta, Dilmar

2017-04-01

This study aimed to evaluate the effect of veterinary pharmaceuticals (VPs) used to control endo- and ectoparasites in ruminants, on the survival and reproduction of the collembolan species Folsomia candida. Standard ecotoxicological tests were conducted in Tropical Artificial Soil and the treatments consisted of increasing dosages of four commercial products with different active ingredients: ivermectin, fipronil, fluazuron and closantel. Ecotoxicological effects were related to the class and mode of action of the different compounds. Fipronil and ivermectin were the most toxic compounds causing a significant reduction in the number of juveniles at the lowest doses tested (LOEC reprod values of 0.3 and 0.2 mg kg -1 of dry soil, respectively) and similar low EC 50 values (fipronil: 0.19 mg kg -1 dry soil, CL 95% 0.16-0.22; ivermectin: 0.43 mg kg -1 dry soil, CL 95% 0.09-0.77), although the effects observed in the former compound were possibly related to a low adult survival (LC 50 of 0.62 mg kg -1 dry soil; CL 95% : 0.25-1.06). For the latter compound no significant lethal effects were observed. Fluazuron caused an intermediate toxicity (EC 50 of 3.07 mg kg -1 dry soil, CL 95% : 2.26-3.87), and also here a decrease in adult survival could explain the effects observed at reproduction. Closantel, despite showing a significant reduction on the number of juveniles produced, no dose-response relationship nor effects higher than 50% were observed. Overall, all tested compounds, especially ivermectin, when present in soil even at sub-lethal concentrations, can impair the reproduction of collembolans and possibly other arthropods. However, the actual risk to arthropod communities should be further investigated performing tests under a more realistic exposure (e.g., by testing the dung itself as the contaminated matrix) and by deriving ecotoxicologically relevant exposure concentration in soil derived from the presence of cattle dung. Copyright © 2017 Elsevier

Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for Intestinal Helminth Infection among US-Bound Refugees from Asia.

PubMed

Maskery, Brian; Coleman, Margaret S; Weinberg, Michelle; Zhou, Weigong; Rotz, Lisa; Klosovsky, Alexander; Cantey, Paul T; Fox, LeAnne M; Cetron, Martin S; Stauffer, William M

2016-08-01

Many U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program. An economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) "No Program," 2) U.S. "Domestic Screening and Treatment," 3) "Overseas Albendazole and Ivermectin" presumptive treatment, and 4) "Overseas Albendazole and Domestic Screening for Strongyloides". Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs). The "No Program" option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The "Overseas Albendazole and Ivermectin" option ($418,824) is less expensive than "Domestic Screening and Treatment" ($3,832,572) or "Overseas Albendazole and Domestic Screening for Strongyloides" ($2,182,483). According to the model outcomes, the most effective treatment option is "Overseas Albendazole and Ivermectin," which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to "No Program". Overseas presumptive treatment for U.S.-bound refugees is a cost-effective intervention that is less expensive and at least as effective as domestic

Identification and Functional Expression of a Glutamate- and Avermectin-Gated Chloride Channel from Caligus rogercresseyi, a Southern Hemisphere Sea Louse Affecting Farmed Fish

PubMed Central

Niemeyer, María Isabel; Marabolí, Vanessa; González-Nilo, F. Danilo; Teulon, Jacques; Sepúlveda, Francisco V.; Cid, L. Pablo

2014-01-01

Parasitic sea lice represent a major sanitary threat to marine salmonid aquaculture, an industry accounting for 7% of world fish production. Caligus rogercresseyi is the principal sea louse species infesting farmed salmon and trout in the southern hemisphere. Most effective control of Caligus has been obtained with macrocyclic lactones (MLs) ivermectin and emamectin. These drugs target glutamate-gated chloride channels (GluCl) and act as irreversible non-competitive agonists causing neuronal inhibition, paralysis and death of the parasite. Here we report the cloning of a full-length CrGluClα receptor from Caligus rogercresseyi. Expression in Xenopus oocytes and electrophysiological assays show that CrGluClα is activated by glutamate and mediates chloride currents blocked by the ligand-gated anion channel inhibitor picrotoxin. Both ivermectin and emamectin activate CrGluClα in the absence of glutamate. The effects are irreversible and occur with an EC50 value of around 200 nM, being cooperative (nH = 2) for ivermectin but not for emamectin. Using the three-dimensional structure of a GluClα from Caenorabditis elegans, the only available for any eukaryotic ligand-gated anion channel, we have constructed a homology model for CrGluClα. Docking and molecular dynamics calculations reveal the way in which ivermectin and emamectin interact with CrGluClα. Both drugs intercalate between transmembrane domains M1 and M3 of neighbouring subunits of a pentameric structure. The structure displays three H-bonds involved in this interaction, but despite similarity in structure only of two these are conserved from the C. elegans crystal binding site. Our data strongly suggest that CrGluClα is an important target for avermectins used in the treatment of sea louse infestation in farmed salmonids and open the way for ascertaining a possible mechanism of increasing resistance to MLs in aquaculture industry. Molecular modeling could help in the design of new, more efficient

Identification and functional expression of a glutamate- and avermectin-gated chloride channel from Caligus rogercresseyi, a southern Hemisphere sea louse affecting farmed fish.

PubMed

Cornejo, Isabel; Andrini, Olga; Niemeyer, María Isabel; Marabolí, Vanessa; González-Nilo, F Danilo; Teulon, Jacques; Sepúlveda, Francisco V; Cid, L Pablo

2014-09-01

Parasitic sea lice represent a major sanitary threat to marine salmonid aquaculture, an industry accounting for 7% of world fish production. Caligus rogercresseyi is the principal sea louse species infesting farmed salmon and trout in the southern hemisphere. Most effective control of Caligus has been obtained with macrocyclic lactones (MLs) ivermectin and emamectin. These drugs target glutamate-gated chloride channels (GluCl) and act as irreversible non-competitive agonists causing neuronal inhibition, paralysis and death of the parasite. Here we report the cloning of a full-length CrGluClα receptor from Caligus rogercresseyi. Expression in Xenopus oocytes and electrophysiological assays show that CrGluClα is activated by glutamate and mediates chloride currents blocked by the ligand-gated anion channel inhibitor picrotoxin. Both ivermectin and emamectin activate CrGluClα in the absence of glutamate. The effects are irreversible and occur with an EC(50) value of around 200 nM, being cooperative (n(H) = 2) for ivermectin but not for emamectin. Using the three-dimensional structure of a GluClα from Caenorabditis elegans, the only available for any eukaryotic ligand-gated anion channel, we have constructed a homology model for CrGluClα. Docking and molecular dynamics calculations reveal the way in which ivermectin and emamectin interact with CrGluClα. Both drugs intercalate between transmembrane domains M1 and M3 of neighbouring subunits of a pentameric structure. The structure displays three H-bonds involved in this interaction, but despite similarity in structure only of two these are conserved from the C. elegans crystal binding site. Our data strongly suggest that CrGluClα is an important target for avermectins used in the treatment of sea louse infestation in farmed salmonids and open the way for ascertaining a possible mechanism of increasing resistance to MLs in aquaculture industry. Molecular modeling could help in the design of new, more efficient

An L319F mutation in transmembrane region 3 (TM3) selectively reduces sensitivity to okaramine B of the Bombyx mori l-glutamate-gated chloride channel.

PubMed

Furutani, Shogo; Okuhara, Daiki; Hashimoto, Anju; Ihara, Makoto; Kai, Kenji; Hayashi, Hideo; Sattelle, David B; Matsuda, Kazuhiko

2017-10-01

Okaramines produced by Penicillium simplicissimum AK-40 activate l-glutamate-gated chloride channels (GluCls) and thus paralyze insects. However, the okaramine binding site on insect GluCls is poorly understood. Sequence alignment shows that the equivalent of residue Leucine319 of the okaramine B sensitive Bombyx mori (B. mori) GluCl is a phenylalanine in the okaramine B insensitive B. mori γ-aminobutyric acid-gated chloride channel of the same species. This residue is located in the third transmembrane (TM3) region, a location which in a nematode GluCl is close to the ivermectin binding site. The B. mori GluCl containing the L319F mutation retained its sensitivity to l-glutamate, but responses to ivermectin were reduced and those to okaramine B were completely blocked.

Community-based trial of annual versus biannual single-dose ivermectin plus albendazole against Wuchereria bancrofti infection in human and mosquito populations: study protocol for a cluster randomised controlled trial.

PubMed

de Souza, Dziedzom K; Ahorlu, Collins S; Adu-Amankwah, Susan; Otchere, Joseph; Mensah, Sedzro K; Larbi, Irene A; Mensah, George E; Biritwum, Nana-Kwadwo; Boakye, Daniel A

2017-10-02

The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission. A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. It is expected that this study will add to

21 CFR 522.1192 - Ivermectin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... after treatment. (iii) Limitations. Do not treat cattle within 35 days of slaughter. Because a withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. A... order of a licensed veterinarian. (2) Cattle—(i) Amount. 200 µg/kg of body weight by subcutaneous...

21 CFR 522.1192 - Ivermectin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... dairy cattle of breeding age. A withdrawal period has not been established for this product in pre... restricts this drug to use by or on the order of a licensed veterinarian. (2) Cattle—(i) Amount. 200 µg/kg.... placei and C. oncophora for 14 days after treatment. (iii) Limitations. Do not treat cattle within 35...

21 CFR 522.1192 - Ivermectin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cattle within 35 days of slaughter. Because a withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... Federal law restricts this drug to use by or on the order of a licensed veterinarian. (2) Cattle—(i...

21 CFR 522.1192 - Ivermectin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... dairy cattle of breeding age. A withdrawal period has not been established for this product in pre... restricts this drug to use by or on the order of a licensed veterinarian. (2) Cattle—(i) Amount. 200 µg/kg.... placei and C. oncophora for 14 days after treatment. (iii) Limitations. Do not treat cattle within 35...

21 CFR 522.1192 - Ivermectin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... dairy cattle of breeding age. A withdrawal period has not been established for this product in pre... restricts this drug to use by or on the order of a licensed veterinarian. (2) Cattle—(i) Amount. 200 µg/kg.... placei and C. oncophora for 14 days after treatment. (iii) Limitations. Do not treat cattle within 35...

21 CFR 558.300 - Ivermectin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... section; and for control of swine dysentery associated with Treponema hyodysenteriae on premises with a history of swine dysentery, but where symptoms have not yet occurred, or following an approved treatment... (e)(4) of this section; and for control of swine dysentery on premises with a history of swine...

21 CFR 558.300 - Ivermectin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section; and for control of swine dysentery associated with Treponema hyodysenteriae on premises with a history of swine dysentery, but where symptoms have not yet occurred, or following an approved treatment... (e)(4) of this section; and for control of swine dysentery on premises with a history of swine...

21 CFR 558.300 - Ivermectin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... section; and for control of swine dysentery associated with Treponema hyodysenteriae on premises with a history of swine dysentery, but where symptoms have not yet occurred, or following an approved treatment... (e)(4) of this section; and for control of swine dysentery on premises with a history of swine...

Long Term Control of Scabies Fifteen Years after an Intensive Treatment Programme

PubMed Central

Marks, Michael; Taotao-Wini, Betty; Satorara, Lorraine; Engelman, Daniel; Nasi, Titus; Mabey, David C.; Steer, Andrew C.

2015-01-01

Introduction Scabies is a major public health problem in the Pacific and is associated with an increased risk of bacterial skin infections, glomerulonephritis and rheumatic fever. Mass drug administration with ivermectin is a promising strategy for the control of scabies. Mass treatment with ivermectin followed by active case finding was conducted in five communities in the Solomon Islands between 1997 and 2000 and resulted in a significant reduction in the prevalence of both scabies and bacterial skin infections. Methods We conducted a prospective follow-up study of the communities where the original scabies control programme had been undertaken. All residents underwent a standardised examination for the detection of scabies and impetigo. Results Three hundred and thirty eight residents were examined, representing 69% of the total population of the five communities. Only 1 case of scabies was found, in an adult who had recently returned from the mainland. The prevalence of active impetigo was 8.8% overall and 12.4% in children aged 12 years or less. Discussion We found an extremely low prevalence of scabies 15 years after the cessation of a scabies control programme. The prevalence of impetigo had also declined further since the end of the control programme. Our results suggest that a combination of mass treatment with ivermectin and intensive active case finding may result in long term control of scabies. Larger scale studies and integration with other neglected tropical disease control programmes should be priorities for scabies control efforts. PMID:26624616

Long Term Control of Scabies Fifteen Years after an Intensive Treatment Programme.

PubMed

Marks, Michael; Taotao-Wini, Betty; Satorara, Lorraine; Engelman, Daniel; Nasi, Titus; Mabey, David C; Steer, Andrew C

2015-12-01

Scabies is a major public health problem in the Pacific and is associated with an increased risk of bacterial skin infections, glomerulonephritis and rheumatic fever. Mass drug administration with ivermectin is a promising strategy for the control of scabies. Mass treatment with ivermectin followed by active case finding was conducted in five communities in the Solomon Islands between 1997 and 2000 and resulted in a significant reduction in the prevalence of both scabies and bacterial skin infections. We conducted a prospective follow-up study of the communities where the original scabies control programme had been undertaken. All residents underwent a standardised examination for the detection of scabies and impetigo. Three hundred and thirty eight residents were examined, representing 69% of the total population of the five communities. Only 1 case of scabies was found, in an adult who had recently returned from the mainland. The prevalence of active impetigo was 8.8% overall and 12.4% in children aged 12 years or less. We found an extremely low prevalence of scabies 15 years after the cessation of a scabies control programme. The prevalence of impetigo had also declined further since the end of the control programme. Our results suggest that a combination of mass treatment with ivermectin and intensive active case finding may result in long term control of scabies. Larger scale studies and integration with other neglected tropical disease control programmes should be priorities for scabies control efforts.

Allosteric Modulation of Ca2+ flux in Ligand-gated Cation Channel (P2X4) by Actions on Lateral Portals*

PubMed Central

Samways, Damien S. K.; Khakh, Baljit S.; Egan, Terrance M.

2012-01-01

Human P2X receptors are a family of seven ATP-gated ion channels that transport Na+, K+, and Ca2+ across cell surface membranes. The P2X4 receptor is unique among family members in its sensitivity to the macrocyclic lactone, ivermectin, which allosterically modulates both ion conduction and channel gating. In this paper we show that removing the fixed negative charge of a single acidic amino acid (Glu51) in the lateral entrance to the transmembrane pore markedly attenuates the effect of ivermectin on Ca2+ current and channel gating. Ca2+ entry through P2X4 receptors is known to trigger downstream signaling pathways in microglia. Our experiments show that the lateral portals could present a novel target for drugs in the treatment of microglia-associated disease including neuropathic pain. PMID:22219189

The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji.

PubMed

Kimura, Eisaku

2011-03-01

Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in

Distribution of animal drugs among curd, whey, and milk protein fractions in spiked skim milk and whey

USDA-ARS?s Scientific Manuscript database

It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labelled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and...

Distribution of animal drugs between skim milk and milk fat fractions in spiked whole milk: Understanding the potential impact on commercial milk products

USDA-ARS?s Scientific Manuscript database

Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA) and ivermectin (IVR)] were used to evaluate drug distribution between milk fat and skim milk fractions of cow milk. Greater than 90% of radioactivity...

Risk factors for epilepsy in Bas-Uélé Province, Democratic Republic of the Congo: a case-control study.

PubMed

Colebunders, Robert; Mandro, Michel; Mokili, John L; Mucinya, Gisele; Mambandu, Germain; Pfarr, Kenneth; Reiter-Owona, Ingrid; Hoerauf, Achim; Tepage, Floribert; Levick, Bethanie; Begon, Michael; Laudisoit, Anne

2016-08-01

The reason for the high prevalence of epilepsy in onchocerciasis endemic areas remains unknown. The aim of this study was to detect risk factors associated with epilepsy in a region endemic for onchocerciasis. In June 2014, a case-control study was performed in Titule, Bas-Uélé Province in the Democratic Republic of the Congo. Individuals with unprovoked convulsive epilepsy of unknown aetiology were enrolled as cases (n=59). Healthy members of families without cases of epilepsy in the same village were recruited as controls (n=61). A multivariate binomial logistic regression analysis was performed to identify potential risk factors associated with epilepsy. To evaluate the potential protective effect of ivermectin treatment on the development of epilepsy, a nested age-matched case-control study was performed including only those who were eligible for ivermectin treatment in the year before they developed epilepsy. Suspected onchocerciasis skin lesions were more often present in cases than in controls: 12/41 (29%) vs. 1/56 (2%), respectively (odds ratio (OR) 20.26, 95% confidence interval (CI) 2.42-170; p<0.01). Ivermectin had been taken 7 months earlier in 29/59 (49%) cases and 29/61 (48%) controls. Onchocerca volvulus (OV) DNA was detected by PCR in skin snips in 26/34 cases (76%) and 10/14 controls (71%) (p=0.7), and there was presence of OV IgG4 antibodies in 35/48 (73%) cases and 15/18 (83%) controls (p=0.5). OV DNA was not detected in the cerebrospinal fluid of cases (controls not tested). Both cases and controls reported frequent bites by blackflies (Diptera, Simuliidae). Bathing daily as opposed to less often (OR 16.7, 95% CI 2.2-125.8; p<0.01), bathing between 11 a.m. and 4 p.m. (OR 12.7, 95% CI 1.6-103.7; p=0.02), and washing clothes between 11 a.m. and 4 p.m. (OR 10.9, 95% CI 1.5-77.3; p=0.02) were all independently associated with epilepsy. Blood screening by specific PCR tests for Toxoplasma and Wuchereria bancrofti was negative in all cases and

Elimination of onchocerciasis from Colombia: first proof of concept of river blindness elimination in the world.

PubMed

Nicholls, Rubén Santiago; Duque, Sofía; Olaya, Luz Adriana; López, Myriam Consuelo; Sánchez, Sol Beatriz; Morales, Alba Lucía; Palma, Gloria Inés

2018-04-11

Onchocerciasis is a chronic parasitic infection originally endemic in 13 discrete regional foci distributed among six countries of Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela). In Colombia, this disease was discovered in 1965 in the Pacific Coast of the country. The National Onchocerciasis Elimination Program was established in 1993 with the aim of eliminating disease morbidity and infection transmission. In 2013, the World Health Organization (WHO) verified Colombia as free of onchocerciasis, becoming the first country in the world to reach such a goal. This report provides the empirical evidence of the elimination of Onchocerca volvulus transmission by Simulium exiguum (s.l.) after 12 years of 6-monthly mass drug administration of Mectizan® (ivermectin) to all the eligible residents living in this endemic area. From 1996 onwards, a biannual community-based mass ivermectin administration programme was implemented, complemented by health education and community participation. In-depth parasitological, serological and entomological surveys were conducted periodically between 1998 and 2007 to evaluate the impact of ivermectin treatment according to the 2001 WHO guidelines. When the interruption of parasite transmission was demonstrated, the drug distribution ceased and a three-year post-treatment surveillance (PTS) period (2008-2010) was initiated. After 23 rounds of treatment, parasitological and ophthalmological assessments showed absence of microfilariae in skin and anterior chamber of the eyes. Serological tests proved lack of antibodies against O. volvulus in children under 10 years-old. A total of 10,500 S. exiguum flies tested by PCR had no L3 infection (infectivity rate = 0.0095%; 95% CI: 0.0029-0.049) during 2004, indicating interruption of parasite transmission. However, biannual ivermectin treatments continued until 2007 followed by a 3-year PTS period at the end of which 13,481 flies were analyzed and no infective flies were

Effect of molecular weight and concentration of legume condensed tannins on in vitro larval migration inhibition of Haemonchus contortus.

