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Typhoid fever as cellular microbiological model.

The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila). The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d) The lines of immune defense between intestinal lumen and internal organs; e) The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge.

Bacterial Adhesion↗

The new quinolones in the treatment of diarrhoea and typhoid fever.

Diarrhoea and typhoid fever are two important diseases in the developing world, particularly the Asian countries. The management of these conditions is becoming increasingly difficult in the face of emerging pathogen resistance. The new fluoroquinolones demonstrate good in vitro activity against the causative pathogens involved, including those that are multidrug resistant. These agents have been shown to be very effective in the treatment of diarrhoea and typhoid in clinical trials, achieving results equal to, or better than, standard drugs. Importantly, fluoroquinolones also considerably shorten the duration of illness, thereby offering rapid relief to the patient.

4-Quinolones↗

Quinolones in the treatment of typhoid fever.

Typhoid fever is a severe systemic disease. Treatment with appropriate antibiotics is essential for enteric fever. Development and rapid dissemination of resistance to chloramphenicol, ampicillin, and cotrimoxazole have complicated the treatment of enteric fever. Therapeutic options for the treatment of multidrug-resistant strains are limited to third generation cephalosporins or fluoroquinolone antibiotics. Recent clinical experiences have shown that quinolones are the drugs of choice for treatment of enteric fever. Studies have shown that shorter courses may be sufficient to cure uncomplicated typhoid fever.

4-Quinolones↗

Evaluation of a new Vi polysaccharide typhoid vaccine in children aged 2-5 years.

Typhoid fever is a major cause of morbidity and mortality in many parts of the world. In view of the increasing resistance of Salmonella typhi against antibiotics and the high costs associated with improving sanitation conditions, vaccination programs would be of great benefit. We report on the evaluation of a new candidate VI (sic) polysaccharide typhoid vaccine (TypheriX (sic), SmithKline Beecham Pharmaceuticals), tested in Filipino children aged 2-5 years where the profile was compared with that of a competitor-vaccine (Typhim (sic), Pasteur Merieux Connaught). Vaccination with the new candidate vaccine was followed by fewer general symptoms (2.9%) than with the competitor vaccine (14.1%), particularly with lower incidence of fever. The new candidate vaccine is also highly immunogenic: >99% of the vacinees were immune 28 days post vaccination with comparable GMTs of 3597 EL.U/ml for TypheriX (sic) and 3365 EL.U/ml for Typhim (sic). This trial shows that the available VI (sic) polysaccharide vaccines provide a reliable means in preventing a disease responsible for a significant morbidity and placing a heavy burden on health budgets.

Child, Preschool↗

Typhoid fever complicating pregnancy.

Typhoid fever in pregnancy may result in infection of the fetus, with consequent abortion. Currently, it is a rare complication of pregnancy in the industrially developed countries. This report documents a case of maternal typhoid fever with septic abortion, in which trans-placental infection of the fetus caused its demise.

Abortion, Septic↗

Typhoid fever in pregnancy. Case report and review of the literature.

The clinical details of two cases of typhoid fever in pregnancy are described. The first patient contracted the disease in the third trimester, with successful outcome for both mother and baby. The second patient became infected in the first trimester, with the complication of underlying cardiac disease. This resulted in typhoid endocarditis contributing to fetal loss. A survey of the literature is presented and treatment recommendations outlined.

Abortion, Spontaneous↗

Furazolidone and chloramphenicol for treatment of typhoid fever.

Seventy-one adults who were hospitalized between March 1985 and March 1987 were entered into a randomized, double-blind study to compare the efficacy and safety of furazolidone and chloramphenicol in therapy for typhoid fever. Patients received chloramphenicol capsules (total daily dosage, 2 g) plus placebo tablets for furazolidone tablets (total daily dosage, 800 mg) plus placebo capsules for 14 days. Seven patients were excluded from the analysis of efficacy because blood, bile, or bone marrow cultures at admission failed to demonstrate the presence of Salmonella typhi. Four additional patients were excluded because of intercurrent illness or failure to return for follow-up visits. Cure was achieved in 31 (97%) of 32 chloramphenicol recipients and 24 (86%) of 28 furazolidone recipients. In the chloramphenicol group, one patient experienced moderate sideroblastic anemia, and another experienced moderate neutropenia. Both adverse reactions resolved spontaneously within 7 days. Mild gastritis was reported by two patients who received furazolidone and one who received chloramphenicol. This study has demonstrated that furazolidone is an effective and safe alternative to chloramphenicol for the treatment of typhoid fever in adults.

Adult↗

Randomized clinical trial of furazolidone for typhoid fever in children.

