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Diagnostic usefulness of Vi-indirect fluorescent antibody test(Vi-IFAT) for typhoid fever--a prospective study.

Although the confirmative diagnosis of typhoid fever is by culture of the causative organism, usually from blood, a serological test is still necessary to provide a more rapid method of diagnosis. The indirect fluorescent antibody test, using a Salmonella typhi Vi antigen and a FITC-conjugated rabbit anti-human polyvalent immunoglobulin, was evaluated for the diagnosis of typhoid fever. Serum specimens were collected from patients with febrile diseases on admission. Of the 32 patients with titers of 1:64 or more, 22 were confirmed to have typhoid fever by blood culture and 7 had fever of undetermined origin that was considered to be typhoid fever clinically. Three patients were diagnosed to have salmonellosis other than typhoid fever. Of the 121 patients with titers of 1:32 or less, 105 patients had non-typhoidal febrile disease, 15 patients had fever of undetermined origin, and one patient was confirmed to have typhoid fever by blood culture. When a Vi antibody titer of 1:64 or more was taken as serological evidence for the diagnosis of typhoid fever, the sensitivity and specificity were 95.7% and 97.2%, respectively. The incidence of positive test results following fever onset was 70.0% within 1 week of fever onset, 88.9% from 1 to 2 weeks, and 100% after 2 weeks. In conclusion, the Vi-indirect fluorescent antibody test(Vi-IFAT) can be employed as a useful serologic test in the diagnosis of typhoid fever.

Antigens, Bacterial↗

[Adenosine deaminase in typhoid fever and other febrile diseases].

The contribution of serum adenosine deaminase (ADA) activity to the diagnosis of typhoid fever was assessed in 246 children and in 46 adults, by Giusti's original technique. Children included otherwise healthy patients admitted for elective surgical conditions or under follow up for epilepsy which were considered to be a control group (n: 81), presumptive viral diseases (n: 31), miscellaneous febrile diseases except for typhoid fever (n: 41), different kinds of bacteremia (n: 6), diarrhea due to Salmonella typhimurium (n: 14), viral hepatitis (n: 24), and culture proven typhoid fever (n: 49). Adult's group included 39 healthy controls and 7 patients with culture proven typhoid fever. Among children mean ADA activity was as follows: control group 28 +/- 7.8, viral disease 35.3 +/- 13.1, miscellaneous febrile disease 36.1 +/- 15.6, bacteremia group: 30.3 +/- 10.3, salmonellosis group 51.6 +/- 9, hepatitis group 68.3 +/- 34.5, typhoid fever group 124.4 +/- 40.8 U/I 37 degrees C. Among adults, values were 18.4 +/- 7.5 for controls and 112.8 +/- 19.2 U/I 37 degrees C in typhoid fever patients. In both adults and children ADA activity was significantly higher in the typhoid fever group (p < 0.0001). Untreated typhoid fever patients had their higher ADA activity between 10th and 15th day of illness. When ADA cut point was set at 80 U/I, sensitivity of the test was 91.8% and specificity was 91.4% as a preliminary clue to the recognition of typhoid fever.

Adenosine Deaminase↗

Multidrug-resistant typhoid fever in Singapore.

A study was conducted to determine the clinical and epidemiological characteristics of multidrug-resistant (MDR) typhoid fever in Singapore. Twenty-one of 121 patients with typhoid fever had MDR typhoid fever after recent travel to the Indian subcontinent. Fifty patients with drug susceptible typhoid fever were also analysed for comparison. Nineteen of the MDR S. typhi isolates had resistance to ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole (TMP-SMX) while the remainder had resistance to ampicillin and TMP-SMX. The predominant presenting symptoms were fever and diarrhoea. Eleven patients with MDR typhoid fever were treated with oral ciprofloxacin and nine with intravenous ceftriaxone. The patients with MDR typhoid fever had a longer duration of fever defervescence (8 +/- 5 days) compared to those with drug-susceptible typhoid fever (5.7 +/- 4.16 days) (p < 0.01). Eighteen patients were cured and one patient defaulted treatment. Two patients relapsed within two months of treatment. The study showed that 17.4% of patients with typhoid fever had imported MDR S. typhi after recent travel to the Indian subcontinent where MDR typhoid fever is prevalent.

