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.

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...

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 administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans.

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.

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...

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

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.

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.

9 CFR 73.12 - Ivermectin. 1

Code of Federal Regulations, 2010 CFR

2010-01-01

... withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Federal... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCABIES IN CATTLE § 73.12 Ivermectin. 1 1 Tissue residues remain following treatment with ivermectin. Cattle treated with ivermectin...

9 CFR 73.12 - Ivermectin. 1

Code of Federal Regulations, 2013 CFR

2013-01-01

... withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Federal... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCABIES IN CATTLE § 73.12 Ivermectin. 1 1 Tissue residues remain following treatment with ivermectin. Cattle treated with ivermectin...

9 CFR 73.12 - Ivermectin. 1

Code of Federal Regulations, 2011 CFR

2011-01-01

... withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Federal... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCABIES IN CATTLE § 73.12 Ivermectin. 1 1 Tissue residues remain following treatment with ivermectin. Cattle treated with ivermectin...

9 CFR 73.12 - Ivermectin. 1

Code of Federal Regulations, 2014 CFR

2014-01-01

... withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Federal... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCABIES IN CATTLE § 73.12 Ivermectin. 1 1 Tissue residues remain following treatment with ivermectin. Cattle treated with ivermectin...

9 CFR 73.12 - Ivermectin. 1

Code of Federal Regulations, 2012 CFR

2012-01-01

... withdrawal time in milk has not been established, do not use in female dairy cattle of breeding age. Federal... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS SCABIES IN CATTLE § 73.12 Ivermectin. 1 1 Tissue residues remain following treatment with ivermectin. Cattle treated with ivermectin...

75 FR 26647 - Implantation or Injectable Dosage Form New Animal Drugs; Ivermectin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-12

... solution in cattle and swine for treatment and control of various internal and external parasites. DATES... Veterinary Medicine (HFV-170), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 240-276... and swine for treatment and control of various internal and external parasites. Sparhawk Laboratories...

75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-12

... FURTHER INFORMATION CONTACT: John K. Harshman, Center for Veterinary Medicine (HFV-170), Food and Drug... and redelegated to the Center for Veterinary Medicine, 21 CFR part 524 is amended as follows: PART 524...)(3) of this section. * * * * * (e) * * * (2) Indications for use--(i) It is used for the treatment...

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 surprisingly revealed that doxycycline was effective at inhibiting the efflux of ivermectin and doramectin (minocycline had no effect). These two avermectins, in combination with doxycycline, should be considered when treating meningeal worms in alpacas. Copyright © 2015 Elsevier B.V. All rights reserved.

[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.

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

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.

78 FR 63870 - New Animal Drugs; Change of Sponsor; Gonadorelin; Ivermectin; Ractopamine; Trimethoprim and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... estrous cycles to allow fixed-time artificial insemination (FTAI) in lactating dairy cows. 141-349 Zoetis...-time artificial insemination (FTAI) in lactating dairy cows, administer to each cow 100 to 200 mcg...

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 placed on their designated pasture unit where they remained for the entire grazing period (84-140 days). Fecal nematode egg counts and body weights were monitored at predetermined intervals throughout each study. Doramectin treatment reduced pretreatment egg counts by between 95 and 100% by 21 days post-treatment. Subsequent rises in egg output from exposure to infective pastures were delayed by two to four weeks resulting in substantial reductions in total egg deposition over the grazing period and, therefore, potential pasture recontamination. Doramectin treatment resulted in substantial average daily weight gain advantages (0.152-0.272 kg) over the grazing season compared to non-medicated controls. Advantages were statistically significant (P < 0.05) in three of the four studies. There were no significant differences (P > 0.05) in average daily gain between the doramectin and ivermectin injectable or ivermectin pour-on treated groups.

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...

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

76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... effectiveness against various species of external and internal parasites when cattle are treated with a topical... control infestations of certain species of external and internal parasites. The supplemental ANADA adds claims for persistent effectiveness against various species of external and internal parasites that were...

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

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.

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.

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.

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

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.

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

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.

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.

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.

Distribution of Animal Drugs between Skim Milk and Milk Fat Fractions in Spiked Whole Milk: Understanding the Potential Impact on Commercial Milk Products.

PubMed

Hakk, Heldur; Shappell, Nancy W; Lupton, Sara J; Shelver, Weilin L; Fanaselle, Wendy; Oryang, David; Yeung, Chi Yuen; Hoelzer, Karin; Ma, Yinqing; Gaalswyk, Dennis; Pouillot, Régis; Van Doren, Jane M

2016-01-13

Seven animal drugs [penicillin G (PENG), sulfadimethoxine (SDMX), oxytetracycline (OTET), erythromycin (ERY), ketoprofen (KETO), thiabendazole (THIA), and ivermectin (IVR)] were used to evaluate the drug distribution between milk fat and skim milk fractions of cow milk. More than 90% of the radioactivity was distributed into the skim milk fraction for ERY, KETO, OTET, PENG, and SDMX, approximately 80% for THIA, and 13% for IVR. The distribution of drug between milk fat and skim milk fractions was significantly correlated to the drug's lipophilicity (partition coefficient, log P, or distribution coefficient, log D, which includes ionization). Data were fit with linear mixed effects models; the best fit was obtained within this data set with log D versus observed drug distribution ratios. These candidate empirical models serve for assisting to predict the distribution and concentration of these drugs in a variety of milk and milk products.

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.

Efficacy of Ivermectin against Cheyletiella yasguri Infestation in Dogs

PubMed Central

Paradis, Manon; Villeneuve, Alain

1988-01-01

Twenty adult dogs (11 Cocker spaniels and 9 miniature Poodles) with naturally occurring cheyletiellosis were treated twice, at a three-week interval, with subcutaneous injections of ivermectin at the dose rate of 300 μg/kg. Ivermectin proved to be very effective against Cheyletiella yasguri infestation in dogs. All treated animals were completely cured after one or two treatments. No adverse reactions were noted. Ivermectin should be avoided in Collies and Collie crosses. PMID:17423097

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...

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.

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.

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....

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...

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 parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations. PMID:28746337

Ivermectin residues in squab.

PubMed

Bennett, D C; Cheng, K M

2012-11-01

No drugs have been approved for the treatment of parasitic nematodes in pigeons, but ivermectin, a broad-spectrum endectocide, has been used extra-label by prescription. Producers currently allow for a 2-wk withdrawal time before marketing squabs. However, because its use is extra-label there is no legal maximum residue limit for ivermectin in squab meat. The purpose of this study was to examine the depletion of ivermectin (passed by the parents to the squabs) from the tissues of squab. Adult pigeons brooding squab were treated with ivermectin in their drinking water (3.3 µg/mL) for 3 d. After dosing the parents, the ivermectin concentration of the breast meat and liver of squabs was found to be greater than the maximum residual limits established for livestock, indicating that ivermectin was transferred from the parents to the squabs. However, ivermectin was not detected in either the breast meat or the livers of squabs 1 wk after dosing. These results indicate that there is a rapid decline in tissue levels of ivermectin in squab.

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...

Topical ivermectin 0.5% lotion for treatment of head lice.

PubMed

Deeks, Louise S; Naunton, Mark; Currie, Marian J; Bowden, Francis J

2013-09-01

To investigate the pharmacology, pharmacokinetics, efficacy, adverse effects, and place in therapy of a single application of topical ivermectin 0.5% lotion for head lice treatment. Literature was obtained by searching MEDLINE, PubMed, CINAHL, and Scopus (January 1980 to January 2013). Abstracts were searched for the terms ivermectin AND (head lice or pediculus or pediculosis), topical ivermectin, ivermectin lotion, ivermectin AND (pharmacology OR pharmacokinetics). The New Drug Application filed with the Food and Drug Administration and the product data sheets for ivermectin were obtained. All English-language articles retrieved from the search were evaluated for relevance to the objective. The recommended first-line head lice treatments in the United States are permethrin 1% or pyrethrins, with malathion 0.5% lotion used as a second-line treatment. Significantly more of the 289 head lice-infested participants using topical ivermectin 0.5% lotion were lice-free at day 15 when compared with vehicle control (73.8% vs 17.6%; P < .001) in 2 studies. Although this rate is lower than other third-line treatments (eg, spinosad 0.9% or benzyl alcohol 5%), topical ivermectin 0.5% lotion is well tolerated (pruritus, the most common adverse event, 0.9%) and requires only a single application. Topical ivermectin 0.5% lotion kills head lice by increasing chloride in muscle cells, causing hyperpolarization and paralysis. Only 1 application is required; when the treated eggs hatch, the lice are not viable because they cannot feed as a result of pharyngeal muscle paralysis. Minimal systemic absorption occurs following topical application. Studies have demonstrated that topical ivermectin 0.5% is a safe and efficacious treatment for head lice. Although it has no documented resistance, there is limited clinical experience, it requires a prescription, and it is expensive. Therefore it should be reserved as a third-line treatment for head lice in the United States.

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 lethal to An. darlingi, modestly inhibits sporogony of P. vivax, and delays time to re-feed at concentrations found in humans up to 12 h post drug ingestion. The LC 50 value suggests that a higher than standard dose (400-μg/kg) is necessary to target An. darlingi. These results suggest that ivermectin MDA has potential in the Amazon region to aid malaria elimination efforts.

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.

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.

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 Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12613000474752.).

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: uses and impact 20 years on.

PubMed

Fox, Leanne M

2006-12-01

Ivermectin was first discovered and used in veterinary medicine over 20 years ago. This review highlights some of the recent published research from 2005 through June 2006 on the use of ivermectin in both helminth and arthropod infection. In recent years, several published studies have detailed the expanding role for ivermectin in multiple endo and ectoparasitic infections, including scabies, pediculosis, soil transmitted helminths, gnathostomiasis and myiasis. In addition, there is increasing experience with parenteral ivermectin for the treatment of disseminated strongyloidiasis. The success of ivermectin in reducing Onchocerca volvulus and Wuchereria bancrofti transmission through universal treatment in disease control programs continues to be well documented, but recent epidemiologic data describe suboptimal response to ivermectin by O. volvulus in a minority of individuals, the molecular markers for which are currently under investigation. Over 20 years of research and clinical use have advanced ivermectin from its beginnings as a veterinary anthelmintic to its significant role in several successful disease control programs. Nevertheless, further research is needed to understand the basis for suboptimal response and to better define optimal drug regimens for varying diseases.

Effects of diet on plasma concentrations of oral anthelmintics for cattle and sheep.

PubMed

Taylor, S M; Mallon, T R; Blanchflower, W J; Kennedy, D G; Green, W P

1992-03-28

Groups of parasite-free lambs and calves which were either housed and fed hay and concentrates or were grazing on pasture were dosed separately with the oral anthelmintics fenbendazole and ivermectin (lambs only). The plasma concentrations of the drugs and their major metabolites were monitored during the period of their metabolism and excretion. The peak plasma concentrations and the availability of the drugs, as estimated by the areas under the plasma concentration-time curves, were significantly less in the grazing animals. When similar groups of lambs were dosed orally with the inert marker chromium EDTA, which has a particle size similar to the anthelmintics, it was observed that a higher percentage of chromium was excreted by the grazing lambs during the first 40 hours after dosing, suggesting that the extent of absorption in the grazing animals was less than in the housed animals.

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

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 combinations compared with i.v. administration.

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...

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.

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.

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 or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. ClinicalTrials.gov NCT03173742.

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 or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. Trial registration ClinicalTrials.gov NCT03173742. PMID:29346388

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 variations of parasite populations in both the host and in refugia. Copyright © 2017 Elsevier B.V. All rights reserved.

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...

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...

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 alternatives to ivermectin. Candidate drugs include moxidectin, a macrofilaricide, doxycycline which targets the Wolbachia endosymbiont, and flubendazole, which shows promise with the newer oral cyclodextrin formulation. PMID:22069350

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.

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.

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

Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment.

PubMed

Bourguinat, Catherine; Pion, Sébastien D S; Kamgno, Joseph; Gardon, Jacques; Duke, Brian O L; Boussinesq, Michel; Prichard, Roger K

2007-08-30

Onchocerca volvulus is the causative agent of onchocerciasis, or "river blindness". Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure. O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 microg/kg or 800 microg/kg. Genotype frequencies were determined in beta-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between beta-tubulin genotype and female parasite fertility. We found a significant selection for beta-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the beta-tubulin "aa" homozygotes from 68.6% to 25.6%, while the "ab" heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the beta-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly. The results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes.

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

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.

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 peritonitis and perihepatitis in reindeer calves due to setariosis. In the case of necessity for animal welfare reasons, treatment during early autumn round ups should be considered. On the population level, massive and routinely applied antiparasitic treatments can improve the health of breeding reindeer and decrease the mortality and the number of carriers but during the outbreak could not prevent its movement and expansion to the North. PMID:19087262

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

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.

