Fasciola hepatica infection in cattle and the use of simulation models for endemic areas.

Fasciolosis is a food-borne disease that causes great distress to a range of hosts, including humans. The objectives of this study were to (1) evaluate the liver damage and carcass weight of cattle naturally infected with Fasciola hepatica from the state of Rio Grande do Sul (RS), Brazil, and to (2) determine the distribution of adult flukes in 12,236 cattle liver from RS. The data from these experiments were used to calculate the overall economic loss due to F. hepatica infection. Eighteen adult Polled Hereford cows were divided into a triclabendazole (TbG) and a F. hepatica-positive group (FhG). For Experiment 1, a generalized linear mixed model revealed a statistical difference in carcass weight (49.8 kg) between TbG and FhG. The Monte Carlo analysis also revealed that the animals' weight differences were due to the disease. For Experiment 2, the prevalence of infected livers was above 16% (1904/12,236), mostly (20.1%) from the south-west region of RS. The Susceptible-infected-recovered (SIR) epidemic model revealed the evolution of the infection using a high infectivity and low recovery rate. Other distinctive scenarios that occur in RS were also established with different rates of infectivity. The economic assessment showed a potential loss of US$45 million to the beef cattle industry of RS, with an overall State cost of US$90.3 million. These novel findings reveal the importance of fasciolosis infection, which can cause a significant health condition and poor animal welfare.

Safety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of Plasmodium cynomolgi Infection in Rhesus Macaques.

Previously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (50% inhibitory concentration [IC50], 10.42 µM) and hypnozoites (IC50, 29.24 µM) in primary macaque hepatocytes when administered as a high dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for 7 consecutive days were evaluated for prophylaxis or radical cure of P. cynomolgi liver stages in rhesus macaques. No inhibition or delay to blood-stage P. cynomolgi parasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for 7 days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in Plasmodium vivax control and as adjunctive therapies against COVID-19 infections.