CAT BITE AND SCRATCH WOUNDS WITH CONSEQUENT PASTEURELLA INFECTION OF MAN* G. H. HANSMANN, M.D., AND MARION TULLY, M.T. Departments of Laboratory Medicine, Columbia and Milwaukee Children's Hospitals, Milwaukee, T h i s report is concerned primarily with an infection of t h e hand which followed a cat-bite. T h e cellulitis which developed was a t first interpreted as being of streptococcic origin, b u t unlike streptococcic cellulitis there was excruciating pain requiring morphine for relief and absence of any i m p o r t a n t rise in temperature. Thirty-three m o n t h s later the same individual was bitten on the opposite hand b y the same cat. A similar train of events followed except t h a t the clinical course of t h e disease was not quite so severe. On each occasion a n organism belonging to t h e genus " P a s t e u r e l l a " was isolated from the wound. T h e two organisms isolated appeared identical. Incidentally, during the cdurse of this study a nine year old girl was scratched on her face and left a r m b y a p e t cat. This resulted in a reddening and a p u r u l e n t discharge from the wounds without further incident. A similar organism was isolated from t h e wounds. T h e purpose of this paper is to report the results of o u r studies of this disease which appears to be a n e n t i t y in the endeavor of extending the knowledge a n d appreciation of the infection. A fewreports of pasteurella infection of m a n following cat-bite have appeared in foreign and Canadian medical literature during the p a s t fifteen years. CLINICAL REPORTS Case 1. The patient was a forty-seven year old white male who was bitten while stroking a pet cat on March 12, 1939. The cat, as far as the owner knew, had been closely confined to quarters since she was a kitten. The bite was inflicted at the right wrist on the thumb side. The injury, even though represented by only two small puncture holes, soon became extremely painful and required sedatives. He remained in bed the following two days with his right arm elevated. He took codeine and aspirin for the relief of pain. During the night of March 14, 1 grain of morphine was also required. On the third day, the pain became even more severe and swelling of the arm and hand continued to increase for which reason he was admitted to the hospital with a tentative diagnosis of streptococcus cellulitis of the * The record of the cases reported were made available by Drs. R. E. Morter and VV. J. Carson. 312 Wisconsin arm. Examination revealed two [juncture marks with a surrounding swelling and a complaint of excruciating pain of the hand and arm. The swelling involved the back of the hand and the forearm with a slight amount of edema of the lower half of the arm. There was a 3 cm. area of extreme erythema about the wound. Temperature, pulse, and respirations were normal and remained so throughout the hospital period of seven days. LABORATORY STUDY The blood count on admission was 5,870,000 red blood cells'and 12,850 white blood cells. The white blood cells rose to 14,200 while in the hospital. The blood count on discharge was 5,730,000 red blood cells and 8,150 white blood cells. Granulocytes accounted for 7.8 per cent of the white blood cells on the initial count of which 97 per cent were segmented. Lymphocytes, monocytes, and basophiles accounted for 18, 3, and 1 per cent respectively. At the time of discharge the blood contained 5 per cent monocytes, 3 per cent eosinophiles, and 1 per cent Turk irritation lymphocytes. The urine was of good gravity and of normal color. No abnormal constituents were found in it. The patient was placed in bed with the arm elevated and wet dressings were applied. Neoprontosil was given. Twenty-three grains of codeine, one-half grain of morphine, and seventy-five grains of aspirin were required for the control of pain between March 15, and March 19. The patient received three diathermy treatments daily during the next seven days. He insisted that pain was relieved by this method of treatment. He was discharged from the hospital on March 22, with only residual redness about the wound. On March 24, a small abscess had formed from which a pure culture of a small, gram negative, bipolar staining, nonmotile bacillus was isolated. An indolent ulcer resulted which finally healed on May 4. The hand returned to full function about July 1. The same