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Diarrhea associated with typhoid fever.

To study the pathogenesis of diarrhea occurring with typhoid fever, we selected 42 patients with diarrhea and blood cultures positive for Salmonella typhi or Salmonella paratyphi A, but without diarrheal copathogens, for measurement of stool output and examination of fecal composition. The mean duration of fever before hospitalization was 9.5 days, and the mean duration of diarrhea was 5.8 days. All patients passed liquid stool on their first day in the hospital, ranging in volume from 4 to 172 ml/kg with a mean of 45 ml/kg. Red blood cells were in the stools of 57% of the patients. All patients had fecal leukocytes with a mean of 4,950 leukocytes/mm3, predominantly polymorphonuclear leukocytes. In the stools, the mean protein concentration was 9.3 g/liter; the mean pH was 6.1, and the mean concentration of electrolytes was as follows: sodium, 47 mEq/liter; potassium, 48 mEq/liter; and chloride, 43 mEq/liter. The mean total CO2 was 24 mmol/liter. During treatment with chloramphenicol, this group of patients showed daily improvement with a drop in both fever and stool output. The results indicate that patients with diarrhea during typhoid fever have a wide range of rates of purging, and the diarrhea is characterized by liquid stool containing large quantities of leukocytes and protein and is resolved by treatment with chloramphenicol.

Adolescent↗

Typhoid fever: successful therapy with cefoperazone.

We compared cefoperazone with chloramphenicol in a randomized trial involving the treatment of 25 children with severe typhoid fever. The clinical characteristics of the two treatment groups were comparable on entry into the study. Four patients died (three receiving chloramphenicol, one cefoperazone), and an additional two patients received dexamethasone (one per group). Excluding these six patients, the response of the cefoperazone group was comparable or superior to that of the chloramphenicol group in terms of the number of days from initiation of therapy to becoming afebrile (P less than .055) and the number of days until negative blood cultures were obtained (P less than .19). There were no relapses or treatment failures in either group. We conclude that cefoperazone is as effective as chloramphenicol in the treatment of severe typhoid fever.

Adolescent↗

Production of specific monoclonal antibodies to Salmonella typhi flagellin and possible application to immunodiagnosis of typhoid fever.

Four murine monoclonal antibodies (MAbs) to Salmonella typhi flagellin were produced. These MAbs did not react with eight other enterobacterial strains tested: Salmonella enteritidis, Salmonella typhimurium, Salmonella paratyphi A, Escherichia coli, Shigella flexneri, Shigella sonnei, Yersinia enterocolitica, and Campylobacter jejuni. All four MAbs cross-reacted with Salmonella muenchen flagellin indicating specificity for d antigenic flagellar epitope. One MAb (C4) was selected to develop a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect S. typhi flagellin in serum samples. By use of this assay S. typhi flagellar antigen was detected in 95.5% of serum samples from patients with positive hemoculture for S. typhi, in 93.6% of samples from patients with positive serodiagnosis of typhoid fever, in 26% of samples collected from patients who were initially hemoculture-positive for S. typhi and who had undergone 7-8 d of chemotherapy, in 8.5% of samples from healthy persons from an endemic area, and in no samples from healthy persons from a nonendemic area. The presence of high levels of flagellin antibody titers did not interfere with the antigen detection. The detection of S. typhi flagellar antigen in patient serum may have practical value for rapid diagnosis of typhoid fever.

Animals↗

Typhoid fever at a resort hotel in New York: a large outbreak with an unusual vehicle.

The largest outbreak of typhoid fever in the United States since 1981 occurred in 1989 among guests and staff at a New York hotel. There were 43 culture-confirmed and 24 probable cases among guests, 1 culture-confirmed case and 1 asymptomatic culture-positive case among hotel employees, and 1 culture-confirmed secondary case. Twenty-one persons were hospitalized and 2 had bowel perforation. Breakfast on 13 June was the only meal consumed by all ill persons (relative risk, infinite; P = .004). In a case-control study, case-patients were more likely than controls to have consumed orange juice (odds ratio, 5.6; 95% confidence interval, 1.1-54.7), which had been prepared in a 208-L container with ample opportunity for hand contact. No other food was associated with illness. S. typhi was isolated from the stool of an asymptomatic food worker who handled orange juice but who was not known to be a typhoid carrier. S. typhi is a foodborne pathogen with continuing potential to cause large outbreaks in the United States.

