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Søgeord (ivermectin) valgt.
21 emner vises.
Kunlakanya Jitobaom, Paleerath Peerapen, Usa Boonyuen, Ittipat Meewan, Chompunuch Boonarkart, Thanyaporn Sirihongthong, Songkran Thongon, Visith Thongboonkerd, Prasert Auewarakul
Journal of Medical Virology, 22.03.2024
Tilføjet 22.03.2024
Malaria Journal, 23.02.2024
Tilføjet 23.02.2024
Abstract Background Mass Drug Administration (MDA) has become a mainstay for the control of several diseases over the last two decades. Successful implementation of MDA programmes requires community participation and can be threatened by systematic non-participation. Such concerns are particularly pertinent for MDA programmes against malaria, as they require multi-day treatment over several consecutive months. Factors associated with non-participation to the MDA campaign with ivermectin (IVM) and dihydroartemisinin-piperaquine (DHP) implemented within the MASSIV cluster randomized trial were determined. Methods Coverage data was extracted from the MASSIV trial study database, with every datapoint being a directly observed therapy (DOT). A complete month of MDA was classified as receiving all three daily doses of treatment. For both ivermectin and DHP, ordinal logistic regression was used to identify individual and household level variables associated with non-participation. Results For ivermectin, 51.5% of eligible participants received all 3 months of treatment while 30.7% received either one or two complete months. For DHP, 56.7% of eligible participants received all 3 months of treatment and 30.5% received either one or two complete months. Children aged 5–15 years and adults aged more than 50 years were more likely to receive at least one complete month of MDA than working age adults, both for ivermectin (aOR 4.3, 95% CI 3.51–5.28 and aOR of 2.26, 95% CI 1.75–2.95) and DHP (aOR 2.47, 95%CI 2.02–3.02 and aOR 1.33, 95%CI 1.01–1.35), respectively. Members of households where the head received a complete month of MDA were more likely to themselves have received a complete month of MDA, both for ivermectin (aOR 1.71, 95%CI 1.35–2.14) and for DHP (aOR 1.64, 95%CI 1.33–2.04). Conclusion Personal and household-level variables were associated with participation in the MDA programme for malaria control. Specific strategies to (increase participation amongst some groups may be important to ensure maximum impact of MDA strategies in achieving malaria elimination. Trial registration: The MASSIV trial is registered under NCT03576313.
Læs mere Tjek på PubMedHaruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama
PLoS One Infectious Diseases, 27.01.2024
Tilføjet 27.01.2024
by Haruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama Objective Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan. Design The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan. Participants Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021. Exposures The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine. Results We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period. Conclusions and relevance This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.
Læs mere Tjek på PubMedMalaria Journal, 18.01.2024
Tilføjet 18.01.2024
Abstract Background Asymptomatic malaria transmission has become a public health concern across malaria-endemic Africa including Ethiopia. Specifically, Plasmodium vivax is more efficient at transmitting earlier in the infection and at lower densities than Plasmodium falciparum. Consequently, a greater proportion of individuals infected with P. vivax can transmit without detectable gametocytaemia. Mass treatment of livestock with macrocyclic lactones (MLs), e.g., ivermectin and doramectin, was suggested as a complementary malaria vector tool because of their insecticidal effects. However, the effects of MLs on P. vivax in Anopheles arabiensis has not yet been fully explored. Hence, comparative in-vitro susceptibility and ex-vivo studies were conducted to evaluate the effects of ivermectin, doramectin and moxidectin sub-lethal concentrations on P. vivax oocyst development in An. arabiensis. Methods The 7-day sub-lethal concentrations of 25% (LC25) and 5% (LC5) were determined from in-vitro susceptibility tests on female An. arabiensis in Hemotek® membrane feeding assay. Next, an ex-vivo study was conducted using P. vivax gametocytes infected patient’s blood spiked with the LC25 and LC5 of the MLs. At 7-days post-feeding, each mosquito was dissected under a dissection stereo microscope, stained with 0.5% (w/v) mercurochrome solution, and examined for the presence of P. vivax oocysts. Statistical analysis was based on a generalized mixed model with binomially distributed error terms. Results A 7-day lethal concentration of 25% (LC25, in ng/mL) of 7.1 (95% CI: [6.3;8.0]), 20.0 (95%CI:[17.8;22.5]) and 794.3 (95%CI:[716.4;1516.3]) were obtained for ivermectin, doramectin and moxidectin, respectively. Similarly, a lethal concentration of 5% (LC5, in ng/mL) of 0.6 (95% CI: [0.5;0.7]), 1.8 (95% CI:[1.6;2.0]) and 53.7 (95% CI:[ 48.4;102.5]) were obtained respectively for ivermectin, doramectin and moxidectin. The oocyst prevalence in treatment and control groups did not differ significantly (p > 0.05) from each other. Therefore, no direct effect of ML endectocides on P. vivax infection in An. arabiensis mosquitoes was observed at the sub-lethal concentration (LC25 and LC5). Conclusions The effects of ivermectin and doramectin on malaria parasite is more likely via indirect effects, particularly by reducing the vectors lifespan and causing mortality before completing the parasite’s sporogony cycle or reducing their vector capacity as it affects the locomotor activity of the mosquito.
