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Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.Typhus (besser: Typhus abdominalis) und Paratyphus sind global bedeutsame systemische Infektionskrankheiten, die durch Salmonella enterica Subspezies enterica Serovar Typhi (Kurzbezeichnung: Salmonella Typhi) bzw. Serovar Paratyphi (Kurzbezeichnung: Salmonella Paratyphi) hervorgerufen werden. Der Verlauf der fäkal-oral übertragenen Erkrankung ist vor allem durch hohes Fieber gekennzeichnet. Unbehandelt kann Typhus schwer verlaufen und zum Tode führen. Die Erkrankung wird zu nahezu 100 % im außereuropäischen Ausland (v. a. in Indien) erworben und ist in Deutschland, Österreich und in der Schweiz meldepflichtig. Als Paratyphus bezeichnet man ein abgeschwächtes Krankheitsbild des Typhus, dessen Erreger Salmonella Paratyphi ist. Verfügbare Impfstoffe schützen nur gegen Salmonella Typhi. Die Resistenz gegen Antibiotika spiegelt die Situation in endemischen Ländern wider und zeigt sich in einem besorgniserregenden Zuwachs von Isolaten mit Multiresistenz. Gegenwärtig werden Cephalosporine der 3. Generation wie Ceftriaxon als Erstlinientherapie empfohlen; sofern es sich um Isolate mit Chinolonempfindlichkeit handelt, können auch weiterhin Fluorchinolone wie Ciprofloxacin verabreicht werden. Entscheidende vorbeugende Maßnahmen für Reisende sind konsequente Wasser- und Nahrungsmittelhygiene sowie Impfprävention, wobei sich mit den bislang verfügbaren Impfstoffen nur Protektionsraten von 50–70 % erreichen lassen. Mit der Zunahme von multiresistenten Erregerstämmen wird ein besser wirksamer Konjugatimpfstoff gegen Salmonella Typhi mit Kreuzreaktivität gegen Salmonella Paratyphi dringender denn je benötigt.

Typhoid and paratyphoid infections (STP) are an important differential diagnosis for Salmonella enteritidis infections (NTS). The aim of this study is to carve out clinical differences between both infections.We retrospectively reviewed all patients admitted to our hospital between 2007 and 2011 with a diagnosis of STP infection. History, clinical course and laboratory findings were compared with age-matched patients suffering from NTS.All patients with an STP-infection showed had a positive travel history (as compared to 11.1% in the NTS group, p0.01). Salmonella were mostly isolated from blood cultures (n=7/9) in the STP group as compared to 1/16 in the NTS group, where S. enteridis was mainly isolated from faecal cultures (p0,01). The duration and height of fever as well as the time of hospitalization were significantly longer with STP infections than with NTS infections. Eosinopenia was observed both in STP-(100%) and NTS-infections (77.8%).A positive travel history is crucial to the identification of a STP infection, as well as an eosinopenia.

Das Projekt „Balanced Lethal System in Salmonella typhi Ty21a“ der AG Bakterielle Tumortherapie des MSZ zielt auf die Entwicklung eines Vakzinstammes, der in der humanen Krebstherapie zum Einsatz kommen soll. Ziel dieser Arbeit war das zuvor etablierte Balanced Lethal System in Salmonella typhi Ty21a zu optimieren., The aim of this project is to develop a bacterial vaccine that will be used in cancer immunotherapy. The aim of this dissertation was to improve the established balanced lethal system in Salmonella typhi Ty21a.

