Typhoidal Salmonella: Distinctive virulence factors and pathogenesis.

Although nontyphoidal Salmonella (NTS; including Salmonella Typhimurium) mainly cause gastroenteritis, typhoidal serovars (Salmonella Typhi and Salmonella Paratyphi A) cause typhoid fever, the treatment of which is threatened by increasing drug resistance. Our understanding of S. Typhi infection in human remains poorly understood, likely due to the host restriction of typhoidal strains and the subsequent popularity of the S. Typhimurium mouse typhoid model. However, translating findings with S. Typhimurium across to S. Typhi has some limitations. Notably, S. Typhi has specific virulence factors, including typhoid toxin and Vi antigen, involved in symptom development and immune evasion, respectively. In addition to unique virulence factors, both typhoidal and NTS rely on two pathogenicity-island encoded type III secretion systems (T3SS), the SPI-1 and SPI-2 T3SS, for invasion and intracellular replication. Marked differences have been observed in terms of T3SS regulation in response to bile, oxygen, and fever-like temperatures. Moreover, approximately half of effectors found in S. Typhimurium are either absent or pseudogenes in S. Typhi, with most of the remaining exhibiting sequence variation. Typhoidal-specific T3SS effectors have also been described. This review discusses what is known about the pathogenesis of typhoidal Salmonella with emphasis on unique behaviours and key differences when compared with S. Typhimurium.

Clinical and laboratory profile of enteric fever in children in northern India.

The diagnosis of enteric fever poses several problems due to the non-specific and wide array of clinical features. A five-year retrospective study enrolling 136 culture-proven cases of enteric fever was undertaken in order to estimate the clinical and laboratory characteristics, fever clearance time and outcome. The common symptoms and signs were: fever, vomiting, cough, anorexia, diarrhoea, abdominal pain, hepatomegaly, splenomegaly and coated tongue. Enteric fever should be considered in the differential diagnosis of febrile patients with abdominal symptoms.

Increasing rates and clinical consequences of nalidixic acid-resistant isolates causing enteric fever in returned travellers: an 18-year experience.

The purpose of this study was to examine the rate and clinical consequences of nalidixic acid-resistant (NAR) isolates in travellers with enteric fever presenting to a hospital in a developed country. We retrospectively examined microbiologically confirmed cases of enteric fever in adult returned travellers over an 18-year period presenting to two tertiary referral hospitals in Melbourne, Australia. There were 59 cases of Salmonella typhi infection, 43 cases of S. paratyphi A infection and two cases of S. paratyphi B infection. Most patients reported recent travel to India (36%) or Indonesia (29%). NAR isolates were commonly encountered (41% of all isolates), particularly from India (75%), Pakistan (80%) and Bangladesh (60%). The number of NAR isolates increased progressively after 2003. Patients with NAR isolates had prolonged mean fever clearance time (5.6 vs. 3.3 days, P = 0.03) and prolonged hospital stay (7.9 vs. 5.7 days, P = 0.02) compared to non-resistant isolates. This represents the largest report of NAR enteric fever in returned travellers. NAR isolates predominate in cases of enteric fever from South Asia and result in prolonged fever clearance time and hospital stay. Empiric therapy with alternative antibiotics such as ceftriaxone or azithromycin should be considered in patients with suspected enteric fever from this region.

Predictive value of clinical and laboratory findings in the diagnosis of the enteric fever.

Although the definitive diagnosis of enteric fever requires the isolation of Salmonella enterica serotype typhi or paratyphi, the diagnosis is usually made according to clinical and laboratory findings. There is usually a diagnostic dilemma. The aim of this study was to determine the minimum required parameters that could be valuable in the diagnosis of enteric fever. A retrospective study was performed to compare the clinical and laboratory findings in 60 patients who proved to have enteric fever by cultures and 58 patients with non-enteric fever. Features independently predictive of enteric fever were assessed by multivariate logistic regression. Sensitivity, specificity and positive predictive and negative predictive values were estimated. Significant clinical features of enteric fever were hepatomegaly, splenomegaly, relative bradycardia, rose spots, leucopenia, trombocytopenia, eosinopenia and elevated AST level. Five of these features were found to be predictive for the diagnosis of enteric fever; splenomegaly, relative bradycardia, rose spots and trombocytopenia and elevated AST level. In conclusion, clinical and laboratory findings can help the clinician to diagnose enteric fever in the absence of microbiological confirmation.

Reversible encephalopathy secondary to paratyphoid infection and concomitant acute Hepatitis A.

Reversible encephalopathy has been described in association with typhoid fever as well as nontyphoidal salmonella infections. A diagnostic dilemma as to the cause of encephalopathy may arise when there is coexistent acute viral hepatitis and suspicion of fulminant liver failure. The authors report a patient who presented with acute icteric hepatitis A infection and a concomitant febrile illness due to Salmonella paratyphi associated with progressive encephalopathy and coma. The young man developed high-grade fever and coma. Concomitant infection with S. paratyphi was diagnosed and the patient's encephalopathy resolved rapidly with antibiotic therapy. This is the first report of a putative association of S. paratyphi infection and reversible encephalopathy. Salmonella and hepatitis A virus infection are both transmitted via the fecal-oral route, and awareness of this association is important in the management of such patients.

