Single Dose Of Ivermectin Research Articles

Cost-effectiveness of mass drug administration for control of scabies in Ethiopia: a decision-analytic model.

The strategies to control scabies in highly endemic populations include individual case/household management and mass drug administration (MDA). We used a decision-analytic model to compare ivermectin-based MDA and individual case/household management (referred to as "usual care") for control of scabies in Ethiopia at different prevalence thresholds for commencing MDA. A decision-analytic model was based on a repeated population survey conducted in Northern Ethiopia in 2018-2020, which aimed to evaluate the secondary impact of single-dose ivermectin MDA for the control of onchocerciasis on scabies prevalence. The model estimates the number of scabies cases and costs of two treatment strategies (MDA and usual care) based on their effectiveness, population size, scabies prevalence, compliance with MDA, medication cost, and other parameters. In the base-case analysis with a population of 100,000 and scabies prevalence of 15%, the MDA strategy was both more effective and less costly than usual care. The probability of MDA being cost-effective at the current cost-effectiveness threshold (equivalent to the cost of usual care) was 85%. One-way sensitivity analyses showed that the MDA strategy remained dominant (less costly and more effective) in 22 out of 26 scenarios. MDA was not cost-effective at scabies prevalence <10%, MDA effectiveness <85% and population size <5,000. An increase in the cost of ivermectin from 0 (donated) to 0.54 US$/dose resulted in a decrease in the probability of MDA being cost-effective from 85% to 17%. At 0.25 US$/dose, the MDA strategy was no longer cost-effective. The model provides robust estimates of the costs and outcomes of MDA and usual care and can be used by decision-makers for planning and implementing scabies control programmes. Results of our analysis suggest that single-dose ivermectin MDA is cost-effective in scabies control and can be initiated at a scabies prevalence >10%.

Mosquitocidal efficacy and pharmacokinetics of single-dose ivermectin versus three-day dose regimen for malaria vector control compared with albendazole and no treatment: An open-label randomized controlled trial

ObjectivesWhen 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. DesignWe 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. ResultsA 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. ConclusionsIt 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.

Efficacy of single-dose oral ivermectin in treatment of rosacea in relation to demodex mites

Background Rosacea is a common chronic inflammatory cutaneous disease. Demodex mites play an important role in the etiology and pathogenesis of rosacea. Despite the various therapeutic options available, rosacea can be difficult to treat in some patients. Topical Ivermectin is approved for the treatment of rosacea. However, oral Ivermectin has not been extensively studied in the treatment of rosacea. This study aimed to (a) evaluate the efficacy, safety, adverse effects, and patient satisfaction of a single 250 µg/kg dose of oral ivermectin in the treatment of different subtypes of rosacea and (b) correlate its efficacy to different clinical variables. Also, it aimed to (c) clarify the possible role played by demodex mites in the pathogenesis of rosacea and the effect of oral Ivermectin on demodex mite count change after treatment, and its possible mechanisms in the treatment of rosacea. Methods This study included 45 rosacea patients; demodex mite count using standardized skin surface biopsies was done before and after receiving a single dose of 250 µg/kg oral Ivermectin. Disease severity was assessed at baseline and after treatment using the 5-point Global Investigator Assessment IGA scale. Patients were followed up every 4 weeks for 3 months. Results The results revealed significant Global Investigator Assessment improvement in included patients and high patient satisfaction rate. This was consistent with Demodex mites count that showed a significant decrease after treatment. A low relapse rate and few side effects were recorded. Conclusion A single 250 µg/kg dose of oral ivermectin is effective, safe, and tolerable in the treatment of different subtypes of rosacea. It exerts its action through both anti-inflammatory and antiparasitic roles.

Human strongyloidiasis: complexities and pathways forward.

Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by Strongyloides stercoralis, a parasitic worm with a complex life cycle. Globally, 300-600 million people are infected through contact with fecally contaminated soil. An autoinfective component of the life cycle can lead to chronic infection that may be asymptomatic or cause long-term symptoms, including malnourishment in children. Low larval output can limit the sensitivity of detection in stool, with serology being effective but less sensitive in immunocompromise. Host immunosuppression can trigger catastrophic, fatal hyperinfection/dissemination, where large numbers of larvae pierce the bowel wall and disseminate throughout the organs. Stable disease is effectively treated by single-dose ivermectin, with disease in immunocompromised patients treated with multiple doses. Strategies for management include raising awareness, clarifying zoonotic potential, the development and use of effective diagnostic tests for epidemiological studies and individual diagnosis, and the implementation of treatment programs with research into therapeutic alternatives and medication safety.