Adult↗

Typhoid perforation. A review of the literature since 1960.

Typhoid fever is still a major health problem in the developing parts of the world, with an estimated annual incidence of 540 per 100,000. Probably one of the most lethal complications of typhoid fever is ileal perforation, which affects especially young men. We reviewed the literature published after 1960 on typhoid perforation in different developing countries, with special attention to the incidence and outcome of typhoid perforation. Information was obtained on a total number of 1,990 cases of typhoid perforation in 66,157 patients with typhoid fever, published in 52 reports all over the world. The overall frequency of intestinal perforation in typhoid fever was 3% with an overall mortality rate of 39.6%. In an endemic area of typhoid fever, the diagnosis of typhoid perforation should be made on physical examination. Surgery is perferable to medical treatment.

Adolescent↗

Susceptibility patterns and serotypes of non-typhoidal salmonella in Trinidad.

OBJECTIVE: To study the serotype distribution of non-typhoidal salmonella isolated from clinical specimens and to evaluate their susceptibility patterns to the most commonly prescribed antimicrobial agents used in this region. METHODS: A retrospective study during the period 1993 1999 was carried out at the Eric Williams Medical Sciences Complex Microbiology Laboratory, a teaching hospital in the northwestern part of Trinidad. Strains of non-typhoidal salmonella were serogrouped with polyvalent Salmonella O antiserum and sent to the local Public Health Laboratory for confirmation and further serotyping. RESULTS: A total of 412 strains of non-typhoidal salmonella were serotyped. Of the 13 serotypes, Salmonella enteritidis was the most prevalent 57%, followed by Salmonella typhimurium, 25%, Salmonella virchow 5% and Salmonella heidelberg, 4%. Three hundred and sixty-two (87.5%) non-typhoidal salmonella were isolated from stool, 38 (9%) from blood, 8 (2%) from urine and 4 about 1% from infected wounds. Of the 13 serotypes only Salmonella enteritidis, Salmonella typhimurium, Salmonella virchow and Salmonella heidelberg were simultaneously isolated from blood and stool. One serotype, Salmonella aberdeen, was encountered for the first time in 1993. All isolates were fully sensitive to chloramphenicol, gentamicin, cefuroxime and ceftrioxone. Resistance to ampicillin, augmentin and co-trimoxazole was less than 4%. One third of all non-typhoidal salmonella isolates were resistant to tetracyclines. CONCLUSION: The most prevalent serotypes were Salmonella enteritidis and Salmonella typhimurium which accounted for 82% of all isolates. The prevalence of resistance of non-typhoidal salmonella to antibiotics was very low (5%). Therefore, due to this low prevalence of resistance, we did not provide details of resistance in relation to serotype. However, it was observed that of the 137 non-typhoidal salmonella resistant to tetracycline, more than 80% were Salmonella enteritidis and Salmonella typhimurium strains. Of the 9 antibiotics, tetracycline was the only drug to which one-third of the non-typhoidal salmonella were resistant. Due to the risk of resistance continued surveillance of susceptibility patterns of non-typhoidal salmonella to antibiotics must be maintained and encouraged.

Anti-Bacterial Agents↗

Chloramphenicol clearance in typhoid fever: implications for therapy.

We prospectively studied the pharmacokinetics of intravenous Chloramphenicol succinate (CS) in children (age 6 months-14 years) with culture proven typhoid fever (n = 30) and non typhoidal illnesses (n = 10). CS was administered in three different dosage regimens (50, 75 and 100 mg/kg/d-q 6 hourly). Liver function tests were monitored. Plasma trough and peak chloramphenicol concentrations were measured by HPLC analysis after 42 hrs. The 50 mg/kg/day dosage schedule was terminated midway through the study, as blood levels were consistently low and two patients with typhoid relapsed, children with typhoid had significantly lower clearance of CS in comparison with those with non-typhoidal illness (0.29 +/- 0.1 versus 0.5 +/- 0.37 1/kg/hr, P 0.05). There was no significant difference between mean peak and trough concentrations of chloramphenicol on 100 mg/kg/day and 75 mg/kg/day in children with typhoid. However, two children on 100 mg/kg/day dosage developed trough concentrations greater than 20 mcg/ml. No correlation was found between CS clearance and serum bilirubin, SGPT (alanine transaminase) and alkaline phosphatase. Our data show altered clearance of CS in children with typhoid and suggests that 75 mg/kg/day may be a safer dose in children with hepatic dysfunction in typhoid.

