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Stability of cholera and typhoid vaccines.

Fluid plain and adsorbed and freeze-dried cholera and tyhpoid vaccines of different composition were examined for thermostability by potency testing (by active mouse protection tests) after exposure to 37 degrees C for 1, 2, 3, 4, 8 and 12 weeks. Loss of potency was evaluated by comparison with samples stored at 4 degrees C. The fluid plain cholera vaccine remained fully potent for 1--3 weeks, the adsorbed vaccine for at least 4 weeks. The fluid typhoid vaccines showed greater thermosensitivity than the fluid plain cholera vaccine. The freeze-dried cholera and typhoid vaccines were both very stable, retaining fully potency after at least 12 weeks' exposure to 37 degrees C. It should be emphasized that the above results apply exclusively to vaccines prepared by the methods used by the authors and formulated to identical compositions.

Animals↗

Incubation period and other features of food-borne and water-borne outbreaks of typhoid fever in relation to pathogenesis and genetics of resistance.

Examination of the incubation period of typhoid fever, the attack rate, and the spread of the case-onset pattern in food-borne and water-borne outbreaks and in experimental infections indicates that typhoid fever arises when organisms invade the circulation by at least two mechanisms--as a result of either the net growth of invading organisms at an early stage or a breakdown in host cellular mechanisms later. The distribution of case-onset patterns suggests that a small number of genes, possibly a single gene, controls host resistance in the early phase. The occurrence of bimodal or even trimodal case-onset patterns in a population exposed to infection by a particular dose of organisms reveals differences in genetic resistance within the population.

Adolescent↗

Spontaneous spleen rupture during typhoid fever.

Typhoid fever currently is an uncommon disease in western countries, and cases usually are imported from endemic areas.1 The most common complications are intestinal bleeding or perforation and necrotizing cholecystitis, although hepatitis, myocarditis, nephritis, and meningitis may occur. Spontaneous spleen rupture during typhoid fever is a known but rare complication. This report describes a new case and reviews the literature.

Adolescent↗

Animal models of Salmonella infections: enteritis versus typhoid fever.

The most common disease syndromes caused by Salmonella serotypes in humans, typhoid fever and enteritis, can be modeled using Salmonella enterica serotype Typhimurium infections in mice and calves, respectively. This article reviews murine typhoid and bovine enteritis and discusses strengths, limitations and distinctive features of these animal models.

Animals↗

Typhoid fever imported from Mexico to Switzerland. Studies on R factor mediated chloramphenicol resistance.

A case of typhoid fever caused by Salmonella typhi occurred in Geneva. The patient was probably infected in Mexico City. The strain isolated from this patient corresponds with the description of the Mexican S. typhi strain, since it is a degraded Vi-strain resistant to chloramphenicol, streptomycin, sulphonamides and tetracyclines. It carried an fi(-) transferable R factor with a CSSuT resistance pattern. It can be accepted that this case forms part of the Mexican outbreak of chloramphenicol-resistant typhoid fever which has already been observed in visitors to Mexico from England and the United States.

Adult↗

Modified Vi tests in the screening of typhoid carriers.

Two tests for the estimation of Vi antibody in sera were studied and their validity in the screening of typhoid carriers was assessed. One was a modified Vi haemagglutination test in which Vi-coated glutaraldehyde-fixed erythrocytes were used as the antigen and Vi antibody resistant to treatment with 2-mercaptoethanol was titrated. The other was a fluorescent Vi antibody test in which acetone-fixed bacterial Vi cells were used as the antigen and the total Vi antibody was titrated. In both tests, the antigens used were stable so that standardization of the tests would not be difficult. The modified Vi haemagglutination test was found equally sensitive but more specific in giving less false positives than the conventional Vi haemagglutination test. The fluorescent Vi antibody test was however found superior to both tests not only in giving less false positives but also in detecting more typhoid carriers.

Agglutination Tests↗

Chemical closet treatment of typhoid carrier faeces.

