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Value of a single-tube widal test in diagnosis of typhoid fever in Vietnam.

The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) or Salmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of >/=100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was >/=100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was >/=100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of >/=200 for O agglutinin or >/=100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care.

Adolescent↗

Serology of typhoid fever in an area of endemicity and its relevance to diagnosis.

Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of > or =0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P < or = 0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available.

Adolescent↗

The role of endotoxin during typhoid fever and tularemia in man. IV. The integrity of the endotoxin tolerance mechanisms during infection.

Volunteers infected with Salmonella typhosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhos) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.

Adult↗

A cost-effectiveness analysis of typhoid fever vaccines in US military personnel.

Typhoid fever has been a problem for military personnel throughout history. A cost-effectiveness analysis of typhoid fever vaccines from the perspective of the US military was performed. Currently 3 vaccine preparations are available in the US: an oral live Type 21A whole cell vaccine; a single-dose parenteral, cell subunit vaccine; and a 2-dose parenteral heat-phenol killed, whole cell vaccine. This analysis assumed all vaccinees were US military personnel. Two pharmacoeconomic models were developed, one for personnel who have not yet been deployed, and the other for personnel who are deployed to an area endemic for typhoid fever. Drug acquisition, administration, adverse effect and lost work costs, as well as the costs associated with typhoid fever, were included in this analysis. Unique military issues, typhoid fever attack rates, vaccine efficacy, and compliance with each vaccine's dosage regimen were included in this analysis. A sensitivity analysis was performed to test the robustness of the models. Typhoid fever immunisation is not cost-effective for US military personnel unless they are considered imminently deployable or are deployed. The most cost-effective vaccine for US military personnel is the single-dose, cell subunit parenteral vaccine.

Cost-Benefit Analysis↗

Differentiation of typhoid fever from fulminant hepatic failure in patients presenting with jaundice and encephalopathy.

OBJECTIVE: To determine the clinical and laboratory features that allow the early diagnosis of typhoid fever in patients who present with jaundice and encephalopathy. PATIENTS AND METHODS: This 12-month prospective study, conducted in Bangalore, India, between 1990 and 1991, evaluated the clinical and laboratory features of all patients (N=47) who presented with encephalopathy within 8 weeks of onset of jaundice. Ciprofloxacin and dexamethasone were used to treat 11 patients diagnosed on blood culture as having typhoid fever. The other 36 patients were presumed to have fulminant hepatic failure with a viral cause and were treated with supportive measures (bioartificial liver support and transplantation were not available). RESULTS: In patients with jaundice and encephalopathy, a liver span of greater than 9 cm on physical examination, thrombocytopenia, elevated alkaline phosphatase level, aspartate aminotransferase level greater than alanine aminotransferase level, and only mild prolongation of the prothrombin time suggested a diagnosis of typhoid fever. All 11 patients diagnosed as having typhoid fever had an excellent response to treatment with ciprofloxacin and dexamethasone with no mortality and with normalization of the liver test results in 2 weeks. On the other hand, 30 of the 36 patients with nontyphoid fulminant hepatic failure died. CONCLUSIONS: In patients presenting with jaundice and encephalopathy, physical examination and simple laboratory tests can help make an early diagnosis of typhoid fever. We believe that patients with a presumptive diagnosis of typhoid fever should be treated with ciprofloxacin and dexamethasone, even before the results of blood cultures are available.

Adult↗

The diagnostic value of the ELISA-Ty test for the detection of typhoid fever in children.

A study on the reliability of an enzyme linked immunosorbent assay (ELISA) for the detection of typhoid fever, the ELISA-Ty test, was conducted, comprising 44 children suffering from bacteriologically confirmed typhoid fever based on the finding of a positive blood culture for Salmonella typhi, 44 children with fever caused by diseases other than typhoid fever based on the finding of negative culture of blood, urine and stool for S. typhi, and 120 healthy children as controls. This ELISA-Ty test measures the concentration of IgM and of IgG against S. typhi in serum. This test is an indirect ELISA test, based on a method that makes use of a mixture of OMPs (outer membrane proteins) in equal proportion serving as antigen, obtained from different strains of S. typhi which are prevalent locally, peroxidase goat antihuman IgG or IgM (Sigma) as conjugate and orthophenylenediamine (Sigma) as chromogen of the substrate. The result of the test was obtained through the assessment of the end product, using a micro ELISA reader (Behring) at wave length of 490 nm. The data revealed that the mean absorbent values found in children with typhoid fever, for IgM and IgG, were significantly higher (p < 0.05) when compared to those in children with non-typhoid fever as well as to those found in children of the control group. The results of this study confirm that the ELISA-Ty test has a high reliability for the detection of typhoid fever in children, based on the finding of a degree of diagnostic sensitivity as high as 95.45% and 90.91% for respectively IgM and IgG, a diagnostic specificity as high as 93.33% for IgM as well as for IgG, a high diagnostic efficiency (94.32% for IgM and 92.05% for IgG), a high diagnostic positive predictive value of 93.33% for IgM and 93.02% for IgG, high negative predictive values of 95.35% for IgM and 91.11% for IgG for use under clinical as well as under field conditions.