PubMed

Naumann, H D; Armstrong, S A; Lambert, B D; Muir, J P; Tedeschi, L O; Kothmann, M M

2014-01-17

The effect of molecular weight of condensed tannins (CT) from a variety of warm-season perennial legumes commonly consumed by sheep and goats on anthelmintic activity has not been previously explored. The objectives of this study were to determine if molecular weight of CT from warm-season perennial legumes could predict the biological activity of CT relative to anthelmintic activity against ivermectin resistant L3 stage Haemonchus contortus (HC) using a larval migration inhibition (LMI) assay. A second objective was to determine if CT from warm-season perennial legumes possess anthelmintic properties against L3 stage (HC). Lespedeza stuevei had the greatest concentration of total condensed tannin (TCT; 11.7%), whereas, with the exception of Arachis glabrata, a CT-free negative control, Leucaena retusa had the least TCT (3.3%). Weight-average molecular weight of CT ranged from 552 Da for L. stuevei to 1483 Da for Lespedeza cuneata. The treatments demonstrating the greatest percent LMI were L. retusa, L. stuevei and Acacia angustissima var. hirta (65.4%, 63.1% and 42.2%, respectively). The ivermectin treatment had the smallest percent LMI (12.5%) against ivermectin resistant L3 HC. There was a weak correlation (R(2)=0.34; P=0.05) between CT MW and percent LMI, suggesting that molecular weight of CT is a weak contributing factor to CT biological activity as it relates to LMI of L3 stage HC. L. stuevei, L. retusa and A. angustissima var. hirta STP5 warrant further evaluation of anthelmintic properties in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

African Programme for Onchocerciasis Control 1995–2015: Model-Estimated Health Impact and Cost

PubMed Central

Coffeng, Luc E.; Stolk, Wilma A.; Zouré, Honorat G. M.; Veerman, J. Lennert; Agblewonu, Koffi B.; Murdoch, Michele E.; Noma, Mounkaila; Fobi, Grace; Richardus, Jan Hendrik; Bundy, Donald A. P.; Habbema, Dik; de Vlas, Sake J.; Amazigo, Uche V.

2013-01-01

Background Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. Methods and Findings With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million. Conclusions Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future. PMID:23383355

African Programme For Onchocerciasis Control 1995-2015: model-estimated health impact and cost.

PubMed

Coffeng, Luc E; Stolk, Wilma A; Zouré, Honorat G M; Veerman, J Lennert; Agblewonu, Koffi B; Murdoch, Michele E; Noma, Mounkaila; Fobi, Grace; Richardus, Jan Hendrik; Bundy, Donald A P; Habbema, Dik; de Vlas, Sake J; Amazigo, Uche V

2013-01-01

Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million. Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.

Macrocyclic lactones in the treatment and control of parasitism in small companion animals.

PubMed

Nolan, Thomas J; Lok, James B

2012-05-01

Macrocyclic lactones (MLs) have many anti-parasitic applications in small companion animal medicine. They were first developed as chemoprophylactics against heartworm (Dirofilaria immitis) infection to be applied monthly for retroactive killing of third- and fourth-stage larvae. ML-containing products formulated for oral (ivermectin, milbemycin oxime), topical (selamectin, moxidectin) or injectable sustained release (moxidectin, ivermectin) are approved for heartworm prevention in dogs or cats. Clearance of microfilariae and gradual or "soft" killing of adult heartworms constitute increasingly prevalent extra-label uses of MLs against D. immitis. Some commercial ML formulations contain sufficient levels of active ingredient (milbemycin oxime, selamectin, moxidectin) to support additional label claims against gastrointestinal nematode parasites such as hookworms (Ancylostoma spp.) and ascarid round worms (Toxocara spp. and Toxascaris leonina). Beyond these approved applications, safe, extra-label uses of MLs against nematodes parasitizing the urinary tract, such as Capillaria spp., and parasites of the tissues, such as Dipetalonema reconditum, Dirofilaria repens, Thelazia spp. and Spirocerca lupi, in dogs and cats as well as exotic pets have been reported. MLs as a group have intrinsic insecticidal and acaricidal activity, and topical or otic formulations of certain compounds (selamectin, moxidectin, milbemycin oxime or ivermectin) are approved for treatment and control of fleas, certain ixodid ticks, sarcoptiform and demodectic mange mites and psoroptiform ear mites. Extra-label applications of MLs against ectoparasites include notoedric mange mites, dermanyssids such as Ornythonussus bacoti, numerous species of fur mite (e.g. Cheyletiella spp. and Lynxacarus) and trombiculids ("chiggers") in cats, dogs and nontraditional or exotic pets.

Integration of mass drug administration programmes in Nigeria: The challenge of schistosomiasis.

PubMed Central

Richards, Frank O.; Eigege, Abel; Miri, Emmanuel S.; Jinadu, M. Y.; Hopkins, Donald R.

2006-01-01

PROBLEM: Annual mass drug administration (MDA) with safe oral anthelminthic drugs (praziquantel, ivermectin and albendazole) is the strategy for control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis. District health officers seek to integrate treatment activities in areas of overlapping disease endemicity, but they are faced with having to merge different programmatic guidelines. APPROACH: We proceeded through the three stages of integrated MDA implementation: mapping the distribution of the three diseases at district level; tailoring district training and logistics based on the results of the mapping exercises; and implementing community-based annual health education and mass treatment where appropriate. During the process we identified the "know-do" gaps in the MDA guidelines for each disease that prevented successful integration of these programmes. LOCAL SETTING: An integrated programme launched in 1999 in Plateau and Nasarawa States in central Nigeria, where all three diseases were known to occur. RELEVANT CHANGES: Current guidelines allowed onchocerciasis and LF activities to be integrated, resulting in rapid mapping throughout the two states, and states-wide provision of over 9.3 million combined ivermectin-albendazole treatments for the two diseases between 2000 and 2004. In contrast, schistosomiasis activities could not be effectively integrated because of the more restrictive guidelines, resulting in less than half of the two states being mapped, and delivery of only 701,419 praziquantel treatments for schistosomiasis since 1999. LESSONS LEARNED: Integration of schistosomiasis into other MDA programmes would be helped by amended guidelines leading to simpler mapping, more liberal use of praziquantel and the ability to administer praziquantel simultaneously with ivermectin and albendazole. PMID:16917658

Onchocerciasis control in the Democratic Republic of Congo (DRC): challenges in a post-war environment.

PubMed

Makenga Bof, J-C; Maketa, V; Bakajika, D K; Ntumba, F; Mpunga, D; Murdoch, M E; Hopkins, A; Noma, M M; Zouré, H; Tekle, A H; Katabarwa, M N; Lutumba, P

2015-01-01

To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI). Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed. Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity. Challenges to CDTI in DRC have been serious adverse reactions to ivermectin in loiasis co-endemic areas and political conflict. Targets for personnel or therapeutic and geographical coverages were not met. Longer term funding and renewed efforts are required to achieve control and elimination of onchocerciasis in DRC. © 2014 John Wiley & Sons Ltd.

A field study on the anthelmintic resistance of Parascaris spp. in Arab foals in the Riyadh region, Saudi Arabia.

PubMed

Alanazi, Abdullah D; Mukbel, Rami M; Alyousif, Mohamed S; AlShehri, Zafer S; Alanazi, Ibrahim O; Al-Mohammed, Hamdan I

2017-12-01

In the last decade, Parascaris spp. resistance to anthelmintics has been recorded in many countries. In Saudi Arabia, there are limited data available on Parascaris spp. resistance to anthelmintics. To determine the current status of ivermectin, abamectin and praziquantel combined, and fenbendazole resistance to Parascaris spp. in horses in Saudi Arabia. Three hundred and forty-one foals from eleven different farms were examined by faecal egg count (FEC). The foals were all Arab horses aged 17.2 ± 4.5 (SD) months. Ivermectin (n = 46 foals), abamectin and praziquantel combined (n = 46), and fenbendazole (n = 46) were administered on day 0 and faeces were collected on day 14. The study comprised 41 untreated foals as controls. Animals that have FEC of ≥100 eggs per gram (EPG) were used to measure anthelmintic efficacy. Parascaris spp. populations were considered susceptible when faecal egg count reduction (FECR) was ≥95% associated with a lower 95% confidence limit (LCL) >90%, suspected resistant when FECR ≤90% or LCL <90% and resistant when FECR <90% and LCL <90%. Prevalence of Parascaris spp. infection was 53% (179/341 horses). Anthelmintic resistance to Parascaris spp. were highest following fenbendazole (55% of farms and 65% of foals) and to a lower extent following ivermectin or the combination of abamectin and praziquantel which comprised 27% of farms (and 46% of foals) and 18% of farms (and 10% of foals), respectively. These data indicate that anthelmintics-resistant Parascaris spp. populations are present on horse farms in Saudi Arabia.

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

PubMed Central

Bellinger, Andrew M.; Jafari, Mousa; Grant, Tyler M.; Zhang, Shiyi; Slater, Hannah C.; Wenger, Edward A.; Mo, Stacy; Lee, Young-Ah Lucy; Mazdiyasni, Hormoz; Kogan, Lawrence; Barman, Ross; Cleveland, Cody; Booth, Lucas; Bensel, Taylor; Minahan, Daniel; Hurowitz, Haley M.; Tai, Tammy; Daily, Johanna; Nikolic, Boris; Wood, Lowell; Eckhoff, Philip A.; Langer, Robert; Traverso, Giovanni

2017-01-01

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy. PMID:27856796

The physicochemical parameters of marker compounds and vehicles for use in in vitro percutaneous absorption studies.

PubMed

Kaca, Monika; Bock, Udo; Tawfik Jalal, Mohamed; Harms, Meike; Hoffmann, Christine; Müller-Goymann, Christel; Netzlaff, Frank; Schäfer, Ulrich; Lehr, Claus-Michael; Haltner-Ukomadu, Eleonore

2008-05-01

In order to prepare for a validation study to compare percutaneous absorption through reconstructed human epidermis with ex vivo skin absorption through human and animal skin, nine test compounds, covering a wide range of physicochemical properties were selected, namely: benzoic acid; caffeine; clotrimazole; digoxin; flufenamic acid; ivermectin; mannitol; nicotine; and testosterone. The donor and receptor media for the test substances, the addition of a solubiliser for the lipophilic compounds, as well as the stability and solubility of the test substances in the vehicles, were systematically analysed. Hydrophilic molecules, being freely soluble in water, were applied in buffered saline solutions. In order to overcome solubility restrictions for lipophilic compounds, the non-ionic surfactant, Igepal CA-630, was added to the donor vehicle, and, in the case of clotrimazole and ivermectin, also to the receptor fluid. The model molecules showed a suitable solubility and stability in the selected donor and receptor media throughout the whole duration of the test.

In Vitro Antimicrobial Susceptibility Patterns of Blastocystis

PubMed Central

Bush, Stephen; Ellis, John; Harkness, John; Stark, Damien

2015-01-01

Blastocystis is the most common human enteric protist with controversial clinical significance. Metronidazole is considered a first-line treatment for Blastocystis infection; however, there has been increasing evidence for the lack of efficacy of this treatment. Treatment failure has been reported in several clinical cases, and recent in vitro studies have suggested the occurrence of metronidazole-resistant strains. In this study, we tested 12 Blastocystis isolates from 4 common Blastocystis subtypes (ST1, ST3, ST4, and ST8) against 12 commonly used antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole, fluconazole, nystatin, and itraconazole) at 10 different concentrations in vitro. It was found that each subtype showed little sensitivity to the commonly used metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and secnidazole). This study highlights the efficacy of other potential drug treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests that current treatment regimens be revised. PMID:25987633

In Vitro Antimicrobial Susceptibility Patterns of Blastocystis.

PubMed

Roberts, Tamalee; Bush, Stephen; Ellis, John; Harkness, John; Stark, Damien

2015-08-01

Blastocystis is the most common human enteric protist with controversial clinical significance. Metronidazole is considered a first-line treatment for Blastocystis infection; however, there has been increasing evidence for the lack of efficacy of this treatment. Treatment failure has been reported in several clinical cases, and recent in vitro studies have suggested the occurrence of metronidazole-resistant strains. In this study, we tested 12 Blastocystis isolates from 4 common Blastocystis subtypes (ST1, ST3, ST4, and ST8) against 12 commonly used antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole, fluconazole, nystatin, and itraconazole) at 10 different concentrations in vitro. It was found that each subtype showed little sensitivity to the commonly used metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and secnidazole). This study highlights the efficacy of other potential drug treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests that current treatment regimens be revised. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Controlled Trial to Assess the Effect of Quinine, Chloroquine, Amodiaquine, and Artesunate on Loa loa Microfilaremia

PubMed Central

Kamgno, Joseph; Djomo, Patrick Nguipdop; Pion, Sébastien D.; Thylefors, Björn; Boussinesq, Michel

2010-01-01

Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species. A controlled trial was conducted to assess the effect of standard doses of quinine, chloroquine, amodiaquine, and artesunate on L. loa microfilaremia. Ninety-eight patients were randomly allocated into five groups (one for each drug and a control group) after stratification on microfilarial load. Loa loa microfilaremia was monitored on days 0, 3, 7, 15, 30, 60, and 90. No significant change in the loads was recorded in any of the treatment groups. A comprehensive review of the effects of antimalarial drugs against filariae is also provided. PMID:20207860

A Chemogenetic Receptor That Enhances the Magnitude and Frequency of Glycinergic Inhibitory Postsynaptic Currents without Inducing a Tonic Chloride Flux.

PubMed

Islam, Robiul; Zhang, Yan; Xu, Li; Sah, Pankaj; Lynch, Joseph W

2017-03-15

The gene transfer-mediated expression of inhibitory ion channels in nociceptive neurons holds promise for treating intractable pain. Chemogenetics, which involves expressing constructs activated by biologically inert molecules, is of particular interest as it permits tunable neuromodulation. However, current chloride-permeable chemogenetic constructs are problematic as they mediate a tonic chloride influx which over time would deplete the chloride electrochemical gradient and reduce inhibitory efficacy. Inflammatory pain sensitization can be caused by prostaglandin E2-mediated inhibition of glycinergic inhibitory postsynaptic currents in spinal nociceptive neurons. We developed a highly conducting (100 pS) inhibitory chemogenetic construct based on a human glycine receptor (α1 Y279F,A288G ) with high ivermectin sensitivity. When virally infected into spinal neurons, 10 nM ivermectin increased the magnitude and frequency of glycinergic postsynaptic currents without activating a tonic chloride flux. The construct should thus produce analgesia. Its human origin and the well-established biocompatibility of its ligand suggest it may be suited to human use.

21 CFR 520.1195 - Ivermectin liquid.

Code of Federal Regulations, 2014 CFR

2014-04-01

... micrograms (mcg) per kilogram (/kg) of body weight as a single dose by stomach tube or as an oral drench. (ii...): Trichostrongylus axei; Large mouth Stomach Worms (adults): Habronema muscae; Bots (oral and gastric stages... larvae)); Hairworms (Trichostongylus axei(adult)); Large mouth Stomach Worms (Habronema muscae (adult...

21 CFR 520.1195 - Ivermectin liquid.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Amount. 200 micrograms (mcg) per kilogram (/kg) of body weight as a single dose by stomach tube or as an...): Trichostrongylus axei; Large mouth Stomach Worms (adults): Habronema muscae; Bots (oral and gastric stages... larvae)); Hairworms (Trichostongylus axei(adult)); Large mouth Stomach Worms (Habronema muscae (adult...

21 CFR 520.1192 - Ivermectin paste.

Code of Federal Regulations, 2010 CFR

2010-04-01

... has not been established, do not use in female dairy cattle of breeding age. [49 FR 22275, May 29...) Cattle—(i) Amount. 23 milligrams per 250 pounds of body weight. (ii) Indications for use. It is used in cattle for the treatment and control of gastrointestinal roundworms (adults and fourth-stage larvae...

21 CFR 520.1192 - Ivermectin paste.

Code of Federal Regulations, 2014 CFR

2014-04-01

... has not been established, do not use in female dairy cattle of breeding age. [49 FR 22275, May 29...) Cattle—(i) Amount. 23 milligrams per 250 pounds of body weight. (ii) Indications for use. It is used in cattle for the treatment and control of gastrointestinal roundworms (adults and fourth-stage larvae...

21 CFR 520.1192 - Ivermectin paste.

Code of Federal Regulations, 2011 CFR

2011-04-01

... has not been established, do not use in female dairy cattle of breeding age. [49 FR 22275, May 29...) Cattle—(i) Amount. 23 milligrams per 250 pounds of body weight. (ii) Indications for use. It is used in cattle for the treatment and control of gastrointestinal roundworms (adults and fourth-stage larvae...

21 CFR 520.1192 - Ivermectin paste.

Code of Federal Regulations, 2013 CFR

2013-04-01

... has not been established, do not use in female dairy cattle of breeding age. [49 FR 22275, May 29...) Cattle—(i) Amount. 23 milligrams per 250 pounds of body weight. (ii) Indications for use. It is used in cattle for the treatment and control of gastrointestinal roundworms (adults and fourth-stage larvae...

21 CFR 520.1195 - Ivermectin liquid.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Habronema and Draschia spp. cutaneous third-stage larvae; Dermatitis caused by neck threadworm microfilariae... Habronema and Draschia spp. cutaneous third-stage larvae; and Dermatitis caused by neck threadworm...

21 CFR 520.1195 - Ivermectin liquid.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Amount. 200 micrograms (mcg) per kilogram (/kg) of body weight as a single dose by stomach tube or as an...): Trichostrongylus axei; Large mouth Stomach Worms (adults): Habronema muscae; Bots (oral and gastric stages... larvae)); Hairworms (Trichostongylus axei(adult)); Large mouth Stomach Worms (Habronema muscae (adult...

Gastrointestinal nematodes and anthelmintic resistance in Danish goat herds☆

PubMed Central

Holm, Signe A.; Sörensen, Camilla R. L.; Thamsborg, Stig M.; Enemark, Heidi L.

2014-01-01

The prevalence of gastrointestinal parasites in Danish goats and the presence of anthelmintic resistance (AR) in 10 selected herds were investigated during April–September 2012. All Danish herds (n = 137) with 10 or more adult goats were invited to participate, and of these 27 herds met the inclusion criterion of more than 10 young kids never treated with anthelmintics. Questionnaire data on management were collected, and faecal samples from 252 kids were analysed by the McMaster technique. From all herds with a mean faecal egg count (FEC) above 300 eggs per g of faeces, pooled samples were stained with peanut agglutinin (PNA) for specific detection of Haemonchus contortus. Strongyle eggs were detected with an individual prevalence of 69%, including Nematodirus battus (3.6%) and other Nematodirus species (15.0%). Eimeria spp. were observed in 99.6% of the kids. H. contortus was found in 11 of 12 (92%) tested herds. Anthelmintics were used in 89% of the herds with mean treatment frequencies of 0.96 and 0.89 treatments per year for kids and adults, respectively. In 2011, new animals were introduced into 44% of the herds of which 25% practised quarantine anthelmintic treatments. In 10 herds the presence of AR was analysed by egg hatch assay and FEC reduction tests using ivermectin (0.3 mg/kg) or fenbendazole (10.0 mg/kg). AR against both fenbendazole and ivermectin was detected in seven herds; AR against fenbendazole in one herd, and AR against ivermectin in another herd. In conclusion, resistance to the most commonly used anthelmintics is widespread in larger goat herds throughout Denmark. PMID:25076056

Controlling scabies in institutional settings: a review of medications, treatment models, and implementation.

PubMed

Scheinfeld, Noah

2004-01-01

Scabies is a global problem and a significant source of morbidity in nursing home residents and workers because of its highly contagious nature. It is also a problem in hospitals that care for the elderly, the debilitated, and the immunocompromised. New outbreaks continue to occur, despite controlling the recurrent epidemics. Scabies manifests as papules, pustules, burrows, nodules, and occasionally urticarial papules and plaques. Most of the patients with scabies experience severe pruritus. A subset of patients have crusted or Norwegian scabies. These patients, who are usually debilitated or immunocompromised, do not experience the urge to scratch, and therefore do not scratch their own skin. Diagnosis of scabies is based on patient history, physical examination, and demonstration of mites, eggs, or scybala (black or brown football-shaped masses of feces of scabies) on microscopic examination. Scabies can be treated with topical or oral therapies. Topical treatments include 5% permethrin cream, 1% lindane (gamma benzene hexachloride) lotion, 6% precipitated sulfur in petrolatum, crotamiton, malathion, allethrin spray, and benzyl benzoate. Ivermectin, the only oral treatment, is not approved for scabies in the US. Most authorities advocate using a scabicide several times, specifically once a week over a period of 2-3 weeks. In an outbreak of scabies in a nursing home, residents, staff, and frequent visitors should all be treated even if they are not symptomatic. Ivermectin is useful in treating patients with Norwegian or crusted scabies, or who are debilitated. Ivermectin has no serious reported adverse effects. Model treatment plans to stop scabies epidemics have been developed. These plans coordinate treatment of all persons exposed (including ivermectin for debilitated patients), isolation of infected patients, disinfection of objects that patients have come into contact with, and education and reassurance of the medical staff. Failure to coordinate notification

Susceptibility of Adult Mosquitoes to Insecticides in Aqueous Sucrose Baits

DTIC Science & Technology

2010-01-01

imidacloprid, followed by spinosad, thiamethoxam , bifenthrin, permethrin, and cyfluthrin. The least effective ingredients were chlorfenapyr and ivermectin...effective active ingredients were fipronil, deltamethrin and imidacloprid, followed by spinosad, thiamethoxam , bifenthrin, permethrin, and cyfluthrin. The...presented. Based on KD50 values, Cx. quinquefasciatus were most suscepti- ble to fipronil > imidacloprid > deltamethrin, spinosad, thiamethoxam , and

Mazzotti reaction after presumptive treatment for schistosomiasis and strongyloidiasis in a Liberian refugee.

