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Rapid diagnosis of typhoid fever by detection of Barber protein and Vi antigen of Salmonella serotype typhi.

Co-agglutination (coagg) and latex agglutination (LA) tests were used for the detection of Salmonella serotype Typhi Vi and Barber protein (BP) antigens in sera from five groups of individuals (A-E). Group A consisted of 30 blood culture-positive cases of typhoid fever and group B consisted of 30 suspected cases of typhoid fever who had sterile blood cultures but positive Widal tests. Thirty cases of pyrexia of unknown origin (PUO) were placed in group C, while group D consisted of 15 cases of septicaemia caused by organisms other than Salmonella serotype Typhi. Group E comprised 50 normal healthy individuals with no history of typhoid fever or TAB vaccination in the previous 5 years. The Vi-LA test performed best with 96.7% of group A sera and 90% of group B sera giving positive results. No false positive results and only 2.58% false negative results were obtained with this test. Considering patients with positive blood culture results or positive Widal tests as true positives, the sensitivities of the Vi-LA, BP-LA, Vi-coagg and BP-coagg tests were 93.3, 91.7, 83.3 and 86.7%, respectively. The specificities of these tests were 100, 98.5, 98.5 and 98.5%, respectively. It is suggested that the Vi-LA test can be used for the rapid and early diagnosis of typhoid fever.

Agglutination Tests↗

PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever.

Host genetic factors may contribute to susceptibility to and outcome in infectious diseases. Recently polymorphisms in PARK2/PACRG, a gene cluster linked to ubiquitination and proteasome-mediated protein degradation, were found to be associated with manifest infection by M. leprae. Here, we address whether these polymorphisms are associated with susceptibility to infection with Salmonella typhi and S. paratyphi A, intracellular pathogens that upon infection of humans share with mycobacteria aspects of the hosts' immune response. The polymorphisms of PARK_e01(-697), PARK2_e01(-2599), rs1333955 and rs1040079 were analysed by polymerase chain reaction and restriction fragment length polymorphism in a case-control study of typhoid and paratyphoid fever patients in an endemic area in Jakarta, Indonesia. For this study, samples were obtained from patients with blood culture-confirmed typhoid fever (n=90), paratyphoid fever (n=26) and fever controls (n=337) in a passive, community-based surveillance and compared to those of randomly selected community controls (n=322) from the same city area. The PARK2_e01(-2599) allele T was significantly associated with typhoid and paratyphoid fever (OR: 1.51, 95%CI: 1.02-2.23) but the other polymorphisms, PARK2_e01(-697), rs1333955 and rs1040079, were not associated. Although within the PARK2/PACRG gene cluster the PARK2_e01(-2599) allele T was most strongly associated with leprosy (OR approximately 3-5), the association with typhoid is much less strong. Our findings suggest that this polymorphism in PARK2/PACRG plays a small but significant role in susceptibility to the intracellular pathogens S. typhi and S. paratyphi.

Adolescent↗

Typhoid fever in Hong Kong children.

Experience with typhoid fever in 111 children over a 5-year period was reviewed. There were 66 boys and 45 girls, ranging in age from 1 to 11.5 years. The symptoms of typhoid fever were quite non-specific. Fever was the most common presenting symptom (in 98.3%). Other common presenting features were diarrhoea (25.7%), constipation (22%), vomiting (21.1%), cough (25%), abdominal pain (27.5%), headache (9.2%), epistaxis, meningism and convulsions. Rose spots were detected in 20% of cases, occurring mainly during the first 2 weeks of illness. Significant Widal reactions were present in 84.7% of cases. Blood and stool cultures were positive in 57% and 44% of cases, respectively. Peripheral blood white cell counts were not found to be of great diagnostic value. Chloramphenicol remained the drug of choice in the treatment of typhoid fever. It was more effective than ampicillin or co-trimoxazole. Complications were uncommon, occurring in only two patients. There were two deaths; both were admitted late and in moribund state. Early diagnosis and treatment is vital in typhoid fever and, as the presenting features are non-specific, a high index of suspicion is required.

Ampicillin↗

Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder.

