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Ultrasound in the diagnosis of typhoid fever.

OBJECTIVES: To establish the efficacy of ultrasound (US) of the abdomen as a diagnostic test in Typhoid. To determine the ultrasound diagnostic criteria in cases of Typhoid. METHODS: The Widal test is the most commonly used method of detecting Typhoid fever, but does not provide results until a week after onset of fever due to the need for enough antibodies to develop to render a positive result. Abdominal Ultrasound was performed within three days of the onset of fever in 80 cases suspected to be having Typhoid fever. Subsequent follow-up scans were performed at five days, ten days and fifteen days. Subsequently, all 80 cases were found to be Widal positive and Salmonella culture was positive in 32 cases. We present our findings in 26 patients in the age group between 4 to 20 years in whom both Widal test and Salmonella culture was subsequently positive. RESULTS: The US findings were as follows: splenomegaly (n-26, 100%); Bowel wall thickening (n-22, 85%); mesenteric lymphadenopathy(n-20,77%); hepatomegaly with normal parenchymal echotexture (n-8, 31%); thickened gall bladder (n-16, 62%); biliary sludge (n-6, 23%); positive US Murphy's sign (n-7, 27%); pericholecystic edema with increased vascularity (n-6, 23%); mucosal ulceration in the wall of the gall bladder (n-1, 3.8%). CONCLUSION: In endemic areas like India, ultrasound findings of hepatomegaly, splenomegaly, ileal and cecal thickening, mesenteric lymphadenopathy and thick-walled gallbladder are diagnostic features of typhoid. Ultrasound can be a non-invasive, economical and a reasonably sensitive tool for diagnosing typhoid when serology is equivocal and cultures are negative.

Abdomen↗

Typhoid intestinal perforation in children: a continuing scourge in a developing country.

Typhoid intestinal perforation is a principal cause of morbidity and mortality affecting both adults and children. This study aims to evaluate the pattern of typhoid intestinal perforation and outcome of its management in Nigerian children. The records of consecutive children managed for typhoid intestinal perforation at Juth, between 1996 and 2005 have been reviewed. There were 184 children (M:F = 1.04:1), with a mean of 5.8 years (range 4 to 15 years). More than a half (62.5%) of the patients were in the 5-6 year age group. The incidence peaked in April-May, and November-December. Increased incidence of typhoid perforation was observed between 2002 and 2005. All patients presented with the classic features of typhoid enteric perforation. Hypokalaemia and anaemia were common at presentation. Only 75 (40.6%) patients had operation within 24 h of perforation. The types of surgery included simple excision of the edges of the peroration and closure (74.5%), wedge resection and closure in (14.5%), segmental resection with primary end-to-end anastomosis (3.6%) and right hemi-colectomy with ileo-colic or ileo-transverse anastomosis. Wound infection and dehiscence, anastomotic breakdown with faecal fistula, intra peritoneal abscesses and chest infections were the main post operative complications. The overall mortality rate was 22.8 (42). Excision and simple closure was associated with the least incidence of anastomotic breakdown and operation time. The incidence of typhoid intestinal perforation is on the increase at our institution. Early limited surgery provides optimal results.

Adolescent↗

Diagnosis of typhoid fever by two serologic methods. Enzyme-linked immunosorbent assay of antilipopolysaccharide of Salmonella typhi antibodies and Widal test.

Serum samples from 85 patients with proven typhoid fever, 11 patients with p-typhoidal fever, 101 patients with febrile non-typhoidal, and 130 healthy subjects were tested for immunoglobulin G (IgG), IgA, and IgM antilipopolysaccharide (LPS) of Salmonella typhi antibodies by enzyme-linked immunosorbent assay (ELISA) and Widal test. The levels of all three classes of immunoglobulin anti-LPS of S. typhi were higher in typhoid patients than in healthy or febrile nontyphoidal groups; we selected various combinations between the three classes of immunoglobulin to obtain the best combination of sensitivity and specificity. The sum of the absorbance values obtained from the ELISA assay for IgG+IgA+IgM (sigma lgs) was the best choice for diagnostic utility for typhoid fever. We selected a positive test at a decision level of sigma lgs > or = 1.2 with a sensitivity of 94% and a specificity of 92% with a frequency of false negative of 5.9%. The frequency of false positives for healthy controls was 7.7% and, for the febrile nontyphoidal group, it was 7.9%. We also compared receiver (or relative) operating characteristic (ROC) curves for the diagnostic usefulness of the ELISA with that of the Widal test, whose merits and limitations, especially in endemic regions, are discussed. The ELISA assay was much more sensitive and specific than any combination of the Widal test, and hence it could be a useful tool for the serologic diagnosis of typhoidal fever with a single blood sample.

