Exploring and Expanding the Fatty-Acid-Binding Protein Superfamily in Fasciola Species.

The liver flukes Fasciola hepatica and F. gigantica infect livestock worldwide and threaten food security with climate change and problematic control measures spreading disease. Fascioliasis is also a foodborne disease with up to 17 million humans infected. In the absence of vaccines, treatment depends on triclabendazole (TCBZ), and overuse has led to widespread resistance, compromising future TCBZ control. Reductionist biology from many laboratories has predicted new therapeutic targets. To this end, the fatty-acid-binding protein (FABP) superfamily has proposed multifunctional roles, including functions intersecting vaccine and drug therapy, such as immune modulation and anthelmintic sequestration. Research is hindered by a lack of understanding of the full FABP superfamily complement. Although discovery studies predicted FABPs as promising vaccine candidates, it is unclear if uncharacterized FABPs are more relevant for vaccine formulations. We have coupled genome, transcriptome, and EST data mining with proteomics and phylogenetics to reveal a liver fluke FABP superfamily of seven clades: previously identified clades I-III and newly identified clades IV-VII. All new clade FABPs were analyzed using bioinformatics and cloned from both liver flukes. The extended FABP data set will provide new study tools to research the role of FABPs in parasite biology and as therapy targets.

An experimental study on triclabendazole resistance of Fasciola hepatica in sheep.

The efficacy of triclabendazole in sheep experimentally infected with Fasciola hepatica was studied. Two groups of 12 lambs were infected with a susceptible (S) or a resistant (R) strain of F. hepatica. Eight weeks after infection, six lambs of each group (ST and RT) were treated with triclabendazole (10mg/kg). The other lambs were used as untreated controls (SC and RC). The parameters studied were: GLDH, gamma-GT, ELISA measuring antibodies against recombinant cathepsin-L(1) and eggs per gram faeces (epg). The lambs were slaughtered 16 weeks after infection and the number of flukes counted. The GLDH, gamma-GT levels and the OD value of the ELISA decreased as a result of the treatment in group ST. Patent infections were observed in all animals of groups SC, RT and RC. In group ST, occasionally a few eggs were found in five lambs. The percentage of flukes was 31.3 in SC and 37.6 in RC. In the treated groups ST and RT, the percentage of flukes was 0.06 and 33.6, respectively. These results corresponded to efficacies of 99.8% in the susceptible and 10.8% in the resistant strain. Since the resistant strain was isolated from a mixed cattle and sheep farm, it confirms the presence of triclabendazole resistance in the Netherlands.

Use of bait containing triclabendazole to treat Fascioloides magna infections in free ranging white-tailed deer.

Triclabendazole-medicated corn bait was given to white-tailed deer (Odocoileus virginianus) on the Welder Wildlife Refuge, Sinton, Texas (USA), at a dose of 11 mg/kg body weight per deer per day for seven days, for control of Fascioloides magna. Medicated bait was offered for one week each during the winters of 1987, 1988, and 1989. Deer collected from treated areas, from baited control and from unbaited control areas were examined before the start of the study in 1987, and four weeks after the end of the baiting period in each of three years. Prior to the study, prevalence of fluke infection was 68%. After treatment with triclabendazole medicated corn, 13 (56%) of 23 deer collected were infected with flukes of which 15% had live parasites; this was evidence for therapeutic treatment. Of the deer collected in the baited and unbaited control areas, 63% and 80%, respectively, were infected only with live flukes. Prevalence of live flukes in deer was significantly (P < 0.05) lower in the treatment pasture than in the baited or unbaited control areas in each of the three years. Efficacy of the baiting system over the three years was 63% when comparing the treatment area and the baited control area.

Efficacy of two formulations of albendazole against liver flukes in cattle.

Albendazole (10 mg/kg of body weight) was administered as a drench suspension or as a feed additive to 24 cattle with naturally acquired infections of Fasciola hepatica and Fascioloides magna. Cattle were euthanatized 16 to 30 days after treatment, and the number of viable flukes was counted. Viable F hepatica and F magna were decreased by 91.4% and 70.6% for drench administration and by 82.9% and 71.9% for the feed additive treatment, respectively. There was no significant difference between the efficacy of the 2 formulations in decreasing viable fluke numbers, compared with untreated controls.