OBJECTIVE: The aim of this study was to identify risk factors for carcinoma of the gallbladder (CaGB) among patients with gallstones (GS) with special reference to role of chronic Salmonella typhi carrier state. METHODS: A prospective case-control study was conducted in a tertiary care center in India. Cases were defined as consecutive patients with CaGB and GS, whereas controls were patients with GS alone. All were assessed clinically and their demographic data, diet, and smoking history recorded. Patients were detected to be typhoid carriers on the basis of Vi serology by enzyme linked immunosorbent assay. Cases (n = 37) and controls (n = 80) were compared by univariate and logistic regression analysis. RESULTS: The mean age of the cases and the controls were 53.4 +/- 11 yr and 43.5 +/- 14 yr, respectively. Among the cases, six (16%) patients were detected to be typhoid carriers, in contrast to two (2.5%) among controls (p = 0.01). Compared to controls, cases were more often older (p = 0.0002), of a lower socioeconomic status (p = 0.0005), and smokers (p = 0.0002). Stepwise logistic regression analysis identified typhoid carrier state (OR = 14; CI 2-92), age > or =47 yr (OR = 5; CI 2-14) and smoking (OR = 11; CI 2-71) as the three independent risk factors for development of CaGB among patients with GS. CONCLUSION: Chronic typhoid carrier state was the most important risk factor among patients with CaGB and gallstones.

Adult↗

[A case report--typhoid fever complicated with liver and gallbladder abscess, treated for long-time as fever of unknown origin].

A 25-year-old male admitted to Kawasaki municipal hospital with the diagnosis of typhoid fever. He had noticed high fever since one month ago, and had been treated with prednisolone with the diagnosis of fever of unknown origin in a hospital. Then he had admitted to St. Marianna University Hospital, and Salmonella Typhi had been detected from his blood and stool. On admission, multiple liver abscess were detected by abdominal ultrasonography. S. Typhi in bile was not eliminated with CP and AMPC, but he was successfully treated with cholecystectomy and the chemotherapy of LVFX. Abscess formation was found in the resected gall bladder wall. Typhoid nodule in the lymph node, liver or other organs is a well known pathological change in the typhoid fever. But abscess formation in the liver or other organs is rare. In this case, multiple abscess is characteristic and this cause is thought to be induced by the factors that the period from onset of typhoid fever to beginning of effective therapy was too long, and that steroid therapy was done without antibiotic therapy.

Abscess↗

[Investigation concerning demand and vaccination applicants to traveler's vaccines (typhoid fever and meningococcal vaccines) not marketed in Japan].

In recent years, the number of Japanese traveling to foreign countries is increasing. Most of them travel to Asian regions where many infectious diseases that are rare or don't occur in Japan still remain endemic or epidemic. Of these infectious diseases typhoid fever and meningococcal infection are now preventable because safe and effective vaccines have been developed and now marketed. However, these vaccines are hardly available in Japan because the Japanese Government has not admitted them. To investigate the demand for the two vaccines, the author personally imported inactivated polysaccharide typhoid vaccine and groups A, C,Y and W135 combined polysaccharide meningococcal vaccine, both manufactured by Aventis-Pasteur. After obtaining approval of the ethical committee of our hospital, vaccination was started. From May 6, 2003 to September 30, 2004, 124 applicants received typhoid vaccine and 35 were injected with meningococcal vaccine. Of 124 vaccinees of typhoid vaccine, 46 went to Afghanistan, 15 to India, 8 to Thailand. Of 35 vaccinees of meningococcal vaccine 6 went to the USA, 5 to Guinea and 3 to England. In addition a total of 12 physicians and nurses having no international scheduled trip were also immunized with meningococcal vaccine. None of these vaccines are widely known in Japan now. Based on our results, however, the expansion of recognition and demand for these two vaccines is expected.

Adult↗

Antibodies to porin antigens of Salmonella typhi induced during typhoid infection in humans.

Immunoglobulin G (IgG)- and IgM-specific antibody titers against Salmonella typhi Ty2 porins have been measured in 30 paired typhoid sera by enzyme-linked immunosorbent assay. These studies have found that IgG serum titers of acute and convalescent sera were 625 and 5,000 times higher, respectively than the control serum titers. The same typhoid sera were titrated with S. typhi Ty2 flagellin and S. typhi lipopolysaccharide. The titers against these antigens were considerably lower than those against the porins. The highest IgM-specific titer has also been found against porins in convalescent-phase sera. However, the largest increase in IgM-specific titer compared with the control group titer was obtained against flagellin during the acute phase of typhoid. The lowest increases in antibody titer were obtained with the IgM-specific anti-lipopolysaccharide in both types of sera. This may be because many normal individuals in endemic areas already have IgM titers against lipopolysaccharide. This study has provided good evidence that porins are excellent antigens and that IgG-specific antiporin titers may be of diagnostic value in typhoid infections in endemic areas.

