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PubMed1993

Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy.

To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-gamma), and cytokine receptors (tumor necrosis factor receptor [TNF-R] p55 and TNF-R p75) were measured in the plasma of 29 adult Nepalese with culture-positive typhoid fever before therapy and on days 4 and 15 after start of therapy with either ceftriaxone at 2 g/day for 3 days or chloramphenicol at 50 mg/kg of body weight per day for 14 days. Bacteriologic cure was defined as blood cultures testing negative on days 4 and 15 after start of therapy; clinical cure was defined as symptomatic improvement within 5 days after start of therapy and absence of relapse. Clinical and bacteriologic cures occurred in 24 patients. There were two clinical failures, two patients who failed to complete therapy because of leukopenia, and one relapse. Mean levels before therapy were elevated compared with those in healthy controls (IL-6, 11.4 pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and fell progressively during and after therapy. For six patients (three in each treatment group) who showed prolonged fever (> 5 days) or relapse, mean levels of IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P < .05). These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever and that these concentrations can be useful in predicting outcome.

Adolescent↗
PubMed1994

Pharmacokinetics of ceftriaxone in patients with typhoid fever.

Ceftriaxone in short courses has emerged as an effective alternative to chloramphenicol for the treatment of typhoid fever. To study the pharmacokinetics of ceftriaxone in acute typhoid fever, 10 febrile Nepalese adolescents and young adults with blood culture-positive illness were treated with 3 g of ceftriaxone (intravenous infusion for 30 min) daily for 3 days. On the 1st and 3rd day of treatment, blood and urine samples were collected at defined intervals for measurements of drug concentrations. Kinetic parameters including concentrations at the end of infusion (Cmax) and 24 h after the end of infusion (Cmin), elimination half-life (t1/2), area under the plasma concentration-time curve (AUC), total plasma clearance, renal clearance, percentage excreted in urine, and volume of distribution were estimated. On day 1, mean values were as follows: Cmax, 291 micrograms/ml; Cmin, 21.7 micrograms/ml; plasma t1/2, 5.2 h; AUC, 1,428 micrograms.h/ml; total plasma clearance, 37 ml/min; renal clearance, 19 ml/min; percentage excreted in urine, 49.7%; and volume of distribution, 16.1 liters. Mean values on day 3 were not significantly different from those on day 1. Compared with published values for healthy volunteers who received the same dose, our mean t1/2s and AUCs were lower and our mean total plasma clearances, renal clearances, and volumes of distribution were higher. The good clinical responses of these patients to therapy and the adequate Cmins support the use of ceftriaxone once daily for the treatment of typhoid fever.

Adolescent↗
PubMed1999

Azithromycin versus ciprofloxacin for treatment of uncomplicated typhoid fever in a randomized trial in Egypt that included patients with multidrug resistance.

To compare clinical and bacteriological efficacies of azithromycin and ciprofloxacin for typhoid fever, 123 adults with fever and signs of uncomplicated typhoid fever were entered into a randomized trial. Cultures of blood were positive for Salmonella typhi in 59 patients and for S. paratyphi A in 3 cases; stool cultures were positive for S. typhi in 11 cases and for S. paratyphi A in 1 case. Multiple-drug resistance (MDR; resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) was present in isolates of 21 of 64 patients with positive cultures. Of these 64 patients, 36 received 1 g of azithromycin orally once on the first day, followed by 500 mg given orally once daily on the next 6 days; 28 patients received 500 mg of ciprofloxacin orally twice daily for 7 days. Blood cultures were repeated on days 4 and 10 after the start of therapy, and stool cultures were done on days 4, 10, and 28 after the start of therapy. All patients in both groups improved during therapy and were cured. Defervescence (maximum daily temperatures of </=38 degrees C) occurred at the following times [mean +/- standard deviation (range)] after the start of therapy: 3.8 +/- 1.1 (2 to 7) days with azithromycin and 3.3 +/- 1.0 (1 to 5) days with ciprofloxacin. No relapses were detected. Cultures of blood and stool during and after therapy were negative in all cases, except for one patient treated with azithromycin who had a positive blood culture on day 4. These results indicated that azithromycin and ciprofloxacin were similarly effective, both clinically and bacteriologically, against typhoid fever caused by both sensitive organisms and MDR S. typhi.

