ABSTRACT
We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.
Subject(s)
Trimeresurus , Animals , Phylogeny , Trimeresurus/metabolism , Snakes/metabolism , Snake Venoms , Phospholipases A2/analysis , Proteome/metabolismABSTRACT
Babesiosis is an emerging zoonotic disease that is typically caused by Babesia microti infection. Clinical treatment of B. microti infection is challenging; hence, it is crucial to find new effective drugs. The current laboratory screening methods for anti-B. microti drugs are not optimized. We conducted drug-suppressive and drug-therapeutic tests to investigate whether use of an immunosuppressant and the target gene-based qPCR are helpful to reduce the number of animals affected and to improve parasite detection in an immunocompetent mouse model. These results were verified by subpassage test. In the drug-suppressive test, no B. microti were observed after immunosuppressant administration or in subpassage mice in the 100 mg/kg robenidine hydrochloride (ROBH) group. The opposite results were observed in the control, 50 mg/kg ROBH, atovaquone (ATO) + azithromycin (AZM), and proguanil hydrochloride (PGH) groups. Significant differences were observed in the EIR and target gene relative values (both P < 0.001) between the control group and any ROBH groups. In the drug-therapeutic test, recrudescence occurred in the 50 mg/kg ROBH, ATO+AZM, and control groups. This was not observed in the 100 mg/kg ROBH group after immunosuppressant administration. Similar findings were observed in the subpassage test. This suggests that a 4-day anti-B. microti drug-suppressive test can be used in preliminary drug screening. Potentially effective drugs can be verified by immunosuppressant test in subsequent drug-therapeutic tests. Thus, a laboratory evaluation method of anti-B. microti drug efficacy was optimized, which is highly accurate and requires a short drug screening time.
Subject(s)
Babesia microti , Babesiosis , Pharmaceutical Preparations , Animals , Babesiosis/drug therapy , Disease Models, Animal , Drug Evaluation, Preclinical , MiceABSTRACT
Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.
Subject(s)
Academies and Institutes , Endemic Diseases/prevention & control , Government Programs , National Health Programs , Schistosomiasis japonica , Animals , Cattle , China/epidemiology , Disease Eradication , Drug Development , Humans , Molluscacides , Schistosomiasis japonica/drug therapy , Schistosomiasis japonica/epidemiology , Schistosomiasis japonica/transmission , VaccinationABSTRACT
As a zoonotic parasitosis caused by the parasitism of Echinococcus larvae, echinococcosis imposes serious disease and economic burdens on human beings and society, and is thus a global public health issue. Its complex life history, wide distribution, the combined influence of various epidemic factors, coupled with the unique natural environment, customs, and religious beliefs in endemic areas, pose a huge challenge to the national echinococcosis control programme in China. Accurate early detection and confirmation of diagnosis of echinococcosis, the use of effective drugs, real-time surveillance of the infection status of populations and various hosts, controlling the source of infection, and blocking the route of transmission are of enormous significance for control. In this paper, the work by NIPD-CTDR on the prevention and control of echinococcosis in China is reviewed, with a view to providing reference for the further promotion of the national echinococcosis control programme.
Subject(s)
Academies and Institutes , Biomedical Research , Echinococcosis , Government Programs , National Health Programs , Zoonoses , Animals , China/epidemiology , Echinococcosis/diagnosis , Echinococcosis/epidemiology , Echinococcosis/prevention & control , Environment , Humans , Prevalence , Public Health , Zoonoses/diagnosis , Zoonoses/epidemiology , Zoonoses/prevention & controlABSTRACT
This study was conducted to investigate the efficacy of a new formulation of MBZ oily suspension (MBZ-OS) in experimentally Echinococcus multilocularis-infected mice. MBZ-OS was prepared and administered to mice infected with E. multilocularis at 12.5 and 25 mg/kg for 14 consecutive days. Then, the cysts were collected, weighed and histologically examined. The results showed that the reduction rate of cyst weight induced by MBZ-OS at two doses was 95.23% and 92.67%, which was significantly higher than that of MBZ-1% tragacanth (positive control) at corresponding concentrations (87.41% and 69.47%), indicating that the treatment of alveolar echinococcosis at lower doses could be achieved by the use of MBZ-OS. This finding shows that MBZ-OS is also a promising formulation for alveolar echinococcosis as well as cystic echinococcosis and deserves to be investigated in clinical applications against echinococcosis.
