Chapter 013, Bacterial Diseases (American College of Laboratory Animal Medicine)

Eine neue Methode zur raschen Erkennung des Choleravibrio und des Typhusbacillus. Available from ASM Archives. Zur Kenntniss der Antitoxinwirkung. Alkoholische Gahrung ohne Hefezellen. Berichte der Deutschen Chemischen Gesellschaft, Remarks on the plague prophylactic fluid.

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Remarks on vaccination against typhoid fever. Sur l'agglutination et la dissolution des globules rouges par le serum d'animaux injectes de sang defibrine. On refractory subcutaneous abscesses caused by a fungus possibly related to the sporotricha. Ueber ein Contagium vivum fluidum als Ursache der Fleckenkrankheit der Tabaksblatter. Centralblatt fur bacteriologie und Parasirenkunde, Part II, 5: The organizing meeting of the Society of American Bacteriologists is held at Yale, December 28, The Society is the first independent organization devoted to the promotion and service of bacteriology in the United States.

It later becomes the American Society for Microbiology. There was no formal published paper but see: Based on work of Walter Reed , it is demonstrated that Yellow Fever is caused by a filterable virus transmitted by mosquitoes. The agent is similar to that reported in by Loffler and Frosch for foot and mouth disease of cattle.

This is the first report of a viral agent known to cause human disease. Based on the findings of the Yellow Fever Commission, an anti-mosquito campaign was carried out, resulting in the eradication of yellow fever in Havana. No account was published immediately, but the papers of the Yellow Fever Commission were published in Papers by various authors of the Yellow Fever Commission.

A new pathogenic mould. Sur l'existencede substances sensibilisatrices dans la plupart des serums antimicrobiens. A new substance indispensable to the development of yeast. On the possibility of the occurrence of trypanosomiasis in India. On the cultivation of Trypanosoma lewisi. Contributions to Medical Research, Ann Arbor: Phenomenes de reduction produits par les microbes. Beitrage zur kenntnis des lebens dur humuspilze und der chemischen vorgange bei der humusbildung. Uber Spirochatenbefunde in Lymphdrusensaft Syphilitischer. Concerning "Sotto-Kin" a bacillus of a disease of the silkworm.

Eine serodiagnostische reaktion bei syphilis. Ueber Bakterien, welche Methan als Kohlenstoffnahrung and energiequelle gebrauchen. A protozoan general infection producing pseudo tubercules in the lungs and focal necroses in the liver, spleen, and lymph nodes. A Centenary Perspective, edited by Wolfgang K. Link to Excerpt from Microbiology: Smith, Erwin, and C. A plant tumour of bacterial origin. A micro-organism which apparently has a specific relationship to Rocky Mountain spotted fever. Die Hauptlinien des Naturlichen Bakterien-Systems. Experimental Transmission of Exanthematous Typhus by body lice Pediculus vestimenti.

Paul Ehrlich announces the discovery of an effective cure Salvarsan for syphilis, the first specific chemotherapeutic agent for a bacterial disease. Ehrlich was a researcher in Koch' s lab, where he worked on immunology. In he became head of the Research Institute for Chemotherapy. He sought an arsenic derivative. The th compound worked.

He brought news of the treatment to London, where Fleming became one of the few physicians to administer it. A more soluble form, Neosalvarsan, is introduced in Ueber Laboratoriumsversuche und klinische Erprobung von Heilstoffen. Francis Peyton Rous discovers a virus that can cause cancer in chickens by injecting a cell free filtrate of tumors.

This is the first experimental proof of an infectious etiologic agent of cancer. In a farmer brought Rous a hen that had a breast tumor. Rous performed an autopsy, extracted tumor cells and injected them in other hens, where sarcoma developed. Rous is awarded the Nobel Prize in Medicine or Physiology in Transmission of a malignant growth by means of a cell free filtrate. A sarcoma of the fowl transmissable by an agent separable from the tumor cells.

An investigation on the nature of ultra-microscopic viruses. Sur un microbe invisible antagoniste des bacilles dysenteriques. The citric acid fermentation of Asperigillus niger. Further studies on Bacterium abortus and related bacteria. A comparison of Bacterium abortus with Bacterium bronchisepticus and with the organism that causes Malta Fever. Some morphological and biological characters of the Spirilla Vibrio fetus, n.

The use of blood agar for the study of streptococci. The soluble specific substances of pnuemococcus, J. A skin test for susceptibility to scarlet fever. Vaccination of bovines against tuberculosis. Eenheid en verscheidenheid in de stofwisseling der microben. Albert Jan Kluyver and Hendrick Jean Louis Donker propose a universal model for metabolic events in cells based on a transfer of hydrogen atoms. The model applies to aerobic and anaerobic organisms. Die einheit in der biochemie. A disease of rabbits characterized by a large mononuclear leucocytosis, caused by a hitherto undescribed bacillus Bacterium monocytogenes.