Adolescent↗
PubMed2000

Failure of short-course ceftriaxone chemotherapy for multidrug-resistant typhoid fever in children: a randomized controlled trial in Pakistan.

The precise duration of therapy of multidrug-resistant (MDR) typhoid with broad-spectrum cephalosporins is uncertain. We prospectively randomized 57 children with culture-proven MDR typhoid to receive treatment with intravenous ceftriaxone (CRO) (65 mg/kg of body weight/day) for 7 days (short course; n = 29) or 14 days (conventional; n = 28). The response to therapy, as evaluated by the serial monitoring of the typhoid morbidity score and bacteriological clearance, was comparable between groups. In contrast to the conventional therapy, 14% of the children receiving CRO for 7 days had a confirmed bacteriological relapse within 4 weeks of stopping therapy.

Ceftriaxone↗
PubMed1976

Oxolinic acid in the treatment of typhoid fever due to chloramphenicol-resistant strains of Salmonella typhi.

Of 28 strains of Salmonella typhosa collected in late 1972 in Vietnam, 4 had minimum inhibitory concentrations to chloramphenicol of >100 mug/ml. Median minimum inhibitory concentrations of all strains to oxolinic acid were 0.39 mug/ml; ampicillin, 6.25 mug/ml; amoxicillin, 0.39 mug/ml. Widespread typhoid fever appeared in mid-1973 with more than three-fourths of strains found to be resistant to chloramphenicol. Peak serum concentrations of oxolinic acid average 3.0 mug/ml after the oral ingestion of 1.0 g. In July 1974, a pilot study was begun to evaluate the efficacy of oxolinic acid in vivo, recognizing the discrepancy between in vitro and in vivo results with many agents evaluated in the treatment of typhoid fever. Seven patients with typhoid fever, six with positive blood cultures, were treated with oxolinic acid (1.5 g twice daily by mouth, a daily dose that averaged 75 mg/kg per day) for 5 to 12 days. In four of six patients, blood cultures became negative at 2 to 3 days, with another being negative at 6 days. Despite negative blood cultures, all but one patient remained clinically ill with temperatures of >39.5 C at 4 to 9 days. All strains were susceptible to 0.19 mug of oxolinic acid per ml, and resistant strains did not occur. One patient died after being changed to ampicillin, one left against advice, three responded to amoxicillin, and one died with pseudomonas bacteremia. Toxicity to oxolinic acid did not occur.

Adolescent↗
PubMed1974

Vi antigen from Salmonella typhosa and immunity against typhoid fever. I. Isolation and immunologic properties in animals.

The role of Vi antigen in human immunity against typhoid fever has been debated for decades. Circumstantial evidence indicates that Vi antigen may play a role in pathogenicity and immunity. A Vi preparation was isolated from Salmonella typhosa, the causative organism in human typhoid fever, by a mild precipitation method. It was significantly more potent in animal studies than preparations from Citrobacter used in the past for human study and less toxic than conventional typhoid vaccines. With this antigen, the role of Vi antigen in human protection is now being investigated.

Animals↗
PubMed1980

Detection of Salmonella typhi D, Vi, and d antigens, by slide coagglutination, in urine from patients with typhoid fever.

Salmonella typhi antigens D, Vi, and d were detected in the urine of 59 out of 61 (97%) bacteriologically confirmed typhoid fever patients by slide coagglutination with monovalent antisera coupled to protein A-rich staphylococci. These antigens were also detected in the urine of an additional 22 patients, 16 of whom subsequently demonstrated seroconversion by S. typhi O antibody agglutination, but from whom the bacterium was not isolated. The remaining 13 patients had negative urine coagglutination results, no isolation of S. typhi from blood or stool specimens, and no demonstration of seroconversion. These results suggest that the method of slide coagglutination of urine can be used to screen patients with suspected typhoid fever with a high degree of reliability. The method may also have potential importance in the diagnosis of typhoid when the bacterium is not isolated.