Subject(s)
Antinematodal Agents/therapeutic use , Echinococcosis/drug therapy , Echinococcus multilocularis/drug effects , Mebendazole/therapeutic use , Animals , Antinematodal Agents/administration & dosage , Antinematodal Agents/chemistry , Dose-Response Relationship, Drug , Drug Compounding , Mebendazole/administration & dosage , Mebendazole/chemistry , MiceABSTRACT
BACKGROUND: Echinococcosis is a serious, zoonotic, parasitic disease with worldwide distribution. According to a epidemiological survey in 2012 in China, there are 20,000 infected patients and more than 50 million people at the risk. As the dog is the main, definitive host, the Government of China encourages monthly praziquantel treatment of every dog. However, this is difficult to achieve in geographically challenging areas, such as the Tibetan plateau, where there are also many dogs without owners. To overcome these problems, we investigated the transmission blocking capacity of a slow-release formulation of praziquantel administered by subcutaneous injection. METHODS: The impact of a slow-release preparation of two pharmacokinetically stereoselective praziquantel enantiomers, i.e., R-(-)-praziquantel (R-PZQ) and S-(+)-praziquantel (S-PZQ) absorbed into a biodegradable polymer was studied in beagle dogs (N = 6). The preparation was given by subcutaneous injection using a single dose of 100 mg/kg. Chiral-selective, high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) were applied to measure the praziquantel enantiomers in the plasma of the dogs. The lower limit for estimating plasma concentrations accurately for R-PZQ was 4 ng/ml and for S-PZQ 20 ng/ml. The pharmacokinetic parameters were calculated by a noncompartmental analysis model using Drug Analyze System (DAS) software 2.0. The SPSS 19.0 software was used for statistical analysis, and the statistical comparison between enantiomers was assessed using the two-tailed t-test. RESULTS: Two hours after administration, peak concentrations of R-PZQ and S-PZQ: 321 ± 26 and 719 ± 263 ng/ml, respectively, were achieved. After 180 days, the average plasma concentration of R-PZQ in the six dogs had decreased to 13 ng/ml. The average concentration value of S-PZQ was higher than that of R-PZQ in the first 90-day period but fell afterwards and could not be accurately estimated when dropping below 20 ng/ml (the lower methodological limit for this enantiomer). Taking all the dogs into account, the average maximum concentration (Cmax) of S-PZQ in plasma over the first 3 months was higher than that of R-PZQ by 114.0% (P < 0.05), while the average mean retention time (MRT) of R-PZQ in plasma was higher than that of S-PZQ by 96.3% (P < 0.05). CONCLUSIONS: Praziquantel given as an in situ slow-release formulation by subcutaneous injection resulted in concentrations of the active principle in beagle dogs, which should be capable of resisting new Echinococcus infections for at least 6 months. The new formulation of praziquantel represents a potential, alternative way of presenting medication against tapeworm infections in dogs.
Subject(s)
Anticestodal Agents/therapeutic use , Dog Diseases/drug therapy , Echinococcosis/veterinary , Praziquantel/therapeutic use , Animals , Anticestodal Agents/administration & dosage , Anticestodal Agents/chemistry , China , Delayed-Action Preparations/therapeutic use , Dogs , Echinococcosis/drug therapy , Praziquantel/administration & dosage , Praziquantel/chemistryABSTRACT
Eucalyptus is a fast-growing plant with rich activities. The roots, stems and leaves of Eucalyptus all have medicinal values. Extracts from different parts of various kinds of Eucalyptus show antiparasitic effects, not only the repelling and killing effects on ectoparasites such as ticks and mites, but also the antiparasitic activities against endoparasites such as helminth and protozoa. This paper reviews the effects of Eucalyptus extracts and their chemical componets on protozoa including flagellates, sporozoan and ciliates.
