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Scabies is the most common neglected tropical disease with cutaneous manifestations, disproportionately affecting socially disadvantaged populations living in overcrowded settings. Scabies infestation is characterised by a generalised intractable pruritus, and is often complicated by secondary bacterial infection, which can lead to a range of complications. Scabies is a clinical diagnosis and requires an adequate degree of suspicion. The use of dermoscopy may improve diagnostic accuracy. In Australia, the first-line treatment recommended for scabies is topical permethrin 5% cream, applied to the whole body and repeated in one week. Oral ivermectin is subsidised by the Pharmaceutical Benefits Scheme with streamlined authority for patients who have completed and failed treatment with topical therapy, have a contraindication to topical treatment or have crusted scabies. Early identification and prompt initiation of treatment is key to minimise the disease burden of scabies., (© 2024 AMPCo Pty Ltd.)

Introduction: Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections., Methods: Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats., Results: Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations., Conclusion: The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Mao et al.)

Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of Fasciola hepatica in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 F. hepatica metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days -8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 F. hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7-100%) and adult parasites (98.9-100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult F. hepatica and Fasciola eggs; however, closantel was not sufficiently efficient against adult flukes., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists, therefore we have nothing to declare., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: When malaria vectors consume ivermectin in a blood meal, their survival probability decreases, potentially reducing malaria transmission during mass drug administrations. However, questions remain regarding the optimal dosing. This study aimed to compare the mosquitocidal effect and pharmacokinetics of two-dose regimens of ivermectin for malaria vector control., Design: We conducted an open-label randomized control trial in Kenya, staggered in blocks with sequential intervention groups and parallel controls. Participants were randomly assigned (2:1:1:1) using computer random-sequence generation, unstratified, with one block of six pharmacokinetics-only participants (single-dose ivermectin) and six blocks of four participants (3:1 intervention vs control), to receive single-dose ivermectin (400 mcg/kg, n = 12), three daily doses (3-day regimen 300 mcg/kg, n = 6), albendazole (400 mg, n = 6), or no treatment (negative control, n = 6). Our primary outcome was Anopheles gambiae survival (time-to-event [days]) after blood feeding up to 10 days after drug administration. We also evaluated pharmacokinetics (peak plasma and capillary blood concentration, areas under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation, time to reach peak plasma and capillary blood concentration, terminal elimination half-life) up to 7 days after treatment., Results: A total of 36 healthy volunteers aged 21-32 years were recruited into the study and followed up to completion, with two participants not attending the visit on day 28. All drug regimens were well-tolerated. Both regimens showed significant mosquitocidal effect in the first 7 days. At 10 days after treatment, the single dose presented superior longevity of effect (adjusted hazard ratio = 3.91; 95% confidence interval = 1.93-7.93; P <0.001) compared with the triple dose (adjusted hazard ratio = 1.79; 95% confidence interval = 0.88-3.62; P = 0.0.11). Albendazole had, overall, no mosquitocidal effect., Conclusions: It is unclear why a single dose led to increased bio-efficacy compared with a triple dose. We recommend trials investigating ivermectin mass drug administrations for malaria control to consider single-dose ivermectin. A single-dose regimen is also expected to present additional operational advantages compared with a 3-day regimen, leading to improved programmatic suitability., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Our study was conducted to determine the impact of scabies in people living in collective living areas such as tent cities and container cities after the February 6 Kahramanmaraş earthquakes and to show the effectiveness of oral ivermectin treatment on scabies cases because topical treatments could not be used in this period when access to water was limited., Methods: Among 233 patients diagnosed and treated with scabies in tent and container cities, 192 patients who met the criteria were included in the study. Descriptive statistics were given as number (n), percentage (%), mean, median, standard deviation (SD). In the comparison of categorical data, the chi-square test was applied; in the comparison of numerical data ANOVA analyses was applied., Results: A total of 192 scabies patients (82.4%), 47.9% (N:92) of whom were women, were included in the study. The frequency of scabies in the total population in tent cities and container cities was found to be at least 0.54%. The most common symptoms were pruritis (99.0%) and rash (97.9%). The most common sites of lesion involvement were the umbilicus (87.0.%), forearm (75.0%), and back (70.3%). After the first dose of ivermectin, 159 (82.8%) patients showed complete recovery, while 30 (15.6%) patients showed partial recovery. 3 (1.6%) patients showed no improvement. After the second dose of ivermectin, 173 (90.1%) patients showed complete recovery. There were two (1.0%) patients who did not show improvement after two doses. Due to the deterioration of urban infrastructure after devastating earthquakes, the irregularity of mass living areas, the lack of hygiene conditions, and the difficulty of accessing clean, usable water, oral ivermectin may be the first choice for treatment in terms of ease of use and effectiveness., Competing Interests: The authors declare there are no competing interests., (©2024 Beyoğlu and Gokler.)

Background: This study examined onchocerciasis transmission in Kwanware and Ottou in the Wenchi Health District of Ghana, where persistent onchocercal microfilariae (mf) levels have been reported since 2012., Methods: This study was conducted from 2019 to 2021 and involved the following: (i) reviewing past records of ivermectin mass drug administration (MDA); (ii) conducting a treatment coverage evaluation survey (CES); (iii) conducting key informant interviews; (iv) prospecting blackfly breeding sites; (v) collecting and dissecting blackflies; and (vi) conducting parasitological and serological surveys., Results: (i) The review indicated ongoing MDA treatment for the past 27 years, with a reported coverage of over 65% in the last 17 yearly rounds; (ii) estimated treatment coverage by the CES in 2019 was 71.3%, with most of those not taking medicine stating that they were not offered; (iii) however, the key informant interviews revealed insufficiencies in reaching a significant number of people for treatment due to remote settlement, mobility, transport logistical issues, failure to register some people for treatment, leading to a false impression of good coverage, and a short distribution time; (iv) the most productive breeding was found within 5 km of Kwanware-Ottou; and (v) blackfly daily biting rates were highest in Kwanware and Ottou, with 199 and 160 bites per day, respectively. Infection in blackflies was found only in Kwanware and Ottou, with infectivity rates of 5.9‰ (per 1000) and 6.7‰, respectively. (vi) The mf prevalence in Ottou and Kwanware, respectively, was 40.0% and 30.0% among adults aged ≥ 20 years, and the anti-(Onchocerca volvulus) Ov16 IgG4 antibodies seroprevalence rates were 8.3% and 13.3% among children aged 5-9 years. These values were reduced to undetectable levels at a radius of 10 km from Ottou., Conclusions: This study confirms that active onchocerciasis transmission centres on Kwanware/Ottou and is confined to a 10 km radius despite 27 yearly treatment rounds. The main contributing factors are suboptimal coverage and high biting rates. Identifying and targeting such a focus with a combination of interventions will be cost-effective in accelerating onchocerciasis elimination in Ghana., (© 2024. The Author(s).)

