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Fenbendazole remains the drug of choice to treat pinworm infection in laboratory rodents. When fenbendazole was last reviewed (15 y ago), the literature supported the drug's lack of toxic effects at therapeutic levels, yet various demonstrated physiologic effects have the potential to alter research outcomes. Although more recent reports continue to reflect an overall discordancy of results, several studies support the premise that fenbendazole affects the bone marrow and the immune system. No effects on reproduction were reported in an extensive study that assessed common treatment protocols in mice, and food intake was unchanged in rats. Behavioral studies are sparse, with only a single report of a subtle change in a rotarod performance in mice. Notably, unexpected results in tumor models during facility treatment with fenbendazole have prompted preclinical and clinical studies of the potential roles of benzimidazoles in cancer.

Trichuris spp. are common helminths in NHP, and benzimidazoles and avermectins have both been used to treat these intestinal parasites. The current study compared the efficacy of fenbendazole and ivermectin against natural infection of Trichuris spp. in African green monkeys ( Chlorocebus sabaeus ). Anthelmintic-naive animals ( n = 65) were randomly assigned to 4 groups: an untreated control group, and 3 groups treated with either fenbendazole, ivermectin, or both compounds. Fecal samples were collected before treatment and on days 7, 14, 28, and 60 after treatment, and fecal egg counts (FEC) were determined by using fecal flotation. The mean percentages of FEC reduction at day 60 were 100%, 86%, and 100% for treatment with fenbendazole, ivermectin, and both compounds, respectively. Analyzing the time series of FEC by using a Bayesian generalized linear model showed no significant difference in the proportional reduction in FEC among the 3 treatment groups, although all FEC from treated groups were significantly lower than the FEC of the control group. In contrast, the probability of shedding was highest in the ivermectin group and the lowest in the animals treated with both compounds. The probability of shedding differed significantly between the fenbendazole and ivermectin groups and between the ivermectin and combined-treatment groups. In conclusion, both fenbendazole and ivermectin are effective anthelmintics in treating Trichuris spp. infection in African green monkeys. All treatment groups showed significant reductions in FEC when compared with baseline counts and control animals; however, fenbendazole may be more effective than ivermectin when used solely or in combination with other anthelmintic treatments.

Spironucleus muris is an intestinal protozoal pathogen that can infect various species of rodents. The infection can have a wide range of clinical presentations, from no signs of disease to death. In addition, this pathogen can adversely affect research results, especially immunologic and gastrointestinal studies. For these reasons, institutions may exclude Spironucleus muris . However, despite rigorous efforts to keep this pathogen out, it can be common in rodent colonies. The current recommended approach to eradicating this pathogen is by testing and culling positive animals. A similar organism, Giardia muris, has been effectively eliminated by using chemotherapeutics. Therefore, the objective of this study was to determine whether S. muris is also susceptible to chemotherapeutics. Naturally infected mice were randomized to treatment groups after confirmation of positive infection via PCR. Mice received either metronidazole, fenbendazole, a combination of metronidazole-fenbendazole, or acidified water (control) treatments for a period of 4 wk. Each week fecal testing of S. muris was performed via PCR to evaluate the effectiveness of the treatments. At the end of the 4 wk period, mice were euthanized via CO₂ inhalation and segments of the proximal gastrointestinal tract were submitted for histopathologic analysis. Treatment with metronidazole or fenbendazole alone or in combination, failed to clear S. muris infected mice. After 4 wk of treatment, none of the mice given fenbendazole via sucralose medicated gel were positive by either PCR or histopathology; however, this finding is most likely due to intermittent shedding rather than chemotherapeutic success. Therefore, the recommendation remains to test-and-cull or rederive mice as necessary to eliminate S. muris from laboratory animal facilities.

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM-FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 μg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM-FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM-FBZ. All baboons treated with IVM-FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM-FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura.

Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered.

This review summarizes findings from toxicologic, carcinogenic, immunologic, and metabolic studies on fenbendazole (FBZ). Currently, FBZ is used to treat or prevent pinworm outbreaks in laboratory rodents. Because antiparasitic treatments usually are not part of experimental designs, interactions from the medication on the outcomes of ongoing experiments are a concern. At therapeutic levels, FBZ does not alter the total content of cytochromes P450 but does induce certain hepatic cytochrome P450 isoforms, namely 1A1, 1A2, and 2B1. Although expressed constitutively at low or undetectable levels, these isoforms particularly are known for bioactivating a number of procarcinogens. Lifetime studies in rats have shown that FBZ is not a carcinogen but that it may behave as a tumor promoter when given after certain initiators. Unlike in other animal species, FBZ treatment-associated myelosuppression has not been reported to occur in rodents. The few currently available immunologic studies in mice, including an autoimmune model, have not shown effects on selected immune responses. However, data from other animal species suggest that the ability of B and T lymphocytes to proliferate in the secondary immune response may be suppressed during treatment with FBZ.

