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1.
G Cancrini  P Tassi  M Coluzzi 《Parassitologia》1989,31(2-3):177-182
The prophylactic efficacy of ivermectin against Dirofilaria repens infections in dogs was investigated. A first trial was carried out on 15 dogs exposed to four inoculations of L3 larvae at 15-day intervals and treated, in groups of five, with 0, 6 or 12 micrograms/kg body weight of ivermectin given per os 30 and 60 days after the first inoculation. Necropsy, performed about 9 months later, revealed that worm burdens were reduced by 86.6 and 92.8% for the 6 and 12 micrograms/kg dose levels, respectively. In a second trial with an otherwise identical protocol, a dose rate of 24 micrograms/kg of ivermectin was tested in 12 dogs. Only one of the six treated dogs was found worm free at necropsy. The worm burden was reduced by 87.9% in treated animals as opposed to controls. A lengthening of the prepatent periods, which might be considered dose related, was apparent in all treated groups. Ivermectin was not completely effective in preventing establishment of experimental infections with D. repens in dogs.  相似文献   

2.
The activity of ivermectin and albendazole against larval Anisakis simplex was tested in vitro and in experimentally infected guinea pigs. Before drug exposure the medium for half of the larvae was adjusted to pH 2.0 with 1 N HCl, whereas the other half was held at pH 7.0. To these solutions, ivermectin was added to full concentrations of 1, 2, 5, 10, 50, 100, or 200 microg/ml, and for albendazole, 300, 400, and 500 microg/ml. Animals from group I were given 0.1 ml of 1% (3.3 mg/kg) ivermectin, whereas guinea pigs from group II were each given 5-7 mg (16.6-23.3 mg/kg) of albendazole orally. The efficacy of both drugs against L, A. simplex was high in vitro and in vivo against the larvae in different organs of guinea pigs.  相似文献   

3.
BACKGROUND: In order to use a combination of ivermectin and albendazole for the elimination of lymphatic filariasis, it is important to assess the potential risk of increased adverse events in individuals infected with both lymphatic filariasis and onchocerciasis. We compared the safety and efficacy of albendazole (400 mg) in combination with ivermectin (150 micrograms/kg), for the treatment of co-infections of Wuchereria bancrofti and Onchocerca volvulus with single infection of W. bancrofti. METHODS: The safety study on co-infections was a crossover, double blind design, while for the single infection of bancroftian filariasis an open design comparing two treatments was used. For co-infection, one group was allocated a single dose of ivermectin (150 micrograms/kg) plus albendazole (400 mg) (Group A). The other group received placebo (Group B). Five days later the treatment regime was reversed, with the Group A receiving placebo and Group B receiving treatment. For the single bancroftian filariasis infection, one group received a single dose of albendazole (400 mg) plus ivermectin (150 microg/kg) (Group C) while the other group received a single dose of albendazole (400 mg) alone (Group D). Blood and skin specimens were collected on admission day, day 0, and on days 2, 3, and 7 to assess drug safety and efficacy. Thereafter, blood and skin specimens were collected during the 12 months follow up for the assessment of drug efficacy. Study individuals were clinically monitored every six hours during the first 48 hours following treatment, and routine clinical examinations were performed during the hospitalisation period and follow-up. RESULTS: In individuals co-infected with bancroftian filariasis and onchocerciasis, treatment with ivermectin and albendazole was safe and tolerable. Physiological indices showed no differences between groups with co-infection (W. bancrofti and O. volvulus) or single infection (W. bancrofti). The frequency of adverse events in co-infected individuals was 63% (5/8, Group A, albendazole + ivermectin) and 57% (4/7, Group B, placebo) and of mild or moderate intensity. In single W. bancrofti infection the frequency of adverse events was 50% (6/12, Group C, albendazole + ivermectin) and 38% (5/13, Group D, albendazole) and of a similar intensity to those experienced with co-infection. There were no differences in adverse events between treatment groups. There was no significant difference in the reduction of microfilaraemia following treatment with albendazole and ivermectin in groups with single or co-infection. CONCLUSION: Our findings suggest that ivermectin plus albendazole is a safe and tolerable treatment for co-infection of bancroftian filariasis and onchocerciasis.  相似文献   

