Ivermectin Treatment Research Articles

Short Term Effect of Ivermectin on the Bacterial Microbiota from Fecal Samples in Chinchillas (Chinchilla lanigera)

The gastrointestinal microbiota plays an important role in health of the host animals and the detrimental influence of pharmaceutical treatment on the fecal microbiota receives an increasing concern. The clinical use of ivermectin on chinchillas has not yet been evaluated. The purpose of our study was to assess the influence of ivermectin injection on the fecal bacterial microbiota of chinchillas. A with-in subject, before and after study was performed on 10 clinically healthy chinchillas during a 14-day period, all chinchillas received the same ivermectin treatment, and the microbiota from their fecal samples before and after administration were compared as two experimental groups. Fecal samples were collected on day 0 (before ivermectin administration) and day 14 (post ivermectin administration). Fecal bacterial microbiota was analyzed by bacterial 16S rRNA gene sequencing. No clinical abnormalities were observed post subcutaneous administration of ivermectin. No significant alteration was found in the abundance and diversity of fecal bacterial microbiota after treatment, but the dominant position of some bacterial species changed. In conclusion, ivermectin administration was associated with minimal alternations of the fecal bacterial microbiota in healthy chinchillas, and these changes had no observed negative effect on general health of chinchillas in short term.

Comparative assessment of different ivermectin and doramectin formulations for mange control in grazing steers

Psoroptic mange causes relevant losses of productivity in cattle. Macrocyclic lactones are one of the main pharmacological tools recommended for controlling it. The aim of the current work was to compare the relationship between the pharmacokinetic behavior and the effectiveness of both ivermectin (IVM) and doramectin (DRM) following their administration as either the traditional (1 %) or long-acting (3.15–3.5 %) injectable formulations to cattle naturally infected with Psoroptes ovis. The overall work involved three trials (1, 2 and 3) carried out on commercial beef cattle farms (grazing systems). In Trial 1, 20 grazing steers with active mange infection were allocated into 2 groups (n = 10) and treated subcutaneously (SC) with either IVM (1 %) or DRM (1%) at 0.2 mg/kg. In Trial 2, 16 grazing steers with active mange divided in 2 groups (n = 8) were treated SC with either IVM 1 % (0.2 mg/kg) or IVM 3.15 % long-acting (0.63 mg/kg). In Trial 3, 2 groups of mange infected steers (n = 8) were treated SC with either IVM 3.15 % (0.63 mg/kg) or DRM 3.5 % (0.7 mg/kg). Blood samples were collected of each experimental group and the drug systemic availability was estimated by measuring of IVM/DRM concentrations by HPLC. Skin scraping samples were collected from each animal and mites were counted at 14, 21 and 28 days post-treatment. In Trial 1, the mite density score on day 14 was significantly lower for DRM (0.60) compared to IVM (1.80) (P = 0.019). Based on the number of animals clinically cured (negative to the presence of mites), the efficacy of DRM was higher (80 %) than that obtained for IVM (10 %) (P < 0.05). DRM systemic exposure measured as AUC was 1.37-fold higher compared to IVM. In Trial 2, even though IVM exposure was significantly greater after the long-acting (3.15 %) compared to the traditional formulation (1 %), none of the treatments significantly reduced the mite density score, with a percentage of animals cured between 0 % and 37.5 % after both IVM treatments. In Trial 3, the 100 % of cured animals were achieved at day 21 (IVM 3.15 %) and at day 28 (DRM 3.5 %) post-treatment. In conclusion, DRM treatment could offer some therapeutic advantages in field situations where IVM fails to control mange. Depending on the level of susceptibility of the mite population, long-acting pharmaceutical formulations can be useful to control Psoroptic mange in cattle. The use of macrocyclic lactones for mange control in cattle should be based on appropriate diagnosis on each individual farm.

