Anthelmintic efficacy of Achillea millifolium against gastrointestinal nematodes of sheep: in vitro and in vivo studies

Achillea millifolium Linn., commonly called 'Pehl-ghasa', is used by farmers in traditional animal health care as a vermifuge. The objective of this study was to evaluate the anthelmintic efficacy of crude aqueous extracts and crude ethanolic extracts of entire A. millifolium against the gastrointestinal nematodes of sheep. The worm motility inhibition assay was used for in vitro studies and faecal egg count reduction assay was used for in vivo studies. In vitro studies revealed significant anthelmintic effects of aqueous extracts and ethanolic extracts on live Haemonchus contortus worms (P < 0.05) as evident from their paralysis and/or death at 8 h post exposure. Aqueous extracts of A. millifolium resulted in a mean worm motility inhibition of 94.44%, while ethanolic extracts resulted in mean worm motility inhibition of 88.88%. The mean mortality index of aqueous extracts was 0.95 while for ethanolic extracts it was 0.9. The lethal concentration 50 was 0.05 mg ml(-1) for aqueous extracts and 0.11 mg ml(-1) for ethanolic extracts. The in vivo anthelmintic activity of aqueous and ethanolic extracts of A. millifolium demonstrated a maximum (88.40%) nematode egg count reduction in sheep treated with aqueous extracts at 2 g kg(-1) body weight on day 15 after treatment. Ethanolic extracts resulted in a maximum of 76.53% reduction in faecal egg counts on day 15 after treatment with 2 g kg(-1) body weight. Thus, the aqueous extracts exhibited greater anthelmintic activity under both in vitro and in vivo conditions, and could be due to the presence of water-soluble active principle/s in A. millifolium. It is concluded that the entire plant of A. millifolium possesses significant anthelmintic activity and could be a potential alternative for treating cases of helminth infections in ruminants.     

Cellular elements in the resistance to candida infection in mice. I. Contribution of T lymphocytes and phagocytes at various stages of infection.

Live organisms (cfu) of Candida albicans per organ were counted 1 hr and 1 to 20 days after an intravenous inoculation into various groups of mice which had distinct levels of immunologic or non-immunologic defense mechanisms. a) The number of cfu in the liver decreased progressively in normal mice, but those in the kidney maintained a constant level during the observation period. b) The number of cfu in the liver decreased progressively also in nude mice. In their kidneys, however, cfu increased progressively at a late stage of infection. c) In lethally irradiated AKR of nude mice in which phagocyte functions were severely depressed, the number of cfu increased progressively in both liver and kidney from the initial stage of infection. d) In immunized AKR mice, growth of C. albicans was suppressed at late stages of infection. Such protective immunity could be transferred partly with immune lymphoid cells but not with hyperimmune serum in the experimental system employed. In protection against candida infection, non-immune phagocytosis and T cell-mediated immunity appear to be required at the early and late stages of infection, respectively.     

The effect of ruminoreticulum bypass in yarded lambs on the efficacy of oxfendazole against resistant Trichostrongylus spp. helminths

An observational study was performed to investigate the effects of yarding and ruminoreticulum bypass on the efficacy of oxfendazole against resistant Trichostrongylus spp. helminths. Ruminoreticulum bypass was observed in 9-month old Perendale lambs using video-taped fluoroscopy and the efficacy of oxfendazole was estimated using the faecal egg count reduction test. Yarding and withholding feed for 24 h before drenching with oxfendazole significantly enhanced the faecal egg count reduction for resistant Trichostrongylus spp. parasites (p < 0.05), but ruminoreticulum bypass of the drench in the yarded animals had no negative effect on anthelmintic efficacy (p > 0.05). The effect of ruminoreticulum bypass on the efficacy of oxfendazole may depend on the resistant parasite species present. The positive effects of yarding sheep for 24 h before drenching, on the efficacy of oxfendazole against resistant Trichostrongylus spp., probably outweigh any negative effects of ruminoreticulum bypass. However further studies are required, with different resistant parasite genera present, before firm recommendations can be made.     

Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes

Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed a numerical method that allows predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the method to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approach is verified against state-of-the-art stochastic simulation. While the method is more accurate than stochastic simulation, it is superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The method’s computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.     

A comparison of the prophylactic and therapeutic effects of poly I:C and endotoxin in mice infected with Mengo virus.

We have compared the protective effect in AKR mice of poly I:C and bacterial endotoxins against lethal doses of Mengo virus. Administered intravenously or intraperitoneally, both interferon inducers protected mice to about the same extent from virus challenges of 2-3 LD50's. Endotoxin, however, was unable to protect the mice effectively against higher challenge doses of virus. Evidence is presented that the level of protection afforded by both inducers is related to the level of circulating interferon produced. We have also shown that a single intravenous dose of poly I:C results in the appearance of two distinct bursts of interferon activity, with maxima at about 2 h and 9 h post injection. Endotoxin, on the other hand, produced only one peak of activity, at 2 h post injection.     

The kinetic disposition of pyrantel citrate and pamoate and their efficacy against pyrantel-resistant Oesophagostomum dentatum in pigs

The pharmacokinetic disposition of pyrantel after intravenous (i.v.) and oral (p.o.) administration as the citrate and p.o. administration as the pamoate salt was determined in pigs. Following i.v. administration pyrantel was quickly cleared from the bloodstream, exhibiting a terminal halflife of 1.75 ± 0.19h and a residence time (MRT) of 2.54 ± 0.27h. After p.o. administration as the citrate salt, the absorption time (MAT) of pyrantel was 2.38 ± 0.25h and although significant quantities of pyrantel were absorbed (mean bioavailability of 41%) the rapid clearance resulted in a MRT of only 4.92 ± 0.36h. By comparison, the significantly extended MAT of the less soluble pamoate salt resulted in reduced circulating concentrations and a significantly lower mean bioavailability of 16%. The poor efficacy of pyrantel citrate against nematodes inhabiting the large intestine of pigs is therefore suggested to result from insufficient quantities of drug passaging to the site of infection. When tested against pyrantel-resistant adult Oesophagostomum dentatum the efficacy of pyrantel citrate was only 23%, whereas the efficacy of the lesser absorbed pyrantel pamoate was 75%. These results indicate that for maximum activity pyrantel should be administered to pigs as the pamoate salt.     

Evaluation of the effectiveness of fluralaner against adult stages of Rhodnius prolixus in dogs

Triatomines are vectors of American Trypanosomiasis also known as Chagas´ disease where several reservoirs including dogs are involved in the transmission cycle of the causal agent (Trypanosoma cruzi). Considering that the prevalence of American trypanosomiasis in dogs is higher than in humans and that dogs in addition are susceptible of this disease, and are involved in peridomestic transmission to humans, the search for new alternatives for vector control of the triatomines responsible for transmission in dogs is required. Over the 20 weeks the study lasted, 600 individual female, adult of Rhodnius prolixus were offered to the 15 dogs treated with a single oral dose of Fluralaner (Bravecto®, MSD). Feeding pattern of triatomines was not affected by the treatment during the whole study. The fluralaner-induced mortality of R. prolixus had a significant effect until week 12 at which time 100% mortality was observed. Mortality decreased to 67.5% at week 16 to practically nil 0.8% on week 20. Fluralaner achieved 100% mortality of triatomines between 12- and 48-h post-feeding. It was demonstrated that a single oral dose of fluralaner in dogs is highly effective in producing mortality in adult R. prolixus for the time guaranteed by the manufacturer for other blood-sucking insects, with a considerable effective residual effect for up to 16 weeks. Due to this high efficacy, fluralaner could be considered in strategies to control the transmission vectors of Chagas disease in dogs and in turn decrease the peri-domestic transmission cycle, particularly in hyperendemic areas.     