Combined effects of Limonene and Ivermectin on P-glycoprotein-9 gene expression of lambs Infected with Haemonchus contortus

Although ivermectin (IVM) has a wide spectrum and long half-life, its frequent use as an anthelmintic for the last 42 years led to its worldwide tolerance by Haemonchus contortus. We evaluated the combination of limonene (LIM), a P-glycoprotein (Pgp) modulator, with IVM in lambs infected with a multidrug-resistant H. contortus. Twenty-four male Dorper lambs were artificially infected with two doses (seven days apart) of 8000 infective larvae of a multidrug-resistant isolate of H. contortus. The infection was patent 25 days later. Fifteen days before treatment with IVM (DAY –15), animals were divided into 4 groups: Infected-untreated control (CTL), IVM, LIM, and LIM+IVM. From DAY –15 to DAY + 14, groups LIM and LIM+IVM received 200 mg/kg of body weight/day of LIM via oral. On DAY 0, a single dose of IVM at 200 µg/kg of body weight was administered orally to groups IVM and LIM+IVM. On DAY + 7 and DAY + 14, fecal egg counts (FEC) were performed and on DAY + 14 animals were euthanized for total worm count (TWC), worm length, fecundity of females, and Pgp-9 gene expression. On DAY + 7, group LIM+IVM had 96.29% efficacy based on Fecal Egg Count Reduction TEST (FECRT) and a highly significant reduction in FEC (P = 0.0005) when compared to CTL. On DAY + 14, the efficacy of LIM+IVM was 82.87% on FECRT, although no differences were found among groups for FEC, TWC, worm length, or Pgp-9 gene expression. Female worms from the CTL group had higher egg counts in their uterus when compared to LIM. No differences were found for hematological or biochemical parameters, body weight, or weight gain among groups. Thus, LIM given daily at 200 mg/kg was safe for animals and, when combined with IVM, decreased egg shedding and could reduce pasture contamination, although it was unable to kill multidrug-resistant H. contortus.

Efficacy, safety, and tolerability of albendazole and ivermectin based regimens for the treatment of microfilaraemic loiasis in adult patients in Gabon: A randomized controlled assessor blinded clinical trial.

There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon. Eligible adult patients with L. loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L. loa microfilaraemia ≤ 100 mf/ml at Day 168. In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80-90% reduction of microfilaraemia was observed in the active treatment groups. The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe. Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027.

Failure of scabies treatment: a systematic review andmeta-analysis.

Treatment failure is considered to be an important factor in relation to the increase in scabies incidence over the last decade. However, the regional and temporal differences, in addition to the predictors of therapy failure, are unclear. We aimed to conduct a systematic review of the prevalence of treatment failure in patients with scabies and investigation of associated factors. We searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Global Health and the Cochrane Central Register of Controlled Trials from inception to August 2021 for randomized and quasi-randomized trials, in addition to observational studies that enrolled children or adults diagnosed with confirmed or clinical scabies treated with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur or lindane, and measured treatment failure or factors associated with treatment failure. We performed a random effects meta-analysis for all outcomes reported by at least two studies. A total of 147 studies were eligible for inclusion in the systematic review. The overall prevalence of treatment failure was 15.2% [95% confidence interval (CI) 12.9-17.6; I2 = 95.3%, moderate-certainty evidence] with regional differences between World Health Organization regions (P = 0.003) being highest in the Western Pacific region (26.9%, 95% CI 14.5-41.2). Oral ivermectin (11.8%, 95% CI 8.4-15.4), topical ivermectin (9.3%, 95% CI 5.1-14.3) and permethrin (10.8%, 95% CI 7.5-14.5) had relatively lower failure prevalence compared with the overall prevalence. Failure prevalence was lower in patients treated with two doses of oral ivermectin (7.1%, 95% CI 3.1-12.3) compared with those treated with one dose (15.2%, 95% CI 10.8-20.2; P = 0.021). Overall and permethrin treatment failure prevalence in the included studies (1983-2021) increased by 0.27% and 0.58% per year, respectively. Only three studies conducted a multivariable risk factor analysis; no studies assessed resistance. A second dose of ivermectin showed lower failure prevalence than single-dose ivermectin, which should be considered in all guidelines. The increase in treatment failure over time hints at decreasing mite susceptibility for several drugs, but reasons for failure are rarely assessed. Ideally, scabicide susceptibility testing should be implemented in future studies.

