Introduction
In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV- 2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.
Methods
We conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.
Results
The Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/-5.2, for A 6.0 +/- 2.9, and for B 4.6 +/-3.2 . 2 Way repeated measures ANOVA of ranked COVID 19 +/- scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p = 0.035) and time effect (p < 0.0001). IV also tended to increase SPO2% compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = -0.52, p = 0.005). No SAE was reported.
Conclusions
12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.
Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.
43% of eyes in bilaterally blind patients were blind because of onchocerciasis. A further 11% were blind from optic atrophy much of which was probably onchocercal in origin. Glaucoma was the next most common cause of blindness in the bilaterally blind (11%). Only 6% of eyes were blind from cataract as the primary cause. In the visually impaired population cataract was the most common primary cause of impaired/blind eyes (31%), followed by onchocerciasis (19%). (BrJ7 Ophthalmol 1994; 78: 8-13)
The Keeler Pulsair EasyEye gives reliable measurements of IOP in African eyes but is significantly affected by CCT. Particularly in borderline cases where management decisions have to be taken, it may be necessary to have pachymetric corrections based on an NCT algorithm, which appears steeper than the GAT algorithm.
IntroductionIn vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV-2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.MethodsWe conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.ResultsThe Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/−5.2, for A 6.0 +/− 2.9, and for B 4.6 +/−3.2. 2 Way repeated measures ANOVA of ranked COVID 19 + / − scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p=0.035) and time effect (p <0.0001). IV also tended to increase SPO2 % compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = −0.52, p = 0.005). No SAE was reported.Conclusions12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.
This paper reviews the current management of onchocerciasis and its future prospects. Onchocerciasis is a disease affecting millions of people in Africa, South and Central America, and Yemen. It is spread by the blackfly as a vector and caused by the filarial nematode, Onchocerca volvulus. A serious attempt was made by the Onchocerciasis Control Program between 1975 and 2002 to eliminate the vector in eleven of the endemic countries in West Africa, and with remarkable success. Formerly, the treatment was with diethyl carbamazine for the microfilaria and suramin for the adult worm. These drugs are now known to be toxic and unsuitable for mass distribution. In particular, they precipitate optic nerve disease. With the discovery of ivermectin, a much safer microfilaricide, and the decision of Merck to distribute the drug free of charge for as long as needed, the strategy of control switched to mass drug administration through community-directed treatment with ivermectin. So far, millions have received this annual or biannual treatment through the African Program for Onchocerciasis Control and the Onchocerciasis Elimination Program for the Americas. However, the problem with ivermectin is that it is a monotherapy microfilaricide which has limited effect on the adult worm, and thus will need to be continued for the life span of the adult worm, which may last up to 15 years. There are also early reports of resistance. Serious encephalopathy and death may occur when ivermectin is used in subjects heavily infested with loiasis. It seems unlikely that a break in transmission will occur with community-directed treatment with ivermectin in Africa because of population migrations and the highly efficient vector, but in the Americas some countries such as Columbia and the Oaxaca focus in Mexico have reported eradication. Vector control is only now applicable in selected situations, and particularly to control the nuisance value of the blackfly. Trials are ongoing for alternatives to ivermectin. Candidate drugs include moxidectin, a macrofilaricide, doxycycline which targets the Wolbachia endosymbiont, and flubendazole, which shows promise with the newer oral cyclodextrin formulation.
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