Child↗

Atypical manifestations of typhoid fever.

BACKGROUND: High fever, toxaemia, constipation during first week of fever, complicated by encephalopathy and perforation during third week of fever are the typical manifestations of typhoid fever. However, the classical presentation of typhoid fever has considerably changed now. AIM: To study atypical presentations of typhoid fever. SETTING: A teaching unit of a hospital in South India METHOD: All culture-positive adult patients of typhoid fever admitted over a period of seven years were studied RESULTS: Thirty-two adult patients were admitted. Fifteen (46.9%) patients presented with atypical manifestations. Atypical manifestations observed were burning micturition with normal urine examination (n= 5, 15.6%) diarrhoea in first week (6.2%), encephalopathy in first week (3.1%), isolated hepatomegaly (6.2%), pneumonitis (3.1%) and bone marrow depression (6.2%). Out of 32 Salmonella typhi culture positive patients, 10 (31.3%) patients had multidrug resistant (MDR) strain. Patients with MDR strains had atypical manifestations (5/10=50%) not significantly more often than patients having multidrug sensitive strains (10/22=45.5%) (Z <2). All patients responded to treatment. CONCLUSION: It appears atypical manifestations do not necessarily mean a worse prognosis in typhoid fever. Patients having high fever presenting with pneumonia, early encephalopathy, early diarrhoea or bone marrow depression in a typhoid endemic area, should be suspected for this disease.

Adolescent↗

Utility of PCR in diagnosis of problematic cases of typhoid.

Typhoid is a global problem. Conventional diagnostic methods have limitations. The Widal test gives a high proportion of false positive results, and indiscriminate use of antibiotics has reduced the utility of blood culture. Consequently, these procedures are inadequate for diagnosing suspected cases of typhoid that do not present clear-cut symptoms. We previously showed that PCR-based diagnosis of typhoid targeting the flagellin gene has unparalleled specificity. We assessed the utility of this method for diagnosis of problematic cases of typhoid. A comparative study of PCR, blood culture, and Widal test was carried out on 55 cases of suspected typhoid with fever for 3-30 days and possessing an ambiguous clinical picture. A control group comprised of 20 healthy persons was also included. The respective positive results by PCR, blood culture, and Widal test for these groups were 58.2 and 0%, 14.5 and 0%, and 52.7 and 45%. Sensitivity of PCR as compared with that of blood culture was significantly better. We concluded that PCR is much superior to conventional methods and, due to its high sensitivity and specificity, can be of great use for rapid and definitive diagnosis of problematic cases of typhoid.

Case-Control Studies↗

[Problems of etiotropic therapy of typhoid fever and approaches to their solution].

The main problems of etiotropic therapy for typhoid fever lie in underestimate of the characteristic features of its pathogenesis and particularly in development of typhoid granulomas and their histogenesis, as well as in wide spread of typhoid fever pathogenic strains resistant to the routine chemotherapeutics, i.e. polyresistant strains. Some problems are due to incorrect choice of the antimicrobials and their combinations, optimal doses, administration routes and pathogenetic therapy. In the XXth centure an increase in the emergence and a change in the nature of the typhoid fever pathogen resistance to antimicrobials were observed. It was shown that from the pharmacologic and pharmacodynamic viewpoints the highest efficacy of typhoid fever therapy should be provided by the following antimicrobials: fluoroquinolones (except for norfloxacin), 3rd and 4th generation cephalosporins, aminopenicillins, chloramhenicol (levomycetin), combinations of 2nd and 3rd generation aminoglycosides with biseptol, aminopenicillins or doxycycline, as well as chloramphenicol combinations with aminopenicillins or 2nd to 4th generation cephalosporins. Practical recommendations for the etiotropic therapy of patients with typhoid fever during its outbreak or epidemic are presented.

Anti-Bacterial Agents↗

Clinical profile of typhoid patients.