PubMed

Olson, Bradley G; Domachowske, Joseph B

2006-05-01

We report a case of the Mazzotti reaction in a 13-year-old Liberian refugee after presumptive treatment of schistosomiasis and strongyloidiasis with ivermectin, praziquantel and albendazole. The patient was hospitalized with fever, urticaria, abdominal pain and angioedema. Twelve hours after treatment with intravenous methylprednisolone he had complete resolution of his symptoms.

Assessment and monitoring of onchocerciasis in Latin America.

PubMed

Rodríguez-Pérez, Mario A; Unnasch, Thomas R; Real-Najarro, Olga

2011-01-01

Onchocerciasis has historically been one of the leading causes of infectious blindness worldwide. It is endemic to tropical regions both in Africa and Latin America and in the Yemen. In Latin America, it is found in 13 foci located in 6 different countries. The epidemiologically most important focus of onchocerciasis in the Americas is located in a region spanning the border between Guatemala and Mexico. However, the Amazonian focus straddling the border of Venezuela and Brazil is larger in overall area because the Yanomami populations are scattered over a very large geographical region. Onchocerciasis is caused by infection with the filarial parasite Onchocerca volvulus. The infection is spread through the bites of an insect vector, black flies of the genus Simulium. In Africa, the major vectors are members of the S. damnosum complex, while numerous species serve as vectors of the parasite in Latin America. Latin America has had a long history of attempts to control onchocerciasis, stretching back almost 100 years. The earliest programmes used a strategy of surgical removal of the adult parasites from affected individuals. However, because many of the adult parasites lodge in undetectable and inaccessible areas of the body, the overall effect of this strategy on the prevalence of infection was relatively minor. In 1988, a new drug, ivermectin, was introduced that effectively killed the larval stage (microfilaria) of the parasite in infected humans. As the microfilaria is both the stage that is transmitted by the vector fly and the cause of most of the pathologies associated with the infection, ivermectin opened up a new strategy for the control of onchocerciasis. Concurrent with the use of ivermectin for the treatment of onchocerciasis, a number of sensitive new diagnostic tools were developed (both serological and nucleic acid based) that provided the efficiency, sensitivity and specificity necessary to monitor the decline and eventual elimination of

Final report of the Conference on the eradicability of Onchocerciasis.

PubMed

Dadzie, Yankum; Neira, Maria; Hopkins, Donald

2003-02-07

Sixty-four experts from a variety of disciplines attended a Conference on the Eradicability of Onchocerciasis at The Carter Center, in Atlanta GA, held January 22-24, 2002. The Conference, which was organized by The Carter Center and the World Health Organization, with funding from the Bill & Melinda Gates Foundation, addressed the question: "Is onchocerciasis (River Blindness) eradicable with current knowledge and tools?" Former US President Jimmy Carter attended part of the final plenary proceedings on January 24.The Conference consisted of a series of presentations by invited expert speakers (Appendix C) and further deliberations in four workgroups (Appendix D) followed by plenary discussion of major conclusions. The presentations underlined epidemiological and entomological differences between onchocerciasis in Africa and the Americas. Whilst onchocerciasis in Africa covers extensive areas and is associated with striking human and fly population migrations and remarkably efficient black fly vectors, in the Americas onchocerciasis is found in limited foci. Human and fly population migration are not major problems in the Americas, where most black fly species are inefficient, though some efficient black flies are also found there. Vector control has been effectively applied in the Onchocerciasis Control Program in West Africa (OCP) with remarkable results, interrupting transmission in most parts of the original Program area. The use of ivermectin has given variable results: while ivermectin treatment has been effective in all endemic areas in controlling onchocerciasis as a public health problem, its potential for interrupting transmission is more promising in hypo- and mesoendemic areas. The African Program for Onchocerciasis Control (APOC), which supports onchocerciasis control in endemic African countries outside the OCP, applies ivermectin, its principal control tool, to communities in high-risk areas as determined by rapid epidemiological mapping of

Mapping the distribution of Loa loa in Cameroon in support of the African Programme for Onchocerciasis Control

PubMed Central

Thomson, Madeleine C; Obsomer, Valérie; Kamgno, Joseph; Gardon, Jacques; Wanji, Samuel; Takougang, Innocent; Enyong, Peter; Remme, Jan H; Molyneux, David H; Boussinesq, Michel

2004-01-01

Background Loa loa has recently emerged as a filarial worm of significant public health importance as a consequence of its impact on the African Programme for Onchocerciasis Control (APOC). Severe, sometimes fatal, encephalopathic reactions to ivermectin (the drug of choice for onchocerciasis control) have occurred in some individuals with high Loa loa microfilarial counts. Since high density of Loa loa microfilariae is known to be associated with high prevalence rates, a distribution map of the latter may determine areas where severe reactions might occur. The aim of the study was to identify variables which were significantly associated with the presence of a Loa microfilaraemia in the subjects examined, and to develop a spatial model predicting the prevalence of the Loa microfilaraemia. Methods Epidemiological data were collected from 14,225 individuals living in 94 villages in Cameroon, and analysed in conjunction with environmental data. A series of logistic regression models (multivariate analysis) was developed to describe variation in the prevalence of Loa loa microfilaraemia using individual level co-variates (age, sex, μl of blood taken for examination) and village level environmental co-variates (including altitude and satellite-derived vegetation indices). Results A spatial model of Loa loa prevalence was created within a geographical information system. The model was then validated using an independent data set on Loa loa distribution. When considering both data sets as a whole, and a prevalence threshold of 20%, the sensitivity and the specificity of the model were 81.7 and 69.4%, respectively. Conclusions The model developed has proven very useful in defining the areas at risk of post-ivermectin Loa-related severe adverse events. It is now routinely used by APOC when projects of community-directed treatment with ivermectin are examined. PMID:15298709

Mapping the distribution of Loa loa in Cameroon in support of the African Programme for Onchocerciasis Control.

PubMed

Thomson, Madeleine C; Obsomer, Valérie; Kamgno, Joseph; Gardon, Jacques; Wanji, Samuel; Takougang, Innocent; Enyong, Peter; Remme, Jan H; Molyneux, David H; Boussinesq, Michel

2004-08-06

BACKGROUND: Loa loa has recently emerged as a filarial worm of significant public health importance as a consequence of its impact on the African Programme for Onchocerciasis Control (APOC). Severe, sometimes fatal, encephalopathic reactions to ivermectin (the drug of choice for onchocerciasis control) have occurred in some individuals with high Loa loa microfilarial counts. Since high density of Loa loa microfilariae is known to be associated with high prevalence rates, a distribution map of the latter may determine areas where severe reactions might occur. The aim of the study was to identify variables which were significantly associated with the presence of a Loa microfilaraemia in the subjects examined, and to develop a spatial model predicting the prevalence of the Loa microfilaraemia. METHODS: Epidemiological data were collected from 14,225 individuals living in 94 villages in Cameroon, and analysed in conjunction with environmental data. A series of logistic regression models (multivariate analysis) was developed to describe variation in the prevalence of Loa loa microfilaraemia using individual level co-variates (age, sex, microl of blood taken for examination) and village level environmental co-variates (including altitude and satellite-derived vegetation indices). RESULTS: A spatial model of Loa loa prevalence was created within a geographical information system. The model was then validated using an independent data set on Loa loa distribution. When considering both data sets as a whole, and a prevalence threshold of 20%, the sensitivity and the specificity of the model were 81.7 and 69.4%, respectively. CONCLUSIONS: The model developed has proven very useful in defining the areas at risk of post-ivermectin Loa-related severe adverse events. It is now routinely used by APOC when projects of community-directed treatment with ivermectin are examined.

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial.

PubMed

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C

2016-03-01

Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥ 4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

PubMed Central

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C.

2016-01-01

Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas. PMID:26967331

[Strongyloidosis. Part IX. Treatment].

PubMed

Soroczan, Wiesław

2002-01-01

The treatment of chronic and massive (uncomplicated) and severe (complicated) disseminated strongyloidosis, was presented from the historical point of view. The sequence of achievements in regard of treatment of the gentian violet, dithiazine iodide, benzimidazoles (thiabendazole, mebendazole, albendazole, cambendazole), ivermectin and cyclosporin A, was described. The recommendations for treatment of strongyloidosis are also given.

Lack of Active Onchocerca volvulus Transmission in the Northern Chiapas Focus of Mexico

PubMed Central

Rodríguez-Pérez, Mario A.; Unnasch, Thomas R.; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L.; Richards, Frank; Peña-Flores, Graciela P.; Orozco-Algarra, María Eugenia; Prado-Velasco, Gibert

2010-01-01

The northern Chiapas onchocerciasis focus has undergone 11 years of ivermectin mass treatment. No evidence of microfilariae in the cornea and/or anterior chamber of the eye or in skin snips was seen in residents examined in 2006 in two sentinel communities (upper limit of the 95% confidence interval [UL 95% CI] = 0.5% and 0.3%, respectively). In children 10 and under, 0 of 305 were found to harbor antibodies to Ov16, a marker of parasite exposure; 0 of 4,400 Simulium ochraceum s.l. collected in 2005 contained parasite DNA, giving an UL 95% CI for the infective rate of 0.9/2,000, and an UL 95% CI of the seasonal transmission potential of 1.2 L3/person. These data, assumed to be representative of the focus as a whole, suggest that there is no ongoing transmission of Onchocerca volvulus in the northern Chiapas focus. Community-wide treatments with ivermectin were halted in 2008, and a post-treatment surveillance phase was initiated. PMID:20595471

Optimization of sample preparation by central composite design for multi-class determination of veterinary drugs in bovine muscle, kidney and liver by ultra-high-performance liquid chromatographic-tandem mass spectrometry.

PubMed

Rizzetti, Tiele M; de Souza, Maiara P; Prestes, Osmar D; Adaime, Martha B; Zanella, Renato

2018-04-25

In this study a simple and fast multi-class method for the determination of veterinary drugs in bovine liver, kidney and muscle was developed. The method employed acetonitrile for extraction followed by clean-up with EMR-Lipid® sorbent and trichloracetic acid. Tests indicated that the use of TCA was most effective when added in the final step of the clean-up procedure instead of during extraction. Different sorbents were tested and optimized using central composite design and the analytes determined by ultra-high-performance liquid chromatographic-tandem mass spectrometry (UHPLC-MS/MS). The method was validated according the European Commission Decision 2002/657 presenting satisfactory results for 69 veterinary drugs in bovine liver and 68 compounds in bovine muscle and kidney. The method was applied in real samples and in proficiency tests and proved to be adequate for routine analysis. Residues of abamectin, doramectin, eprinomectin and ivermectin were found in samples of bovine muscle and only ivermectin in bovine liver. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glycine receptor mechanism illuminated by electron cryo-microscopy

PubMed Central

Du, Juan; Lü, Wei; Wu, Shenping; Cheng, Yifan; Gouaux, Eric

2015-01-01

Summary The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders including autism and hyperekplexia. Understanding of molecular mechanisms and pharmacology of GlyRs has been hindered by a dearth of high-resolution structures. Here we report electron cryo-microscopy structures of the α1 GlyR with strychnine, glycine, or glycine/ivermectin. Strychnine arrests the receptor in an antagonist-bound, closed ion channel state, glycine stabilizes the receptor in an agonist-bound open channel state, and the glycine/ivermectin complex adopts a potentially desensitized or partially open state. Relative to the glycine-bound state, strychnine expands the agonist-binding pocket via outward movement of the C loop, promotes rearrangement of the extracellular and transmembrane domain ‘wrist’ interface, and leads to rotation of the transmembrane domain toward the pore axis, occluding the ion conduction pathway. These structures illuminate GlyR mechanism and define a rubric to interpret structures of Cys-loop receptors. PMID:26344198

Are Fish and Standardized FETAX Assays Protective Enough for Amphibians? A Case Study on Xenopus laevis Larvae Assay with Biologically Active Substances Present in Livestock Wastes

PubMed Central

Martini, Federica; Tarazona, José V.; Pablos, M. Victoria

2012-01-01

Biologically active substances could reach the aquatic compartment when livestock wastes are considered for recycling. Recently, the standardized FETAX assay has been questioned, and some researchers have considered that the risk assessment performed on fish could not be protective enough to cover amphibians. In the present study a Xenopus laevis acute assay was developed in order to compare the sensitivity of larvae relative to fish or FETAX assays; veterinary medicines (ivermectin, oxytetracycline, tetracycline, sulfamethoxazole, and trimethoprim) and essential metals (zinc, copper, manganese, and selenium) that may be found in livestock wastes were used for the larvae exposure. Lethal (LC50) and sublethal effects were estimated. Available data in both, fish and FETAX studies, were in general more protective than values found out in the current study, but not in all cases. Moreover, the presence of nonlethal effects, caused by ivermectin, zinc, and copper, suggested that several physiological mechanisms could be affected. Thus, this kind of effects should be deeply investigated. The results obtained in the present study could expand the information about micropollutants from livestock wastes on amphibians. PMID:22629159

Distribution of Animal Drugs among Curd, Whey, and Milk Protein Fractions in Spiked Skim Milk and Whey.

PubMed

Shappell, Nancy W; Shelver, Weilin L; Lupton, Sara J; Fanaselle, Wendy; Van Doren, Jane M; Hakk, Heldur

2017-02-01

It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labeled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and thiabendazole were used to evaluate the distribution of animal drugs among rennet curd, whey, and protein fractions from skim cow milk. Our previous work reported the distribution of these same drugs between skim and fat fractions of milk. Drug distribution between curd and whey was significantly correlated (R 2 = 0.70) to the drug's lipophilicity (log P), with improved correlation using log D (R 2 = 0.95). Distribution of drugs was concentration independent over the range tested (20-2000 nM). With the exception of thiabendazole and ivermectin, more drug was associated with whey protein than casein on a nmol/g protein basis (oxytetracycline experiment not performed). These results provide insights into the distribution of animal drug residues, if present in cow milk, among milk fractions, with possible extrapolation to milk products.

Interruption of Transmission of Onchocerca volvulus in the Oaxaca Focus, Mexico

PubMed Central

Rodríguez-Pérez, Mario A.; Unnasch, Thomas R.; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L.; Peña-Flores, Graciela P.; Orozco-Algarra, María E.; Arredondo-Jiménez, Juan I.; Richards, Frank; Vásquez-Rodríguez, Miguel A.; Rendón, Vidal García

2010-01-01

All endemic communities of the Oaxaca focus of onchocerciasis in southern Mexico have been treated annually or semi-annually with ivermectin since 1994. In-depth epidemiologic assessments were performed in communities during 2007 and 2008. None of the 52,632 Simulium ochraceum s.l. collected in four sentinel communities was found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the infection rate in the vectors of 0.07/2,000. The prevalence of microfilariae (mf) in the cornea and/or anterior chamber of the eye was also zero (0 of 1,039 residents examined; 95%-UL = 0.35%). Similarly, all 1,164 individuals examined by skin biopsy were mf negative (95%-UL = 0.31%), and sera collected from 3,569 children from 25 communities did not harbor Ov16 IgG4-antibodies (95%-UL = 0.09%). These meet the criteria for absence of morbidity and parasite transmission in the Oaxaca focus. As a result mass treatments with ivermectin were halted in 2009. PMID:20595472

[Entomologic study of loaiasis transmission in the Lekie area (Cameroon)].

PubMed

Demanou, M; Pion, S D; Boussinesq, M

2001-11-01

A number of cases of Loa encephalopathy have been recorded after ivermectin treatment in the Lekie Division, an area of degraded forest located in central Cameroon. An entomological study was carried out in a village of this region between May 1999 and April 2000 to determine whether the high microfilarial loads of Loa found in the population, which can exceed 10,000 microfilariae per ml of blood, were related to high densities of vector populations. The Chrysops collected at 10 catching stations, using hand nets, by persons standing by a wood fire, were dissected to evaluate their level of infection with Loa. The vectorial densities were three-fold higher in the forest stations than in those located near the habitations (2307 and 725 bites per man per year, respectively). These values are lower than those reported from similar studies in Cameroon, Congo and Gabon. Measurement of Chrysops densities does not seem to be an appropriate tool to evaluate the level of endemicity of loiasis, and to delineate the areas where there is a risk of post-ivermectin Loa encephalopathies.

Human Pulmonary Infection by the Zoonotic Metastrongylus salmi Nematode. The First Reported Case in the Americas

PubMed Central

Calvopina, Manuel; Caballero, Henry; Morita, Tatsushi; Korenaga, Masataka

2016-01-01

Pulmonary metastrongylosis, a zoonotic disease found primarily in pigs, is caused by eight different species of the cosmopolitan nematode Metastrongylus genus. To date, only four human cases have been reported, all from Europe. Herein, a severe case of pulmonary infection caused by Metastrongylus salmi in an Ecuadorian man, with successful treatment with ivermectin, is described. PMID:27382078

21 CFR 524.1140 - Imidacloprid and ivermectin.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Conditions of Use in Dogs—(1) Amount. The recommended minimum dosage is 4.5 mg/pound (lb) (10 mg/kilogram (kg... Use. For the prevention of heartworm disease caused by Dirofilaria immitis; kills adult fleas and is...

21 CFR 524.1140 - Imidacloprid and ivermectin.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Conditions of Use in Dogs—(1) Amount. The recommended minimum dosage is 4.5 mg/pound (lb) (10 mg/kilogram (kg... Use. For the prevention of heartworm disease caused by Dirofilaria immitis; kills adult fleas and is...

21 CFR 524.1140 - Imidacloprid and ivermectin.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Conditions of Use in Dogs—(1) Amount. The recommended minimum dosage is 4.5 mg/pound (lb) (10 mg/kilogram (kg... Use. For the prevention of heartworm disease caused by Dirofilaria immitis; kills adult fleas and is...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 522.1193 - Ivermectin and clorsulon.

Code of Federal Regulations, 2014 CFR

2014-04-01

... intramuscular use. Do not treat cattle within 49 days of slaughter. Because a withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Do not use in other animal species... this chapter. (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... use in female dairy cattle of breeding age. A withdrawal period has not been established for this... of this chapter. (e) Conditions of use in cattle—(1) Amount. One mL per 22 pounds (0.5 milligram per kilogram) of body weight applied topically to the back of the animal. (2) Indications for use in cattle...

21 CFR 522.1193 - Ivermectin and clorsulon.

Code of Federal Regulations, 2013 CFR

2013-04-01

... intramuscular use. Do not treat cattle within 49 days of slaughter. Because a withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Do not use in other animal species... this chapter. (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle...

Hyperinfection with Strongyloides in a HIV-negative elderly male

PubMed Central

Girija, S; Kannan, Suresh; Jeyakumari, D; Gopal, R

2012-01-01

Strongyloides stercoralis is an intestinal nematode producing mild infection in the immunocompetent and fatal hyperinfection syndrome in the immunocompromised. An elderly HIV-negative male presented with symptoms of chronic respiratory disease and vague abdominal symptoms. Examination of sputum and stools showed larvae of S. stercoralis. Bacterial and fungal causes of respiratory infections were ruled out. The patient responded to oral ivermectin. PMID:23508878

Knemidokoptes mutans (Acari: Knemidocoptidae) in a great-horned owl (Bubo virginianus).