The search for better treatment strategies for mansonellosis: an expert perspective

ABSTRACT Introduction Four species of the Mansonella genus infect millions of people across sub-Saharan Africa and Central and South America. Most infections are asymptomatic, but mansonellosis can be associated with nonspecific clinical manifestations such as fever, headache, arthralgia, and ocular lesions (M. ozzardi); pruritus, arthralgia, abdominal pain, angioedema, skin rash, and fatigue (M. perstans and perhaps Mansonella sp. ‘DEUX’); and pruritic dermatitis and chronic lymphadenitis (M. perstans). Areas covered We searched the PubMed and SciELO databases for publications on mansonelliasis in English, Spanish, Portuguese, or French that appeared until 1 May 2023. Literature data show that anthelmintics – single-dose ivermectin for M. ozzardi, repeated doses of mebendazole alone or in combination with diethylcarbamazine (DEC) for M. perstans, and DEC alone for M. streptocerca – are effective against microfilariae. Antibiotics that target Wolbachia endosymbionts, such as doxycycline, are likely to kill adult worms of most, if not all, Mansonella species, but the currently recommended 6-week regimen is relatively impractical. New anthelmintics and shorter antibiotic regimens (e.g. with rifampin) have shown promise in experimental filarial infections and may proceed to clinical trials. Expert opinion We recommend that human infections with Mansonella species be treated, regardless of any apparent clinical manifestations. We argue that mansonellosis, despite being widely considered a benign infection, may represent a direct or indirect cause of significant morbidity that remains poorly characterized at present.

BI27 Strongyloides stercoralis screening in dermatology

Abstract Strongyloidiasis is a major neglected tropical disease and chronic parasitic infection caused by Strongyloides stercoralis. An estimated 30–100 million people are infected worldwide, with acquisition via contact with contaminated soil. Accurate data for the UK are unavailable, but there is a prevalence of &amp;gt; 20% in certain immigrant populations. Many cases are asymptomatic; without therapy, the infection may be lifelong. Testing is more common in dermatology since the advent of dupilumab as infection can be life-threatening in the immunocompromised. Symptoms reported with strongyloidiasis include not only pruritus and urticaria but also abdominal and respiratory issues. Standard diagnostic testing of strongyloidiasis relies on demonstration of the parasite in faeces, body fluids or tissue samples, although serology is most often used in dermatology. The aim of our study was to assess why dermatologists are ordering Strongyloides serology and whether the results could identify features of infection. All Strongyloides serology tests sent by dermatology from two centres from January 2021 to December 2022 were analysed. Data collected included demographics, reason for testing, symptoms, foreign travel, test results and treatment. In total, 187 tests were sent. Patient demographics are provided in Table 1. The reasons for testing were before starting dupilumab in 57.2% (n = 107), pruritus in 13.4% (n = 25) and urticaria in 3.2% (n = 6/187). There was a recorded history of other symptoms of strongyloidiasis in five patients, and a recorded history of foreign travel in four. Twelve per cent of results were positive (n = 23/187), 6.9% (n = 13) were borderline and 80.7% (n = 151) were negative. There was no major skew toward a reason for testing in those who were positive/borderline. Eight per cent (n = 3/36) of those with positive/borderline results had other recorded symptoms. Of the positive/borderline results, 31% (n = 11/36) were not treated (mostly because they did not go on to have immunosuppression), 28% (n = 10) were treated with a single dose of ivermectin, 31% (n = 11) with two doses and 8% (n = 3) with four doses. The main reason for Strongyloides testing in dermatology is before starting dupilumab. A low proportion of the patients with positive/borderline results had symptoms, although often this was not recorded. A higher proportion of individuals of Asian or African ancestry had positive/borderline results. We shall also discuss evidence behind the methods of and reasons for Strongyloides testing.Table 1Patient demographicsDemographicAll tests (n = 187)Positive/borderline tests (n = 36)Male115 (61.5)22 (61)Female72 (38.5)14 (39)White52 (27.8)5 (14)Asian95 (50.8)22 (61)Black21 (11.2)5 (14)Other/not stated19 (10.2)5 (14)Data are presented as n (%).

Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial.

To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020-October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200 μg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models. Overall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70-1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0-16.0) and 14.0 (12.0-16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively. In patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test. ClinicalTrials.gov, NCT04703205.

Impact of short-term discontinuation of ivermectin-based chemoprevention on onchocerciasis transmission in endemic settings with long history of mass drug administration.

The control of onchocerciasis currently relies on annual distribution of single dose ivermectin. Because ivermectin has minimal effects on the adult parasite, mass drug administration (MDA) campaigns against onchocerciasis require at least 15 years of annual uninterrupted ivermectin distribution. Mathematical models have predicted that short-term disruption of MDA (as was seen during COVID-19) could impacted the microfilaridermia prevalence depending on the pre-control endemicity and the histories of treatment, requiring corrective measures (such as biannual MDA) to mitigate the effect on onchocerciasis elimination. Field evidence supporting this prediction, however, has yet to be gathered. This study aimed to assess the impact of ~2 years disruption of MDA on onchocerciasis transmission indicators. A cross-sectional survey was carried out in 2021 in seven villages of Bafia and Ndikinimeki, two health districts located in the Centre Region, Cameroon, where MDA has been ongoing for two decades, but interrupted in 2020 as a response to the COVID-19 pandemic. Volunteers aged 5 years and above were enrolled for clinical and parasitological examinations for onchocerciasis. Data were compared with pre-COVID-19 prevalence and intensity of infection from the same communities to measure changes over time. A total of 504 volunteers (50.3% males), aged 5-99 years (Median: 38; IQR: 15-54) was enrolled in the two health districts. The overall prevalence of microfilaridermia in 2021 was similar in Ndikinimeki health district (12.4%; 95% CI: 9.7-15.6) and Bafia health district (15.1%; 95% CI: 11.1-19.8) (p-value = 0.16). Microfilaridermia prevalences were either similar between 2018 and 2021 in the communities of Ndikinimeki health district (19.3% vs 12.8% (p = 0.057) for Kiboum 1; and 23.7% vs 21.4% (p = 0.814) for Kiboum 2), or higher in 2019 compared to 2021 in the communities of Bafia health district (33.3% vs 20.0% (p = 0.035) for Biatsota). The mean microfilarial densities in these communities dropped from 5.89 (95% CI: 4.77-7.28) mf/ss to 2.4 (95% CI: 1.68-3.45) mf/ss (p-value < 0.0001), and from 4.81 (95% CI: 2.77-8.31) mf/ss to 4.13 (95% CI: 2.49-6.86) mf/ss (p-value < 0.02) in Bafia and Ndikinimeki health districts, respectively. Community Microfilarial Load (CMFL) dropped from 1.08-1.33 mf/ss in 2019 to 0.052-0.288 mf/ss in 2021 in Bafia health district while remaining stable in the Ndikinimeki health district. The continued decline in prevalence and CMFL observed ~2 years after MDA disruption is consistent with mathematical predictions (ONCHOSIM) and shows that additional efforts and resources are not needed to mitigate the effects of short-term MDA disruption in highly endemic settings prior to intervention with long treatment histories.

PBPK modeling of ivermectin-Considerations for the purpose of developing alternative routes to optimize its safety profile.