An investigation to test the efficiency of chemical closets in treating excreta from typhoid carriers is described. The use of these closets kept a stream, which had in the past frequently contained Salmonella typhi, typhoid free for 24 months. Selenite broth as made in this laboratory, containing a final concentration of 0.8% sodium hydrogen selenite when inoculated with the water sample, was significantly better than commercial selenite brilliant green enrichment broth for the recovery of S. typhi.

Carrier State↗

Antibody response to somatic antigen of Salmonella typhi in areas endemic and non-endemic for typhoid fever.

In sera obtained between the 6th and the 30th day from 16 Austrian and 26 Hong Kong patients with culturally verified typhoid fever, agglutinating antibodies (microagglutination test) at significant titers were detected in 93% of the Austrian (median titer: 640) but in only 50% of the Hong Kong patients (median titer: 240). Similar results (93% and 54% positive sera respectively) were obtained for specific IgM as assessed by the enzyme-linked immunosorbent assay (ELISA) using lipopolysaccharide of S. typhi as antigen (median relative titer: 0.32 and 0.21 respectively). In contrast, specific IgG at significant concentrations were found in only 69% of the Austrian (median relative titer: 0.16) but 88% of the Hong Kong sera (median relative titer: 0.71). The (IgM-detecting) microagglutination test may be sufficiently diagnostic for typhoid fever in nonendemic areas such as Austria. In endemic regions like Hong Kong, however, tests indicative for early specific IgG are indispensable for serological diagnosis of the disease. The ELISA proved useful and is an example for such tests.

Adult↗

Outbreaks of typhoid fever in the United States, 1960-99.

Although the incidence of typhoid fever in the United States has been low since the 1940s, Salmonella Typhi continues to cause outbreaks. We reviewed reported outbreaks of typhoid fever from 1960 to 1999. There were 60 outbreaks; in 54, exposure occurred within the United States. These 54 outbreaks accounted for 957 total cases (median 10) and 4 deaths. In 36 (67%) outbreaks the route of transmission was identified, and in 16 (62%) of the 26 foodborne outbreaks an asymptomatic carrier was identified by culture or serology. The median incubation period was 2 weeks. Isolates from 10 (40%) of 25 outbreaks were phage type E1. The average frequency of outbreaks decreased from 1.85/year during 1960-79 to 0.85/year during 1980-99 (P=0.0001). S. Typhi outbreaks in the United States are generally small in size but can cause significant morbidity, and are often foodborne, warranting thorough investigation.

Adolescent↗

[Isolation of a highly purified capsular polysaccharide from Salmonella enterica serovar Typhi (Salmonella typhi)--Vi-antigen and its use in serological diagnosis of typhoid fever].

For use in differential diagnostics of typhoid fever, samples of the capsular polysaccharide from Salmonella enterica serovar Typhi (usually named Vi-antigen) were isolated and characterized by physicochemical and serological methods. It was shown that only the sample of Vi-antigen with the minimal (0.57%) admixture of the corresponding lipopolysaccharide (LPS) from S. typhi retained a high serological activity in the tests with monoreceptor anti-Vi sera. However, it exhibited a substantially weaker reaction with sera from normal donors and patients with acute nontyphoid salmonelloses, than Vi-antigen preparations with a higher (0.8-1.2%) LPS content. The chromatographically pure Vi-antigen was purified by triple reprecipitation with hexadecyltrimethylammonium bromide. The content of the LPS admixture in the resulting Vi-antigen samples was quantitatively determined by GC. A high purification level of the Vi-antigen from the LPS admixture allows us to hope that this preparation could serve as a basic component of the test system for the diagnostics of typhoid fever. The English version of the paper.

Chemical Precipitation↗

Clinical significance of hepatic dysfunction with jaundice in typhoid fever.