Das Gen für die Expression von Helicobacter pylori Urease wurde in das Genom von Salmonella typhi Ty21a (Typhoral() integriert. Der resultierende Stamm erhielt die Bezeichnung Salmonella typhi Ty21a(pDB1). Neun gesunden Probanden wurde Salmonella typhi Ty21a(pDB1) verabreicht. In der Kontrollgruppe erhielten drei gesunde Probanden Salmonella typhi Ty21a. Schwerwiegende Nebenwirkungen wurden bei keinem der Probanden beobachtet. Zehn von 12 Probanden zeigten eine humorale Immunantwort gegen Antigene von Salmonella typhi, nachgewiesen über die Detektion spezifischer Antikörper produzierender Zellen, aber bei nur zwei Probanden ließ sich eine Serokonversion nachweisen. Eine zelluläre Immunantwort gegen das H-Antigen von Salmonella typhi konnte bei insgesamt fünf Probanden nachgewiesen werden. Insgesamt sechs Probanden zeigten eine zelluläre Immunantwort gegen Urease von Helicobacter pylori in zumindest einem von drei der zur Anwendung gebrachten Testsysteme (Proliferation, T-cell-Elispot, IFN-gamma Elisa). Eine humorale Immunantwort gegen Urease von Helicobacter pylori konnte bei keinem der Probanden nachgewiesen werden. Ty21a(pDB1) ist somit ein geeigneter Prototyp zur Optimierung einer Salmonella basierte Impfung zur Induktion einer zellulären Immunantwort, die zu einer protektiven Immunität gegenüber Helicobacter pylori führen könnte., Helicobacter pylori urease was expressed in the common live typhoid vaccine Salmonella typhi Ty21a (Typhoral() yielding Salmonella typhi Ty21a(pDB1). Nine volunteers received Salmonella typhi Ty21a(pDB1) and three control volunteers received Salmonella typhi Ty21a. No serious adverse effects were observed in any of the volunteers. Ten out of 12 volunteers developed humoral immune responses to the Salmonella carrier as detected by antigen-specific antibody-secreting cells but only two volunteers seroconverted. A total of five volunteers showed cellular responses to the carrier. Six out of nine volunteers that had received Salmonella typhi Ty21a(pDB1) showed a T-cell response to Helicobacter urease in at least one of the three assays for detection of cellular response (Proliferation, T-cell-Elispot, IFN-gamma Elisa). No volunteer had detectable humoral responses to urease. Salmonella typhi Ty21a(pDB1) is a suitable prototype to optimize Salmonella-based vaccination for efficient cellular responses that could mediate protective immunity against Helicobacter.

Infections caused by Salmonella typhi and Salmonella paratyphi B have special epidemiological significance. However, the enteritis caused by Salmonella enteritidis and Salmonella typhimurium dominates. A complex typing of these serovars is the prerequisite for both, an effective surveillance of salmonellosis and the detection of occurring replacements and variations of the pathogens. The increasing occurrence of Salmonella in spices since 1993 is epidemiologically remarkable. In this connection, serotypes such as Salmonella javiana, S. rubislaw, and monophasic, KCN-positive serovars dominate. The transmission route man-man is of no special epidemiological importance at present in Germany.

We present a case with osteomyelitis of the skull caused by Salmonella typhi 40 years after infection. Determining factors are mentioned.

Among 262 strains of Salmonella typhi from an epidemic outbreak of typhoid fever in Baden-Württemberg in 1974 2 strains were isolated which were tetracyclin resistant and showed no reactions with the Vi testphages T, D6 and VII whilst all other strains belonged to lysotype A, subtype Tananarive. It turned out that the Tc resistance in both strains was caused by a fi- R plasmid which could be transfered to other S. typhi strains, to E. coli K12, S. paratyphi B, S. java and S. typhi-murium as well as from Tc resistant E. coli K12 back to S. typhi. The Tc R plasmid introduced in S. typhi, lysotype A, caused specific restrictions of typing phages T, D6 and VII. Also, the transfer of the plasmids to strains of S. paratyphi B and S. typhi-murium resulted in restrictions of a number of typing phages. Both plasmids had identical patterns of restriction. In this pattern the Tc R plasmid differed from those described in the literature.

The first live oral typhoid vaccine (strain Salmonella typhi Ty 21a) distributed under the trade name of "Vivotif" has been evaluated for safety and efficacy in volunteer studies and in large-scale, placebo-controlled, double-blind field trials. While the data demonstrated that the vaccine was well tolerated, the level of efficacy varied distinctly. It is probable that the differences observed can be chiefly attributed to the various vaccine formulations evaluated to facilitate the passage of the acid-sensitive vaccine strain through the acid environment of the stomach. Based upon these results, the initially marketed formulation (2 bicarbonate capsules + vaccine capsule) was changed to an acid-resistant capsule which was subsequently evaluated in a field trial conducted in Chile and involving 44,000 school age children. Following 4 years of surveillance, a protection rate of 70% was obtained. To further optimize the means of delivering the vaccine, a formulation consisting of lyophilized vaccine reconstituted in a buffer solution is now being evaluated in a Chilean and Indonesian field trial. A similar though less practicable formulation showed excellent efficacy (approximately 95%) in a previous Egyptian field trial.

A CO2-dependent mutant of Salmonella typhi was isolated from anaerobic but not from aerobic blood-cultures of two patients with typhoid fever. Both patients diseased after return from their home country Turkey. The strains developed in a CO2-enriched atmosphere and under anaerobic but not aerobic culture conditions. This property remained stable during 20 subcultures. The fermentative and serological pattern was identical with S. typhi T2. Both strains were of lysovar E1a.

