obvelata)from a large rodent breeding center by cocktail anthelmintic therapy

Transcription

1 Effective eradication of pingworms infection(syphacia muris, Syphacia obvelata)from a large rodent breeding center by cocktail anthelmintic therapy 1 Chung-Tiang LIANG, 1 Ping-Chin LEE, 1 Shiann-Ching WU, 1 Yen-Te HUANG, 1 Wei-Jeng CHANG, 1 Ta-Yu HSC, * 1,2 San-Chi LIANG 1 National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan 115, ROC 2 Laboratory Animal Center, National Defense Medical Center, Taipei, Taiwan 114, ROC ABSTRACT In the routine health monitoring of laboratory animals in our breeding and research center, rat pinworm, Syphacia muris, in research rat colony (10/16)and mice pinworm, Syphacia obvelata, in barrier SPF mice(1/28) were detected. A cocktail anthelmintic regime was designed to eradicate the infection. At first, 0.1% ivermectin solution was sprayed to both mice and rat cages on days 0, 14 and 28, while piperrazine citrate was administrated at a rate of 3 g/liter in the drinking water on days 7, 10, 21, 24, 35, and 38. Further measures were taken by adding ivermectin in the drinking water (0.007 mg/ml) on days 42 and 49 in both rats and mice, followed by oral administration of fenbendazole-medicated chow in rats (150 ppm) and 0.2% thiobendazole- medicated chow in mice weekly for 6 weeks. Other manipulations to facilitate eradication, including the use of filter-top cages in contaminated animal rooms, environmental decontamination by flame, research colony depopulation, breeding cessation and colony size diminishing in infected rooms, were conducted at the same time. The colony was monitored for 24 months after treatments. The examination of 4862 cellophane-tape impressions of the anus, 1082 cecal examination from euthanized rats and mice, as well as 347 MIF concentration stool smear confirmed the efficacy of treatment. This is the first report for the successful eradication of pinworms in large scale of breeding colonies including both rats and mice. *Corresponding author Dr. San-Chi LIANG Laboratory Animal Center, National Defense Medical Center, Taipei, Taiwan 114, ROC TEL: E. mail: simon@ndmctsgh.edu.tw 1

2 INTRODUCTION Pinworms, or oxyurids, belong to the family oxyuridae in the order Ascaridorida [5]. They have three species: Syphacia obvelata, Syphacia muris, and Aspicularis tetraptera. Syphacia obvelata is commonly seen in mice, and Syphacia muris is commonly seen in rats,however, both species of Syphacia spp. can patently infect rats or mice [15]. Pinworm infection with Syphacia obvelata or Syphacia muris is a common problem in laboratory rodent colonies. Although parasitized rodents may lack clinical signs of infection, heavy infection can cause severe gastrointestinal disturbance such as diarrhea, dehydration, rectal proplapse [9] and water transport of electrolyte and water transport [18]. The life cycles of S. obvelata and S. muris are 11 to 15 days and 7 to 9 days respectively. The adult worms inhabit the cecum and colon. After copulation, gravid females travel through the colon, emerge from the anus, and deposit their ova in the perianal region. This creates a therapeutic challenge because even if worms are effectively eradicated, infection can recur. The rodents ingest ova when they clean their perianal region or if larvae hatched from ova deposited around the anus retroinfection into the colon. Therefore, the eradication of pinworms is extremely difficult, especially from a large rodents breeding colony. Numerous anthelmintic have been used to treat pinworm, inducing piperazine citrate [9,13,18,19], piperrazine hexahydrate, or adipate, trichlorfon, dichlorvos, haloxon [18], % oral thiabendazole in food [16,18], pyrantel pamoate [11], ivermectin in drinking water or by spraying [10,11,12,,13,19], ivermectin by oral gastric intubation[1,4], 150 ppm fenbedazole [8]. However, very few successful reports are focused on large scale of breeding colonies, only one case of eradication of Syphacia obvelata in mice breeding colony has been reported [13], but none in both rats and mice breeding colonies with Syphacia obvelata and Syphacia muris infection. Here we report the first case of the successful eradication of pinworm infection in both rat and mice colonies with thousands of animals. Several factors have been considered to lead to our cocktail anthelmintic therapy,such as effectiveness of anthelmintic, labor cost, animal adaptation to treatment, and the availability and transportation of from overseas. Our experience will offer a successful example of pinworm eradication program for large rodents breeding center in the world. MATERIALS and METHODS Laboratory Animals The colonies were maintained in a SPF barrier, with a total 12 animal- holding 2