Læs mere Tjek på PubMedJosé R. Verdú, Vieyle Cortez, Rocío Rosa-García, Antonio J. Ortiz, Urcesino García-Prieto, Jean-Pierre Lumaret, Carmelo García Romero, Francisco Sánchez-Piñero
PLoS One Infectious Diseases, 21.12.2023
Tilføjet 21.12.2023
by José R. Verdú, Vieyle Cortez, Rocío Rosa-García, Antonio J. Ortiz, Urcesino García-Prieto, Jean-Pierre Lumaret, Carmelo García Romero, Francisco Sánchez-Piñero The sustainability of the traditional extensive livestock sector will only be possible if healthy dung-decomposing insect communities are preserved. However, many current pharmaceutical anthelmintics are harmful to dung beetles, their presence can have a negative impact on biological systems. Phytochemical anthelmintics are an alternative to ecotoxic synthetic pharmaceutical anthelmintics, although ecotoxicological tests of their possible indirect effects on dung beetles are required to demonstrate their viability. In this study, the potential ecotoxicity of thymol, carvacrol, cinnamaldehyde and garlic oil (diallyl disulfide and diallyl trisulfide) were tested for the first time. Inhibition of antennal response was measured as a relevant parameter by obtaining relevant toxicity thresholds derived from concentration‒response curves, such as the IC50. All phytochemical compounds tested were demonstrated to be suitable alternative candidates to the highly ecotoxic compound ivermectin, considering their non-toxicity to nontarget organisms. Residues of the phytochemical antiparasitics found in cattle droppings were extremely low, even undetectable in the case of diallyl disulfide and diallyl trisulfide. Furthermore, our results showed that none of the phytochemical compounds have ecotoxic effects, even at extremely high concentrations, including those almost 1000 times higher than what is most likely to be found in dung susceptible to ingestion by dung beetles in the field. We can conclude that the four selected phytochemical compounds meet the requirements to be considered reliable alternatives to ecotoxic veterinary medicinal products, such as ivermectin.
Læs mere Tjek på PubMedBMC Infectious Diseases, 18.11.2023
Tilføjet 18.11.2023
Abstract Background The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by 2030. The strategy to reach this goal is based on ivermectin Mass Drug Administration (MDA) with high geographical and therapeutic coverage. In addition to coverage, high levels of treatment adherence are paramount. We investigated factors associated with ivermectin intake in an area of Ghana with persistent Onchocerca volvulus infection. Methods In August 2021, a cross-sectional mixed-methods study was conducted in 13 onchocerciasis-endemic communities in the Bono Region of Ghana. Individuals aged ≥ 10 years were invited to participate in a questionnaire survey. A total of 48 focus group discussions and in-depth interviews with 10 community drug distributors and 13 community leaders were conducted. Results A total of 510 people participated in the study [median age: 32, interquartile range 30 (20‒50) years]; 274 (53.7%) were females. Of the total, 320 (62.7%) declared that they adhered to each treatment round and 190 (37.3%) admitted they had not taken ivermectin during at least one MDA round, since becoming eligible for treatment. Of 483 participants with complete information, 139 (28.8%) did not take ivermectin during the last round (March 2021), and 24 (5.0%) had never taken ivermectin (systematic non-adherers). Reasons for not taking ivermectin included previous experience/fear of side-effects, being absent during MDA, pregnancy, the desire to drink alcohol, and drug distribution challenges. Being male, having good knowledge and perception of the disease, and not having secondary or higher level of formal education were significantly associated with higher odds of ivermectin intake. Conclusions A relatively high level of non-adherence to ivermectin treatment was documented. There is a need for targeted educational and behavioural change campaigns to reverse these trends and ensure a steady course toward meeting onchocerciasis elimination targets in Ghana.
