Dose-response relationships and tegumental surface alterations in Opisthorchis viverrini following treatment with mefloquine in vivo and in vitro

The treatment and control of opisthorchiasis relies on a single drug, praziquantel; hence, there is a need to develop novel opisthorchicidal drugs. We investigated the in vitro and in vivo activity of the antimalarial mefloquine against Opisthorchis viverrini. Hamsters infected with O. viverrini for 2weeks (juvenile infections) and 4weeks (adult infections) were treated orally with single 200-400-mg/kg oral mefloquine. Worm burden reductions were assessed against untreated control hamsters. Worms were incubated in the presence of 10 and 100µg/ml mefloquine. Scanning electron microscopy was used to examine adult O. viverrini after recovery from hamsters and following in vitro incubation. A single oral dose of 300-mg/kg mefloquine resulted in worm burden reductions of 88.5% (juvenile infection) and 96.0% (adult infections), respectively. Incubation with 10 and 100µg/ml mefloquine resulted in rapid death of O. viverrini. Extensive tegumental disruption such as blebbing, sloughing, and furrowing was seen on worms incubated in vitro and on flukes recovered 48h posttreatment. In conclusion, we have documented promising opisthorchicidal activities in hamsters and in vitro with the tegument being an important drug target. Proof-of-concept studies with mefloquine could be considered in opisthorchiasis patient

Limitations of the land reform in South Africa : an assessment of two farms in the Eastern Cape

The government that was voted in, in 1994 initiated and implemented the Land Reform Programme that had three key elements, namely; Land restitution, redistribution and tenure reform. This study was undertaken to examine the limitations that resulted in some of the projects not to succeed. The study took a form of a case study of two farms that were redistributed in 1997 under the Land Redistribution Programme in the Blue Crane Route Municipal area in the Eastern Cape. The findings confirmed a variety of weaknesses that led to the collapse of these farms. Whilst acknowledging that there are some measures that are put in place to address those limitations the, study shows that there is still scope to do more. It is therefore one’s sincere wish that what transpired out of this study will make a positive contribution by providing some elements that can be used as a remedy in advancing the Land Reform Programme

Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16μg/ml and 0.05μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50=0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191mg/kg and 147mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrin

Opisthorchis viverrini: efficacy and tegumental alterations following administration of tribendimidine in vivo and in vitro

The tegumental changes in adult Opisthorchis viverrini induced by tribendimidine were analyzed by scanning electron microscopy (SEM). We exposed O. viverrini to tribendimidine at a concentration of 10μg/ml for 4h. In addition, hamsters were treated with a single 400mg/kg oral dose of tribendimidine and flukes were recovered from the bile ducts 24, 48, 72, and 96h post-treatment. SEM analysis of the flukes incubated in vitro showed only mild damage of the tegument. Twenty-four hours post-treatment of hamsters, extensive disruption such as sloughing, furrowing, or blebbing of the tegument was evident, which did not increase in severity 48-72h post-treatment. Ninety-six hours after tribendimidine administration, the majority of flukes had been expelled. A single 400mg/kg oral dose of tribendimidine administered to O. viverrini-infected hamsters yielded a worm burden reduction of 63.0%. In conclusion, our experiments confirm that tribendimidine possesses interesting trematocidal properties, which warrant additional investigations and provide further data for subsequent clinical trial

Diversity of human intestinal helminthiasis in Lao PDR

Food-borne trematodiasis is an emerging public health problem, including in Lao PDR. We investigated the diversity of intestinal helminthes and polyparasitism in patients with hepatobiliary or intestinal symptoms in hospital and community-based surveys. Stool samples from 232 individuals aged ≥15 years were examined by the Kato-Katz method (three samples) and a formalin ethyl-acetate concentration technique (one sample). Opisthorchis viverrini and minute intestinal flukes (MIF) were common, with prevalences of 86.2% and 62.9%, respectively. Hookworm was the predominant soil-transmitted helminth (65.9%). The prevalences of Taenia spp., Strongyloides stercoralis and Trichuris trichiura were 22.8%, 10.3% and 8.6%, respectively. Additionally, 97 individuals were purged; O. viverrini and Haplorchis taichui were found in 95 and 76 participants, respectively. Other trematodes included Phaneropsolus bonnei (22.7%), Prosthodendrium molenkampi (14.4%), Haplorchis pumilio (5.2%), Haplorchis yokogawai (3.1%) and Echinochasmus japonicus (3.1%). Co-infection with O. viverrini and MIFs was rampant (81.4%). Polytrematode infection is highly prevalent in Lao PDR and hence requires urgent attentio

Proteomic profile of Bithynia siamensis goniomphalos snails upon infection with the carcinogenic liver fluke Opisthorchis viverrini.