3 rooms. Daily average census of which were approximately 6,100 breeding rats and 12,470 breeding mice, consisted of numerous inbred strains and outbred stocks. Those mice and rats included Wistar, Long-Evans, SD, Lewis, SHR/NCrl, WKY, F344, BN rats and ICR, C57BL/6J, BALB/cAnN, BALB/cByJ, C3H/HeJ, CBA/CaJ, CBA/N, DBA/2J, NZW, CAnNCrj Cg-Foxnl nu /Foxnl nu mice. Management and enviroment The mice and rats were housed in an air-conditioned room in uncovered polycarbonate shoebox cages, ( cm and cm respectively) on hardwood bedding (Beta-chip, Northeastern Inc. Warrensburg, NY). The cage and bedding were changed twice per week, and cages were sanitized in a mechanical cage washer operating at 80 o C (Girton manufacturing Co., Millville, PA.) Water, food, bedding, and supplied materials were all sterilized by autoclave (Eagle 3000 Vacamatic sterilizer, AMSCO, Apex, NC) prior to use. All mice and rats were fed a standard commercial diet (sterilizable PMI 5K55 mouse diet/auto 9F, PMI Feeds Inc. St. Louis MO, USA., crude protein 18%, crude fat 9%, crude fiber 5%, ash 6.5%, minerals 2.5%). All rats were fed a commercial diet (sterilizable PMI 5L65 rodent lab auto diet,pmi Feeds Inc. St. Louis MO, USA., crude protein 23%, crude fat 4.5%, crude fiber 6%, ash 8%). Water, supplied in bottles (400 ml in mice and 700 ml in rat), was available ad libitum. Rooms were maintained at 21±2, with 60±5% relative humidity and a 12/12-h light/dark cycle. Health monitoring A health-monitoring program was routinely conducted to detect diseases in these SPF animals. Eight animals were randomly selected for health monitoring in each room at the assumption of 30 % prevalence with a 95% confidence interval[15].rodents were euthanized, and evaluated serologically for exposure to a panel of adventitious murine viruses and Mycoplasma pulmonis. Serum samples of mice were examinated for ELISA antibodies to the following organisms: pneumonia virus of mice, retrovirus (Reo-3), Sendai virus, lymphocytic choriomeningitis virus, Theiler s encephalomyelitis virus, mouse adenovirus, minute virus of mouse, ectromelia virus, polyoma virus, K virus, Mycoplasma spp. and mice hepatitis virus (Charles River Laboratories, Wilmington, Mass. USA). Serum samples of rats were examinated for ELISA antibodies to the following organisms: pneumonia virus of mice, retrovirus (Reo-3), Sendai virus, lymphocytic choriomeningitis virus, Theiler s encephalomyelitis virus, mouse adenovirus, minute virus of mouse, Toolen s H-1 virus, Kilham s rat virus, sialodacryoadenitis virus, Mycoplasma pulmonis 3