Evaluating post-treatment Loa loa microfilarial densities to classify serious adverse events caused by ivermectin: a retrospective analysis

The elimination of onchocerciasis requires increasing ivermectin treatment coverage in communities hypoendemic for onchocerciasis. In areas where loiasis is co-endemic, this approach is complicated by the risk of serious adverse events following treatment with ivermectin in individuals with a high Loa loa microfilarial density (MFD). We aimed to evaluate the extent to which the pre-treatment MFD can be inferred from post-treatment MFDs. For this retrospective analysis, we used data from seven clinical or community trials (six were used for the main analysis and one for the secondary analysis) conducted in Cameroon, in which MFDs were measured both before and after (within 14 days) receiving a single dose of ivermectin (150-200 μg/kg bodyweight). The primary objective was to establish the receiver operating characteristic curves and the corresponding area under the curve statistics of MFD measured after treatment to classify pre-treatment MFD (MFDD0) according to common risk thresholds of serious adverse events. We assessed the performance of post-treatment MFD to accurately classify MFDD0 according to commonly used thresholds using bootstrap procedures. 281 individuals with MFD measurements available before and 3-10 days after ivermectin treatment were enrolled. Our results show that an MFD of more than 3500 L loa microfilariae per mL of blood (mf per mL) 3 or 4 days after treatment indicates a 68·6% chance (positive predictive value) of an MFDD0 of more than 20 000 mf per mL. An MFD of more than 3500 mf per mL at day 5-10 corresponds to a 72·2% chance of having an MFDD0 of more than 20 000 mf per mL. Conversely, an MFD of less than 2500 microfilariae per mL at day 3-4 or day 5-10 corresponds to a probability of 92·3% or 92·8% (negative predictive value) of having MFDD0 of less than 20 000 mf per mL. An MFD less than 1500 mf per mL on days 3-4 after treatment was associated with a 78·3% probability of having an MFDD0 less than 8000 mf per mL; this probability increased to 89·6% on days 5-10 after treatment. The MFD threshold of 1000 mf per mL within 1 month of treatment, which is commonly used to attribute the occurrence of a serious adverse event to ivermectin, should be revised. In this study, we present tables that can help to assess this attributability as part of mass or individual treatments. None.

Effect of Ivermectin® on survivorship and fertility of Anopheles arabiensis in Ethiopia: an in vitro study

BackgroundInnovative vector control tools are needed to counteract insecticide resistance and residual malaria transmission. One of such innovative methods is an ivermectin (IVM) treatment to reduce vector survival. In this study, a laboratory experiment was conducted to investigate the effect of ivermectin on survivorship, fertility and egg hatchability rate of Anopheles arabiensis in Ethiopia.MethodsAn in vitro experiment was conducted using 3–5 days old An. arabiensis adults from a colony maintained at insectary of Tropical and Infectious Diseases Research Center, Jimma University (laboratory population) and Anopheles mosquitoes reared from larvae collected from natural mosquito breeding sites (wild population). The mosquitoes were allowed to feed on cattle blood treated with different doses of ivermectin (0 ng/ml, 5 ng/ml, 10 ng/ml, 20 ng/ml, 40 ng/ml and 80 ng/ml). During each feeding experiment, the mosquitoes were held in cages and blood-fed using a Hemotek feeder. Mortality and egg production were then recorded daily for up to 9 days. Time to death was analysed by a Cox frailty model with replicate as frailty term and source of mosquito (wild versus laboratory), treatment type (ivermectin vs control) and their interaction as categorical fixed effects. Kaplan Meier curves were plotted separately for wild and laboratory populations for a visual interpretation of mosquito survival as a function of treatment.ResultsBoth mosquito source and treatment had a significant effect on survival (P < 0.001), but their interaction was not significant (P = 0.197). Compared to the controls, the death hazard of An. arabiensis that fed on ivermectin-treated blood was 2.3, 3.5, 6.5, 11.5 and 17.9 times that of the control for the 5 ng/ml, 10 ng/ml, 20 ng/ml, 40 ng/ml, and 80 ng/ml dose, respectively. With respect to the number of hatched larvae, hatched pupae and emerged adults per fed mosquitoes, a significant difference was found between the control and the 5 ng/ml dose group (P < 0.001). The number of hatched larvae and pupae, and emerged adults decreased further for the 10 ng/ml dose group and falls to zero for the higher doses.ConclusionTreating cattle blood with ivermectin reduced mosquito survival, fertility, egg hatchability, larval development and adult emergence of An. arabiensis in all tested concentrations of ivermectin in both the wild and laboratory populations. Thus, ivermectin application in cattle could be used as a supplementary vector control method to tackle residual malaria transmission and ultimately achieve malaria elimination in Ethiopia.