Frederick Griffith discovers transformation in bacteria and establishes the foundation of molecular genetics. He shows that injecting mice with a mixture of live, avirulent, rough Streptococcus pneumoniae Type I and heat-killed, virulent smooth S. Live, virulent, smooth S. Not until the 's, did Avery, Macleod and McCarty take up Griffith's work and try to explain the results. The significance of pneumococcal types. On the antibacterial action of cultures of a Penicillium, with a special reference to their use in the isolation of B.

Ueber die enzymbildung in Bakterien. Decomposition of the capsular polysaccharide of pneumonococcus type III by a bacterial enzyme. Sulfur bacteria use H2S as a source of electrons for the fixation of carbon dioxide. He posits that plants use water as a source and release oxygen.

On the morphology and physiology of the purple and green sulfur bacteria. Variation and type specificity in the bacterial species Haemophilus influenzae. A new series of graded colloidal membranes suitable for general bacteriological use, especially in filterable virus studies.

The susceptibility of the chorio-allantoic membrane of chick embryos to infection with the fowl-pox virus. Isolation of Coccidiodes immitis Stiles from the soil. La microscopie electronique des onjectes biologiques. A study of four serological types. The cultivation and cultural characteristics of Darling's Histoplasma capsulatum. Domagk uses a chemically synthesized antimetabolite, Prontosil, to kill Streptococcus in mice. It is later shown that Prontosil is hydrolyzed in vivo to an active compound, sulfanilamide. One of the first patients to be treated with Protonsil was Domagk's daughter who had a streptococcal infection that was unresponsive to other treatments.

When she was near death, she was injected with large quantities of Protonsil and she made a dramatic recovery. Domagk is awarded the Nobel Prize in Medicine or Physiology in Ein Beitrag zur Chemotherapie der bakteriellen infektionen. Wendell Stanley crystallizes tobacco mosaic virus and shows it remains infectious. However, he does not recognize that the infectious material is nucleic acid and not protein. Isolation of a crystalline protein possessing the properties of tobacco-mosaic virus.

Liquid crystalline substances from virus infected plants. The utilization of CO2 in the dissimilation of glycerol by propionic acid bacteria. L Ellis and M. The growth of bacteriophage. Sanders Penicillin as a chemotherapeutic agent. An enzyme from bacteria able to destroy penicillin. Die Sichtbarmachung der BakteriophagenLyse im Ubermikroskop. Epidemiology of acute coccidioidomycosis with erythema nodoosum "San Joaquin" or "Valley Fever". The relation of p-aminobenzoic acid to the mechanism of the action of sulphanilamide.

Bacteriostatic and bactericidal substances produced by soil Actinomyces. Genetic control of biochemical reactions in Neurospora.

Further observations on penicillin. The Production of antibodies. The agglutination of red blood cells by allantoic fluid chick embryos infected with influenza virus. Demonstration of pneumoccocal antigen in tissues by use of fluorescent antibody. The identification and characterization of bacteriophages with the electron microscope. Sensitization to horse serum by means of adjuvants. Proceedings of the Society for Experimental Biology and Medicine Salvador Luria and Max Delbruck provide a statistical demonstration that inheritance in bacteria follows Darwinian principles.

Particular mutants, such as viral resistance, occur randomly in bacterial populations, even in the absence of the virus. More importantly, they occur in small numbers in some populations and in large numbers in other cultures. The results, known as fluctuation analysis, show that resistance occurs before exposure to the phage and argues against the adaptation hypothesis of mutations.

Mutations of bacteria from virus sensitivity to virus resistance. Further experiments on cellulose digestion by the protozoa in the rumen of cattle. Effects of streptomycin on experimental tuberculosis in guinea pigs. Studies on the chemical nature of the substance inducing transformation of pneumonococcal types.

Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research

Induction of transformation by a deoxyribo-nucleic acid fraction isolated from pnuemococcus type III. Albert Schatz , E. Bugie , and Selman Waksman discover streptomycin, soon to be used against tuberculosis. Streptomycin has the same specific antibiotic effect against gram negative microorganisms as penicillin does on gram positives.

Waksman is awarded the Nobel Prize in Medicine or Physiology in Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Where Does the Trail Lead? Mutation of bacterial viruses affecting their host range. Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides.

Gene recombination in Eschericia coli. Thermal studies on the factors responsible for tumour initiation in crown gall. Activity of vitamin B12 for the growth of Lactobacillus lactis. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. In the report by Richter et al.

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The authors of the latter report thoroughly described several aspects of an outbreak of hyperkeratosis in athymic nude homozygous and heterozygous mice, with hairlessness being a contributing characteristic. Those authors found that transmission was accomplished via direct contact and via contaminated bedding and gloves Clinical signs included flaking of the skin, primarily along the dorsum, and, in some animals, pruritus.

Pathologic changes were characterized as orthokeratotic hyperkeratosis and follicular keratosis; marked acanthosis; and mild neutrophilic, macrophage, and mast cell infiltration While reports of natural infection of mice with this Corynebacterium sp. Nude mice naturally infected with this pathogen would be unsuitable for dermatologic and possibly other research projects. While many species of mites infest wild rodents, only three species of nonburrowing mites are commonly found on laboratory mice and rats. Myobia musculi and Myocoptes musculinus infest mice, while Radfordia affinis infests rats Mice are much more commonly infested than are rats.