4 (Charles River Laboratories, Wilmington, Mass. USA). The tracheal PBS (NaCl mM; KCl 2.75mM; Na 2 HPO 4 0.7mM; KH 2 PO 4 1.5mM, ph 7.2) flush and cecum contents of rats and mice were examed for the following pathogens by bacteriological cultivation: Bordetella bronchiseptica, Corynebacterium kutscheri, Mycoplasma pulmonis (in the trachea PBS flush)and Salmonella spp.(in the cecum contents). For immunosupressed mice, Pseudomonas aeruginosa was also examed both in the trachea PBS flush and cecum contents. The tracheal PBS flush was inoculated on Tryptic soy agar(difco , USA)with 5% defibrinated sheep blood (BAP) in 37 aerobically, Bordetella bronchiseptica was identified by API 20 NE system(biomérieux # , France); Corynebacterium kutscheri was identified by API Coryne system (biomérieux # , France) and Pseudomonas aeruginosa was identified by the colonial morphology on Difco TM Pseudomonas agar F(Difco ). The tracheal PBS flush was inoculated in PPLO broth (per 100ml contained: PPLO broth without crystal violet(difco , USA) 2.1gm; distilled water 60 ml; phenol red(sigma P-4758, USA)2mg; D- (+)- glucose (Sigma G-6152, USA)1%; Penicillin-G(Sigma P-7794, USA)10 5 U; Thallium acetate(sigma T-8266, USA)0.025%; yeasr extract(difco )0.25% and equine serum(hyclone SH , USA)20% that was heat treated by 56 water bath for 30 min.).after 7 days incubation in 37 aerobically, the inoculum was subcultured on PPLO agar(pplo broth with Agar Noble(Difco , USA) 0.8%)for 5 to 7 days in 37, 5% CO 2 condition.the suspected colonies of M. pulmonis were examed under stereomicroscope and picked out for the species confirmation by PCR method. The cecum content was inoculated in GN broth, Hajina(Difco )in 37 aerobically and subcultured on Difco TM Pseudomonas agar F for Pseudomonas aeruginosa isolation and identification; on Hectoen entric agar (Oxoid CM 419, England) for Salmonella spp. isolation. The Salmonella spp. were identified by ATB ID 32GN system(biomérieux # , France). The ears and the surrounding pelage from each animal were examined directly under anatomical microscopy (Leica intralux ) for ectoparasites. The cecal contents were put into petri dish with 2-3ml saline for further endoparasite examination. Cellophane tape impressions were performed for pinworm examination. The tissues samples were routinely processed to paraffin-embedded blocks. Sections (6µm) were stained with GM haematoxyline and eosin (H&E) 4

5 Parasite examination during treatment period At the first 9 weeks treatment period (days 0-63), we used cellophane tape impression for monitoring each room every other week. Sixteen to 20 samples per room, with each one from different cages, were randomly collected for pinworm examination. At the second stage (days ), the test sample number increased to 30 for cellophane tape examination per month, and 10 animals were sacrificed for cecal adult worm examination in the rooms with positive results, including C57BL/6J, BALB/cAnN, BALB/cByJ, CAnNCrj Cg-Foxnl nu /Foxnl nu mice. Meanwhile, the inbred foundation strains increased to 40 sections from different cages per room, 20 sections monthly for other animal rooms. In the two stages of intensive pinworm monitoring period (days 0-210), routine quarterly comprehensive health monitoring were also taken, 8 animal per room for complete parasitological examination, including MIF, direct smear and cellophane tape impression. Direct smear Added 2-3 ml saline, 0.9% NaCl, to 1 gram of cecal contents, mixed and examined under light microscopy. Merthiolate iodine formaldehyde (MIF) concentration method Combine 9.4ml of solution I {distilled water 50ml, formaldehyde 5ml, thimerosal (tincture of merthiolate, 1:1000) 40ml, glycerin 1ml} with 0.6ml of solution II (DW 100ml, potassium iodide 10g, iodine crystals 5g) to make the MIF working solution. One gram of fresh cecal stool, pool 4(rats) to 8(mice) animals stool in one tube to examine, was added to the MIF working solution, mixed, then stood overnight 24 hours, collected the interface and bottom layer. Added 3 ml ether, then homogenized and centrifuged at 2, 000 rpm for 2 min., the smear of sediment was examined for eggs and protozoa.. Treatment regimen At first, we used the same anthelmintic regimen for six consecutive weeks in barrier SPF rats and mice. We used 0.1 % ivermectin to spray the whole cages, 1.8 to 2.7 mg for each mice cage and 3.6 to 5.4 mg for each rats and hamster cage, once a week, on days 0, 14, part 1% ivermectin (Ivomec, 10 mg/ml, MSD Agvet Merk, Shark & Dohme BV Co. Inc., Haarlem, Netherlands) injectable solution mixed with 9 parts tap water in a 22-oz spray bottle. Each aquirt at the mist setting delivers approximately 2 to 3 ml (1.8 to 2.7 mg) ivermectin over the entire mice cages, 3.6 to 5.4 mg for each rat cage.once a week, on days 42, 49 for rats and mice. Piperazine citrate was administrated at a rate of 3 g/liter in the drinking water, twice a week, on days 7, 10, 21, 24, 35, and 38. In mice, pinworm eggs persisted for 10 and 5