4.
The effect of four avermectins on the population growth of pest mite Lepidoglyphus destructor was tested in laboratory experiments. The avermectins (abamectin, doramectin, emamectin-benzoate and ivermectin) of analytical purity were incorporated into an experimental diet at the same molar concentrations, ranging from 0.16 to 8 nmol/3 g of diet. Using an initial population of 50 mites, the population growth was recorded after 21 days at 85 % relative humidity and 25 °C; 12 repeats were performed per avermectin concentration and control. The diets containing the avermectins successfully suppressed the population growth of L. destructor. The EC(50) recalculated to ng of substance per g of diet showed different suppressive effects of the avermectins: doramectin (181 ng/g diet), abamectin (299 ng/g diet), emamectin-benzoate (812 ng/g diet) and ivermectin (992 ng/g diet). Of the tested avermectins, abamectin is registered for the control of phytophagous mites and ivermectin against parasitic mites, i.e., Psoroptes ovis. Although emamectin-benzoate and ivermectin were less effective on L. destructor, all of the tested avermectins are highly suitable compounds for the control of synanthropic mites.  相似文献   

5.
Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10–15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy.  相似文献   

6.
6-BA、IBA、2;4-D对杖藤组培增殖的影响   总被引:2,自引:0,他引:2       下载免费PDF全文
研究了6 BA、IBA和2,4 D对杖藤组培物增殖的影响。结果表明,6 BA对增殖芽数、丛芽率和母芽高均有显著的作用,IBA和2,4 D仅对增殖芽数有显著影响。适宜于增殖培养的激素浓度分别为6 BA4.0mg/L,IBA0.25mg/L,2,4 D0.25mg/L。以此激素浓度组合,连续增殖培养6~7代后,平均的增殖芽数可稳定在10个左右。  相似文献   

7.
In vivo ivermectin resistance was selected in an isolate of Trichostrongylus colubriformis (TcR) already known to be benzimidazole resistant. This was accomplished in sheep by using levels of ivermectin calculated to reduce the fecal egg output from each generation of T. colubriformis by congruent to 95%. The first indication of ivermectin resistance was observed with the F10. A dosage-titration trial comparing the parent TcR with the ivermectin-selected F21 demonstrated that the latter was congruent to 20 times more resistant to oral ivermectin therapy in experimentally infected sheep than was the parent isolate. Treatment of the F16 generation with 50 mg/kg of thiabendazole resulted in only 54% egg reduction and confirmed that benzimidazole resistance was stable.  相似文献   

8.
The comparative efficacy of 2 anthelmintics (ivermectin and levamisole) against Baylisascaris transfuga migrating and encapsulated larvae was studied in mice. A total of 60 BALB/c mice inoculated each with about 1,000 embryonated B. transfuga eggs were equally divided into 6 groups (A-F) randomly. Mice of groups A and B were treated with ivermectin and levamisole, respectively, on day 3 post-infection (PI). Mice of groups A-C were killed on day 13 PI. Similarly, groups D and E were treated with ivermectin and levamisole, respectively, on day 14 PI, and all mice of groups D-F were treated on day 24 PI. The groups C and F were controls. Microexamination was conducted to count the larvae recovering from each mouse. The percentages of reduction in the number of migrating larvae recovered from group A (ivermectin) and B (levamisole) were 88.3% and 81.1%, respectively. In addition, the reduction in encapsulated larvae counts achieved by ivermectin (group D) and levamisole (group E) was 75.0% and 49.2%, respectively. The results suggested that, to a certain extent, both anthelmintics appeared to be more effective against migrating larvae than encapsulated larvae. However, in the incipient stage of infection, ivermectin may be more competent than levamisole as a larvicidal drug for B. transfuga.  相似文献   