Bilirubin↗

The early diagnosis of typhoid fever prior to the Widal test and bacteriological culture results.

In an attempt to evaluate various clinical and laboratory features available within 24 h of admission, prior to the Widal test and bacteriological culture results as potential diagnostic aids in typhoid fever, we undertook a retrospective unit-based case control study in 90 febrile adult and paediatric patients admitted to King Edward VIII Hospital, Durban, South Africa with an initial diagnosis of typhoid fever. A total of 30 blood culture-proven typhoid fever patients (cases) were matched to 60 patients confirmed as not having typhoid fever (controls) by age, sex, race and severity of illness on admission. Features significantly associated with a final diagnosis of typhoid fever were: a pre-admission duration of fever > or = 7 days (odds ratio (OR) 6.9); hepatomegaly (OR 3.2); a normal leucocyte count (OR 10.8); a leucocyte count of < 10.0 x 10(3)/mm3 (OR 30.2); and leucopenia due to absolute neutropenia with a relative lymphocytosis (OR 11.8). Although the sensitivity, specificity and predictive values of any of these features cannot be used reliably to distinguish typhoid fever from other non-typhoidal febrile illness, it is concluded that leucopenia due to absolute neutropenia with relative lymphocytosis, when present, is highly suggestive of typhoid fever. A leucocyte count of > 10.0 x 10(3)/mm3 (OR 0.03) provides strong presumptive evidence against such a diagnosis.

Adolescent↗

Helicobacter pylori infection and typhoid fever in Jakarta, Indonesia.

We evaluated the association between typhoid fever and Helicobacter pylori infection, as the latter microorganism may influence gastric acid secretion and consequently increase susceptibility to Salmonella typhi infection. Anti-H. pylori IgG and IgA antibody titres (ELISA) and gastrin concentration (RIA) were determined in the plasma of 87 blood culture-confirmed typhoid fever cases (collected after clinical recovery) and 232 random healthy controls without a history of typhoid fever, in the Jatinegara district, Jakarta. Patients with typhoid fever more often than controls were seropositive for H. pylori IgG (67% vs. 50%, P<0.008), when antibody titres were dichotomized around median titres observed in controls. H. pylori IgA seropositivity was not associated with typhoid fever. Plasma gastrin concentrations indicative of hypochlorhydria (i.e. gastrin > or =25 or > or =100 ng/l) were not significantly elevated in typhoid fever cases compared to controls (P=0.54 and P=0.27 respectively). In a multivariate analysis, typhoid fever was independently associated with young age (<33 years, median age of the controls) [odds ratio (OR) 7.93, 95% confidence interval (CI) 3.90-16.10], and H. pylori IgG seropositivity (OR 1.93, 95% CI 1.10-3.40). Typhoid fever was independently associated with H. pylori IgG seropositivity, but not with elevated gastrin concentration. Therefore, the association suggests a common risk of environmental exposure to both bacteria, e.g. poor hygiene, rather than a causal relationship via reduced gastric acid production.

Adolescent↗

Immigration of Ethiopians with typhoid fever to Israel: apparent lack of influence on the local population.

The epidemiology of typhoid fever in Western countries may be affected by immigration from developing countries. We studied the immigration of Ethiopian Jews to Israel to find the effects of an influx of many individuals infected with typhoid into an area with a low incidence of the disease. Typhoid fever affected 204 Israelis and 121 (1.1%) of 10,654 Ethiopian immigrants during the period of 1984-1985. Of those Ethiopian cases, 107 occurred during a 3-month period. During the 5 months following that 3-month period, there was no increase in the number of cases of typhoid among Israelis. Although after that time there was a local waterborne outbreak of typhoid that affected 83 Israelis, no Ethiopians resided in the area where the outbreak occurred; therefore, we concluded that these 83 cases of typhoid fever were not related to the immigration of Ethiopians into Israel. In fact, if those 83 cases were excluded from the statistical analysis, there was no increase in the occurrence of typhoid during the 2-year period studied. Therefore, the immigration of many people with typhoid into an area of low incidence does not necessarily confer a risk of infection to the local population.