Although single-dose ivermectin has been widely used in mass-drug administration programs for onchocerciasis and lymphatic filariasis for many years, ivermectin may have utility as an endectocide with mosquito-lethal effects at dosages greater and longer than those used to treat helminths. The final physiologically-based pharmacokinetic (PBPK) model for ivermectin described here was able to capture, with reasonable accuracy, observed plasma drug concentration-time profiles and exposures of ivermectin after a single oral dose of the drug in healthy male (dose range 6-30 mg) and female subjects, in both fasted and fed states, in African patients with onchocerciasis (150 μg/kg) and in African children. The PBPK model can be used for further work on lactation, pediatric dosing (considering CYP3A4 and Pg-p ontogenies), and pregnancy, especially if nonstandard doses will be used. The key findings of our study indicate that absorption of ivermectin may be highly dependent on bile micelle-mediated solubility. The drug is highly lipophilic and permeable, and its plasma exposure appears to be associated with the body mass index of an individual. These are all factors that need to be considered when extrapolating to more complex oral formulations or alternative routes of administration. Administering lower doses over a longer period may attenuate the dependence on bile micelle-mediated solubility. With relevant inputs, the verified PBPK model developed here could be used to simulate plasma exposures following administration of ivermectin by complex generics in development.

Cutaneous Larvae Migrans Treated with a Single Dose of Ivermectin

Hookworm-related cutaneous larva migrans (HrCLM) is a clinical diagnosis based on a history of exposure to contaminated soil and is associated with a characteristic red serpiginous lesion that migrates within the epidermis. Our patient presented with a red, tortuous migratory rash with localized pruritus on the left plantar foot of 1-month duration. He lacked recent travel history outside the southeastern United States. Upon admission, he presented with peripheral blood eosinophilia, an uncommon feature of HrCLM. A single dose of ivermectin was sufficient for treatment, and symptoms resolved within 3 days. This case highlights the increased incidence of domestically acquired hookworm infections, explores this epidemiological shift, and emphasizes relevant differential diagnoses.

Single Dose of Ivermectin is not Useful in Patients with Hematological Disorders and COVID-19 Illness: A Phase II B Open Labelled Randomized Controlled Trial.

Repurposed drugs may reduce morbidity and mortality in patients with hematological disorders who develop COVID-19 illness. 112 patients with predominantly hematological illnesses were randomized to receive standard of care, ivermectin 12 mg [Iv 12] or 24 mg [Iv24] for asymptomatic, mild, or moderate COVID 19 illness. Serial respiratory samples for rRT-PCR samples were sent on Day 3, 5 and 7. rRT-PCR negativity and ≥ 2 log10 reduction in viral loads on day 3, 5 and 7 were similar between the 3 treatment groups across all disease categories. Symptom progression occurred in 26 patients [21.6%] with no difference across 3 treatment groups. Twenty-two patients [18.3%] have expired while 98 [81.7%] survived. Survival rates were similar across treatment groups [controls—80.5%, Iv12—77.5%, Iv24—87.2% respectively]. Overall, poorer survival was seen with moderate illness compared to others [51.6% vs 92.1%; p = 0.000] and was the only significant risk factor identified on multivariate analysis. In this Phase II randomised trial, single dose of 12 or 24 mg of ivermectin did not reduce viral loads, prevent symptom progression, or reduce mortality in patients with predominantly haematological illnesses who develop mild to moderate COVID 19 illness.

Atypical imported loiasis characterised by recurrent anaemia in a patient from China