The life cycles of all three mites are direct, with all stages egg, nymph, and adult present on the host. Consequently, hairless mice are not susceptible. Life cycles require roughly 3 weeks for completion. Transmission is via direct contact. Once a facility is infested, eradication of the parasites is achievable but labor-intensive.

Clinical signs vary in severity depending upon host factors and mite species. C57BL and related strains are most susceptible to severe disease, due to overexuberant type 1 hypersensitivity reactions Infestation may be asymptomatic or may cause wasting; scruffiness; pruritus; patchy alopecia, which may be extensive; accumulation of fine bran-like material, mostly over affected areas; self-trauma to the point of excoriation or amputation; and secondary pyoderma 20 , , Lesions are most common on the dorsum, primarily on the back of the neck and interscapular region.

Pathologic changes include hyperkeratosis, erythema, mast cell infiltration, ulcerative dermatitis, splenic lymphoid and lymph node hyperplasia, and eventual secondary amyloidosis , , Mite infestation has reportedly caused secondarily amyloidosis; altered behavior ; selective increases in immunoglobulin G1 IgG1 , IgE, and IgA levels and depletion of IgM and IgG3 levels in serum; lymphocytopenia; granulocytosis; increased production of IL-4; and decreased production of IL-2 , These immunologic changes are consistent with a Th2-type response, with marked systemic consequences The primary importance of LCMV is as a zoonosis and as a contaminant of transplantable tumors and cultured cell lines , , , Natural infections of mice with LCMV are uncommon, and only mice and hamsters are known to transmit the infection, although rats and many other mammals and chickens are also susceptible , Along with implantation of infected tumors, transmission is via exposure of mucous membranes and broken skin to infectious urine, saliva, and milk and possibly via ingestion In addition, both transovarian and transuterine transmission occur in mice Patterns of infection differ depending on host and pathogen factors, including mouse strain and age, inoculum dose, route of inoculation, and virus strain , , Typical clinical patterns include the persistent tolerant infection, which follows in utero or neonatal infection.

Persistent infection of T-helper lymphocytes, viremia, and lifelong viral shedding occur Clinical signs include initial growth retardation and eventual immune complex glomerulonephritis accompanied by emaciation, ruffled fur, hunched posture, ascites, and, occasionally, death Pathologic features of this pattern, including ICG, stem from unabated B-cell activity, including production of pathologic amounts of anti-LCMV antibodies, lymphoid hyperplasia, and perivascular lymphocyte accumulation In contrast, T-cell activity is diminished.

Eventually, immune tolerance breaks down, resulting in chronic illness with widespread lymphocytic infiltration and vasculitis A second clinical pattern is that of the nontolerant infection This pattern occurs with acute infection of postneonatal mice. Viremia occurs without viral shedding.

Infected mice either die or eliminate the virus, frequently without showing signs of disease Pathologic features of this pattern include necrotizing hepatitis and generalized lymphoid depletion Lymphocytic choriomeningitis is generally seen only following experimental intracerebral inoculation and is not a feature of natural infection Intestinal intraepithelial lymphocytes are also activated Virus-specific antibody is also induced Several investigators have reported effects of LCMV on research; however nearly all of this information comes from experimental infections Natural infection of laboratory mice would jeopardize human health and interfere with a variety of research endeavors, especially those involving the immune system and central nervous system CNS.

Multiple strains exist Mice and mouse cell cultures are the only hosts Rats are not susceptible. The major importance of LDEV is as a contaminant of transplantable tumors and of inocula of other infectious agents serially passaged in mice , , Transmission is via transplantation of contaminated tumors, cells, or serum but may also occur via direct contact, bite wounds, and transplacental or transmammary passage; however, given the short period when viral shedding occurs, the latter routes are less important , Clinical signs are limited to neurologic disorder in selected mouse strains that have been immunosuppressed Generally, however, there are no clinical signs of infection Pathologic changes have not been described in natural infections and are mainly in lymphoid organs in experimental infections.

Virus replication occurs for one cell cycle only in a small population of macrophages. The virus is therefore concentrated in organs with high macrophage populations Transient thymic necrosis, splenomegaly, and lymphocytopenia occur early in the infection LDEV causes persistent viremia, which induces antiviral antibodies and, eventually, circulating antigen-antibody complexes , which may result in a mild membranous glomerulonephritis The diagnostic hallmark of LDEV infection is elevation of lactate dehydrogenase LD levels in serum, which occurs due to reduced clearing of one LD isozyme Levels of other enzymes in serum are also elevated although not to the same extent.

Clearly, infection of laboratory mice with LDEV could seriously alter research results, especially where immune system function is involved, without any outward evidence of infection. TMEV has been found infrequently in laboratory mice and even less often in rats Its primary importance is as a model of poliomyelitis, multiple sclerosis, and virus-induced demyelinating disease , Multiple strains exist and are classified according to virulence.