Emigration and Immigration↗

Blood culture confirmed typhoid fever in a provincial hospital in the Philippines.

Epidemiological features of blood culture confirmed typhoid fever and antibiotic sensitivity of isolated Salmonella typhi strains were investigated in Bohol Province in Central Philippines from where no earlier information of these was avialable. Typhoid fever is endemic elsewhere in the Philippines (eg Metropolitan Manila and surroundings) where also multidrug resistant S. typhi strains have been detected. A laboratory for surveillance of invasive bacterial infections was established in a tertiary care government hospital, in Bohol, Central Philippines, in 1994. Patients with suspected typhoid fever or other serious infection were managed and blood cultures from them were taken according to clinicians' judgment. Blood cultures were processed and the isolated bacteria identified using generally accepted methods. S. typhi and other Salmonella isolates were identified using commercial antisera. Patient data were collected from hospital records. Of a total of 4,699 blood cultures done during a period of 3 3/4 years, 1,530 (32%) were requested for suspected typhoid fever. S. typhi was the most common pathogen isolated from 422 patients (8.9%), followed by S. paratyphi A from 55 patients (1%). Most patients were young adults (43%) and school age children (28%). Male:female ratio was 1.5:1. Among the 422 patients, there were 9 (2%) deaths due to typhoid fever, all with complications. All S. typhi isolates were sensitive to chloramphenicol, cotrimoxazole, and ampicillin. Our observation on blood culture confirmed typhoid fever demonstrates its importance as a major infectious disease in Bohol and gives a sound basis for treatment of typhoid patients and for further clinical and epidemiologic studies of typhoid fever and for following antibiotic sensitivity of S. typhi in Bohol and elsewhere in the Philippines.

Adolescent↗

An algorithm for the clinical differentiation of malaria and typhoid: a preliminary communication.

The objective of this study was to determine which clinical features of typhoid and malaria are most helpful in distinguishing the two diseases among Papua New Guinean highlanders. In a study of 35 patients with culture-positive typhoid and 49 with blood-slide-positive malaria (Group 1), the odds of typhoid were increased most in patients with altered bowel habit, an illness of more than 2 week's duration, tremor or the presence of typhoid facies. The odds of typhoid were lowest in patients with pallor or jaundice. These findings were used to derive a clinical diagnostic algorithm, which was then evaluated in a further group of 34 typhoid patients and 41 malaria patients (Group 2). The sensitivity of the algorithm in diagnosing malaria was 91% in Group 1 and 71% in Group 2, with specificities of 85% and 79% respectively. For typhoid, the sensitivity of the algorithm was 85% and 79% for Groups 1 and 2, respectively, and the specificities were 91% and 71%. We conclude that the algorithm merits further evaluation in a primary health care setting and may prove useful in making an earlier diagnosis of typhoid.

Algorithms↗

Typhoid fever: clinical diagnosis versus laboratory confirmation.

BACKGROUND: Recently there has been an increase in the clinically diagnosed typhoid fever in various parts of Nigeria with subsequent increase in public fear of possible epidemics of the disease. In this study the accuracy of clinically diagnosed typhoid fever were investigated. METHODS: Blood and stool specimens from 260 patients clinically diagnosed typhoid fever were investigated using Widal test and bacteriological culture methods respectively. RESULTS: One hundred and thirty-four (51.5%) of the cases investigated were positive and that there was a significant difference (P < 0.05) between the clinically diagnosed and bacteriologically confirmed typhoid fever cases. Causative organisms were Salmonella typhi 46 (34.3%); S paratyphi B 34 (25.4%); S paratyphi A 24 (17.9%); S paratyphi C 20 (14.9%); other Salmonella spp 10 (7.5%). Young adults and males were predominantely affected. CONCLUSION: Most of the clinically diagnosed typhoid cases were misdiagnosis and the hue and cry by the general public on the epidemic of typhoid fever could not be justified. It is recommended that careful detailed history taking, meticulous clinical examination and prompt bacteriological culturing of specimens from suspected typhoid cases will improve the accuracy of clinically diagnosed typhoid fever.