Cutaneous larva migrans (CLM), commonly referred to as creeping eruption, is an infectious condition caused by various types of hookworms. It primarily affects the superficial layers of the skin owing to the absence of hyaluronidases and proteases. Typically, the distal lower extremities are the most commonly affected areas. The presence of distinctive lesions characterized by erythematous, winding, or serpentine tracks, slightly elevated from the skin surface, is indicative of the condition. Diagnosis primarily relies on clinical observation. Dermoscopy reveals multiple segmented yellowish-linear regions corresponding to pustules along the larval path. Treatment typically involves the use of topical and oral ivermectin, oral albendazole, and topical thiabendazole cream., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD-IVITAB, 16 healthy adults were enrolled in a phase I, single-center, open-label, randomized, 2-period, crossover, single-dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD-IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD-IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD-IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for C max , AUC 0-∞ , and AUC 0-last , which were 1.52 [90% CI: 1.13-2.04], 1.27 [0.99-1.62], and 1.29 [1.00-1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD-IVITAB formulation, with a median T max at 3.0 h [range 2.0-4.0 h] versus 4.0 h [range 2.0-5.0 h] with STROMECTOL (P = .004). With CHILD-IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD-IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient-friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg., (© 2024 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

The metastrongyloids Aelurostrongylus abstrusus and Troglostrongylus brevior are primary causes of feline clinical respiratory disease. The present field trial evaluated the clinical efficacy of a spot-on formulation containing eprinomectin, esafoxolaner and praziquantel (NexGard® Combo) administered per label recommendations to cats affected with aelurostrongylosis and/or troglostrongylosis. Overall, 36 naturally infected cats were randomly assigned to Group 1 (G1) or Group 2 (G2) of 18 cats each. The two groups included 6 cats with A. abstrusus, T. brevior and mixed infection, each. All cats completed the study. Cats in G1 were treated on study Days (SDs) 0 and 28±2. Cats in G2 served as negative control until SD 56±2 and were then treated on SD 56±2 and 84±2. On SD 0/-7, 28±2 and SD 56±2 all cats were subjected to parasitological (quali-quantitative Baermann) and clinical examinations (physical exams and thoracic X-rays). Hematology and biochemistry analyses were performed on SD 0/-7 and SD 56±2. On SD 84±2 quali-quantitative Baermann, clinical examination and thorax radiography were performed on all G2 cats and on two G1 cats that still had radiographic alterations on SD 56±2. On SD 112±2 all G2 cats were subjected to parasitological and clinical evaluations and one cat from G1 that still had radiographic signs at SD 84±2 was clinically and radiographically evaluated. Efficacy criteria were the reduction of larval shedding in faeces and the clinical response in terms of pathological and radiographic scores after treatment compared to the baseline. An efficacy of 100 % based on LPG reduction was recorded after one (20/24 cats) or two (all 24 cats) treatments in cats with single infection by A. abstrusus or T. brevior. For cats with mixed infections, larval shedding was stopped after one (11/12 cats) or two (all 12 cats) treatments. Statistically significant clinical and radiographic improvement was evident in all study cats after 2 treatments. The present data show that two monthly treatments with NexGard® Combo stopped larval shedding and led to a significant clinical recovery and a complete resolution of radiographic abnormalities in cats infected with A. abstrusus and/or T. brevior., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donato Traversa and co-workers reports financial support was provided by Boehringer Ingelheim Animal Health. Eric Tielemans, Frederic Beugnet, Camille Gamblin reports a relationship with Boehringer Ingelheim Animal Health that includes: employment. Donato Traversa and Angela Di Cesare reports a relationship with Boehringer Ingelheim Animal Health that includes: consulting or advisory. This Study has been supported by Boehringer Ingelheim, of which ET, FB and CG are employees. DT and ADC have acted as consultants for Boehringer Ingelheim., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The control of the Soil-Transmitted Helminths (STH) infections primarily relies on the school-based Preventive Chemotherapy (PCT) with mebendazole. Given the efficacy of ivermectin on STH, the control of the latter is expected to be potentialized in areas where ivermectin is also distributed for onchocerciasis and/or lymphatic filariasis control/elimination. This study aimed to assess the prevalence and intensity of STH in the Lomie Health District where annual school-based deworming campaigns and community-directed treatments with Ivermectin have been underway for almost two decades., Methodology/principal Findings: A quantitative cross-sectional study was conducted in 10 schools of the Lomie Health District, East Region, Cameroon. Stool samples were collected from school-aged children and analysed using the Kato-Katz technique. Semi-structured questionnaires were administered to enrolees to assess compliance with water, sanitation, and hygiene (WASH). Of the 491 children (median age: 9 years; IQR: 7-10) enrolled, 83.9% (95% CI: 80.3-87.1) were infected with at least one STH species. Trichuris trichiura was the predominant species (78.5%), and no hookworm was found. The prevalence trend slightly decreased between 1987 and 2010 (~8%) and remained unchanged since 2010 (p-value = 0.05). Overall, 46.8% and 41.8% of children were heavy-to-moderately infected with Ascaris lumbricoides and T. trichiura. Poor hand hygiene (OR: 2.24, 95% IC: 1.4-3.4, p-value = 0.0002) and the use of river as a source of drinking water (OR: 14.8, 95% IC: 6.9-33.3, p-value = 0.0001) were the main risk factors associated with the STH infection in Lomie Health District., Conclusions/significance: The persistent high prevalence and intensity of STH infection despite 16 years of mebendazole-based PCT and expected collateral impact of ivermectin mass distribution, points to plausible implementation gaps, poor compliance to WASH or sub-optimal efficacy of the anthelminthics used. This study highlights the need to further assess the cause of the persistent high prevalence and implement context-adapted control measures in order to curb STH transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Efon-Ekangouo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Human onchocerciasis remains a public health problem in Ghana. Mass drug administration (MDA) with ivermectin (IVM) has reduced disease morbidity and prevalence, but the transmission of onchocerciasis remains ongoing in several endemic foci. We investigated parasite transmission in some endemic communities in Ghana that had received > 18 rounds of annual MDA with IVM and determined the species composition of black fly (Simulium damnosum) vectors in these areas., Methods: Adult female black flies were collected using human landing catches and identified as either forest or savanna species using morpho-taxonomic keys. The adult flies underwent dissection to determine their parity and detect any O. volvulus larvae, followed by the calculation of entomological indices. Simulium damnosum s.l. larvae were collected and preserved in freshly prepared Carnoy's fixative and were later used for cytotaxonomic studies., Results: A total of 9,983 adult flies were caught: 6,569 and 3,414 in the rainy and dry seasons respectively. Black fly biting activities over the study period showed bimodal or trimodal patterns. The highest monthly biting rate (MBR) of 10,578.75 bites/person/month was recorded in July in Beposo, while the highest monthly transmission potential of 100.69 infective bites/person/month was recorded in Asubende in August. Morphological analysis of 2,032 flies showed that 99.8% (2,028) of the flies were savanna species, with only 4 (0.2%) adult flies being of the forest species. Cytogenetic studies on 114 black fly larvae revealed three cytospecies (Simulium damnosum s.s., S. sirbanum and S. sanctipauli) in the study area., Conclusions: The present studies confirmed an ongoing transmission of onchocerciasis in the study communities except Abua-1. It also provides further information on biting behaviors and onchocerciasis transmission indices in the study communities. Further, our data confirmed the savanna species (S. damnosum s.s. and S. sirbanum) of the S. damnosum s.l. to be the major vectors of onchocerciasis in the study areas, with only an occasional influx of forest cytotypes., (© 2024. The Author(s).)