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

PubMed Central

Bourguinat, Catherine; Pion, Sébastien D. S.; Kamgno, Joseph; Gardon, Jacques

2007-01-01

Background Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure. Methods and Findings O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 µg/kg or 800 µg/kg. Genotype frequencies were determined in β-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between β-tubulin genotype and female parasite fertility. We found a significant selection for β-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the β-tubulin “aa” homozygotes from 68.6% to 25.6%, while the “ab” heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the β-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly. Conclusions The results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. PMID:17989786

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

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 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-albendazole compared to those treated with albendazole alone (RR = 1.29, 95% CI = 0.81-2.05). Our findings suggest a good tolerability and higher efficacy of ivermectin-albendazole against T. trichiura compared to the current standard single-dose albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.

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 treated with ivermectin-albendazole compared to those treated with albendazole alone (RR = 1.29, 95% CI = 0.81–2.05). Conclusions Our findings suggest a good tolerability and higher efficacy of ivermectin-albendazole against T. trichiura compared to the current standard single-dose albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results. PMID:29702653

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 to moxidectin resistance in H. contortus. Possible over expression of Hco-PGP-9.1 in the female reproductive system in resistant worms could reduce paralysis of the uterus by macrocyclic lactones, allowing continued egg release in drug challenged resistant worms.

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

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.

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.

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

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.

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

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.

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.

Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection.

PubMed

Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

2016-01-18

Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe).In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence).In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence).In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials).Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole.

Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

PubMed Central

Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

2016-01-01

Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence). In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials). Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Authors' conclusions Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole. Ivermectin versus benzimidazoles for treating Strongyloides stercoralis infection What is strongyloides infection and how might ivermectin work Strongyloides stercoralis is a parasite that lives in the gut of infected people. The infection is not serious for most people, but it can be fatal in people with immune deficiency. People become infected when they come in contact with soil or water contaminated with infectious worms. The chronic infection usually causes skin rash, vomiting, diarrhoea, and constipation, and respiratory problems, such as asthma-like illness. This disease may be treated with ivermectin or albendazole or thiabendazole. We wanted to know if ivermectin was better or worse than the other alternative therapies. What the research says We reviewed the evidence about the effect of ivermectin compared with albendazole and thiabendazole. After searching for relevant trials up to August 2015, we included seven randomized controlled trials, enrolling 1147 adults with chronic strongyloides infection, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America, and Europe). Four trials assessed the effectiveness of ivermectin compared with albendazole and three trials assessed the effectiveness of ivermectin compared with thiabendazole. Comparison ivermectin versus albendazole Treatment with ivermectin probably cures more people than albendazole (moderate quality evidence), and may be equally or better tolerated (low quality evidence). The included trials did not report serious adverse events or death. Comparison ivermectin versus thiabendazole Treatment with ivermectin and thiabendazole may cure similar numbers of people with strongyloides infection (low quality evidence), but ivermectin is probably better tolerated (moderate quality evidence). The included trials did not report serious adverse events or death. PMID:26778150

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-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection. PMID:18820741

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

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.

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.

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

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

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, this will have major consequences for epilepsy treatment in onchocerciasis-endemic regions. Ivermectin is donated for free and in non Loa-Loa–endemic regions has negligible side effects. Reducing the burden of epilepsy will have a major impact on quality of life and socioeconomic status of families with affected members in Africa. Trial Registration ClinicalTrials.gov NCT03052998; https://clinicaltrials.gov/ct2/show/NCT03052998 (Archived by WebCite at http://www.webcitation.org/6roFVQSG0) PMID:28855148

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.

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.

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 flock treated farm, closantel efficacy in grazing lambs was 84% (95%CI: 81%-88%) in the first year, but 100% in the second year. Levamisole was effective against overall GIN in lambs on only two farms. Ivermectin and fenbendazole resistance continued to be present, particularly in Haemonchus sp. Closantel had excellent efficacy against Haemonchus sp. over the two year study period, regardless of treatment group, and therefore should be considered one viable component of sustainable integrated parasite control programs for farms with documented anthelmintic resistance and problems with haemonchosis. Copyright © 2016 Elsevier B.V. All rights reserved.

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 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.

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 fact, the efficacy against Cooperia spp. was 83% (IVM), 98% (RBZ) and 98% (IVM+RBZ), while the efficacy against Haemonchus spp. was 0% (IVM), 97% (RBZ) and 100% (IVM+RBZ). The combination was the only treatment that achieved 100% clinical efficacy against IVM-resistant Haemonchus spp. The total egg excretion was reduced to 49.9% (IVM alone group), 6.3% (RBZ alone group) and 1.8% (IVM+RBZ combined group) compared to the untreated control. Although the combined treatment did not significantly increase the overall clinical efficacy in the current natural field conditions, an additive effect was achieved against IVM-resistant nematodes. In fact, the combination obtained significantly higher efficacy against IVM-resistant Haemonchus spp. than RBZ alone. Additionally, the epidemiological relevance of the reduction in the number of eggs excreted following the combined treatment is not negligible and should be taken into account in future studies. Further work is required to understand the advantages of nematodicidal combinations in different natural anthelmintic resistance scenarios. Copyright © 2016 Elsevier B.V. All rights reserved.

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 oral administration can be explained by an enhanced drug exposure of the worms located at the lumen of the large intestine. These findings may have a direct impact on the practical use of macrocyclic lactones in horses. Copyright © 2017 Elsevier B.V. All rights reserved.

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; 1.15- 4.83) and participants who know at least one CDD in their village (AOR = 2.83, 95% CI; 1.26- 6.40). The majority of the study participants in the present study area complied with ivermectin treatment. Nevertheless, intervention packages should consider factors such as age, residence duration and community's perception of the disease to improve compliance and make drug distribution sustainable.

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

[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.

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.

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).

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 ppm) and cypermethrin (150 ppm) was less efficacious than the amitraz alone. A generic product based on amitraz + citronella (208 ppm + 10 ppm, respectively) was shown to be less efficacious than the name-brand amitraz product. Products containing the organophosphate chlorpyrifos or trichlorfon exhibited intermediate efficacies of approximately 60% at the Tarso farm. We conclude that at these two locations, there is a high degree of resistance to many of the acaricides available in Colombia and confirm suspicions that ivermectin is no longer able to eliminate tick infestations. PMID:25987840

[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.

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 a good choice for assessing the success of control programs.

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 Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission.From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 µg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced "beyond-filariasis" benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites.The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 µg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.)The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was the programme's success in mobilizing hundreds of millions of local people, who not only took drugs but many of them actively supported MDAs as drug distributors and volunteers. Beyond filariasis, the role people can play in supplementing rural health services is now a topic of discussion and a source of hope for a new sustainable system.

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.

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 unknown. In the patient in the present report, ILE was used successfully to treat ivermectin toxicosis, and results of serial measurement of serum ivermectin concentration supported the proposed lipid sink mechanism of action.

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 absence of nocturnal itching as well as dermatologic evidence of scabies, and negative skin scraping. Patients showing evidence of active scabies or having new lesions during the follow-up visits were given a second dose of ivermectin. All members of the household and immediate family were treated with either topical 5% permethrin cream or 1% gamma benzene hexachloride to reduce the chance of reinfestation.

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 Trichostrongylus were detected after treatment with Albendazole and Ivermectin. The questionnaire survey revealed that Albendazole was the most commonly (90%) used anthelmintic to treat nematodes in sheep, followed by Tetramisole (36%) and Tetraclozan (Tetramisole-Oxyclozanide combination) (20%). Respondents expressed that anthelmintic selection was made based on veterinarian prescription (84%), colour (27%), efficacy (4%), price affordability (1%) and availability (1%). This study demonstrated that the tested anthelmintics had an acceptable level of efficacy against GINs of sheep.

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

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 drugs whilst functional expression of the receptor allows a first stage of testing of their efficacy. PMID:25255455

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 drugs whilst functional expression of the receptor allows a first stage of testing of their efficacy.

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

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.

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.

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.

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 the most common adverse events after treatment; abdominal cramps were reported by 13 (12·0%) children for albendazole plus ivermectin, 10 (9·3%) for albendazole plus mebendazole, 20 (18·2%) for albendazole plus oxantel pamoate, and 16 (14·5%) for mebendazole; headaches were reported by 5 (4·6%) children for albendazole plus ivermectin, 6 (5·6%) for albendazole plus mebendazole, 12 (10·9%) for albendazole plus oxantel pamoate, and 7 (6·4%) for mebendazole. Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura. Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes. Medicor Foundation and Swiss National Science Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

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 rights reserved.

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.

Assessment of topical versus oral ivermectin as a treatment for head lice.

PubMed

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

2014-01-01

Many medications are available for treatment of pediculosis capitis including ivermectin. Our aim is to compare the efficacy and safety of topical versus oral ivermectin in treatment of pediculosis capitis. Sixty-two patients with proved head lice infestation were included and divided into group I (31 patients; received single topical application of 1% ivermectin) and group II (31 patients; received single dose of oral ivermectin). Treatment was repeated after 1 week for nonresponders. At 1 week after treatment, the eradication rates and improvement of pruritus were significantly higher among patients who received topical than oral ivermectin. When a second treatment, topical or oral, was given to nonresponders, the cure rates of infestation and pruritus was 100% and 97% among patients treated with topical and oral ivermectin, respectively with no significant difference between the two groups. This study suggests that both topical and oral ivermectin demonstrate high efficacy and tolerability in treatment of pediculosis capitis. However, a single treatment with topical ivermectin provides significantly higher cure of infestation and faster relief of pruritus than oral ivermectin. In addition, whether topical or oral ivermectin is used to treat head lice, a second dose is required in some cases to ensure complete eradication. © 2014 Wiley Periodicals, Inc.

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

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.

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.

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.

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

Efficacy of ivermectin as an anthelmintic in leopard frogs.

PubMed

Letcher, J; Glade, M

1992-02-15

Ivermectin administered cutaneously at dosages of 2 mg/kg of body weight eliminated nematode infections in leopard frogs. Three clinical trials were conducted. In the first trial, 5 groups of 11 frogs were given ivermectin IM at dosages of 0, 0.2, 0.4, 2, or 20 mg/kg. All frogs given ivermectin IM at dosages of 2.0 mg/kg or greater died. In trial 2, 44 frogs, allotted to 5 groups, were given ivermectin cutaneously at 0, 0.2, 2, or 20 mg/kg. Cutaneously administered ivermectin was not toxic at dosages up to 20 mg/kg. In trial 3, nematode infections were eliminated in all 10 frogs treated cutaneously with ivermectin at 2.0 mg/kg.

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.

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.

[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.

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, 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...

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 initial mite counts or skin scores used as the covariate to account for variations in disease severity. Planned pairwise comparisons were used to identify differences between treatment groups. The efficacy of Advocate(®) increased with its rate of application across all measures of efficacy. Although ivermectin was shown to be more effective than Advocate(®) applied once weekly, both treatment protocols produced clinically satisfactory results. It was concluded that weekly application of Advocate(®) can be recommended as effective for the treatment of canine generalized demodicosis without the potential for toxicity associated with ivermectin. Copyright © 2014 The Authors. Published by Elsevier B.V. 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 farm at 2x (13.2 mg base/kg); 18 foals were examined, 13 with ascarid eggs (23% red.) and 15 with strongyle eggs (27% red.).

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...

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

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.

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).

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, 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...

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.

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 comparing phylogeny to transcriptional patterns revealed that NPCs have rapidly evolved and separate members respond to either blood meals or to ivermectin. We present evidence of increased ivermectin susceptibility in older An. gambiae mosquitoes that had previously bloodfed. Differential expression analysis suggests complex midgut interactions resulting from ivermectin ingestion that likely involve blood meal digestion physiological responses, midgut microflora, and innate immune responses. Thus, the transcription of certain gene families is consistently affected by ivermectin ingestion, and may provide important clues to ivermectin's broad effects on malaria vectors. These findings contribute to the growing understanding of ivermectin's potential as a transmission control tool.

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.

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.

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 found (infectivity rate = 0%; 95% CI: 0.0-0.014). These results fulfilled the WHO criteria for onchocerciasis elimination. Consequently, in 2013 Colombia was verified as free of onchocerciasis, demonstrating that elimination of this neglected tropical disease is an achievable goal and paving the way for an elimination agenda to be followed by other endemic countries in Latin America and Africa.

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

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

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.

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

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).

Lack of efficacy of monepantel against trichostrongyle nematodes in a UK sheep flock.

PubMed

Hamer, Kim; Bartley, Dave; Jennings, Amy; Morrison, Alison; Sargison, Neil

2018-06-15

Monepantel resistance was diagnosed during routine monitoring of the effectiveness of a farm's roundworm control strategy. Weaned lambs had become ill thrifty and developed diarrhoea, despite the routine use of monepantel. This clinical presentation was caused by trichostrongylosis. The faecal egg count reduction was 76.7% (95% CI: 55.1-82.2%) following treatment with 2.5 mg/kg monepantel. Predominantly Trichostrongylus vitrinus along with small proportions of Oesophagostomum venulosum and Trichostrongylus vitrinus were identified by deep amplicon sequencing of pools of larvae recovered from pre and post monepantel treatment coprocultures and on postmortem examinations. The undifferentiated FECRT showed resistance to monepantel, but not to levamisole, ivermectin, or moxidectin. Examination of farm anthelmintic treatment and animal movement records suggested that treatments before movement onto silage aftermaths, putatively with low numbers of susceptible nematodes in refugia, may have placed a high selection pressure on monepantel resistance. Effective control of parasitic gastroenteritis using anthelmintic drugs is a prerequisite for sustainable sheep production. This case reiterates the need for care when combining anthelmintic treatments with movements to safe grazing, and the value of monitoring of anthelmintic efficacy as part of iterative planned animal health management. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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.