9.
The effect of ivermectin or diethylcarbamazine (DEC) on Wuchereria bancrofti molting from the third to the fourth larval stage (L3 to L4) was evaluated in vitro. L3 larvae were harvested from laboratory-reared Aedes togoi 2 wk after feeding upon a microfilaremic human volunteer. The larvae were kept in an artificial medium (Franke's NI medium) with 10% human serum under an atmosphere of 5% CO2 for 20 days. Experimental tubes also contained ivermectin (0.1-1,000 ng/ml) or DEC (0.1-10,000 ng/ml). An estimated concentration of 50 ng/ml ivermectin inhibited molting in 50% of the larvae expected to molt. For DEC, this value was roughly 1,000 ng/ml. In this in vitro culture system, ivermectin inhibited the L3 to L4 molt of W. bancrofti and was roughly 20-fold more potent in this activity than DEC.  相似文献   

10.
The toxicity of dung from cattle treated with an ivermectin sustained-release bolus was estimated in terms of ivermectin or ivermectin equivalents, using a laboratory bioassay with the dung fly Neomyia cornicina Fabricius (Diptera, Muscidae). The mortalities of flies measured 7 days after feeding for 24 h on dung containing known concentrations of ivermectin (between 0.125 and 1 g ivermectin per gram fresh dung) were compared with the mortalities of insects fed for 24 h on dung from cattle treated 21 days previously with an ivermectin sustained-release bolus. The toxicity of the bolus dung was equivalent to dung containing 0.66 g ivermectin per gram fresh dung. To determine whether insects could differentiate between control dung and dung from bolus-treated cattle, choice-chamber tests were carried out. There was no significant difference in the percentage of females that chose either dung type, suggesting that they were unable to distinguish the dung of bolus-treated cattle from control dung. Results are discussed in relation to the impact that bolus use can have on the insect fauna of cattle dung.  相似文献   

11.
This paper presents a summary of reported cases of Serious Adverse Events (SAEs) following treatment with Mectizan® (ivermectin, Merck, Sharpe &; Dohme) in onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001 through a passive surveillance system. A total of 207 SAE cases were reported out of approximately 165 million reported treatments delivered during the period under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000 reported treatments. The mean age was 40 years and 70% of the cases were males. The mean time between ivermectin intake and onset of illness was 1 day. For 57% of the cases (n = 118), that was their first exposure to ivermectin. The majority of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence of SAE reporting in 1989–1991 and 1994–1995 when the program expanded to ivermectin-naïve populations. Fifty-five percent of the cases from Cameroon (i.e. 97 out of 176 cases) were encephalopathic and were reported from the central-southern region of the country; two-thirds of these cases were 'probable' or 'possible' cases of Loa loa encephalopathy temporally related to ivermectin treatment. Reporting bias may explain some but not all of the differences in SAE reporting between the 34 onchocerciasis-endemic countries that have, or have had, mass treatment programs. Further research is needed to understand the apparent clustering of encephalopathy cases in central-southern Cameroon since L. loa infection alone probably does not explain the increased incidence of this type of SAE from this region.  相似文献   