6 22-23 days after the start of treatment. Accordingly, we used ivermectin, mg/ml, in drink water for further treatment, once a week, on days 42, 49 for rats and mice. Other manipulations to facilitate eradication including the use of filter tops in contaminated animal rooms. Environmental decontamination by flame in the barrier areas and research colony depopulation were done. Breeding cessation and decreased colony size from 1300 cages, 6000 mice including C57BL/6J, BALB/cAnN and BALB/cByJ, to 300 cages in the infectious B116 room, 5 mice per cage. The cocktail anthelmintic treatment was different between rats and mice in another 6 week preventive treatment period(figure1).oral 150 ppm fenbendazole-medicated chow (Altromin Gmbh diet 1324,Germany) was feed, for another 6 weeks in rats; oral 0.2% thiobendazole-medicated chow (Altromin Gmbh diet 1434,Germany) was feed, for 6 weeks in mice on 56 to 105 days respectively(fig 2).These preventive oral treatment regiment were followed previous reports in mice[16,18] and rats [8]. RESULTS In our routine health monitoring examination, the serology test showed that no pathogen was detected. No pathogens or potential pathogens were detected in the intestinal contents and tracheal lavage speciments based on routine bacteriological cultures. However, parasite examination demonstrated rat pinworm, Syphacia muris, in research colony (10/16) and mice pinworm, Syphacia obvelata, in our barrier SPF mice (1/28). Those two types of Syphacia spp. eggs were very similar in shape. However,differentiation from eggs of S. muris can be done on the size. Syphacia obvelata eggs are larger ( µm) than those of S. muris (75 29 µm) and show asymmetrical, crescent-shaped (Fig 1). All of these research colony were euthanized by CO2 at the first day found pinworm eggs positive, did not treat any more. In the two stage of treatment, pinworm eggs were found in days 10 and by cellophane tape impression. Those are localized in room B116, including BALB/cByJ and C57BL/6J mice. The cellophane tape impressions were taken, one from each different cage on days and It got negative results of 0/245 and 0/244 respectively (Table 1). The examination of 4,862 cellophane-tape impressions of the anus, 1082 cecal examination from euthanized rats and mice, as well as 347 MIF concentration stool smear during and after treatment period and for 24 months afterwards confirmed the efficacy of treatment.(table 1, 2). 6

7 Fig1. Cellophane tape preperation of Syphacia spp. eggs. Syphacia obvelata eggs are larger ( µm) than those of S. muris (75 29 µm) and show asymmetrical, crescent-shaped. A. Syphacia obvelata eggs, 100 B.Syphacia obvelata eggs, 400 C. Syphacia muris eggs, 200 D. Syphacia muris eggs, 400 (Mice) (Rat) (Day) 1% ivermectin spray whole cages, 1.8 to 2.7 mg for mice cages, 3.6 to 5.4 for rat cages Piperazine citrate administrated at a rate of 3 g/l in the drinking water, twice a week 7

