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SUMMARYIn the period 1960–70 meat and poultry products caused over 70% of successfully investigated outbreaks of human salmonellosis. The number of human incidents of salmonellosis declined from 1960 to 1966, but then more than doubled between 1966 and 1971. This increase was mainly due to a threefold increase of incidents of salmonella serotypes other than Salmonella typhimurium. The serotypes which increased most and contributed significantly to this trend were S. enteritidis, S. panama, S. Stanley, S. virchow, S. Agona, S. 4,12:d:- and S. indiana.Strong evidence exists that these serotypes have a path of infection from animal feedingstuffs to the pig and poultry animal reservoirs to pork and poultry foods to man. Cattle appear to be a less important source than pigs and poultry and this may be because the nature and content of their feed is different.The importance of the control of the pig and poultry reservoirs of salmonella infections is stressed and a significant role of animal feedingstuffs in the maintenance of these reservoirs strongly suggested.

The synthetic disaccharide 3- O -α-tyvelopyranosyl-α-D-mannopyranoside, identical to the O antigen 9 determinant in Salmonella , covalently linked to bovine serum albumin and suspended in Freund complete adjuvant, was used as an immunogen in mice. Antibodies in high titer were formed against the O9 determinant as estimated by a bactericidal assay, whereas only low titers of hemagglutinating antibodies were found. A sensitive in vivo assay demonstrated that in immunized mice, after challenge with two strains of equal virulence but with different O antigens (O9, 12 and O4, 5, 12, respectively), the growth of the strain with the O9 determinant was suppressed in comparison to that with the O4 determinant.

Clindamycin phosphate was given in a dose of 3.9 gr/24 hr (60 mg/kg/24 hr for children) to 20 patients aged from 6 to 84 years and suffering from a severe infection, due to Bacteroides fragilis in 10 cases. This antibiotic was given by continuous i.v. infusion without any serious side-effects. The average serum and urinary levels obtained were 11.3 and 650 gamma/ml respectively. In the majority of cases this indicates marked antibacterial activity, not only against gram-positive germs but also against B. fragilis. The overall therapeutic assessment can be summarized as follows: 12 recoveries (eight B. fragilis infections), three partial successes and four failures (one Cl. perfringens septicemia and one B. fragilis septicemia). The results are uninterpretable in the latter case.

Gastroenteritis caused by infectious agents still poses an annoying and sometimes serious problem even in well sanitated populations. Infectious non bacterial gastroenteritis, after many years of neglect, is now again receiving the investigative attention it deserves.

ACUTE ARTHRITIS CAUSED BY GRAM-NEGATIVE BACILLI: A CLINICAL CHARACTERIZATION DON GOLDENBERG;KENNETH BRANDT;EDGAR CATHCART;ALAN COHEN; Medicine

Summary Suspensions of Salmonella typhimurium, Shigella dysenteriae and Botulinum-A-toxin or saline for controls resp. have been injected to 132 male Wistar rats. The basal function of the adrenal was altered by 2 I. U./100 g ACTH and 5 × 0,02 mg/100 g/die dexamethason resp. in 32 animals each. The animals are sacrificed after 2, 6, 10 and 14 hours after injection. Glutaraldehyde-OsC4-fixation of the adrenals by immersion. Araldite embedding. Zeiss EM 9 S 2. Both endotoxins rapidly cause aggregation of thrombocytes and formation of fibrin, release of monocytes into the circulation, disturbance of permeability of the capillary wall with interstitial edema and interstitial fibrin deposits. Lesions of cortical cells and endothelial cells are not visible. Intracortical hemorrhage 14 hours after injection of toxins is regarded as the result of consumption-coagulopathia. The functional state of the cortical cells has no influence on the hemorrhage. But hemorrhage can be forced by isolated dexamethason depending blockade of the RHS of the adrenal as a special case of generalized Sanarelli-Shwartzman reaction. Botulinum-A-toxin does not lead to early alteration of thrombocytes. Platelet aggregation appears first after 14 hours. With Botulinum-A-toxin hemorrhage in the adrenal can be produced only, if at the same time the RHS is blocked. In our study this was done by dexamethason induced regressive transformation of the adrenal cortex.