Beverages↗

Phospholipase A2 is a circulating mediator in typhoid fever.

Circulating proinflammatory mediators have not been found in studies on typhoid fever, although the patients suffer from a systemic disease with characteristic protracted fever. The 14-kDa group II extracellular phospholipase A2 (PLA2) is induced by interleukin-1 and tumor necrosis factor and may mediate some of the effects of these cytokines. Circulating PLA2 concentrations were measured in 12 typhoid fever patients on various days after admission and after recovery. On admission, mean concentrations of PLA2 were elevated (1444 +/- 1560 ng/mL) and decreased gradually and significantly to day 14 (55 +/- 48 ng/mL). patients with complicated disease had significantly higher PLA2 levels on admission. PLA2 was not produced in a lipopolysaccharide-stimulated whole blood culture, indicating that PLA2 originates from other types of cells. These data indicate that PLA2 may be a mediator of disease in protracted inflammatory diseases such as thyroid fever.

Adolescent↗

The efficacy and safety of pefloxacin in the treatment of typhoid fever in Algeria.

The efficacy and safety of pefloxacin 400 mg twice daily for seven days in the treatment of typhoid fever was investigated in an open, non-comparative study involving 37 patients infected with Salmonella typhi. Between day 5 and the end of treatment, all patients showed clinical improvement. The clinical cure rate at the end of the treatment period was 89.2%. One month after the end of treatment, the final assessment showed a clinical cure rate of 94.6% with relapses occurring in only two patients. Both these patients belonged to the group with negative blood cultures but positive serodiagnostic tests. Bacteriological tests confirmed eradication of the pathogen in 94.6% of patients and the relapses in the two serologically positive patients. Temperature became normal in a mean of 5.14 days. Clinical adverse reactions were reported in 5.9% (3/51) of patients (vomiting in two, transient pruritic rash in one). The results of this study indicate that a seven-day course of pefloxacin 400 mg twice daily provides a suitable alternative in the treatment of typhoid fever.

Administration, Oral↗

Randomized prospective study comparing two dosage regimens of ciprofloxacin for the treatment of typhoid fever.

Sixty-two patients with blood culture-proven typhoid fever were randomly assigned to receive either 500 or 750 mg of ciprofloxacin orally, twice daily for 7 days or for two days following defervescence, whichever was greater. Thirty-four and 28 patients received 500 mg and 750 mg respectively. Strains of Salmonella typhi resistant to ampicillin, chloramphenicol and co-trimoxazole were isolated from the blood of 27 patients (43.5%). No resistance to ciprofloxacin was encountered. Both regimens were equally effective; fever subsided in mean times of 4.9 +/- 1.7 days in the 500 mg group and 5.2 +/- 2.2 days in the 750 mg group (P = 0.54). All patients were cured, although one patient in the 750 mg group experienced a presumed relapse two months following completion of therapy. Ciprofloxacin administered for 7-10 days was adequate treatment for 57 of the 62 patients (92%); only five patients required therapy for more than 10 days. Patients with pretreatment symptoms of > or = 10 days duration defervesced in a mean of 5.7 +/- 2.3 days compared with 4.5 +/- 1.3 days (P = 0.01) for those with symptoms of shorter duration. We conclude that 500 mg of ciprofloxacin taken orally twice daily is adequate treatment for typhoid fever.

Administration, Oral↗

Treatment of typhoid fever with azithromycin versus chloramphenicol in a randomized multicentre trial in India.