PubMed

Schulz, T A; Stewart, J S; Fowler, M E

1989-07-01

A routine examination of a captive juvenile great-horned owl (Bubo virginianus) revealed bilateral proliferative papillary hyperkeratosis on the feet. Microscopic examination of skin scrapings produced numerous mites identified as Knemidokoptes mutans. This is the first record of this parasite in a great-horned owl. A single dose of ivermectin (200 micrograms/kg) was effective in treatment of this infection.

Crusted scabies of the scalp in a patient with systemic lupus erythematosus.

PubMed

Yee, Brittany E; Carlos, Casey A; Hata, Tissa

2014-10-15

Crusted scabies is a severe, hyperkeratotic, psoriasiform disorder associated with immune suppression. Affected individuals typically present with crusted hyperkeratotic lesions in a variety of locations. This condition can lead to severe complications: institutional outbreaks and secondary bacterial infections associated with sepsis and high mortality. A 37-year-old woman with a 12-year history of systemic lupus erythematosus treated with prednisone, methotrexate, and plaquenil presented with a three-week history of a painful scalp rash with adherent yellow scale. Skin biopsy and tissue culture were consistent with a diagnosis of crusted scabies with superficial bacterial infection. The patient was treated with oral ivermectin and permethrin cream, as well as ciprofloxacin for the bacterial infection. At one-week follow-up, the scalp was no longer tender and hyperkeratotic plaques had significantly improved. At one-month follow-up, the affected scalp demonstrated further improvement with decreasing erythema and alopecia with follicular ostia. Our case highlights the atypical presentation of crusted scabies with primary scalp involvement and need for vigilance in recognizing and appropriately treating this condition to prevent the consequences of longstanding infection. Combination treatment with ivermectin and permethrin is appropriate management for this condition.

Intestinal Parasites and Anthelmintic Treatments in a Laboratory Colony of Wild-caught African Pouched Rats (Cricetomys ansorgei)

PubMed Central

Cullin, Cassandra O; Sellers, Matthew S; Rogers, Erin R; Scott, Kathleen E; Lee, Danielle N; Ophir, Alexander G; Jackson, Todd A

2017-01-01

African giant pouched rats (Cricetomys spp.) are large rodents native to subSaharan Africa. Wild-caught pouched rats identified as Cricetomys ansorgei (n = 49) were imported from Tanzania. A survey of gastrointestinal parasitism by fecal flotation revealed the presence of multiple parasites, including Nippostrongylus spp., Heterakis spp., Trichuris spp., Hymenolepis spp., Raillietina spp., and Eimeria spp. Oral self-administered fenbendazole (150 ppm), topical moxidectin (2 mg/kg), pyrantel pamoate (15 mg/kg), piperazine (100 mg/kg daily), and injectable ivermectin (0.25 mg/kg) were used to determine effective treatment options for the gastrointestinal parasites present in the colony. Pyrantel pamoate in a treat vehicle and piperazine in water bottles were easily administered and significantly reduced the numbers of animals shedding Nippostrongylus spp. and Heterakis spp. during the study. Moxidectin and ivermectin were clinically ineffective at reducing fecal egg shedding. Fenbendazole was most effective at clearing infection with Trichuris spp. Although 10 mg/kg praziquantel was ineffective, a single dose of 30 mg/kg praziquantel significantly reduced the number of African pouched rats that shed cestode embryos. A combination treatment may be necessary to successfully treat all parasites present in any given animal. PMID:28935004

[Gnathostomosis, an exotic disease increasingly imported into Western countries].

PubMed

Clément-Rigolet, Marina C; Danis, Martin; Caumes, Eric

2004-12-04

AN INCIDENTAL HELMITHIASIS IN MAN: Gnathostomiasis is an helminthic disease of animals due to a nematode belonging to the gender Gnathostoma. This gender includes many species, the most frequent being Gnathostoma spinigerum. Man is an incidental host. Human gnathostomiasis is endemic in some countries of South-East Asia, and Latin America. It is due to the consumption of raw or insufficiently cooked meat or fish. Since the beginning of the eighties, there is an increasing number of cases of gnathostomiasis described in Western countries in travellers returning from endemic countries. IN THE SKIN OR THE VISCERA: Gnathostomiasis is a cause of cutaneous and/or visceral larva migrans syndrome. Some visceral involvement, more particularly neurological forms, may lead to significant morbidity and mortality. The diagnosis is occasionally confirmed by the identification of the Gnathostoma larva in the skin or viscera. Most often the diagnosis relies on epidemiological, clinical and biological (hypereosinophilia, positive serologic test) grounds. ALBENDAZOLE AND IVERMECTINE: The first line treatment is albendazole, 400 mg once or twice a day during 21 days. The efficacy of ivermectin needs to be assessed more precisely. Relapses may occur up to 24 months after apparent cure.

A real-time PCR approach to identify anthelmintic-resistant nematodes in sheep farms.

PubMed

Milhes, M; Guillerm, M; Robin, M; Eichstadt, M; Roy, C; Grisez, C; Prévot, F; Liénard, E; Bouhsira, E; Franc, M; Jacquiet, P

2017-03-01

Resistance to fenbendazole, ivermectin, and moxidectin was explored by a fecal egg count reduction test in four meat sheep flocks in southwestern France where anthelmintic resistance was suspected. The FECR test results of the present study confirmed the presence of benzimidazole resistance in three out of the four farms and the presence of ivermectin resistance in one flock. In addition, a suspicion of moxidectin resistance was shown in this latter farm. Both conventional morphological and molecular identifications were performed on larval cultures before and after the treatment in the studied farms. A high positive correlation was found between the number of larvae counted under binocular microscope and the number of larvae estimated by the qPCR analysis (R 2  = 0.88) and a high Cohen's Kappa value (0.91) in the detection of strongylid larvae in larval cultures. According to qPCR results, Trichostrongylus species demonstrated high levels of BZ resistance and Teladorsagia circumcincta was involved in the IVM resistance in one farm. The molecular procedures used in this study have the potential to be beneficial for anthelmintic resistance surveillance in sheep industry.

Effectiveness evaluation of several cattle anthelmintics via the fecal egg count reduction test.

PubMed

Yazwinski, T A; Tucker, C A; Hornsby, J A; Powell, J G; Reynolds, J L; Johnson, Z B; Lindsey, W; Silver, T K

2009-07-01

Utilizing groups of cograzed, naturally infected beef-type heifers, three fecal egg count reduction tests were conducted in the later months of 2007 at the University of Arkansas. Each test was 28 days in length consisting of individual animal fecal nematode egg counts and coprocultures. Both original and generic ivermectin injectable formulations were used in two of the tests at 0.2 mg/kg BW, with FECR percentages never exceeding 90% in either test. Oral fenbendazole was evaluated at 5 and 10 mg/kg BW, with FECR%'s exceeding 90% on all occasions, but with a precipitous drop when recently treated animals were treated at the lower dose. Evaluated in one test, injectable moxidectin given at 0.2 mg/kg BW resulted in egg count reductions of 96-92% (days 7 to 28). Also evaluated in one test, albendazole delivered orally at 10 mg/kg BW was 98% and 97% effective at 17 and 28 days post-treatment. For all tests, coprocultures conducted post-treatment contained only Cooperia spp. larvae (benzimidazole use), relatively unmodified percentages of Cooperia spp. and Haemonchus spp. larvae (ivermectin use), and primarily Cooperia spp. larvae with a small percentage of Haemonchus spp. larvae (moxidectin use).

Epidemiology, Diagnosis, and Treatment of Scabies in a Dermatology Office.

PubMed

Anderson, Kathryn L; Strowd, Lindsay C

Scabies is a neglected skin disease, and little is known about current incidence and treatment patterns in the United States. The purpose of this study was to examine demographic data, treatment types, success of treatment, and misdiagnosis rate of scabies in an outpatient dermatology clinic. A retrospective chart review of patients diagnosed with scabies within the past 5 years was performed. A total of 459 charts were identified, with 428 meeting inclusion criteria. Demographic data, diagnostic method, treatment choice, misdiagnosis rate, treatment failure, and itching after scabies are also reported. Children were the largest age group diagnosed with scabies, at 38%. Males (54%) were diagnosed with scabies more than females. The majority of diagnoses were made by visualizing ova, feces, or mites on light microscopy (58%). At the time of diagnosis, 45% of patients had been misdiagnosed by another provider. Topical permethrin was the most common treatment used (69%), followed by a combination of topical permethrin and oral ivermectin (23%), oral ivermectin (7%), and other treatments (1%). Our findings suggest that more accurate and faster diagnostic methods are needed to limit unnecessary treatment and expedite appropriate therapy for scabies. © Copyright 2017 by the American Board of Family Medicine.

Human Pulmonary Infection by the Zoonotic Metastrongylus salmi Nematode. The First Reported Case in the Americas.

PubMed

Calvopina, Manuel; Caballero, Henry; Morita, Tatsushi; Korenaga, Masataka

2016-10-05

Pulmonary metastrongylosis, a zoonotic disease found primarily in pigs, is caused by eight different species of the cosmopolitan nematode Metastrongylus genus. To date, only four human cases have been reported, all from Europe. Herein, a severe case of pulmonary infection caused by Metastrongylus salmi in an Ecuadorian man, with successful treatment with ivermectin, is described. © The American Society of Tropical Medicine and Hygiene.

Demodicosis in red-handed tamarins (Saguinus midas).

PubMed

James, S B; Raphael, B L

2000-06-01

Two nonrelated but paired red-handed tamarins (Saguinus midas) presented with diffuse, multifocal, raised, nonpruritic, hyperkeratotic lesions on the appendages and face. Skin biopsies identified acarids and skin scrapings confirmed demodex-like mites. The animals were treated with ivermectin, at the endoparasite dose, which initially resulted in resolution of clinical signs; however, signs recurred after numerous treatments. After four treatments with amitraz dips, demodicosis lesions resolved.

Anthelmintic resistance in gastrointestinal nematodes in goats and evaluation of FAMACHA diagnostic marker in Uganda.

PubMed

Nabukenya, Immaculate; Rubaire-Akiiki, Chris; Olila, Deogracious; Muhangi, Denis; Höglund, Johan

2014-10-15

Gastrointestinal nematodes (GIN) are a challenge to goat production globally causing reduced growth, morbidity and mortality. We report here results of the first nation-wide anthelmintic resistance (AR) study and validation of assessment of clinical anaemia with FAMACHA eye scores in goats in Uganda. From August to December 2012 the efficacy of albendazole (7.5mg/kg), levamisole (10.5mg/kg) and ivermectin (0.3mg/kg) against strongyle nematodes was tested on 33 goat farms in Soroti, Gulu, Mpigi, Mbarara and Ssembabule districts of Uganda. Altogether 497 goats were subjected to a total of 45 different faecal egg count reduction tests (FECRT), each involving 5-20 goats. On one farm all substances were tested. Faecal and blood samples were collected and FAMACHA eye scores evaluated on the day of treatment and 15 days later. A questionnaire survey was conducted on frequency, type and dose of anthelmintics used, farm size and grazing management system. Examination of infective third stage larvae (L3) from pooled faecal cultures demonstrated Haemonchus to be the predominant genus (>75%). Resistance to at least one anthelmintic group was detected on 61% of the 33 farms and in 49% of the 45 test groups. Prevalence of resistance to ivermectin, levamisole and albendazole was respectively 58%, 52% and 38%. Correlation between pre-treatment packed cell volume determinations and FAMACHA scores (r(498) = -0.89) was significant. Paddock grazing system (Odds ratio 4.9, 95% CI 1.4-17.3) and large farm size of >40 goats (odds ratio 4.4, 95% CI 1.2-16.1) were significant predictors of AR. In all districts, resistance to all three anthelmintics was higher on large-scale goat farms practising mostly paddock grazing. Interestingly, resistance to albendazole, the most commonly used anthelmintic in Uganda, was lower than that to ivermectin and levamisole. We recommend adaptation of FAMACHA to goats to help restrict anthelmintic treatment to heavily infected individuals. This will limit

Elimination of onchocerciasis in Ecuador: findings of post-treatment surveillance.

PubMed

Guevara, Ángel; Lovato, Raquel; Proaño, Roberto; Rodriguez-Perez, Mario A; Unnasch, Thomas; Cooper, Philip J; Guderian, Ronald H

2018-04-24

The Esmeraldas focus of onchocerciasis in Ecuador expanded geographically during the 1980s and was associated with severe ocular and skin disease. Mass drug administration (MDA) with ivermectin started in 1991, initially once but later twice a year, in the principle endemic focus followed by all satellite foci. Treatment was stopped in 2009 when entomological assessments determined that transmission of Onchocerca volvulus had been interrupted. Three years after the cessation of ivermectin treatment in 2012, as defined by the WHO guidelines for onchocerciasis elimination, blackfly collections were done in four sentinel sites in former hyperendemic areas. The presence of infective larvae in local vectors, Simulium exiguum and Simulum quadrivittatum, was assessed by detection of O. volvulus DNA by PCR. Additional flies captured in four extra-sentinel sites located in former hyper- and mesoendemic dispersed isolated areas were also assessed. The results from 68,310 captured blackflies, 40,114 from four sentinel villages in the previously hyperendemic areas (Corriente Grande, El Tigre, San Miguel on Río Cayapas and Naranjal on Río Canandé) and 28,197 from extra-sentinel locations, were all negative for the presence of O. volvulus. These extra-sentinel sites (Hualpí on Río Hoja Blanca, Capulí on Río Onzole, La Ceiba on Río Tululví and Medianía on Río Verde) were included to provide additional evidence of the impact of MDA on the transmission of O. volvulus in isolated endemic areas. Our data indicate that transmission of O. volvulus has been stopped in all endemic areas in Ecuador, including all satellite foci outside the main focus. These findings indicate that a strategy of ivermectin distribution twice a year to over 85% of the treatment-eligible population was effective in eliminating the infection from Ecuador in a focus with a highly competent primary vector, S. exiguum, and where the infection rates were equal to or greater than observed in many

21 CFR 520.1198 - Ivermectin and praziquantel paste.

Code of Federal Regulations, 2014 CFR

2014-04-01

...; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral and gastric stages)—Gasterophilus spp...; Hairworms (adults)—Trichostrongylus axei; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral...

21 CFR 520.1198 - Ivermectin and praziquantel paste.

Code of Federal Regulations, 2013 CFR

2013-04-01

...; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral and gastric stages)—Gasterophilus spp...; Hairworms (adults)—Trichostrongylus axei; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral...

21 CFR 520.1193 - Ivermectin tablets and chewables.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Dogs. For use in dogs 6 weeks of age and older as follows: (i) Amount. 6.0 mcg per kilogram (kg) of.... (ii) Indications for use. To prevent canine heartworm disease by eliminating the tissue stage of... for use. To prevent feline heartworm disease by eliminating the tissue stage of heartworm larvae...

21 CFR 520.1193 - Ivermectin tablets and chewables.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Dogs. For use in dogs 6 weeks of age and older as follows: (i) Amount. 6.0 mcg per kilogram (kg) of.... (ii) Indications for use. To prevent canine heartworm disease by eliminating the tissue stage of... for use. To prevent feline heartworm disease by eliminating the tissue stage of heartworm larvae...

21 CFR 520.1193 - Ivermectin tablets and chewables.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Dogs. For use in dogs 6 weeks of age and older as follows: (i) Amount. 6.0 mcg per kilogram (kg) of.... (ii) Indications for use. To prevent canine heartworm disease by eliminating the tissue stage of... for use. To prevent feline heartworm disease by eliminating the tissue stage of heartworm larvae...

21 CFR 520.1197 - Ivermectin sustained-release bolus.

Code of Federal Regulations, 2014 CFR

2014-04-01

... withdrawal time has not been established, do not use in female dairy cattle of breeding age. Do not slaughter cattle within 180 days of treatment. Consult your veterinarian for assistance in the diagnosis, treatment..., and ticks Amblyomma americanum. (3) Limitations. The bolus was specifically designed for use in cattle...

21 CFR 520.1197 - Ivermectin sustained-release bolus.

Code of Federal Regulations, 2011 CFR

2011-04-01

... withdrawal time has not been established, do not use in female dairy cattle of breeding age. Do not slaughter cattle within 180 days of treatment. Consult your veterinarian for assistance in the diagnosis, treatment..., and ticks Amblyomma americanum. (3) Limitations. The bolus was specifically designed for use in cattle...

21 CFR 520.1197 - Ivermectin sustained-release bolus.

Code of Federal Regulations, 2010 CFR

2010-04-01

... withdrawal time has not been established, do not use in female dairy cattle of breeding age. Do not slaughter cattle within 180 days of treatment. Consult your veterinarian for assistance in the diagnosis, treatment..., and ticks Amblyomma americanum. (3) Limitations. The bolus was specifically designed for use in cattle...

21 CFR 520.1197 - Ivermectin sustained-release bolus.

Code of Federal Regulations, 2013 CFR

2013-04-01

... withdrawal time has not been established, do not use in female dairy cattle of breeding age. Do not slaughter cattle within 180 days of treatment. Consult your veterinarian for assistance in the diagnosis, treatment..., and ticks Amblyomma americanum. (3) Limitations. The bolus was specifically designed for use in cattle...

21 CFR 520.1198 - Ivermectin and praziquantel paste.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... cutaneous third-stage larvae; Dermatitis caused by neck threadworm microfilariae, Onchocerca sp. (ii... Draschia spp. cutaneous third-stage larvae; Dermatitis caused by neck threadworm microfilariae, Onchocerca...

21 CFR 520.1198 - Ivermectin and praziquantel paste.

Code of Federal Regulations, 2011 CFR

2011-04-01

...; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral and gastric stages)—Gasterophilus spp...; Hairworms (adults)—Trichostrongylus axei; Large-mouth Stomach Worms (adults)—Habronema muscae; Bots (oral...

Treatment options for demodex blepharitis: patient choice and efficacy.

PubMed

Hirsch-Hoffmann, S; Kaufmann, C; Bänninger, P B; Thiel, M A

2015-04-01

Demodex mites are microscopic parasites that live around hair follicles or sebaceous glands and may cause chronic blepharitis. The aim of this outcome analysis was to assess the efficacy and patient preferences with regard to the currently recommended treatment options. All patients with microscopic evidence for Demodex blepharitis were informed about the currently published treatments and instructed about daily lid hygiene. Additional topical treatment options included tea tree oil (TTO) 5%, a cleansing foam containing 0.02% TTO (Naviblef®), and metronidazole 2% ointment. Systemic treatment options included oral ivermectin 6 mg on day 1 and 14 and metronidazole 500 mg twice daily for 10 days. All patients were reviewed after 2 months for symptoms and for a mite count on 10 epilated lashes. Ninety-four of 96 patients with Demodex blepharitis opted for an additional treatment. The mean mite count after 2 months of treatment were 13.3 with 5% TTO (n=6), 12.0 with 0.02% TTO (n=38), 9.4 with metronidazole ointment (n=5), 12.8 with ivermectin (n=27) and 22.0 with oral metronidazole (n=5). While there are several published treatment options available, none of these options seem to be clearly effective in Demodex blepharitis. Georg Thieme Verlag KG Stuttgart · New York.

Adverse effects of ketoconazole in dogs--a retrospective study.

PubMed

Mayer, Ursula K; Glos, Katharina; Schmid, Matthias; Power, Helen T; Bettenay, Sonya V; Mueller, Ralf S

2008-08-01

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

Immunohistological studies on neoplasms of female and male Onchocerca volvulus: filarial origin and absence of Wolbachia from tumor cells

PubMed Central

BRATTIG, N. W.; HOERAUF, A.; FISCHER, P. U.; LIEBAU, E.; BANDI, C.; DEBRAH, A.; BÜTTNER, M.; BÜTTNER, D. W.

