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1 Vol. 40 Observations on the Transmission of Salmonellosis in Man* ERWIN NETER, M.D., F.A.P.H.A. Department of Bacteriology of the Children's Hospital and the Department of Bacteriology and Immunology of the University of Buffalo, School of Medicine, Buffalo, N. Y. SALMONELLOSIS, according to modern nomenclature, is a malady caused by any of the numerous members of the genus Salmonella. This genus includes the typhoid bacillus, as well as more than 150 types of organisms which, for the sake of convenience, may be referred to as paratyphoid bacilli. In the present report the term salmonellosis is employed to connote an infection caused by these microorganisms, with the exception of the typhoid bacillus. The advances made in our knowledge of the mode of transmission, prevention by sanitary methods, active immunization, and chemotherapy of typhoid fever are distinctly more far-reaching than those regarding* paratyphoid infections. In the first place, typhoid fever originates, directly or indirectly, from man only, whereas paratyphoid infections may be traced to animals as well. Active immunization with a potent vaccine against typhoid fever is very effective, whereas immunization against paratyphoid infection, largely because of the numerous antigenic types of salmonellae encountered, is of limited value only. Finally, from preliminary data available, it is apparent that the new antibiotic chloromycetin is of distinct value in the therapy of typhoid fever but far less * Presented before the Laboratory Section of the American Public Health Association at the Seventyseventh Annual Meeting in New York, N. Y., October 28, effective in the treatment of experimental salmonella infections of animals and of the human disease. Bearing these facts in mind, every effort should be made to prevent salmonella infection in man. To this end, an understanding of the mode of transmission is indispensible. On numerous occasions, larger and smaller outbreaks of salmonellosis have been traced to carriers and to contaminated water or food. On the other hand, the origin of the infection in an extraordinary large number of sporadic cases has remained obscure. In this report, data on man-to-man transmission of salmonellae are presented, and the implications of the observations are briefly discussed from the public health point of view. THE PROBLEM OF THE INTRAUTERINE TRANSPLACENTAL TRANSMISSION OF SALMONELLOSIS Although the possibility of the hematogenous infection of the fetus, resulting in salmonellosis of the newly-born, was considered as a possibility by several authors, including Abramson,- such an occurrence must be extremely rare. As a matter of fact, the placenta can be an effective barrier, as the bacteriological data of -Salmonella c-holeraesuis bacteremia during pregnancy studied by us indicate. The particular patient in question harbored this-organism in the blood for at least 6 days prior to delivery and [9291

2 930 AMERICAN JOURNAL OF PUBLIC HEALTH August, 1950 the blood culture was still positive on the day of the birth of the child. Although bacteriological examination of the placenta revealed the presence of numerous paratyphoid bacilli, blood and mouth cultures of the baby were sterile. It is evident, then, that salmonella bacteremia during pregnancy does not necessarily result in infection of the fetus. TRANSMISSION OF SALMONELLOSIS DURING DELIVERY In view of the well known susceptibility of young children and animals to -salmonellosis, it is not surprising to find a considerable number of outbreaks of this disease in nurseries and among flocks of recently born animals. In infants, the infection may result from contact, directly or indirectly, with attendants, either the mother, nurses, or physicians. An illustrative example is the outbreak of Salmonella typhimurium infection involving 17 cases, reported by Abramson.1 This epidemic originated from one of the mothers of the maternitv hospital, spread, probably through contaminated bedpans, to two other mothers, affected 14 infants, some of them becoming infected from a nurse who had become infected herself, and involved a member of the medical house-staff. In this and similar outbreaks the precise mode of transmission of the disease from mother to baby remains undetermined. That salmonella may be transmitted during delivery is illustrated by the following unusual observation. Mrs. M. was admitted to the maternity division of this hospital. According to the obstetrical history she was not suffering and had not suffered from any intestinal disorder. A premature infant was delivered after 2½Y2 hours of labor, 3½2 hours following rupture of the membranes at home. Because of the prematurity, the infant was immediately taken to the premature nursery and did not have any further contact with the mother during hospitalization. On the third day of life the infant, weighing 4 lbs. 3 oz., developed diarrhea and on the fifth day of life the temperature, which had been normal, suddenly reached 1040 F. A blood culture taken at that time revealed the presence of two colonies per ml. of blood of S. oranienburg. On the same day the paratyphoid bacillus was recovered also from the feces. Following supportive treatment and chemotherapy with streptomycin, the child was discharged on the 38th day of life in good condition. The attempt to isolate salmonella from the attendants (nurses, etc.) at the premature nursery failed. However, the same type of paratyphoid bacillus was easily recovered from the feces of the mother. A more careful history taken subsequent to the diagnosis of the disease revealed that the mother had had very mild diarrhea one week prior to delivery. It is evident then that the infection of the new-born baby must have taken place during the actual delivery, since it is most unlikely that the mother suffered from salmonella bacteremia. The presence of this child, first in the premature nursery and then in the isolation ward, resulted in cross-infection of two infants, in spite of all precautions which were carried out at that time. It is interesting to note that the development of diarrhea preceded the rise in temperature and that numerous paratyphoid bacilli were present in the feces on the first day of elevated temperature. It is obvious that the child could have served as a source of cross-infection on the very first day of clinical manifestations, and it may be assumed that the bacteremia was the result of the intestinal infection and not, as in typhoid fever, its source. This experience of transmission of S. oranienburg during delivery of a premature infant parallels the observation of Watt and Carlton 2 on a similar mode