8 Ivermectin mg/ml in drinking water Oral thiabendazole-medicated chow (0.2%) was feed Oral fenbendazole-medicated chow (150 ppm) was feed No any treatment, fresh water and normal chow suppled Fig 2. Schematic representation of treatment regimens used for eradication of Syphacia obvelata and Syphacia muris. Shaded intervals indicate duration of anthelmintic treatment. Table 1. Results of parasite examination of mice colony Days Cellophane tape MIF Direct smear Pre-Rx a 1/224 1/28 1/ b /102 (10 th day) / /265 (22 nd, 23 rd day) / / / / /903 0/181 0/ /582 0/53 0/394 Total 4/2821 1/262 1/665 a. Pre-Rx-30 day period prior to start of treatment b. Day 0: 11/20/2000 Table 2. Results of parasite examination of rats Days Cellophane tape MIF Direct smear Pre-Rx a 0/118 (10/16) b 0-7 c / / / / /

9 /814 0/25 0/ /509 0/60 0/258 Total 0/2041 0/85 0/417 a. Pre-Rx-30 day period prior to start of treatment b. Clean conventional research colony were found pinworm postive on 11/9/2001, those animals were all euthanized on 11/10/2000. c. Day 0: 11/20/2000 DISCUSSION In the present work, due to oral fenbendazole and thiabendazole-medicated chow cann t not available right now from USA saler, a treatment consisted of alternating the two drugs (piperazine and ivermectin spraying) over the first 8-week period, associated with hygiene and filter-top cages were tested in our animal facility. Ivermectin is the 22,23-dihydro derivative of avermectinb1, amacrocyclic lactone produced by an actinomycete, Streptomyces avermitilis.it is active at extremely low dosage against a wide varity of nematode and arthropod parasites, apparently by its action on the mediation of neurotransmission by γ -aminobutyric acid(gaba).it is effective only on GABA-dependent neurotransmission parasites [2].Ivermectin emerged as the larvicidal drug of choice owning to its high efficacy and underdetectable toxic side effect, no toxicity was observed even at the highest dose (25mg/kg) [17]. The pinworm eggs persisted for 10 and days after start of treatment. The reason might be mice didn t drink piperazine citrate very well and ivermectin has no activity against pinworm ova [10]. However, after the first 8 weeks (56days) treatment, no more eggs were detected. These results strongly indicate the treatment regiments are effective. A few mice, FVB and C57BL/6J mice, developed blindness when spraying 1% ivermectin to the whole cages, so we changed the treatment regimen of mice in the seven to eight week from piperazine in drinking water and spraying ivermectin to the 0.007mg ivermectin in drinking water for two consecutive weeks. The daily water intake was15 ml per 100g body weight for mice and 10 ml for rats [6]. From these data, the daily doses of piperazine would be 315 mg/kg/day for mice and 210 mg/kg/day for rats and daily doses of ivermectin would be 1.05 mg/kg/day for mice and 0.7 mg/kg/day for rats [19]. That s the reason why we use mg/ml ivermectin[13,19] in drinking water and adjust piperazine citrate from 2.1g/L in drinking water [13,16,19] to 3 g/l for more anthelmintic effect [18].Piperazine compound are less effective against 9