Value of clinical features in the diagnosis of enteric fever.

There is no objective data on the value of individual clinical symptoms or signs in the diagnosis of enteric fever in a febrile patient. The purpose of the study was to assess the value of some clinical and simple laboratory features in the diagnosis of enteric fever. One hundred & six patients with microbiologically confirmed enteric fever and 170 patients with other established febrile illnesses were included in the evaluation. History of stepladder pattern of rise of temperature, loose motions, relative bradycardia and coated tongue proved to be powerful markers of enteric fever with high specificity (100%, 94.71%, 94.71%, 94.12% respectively), positive and negative predictive values. Headache, hepatomegaly and splenomegaly were moderately powerful. ESR and WBC count appeared to have little value in the diagnosis of enteric fever. Pattern of onset and loose motions did not discriminate between typhoid and paratyphoid fever. Most of these patients had illness persisting beyond one week by which viral infections and infectious enterocolitides were largely excluded. Elucidation of power of these markers in distinguishing enteric fever from other febrile illnesses with the help of better designed prospective studies would lessen our dependence on expensive and time consuming laboratory investigations.

[Typhoid fever in school children: by what measures is the modification of the clinical course due to oral vaccination?]. / Fiebre tifoidea en escolares: en que medida la clinica es modificada por el uso de una vacuna oral?

The clinical course of infection by Salmonellae was compared between patients who had been vaccinated against typhoid fever using the Ty21a vaccine and those who had not. Of 2566 bacteriological confirmed cases 84% were infected with S typhi, 14% with S paratyphi B and 2% with S paratyphi A. Among patients with typhoid fever, 34% were treated in hospital, 3.5% had relapses, 5.4% developed complications and 1 patient died (0.05%). Among patients with paratyphoid fever, 18% were treated in hospital, 0.6% had relapses, 1.4% developed complications and there were no deaths. These figures were similar among vaccinated and non-vaccinated cases. A slightly greater proportion of vaccinated cases were treated in hospital (38 vs 30%). Thus, use of oral vaccination against typhoid fever does not alter the clinical course of infection with Salmonellae.

[Classification of septicemias. A clinical and pathogenic approach]. / Clasificacion de las septicemias. Concepcion etiopatogenica y clinica.

Classic sepsis is characterized by the presence of bacteria in blood originating from a primary infection site with secondary location at other sites. Some infectious diseases like typhoid and paratyphoid fever, brucellosis an others share this pathogenetic mechanism but have a characteristic clinical course and usually a good prognosis. After analyzing the differences between the 2 types the author proposes the terms "non specific" and "specific" for each type of sepsis, respectively. The differences between the 2, the organism involved and different reaction of the host in types, may be related to different pathogenetic effects of each case.

[Clinical research on patients with typhoid and paratyphoid fever (1984-1987). Research Group for Infectious Enteric Diseases, Japan].

Patients with typhoid or paratyphoid fever, admitted to 14 hospitals for infectious diseases during 1984-1987, were epidemically and clinically studied. Of the total number of 183 typhoid, 49 paratyphoid fever patients, those infected overseas was 44.3% and 71.4% respectively, giving an overall annual decrease, yet marking an increased ratio of overseas infection. Patients aged 20s-30s and males were dominant. One hundred and seventy six cases (96.2%) of typhoid and all the paratyphoid fever cases were bacteriologically diagnosed. The period from the onset to the diagnosis was around 14 days in most cases, but beyond 29 days in over 10% of the cases. We would like to emphasize that enteric fever, focusing on high fever, bradycardia, roseola, hepatosplenomegaly, leukopenia, elevated serum-GOT GPT and LDH, can be easily diagnosed by blood/stool culture before beginning chemotherapy. Intestinal bleeding was recognized in 24 cases (13.1%) of typhoid and 4 (8.2%) of paratyphoid fever, intestinal perforation in 2 (1.1%) and death in 1 (0.5%) of typhoid fever. CP was most commonly used in chemotherapy. Bacteriological relapse was recognized in 7/127 cases (5.5%) of typhoid, 6/48 (13.0%) of paratyphoid fever those followed beyond 3 weeks, though eradication was attained by retreatment. One strain of S. typhi resistant to CP.ABPC.KM.SM was isolated in 1986 from a patient infected overseas. New quinolones seem reliable in our preliminary studies.

Fatal complications of acute enteric fevers.

Eighty eight patients presenting with fatal typhoid complications were studied in Abbassia and Embaba fever hospitals during a 4 years period (1987-1991). Criterion of inclusion in the study was either positive blood culture in 70 (80%) cases or postmortem gross appearance of typhoid fever in 18 (20%) cases. Positive blood culture cases included 54 (77%) S. typhi and 16 (23%) S. paratyphi A. Seven (10%) cases were resistant in vitro to chloramphenicol. Postmortem examination performed in 18 (20%) cases revealed typical typhoid ulcers in ileum, jejunum and large intestine. The main clinical picture of 31 toxic, 22 encephalitic or meningeal irritating, 15 gastroenteritic, 9 pneumonic, 8 perforated and 3 haemorrhagic enteric fever cases were discussed. The tetrad of fever, toxic look, bronchitic chest, tumid tympanitic abdomen and splenomegaly was a good sign for suggestion of typhoid diagnosis.