Læs mere Tjek på PubMedViviane P Sprecher, Daniela Hofmann, Vanthanom Savathdy, Phengsavanh Xayavong, Chomseng Norkhankhame, Rekol Huy, Virak Khieu, Somphou Sayasone, Jan Hattendorf, Jennifer Keiser
Lancet Infectious Diseases, 8.11.2023
Tilføjet 8.11.2023
Moxidectin was non-inferior to ivermectin in terms of efficacy in the treatment of strongyloidiasis. Additionally, both drugs had a similar safety profile. The fixed dose and lower cost of moxidectin compared with ivermectin make it a valuable alternative for people with strongyloidiasis.
Læs mere Tjek på PubMedKenneth Bentum Otabil, María‐Gloria Basáñez, Blessing Ankrah, Stephen Agyemang Opoku, Dennis Ofori Kyei, Rhoda Hagan, Richmond Ababio, Emmanuel John Bart‐Plange, Theophilus Nti Babae, Prince‐Charles Kudzordzi, Vera Achiaa Darko, Joseph G. Bamfo, Joseph Ameyaw, Abdul Sakibu Raji, Amber Hadermann, Henk D. F. H. Schallig, Robert Colebunders
Tropical Medicine & International Health, 18.10.2023
Tilføjet 18.10.2023
Malaria Journal, 30.09.2023
Tilføjet 30.09.2023
Abstract Background Ivermectin (IVM) mass drug administration is a candidate complementary malaria vector control tool. Ingestion of blood from IVM treated hosts results in reduced survival in mosquitoes. Estimating bio-efficacy of IVM on wild-caught mosquitoes requires they ingest the drug in a blood meal either through a membrane or direct feeding on a treated host. The latter, has ethical implications, and the former results in low feeding rates. Therefore, there is a need to develop a safe and effective method for IVM bio-efficacy monitoring in wild mosquitoes. Methods Insectary-reared Anopheles gambiae s.s. were exposed to four IVM doses: 85, 64, 43, 21 ng/ml, and control group (0 ng/ml) in three different solutions: (i) blood, (ii) 10% glucose, (iii) four ratios (1:1, 1:2, 1:4, 1:8) of blood in 10% glucose, and fed through filter paper. Wild-caught An. gambiae s.l. were exposed to 85, 43 and 21 ng/ml IVM in blood and 1:4 ratio of blood-10% glucose mixture. Survival was monitored for 28 days and a pool of mosquitoes from each cohort sacrificed immediately after feeding and weighed to determine mean weight of each meal type. Results When administered in glucose solution, mosquitocidal effect of IVM was not comparable to the observed effects when similar concentrations were administered in blood. Equal concentrations of IVM administered in blood resulted in pronounced reductions in mosquito survival compared to glucose solution only. However, by adding small amounts of blood to glucose solution, mosquito mortality rates increased resulting in similar effects to what was observed during blood feeding. Conclusion Bio-efficacy of ivermectin is strongly dependent on mode of drug delivery to the mosquito and likely influenced by digestive processes. The assay developed in this study is a good candidate for field-based bio-efficacy monitoring: wild mosquitoes readily feed on the solution, the assay can be standardized using pre-selected concentrations and by not involving treated blood hosts (human or animal) variation in individual pharmacokinetic profiles as well as ethical issues are bypassed. Meal volumes did not explain the difference in the lethality of IVM across the different meal types necessitating further research on the underlying mechanisms.