Mange: Epidemiology and ivermectin efficacy in goats and application of zero-inflated negative binomial regression in Uba Debre Tsehay, southern Ethiopia

Mites are one of the most common and widely distributed ectoparasites of goats in Ethiopia, contributing to major burdens in livestock productivity in the country. Between February 2021 and July 2021, this study was conducted to estimate the prevalence of mange mites, assess the potential risk factors, identify the species infesting goats, and evaluate the efficacy of ivermectin in naturally infested goats in the Uba Debere Tsehay district of Gofa Zone, Southern Ethiopia. A cross-sectional study, longitudinal field efficacy, and questionnaire survey were conducted. A total of 384 goats suspected of having mange were scraped for mite prevalence and count. The mite count data were analyzed using zero-inflated negative binomial (ZINB) models with explanatory variables. The ZINB models indicated that a substantial proportion of the observed zero mite count reflected a failure to detect mites in suspected goats, meaning that the estimated true prevalence was much higher than the apparent prevalence as calculated using a simple proportion of nonzero mite counts. Overall prevalence of mange was 21.87% (84/384) in the study areas. Sarcoptes species (21.09%) and Demodex species (0.78%) were the mite genera identified in this study. Among goats with poor, medium, and good body conditions, mite prevalence was 36.3%, 12.3%, and 10.9%, respectively. Both the prevalence and intensity of infestation were significantly associated with body condition scores, but other risk factors were not. The questionnaire survey indicated that 85.94% of the participants preferred to use modern treatment options (ivermectin 1%, injection) and 76.56% (98/128) respondents replied that ivermectin treatment is effective. Wilcoxon rank-sum test analysis shows that there was significantly (P<0.05) fewer mites counted on goats treated with ivermectin than on untreated goats at each count up to day 56 after treatment. No live mites were found on any treated animal on days 28 and 56. Mixed ANOVA indicated that there was a significant difference within treatment groups. This study showed that mites are one of the constraints to goat production in the study area and ivermectin was highly effective against Demodex and Sarcoptes mites in goats. Hence, there is a need to create awareness about the impact of mange on goat production, and appropriate ivermectin treatment against mites should be implemented.

Association between ivermectin treatment and mortality in COVID-19: A hospital-based case-control study.

This study was designed to test the hypothesis that exposure to ivermectin in early disease prevents mortality due to COVID-19. A secondary objective was to see if the drug has any impact on the length of hospital stay among the survivors. It was a hospital-based retrospective case-control study conducted at a tertiary teaching hospital in India. All patients with a diagnosis of COVID-19 who were admitted between 1st April and 15th May 2021 and received inpatient care were included. Important variables like demographic details, dates of admission and discharge or death, symptoms at the time of admission, comorbidities, severity of illness at the time of admission, whether ivermectin was administered or not during the course of the illness and other treatments received as part of the standard of care were retrieved from the medical records. Of the 965 patients who received inpatient care, 307 died during their hospital stay while 658 were successfully discharged. The proportion of cases treated with ivermectin was 17.26% among the non-survivors (53/307) and 17.93% among the survivors (118/658). The effect was statistically insignificant (crude OR = 0.954; 95% CI: 0.668-1.364, P = 0.80). Among the survivors, the median length of stay was 11 days for patients who received ivermectin (IQR: 7-15) as well as for those who did not (IQR: 7-16). This study did not show any effect of ivermectin on in-patient mortality in patients with COVID-19 and there was no effect of the drug on the length of hospital stay among the survivors.

Gut microbiota of endangered Australian sea lion pups is unchanged by topical ivermectin treatment for endemic hookworm infection.