In March, 2021, a 49-year-old man was admitted to The Fourth People's Hospital of Nanning (Nanning, China) with recurrent dizziness and fatigue that had persisted for more than 1 year. Physical examination revealed paleness on his face and a slightly yellow sclera. He had no hepatomegaly, but he had splenomegaly. His laboratory results showed a low haemoglobin concentration of 84 g/L, a normal blood eosinophil percentage of 3·1%, a high reticulocyte percentage of 4·6%, haemoglobinuria (score of 2+), a low haptoglobin concentration of 1·01 mg/dL (normal range 32–205 mg/dL), a high lactic acid dehydrogenase concentration of 750 U/L (normal range 120–160 U/L), and a high 3-hydroxybutyrate dehydrogenase concentration of 711 U/L (normal range 72–182 U/L). He had a history of haemolytic anaemia, and the lowest haemoglobin concentration recorded was 46 g/L. The patient had previously received four blood transfusions. He had a history of malaria in Ghana and the Democratic Republic of the Congo and thus was tested for malaria. However, microfilariae (an average of 180 per mL) were incidentally discovered on examining peripheral blood samples collected on the day and night of admission. The microfilariae were 225–251 μm long and 6–8 μm wide (figure). A bone marrow smear showed two microfilariae; however, cerebrospinal fluid and urine samples showed no microfilariae. PCR identified a 286 bp filarial-specific internal transcribed spacer 1 (ITS1) fragment and a 712 bp fragment of mitochondrial cytochrome c oxidase subunit 1 (COX1). Analysis with the basic local alignment search tool on the National Center for Biotechnology Information website showed that the ITS1 and COX1 fragments had the highest similarity with those of Loa loa (99% [MK978707] and 95% [HQ186250], respectively). Review of the patient's malaria thick blood smear slide from March, 2020, revealed the presence of two microfilariae, which has not been reported previously. Additionally, in June, 2020, liver fluke eggs in the patient's stool had been reported previously and he had received albendazole (650 mg) twice daily for 7 days. Following the identification of L loa, a diagnosis of atypical imported loiasis was established and the patient was treated at our hospital with a single dose of ivermectin (150 μg/kg) orally for anti-filariasis treatment, without intervention for anaemia. 2 weeks after treatment, a peripheral blood smear showed that the number of microfilariae had decreased to nine per mL on average, and his haemoglobin concentration had increased to 120 g/L and his eosinophil percentage had increased to 22·1%. 6 weeks after treatment, his haemoglobin concentration had increased to 147 g/L, with no microfilariae detected in his peripheral blood, suggesting that his anaemia was caused by filariasis.

High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 μg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 μg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load.

Tests on the efficacy of amitraz, ivermectin and eprinomectin for control of lice in goats

Ectoparasitic infestations with Linognathus stenopsis and Bovicola caprae are a serious concern in goat farms, especially during the winter and spring. This study tested the efficacy of three modern insecticide drugs (ivermectin, eprinomectin and amitraz) applied via different routes for control of sucking and chewing lice in naturally co-infected goats. Each of drugs was tested on 30 goats. The animals from the first flock were treated with a single dose of ivermectin, applied subcutaneously at 0.2 mg/kg, the second one received a single spot on treatment with 1 mg/kg еprinomectin and the third flock was treated twice with amitraz, through spraying at a dose of 4 mL/1 L water. The results were evaluated before the treatments and at post treatment days 3, 14 and 60. On post treatment day 60, the application of ivermectin resulted in reduction of Bovicola caprae population by 73.05%, and for that of Linognathus stenopsis: by 92.70%. Eprinomectin demonstrated 100% reduction of both lice. The reduction of L. stenopsis and B. caprae caused by amitraz was by 92.20% and by 98.61% respectively. The macrocyclic lactone eprinomectin showed the highest efficacy (Р&lt;0.05), was not toxic for goats and therefore, may be used as a treatment of choice for lice control.

MDA IN JHARKHAND: CAN IT BE AN OPPORTUNISTIC INTERVENTION TO REDUCE COVID-19 INFECTION, SIMDEGA DISTRICT JHARKHAND

Ivermectin, an FDA approved drug was used earlier for the control of various parasitic diseases such as Onchocerciasis, Lymphatic Filariasis in African and Asian countries. In the current pandemic situation, Ivermectin has also been explored as a prophylactic and therapeutic option for COVID-19 infection. This study explores the role of single dose Ivermectin as a part of triple drug therapy (IDA: Ivermectin + Diethylcarbamazine + Albendazole) along with Mass drug administration (MDA) under the National Filariasis Elimination Programme in Simdega District of Jharkhand state in India. MDA with IDA was conducted during 10-31st August 2020 in Simdega. Trend of COVID-19 cases before and after MDA was analyzed to assess the effect of a single dose of Ivermectin in reducing the number of COVID-19 cases in Simdega. In this study, a One Way ANOVA test was used to find the significance shows that less significant difference in the mean number of cases reported before and after the MDA in Simdega. Time series analysis also didn’t show any significant difference in predicted and actual number of COVID-19 cases during the subsequent follow up after MDA in Simdega. The study also concludes that age appropriate single dose of Ivermectin was not associated with any significant decrease in the number of COVId-19 cases in Simdega.