Efficacy of triclabendazole against natural infections of Fascioloides magna in wapiti.

Fourteen free-ranging adult wapiti (Cervus elaphus nelsoni) were captured in Banff National Park, Alberta (Canada) and held in captivity near Edmonton. A 24% suspension of triclabendazole at doses of 30 to 100 mg/kg body weight was drenched into the rumen of eight females and four males. Two male wapiti were used as untreated controls. Animals were killed and examined at 4 (n = 3), 6 (n = 4), or 8 (n = 4) wk after treatment. Efficacy was 90% against immature Fascioloides magna collected 4 wk after treatment and 98% against adult flukes collected 4, 6 or 8 wk after treatment. All 32 flukes recovered from control wapiti were active and apparently healthy. Treatment at 50 to 60 mg/kg is recommended against F. magna in wapiti. A protocol for treating infected wapiti is outlined.

Use of albendazole in feed to control Fascioloides magna infections in captive white-tailed deer (Odocoileus virginianus).

Thirty-six adult white-tailed deer (Odocoileus virginianus) naturally infected with Fascioloides magna were captured and randomly assigned to four groups. Each group was fed pelleted feed coated with albendazole for each of seven consecutive days to deliver the drug at a dose rate of approximately 0.0, 5.0, 8.5, or 16.5 mg/kg bodyweight/day. At 7 wk posttreatment, each animal was euthanized and necropsied. Effects of albendazole treatment included significant reduction (P less than 0.05) in parasite egg count per gram of feces and increase in serum albumin concentration (P less than 0.05). Smaller parasites or remains of dead parasites were seen at the end of migratory tracks in the treated groups. Efficacy of the drug was 82 to 84%.

Efficacy of triclabendazole against fascioloidiasis (Fascioloides magna) in naturally infected white-tailed deer (Odocoileus virginianus).

The efficacy of triclabendazole was evaluated in the treatment of naturally acquired Fascioloides magna infections in white-tailed deer (Odocoileus virginianus). Twenty white-tailed deer were captured on the Welder Wildlife Refuge (Sinton, San Patricio County, Texas, USA) and maintained in a 64 x 64 m deer enclosure. Ten deer were given a 5% suspension of triclabendazole orally at a dosage of 10 mg/kg body weight and 10 deer were given a placebo. Three wk later the deer were euthanized and examined for parasites. At necropsy 19 deer were infected. All specimens of F. magna from the tissues of the triclabendazole treated deer were dead or severely affected by the drug as indicated by changes in their size, color, movement and texture relative to those from control deer. The drug was considered 100% effective against this parasite. Adverse reactions of the deer to the drug were not observed.

Efficacy of triclabendazole against experimentally induced Fascioloides magna infections in sheep.

Efficacy of oral administration of 20 mg of triclabendazole/kg of body weight was evaluated against 12-week Fascioloides magna infections in 12 sheep, each inoculated orally with 250 viable metacercariae. From 6 sheep treated with triclabendazole, 1 immature F magna was recovered, whereas 116 F magna with a mean length of 19 +/- 6.5 mm were recovered from 6 untreated control sheep. Efficacy of triclabendazole was 99.14%. Signs of toxicosis or illness were not observed in the sheep.

Evaluation of clorsulon against immature Fascioloides magna in cattle and sheep.

Efficacy of clorsulon was evaluated against infection with immature Fascioloides magna in 24 cattle and 12 sheep. Infections were induced by oral administration of 600 metacercariae/host. In cattle, clorsulon at dosages of 7 and 21 mg/kg of body weight was 65 and 100% effective against 8-week-old flukes, and 20 and 74% effective against 16-week-old flukes, respectively. In sheep, clorsulon at a dosage of 21 mg/kg was 92% effective against 8-week-old flukes. Significantly (P less than 0.05) more F magna were recovered from untreated sheep than from untreated cattle.

Efficacy of clorsulon against Fascioloides magna infection in sheep.