The gut microbiota is essential for the development and maintenance of the hosts' immune system. Disturbances to the gut microbiota in early life stages can result in long-lasting impacts on host health. This study aimed to determine if topical ivermectin treatment for endemic hookworm (Uncinaria sanguinis) infection in endangered Australian sea lion (Neophoca cinerea) pups resulted in gut microbial changes. The gut microbiota was characterised for untreated (control) (n = 23) and treated (n = 23) Australian sea lion pups sampled during the 2019 and 2020/21 breeding seasons at Seal Bay, Kangaroo Island. Samples were collected pre- and post-treatment on up to four occasions over a four-to-five-month period. The gut microbiota of untreated (control) and treated pups in both seasons was dominated by five bacterial phyla, Fusobacteria, Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. A significant difference in alpha diversity between treatment groups was seen in pups sampled during the 2020/21 breeding season (p = 0.008), with higher richness and diversity in treated pups. Modelling the impact of individual pup identification (ID), capture, pup weight (kg), standard length (cm), age and sex on beta diversity revealed that pup ID accounted for most of the variation (35% in 2019 and 42% in 2020/21), with pup ID, capture, and age being the only significant contributors to microbial variation (p < 0.05). There were no statistically significant differences in the composition of the microbiota between treatment groups in both the 2019 and 2020/21 breeding seasons, indicating that topical ivermectin treatment did not alter the composition of the gut microbiota. To our knowledge, this is the first study to characterise the gut microbiota of free-ranging Australian pinniped pups, compare the composition across multiple time points, and to consider the impact of parasitic treatment on overall diversity and microbial composition of the gut microbiota. Importantly, the lack of compositional changes in the gut microbiota with treatment support the utility of topical ivermectin as a safe and minimally invasive management strategy to enhance pup survival in this endangered species.

Ivermectin Attenuates CCl4-Induced Liver Fibrosis in Mice by Suppressing Hepatic Stellate Cell Activation.

Liver fibrosis, a common liver dysfunction with high morbidity and mortality rates, is the leading cause of cirrhosis and hepatocellular carcinoma, for which there are no effective therapies. Ivermectin is an antiparasitic drug that also has been showing therapeutic actions in many other diseases, including antiviral and anticancer actions, as well as treating metabolic diseases. Herein, we evaluated the function of ivermectin in regulating liver fibrosis. Firstly, carbon tetrachloride (CCl4)-injected Balb/c mice were used to assess the antifibrosis effects of ivermectin in vivo. Further, CFSC, a rat hepatic stellate cell (HSC) line, was used to explore the function of ivermectin in HSC activation in vitro. The in vivo data showed that ivermectin administration alleviated histopathological changes, improved liver function, reduced collagen deposition, and downregulated the expression of profibrotic genes. Mechanistically, the ivermectin treatment inhibited intrahepatic macrophage accumulation and suppressed the production of proinflammatory factors. Importantly, the ivermectin administration significantly decreased the protein levels of α-smooth muscle actin (α-SMA) both in vivo and in vitro, suggesting that the antifibrotic effects of ivermectin are mainly due to the promotion of HSC deactivation. The present study demonstrates that ivermectin may be a potential therapeutic agent for the prevention of hepatic fibrosis.

Strongyloides westeri infection on a Thoroughbred breeding farm in Ireland (2014–2019): Prevalence, risk factors and peripartum ivermectin

SummaryBackgroundThe mean proportion of Strongyloides westeri (S. westeri) infected foals on Thoroughbred breeding farms in central Kentucky has been reported as 30%. The prevalence of S. westeri in Ireland and the effect of peripartum ivermectin treatment of the dam are unknown.ObjectivesThe objectives of the study were to determine the proportion of foals infected and the prevalence of positive S. westeri faecal egg count (FEC) tests within defined age groups on a Thoroughbred breeding farm in Ireland between 2014 and 2019 inclusive and, furthermore, to identify risk factors for infection and the effect of peripartum ivermectin treatment. We hypothesised no significant difference in S. westeri infection in progeny &lt;365 days of age, where the dam received peripartum ivermectin treatment between 30 days pre‐ and 7 days post‐foaling, versus no treatment.Study designRetrospective observational cohort.MethodsFarm records of 1420 FECs for 459 foals were reviewed. Positive test prevalence and proportion of foals infected were determined using days between birth and each FEC result, up to 365 days. A mixed effects logistic regression model was constructed to examine the association between date of sample collection, year, age at sampling, peripartum dam ivermectin treatment and S. westeri patent infection in progeny &lt;365 days of age.ResultsTest prevalence and proportion of foals infected increased from 0.09 to 0.43 and 0.17 to 0.52, respectively. The risk of positive S. westeri infection was linearly and positively associated with day of the year (OR = 1.75; 95% CI: 1.14, 2.7; p = 0.01) and negatively associated with age (OR = 0.37; 95% CI: 0.23, 0.59; p = &lt;0.001). Peripartum ivermectin treatment was associated with reduced S. westeri infection in progeny &lt;365 days of age (OR = 0.24; 95% CI: 0.07, 0.79; p = 0.02).Main limitationsFaecal egg counts performed by trained lay personnel. Dynamic population.ConclusionsIncreasing prevalence of S. westeri infection may reflect cumulative environmental contamination.

