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Detection of antibodies to Salmonella "O" antigens in typhoid fever by counterimmunoelectrophoresis. II. Assessment in patients with typhoid fever and in a healthy population.

Two different population groups were studied. In one, 50 patients with a confirmed diagnosis of typhoid fever. Serum determinations were made for the detection of antibodies to S. typhi somatic antigen using Widal technique, surface fixation test and counterimmunoelectrophoresis (CIE). In the other group, 350 healthy subjects were studied to determine the minimum diagnostic titer by means of CIE. It was possible to establish that a 1:16 titer was suggestive of typhoid fever when CIE techniques were used. Surface fixation test showed the highest sensitivity levels. CIE with sensitivity levels similar to those found in Widal's reaction exceeds the other test because of its standardization and greater reproducibility.

Adolescent

Therapy of antimicrobial-resistant typhoid fever.

Antimicrobial-resistant typhoid fever in Saigon was studied by examining in vitro antimicrobial susceptibilities of Salmonella typhi strains and conducting a randomized clinical trial of ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ). Isolates of S. typhi were obtained from blood or stool cultures of 90 patients. Of 87 isolates tested for antimicrobial susceptibility, 65 (75%) were resistant (R) to chloramphenicol, streptomycin, sulfonamide, and tetracycline, and 22 (25%) were susceptible (S). The drug resistance was transferable to Escherichia coli and was found in 11 different Vi-phage types. All isolates were susceptible to ampicillin and to TMP-SMZ. Agar dilution studies of TMP and SMZ showed synergistic inhibition of growth in all 18 S isolates and in 12 of 48 R isolates tested. The clinical trial of ampicillin and TMP-SMZ showed that both drugs were equally effective. Treatment failure with both drugs was more frequent in patients with S isolates than in patients with R isolates. Therefore, in an area where antimicrobial-resistant typhoid fever exists, patients with R isolates should receive either ampicillin or TMP-SMZ, but patients with S isolates should be treated with chloramphenicol.

Ampicillin

Plasma kallikrein activation and inhibition during typhoid fever.

As an ancillary part of a typhoid fever vaccine study, 10 healthy adult male volunteers (nonimmunized controls) were serially bled 6 days before to 30 days after ingesting 10(5)Salmonella typhi organisms. Five persons developed typhoid fever 6-10 days after challenge, while five remained well. During the febrile illness, significant changes (P < 0.05) in the following hematological parameters were measured: a rise in alpha(1)-antitrypsin antigen concentration and high molecular weight kininogen clotting activity; a progressive decrease of platelet count (to 60% of the predisease state), functional prekallikrein (55%) and kallikrein inhibitor (47%) with a nadir reached on day 5 of the fever and a subsequent overshoot during convalescence. Despite the drop in functional prekallikrein and kallikrein inhibitor, there was no change in factor XII clotting activity or antigenic concentrations of prekallikrein and the kallikrein inhibitors, C1 esterase inhibitor (C1-INH) and alpha(2)-macroglobulin. Plasma from febrile patients subjected to immunoelectrophoresis and crossed immunoelectrophoresis contained a new complex displaying antigenic characteristics of both prekallikrein and C1-INH; the alpha(2)-macroglobulin, antithrombin III, and alpha(1)-antitrypsin immunoprecipitates were unchanged. Plasma drawn from infected-well subjects showed no significant change in these components of the kinin generating system. The finding of a reduction in functional prekallikrein and kallikrein inhibitor (C1-INH) and the formation of a kallikrein C1-INH complex is consistent with prekallikrein activation in typhoid fever. The correlation of these changes with the drop in platelet count suggests that a common mechanism may be responsible.

Adult

Typhoid fever in children: a forgotten disease?

All indexed cases of typhoid fever occurring in children over a ten-year period in Jacksonville, Fla, were studied retrospectively. This review revealed that anorexia was the most common gastrointestinal complaint and that neurologic symptoms and signs were nearly as common as gastrointestinal signs. There was a significant delay in diagnosis in most cases because typhoid fever was not included in the differential diagnosis upon admission. This is probably due to the decline in the incidence of typhoid fever in the United States and the resultant lowering of the index of suspicion for the disease on the part of physicians in general. Representative cases are presented in detail.

Adolescent

Detection of antibodies to Salmonella "O" antigens in typhoid fever by counterimmunoelectrophoresis. I. Description of technique.

In the serum of patients with typhoid fever counterimmunoelectrophoretic techniques were used for the detection of antibodies to Salmonella "O" antigen. Lipopolysacharides (LPS) obtained with phenol and water from Salmonella typhi (antigens 0, 9 and 12) were used. Positive results were obtained in those patients with typhoid fever (20). The lower and higher titration levels were 1:8 and 1:32 respectively; the geometric mean was 1:16. The variation coefficient during the intra assay tests was 0.19, and remained stable throughout the inter-assay tests. Reproducibility, as well as a rapid technique, make this test a valuable tool for the serologic diagnosis of typhoid fever.