Scabies is a prevalent ectoparasitic infectious disease, caused by the mite Sarcoptes scabiei. As a consequence of the infestation, localised cutaneous inflammation, pruritus and polymorphic skin lesions develop. The primary symptoms of scabies manifest as hypersensitivity-like reactions and immune responses, the precise mechanisms of which remain poorly defined. The objective of this study was to evaluate the effects of oral ivermectin treatment in patients with scabies on the systemic immune response and the patient's quality of life (QoL). Patients admitted to the dermatology outpatient clinic and diagnosed with scabies were administered oral ivermectin treatment following diagnosis at week 0 and 2. Laboratory tests were conducted to measure complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels before treatment and at week 4. The systemic immune-inflammation index (SII) was calculated using the platelet, neutrophil and lymphocyte counts. Additionally, data pertaining to the Dermatological Life Quality Index (DLQI) were recorded. In 119 patients (51 males) diagnosed with scabies, increases in ESR, CRP, and SII values and decreases in inflammatory cell counts and DLQI scores were observed one month after treatment with oral ivermectin. The results of the study showed that the use of oral ivermectin, a scabicidal agent, triggered the inflammatory response and improved the QoL of the patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Currently, for veterinary oral formulations containing one or more active pharmaceutical ingredient (API) that are not systemically absorbed and act locally within the gastrointestinal (GI) tract, the use of terminal clinical endpoint bioequivalence (BE) studies is the only option for evaluating product BE. This investigation explored the use of a totality of evidence approach as an alternative to these terminal studies., Methods: Three formulations of tablets containing ivermectin plus praziquantel were manufactured to exhibit distinctly different in vitro release characteristics. Because these APIs are highly permeable, plasma drug concentrations served as a biomarker of in vivo dissolution. Tablets were administered to 27 healthy Beagle dogs (3-way crossover) and the rate and extent of exposure of each API for each formulation was compared in a pairwise manner. These results were compared to product relative in vitro dissolution profiles in 3 media. In vivo and in vitro BE predictions were compared., Results: In vivo/in vitro inconsistencies in product relative performance were observed with both compounds when considering product performance across the 3 dissolution media. Formulation comparisons flagged major differences that could explain this outcome., Conclusions: The finding of an inconsistent in vivo/in vitro relationship confirmed that in vitro dissolution alone cannot assure product BE for veterinary locally acting GI products. However, when combined with a comparison of product composition and manufacturing method, this totality of evidence approach can successfully alert scientists to potential therapeutic inequivalence, thereby supporting FDA's efforts to Replace, Reduce, and/or Refine terminal animal studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Chronic myeloid leukemia is a hematological cancer, where disease relapse and drug resistance are caused by bone-hosted-residual leukemia cells. An innovative resolution is bone-homing and selective-active targeting of anticancer loaded-nanovectors. Herein, ivermectin (IVM) and methyl dihydrojasmonate (MDJ)-loaded nanostructured lipid carriers (IVM-NLC) were formulated then dually decorated by lactoferrin (Lf) and alendronate (Aln) to optimize (Aln/Lf/IVM-NLC) for active-targeting and bone-homing potential, respectively. Aln/Lf/IVM-NLC (1 mg) revealed nano-size (73.67 ± 0.06 nm), low-PDI (0.43 ± 0.06), sustained-release of IVM (62.75 % at 140-h) and MDJ (78.7 % at 48-h). Aln/Lf/IVM-NLC afforded substantial antileukemic-cytotoxicity on K562-cells (4.29-fold lower IC 50 ), higher cellular uptake and nuclear fragmentation than IVM-NLC with acceptable cytocompatibility on oral-epithelial-cells (as normal cells). Aln/Lf/IVM-NLC effectively upregulated caspase-3 and BAX (4.53 and 15.9-fold higher than IVM-NLC, respectively). Bone homing studies verified higher hydroxyapatite affinity of Aln/Lf/IVM-NLC (1 mg; 22.88 ± 0.01 % at 3-h) and higher metaphyseal-binding (1.5-fold increase) than untargeted-NLC. Moreover, Aln/Lf/IVM-NLC-1 mg secured 1.35-fold higher in vivo bone localization than untargeted-NLC, with lower off-target distribution. Ex-vivo hemocompatibility and in-vivo biocompatibility of Aln/Lf/IVM-NLC (1 mg/mL) were established, with pronounced amelioration of hepatic and renal toxicity compared to higher Aln doses. The innovative Aln/Lf/IVM-NLC could serve as a promising nanovector for bone-homing, active-targeted leukemia therapy., Competing Interests: Declaration of competing interest The authors confirm that there are no conflicts of interest associated with this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background & Aim: Rosacea is a chronic inflammatory, multifactorial disease for which combination therapy could be an effective treatment. In this study, we evaluate the effect of the combination therapy of brimonidine 0.33% and ivermectin 1% as a single cream for the treatment of papulopustular rosacea., Method: A stable and appropriate formulation was prepared by adding the aqueous phase to the lipid phase while being stirred. The stability and physicochemical properties of the formulation were evaluated under accelerated conditions. Twelve patients (36-60 years) with mild to moderate papulopustular rosacea and a Demodex count of five or more were treated with the combination of brimonidine 0.33% and ivermectin 1% cream. Clinician's Erythema Assessment (CEA), Patients Self-Assessment (PSA), skin erythema (ΔE) and lightness (ΔL), and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, pH, and sebum content, as well as erythema and melanin index and ultrasound parameters, were measured before treatment and 4 and 8 weeks after. Adverse drug reactions were also recorded., Results: CEA and PSA decreased significantly from 3 to 2 after 8 weeks, respectively (p-value = 0.014 for CEA and 0.010 for PSA). ΔE and ΔL, as well as skin erythema index and TEWL improved after 8 weeks of treatment (p < 0.05). Two patients withdrew from the study in the first week because of local adverse effects; one developed flushing following treatment and left the investigation after 4 weeks and another patient withdrew from the study after 4 weeks due to deciding to become pregnant., Conclusion: Eight-week treatment with the combination of brimonidine 0.33% and ivermectin 1% was shown to be effective for improvement of erythema and inflammatory lesions in mild to moderate papulopustular rosacea., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Treatment of livestock with endectocides such as ivermectin is viewed as a complementary vector control approach to address residual transmission of malaria. However, efficacy of this treatment may vary between animal species. Hence, our purpose was to investigate the effects of ivermectin treatments of common livestock species on life history traits of the opportunistic malaria vector Anopheles coluzzii. Sheep, goats and pigs were treated using injectable veterinary ivermectin formulation at the species-specific doses (recommended dose for all species and high dose in pig). Mosquito batches were exposed to treated and control (not injected) animals at different days after treatment. Daily mosquito mortality was recorded and fecundity assessed through the count of gravid females and the number of eggs they developed. The recommended dose of ivermectin induced a significant decrease in mosquito survival for up to 7 days after injection (DAI), with a decrease of 89.7%, 66.7%, and 48.4% in treated pigs, goats and sheep, respectively, compared to control animals. In treated pigs, the triple therapeutic dose decreased mosquito survival of 68.97% relatively to controls up to 14 DAI. The average number in gravid females Anopheles that survived after feeding on treated animals were reduced when blood-meals were taken on sheep (2.57% and 42.03% at 2 and 7 DAI), or on goats (decrease of the 28.28% and 73.64% respectively at 2 and 7 DAI). This study shows that ivermectin treatments to animals negatively impacts An. coluzzii life history traits and could reduce vector densities in areas where livestock live near humans. However, due to short-term efficacy of single dose treatments, repeated treatments and potentially increased dosages would be required to span the transmission season. The use of long-acting ivermectin formulations is discussed as a mean for extending efficacy while remaining cost effective., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pooda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.