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.

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

Constraints in animal health service delivery and sustainable improvement alternatives in North Gondar, Ethiopia.

PubMed

Kebede, Hassen; Melaku, Achenef; Kebede, Elias

2014-11-12

Poor livestock health services remain one of the main constraints to livestock production in many developing countries, including Ethiopia. A study was carried out in 11 districts of North Gondar, from December 2011 to September 2012, with the objective of identifying the existing status and constraints of animal health service delivery, and thus recommending possible alternatives for its sustainable improvement. Data were collected by using pre-tested questionnaires and focus group discussion. Findings revealed that 46.34% of the responding farmers had taken their animals to government veterinary clinics after initially trying treatments with local medication. More than 90.00% of the clinical cases were diagnosed solely on clinical signs or even history alone. The antibacterial drugs found in veterinary clinics were procaine penicillin (with or without streptomycin), oxytetracycline and sulphonamides, whilst albendazole, tetramisole and ivermectin were the only anthelmintics. A thermometer was the only clinical aid available in all clinics, whilst only nine (45.00%) clinics had a refrigerator. In the private sector, almost 95.00% were retail veterinary pharmacies and only 41.20% fulfilled the requirement criteria set. Professionals working in the government indicated the following problems: lack of incentives (70.00%), poor management and lack of awareness (60.00%) and inadequate budget (40.00%). For farmers, the most frequent problems were failure of private practitioners to adhere to ethical procedures (74.00%) and lack of knowledge of animal diseases and physical distance from the service centre (50.00%). Of all responding farmers, 58.54% preferred the government service, 21.14% liked both services equally and 20.33% preferred the private service. Farmers' indiscriminate use of drugs from the black market (23.00%) was also mentioned as a problem by private practitioners. Sustainable improvement of animal health service delivery needs increased awareness for all stakeholders and a well-regulated private service in order to mitigate the constraints apparent in the government service.

Controlled tests of ivermectin against migrating Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M

1981-06-01

Twelve pony foals were reared worm-free and inoculated with Strongylus vulgaris. On day 7 after inoculation, 6 ponies were given ivermectin IM at a dose of 200 micrograms/kg of body weight and on day 28 were necropsied. Ivermectin was effective in eliminating early 4th-stage S vulgaris larvae and reducing clinical signs associated with acute arteritis. After administrative ivermectin was effective against early 4th-stage Strongylus vulgaris larvae in ponies when administered at 100, 300, or 800 micrograms/kg of body weight. The purpose of the present study was to report on a more extensive trial, using a single dosage of ivermectin.

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

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.

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.

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

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.

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 recommended that the practice of routine deworming of three to four times a year should be avoided, as it can lead to emergence of anthelmintic resistance.

Effects of the Veterinary Pharmaceutical Ivermectin in Indoor Aquatic Microcosms

PubMed Central

Boonstra, Harry; Reichman, Erik P.

2010-01-01

The effects of the parasiticide ivermectin were assessed in plankton-dominated indoor microcosms. Ivermectin was applied once at concentrations of 30, 100, 300, 1000, 3000, and 10,000 ng/l. The half-life (dissipation time 50%; DT50) of ivermectin in the water phase ranged from 1.1 to 8.3 days. The lowest NOECcommunity that could be derived on an isolated sampling from the microcosm study by means of multivariate techniques was 100 ng/l. The most sensitive species in the microcosm study were the cladocerans Ceriodaphnia sp. (no observed effect concentration, NOEC = 30 ng/l) and Chydorus sphaericus (NOEC = 100 ng/l). The amphipod Gammarus pulex was less sensitive to ivermectin, showing consistent statistically significant reductions at the 1000-ng/l treatment level. Copepoda taxa decreased directly after application of ivermectin in the highest treatment but had already recovered at day 20 posttreatment. Indirect effects (e.g., increase of rotifers, increased primary production) were observed at the highest treatment level starting only on day 13 of the exposure phase. Cladocera showed the highest sensitivity to ivermectin in both standard laboratory toxicity tests as well as in the microcosm study. This study demonstrates that simple plankton-dominated test systems for assessing the effects of ivermectin can produce results similar to those obtained with large complex outdoor systems. PMID:20422169

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

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

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 with prominent characteristics that is promising for the development of targeted oral drug delivery.

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.

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

“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

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

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.

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 the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages. PMID:21171970

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 self-reported clinical symptoms. Clinical symptoms ascertained on the day of treatment and 24–72 hrs after, did not identify any adverse events. Significance Two community ivermectin MDAs delivered 12 months apart by trained Aboriginal researchers in collaboration with non-Indigenous researchers resulted in a sustained and significant reduction in Strongyloides seroprevalence over 18 months. Similar reductions were seen in the baseline cohort and new entrants. PMID:28505198

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 further evaluations are needed across the country to assist the NTDP with programme decision making.

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.

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.

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.

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 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.

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

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.

Community-directed mass drug administration is undermined by status seeking in friendship networks and inadequate trust in health advice networks.

PubMed

Chami, Goylette F; Kontoleon, Andreas A; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B; Tukahebwa, Edridah M; Dunne, David W

2017-06-01

Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence effective MDA implementation by CMDs. In Mayuge District, Uganda, census-style surveys were conducted for 16,357 individuals from 3,491 households in 17 villages. Praziquantel, albendazole, and ivermectin were administered for one month in community-directed MDA to treat Schistosoma mansoni, hookworm, and lymphatic filariasis. Self-reported treatment outcomes, socioeconomic characteristics, friendship networks, and health advice networks were collected. We investigated systematically missed coverage and noncompliance. Coverage was defined as an eligible person being offered at least one drug by CMDs; compliance included ingesting at least one of the offered drugs. These outcomes were analyzed as a two-stage process using a Heckman selection model. To further assess if MDA through CMDs was working as intended, we examined the probability of accurate drug administration of 1) praziquantel, 2) both albendazole and ivermectin, and 3) all drugs. This analysis was conducted using bivariate Probit regression. Four indicators from each social network were examined: degree, betweenness centrality, closeness centrality, and the presence of a direct connection to CMDs. All models accounted for nested household and village standard errors. CMDs were more likely to offer medicines, and to accurately administer the drugs as trained by the national control programme, to individuals with high friendship degree (many connections) and high friendship closeness centrality (households that were only a short number of steps away from all other households in the network). Though high (88.59%), additional compliance was associated with directly trusting CMDs for health advice. Effective treatment provision requires addressing CMD biases towards influential, well-embedded individuals in friendship networks and utilizing health advice networks to increase village trust in CMDs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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)

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.

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.

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.

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.

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 of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time.

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 an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time. PMID:24289520

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

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 (

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.

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.

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.

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.

Prevalence of anthelmintic resistance on Lithuanian sheep farms assessed by in vitro methods.

PubMed

Kupčinskas, Tomas; Stadalienė, Inga; Šarkūnas, Mindaugas; Riškevičienė, Vita; Várady, Marian; Höglund, Johan; Petkevičius, Saulius

2015-12-16

This study examines the prevalence of drug resistance in gastrointestinal nematodes to macrocyclic lactones (ML) and benzimidazoles (BZ) in Lithuanian sheep using sensitive and precise in vitro methods. The survey was conducted from August 2013 to November 2014. Thirty-three farms with sheep previously treated with BZ and ivermectin (IVM) were included in the study. On 12 farms where only BZ were used, egg hatch discrimination dose testing (EHDDT) was conducted to detect anthelmintic resistance (AR) to BZ. On eight farms where only ML were used, micro agar larval development testing (MALDT) was conducted to detect AR to ivermectin (IVM). On the remaining 13 farms, where both classes of drugs were used, EHDDT and MALDT were both applied to detect multidrug resistance to BZ and IVM. BZ-resistant gastrointestinal nematodes were found on all 25 farms with a previous history of BZ use. High levels of resistance (>40 % of hatching) were recorded on 36 % of these farms, and low levels (<20 % of hatching) on 40 % of farms. IVM-resistant populations were found on 13 out of 21 sheep farms using this drug. Of these 13 farms with AR to IVM, low levels of resistance (<30 % development) were recorded on 84.6 % of farms and high levels (>30 % development) on 15.4 % of farms. No resistance to IVM was recorded on 38.1 % of farms. Multi-drug resistance was detected on five farms out of 13 (38.5 %) using both classes of drugs. The present study demonstrates the existence of AR to BZ and ML on Lithuanian sheep farms thus confirming results in a previous in vivo study. Cases of multi-drug resistance were recorded in the present study and require further consideration. An appropriate strategy for anthelmintic treatment, measures to prevent gastrointestinal nematode infection and a better understanding of the management practices associated with resistance may slow down further development of AR.

DenguePredict: An Integrated Drug Repositioning Approach towards Drug Discovery for Dengue.

PubMed

Wang, QuanQiu; Xu, Rong

2015-01-01

Dengue is a viral disease of expanding global incidence without cures. Here we present a drug repositioning system (DenguePredict) leveraging upon a unique drug treatment database and vast amounts of disease- and drug-related data. We first constructed a large-scale genetic disease network with enriched dengue genetics data curated from biomedical literature. We applied a network-based ranking algorithm to find dengue-related diseases from the disease network. We then developed a novel algorithm to prioritize FDA-approved drugs from dengue-related diseases to treat dengue. When tested in a de-novo validation setting, DenguePredict found the only two drugs tested in clinical trials for treating dengue and ranked them highly: chloroquine ranked at top 0.96% and ivermectin at top 22.75%. We showed that drugs targeting immune systems and arachidonic acid metabolism-related apoptotic pathways might represent innovative drugs to treat dengue. In summary, DenguePredict, by combining comprehensive disease- and drug-related data and novel algorithms, may greatly facilitate drug discovery for dengue.

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.

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.

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.

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.

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 Cameroon varies with bioecological zones and IVM MDA history. The zones with high prevalence and intensities lie in forested areas while those with low endemicity are in the savanna areas. MDA with ivermectin induced significant reduction in the endemicity of mansonellosis in the decidious equatorial rainforest. In contrast, the prevalence and intensity remained relatively high and stable in the dense humid equatorial rainforest zones even after a decade of mass drug administration with ivermectin. Since it is known that M. perstans down-regulates host's immune system, the findings from this work would be useful in designing studies to understand the impact of M. perstans on host immune response to vaccination and co-infection with other pathogens such as Mycobacterium spp. and Plasmodium spp. in areas of contrasting endemicities.

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. .

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.

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, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups. Conclusion/Significance This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness. Trial Registration ClinicalTrials.gov NCT00765024 PMID:21572981

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.

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.

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

[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.

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.

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

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 assess the robustness of model outcomes. Compared with metronidazole 0.75% cream BID, ivermectin 1% cream QD was associated with higher costs but provided greater clinical benefit, with an ICER of $13,211 per QALY gained. For a cohort of 1,000 patients, ivermectin 1% cream QD provided an additional 72,922 disease-free days (200 years) over a 3-year period compared with metronidazole 0.75% cream BID, leading to a lower cost per disease-free day for ivermectin 1% cream QD ($4.54) compared with metronidazole 0.75% cream BID ($4.85). Ivermectin 1% cream QD was associated with lower total costs and greater clinical benefit compared with azelaic acid 15% gel BID at year 3 and dominated this treatment. After 3 years, ivermectin 1% cream QD was associated with the lowest health care costs ($62,767 compared with $73,284 for metronidazole 0.75% cream BID and $77,208 for azelaic acid 15% gel BID), reflecting a 15% reduction in physician visit costs, when compared with metronidazole 0.75% cream BID, and almost a 20% reduction, when compared with azelaic acid 15% gel BID. The univariate sensitivity analyses indicated that the results are sensitive to the time horizon selected: the longer the time horizon, the more beneficial the results for ivermectin 1% cream QD relative to the comparators, although even at 1 year, ivermectin 1% cream QD dominated azelaic acid 15% gel BID. The PSA suggested that ivermectin 1% cream QD was the most likely treatment to be cost-effective at a willingness-to-pay threshold of $15,000 and above. Ivermectin 1% cream QD had favorable incremental cost-effectiveness when compared with metronidazole 0.75% cream BID and dominated azelaic acid 15% gel BID in the treatment of papulopustular rosacea in the United States. Therefore, ivermectin 1% cream QD may be a good first-line treatment for papulopustular rosacea, providing additional clinical benefit at no or low additional cost. This study was sponsored by Galderma Laboratories. The sponsor was involved in the design of the model structure but not in the collection of the data used to populate the m

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. These results suggest that significant alterations in the immune response of ponies to S. vulgaris does not occur after intravascular killing of larvae by ivermectin treatments.

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.

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.

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.

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.