Antibodies, Bacterial↗

Enzyme-linked immunosorbent assay for detection of Salmonella typhi Vi antigen in urine from typhoid patients.

Because typhoid fever continues to be a major cause of illness in many developing countries, there is a clear need for a sensitive and specific test that will permit rapid laboratory diagnosis of the disease. An enzyme-linked immunosorbent assay (ELISA) has recently been developed and tested, both in the laboratory and in a clinical situation, for its ability to detect Vi antigen in urine. The ELISA was capable of detecting as little as 1 ng of purified Vi antigen per ml in urine, compared with 100 ng/ml detectable by a previously tested coagglutination method. It could also detect antigen in urine diluted as much as 1:1,024 in normal urine. In tests of urine specimens from six stool culture-positive persons in a small typhoid outbreak in the United States, the ELISA detected antigen in specimens from four of the six patients. The ELISA also proved to be specific, giving no false-positive results for specimens from 50 persons who did not have typhoid fever. The apparent high sensitivity and specificity of this ELISA make it a promising test for rapid diagnosis of typhoid fever.

Antigens, Bacterial↗

Serodiagnosis of typhoid fever by enzyme-linked immunosorbent assay determination of anti-Salmonella typhi lipopolysaccharide antibodies.

Serum samples from 22 patients with proven typhoid fever, 60 febrile nontyphoidal patients, and 120 healthy subjects were tested for immunoglobulin A (IgA), IgG, and IgM anti-Salmonella typhi lipopolysaccharide antibodies by an enzyme-linked immunosorbent assay. The levels of all three classes of immunoglobulin anti-lipopolysaccharide were higher in typhoid patients than in controls; the test for IgM anti-lipopolysaccharide gave the best discrimination between typhoid and nontyphoidal sera. The absorbance values obtained with the enzyme-linked immunosorbent assay for IgM anti-lipopolysaccharide were highly correlated to the titers of anti-O agglutinins. However, the enzyme-linked immunosorbent assay was much more specific than the Widal test, and hence it could be a useful tool for the serological diagnosis of typhoid fever with a single blood sample.

Antibodies, Bacterial↗

Evaluation of passive bacterial agglutination for the diagnosis of typhoid fever.

We evaluated the reliability of a passive bacterial agglutination test to detect Salmonella typhi somatic antigen(s) in the sera of patients with typhoid fever. It was positive in 32 of 33 bacteriologically proven typhoid fever cases. Among 13 patients with a presumptive diagnosis of typhoid fever, 11 were positive by passive bacterial agglutination. The serum of one patient with paratyphoid A was also positive. Among 50 febrile patients without typhoid fever, one was persistently positive during the course of illness; 49 were negative. The sensitivity, specificity, and accuracy indices of the passive bacterial agglutination test were over 95%. The positive and negative predictive values were 94 and 98%, respectively.

Agglutination Tests↗

Detection of Salmonella typhi in the blood of patients with typhoid fever by polymerase chain reaction.

A polymerase chain reaction (PCR)-based test was developed for the detection of Salmonella typhi in the blood specimens from patients with typhoid fever. Two pairs of oligonucleotide primers were designed to amplify a 343-bp fragment of the flagellin gene of S. typhi. Amplified products were analyzed by agarose gel electrophoresis and Southern blot hybridization by using a 32P-labeled 40-base probe internal to the amplified DNA. The nested PCR with two pairs of primers could detect 10 organisms of S. typhi as determined by serial dilutions of DNA from S. typhi. The peripheral mononuclear cells from 11 of 12 patients with typhoid fever confirmed by blood culture were positive for DNA fragment of the flagellin gene of S. typhi, whereas 10 blood specimens of patients with other febrile diseases were negative. With the nested PCR, S. typhi DNAs were detected from blood specimens of four patients with suspected typhoid fever on the basis of clinical features but with negative cultures. We suggest that the PCR technique could be used as a novel diagnostic method of typhoid fever, particularly in culture-negative cases.

Bacteremia↗

Molecular analysis of isolates of Salmonella typhi obtained from patients with fatal and nonfatal typhoid fever.