Adolescent↗

Diagnostic value of the Widal test for typhoid fever in Singapore.

A study was conducted to assess the diagnostic value of the Widal test in patients with bacteraemic typhoid fever. The Widal test was carried out on 25 bacteriologically proven cases of typhoid fever and 50 patients with non-typhoid fever. All the patients with non-typhoid fever had an O agglutinin titre of less than 1:40, while 82% had an H agglutinin titre of less than 1:40. In the patients with typhoid fever, 56% had an O agglutinin titre of greater than or equal to 1:40 and 72% had an H agglutinin titre of greater than or equal to 1:40. Typhoid patients with titres greater than or equal to 1:40 for O and H antigens of Salmonella typhi were significantly different (P less than 0.01) from those with non-typhoid fever. The O agglutinin was highly specific (100%) in the diagnosis of the disease. The study shows that a single Widal test is useful in the diagnosis of typhoid fever in Singapore.

Adolescent↗

Evaluation in Papua New Guinea of a urine coagglutination test and a Widal slide agglutination test for rapid diagnosis of typhoid fever.

Two simple rapid tests for the laboratory diagnosis of typhoid fever were evaluated, a coagglutination test for detecting Salmonella typhi antigens in urine and a Widal slide agglutination for detecting serum antibodies. Ninety-two culture-confirmed typhoid cases were compared with 64 non-typhoid fever patients, 50 close contacts of typhoid patients, 30 vaccinated staff and 72 healthy community members. A strong urine Vi coagglutination was found to be 86.5% sensitive and 91.8% specific for typhoid, but was not always easy to read. The slide Widal H was found to be 99% sensitive and 95% specific whereas the slide Widal O was 98% sensitive and 98% specific. These data suggest that a single slide Widal O, at a reciprocal titre of 40, is the most suitable rapid test for the diagnosis of typhoid in a population with low typhoid antibody levels in the community, few other cross-reacting Salmonella infections, and a tendency for patients to present late in the infection.

Adolescent↗

Identification of typhoid fever and paratyphoid fever cases at presentation in outpatient clinics in Jakarta, Indonesia.

In Jakarta, Indonesia, over 80% of patients with typhoid fever or paratyphoid fever are treated in outpatient settings. In a community-based prospective passive surveillance study, we identified 59 typhoid, 23 paratyphoid fever and 259 non-enteric fever outpatients, all blood culture-confirmed. We compared their symptoms with the aim of developing a clinical prediction rule that may help direct empirical antibiotic treatment to cases with suspected (para)typhoid fever, rather than all febrile patients, or refer patients for additional diagnostic tests. Paratyphoid fever (Salmonella paratyphi A) could not be distinguished clinically from typhoid fever. Decisions on empirical antibiotic treatment and advice on hygiene measures in patients with suspected (para)typhoid fever should take into account chills and absence of cough in the first week of fever and delirium in the second week of illness. This prediction rule increases the likelihood of (para)typhoid fever from 1:10 in the first week to, at most, 2:3 in the second week of a febrile illness. However, we were not able to propose a robust clinical prediction rule that could be used as absolute screening method for decisions on additional diagnostic tests, because of the low sensitivity of presenting symptoms in (para)typhoid fever.

Abdominal Pain↗

A simple validated prediction rule to diagnose typhoid fever in Turkey.

The goal of this study was to develop a simple prediction rule for the diagnosis of typhoid fever. A model for the prediction of patients with typhoid fever at hospital admission was derived and validated by assigning weighted point values to independent predictive factors associated with a diagnosis of typhoid fever at hospital admission. Patient demographic, clinical and laboratory variables were used to compare patients with blood culture-confirmed typhoid fever with patients with fever of unknown origin. The model was derived and validated in two separate cohorts of patients from Dicle University Hospital in Diyarbakir, Turkey. A total of 371 patients were enrolled. A diagnostic index score was created using seven independent predictive factors associated with typhoid fever at hospital admission: age <30 years, abdominal distention, confusion, leukopenia, relative bradycardia, positive Widal test and a typhoid tongue. A clinical prediction rule helped to differentiate patients with typhoid fever.