The conditions of heating necessary to destroy salmonellae in liquid whole egg have been compared with those necessary to destroy the activity of the α-amylase of whole egg. All conditions of pasteurizing from the mildest at 61·1° C. (142° F.) for 1 min. to the most severe at 65·5° C. (150° F.) for 5 min. eliminated Salm. typhimurium. The heat-resistant strain of Salm. senftenberg N.C.T.C. 9959 (775 W) was not recovered after heating at 64·4° C. (148° F.) for 2½ min. and at the lower temperatures when the heating period was 3 min. or more. The activity of α-amylase was also destroyed by heating at 64·4° C. (148° F.) for 2½ min. but not at lower temperatures.Because the baking properties of egg are not impaired by heating at 64·4° C. (148° F.) for 2½ min. it is proposed that the inactivation of the α-amylase of whole egg can be used as a test for controlling the pasteurization process, and a routine test has been developed which can be completed within 1 hr.

Extract In spite of numerous publications on the salmonellae and their effects on various hosts, few countries can assess accurately the annual toll of human illness or economic losses in. livestock as a result of these infections. Attempts are being made, at both international and national levels, to remedy this deficiency, particularly as food-borne salmonellosis in countries with high standards of living and hygiene is becoming a very real problem. Increasing mass food preparation, inadequate storage facilities or methods, a trend towards eating raw or insufficiently cooked fcods, increasing international trade, and possibly decreasing personal resistance, have all been cited as contributing factors. Epidemiological studies have documented the vulnerability of the young, the elderly and those with intercurrent disease or those living in institutions. As the main source of infection for man is food of animal origin (Anon., 1967a), all aspects of the livestock and food industries can expect incr...

Summary A case of osteomyelitis due to S. enteritidis is reported and the characteristics of this type of osteomyelitis are outlined. This patient showed a quick repair under treatment with Chloromycetin but low-grade infection with repeated flare-ups still persists five years after the onset of the disease. The case was peculiar in the severe anemia that accompanied the bone infection. This was probably toxic in nature.

SUMMARYDuring a laboratory study of diarrhoea in a large urban area during the years 1953–68, 5319 Sonne dysentery infections in 2620 households and six cases of Flexner dysentery in five households were confirmed. The annual incidence per 10,000 population fluctuated between 2 and 31 with an average of 12.Shigella sonnei was found in 10% of new cases of diarrhoea investigated. Plural infections were found in 58% of the households studied and 30% of all contacts examined were shown to be infected. Among these contacts the infection rate was higher for children (42%) than adults (20%), and higher for adult females (24%) than males (16%). The duration of infection was under 2 weeks in nearly half the index cases followed up and longer than 2 months in only 3%, Intermittent excretion was observed in 15%. Repeated Sonne dysentery infection and illness was observed after intervals as short as 5 months. Antibiotic sensitivity was recorded after 1955 and colicine typing after 1960. Changes in antibiotic sensitivity were noted. Children of primary-school age were most susceptible to Sonne dysentery, but symptoms in ill cases were as severe in adults as in children. During years of high incidence cases were concentrated within a small number of primary schools.Sh. sonnei infections were compared with salmonella infections studied concurrently. Sonne dysentery was a winter disease and most cases were under 11 years old, and case-to-case infection was the usual means of spread. Salmonellosis was prevalent in summer and affected nearly as many adults as children, often persons sharing an article of food. It was more prolonged and severe than Sonne dysentery, but less infectious. In all these respects S. typhimurium occupied an intermediate place between Sonne dysentery and ‘other salmonellas’.

The salmonella serotypes encountered in Accra, Ghana, between 1952 and 1955 are listed. Forty-five identified and three unidentifiable types were isolated from human sources ; 14 of them are provisional new serotypes first isolated in Accra whose antigenic formulae have not yet been finally determined by the customary mirror absorption tests. Multiple infections of the same patient were not uncommon. Patients whose commensal intestinal bacteria hhave been inhibited by antibiotics appear to run a greater chance of acquiring salmonellae than normal people.