Background: The risk of developing strongyloidiasis hyperinfection syndrome appears to be elevated among individuals who initiate corticosteroid treatment. Presumptive treatment or treatment after screening for populations from Strongyloides stercoralis-endemic areas has been suggested before initiating corticosteroids. However, potential clinical and economic impacts of preventative strategies have not been evaluated., Methods: Using a decision tree model for a hypothetical cohort of 1000 individuals from S. stercoralis-endemic areas globally initiating corticosteroid treatment, we evaluated the clinical and economic impacts of two interventions, 'Screen and Treat' (i.e. screening and ivermectin treatment after a positive test), and 'Presumptively Treat', compared to current practice (i.e. 'No Intervention'). We evaluated the cost-effectiveness (net cost per death averted) of each strategy using broad ranges of pre-intervention prevalence and hospitalization rates for chronic strongyloidiasis patients initiating corticosteroid treatment., Results: For the baseline parameter estimates, 'Presumptively Treat' was cost-effective (i.e. clinically superior with cost per death averted less than a threshold of $10.6 million per life) compared to 'No Intervention' ($532 000 per death averted) or 'Screen and Treat' ($39 000 per death averted). The two parameters contributing the most uncertainty to the analysis were the hospitalization rate for individuals with chronic strongyloidiasis who initiate corticosteroids (baseline 0.166%) and prevalence of chronic strongyloidiasis (baseline 17.3%) according to a series of one-way sensitivity analyses. For hospitalization rates ≥0.022%, 'Presumptively Treat' would remain cost-effective. Similarly, 'Presumptively Treat' remained preferred at prevalence rates of ≥4%; 'Screen and Treat' was preferred for prevalence between 2 and 4% and 'No Intervention' was preferred for prevalence <2%., Conclusions: The findings support decision-making for interventions for populations from S. stercoralis-endemic areas before initiating corticosteroid treatment. Although some input parameters are highly uncertain and prevalence varies across endemic countries, 'Presumptively Treat' would likely be preferred across a range for many populations, given plausible parameters., (Published by Oxford University Press on behalf of International Society of Travel Medicine 2023.)

Background: Evidence on ivermectin as a treatment for Covid-19 is controversial. A Cochrane review concluded that the efficacy and safety of ivermectin is uncertain (evidence up to April 2022) and WHO recommended its use only in the setting of clinical trials. This study aimed to assess the efficacy and safety of oral ivermectin in hospitalized patients with mild to moderate Covid-19., Trial Design and Methods: A double-blind, randomized placebo-controlled clinical trial was conducted among RT-PCR-confirmed, adults, hospitalised within the first four days of symptoms. Patients received oral ivermectin 24 mg or placebo daily for five days. RT-PCR was repeated on days five and ten. Clinical progression was monitored using the World Health Organization Clinical Progression Scale. Serum ivermectin levels were measured on days three, five, and seven. The primary outcome was the difference in the viral load between day zero and ten in the two groups., Results: Out of 1699 patients screened, 249 underwent randomization and 127 received ivermectin, and 122 placebo. D10 median viral load for E gene (IQR) was 2,000 copies/mL (100 - 20,500) with ivermectin (n = 80) and 4,100 copies/mL (1,000-65,600) with placebo (n = 81, p = 0.028), per protocol analysis. The difference in Log viral load between day zero and ten between ivermectin and placebo was 3.72 and 2.97 respectively (p = 0.022). There was no significant difference in the WHO clinical progression scale or the adverse effects. Ivermectin blood levels taken before or with meals were not significantly different. Only 7 and 17 patients achieved blood levels above 160ng/ML and 100ng/ML respectively and they did not achieve a significantly lower viral load., Conclusion: Although ivermectin resulted in statistically significant lower viral load in patients with mild to moderate Covid-19, it had no significant effect on clinical symptoms., Trial Registration Number: SLCTR/2021/020, Sri Lanka Clinical Trials Registry. 19/07/2021., (© 2024. The Author(s).)

Background: The World Health Organization's 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection., Methodology/principal Findings: We collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 ("special intervention zones" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas)., Conclusions/significance: Trends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vinkeles Melchers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The World Health Organization (WHO) endorsed the use of triple-drug mass drug administration (MDA) regimen with ivermectin, diethylcarbamazine (DEC) and albendazole (commonly abbreviated as IDA) to accelerate the elimination of lymphatic filariasis (LF) as a public health problem in settings where onchocerciasis is not co-endemic. The National Programme for Elimination of LF (NPELF) in Kenya was among the first adopters of the IDA-MDA and two annual rounds were provided in 2018 and 2019 to the residents of Lamu County and Jomvu sub-County in the coast region. This study documented the feasibility of successfully delivering the two rounds of IDA-MDA. An operational research study was undertaken to determine efficient sampling strategies, indicators, and the appropriate population groups that could be used for the monitoring and evaluation of LF programs using IDA-MDA for the elimination of the disease as a public health problem. Two cross-sectional surveys were conducted at baseline in 2018 before IDA-MDA and an impact assessment 17 months after the second round of IDA-MDA. The reported epidemiological treatment coverage was at least 80% in all implementation units during each round of IDA-MDA. Blood samples were tested for filarial antigenemia using commercial Filariasis Test Strips (FTS) and any individual found to be positive was tested again at night for the presence of microfilariae in finger prick blood smears using microscopy. The overall prevalence of circulating filarial antigen (CFA) was relatively low at the baseline survey with Jomvu having 1.39% (95% CI: 0.91, 2.11) and Lamu having 0.48% (95% CI: 0.21, 1.13). Significant reduction in CFA prevalence was observed during the impact assessment after the two annual rounds of mass treatment. The overall relative reduction (%) in CFA prevalence following the two rounds of MDA with IDA was significant in both Jomvu (52.45%, Z = -2.46, P < 0.02) and Lamu (52.71%, Z = -1.97, P < 0.05). Heterogeneity, however, was observed in the CFA prevalence reduction between random and purposive clusters, as well as between adult and child populations. The results of the impact assessment survey offered strong evidence that it was safe to stop the IDA-MDA in the two EUs because transmission appears to have been interrupted. It is also important to implement a post-treatment surveillance system which would enable efficient detection of any recrudescence of LF transmission at a sub-evaluation unit level. Our findings show that IDA-MDA may be considered for acceleration of LF elimination in other settings where onchocerciasis is not co-endemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Njenga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Systemic use of Ivermectin has been reported to incite blindness in humans and veterinary patients. This study was designed to investigate the systemic and intravitreal effect of Ivermectin on ocular and retinal health and its attenuation with topical Dexamethasone., Methods: Systemic injection of Ivermectin@ 1.6 mg/kg S/C was administered, thrice a week for three weeks to New Zealand White rabbits ( N  = 4) with and without topical drops of Verapamil ( N  = 4). Pre and post-treatment ocular examination was conducted. At the end of three weeks the eyes were collected for histopathology.0.2 ml of Ivermectin solution (1.6 mg/ml) was injected intravitreally in one eye of the rabbit ( N  = 8), Half the rabbits received 0.1% dexamethasone drops thrice daily for 7 days, while the controls received PBS. Pre and post-treatment, detailed examination was conducted, which included the Schirmer Tear test, Fluorescein staining, Intraocular pressure, slit lamp biomicroscopy and fundus photography. The retina was harvested for histopathological and tunnel assay., Results: Systemic therapy with Ivermectin, with and without Verapamil did not incite any adverse response in the eye. Intravitreal Ivermectin evoked severe uveitis 4/4, cataract 3/4, corneal erosion 3/4 eyes and severe inflammatory response. Eyes that received dexamethasone were rescued from the adverse changes as demonstrated clinically, by histopathology and prevention of apoptosis., Conclusions: Intravitreal Ivermectin incites severe inflammatory response. Topical dexamethasone counters the ocular toxicity incited by Ivermectin.