Subject(s)
Eucalyptus , Antiprotozoal Agents , Oils, Volatile , Plant Extracts , Plant LeavesABSTRACT
Objective: To evaluate the effects of a aminoalcohol-carbazole compound BTB3 against Echinococcus granulosus in vitro. Methods: The protoscoleces from sheep and germinal cells from secondary-infected mice were cultured and treated with 1, 2, 4, 8, 10 and 20 µg/ml BTB3 for 3 days. The viability of protoscoleces and cells was determined by the methylene blue exclusion method and CCK-8 assay. Meanwhile, the effect of 10 µg/ml BTB3 on germinal cells was assessed by scanning electron microscopyï¼SEMï¼. The metacestodes were treated with 1, 5 and 10 µg/ml BTB3 for two weeks, and the integrity of the metacestodes was evaluated by SEM. Results: The 10 µg/ml and 20 µg/ml BTB3 caused a death rate of ï¼100.0±0.0ï¼% and ï¼85.2±7.2ï¼% respectively for protoscoleces. As the concentration decreased, the death rate remained below 10%. Moreover, the activity inhibition rate on germinal cells was about 100% for 8, 10 and 20 µg/ml BTB3, and was reduced with the decrease of BTB3 concentration other than the afore-mentioned three. SEM revealed detachment, shrinkage, and cavitation of germinal cells after BTB3 treatment. And the metacestodes all showed the loss of turgidity after BTB3 treatment for 14 days, which indicated cell detachment and uneven distribution of cells in internal cyst of metacestodes. Conclusion: BTB3 has strong effects against Echinococcu granulosus protoscoleces, germinal cells and metacestodes in vitro, which make it a potential drug against hydatid diseases.
Subject(s)
Echinococcosis , Echinococcus granulosus , Alcohols , Animals , Carbazoles , Mice , Microscopy, Electron, Scanning , SheepABSTRACT
Objective: To investigate the effect of Eucalyptus robusta leaves extract against Echinococcus granulosus protoscolices in vitro. Methods: Mature leaves of Eucalyptus robusta were collected on 24th day in each month from January to December 2012, and air-dried in the room. Ultrasonic extraction of the leaves was done with 4 solvents with different polarity, petroleum ether, dichloromethane, ethyl acetate and anhydrous ethanol. Protoscolices were incubated with the extract at various concentrations for 72 h, and mortality and median lethal doseï¼LC50ï¼ was calculated. Results: The extracts were different in characteristics and yield. The petroleum ether extract was in the form of black oil, while dichloromethane, ethyl acetate and anhydrous ethanol extracts were in the form of dark green, pink and white powder respectively. The average yields by petroleum ether, dichloromethane, ethyl acetate, and anhydrous ethanol were 4.4%, 2.1%, 2.3% and 2.3%, respectively. The extract yield was highest for petroleum ether, with a yield of 5.4% in May. The mortality of protoscoleces in all monthly groups of petroleum ether and dichloromethane extracts reached 100% with the concentration of 100 µg/ml and the same mortality reached in most groups of petroleum ether extracts with the concentration of 50 µg/ml. The effects of dichloromethane extracts were less than petroleum ether extracts, but significantly stronger than those of ethyl acetate and ehanol extracts. Further studies conducted on petroleum ether and dichloromethane extracts showed, the lethal effect of petroleum ether extract ranked in month of preparation from strong to weak as June>March>November>April>February>May>October>August>December>July>January>September. In June, the LC50 was 2.577 µg/ml and 95% confidence interval was 0.85-6.22 µg/ml. The lethal effect of dichlorom ethane extract ranked in month of preparation from strong to weak as November>May>October>April>July>December>June>September>August>February>March>January. In November, the LC50 was 21.85 µg/ml, and 95% confidence interval was 12.38-36.28 µg/ml. Conclusion: The Eucalyptus robusta leaves contain potential compounds against Echinococcus granulosus. Further experiments of isolation, analysis and identification are needed.