Diagnostic challenges in monitoring and evaluating annual ivermectin (Mectizan®) treatment intervention strategy to determine onchocerciasis elimination status

Ability to accurately detect an active infection depends largely on the high accuracy (sensitivity and specificity) of a diagnostic test. There is no single diagnostic tool that meets the criteria of been simple, measurable, accurate, repeatable and timely (SMART). Combining the screening and confirmation tests have been relied upon in determining the true epidemiological situation of ongoing ivermectin or Mectizan® treatment intervention strategy. Antibody detection assays have been evaluated as screening tools using various formats like different types of agglutination protocol, enzyme linked immunosorbent assays (ELISA) and nucleic acid amplification tests (NAAT). Despite these developments, presence of any stage of the parasite antigen, microfilaria (fourth larva, L4) and macrofilaria (adult worm) confirms active infection. The standard microscopic examination of skin snips for emerged microfilaria obtained with a scleral biopsy punch is capable of spreading blood viral diseases. The sensitivity of the test has decreased following post-treatment with ivermectin and surveillance for recrudescence is inevitable. On one hand, the time preceding when parasite materials liberated as against when detectable immune responses were invoked decreases the sensitivity of serological tests. The DNA molecular based tests with the attendant complexity of protocol remained a technical barrier that has been surmounted with the development of loop- mediated isothermal amplification (LAMP). This technique amplifies DNA with high specificity, sensitivity and rapidity under isothermal conditions. It will serve as alternative definitive diagnostic test to skin microfilaria detection. A combination of LAMP with IgG4 antibodies against O. volvulus 16 kiloDalton (Ov16) antigen is used as a rapid qualitative test of human finger-prick blood, serum and plasma now widely applied in disease endemic countries. Also, diethyl carbamazine (DEC) patch skin test for popular eruption indicative of positive infection attracted further re-evaluation as non-invasive screening tool devoid of skin biopsy and blood sample collection.

Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19

Background US poison control centers reported increased cases of ivermectin toxicity during the COVID-19 pandemic. Previous descriptions of ivermectin toxicity have evaluated heterogeneous groups with a variety of ivermectin sources and dosage patterns. We sought to compare the clinical effects of ivermectin toxicity in patients taking human- vs. veterinary-formulations and acute- vs. chronic-ingestion patterns. Methods We performed a retrospective analysis of cases from the Oregon Poison Center of ivermectin exposures for the prevention or treatment of COVID-19 that resulted in a healthcare visit over a 24-week period (14 August 2021 − 31 January 2022). Results We identified 37 cases of ivermectin toxicity. The median age of patients was 64 years, and most patients were male. The majority of patients were hospitalized (21) or treated in an emergency department (13). A minority were treated in an outpatient setting (3) and one patient died. Seventeen ingested veterinary formulations and fifteen ingested prescription tablets. Patients reported taking ivermectin for treatment (23) and prevention (14) of COVID-19. Clinical effects included neurotoxicity (30), gastrointestinal symptoms (14), and musculoskeletal complaints (7). Patients taking veterinary products took higher doses of ivermectin and had higher rates of altered mental status than those taking prescription tablets. Patients taking ivermectin chronically took smaller doses (daily dose of 13.5 mg) over a prolonged period (median 3.8 weeks) and developed toxicity that was milder than those with acute ingestions. Conclusion Ivermectin toxicity developed in predominantly male patients >60 years old who ingested higher than recommended doses and developed neurologic symptoms. Patients who took a veterinary formulation of ivermectin ingested large single doses or large daily doses for several days and developed rapid onset of neurotoxicity. Patients with chronic toxicity developed milder symptoms and tended to take typical therapeutic doses, but continued therapy for weeks rather than days.