Læs mere Tjek på PubMedAmerican Journal of Tropical Medicine and Hygiene, 6.09.2023
Tilføjet 6.09.2023
Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 109 Issue: 3 Pages: 650-655
Læs mere Tjek på PubMedJournal of the American Medical Association, 16.08.2023
Tilføjet 16.08.2023
In the Original Investigation titled “Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial,” published in the October 25, 2022, issue of JAMA, a nonauthor collaborator’s surname was incorrectly listed. The full name should have been listed as Upinder Singh. This article was corrected online.
Læs mere Tjek på PubMedHutchins, H., Bradley, J., Pretorius, E., Teixeira da Silva, E., Vasileva, H., Jones, R. T., Ndiath, M. O., dit Massire Soumare, H., Mabey, D., Nante, E. J., Martins, C., Logan, J. G., Slater, H., Drakeley, C., D'Alessandro, U., Rodrigues, A., Last, A. R.
BMJ Open, 7.07.2023
Tilføjet 7.07.2023
IntroductionAs malaria declines, innovative tools are required to further reduce transmission and achieve elimination. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) is capable of reducing malaria transmission where coverage of control interventions is already high, though the impact is short-lived. Combining ACT with ivermectin, an oral endectocide shown to reduce vector survival, may increase its impact, while also treating ivermectin-sensitive co-endemic diseases and minimising the potential impact of ACT resistance in this context. Methods and analysisMATAMAL is a cluster-randomised placebo-controlled trial. The trial is being conducted in 24 clusters on the Bijagós Archipelago, Guinea-Bissau, where the peak prevalence of Plasmodium falciparum (Pf) parasitaemia is approximately 15%. Clusters have been randomly allocated to receive MDA with dihydroartemisinin–piperaquine and either ivermectin or placebo. The primary objective is to determine whether the addition of ivermectin MDA is more effective than dihydroartemisinin–piperaquine MDA alone in reducing the prevalence of P. falciparum parasitaemia, measured during peak transmission season after 2 years of seasonal MDA. Secondary objectives include assessing prevalence after 1 year of MDA; malaria incidence monitored through active and passive surveillance; age-adjusted prevalence of serological markers indicating exposure to P. falciparum and anopheline mosquitoes; vector parous rates, species composition, population density and sporozoite rates; prevalence of vector pyrethroid resistance; prevalence of artemisinin resistance in P. falciparum using genomic markers; ivermectin’s impact on co-endemic diseases; coverage estimates; and the safety of combined MDA. Ethics and disseminationThe trial has been approved by the London School of Hygiene and Tropical Medicine’s Ethics Committee (UK) (19156) and the Comite Nacional de Eticas de Saude (Guinea-Bissau) (084/CNES/INASA/2020). Results will be disseminated in peer-reviewed publications and in discussion with the Bissau-Guinean Ministry of Public Health and participating communities. Trial registration numberNCT04844905.
Læs mere Tjek på PubMedClinical Infectious Diseases, 27.06.2023
Tilføjet 27.06.2023
AbstractBackgroundThe currently recommended benzimidazole monotherapy is insufficiently effective to control infection with the soil-transmitted helminth Trichuris trichiura. Ivermectin-albendazole combination has shown promising, but setting-dependent efficacy, with therapeutic underperformance in Côte d’Ivoire. We evaluated whether moxidectin-albendazole could serve as alternative to albendazole monotherapy in Côte d’Ivoire.MethodsIn this community-based randomized, placebo-controlled, parallel-group superiority trial, 12-60 year-olds were screened for T. trichiura eggs in their stool using quadruplicate Kato-Katz thick smears. Diagnostically and clinically eligible participants were randomly assigned (1:1:1) to receive single oral doses of moxidectin (8 mg) and albendazole (400 mg), ivermectin (200 µg/kg) and albendazole (400 mg), or albendazole (400 mg) and placebo. The primary outcome was proportion cured, i.e. cure rate (CR), assessed at 2-3 weeks post-treatment. Safety endpoints were assessed pre-treatment, and at three and 24 hours post-treatment.ResultsFor the 210 participants with primary outcome data, we observed CRs of 15.3% (11/72) in the moxidectin-albendazole and 22.5% (16/71) in the ivermectin-albendazole arm, which did not differ significantly from the CR of 13.4% (9/67) in the albendazole arm (differences: 1.8%-points [95% confidence interval: -10.1 to 13.6]; 9.1%-points [-3.9 to 21.8], respectively). Most common adverse events were abdominal pain (range across arms: 11.9-20.9%), headache (4.7-14.3%), and itching (5.8-13.1%), which were predominantly mild and transient.ConclusionsAll therapies showed similar low efficacy in treating trichuriasis in Côte d’Ivoire. Alternative treatment options need to be evaluated and further analyses conducted to understand the lack of enhanced activity of the combination therapies in Côte d’Ivoire.Clinical Trials RegistrationClinicalTrials.gov (NCT04726969).