Because the virus naturally infects the intestinal mucosa, transmission is primarily fecal-oral, although the infection is not highly contagious. Viral shedding occurs for roughly 2 months In addition, transplacental transmission has been documented 2 , and mouse and rat cell cultures may be infected. Generally, no clinical signs of infection are observed.

However, viremia may disseminate virus from the intestine to many tissues, including the liver, spleen, and CNS, where spread via direct extension occasionally results in unilateral or bilateral flaccid paralysis of the hind limbs and, rarely, other neurologic signs , Mouse strains differ in their susceptibility to demyelinating disease , , which is usually induced via experimental inoculation.

In addition, intraperitoneal inoculation results in acute myositis that progresses to a chronic inflammatory muscle disease which may be immune system mediated Clearing of the virus depends on the involvement of virus-specific cytotoxic T lymphocytes and IL-2 , Natural infection of mice has reportedly interfered with the study of other viral infections In addition, TMEV slows the conduction of spinal motor and somatosensory evoked potentials and could compromise studies involving the CNS.

Mouse adenoviruses are dsDNA viruses of the family Adenoviridae. Infections in the mouse, the principal host, have been reported only rarely. Infection of rats has been suspected based on serologic and morphologic studies Transmission of both strains is by contact. MAd-1 has a systemic distribution pattern and may be shed in the urine for up to 2 years This ability of MAd-1 to persist cannot be explained by the model of reduced class I MHC-associated antigen presentation proposed for human adenoviruses Clinical signs have never been observed during natural infection with either strain.

Susceptible mice show symptoms of acute CNS disease, including tremors, seizures, ataxia, and paralysis. Light microscopic examination of CNS tissue revealed petechial hemorrhages, edema, neovascularization, and mild inflammation in the brain and spinal cord In other studies, pathologic lesions were most prominent in the kidneys, heart, spleen, adrenal glands, pancreas, liver, and intestines 52 , , , , MAd-2 may be shed in the feces for 3 weeks in immunocompetent mice and for at least 6 months in athymic mice In contrast to MAd-1, infection with MAd-2 is localized to the intestine, causes no clinical signs, and results in pathologic changes that are limited to intranuclear inclusions in crypt and villous cells of the small intestine Immunity to adenoviruses is primarily humoral.

Mouse adenovirus infection, while uncommon, may interfere with a variety of studies, particularly those involving the CNS, renal, and gastrointestinal systems. Ectromelia virus is the causative agent of mousepox. It is a dsDNA virus in the family Poxviridae. Mice are the natural hosts. Rats may be transiently infected only experimentally Reports of natural infection in laboratory mice have become rare in the United States but continue to be common in Europe.

However, clinical mousepox was recently reported in mice at a U. The mice had been injected with contaminated, commercially produced pooled mouse serum Serologic surveys conducted in the United States occasionally reveal seropositive mice, further confirming that the agent is present.

Transmission is primarily via direct contact and fomites, with skin abrasions serving as portals of entry. Resistance to mousepox varies among mouse strains and is dependent upon multiple genes 76 , In these mice, clinical signs are evident in nearly all members of the colony and consist of foot swelling, pocks, lethargy, depression, and sudden death Following entry via broken skin, the virus replicates locally in skin and lymph nodes and then causes mild, primary viremia and spreads to the liver and spleen.

Massive replication in the macrophages of these organs results in a greater secondary viremia. The virus then localizes in many tissues but most prominently in the skin, conjunctiva, and lymph nodes Pathologic changes include massive splenic, lymph node, thymic, and hepatic necrosis; small intestinal mucosal erosions; and cytoplasmic inclusions in the skin and liver.

Distal portions of the tail and limbs may necrose and slough, giving rise to the name ectromelia While virus persists for several months in the spleens of infected mice, it is shed in the feces for only about 3 weeks Multiple strains of ectromelia virus exist, with the Moscow strain being most virulent. Natural infection of laboratory mice with ectromelia virus would severely compromise most research efforts involving mice. Relatively little is known of the natural biology of H-1 virus, and its significance is low in rats, the natural host, since natural infection does not cause clinical disease and effects on research are few The primary importance of H-1 virus is as a model for experimentally produced malformations in the CNS and skeletal system of rats Transmission is via exposure to infectious urine, feces, nasal secretions, and milk Natural infection with H-1 virus does not cause disease.

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However, pathologic changes observed in experimental H-1 virus infection derive from the need for parvoviruses to infect replicating cells, wherein they are lytic Reports of H-1 virus affecting research are limited to hepatocellular necrosis in rats exposed to pathogens or chemicals causing liver injury and possibly to a reduction of the incidence of Yersinia -associated arthritis , , although in the latter studies other copathogens may also have been present. In spite of the paucity of data incriminating H-1 virus as a confounder of research, natural infection of laboratory rats could alter studies of fetal development.

More is known of the natural biology of KRV than of H-1 virus. As with H-1 virus, rats are the natural host of KRV. Transmission is via direct contact with infectious urine, feces, nasal secretions, and milk or by contact with contaminated fomites. The latter is probably more important than for many other rodent viruses, since parvoviruses are highly resistant to environmental extremes and are highly contagious. In addition, transplantable tumors and cell cultures may be infected , Rats may remain persistently infected for variable times depending upon their age at infection.