Agglutination Tests↗
PubMed1992

Diagnosis of typhoid fever by detection of Salmonella typhi antigen in urine.

A monoclonal antibody specific for group D Salmonella antigen 9 was used in an indirect enzyme-linked immunosorbent assay (ELISA) for detecting the antigen in urine specimens collected from patients with clinical typhoid fever in Jakarta, Indonesia. The ELISA had a sensitivity of 95% in identifying patients in whom Salmonella typhi was isolated from hemocultures, 73% in patients in whom S. typhi was isolated from stool specimens, and 40% in patients in whom the organism was isolated from bone marrow cultures. Among patients in whom S. typhi was isolated from blood cultures, the ELISA had a sensitivity of 65% when a single urine specimen was examined and 95% when serially collected urine specimens were examined. A dot blot immunoassay performed on a nitrocellulose filter in parallel had a sensitivity of 85%, versus 83% for the plate ELISA in which S. typhi was isolated from blood, bone marrow, and/or stool specimens. Since S. typhi antigen is intermittently excreted in the urine of patients with typhoid fever, serially collected urine from patients with typhoid should be tested for antigen 9.

Antigens, Bacterial↗
PubMed1996

Epidemic typhoid in Chile: analysis by molecular and conventional methods of Salmonella typhi strain diversity in epidemic (1977 and 1981) and nonepidemic (1990) years.

From 1977 to 1986, Chile experienced an important typhoid fever epidemic, despite statistics that indicated apparently improving levels of sanitation of drinking water and sewage disposal. The lack of antibiotic resistance among the Salmonella typhi strains isolated during this period, the mild clinical presentation of the disease, and the initially low level of efficacy of the S. typhi Ty21a vaccine in the population exposed to the epidemic suggested that this epidemic might have resulted from the dissemination of S. typhi strains with unique characteristics. To investigate this hypothesis, we used conventional methods (bacteriophage typing and biotyping) and molecular methods (restriction fragment length polymorphism analysis, ribotyping, IS200 typing, and PCR amplification of the fliC-d gene) to study a population of 149 S. typhi isolates during 1977, 1981, and 1990, the years that included periods with low (when the disease was endemic) and high (when the disease was epidemic) morbidities. Our results indicate that these S. typhi isolates in Chile represent a number of highly diverse variants of the clone of S. typhi with a worldwide distribution described by Selander et al. (R. K. Selander, P. Beltran, N.H. Smith, R. Helmuth, F.A. Rubin, D.J. Kopecko, K. Ferris, B.D. Tall, A. Cravioto, and J.M. Musser, Infect. Immun. 58:2262-2275, 1990). For example, we detected 26 PstI and 10 ClaI ribotypes among 47 and 16 S. typhi strains belonging to this clone, respectively. These results suggest that the Chilean epidemic was probably produced by multiple sources of infection because of deficient sanitary conditions. These findings illustrate the usefulness of molecular methods for characterizing the potential causes of the typhoid epidemics and the possible routes of transmission of S. typhi strains in typhoid epidemics.

Bacterial Typing Techniques↗
PubMed2001

Quantitation of bacteria in bone marrow from patients with typhoid fever: relationship between counts and clinical features.