Agglutination Tests↗

Is operative management effective in treatment of perforated typhoid?

BACKGROUND: Salmonella typhi infection continues to be a significant problem worldwide. Patients suffering from "typhoid" in endemic regions such as West Africa often present late in the course of the disease with symptoms of malnutrition and peritonitis. Clinical peritonitis in these patients is invariably associated with perforation of the terminal ileum and purulent peritonitis. Operative intervention and its success have not been well documented. The purpose of this article is to review the experience of 1 hospital in West Africa and the efficacy of operative management of perforated intestine from typhoid. METHODS: A retrospective review of all patients admitted between January and October of 2003 to the Carolyn Kempton Memorial Hospital in Togo, West Africa, with the diagnosis of typhoid. Demographic data including age, sex, number of perforations, and outcome were obtained. All patients were treated with ampicillin, gentamycin, and flagyl or chloramphenicol as the sole antibiotic therapy along with operative management. RESULTS: One hundred ninety-one patients with typhoid were admitted. One hundred twelve patients underwent laparotomy for perforation, 18 of whom died from persistent typhoid septicemia for a mortality rate of 16%. Reoperative management was used in some patients who did not respond immediately. CONCLUSIONS: Primary repair of typhoid perforation is a safe and effective treatment. Patients with persistent septicemia after laparotomy most likely have resistant Salmonella typhi infection. Availability of second-line antibiotic therapy in these third world countries would likely improve outcomes. Prospective studies on appropriate antibiotic therapy along with operative management in endemic areas are necessary until resources are available for preventative measures.

Adolescent↗

Typhoid fever in children: some epidemiological considerations from Karachi, Pakistan.

BACKGROUND: The morbidity of typhoid fever is highest in Asia with 93% of global episodes occurring in this region. Southeast Asia has an estimated incidence of 110 cases/100,000 population, which is the third highest incidence rate for any region. Pakistan falls into this region. There is also a considerable seasonal variation of typhoid fever, carrying significant public health importance. Children are worst affected. Population-based data from Pakistan are scarce. METHODS: From June 1999 to December 2001 a fortnightly surveillance system was established in two squatter settlements in Karachi, Pakistan, with two study centers, each staffed by a doctor and five community health workers. Cases of continuous high-grade fever for three or more days were referred to these centers and screened clinically. Blood culture and Typhidot tests were done. RESULTS: One-third of the 4198 cases with febrile episodes of three or more days detected in the community were screened at the centers; 341 were clinically suspected of having typhoid fever. Forty-nine were positive by culture whereas 161 were positive by serology. Ten cases were multi-drug resistant. Incidence of culture-proven typhoid was estimated to be 170 (95% CI: 120, 220)/100,000 population, whereas serology-based incidence was 710 (95% CI: 620, 810)/100,000 population. Peak incidence was noted in October followed by May and June. CONCLUSION: Passive surveillance, even when augmented by household visits, misses a significant portion of suspected cases. Morbidity of typhoid is quite high in Pakistan and needs public health intervention. Hot months have higher incidence of typhoid. Healthcare behavior studies will help to develop a better surveillance system.

Adolescent↗

Risk factors associated with typhoid fever in Son La province, northern Vietnam.

Between July and December 2002, we undertook a hospital-based case-control study to identify risk factors associated with typhoid fever in Son La province, northern Vietnam. Among 617 suspected cases, 90 cases of typhoid fever were confirmed by blood or stool culture. One hundred and eighty controls (neighbours of typhoid cases matched for gender and age) were chosen. Participants were interviewed at home using a standardized questionnaire. Seventy-five per cent of cases were aged 10-44 years. No cases in patients aged less than 5 years were recorded in this study. In a conditional logistic regression analysis recent contact with a typhoid patient (OR = 3.3, 95% CI 1.7-6.2, P < 0.001), no education (OR = 2.0, 95% CI 1.0-3.7, P = 0.03) and drinking untreated water (OR = 3.9, 95% CI 2.0-7.5, P < 0.001) were independently associated with typhoid fever. Improving quality of drinking water must be a priority and health education strategies targeted at individuals with no schooling, and contacts of patients, would be expected to decrease the burden of typhoid fever.

Adolescent↗

The malaria and typhoid fever burden in the slums of Kolkata, India: data from a prospective community-based study.