10 immature oxyurids[8].the administration of piperazine citrate at mg/kg in drinking water for a week,followed by an interruption for a week and another treatment during the third week has been used extensively[9].this protocol is carried out easily and reduces the number of oxyurids,but generally does not eradicate the parasites. Combined ivermectin and piperazine citrate treatment in tape water have been tried successful [13,19 ]. Single treatment of ivermectin and piperazine citrate treatment may proved unsuccessful in the eradication of pinworms, since virable eggs were detected from two to four months after the end of treatment[13]. For preventing the recurrence the eggs from environmental contamination, another 6 weeks second stage oral treatment was carried on. These include 6-week oral 0.2% thiabendazole-mediated chow in mice and 150 ppm fenbendazole-mediated chow diet in rats was chosen with excellent results. Fenbendazole and thiabendazole are all benzimidazole anthelmintic. They are very safe and convinent. The LD 50 of fenbendazole in laboratory animals exceeds 10g/kg when administered PO. Feeding 150 ppm fenbendazole mediated chow for treatment of Syphacia muris in rat may need five 7-day periods, no other manipulation to facilitate eradication [8]. Feeding 0.1% thiabendazole-mediated chow is a more potent anthelmintic than piperazine,had the advantages of being ovicidal, cheap, readily available and safe to use for Syphacia obvelata [16].We decide to follow these two drug in the second stage treatment of pinworm,for rat and mice respectively. Intensive cellophane-tape impressions were taken during and after treatment period and for 24 months afterwards confirmed the efficacy of treatment. The long period of treatment and post-treatment surveillance was considered crucial because Syphacia muris egg may have persisted on the perianal region for up to 17 to 22 days [7,8], compared with present study that Syphacia obvelata eggs were found days after treatment. Our observation that two courses of piperazine with one ivermectin treatment are insufficient to eliminate pinworm infection is in agreement with other reports [1,4,10]. Ivermectin (2 mg/kg) given three times at 7-day or 9-day intervals to rats was effective for eradication of pinworms. In contrast, treatment given two times was ineffective [7]. Ivermectin eliminate adult worm but had no effect on ova, it needed four or five 4 day course of ivermectin treatment [10]. Ova are very light and easily aerosolized, thus easily transmitted directly as well as by fomites [12]. Anal tape preparations might be not a reliable diagnostic aid and merely consisted of limited means of identifying infected animals in rabbit pinworm 10

11 Passalurus ambiguous [3] and Aspicuris tetraptera because they normally deposited eggs in the colon rather than perianal region [18]. However, it had 88% sensitivity in detecting pinworms [7].Cellophane tape impression may give 5-25% intermittently false negative results during the follow-up period [10]. However, most of the reports still use cellophane tape impressions [1,3,,7,8,10,12,13], cecal contents examied for adult worms [1,8,10], as well as floatation[10] for pinworm diagnostic criteria. A report said that S. obvelata in mice when eggs were not detectable by anal tape 5 days post-treatment [7]. This apparent persistence of eggs could be the result of low-level chronic or intermitted shedding by a small population of nematodes that was not immediately eliminated by treatment [7]. Here we report the first case of the successful eradication of pinworm infection in both rat and mice colonies with thousands of animals. Several factors have been considered to lead to our cocktail anthelmintic therapy, such as effectiveness of anthelmintic, labor cost, animal adaptation to treatment, and the availability and transportation of treatment chow diets from overseas. Our experience will offer a successful example of pinworm eradication program for large rodents breeding center in the world. REFERENCES 1. Battles AH, Adams SW, Courtney CH, Mladinich CRT. Efficiency of ivermectin against natural infection of Syphacia muris in rats. Lab Anim Sci 37 (6): , CampbellWC, Fisher MH, Stapley EO, Albers-Schonberg G, Jacob TA. Ivermectin:a potent new antiparasitic agent. Science221: , Duwel D, Brech K. Control of oxyuriasis in rabbits by fenbendazole. Lab Anim 15: , Flynn BM, Brown PA, Eckstein JM,Strong D.Treatment of Syphacia obvelata in mice using ivermectin. Lab Anim Sci 39 (5): , Flynn RJ. Chapter 7 Nematodes. In:Parasites of laboratory animals. Flynn RJ, ed. 1st ed. Iowa Sate University Press, Ames, USA, , Harkness JE and Wagner JE. Chapter 2 Biology and husbandry In :The biology and medicine of rabbits and rodents., C. Cann, S. Hunsberger, and S. Rockwell eds.,3rd ed. Williams and Wilkins, USA, pp13-73, Huerkamp MJ. Ivermectin eradication of pinworms from rats kept in ventilated cages. Lab Anim Sci 43 (1): 86-90, Huerkamp MJ, Benjamin KA, Zitzow LA, Pullium JK, Lloyd JA, Thompson WD, Webb SK, Lehner NDM. Fenbendazole treatment without 11