Subject(s)
Echinococcus granulosus , Eucalyptus , Alkanes , Animals , Lethal Dose 50 , Plant Extracts , Plant LeavesABSTRACT
INTRODUCTION: Different results have been achieved in the evaluation of antiparasitic drug activity in Mongolian jirds, hamsters, and BALB/c mice infected with Babesia microti. The aims of the present study were to find a preferable method for drug screening and to re-evaluate the activity of several drugs against B. microti. METHODOLOGY: The activity of 19 drugs on B. microti-infected BALB/c mice was evaluated. The study was built on Peters' four-day suppressive test, and the pathogenicity of the blood from the treated mice was also used as indicator. RESULTS: The results showed that 15 of the 19 drugs had little or no in vivo effect against B. microti. The inhibitory rates of atovaquone and azithromycin were high at all doses, but the microscopy-negative blood of recovered mice was still infectious. Similar to robenidine hydrochloride at 25 and 50 mg/kg, primaquine at 100 mg/kg had a 100% inhibitory rate. Robenidine hydrochloride achieved a 100% inhibitory rate at 100 mg/kg, and the blood of recovered mice did not result in parasitemia in subpassage experiments. Parasite-negative blood from mice treated with antimalarial drugs (clinically used for babesiosis) still caused parasitemia in subpassage experiments. This suggests that these drugs cannot eradicate the parasites. CONCLUSIONS: Peters' four-day suppressive test and the pathogenicity of the blood from the treated mice are suitable methods for preliminary investigating possible drugs against B. microti. Considering that robenidine hydrochloride achieved the best activity against B. microti in BALB/c mice in our study, further studies are needed.
Subject(s)
Antiprotozoal Agents/administration & dosage , Babesia microti/drug effects , Babesiosis/parasitology , Blood/parasitology , Animals , Disease Models, Animal , Female , Mice, Inbred BALB C , Parasitic Sensitivity Tests/methods , Time Factors , Treatment OutcomeABSTRACT
The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 µg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 µg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 µg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0.7 versus 10.7 ± 2.7 µg/mL) lower than that in the corresponding non-infected mice, but its level was above the determined in vitro LC95 (95 % lethal concentration) value of 6.12 µg/mL. Meanwhile, longer T 1/2 value of 159.2 ± 129.3 h in infected mice led to significant increase in AUC0-∞ value (1969.3 ± 1057.7 vs 486.4 ± 53.0 µg/mL·h), relative to corresponding non-infected mice. In addition, the mean residence time (MRT0-∞) in infected mice was also significantly longer than that in non-infected mice. All these results may beneficial for the treatment. According to the results, we suggest that higher ratios of mefloquine concentration in erythrocytes to plasma may offer a way to transport mefloquine to the worm gut through ingestion of erythrocytes by the worms, where the gut is the site for displaying the effect by mefloquine.
Subject(s)
Erythrocytes/chemistry , Mefloquine/administration & dosage , Schistosoma japonicum/drug effects , Schistosomiasis japonica/parasitology , Administration, Oral , Animals , Erythrocytes/metabolism , Humans , Mefloquine/analysis , Mefloquine/pharmacokinetics , Mice , Schistosomiasis japonica/drug therapy , Schistosomiasis japonica/metabolismABSTRACT
OBJECTIVE: To study the metabolism of niclosamide in plasma, and the protective effect of its oral administration on Schistosoma japonicum cercarial invasion in mice. METHODS: Twenty-four female Kunming mice were randomly divided into 8 groups, each with 3 mice. Each mouse was treated orally with 120 mg niclosamide per kilogram of body weight (120 mg/kg). The plasma samples were collected at 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after treatment by retro-orbital blood sampling. The blood drug concentration was determined by HPLC. The pharmacokinetics parameters were calculated such as peak concentration (Cmax), peak time (Tmax), mean residence time (MRT), and elimination half life (T½). Thirty Kunming mice were randomly divided into 6 groups. Among them, 5 groups were treated orally with 40, 80, 120, 160, and 200 mg/kg niclosamide, respectively. The remaining untreated group