patient reported above entered the hospital on December 12,1941. This time he had been bitten on the left hand by the same cat. The train of events on this admission was similar to that of the admission in 1939 except that all symptoms and signs were not as severe. A similar organism was isolated from the wound. Case 2. The patient entered the hospital on July 25, 1941, and was discharged on August 1, 1941. Two days before admission she was scratched on the face and left arm by her pet cat which she was carrying as a dog came up barking. The wounds were superficial and not ^M ^ fl 313 CAT BITE WITH PASTEURELLA painful. They became swollen, reddened and discharged a small amount of pus. A gram negative bacillus similar to those described above was isolated from the wounds. LABORATORY INVESTIGATION Bacteriologic study The three organisms isolated during the course of this study appeared identical from results obtained on food requirements, staining reactions, and biological characteristics. The colonies were small, whitish, elevated, smooth, glistening aggre- above, and with morphological characteristics, and staining reaction of Pasteurella is found to be nonmotile and ferments dextrose, saccharose, and galactose, and fails to ferment lactose, produces indol, and does not elaborate an hemolysin should call for a consideration of the Pasteurella strain associated with cat-bite wound infection. Immunologic study The organism isolated from the initial infection failed to be agglutinated by serum of the host which was drawn about one month after the onset of the CHART 1 - + + + + + + + - + + + - — — + — — — — — — — — — — + + + — — — — — — — + + + + + + + + + + + + GELATIN ze LEAD ACETATE C -\- HEMOLYSIS | DEXTRIN | " — .— ! RAFFINOSE DULCUTOL | SALICIN MALTOSE GALACTOSE + + + + — + + | + + + + + | + + + + + + + LEVULOSE <3 XYLOSE z •j- — — — — + + + + + + + + + + O H Z -f- + + + + + + + + + SACCHAROSE LACTOSE DEXTROSE | X, XX, 14 2 5 4 12 8 1 -f- BIBL'Y NO. BIOCHEMICAL CHARACTERISTICS OF PASTEURELLA AVICTDA AND OF PASTEURELLA FROM AIRWAYS OF CATS AND FROM WOUNDS OF THE HUMAN INFLICTED BY CATS — — — — ' — Xi X2 Xa = Pasteurella organisms isolated by authors, + = action, — = no action. Blank = no record. Action = acid only on carbohydrate mediums. gations one to two millimeters in diameter with entire margins. Growth was enhanced about 50 per cent by the addition of blood to the medium. The organisms were very small coccoid bacillary forms which were gram negative with distinct bipolar staining appearance. The organisms were non-motile. Biochemical characteristics are tabulated in the following chart under designation Xi, X 2 , and X3. It will be noted in chart 1 that the organisms isolated in this study compare quite favorably with those isolated from the airways of cats and other organisms isolated from cat-bite wounds of man as well as Pasteurella avicida as described by Bergey2. They were otherwise biologically similar except that some of the strains described in the literature were absolute in their hemoglobin requirement. An organism which has food requirements as stated FIG. 1. APPROX. X 2000 Xote very small coccoid, rod-shaped organism infection. It was, however, agglutinated by serum produced by Dr. James Foerester of the University of Pennsylvaniawitha strain of Pasteurella avicida. 314 G. H. HANSMANN AND MARION TTLLY An immune serum produced with this organism agglutinated it in a dilution of 1:620. Serum produced with this organism did agglutinate the other two strains here isolated. It did not agglutinate Salmonella and Salmonella thyphimurium (5 and 5A) described by Bergey. The cross immunity between genus Pasteurella and genus Salmonella has been pointed out by Pirosky11. We failed to establish any such immunological relationship. The serum failed to agglutinate strains of Brucella suis, Pasteurella tularense, Eberthella typhosis, amount of slightly turbid fluid. The liver and spleen were severely damaged. The histologic FIG. 3. APPROX. X 90. LUNG OF GUINEA PIG FIVE DAYS AFTER INOCULATION Note proliferation of bronchiole epithelium, fibrinous plugs in bronchioles and interstitial pneumonitis. FIG. 2. APPROX. X 90. LUNG OF GUINEA PIG FIVE DAYS AFTER INOCULATION Note proliferation of bronchiole epithelium and pleural endothelium with interstitial pneumonitis. Salmonella paratyphosis A and B, and several