Ivermectin treatment response in two rural villages with a high prevalence of onchocerciasis and epilepsy, Mahenge Tanzania.

Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean microfilarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the microfilarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High microfilarial density at baseline was the only significant predictor associated with higher microfilarial density in the post-ivermectin skin snips. Our study reports a decrease in microfilarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge.

Ivermectin for Treatment of COVID-19?

Many attempts have been made to repurpose existing and approved drugs for the treatment of COVID-19 infection. This involves anti-malarial drugs such as hydroxychloroquine and chloroquine, which have been shown to be less successful than initially believed, with a substantial risk of often fatal complications and interactions. This also involves Remdesivir, which has been shown to decrease recovery time significantly in hospitalized patients. However, for patients who are not yet hospitalized, there is no currently accepted treatment. Treating patients before they need to be admitted or even prophylactically could greatly decrease the load on hospitals, protect healthcare workers and reduce the spread of COVID-19. An in-vitro study indicated that Ivermectin was dynamic against COVID-19-infected cell. Ivermectin has antimicrobial, antiviral, and anticancer, immunomodulatory properties. This drug could reduce the viral load in COVID-9 infected patients, with potential effect on disease progression and spread. Therefore, Ivermectin may be a therapeutic choice for treatment of COVID-19, however, there is still a lack of evidence-based studies to support ivermectin treatment of patients with COVID-19.

Shortened egg reappearance periods of equine cyathostomins following ivermectin or moxidectin treatment: morphological and molecular investigation of efficacy and species composition

Macrocyclic lactones have been the most widely used drugs for equine parasite control during the past four decades. Unlike ivermectin, moxidectin exhibits efficacy against encysted cyathostomin larvae, and is reported to have persistent efficacy with substantially longer egg reappearance periods. However, shortened egg reappearance periods have been reported recently for both macrocyclic lactones, and these findings have raised several questions: (i) are egg reappearance period patterns different after ivermectin or moxidectin treatment? (ii) Are shortened egg reappearance periods associated with certain cyathostomin species or stages? (iii) How does moxidectin’s larvicidal efficacy affect egg reappearance period? To address these questions, 36 horses at pasture, aged 2–5 years old, were randomly allocated to three treatment groups: 1, moxidectin; 2, ivermectin; and 3, untreated control. Strongylid fecal egg counts were measured on a weekly basis, and the egg reappearance period was 5 weeks for both compounds. Strongylid worm counts were determined for all horses: 18 were necropsied at 2 weeks post-treatment (PT), and the remaining 18 at 5 weeks PT. Worms were identified to species morphologically and by internal transcribed spacer-2 (ITS-2) rDNA metabarcoding. Moxidectin and ivermectin were 99.9% and 99.7% efficacious against adults at 2 weeks post treatment, whereas the respective efficacies against luminal L4s were 84.3% and 69.7%. At 5 weeks PT, adulticidal efficacy was 88.3% and 57.6% for moxidectin and ivermectin, respectively, while the efficacy against luminal L4s was 0% for both drugs. Moxidectin reduced early L3 counts by 18.1% and 8.0% at 2 or 5 weeks, while the efficacies against late L3s and mucosal L4s were 60.4% and 21.2% at the same intervals, respectively. The luminal L4s surviving ivermectin treatment were predominantly Cylicocyclus (Cyc.) insigne. The ITS-2 rDNA metabarcoding was in good agreement with morphologic species estimates but suggested differential activity between moxidectin and ivermectin for several species, most notably Cyc. insigne and Cylicocyclus nassatus. This study was a comprehensive investigation of current macrocyclic lactone efficacy patterns and provided important insight into potential mechanisms behind shortened egg reappearance periods.

Suppression of classical nuclear import pathway by importazole and ivermectin inhibits rotavirus replication.

