National strategy on the integration of sleep and circadian rhythms into public health research and policies: Report from the Canadian Sleep and Circadian Network.

Scientists in sleep and circadian rhythms, public health experts, healthcare providers, partners, and stakeholders convened in 2020 for a 2-day meeting organized by the Canadian Sleep and Circadian Network to develop a national strategy for integrating sleep and circadian rhythms into public health and policies in Canada. The objective of this paper is to present the national strategy that emerged from this meeting of 60 participants from across Canada. The meeting focused on 4 key target priorities: (1) atypical working schedules, (2) sleep and circadian rhythms of children and adolescents, (3) insomnia, and (4) impact of sleep apnea on health.

Clinical validation of molecular markers of macrocyclic lactone resistance in Dirofilaria immitis.

Prophylaxis with macrocyclic lactone (ML) endectocides is the primary strategy for heartworm control. Recent evidence has confirmed that ML-resistant Dirofilaria immitis isolates have evolved. Comparison of genomes of ML-resistant isolates show they are genetically distinct from wild-type populations.

G-protein-coupled receptor genes of Dirofilaria immitis.

The diversity and uniqueness of nematode heterotrimeric G-protein-coupled receptors (GPCRs) provides impetus for identifying ligands that can be used as therapeutics for treating diseases caused by parasitic nematode infections. In human medicine, GPCRs have represented the largest group of 'drugable' targets exploited in the market today. In the filarial nematode Dirofilaria immitis, which causes heartworm disease, the macrocyclic lactones (ML) have been used as the sole preventatives for more than 25 years and now there is confirmed ML resistance in this parasite.

Dirofilaria immitis JYD-34 isolate: whole genome analysis.

Background: Macrocyclic lactone (ML) anthelmintics are used for chemoprophylaxis for heartworm infection in dogs and cats. Cases of dogs becoming infected with heartworms, despite apparent compliance to recommended chemoprophylaxis with approved preventives, has led to such cases being considered as suspected lack of efficacy (LOE). Recently, microfilariae collected from a small number of LOE isolates were used as a source of infection of new host dogs and confirmed to have reduced susceptibility to ML in controlled efficacy studies using L3 challenge in dogs.

Genetic profiles of ten Dirofilaria immitis isolates susceptible or resistant to macrocyclic lactone heartworm preventives.

Background: For dogs and cats, chemoprophylaxis with macrocyclic lactone (ML) preventives for heartworm disease is widely used in the United States and other countries. Since 2005, cases of loss of efficacy (LOE) of heartworm preventives have been reported in the U.S.

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

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.

Polymorphism in ABC transporter genes of Dirofilaria immitis.

Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and occasionally in humans. Prevention of the disease has been mainly by monthly use of the macrocyclic lactone (ML) endectocides during the mosquito transmission season. Recently, ML resistance has been confirmed in D.

Isothermal Diagnostic Assays for Monitoring Single Nucleotide Polymorphisms in Necator americanus Associated with Benzimidazole Drug Resistance.

Background: Soil-transmitted helminths (STHs) are the most prevalent intestinal helminths of humans, and a major cause of morbidity in tropical and subtropical countries. The benzimidazole (BZ) drugs albendazole (ABZ) and mebendazole (MBZ) are used for treatment of human STH infections and this use is increasing dramatically with massive drug donations. Frequent and prolonged use of these drugs could lead to the emergence of anthelmintic resistance as has occurred in nematodes of livestock.

Polymorphism in ion channel genes of Dirofilaria immitis: Relevant knowledge for future anthelmintic drug design.

Dirofilaria immitis, a filarial parasite, causes cardiopulmonary dirofilariasis in dogs, cats and wild canids. The macrocyclic lactone (ML) class of drugs has been used to prevent heartworm infection. There is confirmed ML resistance in D.

Interaction of macrocyclic lactones with a Dirofilaria immitis P-glycoprotein.

Dirofilaria immitis, a filarial nematode, causes dirofilariasis or heartworm disease in dogs, cats and wild canids. Effective prevention of the disease is mainly by the use of the macrocyclic lactone class of drugs as heartworm preventives, and no other class of drugs is effective for preventing infection. Macrocyclic lactones have been used for prevention of heartworm infection for more than 26years.

ABC-B transporter genes in Dirofilaria immitis.

Dirofilaria immitis is a filarial nematode causing infection and heartworm disease in dogs and other canids, cats, and occasionally in humans. Prevention with macrocyclic lactones (ML) is recommended during the mosquito transmission season. Recently, ML resistance has been reported.

Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance.

Macrocyclic lactone (ML) endectocides are used as chemoprophylaxis for heartworm infection (Dirofilaria immitis) in dogs and cats. Claims of loss of efficacy (LOE) of ML heartworm preventives have become common in some locations in the USA. We directly tested whether resistance to MLs exists in LOE isolates of D.