Background: Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA., Methodology: In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf., Principal Findings: Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections., Conclusions/significance: This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mayfield et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Uganda, 15 of 17 foci have interrupted transmission of onchocerciasis (river blindness) and stopped mass drug administration (MDA) of ivermectin. This 2016 study describes the results of a knowledge, attitude, and practices survey regarding river blindness among participants (N = 1,577) 3-5 years after ivermectin MDA was halted in three foci: Imaramagambo halted in 2012, Kashoya-Kitomi in 2013, and Mt. Elgon in 2011. The study showed high levels of composite knowledge (focus-specific range: 66.8-81.2%) related to river blindness transmission, signs, symptoms, and treatment. However, 38.1% of respondents did not know that blackflies transmitted river blindness. Notably, 72.2% claimed they had not been informed why MDA was stopped, 56.3% did not believe river blindness had been eliminated, and 83.1% wanted ivermectin MDA to resume. During the 3-5 year post-treatment surveillance period, only 27.7% (438 of 1,577) reported being informed of what to do once treatments stopped, with the most knowledgeable hailing from the Mt. Elgon focus (47.9%). This study reinforces the need for programs to intensify health education and information dissemination when MDA is stopped. Programs must remind residents that although biting insects may persist, they no longer transmit river blindness. Incorporating messages about the elimination of river blindness into community health education campaigns can help improve the community's perceptions related to the disease's absence and the ending of a long-standing MDA intervention.

Background: Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA., Methods: This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA., Results: Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA., Conclusions: Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030., (© 2024. The Author(s).)

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.

Murine fur mites are commonly excluded in modern research animal programs, yet infestations continue to persist due to challenges in detection and control. Because all diagnostic methods and treatment options have limitations, programs must make many operational decisions when trying to eradicate these ectoparasites. The primary aim of this study was to assess various durations of treatment time with an ivermectin-compounded diet in eliminating Radfordia affinis in mice as determined by PCR testing and pelt examination. A shorter treatment duration would be highly advantageous as compared with the current regimen of 8 wk as it would minimize cost and time for animal management programs, impediments to research, and ivermectin drug effects on infested animals. Five experimental groups of R. affinis -positive mice received dietary ivermectin for 0, 2, 4, 6, or 8 wk. A fur mite-negative, naïve mouse was added to each group every 8 wk to perpetuate the infestation and amplify any remaining populations of fur mites. At 16 wk after the respective treatment end, PCR testing was performed for all treated groups in conjunction with the positive control group (no treatment). Visual examination of pelts for mites and eggs via direct microscopy was also performed at each time point. All treated mice were free of R. affinis at 16 wk after the end of treatment as confirmed by both PCR testing and pelt examination. These findings indicate that a dietary ivermectin treatment duration of as little as 2 wk is effective in eliminating R. affinis , making successful eradication initiatives more achievable.

In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.

Background: The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008-2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys., Methods: Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy., Results: A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense., Conclusions: More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence., (© 2024. The Author(s).)

Background: The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis ® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg)., Methods: This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis ® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms., Results: The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria., Conclusions: Eprinomectin (Eprecis ® , 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats., (© 2024. The Author(s).)

Chronic myeloid leukemia is a life-threatening blood-cancer prevalent among children and adolescents. Research for innovative therapeutics combine drug-repurposing, phytotherapeutics and nanodrug-delivery. Ivermectin (Ivn) is a potent anthelmintic, repurposed for antileukemic-activity. However, Ivn exerts off-target toxicity. Methyl-dihydrojasmonate (MJ) is a phytochemical of known antileukemic potential. Herein, we developed for the first-time Ivn/MJ-coloaded nanostructured-lipid-carrier (Ivn@MJ-NLC) for leveraging the antileukemic-activity of the novel Ivn/MJ-combination while ameliorating possible adverse-effects. The developed Ivn@MJ-NLC possessed optimum-nanosize (97 ± 12.70 nm), PDI (0.33 ± 0.02), entrapment for Ivn (97.48 ± 1.48 %) and MJ (99.48 ± 0.57 %) and controlled-release of Ivn (83 % after 140 h) and MJ (80.98 ± 2.45 % after 48 h). In-vitro K562 studies verified Ivn@MJ-NLC prominent cytotoxicity (IC 50  = 35.01 ± 2.23 µg/mL) with pronounced Ivn/MJ-synergism (combination-index = 0.59) at low-concentrations (5-10 µg/mL Ivn). Superior Ivn@MJ-NLC cytocompatibility was established on oral-epithelial-cells (OEC) with high OEC/K562 viability-ratio (1.49-1.85). The innovative Ivn@MJ-NLC enhanced K562-nuclear-fragmentation and afforded upregulation of caspase-3 and BAX (1.71 ± 0.07 and 1.45 ± 0.07-fold-increase, respectively) compared to control. Ex-vivo hemocompatibility and in-vivo-biocompatibility of parenteral-Ivn@MJ-NLC, compared to Ivn-solution, was verified via biochemical-blood analysis, histological and histomorphometric studies of liver and kidney tissues. Our findings highlight Ivn@MJ-NLC as an Ivn/MJ synergistic antileukemic platform, ameliorating possible adverse-effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The feline MDR1 mutation (ABCB11930&#95;1931delTC) has been associated with neurological toxicosis after topical application of eprinomectin products labeled for feline use. Information was collected from veterinarians who submitted samples for ABCB11930&#95;1931delTC genotyping. In most cases, the submission form indicated an adverse event involving eprinomectin, in other cases submitting veterinarians were contacted to determine whether the patient had experienced an adverse drug event involving eprinomectin. If so, additional information was obtained to determine whether the case met inclusion criteria. 14 cases were highly consistent with eprinomectin toxicosis. Eight cats were homozygous for ABCB11930&#95;1931del TC (3 died; 5 recovered). Six cats were homozygous wildtype (2 died; 4 recovered). The observed ABCB11930&#95;1931delTC frequency (57%) was higher than the expected frequency (≤1%) in the feline population (Fisher Exact test, p < 0.01). Among wildtype cats, four were concurrently treated with potential competitive inhibitors of P-glycoprotein. Results indicate that topical eprinomectin products, should be avoided in cats homozygous for ABCB11930&#95;1931delTC. This is a serious, preventable adverse event occurring in an identifiable subpopulation treated with FDA-approved products in accordance with label directions. Acquired P-glycoprotein deficiency resulting from drug interactions may enhance susceptibility to eprinomectin-induced neurological toxicosis in any cat, regardless of ABCB1 genotype., (© 2024 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