Clinical signs of infection are rarely observed but have been reported in rats at day 13 of gestation Rats in that outbreak had reproductive anomalies, including increased fetal resorptions, as well as runting, ataxia, cerebellar hypoplasia, and jaundice of many offspring. In another report, scrotal cyanosis, abdominal swelling, dehydration, and death occurred in young rats exposed to serologically positive adults Like other parvoviruses, KRV infects actively replicating cells and results in cell lysis and tissue destruction.

Therefore, KRV causes lesions primarily during fetal development and neonatal life. Infection may persist for variable times depending upon the age of the rat at infection, but it generally does not last beyond about 3 to 4 months Lesions may occur in multiple organs, including the CNS and gastrointestinal and reproductive systems ; they consist of focal necrosis, frequently in the liver; hemorrhage; and hypoplasia Lastly, KRV may alter leukocyte adhesion to rat aortic endothelium and may reduce the incidence of Yersinia -associated arthritis , , although in those three studies other copathogens may also have been present.

KRV could profoundly interfere with research involving a variety of body systems, especially if infection occurred during fetal development. Minute virus of mice MVM is an ssDNA virus of the family Parvoviridae and therefore shares many biological features with other murine parvoviruses such as mouse parvovirus-1, H-1 virus, and Kilham rat virus. Like other parvoviruses, MVM is extremely contagious. Transmission is primarily via exposure to infectious feces and urine but may also be via fomites and via exposure to nasal secretions.

In addition, MVM is commonly found as a contaminant of transplantable tumors and mouse leukemia virus stocks , Multiple strains have been described. Mouse strains differ in their susceptibility to MVM 78 , 79 , ; however, there are usually no clinical signs with MVM infection, and natural infections cause no pathologic changes. Experimental infection will, however, cause damage to multiple organs if infection occurs during fetal development or shortly after birth 78 , , While direct evidence of interference with research is limited to a report of myelosuppression , it can be surmised that MVM may interfere with research involving the immune system, since MVM I infection results in T-lymphocyte lysis and altered B- and T-lymphocyte activities and MVM p suppresses the growth of ascites tumors Mouse hepatitis virus MHV is probably the most important pathogen of laboratory mice.

Rats may also become infected but only as sucklings and only under experimental conditions It is extremely contagious and is transmitted primarily via aerosol, direct contact, fomites, and, experimentally, via transplantable tumors and transplacental passage , , Susceptibility, tissue tropism, clinical signs, and pathologic lesions are dependent on several host, environmental, and pathogen factors 30 , 70 , , Approximately 25 strains or isolates of MHV have been described and have been classified as either respiratory or enterotropic.

Recently, an outbreak of a highly hepatotropic strain of MHV was reported from a breeding colony of nude mice in Taiwan The presence or absence of the MHV receptor, a glycoprotein in the carcinoembryonic antigen family of the Ig superfamily, may determine tissue tropism Respiratory polytropic strains establish in the nasal mucosa, descend to the lungs, and disseminate hematogenously throughout the body or ascend along neurons to the CNS 35 , , , Intestinal involvement is usually absent.

Enterotropic strains may also become established in the nasal mucosa or in the intestinal tract and disseminate only locally to the liver, abdominal lymph nodes, and, in some cases, the CNS , Pulmonary involvement is uncommon.

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While polytropic strains have historically been considered more common, this situation is thought to have reversed 95 , Lesions are present for only 7 to 10 days following infection, are dependent upon strain of virus, and are characterized by multifocal necrosis. Additionally, multinucleate syncytial giant cell formation occurs and may be associated with fragmentation and rearrangement of the Golgi apparatus Lesions due to polytropic strains may be observed in the olfactory mucosa, brain, lungs, and liver, while lesions due to enterotropic strains are generally, though not always, confined to the intestinal tract.

Lesions caused by either strain tend to be more severe and widespread in immunocompromised mice Most infections follow one of three clinical patterns Enzootic subclinical infection, commonly seen in breeding colonies, occurs when infection is endemic in the colony and is maintained only by the continual arrival of susceptible animals newborns. No carrier state exists, although in a recent study viral RNA was detected in the liver up to 60 days after infection Adults are asymptomatic, and their young become asymptomatically infected by the time passively transferred maternal immunity wanes at weaning.

Epizootic clinical infection occurs less commonly when the pathogen is introduced to a naive colony. Adult infections are again usually asymptomatic. Clinical signs depend upon the virus and mouse strains and are most evident in infant mice; typically, they include diarrhea, poor growth, and death. As the infection becomes established in the colony, the epizootic pattern is replaced with the enzootic pattern.