2010-01-01

SUMMARY Up to 5% of untreated female Onchocerca volvulus filariae develop potentially fatal pleomorphic neoplasms, whose incidence is increased following ivermectin treatment. We studied the occurrence of 8 filarial proteins and of Wolbachia endobacteria in the tumor cells. Onchocercomas from patients, untreated and treated with antibiotics and anthelminthics, were examined by immunohistology. Neoplasms were diagnosed in 112 of 3587 female and in 2 of 1570 male O. volvulus. The following proteins and other compounds of O. volvulus were expressed in the cells of the neoplasms: glutathione S-transferase 1, lysosomal aspartic protease, cAMP-dependent protein kinase, alpha-enolase, aspartate aminotransferase, ankyrin E1, tropomyosin, heat shock protein 60, transforming growth factor-beta, and prostaglandin E2. These findings prove the filarial origin of the neoplasms and confirm the pleomorphism of the tumor cells. Signs indicating malignancy of the neoplasms are described. Wolbachia were observed in the hypodermis, oocytes, and embryos of tumor-harbouring filariae using antibodies against Wolbachia surface protein, Wolbachia HtrA-type serine protease, and Wolbachia aspartate aminotransferase. In contrast, Wolbachia were not found in the cells of the neoplasms. Further, neoplasm-containing worms were not observed after more than 10 months after the start of sufficient treatment with doxycycline or doxycycline plus ivermectin. PMID:20199697

Detection of Onchocerca volvulus (Nematoda: Onchocercidae) infection in vectors from Amazonian Brazil following mass Mectizan distribution.

PubMed

Marchon-Silva, Verônica; Caër, Julien Charles; Post, Rory James; Maia-Herzog, Marilza; Fernandes, Octavio

2007-05-01

Detection of Onchocerca volvulus in Simulium populations is of primary importance in the assessment of the effectiveness of onchocerciasis control programs. In Brazil, the main focus of onchocerciasis is in the Amazon region, in a Yanomami reserve. The main onchocerciasis control strategy in Brazil is the semi-annually mass distribution of the microfilaricide ivermectin. In accordance with the control strategy for the disease, polymerase chain reaction (PCR) was applied in pools of simuliids from the area to detect the helminth infection in the vectors, as recommended by the Onchocerciasis Elimination Program for the Americas and the World Health Organization. Systematic sampling was performed monthly from September 1998 to October 1999, and a total of 4942 blackflies were collected from two sites (2576 from Balawaú and 2366 from Toototobi). The molecular methodology was found to be highly sensitive and specific for the detection of infected and/or infective blackflies in pools of 50 blackflies. The results from the material collected under field conditions showed that after the sixth cycle of distribution of ivermectin, the prevalence of infected blackflies with O. volvulus had decreased from 8.6 to 0.3% in Balawaú and from 4 to 0.1% in Toototobi.

Progress toward elimination of onchocerciasis in the Americas - 1993-2012.

PubMed

2013-05-24

Onchocerciasis (river blindness) is caused by the parasitic worm Onchocerca volvulus, transmitted to humans by the bite of infected black flies of the genus Simulium, and is characterized by chronic skin disease, severe itching, and eye lesions that can progress to complete blindness. Currently, among approximately 123 million persons at risk for infection in 38 endemic countries, at least 25.7 million are infected, and 1 million are blinded or have severe visual impairment. Periodic, communitywide mass drug administration (MDA) with ivermectin (Mectizan, Merck) prevents eye and skin disease and might interrupt transmission of the infection, depending on the coverage, duration, and frequency of MDA. The Onchocerciasis Elimination Program for the Americas (OEPA) was launched in response to a 1991 resolution of the Pan American Health Organization (PAHO) calling for the elimination of onchocerciasis from the Americas. By the end of 2012, transmission of the infection, judged by surveys following World Health Organization (WHO) guidelines, had been interrupted or eliminated in four of the six endemic countries in the WHO Americas Region. Thus, in 2013, only 4% (23,378) of the 560,911 persons originally at risk in the Americas will be under ivermectin MDA. Active transmission currently is limited to two foci among Yanomami indigenes in adjacent border areas of Venezuela and Brazil.

Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

PubMed

Dai, Cunchun; Qu, Shaoqi; Zhang, Ruili; Zhao, Li; Li, Yuwen; Zhu, Jiajia; Wang, Chunmei; Guo, Hui; Hao, Zhihui

2018-02-01

The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

Molecular Cloning and Characterization of a P-Glycoprotein from the Diamondback Moth, Plutella xylostella (Lepidoptera: Plutellidae)

PubMed Central

Tian, Lixia; Yang, Jiaqiang; Hou, Wenjie; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Zhou, Xuguo; Wu, Qingjun

2013-01-01

Macrocyclic lactones such as abamectin and ivermectin constitute an important class of broad-spectrum insecticides. Widespread resistance to synthetic insecticides, including abamectin and ivermectin, poses a serious threat to the management of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), a major pest of cruciferous plants worldwide. P-glycoprotein (Pgp), a member of the ABC transporter superfamily, plays a crucial role in the removal of amphiphilic xenobiotics, suggesting a mechanism for drug resistance in target organisms. In this study, PxPgp1, a putative Pgp gene from P. xylostella, was cloned and characterized. The open reading frame (ORF) of PxPgp1 consists of 3774 nucleotides, which encodes a 1257-amino acid peptide. The deduced PxPgp1 protein possesses structural characteristics of a typical Pgp, and clusters within the insect ABCB1. PxPgp1 was expressed throughout all developmental stages, and showed the highest expression level in adult males. PxPgp1 was highly expressed in midgut, malpighian tubules and testes. Elevated expression of PxPgp1 was observed in P. xylostella strains after they were exposed to the abamectin treatment. In addition, the constitutive expressions of PxPgp1 were significantly higher in laboratory-selected and field-collected resistant strains in comparison to their susceptible counterpart. PMID:24264038

Demodex folliculitis mimicking acute graft-vs-host disease.

PubMed

Cotliar, Jonathan; Frankfurt, Olga

2013-12-01

Acute graft-vs-host disease (GVHD) typically requires high-dose systemic steroids as first-line treatment. Like drug eruptions, viral exanthema, and toxic erythema of chemotherapy, Demodex folliculitis is a clinical mimicker of acute GVHD and requires nonimmunosuppressive therapy. This case of Demodex folliculitis mimicking acute GVHD highlights the need for skin biopsy in patients who have undergone a stem cell transplant with eruptions on the head and neck. A 46-year-old white woman with a history of Fms-like tyrosine kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day history of a nonpruritic eruption on her face and neck 28 days after undergoing a double umbilical cord blood hematopoietic stem cell transplant (HSCT). Findings from the skin biopsy demonstrated a deep dermal lymphocytic infiltrate adjacent to follicular units along with an abundance of Demodex mites noted within the hair follicles consistent with Demodex folliculitis. Oral ivermectin, 12 mg, was given, and the eruption cleared within 24 hours. To our knowledge, this is only the fifth reported case of Demodex folliculitis following HSCT, but the first ever reported to be successfully treated with oral ivermectin. Demodex folliculitis should be added to the differential diagnosis of skin eruptions that arise after HSCT.

Evaluation of the biliary and brain distribution of technetium Tc 99m sestamibi in healthy dogs with the ABCB1 wildtype genotype before and after treatment with spinosad.

PubMed

MacKay, Christopher S; Mattoon, John S; Roberts, Gregory D; Tucker, Russell L; Morimoto, Trevor R; Mealey, Katrina L

2012-06-01

To determine whether the reported drug-drug interaction between the flea medication spinosad and ivermectin is attributable to inhibition of P-glycoprotein by spinosad. 6 healthy adult dogs with the ABCB1 wildtype genotype. The study was conducted as a prospective, masked, randomized crossover design. Six dogs were allocated to 2 groups; each dog served as its own control animal. Dogs in one of the groups received spinosad at the manufacturer's recommended dose; the other group received no treatment. Forty-eight hours later, scintigraphic imaging of the head and abdomen were performed with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs in each group received the alternate treatment, and scintigraphic imaging again was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature ratios of technetium Tc 99m sestamibi were calculated for each dog and compared between treatments. No significant differences in gallbladder-to-liver or brain-to-neck musculature ratios were found between treatments. Results provided evidence that spinosad did not inhibit P-glycoprotein function 48 hours after spinosad was administered at the manufacturer's recommended dose. Further investigations will be necessary to elucidate the mechanism of the reported toxic interaction between spinosad and ivermectin.

Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

PubMed

Abdel-Raheem, Talal A; Méabed, Eman M H; Nasef, Ghada A; Abdel Wahed, Wafaa Y; Rohaim, Rania M A

2016-10-01

The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 μg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient.

Field evaluation of the efficacy of common anthelmintics used in the control of gastrointestinal nematodes of sheep in Dabat district, Northwest Ethiopia.

PubMed

Seyoum, Zewdu; Demessie, Yitayew; Bogale, Basazinew; Melaku, Achenef

2017-01-01

Gastrointestinal nematode (GIN) infections are the main impediments that restrict the welfare and productivity of small ruminant in the world. Effective management of GINs in grazing sheep relies heavily on the use of highly efficacious anthelmintic drugs. However, anthelmintic resistance is becoming a significant concern in the world, and this phenomenon severely threatens the potential utilisation of this control strategy. Therefore, this study was conducted 1) to evaluate the efficacy of commonly used anthelmintic on GINs in naturally infected sheep and 2) to assess the farmers' perception on anthelmintics utilisation practices in Dabat district, Northwest Ethiopia. One hundred twenty nematode infected sheep were used in this study. Sheep were selected based on the egg count (≥150 eggs per gram of faeces). The animals were allocated randomly into four groups (30 animals per group). Group-I, II and III were treated with Albendazole, Tetramisole, and Ivermectin, respectively. The 4th group was left untreated (as control). Faecal samples were collected on day 0 (before treatment), on day 3, 7, 10 and 14 (post-treatment). The modified McMaster technique was used for quantifying the eggs. Faecal egg count reduction test (FECRT) was applied to determine the efficacy of anthelmintic at day 14 (post-treatment). In addition, a questionnaire survey was conducted on 100 randomly selected sheep owners. All anthelmintics tested revealed significant ( P  < 0.05) reduction in nematode egg excretion in the sheep post-treatment. Faecal egg count reduction (FECR) levels for Albendazole, Tetramisole, and Ivermectin were 97.2, 98.9 and 97.7%, respectively. Post-treatment egg counts and percentage reduction of egg counts were not significantly different ( P  > 0.05) among the treatment groups. The nematode genera identified before treatment were Haemonchus , Trichostrongylus , Cooperia , Trichuris , Teladorsagia , Bunostomum, and Strongyloides. Haemonchus and

Characterisation of P-glycoprotein-9.1 in Haemonchus contortus.

PubMed

Godoy, Pablo; Che, Hua; Beech, Robin N; Prichard, Roger K

2016-01-28

The existence nematodes of veterinary importance such as Haemonchus contortus resistant to anthelmintic drugs, including the macrocyclic lactones, has become a major concern in animal health. Macrocyclic lactone resistance in H. contortus seems to be multigenic including the active efflux of these drugs by P-glycoproteins, members of the ABC transporter family, present in this parasite. The goals of the present work were to determine the activity of H. contortus P-glycoprotein 9.1 (Hco-PGP-9.1) and its interaction with the avermectins, ivermectin, abamectin, and also the milbemycin, moxidectin. Additionally, the localisation of Hco-PGP-9.1 was sought in adult worms. Hco-Pgp-9.1 was cloned and expressed in mammalian cells and its expression profile was determined at the transcriptional and protein level by qRT-PCR and Western-blot, respectively. The nematode transport activity was assessed using the tracer dye Rhodamine 123. A ligand competition assay between different macrocyclic lactones and Rhodamine 123 was used to establish whether or not there was interaction between Hco-PGP-9.1 and the avermectins (abamectin and ivermectin) or moxidectin. In addition, immunostaining was carried out to localise Hco-PGP-9.1 expression in the transgenic cells and in adult female parasites. Hco-PGP-9.1 was expressed in the cell membrane of the transfected host cells and was able to extrude Rhodamine 123. Ivermectin and abamectin, but not moxidectin, had a pronounced inhibitory effect on the ability of Hco-PGP-9.1 to transport Rhodamine 123. Antibodies raised against Hco-PGP-9.1 epitopes localised to the uterus of adult female H. contortus. These results suggest a strong interaction of the avermectins with Hco-PGP-9.1. However, possibly due to its physico-chemical properties, moxidectin had markedly less effect on Hco-PGP-9.1. Because of the greater interaction of the avermectins than moxidectin with this transporter, it is more likely to contribute to avermectin resistance than

[Norwegian scabies in a pediatric patient with Down syndrome, a case report].

PubMed

Mantero, Natalia M; Jaime, Lorena J; Nijamin, Tamara R; Laffargue, Jorge A; De Lillo, Leonardo; Grees, Susana A

2013-12-01

Norwegian (crusted) scabies is a rare and extreme manifestation of scabies that can be observed mainly among immunosuppressed patients. Due to the high number of scabies mites present in each lesion, crusted scabies symptoms are much more intense than in usual scabies and it is thus highly contagious. A case study of a child with Down syndrome and Norwegian scabies who shows a good response to a treatment combining keratolytics, emollients, ivermectin and topical scabicides is described.

Late-onset onchocercal skin disease among Ethiopian immigrants.

PubMed

Baum, S; Greenberger, S; Pavlotsky, F; Solomon, M; Enk, C D; Schwartz, E; Barzilai, A

2014-11-01

Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 μg mg(-1). Thirteen patients responded to the treatment. Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history. © 2014 British Association of Dermatologists.

Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones as a general cellular response to stress.

PubMed

Jordão, Rita; Campos, Bruno; Lemos, Marco F L; Soares, Amadeu M V M; Tauler, Romà; Barata, Carlos

2016-06-01

Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia magna. Previous results characterized gene transcripts of genes encoding and efflux activities of four putative ABCB1 and ABCC transporters that were chemically induced but showed low specificity against model transporter substrates and inhibitors, thus preventing us from distinguishing between activities of different efflux transporter types. In this study we report on the specificity of induction of ABC transporters and of the stress protein hsp70 in clones selected to be genetically resistant to ABCB1 chemical substrates. Clones resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive transcriptional responses of transporter protein coding genes and of putative transporter dye activities. Expression of hsp70 proteins also varied across resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene transporter and of putative dye transporter activity were also induced to a greater extent in the pentachlorophenol resistant clone. Observed higher dye transporter activities in individuals from clones resistant to mitoxantrone and ivermectin were unrelated with transcriptional levels of the studied four abcc and abcb1 transporter genes. These findings suggest that Abcb1 induction in D. magna may be a part of a general cellular stress response. Copyright © 2016 Elsevier B.V. All rights reserved.

The combined effect of the Lymphatic Filariasis Elimination Programme and the Schistosomiasis and Soil-transmitted Helminthiasis Control Programme on soil-transmitted helminthiasis in schoolchildren in Tanzania.

PubMed

Massa, Khalid; Magnussen, Pascal; Sheshe, Amir; Ntakamulenga, Robert; Ndawi, Benedict; Olsen, Annette

2009-01-01

The combined effect of the Lymphatic Filariasis Elimination Programme (LFEP) and the National Schistosomiasis and Soil-transmitted Helminthiasis Control Programme (NSSCP) on soil-transmitted helminthiasis (STH) was evaluated. In September 2004, before mass drug administration (MDA) with ivermectin and albendazole by the LFEP in October, the prevalence and intensity of STH were recorded in 228 pupils in one primary school. After 8 months, all available pupils were re-examined, and the prevalence of Ascaris lumbricoides, Trichuris trichiura and hookworm had decreased from 0.9 to 0.7% (P=0.84), from 4.8 to 0.7% (P=0.004) and from 45.6 to 11.9% (P<0.001), respectively. Overall, 81.2% of the schoolchildren stated that they were treated by the LFEP in October 2004. After the 8 months follow-up, pupils were treated with praziquantel and albendazole by the present project (substitute for the NSSCP). After another 4 months (at 12 months follow-up), the prevalence of hookworm infection was reduced to 4.8% (P=0.003), while the prevalence of T. trichiura was reduced to 0.3% (P=0.54) and the prevalence of A. lumbricoides remained unchanged. Mass co-administration of ivermectin and albendazole by the LFEP had a significant effect on STH, which was further amplified by treatment with praziquantel and albendazole 4 months later.

Sorption, Leaching, and Surface Runoff of Beef Cattle Veterinary Pharmaceuticals under Simulated Irrigated Pasture Conditions

PubMed Central

Popova, Inna E.; Bair, Daniel A.; Tate, Kenneth W.; Parikh, Sanjai J.

2014-01-01

The use of veterinary pharmaceuticals in beef cattle has led to concerns associated with the development of antibiotic resistance in bacteria and endocrine disruption in aquatic organisms. Despite the potential negative consequences, data on the transport and mitigation of pharmaceuticals in grazed watersheds with irrigated pasture are scarce. The objective of this study was to assess the transport of common beef cattle pharmaceuticals (i.e., oxytetracycline, chlortetracycline, ivermectin) via surface runoff and leachate from manure amended to grass-vegetated soil boxes under irrigated pasture conditions. The transport of pharmaceuticals from animal manure in surface runoff and soil leachate was relatively low and appears to be limited by desorption and transport of pharmaceuticals entrained in the manure. In surface runoff, less than 4.2% of applied pharmaceuticals in manure (initial concentration: 0.2 mg kg−1 of manure) were detected after three weeks of irrigation. Concentrations of pharmaceuticals in surface runoff and leachate never exceeded 0.5 µg L−1. The major portion of pharmaceuticals (up to 99%) was retained in the manure or in the soil directly beneath the manure application site. Based on the minimal transport of oxytetracycline, chlortetracycline, and ivermectin, the risk of significant transport for these targeted beef cattle pharmaceuticals to surface water and groundwater from manure on irrigated pasture appears to be relatively low. PMID:24216368

Prediction of community prevalence of human onchocerciasis in the Amazonian onchocerciasis focus: Bayesian approach.

PubMed

Carabin, Hélène; Escalona, Marisela; Marshall, Clare; Vivas-Martínez, Sarai; Botto, Carlos; Joseph, Lawrence; Basáñez, María-Gloria

2003-01-01

To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the factors that influence prevalence of microfilariae in the Amazonian focus of onchocerciasis and predict the probability of any community being at least mesoendemic (>20% prevalence of microfilariae), and thus in need of priority ivermectin treatment. Models were developed with data from 732 individuals aged > or =15 years who lived in 29 Yanomami communities along four rivers of the south Venezuelan Orinoco basin. The models' abilities to predict prevalences of microfilariae in communities were compared. The deviance information criterion, Bayesian P-values, and residual values were used to select the best model with an approximate cross-validation procedure. A three-level model that acknowledged clustering of infection within communities performed best, with host age and sex included at the individual level, a river-dependent altitude effect at the community level, and additional clustering of communities along rivers. This model correctly classified 25/29 (86%) villages with respect to their need for priority ivermectin treatment. Bayesian methods are a flexible and useful approach for public health research and control planning. Our model acknowledges the clustering of infection within communities, allows investigation of links between individual- or community-specific characteristics and infection, incorporates additional uncertainty due to missing covariate data, and informs policy decisions by predicting the probability that a new community is at least mesoendemic.

Facial Dermatitis and Rosacea.

PubMed

Fowler, Joseph F

2016-06-01

Rosacea is a chronic skin disorder associated with flushing, erythema, dryness, burning and stinging, and inflammatory papules and pustules. New treatments available or in development target the inflammatory and erythematous components of the disease. These agents include the selective α2 receptor agonist brimonidine, the topical agents ivermectin cream 1% and azelaic acid foam 15%, and use of tetracyclinetype antibiotics, which affect the cathelicidin pathway. Semin Cutan Med Surg 35(supp6):S107-S109. 2016 published by Frontline Medical Communications.

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (b) Sponsors. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1... disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for 1 month (30 days...

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... heartworm disease caused by Dirofilaria immitis in adult dogs. (3) Limitations. Federal law restricts this... § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer tablets to provide 6...

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... heartworm disease caused by Dirofilaria immitis in adult dogs. (3) Limitations. Federal law restricts this... § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer tablets to provide 6...

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... (b) Sponsors. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1... disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for 1 month (30 days...

21 CFR 520.1199 - Ivermectin, pyrantel, and praziquantel tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (b) Sponsors. See No. 051311 in § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1... disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for 1 month (30 days...