Læs mere Tjek på PubMedMalaria Journal, 25.06.2023
Tilføjet 25.06.2023
Abstract Background Ivermectin (22,23-dihydroavermectin B1a: H2B1a) is an endectocide used to treat worm infections and ectoparasites including lice and scabies mites. Furthermore, survival of malaria transmitting Anopheles mosquitoes is strongly decreased after feeding on humans recently treated with ivermectin. Currently, mass drug administration of ivermectin is under investigation as a potential novel malaria vector control tool to reduce Plasmodium transmission by mosquitoes. A “post-ivermectin effect” has also been reported, in which the survival of mosquitoes remains reduced even after ivermectin is no longer detectable in blood meals. In the present study, existing material from human clinical trials was analysed to understand the pharmacokinetics of ivermectin metabolites and feeding experiments were performed in Anopheles stephensi mosquitoes to assess whether ivermectin metabolites contribute to the mosquitocidal action of ivermectin and whether they may be responsible for the post-ivermectin effect. Methods Ivermectin was incubated in the presence of recombinant human cytochrome P450 3A4/5 (CYP 3A4/5) to produce ivermectin metabolites. In total, nine metabolites were purified by semi-preparative high-pressure liquid chromatography. The pharmacokinetics of the metabolites were assessed over three days in twelve healthy volunteers who received a single oral dose of 12 mg ivermectin. Blank whole blood was spiked with the isolated metabolites at levels matching the maximal blood concentration (Cmax) observed in pharmacokinetics study samples. These samples were fed to An. stephensi mosquitoes, and their survival and vitality was recorded daily over 3 days. Results Human CYP3A4 metabolised ivermectin more rapidly than CYP3A5. Ivermectin metabolites M1–M8 were predominantly formed by CYP3A4, whereas metabolite M9 (hydroxy-H2B1a) was mainly produced by CYP3A5. Both desmethyl-H2B1a (M1) and hydroxy-H2B1a (M2) killed all mosquitoes within three days post-feeding, while administration of desmethyl, hydroxy-H2B1a (M4) reduced survival to 35% over an observation period of 3 days. Ivermectin metabolites that underwent deglycosylation or hydroxylation at spiroketal moiety were not active against An. stephensi at Cmax levels. Interestingly, half-lives of M1 (54.2 ± 4.7 h) and M4 (57.5 ± 13.2 h) were considerably longer than that of the parent compound ivermectin (38.9 ± 20.8 h). Conclusion In conclusion, the ivermectin metabolites M1 and M2 contribute to the activity of ivermectin against An. stephensi mosquitoes and could be responsible for the “post-ivermectin effect”.