Lowered peripheral lymphocyte count, reduced serum antibody response and partially reduced protection against infection with virulent strain of Salmonella enteritidis after immunization with live vaccine of S. enteritidis were observed in mice thymectomized at birth. However, the cellular resistance, which was observed in vitro in peritoneal macrophages from immunized animals, was not found to be reduced by neonatal thymectomy of mice. From these facts, the immunological dependence of cellular immunity on thymus in neonatal life was discussed.

A case of infection due to S. choleraesuis var. Kunzendorf with certain unusual clinical features, is reported. The evolution of the clinical picture in this case differs from that hitherto described in such infections, in that the pathologic process began as a bronchopneumonia due to S. choleraesuis, with subsequent empyema, pneumothorax and septicemia. Review of the literature failed to reveal another case with such a clinical sequence. The patient recovered following administration of 292 gm. of chloromycetin. It is pointed out that specific therapy must be administered over a long period, since this organism may remain dormant despite apparent clinical improvement.

1. Faeces from rural, outwardly healthy Bantu school children from a Native Reserve region have been bacteriologically examined seven times at regular intervals over a period of one year. 2. Of 75 children, 44·0% experienced at least one salmonella infection and 29·3% one shigella infection; considering the infections together, salmonellae or shigellae were recovered from 72·0% of the individuals. The observations are discussed and the view is expressed that over a period of one year, practically all children experience one, and many of them several, attacks by these pathogens. 3. In the majority of cases, the infections appeared to be subclinical and of short duration. There was no evidence proving the existence of chronic carriers. 4. Salmonelloses showed a seasonal dependence with the highest incidence in early summer, i.e. December. Shigelloses was distributed evenly throughout the year. 5. The recovered salmonellae were of twenty types. Salm. typhi, Salm. paratyphi A, B and C were not isolated. Members of all shigella groups were encountered. 6. All the recovered strains from the Tlaseng area were sensitive to streptomycin, chioromycetin, terramycin, achromycin and neomycin, and most of them to aureomycin and erythromycin. In comparison, salmonella strains isolated from the Johannesburg urban area showed signs of increased resistance to the same antibiotics. 7. Water was probably implicated in the conveyance of the infections. We should like to express our thanks to the Director of this Institute, Prof. E. H. Cluver, for permission to publish this paper; to Mr R. G. Robinson for assessing the micro-organisms' sensitivity/resistance to antibiotics; to Dr P. A. Christensen for statistical advice; and to Dr A. R. P. Walker (of the Human Biochemistry Research Unit, Council for Scientific and Industrial Research), who incurred the major portion of the expenses of transport by permitting us to accompany him during his investigation on bilharziasis and nutritional state in the Bantu school children.

In the Netherlands salmonellose due toS. bareilly was noted for the first time in 1948, initially only in man, but in the beginning of 1951 also in chicks. Between the end of March and the latter half of June the number of human cases has distinctly increased. Nine patients appeared to have had a recent contact with chicks which excretedS. bareilly or harboured this germ in their organs. The percentage of excreters of germs among chicks decreased after the first months. 481 eggs lain in autumn by young hens from poultry farms which had been found contaminated in spring 1951 did not containS. bareilly. Also a diseased person can spread the disease either by direct contact or by contaminating foodstuffs. In the course of our investigationS. bareilly has been incidentally cultivated from a rat and from material originating from a deer.