21 CFR 520.1200 - Ivermectin, fenbendazole, and praziquantel tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... heartworm disease caused by Dirofilaria immitis in adult dogs. (3) Limitations. Federal law restricts this... § 510.600(c) of this chapter. (c) Conditions of use in dogs—(1) Amount. Administer tablets to provide 6...

Rapid Suppression of Onchocerca volvulus Transmission in Two Communities of the Southern Chiapas Focus, Mexico, Achieved by Quarterly Treatments with Mectizan

PubMed Central

Rodríguez-Pérez, Mario A.; Lutzow-Steiner, Miguel A.; Segura-Cabrera, Aldo; Lizarazo-Ortega, Cristian; Domínguez-Vázquez, Alfredo; Sauerbrey, Mauricio; Richards, Frank; Unnasch, Thomas R.; Hassan, Hassan K.; Hernández-Hernández, Raymundo

2008-01-01

The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission. PMID:18689630

Galactolipids from Bauhinia racemosa as a new class of antifilarial agents against human lymphatic filarial parasite, Brugia malayi.

PubMed

Sashidhara, Koneni V; Singh, Suriya P; Misra, Sweta; Gupta, Jyoti; Misra-Bhattacharya, Shailja

2012-04-01

Bioassay guided fractionation of ethanolic extract of the leaves of Bauhinia racemosa led to the isolation of galactolipid and catechin class of the compounds (1-7) from the most active n-butanol fraction (F4). Among the active galactolipids, 1 emerged as the lead molecule which was active on both forms of lymphatic filarial parasite, Brugia malayi. It was found to be better than the standard drug ivermectin and diethylcarbamazine (DEC) in terms of dose and efficacy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The Molecular Determinants of Small-Molecule Ligand Binding at P2X Receptors

PubMed Central

Pasqualetto, Gaia; Brancale, Andrea; Young, Mark T.

2018-01-01

P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP—their physiological ligand—is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo- state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators. P2X receptors are attractive drug targets, and a wide array of potent, subtype-selective modulators (mostly antagonists) have been developed. In 2016, crystal structures of human P2X3 in complex with the competitive antagonists TNP-ATP and A-317491, and Ailuropoda melanoleuca P2X7 in complex with a series of allosteric antagonists were published, giving fascinating insights into the mechanism of channel antagonism. In this article we not only summarize current understanding of small-molecule modulator binding at P2X receptors, but also use this information in combination with previously published structure-function data and molecular docking experiments, to hypothesize a role for the dorsal fin loop region in differential ATP potency, and describe novel, testable binding conformations for both the semi-selective synthetic P2X7 agonist 2′-(3′)-O-(4-benzoyl)benzoyl ATP (BzATP), and the P2X4-selective positive allosteric modulator ivermectin. We find that the distal benzoyl group of BzATP lies in close proximity to Lys-127, a residue previously implicated in BzATP binding to P2X7, potentially explaining the increased potency of BzATP at rat P2X7 receptors. We also present molecular docking of ivermectin to rat P2X4 receptors, illustrating a plausible

Important progress towards elimination of onchocerciasis in the West Region of Cameroon.

PubMed

Kamga, Guy-Roger; Dissak-Delon, Fanny N; Nana-Djeunga, Hugues C; Biholong, Benjamin D; Ghogomu, Stephen Mbigha; Souopgui, Jacob; Kamgno, Joseph; Robert, Annie

2017-08-03

After more than a decade of community-directed treatment with ivermectin (CDTI) in the West Region of Cameroon, epidemiological evaluation conducted in 2011 showed that onchocerciasis endemicity was still high in some communities. The conceptual framework for onchocerciasis elimination recommends in such case, to conduct additional phase 1A surveys at intervals of three to four years. Therefore, to assess the progress made towards the elimination of onchocerciasis in the West CDTI projects, we conducted a cross-sectional survey in May 2015 in 15 unevaluated communities where the highest baseline endemicity level were found in 1996. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual adherence to ivermectin treatment was also assessed. Analyses of data were weighted proportionally to age and gender distribution in the population. The mean age was 28.4 ± 22.2 years and there were 55% of women among the 2058 individuals examined. The weighted prevalences were 5.5%, 2.1% and 1.7% for microfilaridermia, nodule and cutaneous signs, respectively. The weighted microfilaridermia prevalences varied from 4.0 in 5-9 years old to 11.6% in 40-49 years old. In the 30 children under 10 years examined in Makouopsap, the weighted prevalences were 49.9% for microfilaridermia and 13.3% for nodule. In surveyed communities, the weighted prevalences varied from 0 to 41.6% for microfilaridermia, with 11 (73.3%) communities having <5%. Except Makouopsap which had 41.6%, all the surveyed communities were below 15% for microfilaridermia prevalence. The community microfilarial load (CMFL) expressed in microfilariae/skin snip (mf/ss), also significantly dropped by 98-100%, from 3.75-33.16 mf/ss in 1996 to 0-0.94 mf/ss in 2015. The weighted therapeutic coverage in 2014 was 69.4% and the 5 years' adherence was only 39.3% among participants. After more than 15 years of CDTI, there is

Extracts of Euphorbia hirta Linn. (Euphorbiaceae) and Rauvolfia vomitoria Afzel (Apocynaceae) demonstrate activities against Onchocerca volvulus microfilariae in vitro.

PubMed

Attah, Simon K; Ayeh-Kumi, Patrick F; Sittie, Archibald A; Oppong, Isaac V; Nyarko, Alexander K

2013-03-18

Onchocerciasis transmitted by Onchocerca volvulus is the second major cause of blindness in the world and it impacts negatively on the socio-economic development of the communities affected. Currently, ivermectin, a microfilaricidal drug is the only drug recommended for treating this disease. There have been speculations, of late, concerning O. volvulus resistance to ivermectin. Owing to this, it has become imperative to search for new drugs. World-wide, ethnomedicines including extracts of Euphorbia hirta and Rauvolfia vomitoria are used for treating various diseases, both infectious and non-infectious. In this study extracts of the two plants were evaluated in vitro in order to determine their effect against O. volvulus microfilariae. The toxicity of the E. hirta extracts on monkey kidney cell (LLCMK2) lines was also determined. The investigations showed that extracts of both plants immobilised microfilariae at different levels in vitro and, therefore, possess antifilarial properties. It was found that all the E. hirta extracts with the exception of the hexane extracts were more effective than those of R. vomitoria. Among the extracts of E. hirta the ethyl acetate fraction was most effective, and comparable to that of dimethanesulphonate salt but higher than that of Melarsoprol (Mel B). However, the crude ethanolic extract of E. hirta was found to be the least toxic to the LLCMK2 compared to the fractionated forms. Extracts from both plants possess antifilarial properties; however, the crude extract of E. hirta was found to be least toxic to LLCMK2.

Prediction of community prevalence of human onchocerciasis in the Amazonian onchocerciasis focus: Bayesian approach.

PubMed Central

Carabin, Hélène; Escalona, Marisela; Marshall, Clare; Vivas-Martínez, Sarai; Botto, Carlos; Joseph, Lawrence; Basáñez, María-Gloria

2003-01-01

OBJECTIVE: To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the factors that influence prevalence of microfilariae in the Amazonian focus of onchocerciasis and predict the probability of any community being at least mesoendemic (>20% prevalence of microfilariae), and thus in need of priority ivermectin treatment. METHODS: Models were developed with data from 732 individuals aged > or =15 years who lived in 29 Yanomami communities along four rivers of the south Venezuelan Orinoco basin. The models' abilities to predict prevalences of microfilariae in communities were compared. The deviance information criterion, Bayesian P-values, and residual values were used to select the best model with an approximate cross-validation procedure. FINDINGS: A three-level model that acknowledged clustering of infection within communities performed best, with host age and sex included at the individual level, a river-dependent altitude effect at the community level, and additional clustering of communities along rivers. This model correctly classified 25/29 (86%) villages with respect to their need for priority ivermectin treatment. CONCLUSION: Bayesian methods are a flexible and useful approach for public health research and control planning. Our model acknowledges the clustering of infection within communities, allows investigation of links between individual- or community-specific characteristics and infection, incorporates additional uncertainty due to missing covariate data, and informs policy decisions by predicting the probability that a new community is at least mesoendemic. PMID:12973640

A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

PubMed

Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

2015-04-01

Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

Sorption, Leaching, and Surface Runoff of Beef Cattle Veterinary Pharmaceuticals under Simulated Irrigated Pasture Conditions.

PubMed

Popova, Inna E; Bair, Daniel A; Tate, Kenneth W; Parikh, Sanjai J

2013-07-01

The use of veterinary pharmaceuticals in beef cattle has led to concerns associated with the development of antibiotic resistance in bacteria and endocrine disruption in aquatic organisms. Despite the potential negative consequences, data on the transport and mitigation of pharmaceuticals in grazed watersheds with irrigated pasture are scarce. The objective of this study was to assess the transport of common beef cattle pharmaceuticals (oxytetracycline, chlortetracycline, and ivermectin) via surface runoff and leachate from manure amended to grass-vegetated soil boxes under irrigated pasture conditions. The transport of pharmaceuticals from animal manure in surface runoff and soil leachate was relatively low and appears to be limited by desorption and transport of pharmaceuticals entrained in the manure. In surface runoff, less than 4.2% of applied pharmaceuticals in manure (initial concentration: 0.2 mg kg of manure) was detected after 3 wk of irrigation. Concentrations of pharmaceuticals in surface runoff and leachate never exceeded 0.5 μg L. The major portion of pharmaceuticals (up to 99%) was retained in the manure or in the soil directly beneath the manure application site. Based on the minimal transport of oxytetracycline, chlortetracycline, and ivermectin, the risk of significant transport for these targeted beef cattle pharmaceuticals to surface water and groundwater from manure on irrigated pasture appears to be relatively low. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Lagochilascariasis leading to severe involvement of ocular globes, ears and meninges.

PubMed

Aquino, Renata T R; Magliari, Maria E R; Vital Filho, José; Silva, Maria A L G; Lima, Carlos A da Conceição; Rocha, Antonio J; Silva, Carlos J; Rewin, Jonathan A; Nahas, Tatiana R; Chieffi, Pedro Paulo

2008-01-01

A case report of a 31 year-old woman from Paraíba State (North-Eastern Brazil) that presented severe involvement of ocular globes, ears and meninges. Diagnosis was established after enucleation of her left eye, when adult worms were seen in the midst of a granulomatous inflammatory process. Her response to the initial treatment with levamisole and cambendazole was good, but there was a relapse after the fifth month of treatment even with maintenance doses of both medications. She later received ivermectin and albendazol and responded well.

The onchocerciasis chronicle: from the beginning to the end?

PubMed

Crump, Andy; Morel, Carlos M; Omura, Satoshi

2012-07-01

The year 2012 marks the 25th anniversary of the donation of ivermectin to fight onchocerciasis and the projected date for elimination of transmission of the disease in the Americas. This review looks at the history of onchocerciasis, from its discovery through to 2025, by which time it is projected that the disease will have been eliminated as a public health problem, except in a handful of sub-Saharan countries, where it should be well on the way towards elimination. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Review of the Pharmacology and Clinical Uses of Ivermectin

PubMed Central

Barragry, Thomas B.

1987-01-01

The avermectins were introduced in 1981 and constitute a potent new class of anthelmintic agents. They are naturally-derived products of microbial action displaying an exceptionally wide range of antiparasitic efficacy against internal and external parasites of domestic animals. This paper reviews their isolation and chemistry, mechanism of action, chemical efficacy and safety in cattle, sheep, swine, horses and dogs. PMID:17422843

Extracts of Euphorbia hirta Linn. (Euphorbiaceae) and Rauvolfia vomitoria Afzel (Apocynaceae) demonstrate activities against Onchocerca volvulus Microfilariae in vitro

PubMed Central

2013-01-01

Background Onchocerciasis transmitted by Onchocerca volvulus is the second major cause of blindness in the world and it impacts negatively on the socio-economic development of the communities affected. Currently, ivermectin, a microfilaricidal drug is the only drug recommended for treating this disease. There have been speculations, of late, concerning O. volvulus resistance to ivermectin. Owing to this, it has become imperative to search for new drugs. World-wide, ethnomedicines including extracts of Euphorbia hirta and Rauvolfia vomitoria are used for treating various diseases, both infectious and non-infectious. Method In this study extracts of the two plants were evaluated in vitro in order to determine their effect against O. volvulus microfilariae. The toxicity of the E. hirta extracts on monkey kidney cell (LLCMK2) lines was also determined. Results The investigations showed that extracts of both plants immobilised microfilariae at different levels in vitro and, therefore, possess antifilarial properties. It was found that all the E. hirta extracts with the exception of the hexane extracts were more effective than those of R. vomitoria. Among the extracts of E. hirta the ethyl acetate fraction was most effective, and comparable to that of dimethanesulphonate salt but higher than that of Melarsoprol (Mel B). However, the crude ethanolic extract of E. hirta was found to be the least toxic to the LLCMK2 compared to the fractionated forms. Conclusions Extracts from both plants possess antifilarial properties; however, the crude extract of E. hirta was found to be least toxic to LLCMK2. PMID:23506674

Electron Microscopic Alterations in Pediculus humanus capitis Exposed to Some Pediculicidal Plant Extracts

PubMed Central

Akkad, Dina M. H. El; El-Gebaly, Naglaa Saad M.; Yousof, Hebat-Allah Salah A.; Ismail, Mousa A. M.

2016-01-01

Head lice, Pediculus humanus capitis, infestation is an important public health problem in Egypt. Inadequate application of topical pediculicides and the increasing resistance to the commonly used pediculicides made the urgent need for the development of new agents able to induce irreversible changes in the exposed lice leading to their mortality. The aim of the present work is to evaluate pediculicidal efficacy of some natural products such as olive oil, tea tree oil, lemon juice, and ivermectin separately in comparison with tetramethrin-piperonyl butoxide (licid), as a standard pediculicide commonly used in Egypt. The effects of these products were evaluated by direct observation using dissecting and scanning electron microscopes (SEM). Results showed that after 1 hr exposure time in vitro, absolute (100%) mortalities were recorded after exposure to 1% ivermectin and fresh concentrate lemon juice. The mortalities were decreased to 96.7% after exposure to tea tree oil. Very low percentage of mortality (23.3%) was recorded after 1 hr of exposure to extra virgin olive oil. On the other hand, the reference pediculicide (licid) revealed only mortality rate of 93.3%. On the contrary, no mortalities were recorded in the control group exposed to distilled water. By SEM examination, control lice preserved outer smooth architecture, eyes, antenna, respiratory spiracles, sensory hairs, and legs with hook-like claws. In contrast, dead lice which had been exposed to pediculicidal products showed damage of outer smooth architecture, sensory hairs, respiratory spiracles and/or clinching claws according to pediculicidal products used. PMID:27658606

Multiple resistance to acaricides in field populations of Rhipicephalus microplus from Rio Grande do Sul state, Southern Brazil.

PubMed

Klafke, Guilherme; Webster, Anelise; Dall Agnol, Bruno; Pradel, Endrigo; Silva, Jeniffer; de La Canal, Luiz Henrique; Becker, Marcelo; Osório, Mateus Felipe; Mansson, Melanie; Barreto, Rafael; Scheffer, Ramon; Souza, Ugo Araújo; Corassini, Vivian Bamberg; Dos Santos, Julsan; Reck, José; Martins, João Ricardo

2017-01-01

Acaricide resistance is a major obstacle to the control of Rhipicephalus microplus. Historically, the indiscriminate use of chemical compounds has contributed to the selection of populations resistant to different classes of acaricides. Therefore, multiple acaricide resistance is an important threat to the chemical control of the cattle tick. To investigate the occurrence and extent of multiple resistance to acaricides in Southern Brazil we performed larval tests with cypermethrin, chlorpyriphos, amitraz, fipronil and ivermectin on 104 cattle tick field samples from different ranches in Rio Grande do Sul, between the years 2013 and 2015. Adult immersion tests with a commercial formulation mixture of chlorpyriphos and cypermethrin were performed on 75 samples. Four levels of resistance were established according to the mortality of larvae: Level I: mortality between 82% and 95%; Level II: mortality between 57% and 82%; Level III: mortality between 25% and 57%; and Level IV: mortality lower than 25%. Resistance to cypermethrin was detected in 98.08% of the samples evaluated, mostly at resistance level IV. The frequency of samples resistant to amitraz, chlorpyriphos, ivermectin and fipronil was 76.92%, 60.58%, 60.58% and 53.85% respectively. Multiple resistance to three or more compounds was found in 78.85% of the samples. The results obtained in this study are alarming and reveal a new scenario for the challenge of tick control using chemicals. This is an issue of high importance to cattle production systems where this tick is responsible for a high economic impact. Copyright © 2016 Elsevier GmbH. All rights reserved.

DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis.

PubMed

Yin, Jinlong; Park, Gunwoo; Lee, Jeong Eun; Choi, Eun Young; Park, Ju Young; Kim, Tae-Hoon; Park, Nayun; Jin, Xiong; Jung, Ji-Eun; Shin, Daye; Hong, Jun Hee; Kim, Hyunggee; Yoo, Heon; Lee, Seung-Hoon; Kim, Youn-Jae; Park, Jong Bae; Kim, Jong Heon

2015-09-01

Upregulation of microRNA-21 (miR-21) is known to be strongly associated with the proliferation, invasion, and radio-resistance of glioma cells. However, the regulatory mechanism that governs the biogenesis of miR-21 in glioma is still unclear. Here, we demonstrate that the DEAD-box RNA helicase, DDX23, promotes miR-21 biogenesis at the post-transcriptional level. The expression of DDX23 was enhanced in glioma tissues compared to normal brain, and expression level of DDX23 was highly associated with poor survival of glioma patients. Specific knockdown of DDX23 expression suppressed glioma cell proliferation and invasion in vitro and in vivo, which is similar to the function of miR-21. We found that DDX23 increased the level of miR-21 by promoting primary-to-precursor processing of miR-21 through an interaction with the Drosha microprocessor. Mutagenesis experiments critically demonstrated that the helicase activity of DDX23 was essential for the processing (cropping) of miR-21, and we further found that ivermectin, a RNA helicase inhibitor, decreased miR-21 levels by potentially inhibiting DDX23 activity and blocked invasion and cell proliferation. Moreover, treatment of ivermectin decreased glioma growth in mouse xenografts. Taken together, these results suggest that DDX23 plays an essential role in glioma progression, and might thus be a potential novel target for the therapeutic treatment of glioma. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Strategies and tools for the control/elimination of lymphatic filariasis.

PubMed Central

Ottesen, E. A.; Duke, B. O.; Karam, M.; Behbehani, K.

1997-01-01

Lymphatic filariasis infects 120 million people in 73 countries worldwide and continues to be a worsening problem, especially in Africa and the Indian subcontinent. Elephantiasis, lymphoedema, and genital pathology afflict 44 million men, women and children; another 76 million have parasites in their blood and hidden internal damage to their lymphatic and renal systems. In the past, tools and strategies for the control of the condition were inadequate, but over the last 10 years dramatic research advances have led to new understanding about the severity and impact of the disease, new diagnostic and monitoring tools, and, most importantly, new treatment tools and control strategies. The new strategy aims both at transmission control through community-wide (mass) treatment programmes and at disease control through individual patient management. Annual single-dose co-administration of two drugs (ivermectin + diethylcarbamazine (DEC) or albendazole) reduces blood microfilariae by 99% for a full year; even a single dose of one drug (ivermectin or DEC) administered annually can result in 90% reductions; field studies confirm that such reduction of microfilarial loads and prevalence can interrupt transmission. New approaches to disease control, based on preventing bacterial superinfection, can now halt or even reverse the lymphoedema and elephantiasis sequelae of filarial infection. Recognizing these remarkable technical advances, the successes of recent control programmes, and the biological factors favouring elimination of this infection, the Fiftieth World Health Assembly recently called on WHO and its Member States to establish as a priority the global elimination of lymphatic filariasis as a public health problem. PMID:9509621

Norwegian crusted scabies: an unusual case presentation.