OBJECTIVE: The present study was undertaken to determine the clinical profile of typhoid fever in hospitalised patients. DESIGN: Prospective cross-sectional study. SETTING: Kathmandu Medical College and Teaching Hospital. METHOD: Total of thirty patients above fifteen years of age who had clinical features strongly suggestive of typhoid fever and on blood culture found to be positive for Salmonella typhi were analysed for clinical features. RESULT: Among total of thirty cases, there were 17 (57%) males and 13 (43%) females. 86% of cases of typhoid fever clustered around 15-30 years of age. Predominant symptoms were fever (100%), headache (90%), abdominal Pain (37%) and constipation (33%). Common clinical signs were splenomegaly (37%), relative bradycardia (27%) and hepatomegaly (17%). None of the patients presented with complications. CONCLUSION: The clinical profile of typhoid fever in our study revealed not much difference from that of other studies on typhoid fever. Rose spots were not noticed and we did not find a single case of complication of typhoid fever. Probably early initiation of antibiotics prevented the complications.

Adolescent↗

Typhoid fever in an 8-month-old infant.

Typhoid fever occurs both in epidemic and endemic forms and is a public health problem in developing countries. Typhoid fever is rare under 2 years of age. The clinical profile of typhoid fever in an infant is variable and non-specific. The absence of specific symptoms or signs makes the clinical diagnosis of typhoid fever difficult. The problem in diagnosing typhoid fever in a young infant is highlighted with a brief literature review on the subject. A rare case of typhoid fever in an 8 month old infant is reported.

Female↗

Comparative study between paratyphoid A and typhoid fever cases.

Twenty eight positive blood culture paratyphoid A fever cases were studied. Forty two positive blood culture typhoid cases were taken as controls. Cases and controls were subjected to: 1) careful history, 2) thorough clinical examination, 3) two blood cultures for salmonella, 4) Widal agglutination test, 5) total and differential white blood count, 6) urine and stool cultures following therapy. There was no significant difference in the clinical picture between acute paratyphoid A fever and acute typhoid fever except the significant decrease of anorexia (57%), toxic look (54%), coated tongue (64%) in acute paratyphoid A cases when compared to acute typhoid cases. The prevalence of extraintestinal symptoms in paratyphoid A cases may mimic viral infections. Three of the 4 classical signs namely; toxic look (54%), bronchitic chest (50%), splenomegaly (72%) and tympanitis (64%) were good bed side suggestive clinical diagnostic aids in paratyphoid A cases. Blood culture was the cornerstone of diagnosis of paratyphoid A cases. In 6 (21%), only the second blood sample was positive stressing the value of multiple cultures. Significant Widal antibody titre was elicited in only about half (57%) of paratyphoid A cases which was significantly lower than typhoid cases (83%). Leucopenia was found in only 25% of paratyphoid A cases. Eosinopenia was constant and is considered as a diagnostic and prognostic aid. No correlation was elicited between either the height of antibody titre or the height of leucocytic count and the severity of illness. There was no significant difference in the response to therapy or the occurrence of complications between paratyphoid A cases and typhoid cases. Up to the current knowledge, this is the first report on comparative study between acute paratyphoid A fever and acute typhoid fever in Egypt from clinical, diagnostic, therapeutic and prognostic points of view.

Acute Disease↗

Enteric fever among Israeli travelers in Nepal: the need for typhoid vaccination.

Enteric fever is still an endemic disease in many developing countries. Most authorities recommend typhoid vaccination for travelers from developed countries to developing countries, particularly in the Indian subcontinent. The Ministry of Health in Israel, however, does not recommend typhoid vaccination to Israeli travelers going to any developing countries. In a study undertaken at a Western-run clinic in Kathmandu, Nepal, we found the rate of typhoid fever infection to be seven times higher among 243 Israeli travelers treated at the clinic for all causes than among 2,866 other Western tourists. The typhoid vaccination rate of the Israeli tourists was 6% compared with 91% for the other Western tourists. We could not detect any differences between the Israeli tourists and the others except for the vaccination status. We conclude that the high rate of enteric fever among Israelis is due to the lack of typhoid vaccination, and we recommend typhoid vaccine for all travelers to the Indian subcontinent.

Adult↗

A simple and rapid diagnostic test for typhoid fever.

Barber protein sensitized latex particles were used in the latex agglutination test for the diagnosis of typhoid fever and the result compared with that of Widal 'O' and 'H' agglutination test. The latex agglutination test was positive in all 20 bacteriologically proved typhoid patients, in 81 of 85 (95.3%) typhoid suspected patients, and only in 2 of 85 (2.3%) blood donors. In contrast, the positive rates were 60% for both 'O' and 'H' Widal agglutinations in bacteriologically proved typhoid patients, 34.2% and 71.7% respectively in typhoid suspected patients, and none of blood donors were positive. The sensitivity and specificity of the latex agglutination test were 100% and 97.6% respectively with positive and negative predictive values of 90.9% and 100% respectively. The latex agglutination test may be particularly useful for the presumptive diagnosis of typhoid fever in remote health centres.