Læs mere Tjek på PubMedAchaporn Yipsirimetee, Phornpimon Tipthara, Borimas Hanboonkunupakarn, Rupam Tripura, Dysoley Lek, Krittikorn Kümpornsin, Marcus C. S. Lee, Jetsumon Sattabongkot, Arjen M. Dondorp, Nicholas J. White, Kevin C. Kobylinski, Joel Tarning, Kesinee ChotivanichaDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandbMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandcCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomdNational Center for Parasitology, Entomology and Malaria Control, Phnom Penh, CambodiaeWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United KingdomfCalibr, Division of the Scripps Research Institute, La Jolla, California, USAgMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandhDepartment of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
Antimicrobial Agents And Chemotherapy, 21.06.2023
Tilføjet 21.06.2023
American Journal of Tropical Medicine and Hygiene, 7.06.2023
Tilføjet 7.06.2023
Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 108 Issue: 6 Pages: 1183-1187
Læs mere Tjek på PubMedMalaria Journal, 5.06.2023
Tilføjet 5.06.2023
Abstract Background Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. Methods The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. Results 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. Conclusions The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (
Læs mere Tjek på PubMedFaruk Dube, Andrea Hinas, Nicolas Delhomme, Magnus Åbrink, Staffan Svärd, Eva Tydén
PLoS One Infectious Diseases, 4.05.2023
Tilføjet 4.05.2023
by Faruk Dube, Andrea Hinas, Nicolas Delhomme, Magnus Åbrink, Staffan Svärd, Eva Tydén Parasitic nematodes pose a significant threat to human and animal health, as well as cause economic losses in the agricultural sector. The use of anthelmintic drugs, such as Ivermectin (IVM), to control these parasites has led to widespread drug resistance. Identifying genetic markers of resistance in parasitic nematodes can be challenging, but the free-living nematode Caenorhabditis elegans provides a suitable model. In this study, we aimed to analyze the transcriptomes of adult C. elegans worms of the N2 strain exposed to the anthelmintic drug Ivermectin (IVM), and compare them to those of the resistant strain DA1316 and the recently identified Abamectin Quantitative Trait Loci (QTL) on chromosome V. We exposed pools of 300 adult N2 worms to IVM (10−7 and 10−8 M) for 4 hours at 20°C, extracted total RNA and sequenced it on the Illumina NovaSeq6000 platform. Differentially expressed genes (DEGs) were determined using an in-house pipeline. The DEGs were compared to genes from a previous microarray study on IVM-resistant C. elegans and Abamectin-QTL. Our results revealed 615 DEGs (183 up-regulated and 432 down-regulated genes) from diverse gene families in the N2 C. elegans strain. Of these DEGs, 31 overlapped with genes from IVM-exposed adult worms of the DA1316 strain. We identified 19 genes, including the folate transporter (folt-2) and the transmembrane transporter (T22F3.11), which exhibited an opposite expression in N2 and the DA1316 strain and were deemed potential candidates. Additionally, we compiled a list of potential candidates for further research including T-type calcium channel (cca-1), potassium chloride cotransporter (kcc-2), as well as other genes such as glutamate-gated channel (glc-1) that mapped to the Abamectin-QTL.
Læs mere Tjek på PubMedJournal of the American Medical Association, 22.03.2023
Tilføjet 22.03.2023
A Cochrane meta-analysis of 11 eligible trials examining the efficacy of ivermectin for the treatment of COVID-19 published through April 2022 concluded that ivermectin has no beneficial effect for people with COVID-19. Since May 2022, an additional 3 large randomized clinical trials including several thousand participants have been published, each reaching a similar conclusion.
Læs mere Tjek på PubMedJournal of the American Medical Association, 22.03.2023
Tilføjet 22.03.2023
This platform randomized clinical trial examines the effectiveness of ivermectin at a targeted dose of 600 μg/kg daily compared with placebo for the treatment of early mild to moderate COVID-19.
Læs mere Tjek på PubMedTrends in Parasitology, 17.02.2023
Tilføjet 18.02.2023
Ivermectin and moxidectin, two macrocyclic lactones (MLs), are exceptionally effective antiparasitic agents characterized by a broad spectrum of activity and a wide safety margin. Both drugs were initially developed for use in veterinary medicine for treatment of parasites in livestock and companion animals [1,2]. The first ivermectin formulation for humans was registered by Merck Laboratories in 1987 against onchocerciasis, got officially approved for its use against onchocerciasis and strongyloidiasis in 1996 by the US Federal Food and Drug Administration (FDA), and has since been used and distributed also as an off-label anthelmintic (see Glossary) drug against additional indications [e.g., lymphatic filariasis (LF)] to hundreds of millions of people each year.
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