To compare the clinical and bacteriological efficacies of azithromycin and chloramphenicol for treatment of typhoid fever, 77 bacteriologically evaluable adults, with blood cultures positive for Salmonella typhi or Salmonella paratyphi A susceptible to their assigned drugs, were entered into a randomized open trial at four hospitals in India. Forty-two patients were randomized to receive azithromycin 500 mg p.o. od for 7 days and 35 to receive chloramphenicol 2-3 g p.o. od in four divided doses for 14 days. Thirty-seven patients (88%) in the azithromycin group responded with clinical cure or improvement within 8 days and 30 patients (86%) in the chloramphenicol group responded with cure or improvement. By day 14 after the start of treatment, all patients treated with azithromycin and all except two of the patients treated with chloramphenicol (94%) were cured or improved. Blood cultures repeated on day 8 after start of therapy showed eradication of organisms in 100% of patients in the azithromycin group and 94% of patients in the chloramphenicol group. By day 14 the eradication rate in the chloramphenicol group had increased to 97%. Stool cultures on days 21 and 35 after start of treatment showed no prolonged faecal carriage of Salmonella spp. in either group. These results indicate that azithromycin given once daily for 7 days was effective therapy for typhoid fever in a region endemic with chloramphenicol-resistant S. typhi infection and was equivalent in effectiveness to chloramphenicol given to patients with chloramphenicol-susceptible infections.

Adolescent↗

Complications of bacteriologically confirmed typhoid fever in children.

To find the incidence, markers and nature of complications of typhoid fever, we studied 102 children with cultures positive for Salmonella typhi in a cross-sectional study, prospectively, over a period of almost 5 years. All isolates were sensitive to commonly used antibiotics. One third of these children developed complications which included: anicteric hepatitis, bone marrow suppression, paralytic ileus, myocarditis, psychosis, cholecystitis, osteomyelitis, peritonitis, pneumonia, haemolysis, and syndrome of inappropriate release of antidiuretic hormone (SIADH). Twelve children developed multiple complications. If hepatitis is excluded from the complications, the rate of complications in bacteriologically confirmed cases of typhoid fever drops to 11 per cent. These complications were not related to: the age or sex of patients, duration of illness before admission, use of antibiotics before admission, nutritional status, level of 'O' or 'H' titre, presence of IgM or IgG antibodies, or treatment with chloramphenicol or ampicillin. Children with splenomegaly, thrombocytopenia or leukopenia were more likely to develop complications.

Adolescent↗

Bone marrow histiocytic hyperplasia and hemophagocytosis with pancytopenia in typhoid fever.

Typhoid fever was associated with pancytopenia in five patients. Bone marrow examinations revealed histiocytic hyperplasia with marked phagocytosis of platelets, leukocytes, and red blood cells in these individuals. This phagocytosis may contribute to the pancytopenia that occurs in some patients with typhoid fever. The striking degree of the histiocytic hemophagocytosis is reminiscent of the malignant disease, histiocytic medullary reticulosis. The importance of careful exclusion of infectious etiologies in illnesses involving marrow histiocytic proliferation is emphasized.

Adolescent↗

Waterborne typhoid fever in Haifa, Israel: clinical, microbiologic, and therapeutic aspects of a major outbreak.

A major outbreak of waterborne typhoid fever involving 77 verified cases occurred in 1985 in a large suburban area of Haifa, Israel. The authors summarize the clinical, microbiologic, and therapeutic aspects of these patients. Fever, usually higher than 39 degrees C, was the hallmark of the disease. Other manifestations of typhoid, although relatively frequent, are presented as part of a mild nonspecific symptom complex, often found only in the prodromal period. An elevated level of serum glutamic-oxaloacetic transaminase (mean, 81 IU/ml) was the most characteristic laboratory abnormality, occurring in 94% of the patients. Blood cultures were positive in 46 of the 50 patients (92%), and were not affected by prior outpatient antibiotic therapy. The first blood culture was diagnostic in 93% of the cases. Although fever tended to disappear more rapidly among patients receiving ampicillin than among those treated with chloramphenicol, results of therapy were similar in both groups. Nevertheless, the relapse rate of 36% among 25 chloramphenicol-treated patients was significantly higher than the 9% noted among 22 patients treated with ampicillin. Except for one case of hemolytic anemia, serious complications were conspicuously absent, and outcomes were uniformly favorable.