PubMed

Maghrabi, Michael M; Lum, Shireen; Joba, Ameha T; Meier, Molly J; Holmbeck, Ryan J; Kennedy, Kate

2014-01-01

Scabies is a contagious condition that is transmitted through direct contact with an infected person and has been frequently associated with institutional and healthcare-facility outbreaks. The subtype Norwegian crusted scabies can masquerade as other dermatologic diseases owing to the heavy plaque formation. Successful treatment has been documented in published reports, including oral ivermectin and topical permethrin. Few case studies documenting the treatment of Norwegian crusted scabies have reported the use of surgical debridement as an aid to topical and/or oral treatment when severe plaque formation has been noted. A nursing home patient was admitted to the hospital for severe plaque formation of both feet. A superficial biopsy was negative for both fungus and scabies because of the severity of the plaque formation on both feet. The patient underwent a surgical, diagnostic biopsy of both feet, leading to the diagnosis of Norwegian crusted scabies. A second surgical debridement was then performed to remove the extensive plaque formation and aid the oral ivermectin and topical permethrin treatment. The patient subsequently made a full recovery and was discharged back to the nursing home. At 2 and 6 months after treatment, the patient remained free of scabies infestation, and the surgical wound had healed uneventfully. The present case presentation has demonstrated that surgical debridement can be complementary to the standard topical and oral medications in the treatment of those with Norwegian crusted scabies infestation. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models

PubMed Central

Stolk, Wilma A; Prada, Joaquin M; Smith, Morgan E; Kontoroupis, Periklis; de Vos, Anneke S; Touloupou, Panayiota; Irvine, Michael A; Brown, Paul; Subramanian, Swaminathan; Kloek, Marielle; Michael, E; Hollingsworth, T Deirdre; de Vlas, Sake J

2018-01-01

Abstract Background With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. Methods We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Results Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Conclusions Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies. PMID:29860286

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models.

PubMed

Stolk, Wilma A; Prada, Joaquin M; Smith, Morgan E; Kontoroupis, Periklis; de Vos, Anneke S; Touloupou, Panayiota; Irvine, Michael A; Brown, Paul; Subramanian, Swaminathan; Kloek, Marielle; Michael, E; Hollingsworth, T Deirdre; de Vlas, Sake J

2018-06-01

With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

Short communication: Macrocyclic lactone residues in butter from Brazilian markets.

PubMed

Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte

2015-06-01

Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Cephenemyia stimulator and Hypoderma diana infection of roe deer in the Czech Republic over an 8-year period.

PubMed

Salaba, Ondrej; Vadlejch, Jaroslav; Petrtyl, Miloslav; Valek, Petr; Kudrnacova, Marie; Jankovska, Ivana; Bartak, Miroslav; Sulakova, Hana; Langrova, Iva

2013-04-01

A survey of naso-pharyngeal and subcutaneous myiasis affecting roe deer (Capreolus capreolus) was conducted in the Czech Republic over an 8-year period (1999-2006). A total of 503 bucks and 264 does from six hunting localities were examined. The sampling area comprised predominantly agricultural lowlands and a mountain range primarily covered by forest. Since 1997, the deer have been treated each winter across the board with ivermectin (150 mg/kg, CERMIX® pulvis, Biopharm, CZ). Parasites found were the larvae of Hypoderma diana and Cephenemyia stimulator. There were no significant differences in warble fly infection among captured animals in the individual hunting localities. Overall, 146 (28.8%) of 503 animals (bucks) were infected with Cephenemyia stimulator larvae; body size of the second instar larva reached 13-18 mm. The prevalence ranged from 16.1 to 42.9% per year, and the mean intensity from 6 to 11 larvae per animal. Additionally, a total of 264 roe deer (does) were examined for H. diana larvae, and 77 (29.1%) were found to be positive; body size of the second instar larva reached 17 mm. The prevalence ranged from 18.8 to 50.0% per year, and the mean intensity from 13 to 22 larvae per animal. The results showed that the bot flies, Cephenemyia stimulator as well as H. diana, are common parasites in roe deer in the Czech Republic, and that through the help of treatment (ivermectin), it is possible to keep parasite levels low. The body weights of infected and non-infected H. diana deer did not differ significantly.

Enterobius vermicularis: an unusual cause of recurrent urinary tract infestation in a 7-year-old girl: case report and review of the literature.

PubMed

Patel, Bhupeshwari; Sharma, Tanya; Bhatt, Girish Chandra; Dhingra Bhan, Bhavna

2015-04-01

Enterobius vermicularis, the pinworm, is one of the most prevalent intestinal parasites in the world. Ectopic infestations in the genital or urinary tracts rarely occur and chronic enterobiasis of the urinary tract has rarely been reported. Here we present such a case in a 7-year-old girl presenting with fever, pain in the abdomen, vomiting and burning micturition. Ultrasonography and micturating cystourethrogram (MCU) studies were normal. The ova were demonstrated from both the patient's urine and stool specimen. This child was treated successfully with Albendazole and Ivermectin. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Extensive cutaneous larva migrans with folliculitis mimicking multimetameric herpes zoster presentation in an adult traveler returning from Thailand.

PubMed

Malvy, Denis; Ezzedine, Khaled; Pistone, Thierry; Receveur, Marie-Catherine; Longy-Boursier, Maïté

2006-01-01

Hookworm-related cutaneous larva migrans (CLM) is a frequent cutaneous disease among travelers returning from the tropics. It can be misdiagnosed or treated incorrectly. We present a 42-year-old French patient who contracted the disease during a holiday in Thailand and who experienced an extensive CLM syndrome with a less frequent abdominal localization and a pseudo-multimetameric homolateral topography. The condition was late diagnosed and secondarily efficiently cured by a unique administration of ivermectin. Simple anamnestic information--often revealing beach activities--and clinical aspect of the creeping eruption allow to prevent diagnosis delay and to avoid aggressive or inadequate intervention.

Potential vectors of loiasis and other tabanids on the island of Bioko, Equatorial Guinea.

PubMed

Cheke, R A; Mas, J; Chainey, J E

2003-06-01

The biting flies Chrysops dimidiatus Wulp and C.silaceus Austen (Diptera: Tabanidae), vectors of Loa loa (Cobbold) (Nematoda: Onchocercidae) on the African mainland, were found to be widespread on the island of Bioko (Equatorial Guinea) during 1996-2001. These tabanids were particularly prevalent in the southern part of Bioko, indicating potential transmission of loiasis on the island. The only other tabanids previously recorded on Bioko, Tabanus argenteus Surcouf (from 1915) and Haematopota near heptagramma Speiser (from 1933), were also collected. The possibility of loiasis being endemic on Bioko contra-indicates ivermectin treatment of onchocerciasis cases, due to risks of adverse side-effects.

Long-Lasting Insecticidal Nets Are Synergistic with Mass Drug Administration for Interruption of Lymphatic Filariasis Transmission in Nigeria

PubMed Central

Eigege, Abel; Miri, Emmanuel; Sallau, Adamu; Umaru, John; Mafuyai, Hayward; Chuwang, Yohanna S.; Danjuma, Goshit; Danboyi, Jacob; Adelamo, Solomon E.; Mancha, Bulus S.; Okoeguale, Bridget; Patterson, Amy E.; Rakers, Lindsay; Richards, Frank O.

2013-01-01

In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission. PMID:24205421

Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

PubMed

Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

2015-08-15

Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult

Effects of Insecticides on the Fluidity of Mitochondrial Membranes of the Diamondback Moth, Plutella xylostella, Resistant and Susceptible to Avermectin

PubMed Central

Hu, J.; Liang, P.; Shi, X.; Gao, X.

2008-01-01

The effects of various insecticides on the fluidity of mitochondrial membranes and cross-resistance were investigated in the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae) using strains that were both resistant and susceptible to avermectin. The resistant strain of P. xylostella, AV-R, developed 1078-fold resistance to avermetins with a high level of cross-resistance to the analogs of avermectins, ivermectin and emamectin benzoate. It had more than 1000 times greater resistance when compared with the avermectin-susceptible strain, XH-S. Mitochondrial membrane fluidity was measured by detecting fluorescence polarization using DPH (1,6-Diphenyl -1,3,5-hexatriene) as the fluorescence probe. Abamectin, emamectin benzoate, ivermectin, cypermethrin and fenvalerate decreased the fluidity of mitochondrial membranes in the XH-S strain at 25°C. However, fipronil and acephate did not change the fluidity of mitochondrial membrane when the concentration of these insecticides was 1×10-4 mol/L. Membrane fluidity increased as the temperature increased. The thermotropic effect on the polarization value of DPH increased as the insecticide concentration was increased. There was a significant difference of mitochondrial membrane fluidity between both XH-S and AV-R when temperature was less than 25°C and no difference was observed when the temperature was more than 25°C. The low-dose abamectin (0.11 mg/L) in vivo treatment caused a significant change of membrane fluidity in the XH-S strain and no change in the AV-R strain. However, a high-dose abamectin (11.86 mg/L) resulted in 100% mortality of the XH-S strain. In vivo treatment may cause a significant change of membrane fluidity in the AV-R strain PMID:20345311

A novel rapid test for detecting antibody responses to Loa loa infections.

PubMed

Pedram, Bijan; Pasquetto, Valérie; Drame, Papa M; Ji, Yongchang; Gonzalez-Moa, Maria J; Baldwin, Richard K; Nutman, Thomas B; Biamonte, Marco A

2017-07-01

Ivermectin-based mass drug administration (MDA) programs have achieved remarkable success towards the elimination of onchocerciasis and lymphatic filariasis. However, their full implementation has been hindered in Central Africa by the occurrence of ivermectin-related severe adverse events (SAEs) in a subset of individuals with high circulating levels of Loa loa microfilariae. Extending MDA to areas with coincident L. loa infection is problematic, and inexpensive point-of-care tests for L. loa are acutely needed. Herein, we present a lateral flow assay (LFA) to identify subjects with a serological response to Ll-SXP-1, a specific and validated marker of L. loa. The test was evaluated on serum samples from patients infected with L. loa (n = 109) and other helminths (n = 204), as well as on uninfected controls (n = 77). When read with the naked eye, the test was 94% sensitive for L. loa infection and was 100% specific when sera from healthy endemic and non-endemic controls or from those with S. stercoralis infections were used as the comparators. When sera of patients with O. volvulus, W. bancrofti, or M. perstans were used as the comparators, the specificity of the LFA was 82%, 87%, and 88%, respectively. A companion smartphone reader allowed measurement of the test line intensities and establishment of cutoff values. With a cutoff of 600 Units, the assay sensitivity decreased to 71%, but the specificity increased to 96% for O. volvulus, 100% for W. bancrofti, and 100% for M. perstans-infected individuals. The LFA may find applications in refining the current maps of L. loa prevalence, which are needed to eliminate onchocerciasis and lymphatic filariasis from the African continent.

Dermatological manifestations in onchocerciasis: A retrospective study of 400 imported cases.

PubMed

Puente, Sabino; Ramirez-Olivencia, German; Lago, Mar; Subirats, Mercedes; Perez-Blazquez, Eugenio; Bru, Fernando; Garate, Teresa; Vicente, Belén; Belhassen-Garcia, Moncef; Muro, Antonio

2017-12-20

Onchocerciasis is caused by Onchocerca volvulus and mainly leads to pruritus and skin and visual disorders, including blindness. Seventeen million people are infected in 38 countries; 31 of these are in sub-Saharan Africa, six in Latin America and one on the Arabian Peninsula. More than 99% of cases occur in sub-Saharan Africa where 120 million people are at risk of infection. Eye disorders have been well-documented; however, skin disorders have not been described accurately. The objective of our study was to describe the epidemiology, main skin manifestations and treatment of imported onchocerciasis. A retrospective study was thus conducted by analysing the main demographic, clinical and treatment data regarding a cohort of 400 patients attending a reference clinical unit over a 17-year period. Most patients were female (55%) with mean age 37.5±16.7 years. All the migrants came from sub-Saharan countries. The most frequently occurring dermatological symptom was pruritus. Ivermectin had been used as first-line therapy and adverse reactions had been described in 11 patients (3.2%). The results indicate the fact that there should be a clinical suspicion of onchocerciasis regarding immigrants from endemic areas having skin lesions compatible with the disease's profile or asymptomatic patients having eosinophilia or unexplained high IgE. Moreover, skin snips from the buttocks region were very fruitful and treatment with ivermectin was seen to be safe. This is the largest case series regarding imported onchocerciasis described up to the present time. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Efficacy of commonly used anthelmintics: first report of multiple drug resistance in gastrointestinal nematodes of sheep in Trinidad.

PubMed

George, N; Persad, K; Sagam, R; Offiah, V N; Adesiyun, A A; Harewood, W; Lambie, N; Basu, A K

2011-12-29

In Trinidad, small ruminant farms are semi-intensively managed under tropical conditions which support the development and survival of the infective stages of the helminths. Local farmers use anthelmintics to control gastrointestinal nematodes frequently. Frequent use of anthelmintics has the potential to select for populations of nematodes resistance to those chemicals. Hence, an attempt was made to study the efficacy of commonly used drugs on gastrointestinal nematodes of sheep. Three farms situated in different counties in Trinidad were selected. Sheep aged 6-15 months and not treated with anthelmintics for a minimum of six months previous and with faecal egg count (FEC)>150 eggs per gram were selected for study. They were allocated into 5 groups, each consisting 10 animals. The Group TA animals were treated once with albendazole (5mg/kg. b.wt.), group TF with fenbendazole (5mg/kg.b.wt.), group TI animals with ivermectin (200 μg/kg b.wt.), group TL with levamisol (7.5mg/kg b.wt.). The group NTC animals were not given any drug and served as control. The number of nematode eggs per gram of faeces from each animal was determined before treatment and at 14 days after treatment. The anthelmintic susceptibility to different drugs was detected by FECRT (in vivo) with EPG recorded at 14 day post-treatment. The data analysis using FECRT revealed that efficacy of albendazole (46-62%), fenbendazole (44-61%) and levamisol (53-81%) were reduced compared to ivermectin (95-97%). An attempt has also been made to find a suitable method for calculation of FECR (%). Copyright © 2011 Elsevier B.V. All rights reserved.

Methods for assessing the impact of avermectins on the decomposer community of sheep pastures.

PubMed

King, K L

1993-06-01

This paper outlines methods which can be used in the field assessment of potentially toxic chemicals such as the avermectins. The procedures focus on measuring the effects of the drug on decomposer organisms and the nutrient cycling process in pastures grazed by sheep. Measurements of decomposer activity are described along with methods for determining dry and organic matter loss and mineral loss from dung to the underlying soil. Sampling methods for both micro- and macro-invertebrates are discussed along with determination of the percentage infection of plant roots with vesicular-arbuscular mycorrhizal fungi. An integrated sampling unit for assessing the ecotoxicity of ivermectin in pastures grazed by sheep is presented.

Case report: Loiasis with peripheral nerve involvement and spleen lesions.

PubMed

Gobbi, Federico; Boussinesq, Michel; Mascarello, Marta; Angheben, Andrea; Gobbo, Maria; Rossanese, Andrea; Corachán, Manuel; Bisoffi, Zeno

2011-05-01

Loiasis, which is caused by the filarial nematode Loa loa, affects millions of persons living in the rainforest areas and savannah regions of central Africa. Typical manifestations are calabar swellings and the eyeworm. We report a case of loiasis with unusual clinical complications: a peripheral neuropathy and focal hypo-echogenic lesions of the spleen, which disappeared after treatment with albendazole and ivermectin. The literature reports that L. loa infection can be associated with various manifestations, some of them being serious. More information is needed to better characterize the protean manifestations of the disease in loiasis-endemic areas to evaluate the true incidence of loiasis.

Loiasis with Peripheral Nerve Involvement and Spleen Lesions

PubMed Central

Gobbi, Federico; Boussinesq, Michel; Mascarello, Marta; Angheben, Andrea; Gobbo, Maria; Rossanese, Andrea; Corachán, Manuel; Bisoffi, Zeno

2011-01-01

Loiasis, which is caused by the filarial nematode Loa loa, affects millions of persons living in the rainforest areas and savannah regions of central Africa. Typical manifestations are calabar swellings and the eyeworm. We report a case of loiasis with unusual clinical complications: a peripheral neuropathy and focal hypo-echogenic lesions of the spleen, which disappeared after treatment with albendazole and ivermectin. The literature reports that L. loa infection can be associated with various manifestations, some of them being serious. More information is needed to better characterize the protean manifestations of the disease in loiasis-endemic areas to evaluate the true incidence of loiasis. PMID:21540382

[Filariasis control: entry point for other helminthiasis control programs?].

PubMed

Boussinesq, M

2006-08-01

Filariasis control programs are based on a decentralized drug distribution strategy known as "community-directed". This strategy could also be applied to the control of schistosomiasis and intestinal nematode infections. Integration of these control programs could be highly cost-effective. However, as a prerequisite for integration, it would be necessary to identify zones where these helminthic infections co-exist, specify the population categories that should receive each medication (ivermectin, albendazole, mebendazole, and praziquantel), check that combined administration of these drugs is safe and ensure that an integrated program would have no detrimental effect on the health care system and on the efficacy of ongoing programs.

Developmental morphology of Knemidokoptes pilae on an infested red-crowned parakeet (Cyanoramphus novaezelandiae).

PubMed

Kim, Kyoo-Tae; Lee, Seung-Hun; Kwak, Dongmi

2016-03-01

A captive 4-year-old female red-crowned parakeet (Cyanoramphus novaezelandiae) presented with anorexia, diminished activity and thick, beige, crusted lesions over the cere, legs, wings and cloaca. Deep skin scrapings from various lesions identified Knemidokoptes pilae as the causative agent. For treatment, the crusts were debrided, and the lesions were topically treated with ivermectin, chlorhexidine and silver sulfadiazine. The parakeet died the day after treatment. Previous studies examining K. pilae have focused primarily on the morphologic characteristics of adult female mites. This study presents a more comprehensive morphologic analysis, with examination of K. pilae at different stages of development (eggs, larvae and adult males and females).

Localised sarcoptic mange in dogs: a retrospective study of 10 cases.

PubMed

Pin, D; Bensignor, E; Carlotti, D-N; Cadiergues, M C

2006-10-01

The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.

Epidemiology and control of scabies in an Egyptian village.

PubMed

Hegazy, A A; Darwish, N M; Abdel-Hamid, I A; Hammad, S M

1999-04-01

Some studies have addressed the epidemiology of scabies among rural populations in developing countries; however, the epidemiology of scabies among the rural population in Egypt is unknown. We sought to determine the magnitude of scabies infestation in an Egyptian village and to evaluate the control measures after 1 year. This study was carried out on 3147 residents of Mit-Moaned village in Dakahlia govemorate, Egypt. It was a cross-sectional follow-up study where the same individuals examined in round I were re-examined in round III. The two rounds were separated by a period of 1 year, during which infested patients were followed up and new cases were discovered (round II). Patients and their household contacts received treatment with topical permethrin. Patients showing resistance to permethrin received a single oral dose of ivermectin. In round III, the overall prevalence rate of scabies was reduced from 5.4% in round I to 1.1%. The incidence of new cases among susceptible persons during round II was 1.1%. Scabies was significantly (P < 0.05) more prevalent among families of large size, high crowding index at night, low socioeconomic standards, and those receiving their water supply from a hand pump. Children younger than 10 years showed the highest prevalence. Our data provide the first complete picture of the epidemiology of scabies in rural Egypt. The epidemiologic characteristics of the disease should be considered in the design of disease control programs for other villages with scabies epidemics. Our findings revealed that good control was achieved with the following: increased awareness and better case finding, education of the staff at the rural health unit, improved hygiene measures, and massive treatment campaigns using effective drugs such as topical permethrin and oral ivermectin.

Anthelmintic resistance in equine nematodes

PubMed Central

Matthews, Jacqueline B.

2014-01-01

Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin, moxidectin). Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC)-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop diagnostics

Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus.

PubMed

Botto, Carlos; Basañez, María-Gloria; Escalona, Marisela; Villamizar, Néstor J; Noya-Alarcón, Oscar; Cortez, José; Vivas-Martínez, Sarai; Coronel, Pablo; Frontado, Hortencia; Flores, Jorge; Graterol, Beatriz; Camacho, Oneida; Tovar, Yseliam; Borges, Daniel; Morales, Alba Lucia; Ríos, Dalila; Guerra, Francisco; Margeli, Héctor; Rodriguez, Mario Alberto; Unnasch, Thomas R; Grillet, María Eugenia

2016-01-27

The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. From 2010 to 2012-2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012-2013 were, respectively, under 1% and 20 L3/person/transmission season. Serology in children aged 1-10 years demonstrated that although 26 out of 396 (7%) individuals still had Ov-16 antibodies, only 4/218 (2%) seropositives were aged 1-5 years. We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75% of the Yanomami population and 70% of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus.