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.

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.

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.

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.

Changes in the use profile of Mectizan: 1987-1997.

PubMed

Brown, K R

1998-04-01

The usually conservative approach of Merck & Co. to drug development became even more so in the Mectizan (ivermectin, MSD) programme because of adverse experiences following 'extra-label' use in Collie dogs and the discovery of a low threshold for acute neurotoxicity in CF-1 mice. Although a very cautious approach and rapid development programme ensued, Merck remained conservative and excluded children under the age of 5 years, pregnant women, and mother who were nursing children under the age of 3 months from treatment. A subsequent, more relaxed set of standards was based on vast human clinical experience, inadvertent use in hundreds of pregnant women without ill-effect, and new laboratory information indicating that the presence of a protective blood-brain barrier protein component (P-glycoprotein) helped to stop Mectizan from crossing the placenta and from crossing the blood-brain barrier in most animal species, including humans. This has allowed more groups to be included in Mectizan treatments: pregnant women living in areas where the risk of loss of sight because of onchocerciasis is very high; and women who are nursing children as young as 1 week of age. Mass distribution of the drug continues to be largely under community control and the likelihood of serious adverse experiences related to finding a human population with unusually low levels of P-glycoprotein (or no P-glycoprotein) seems remote.

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 immitis. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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.

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.

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.

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

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.

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.

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

Anthelmintic resistance in gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul, Brazil

PubMed Central

Ramos, Fernanda; Portella, Luiza Pires; Rodrigues, Fernando de Souza; Reginato, Caroline Zamperete; Pötter, Luciana; Cezar, Alfredo Skrebsky; Sangioni, Luís Antônio; Vogel, Fernanda Silveira Flores

2016-01-01

Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70–100 calves or more of both genders with ≥200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7–10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7–10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups were effective against multi-drug resistant gastrointestinal nematodes. PMID:27054068

Anthelmintic resistance in gastrointestinal nematodes of beef cattle in the state of Rio Grande do Sul, Brazil.

PubMed

Ramos, Fernanda; Portella, Luiza Pires; Rodrigues, Fernando de Souza; Reginato, Caroline Zamperete; Pötter, Luciana; Cezar, Alfredo Skrebsky; Sangioni, Luís Antônio; Vogel, Fernanda Silveira Flores

2016-04-01

Gastrointestinal nematodes resistant to anthelmintics have been reported in several regions of Brazil, and they may be associated with economic losses for the cattle industry. This study aimed to evaluate the resistance status of gastrointestinal nematodes from naturally infected beef cattle to several commercially available anthelmintics, as well as to test the efficacy of combinations of anthelmintics against multi-resistant gastrointestinal nematodes. Ten farms located in Rio Grande do Sul state were selected by: farmers' consent; extensive raising system; availability of calves aged from 7 to 9 months naturally infected by gastrointestinal nematodes; absence of anthelmintic treatment for 60 days before the study; and presence of 70-100 calves or more of both genders with ≥ 200 eggs per gram of feces (EPG) (sensitivity of 50 EPG). These calves were distributed into 10 groups (of 7-10 animals) per farm and treated with ivermectin, doramectin, eprinomectin, fenbendazole, closantel, nitroxynil, disophenol, levamisole, albendazole, or moxidectin. Feces were collected 2 days before treatment and 14 days after treatment. Additional groups of 7-10 calves were used to test six different two-drug combinations at four of the studied farms. In general terms, fenbendazole was the most effective drug, followed by levamisole, disophenol, and moxidectin. However, parasite resistance to multiple drugs was found in all herds, especially in the genera Cooperia spp., Trichostrongylus spp., and Haemonchus spp.. Some of the two-drug combinations were effective against nematode populations identified as resistant to the same compounds when used as single drugs. The most effective combinations were moxidectin + levamisole, doramectin + fenbendazole, and levamisole + closantel. In this study, parasites resistant to the main commercially available anthelmintics were found in all herds, and some combinations of two active components belonging to different chemical groups were effective against multi-drug resistant gastrointestinal nematodes.

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.

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.

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.

[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.

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.

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 than 14 days to complete ivermectin distribution than other CDD, who only distributed ivermectin. Data obtained in interviews with present and past CDD appear vital for informing, directing, protecting and enhancing the performance of CDTI programmes, in Nigeria and elsewhere.

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 worm viability, dermal microfilarial density, anti-onchocystatin IgG in sera, and eosinophil counts in nodules. Only the gold-standard antibiotic regimen achieved significant killing of adult worms, a profound reduction in microfilarial load, and a sustained increase in local tissue eosinophilia. A small but statistically significant elevation in anti-onchocystatin IgG was observed for several weeks after immunisation in the immunotherapy-only group, but the antibody response in the immunochemotherapy group was more variable. At 12 weeks post-treatment, only a transient and non-significant increase in eosinophil counts was apparent in the immunochemotherapy group. We conclude that the addition of onchocystatin immunotherapy to a sub-lethal antibiotic regimen is insufficient to induce adulticidal activity, although with booster immunisations or the targeting of additional filarial immunomodulatory proteins, the efficacy of this strategy could be strengthened. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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.

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.

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.

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.

Advances in control of ectoparasites in large animals.

PubMed

Hiepe, T

1988-11-01

In continuation of a publication on "Large-scale management systems and parasite populations: ectoparasites" in Vet. Parasitol. 11 (1982): 61-68, advances and present state of the control of ectoparasites in herds of cattle, sheep and camels are discussed. An intensified animal production necessitates permanent veterinary control of the status of ectoparasites. Strategically, control is basically directed towards achieving three aims: eradication, reduction of losses by means of dilution of ectoparasites regulations, and therapeutic measures. In the last few years, important progress has been made in effective ectoparasites control, mainly resulting from the discovery of new insecticides and acaricides, the improvement of the application techniques and the recent results in the biological control of arthropods; finally, an immunological approach will open new alternative ways of control. The control of mange and demodicosis in cattle; sarcoptic mange and sucking lice infestations in pigs; mange, biting lice infestations and nasal bots in sheep; ectoparasite infestations in camels and tick infestations are the main topics of the paper. The discovery of Ivermectin, a derivate of Streptomyces avermitilis which is now already fully integrated in to the spectrum of antiparasitic drugs, created a new generation of broad spectrum insecticides/acaricides. Current problems of the chemical control of arthropods, like the risk of residues in meat, milk and their products, the insecticide resistance and the possible environment pollution are critically outlined. But on the other hand, it can be predicted hypothetically that the amount of pest control measures in farm animals will increase in the near future to eliminate arthropods as causes of skin diseases and of damages to hides entailing negative effects on leather processing and as vectors of important infection agents. Finally, the proposal is submitted to elaborate international control programmes against ectoparasite species of global importance.

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.

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 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.

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

A computational analysis of the binding mode of closantel as inhibitor of the Onchocerca volvulus chitinase: insights on macrofilaricidal drug design

NASA Astrophysics Data System (ADS)

Segura-Cabrera, Aldo; Bocanegra-García, Virgilio; Lizarazo-Ortega, Cristian; Guo, Xianwu; Correa-Basurto, José; Rodríguez-Pérez, Mario A.

2011-12-01

Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan® (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of novel drugs against the adult parasite of O. volvulus and such findings could be extrapolated to other filarial neglected diseases.

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 homes of some of the rural villagers, non-yearly compliance with regimen administration, poor health sensitization and education and lack of incentives orpoor incentives to the village-based health workers (VBHWs). Intensification of efforts to cover the lapses in the utilization of the regimen is advocated for a more effective control of the disease.

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.

Risk-based approach to developing a national residue sampling plan for testing under European Union regulation for veterinary medicinal products and coccidiostat feed additives in domestic animal production.

PubMed

Danaher, Martin; Shanahan, Conor; Butler, Francis; Evans, Rhodri; O'Sullivan, Dan; Glynn, Denise; Camon, Tim; Lawlor, Peadar; O'Keeffe, Michael

2016-07-01

A ranking system for veterinary medicinal products and coccidiostat feed additives has been developed as a tool to be applied in a risk-based approach to the residue testing programme for foods of animal origin in the Irish National Residue Control Plan (NRCP). Three characteristics of substances that may occur as residues in food are included in the developed risk ranking system: Potency, as measured by the acceptable daily intake assigned by the European Medicines Agency Committee for Medicinal Products for Veterinary Use, to each substance; Usage, as measured by the three factors of Number of Doses, use on Individual animals or for Group treatment, and Withdrawal Period; and Residue Occurrence, as measured by the number of Non-Compliant Samples in the NRCP. For both Number of Doses and Non-Compliant Samples, data for the 5-year period 2008-12 have been used. The risk ranking system for substances was developed for beef cattle, sheep and goats, pigs, chickens and dairy cattle using a scoring system applied to the various parameters described above to give an overall score based on the following equation: Potency × Usage (Number of Doses + Individual/Group Use + Withdrawal Period) × Residue Occurrence. Applying this risk ranking system, the following substances are ranked very highly: antimicrobials such as amoxicillin (for all species except pigs), marbofloxacillin (for beef cattle), oxytetracycline (for all species except chickens), sulfadiazine with trimethoprim (for pigs and chickens) and tilmicosin (for chickens); antiparasitic drugs, such as the benzimidazoles triclabendazole (for beef and dairy cattle), fenbendazole/oxfendazole (for sheep/goats and dairy cattle) and albendazole (for dairy cattle), the avermectin ivermectin (for beef cattle), and anti-fluke drugs closantel and rafoxanide (for sheep/goats); the anticoccidials monensin, narasin, nicarbazin and toltrazuril (for chickens). The risk ranking system described is a relatively simple system designed to provide a reliable basis for selecting the veterinary medicinal products and coccidiostat feed additives that might be prioritised for residue testing.

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

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.

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

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.

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...

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

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.

[Research and pharmaceutical development on the subject of communicable diseases in the intertropical region].

PubMed

Trouiller, P

1996-01-01

The development of the antimalarial drugs mefloquine and halofantrine in 1988 by American military research teams marked a start in the decline in investment in tropical disease research and drug development. The globalization of the market, increased clinical costs, and constraints on public health spending caused the pharmaceutical industry to concentrate on more profitable market segments (cardiovascular drugs, antineoplastics, anti-infection drugs, etc.). The market in developing countries represents a large volume, but a very low return because the added value is small, generic drugs are used and the state of the populations is impoverished. The ten or so drugs that have been developed recently result from chance (eflornithine), veterinary research (ivermectin), fortuitous analysis of traditional pharmacopoeia (artemether) or reevaluations of former drugs (amopyroquine). The deficiency of research and drug development for diseases of the intertropical zone has a direct negative effect on public health and also reveals health policy inconsistencies, particularly the incompatibility of the pharmaceutical industry's interests and international health priorities. The problem is also aggravated by the closed approach of external health assistance (official development aid) which aims to minimize costs by favoring primary health care.

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.

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-gated currents comparable to those of wild-type P2X4R. Finally, a P2X4/2R chimera did not respond to IVM but Zn(II) elicited a 2.7 ± 0.6-fold increase in the ATP-gated current. The application of IVM plus Zn(II) evoked a 2.7 ± 0.9-fold increase in the ATP-gated currents. In summary, allosteric modulators caused additive ATP-gated currents; consistent with lateral fenestration enlargement. Energy calculations demonstrated a favorable transition of the holo receptor state following both allosteric modulators binding, as expected for allosteric interactions. PMID:29326590

The identification of cattle nematode parasites resistant to multiple classes of anthelmintics in a commercial cattle population in the US.

PubMed

Gasbarre, Louis C; Smith, Larry L; Lichtenfels, J Ralph; Pilitt, Patricia A

2009-12-23

Resistance to modern anthelmintics by ruminant nematode parasites is an increasing problem throughout the world. To date the problem has largely been reported in parasites of small ruminants, but there are increasing reports of such resistance in nematodes recovered from cattle. Until now there have been no published reports of drug resistant parasites from cattle in North America. In 2002 a producer in the upper Midwest who backgrounds young cattle acquired from the southeastern US experienced lower than expected weight gain as well as apparent parasitic gastroenteritis in his cattle during the fall. Fecal sample results supported the suspicion that decreased productivity and diarrhea were the result of GI nematode parasitism. The operation used intensive grazing management and practiced strategically timed deworming for >17 year. In 2003, all animals were dewormed the first week of May with Ivomec Plus, then with Dectomax Injectable on 4 June and 17 July. On 31 July, 10 randomly taken fecal samples showed EPG values from 0 to 55. To assess whether the apparent decreased drug efficacy was the result of drug resistance in the nematode population, on 18 August approximately 150 heads, previously strategic timed dewormed, of 9-11 month old cattle from one pasture were selected for study. The calves were randomly assigned to 1 of 6 treatment groups: untreated (U), ivermectin injectable (I), moxidectin pour-on (M), doramectin injectable (D), eprinomectin pour-on (E), albendazole oral (A). Cattle were weighed prior to treatment and the drug was dosed according to label directions. Seven days later, 3 calves from each group were slaughtered for worm recovery. Fecal samples taken from the remaining animals at 14 days after treatment showed that the reduction of mean fecal EPG value for each group was: U-46%, I-52%, M-72%, D-61%, E-8%, and A-68%. Worm recovery from the slaughter calves showed that all groups harbored significant numbers of Haemonchus placei and H. contortus. In addition, all avermectin-treated groups contained significant numbers of Cooperia punctata, and smaller numbers of C. oncophora and C. spatulata. These results imply that the pastures studied contain substantial numbers of H. contortus resistant to both avermectins and benzimidazoles, and H. placei and Cooperia sp. resistant to all the commonly used avermectin anthelmintics. This is the first report of anthelmintic resistance in American cattle parasites.