Rotavirus is the foremost cause of acute gastroenteritis among infants in resource-poor countries, causing severe morbidity and mortality. The currently available rotavirus vaccines are effective in reducing severity of the disease but not the infection rates, thus antivirals as an adjunct therapy are needed to reduce the morbidity in children. Viruses rely on host cellular machinery for nearly every step of the replication cycle. Therefore, targeting host factors that are indispensable for virus replication could be a promising strategy. To assess the therapeutic potential of ivermectin and importazole against rotaviruses. Antirotaviral activity of importazole and ivermectin was measured against various rotavirus strains (RV-SA11, RV-Wa, RV-A5-13, RV-EW) in vitro and in vivo by quantifying viral protein expression by western blot, analysing viroplasm formation by confocal microscopy, and measuring virus yield by plaque assay. Importin-β1 and Ran were found to be induced during rotavirus infection. Knocking down importin-β1 severely impaired rotavirus replication, suggesting a critical role for importin-β1 in the rotavirus life cycle. In vitro studies revealed that treatment of ivermectin and importazole resulted in reduced synthesis of viral proteins, diminished production of infectious virus particles, and decrease in viroplasm-positive cells. Mechanistic study proved that both drugs perform antirotavirus activity by inhibiting the function of importin-β1. In vivo investigations in mice also confirmed the antirotavirus potential of importazole and ivermectin at non-toxic doses. Treatments of rotavirus-infected mice with either drug resulted in diminished shedding of viral particles in the stool sample, reduced expression of viral protein in the small intestine and restoration of damaged intestinal villi comapared to untreated infected mice. The study highlights the potential of importazole and ivermectin as antirotavirus therapeutics.

Ivermectin treatment in rosacea: How novel smartphone technology can support monitoring rosacea-associated signs and symptoms.

Rosacea lessens patients' quality of life not only by visible symptoms like erythema, papules, and pustules but also by invisible symptoms like stinging, burning, and dryness. Ivermectin 1% cream has recently been introduced as an efficient therapy for papules and pustules in rosacea patients. To investigate the potential of ivermectin 1% cream to improve rosacea-associated erythema and invisible symptoms by combining established questionnaires with the novel photography and analysis tool Scarletred®Vision. We performed an open monocentric pilot study including 25 Caucasian patients presenting with moderate to severe rosacea with erythema, less than 10 papules and/or pustules, and ≥ 15 Demodex mites/cm2 . Patients applied 1g of ivermectin 1% cream (Soolantra®) once a day for ≥16 weeks. Skin symptoms were recorded at baseline, week 8 and ≥ week 16. Grade of erythema was determined by clinician erythema assessment (CEA) and patient self-assessment (PSA). Severity of invisible skin symptoms (stinging and/or burning, dryness, itching) were assessed by questionnaire. Erythema and skin texture were additionally quantified using Scarletred®Vision. Ivermectin 1% cream significantly reduced invisible symptoms of rosacea (stinging and/or burning, dryness: p < 0.0001; itching p < 0.001; at ≥16 weeks). Analysis with Scarletred®Vision confirmed CEA and PSA results for improvement of erythema (p < 0.0001; at ≥16 weeks) and skin roughness (p < 0.001; at ≥16 weeks). Treatment with ivermectin 1% cream is efficient in treating not only rosacea-associated papules and pustules but also erythema and invisible skin symptoms.

The National COVID-19 Clinical Evidence Taskforce: pregnancy and perinatal guidelines.

IntroductionPregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID‐19) than non‐pregnant women of a similar age. Early in the COVID‐19 pandemic, it was clear that evidenced‐based guidance was needed, and that it would need to be updated rapidly. The National COVID‐19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID‐19, including during pregnancy. Care for pregnant and breastfeeding women and their babies was included as a priority when the Taskforce was set up, with a Pregnancy and Perinatal Care Panel convened to guide clinical practice.Main recommendationsAs of May 2022, the Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth. This includes supporting usual practices for the mode of birth, umbilical cord clamping, skin‐to‐skin contact, breastfeeding, rooming‐in, and using antenatal corticosteroids and magnesium sulfate as clinically indicated. There are 11 recommendations for COVID‐19‐specific treatments, including conditional recommendations for using remdesivir, tocilizumab and sotrovimab. Finally, there are recommendations not to use several disease‐modifying treatments for the treatment of COVID‐19, including hydroxychloroquine and ivermectin. The recommendations are continually updated to reflect new evidence, and the most up‐to‐date guidance is available online (https://covid19evidence.net.au).Changes in management resulting from the guidelinesThe National COVID‐19 Clinical Evidence Taskforce has been a critical component of the infrastructure to support Australian maternity care providers during the COVID‐19 pandemic. The Taskforce has shown that a rapid living guidelines approach is feasible and acceptable.