strains of Pasteurella obtained from Roscnbusch and Merchant13. The serum also did not agglutinate a strain of influenza identified with specific " B " serum or the Pasteurella pseudotuberculosis isolated by Moss and Battles 1 . Animal pathogenicity studies Guinea pigs: Guinea pigs inoculated intraperitoneally with a suspension of a twenty-four hour culture of the organism in doses ranging from 1.0 to 0.25 cc. regularly died of a diffuse peritonitis and in one case an extensive pneumonitis had developed. The exudate in the peritoneal cavity was attended with abdundant fibrin and a copious FIG. 4. APPROX. X 90. SPLEEN OF GUINEA PIG THIRTY-SIX HOURS AFTER INOCULATION. Note thick fibrinous exudate on surface and disappearance of lymphoid cells. features of the lesions, in addition to the extensive fibrinous exudate which extended into the liver and CAT BITE WITH PASTEURELLA lung, were a pronounced endothelial cell response in the spleen (late), thrombophlebitis (early), proliferation of the epithelium of the bronchioles (late), toxic necrosis of lymphocytes in the splenic pulp (early), and focal necrosis in the liver and adrenal. The survival period after inoculation varied with the dosage. One cubic centimeter of the suspension caused death in 16 hours, while the animals lived one to five days after an inoculation of 0.25 cc. 315 toneally, while 0.S cc. caused death in forty-eight hours. There was a diffuse peritonitis in each instance. Two cubic centimeters administered intravenously caused death in twelve hours. One cubic centimeter inoculated into the trachea caused death in seventeen hours. There was an extensive t*5 •* * . 'A \ ' «" 5Ti 3f *"'•' ys ®> Fic. 5. APPROX. X 90. SPLEEN OF RABBIT TWENTY FOUR HOURS AFTER INOCULATION Note marked destruction of cells Subcutaneous inoculation resulted in a local abscess which healed. The guinea pig was examined six weeks after inoculation and no residual pathology was noted except for the healed local lesions. Mouse: A mouse was inoculated intraperitoneally with 0.5 cc of a twenty-four culture of the organism. The mouse died forty-eight hours later. A diffuse peritonitis as noted in the guinea pigs was found. Rabbits: Rabbits were inoculated intraperitoneally, intravenously, and intratracheal!}-. The organism caused death by all routes. Death was caused in twelve hours from 1.5 cc. intraperi- Fic. 6. APPROX. X 1900. ADRENAL OF GUINEA PIG FIVE DAYS AFTER INOCULATION Note phagocytosis of adrenal cells hemorrhagic tracheitis and confluent hemorrhagic bron chopn eu monia. Histologic features of the lesions were similar to those in the guinea pig. The spleen was almost devoid of lymphocytes except for a small collar about the splenic corpuscles. COMMENT Rivers and Bayne-Jones12, while searching the ainvavs of cats for hemolytic streptococci, came 316 G. H. HANSMANN AND MARION TULLY upon seven strains of influenze-like bacilli, six of which required the "A" factor for growth. The seventh strain was hemolytic and required whole blood for growth. The food requirements of these organisms were not significantly unlike certain strains of Pasteurella isolated from man following cat-bites. The organisms had colony characteristics which were quite similar to Pasteurella and they did not produce an hemolysin and did produce indol. The saccharolytic variations from typical Pasteurella strains may be considered minor. The hemolytic organism may have been an atypical Whether or not the organism is a harmless parasite in the throat of cats or whether it is the proposition of a cat that has recovered from an infection carrying the organism is yet not clear. Most strains of organisms isolated from cat-bite wound infection grow much better on mediums containing blood or upon chocolate agar. Some strains are strict in this requirement. Others require hemoglobin upon isolation, but after a number of transplants will adapt themselves to more simple mediums containing no hemoglobin. Our strains grew on ordinary mediums from the begin- "•">W*.JI *v- JL - * * * * ' * . % •»„ i • « -r - - * , ft * * % . M § •" %*> ** •.. * * f K %% * If? 4? •r y. ft. ' ^v py&fc".. ^M **** FIG. 7. APPROX. X 450. SPLEEN OF GUINEA PIG FIVE DAYS AFTER INOCULATION Note marked endothelial proliferation strain of Pasteurella now known as Pasteurella hemolytica. The authors classified their organisms as parainfluenza