Enteric fever is the only bacterial infection of humans for which bone marrow examination is routinely recommended. A prospective study of the concentrations of bacteria in the bone marrow and their relationship to clinical features was conducted with 120 Vietnamese patients with suspected enteric fever, of whom 89 had confirmed typhoid fever. Ninety-three percent of the Salmonella enterica serovar Typhi samples isolated were resistant to ampicillin, chloramphenicol, and co-trimoxazole. For 81 patients with uncomplicated typhoid and satisfactory bone marrow aspirates, the number of serovar Typhi CFU in bone marrow aspirates was a median value of 9 (interquartile range [IQR], 1 to 85; range, 0.1 to 1,580) compared to 0.3 (IQR, 0.1 to 10; range, 0.1 to 399) CFU/ml in simultaneously sampled blood. The ratio of individual blood counts to bone marrow counts was 10 (IQR, 2.3 to 97.5). The number of bacteria in blood but not bone marrow was correlated inversely with the duration of preceding fever. Thus, with increasing duration of illness the ratio of bone marrow-to-blood bacterial concentrations increased; the median ratio was 4.8 (IQR, 1 to 27.5) during the first week compared with 158 (IQR, 60 to 397) during the third week. After lysing the host cells, the median ratio of viable bone marrow to blood increased, reflecting the higher concentration of intracellular serovar Typhi in the bone marrow. Effective antibiotic pretreatment had a significantly greater effect in reducing blood counts compared to bone marrow counts (P < 0.001). Thus, bacteria in the bone marrow of typhoid patients are less affected by antibiotic treatment than bacteria in the blood. The numbers of bacteria in bone marrow correlated negatively with the white blood cell (R = -0.3, P = 0.006) and platelet counts (R = -0.32, P = 0.01) and positively with fever clearance time after treatment (R = 0.4, P < 0.001). The bacterial load in bone marrow therefore may reflect the clinical course of the infection, and high levels may suppress neutrophil proliferation.

Adolescent↗
PubMed2004

Evaluation of rapid diagnostic tests for typhoid fever.

Laboratory diagnosis of typhoid fever requires isolation and identification of Salmonella enterica serotype Typhi. In many areas where this disease is endemic, laboratory capability is limited. Recent advances in molecular immunology have led to the identification of sensitive and specific markers for typhoid fever and technology to manufacture practical and inexpensive kits for their rapid detection. We evaluated three commercial kits for serologic diagnosis of typhoid fever. Patients presenting with > or = 4 days of fever were enrolled at two hospitals in Southern Vietnam. Cases were patients with serotype Typhi isolated from blood samples, and controls were patients with other laboratory-confirmed illnesses. Serotype Typhi isolates were confirmed and tested for antimicrobial susceptibility at the Pasteur Institute in Ho Chi Minh City. The Widal test was run at the hospitals and the Pasteur Institute. Sera were shipped frozen to the Centers for Disease Control and Prevention and tested by using Multi-Test Dip-S-Ticks, TyphiDot, and TUBEX to detect immunoglobulin G (IgG), IgG and IgM, and IgM, respectively. Package insert protocol instructions were followed. We enrolled 59 patients and 21 controls. The sensitivity and specificity findings were as follows: 89 and 53% for Multi-Test Dip-S-Ticks, 79 and 89% for TyphiDot, 78 and 89% for TUBEX, and 64 and 76% for Widal testing in hospitals and 61% and 100% for Widal testing at the Pasteur Institute. For all assays, the sensitivity was highest in the second week of illness. The Widal test was insensitive and displayed interoperator variability. Two rapid kits, TyphiDot and TUBEX, demonstrated promising results.

Adolescent↗
PubMed2005

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↗
PubMed1974

Haemolytic-uraemic syndrome in typhoid fever.

Among 48 patients with a typhoid infection 6 (12.5%) developed the haemolytic-uraemic syndrome. Neither glucose-6-phosphate dehydrogenase deficiency nor therapy with chloramphenicol could be incriminated as the causal factor. Evidence presented here suggests that the mechanism is localized intravascular coagulation.The presence of leucocytosis in typhoid fever suggests a complication and should alert one to the possibility of the haemolytic-uraemic syndrome. Furthermore, in our area typhoid should be suspected as a cause in any patient presenting with acute renal failure.