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

Lack of resistance after re-exposure of cattle cured of Onchocerca ochengi infection with oxytetracycline.

PubMed

Nfon, Charles K; Makepeace, Benjamin L; Njongmeta, Leo M; Tanya, Vincent N; Trees, Alexander J

2007-01-01

Although vector control and ivermectin chemotherapy have led to a dramatic reduction in the incidence of river blindness (onchocerciasis), there is a consensus that additional control tools are required to sustain and extend this success. The recognition of endosymbiotic bacteria (Wolbachia) in filariae and their targeting by antibiotics constitutes the most significant and practicable opportunity for a macrofilaricidal therapy in the short-to-medium-term. Using Onchocerca ochengi in cattle, an analog of human onchocerciasis, we have previously shown that oxytetracycline is macrofilaricidal, and protective immunity exists naturally in a subset of animals termed putatively immune. Here, we report that although 24 weeks of weekly oxytetracycline treatment eliminated adult worms, cured animals remained susceptible to re-infection by natural challenge when compared with putatively immune cattle. However, their susceptibility was not significantly different from that of concurrently exposed, heavily infected animals. Thus, cattle cured by oxytetracycline are neither hypo-susceptible nor hyper-susceptible.

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.

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...

[Contribution to one world, one health: a dog with demodicosis.].

PubMed

Beyazit, Ayşen; Inceboz, Tonay; Over, Leyla

2010-01-01

Dogs are the most preferred pet animal in the world. Canine demodicosis is a skin disease of dogs in which there is proliferation of Demodex canis, an acarine parasite of canine hair follicles, and is typically manifested by alopecia as well as inflammation of hair follicles and sebaceous glands. Secondary bacterial infection often induces pustule and a crusting dermatitis. Two years ago, a police dog eight years old, without any previous health problem, was brought to a private veterinary clinic for edematous and inflammatory lesions on the soles of its feet. In the clinic, antibacterial and antimicotics were applied for treatment of the lesions, but ten months after completion of the therapy the lesions relapsed and the treatment was repeated. But again six months after the last treatment, the lesions spread widely and the general health status of the dog began to worsen. Finally the dog was brought for treatment to the Izmir Bornova Veterinary Research Institution. Microscopic examination of all the skin scrapings revealed the presence of 10-15 adult Demodex mites per cm(2) and the diagnosis was pododemodicosis. Treatment was performed with ivermectin, antibacterial drugs and beta-glucan. The density of Demodex was reduced after two months of therapy and there was clinical and microscopical improvement. Six months after completion of the therapy the lesions disappeared completely.

Evaluation of certain veterinary drug residues in food. Seventy-eighth report of the Joint FAO/WHO Expert Committee on Food Additives.

PubMed

2014-01-01

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues of food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including extrapolation of maximum residue limits (MRLs) to minor species, MRLs for veterinary drug residues in honey, MRLs relating to fish and fish species, dietary exposure assessment methodologies, the decision-tree approach to the evaluation of residues of veterinary drugs and guidance for JECFA experts. Summaries follow of the Committee's evaluations of toxicology and residue data on a variety of veterinary drugs: two anthelminthic agents (derquantel, monepantel), three antiparasitic agents (emanectin benzoate, ivermectin, lasalocid sodium), one antibacterial, antifungal and anthelminthic agent (gentian violet), a production aid (recombinant bovine somatotropins) and an adrenoceptor agonist and growth promoter (zilpaterol hydorchloride). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs)) and proposed MRLs.

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.

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.

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

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 (or eliminate) onchocerciasis in Africa. PMID:24069497

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.

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

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 onchocerciasis foci in Africa.

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.

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.

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.

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

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.

Clinical efficacy of 9-oxo-10, 11-dehydroageraphorone extracted from Eupatorium adenophorum against Psoroptes cuniculi in rabbits.

PubMed

Hu, Yang; Liao, Fei; Hu, Yanchun; Luo, Biao; He, Yajun; Mo, Quan; Zuo, Zhicai; Ren, Zhihua; Deng, Junliang; Wei, Yahui

2014-12-20

Animal acariasis is one of the important veterinary skin diseases. Chemical drugs have been widely used to treat and control this kind of disease. But many chemicals control could increase resistance in target species, toxicity and environmental hazards. We found that the 9-oxo-10, 11-dehydroageraphorone (euptox A) extracted from E. adenophorum has strong toxicity against P. cuniculi in vitro, but the in vivo acaricidal actions of euptox A have yet to be investigated. A 14-day experiment was performed using rabbits that were naturally infested with P. cuniculi on a farm. Rabbits were randomly divided into five groups; animals in groups A, B and C were treated in each ear topically with 4.0 ml of 2.0 and 1.0 g/L (w/v) euptox A, respectively. Animals in groups D and E were treated with ivermectin (by injection; positive controls) and glycerol with water only (by embrocation; negative controls), respectively. Each rabbit was treated twice with separate treatments on days 0 and 7. Rabbits were observed daily and detailed examinations were performed on days 0, 7 and 14, to inspect the presence or absence of mites and scabs/crusts. Seven days after the initial treatment, the mean clinical scores (presence of scabs/crusts) decreased from 3.48, 3.37, 3.43 and 3.45 to 0.37, 0.42, 0.78 and 0.38 in the ears of animals in groups A, B , C and D, respectively, which were similar to the observations recorded in the positive control rabbits. However, the clinical score for negative control rabbits did not increase significantly (P > 0.05) during the experiment, and this changed from 3.32 to 3.37 in the ears, and there were no significant differences in clinical efficacy between left and right ears. After two treatments (0 and 7 d), the rabbits in groups A, B, C and D had recovered completely 14 days after the last treatment and no recurrences of infection were observed. These results indicate that euptox A was potent compounds for the effective control of animal P. cuniculi in vivo.

The efficacy of a combined oral formulation of derquantel-abamectin against anthelmintic resistant gastro-intestinal nematodes of sheep in the UK.

PubMed

Geurden, Thomas; Hodge, Andrew; Noé, Laura; Winstanley, Dana; Bartley, David J; Taylor, Mike; Morgan, Colin; Fraser, Sarah J; Maeder, Steven; Bartram, David

2012-10-26

The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(®) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P<0.0001), whereas the percentage reduction in worm counts for the MOX- (P>0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P ≤ 0.003). For MOX the egg counts were significantly (P ≤ 0.003) lower compared to the untreated group at each farm, with reductions varying from 98.2 to 100%. The post-treatment copro-cultures for larva identification indicated that T. circumcincta was the most abundant worm species after treatment (52-99% of the larvae). The results of these studies confirm the high efficacy of the DQL+ABA combination formulation against anthelmintic resistant nematodes in the UK. Copyright © 2012 Elsevier B.V. All rights reserved.

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 males that had not been in the ivermectin treatment environment. Conclusions Spiking bloodmeals with ivermectin has shown potential as a viable treatment to eliminate female An. arabiensis from laboratory colonies although its practical use in a mass-rearing facility still needs to be tested. PMID:23822117

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

Evaluation of certain veterinary drug residues in food. Eighty-first report of the Joint FAO/WHO Expert Committee on Food Additives.

PubMed

2016-01-01

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including MRLs for generic fish species, acute reference doses (ARfDs) for veterinary drugs, an approach for dietary exposure assessment of compounds used for multiple purposes (i.e veterinary drugs and pesticides), dietary exposure assessment for less-than-lifetime exposure, and the assessment of short-term (90-day and 12-month) studies in dogs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two insecticides (diflubenzuron and teflubenzuron), an antiparasitic agent (ivermectin), an ectoparasiticide (sisapronil) and a β2-adrenoceptor agonist (zilpaterol hydrochloride). In addition, the Committee considered issues raised in concern forms from the Codex Committee on Residues of Veterinary Drugs in Foods on lasalocid sodium, an antiparasitic agent. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs), ARfDs and proposed MRLs.

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

[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.

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.

[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.

Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry.

PubMed

Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C

2009-11-13

LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish.

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.

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.

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/

Dioctophyma renale (Goeze, 1782) Infection in a Domestic Dog from Hamedan, Western Iran

PubMed Central

ZOLHAVARIEH, Seyed Masoud; NORIAN, Alireza; YAVARI, Morteza

2016-01-01

Dioctophyma renale infection is found in a wide range of mammalian species, typically in temperate areas of the world. Here, we report for the first time, the parasitism of a domestic dog by D. renale in Hamedan, Iran, a mountainous cold region, lacking significant amounts of rainfall, high humidity and temperature. A 2.5 yr old male mixed breed dog was presented with a two months history of progressive hematuria and muscle weakness. Complete blood count and serum biochemistry were performed with results indicating impaired renal function. Urinalysis, showed hematuria as well as parasitic eggs, suggestive of D. renale infection. Urinary system ultrasonography revealed a hypoecogenic tubular structure in the right kidney. The animal was treated with fenbendazole (45 mg/kg, PO, QD - five days) and ivermectin (0.02 mg/kg, SC, single dose). One week later, repeated laboratory examination confirmed presence of at least one alive worm in the affected kidney. A unilateral nephrectomy was performed; one female (60 × 5 cm) and one male (30 × 3.8 cm) live worm were taken out of the extremely thin walled right kidney. One month later, due to failure of the remained kidney and poor condition, the patient deceased. We conclude that dioctophymosis can be found in cold and or relatively dry area. Moreover, the results showed that the worm was not affected with common anthelmintic drugs. PMID:27095981

Dioctophyma renale (Goeze, 1782) Infection in a Domestic Dog from Hamedan, Western Iran.

PubMed

Zolhavarieh, Seyed Masoud; Norian, Alireza; Yavari, Morteza

2016-01-01

Dioctophyma renale infection is found in a wide range of mammalian species, typically in temperate areas of the world. Here, we report for the first time, the parasitism of a domestic dog by D. renale in Hamedan, Iran, a mountainous cold region, lacking significant amounts of rainfall, high humidity and temperature. A 2.5 yr old male mixed breed dog was presented with a two months history of progressive hematuria and muscle weakness. Complete blood count and serum biochemistry were performed with results indicating impaired renal function. Urinalysis, showed hematuria as well as parasitic eggs, suggestive of D. renale infection. Urinary system ultrasonography revealed a hypoecogenic tubular structure in the right kidney. The animal was treated with fenbendazole (45 mg/kg, PO, QD - five days) and ivermectin (0.02 mg/kg, SC, single dose). One week later, repeated laboratory examination confirmed presence of at least one alive worm in the affected kidney. A unilateral nephrectomy was performed; one female (60 × 5 cm) and one male (30 × 3.8 cm) live worm were taken out of the extremely thin walled right kidney. One month later, due to failure of the remained kidney and poor condition, the patient deceased. We conclude that dioctophymosis can be found in cold and or relatively dry area. Moreover, the results showed that the worm was not affected with common anthelmintic drugs.

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.

Pooling sheep faecal samples for the assessment of anthelmintic drug efficacy using McMaster and Mini-FLOTAC in gastrointestinal strongyle and Nematodirus infection.

PubMed

Kenyon, Fiona; Rinaldi, Laura; McBean, Dave; Pepe, Paola; Bosco, Antonio; Melville, Lynsey; Devin, Leigh; Mitchell, Gillian; Ianniello, Davide; Charlier, Johannes; Vercruysse, Jozef; Cringoli, Giuseppe; Levecke, Bruno

2016-07-30

In small ruminants, faecal egg counts (FECs) and reduction in FECs (FECR) are the most common methods for the assessment of intensity of gastrointestinal (GI) nematodes infections and anthelmintic drug efficacy, respectively. The main limitation of these methods is the time and cost to conduct FECs on a representative number of individual animals. A cost-saving alternative would be to examine pooled faecal samples, however little is known regarding whether pooling can give representative results. In the present study, we compared the FECR results obtained by both an individual and a pooled examination strategy across different pool sizes and analytical sensitivity of the FEC techniques. A survey was conducted on 5 sheep farms in Scotland, where anthelmintic resistance is known to be widespread. Lambs were treated with fenbendazole (4 groups), levamisole (3 groups), ivermectin (3 groups) or moxidectin (1 group). For each group, individual faecal samples were collected from 20 animals, at baseline (D0) and 14 days after (D14) anthelmintic administration. Faecal samples were analyzed as pools of 3-5, 6-10, and 14-20 individual samples. Both individual and pooled samples were screened for GI strongyle and Nematodirus eggs using two FEC techniques with three different levels of analytical sensitivity, including Mini-FLOTAC (analytical sensitivity of 10 eggs per gram of faeces (EPG)) and McMaster (analytical sensitivity of 15 or 50 EPG).For both Mini-FLOTAC and McMaster (analytical sensitivity of 15 EPG), there was a perfect agreement in classifying the efficacy of the anthelmintic as 'normal', 'doubtful' or 'reduced' regardless of pool size. When using the McMaster method (analytical sensitivity of 50 EPG) anthelmintic efficacy was often falsely classified as 'normal' or assessment was not possible due to zero FECs at D0, and this became more pronounced when the pool size increased. In conclusion, pooling ovine faecal samples holds promise as a cost-saving and efficient strategy for assessing GI nematode FECR. However, for the assessment FECR one will need to consider the baseline FEC, pool size and analytical sensitivity of the method. Copyright © 2016. Published by Elsevier B.V.