UNLABELLED: The snail Bithynia siamensis goniomphalos acts as the first intermediate host for the human liver fluke Opisthorchis viverrini, the major cause of cholangiocarcinoma (CCA) in Northeast Thailand. The undisputed link between CCA and O. viverrini infection has precipitated efforts to understand the molecular basis of host-parasite interactions with a view to ultimately developing new control strategies to combat this carcinogenic infection. To date most effort has focused on the interactions between the parasite and its human host, and little is known about the molecular relationships between the liver fluke and its snail intermediate host. In the present study we analyse the protein expression changes in different tissues of B. siamensis goniomphalos induced by infection with larval O. viverrini using iTRAQ labelling technology. We show that O. viverrini infection downregulates the expression of oxidoreductases and catalytic enzymes, while stress-related and motor proteins are upregulated. The present work could serve as a basis for future studies on the proteins implicated in the susceptibility/resistance of B. siamensis goniomphalos to O. viverrini, as well as studies on other pulmonate snail intermediate hosts of various parasitic flukes that infect humans. BIOLOGICAL SIGNIFICANCE: Despite the importance and high prevalence of opisthorchiasis in some regions of Southeast Asia and the direct relationship between infection by Opisthorchis viverrini and the incidence of cholangiocarcinoma, little is known of the modifications induced by this parasite in its snail intermediate hosts. This time-course study provides the first in-depth quantitative proteomic analysis of experimentally infected Bithynia siamensis goniomphalos. We show how motor and stress-related proteins are upregulated in infected snails, while O. viverrini infection downregulates the expression of oxidoreductases and catalytic enzymes. This work serves as a basis for the development of new strategies, focused on the invertebrate intermediate hosts, to control parasite transmission.This work was supported by project (613669) and program (1037304) grants from the National Health and Medical Research Council of Australia (NHMRC) and a Tropical Medicine Research Collaboration (TMRC) grant from the National Institute of Allergy and Infectious Disease, National Institutes of Health, USA (P50AI098639). AL is supported by a NHMRC principal research fellowship. Funding from Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No PHD/0027/2551) to SP and ST is also gratefully acknowledged.This is the accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S1874391914004424

Evaluation of the Cariogram for root caries prediction

<p>The relative expression of plasma proteins at 24, 48 and 96 hpi of infected snails were compared against the control group (uninfected snails). Proteins were grouped into 7 different categories based on GO annotation and clustering was performed using Euclidean distances based on the expression patterns. Color intensity reflects the corresponding log₂ fold change and significant up-regulation shown in red, significant down-regulation is shown in blue, and no statistically significant change in abundance is shown in gray.</p

Prevalence of the Intestinal Flukes Haplorchis taichui and H. yokogawai in a Mountainous Area of Phongsaly Province, Lao PDR

Phongsaly Province, located in the northernmost area of Lao PDR, was previously suggested to be endemic for the liver fluke Opisthorchis viverrini infection. To confirm, or rule out, this suggestion, the Phonxay village in the Khoua District, Phongsaly Province, was selected for a survey. Ten volunteers (8 men and 2 women aged 31-57 years) who consumed raw freshwater fish and had gastrointestinal troubles were treated with a single dose of praziquantel (40 mg/kg) and pyrantel pamoate (10 mg/kg) and purged with magnesium sulfate to recover any worm parasites. Eight of the 10 volunteers expelled 1 or more species of trematodes, nematodes, or cestodes (worm positive rate; 80%). The worms were morphologically identified as H. taichui (861 worms from 8 people), H. yokogawai (59 from 6 people), Phaneropsolus bonnei (1 from 1 person), Trichostrongylus sp. (2 from 2 people), Ascaris lumbricoides (2 from 1 person), Enterobius vermicularis (11 from 3 people), and Taenia saginata (1 strobila with scolex from 1 person). The results indicate that the mountainous area of Phongsaly Province, Lao PDR, is not endemic for the liver fluke but endemic for intestinal flukes, in particular, Haplorchis taichui and H. yokogawai

Prevalence of zoonotic trematodes in fish from a Vietnamese fish-farming community

The prevalence of fish-borne zoonotic trematode (FZT) metacercariae was investigated in fish farmed by rural households in Nghe An Province, located in northern Vietnam. In total, 716 fish, including tilapia (Oreochromis niloticus) and 6 carp species, i.e., grass carp (Ctenopharyngodon idellus), bighead carp (Aristichthys nobilis), mrigal (Cirrhinus mrigala), common carp (Cyprinus carpio), silver carp (Hypophthalmychthys molitrix), and roha (Labeo rohita), collected from 53 fish farms were examined. The overall prevalence of FZT metacercariae was 44.6%, ranging from 12.5% to 61.0% in fish species collected from grow-out ponds, which are the production system for growing fish from fingerling size to market size. The overall prevalence was 43.6% in fingerlings cultured in nurseries, ranging from 7.4% to 62.8% for different fish species. The FZT species recovered were heterophyids and echinostomatids and included Haplorchis pumilio, H. taichui, H. yokogawai, Centrocestus formosanus, Stellantchasmus falcatus, and Echinochasmus japonicus, all of which are intestinal flukes in humans, other mammals, and birds. This is the first report of H. yokogawai and E. japonicus in fish in Vietnam, and the first record for S. falcatus in northern Vietnam. Although a previous cross-sectional survey of the people living in these fish farm households revealed a very low prevalence of FZTs (&lt;1%), our results demonstrate that intestinal flukes are common in farmed fish in this area, suggesting that reservoir hosts such as dogs, cats, and pigs are more important in sustaining the life cycles of these flukes in fish farms than human hosts. This has implications for the effectiveness of control programs focused mainly on treatment of humans

Emerging Foodborne Trematodiasis

Foodborne trematodiasis is emerging because of increased aquaculture