12.
《Theriogenology》1986,26(6):721-732
Sixty anestrous ewes were used to determine the effects of artificial photoperiod and/or melatonin feeding on seasonality of reproduction. Treatments included natural daylight (ND), 8 h of light, 16 h of darkness (8L: 16D), natural daylight plus 3.5 mg melatonin fed per ewe daily (ND + MEL), and 8L: 16D plus 3.5 mg melatonin fed per ewe daily (8L: 16D + MEL). The percentage of ewes lambing was lower (P < 0.05) for ND treated ewes (40%) than for ewes in 8L: 16D (100%), ND + MEL (91.7%), or 8L: 16D + MEL (93.3%). The earliest mean conception date was for ewes in the 8L: 16D + MEL treatment. This was 10 days earlier than for ewes in the ND treatment (P < 0.05). ND and ND + MEL treated ewes had fewer lambs (P < 0.05) and lighter litter weight (P < 0.05) per ewe lambing than did 8L: 16D and 8L: 16D + MEL treated ewes. Serum progesterone levels above 1.0 ng/ml were reached and maintained approximately 3 wk earlier in the 8L: 16D, 8L: 16D + MEL, and ND + MEL treated ewes than in the ND treated ewes (P < 0.05). Ewes in ND treatment had higher overall serum prolactin levels (P < 0.05) than did ewes in all other treatments. Results indicate that the 8L: 16D treatment and/or feeding melatonin can hasten cyclicity in ewes and increase the number of ewes conceiving.  相似文献   

13.
伊维菌素作为一种高效的抗寄生虫兽药,在畜禽业有着广泛的应用。但药物随着畜禽动物的代谢产物的排放而进入自然生态系统也成为逐渐显现的环境问题。由于药物具有在自然环境中难以快速降解和对水生枝角类高毒性的特点,因此流入天然水体的伊维菌素存在着影响水生态平衡的风险。为了比较全面评估药物对水生动物潜在的毒害作用,研究模拟天然河道环境,对药物在底质中的降解速率进行了测定,并选取7种占据不同生态位的水生生物作为试验对象,通过关于急性毒性的国家标准试验方法来初步评价药物对水生态系统的风险。结果显示伊维菌素在自然水体中降解缓慢,在泥水混合25℃恒温条件下,70d的降解率仅为28.3%。急性毒性试验结果显示伊维菌素对发光细菌(Photobacterium)并不表现出毒性,对淡水小球藻(Chlorella vulgaris)的96h EC50=19.80 mg/L,属中毒;而对其他实验生物则表现出了较高的毒性,伊维菌素对斑马鱼(Brachydanio rerio)、食蚊鱼(Gambusia affinis)和鲫鱼鱼苗(Carassius carassius)的96h LC50分别为40.48、34.81和13.79μg/L,对罗氏沼虾(Macrobrachium rosenbergii)的96h LC50=7.87μg/L,对大型溞(Daphniamagna)的24h LC50=4.81 ng/L,均属极高毒。因此残留在天然水体的伊维菌素对水生态中的生物有较大影响,对含伊维菌素的废弃物排放进行监控和科学管理非常必要。  相似文献   

14.

Background

The risk of severe adverse events following treatment of onchocerciasis with ivermectin in areas co-endemic with loiasis currently compromises the development of control programmes and the treatment of co-infected individuals. We therefore assessed whether doxycycline treatment could be used without subsequent ivermectin administration to effectively deliver sustained effects on Onchocerca volvulus microfilaridermia and adult viability. Furthermore we assessed the safety of doxycycline treatment prior to ivermectin administration in a subset of onchocerciasis individuals co-infected with low to moderate intensities of Loa loa microfilaraemia.

Methods

A double-blind, randomized, field trial was conducted of 6 weeks of doxycycline (200 mg/day) alone, doxycycline in combination with ivermectin (150 µg/kg) at +4 months or placebo matching doxycycline + ivermectin at +4 months in 150 individuals infected with Onchocerca volvulus. A further 22 individuals infected with O. volvulus and low to moderate intensities of Loa loa infection were administered with a course of 6 weeks doxycycline with ivermectin at +4 months. Treatment efficacy was determined at 4, 12 and 21 months after the start of doxycycline treatment together with the frequency and severity of adverse events.