Background: WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa., Methods: For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986., Findings: Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I 2 was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission., Interpretation: Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission., Funding: The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking., Translations: For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low., Competing Interests: Potential conflicts of interest. J. D. K. reports reviewing and providing comments on this article as part of their job at the World Health Organization. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames., Methods: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting., Results: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult., Conclusions: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT., Competing Interests: Potential conflicts of interest . R. A. reports funding for their institution Imperial College from Leiden Labs, Gates Foundation, and CIFF, leadership roles with Flora and Fauna International, Chairman Oriole Global Health Ltd, and Trusted Banga Trust, and stock with GSK, AstraZeneca, Pfizer. L. E. C. reports funding paid to their institution from March to July 2023 from APW on strongyloidiasis control from WHO Geneva and subcontract on VL modeling for LSTM. K. G. reports that their salary is paid by the Bill & Melinda Gates Foundation “Filling the Gaps Grant” and USAID “Coalition for Operational Research on NTDs.” J. D. K. reports receiving grants from Bayer AG, Carter Center, Cytiva, EISAI Co Ltd, EMS Brazil, Fred Hollows Foundation, Fundacion Anesvad, Fundacion Mundo Sano, Gilead Sciences Inc, Glaxo Smith Kline, Johnson and Johnson Family of Companies, Contribution Fund, Inc, Merck & Co Inc, Merck KGAA, Merck Sharp & Dohme Corp., Novartis, Sanofi Aventis, The Task Force for Global Health, which receives an operating budget and research funds from Pfizerr Inc, the manufacturers of Zithromax (azithromycin) and Wellcome Trust. K. K. reports receiving support for attending meetings and/or travel from the NTD Modelling Consortium: Informing program decision-making (Bill and Melinda Gates Foundation). A. K. reports receiving consulting fees from the Coalition for Operational Research for NTDs and is a member of the Mectizan Expert Committee and received support for travel to the biannual meeting. P. D. reports support for travel from the Bill & Melinda Gates Foundation. M. G. B. reports grant jointly funded by the UK MRC and the UK Foreign Commonwealth & Development Office (FCDO) under the MRC/FCDO Concordat atreement, also part of the EDCPT2 program supported by the European Union. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies., Methods: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs., Results: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI., Conclusions: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction., Competing Interests: Potential conflicts of interest. H. C. T. reports funding from Medicines Development for Global Health (MDGH) as a consultant. B. R. and S. K. are staff members of MDGH. A. C. K. was a staff member of the UNICEF/United Nations Development Programme/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (WHO/TDR) and was responsible for managing WHO/TDR's program for development of moxidectin that resulted in the data licensed to MDGH. K. K. and M. G. B. report financial support from the Bill & Melinda Gates Foundation for attending technical meetings. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Lymphatic filariasis is a neglected tropical disease that affects the lymphatic system of humans. The major etiologic agent is a nematode called Wuchereria bancrofti, but Brugia malayi and Brugia timoriare sometimes encountered as causative agents. Mosquitoes are the vectors while humans the definitive hosts respectively. The burden of the disease is heavier in Nigeria than in other endemic countries in Africa. This occurs with increasing morbidity and mortality at different locations within the country, the World Health Organization recommended treatments for lymphatic filariasis include the use of Albendazole (400mg) twice per year in co-endemic areas with loa loa, Ivermectin (200mcg/kg) in combination with Albendazole (400mg) in areas that are co-endemic with onchocerciasis, ivermectin (200mcg/kg) with diethylcarbamazine citrate (DEC) (6mg/kg) and albendazole (400mg) in areas without onchocerciasis. This paper covered a systematic review, meta-analysis, and scoping review on lymphatic filariasis in the respective geopolitical zones within the country. The literature used was obtained through online search engines including PubMed and Google Scholar with the heading "lymphatic filariasis in the name of the state", Nigeria. This review revealed an overall prevalence of 11.18% with regional spread of Northwest (1.59%), North Central and North East, (4.52%), South West (1.26%), and South-South with South East (3.81%) prevalence. The disease has been successfully eliminated in Argungu local government areas (LGAs) of Kebbi State, Plateau, and Nasarawa States respectively. Most clinical manifestations (31.12%) include hydrocele, lymphedema, elephantiasis, hernia, and dermatitis. Night blood samples are appropriate for microfilaria investigation. Sustained MDAs, the right testing methods, early treatment of infected cases, and vector control are useful for the elimination of lymphatic filariasis for morbidity management and disability prevention in the country. Regional control strategies, improved quality monitoring of surveys and intervention programs with proper records of morbidity and disability requiring intervention are important approaches for the timely elimination of the disease in Nigeria., Competing Interests: All authors declare no competing interests., (Copyright: Timothy Waje et al.)

Current WHO guidelines for onchocerciasis elimination provide requirements for stopping mass drug administration of ivermectin and the verification of elimination of transmission. These guidelines also recommend post-elimination surveillance (PES) based on entomological surveys. Serological markers in humans could complement entomological PES once the longevity of anti-OV-16 antibody responses is better understood. In 2014-2015 we evaluated ELISA anti-OV-16 IgG4 antibody persistence among previously seropositive people from the central endemic zone of Guatemala. The country stopped all onchocerciasis program interventions in 2012 and was verified by WHO as having eliminated transmission of onchocerciasis in 2016. A total of 246 participants with prior OV-16 ELISA results from 2003, 2006, 2007, or 2009 were enrolled in a follow-up study. Of these, 77 people were previously OV-16 seropositive and 169 were previously seronegative. By 2014 and 2015, 56 (72.7%) previously seropositive individuals had sero-reverted, whereas all previous negatives remained seronegative. The progression of antibody responses over time was estimated using a mixed-effects linear regression model, using data from seropositive participants who had sero-reverted. The temporal variation showed a mean activity unit decay of 0.20 per year (95% credible interval [CrI]: 0.17, 0.23), corresponding to an estimated antibody response half-life of 3.3 years (95% CrI: 2.7, 4.1). These findings indicate that the majority of seropositive people will sero-revert over time.

Background: Current soil-transmitted helminth (STH) control guidelines endorse the use of albendazole or mebendazole for school-based targeted preventive chemotherapy (PC), yet their reduced efficacy against Strongyloides stercoralis and Trichuris trichiura presents significant limitations. Emerging evidence indicates that community-wide PC [or mass drug administration (MDA)] using ivermectin, commonly used in other neglected tropical disease (NTD) control programs, may play an important role in controlling these parasites. We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations., Methods: We searched Pubmed, EMBASE, and Web of Science on February 14, 2023, for studies that investigated the effectiveness of ivermectin PC, either alone or in combination with other anthelmintic drugs, on STH infections, and provided a measure of STH prevalence before and after PC. We calculated pooled prevalence reductions for each STH using random-effects meta-analyses. Our protocol is available on PROSPERO (registration number CRD42023401219)., Results: A total of 21 were eligible for the systematic review, of which 15 were eligible for meta-analysis. All studies delivered ivermectin through MDA. The pooled prevalence reduction of S. stercoralis following MDA with ivermectin alone was 84.49% (95% CI 54.96-94.66) across five studies and 81.37% (95% CI 61.62-90.96) across seven studies with or without albendazole. The prevalence reduction of T. trichiura was 49.93% (95% CI 18.23-69.34) across five studies with ivermectin alone, and 89.40% (95% CI 73.66-95.73) across three studies with the addition of albendazole. There was high heterogeneity for all syntheses (I 2  > 65%)., Conclusions: This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S. stercoralis and T. trichiura. Based on these findings, revising international STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination of STHs and other NTDs., (© 2024. The Author(s).)