Adolescent↗

Management of ileal perforation due to typhoid fever.

The results of the surgical management of 161 cases of ileal perforation due to typhoid fever are presented. Most were seen after an illness of 2-4 weeks, and because of delays in seeking hospital admission, more than half were explored more than 24 hours after their perforation occurred. All patients were prepared for operation with nasogastric suction, intravenous fluids, and antibiotics. At laparotomy, 80% had considerable quantities of pus and small bowel contents in the peritoneal cavity and the remainder had localized abscesses; there were no instances of localization of the perforation. One hundred three of these patients underwent simple closure of their perforations, while 43 underwent small bowel resection, usually because of multiple perforations. Exteriorization or drainage were performed only in patients too sick to tolerate a more appropriate procedure. The overall mortality was 9.9%. The authors believe that typhoid perforations can best be dealt with at operation. Delay in operative intervention adversely affects the survival rate after surgery. Chloramphenicol is used as the drug of choice.

Chloramphenicol↗

Improvement in survival from typhoid ileal perforation. Results of 221 operative cases.

Typhoid ileal perforation remains a frequently fatal illness in the developing world. The purpose of a retrospective review of 195 cases was to ascertain prognostic indices and therapeutic options influencing outcome. The overall mortality rate of 31% was worsened by extremes of age (p less than 0.025), generalized peritonitis (p less than 0.025), lower white blood cell count (p less than 0.05), increased number of perforations (p less than 0.005), and postoperative enterocutaneous fistula (p less than 0.005). Double-layer closure of the perforation lowered the mortality rate compared with single-layer closure (p less than 0.01). Broader-spectrum antibiotics, in the form of chloramphenicol with gentamycin, metronidazole, or both, reduced the mortality rate compared with chloramphenicol alone (p less than 0.05). Based on these findings, a prospective series was initiated in which all patients were treated with two-layer closure and chloramphenicol, gentamycin, and metronidazole. The mortality rate of 8% for the 26 patients treated in this manner confirmed the improved survival with these treatment modalities. Improved survival from typhoid perforation is possible with simple, low-cost measures.

Adolescent↗

Typhoid fever and asymptomatic human immunodeficiency virus infection. A report of 10 cases.

Ten patients with asymptomatic human immunodeficiency virus (HIV) infection were treated for typhoid fever at King Edward VIII Hospital, Durban, South Africa, from 1993 through 1995. The mean age was 23.7 years (range, 8-33 years), with a female-to-male ratio of 9 to 1 and mortality and morbidity rates of 20% and 10%, respectively. Common presenting manifestations were fever (100%), relative bradycardia (50%), and diarrhea (40%). With respect to epidemiologic and clinical characteristics, we noted no significant differences among these 10 HIV-positive and 32 HIV-negative patients treated for typhoid fever during the same period. However, we found hepatic dysfunction in the form of an isolated increase in aspartate aminotransferase (p < 0.01) and abnormal urinary findings suggestive of glomerulonephritis (p = 0.01) more frequently in HIV-positive patients.

Adolescent↗

Once daily ceftriaxone vs. chloramphenicol for treatment of typhoid fever in children.

In a prospective, randomized, open study ceftriaxone was compared with chloramphenicol for treatment of 59 children who had bacteriologically confirmed acute typhoid fever. Ceftriaxone was administered intramuscularly in a once a day dose of approximately 80 mg/kg body weight for 5 days. Chloramphenicol was given orally for 3 weeks in a daily dosage of 50 to 100 mg/kg body weight divided into 4 doses. In the ceftriaxone group 23 of 29 patients were cured, 2 improved, 1 failed and 2 relapsed. For those who received chloramphenicol 22 of the 30 patients were cured, 5 improved, 1 failed and 2 relapsed. In none of the patients in either group were adverse effects recorded. The overall results of this comparative study suggest that short term treatment of typhoid fever with ceftriaxone is as effective and safe as conventional treatment with chloramphenicol.