12 enviromental decomtamination eradicates Syphacia muris from all rats in a large, complex research institution. Lab Anim Sci 39 (3): 9-12, Hoag WG. Oxyuriasis in laboratory mouse colonies. Am J Vet Res Jan: , Klement P, Augustine JM, Delaney KH, Klement G, Weitz JI. An oral ivermectin regimen that eradicates pinworms (Syphacia spp.) in laboratory rats and mice. Lab Anim Sci 46 (3): , Kubo N, Iwaki T, Hara T, Shibahara T. Effective eradication of rat pinworm, Syphacia muris, by anthelmintic therapy with pyrantel pamoate and ivermectin. (in Japanese) 實驗動物技術 34 (1): 17-26, LeBlanc SA, Faith RE, Montgomery CA. Use of topical ivermectin treatment for Syphacia obvelata in mice Lab Anim Sci 43 (5): , Lipman NS, Dalton SD, Stuart AR, Arruda K. Eradication of pinworms (Syphacia obvelata) from a large mouse breeding colony by combination oral anthelmintic therapy. Lab Anim Sci 44 (5): , Mullink JWMA. Pathological effects of oxyuriasis in the laboratory mouse. Lab Anim 4: , National Research Council. Infectious disease of mice and rats: Institute of Laboratory Animal Resources. Committee on Infectious Diseases of Mice and Rats. National Academy Press, Wasington, D.C., Owen D, Turton JA. Eradication of the pinworm Syphacia obvelata from an animal unit by anthelmintic therapy. Lab Anim 13: , Sayles PC, Jacobson RH. Effects of various anthelmintic on larval stages of Nematospiroides dubius (nematode).j Parasitol 69(6) , Taffs LF. Pinworm infections in laboratory rodents: a review, Lab Anim 10: 1-13, Zenner L. Effective eradication of pinworms (Syphacia muris, Syphacia obvelata and Aspiculuris tetraptera) from a rodent breeding colony by oral anthelmintic therapy. Lab Anim 32: , 大小鼠繁殖中心蟯蟲感染之雞尾酒療法 1 梁鍾鼎 1 李秉進 1 吳憲青 1 黃彥智 1 張維正 1 許德育 1,2 * 梁善居 12

13 1 財團法人國家實驗研究院國家實驗動物中心, 115 台北市南港區研究院路二段 128 號 2 國防大學實驗動物中心, 114 台北市內湖區民權東路 161 號 摘要國家實驗動物中心在 89 年 11 月每季例行健康監測時發現外圍研發動物 SD 大鼠出現大鼠蟯蟲 (Syphacia muris, 10/16), 隔離區小鼠發現小鼠蟯蟲 (Syphacia obvelata, 1/28), 立即撲殺外圍所有動物, 並對隔離區動物開始投藥, 使用 0.1% Ivermectin 噴灑鼠籠, 一週一次, 分別於第 天間隔投藥 在第 及 38 天時全面供應動物房 piperrazine citrate,3 g/l 加於飲水中投藥, 每週二次 但在投藥過程中, 肛門貼片發現蟯蟲卵於投藥期第 10 及 天仍出現於感染房 BALB/c 小鼠 所以決定於第 42,49 天使用 mg/ml Ivermectin 添加於飲水中, 一週一次 同時於 天大鼠使用 150 ppm fenbendazole 加藥飼料, 小鼠使用 0.2% thiobendazole 加藥飼料 其它配合措施包括感染動物房全面鼠籠加蓋, 可疑污染區以噴火殺蟲卵, 研發組動物全數撲殺, 感染區減產及停止配種, 經連續 2 年監測, 總計肛門貼片檢查 4862 項次, 腸道抹片 1082 項次,MIF 濃縮蟲卵 347 項次檢查, 未發現蟲卵及成蟲 關鍵字 : 蟯蟲 雞尾酒療法 13