Aim: This study focused on evaluating the influence of geometric dimensions on the drug release kinetics of 3D-printed tablets. Materials & methods: An ink based on Gelucire 50/13 was prepared to print ivermectin-loaded tablets. The ink was characterized physicochemically and tablet dissolution tests were carried out. Results: The results confirmed the suitability of the ink for 3D printing at a temperature >46°C. Changes in the crystallinity of ivermectin were observed without chemical interactions with the polymer. 3D printed tablets with varied proportional sizes showed dual behavior in their release profiles, while tablets with only thickness reduction exhibited zero-order kinetics. Conclusion: These findings highlight the versatility of 3D printing to create systems with specific and customized release profiles.

Amblyomma maculatum, the Gulf Coast tick, infests a wide range of vertebrate species including livestock, dogs, cats, and humans. It is a species of significant veterinary and public health importance, especially as a vector of diseases, for instance American canine hepatozoonosis or tidewater spotted fever. An experimental study was conducted to evaluate the efficacy of NexGard ® Combo, a topical endectoparasiticide product for cats combining eprinomectin, praziquantel and esafoxolaner, against induced infestations of A. maculatum in cats. This Good Clinical Practice (GCP) study used a randomized, negative controlled, masked design. Ten cats were allocated to an untreated group and ten to a treated group, dosed once on Day 0 at the minimum label dose. On Days -2, 7, 14, 21, 28, 35, and 42, cats were infested with ~50 unfed adult A. maculatum. On Days 3, 10, 17, 24, 31, 38, and 45, i.e., 72 h after treatment and subsequent infestations, ticks were removed, counted and the numbers of live attached tick in each group were used for efficacy calculations. At each time-point, all untreated cats were adequately infested, demonstrating a vigorous tick population and an adequate study model. The curative efficacy after a single application against existing tick infestation, 72 h after treatment, was 98.7%. The preventive efficacy, 72 h after weekly infestations, over the following five weeks ranged from 93.8% to 99.4%., (© E. Tielemans et al., published by EDP Sciences, 2024.)

Gastrointestinal nematodes (GINs) can negatively impact all production classes of cattle, particularly growing cattle. A global decline in efficacy of broad-spectrum single-active anthelmintics requires alternative GIN control methods without the aid of novel drug classes. Here, we present a new fixed-dose combination injectable (FDCI) endectocide for cattle that combines doramectin (5 mg/ml) and levamisole hydrochloride (150 mg/ml). A 56-day comparative performance confinement backgrounding trial was conducted in stocker beef heifers (n = 1548) with confirmed GIN infections to (1) compare the Day 14 post-treatment effectiveness of the new FDCI endectocide to pen mates treated with the injectable single-active endectocide ivermectin, as evidenced by fecal egg counts (FECs) conducted for a randomly selected subset (10%) of both treatment groups, and (2) determine if the greater GIN control by the FDCI evidenced in the subsample improved growth performance in all FDCI-treated heifers. Heifers were procured in four cohorts, with a 10-week timeframe between enrollment of the first and last cohort. Treatment groups were comingled within dirt-floor pens (n = 31; 7-8 per cohort) and offered a standard backgrounding diet ad libitum for the study duration. Heifers with enrollment FEC ≥ 30 eggs per gram (EPG) were randomly allocated to receive the FDCI (n = 773) or ivermectin (n = 775) on Day 0. Day 0 FECs conducted on 10% of enrolled heifers (FDCI, n = 78; ivermectin, n = 79) were not different between treatment groups (p = 0.491). Day 14 FECs for the same heifers were reduced compared to Day 0 within each treatment group. Heifers given the FDCI had lower Day 14 AM FECs and higher FEC reduction test (FECRT) result (0.07 EPG; 0.999) than ivermectin-treated heifers (21.58 EPG; FECRT = 0.850). Mean body weight (BW) was not different between treatment groups on Day 0 (p = 0.2762) and Day 14 (p = 0.2010) but was significantly greater (p = 0.0007) for FDCI-treated heifers compared to ivermectin-treated heifers on Day 56. Compared to ivermectin-treated heifers, overall average daily gain from all evaluation periods (Day 0-14, Day 14-56, and Day 0-56) was greater (p ≤ 0.0052) in FDCI-treated heifers, and FDCI-treated heifers had 4.223 kg greater total weight gain over the 56-day study. The FDCI (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) was highly effective in reducing GIN infections and thus promoted improved growth performance in beef heifers over a 56-day backgrounding period., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew A. DeRosa reports a relationship with Zoetis Inc that includes: employment. Susan Holzmer reports a relationship with Zoetis Inc that includes: employment. Jase J. Ball reports a relationship with Zoetis Inc that includes: employment. Landon P. Watkins reports a relationship with Zoetis Inc that includes: employment. Mitchell Blanding reports a relationship with Zoetis Inc that includes: employment. Mark Alley reports a relationship with Zoetis Inc that includes: employment. Thomas H. Short reports a relationship with Zoetis Inc that includes: employment. David T. Bechtol reports a relationship with Agri Research LLC that includes: employment. Audie R. Waite reports a relationship with Agri Research LLC that includes: employment. Elizabeth J Rigoni reports a relationship with Zoetis Inc that includes: employment. Jezaniah K Tena reports a relationship with Zoetis Inc that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vector control interventions in sub-Saharan Africa rely on insecticide-treated nets and indoor residual spraying. Insecticide resistance, poor coverage of interventions, poor quality nets and changes in vector behavior threaten the effectiveness of these interventions and, consequently, alternative tools are needed. Mosquitoes die after feeding on humans or animals treated with ivermectin (IVM). Mass drug administration (MDA) with IVM could reduce vector survival and decrease malaria transmission. The entomological impact of MDA of combined IVM and dihydroartemisinin-piperaquine was assessed in a community-based, cluster-randomized trial., Methods: A cluster-randomized trial was implemented in 2018 and 2019 in 32 villages in the Upper River Region, The Gambia. The with the inhabitants of 16 intervention villages eligible to receive three monthly rounds of MDA at the beginning of the malaria transmission season. Entomological surveillance with light traps and human landing catches (HLC) was carried out during a 7- to 14-day period after each round of MDA, and then monthly until the end of the year. The mosquitocidal effect of IVM was determined by direct membrane feeding assays., Results: Of the 15,017 mosquitoes collected during the study period, 99.65% (n = 14,965) were Anopheles gambiae sensu lato (An. gambiae s.l.), comprising Anopheles arabiensis (56.2%), Anopheles coluzzii (24.5%), Anopheles gambiae sensu stricto (An. gembiae s.s.; 16.0%) and Anopheles funestus sensu lato (An. funestus s.l.; 0.35%). No effect of the intervention on vector parity was observed. Vector density determined on light trap collections was significantly lower in the intervention villages in 2019 (adjusted incidence rate ratio: 0.39; 95% confidence interval [CI]: 0.20, 0.74; P = 0.005) but not in 2018. However, vector density determined in HLC collections was similar in both the intervention and control villages. The entomological inoculation rate was significantly lower in the intervention villages than in the control villages (odds ratio: 0.36, 95% CI: 0.19, 0.70; P  = 0·003). Mosquito mortality was significantly higher when blood fed on IVM-treated individuals up to 21 days post-treatment, particularly in adults and individuals with a higher body mass index., Conclusion: Mass drug administration with IVM decreased vector density and the entomological inoculation rate while the effect on vector parity was less clear. Survival of mosquitoes fed on blood collected from IVM-treated individuals was significantly lower than that in mosquitoes which fed on controls. The influence of host characteristics on mosquito survivorship indicated that dose optimization could improve IVM efficacy. Future detailed entomological evaluation trials in which IVM is administered as stand-alone intervention may elucidate the contribution of this drug to the observed reduction in transmission., (© 2022. The Author(s).)