Molecular characterization of a total of 52 human isolates of Salmonella typhi from Papua New Guinea was performed by using pulsed-field gel electrophoresis (PFGE) after digestion of chromosomal DNA with three restriction endonucleases, XbaI (5'-TCTAGA-3'), AvrII (5'-CCTAGG-3'), and SpeI (5'-ACTAGT-3'). Of the 52 isolates tested, 11 were obtained from patients with fatal typhoid fever and 41 were obtained from patients with nonfatal disease. The 52 isolates showed limited genetic diversity as evidenced by only three different PFGE patterns detected following digestion with XbaI (patterns X1 to X3; F [coefficient of similarity] = 0.86 to 1.0), four patterns detected following digestion with AvrII (patterns A1 to A4; F =0.78 to 1.0), and two patterns detected following digestion with SpeI (patterns S1 and S2; F = 0.97 to 1.0). Of the 52 isolates, 37 were phage typed, and all belonged to phage type D2. All 11 isolates obtained from patients with fatal typhoid fever were identical (F = 1.0) and possessed the PFGE pattern combination X1S1A1, whereas the 41 isolates from patients with nonfatal typhoid fever had various PFGE pattern combinations, the most common being X2S1A2 (39%), X1S1A1 (24%), and X1S1A2 (15%). Thus, all the isolates from patients with the fatal disease had the X1 and A1 patterns, whereas the majority of the isolates from patients with nonfatal typhoid fever possessed the X2 and A2 patterns. The data suggest that there is an association among strains of S. typhi between genotype, as assessed by PFGE patterns, and the capability to cause fatal illness. Analysis of blood and fecal isolates of S. typhi from the same patient also indicated that some genetic changes occur in vivo during the course of infection.

Base Sequence↗

Salmonella enterica serovar Typhi O:1,9,12 polysaccharide-protein conjugate as a diagnostic tool for typhoid fever.

Serologic tests play an important role in diagnosis of typhoid fever. In an effort to develop a more defined reagent for these tests, purified Salmonella enterica serovar Typhi (ST) O:1,9,12 polysaccharide was conjugated to human serum albumin (HSA), and the conjugate was purified chromatographically to yield a reagent with 2 moles ST O polysaccharide per mole HSA. In 40 patients with bacteriologically confirmed typhoid fever, significant dot immunobinding titers (> or =20,000) were present in 28 (70%) tested with 100 ng of ST O antigen-HSA (ST O-HSA) conjugate, in 38 (95%) tested with 100 ng of ST lipopolysaccharide, and in 16 (40%) tested with purified unconjugated ST O chains. In sera from 22 patients with other nontyphoid fevers, 2 (9.1%) had such reactivities with 100 ng of ST O-HSA, 1 (4.5%) had such reactivity with 100 ng of ST lipopolysaccharide (4.5%), and none reacted with 100 ng of unconjugated ST O chains. None of the 17 healthy-control sera reacted significantly with any of the ST reagents. None of the patient or control sera reacted with unconjugated HSA. The sensitivity of dot immunobinding for typhoid fever was 70% with 100 ng of ST O-HSA, somewhat lower than that with 100 ng of ST lipopolysaccharide (95%) but similar to that of the Widal H agglutination test with a > or =1/160 cutoff (74%). Specificities of these tests were 91%, 95%, and 86%, respectively. These preliminary results suggest that ST O polysaccharide-protein conjugates could provide a nontoxic, easily quality-controlled synthetic reagent for analysis of human immune responses to ST as well as for the development of new diagnostics and vaccines for typhoid fever.

Antibodies, Bacterial↗

Impact of age and drug resistance on mortality in typhoid fever.

The risk factors for mortality were analysed in a consecutive group of 1158 children presenting to the Aga Khan University Medical Center, Karachi, with multidrug resistant typhoid fever that had been proved on culture. There were 19 deaths, representing an overall case fatality rate of 1.6%. Multidrug resistant typhoid was associated with a more severe clinical illness and higher rates of toxicity, hepatomegaly, hypotensive shock, and death. Irrespective of drug resistance status, typhoid fever was found to be a more severe illness in young infants with significantly higher rates of diarrhoea, hypotensive shock, and mortality. Univariate analysis of admission characteristics associated with increased risk for mortality revealed significant association with younger age (p < 0.05), hypotensive shock or hypothermia (p < 0.001), obtundation (p < 0.001), seizures (p < 0.05), anaemia at admission (p < 0.005), and leucocytosis (p < 0.001). Logistic regression analysis of risk factors for mortality showed persistent association of hypothermia, toxicity, and anaemia with mortality. The data provides evidence that multidrug resistant typhoid in childhood is associated with increased risk of mortality, especially in infancy and closer attention to several risk factors for increased morbidity and case fatality rates may lead to improved outcome of treatment.