3 SALMONELLOSIS IN MAN Vol of infection of a new-born premature infant with S. typhimurium. The case of Watt and Carlton differed from our own, inasmuch as the mother actually suffered from diarrheal disease during delivery and, 6 hours after the birth of the infant, her temperature rose to In this instance, too, salmonellosis was introduced into the premature nursery, involving 4 other children. Based on these observations it is evident that careful histories must be taken of mothers whose babies are to be placed in a nursery, particularly nurseries for premature infants, if cross-infection originating from an infant exposed to an enteric pathogen during delivery is to be avoided. In this connection it is interesting to note that, according to Franklin and Loeb,3 24 per cent of infants at time of delivery harbored Escherichia coli on the eyelids immediately after birth. THE POSSIBLE DISSEMINATION OF SAL- MONELLA FROM THE RESPIRATORY TRACT On two occasions, cross-infection was observed at this institution in spite of all possible precautions to prevent the dissemination of paratyphoid bacilli through feces or urine. The possibility was considered that salmonellae may be present in the respiratory tract and be spread like an air-borne infection. Recently, then, a study was commenced to determine whether or not in children, suffering from gastroenteritis or enterocolitis, the pathogenic agent is present in the nasopharynx or in the throat. It was found that two patients, one suffering from acute enterocolitis complicated by bacteremia due to S. oranienburg, the other from gastroenteritis and bacteremia caused by S. ckoleraesuis, harbored the pathogen in both the nasopharynx and the throat. In fact, S. oranienburg was the predominant organism in the nasopharynx. It was this baby who served as a source of crossinfection of a premature child in the premature nursery and, following transfer, of another baby in the isolation ward. Both children developed salmonellosis following hospitalization for 4 weeks and 11 days, respectively. From these preliminary observations it may be tentatively concluded that an additional avenue of exit of salmonellae in patients clinically diagnosed as having enteric disease may be the upper respiratory tract. If this observation can be corroborated it may be advisable to take precautions not only against fecal spread but also against air-borne transmission of salmonellae. THE SCOPE OF THE CONVALESCENT SAL- MONELLA CARRIER PROBLEM Although reference is frequently made in the literature to both convalescent and permanent salmonella carriers as sources of infection, additional data on this problem are desirable. A study was undertaken, therefore, to determine the percentage of children who had recovered clinically from salmonellosis but still harbored the pathogen in the intestinal tract at the time of discharge from the hospital. In all, 43 patients were investigated. The type of salmonella was determined in each instance. Of these 43 cases, according to the last culture prior to discharge from the hospital, 26 still excreted the paratyphoid bacillus with the feces and only 17 did not. In addition, there were two adults who were carriers, following a very mild episode of salmonellosis and several children whose fecal specimens were sent to this laboratory for the etiological diagnosis of the disease. It is quite possible that the percentage of convalescent carriers may be even greater than the figures just cited here, had the criterion of the carrier state been based on more than one negative culture. The questions as to how long the excretion of paratyphoid bacilli in children continues and whether or not the return to their homes resulted in infection of contacts, cannot