Background: Although the malaria burden has substantially decreased in sub-Saharan Africa, progress has stalled. We assessed whether mass administration of ivermectin (a mosquitocidal drug) and dihydroartemisinin-piperaquine (an antimalarial treatment) reduces malaria in The Gambia, an area with high coverage of standard control interventions., Methods: This open-label, cluster-randomised controlled trial was done in the Upper River region of eastern Gambia. Villages with a baseline Plasmodium falciparum prevalence of 7-46% (all ages) and separated from each other by at least 3 km to reduce vector spillover were selected. Inclusion criteria were age and anthropometry (for ivermectin, weight of ≥15 kg; for dihydroartemisinin-piperaquine, participants older than 6 months); willingness to comply with trial procedures; and written informed consent. Villages were randomised (1:1) to either the intervention (ivermectin [orally at 300-400 μg/kg per day for 3 consecutive days] and dihydroartemisinin-piperaquine [orally depending on bodyweight] plus standard control interventions) or the control group (standard control interventions) using computer-based randomisation. Laboratory staff were masked to the origin of samples. In the intervention group, three rounds of mass drug administration once per month with ivermectin and dihydroartemisinin-piperaquine were given during two malaria transmission seasons from Aug 27 to Oct 31, 2018, and from July 15 to Sept 30, 2019. Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03576313., Findings: Between Nov 20 and Dec 7, 2017, 47 villages were screened for eligibility in the study. 15 were excluded because the baseline malaria prevalence was less than 7% (figure 1). 32 villages were enrolled and randomised to either the intervention or control group (n=16 in each group). The study population was 10 638, of which 4939 (46%) participants were in intervention villages. Coverage for dihydroartemisinin-piperaquine was between 49·0% and 58·4% in 2018, and between 76·1% and 86·0% in 2019; for ivermectin, coverage was between 46·9% and 52·2% in 2018, and between 71·7% and 82·9% in 2019. In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group (odds ratio [OR] 0·30, 95% CI 0·16-0·59; p<0·001). A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66-1·25; p=0·537). In 2019, adverse events were recorded in 386 (9·7%) of 3991 participants in round one, 201 (5·4%) of 3750 in round two, and 168 (4·5%) of 3752 in round three. None of the 11 serious adverse events were related to the intervention., Interpretation: The intervention was safe and well tolerated. In an area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin-piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed., Funding: Joint Global Health Trials Scheme., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ivermectin has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. It is unknown whether this inhibition of SARS-CoV-2 replication correlates with improved clinical outcomes. To assess the effectiveness and safety of ivermectin in hospitalized patients with COVID-19. A total of 286 patients with COVID-19 were included in the study. Univariate analysis of the primary mortality outcome and comparisons between treatment groups were determined. Logistic regression and propensity score matching (PSM) was used to adjust for confounders. Patients in the ivermectin group received 2 doses of Ivermectin at 200 μg/kg in addition to usual clinical care on hospital Days 1 and 3. The ivermectin group had a significantly higher length of hospital stay than the control group; however, this significance did not maintain on multivariable logistic regression analysis. The length of intensive care unit (ICU) stay and duration of mechanical ventilation were longer in the control group. However, a mortality benefit was not seen with ivermectin treatment before and after PSM (p values = 0.07 and 0.11, respectively). ICU admission, and intubation rate were not significantly different between the groups (p = 0.49, and p = 1.0, respectively). No differences were found between groups regarding the length of hospital stay, ICU admission, intubation rate, and in-hospital mortality., (© 2021 Wiley Periodicals LLC.)

Community-directed treatment with ivermectin (CDTi) is the primary strategy employed to control and eliminate human onchocerciasis in Ethiopia. After long-term mass distribution for onchocerciasis, ivermectin is expected to have additional benefits beyond the envisioned targets by reducing the burden of other co-endemic parasitic infections as to STHs. To date, studies focused on the collateral impact of CDTi on STH in Ethiopia are scanty. Two community-based cross-sectional surveys (baseline in 1997 and post-CDTi in 2017) were conducted to evaluate the impact of long-term CDTi employed to control and eliminate onchocerciasis on the burden of STH infections in Yeki district of southwest Ethiopia. Stool samples were collected and examined using Ritchie`s concentration and Kato-Katz techniques in the baseline and current study, respectively. Overall, 188(38.3%, 95% Confidence interval (CI) 34.1-42.7%) individuals were positive at least for any of the STH species from 491 study participants in the post-CDTi. The prevalence of A. lumbricoides, hookworms, and T. trichiura was 11.2% (95% CI 8.7-14.3%), 16.3% (95% CI 13.3-19.8%), and 29.9% (95% CI 26.1-34.1%), respectively. Individuals aged 5-9 years had a significantly higher prevalence of A. lumbricoides (Adjusted odds ratio (AOR) 6.5, 95% CI 1.7-25.4), T. trichuria (AOR 8, 95% CI 2.6-25.1), and any STH infection (AOR 5, 95% CI 1.7-14.7) than those of ≥ 51 years. Also, significantly higher prevalences of T. trichuria infection were observed in individuals aged 10-14 years (AOR 4.1, 95% CI 1.7-9.9), 15-20 years (AOR 3.1, 95% CI 1.2-8.1), 21-30 years (AOR 2.4, 95% CI 1.1-5.5), and 31-40 years (AOR 3.2, 95% CI 1.3-7.5) compared with those of ≥ 51 years. The prevalence of A. lumbricoides was significantly higher in males (AOR 0.5, 95% CI 0.3-0.9). Of the 491 study participants, only data from 400 individuals who had not been involved in a mass drug administration (MDA) with other STH anthelmintics were considered in the comparative analysis. Before CDTi, the prevalence of A. lumbricoides, T. trichiura, hookworm, and any STH infection was 47.1% (95% CI 41.6-52.7%), 3.3% (95% CI 1.8-5.9%), 37.9% (95% CI 32.7-43.5%), and 58.8% (95% CI 53.2-64.1%), respectively. Long-term CDTi considerably reduced the prevalences of A. lumbricoides and hookworm by 76.2% and 56.9%, respectively (p < 0.001). Nonetheless, CDTi did not affect the prevalence of T. trichiura infection and, in contrast, it was significantly higher in the current study (P < 0.001). Overall post-CDTi prevalence of any STH infection was considerably lower than reported in the baseline (p < 0.001). It is evidenced that long-term CDTi for onchocerciasis control and elimination had additional benefits by reducing the prevalence of STH infections specifically of A. lumbricoides and hookworm, but had no impact on infections with T. trichuria. Our finding of additional health benefits of large-scale ivermectin administration taking it will aid to increase positive engagement and sustain participation of communities during MDA campaigns, and strengthen governmental and non-governmental organizations (NGOs) support for the undergoing national onchocerciasis elimination program., Competing Interests: The authors have declared that no competing interests exist.

Background: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG., Methodology: All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy., Principal Findings: Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007)., Conclusion: IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG., Trial Registration: Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936., Competing Interests: The authors have declared that no competing interests exist. Author Steven Kumai was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

The global COVID-19 pandemic has affected the world's population by causing changes in behavior, such as social distancing, masking, restricting people's movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150-200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19., (© 2022. The Author(s).)