served as control. One hour post-treatment, each mouse was infected with 40 ± 2 Schistosoma japonicum cercariae. Another 35 mice treated with 200 mg/kg niclosamide were randomly divided into 7 groups. Mice in each group were infected with 40 ± 2 S. japonicum cercariae on 0.25, 1, 4, 8, 12, and 24 h after treatment, named as group A, B, C, D, E, and F. Five untreated mice served as control (group G). All mice were sacrificed 35 days post-infection. Mean worm burden and worm reduction were calculated. RESULTS: At a dose of 120 mg/kg niclosamide, the blood drug concentration was (0.40 ± 0.28) µg/ml at 0.25 h post-treatment, reached a peak of (0.91 ± 0.34) µg/ml at 1 h, and decreased to (0.49 ± 0.38) µg/ml at 2 h, and got close to 0 at 16 h. The mean residence time (MRT) in mice was (6.78 ± 1.47) h, and the elimination half time was (6.80 ± 7.05) h. No significant difference was found in worm burden between different dose groups and control group (P > 0.05). The mean worm burden in group A was significantly lower than that of the control (P < 0.05) with a mean worm reduction of 79.1%. And there was no significant difference in worm burden between other groups and the control (P > 0.05). CONCLUSIONS: The blood drug concentration increases rapidly by gavage administration of 120 mg/kg niclosamide, reaching to the maximum concentration at 1 h post-treatment. It shows a certain potective effect of oral administration of 200 mg/kg niclosamide on Schistosoma japonicum cercarial invasion at 0.25 h after treatment.
Subject(s)
Cercaria , Schistosoma japonicum , Schistosomiasis japonica , Administration, Oral , Animals , Disease Models, Animal , Female , Mice , Niclosamide , Treatment OutcomeABSTRACT
Parasitic infections, especially the gastrointestinal and lung nematode infections, are most common in livestock in temperate areas, and it is the major constraints affecting livestock production. In grazing season, outdoor activities of animals cause inconvenience to the application of antiparasitic drugs. Therefore, controlled drug delivery systems can prolong the effect time and reduce the difficulty of drug administration. This review summarizes several types of long-term delivery devices and dosage forms including intraruminal devices, long-acting injectables, in-situ forming implants, novel microparticles and nanoparticles. Their advantages and drawbacks are dicussed.
Subject(s)
Drug Delivery Systems , Parasitic Diseases, Animal/drug therapy , Veterinary Drugs/administration & dosage , Animals , Livestock/parasitology , Nanoparticles , Nematode Infections/drug therapy , Nematode Infections/veterinary , Veterinary Drugs/therapeutic useABSTRACT
BACKGROUND: Cystic echinococcosis is a serious zoonotic infection worldwide caused by metacestodes of Echinococcus gruanulosus. Mebendazole and albendazole are the only two drugs used in the treatment of this disease with cure rates only about 30% due to the poor oral absorption. Thus an alternative treatment for this disease is needed. METHODS: A mebendazole oily suspension (MBZ-OS) was prepared and orally administrated to mice infected with echinococcus cysts for 8 months at 12.5 mg/kg and 25 mg/kg for 14 consecutive days. Mebendazole suspended in 1% tragacanth (MBZ-1% tragacanth) served as treated control. In addition, liver and serum samples were collected from these treated mice (25 mg/kg) for histopathology examination and liver function test. For pharmacokinetic analysis, plasma, parasite (cyst wall and cyst fluid) and tissue samples were collected at 0.25, 0.5, 1, 2, 4, 8, 16 and 24 h after orally administrating MBZ-OS and MBZ-1% tragacanth to E. granulosus-infected mice at 25 mg/kg. These samples were then processed and quantitatively analyzed by HPLC. RESULTS: The administration of MBZ-OS resulted in a treatment efficacy with the cyst weight reductions higher than 80%, significantly better than the corresponding MBZ-1% tragacanth groups. The better treatment efficacy of MBZ-OS was related to the higher drug concentration in plasma, parasites and tissues. It was also shown that the injury of the liver was not significantly altered by taking MBZ-OS compared to the untreated control. CONCLUSION: These findings demonstrate that MBZ-OS is a promising new formulation of MBZ for treatment of hydatid diseases without showing significantly liver toxicity.