bacilli. Animal pathogenicity tests and immunologic reactions may have more nearly allied them with the Pasteurella genus. Kremsreiter5, Rimpau 9 , Foerster3, Schenk14, and Leuze 8 isolated Pasteurella strains from throats of healthy cats. In Schenk's investigation the percentage of recovery of this organism was six from six sick cats and from nine out of fourteen healthy cats. I t appears that the organism is a harmless parasite apparently becoming more numerous during illness of the animal. The history of our case would indicate that a healthy cat had harbored the organism for at least thirty-three months. ning, but growth was always more abundant on the mediums containing blood. When these features are coupled with the facts that the organism does not produce an hemolysin, has colony characteristics as well as staining reactions quite similar to influenza strains, and is non-motile, it appears to the authors that this organism should be given careful consideration when an indol producing organism thought to be a member of the influenza group is up for consideration. Animal pathogenicity tests and serological investigations should be helpful. After a careful consideration of this subject the authors reflect upon how frequently strains of Pasteurella may have passed for influenza bacilli in the routine bacteriological studies. CAT BITE WITH PASTEURELLA Even though the Pasteurella micro-organism associated with cat-bite wound infection is a harmless parasite in the throat of cats, it is distinctly pathogenic when inoculated into guinea pigs, mice, rabbits, and man. Kapel and Holm4 first called attention to the relationship of cat-bite and Pasteurella infection of man. Their observation has since been confirmed by Foerster3, Leuze7, Kremsreiter5, Rimpau9, Kristensen6, Schenk14, Allin1, and the authors. The clinical syndrome is quite similar in all cases; namely excruciating pain, little or no rise in temperature, swelling of the arm, 317 A brief statement of the work of Rosenbusch and Merchant1* may help us in the visualization of the proper position of the species of Pasteurella associated with cat-bite and scratch wound. Revoltee, in 1877, isolated the first member of the genus Pasteurella following, his study of foul cholera. Soon thereafter, similar or closely allied organisms were isolated from hemorrhagic septicemias of foul cholera, cattle, rabbit, swine, deer, y ' jlf-v# ,;'•- .>- , .-4- / , - ». .y r J ,y< TT :< ; hi -" ^ v.- 4 / . l - J • ' - . ' , ' 'i{ •>••>•. ' V »» C V >•*>' V: y { v / y '• y, >;. FIG. 8. APPROX. X 185. ADRENAL or GUINEA PIG FIVE DAYS AFTER INOCULATION Note focal necrosis and fatty change in adrenal cells localization of a small abscess from which the organism is isolated, the formation of.a slowly healing ulcer at the point of the abscess and absence of important lymph node involvement. In our case the pain began soon after the man was bitten. Rarely, several days elapse between the bite and the onset of severe pain. There is usually no further consequence of the infection. However, in one of the cases reported by Allin1, a subperiosteal abscess due to the same organism developed at the site of a cat-bite eleven months after the wound had been inflicted. Future observations may associate the occasional cryptogenic systemic pasteurella infections which occur in man to animal bites or injuries obtained in the handling of animals. FIG. 9 APPROX. X 185. LIVER OF RABBIT SEVENTEEN HOURS AFTER INOCULATION Note focal necrosis, fibrinous deposit in sinuses, and thrombophlebitis. horses, sheep, and goats. Kitt, in 1885, designated the organisms as "Bacterium bipolar-multicidum," inferring that it was a bipolar staining organism which cut across many host species lines. Hueppe (1886), named the organism "Bacterium septicemia hemorrhagica." These two authors were the first exponents of the unicist school. In light of our present knowledge, the work of Lignieres (1900), set back our thinking through the introduction of a zoologic species classification; that is, he named the organism according to the 318 G. H. HANSMANN AND MARION Tt'UA" species of animal from which it was isolated. A member of the ubiquitous Pasteurella genus has now been isolated from the horse, bird, cat, dog, rat, guinea pig, and man, in addition to the animals enumerated above. Baumgarten (1911), was one of the first