Adolescent

Spatial-temporal and phylogenetic analyses of epidemiologic data to help understand the modes of transmission of endemic typhoid fever in Samoa.

Salmonella enterica serovar Typhi (S. Typhi) is either widely distributed or proximally transmitted via fecally-contaminated food or water to cause typhoid fever. In Samoa, where endemic typhoid fever has persisted over decades despite water quality and sanitation improvements, the local patterns of S. Typhi circulation remain unclear. From April 2018-June 2020, epidemiologic data and GPS coordinates were collected during household investigations of 260 acute cases of typhoid fever, and 27 asymptomatic shedders of S. Typhi were detected among household contacts. Spatial and temporal distributions of cases were examined using Average Nearest Neighbor and space-time hotspot analyses. In rural regions, infections occurred in sporadic, focal clusters contrasting with persistent, less clustered cases in the Apia Urban Area. Restrictions to population movement during nationwide lockdowns in 2019-2020 were associated with marked reductions of cases. Phylogenetic analyses of isolates with whole genome sequences (n = 186) revealed one dominant genotype 3.5.4 (n = 181/186) that contains three Samoa-exclusive sub-lineages: 3.5.4.1, 3.5.4.2, and 3.5.4.3. Variables of patient sex, age, and geographic region were examined by phylogenetic groupings, and significant differences (p<0.05) associated genetically-similar isolates in urban areas with working ages (20-49 year olds), and in rural areas with age groups typically at home (<5, 50+). Isolates from asymptomatic shedders were among all three sub-lineages. Whole genome sequencing provided evidence of bacterial genetic similarity, which corroborated 10/12 putative epidemiologic linkages among cases and asymptomatic shedders, as well as 3/3 repeat positives (presumed relapses), with a median of one single nucleotide polymorphism difference. These findings highlight various patterns of typhoid transmission in Samoa that differ between urban and rural regions as well as genomic subtypes. Asymptomatic shedders, detectable only through household investigations, are likely an important reservoir and mobile agent of infection. This study advances a "Samoan S. Typhi framework" that supports current and future typhoid surveillance and control efforts in Samoa.

Humans

Salmonella typhi--induced stimulation of blood lymphocytes from persons with previous typhoid fever.

In 21 persons with previous typhoid fever and in 15 controls thymidine incorporation of blood lymphocytes stimulated in vitro by killed Salmonella typhi was studied. The optimal culture conditions were established to be a cell density of 10(5) cells per vial, stimulated with 10(8) S. typhi and incubated for 5 days. The lymphocytes response to S. typhi was significantly higher in the typhoid group than in the controls. The lymphocyte responsiveness was not correlated to the time elapsed since the attack, and was not found different in patients who had had typhoid relapse. No difference was found in lymphocyte response to the mitogens PHA, PWM and Con-A between the typhoid group and the controls.

Adolescent

Typhoid fever.

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Humans

[Pleuro-pulmonary complications of typhoid fever. 1case].

The authors report a case of typhoid fever with pleuro-pulmonary complications and recall their characteristics: Usually early (second week), may appear under treatment, whereas the disease evolves normally. Characterised by the absence of infective phenomena, the multiple manifestations, the fleeting course and the favourable prognosis. This corresponds to the pleuro-pulmonary typhus syndrome described long ago, which is probably due to immunological phenomena. Sometimes late, evolving towards suppuration, abscess formation and empyema with presence of typhoid bacilli, rarely seen nowadays.

Humans

Comparison of trimethoprim-sulfamethoxazole and amoxicillin in therapy of chloramphenicol-resistant and chloramphenicol-sensitive typhoid fever.

The efficacy of orally administered trimethoprim-sulfamethoxazole was compared with that of oral amoxicillin in therapy of typhoid fever due to both epidemic chloramphenicol-resistant and endemic chloramphenicol-sensitive Salmonella typhi. Both drug regimens were effective and of comparable value in treatment of chloramphenicol-resistant infections, as measured by duration of fever (124 hr and 115 hr, respectively) and duration of bacteremia (1.0 and 0.4 days, respectively). Trimethoprim-sulfamethoxazole therapy of infections due to chloramphenicol-sensitive S. typhi resulted in more rapid lysis of fever than did amoxicillin therapy. Trimethoprim and sulfamethoxazole were not synergistic in vitro against the chloramphenicol-resistant strain of S. typhi, and the role of sulfamethoxazole in treatment of such infections appears to be minimal. Oral administration of trimethoprim-sulfamethoxazole is effective therapy of chloramphenicol-resistant, and probably of ampicillin-amoxicillin-resistant, typhoid fever.

Adolescent

Development of specific cellular immunoreactivity in typhoid fever.