Adolescent↗
PubMed1970

Effect of trimethoprim-sulphamethoxazole on typhoid and salmonella carriers.

Four chronic typhoid carriers from the Aberdeen typhoid outbreak of 1964 were treated with trimethoprim-sulphamethoxazole. The male carrier remained clear of infection following treatment but the three female carriers, all with gall bladder abnormalities, remained excretors. A convalescent typhoid excretor also remained clear of infection after treatment as well as two other salmonella carriers, one of whom has been a chronic carrier for 24 years.

Adult↗
PubMed1985

Gastric acid secretion in patients with typhoid fever.

Gastric secretory studies were carried out in the following groups of patients: group A, 30 Salmonella typhi positive enteric patients, group B, 15 non-enteric fever patients and group C, 20 healthy controls. Patients with typhoid were divided into two subgroups on the basis of the severity of the disease: group A1 (17) consisted of uncomplicated cases of enteric fever and group A2 (13) comprised of those who had associated complications. During convalescence both groups of typhoid patients showed significantly lower basal acid output (BAO) and maximal acid output (MAO) levels compared with controls and patients with non-enteric fever. Patients in group A2 had significantly lower MAO levels compared with group A1 but the BAO levels showed no such difference. In contrast BAO and MAO levels during convalescence in patients with non-enteric fever were similar to those in the control group. After two months, there was a significant increase in both the BAO and MAO levels in groups A1 and A2. The levels in group A2, however, remained significantly lower compared with group A1, controls and patients with non-enteric fever. Histologically, the gastric mucosa did not show any significant abnormality in either group of typhoid patients. The results suggest that depressed gastric secretion is the result of enteric infection and is related to the severity of the disease process.

Adolescent↗
PubMed1984

Typhoid masquerading as Japanese encephalitis.

We describe a variant of typhoid which was clinically indistinguishable from Japanese Encephalitis (JE). The strongly encephalitic presentation led to a potentially serious delay in starting specific antibiotic therapy. Awareness of the usual form of typhoid is of great importance to Army doctors because of the presence of British soldiers and families in the Dharan area of southern Nepal where both typhoid and JE are endemic.

Adult↗
PubMed1988

Influence of tetanus and typhoid vaccines on hepatic drug metabolism.

Several experiments suggested that vaccines might inhibit liver drug-metabolizing enzymes, an assumption in agreement with other findings obtained with most immuno-enhancing agents. A direct, non-specific activation of macrophages with subsequent release of interleukin 1 may account for this inhibition. The purpose of the present study was to investigate whether tetanus and typhoid vaccines exerted such an influence on pentobarbital sleeping time in mice and antipyrine elimination in rabbits, both in vivo correlates of the activity of these enzymes. It is shown that tetanus (unlike typhoid) vaccination in both species can lead to a marked but transient impairment of hepatic drug metabolism in these conditions. The reason for this discrepancy is unclear. The assumption that aluminium hydroxide might play a critical role, as this adjuvant is included in the formulation of tetanus vaccine in contrast to that of typhoid vaccine, is not supported by our findings since aluminium hydroxide alone failed to exert any influence in our experimental conditions. Further studies are therefore warranted to elucidate the mechanism of this inhibition of the activity of hepatic drug-metabolizing enzymes.

Aluminum Hydroxide↗
PubMedDate not supplied

Antibiotic therapy for typhoid fever.

A retrospective clinical study was conducted to evaluate the efficacies of various kinds of antibiotics on 804 patients with typhoid fever. Of 16 regimens studied, ofloxacin and enoxacin achieved 100 cure rates without relapse or carriage of Salmonella typhi within 3 months. Their good safety profiles and relatively lower costs were very cost-effective for treatment of typhoid fever, and they can be recommended as the first-line choices for routine management of this disease. In addition, our results suggested that ceftriaxone treatment of typhoid fever should be given at higher dose: not less than 3 g once daily, or over a longer period, to reduce the incidence of relapse.

Adult↗