Adolescent↗

An update on concurrent malaria and typhoid fever in Cameroon.

Malaria and typhoid fever are endemic diseases in Cameroon, with overlapping signs and symptoms. While the high prevalence of malaria is an established fact, it is only within the past 5 years that an unusually high number of illnesses have been diagnosed as malaria co-existing with typhoid fever. The Widal test is widely used as the sole laboratory test for the diagnosis of typhoid fever. To investigate the extent of the malaria and typhoid fever association, we used blood and stool cultures as additional diagnostic tests for typhoid fever. We report that, of 200 patients presenting with fever, 17.0% had concurrent malaria and typhoid fever (Salmonella typhi) based on bacteriological proven diagnosis as compared with 47.9% based on the Widal test. A higher proportion of patients (32.5%) had malaria coexisting with S. typhimurium when compared to S. paratyphi (2%) and S. typhi (P < 0.05). We conclude that the number of fever cases diagnosed as malaria co-existing with typhoid fever is overestimated.

Adolescent↗

One-step 2-minute test to detect typhoid-specific antibodies based on particle separation in tubes.

Typhoid fever is caused by Salmonella typhi. Detection of anti-S. typhi antibodies in the patient is a useful diagnostic aid. Among the various methods developed over the years for this purpose, the Widal test, based on bacterial agglutination, has remained the most widely used, even though it is neither specific nor sensitive. Its popularity stems from the fact that it is simple to use and inexpensive. We describe a new test which also uses a simple one-step procedure but is more rapid and accurate than the Widal. The new test (TUBEX) detects anti-Salmonella O9 (both immunoglobulin M [IgM] and IgG) antibodies in patients by inhibiting the binding between an anti-O9 IgM monoclonal antibody (MAb) conjugated to colored latex particles and S. typhi lipopolysaccharide (LPS) conjugated to magnetic latex particles. The reactants are mixed in a specially designed microtube for 2 min, and the result is read based on the resultant color of the supernatant following forced sedimentation of the magnetic beads. In the absence of inhibitory antibodies, there is a color change (from blue to red) due to cosedimentation of the indicator particles with the magnetic particles, whereas if these antibodies are present, they prevent such a change to a degree dependent on their concentration. Preliminary examination of TUBEX using the anti-O9 MAb and irrelevant MAbs as inhibitors revealed the test to be specific and reproducible, with an analytical sensitivity of 16 micrograms per ml of antibody. The reagents remained stable for at least 9 months when kept at 4 degrees C. In the examination of 16 stored sera obtained from 14 patients with proven cases of typhoid fever and 78 serum samples from 75 subjects without typhoid fever, TUBEX was found to be 100% sensitive and 100% specific. The nontyphoid group comprised 26 healthy blood donors, 30 antinuclear antibody (ANA)-negative patients, 9 ANA-positive patients, of whom 1 was positive for anti-DNA antibody, 4 typhus patients, and 6 septicemic patients. In addition, the sera obtained from 11 patients clinically diagnosed as having typhoid fever were all positive in the test. The TUBEX results correlated to some extent, albeit insignificantly (r = 0.38, P = 0.07), with those of an enzyme-linked immunoassay (ELISA) which used a similar detection format (inhibition) and reagents (S. typhi LPS and anti-O9 antibody). TUBEX correlated very well with ELISAs which detected anti-S. typhi LPS IgM (r = 0.58, P = 0.003) or IgG (r = 0.54, P = 0.006) antibodies from the typhoid patients. There was no correlation with the Widal test. The TUBEX test, if performed on slides (instead of tubes) or with soluble antigen (instead of antigen-conjugated magnetic beads), suffered significantly in sensitivity. Direct agglutination tests using LPS-conjugated indicator particles performed either on slides or in microwells also failed to detect antibodies from the majority of typhoid patients. Thus, TUBEX appears to be well designed and well suited for use in the laboratory or by the bedside as a simple, rapid aid to the routine diagnosis of typhoid fever.

Antibodies, Bacterial↗