to object to the validity of the zoological classification because there was no species specificity in cross pathogenicity or cross immunity. Cultural, biochemical, and serologic characterization of the genus has supported his stand. These studies led to a division of the genus into two groups, namely typical and atypical or Pasteurella hemolytica. The work of Rosenbusch and Merchant13 removes the atypical forms through their ability to hemolyze blood and inability to form indol. The atypical strains also ferment inositol, lactose, maltose, trehalose. The authors further subdivided the typical strains roughly into three groups through the use of xylose, arabinose, and dulcitol. Group I ferments arabinose and dulcitol, but not xylose. Group I I ferments xylose, but not arabinose or dulcitol. Group I I I ferments xylose, arabinose, and dulcitol. There were a number of variants which did not fall into the above groups. Agglutination tests with serum produced from organisms derived from various hosts failed to reveal any host specificity. The conclusion arrived at was that a single name would include all typical strains. They suggested the name "Pasteurella multocida." According to their discussion our organism falls in the group of typical Pasteurella organisms. I t has also been agglutinated by a serum produced with the species Pasteurella avicida. Accepting transfer of the Pasteurella tularense to the Brucella genus or to a separate genus and the designation of Pasteurella pestis and Pasteurella pseudotuberculosis as distinct species, the authors would be content to classify this organism as Pasteurella avicida or better still, in our opinion, as Pasteurella multocida. However, it now seems likely that the organisms isolated from cat-bite wounds of men will be sufficiently homologous to warrant a definitive species name. CONCLUSIONS Two Pasteurella infections and one reinfection in man are reported through cat-bite and scratch wounds. The Pasteurella organisms isolated here and the Pasteurella organisms isolated elsewhere from catbite and scratch wounds are quite homologous. The reinfection of man caused by a wound in- ^M flicted by the cat which caused the initial infected wound indicates that the organism remains as a harmless parasite in the airways of healthy cats for a long time. The condition appears to be a clinical and microbiologic entity. The literature has it that the organism lies dormant in tissue, particularly bone, for months. All of the consequences of the infection may not yet be recognized. REFERENCES 1. ALLIN, A. E.: Cat-bite wound infection. Canad. M. A. J., 46: 48, 1942. 2. Bergey's Manual of Determinative Bacteriology, 5th edition, Williams & Wilkins, Baltimore, 1939. 3. FOERSTER, W.: Pasteurella-Bakterien als Krankheitserreger beim Menschen. Klin. Wchnschr., 17:599,1938. 4. KAPEL, O., AND HOLM, J.: Pasteurella infection in man after cat-bite. Hospitalstid., 73: 1044, 1930. 5. KREMSREITER, J.: Menschenpathogene Haemoglobinophile Baketeien in den Luftwegen einer gesunden Katze. Arch. Arch. f. Hyg., 188: 87, 1937. . 6. KRISTENSEN, M.: Pasteurella-Bakterien als Kran- " kheitserreger beim Menschen. Bemerkungen zu der Arbeit von Wolfgang Foerster. Klin. Wchnschr., 17:939,1938. 7. LEUZE, ERICH: New points in the pathology of cat-bites. Rev. mecl. veterinaire, 91: 221, 1939. 8. LEUZE, ERICH: Neue Gesichtspunkte in der Pathologie des Katzenbisses. Zentralbl. f. Chir., 64: 2741,1937. 9. RIMPAU, W.: Ueber infektionen des Menschen durch Haus und Stalltiere. Miinchen. med. Wchnschr., 84:413, 1937. 10. Moss, E. S., AND BATTLE, J. D., JR.: Human infection with Pasteurella pseudotuberculosis rodentium of Pfeiffer. Report of case, Am. J. Clin. Path., 11:677,1941. 11. PIROSKY, I.: Sur la spScificite et sur leurs affinites serologiques avec les antigenes glucido-lipidiques des Salmonella. Compt. rend. Soc. de biol., 128: 347, 1938. 12. RIVERS, T. M., AND BAYNE-JONES, STANHOPE: Influenze-like bacilli isolated from cats., J. Exper. med., 37: 131, 1923. 13. ROSENBUSCH, C. T., AND MERCHANT, I. A.: Study of hemorrhagic septicemia Pasteurellae, J. Bact., 37: 69, 1939. 14. SCHENK, H.: Pasteurellen in den Luftwegen von Katzen als Ursache von Wundinfektionen beim Menschen nach Katzenbiss. Staatliche bacteriologischer. Untersuchunganstalt, Miinchen, 1938. • ™
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