Summary 1. Two outbreaks of Salmonella infection of the newborn infant are reported. The first outbreak, due to S. oranienburg , affected eighteen of the thirty-four exposed infants. Only eight of thirty-three infants exposed in the second outbreak became infected with S. bareilly . 2. The patients in the S. oranienburg epidemic were seriously ill, three fatally. The signs were, in order of frequency, diarrhea, emesis, shock, leucocytosis, cyanosis, acidosis, nitrogen retention and anuria. The patients in the S. bareilly outbreak were only mildly ill. The most common signs were diarrhea, acidosis, and nitrogen retention. 3. Aureomycin was ineffective against S. oranienburg in doses of 25 mg. per kilogram. It may have been somewhat effective against S. bareilly . 4. In the three fatal cases due to S. oranienburg , the characteristic pathological lesions were those of acute gastroenteritis, of vascular damage, and of degeneration in the liver, kidneys, heart, and adrenals. 5. Epidemiological studies demonstrated that conclusions concerning the causation of a Salmonella outbreak can be drawn only after complete identification of the organisms is done in all cases. Many of the personnel were found to be harboring Salmonella strains unrelated to those causing infection in the infants. 6. Simple bacteriological techniques available to any hospital laboratory enable rapid identification of the cause and source of the infection. 7. Periodic cultures should be done at regular intervals on the stools of all personnel assigned to the nursery, pediatric service, and milk formula kitchen. 8. Frequent bacteriological checkups should be conducted of food, utensils, and instruments in the nursery and milk formula kitchen.

DURING the sixteen-year period from 1940 through 1955, the Diagnostic Laboratory of the Massachusetts Department of Public Health cultured for bacterial enteric pathogens 144,538 specimens consisting of stools, bloods, urines, pus, exudates and related material. The New York Salmonella Center at the Beth Israel Hospital typed 2625 cultures, or most of the salmonellas other than Salmonella typhi (not including repeat specimens) that have been isolated by the Diagnostic Laboratory during this period. By means of questionnaires answered by numerous health officers and their assistants, as well as physicians and nurses, the bare records of the salmonella types reported have been . . .

NontyphoidalSalmonellaendocarditis is a distinctly rare clinical entity. Since 1939 only 23 confirmed cases have been recorded although over 50 have appeared in the literature.1-3It would appear that endocarditis due to these organisms is more common than myocarditis and pericarditis.4-5The clinical course of acute bacterial endocarditis due to a nontyphoidalSalmonella, Salmonellatype C (thompson) is presented. Report of a Case A 56-year-old white hog tender was admitted to the Naval Hospital, Philadelphia on Sept 9, 1965, because of diarrhea of two months' duration. The patient recalled drinking water from a contaminated well shortly before the onset of frequent watery nonbloody bowel movements with chills, fever, tinnitus, blurred vision, and weight loss. Several medications including antibiotics and antispasmodics were given without relief. Medical history and systemic review were unremarkable. Physical examination revealed a cachectic febrile man whose blood pressure was 80/60 mm Hg; pulse rate, 110 beats

The use of corticosteroids in stabilizing the clinical course of celiac crisis in three patients is described. Corticosteroids were administered to the first patient after failure to respond to a gluten-free, disaccharide-free diet; in the other two patients, corticosteroids were given as soon as celiac crisis was recognized. All showed a dramatic clinical response to corticosteroid therapy. The three patients presented with acute gastroenteritis, accompanied by shock, acidosis, hypoproteinemia, and hypokalemia. Salmonella infantis was isolated from the blood and stools of one patient. Intestinal biopsies showed severe mucosal damage. Although death from celiac disease is virtually nonexistent at present, celiac crisis may be life threatening. Corticosteroids during the acute phase may effect c rapid reversal of symptoms.

1. The effect of either or both caloric and protein deficiency on the susceptibility of rats and mice to peroral infection withSalmonella typhi muriumwas studied.2. Moderate restriction of food intake (80% of normal diet) for a period of 5 weeks was without influence on the infection susceptibility of rats, even when the diet fed was low in protein.3. Long-term restriction of food intake (10 weeks) led to a marked lowering of the resistance of rats to the infection, there being a direct relation between the magnitude of the intake restriction and the extent of the resulting loss of resistance.4. The infection resistance of rats was lowered more markedly by a given total restriction of food intake, when the latter was imposed in the form of a gradually reduced ration, than when it was imposed in a uniformly restricted ration. The effect so produced was independent of the protein content of the diet.5. The effect of gradual food restriction was diminished by gradual supplementation of the diet with non-proteins and was augmented by gradual supplementation of the same diet with protein.6. In mice kept on a restricted diet loss of resistance toS. typhi muriumhas been shown to be due to a deficiency of both calories and protein.