A retrospective case note review was undertaken to assess the clinical significance of hepatic dysfunction with jaundice in typhoid fever. Of the 57 patients, 21 (36.8%) had jaundice, while 36 (63.2%) did not have jaundice. Significantly higher proportions of jaundiced patients were females (P = 0.04). Confusion (P = 0.01), upper abdominal pain (P = 0.02), right upper quadrant tenderness (P = 0.0001), and low prothrombin index (P = 0.04) were statistically significant occurrences in jaundiced patients on admission. Admission mean values of serum bilirubin (P = 0.0001), gamma-glutamyltranspeptidase (GGT; P = 0.009), and alanine aminotransferase (ALT; P = 0.0005) were significantly higher in icteric patients while mean values of total serum protein (P = 0.0009) and albumin (P = 0.0001) were significantly higher in anicteric patients. There were no deaths. Glomerulonephritis occurred significantly (P = 0.001) more frequently in icteric patients. It is concluded that hepatic dysfunction with jaundice in typhoid fever indicates more severe hepatic injury, which may precipitate the development of clinically detectable glomerulonephritis.

Adolescent↗

Reactivity of typhoid patients sera with stress induced 55 kDa phenotype in Salmonella enterica serovar Typhi.

Salmonella faces a variety of stresses including acid and heat, in the natural environment whether in the gastrointestinal tract of mammalian host or in the external environment during transmission where survival and multiplication is a priority for the pathogen. In the present study, Salmonella enterica serovar Typhi was grown under acid (inorganic and organic) as well as heat stress and the outermembrane protein (OMP) profiles were compared. A 55 kDa OMP was found to be expressed with high intensity under the selected stress conditions in comparison to normal conditions. The protein expressed under acidic stress reacted with antibodies raised against heat shock protein indicating the similarity of atleast some of the epitopes. In vivo immunogenicity (reactivity with typhoid patient sera) revealed that the 55kDa protein under each stress condition was reactive with 83% of the typhoid sera. In the light of role of the stress induced proteins in pathogenesis of microbial infections and their immunogenic potential, these findings may be relevant for a better understanding of the host-microbe interactions and for future development of diagnostic and preventive strategies.

Acids↗

Isolated thrombocytopenia: the presenting finding of typhoid fever.

Thrombocytopenia is generally seen as a complication in typhoid fever. However, it can also be encountered as a presenting sign on admission. A 29-year-old man with complaints of fever and diarrhoea was hospitalized because of isolated thrombocytopenia encountered on routine complete blood count examination. The diagnosis of typhoid fever was established when Salmonella typhi was isolated from the blood cultures. The platelet count returned to normal level within the first week of ceftriaxone therapy. Possible mechanisms of thrombocytopenia were discussed.

Adult↗

HLA-DRB1*12 is associated with protection against complicated typhoid fever, independent of tumour necrosis factor alpha.

We investigated whether HLA-DR2 or -DR12 alleles in 63 Javanese patients with complicated or non-complicated typhoid fever were associated with severity of disease. No association was observed between HLA type and susceptibility to disease. However, in patients we did find a negative association of DR12 (DRB1*12021) with complicated typhoid fever (P = 0.05; OR = 0.3; 95% CI: 0.1-1.0). No effect of DR2 (DRB1*1502) on outcome (P = 0.46; OR = 1.5; 95% CI: 0.5-4.5) was demonstrated. The odds ratio for DR12 remained unchanged after adjusting for DR2. Tumour necrosis factor alpha (TNF-alpha) production capacity in lipopolysaccharide (LPS)-stimulated whole blood culture, as measured by non-equilibrium radioimmunoassay, was significantly lower in complicated than in non-complicated cases (P = 0.02), confirming previous data. No significant correlation of either DR12 (P = 0.47) or DR2 (P = 0.89) was found with TNF-alpha production capacity. Apparently, protection against complications by DR12 is attributable to other mechanisms.

Adolescent↗

Outcome in three groups of patients with typhoid fever in Indonesia between 1948 and 1990.