Adolescent↗

Gastric acid secretion in typhoid fever.

Gastric acid secretion was studied in 20 patients with typhoid fever (Group A), ten patients with fever other than typhoid (Group B), and ten healthy adults of matched age and sex (Group C). Patients with typhoid showed reduced acid secretion at the time of fever and one week after subsidence of fever as compared to Group C. In uncomplicated patients (Group A1), these values rose thereafter but in complicated patients (Group A2) they remained low even 12 weeks after subsidence of fever. This suggests that these patients had pre-existing hypochlorhydria which predisposed them to a severe form of disease. There may be many factors playing a significant role in making typhoid patients more prone to develop complications but the importance of gastric acid levels has also to be considered.

Adolescent↗

Typhoid fever as a cause of opportunistic infection: case report.

BACKGROUND: Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica subspecies enterica serotype typhi, which is acquired by ingestion of contaminated food and water. Each year the disease affects at least 16 million persons world-wide, most of whom reside in the developing countries of Southeast Asia and Africa. In Italy the disease is uncommon with a greater number of cases in Southern regions than in Northern ones. CASE PRESENTATION: We report on a 57-year-old Sri-Lankan male affected by typhoid fever, the onset of which was accompanied by oropharyngeal candidiasis. This clinical sign was due to a transient cell-mediated immunity depression (CD4+ cell count was 130 cells/mm3) probably caused by Salmonella typhi infection. Human immunodeficiency virus infection was ruled out. Diagnosis of typhoid fever was made by the isolation of Salmonella typhi from two consecutive blood cultures. The patient recovered after a ten days therapy with ciprofloxacin and his CD4+ cell count improved gradually until normalization within 3 weeks. CONCLUSION: Our patient is the first reported case of typhoid fever associated with oropharyngeal candidiasis. This finding suggests a close correlation between Salmonella typhi infection and transitory immunodepression.

Anti-Infective Agents↗

Vaccines against cholera, typhoid fever and shigellosis for developing countries.

Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant burden, especially among the poor in countries where these illnesses are endemic. Older-generation, parenteral, whole-cell vaccines against cholera and typhoid fever were abandoned in many countries as public health tools because of problems with insufficient protection and/or inadequate safety profiles. Modern-generation licensed vaccines are available for cholera and typhoid fever, but are not widely used by those in greatest need. A number of experimental candidates exist for all three diseases. Future research should focus on generating the evidence necessary to obtain a consensus on the deployment of existing vaccines against cholera and typhoid fever, and on clinical evaluation of pipeline vaccine candidates against all three diseases.

Bacterial Vaccines↗

A single dose, combined vaccine against typhoid fever and hepatitis A: consistency, immunogenicity and reactogenicity.

BACKGROUND: Vaccines against hepatitis A and typhoid fever are well established and have an excellent safety and immunogenicity profile. Yet these diseases, which share the same geographic distribution, remain an important cause of morbidity in travelers to endemic countries. Combined vaccination provides dual protection and improves compliance and coverage for travelers. METHODS: This multicenter study evaluated the consistency of three lots of combined hepatitis A and typhoid fever vaccine. A total of 462 healthy subjects, aged 15-50 years, were enrolled and randomly allocated to 3 groups. The single dose of vaccine contains 25 microg typhoid Vi polysaccharide and at least 1,440 ELISA units of inactivated hepatitis A in a 1 mL dose. RESULTS: Bioequivalence of all production lots was shown in terms of safety and immunogenicity. Pain at injection site was the most frequent reported local symptom, and headache was the most frequent reported general symptom. As early as 14 days after immunization >95% of the subjects were positive for anti-Vi antibodies and >86% were positive for anti-HAV antibodies. The GMTs and seropositivity rates were maintained during the 6 month follow-up. CONCLUSION: The first combined vaccine against typhoid fever and hepatitis A was safe and elicited a very good immune response, with the majority of subjects seropositive at 1 month for both antigens. This combined vaccine offered more convenience and rapid seroconversion to travelers.

Adolescent↗