Recent research has indicated that the malaria burden in Asia may have been vastly underestimated. We conducted a prospective community-based study in an impoverished urban site in Kolkata, India, to estimate the burden of malaria and typhoid fever and to identify risk factors for these diseases. In a population of 60452 people, 3605 fever episodes were detected over a 12-month period. The blood films of 93 febrile patients contained Plasmodium (90 P. vivax, 2 P. falciparum and 1 P. malariae). Blood cultures from 95 patients grew Salmonella enterica serotype Typhi. Malaria patients were found to be significantly older (mean age 29 years) compared with patients with typhoid fever (15 years; P<0.001) but had similar clinical features on presentation. Having a household member with malaria, illiteracy, low household income and living in a structure not built of bricks were associated with an increased risk for malaria. Having a household member with typhoid fever and poor hygiene were associated with typhoid fever. A geographic analysis of the spatial distribution of malaria and typhoid fever cases detected high-risk neighbourhoods for each disease. Focal interventions to minimise human-vector contact and improved personal hygiene and targeted vaccination campaigns could help to prevent malaria and typhoid fever in this site.

Adolescent↗

Risk factors for typhoid fever in the Mekong delta, southern Viet Nam: a case-control study.

In order to identify risk factors for typhoid fever in a highly endemic area, we undertook a case-control study in the Mekong delta, Viet Nam. Cases were 144 consecutive patients admitted to hospital with blood culture-confirmed typhoid fever. Two controls (1 in the hospital and 1 in the community) were chosen for each case. Standardized interviews were conducted with questions regarding recent contact with a typhoid fever patient, eating habits, hygiene and socio-economic level. Cases were more likely to have been in contact with a patient with typhoid fever than hospital controls (adjusted odds ratio (OR) = 5.2, 95% confidence interval (95% CI) 1.7-15.9) or community controls (adjusted OR = 11.9, 95% CI 2.3-60.7); 11% and 14% of typhoid fever cases (compared to hospital or community controls, respectively) were attributable to recent contact with a patient with this disease. These findings suggest that strategies directed towards the persons in contact with a patient might reduce the incidence of secondary cases of typhoid fever.

Adolescent↗

Carcinoma of the gallbladder--is it a sequel of typhoid?

Gallbladder diseases, including carcinoma, are common in the northern part of India and so are Salmonella typhi infection and typhoid carrier state. This study was aimed to find out the association of typhoid carrier state in patients with cholelithiasis, carcinoma of the gallbladder, and controls. The three groups are comparable in age and sex composition. This is the first study of its kind from an area of high endemicity for both typhoid infection and carcinoma of the gallbladder. A case-control study was carried out to detect typhoid carrier state among the patients with biliary diseases and healthy controls, using indirect haemagglutination assay measuring antibodies against highly purified S. typhi Vi polysaccharide antigen. A significantly high Vi positivity was observed in patients with gallbladder carcinoma (29.4%) compared to controls (5%) (chi2 = 6.325, P < 0.004, OR = 7.19) and patients with cholelithiasis (10.7%) (chi2 = 5.066, P < 0.01, OR = 3.86). There is 8.47 times more risk of developing carcinoma of the gallbladder in culture-positive typhoid carriers than the noncarriers. The present study suggests the typhoid carrier state to be one of the possible mechanisms of gallbladder carcinogenesis.

Adult↗

Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia.

To identify risk factors for typhoid fever in Semarang city and its surroundings, 75 culture-proven typhoid fever patients discharged 2 weeks earlier from hospital and 75 controls were studied. Control subjects were neighbours of cases with no history of typhoid fever, not family members, randomly selected and matched for gender and age. Both cases and controls were interviewed at home by the same trained interviewer using a standardized questionnaire. A structured observation of their living environment inside and outside the house was performed during the visit and home drinking water samples were tested bacteriologically. Univariate analysis showed the following risk factors for typhoid fever: never or rarely washing hands before eating (OR = 3.28; 95% CI = 1.41-7.65); eating outdoors at least once a week (OR = 3.00; 95% CI = 1.09-8.25); eating outdoors at a street food stall or mobile food vendor (OR = 3.86; 95% CI = 1.30-11.48); consuming ice cubes in beverage in the 2-week period before getting ill (OR = 3.00, 95% CI = 1.09-8.25) and buying ice cubes from a street vendor (OR = 5.82; 95% CI = 1.69-20.12). Water quality and living environment of cases were worse than that of controls, e.g. cases less often used clean water for taking a bath (OR = 6.50; 95% CI = 1.47-28.80), for brushing teeth (OR = 4.33; 95% CI = 1.25-15.20) and for drinking (OR = 3.67; 95% CI = 1.02-13.14). Cases tended to live in houses without water supply from the municipal network (OR=11.00; 95% CI = 1.42-85.2), with open sewers (OR = 2.80; 95% CI = 1.0-7.77) and without tiles in the kitchen (OR = 2.67; 95% CI = 1.04-6.81). Multivariate analysis showed that living in a house without water supply from the municipal network (OR = 29.18; 95% CI = 2.12-400.8) and with open sewers (OR = 7.19; 95% CI = 1.33-38.82) was associated with typhoid fever. Never or rarely washing hands before eating (OR = 3.97; 95% CI = 1.22-12.93) and being unemployed or having a part-time job (OR = 31.3; 95% CI = 3.08-317.4) also were risk factors. In this population typhoid fever was associated with poor housing and inadequate food and personal hygiene.