We evaluated the efficacy of fenbendazole (FBZ) and milbemycin oxime (MO) in the treatment of baboons (Papio cynocephalus anubis) with naturally acquired Trichuris trichiura infection by comparing fecal egg count reduction (FECR) tests. We assigned 7 baboons, each singly housed and confirmed infected with T. trichiura, to treatment groups of FBZ (n=3) or MO (n=3), or as a control (n=1). All (100%) baboons that received FBZ stopped shedding T. trichiura eggs within 6 d of treatment, and fecal egg counts remained negative at 65 d after treatment. Although the number of T. trichiura eggs shed per gram of feces from 2 (67%) baboons decreased significantly after the second treatment with MO, this regimen never totally eliminated eggs of T. trichiura. The results of our study indicate that FBZ was more effective for treating baboons with T. trichiura than was MO.

A group of 12 domestic pigeons (Columba livia domestica) was treated for capillariasis by use of fenbendazole at 30 mg/kg orally once daily for 5 d. After treatment, 8 of the 12 pigeons exhibited signs of anorexia, lethargy, and dehydration; these birds died within 2 d after the onset of clinical signs. A total of 6 birds were necropsied, and all had unremarkable gross findings. Microscopic examination of tissues revealed acute hemorrhagic enteritis, diffuse lymphoplasmacytic enteritis, small intestinal crypt necrosis, periportal lymphoplasmacytic hepatitis, bile duct hyperplasia, and renal tubular necrosis. Erythrocytes in blood samples collected from surviving birds demonstrated polychromasia compatible with a regenerative anemia. The clinical and histopathologic findings in these pigeons were consistent with recent reports of fenbendazole toxicity in domestic pigeons and other columbiform birds.

Fenbendazole is commonly used in laboratory animal medicine as an anthelmintic for elimination of pinworms. It is generally regarded as a safe drug with minimal side effects. In our facility, 2 breeding colonies of rats were treated with fenbendazole to eliminate pinworms. Analysis of the breeding records revealed that feeding Sprague-Dawley rats a diet containing fenbendazole on a continuous basis for 7 consecutive weeks was associated with a significant reduction in litter size. Although the mechanism underlying this effect is unknown, the finding prompts caution when using fenbendazole to treat valuable breeding colonies or strains that are poor breeders.

Pinworm infection in rodent laboratories is common and often treated with fenbendazole, which is effective and has a low toxicity level. However, very little is known about the behavioral effects of the drug. The purpose of this study was to determine the behavioral effects of fenbendazole on rats tested by using various conditioning and timing procedures. These behavioral effects were examined both between animals (i.e., control versus medicated treatments) and within animals (baseline-treatment-baseline design). Fenbendazole reduced the detection of pinworm eggs, and it had no significant behavioral effects across multiple levels of analysis (e.g., from overall response rates to response patterns to interresponse intervals). All behavioral differences (e.g., discrimination ratios) were a result of task variables. These results suggest that behavioral studies are unlikely to be influenced by fenbendazole treatment given before or during a study.

Rodent pinworms rarely cause clinical disease, but infestation can affect experimental results. Our facility maintained a colony of Wistar rats for behavioral pharmacology studies that had been infested with Syphacia muris for > 15 years. The laboratory in which the animals were housed encompassed several rooms and contained a variety of complex behavioral equipment, including > 60 operant chambers. Several prior attempts to eliminate the pinworms were unsuccessful because of inadequate duration of treatment and incomplete environmental decontamination. Many of the rats in this colony were food-restricted as part of behavioral studies. Pinworms were eliminated from these animals by treating them with 450 ppm fenbendazole-containing feed for 3 consecutive weeks followed by 6 weeks of alternating every other week with standard rodent diet. Rats not on food restriction protocols were treated on the same schedule with 150 ppm fenbendazole-containing feed. Environmental decontamination of eggs from the behavioral equipment was not attempted. One year after treatment, the colony has remained free of S. muris. We adapted previously published protocols to our situation, including the problem of food-restricted rats and unfeasible environmental decontamination, to eradicate S. muris from our colony.