Acute Disease↗

Comparative efficacies of aztreonam and chloramphenicol in children with typhoid fever.

We compared aztreonam with chloramphenicol in a randomized trial involving the treatment of 36 children with typhoid fever. Eighteen children were randomized to receive aztreonam, 150 mg/kg/day intravenously, and 18 to receive chloramphenicol, 100 mg/kg/day orally. On entry in the study the clinical characteristics of the two treatment groups were comparable. The duration of therapy was 14.9 +/- 3.6 days for the aztreonam group and 12.8 +/- 2.6 days for the chloramphenicol group. The mean duration of fever was 5.9 +/- 3.1 days and 4.05 +/- 2.1 days for aztreonam and chloramphenicol groups respectively (P greater than 0.05). Clinical cure was observed in all patients treated with aztreonam and in 17 of 18 children given chloramphenicol; one patient died in the latter group. There were no relapses in either group. We observed clinical adverse reactions during the treatment with aztreonam in 2 patients. All strains of Salmonella typhi were susceptible to aztreonam, 1 strain was resistant to chloramphenicol and 3 strains were resistant to ampicillin. Aztreonam appears to be a satisfactory alternative to chloramphenicol in cases of typhoid fever caused by resistant strains or when chloramphenicol is contraindicated.

Adolescent↗

Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone.

We randomly allocated 80 children with suspected multidrug-resistant tyhpoid fever to therapy with either cefixime or ceftriaxone. Of these, an alternative diagnosis was subsequently made in 10 children and another 10 were excluded because cultures were negative. In 9 cases the typhoidal organisms isolated were susceptible to first-line drugs. In all, 50 children were randomly allocated to receive therapy with either intravenous ceftriaxone (65 mg/kg/day once daily, Group A, n = 25) or oral cefixime (10 mg/kg/day divided every 12 hours, Group B, n = 25) for 14 days. The two groups were comparable in their clinical characteristics, duration and severity of illness at the time of admission. The time to defervescence was comparable in both groups (8.3 +/- 3.7 vs. 8.0 +/- 4.1 days, P = not significant). An equal number (3 in each group) failed to respond and underwent a change in therapy. Three children in Group A and one in Group B relapsed. No adverse effects were seen in either group during the course of therapy. Our data suggest that oral cefixime can be used as effectively as parenterally administered ceftriaxone for management of typhoid fever in children.

Administration, Oral↗

Clinical and bacteriological profiles of patients with typhoid fever treated during 1975-1998 in the Tokyo Metropolitan Komagome Hospital.

Patients with typhoid fever presenting to the Tokyo Metropolitan Komagome Hospital during the period 1975-1998 were retrospectively investigated. All cases were diagnosed by a positive culture for Salmonella typhi in either of their clinical specimens. Of the total number of 130 patients, 57% contracted the disease abroad; this population increased in later years as the total numbers of cases decreased. The period from disease onset to diagnosis averaged 14 days with 20% of the cases requiring over three weeks to establish a diagnosis. As for symptomatology relative bradycardia was seen in less than half of the cases, and rose spots or splenomegaly in less than one third. A positive blood culture was the most frequent test establishing the diagnosis followed by a positive stool culture. Intestinal bleeding was recognized in as many as 35 cases (27%) and even intestinal perforation occurred in two cases (1.5%). Chloramphenicol was most commonly employed during the early study period, however, during the late period it was replaced by fluoroquinolones. The clinical cure rate was 98% with regimens that include fluoroquinolones/quinolone; however it was 87% with the other antimicrobial regimens. Bacteriological relapse occurred in 25% of the non-fluoroquinolone group while only in 2.0% in the fluoroquinolone/quinolone group. Four strains of Salmonella typhi that were multi-resistant to chloramphenicol, ampicillin and cotrimoxazole were isolated in travelers from Asia. Early diagnosis by appropriate bacteriological examination regardless of classical symptomatology should be stressed and the use of fluoroquinolones is warranted in the treatment of typhoid fever.

Adolescent↗