Diagnostic, treatment, and prevention protocols for canine heartworm infection in animal sheltering agencies.

PubMed

Colby, Kathleen N; Levy, Julie K; Dunn, Kiri F; Michaud, Rachel I

2011-03-22

The high prevalence of heartworm infection in shelter dogs creates a dilemma for shelter managers, who frequently operate with insufficient funding, staffing, and expertise to comply with heartworm guidelines developed for owned pet dogs. The purpose of this study was to survey canine heartworm management protocols used by 504 animal sheltering agencies in the endemic states of Alabama, Florida, Georgia, and Mississippi. Open-admission shelters, which tended to be larger and more likely to perform animal control functions, were less likely (41%) to test all adult dogs than were limited-admission shelters (80%), which tended to be smaller non-profit humane agencies, and foster programs (98%) based out of private residences. Open-admission shelters were more likely to euthanize infected dogs (27%) or to release them without treatment (39%), whereas limited-admission shelters and foster programs were more likely to provide adulticide therapy (82% and 89%, respectively). Of the 319 agencies that treated infections, 44% primarily used a standard two-dose melarsomine protocol, and 35% primarily used a three-dose split-treatment melarsomine protocol. Long-term low-dose ivermectin was the most common treatment used in 22% of agencies. Open-admission shelters were less likely (35%) to provide preventive medications for all dogs than were limited-admission shelters (82%) and foster programs (97%). More agencies used preventives labeled for monthly use in dogs (60%) than ivermectin products labeled for livestock (38%). The most common reason diagnostic testing and preventive medication was not provided was cost. These results indicate a lack of protocol uniformity among agencies and insufficient resources to identify, treat, and prevent infection. Sheltering agencies and companion animal health industries should develop guidelines that are feasible for use in sheltering agencies and provide improved access to preventive and treatment strategies for management of Dirofilaria

Co-endemicity of loiasis and onchocerciasis in rain forest communities in southwestern Nigeria.

PubMed

Ojurongbe, Olusola; Akindele, Akeem Abiodun; Adeleke, Monsuru Adebayo; Oyedeji, Matthew Oyebode; Adedokun, Samuel Adeyinka; Ojo, Josephine Folashade; Akinleye, Callistus Adewale; Bolaji, Oloyede Samuel; Adefioye, Olusegun Adelowo; Adeyeba, Oluwaseyi Adegboyega

2015-03-01

Loiasis is currently receiving attention as a disease of public health importance because of the possibility of increased risk of developing neurologic serious adverse event following mass ivermectin treatment against onchocerciasis in individual co-infected with Onchocerca volvulus and Loa loa. Rapid assessment procedure for loiasis (RAPLOA) was conducted in 12 communities covering the 3 senatorial districts of Osun State, Nigeria. A total of 960 people were interviewed for history of eye worm using the WHO guidelines for rapid assessment. The survey confirmed the presence of loiasis in all the 12 communities with 4 in Osun East/Ife south senatorial district being at high risk with a prevalence of over 40%. Based on the RAPLOA results, communities within Osun East/Ife south senatorial district were selected for microfilaraemic assessment of L. loa and O. volvulus. A total of 1115 and 1091 individuals were screened for L. loa and O. volvulus microfilaria worms respectively. 160 (14.3%) had L. loa microfilaria detected in their blood with 8 (5.0%) individuals having L. loa loads above 8000 mf/ml. 166 (15.2%) subjects had O. volvulus microfilaria (range 4-504 mf/ml) detected in their skin snip. 30 (2.69%) subjects were co-infected with both L. loa and O. volvulus. There was a significant variation in the prevalence (2.1% to 33.3%) of onchocerciasis in the communities studied (p = 0.001). Five (41.7%) of the studied communities had a prevalence that is equal to or greater than 20%. Low prevalence of onchocerciasis and loiasis co-infection in this study suggests that loiasis may not pose a serious epidemiological threat to the continuous distribution and sustainability of ivermectin for the treatment of onchocerciasis. Evaluation of the interruption of onchocerciasis transmissions in this region using all the indicators set forth by WHO is therefore suggested.

Activity of Oxantel Pamoate Monotherapy and Combination Chemotherapy against Trichuris muris and Hookworms: Revival of an Old Drug

PubMed Central

Keiser, Jennifer; Tritten, Lucienne; Silbereisen, Angelika; Speich, Benjamin; Adelfio, Roberto; Vargas, Mireille

2013-01-01

Background It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. Methodology We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. Principal Findings We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. Conclusion/Significance Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched. PMID:23556013

Demodex gatoi -associated contagious pruritic dermatosis in cats - a report from six households in Finland

PubMed Central

Saari, Seppo AM; Juuti, Kirsi H; Palojärvi, Joanna H; Väisänen, Kirsi M; Rajaniemi, Riitta-Liisa; Saijonmaa-Koulumies, Leena E

2009-01-01

Background Demodex gatoi is unique among demodectic mites. It possesses a distinct stubby appearance, and, instead of residing in the hair follicles, it dwells in the keratin layer of the epidermis, causing a pruritic and contagious skin disease in cats. Little is known of the occurrence of D. gatoi in Europe or control of D. gatoi infestation. Case presentation We describe D. gatoi in 10 cats, including five Cornish Rex, two Burmese, one Exotic, one Persian and one Siamese, living in six multi-cat households in different locations in Finland containing 21 cats in total. Intense pruritus was the main clinical sign. Scaling, broken hairs, alopecia and self-inflicted excoriations were also observed. Diagnosis was based on finding typical short-bodied demodectic mites in skin scrapings, skin biopsies or on tape strips. Other pruritic skin diseases, such as allergies and dermatophytoses, were ruled out. In one household, despite finding several mites on one cat, all six cats of the household remained symptomless. Amitraz used weekly at a concentration of 125-250 ppm for 2-3 months, proved successful in three households, 2% lime sulphur weekly dips applied for six weeks in one household and peroral ivermectin (1 mg every other day for 10 weeks) in one household. Previous trials in four households with imidacloprid-moxidectin, selamectin or injected ivermectin given once or twice a month appeared ineffective. Conclusion D. gatoi-associated dermatitis is an emerging contagious skin disease in cats in Finland. Although pruritus is common, some cats may harbour the mites without clinical signs. In addition, due to translucency of the mites and fastidious feline grooming habits, the diagnosis may be challenging. An effective and convenient way to treat D. gatoi infestations has yet to emerge. PMID:19843334

Targeted Drug Delivery and Treatment of Endoparasites with Biocompatible Particles of pH-Responsive Structure.

PubMed

Mathews, Patrick D; Fernandes Patta, Ana C M; Gonçalves, Joao V; Gama, Gabriella Dos Santos; Garcia, Irene Teresinha Santos; Mertins, Omar

2018-02-12

Biomaterials conceived for vectorization of bioactives are currently considered for biomedical, biological, and environmental applications. We have produced a pH-sensitive biomaterial composed of natural source alginate and chitosan polysaccharides for application as a drug delivery system via oral administration. The composite particle preparation was in situ monitored by means of isothermal titration calorimetry. The strong interaction established between the macromolecules during particle assembly led to 0.60 alginate/chitosan effective binding sites with an intense exothermic effect and negative enthalpy variation on the order of a thousand kcal/mol. In the presence of model drugs mebendazole and ivermectin, with relatively small and large structures, respectively, mebendazole reduced the amount of chitosan monomers available to interact with alginate by 27%, which was not observed for ivermectin. Nevertheless, a state of intense negative Gibbs energy and large entropic decrease was achieved, providing evidence that formation of particles is thermodynamically driven and favored. Small-angle X-ray scattering provided further evidence of similar surface aspects independent of the presence of drug. The physical responses of the particles to pH variation comprise partial hydration, swelling, and the predominance of positive surface charge in strong acid medium, whereas ionization followed by deprotonation leads to compaction and charge reversal rather than new swelling in mild and slightly acidic mediums, respectively. In vivo performance was evaluated in the treatment of endoparasites in Corydoras fish. Systematically with a daily base oral administration, particles significantly reduced the infections over 15 days of treatment. The experiments provide evidence that utilizing particles granted and boosted the action of the antiparasitic drugs, leading to substantial reduction or elimination of infection. Hence, the pH-responsive particles represent a biomaterial

Macrocyclic lactones differ in interaction with recombinant P-glycoprotein 9 of the parasitic nematode Cylicocylus elongatus and ketoconazole in a yeast growth assay.

PubMed

Kaschny, Maximiliane; Demeler, Janina; Janssen, I Jana I; Kuzmina, Tetiana A; Besognet, Bruno; Kanellos, Theo; Kerboeuf, Dominique; von Samson-Himmelstjerna, Georg; Krücken, Jürgen

2015-04-01

Macrocyclic lactones (MLs) are widely used parasiticides against nematodes and arthropods, but resistance is frequently observed in parasitic nematodes of horses and livestock. Reports claiming resistance or decreased susceptibility in human nematodes are increasing. Since no target site directed ML resistance mechanisms have been identified, non-specific mechanisms were frequently implicated in ML resistance, including P-glycoproteins (Pgps, designated ABCB1 in vertebrates). Nematode genomes encode many different Pgps (e.g. 10 in the sheep parasite Haemonchus contortus). ML transport was shown for mammalian Pgps, Pgps on nematode egg shells, and very recently for Pgp-2 of H. contortus. Here, Pgp-9 from the equine parasite Cylicocyclus elongatus (Cyathostominae) was expressed in a Saccharomyces cerevisiae strain lacking seven endogenous efflux transporters. Pgp was detected on these yeasts by flow cytometry and chemiluminescence using the monoclonal antibody UIC2, which is specific for the active Pgp conformation. In a growth assay, Pgp-9 increased resistance to the fungicides ketoconazole, actinomycin D, valinomycin and daunorubicin, but not to the anthelmintic fungicide thiabendazole. Since no fungicidal activity has been described for MLs, their interaction with Pgp-9 was investigated in an assay involving two drugs: Yeasts were incubated with the highest ketoconazole concentration not affecting growth plus increasing concentrations of MLs to determine competition between or modulation of transport of both drugs. Already equimolar concentrations of ivermectin and eprinomectin inhibited growth, and at fourfold higher ML concentrations growth was virtually abolished. Selamectin and doramectin did not increase susceptibility to ketoconazole at all, although doramectin has been shown previously to strongly interact with human and canine Pgp. An intermediate interaction was observed for moxidectin. This was substantiated by increased binding of UIC2 antibodies in the

Macrocyclic Lactones Differ in Interaction with Recombinant P-Glycoprotein 9 of the Parasitic Nematode Cylicocylus elongatus and Ketoconazole in a Yeast Growth Assay

PubMed Central

Kaschny, Maximiliane; Demeler, Janina; Janssen, I. Jana I.; Kuzmina, Tetiana A.; Besognet, Bruno; Kanellos, Theo; Kerboeuf, Dominique; von Samson-Himmelstjerna, Georg; Krücken, Jürgen

2015-01-01

Macrocyclic lactones (MLs) are widely used parasiticides against nematodes and arthropods, but resistance is frequently observed in parasitic nematodes of horses and livestock. Reports claiming resistance or decreased susceptibility in human nematodes are increasing. Since no target site directed ML resistance mechanisms have been identified, non-specific mechanisms were frequently implicated in ML resistance, including P-glycoproteins (Pgps, designated ABCB1 in vertebrates). Nematode genomes encode many different Pgps (e.g. 10 in the sheep parasite Haemonchus contortus). ML transport was shown for mammalian Pgps, Pgps on nematode egg shells, and very recently for Pgp-2 of H. contortus. Here, Pgp-9 from the equine parasite Cylicocyclus elongatus (Cyathostominae) was expressed in a Saccharomyces cerevisiae strain lacking seven endogenous efflux transporters. Pgp was detected on these yeasts by flow cytometry and chemiluminescence using the monoclonal antibody UIC2, which is specific for the active Pgp conformation. In a growth assay, Pgp-9 increased resistance to the fungicides ketoconazole, actinomycin D, valinomycin and daunorubicin, but not to the anthelmintic fungicide thiabendazole. Since no fungicidal activity has been described for MLs, their interaction with Pgp-9 was investigated in an assay involving two drugs: Yeasts were incubated with the highest ketoconazole concentration not affecting growth plus increasing concentrations of MLs to determine competition between or modulation of transport of both drugs. Already equimolar concentrations of ivermectin and eprinomectin inhibited growth, and at fourfold higher ML concentrations growth was virtually abolished. Selamectin and doramectin did not increase susceptibility to ketoconazole at all, although doramectin has been shown previously to strongly interact with human and canine Pgp. An intermediate interaction was observed for moxidectin. This was substantiated by increased binding of UIC2 antibodies in the

Population biology of human onchocerciasis.

PubMed Central

Basáñez, M G; Boussinesq, M

1999-01-01

Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology. PMID:10365406

The main factors influencing canine demodicosis treatment outcome and determination of optimal therapy.

PubMed

Arsenović, Milica; Pezo, Lato; Vasić, Nebojša; Ćirić, Rodoljub; Stefanović, Milan

2015-07-01

The main idea of this research was to evaluate the efficacy of canine demodicosis conventional treatments using mathematical analyses. All available papers published between 1980 and 2014 were used in this study. One hundred six clinical trials enrolling 3414 cases of generalized demodicosis in dogs are studied. Dogs entered in the analysis were only the ones in which the disease occurred naturally, excluding the studies in which transplantation of Demodex canis mites was done from other animals. In conventional acaricide treatments, sorted according to active substances (moxidectin, amitraz, doramectin, ivermectin, and milbemycin oxime), the way of application (spot-on, dips, orally, or subcutaneous), concentration, and interval of application were used as input parameters in mathematical modeling. Data of interest were the treatment outcome, the number of dogs that went into remission, the number of animals not responding to treatment microscopically, the average duration of therapy, the follow-up period, the number of patients with disease recurrence, the number of adverse effects, and the number of animals with side effects. Dogs lost to follow-up or when the treatment was discontinued, due to various reasons not in connection with the therapy protocol, were not considered. Statistical and mathematical analyses were applied for prediction of the drugs' effectiveness. Developed mathematical models showed satisfactorily r (2), higher than 0.87. Good evidence for recommending the use of milbemycin oxime PO (0.5 mg/kg, daily) and moxidectin spot-on (Advocate®, Bayer) weekly is found. A bit less effective therapies were based on ivermectin PO (0.5 mg/kg, daily), moxidectin PO (0.35 mg/kg, daily), and amitraz dips (0.05 % solution, weekly), respectively. It is important to keep in mind that Advocate® is recommended by the manufacturer for use in milder cases.

A novel clinical grading scale to guide the management of crusted scabies.

PubMed

Davis, Joshua S; McGloughlin, Steven; Tong, Steven Y C; Walton, Shelley F; Currie, Bart J

2013-01-01

Crusted scabies, or hyperinfestation with Sarcoptes scabiei, occurs in people with an inadequate immune response to the mite. In recent decades, data have emerged suggesting that treatment of crusted scabies with oral ivermectin combined with topical agents leads to lower mortality, but there are no generally accepted tools for describing disease severity. Here, we describe a clinical grading scale for crusted scabies and its utility in real world practice. In 2002, Royal Darwin Hospital (RDH), a hospital in tropical Australia developed and began using a clinical grading scale to guide the treatment of crusted scabies. We conducted a retrospective observational study including all episodes of admission to RDH for crusted scabies during the period October 2002-December 2010 inclusive. Patients who were managed according to the grading scale were compared with those in whom the scale was not used at the time of admission but was calculated retrospectively. There were 49 admissions in 30 patients during the study period, of which 49 (100%) were in Indigenous Australians, 29 (59%) were male and the median age was 44.1 years. According to the grading scale, 8 (16%) episodes were mild, 24 (49%) were moderate, and 17 (35%) were severe. Readmission within the study period was significantly more likely with increasing disease severity, with an odds ratio (95% CI) of 12.8 (1.3-130) for severe disease compared with mild. The patients managed according to the grading scale (29 episodes) did not differ from those who were not (20 episodes), but they received fewer doses of ivermectin and had a shorter length of stay (11 vs. 16 days, p = 0.02). Despite this the outcomes were no different, with no deaths in either group and a similar readmission rate. Our grading scale is a useful tool for the assessment and management of crusted scabies.

The Penultimate Arginine of the Carboxyl Terminus Determines Slow Desensitization in a P2X Receptor from the Cattle Tick Boophilus microplus

PubMed Central

Bavan, Selvan; Farmer, Louise; Singh, Shire K.; Straub, Volko A.; Guerrero, Felix D.

2011-01-01

P2X ion channels have been functionally characterized from a range of eukaryotes. Although these receptors can be broadly classified into fast and slow desensitizing, the molecular mechanisms underlying current desensitization are not fully understood. Here, we describe the characterization of a P2X receptor from the cattle tick Boophilus microplus (BmP2X) displaying extremely slow current kinetics, little desensitization during ATP application, and marked rundown in current amplitude between sequential responses. ATP (EC50, 67.1 μM) evoked concentration-dependent currents at BmP2X that were antagonized by suramin (IC50, 4.8 μM) and potentiated by the antiparasitic drug amitraz. Ivermectin did not potentiate BmP2X currents, but the mutation M362L conferred ivermectin sensitivity. To investigate the mechanisms underlying slow desensitization we generated intracellular domain chimeras between BmP2X and the rapidly desensitizing P2X receptor from Hypsibius dujardini. Exchange of N or C termini between these fast- and slow-desensitizing receptors altered the rate of current desensitization toward that of the donor channel. Truncation of the BmP2X C terminus identified the penultimate residue (Arg413) as important for slow desensitization. Removal of positive charge at this position in the mutant R413A resulted in significantly faster desensitization, which was further accentuated by the negatively charged substitution R413D. R413A and R413D, however, still displayed current rundown to sequential ATP application. Mutation to a positive charge (R413K) reconstituted the wild-type phenotype. This study identifies a new determinant of P2X desensitization where positive charge at the end of the C terminal regulates current flow and further demonstrates that rundown and desensitization are governed by distinct mechanisms. PMID:21212138

Time Series Analysis of Onchocerciasis Data from Mexico: A Trend towards Elimination

PubMed Central

Pérez-Rodríguez, Miguel A.; Adeleke, Monsuru A.; Orozco-Algarra, María E.; Arrendondo-Jiménez, Juan I.; Guo, Xianwu

2013-01-01

Background In Latin America, there are 13 geographically isolated endemic foci distributed among Mexico, Guatemala, Colombia, Venezuela, Brazil and Ecuador. The communities of the three endemic foci found within Mexico have been receiving ivermectin treatment since 1989. In this study, we predicted the trend of occurrence of cases in Mexico by applying time series analysis to monthly onchocerciasis data reported by the Mexican Secretariat of Health between 1988 and 2011 using the software R. Results A total of 15,584 cases were reported in Mexico from 1988 to 2011. The data of onchocerciasis cases are mainly from the main endemic foci of Chiapas and Oaxaca. The last case in Oaxaca was reported in 1998, but new cases were reported in the Chiapas foci up to 2011. Time series analysis performed for the foci in Mexico showed a decreasing trend of the disease over time. The best-fitted models with the smallest Akaike Information Criterion (AIC) were Auto-Regressive Integrated Moving Average (ARIMA) models, which were used to predict the tendency of onchocerciasis cases for two years ahead. According to the ARIMA models predictions, the cases in very low number (below 1) are expected for the disease between 2012 and 2013 in Chiapas, the last endemic region in Mexico. Conclusion The endemic regions of Mexico evolved from high onchocerciasis-endemic states to the interruption of transmission due to the strategies followed by the MSH, based on treatment with ivermectin. The extremely low level of expected cases as predicted by ARIMA models for the next two years suggest that the onchocerciasis is being eliminated in Mexico. To our knowledge, it is the first study utilizing time series for predicting case dynamics of onchocerciasis, which could be used as a benchmark during monitoring and post-treatment surveillance. PMID:23459370