Adolescent↗

Enhanced detection rate of typhoid fever in children in a periurban slum in Karachi, Pakistan using polymerase chain reaction technology.

OBJECTIVE: Yield of blood culture in clinically suspected cases of typhoid fever is low, whereas indirect serological diagnostic tests are unreliable. Hence, polymerase chain reaction (PCR)-based detection of Salmonella enterica Serovar typhi was used as an aid for diagnosis of typhoid fever in addition to other diagnostic tests. Two periurban communities in Karachi were selected for an epidemiological study of typhoid fever. The aim of the study was to assess whether PCR increased the detection rate of typhoid fever in children in the community. MATERIAL AND METHODS: Children aged 2 to 14 years presenting with fever lasting for three or more days were selected. PCR using Hashimoto's protocol based on ViaB gene sequence was used in addition to blood culture and other serological tests. RESULTS: Of the 214 children included in the study, blood culture was found positive for S. enterica S. typhi in 26 (12.4%) cases, whereas 24 children (11.7%) were diagnosed as suffering from typhoid fever when the PCR-based method was used. Both tests were positive in only 10 (4.9%) children. The number of children found positive for either test was 40. PCR increased the rate of detection of typhoid fever by 51%. CONCLUSION: The sensitivity, specificity, +ve and -ve predictive values of PCR in this study were 40%, 93%, 45% and 92%, respectively.

Adolescent↗

Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam.

The influence of genes of the major histocompatibility complex (MHC) class II and class III loci on typhoid fever susceptibility was investigated. Individuals with blood culture-confirmed typhoid fever and control subjects from 2 distinct geographic locations in southern Vietnam were genotyped for HLA-DRB1 and HLA-DQB1 alleles, the gene that encodes tumor necrosis factor (TNF)-alpha (TNFA [-238] and TNFA [-308]), the gene that encodes lymphotoxin-alpha, and alleles of the TNF-alpha microsatellite. HLA-DRB1*0301/6/8, HLA-DQB1*0201-3, and TNFA*2 (-308) were associated with susceptibility to typhoid fever, whereas HLA-DRB1*04, HLA-DQB1*0401/2, and TNFA*1 (-308) were associated with disease resistance. The frequency of all possible haplotypes of the 3 individually associated loci were estimated and were found to be significantly different in typhoid case patients and control subjects (chi2=55.56, 32 df; P=.006). Haplotypes that were either protective (TNFA*1 [-308].DRB1*04) or predisposed individuals to typhoid fever (TNFA*2 [-308].DRB1*0301) were determined. This report identifies a genetic association in humans between typhoid fever and MHC class II and III genes.

Alleles↗

Investigation of concurrent outbreaks of gastroenteritis and typhoid fever following a party on a floating restaurant, France, March 1998.

A retrospective cohort study was carried out to investigate concurrent outbreaks of gastroenteritis and typhoid fever that occurred among guests of a supper on a floating restaurant in France in March 1998. A total of 133 guests (attack rate = 90%) reported gastroenteritis within 12 days of the supper. Twenty-seven guests developed typhoid fever (attack rate = 18%) of whom 15 were confirmed by stool or blood culture. All patients with typhoid fever had had an initial gastroenteritis. The results suggest that the same food items served during the supper, chicken and rice, were the vehicles of both gastroenteritis and typhoid fever, but the authors could not determine the specific source of infection. Initial gastroenteritis has been described as a clinical manifestation of typhoid fever but whether or not these two syndromes (gastroenteritis and typhoid fever) were due to the same etiology remains unclear in this outbreak.