Subject(s)
Anthelmintics/pharmacokinetics , Echinococcosis/drug therapy , Mebendazole/pharmacokinetics , Animals , Anthelmintics/administration & dosage , Anthelmintics/chemistry , Chemistry, Pharmaceutical , Drug Evaluation, Preclinical , Echinococcosis/parasitology , Echinococcus/drug effects , Echinococcus/physiology , Female , Humans , Male , Mebendazole/administration & dosage , Mebendazole/chemistry , Mice , Treatment OutcomeABSTRACT
BACKGROUND: Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. METHOD: We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment. RESULTS: 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel. CONCLUSION: Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55086560.
Subject(s)
Anthelmintics/therapeutic use , Clonorchiasis/drug therapy , Coinfection/drug therapy , Helminthiasis/drug therapy , Mebendazole/therapeutic use , Phenylenediamines/therapeutic use , Praziquantel/therapeutic use , Adult , Animals , Ascariasis/drug therapy , Female , Humans , Male , Mebendazole/adverse effects , Middle Aged , Phenylenediamines/adverse effects , Praziquantel/adverse effectsABSTRACT
OBJECTIVE: To determine the contributions of main chemical compositions of extracts of Eucalyptus camaldulensis represented by GC/MS elute peaks to the molluscicidal activities, and explore a shortcut of looking for the effective components from natural products. METHODS: E. camaldulensis leaves were collected consecutively in 12 months at the same place, extracted with dichloromethane, analyzed by GC/MS, and their LC50(s) of molluscicidal activities were tested according to the method recommended by WHO. The correlation of the main components in 12 extracts and their molluscicidal activities were analyzed by the grey relative correlation analysis model with software GTMS 3.0. RESULT: All the dichloromethane extracts of eucalyptus leaves showed excellent molluscicidal activities with the highest LC50 of 0.257mg/L and 0.242mg/L for the samples in June and July and the lowest LC50 of 6.802 mg/L and 5.406 mg/L in December and January respectively. The structures of 16 main chemical components were elucidated by GC/MS and NIST Mass Spectral Library, most of which were monoterpenes and sesquiterpenoids. The gray correlation coefficients with activity were all over 0.5, the first five over 0.9 were 4,4, 8-Trimethyltricyclo [6.3.1.0 (1,5) ]dodecane-2,9-diol, (-)-Spathulenol, a structural isomer of (-)-Spathulenol, Eucalyptol and Ledol. CONCLUSION: The most main ingredients in the dichloromethane extracts of E. camaldulensis leaves show good correlations with the molluscicidal activity, which suggests that the molluscicidal role is synergistically played by the multiple components together.
Subject(s)
Biological Products/analysis , Eucalyptus/chemistry , Gas Chromatography-Mass Spectrometry , Molluscacides/analysis , Plant Extracts/analysis , Snails , Animals , Biological Products/chemistry , Molluscacides/chemistry , Plant Extracts/chemistrySubject(s)
Anthelmintics/pharmacology , Echinococcosis/parasitology , Echinococcus granulosus/growth & development , Echinococcus granulosus/pathogenicity , Animals , Anthelmintics/therapeutic use , Culture Media , Echinococcosis/drug therapy , Echinococcus granulosus/drug effects , Echinococcus granulosus/ultrastructure , Parasitic Sensitivity TestsABSTRACT
This scoping review analyzes the research gaps of three diseases: schistosomiasis japonica, malaria and echinococcosis. Based on available data in the P.R. China, we highlight the gaps between control capacity and prevalence levels, and between diagnostic/drug development and population need for treatment at different stages of the national control programme. After reviewing the literature from 848 original studies and consultations with experts in the field, the gaps were identified as follows. Firstly, the malaria research gaps include (i) deficiency of active testing in the public community and no appropriate technique to evaluate elimination, (ii) lack of sensitive diagnostic tools for asymptomatic patients, (iii) lack of safe drugs for mass administration. Secondly, gaps in research of schistosomiasis include (i) incongruent policy in the implementation of integrated control strategy for schistosomiasis, (ii) lack of effective tools for Oncomelania sp. snail control, (iii) lack of a more sensitive and cheaper diagnostic test for large population samples, (iv) lack of new drugs in addition to praziquantel. Thirdly, gaps in research of echinococcosis include (i) low capacity in field epidemiology studies, (ii) lack of sanitation improvement studies in epidemic areas, (iii) lack of a sensitivity test for early diagnosis, (iv) lack of more effective drugs for short-term treatment. We believe these three diseases can eventually be eliminated in mainland China if all the research gaps are abridged in a short period of time.