The sanation of carriers of Salmonella germs by means of bactericidal chemotherapy in combination with cholecystectomy is not to be expected in many patients with older age or when concomitant diseases are present. Therefore was tested, whether an exclusive therapy with trimethoprim-sulphamethoxazol (sulprim) is an effective method for the sanation of carriers of the salmonella germs with renunciation of cholecystectomy. Since 1973 up to now 20 carriers of germs have been treated for 12 weeks with daily 2 X 2 tablets of sulprim. Of these patients 84-year-old female patient died of massive pulmonary.

Between 1.1.1970 and 31.12.1973 3639 strains were typed with the aid of phage typing. Of these strains 1793 belonged to S. typhi and 1846 to S. parathyphi-B. 40 S. typhi phage types were found. 9 of these occurred in a frequency of more than 1% (relevant to foci). These were E1 (25.7%) (of this E1a 19.7%, E1b 5.9%), A (16.6%), F1 (7.5%), D1 (59%), C1 (5.4%) D2 (2.3%), 46 (2.1%), 28 (1.9%). Among S. paratyphi-B 24 phage types resp. varieties were found, 14 of these occurred in a frequency of more than 1% (relevant to foci). The phage types comprised Taunton (36.8%), 1 m.c. (10.3%), 3aI m.c. (7.5%), B.A.O.R. (6.8%), 3 a m.c. (4.9%), Dundee (4.6%), 3 aI var. 1 (4.6%), Beccles m.c. (2.4%), 3 b m.c. (2.3%), 3 aI var. (2%), 1 var. (1.8%), 3 aI var. 4 (1.1%). As far as it came to be known the epidemiological relations and particularities of the different S. typhi and S. paratyphi-B phage types are discussed. In th period of this report only one larger epidemic outbreak of S. paratyphi-B (type Taunton) occurred. Possibly the cause of this was contaminated milk.

The second in the series "Microbial emission, immission and changes in the germ count in the cooling water of wet cooling towers" describes measuring methods and results of the measurements for determining the emission values and the changes in the germ count in the cooling system. The content of colony-forming units (KBE) in the cooling water varied widely, depending on the germ content of the surface water and the preparation of the cooling water (filtration, chemical conditioning). In summer the KBE values were as a rule higher than the values recorded in winter (factor of about 10). The introduction of cooling tower water into the surface water thus did not result in any noticeable changes in germ content, either in summer or in winter. An emission rate of 8.3 10(7) KBE/s (CSA) measured at the top of the cooling tower was the maximum emission value recorded. This resulted in a total germ content in the plume of 1.2 . 10(4) KBE/m3. In order to place this finding into perspective, it should be noted that fluctuations in the KBE values of the air of considerably more than 1000 KBE/m3 can occur because of biological release and meteorological conditions alone (see IVth communication). The KBE-P values recorded (content of particles with units which are capable of forming colonies) in the plume were of the same order as the KBE values. From this it can be concluded that the drops of cooling water which are swept away with the plume are normally only charged with individual colony-forming units. It is worth noting that the KBE values of the plume are only indirectly dependent on the KBE values of the cooling water used in the cooling tower.

Two newborn infants were infected with Salmonella originating from their mothers. After infection of a newborn infant with Salmonella typhi from a mother, known for a long time to be a chronic carrier, no pathological findings were observed but the child continued to secrete typhoid bacilli for three years. The infection of the second child with S. panama, from a mother recognized as a carrier post-partum, caused a fulminating diarrhoea accompanied by septicaemia which had a fetal outcome.

In the period between 1.1.1974 and 31.12.1978 phage typing of 2058 strains of S. typhi and 1672 strains of S. paratyphi-B was carried out. 45 S. typhi phage types were found, 11 of these occurred in a frequency of more than 1% (relevant to foci). These were E1 a (21.6%), A (17.7%), F1 (5.8%), D1 (5.5%), C1 (4.6%), E1b (4.1%), D2 (2.5%), 40 (1.5%), 29 (1.3%), B2 (1.0%), 46 (1.0%). Among S. paratyphi-B strains 23 phage types or varieties were observed, 11 of these occurred in a frequency more than 1% (relevant to foci): Taunton (46.9%), 1 m.c. (7.8%), 3aI m.c. (7.7%), B.A.O.R. (6.5%), 3aI var. 1 (5.5%), Dundee (4.4%), 3a m.c. (3.0%), 3b m.c. (2.2%), Beccles m.c. (1.9%), Jersey (1.5%), 1 var. 1 (1.4%). In the year 1974 two epidemics of typhoid fever occurred, one with 417 cases (phage type A, subtype Tananarive) and the other with 41 cases (phage type E1a). In the year 1977 there was an outbreak of paratyphoid B fever with 53 cases (phage type 3aI var. 1). The increasing number of imported cases of typhoid and paratyphoid fever from other countries is remarkable. The age distribution of typhoid and paratyphoid bacilli carriers shows that persons who are older than 60 years represent the age group in which carriers occur most frequently.