Immunity to MHV is primarily but not entirely cell mediated; is partially protective between closely related virus strains; and is known to involve T lymphocytes, macrophages, IFN, and NK cells , , , , , Numerous reports document effects of natural or experimental infection with MHV on host physiology and research. In immunocompromised mice, these effects include necrotic changes in several organs, including the liver, lungs, spleen, intestine, brain, lymph nodes, and bone marrow; differentiation of cells bearing T-lymphocyte markers; altered enzyme activities, bilirubin concentration, and antibody responses to sheep erythrocytes in serum; enhanced phagocytic activity of macrophages; rejection of xenograft tumors; impaired liver regeneration; and hepatosplenic myelopoiesis , Clearly, natural MHV infection of laboratory mice with MHV may affect a plethora of scientific studies and seriously compromise the value of these animals as research subjects.

Mark Papich | NC State Veterinary Medicine

Sialodacryoadenitis virus SDAV is a common, important, and highly contagious pathogen of laboratory rats. Transmission is via direct contact and fomites Infant mice, but not adult immunocompetent or scid mice, are susceptible to experimental infection 33 , , Natural infection of mice has not been reported Enzootic infection occurs in breeding colonies and is sustained only by the continual introduction of susceptible hosts newborns. Suckling rats develop transient conjunctivitis. Weanlings and adults are asymptomatic Epizootic infection occurs when the agent is introduced to a fully susceptible population.

Clinical signs are again transient, may vary in severity, and include cervical edema, sneezing, photophobia, conjunctivitis, nasal and ocular discharge, porphyrin staining, and corneal ulceration and keratoconus , Multiple strains of SDAV exist , and tissue tropisms differ somewhat among strains SDAV has a tissue tropism for tubuloalveolar glands of the serous or mixed serous-mucous types Therefore, inflammatory changes consisting primarily of diffuse necrosis are seen in the lacrimal including the Harderian glands and submandibular and orbital salivary glands.

Secondary damage may occur to structures of the eye. Cervical lymph nodes and the thymus may also be mildly necrotic. Some strains of SDAV affect the respiratory tract, where pathologic changes may include patchy necrotizing rhinitis, tracheitis, bronchitis, and bronchiolitis, with multifocal pneumonitis 51 , , Virus is present in tissues for only about 1 week. There is no carrier state, so clinical signs and pathologic changes are transient. In athymic rats, infection is more severe, is persistent, and may be fatal SDAV has been shown to alter estrous cycles, increase embryonic and postnatal mortality , cause depletion of epidermal growth factor in submaxillary salivary glands , cause anorexia and weight loss , , and reduce IL-1 production by alveolar macrophages Natural infections of laboratory rats with SDAV would be expected to interfere with studies involving the lacrimal, salivary, respiratory, ocular, olfactory, reproductive, and immune systems and to interfere with growth of infected newborns.

Corynebacterium kutscheri is a gram-positive bacillus that infects both mice and rats. The oral cavity and large intestine most commonly serve as reservoir sites for a latent carrier stage 8 , 9. Natural infections are usually subclinical 8 , 9 and are revealed only by the immunosuppressive effects of certain drugs, experimental manipulations, or other infectious agents Clinical signs in rats, when present, usually include dyspnea with abnormal lung sounds, weight loss, humped posture, and anorexia.

Hematogenous spread occurs in both species and accounts for abscess formation in various organs. In rats, abscesses commonly develop in the lungs and extend to the pleura, while in mice, abscesses occur more often in the kidneys and liver , Strain differences in colonization sites 9 and susceptibility have been reported. Strain susceptibility may reflect differences in the efficiency of mononuclear phagocytes or cytokine responses Experimental procedures that cause immunosuppression of rats or mice may result in the unwanted development of active C. Encephalitozoon cuniculi is a microsporidian protozoan parasite infecting a wide range of hosts, including laboratory mice and rats.

At least three strains have been identified based on host specificity and other criteria The prevalence remains high in many rabbitries, and rabbits may serve as a source of infection for mice and rats In contrast, the prevalence is low in modern rodent facilities. The primary significance of E.

In addition to infected tumors, transmission is via exposure to infectious urine. Following ingestion, sporoplasm from infectious spores gains entrance to host intestinal epithelium, where multiplication occurs. Continued multiplication results in eventual host cell rupture, with dissemination to other organs, including the brain, kidneys, liver, and lungs Infection is usually asymptomatic in immunocompetent rodents.

Lesions are most commonly found in the kidneys and brain. In the kidneys, lesions consist of intracellular parasites in the renal tubular epithelium and inflammatory changes, with eventual focal destruction of tubules and replacement by fibrous connective tissue, resulting in pitting of the renal surface In the brain, lesions consist of meningoencephalitis.

In rats, but not in mice, there is also multifocal granulomatous inflammation Macrophage microbicidal activity may involve nitrite NO 2 Natural infection of laboratory mice and rats would compromise studies involving the gastrointestinal, renal, and central nervous system and possibly others. Bordetella bronchiseptica is a gram-negative rod commonly found inhabiting the respiratory tracts of rabbits. Transmission is via aerosol, fomites, and contact and occurs early in life. There is a high prevalence of seropositivity in laboratory rabbits Most infections are asymptomatic and become problematic only in association with Pasteurella multocida infection I have also treated cases of rabbit bordetellosis in which no other pathogens could be identified or where a primary infection with P.