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.

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.

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 in progress.

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-domestic vegetation. Attractive toxic sugar baited resting places may provide an additional vector control method to complement with existing strategies.

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.

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:21039971

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 onchocerciasis as a result of successful control. As a result of these advances, a strategy for the elimination of onchocerciasis was developed, based upon mass distribution of ivermectin to afflicted communities for periods lasting long enough to ensure that the parasite population was placed on the road to local elimination. This strategy has been applied for the past decade to the foci in Latin America by a programme overseen by the Onchocerciasis Elimination Program for the Americas (OEPA). The efforts spearheaded by OEPA have been very successful, eliminating ocular disease caused by O. volvulus, and eliminating and interrupting transmission of the parasite in 8 of the 13 foci in the region. As onchocerciasis approaches elimination in Latin America, several questions still need to be addressed. These include defining an acceptable upper limit for transmission in areas in which transmission is thought to have been suppressed (e.g. what is the maximum value for the upper bound of the 95% confidence interval for transmission rates in areas where transmission is no longer detectable), how to develop strategies for conducting surveillance for recrudescence of infection in areas in which transmission is thought to be interrupted and how to address the problem in areas where the mass distribution of ivermectin seems to be unable to completely eliminate the infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Current situation and developmental trend of anthelmintics by bibliometrics].

PubMed

Zheng, Qi; Chen, Ying; Tian, Li-Guang; Zhou, Xiao-Nong

2009-08-01

To understand the current situation and developmental trend of anthelmintics in English journals through a bibliometric analysis. The literature was searched in Pubmed Database (1997-2007) using the following key words: "drug therapy", "anthelmintics", "humans", "pharmacology", and "parasitology". Access Database was constructed by relative literature through proper data admission method. The relative articles in the database were sorted by different categories, such as "research categories", "publishing year" and "research drug". Data were analyzed by using SPSS software. The annual number of anthelmintics articles increased steadily from year 1997 to 2007. The average number of annual increase was about 6. The major research category was applied research. The major diseases were schistosomiasis, filariasis, ascariasis, echinococcosis and hookworm disease. The number of articles on schistosomiasis was higher than that of other four diseases (P<0.05). The major drugs involved were albendazole, praziquantel, mebendazole, ivermectin and diethylcarbamazine. Articles on the anthelmintics were published mostly in medical journals. From the total database, articles published at the top five journals occupied 5.52%, 4.39%, 3.76%, 3.26%, and 3.26%, respectively. Increasingly importance has been attached to anthelmintics in the last decade. Meanwhile, the researchers focused on a few anthelmintics, and it is inevitable to develop new drugs.

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.

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.

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.

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

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 presence of ivermectin, moxidectin, daunorubicin and ketoconazole but not selamectin. These results demonstrate direct effects of MLs on a recombinant nematode Pgp in an ML-specific manner.

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 presence of ivermectin, moxidectin, daunorubicin and ketoconazole but not selamectin. These results demonstrate direct effects of MLs on a recombinant nematode Pgp in an ML-specific manner. PMID:25849454

Motility in the L3 stage is a poor phenotype for detecting and measuring resistance to avermectin/milbemycin drugs in gastrointestinal nematodes of livestock.

PubMed

George, Melissa M; Lopez-Soberal, Lorraine; Storey, Bob E; Howell, Sue B; Kaplan, Ray M

2018-04-01

Motility is a commonly used in vitro phenotype for assessing anthelmintic activity of candidate compounds, and for detecting anthelmintic resistance in nematodes. Third-stage larvae (L3) of parasitic nematodes are commonly used in motility-based assays because L3 are simple to obtain and can remain viable in storage for extended periods. To improve the measurement of motility of microscopic stages of nematodes, our laboratory developed the Worminator, which quantitatively measures motility of parasites. Using the Worminator, we compared the dose-response characteristics of several avermectin/milbemycin (AM) compounds using L3 from both AM-susceptible and AM-resistant Cooperia spp. (abamectin, doramectin, eprinomectin, ivermectin, moxidectin) and Haemonchus contortus (eprinomectin, ivermectin, moxidectin). Concentrations tested with the Worminator ranged from 0.156 to 40 μM. Differences in EC 50 between AM-susceptible and AM-resistant isolates of Cooperia spp. and Haemonchus contortus were small, with resistance ratios ranging from 1.00 to 1.34 for Cooperia spp., 0.99 to 1.65 for Haemonchus contortus. Larval migration inhibition assays were conducted using the same isolates and were equally ineffective for detection of resistance with resistance ratios less than 2.0. These results contrast with those of the Larval Development Assay where we obtained a resistance ratio of 16.48 using the same isolates of Haemonchus contortus. Moreover, even at the highest concentration tested (40 μM), 100% inhibition of motility was never achieved and EC 50 for Worminator assays were more than 100× higher than peak plasma levels achieved in vivo following treatment. These data demonstrate that dose-response characteristics for inhibition of motility in L3 of gastrointestinal nematodes of livestock do not significantly differ for AM-susceptible and AM-resistant isolates. These data challenge the suitability of motility as a phenotype for detecting and measuring resistance to AM drugs in gastrointestinal nematodes of livestock. Copyright © 2017. Published by Elsevier Ltd.

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.

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.

Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy

PubMed Central

Albonico, M.; Levecke, B.; LoVerde, P.T.; Montresor, A.; Prichard, R.; Vercruysse, J.; Webster, J.P.

2017-01-01

In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. PMID:27842865

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.

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.

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 time, control measures should include the treatment of all household contacts. Mass treatment with ivermectin may reduce the incidence of head lice infestation and associated morbidity in resource-poor communities. PMID:20428365

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 household contacts. Mass treatment with ivermectin may reduce the incidence of head lice infestation and associated morbidity in resource-poor communities.

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 onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.

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.

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.

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

Prevalence of gastrointestinal helminths and anthelmintic resistance on small-scale farms in Gauteng Province, South Africa.

PubMed

Tsotetsi, Ana Mbokeleng; Njiro, Stephen; Katsande, Tendai Charles; Moyo, Gugulethu; Baloyi, Faculty; Mpofu, Jaison

2013-03-01

The present study was conducted to determine the prevalence and distribution of gastrointestinal helminths, to detect the presence of anthelmintic resistance in livestock from small-scale farms and to determine the level of helminthosis awareness among small-scale farmers in Gauteng Province, South Africa. Blood and faecal samples were collected from cattle (n = 314), sheep (n = 256) and goats (n = 311). Faecal egg counts and cultures were done, helminth genera identified and packed cell volume was assessed to detect anaemia. A faecal egg count reduction test was used to determine anthelmintic resistance against albendazole (7.5 mg/kg), levamisole (5 mg/kg) and ivermectin (0.2 mg/kg) on five small ruminant farms. A high prevalence of both nematodes and trematodes was observed; however, only 1 % of cattle had high nematode egg counts compared to goats (30 %) and sheep (32 %). Only 5 % of the animals were anaemic. Haemonchus and Calicophoron were the most dominant helminth genera in the studied ruminants. Anthelmintic resistance was detected against the three tested drugs on all the screened farms, except against albendazole and levamisole in sheep from Hammanskraal and Nigel, respectively. About 88 % of interviewed farmers were aware of veterinary helminthosis, 67 % treated against helminths and 83 % provided their livestock with nutritional supplements. This study showed that a high prevalence of helminthosis and anthelmintic resistance does occur in the study area, thus relevant strategic interventions are recommended.

Studies on the biology, chemotherapy and distribution of warble fly in Pakistan.

PubMed

Khan, M Qasim; Irshad, H; Jahangir, M; Razzaq, A

2012-12-01

This paper presents data on the prevalence, biology and control of warble fly infestation (WFI) in cattle and goats in Pakistan. A questionnaire for obtaining information on biology and prevalence was circulated amongst field veterinary staff and livestock farmers in all five provinces (Punjab, Sindh, Balochistan, Khyber Pakhtunkhwa [KPK] and Gilgit-Baltistan) and in the Federally Administered Tribal Areas of the country. A total of 1,019 questionnaires were received (Punjab = 296, Sindh = 246, KPK = 318, Balochistan = 151, Gilgit-Baltistan = 8). Warble fly infestation was reported from each province and from the federally administered tribal areas, particularly from hilly, semi-hilly and sandy desert areas (the Cholistan desert, which adjoins the Rehim Yar Khan, Bahawalpur and Bahawalnagar districts, and the Nara area of Sanghar district). Warbles (nodules) started appearing on the backs of the infested animals from September through December and disappeared from October through March. The prevalence of WFI varied from 5% to 75%. It was highest in hilly areas and gradually decreased towards the plains. A map was developed of warble fly-infested areas. Four field trials were conducted to study the efficacy of different drugs indicated for the control of warble fly infestation. A total of 2,094 cattle and 3,876 goats were given five different injectables (avermectins); namely, Ivomec, Endectin, Euvectin, Dectomax and Promectin (ivermectin) during the first three weeks of September. A control group was given normal saline. All the medicines were found to be effective in controlling infestation.

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%.

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

Strongyloidiasis Current Status with Emphasis in Diagnosis and Drug Research

PubMed Central

Minori, Karen

2017-01-01

Strongyloidiasis is a parasitic neglected disease caused by the nematode Strongyloides stercoralis affecting 30 to 100 million people worldwide. Complications, strongly associated with alcoholism, organ transplants, and HTLV-1 virus, often arise due to late diagnosis, frequently leading to patient death. Lack of preemptive diagnosis is not the only difficulty when dealing with this parasite, since there are no gold standard diagnostic techniques, and the ones used have problems associated with sensitivity, resulting in false negatives. Treatment is also an issue as ivermectin and benzimidazoles administration leads to inconsistent cure rates and several side effects. Researching new anti-Strongyloides drugs is a difficult task since S. stercoralis does not develop until the adult stages in Mus musculus (with the exception of SCID mice), the main experimental host model. Fortunately, alternative parasite models can be used, namely, Strongyloides ratti and S. venezuelensis. However, even with these models, there are other complications in finding new drugs, which are associated with specific in vitro assay protocol steps, such as larvae decontamination. In this review, we highlight the challenges associated with new drug search, the compounds tested, and a list of published in vitro assay methodologies. We also point out advances being made in strongyloidiasis diagnosis so far. PMID:28210503

Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

PubMed

Albonico, M; Levecke, B; LoVerde, P T; Montresor, A; Prichard, R; Vercruysse, J; Webster, J P

2015-12-01

In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

A randomized triple blind trial to assess the effect of an anthelmintic programme for working equids in Morocco

PubMed Central

2011-01-01

Background Gastro-intestinal parasitism has been identified as a significant cause of disease in working equids in many countries. This randomized triple-blind trial was designed to assess the impact of an anthelmintic treatment programme (using oral ivermectin and fenbendazole) comparing treated and placebo control populations of working donkeys, mules and horses in field conditions in Morocco. In particular, we assessed animal body weight and condition score, together with a questionnaire-based owner evaluation of number of subjective animal health parameters. Faecal worm egg count was also measured. Results 239 animals completed the full study, 130 in the treatment group and 109 in the control group. Although the average animal weight increased during the study, this change was not significantly different between the two groups. Animals in the treatment group had a significantly lower strongyle worm egg count and increased in body condition score compared to animals in the control group at each examination during the study period. Owners of animals in the treatment group reported improvement in health and work ability and a beneficial effect on pruritus during the early period of the study. These differences in owner perception between treatment groups had disappeared in the latter stages of the study. Conclusion This study demonstrated that a routine anthelmintic treatment programme of three treatments annually can have a significant effect on faecal worm egg count. There may be beneficial consequences for the animal health and productivity. Further research on other populations of working equids in different environments would facilitate the objective planning of effective parasite control strategies for specific situations and provide better understanding of the likely clinical benefits of such programmes. PMID:21208398

Inhibitory effects of some drugs on carbonic anhydrase enzyme purified from Kangal Akkaraman sheep in Sivas, Turkey.