In summary, we would like to emphasize that the significance of modern waste water purification plants is generally recognized today. However, salmonella concentration in the water of the Mur river has not decreased, in spite of increased numbers of waste water purification plants and related measures taken in the past decade. This statement is not a criticism, but a deplorable fact which must be acknowledged by all who are involved in the combat against salmonellas.

We investigated the heat production of 42 different Salmonella strains belonging to the serogroups A, B, C, D and E. Using Columbia- and Brain Heart Infusion Broth as growth media, we found 3 different types of heat profiles. Salmonella typhi and Salmonella choleraesuis showed thermograms which differed in shape from the remaining serotypes. The thermograms of one Salmonella dublin isolate which showed an atypical biochemical behaviour could not be put into proper relation to one of these 3 microcalorimetric types.

3715 strains of salmonella have been isolated from various sources from 1976 to 1985. 26 of these isolates have been S. typhi and paratyphi B, 3689 isolates were nontyphoid strains. 7 isolates of S. typhi and S. paratyphi have been isolated from blood cultures. All persons infected with these strains have acquired these organisms in tropical and subtropical areas. In contrast, salmonella gastroenteritis is mainly confined to the intestinal tract. 21 isolates of nontyphoid salmonellae, however, have been isolated from blood cultures. The vast majority of these patients showed compromised host defense mechanisms. Newborn infants up to 3 months are considered particularly vulnerable for bloodstream invasion with nontyphoid salmonellae. Patients with chronic consuming disorders, solid tumors and haematologic malignancies, and the treatment of these ailments with immunosuppressive drugs and corticosteroids predisposes patients for extraintestinal spread of an enteric salmonella infection. Corticosteroid therapy seems to be particularly responsible for a fulminant course of the disease and poor outcome of the infection.

The carriers of salmonella typhi and paratyphi B are the central figures of the epidemiology of typhoid illnesses. The files available at the medical authorities' office of the Hansestadt Lübeck, with regards to all 543 carriers registered up to 1972, have been analysed, and 102 of 108 carriers who were inhabitants of Lübeck on 31.10.72, have been interviewed in their lodgings.--Following results are mentionable: 1. 55 carriers have been traced during a hospital stay, 22 of them were under hospital treatment because of cholecystectomy. 2. The circle of persons to be obligated for medical examination as per $ 17 of the Federal Republic of Germany's law of epidemics has proved as too small. For instance two female carriers--known since years--did their job without any hindering as plates washer or waitress in restaurants. 3. 21 persons=4% of the patients excreted salmonellae in urine only. 4. 10% of the carriers of salmonella typhi and 16% of the carriers of salmonella paratypi B had in their faeces as least 5-years intervals of non-excretion. 5. The precentage of carriers with at least 5-years intervals of non-excretion in urine was significantly larger than the corresponding percentage in faeces. 6. Falling ill of 280 persons out of the environs of the carriers have been lead back to the latters. 73% of these infections were placed by the carriers before their detection through the medical authorities' office. 7. For 10 patients whose health was recreated excretion did not cease promptly after the cholecystecystectomy. Salmonellae had been found in the faeces for several months more, at two persons even two years after the operation. 8. For 8 carriers a final decision with regards to the success of cholecystectomy is impossible because they denied a duodenal soundation. 9. 123 persons of 23% of total 543 carriers had--before their ascertation--professions not allowed for those persons. Efforts for a successful job arrangement, possibly combined with a change in profession, always met to obstacles. 10. More than 80% of the carriers who were interviewed ignored the directions about personal hygiene. 11. Difficulties arose during a stay in sanatories, hospitals and old age homes. 12. While 60 of the carriers contemplate their situation with indifference other 42 patients are psychically influenced. 5 of them suffer from a psychical trauma. 13. The environment often tends to overrate the danger resulting from carriers. 14. Information of the carriers must be improved.

From 1969 to January 1976 82 chronic carriers underwent a sanitation treatment. This treatment consists in an antibiotic combination treatment with ampicillin and canamycin during 24 to 18 days, in which case possibly simultaneously the cholecystectomy is striven for. In chronic carriers of S. typhi in 37 cases the combined antibiotic-operative treatment led to the permanent success. In chronic carriers of S. paratyphi B 21 of 22 cases were present. In patients with condition after cholecystectomy in every case one failure was present. In purely conservative approach the coefficient of success was 50 and 78%.

We tested the effect of lysozyme on the nasal mucosa in a controlled double-blind in vivo study. The administration of non-pathogenic vaccine strains of living measles virus and of living Vivotif bacteria (attenuated Salmonella typhi) to 14 healthy subjects showed that lysozyme possesses a clear antimicrobial and antiviral effect.