Results

One hundred and four (60.5%) participants completed all treatment allocations and follow up assessments over the 21-month trial period. At 12 months, doxycycline/ivermectin treated individuals had lower levels of microfilaridermia and higher frequency of amicrofilaridermia compared with ivermectin or doxycycline only groups. At 21 months, microfilaridermia in doxycycline/ivermectin and doxycycline only groups was significantly reduced compared to the ivermectin only group. 89% of the doxycycline/ivermectin group and 67% of the doxycycline only group were amicrofilaridermic, compared with 21% in the ivermectin only group. O. volvulus from doxycycline groups were depleted of Wolbachia and all embryonic stages in utero. Notably, the viability of female adult worms was significantly reduced in doxycycline treated groups and the macrofilaricidal and sterilising activity was unaffected by the addition of ivermectin. Treatment with doxycycline was well tolerated and the incidence of adverse event to doxycycline or ivermectin did not significantly deviate between treatment groups.

Conclusions

A six-week course of doxycycline delivers macrofilaricidal and sterilizing activities, which is not dependent upon co-administration of ivermectin. Doxycycline is well tolerated in patients co-infected with moderate intensities of L. loa microfilariae. Therefore, further trials are warranted to assess the safety and efficacy of doxycycline-based interventions to treat onchocerciasis in individuals at risk of serious adverse reactions to standard treatments due to the co-occurrence of high intensities of L. loa parasitaemias. The development of an anti-wolbachial treatment regime compatible with MDA control programmes could offer an alternative to the control of onchocerciasis in areas of co-endemicity with loiasis and at risk of severe adverse reactions to ivermectin.

Trial Registration

Controlled-Trials.com ISRCTN48118452  相似文献   

15.
Single oral doses of ivermectin were given to dogs with moderate or heavy infections of Ancylostoma caninum (egg counts ranging from 7,100 to 41,700 eggs/g feces) at 100, 50, 30, or 10 micrograms/kg body weight. Each of these dosages was effective in clearing the infection completely, so that numerous worms were passed in the feces on days 1-3, but no worm was recovered from the intestinal tract at necropsy on day 4 after treatment. In contrast, an average of 178 worms per dog was recovered at necropsy from the vehicle-treated control and the untreated animals. Albendazole, a known anti-hookworm agent, even in a dose of 400 mg, eliminated only 21-65% of the worms harbored by the infected animals. No untoward reaction to ivermectin or significant pathological change was noted in the experimental animals. In vitro experiments demonstrated that ivermectin: (1) was highly detrimental to actively motile adult worms in concentrations greater than 5.60 micrograms/ml; (2) was detrimental to eggs inside the uterine tissue of female worms in dosages at or greater than 10 micrograms/kg body weight; and (3) killed infected larvae in concentrations as low as 0.0025 micrograms/ml.  相似文献   

16.
Third larval stages (L3) removed from fish fillets, fourth larval stages (L4) raised in in vitro culture, and adults of Pseudoterranova decipiens, collected from grey seal (Halichoerus grypus) stomachs, were exposed to the broad spectrum anthelmintic, ivermectin. L3 and L4 parasites were exposed, in vitro, to 500, 100, 50, 20, 5 and 1 micrograms/ml concentrations of the drug, in culture media. Adult P. decipiens were exposed in vitro to a concentration of 500 micrograms/ml ivermectin, only. Controls consisted of parasites placed in culture media alone or culture media plus drug vehicle. These three developmental stages of P. decipiens were all found to be susceptible to the effects of ivermectin.  相似文献   

17.
Spin label electron paramagnetic resonance (EPR) spectroscopy was used to study the mechanisms of action of ivermectin and curcumin against Leishmania (L.) amazonensis promastigotes. EPR spectra showed that treatment of the parasites with both compounds results in plasma membrane rigidity due to oxidative processes. With the IC50 and EPR measurements for assays using different parasite concentrations, estimations could be made for the membrane-water partition coefficient (KM/W), and the concentration of the compound in the membrane (cm50) and in the aqueous phase (cw50), which inhibits cell growth by 50%. The KM/W values indicated that ivermectin has a greater affinity than curcumin for the parasite membrane. Therefore, the activity of ivermectin was higher for experiments with low cell concentrations, but for concentrations greater than 1.5 × 108 parasites/mL the compounds did not show significantly different results. The cm50 values indicated that the concentration of compound in the membrane leading to growth inhibition or membrane alteration is approximately 1 M for both ivermectin and curcumin. This high membrane concentration suggests that many ivermectin molecules per chlorine channel are needed to cause an increase in chlorine ion influx.  相似文献   