ABSTRACT
OBJECTIVE: To observe the ultrastructural alterations of adult Schistosoma japonicum induced by synthetic trioxolane OZ78. METHODS: Eight out of ten mice infected with 40-60 S. japonicum cercariae for 35 d were treated orally with OZ78 at a single dose of 400 mg/kg. Four groups of two mice were killed at 24 h, 3 d, 7 d, and 14 d post treatment, and schistosomes were recovered by perfusion technique, fixed, and examined by transmission electron microscopy. Schistosomes obtained from the remaining two untreated mice served as control. RESULTS: After infected mice were treated with OZ78 for 24 h, the prominent alterations in tegument of both male and female worms were observed, which revealed in flattened surface due to swelling of cytoplasmic processes, irregular expansion in distal end of cytoplasmic processes accompanied by decrease in rod-like and discoid-like secretory bodies, focal lysis of tegumental matrix; fusion of some cytoplasmic processes to form a large piece, disruption or disappearance of basal membrane, and destruction of internal structures in sensory organelles. In the subtegument, no or slight swelling and focal lysis of muscle bundles were seen, while the syncytium beneath the muscle showed enlargement of nucleus with indistinction of partial nuclear membrane, formation of small vacuoles due to focal lysis of chromatin, and emergence of degenerated mitochondria in perinuclear cytoplasm. As to parenchymal tissues, the major alterations included degeneration of mitochondria, formation of some small vacuoles and myelin-like structures. In gut epithelial cells, the prominent alterations were irregular enlargement of nucleus with light lysis of nucleoli and fusion of partial bi-layer nuclear membrane, degeneration of mitochondria in cytoplasm and collapse of microvilli. At this time point, in the vitelline cells of female worms, the most significant alteration was the collapse of many vitelline droplets, which led to release of the vitelline balls, followed by their lysis and fusion. Three to 7 d post treatment, the damage to the worms aggravated either in extent or in severity along with time. The significant damages to male and female worms were fusion of cytoplasmic processes, peeling or collapse of damaged cytoplasmic processes resulting in exposure of muscle bundles, severe destruction of sensory organelles and syncytium, focal or extensive swelling and lysis of muscle bundles, emergence of some larger piece of degenerated parenchymal tissues and severe damage to the gut epithelial cell. While in the vitelline cells of female worms, decrease in the number of vitelline droplet, focal lysis of nucleus and extensive lysis of parenchymal tissues among the vitelline cells were also observed. Fourteen days post OZ78 dosing, male and female worms which survived the treatment showed some renovation in damaged tegument and subtegument, while most gut epithelial cells and vitelline cells still revealed in prominent injury. CONCLUSION: The results demonstrate that OZ78 possesses an extensive damage to the ultrastructure in tegument and subtegument tissues including syncytium, parenchymal tissues, gut epithelial cells, and vitelline cells of adult S. japonicum.
Subject(s)
Adamantane/analogs & derivatives , Schistosoma japonicum/ultrastructure , Schistosomiasis japonica/parasitology , Schistosomicides/pharmacology , Adamantane/pharmacology , Animals , Female , Male , Mice , Mice, Inbred Strains , Schistosoma japonicum/drug effects , Schistosomiasis japonica/drug therapyABSTRACT
Synthesized fenbendazole prodrug N-methoxycarbonyl-N'-(2-nitro-4-phenylthiophenyl) thiourea (MPT) was analyzed in vitro in artificial gastric juice, intestinal juice and mouse liver homogenate model by using HPLC method, and metabolic curve was then generated. MPT was tested against Echinococcus granulosus protoscolices in vitro. The result showed that MPT could be metabolized in the three biological media, and to the active compound fenbendazole in liver homogenate, with a metabolic rate of 7.92%. Besides, the prodrug showed a weak activity against E. granulosus protoscolices with a mortality of 45.9%.