Establishment of macrocyclic lactone resistant Dirofilaria immitis isolates in experimentally infected laboratory dogs.

Background: Strains of Dirofilaria immitis suspected of lack of efficacy (LOE) to macrocyclic lactone (ML) preventive drugs have been increasingly reported in dogs by practicing veterinarians since 2005 in the Lower Mississippi Delta region. If proven, and not controlled in the early stages, the emergence of ML drug resistance threatens to become a widespread problem in the US that may limit the effectiveness of current preventive drug treatment methods.

Methods: To validate practice reports, a statewide survey of Louisiana veterinarians was done to define the extent of the problem and identify focal 'hotspots' of reported ML LOEs using Geographic Information Systems (GIS) methods.

Reproductive status of Onchocerca volvulus after ivermectin treatment in an ivermectin-naïve and a frequently treated population from Cameroon.

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.

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

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.

Single nucleotide polymorphisms in β-tubulin selected in Onchocerca volvulus following repeated ivermectin treatment: possible indication of resistance selection.

The control of onchocerciasis or river blindness by mass treatment of the population with ivermectin (IVM) has been a great success until now, so that in certain foci its elimination has become feasible. However, after more than 20 years of repeated IVM mass treatment, the disease still persists in many endemic countries. Sub-optimal responses and genetic changes have been reported in Onchocerca volvulus populations under high IVM pressure but more work is needed to determine whether resistance is developing.

Genetic diversity of Plasmodium falciparum merozoite surface protein-1 block 2 in sites of contrasting altitudes and malaria endemicities in the Mount Cameroon region.

The present study analyzed the relationship between the genetic diversity of Plasmodium falciparum and parasitologic/entomologic indices in the Mount Cameroon region by using merozoite surface protein 1 as a genetic marker. Blood samples were collected from asymptomatic children from three altitude zones (high, intermediate, and low). Parasitologic and entomologic indices were determined by microscopy and landing catch mosquito collection/circumsporozoite protein-enzyme-linked immunosorbent assay, respectively.

Evidence for macrocyclic lactone anthelmintic resistance in Dirofilaria immitis.

Reports of loss-of-efficacy (LOE) events in dogs infected with Dirofilaria immitis despite adherence to accepted prophylaxis regimens with a macrocyclic lactone anthelmintic are attracting considerable attention. It is crucially important to distinguish among several possible causes for these LOE reports, one of which is the evolution of resistance to these drugs in heartworms. We review here recent evidence at the molecular level that supports the hypothesis that parasites derived from LOE cases have experienced a strong selection event and that these populations are characterized by very high frequencies of single-nucleotide polymorphisms in a D.

Macrocyclic lactone resistance in Dirofilaria immitis.

Microfilariae were isolated from a Katrina rescue dog that remained microfilariaemic despite successful adulticidal treatments and repeated treatment with high doses of macrocyclic lactones (MLs). The microfilariae were genotyped at two P-glycoprotein single nucleotide polymorphic sites which had been found to correlate with reduced sensitivity to MLs. The genetic polymorphism (GG-GG), previously found to be associated with insensitivity to MLs in vitro, was present at a frequency of 45.

Genetic polymorphism in Dirofilaria immitis.

Dirofilaria immitis is the causative agent of heartworm disease. Reports of macrocyclic lactone inefficacy prompted an investigation of genetic polymorphism in D. immitis.

Correlation between loss of efficacy of macrocyclic lactone heartworm anthelmintics and P-glycoprotein genotype.

Macrocyclic lactone (ML) molecules have been used for heartworm control for more than 25 years. However, in recent years, there have been reports of loss of efficacy of ML heartworm preventatives against Dirofilaria immitis in some locations in the United States. Macrocyclic lactone resistance is a common problem in nematode parasites of livestock, and more recently, evidence of ivermectin resistance has been reported in the human filarial nematode Onchocerca volvulus.

Analysis of the mdr-1 gene in patients co-infected with Onchocerca volvulus and Loa loa who experienced a post-ivermectin serious adverse event.

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.

P-glycoprotein-like protein, a possible genetic marker for ivermectin resistance selection in Onchocerca volvulus.

Ivermectin (IVM) is the only safe drug for mass-treatment of onchocerciasis. IVM resistance has been reported in gastrointestinal nematode parasites of animals. A reduction in response to IVM in Onchocerca volvulus could have significant consequences for the onchocerciasis control programs.

Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment.

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.

Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus.

Ivermectin resistance is common in trichostrongylid nematodes of livestock, such as Haemonchus contortus. This anthelmintic is the only drug approved for mass administration to control onchocerciasis caused by the nematode parasite, Onchocerca volvulus. In parts of West Africa up to 18 rounds of ivermectin treatment have been administered to communities and there are reports of poor parasitological responses to treatment.