Development of cellular immunoreactivity to Salmonella typhi and Salmonella paratyphi-A was studied by the leukocyte migration inhibition test in 9 patients with typhoid fever and in 2 patients with paratyphoid fever. Cellular reactivity could be demonstrated from the first days of the disease in all the subjects. The most pronounced migration inhibition was observed during the febrile period. It is suggested that specific cellular reactivity may play a pathogenetic role in typhoid fever.

Adult

[Wilms' tumor, multiple intestinal parasitosis and typhoid fever].

The case was that of a 21-month-old infant who presented a great inoperable Wilm's tumor that was treated with vincristine to the point of practically disappearing. Severe typhoid fever that was complicated by multiple intestinal parasitoses (ascariasis, trichuriasis, giardiasis and strongyloidiasis) appeared. Possibly, tumoral necrosis, salmonellosis and the parasitoses formed a sac that opened to the hepatic angle of the colon. Finally, multiple liver metastases were discovered and confirmed pathologically. The patient died 36 hours after surgical reexamination and liver biopsies, from causes not clearly explained. Comments are made on the diagnostic problems originated by rareness of the association of typhoid fever resistant to chloramphenicol, intestinal parasitoses and a great Wilms' tumor and the possible influence of chemotherapy and radiotherapy in the evolution of the case.

Biopsy

Detection of Vi-negative Salmonella enterica serovar typhi in the peripheral blood of patients with typhoid fever in the Faisalabad region of Pakistan.

The synthesis and transportation proteins of the Vi capsular polysaccharide of Salmonella enterica serovar Typhi (serovar Typhi) are encoded by the viaB operon, which resides on a 134-kb pathogenicity island known as SPI-7. In recent years, Vi-negative strains of serovar Typhi have been reported in regions where typhoid fever is endemic. However, because Vi negativity can arise during in vitro passage, the clinical significance of Vi-negative serovar Typhi is not clear. To investigate the loss of Vi expression at the genetic level, 60 stored strains of serovar Typhi from the Faisalabad region of Pakistan were analyzed by PCR for the presence of SPI-7 and two genes essential for Vi production: tviA and tviB. Nine of the sixty strains analyzed (15%) tested negative for both tviA and tviB; only two of these strains lacked SPI-7. In order to investigate whether this phenomenon occurred in vivo, blood samples from patients with the clinical symptoms of typhoid fever were also investigated. Of 48 blood samples tested, 42 tested positive by fliC PCR for serovar Typhi; 4 of these were negative for tviA and tviB. Three of these samples tested positive for SPI-7. These results demonstrate that viaB-negative, SPI-7-positive serovar Typhi is naturally occurring and can be detected by PCR in the peripheral blood of typhoid patients in this region. The method described here can be used to monitor the incidence of Vi-negative serovar Typhi in regions where the Vi vaccine is used.

Bacterial Proteins

Sequential changes in the concentration of specific serum proteins during typhoid fever infection in man.

An automated immunoprecipitin system has been utilized to quantitate the concentration of 10 specific proteins in the plasma of man. Values obtained by this technique are in agreement with the published concentrations for these specific plasma proteins. This technique was utilized to determine the sequential change s in 10 individual plasma proteins of volunteers exposed to Salmonella typhi. In those volunteers who developed typical typhoid fever, plasma concentrations of the acute phase proteins, alpha1-acid glycoprotein, alpha1-antitrypsin, and haptoglobin, as well as C3 complement were significantly increased with the onset of febrile illness. In contrast, the concentration of plasma albumin and tranferrin were depressed while plasma IgM became elevated during early convalescence from this infection. No significant changes were observed in the plasma concentrations of alpha2-macroglobulin, IgG, or IgA. In the exposed volunteers who did not become ill, the only significant change was a brief depression of alpha1-antitrypsin. During typhoid fever the patterns of change for individual plasma acute-phase globulins were different from those reported for patients with hepatitis, myocaridal infarction, or surgery.

Adult

[Treatment of typhoid fever with chloramphenicol or ampicillin combined with oxyphenbutazone].

Ninety-four patients with typhoid fever were treated, at random, with three therapeutic regimens: chloramphenicol alone, chloramphenicol plus oxyphenbutazone, and ampicillin plus oxyphenbutazone. The results are evaluated analyzing the body temperature graph and by serial blood had bone marrow cultures taken at intervals until they became negative. Bacteriologic diagnosis was confirmed by blood culture (39.3%) and/or bone marrow culture (77%). The mean duration of fever was 3.3 days for the group treated with chloramphenicol-oxyphenbutazone, 4.3 for those with chloramphenicol alone and 5 days for the group ampicillin-oxyphenbutazone; at the same time, blood cultures became negative at 4.4, 5.5 and 4.4 days respectively. Negativization of bone marrow cultures was not influenced by the addition of oxyphenbutazone. It is concluded that the influence of oxyphenbutazone in shortening the febrile period or in the negativization of blood cultures is not significant. It is considered that oxyphenbutazone is not an important therapeutic tool in this group of diseases.

Administration, Oral