The distribution of species and serotypes of Salmonella among 2,498 cultures which were isolated in the United States and its territories is presented. These isolates were received for examination during the 12-month period between October 1, 1966 and September 30, 1967. These and other data obtained from the Salmonella Surveillance Summaries for the past five years indicate that a relatively small number of species and serotypes of Salmonella are regularly isolated from diagnostic specimens. Of approximately 1,300 presently known Salmonella species and serotypes, 33 account for almost 90% of the isolates reported from humans and approximately 80% of the isolates from nonhuman sources. The 50 most prevalent species and serotypes account for 97% of the isolates from humans. An abbreviated antigenic schema based on these 50 species and serotypes of Salmonella , in conjunction with adequate biochemical tests, permits complete bacteriological characterization of the common Salmonella

Summary Lactic dehydrogenase, alkaline phosphatase and a magnesium-independent adenosine triphosphatase were assayed in normal, diarrhoeal and cholera stools. The diarrhoeas, examined bacteriologically, included bacillary dysentery, salmonellosis, amoebiasis and non-specific gastro-enteritis. Alkaline phosphatase levels were found to be similar in normal and cholera stools, whereas lactic dehydrogenase was 30-fold higher and adenosine triphosphatase four-fold higher in cholera. The distribution of activity of lactic dehydrogenase was higher, and of the phosphatases lower in cholera than in the stools of bacterial infections showing evidence of tissue necrosis. The levels of activity of all three enzymes in cholera stool were found to reach a maximum between 9 and 17 hr after onset of purging. It is suggested that these findings indicate an increased permeability of the intestinal epithelium in cholera, leading to a leak of cell enzymes into the intestinal lumen.

An outbreak of Salmonella typhimurium infection in a large general hospital is described. The outbreak was spread over some 20 weeks and gave rise to 102 cases of enteritis and there were at least 150 symptomless excreters of the organism.Evidence is presented to support the view that the method of spread was by cross-infection, not by contamination of food in bulk. Control measures, which ultimately brought the outbreak to an end, were instituted on this basis.We wish to thank Dr A. J. H. Tomlinson and his staff at the Public Health Laboratory, County HallS.E. 1 for the generous assistance they gave us in examining all the specimens from the hospital staff during the outbreak. The resources of the Department of Bacteriology of the Postgraduate Medical School were at that time largely devoted to teaching and adequate investigations could not have been made without this help. Dr Tomlinson also gave us much advice both during and after the outbreak for which we are most grateful.Dr E. S. Anderson, Director of the Central Enteric Reference Laboratory and Bureau, Colindale, London, N.W. 9, very kindly undertook the phage-typing of many of the strains of Salmonella typhimurium isolated and we wish to express our thanks to him for this and other help he gave us in the investigation of the outbreak.Our thanks are also due to Dr Joan Taylor, Director of the Salmonella Reference Laboratory, Colindale, for her help and interest.Discussions with Dr R. M. Fry and Dr Joan Boissard in Cambridge in connexion with their investigations of a similar outbreak were most interesting and valuable and it gives us pleasure to thank them.We also acknowledge gratefully the help and co-operation of our colleagues at Hammersmith Hospital, especially Dr C. E. Roberts, the Medical Superintendent, and of those at the Postgraduate Medical School.

SummaryMice infected with S. typhimurium were maintained for 3 weeks either in a warm environmental temperature of 29° to 36°C or a moderate temperature 21° to 25°C. At the warmer temperature, subcutaneous injections of cortisone were more effective in reducing survival. Room temperature had no significant effect upon survival of those infected mice which received the Aqueous Vehicle of cortisone.