In a study to evaluate the efficacy of clorsulon against Fascioloides magna infection in sheep, 12 ewes were inoculated orally with 100 metacercariae of F magna, and 6 were treated with clorsulon (15 mg/kg of body weight) 8 weeks after inoculation. The sheep were euthanatized 16 weeks after inoculation, flukes were recovered, and the liver and other tissues were subjectively scored for the severity of lesions (0 to 4+). The number of flukes recovered from the clorsulon-treated group (3.8 +/- 1.2 flukes) was significantly (P = 0.025) lower than the number of flukes recovered from the group of untreated controls (10.0 +/- 6.6 flukes). The severity of lesions was significantly (P = 0.004) reduced (45.9%) in the treated group (2.0 +/- 1.1), compared with that in the untreated controls (3.7 +/- 0.5). In the untreated group, 3 sheep died and 1 became moribund 14 to 16 weeks after inoculation. The data suggested that a single treatment with clorsulon at a dosage of 15 mg/kg 8 weeks after inoculation was not effective in preventing F magna infection in sheep, because the survival of only a few F magna is potentially fatal in sheep within 6 months after infection.

Efficacy of clorsulon and albendazole against Fascioloides magna in naturally infected white-tailed deer.

The efficacy of clorsulon and of albendazole against Fascioloides magna were evaluated in 36 naturally infected white-tailed deer (Odocoileus virginianus) in southern Texas. A single oral dose of clorsulon suspension (12 to 30 mg/kg of body weight; mean = 24 mg/kg) was given to each deer and killed 153 (92%) of 167 mature flukes and 4 (80%) of 5 immature flukes recovered at necropsy. A single oral dose of albendazole paste (17 to 46 mg/kg; mean = 26 mg/kg) was given to each deer and killed 148 (89%) of 167 mature flukes and 4 (67%) of 6 immature flukes recovered at necropsy. In 82 nontreated control deer, 271 live flukes were recovered; dead flukes were not recovered.

Efficacy of albendazole against Fascioloides magna in sheep.

Sheep experimentally infected with Fascioloides magna were used in a controlled study to determine the flukicide activity of different doses of albendazole (methyl [5(propylthio)-1H-benzimidazol-2-yl] carbamate). Sheep, about 4 months old, were inoculated with 100 metacercariae of F magna and treated with the various doses of albendazole 10 weeks later. At 6 weeks after treatment, the sheep were necropsied, flukes were recovered and measured, and the pathologic changes were recorded. The sheep were given different doses of albendazole (5, 7.5 [single dose or double dose], 10, and 15 mg/kg) and were compared with both nontreated inoculated and nontreated noninoculated controls. There were up to 70% fewer worms recovered in the group given 2 doses of 7.5 mg/kg than there were in the nontreated controls. There was also a significant reduction in flukes recovered in the groups given the 7.5, 10, and 15 mg/kg doses. Because a single F magna fluke has the potential to kill a sheep, it is imperative to consider the number of sheep with no flukes after treatment. According to that criterion, 50% of the sheep were protected at dose rates of 7.5 (single dose, double dose), 10, and 15 mg/kg of body weight.

A study on fasciolopsiasis in Bangladesh.

A study of infection with F. buski in children has been carried out in a rural area of Bangladesh. The rate of ova production was inversely related to the worm load. Subjects infected with F. buski had higher total leukocyte counts than the control subjects, but the two groups were not different with regard to haemoglobin level and other parameters of nutrition. These findings have been discussed. There was a high rate of infection (36.2%). Up to the age of 7 years, males and females were equally affected, but above this age the females predominated.

[The prevention and therapy of fascioloidiasis using bithionol sulfoxide]. / Prevence a terapie fascioloidózy skotu bithionolsulfoxidem.

The elimination of the sources of invasion, i. e. hay and forage coming from the infested biotopes, combined with the administration of bithionol sulphoxide, resulted in a reduction of the invasion of cattle by Fascioloides magna from 21.1 to 3.2% within two years. The Czechoslovak-produced bithionol sulphoxide, administered at a rate of 40 to 50 mg per kg body weight as medicated feed, showed 100% effectiveness. At doses higher than 30 mg per kg body weight, the protective period should be prolonged to three or four weeks.