Adolescent↗

Low sensitivity of counter-current immuno-electrophoresis for serodiagnosis of typhoid fever.

Counter-current immuno-electrophoresis was evaluated as a diagnostic test for the serodiagnosis of typhoid fever with somatic (O), flagellar (H) and capsular polysaccharide (Vi) antigens of Salmonella typhi on the sera of patients who were blood culture positive (confirmed typhoid cases) or had high Widal agglutination titres, > or = 320, (presumptive typhoid cases). Of the 37 sera from confirmed cases, 30% showed positivity with O antigen, 24% with H antigens and 51% with Vi antigen. In patients with a presumptive diagnosis, 45% were positive for O antibody, 27% for flagellar antibody and 52% for Vi antibody. When all three antigens were combined the reactivity to any of the antigens was found to be 59% in confirmed typhoid cases, 79% in presumptive typhoid cases and 93% in patients who were simultaneously positive by blood culture and Widal agglutination. However, none of the sera from 45 controls gave a positive precipitation reaction with any of the antigens. It is concluded that counter-current immuno-electrophoresis is a rapid test with low sensitivity and high specificity with Vi antigen, a panel of antigens being most effective, and is, therefore, recommended for rapid diagnosis of typhoid fever.

Agglutination Tests↗

Diagnosis of typhoid fever: detection of Salmonella typhi porins-specific antibodies by inhibition ELISA.

Porins are highly immunogenic outer membrane proteins of Salmonella. Sera from typhoid patients contained a high level of IgG antibodies directed to porins of Salm. typhi. Since porins are highly conserved proteins, anti-porins antibodies both from typhoid patients and healthy normals reacted with porins from several Gram-negative bacteria. Therefore, in order to improve the specificity of detecting Salm. typhi porins-specific antibodies, an inhibition ELISA was developed using enzyme-conjugated MoAbs (MP1 and MPN4) specific to Salm. typhi porins. Sera from typhoid patients with positive haemoculture (16 out of 17) inhibited the binding of MP1 to porins, thus showing a positive test for typhoid, whereas sera from patients with other Gram-negative bacterial infections (n = 7) and from healthy volunteers (66 out of 67) were found to be negative. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of this assay were 94.1, 98.7, 97.8, 94.1 and 98.7% respectively. The validity of our inhibition ELISA for typhoid was higher than that of the Widal test. The diagnosis of typhoid fever as early as 3 days after the onset of fever, using a single specimen is possible.

Adolescent↗

Typhoid Toxin of Salmonella enterica Induces ISG15 Responses Mediating Host Cell Survival and Counteracting Intracellular Infection.

The typhoid toxin is a secreted virulence factor of typhoidal serovars of the bacterial pathogen Salmonella enterica implicated in typhoid fever and chronic infections. The toxin causes a DNA damage response in human cells, characterised by cell-cycle arrest and cellular distension, resulting in cellular senescence and increased bacterial burden. To better understand host responses to typhoid toxin, we performed a transcriptomic analysis of intoxicated host cells and found that the toxin induced expression of genes relating to the type-I interferon response, including the ubiquitin-like protein ISG15. ISG15 was upregulated in a STING-dependent manner, reduced bacterial burden, and was found to be critical to host cell survival in response to the typhoid toxin and interferon. This highlights ISG15 as an important component of the host cell defence to the typhoid toxin.

Humans↗

[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.

Adolescent↗

Detection of urinary Vi antigen as a diagnostic test for typhoid fever.

Since Vi antigen is limited primarily to Salmonella typhi, it has been thought that detection of the antigen may be a useful method for diagnosing acute typhoid fever. The slide coagglutination method and enzyme-linked immunosorbent assay have recently been suggested as ways to detect small quantities of Vi antigen in urine. In Santiago, Chile, we compared the results of these two methods in patients with acute typhoid fever, paratyphoid fever, and other febrile illnesses and in afebrile control subjects. Using a cut-off value that maximally separated typhoid patients from controls, the enzyme-linked immunosorbent assay was positive in 62.4% of 141 patients with culture-proven typhoid infections and in 13.2% of 159 afebrile control subjects. The enzyme-linked immunosorbent assay was false positive in 64.7% of 34 culture-proven paratyphoid A or B patients and 47.1% of 21 patients with other nontyphoidal febrile illnesses. The coagglutination test was positive in 34% of typhoid patients, 14% of afebrile control subjects, and 46% of febrile control subjects. We conclude that these tests when performed with the Vi antibodies employed in this study are of little value for the diagnosis of typhoid fever in this setting.

Adolescent↗