EFFECT OF DIFFERENT DOSES OF IVERMECTIN ON BIOMARKER HORMONE OF ADRENAL GLAND AND HISTOLOGY OF IT IN LOCAL FEMALE RABBITS

Ivermectin (IVM) is a lipophilic anthelmintic drug widely used for the control of internal and external parasites in both human and veterinary medicin. This study aimed to investigate the effect of different dose of Ivermectin (IVM) on the Cortisol hormones (functionally and histologically) of twenty four of mature female rabbits in basrah. Animals were randomly divided into four groups (six for each). The first group was left without treatment (control group), second, third and fourth group treated weekly by injection s/c ivermectin for 8 week at dose (0.5mg, 1mg and 2 mg / kg.bw ) respectly .Results conducted to increase significant in cortisol concentration in fourth group ,while the first and second and third group did not affected when compared with fourth group or within them .The histopathological changes as a results of ivermectin treatment in adrenal there is representive by vacuolation of zona glomerulosa and zona fasculata in group fourth and less effect in other treatment. We concluded high dose of ivermectin and prolong period may affected on adrenal gland function.

Changes in SpO2 on Room Air for 34 Severe COVID-19 Patients after Ivermectin-Based Combination Treatment: 62% Normalization within 24 Hours

The emergence of COVID-19 in March 2020 challenged Zimbabwe to respond with limited medical facilities and therapeutic options. Based on early clinical indications of efficacy for the macrocyclic lactone, Ivermectin (IVM), against COVID-19, IVM-based combination treatments were deployed to treat it. Oxygen saturation (SpO2) data were retrospectively analyzed for 34 severe, hypoxic COVID-19 patients all on room air (without supplemental oxygen). The patients, median age 56.5, were treated at clinics or at home between August 2020 and May 2021. All but three of these 34 patients had significantly increased SpO2 values within 24 h after the first IVM dose. The mean increase in SpO2 as a percentage of full normalization to SpO2 = 97 was 55.1% at +12 h and 62.3% at +24 h after the first IVM dose (paired t-test, p &lt; 0.0000001). These results parallel similar sharp, rapid increases in SpO2, all on room air, for 24 mostly severe COVID-19 patients in the USA (California) who were given an IVM-based combination treatment. All patients in both of these critical series recovered. These rapid increases in SpO2 values after IVM treatment stand in sharp contrast to declines in SpO2 and associated pulmonary function through the second week following the onset of moderate or severe COVID-19 symptoms under standard care.

Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction

Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis, with a survival rate of less than 5 years in advanced stages. Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types. This is the first study to evaluate the anticancer effects of the combination of ivermectin and gemcitabine in pancreatic cancer. We found that the ivermectin–gemcitabine combination treatment suppressed pancreatic cancer more effectively than gemcitabine alone treatment. The ivermectin–gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by the downregulation of cyclin D1 expression and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT-3) signaling pathway. Ivermectin–gemcitabine increased cell apoptosis by inducing mitochondrial dysfunction via the overproduction of reactive oxygen species and decreased the mitochondrial membrane potential. This combination treatment also decreased the oxygen consumption rate and inhibited mitophagy, which is important for cancer cell death. Moreover, in vivo experiments confirmed that the ivermectin–gemcitabine group had significantly suppressed tumor growth compared to the gemcitabine alone group. These results indicate that ivermectin exerts synergistic effects with gemcitabine, preventing pancreatic cancer progression, and could be a potential antitumor drug for the treatment of pancreatic cancer.