The efficacy of furazolidone and chloramphenicol was compared in a randomized trial involving 133 children with bacteriologically confirmed typhoid fever. Sixty-five children were randomized to receive furazolidone, 7.5 mg/kg/day, and 68 children to receive chloramphenicol, 75 mg/kg/day. Both drugs were administered orally. The clinical characteristics of the two treatment groups were comparable on admission. All the strains of Salmonella typhi isolated from the furazolidone group were susceptible to furazolidone. However, of the 68 strains of S. typhi isolated from the chloramphenicol group, 10 were susceptible and 58 were resistant to chloramphenicol. Clinical and bacteriologic cure was observed in 56 (86.2%) children treated with furazolidone and in 35 (51.5%) children given chloramphenicol who were infected with S. typhi strains, irrespective of susceptibility pattern (P = 0.00003). Cure was achieved in 86.2% of furazolidone recipients and 90.0% of chloramphenicol recipients who were infected with strains of S. typhi susceptible to both drugs (P = 0.6). The difference in cure rate was statistically significant (P = 0.000003) when the two treatment groups infected with furazolidone-susceptible but chloramphenicol-resistant strains of S. typhi were compared. There was no relapse or carriers in either of the groups. Furazolidone appears to be a satisfactory alternative to chloramphenicol in the treatment of typhoid fever caused by chloramphenicol-resistant strains of S. typhi.

Carrier State↗

Pancreatic disturbances and typhoid fever.

During an 8-year period, 14 adult patients were hospitalized with typhoid fever confirmed by positive blood cultures for Salmonella typhi. Among these patients, we have retrospectively (n = 7) and prospectively (n = 7) evaluated pancreatic disturbance by serum amylase and lipase measurements at the time of admission. In 7 (50%) biological signs of pancreatitis were noted: mean amylase level 81 IU (range 30-201 IU, normal value less than 40 IU), mean lipase level 949 IU (range 468-2,000 IU, normal value less than 300 IU). Clinical signs of pancreatitis were observed in 4 cases, one of whom had a concomitant salmonella biliary tract infection and gall stones demonstrated by laparotomy and the others a normal biliary ultrasonographic examination with a swelling of the pancreas. No alcohol or drug use or other infection were noted before admission. This study suggests that biological or clinical pancreatitis should be considered as a frequent complication of typhoid fever. S. typhi should therefore be added to the list of pathogens implicated in the pathogenesis of non-alcoholic or non-lithiasic pancreatitis.

Acute Disease↗

Therapy of multidrug resistant typhoid in 58 children.

Treatment of children with infections caused by Salmonella typhi strains resistant to the commonly used oral antimicrobials is a special problem. As children cannot be treated with quinolones, there is no form of oral therapy. Third generation cephalosporins, which have been shown to be effective against typhoid caused by ampicillin sensitive strains of S. typhi were effective against typhoid caused by ampicillin, chloramphenicol and sulfamethoxazole/trimethoprim-resistant strains. We treated 28 children with ceftriaxone and 8 with cefotaxime. We found ceftriaxone to be more effective than cefotaxime with significantly lower relapse rate. Antibiotic therapy of 19 other children, initially treated in a similar manner, was altered for ease of therapy or due to poor response to therapy. The high cost of this parenteral therapy and the problems in its delivery point to the need for safe, effective oral therapy.

Adolescent↗

Salmonella and Shigella infections in Switzerland, with special reference to typhoid vaccination for travellers.

This prospective study reveals that 48% of 368 salmonelloses and 81% of 43 shigelloses diagnosed within one year in the Zurich area were imported from abroad. Travellers in close contact with the local population have a higher risk of being affected by typhoid fever or shigellosis than the average tourist. The clinical course was generally mild, and there was no lethal case. As the incidence of Salmonella typhi is very low, typhoid vaccination is recommended only for high-risk travellers.

Adolescent↗

Estimating the incidence of typhoid fever and other febrile illnesses in developing countries.

To measure the incidence of typhoid fever and other febrile illnesses in Bilbeis District, Egypt, we conducted a household survey to determine patterns of health seeking among persons with fever. Then we established surveillance for 4 months among a representative sample of health providers who saw febrile patients. Health providers collected epidemiologic information and blood (for culture and serologic testing) from eligible patients. After adjusting for the provider sampling scheme, test sensitivity, and seasonality, we estimated that the incidence of typhoid fever was 13/100,000 persons per year, and the incidence of brucellosis was 18/100,000 persons per year in the district. This surveillance tool could have wide applications for surveillance for febrile illness in developing countries.

Adult↗

Ciprofloxacin treatment failure in typhoid fever case, Pakistan.