PubMed

Koçyiğit, Ümit M; Durna Daştan, Sevgi; Taslimi, Parham; Daştan, Taner; Gülçin, İlhami

2018-01-01

In this study, carbonic anhydrase (CA) enzyme was purified and characterized from blood samples of Kangal Akkaraman sheep and inhibitory properties on certain antibiotics were examined. CA purification was composed of preparation of the hemolysate and conducting the Sepharose-4B-tyrosine-sulfanilamide affinity gel chromatography in having specific activity of 11626 EU mg -1 , yield of 14.40%, and 242.76-fold purification. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed to assess the enzyme purity and a single band was observed. Some antibiotics were exhibited in vitro inhibition on the CA activity. IC 50 values of these inhibitors were calculated by plotting activity percentage. IC 50 values of certain drugs (dexamethasone; caffeine; metamizole sodium; tetramisol; ceftiofur HCl; ivermectin; tavilin 50; penokain G; neosym; and sulfamezathine) were found as 0.38, 8.24, 285.53, 114.77, 5.33, 2.76, 27.58, 213.50, 208.28, and 36.60 μM, respectively. K i values of different drugs on Kangal Akkaraman sheep blood CA activity were found in the range of 0.21 ± 0.038-266.64 ± 37.11 μM. © 2017 Wiley Periodicals, Inc.

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

78 FR 52429 - New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-23

... 558 [Docket No. FDA-2013-N-0839] New Animal Drugs; Withdrawal of Approval of New Animal Drug...: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the withdrawal of approval of three new animal drug applications (NADAs) at the sponsors' request...

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

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.

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.

75 FR 11451 - New Animal Drugs for Use in Animal Feeds; Zilpaterol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-11

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Zilpaterol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of three abbreviated new animal drug applications (ANADAs) filed...

75 FR 34361 - New Animal Drugs for Use in Animal Feeds; Florfenicol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-17

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Florfenicol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

21 CFR 500.51 - Labeling of animal drugs; misbranding.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Labeling of animal drugs; misbranding. 500.51... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Animal Drug Labeling Requirements § 500.51 Labeling of animal drugs; misbranding. (a) Among the representations on the label or labeling of an animal...

76 FR 79064 - New Animal Drugs for Use in Animal Feeds; Monensin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

.... FDA-2011-N-0003] New Animal Drugs for Use in Animal Feeds; Monensin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

77 FR 4228 - New Animal Drugs for Use in Animal Feeds; Monensin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] New Animal Drugs for Use in Animal Feeds; Monensin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

21 CFR 500.51 - Labeling of animal drugs; misbranding.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Labeling of animal drugs; misbranding. 500.51... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Animal Drug Labeling Requirements § 500.51 Labeling of animal drugs; misbranding. (a) Among the representations on the label or labeling of an animal...

75 FR 5887 - New Animal Drugs for Use in Animal Feeds; Ractopamine; Monensin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Ractopamine; Monensin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal drug application (NADA) filed by Elanco...

75 FR 54019 - New Animal Drugs for Use in Animal Feed; Ractopamine

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feed; Ractopamine AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of two supplemental new animal drug applications (NADAs) filed by...

77 FR 22667 - New Animal Drugs for Use in Animal Feeds; Tiamulin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

.... FDA-2012-N-0002] New Animal Drugs for Use in Animal Feeds; Tiamulin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the withdrawal of approval of those parts of a new animal drug application...

21 CFR 500.51 - Labeling of animal drugs; misbranding.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Labeling of animal drugs; misbranding. 500.51... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Animal Drug Labeling Requirements § 500.51 Labeling of animal drugs; misbranding. (a) Among the representations on the label or labeling of an animal...

21 CFR 500.51 - Labeling of animal drugs; misbranding.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Labeling of animal drugs; misbranding. 500.51... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Animal Drug Labeling Requirements § 500.51 Labeling of animal drugs; misbranding. (a) Among the representations on the label or labeling of an animal...

75 FR 9334 - New Animal Drugs for Use in Animal Feeds; Chlortetracycline

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Chlortetracycline AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by ADM...

77 FR 24138 - New Animal Drugs for Use in Animal Feeds; Tiamulin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

.... FDA-2012-N-0002] New Animal Drugs for Use in Animal Feeds; Tiamulin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

21 CFR 500.51 - Labeling of animal drugs; misbranding.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Labeling of animal drugs; misbranding. 500.51... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Animal Drug Labeling Requirements § 500.51 Labeling of animal drugs; misbranding. (a) Among the representations on the label or labeling of an animal...

75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

... [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations by...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Use of animal drugs. 318.20 Section... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if such residues are from drugs which have been approved by the Food and Drug Administration and any such...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Use of animal drugs. 318.20 Section... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if such residues are from drugs which have been approved by the Food and Drug Administration and any such...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Use of animal drugs. 318.20 Section... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if such residues are from drugs which have been approved by the Food and Drug Administration and any such...

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.

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.

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-onchocerciasis endemic regions in Africa. Our data suggests that Ivermectin protects against epilepsy in an onchocerciasis endemic region. However, a prospective population based intervention study is needed to confirm this. PMID:28708828

P-glycoproteins and other multidrug resistance transporters in the pharmacology of anthelmintics: Prospects for reversing transport-dependent anthelmintic resistance

PubMed Central

Lespine, Anne; Ménez, Cécile; Bourguinat, Catherine; Prichard, Roger K.

2011-01-01

Parasitic helminths cause significant disease in animals and humans. In the absence of alternative treatments, anthelmintics remain the principal agents for their control. Resistance extends to the most important class of anthelmintics, the macrocyclic lactone endectocides (MLs), such as ivermectin, and presents serious problems for the livestock industries and threatens to severely limit current parasite control strategies in humans. Understanding drug resistance is important for optimizing and monitoring control, and reducing further selection for resistance. Multidrug resistance (MDR) ABC transporters have been implicated in ML resistance and contribute to resistance to a number of other anthelmintics. MDR transporters, such as P-glycoproteins, are essential for many cellular processes that require the transport of substrates across cell membranes. Being overexpressed in response to chemotherapy in tumour cells and to ML-based treatment in nematodes, they lead to therapy failure by decreasing drug concentration at the target. Several anthelmintics are inhibitors of these efflux pumps and appropriate combinations can result in higher treatment efficacy against parasites and reversal of resistance. However, this needs to be balanced against possible increased toxicity to the host, or the components of the combination selecting on the same genes involved in the resistance. Increased efficacy could result from modifying anthelmintic pharmacokinetics in the host or by blocking parasite transporters involved in resistance. Combination of anthelmintics can be beneficial for delaying selection for resistance. However, it should be based on knowledge of resistance mechanisms and not simply on mode of action classes, and is best started before resistance has been selected to any member of the combination. Increasing knowledge of the MDR transporters involved in anthelmintic resistance in helminths will play an important role in allowing for the identification of markers to monitor the spread of resistance and to evaluate new tools and management practices aimed at delaying its spread. PMID:24533264

21 CFR 510.7 - Consignees of new animal drugs for use in the manufacture of animal feed.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Consignees of new animal drugs for use in the manufacture of animal feed. 510.7 Section 510.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Provisions § 510.7 Consignees of new animal drugs for use in the manufacture of animal feed. (a) A new animal...

21 CFR 510.7 - Consignees of new animal drugs for use in the manufacture of animal feed.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Consignees of new animal drugs for use in the manufacture of animal feed. 510.7 Section 510.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Provisions § 510.7 Consignees of new animal drugs for use in the manufacture of animal feed. (a) A new animal...

78 FR 52852 - New Animal Drugs; Carprofen; Enrofloxacin; Florfenicol; Tildipirosin; Zilpaterol

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-27

..., 556, and 558 [Docket No. FDA-2013-N-0002] New Animal Drugs; Carprofen; Enrofloxacin; Florfenicol.... SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications (NADAs) and abbreviated new animal drug applications...

78 FR 76059 - New Animal Drugs for Use in Animal Feeds; Bambermycins

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

.... FDA-2012-N-0002] New Animal Drugs for Use in Animal Feeds; Bambermycins AGENCY: Food and Drug... amending the animal drug regulations to remove dairy replacement heifers from the pasture cattle class for....gov . SUPPLEMENTARY INFORMATION: FDA has noticed that the animal drug regulations for bambermycins...

78 FR 25182 - New Animal Drugs; Dexmedetomidine; Lasalocid; Melengestrol; Monensin; and Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... [Docket No. FDA-2013-N-0002] New Animal Drugs; Dexmedetomidine; Lasalocid; Melengestrol; Monensin; and... Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications and abbreviated new animal drug applications during March 2013. FDA...

75 FR 54492 - Oral Dosage Form New Animal Drugs; Tiamulin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tiamulin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Novartis Animal...

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 resistance, respectively. For adult tests with amitraz 50% and 17% of the field populations showed average and high resistance, with evidences of average resistance to alpha-cypermethrin in 50% of the samples and average resistance against ivermectin in 25% of the farms. No statistical difference amongst the three bioassays was found and acaricide resistance was confirmed by logistic regression analysis; hence resistance (dose-responses) in each field populations differed, depending on the choice of the acaricide, frequent usage, frequency of treatment and farm management. The effective estimated dose needed to eliminate 99% of ticks is higher than dose recommended by the manufacturer. In conclusion, amitraz showed the highest resistance followed by ivermectin and alpha-cypermethrin and reveals differences on resistance in each individual field population. This information is important in order to establish the monitoring of resistance on each farm individually, contributing to the rational use of acaricides included in an integrated control program for R. microplus.

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 resistance, respectively. For adult tests with amitraz 50% and 17% of the field populations showed average and high resistance, with evidences of average resistance to alpha-cypermethrin in 50% of the samples and average resistance against ivermectin in 25% of the farms. No statistical difference amongst the three bioassays was found and acaricide resistance was confirmed by logistic regression analysis; hence resistance (dose-responses) in each field populations differed, depending on the choice of the acaricide, frequent usage, frequency of treatment and farm management. The effective estimated dose needed to eliminate 99% of ticks is higher than dose recommended by the manufacturer. In conclusion, amitraz showed the highest resistance followed by ivermectin and alpha-cypermethrin and reveals differences on resistance in each individual field population. This information is important in order to establish the monitoring of resistance on each farm individually, contributing to the rational use of acaricides included in an integrated control program for R. microplus. PMID:28388639

75 FR 60308 - New Animal Drugs for Use in Animal Feeds; Melengestrol

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Melengestrol AGENCY: Food and Drug... amending the animal drug regulations to more accurately reflect the recent approval of two supplemental new animal drug applications (NADAs) filed by Pharmacia & Upjohn Co., a Division of Pfizer, Inc. The...

75 FR 12981 - Oral Dosage Form New Animal Drugs; Tetracycline Powder

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tetracycline Powder AGENCY: Food and Drug... amending the animal drug regulations to reflect approval of a supplemental new animal drug application... approval of this product. This change is being made to improve the accuracy of the animal drug regulations...

77 FR 4226 - Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Danofloxacin AGENCY: Food... amending the animal drug regulations to reflect approval of a supplemental new animal drug application.... 801-808. List of Subjects in 21 CFR Part 522 Animal drugs. Therefore, under the Federal Food, Drug...

78 FR 75570 - Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products Administered...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-12

... Medicated Feed or Drinking Water of Food-Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning Product Use Conditions With Guidance for Industry 209; Availability AGENCY: Food and Drug... availability of a guidance for industry 213 entitled ``New Animal Drugs and New Animal Drug Combination...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if...

76 FR 65109 - New Animal Drugs for Use in Animal Feeds; Melengestrol; Monensin; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

.... FDA-2011-N-0003] New Animal Drugs for Use in Animal Feeds; Melengestrol; Monensin; Tylosin AGENCY...) is amending the animal drug regulations to reflect approval of a supplemental abbreviated new animal drug application (ANADA) filed by Ivy Laboratories, Division of Ivy Animal Health, Inc. The...

21 CFR 558.355 - Monensin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Monensin. 558.355 Section 558.355 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 Animal Feeds § 558.355 Monensin. (a)...

77 FR 22327 - Draft Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-13

... or on Medicated Feed or Drinking Water of Food-Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning Product Use Conditions With GFI 209; Availability AGENCY: Food and Drug... availability of a draft guidance for industry (draft GFI 213) entitled ``New Animal Drugs and New Animal Drug...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 516.30 - Annual reports for a MUMS-designated drug.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.30 Annual reports for a MUMS-designated drug... investigational new animal drug file addressed to the Director of the Office of Minor Use and Minor Species Animal...

21 CFR 530.41 - Drugs prohibited for extralabel use in animals.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... 530.41 Section 530.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... substances are prohibited for extralabel animal and human drug uses in food-producing animals. (1... following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses...

21 CFR 530.41 - Drugs prohibited for extralabel use in animals.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... 530.41 Section 530.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... substances are prohibited for extralabel animal and human drug uses in food-producing animals. (1... following drugs, families of drugs, and substances are prohibited for extralabel animal and human drug uses...

21 CFR 510.7 - Consignees of new animal drugs for use in the manufacture of animal feed.

Code of Federal Regulations, 2010 CFR

2010-04-01

... manufacture of animal feed. 510.7 Section 510.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Provisions § 510.7 Consignees of new animal drugs for use in the manufacture of animal feed. (a) A new animal drug intended for use in the manufacture of animal feed shall be deemed to be unsafe unless at the time...