The pinworm Syphacia muris was eradicated from rats after treatment with fenbendazole-medicated chow (150 ppm) and without environmental decontamination for > 54 months. However, this regimen was successful only when the treatment was delivered and efficacy monitoring was done by personnel of the institutional animal resources program. The same pinworm elimination program failed 7 to 24 months after the cessation of treatment in a satellite colony in which animal care, including provision of medicated diet and sample collection for efficacy monitoring, was provided by research personnel. A failure to uniformly deliver adequate therapeutic doses or reinoculation of rats with pinworm eggs from the contaminated environment could not be excluded as causes of the failure. However, there were risk factors, and animal care practices unique to the satellite colony that may have facilitated the re-emergence of pinworms. These risk factors included hand-washing of cages, storage of contact bedding in areas that were not vermin-proof, and animal care provided by personnel having contact with rodents of pet-store origin.

This study evaluates the efficacy of various treatment methods to eradicate Dentostomella translucida from Mongolian gerbil colonies. The following five treatment methods were instituted in naturally infected groups of 10 gerbils each: topical ivermectin misting, ivermectin-medicated drinking water, piperazine citrate-medicated drinking water, fenbendazole-medicated feed, and a combination of ivermectin-medicated drinking water and fenbendazole-medicated feed. Treatment success was assessed by using weekly fecal flotations, with necropsy examinations performed on fecal-negative gerbils (except those in the misted group) at 5 weeks after the last treatment. Topical ivermectin misting left 40% of gerbils fecal-positive. With piperazine citrate-medicated drinking water, 60% of the gerbils were fecal-positive; the remaining 40% had adult worms in their digestive tract at necropsy. Ivermectin-medicated drinking water caused 80% of the gerbils to be negative on fecal flotation. On necropsy, however, all but one of these gerbils harbored adult pinworms. Treatments with fenbendazole-supplemented feed alone or in combination with ivermectin-treated water resulted in no fecal shedding or evidence of adult pinworms on necropsy examination. Of the five treatments evaluated, only those using fenbendazole-medicated feed (150 ppm) provided a practical and reliable treatment method to eradicate pinworm infections in Mongolian gerbil colonies.

Syphacia muris parasitism was eliminated from rats and voles by feeding fenbendazole-medicated chow (150 ppm) for five 7-day periods; treatment periods were separated by 7-day periods of feeding non-medicated chow, yielding atotal treatment course of 9 weeks. No other manipulations to facilitate eradication, including the use of filter tops, autoclaved cages, environmental decontamination, colony depopulation, breeding cessation, and research restriction, were done. The examination of 3143 cellophane-tape impressions of the anus and 160 cecal examinations from euthanized rats and voles during the treatment period and for 7 months afterwards confirmed the efficacy of treatment. Treatment was rapidly effective in voles. In rats, pinworm eggs persisted at high levels for 2 weeks after the start of treatment, but no eggs were found after 22 days.

Two cases of gongylonematiasis in common marmosets of two research facilities in Germany are reported. The helminthiasis was transmitted from colony A to colony B by one infected female and within colony B by cockroaches (Blatella germanica). Four of 40 cockroaches examined in colony B were infected with rhabditiform larvae. Clinical signs of disease in the infected animals consisted of intense itching and scratching of the edematous and slightly hyperemic perioral tissues. Histologically the adult helminths lodged predominantly in the mucous membranes of the upper and lower lips; they were less frequently present in the labial cutaneous parts or in the tongue and could not be seen in the esophageal wall, bronchi, or abdominal organs. The helminthic infection probably caused minor to moderate mixed inflammatory infiltrates of the periesophageal connective tissues and intense inflammation of the deep lingual muscular tissues. Lesions of the mucosal membranes of the lips and tongue had predominant accumulations of neutrophilic granulocytes, lymphocytes, and mostly degranulated mast cells with only a few eosinophilic granulocytes. In the cutaneous part of the lips multifocal microabscesses were considered to be secondary lesions from the intense scratching.

Immunologic function was tested both in vivo and in vitro in mice undergoing prophylactic anthelminthic therapy with three agents to assess whether these drugs affected immune responses. This study was performed because investigators often are concerned about the effect of drug treatment on the induction of specific immune responses. While helminthic infestation is recognized as deleterious to the host, it is unclear whether anthelminthic treatment might be immunosuppressive. The effects of piperazine or trichlorphon administered to drinking water or fenbendazole administered in feed were insignificant in BALB/c mice. The induction of allospecific cytolytic T lymphocytes (CTLs) in vitro, influenza specific memory T cells in vivo, influenza specific antibody secretion in vivo, or influenza-specific helper T cells and CTLs in vitro were examined. Results of this study indicate that anthelminthic treatments did not interfere with immune responses.