We report a case of ciprofloxacin treatment failure in a typhoid fever patient at a tertiary care hospital in Rawalpindi, Pakistan. This case shows not only the emergence of fluoroquinolone resistance in typhoid salmonellae but also the inadequacy of the current laboratory guidelines for detection of this resistance.

Adolescent↗

Bone marrow aspirate culture superior to streptokinase clot culture and 8 ml 1:10 blood-to-broth ratio blood culture for diagnosis of typhoid fever.

We compared the sensitivities of bone marrow aspirate culture (BMAC), 3 ml 1:4 and 8 ml 1:10 blood-to-broth ratio blood cultures (BC), 8 ml streptokinase clot culture (STKCC) and rectal swab culture (RSC) for isolating Salmonella typhi and S. paratyphi A from 61 patients with typhoid or paratyphoid fever in Jakarta, Indonesia. BMAC (92%) was significantly more sensitive than 8 ml BC (62%), 8 ml STKCC (51%), 3 ml BC (44%), RSC (56%) and the 19 ml combination of all three BC methods (71%). The combination of the three BC methods and RSC had an isolation rate of 87%. In Jakarta the diagnosis of typhoid fever cannot be confidently excluded unless a BMAC is done.

Adolescent↗

Treatment of typhoid fever: randomized trial of a three-day course of ceftriaxone versus a fourteen-day course of chloramphenicol.

To compare the efficacy of a short course of ceftriaxone with a standard course of chloramphenicol for typhoid fever, a randomized trial was conducted in 46 patients (30 adults and 16 children) who were blood culture-positive for Salmonella typhi or S. paratyphi. Ceftriaxone was given intravenously once a day for three days to 15 adults at a dose of 2 g/day and to eight children at a dose of 50 mg/kg/day. Chloramphenicol was given orally four times a day to an equal number of patients at a dose of 60 mg/kg/day until defervescence, followed by 40 mg/kg/day for a total of 14 days. Clinical cure without complications or relapse occurred in 19 patients (83%) treated with ceftriaxone and in 20 patients (87%) treated with chloramphenicol (P > 0.05). Four patients with clinical failures in the ceftriaxone group included two with fever lasting six days or more, one with altered sensorium, and one with relapse; three patients treated with chloramphenicol developed leukopenia and thrombocytopenia and were switched to amoxicillin therapy. Bacteriologically, blood cultures of all 46 patients were sterile three days after the start of treatment, and remained so through day 15 of follow-up. These results extend previous observations on the efficacy of ceftriaxone in short courses for both adults and children with typhoid fever.

Administration, Oral↗

Correlation of clinical and hematologic profiles with bone marrow responses in typhoid fever.

Thirty-six adult patients with typhoid fever were studied. Severe, moderate, and mild typhoid fevers were observed in 17 (47.2%), 17 (47.2%), and two (5.6%) patients, respectively. Twenty-eight (77.8%) had either isolated anemia (i.e., anemia unaccompanied by other blood component cytopenias) or mixed cytopenias. Three patients (8.3%) had pancytopenia. Sixteen patients (44.5%) had either total or partial bone marrow suppression. In five (31.3%) with partial suppression, the effect of bone marrow suppression was not reflected in peripheral blood. Sixteen (48.5%) of 33 had peripheral blood cytopenias that were not accompanied by concurrent bone marrow suppression, suggesting a peripheral mechanism responsible for the blood dyscrasia in those cases. No patient had evidence of disseminated intravascular coagulopathy. There was no correlation between clinical severity of disease and bone marrow changes. Bone marrow/peripheral blood changes did not influence the outcome of the disease, since all the patients recovered fully after treatment.

Adolescent↗

Influence of sex on clinical features, laboratory findings, and complications of typhoid fever.

Clinical features, laboratory findings, and complications of typhoid fever were correlated with sex through a retrospective case note review of 102 hospitalized culture-positive patients in Durban, South Africa. Intestinal perforation (P = 0.04), occult blood losses in stools (P = 0.04), and a mild reticulocytosis in the absence of hemolysis (P = 0.02) occurred more frequently in males than in females. A single pretreatment Widal O antibody titer > or = 1:640 was also a statistically significant occurrence in males (P = 0. 006). Female patients were significantly more severely ill (P = 0.0004) on admission and had chest signs consistent with bronchopneumonia (P = 0.04), transverse myelitis (P = 0.04), abnormal liver function test results (P = 0.0003), and abnormal findings in urinalyses (P = 0.02). Typhoid hepatitis (P = 0.04) and glomerulonephritis (P = 0.02) were present significantly more frequently in females. Whether these differences were due to differences in host's immune response to acute infection need to be determined in a prospective study.

Adolescent↗