Adolescent↗

Value of single Widal test in the diagnosis of typhoid fever.

The usefulness of single Widal test in the diagnosis of typhoid fever was investigated. The test was done on 50 normal children, 50 children with non typhoidal fevers and 30 culture proved typhoid cases. Twenty one (70%) and nine (30%) of thirty typhoid fever cases had 'O' and 'H' agglutinin titer levels of more than or equal to 1:160, respectively as compared to only 3 (3%) and to 1 (1%) among controls. These differences were significant (p < 0.001). Twenty two (73.3%) out of thirty typhoid fever cases had either an 'O' or 'H' agglutinin titer of more than or equal to 1:160 as compared to only 3 (3%) among controls. An 'O' agglutinin titer of 1:160 had a specificity of 97%, a sensitivity of 70% and an accuracy of 90%. An 'H' agglutinin in titer of 1:160 was had a specificity of 97%, a sensitivity of 30% and an accuracy of 83.1%. Based on the above analysis, 'O' or 'H' titers of 1:160 or more were indicative of typhoid fever. Similarly, when the 2 titers were considered together, either 'O' or 'H' titers of 1:160 or more were suggestive.

Agglutination Tests↗

Value of a single Widal test in the diagnosis of typhoid fever.

Results of a single Widal test in patients with bacteriologically confirmed typhoid fever (116), clinically suggestive but culture negative fever (170) and non-typhoidal febrile illness (98) and in normal control children (54) were analysed. Positive Widal test (antibody titre against S. typhi O antigen of 1:160) was recorded in 61.2 per cent of patients with bacteriologically confirmed typhoid fever and in 58.8 per cent with culture negative but clinically suggestive typhoid fever. In contrast, the same titre was observed in 10.2 per cent patients with other febrile illnesses of known etiology and in 1.8 per cent of normal children. Differences in the positivity of Widal test in patients with bacteriologically confirmed typhoid fever and clinically suggestive but culture negative fever were highly significant (P < 0.000001) when compared to that of patients with non-typhoidal febrile illnesses and normal controls. High specificity and positive predictive value in 1:160 dilution makes the Widal test acceptable as a diagnostic tool.

Antibodies, Bacterial↗

Typhoid hepatitis.

Typhoid Hepatitis is a rare presentation of typhoid fever, clinically suspected in patients with persistent fever hepatomegaly and jaundice and especially in cases where the liver function tests show predominantly conjugated hyperbilirubinemia, modest elevation of liver enzymes and negative serology for viral hepatitis. From January, 1989 to December, 1994, 476 cases were included in this study, 204 with typhoid fever admitted in JPMC Karachi and 272 in Civil Hospital, Quetta. Eleven percent cases had typhoid hepatitis. Nineteen (4%) cases were initially diagnosed as viral hepatitis and 33 (7%) developed jaundice later on. As typhoid is prevalent in Pakistan and typhoid hepatitis is a challenging problem, accurate and simple methods are required for diagnosis in all febrile cases. It should particularly be considered as a differential diagnosis for cases with fever, jaundice and hepatomegaly.

Adolescent↗

Risk Factors for Typhoid Fever in Travelers.

Background: The incidence of typhoid fever in the developing world remains high and has been estimated at 540 cases per 100,000 of the population per year. International travelers to such areas are at risk of infection, especially if they travel under low hygienic standards. Methods: In order to identify the risk factors leading to infection in travelers and expatriates, travel histories, anamnestic and clinical features of 31 patients with typhoid fever, who presented to a German travel clinic, were investigated. Results: Compared to the total patient population of the outpatient clinic during the period of investigation (n = 17,029 patients), patients who presented with typhoid fever were older (39 years versus 31 years, p <.001) and traveled longer (58 days versus 19 days, p <.001). While only 19.2% of the total patient population had traveled to the Indian subcontinent prior to referral, 35.4% of the patients with typhoid fever had acquired the infection there (p <.001). Similar results were obtained for South East Asia and Indonesia: twenty percent of the total patient population traveled there in contrast with 32.2% of patients with typhoid fever (p <.001). Latin America was visited by 16.3% of all patients, but only 6.4% of patients with typhoid (p <.001).

Journal Article↗