Rabbits also occasionally develop B. Typical pathologic changes of the lower respiratory tract are those of suppurative bronchopneumonia and interstitial pneumonitis Microscopically, there may be prominent peribronchial lymphocyte cuffing Similar effects in rabbits could facilitate infection and clinical disease caused by copathogens such as P. It has been reported that rabbits with B. Clinical bordetellosis would compromise the usefulness of laboratory rabbits used in respiratory studies. However, given the high prevalence of latent B.

Clinically affected rabbits should be treated immediately or, preferably, culled. As described above, CAR bacillus is a gram-negative, filamentous, rod-shaped, gliding bacterium. Infection of laboratory rabbits has been reported in the United States and Japan Clinical disease in rabbits has not been demonstrated or induced. Lesions consisted of slight hypertrophy and hyperplasia of ciliated upper respiratory epithelium, with occasional loss of cilia and mild inflammation of the lamina propria. Others have reported seroconversion without the development of either lesions or clinical disease following experimental infection of rabbits with CAR bacillus of rat or mouse origin.

Natural infection of rabbits may confound studies in which upper airway architecture is evaluated histologically. Infection is nearly ubiquitous among rabbit colonies; within a colony, infection is also common, frequently occurs at birth, and increases with age. Transmission is by direct contact and, to a lesser extent, fomite, aerosol, and sexual exposure. Disease susceptibility depends upon host, environmental, and bacterial factors. Differences in susceptibility have been reported among rabbit strains Environmental factors such as shipping, experimentation, wide temperature fluctuations, and high ammonia levels increase susceptibility Lastly, bacterial strains differ in many aspects including growth characteristics and colonization site.

The colonization site may indirectly affect virulence, probably due to production of specific adhesion molecules 59 , , Bacterial strains also differ in endotoxin and exotoxin production and in their ability to resist phagocytosis and killing by neutrophils. However, these factors have not been absolutely correlated with virulence , , Bacterial strains have been grouped based on an indirect hemagglutination assay or gel diffusion precipitin test.

The majority of rabbits infected with P. Transition from asymptomatic to symptomatic infection is related to factors discussed above. When present, clinical signs can occur in nearly any organ, probably due to hematogenous spread of the organism. The most common presentations, in descending order of occurrence, are rhinitis snuffles , conjunctivitis, pneumonia, otitis media, otitis interna, abscesses, genital tract infections, and septicemia Physiologic alterations may also occur Colonization often occurs initially in the pharynx.

The infection quickly spreads to the nasal cavity, from which it disseminates via direct or hematogenous spread to the lungs, middle ear, conjunctival sac, subcutaneous tissues, and visceral organs Regardless of the organ system affected, the hallmark of P. The accompanying exudate is most often purulent. Microscopically, affected tissues may be edematous, hyperemic, congested, and necrotic As alluded to above, the factors responsible for tissue damage are incompletely known but may include the production of toxins, antiphagocytic substances, or adhesions Large amounts of thick pus may also place direct pressure on adjacent tissues, such as in the lungs, and may further compromise organ function.

Eventual natural infection of laboratory rabbits with P. While latent nasal colonization will probably have no effect on experimental studies, clinical pasteurellosis could invalidate several types of studies, particularly those involving the respiratory tract. Adenoviruses are dsDNA viruses that have been recovered from many animal species. However, adenovirus infections are uncommon in rabbits and have been reported only in Europe. Bodon and coworkers 54 , 55 reported isolating an adenovirus from the spleen, kidney, lungs, and intestines of 6- to 8-week-old rabbits with diarrhea.

The virus agglutinated rabbit erythrocytes. Little information is available on the mechanisms and consequences of adenovirus infection in rabbits. Therefore, much of what is known about adenovirus infection of rabbit tissues comes from studies with rabbit models and adenoviruses from other species. Reddick and Lefkowitz observed persistent viral infection of lymphoid tissues following experimental infection of rabbits with human adenovirus type 5. Recombinant adenoviruses have successfully infected rabbit hepatocytes , autologous rabbit vascular interposition grafts , and cultured rabbit corneal epithelial cells Others have used an in vivo rabbit model system to test the efficacy of novel antiviral drugs against human adenovirus type 5 infections These studies illustrate the utility of rabbit-adenovirus model systems.

It is likely that endogenous infections with rabbit adenovirus would interfere with such studies as well as with research on rabbit intestinal physiology or with adenovirus vaccine studies conducted in rabbits Two distinct forms of coronavirus infection have been reported in rabbits. The inability to culture these viruses in vitro has limited experimental study of them.

Rabbit enteric coronavirus, an ssRNA virus, has been detected in the feces of young rabbits with diarrhea in Canada and Europe , , , Serologic surveys have extended knowledge of the range of infected rabbitries to the United States However, only one natural outbreak of disease has been reported, in Germany The cecum was distended with watery fluid, and diffuse inflammation and mucosal edema were found throughout the intestinal tract.

In experimental infections, clinical signs are limited to variable fecal water content without mortality , In one study, the small intestines were congested, with transient evidence of villus tip and M cell necrosis, atrophy, and crypt hyperplasia.