75 FR 7555 - New Animal Drugs for Use in Animal Feeds; Bacitracin Zinc; Nicarbazin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Bacitracin Zinc; Nicarbazin AGENCY: Food... amending the animal drug regulations to reflect approval of an original abbreviated new animal drug... generic copy of NADA 141-146, sponsored by Phibro Animal Health, for combination use of BACIFERM...

76 FR 60721 - New Animal Drugs for Use in Animal Feeds; Melengestrol; Monensin

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

.... FDA-2011-N-0003] New Animal Drugs for Use in Animal Feeds; Melengestrol; Monensin AGENCY: Food and... amending the animal drug regulations to reflect approval of a supplemental abbreviated new animal drug application (ANADA) filed by Ivy Laboratories, Division of Ivy Animal Health, Inc. The supplemental ANADA...

75 FR 20917 - New Animal Drugs for Use in Animal Feeds; Melengestrol, Monensin, and Ractopamine

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Melengestrol, Monensin, and Ractopamine... (FDA) is amending the animal drug regulations to reflect approval of a supplemental abbreviated new animal drug application (ANADA) filed by Ivy Laboratories, Div. of Ivy Animal Health, Inc. The...

77 FR 26161 - New Animal Drugs; Ceftiofur Crystalline Free Acid; Gamithromycin; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-03

... [Docket No. FDA-2012-N-0002] New Animal Drugs; Ceftiofur Crystalline Free Acid; Gamithromycin; Tylosin... (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs) during February 2012. FDA is also...

77 FR 76862 - New Animal Drugs; Enrofloxacin; Melengestrol; Meloxicam; Pradofloxacin; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

..., and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Enrofloxacin; Melengestrol; Meloxicam... Administration (FDA) is amending the animal drug regulations to reflect approval actions for new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs) during November 2012. FDA is also...

77 FR 60301 - New Animal Drugs; Butorphanol; Doxapram; Triamcinolone; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

..., and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Butorphanol; Doxapram; Triamcinolone; Tylosin... (FDA) is amending the animal drug regulations to reflect the withdrawal approval of a new animal drug application (NADA) and three abbreviated new animal drug applications (ANADAs) at the sponsors' request...

21 CFR 558.78 - Bacitracin zinc.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Bacitracin zinc. 558.78 Section 558.78 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 Animal Feeds § 558.78 Bacitracin zinc. (a)...

21 CFR 558.78 - Bacitracin zinc.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Bacitracin zinc. 558.78 Section 558.78 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 Animal Feeds § 558.78 Bacitracin zinc. (a)...

21 CFR 530.20 - Conditions for permitted extralabel animal and human drug use in food-producing animals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... illegal drug residues occur in any food-producing animal subjected to extralabel treatment. (b) The... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Conditions for permitted extralabel animal and human drug use in food-producing animals. 530.20 Section 530.20 Food and Drugs FOOD AND DRUG...

21 CFR 530.20 - Conditions for permitted extralabel animal and human drug use in food-producing animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... illegal drug residues occur in any food-producing animal subjected to extralabel treatment. (b) The... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Conditions for permitted extralabel animal and human drug use in food-producing animals. 530.20 Section 530.20 Food and Drugs FOOD AND DRUG...

21 CFR 530.20 - Conditions for permitted extralabel animal and human drug use in food-producing animals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... illegal drug residues occur in any food-producing animal subjected to extralabel treatment. (b) The... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Conditions for permitted extralabel animal and human drug use in food-producing animals. 530.20 Section 530.20 Food and Drugs FOOD AND DRUG...

21 CFR 530.20 - Conditions for permitted extralabel animal and human drug use in food-producing animals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... illegal drug residues occur in any food-producing animal subjected to extralabel treatment. (b) The... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Conditions for permitted extralabel animal and human drug use in food-producing animals. 530.20 Section 530.20 Food and Drugs FOOD AND DRUG...

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.

77 FR 32897 - New Animal Drugs; Change of Sponsor's Name

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

.... FDA-2012-N-0002] New Animal Drugs; Change of Sponsor's Name AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug... 21 CFR Part 510 Administrative practice and procedure, Animal drugs, Labeling, Reporting and...

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.

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.

76 FR 2807 - New Animal Drugs; Change of Sponsor; Follicle Stimulating Hormone

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

... [Docket No. FDA-2010-N-0002] New Animal Drugs; Change of Sponsor; Follicle Stimulating Hormone AGENCY...) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug... currently listed in the animal drug regulations as a sponsor of an approved application. Accordingly, Sec...

75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... 558 [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride; Nitromide and Sulfanitran AGENCY...) is amending the animal drug regulations by removing those portions that reflect approval of eight new...

Diagnosis-based treatment of helminths in captive and wild cheetahs (Acinonyx jubatus).

PubMed

Mény, Marie; Schmidt-Küntzel, Anne; Marker, Laurie L

2012-12-01

This study was designed to identify endoparasites in captive cheetahs (Acinonyx jubatus) living in a seminatural captive environment in north-central Namibia. Results were used to assess the need for anthelmintic treatment and for the selection of an appropriate drug. The study assessed fecal parasite excretion qualitatively and quantitatively using a fecal flotation method during the winter of 2009. Four different species of parasites (two nematodes and two coccidias) were identified. Parasite excretion rates were found to be significantly lower than that of wild cheetahs living in the same area. Samples of the wild cheetahs were obtained at the time of anesthesia or were attributed to the wild individuals using genetic profiling. Captive cheetahs were dewormed with fenbendazole, whereas wild cheetahs were treated using ivermectin. Efficacy of these treatments was demonstrated at the end of the study.

21 CFR 558.600 - Tiamulin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Tiamulin. 558.600 Section 558.600 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 558.600 - Tiamulin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Tiamulin. 558.600 Section 558.600 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 558.600 - Tiamulin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Tiamulin. 558.600 Section 558.600 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...

76 FR 38554 - Oral Dosage Form New Animal Drugs; Amprolium

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by Cross...

77 FR 4226 - Oral Dosage Form New Animal Drugs; Gentamicin Sulfate

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Gentamicin Sulfate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA...

75 FR 76259 - Oral Dosage Form New Animal Drugs; Tylosin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new animal drug application (ANADA) filed by...

77 FR 4224 - New Animal Drugs; Change of Sponsor's Name

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

.... FDA-2011-N-0003] New Animal Drugs; Change of Sponsor's Name AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug.... 801-808. List of Subjects in 21 CFR Part 510 Administrative practice and procedure, Animal drugs...

21 CFR 558.600 - Tiamulin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tiamulin. 558.600 Section 558.600 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 207.20 - Who must register and submit a drug list.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., preparation, propagation, compounding, or processing of an animal feed bearing or containing an animal drug (i... drug application, a new animal drug application, an abbreviated new animal drug application, a... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Who must register and submit a drug list. 207.20...

21 CFR 207.20 - Who must register and submit a drug list.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., preparation, propagation, compounding, or processing of an animal feed bearing or containing an animal drug (i... drug application, a new animal drug application, an abbreviated new animal drug application, a... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Who must register and submit a drug list. 207.20...

21 CFR 207.20 - Who must register and submit a drug list.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., preparation, propagation, compounding, or processing of an animal feed bearing or containing an animal drug (i... drug application, a new animal drug application, an abbreviated new animal drug application, a... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Who must register and submit a drug list. 207.20...

21 CFR 207.20 - Who must register and submit a drug list.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., preparation, propagation, compounding, or processing of an animal feed bearing or containing an animal drug (i... drug application, a new animal drug application, an abbreviated new animal drug application, a... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Who must register and submit a drug list. 207.20...

21 CFR 207.20 - Who must register and submit a drug list.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., preparation, propagation, compounding, or processing of an animal feed bearing or containing an animal drug (i... drug application, a new animal drug application, an abbreviated new animal drug application, a... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Who must register and submit a drug list. 207.20...

21 CFR 530.21 - Prohibitions for food-producing animals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Prohibitions for food-producing animals. 530.21... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.21 Prohibitions for...

76 FR 16534 - New Animal Drugs for Use in Animal Feeds; Florfenicol; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

.... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Florfenicol; Correction AGENCY: Food and...) published a document in the Federal Register of June 17, 2010 (75 FR 34361) revising the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA). That document contained...

21 CFR 530.21 - Prohibitions for food-producing animals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Prohibitions for food-producing animals. 530.21... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.21 Prohibitions for...

21 CFR 530.21 - Prohibitions for food-producing animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Prohibitions for food-producing animals. 530.21... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.21 Prohibitions for...

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.

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

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.

21 CFR 510.7 - Consignees of new animal drugs for use in the manufacture of animal feed.

Code of Federal Regulations, 2011 CFR

2011-04-01

... notice from the Secretary, to the effect that with respect to the use of such drug in animal feed the... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Consignees of new animal drugs for use in the manufacture of animal feed. 510.7 Section 510.7 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

76 FR 79064 - New Animal Drugs; Change of Sponsor; Zinc Gluconate

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-21

... [Docket No. FDA-2011-N-0003] New Animal Drugs; Change of Sponsor; Zinc Gluconate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug application (NADA) for zinc...

21 CFR 500.46 - Hexachlorophene in animal drugs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Hexachlorophene in animal drugs. 500.46 Section...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Specific Administrative Rulings and Decisions § 500.46 Hexachlorophene in animal drugs. (a) The Commissioner of Food and Drugs has determined that there are no adequate...

21 CFR 500.46 - Hexachlorophene in animal drugs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hexachlorophene in animal drugs. 500.46 Section...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Specific Administrative Rulings and Decisions § 500.46 Hexachlorophene in animal drugs. (a) The Commissioner of Food and Drugs has determined that there are no adequate...

21 CFR 500.46 - Hexachlorophene in animal drugs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hexachlorophene in animal drugs. 500.46 Section...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Specific Administrative Rulings and Decisions § 500.46 Hexachlorophene in animal drugs. (a) The Commissioner of Food and Drugs has determined that there are no adequate...

76 FR 40229 - Oral Dosage Form New Animal Drugs; Change of Sponsor

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

.... FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Change of Sponsor AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for a new animal drug application (NADA) from Virbac AH...

75 FR 54018 - Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

.... FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Praziquantel and Pyrantel AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by...

21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food... approved human drug or an approved animal drug. The agency will publish in the Federal Register a notice of...

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

21 CFR 558.115 - Carbadox.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 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 Animal Feeds § 558.115 Carbadox. (a) Approvals. Type A medicated articles: 2.2. percent (10 grams per...

21 CFR 558.115 - Carbadox.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 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 Animal Feeds § 558.115 Carbadox. (a) Approvals. Type A medicated articles: 2.2. percent (10 grams per...

21 CFR 558.115 - Carbadox.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 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 Animal Feeds § 558.115 Carbadox. (a) Approvals. Type A medicated articles: 2.2. percent (10 grams per...

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 binding conformation between the first and second transmembrane domains which not only tallies with previous mutagenesis studies, but would also likely have the effect of stabilizing the open channel structure, consistent with the mode of action of this positive allosteric modulator. From our docking simulations and analysis of sequence homology we propose a series of mutations likely to confer ivermectin sensitivity to human P2X1. PMID:29456508

21 CFR 211.173 - Laboratory animals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Laboratory animals. 211.173 Section 211.173 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Laboratory animals. Animals used in testing components, in-process materials, or drug products for compliance...

21 CFR 211.173 - Laboratory animals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Laboratory animals. 211.173 Section 211.173 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Laboratory animals. Animals used in testing components, in-process materials, or drug products for compliance...

21 CFR 211.173 - Laboratory animals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Laboratory animals. 211.173 Section 211.173 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Laboratory animals. Animals used in testing components, in-process materials, or drug products for compliance...

21 CFR 211.173 - Laboratory animals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Laboratory animals. 211.173 Section 211.173 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Laboratory animals. Animals used in testing components, in-process materials, or drug products for compliance...

21 CFR 211.173 - Laboratory animals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Laboratory animals. 211.173 Section 211.173 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Laboratory animals. Animals used in testing components, in-process materials, or drug products for compliance...

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... drugs intended for use in milk-producing animals. 510.106 Section 510.106 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW... antibiotic-containing drugs intended for use in milk-producing animals. Whenever the labeling of an...

21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... drugs intended for use in milk-producing animals. 510.106 Section 510.106 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW... antibiotic-containing drugs intended for use in milk-producing animals. Whenever the labeling of an...

21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

Code of Federal Regulations, 2010 CFR

2010-04-01

... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... RESIDUES OF NEW ANIMAL DRUGS IN FOOD General Provisions § 556.1 General considerations; tolerances for residues of new animal drugs in food. (a) Tolerances established in this part are based upon residues of...

21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

Code of Federal Regulations, 2011 CFR

2011-04-01

... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... RESIDUES OF NEW ANIMAL DRUGS IN FOOD General Provisions § 556.1 General considerations; tolerances for residues of new animal drugs in food. (a) Tolerances established in this part are based upon residues of...

21 CFR 501.100 - Animal food; exemptions from labeling.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Animal food; exemptions from labeling. 501.100 Section 501.100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ANIMAL FOOD LABELING Exemptions From Animal Food...