Efficacy and safety of co-administered ivermectin and albendazole in school-aged children and adults infected with Trichuris trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania: a double-blind, parallel-group, phase 3, randomised controlled trial

Preventive chemotherapy with albendazole or mebendazole remains one of the cornerstones of soil-transmitted helminth control. However, these drugs are less effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence is lacking. We aimed to demonstrate superiority of co-administered ivermectin-albendazole over albendazole monotherapy in three distinct epidemiological settings. We conducted a double-blind, parallel-group, phase 3, randomised controlled trial in community members aged 6-60 years infected with T trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania, between Sept 26, 2018, and June 29, 2020. Participants with at least 100 T trichiura eggs per g of stool at baseline were randomly assigned (1:1) using computer-generated randomisation sequences in varying blocks of four, six, and eight, stratified by baseline T trichiura infection intensity, to orally receive either a single dose of ivermectin (200 μg/kg) plus albendazole (400 mg) or albendazole (400 mg) plus placebo. Patients, field staff, and outcome assessors were masked to treatment assignment. The primary outcome was cure rate against T trichiura, defined as the proportion of participants with no eggs in their faeces 14-21 days after treatment, assessed by Kato-Katz thick smears, and analysed in the available-case population according to intention-to-treat principles. Safety was a secondary outcome and was assessed 3 h and 24 h after drug administration. The trial is registered at ClinicalTrials.gov, NCT03527732. Between Sept 13 and Dec 18, 2019, Jan 12 and April 5, 2019, and Sept 26 and Nov 5, 2018, 3737, 3694, and 1435 community members were screened for trial eligibility in Côte d'Ivoire, Laos, and Pemba Island, respectively. In Côte d'Ivoire, Laos, and Pemba Island, 256, 274, and 305 participants, respectively, were randomly assigned to the albendazole group, and 255, 275, and 308, respectively, to the ivermectin-albendazole group. Primary outcome data were available for 722 participants treated with albendazole and 733 treated with ivermectin-albendazole. Ivermectin-albendazole showed significantly higher cure rates against T trichiura than albendazole in Laos (66% [140 of 213]vs 8% [16 of 194]; difference 58 percentage points, 95% CI 50 to 65, p<0·0001) and Pemba Island (49% [140 of 288]vs 6% [18 of 293], 43 percentage points, 36 to 49, p<0·0001) but had similar efficacy in Côte d'Ivoire (14% [32 of 232]vs 10% [24 of 235], 4 percentage points, -2 to 10, p=0·24). No serious adverse events were reported; observed events were mostly classified as mild (95% [266 of 279] in the albendazole group and 91% [288 of 317] in the ivermectin-albendazole group), and all were transient in nature. Treatment with ivermectin-albendazole resulted in higher efficacy against trichuriasis than albendazole alone in Laos and Pemba Island but not in Côte d'Ivoire. We recommend implementation of this combination therapy for soil-transmitted helminth control in countries with high T trichiura prevalence and proven enhanced efficacy of this treatment, particularly where ivermectin is beneficial against other endemic helminthiases. Bill & Melinda Gates Foundation.

A Reevaluation of the Tolerability and Effects of Single-Dose Ivermectin Treatment on Onchocerca volvulus Microfilariae in the Skin and Eyes in Eastern Ghana.

ABSTRACT.Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 μg/kg. Most participants (184–231, 79.7%) enrolled were treatment-naïve. The baseline geometric mean skin Mf count was 12.67/mg (range 3–86). Although persons with MfAC at baseline (64/231, 27%) had significantly higher skin Mf counts than people without MfAC, 7 of 39 (15%) of persons with skin Mf counts in the range of 3–5 Mf/mg had MfAC. Skin Mf were detected in 14% (31/218) and 45% (96/216) of participants 3 and 6 months after IVM treatment, respectively. MfAC were detected in 12 of 212 (5.7%) study participants at 6 months. 81% (187 of 231) of participants experienced 439 adverse events within 7 days after treatment; all adverse events were mild (96.1%) or moderate. This study has provided new data on the kinetics of Mf in the skin and eyes after IVM treatment of persons with light to moderate intensity Onchocerca volvulus infections that are common in Africa at this time.