Clinical efficacy of antiparasite treatments against intestinal helminths and haematic protozoa in Gallotia caesaris (lizards)

Intestinal helminths and blood protozoa are common parasites of lizards. In captivity they can be a serious problem, but no information on treatments is available. In this study, several antiparasitic drugs were studied in Gallotia caesaris (Lacertida) from La Gomera, the Canary Islands, Spain. A lack of efficacy of chloroquine, and a decrease in haemogregarine (Apicomplexa) infection by atovaquone-proguanil was demonstrated. Furthermore, a positive effect of fenbendazole against intestinal nematode infection was observed. In the Canary Islands, Gallotia bravoana and Gallotia simonyi (Lacertida) are included in a captive breading recovery plan. The present results are useful in order to keep these animals in good condition and to control their parasites. Moreover, these results are important for reptiles kept as pets, due to the previous lack of knowledge of parasite management.     

Pharmacokinetics and pharmacodynamics of the reverse transcriptase inhibitor tenofovir and prophylactic efficacy against HIV-1 infection

Antiviral pre-exposure prophylaxis (PrEP) through daily drug administration can protect healthy individuals from HIV-1 infection. While PrEP was recently approved by the FDA, the potential long-term consequences of PrEP implementation remain entirely unclear. The aim of this study is to predict the efficacy of different prophylactic strategies with the pro-drug tenofovir-disoproxil-fumarate (TDF) and to assess the sensitivity towards timing- and mode of TDF administration (daily- vs. single dose), adherence and the number of transmitted viruses. We developed a pharmacokinetic model for TDF and its active anabolite tenofovir-diphosphate (TFV-DP) and validated it with data from 4 different trials, including 4 distinct dosing regimes. Pharmacokinetics were coupled to an HIV model and viral decay following TDF mono-therapy was predicted, consistent with available data. Subsequently, a stochastic approach was used to estimate the % infections prevented by (i) daily TDF-based PrEP, (ii) one week TDF started either shortly before, or -after viral exposure and (iii) a single dose oral TDF before viral challenge (sd-PrEP). Analytical solutions were derived to assess the relation between intracellular TFV-DP concentrations and prophylactic efficacy. The predicted efficacy of TDF was limited by a slow accumulation of active compound (TFV-DP) and variable TFV-DP half-life and decreased with increasing numbers of transmitted viruses. Once daily TDF-based PrEP yielded [Formula: see text]80% protection, if at least 40% of pills were taken. Sd-PrEP with 300 mg or 600 mg TDF could prevent [Formula: see text]50% infections, when given at least before virus exposure. The efficacy dropped to [Formula: see text]10%, when given 1 h before 24 h exposure. Efficacy could not be increased with increasing dosage or prolonged administration. Post-exposure prophylaxis poorly prevented infection. The use of drugs that accumulate more rapidly, or local application of tenofovir gel may overcome the need for drug administration long before virus exposure.     

Therapeutic efficacy of Hypericum perforatum L. extract for mice infected with an influenza A virus

Hypericum perforatum L., a plant used in Chinese herbal medicine, has been proven effective against many viral diseases. In the present study, the therapeutic efficacy of an extract of H.?perforatum (HPE) against influenza A virus (IAV) was investigated in mice. Whether HPE would be a promising agent for influenza treatment was evaluated by measuring the protection rate, mean survival days, lung index, and viral titer, as well as the secretion of IL-6, interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ) in lung tissue and serum on days 3 and 5 post-infection. The results showed that HPE could reduce the lung index and viral titer of mice infected with IAV, decrease mortality, and prolong the mean survival time. HPE decreased the concentration of IL-6 and TNF-α in lung tissue and serum on day 5 post-infection. In contrast, HPE enhanced the lung and serum levels of IL-10 and IFN-γ on the days 3 and 5 post-infection. Our study indicates that HPE has significant therapeutic efficacy for mice infected with IAV. The possible reasons for these results were concluded to be pertaining to up-regulating the expression of IL-10 and IFN-γ, and down-regulating the secretion of IL-6 and TNF-α in lung and serum.     

Therapeutic efficacy of various formulations of cycloferon in the treatment of infectious mononucleosis in children

One hundred twenty six children at the age of 4 to 7 years with infectious mononucleosis were observed. The subjects under the complex therapy were treated with cycloferon suppositoria (1st group), intramuscular cycloferon (2nd group) or placebo (3rd group). The results demonstrated similar therapeutic efficacy of the parenteral cycloferon and rectal suppositoria (a novel cycloferon formulation).