1. Faeces from rural, outwardly healthy Bantu school children from a Native Reserve region have been bacteriologically examined seven times at regular intervals over a period of one year.2. Of 75 children, 44·0% experienced at least one salmonella infection and 29·3% one shigella infection; considering the infections together, salmonellae or shigellae were recovered from 72·0% of the individuals. The observations are discussed and the view is expressed that over a period of one year, practically all children experience one, and many of them several, attacks by these pathogens.3. In the majority of cases, the infections appeared to be subclinical and of short duration. There was no evidence proving the existence of chronic carriers.4. Salmonelloses showed a seasonal dependence with the highest incidence in early summer, i.e. December. Shigelloses was distributed evenly throughout the year.5. The recovered salmonellae were of twenty types.Salm. typhi, Salm. paratyphi A, BandCwere not isolated. Members of all shigella groups were encountered.6. All the recovered strains from the Tlaseng area were sensitive to streptomycin, chioromycetin, terramycin, achromycin and neomycin, and most of them to aureomycin and erythromycin. In comparison, salmonella strains isolated from the Johannesburg urban area showed signs of increased resistance to the same antibiotics.7. Water was probably implicated in the conveyance of the infections.We should like to express our thanks to the Director of this Institute, Prof. E. H. Cluver, for permission to publish this paper; to Mr R. G. Robinson for assessing the micro-organisms' sensitivity/resistance to antibiotics; to Dr P. A. Christensen for statistical advice; and to Dr A. R. P. Walker (of the Human Biochemistry Research Unit, Council for Scientific and Industrial Research), who incurred the major portion of the expenses of transport by permitting us to accompany him during his investigation on bilharziasis and nutritional state in the Bantu school children.

A solitary, benign, keratinizing, squamous cell papilloma was found in the lingula of a 74-year-old-man. The patient had been a heavy smoker for many years and gave a history of chest pain, weight loss, night sweats, and a productive cough with streaking hemoptysis. A Salmonella typhimurium abscess was found distal to the tumor. Lobectomy was performed. There has been no evidence of recurrence in a 3-year follow-up. The world literature since 1892 contains five previous reports of solitary squamous cell papillomas of tracheobronchial origin.

1. A good immunity was produced in chickens against oral infection with Salm. gallinarum by the use of either of two live attenuated vaccines, one smooth, 9S and one rough, 9R. Dead vaccines had little or no effect.2. The immunity possessed by chickens vaccinated with 9R at 7 weeks of age commenced to wane 12 weeks later. Chickens similarly vaccinated with 9S were completely immune 4, 12 and 34 weeks later. When tested during the active laying period (at 20 weeks after vaccination) their immunity, although substantial, was not complete.3. Vaccine 9R did not produce demonstrable agglutinins against smooth Salm. gallinarum in chickens. It was non-lethal to 1-day-old chicks and was never found to revert to the smooth virulent form in vitro or in vivo. By contrast, vaccine 9S produced agglutinins and was lethal for 1-day-old chicks, its virulence not being increased by passage. No deaths were ever observed when this vaccine was used in either chickens of 5–12 weeks old or laying hens.4. Although both vaccines produced a good immunity when employed in laying hens, vaccination with 9S was accompanied by a marked reduction in egg production; this was not the case with 9R.5. An immunity of the interference type was also evoked by both live vaccines. This immunity was still produced to some extent in chickens injected with 9S, 2 days after they were infected with Salm. gallinarum by mouth.6. The interference effect could not be produced by the use of either dead Salm. gallinarum vaccines or certain non-specific substances. The intravenous injection of indian ink had a marked adverse effect on the course of the disease. Injecting chickens with a virulent strain of Bacterium coli at the same time as they were infected with Salm. gallinarum resulted in the latter infection running a milder course than would normally have been expected.

SummaryS. typhosa strains Ty 2 and Vi I grew at the same rate when inoculated into the allantoic cavity of 10-day chick embryos, reaching concentrations of 109 viables per ml within 16 hours. Although Ty 2 in small inocula produced a fatal infection in more embryos, comparable numbers of Vi I also killed a significant proportion of the embryos within similar intervals. Both strains produced marked hypoglycemia in 10-day embryos after 16 hours although the yolksac glycogen levels were not reduced. Embryos 16 days old were more resistant to fatal infection; in these, normal blood glucose levels were maintained. Hypoglycemia did not appear to be due to extensive systemic invasion of the embryo by S. typhosa.