18.
Laboratory selection of Haemonchus contortus for resistance to ivermectin   总被引:1,自引:0,他引:1  
The eighth generation of adult Haemonchus contortus, selected by subjecting infected pairs of sheep to suboptimal ivermectin treatment once per generation from parent (P; BBH isolate) through F7 (IV-A; selected isolate), required an approximate 4-fold increase in the ivermectin dose to produce 95% efficacy compared with its contemporary parent isolate. In a dose titration experiment the dose-response curve of the drug pressure-derived isolate, IV-A, was significantly (0.02 less than P less than 0.05) less steep than was the response curve of the parent, BBH, isolate. Potency estimates based upon these nonparallel dose-response curves would not remain constant over a range of efficacy levels but would decrease rapidly at efficacies greater than 95%. Passage of a closed population of the F8 generation of IV-A sequentially through pairs of sheep for an additional 11 generations (F8A-F8K) without additional drug pressure being applied produced no reversion to sensitivity to ivermectin relative to the F7 generation, thus suggesting that the selected "resistance" was stable.  相似文献   

19.
Avermectins are a new class of macrocyclic lactones derived from mycelia of the soil actinomycete, and are used as effective agricultural pesticides and antiparasitic agents. However, run-off from crops treated with avermectins may contaminate various bodies of water, and accumulated to certain concentrations to impact the development of aquatic animals. Here, we tested the genotoxicity of three avermectins(abamectin, ABM; ivermectin, IVM; and emamectin benzoate, EMB) on Polypedates megacephalus tadpoles by the alkaline single-cell gel electrophoresis assay. Tadpoles were treated for 48 h in the laboratory with different concentrations of these three agents, 0.006, 0.012, 0.018, 0.024, 0.030 mg/L for ABM, 0.003, 0.006, 0.009, 0.012, 0.015 mg/L for IVM and 0.04, 0.06, 0.08, 0.10, 0.12 mg/L for EMB, and then measured their DNA damage by the Comet assay tail factor %. The concentrations of resulted in highly significant increases in DNA damage of the tadpoles were found above the concentration threshold of 0.012 mg/L ABM, 0.003 mg/L IVM and 0.06 mg/L EMB and linear correlations between the intensity of DNA damage and the concentrations of these three avermectins. Our results showed clearly that avermectins caused dose dependent DNA damage on amphibian tadpoles, and there might be a control on the misuse of avermectins.  相似文献   

20.
'早红'草莓高效遗传转化受体系统的建立   总被引:2,自引:0,他引:2  
本文以草莓主栽品种'早红'组培苗离体叶片和叶柄为外植体,进行叶龄、暗培养、植物生长调节剂配比及抗生素敏感性研究,建立草莓高效遗传转化的受体系统.在含3.0 mg/L 6-BA与0.1 mg/L 2,4-D的MS培养基上,30 d叶龄的叶片再生频率高达98.31%,平均每叶片再生芽数5.09个,叶柄切段的再生频率为89.25%,平均每叶柄切段再生芽数4.92个,叶片的再生频率略高于叶柄;不定芽在含0.2 mg/L 6-BA与0.2 mg/L GA_3的MS继代培养基上培养成苗.将生长状态良好的不定芽转至含0.2 mg/L IBA的1/2 MS培养基上生根,生根率达100%,平均生根数量16.27条,平均根长1.85 cm.抗生素敏感性试验表明,草莓外植体适宜的卡那霉素选择压力为25 mg/L,头孢霉素的筛选浓度为300mg/L.本研究建立的再生体系可作为草莓遗传转化的受体系统.  相似文献   

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