4 932 AMERICAN JOURNAL OF PUBLIC HEALTH August, 1950 be answered. It is evident, however, that every attempt should be made to lower the percentage of carriers on discharge from the hospital. As shown by Seligmann and associates,4 streptomycin is of very limited usefulness in this respect. Whether or not aureomycin or chloromycetin will be more effective, remains to be seen. The results with chloromycetin in the treatment of experimental salmonella infections proved to be disappointing (Seligmann and Wassermann 5). At this hospital two convalescent salmonella carriers were treated with large doses of aureomycin (500 mg. per kg. per 24 hours) and later with chloromycetin (500 mg. per kg. per 24 hours) for one week each but continued to excrete salmonellae with the feces. The search for a more effective method for the treatmnt of carriers must continue. THE PROBLEM OF THE SPORADIC CASE Without question, sporadic salmonellosis occurs much more frequently than is apparent from the statistics on cases reported to health departments. In part, this is due to the fact that bacteriological studies are frequently not carried out, particularly on mild and atypical sporadic cases. Furthermore, often the source of the infection remains unknown because of lack of epidemiological studies. Although it must be admitted that the search for the source in sporadic cases is frequently unsuccessful, attempts to trace the infection should be undertaken more often. To illustrate this point, the following observation may be briefly cited. M. W. was admitted to the hospital with a diagnosis of acute appendicitis. Following the removal of the not-acutely inflamed appendix on the first day of hospitalization, the child developed diarrhea, and Salmonella typhimurium could be readily isolated from the feces. A careful history, then, revealed that the brother of the patient, two to three weeks before, had had diarrhea for one day. The feces of the brother was examined and the same type of salmonella was recovered without difficulty. If one is to obtain a more adequate appraisal of the magnitude of the salmonellosis problem more bacteriological and epidemiological studies must be undertaken. SUMMARY AND CONCLUSIONS Too frequently, the true nature of mild and atypical forms of salmonellosis remains unrecognized and, even when the etiological diagnosis has been established, the source and mode of transmission of the malady remains undetermined. The observations reported in this communication may aid in the elucidation of this complex and important problem. 1. Salmonellosis may be transmitted during delivery from a mother suffering from diarrheal disease or, as in the case presented here, from a mother who had become a convalescent carrier. 2. The admission into a nursery of an infant thus exposed may result in cross-infection of exposed individuals. This sequence of events may be prevented, if the admission of infants born to mothers who present evidence or give a history of recent diarrheal disease is deferred. 3. Salmonellae may be present in the nasopharynx and throat of children suffering from salmonellosis. It is possible that in these instances the disease may be spread like an air-borne infection. Consideration should be given to the prevention of dissemination of salmonellae by this route. 4. A series of 43 children suffering from salmonellosis were studied to determine the frequency of the convalescent carrier state. Of these- patients, twenty-six still excreted the paratyphoid bacillus in the feces subsequent to clinical recovery, as shown by a positive culture prior to discharge from the hospital. The public health significance of this observation is obvious. 5. Attempts to eliminate salmonellae in two cases of convalescent carriers by means of the administration of large doses of both aureomycin and chloromycetin for a period of seven days failed in both instances.

5 Vol.40 SALMONELLOSIS IN MAN 933 REFERENCES 1. Abramson, H. Infection with Salmonella typhimurium in the Newborn. Am. J. Dis. Child. 74: 576 (Nov.), Watt, J., and Carlton, E. Studies of the Acute Diarrheal Diseases. XVI. An Outbreak of Salmonella typhimurium Infection among Newborn Premature Infants. Pub. Health Rep. 60:734 (June 29), Franklin, H. C., and Loeb, L. N. Bacterial Flora in Infants Encountered at Time of Delivery. Am. J. Obst. & Gynec. 56:738 (Oct.), Seligmann, E., Barash, L., and Cohlan, S. Q. Streptomycin Treatment of Salmonella Enteritis in Infants. J. Pediat. 30:182 (Feb.), Seligmann, E., and Wassermann, M. Action of Chloromycetin on Salmonella. Proc. Soc. Exper. Biol. & Med. 71:253 (June), Atomic Energy Training Center The University of Rochester has opened a new million dollar center, financed by the Atomic Energy Commission, for research and training of physicians and technicians in medical problems relative to atomic energy development. Attached to the University of Rochester School of Medicine and Dentistry, the center is planned to help meet the nation's need: 1. to train medical and staff personnel of the armed forces for atomic warfare defense; 2. to build up a nucleus of civilian medical personnel having a knowledge of atomic energy; 3. to supply a source of trained research scientists in the branches of medicine, biology, physics, biophysics, physiology, chemistry and biochemistry, in which the new technics of nuclear energy may be employed; 4. to supply the necessary scientific personnel for the various regional laboratories of the A. E. C. The new facilities permit expansion of the University of Rochester's studies for the United States Government in the medical and biologic aspects of radio-.active substances that have been in progress for a number of years. Postgraduate training is being given in the treatment of radiation sickness, the use of radioisotopes for tracer studies, and therapy and instruction in such subjects as pharmacology and toxicology of radioactive materials, principles of shielding, design of radiochemical laboratories, technic of personnel monitoring, hazards of reactor operation, prevention of radioactive contamination and methods of decontamination, and the disposal of radioactive waste materials. Cancer research is among the electives open to trainees. Henry A. Blair, Ph.D., physiologist and biophysicist, is director of the project.

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