The outcome in three groups of patients with bacteriologically confirmed typhoid fever caused by Salmonella typhi, treated during three episodes between 1948 and 1990 in Java, Indonesia, was compared by retrospective analysis of hospital records. The study population consisted of three groups of patients. Group I (n = 50) was treated in Batavia (the present Jakarta) from 1948 to 1950, Group II (n = 61) in Yogyakarta from 1952 to 1956, Group III (n = 105) in Semarang from 1989 to 1990. Main outcome measures were days until defervescence, early relapses during hospitalization, duration of hospital stay, complications and mortality. Group I received supportive treatment only, Group II low doses of chloramphenicol (total 12.5 g) and Group III full doses of chloramphenicol (total 27 g); occasionally other antibiotics were used. In Group I, II and III the mean number of days until defervescence was 16, 8 and 6 and the mean number of days in hospital 43, 47 and 15, respectively. Mortality was 26%, 10% and 5% and complications occurred in 38%, 18% and 13%, respectively. Between Group I and Group II the differences in mortality and complications were statistically significant (P < 0.05). Compared to Group I the proportion of early relapses was higher in Group II, but was zero in Group III. There were significantly fewer gastrointestinal complications in Group II than in Group I (P < 0.01) and even fewer in Group III. When no antibiotic against S. typhi was available, typhoid fever had a protracted course, and only 74% of patients survived. Even with low dosages of chloramphenicol, defervescence was earlier and mortality and complications decreased dramatically, but early relapses were frequent. Full doses of chloramphenicol for a sufficient period of time only slightly reduced mortality and complications further, but eliminated early relapses completely.

Adolescent↗

Hemolytic uremic syndrome in association with typhoid fever.

BACKGROUND: Hemolytic uremic syndrome (HUS) has been associated with typhoid fever caused by Salmonella typhi. The pathogenesis of HUS in the context of S typhi infection is not known. The authors report on a patient with typhoid fever in whom HUS and myocarditis developed during the course of his illness and in whom there was no evidence of a Shiga-toxin (Stx)-producing organism. METHODS: Antibodies directed against the Escherichia coli O157:H7 and S typhi lipopolysaccharide (LPS) were sought in the serum sample taken during the acute phase using line-blot immunoassays. Polymerase chain reaction was performed to detect the presence of stx1 and stx2 genes in the patient's S typhi isolate. RESULTS: There was no evidence for immunoglobulin (Ig) M and IgA against the LPS of E coli O157:H7, whereas anti-S typhi LPS IgM and IgA were strongly positive. In the polymerase chain reaction, DNA from the Stx-producing E coli controls yielded stx1 and stx2 fragments of the expected sizes on agarose gel electrophoresis, whereas no stx1 and stx2 fragments were obtained from the S typhi isolate. The S typhi did, however, yield a band when amplified with primers specific for viaB, an S typhi gene. CONCLUSION: S typhi may be responsible for some cases of HUS, and the inciting toxin may not be Stx.

Adult↗

Negative regulation of Salmonella pathogenicity island 2 is required for contextual control of virulence during typhoid.

Salmonella enterica relies on a type III secretion system encoded in Salmonella pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control in vivo remain unclear, particularly with regard to negative regulators that control the contextual activation of SPI-2. Here, we identified and characterized YdgT as a negative modulator of the SPI-2 pathogenicity island and established that this negative regulation is central to systemic pathogenesis because ydgT mutants overexpressing typhoid virulence genes were ultimately attenuated during infection. ydgT mutants displayed a biphasic virulence phenotype during in vivo competitive infections that consisted of an early "gain-of-virulence" dependent on SPI-2 activation, followed by attenuation later in infection indicating that proper contextual regulation of SPI-2 by YdgT is necessary for full virulence during systemic colonization. These data suggest that overexpression of virulence-associated type III secretion genes can have an adverse effect on bacterial pathogenesis in vivo.

Animals↗

Prognostic indices of typhoid perforation.

Fifty-eight cases of typhoid perforation are presented. Each case was treated surgically, and the causes of the high post-operative mortality rate are discussed. In this series of patients, the chances of survival after typhoid perforation seem to depend on the following factors: Fever: There is a significantly better prognosis if the perforation occurs in the first week of fever. Period before surgical treatment: The longer the time interval between perforation and surgery, the worse is the prognosis. Serology: Patients giving a negative Widal result and showing a high 'H' antigen titre are more likely to survive. Size of perforation: A patient who has a perforation larger than 10 mm in diameter appears to have a poor chance of survival, but this is not statistically significant. Type of surgery: Resection of the ileum with end to end anastomosis apparently gives the best prognosis, and simple closure of the perforation seems the next best. Drainage of the peritoneum and ileostomy appear mainly ineffective, but these were only carried out in severe cases.

Adolescent↗