The cecal contents were watery The virus hemagglutinates rabbit erythrocytes but has not been shown to be cytopathic for a variety of cell lines , There is a high level of serologic cross-reactivity between rabbit enteric coronavirus and other mammalian group 1 viruses Therefore, natural infection of laboratory rabbits would not only interfere with research involving the intestinal tract but would also confound research with polyclonal anti-mammalian coronavirus serum produced in infected antibody-producing rabbits.

Lapine parvovirus is an ssDNA virus. Infection has been identified serologically in commercial rabbitries in the United States, Europe, and Japan Like other parvoviruses, transmission is fecal-oral. Clinical signs in neonatal rabbits consist of anorexia and listlessness. Pathologic changes consist of catarrhal enteritis with hyperemia of the small intestine, hypersecretion of intestinal mucus, and exfoliation of small intestinal epithelial cells. Virus can be detected in most visceral organs Natural infection of laboratory rabbits could interfere with research in which rabbit cell cultures or in vitro immunologic assays are used and in research in which architectural changes in visceral organs would be confounding.

Rabbit oral papillomavirus is a dsDNA virus of the family Papovaviridae. The prevalence of infection is low in laboratory rabbit colonies. Development of lesions may be facilitated by damage to the oral mucosa When present, lesions are usually found on the ventral surface of the tongue but may also be found on the mucosal surface of the buccal cavity ; they consist of small whitish growths which may eventually ulcerate before disappearing Histologically, the lesions appear as papillomas Rotaviruses are classified into groups and subgroups The isolate infecting rabbits, group A serotype 3, also infects humans and other animals.

Infection is common in both wild and laboratory rabbits. The virus is extremely contagious, and transmission is fecal-oral. Clinical signs vary depending on host age, exposure history, and the presence of other synergistic organisms In endemically infected colonies, outbreaks are most common in recently weaned rabbits, probably due to waning of passively transferred maternal antibodies. Disease is most severe in preweanlings from naive colonies.

Clinical signs include severe diarrhea, anorexia, dehydration, and high mortality Pathologic changes include marked congestion, distension, and petechiation of the colon ; small intestinal distension with mucosal hemorrhages; and a fluid-filled cecum It should be borne in mind, however, that in most reports of outbreaks, attempts to demonstrate the presence of other pathogens have not been made.

J Vet Pharmacol Ther. J Zoo Wildl Med. Veterinary Microbiology Jul 16; Epub Jan 9. Journal of Clinical Microbiology Nov;51 Journal of Veterinary Internal Medicine Jan;28 1: Epub Nov 1. Equine Veterinary Journal Jul Journal of the American Veterinary Medical Association. Journal of Veterinary Behavior: Clinical Applications and Research. Louis, Missouri, pages , Equine Veterinary Journal Mar;45 2: American Journal of Veterinary Research 73 7: Journal of Veterinary Pharmacology and Therapeutics doi: Antimicrobial Agents and Chemotherapy.

Veterinary Journal Nov; 2: Equine Veterinary Journal Sep Veterinary Surgery Jul;40 5: Veterinary Medicine International Epub Jun Journal of Feline Medicine and Surgery ; The Veterinary Journal — Journal of Avian Medicine and Surgery Mar;25 1: Journal of Veterinary Pharmacology and Therapeutics Feb;34 1: Kukanich B, Papich MG. American Journal of Veterinary Research Feb;72 2: Epub Dec 8. American Journal of Veterinary Research Dec;71 Journal of Veterinary Pharmacology and Therapeutics Dec;33 6: American Journal of Veterinary Research Nov;71 Journal of Zoo and Wildlife Medicine Sep;41 3: Am J Vet Res Apr; 71 4: American Journal of Veterinary Research Jul;71 7: Journal of Equine Veterinary Science 30 Louis, Missouri, USA ; pp Journal of Veterinary Pharmacology and Therapeutics 33 2: Equine Veterinary Journal 42 3: American Journal of Veterinary Research 71 3: Am J Vet Res.

Epub Dec Epub Dec 9. J Vet Diagn Invest. MG Papich, Sponsor of two monographs: An Introduction to the Discipline. Veterinary Pharmacology and Therapeutics, 9th Edition. Drugs Affecting Animal Behavior. Sulfonamides and Potentiated Sulfonamides. Penicillins, Cephalosporins, and Related Drugs. Antifungal and Antiviral Drugs. Immunosuppressive Drugs and Cyclosporine. Drugs Affecting Gastrointestinal Function. Drugs that Affect the Respiratory System. American Journal of Veterinary Research May;70 5: Journal of Pharmaceutical Sciences. Clinical Cancer Research Feb 15;15 4: Epub Jan American Journal of Veterinary Research Dec;69 Veterinary Dermatology Dec;19 6: American Journal of Veterinary Research Aug;69 8: Journal of Veterinary Pharmacology and Therapeutics Aug;31 4: American Journal of Veterinary Research Guide to Antimicrobial Use in Animals.

Blackwell Publishing, LTD, Approved Guideline — Third Edition.