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A randomised clinical trial in 124 adult patients with typhoid fever, proved by blood culture, showed that amoxycillin in a dosage of 1 g. six-hourly for fourteen days is an alternative to chloramphenicol, which has hitherto been regarded as the drug of choice.
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.
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.
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.
Lipopolysaccharides (LPS) of Salmonella typhi strains, isolated from carriers and patients suffering from typhoid fever, were characterised according to their biochemical properties, morphological structure and degree of aggregation of complexes. All preparations of LPS, regardless of their origin, were morphologically heterogeneous. Free electrophoresis and immunoelectrophoresis demonstrated that LPS preparations were composed of components possessing different mobilities in electric fields. LPS of bacterial strains isolated from both carriers and patients, split upon reaction in immunoelectrophoresis with specific antiserum 73, rabbit antiserum to Salmonella typhi Vi Bhatnagar and 0-901 split into anodic and cathodic fractions. The anodic fraction reacted similarly as Vi antigen. LPS from Salmonella typhi Ty-2 yielded only the cathodic fraction, typical for O antigen. LPS from strains which were passaged twice in nutritional medium possessed identical properties as LPS from fresh cultures of Salmonella typhi. Electron microscopy revealed that LPS appears as long bands, rods, ellipsoid forms and amorphous material. Contrary to amorphous material, the bands, rods and ellipsoid forms possessed three-layer structure.
The results of the monthly registration of typhoid cases in all union republics and in the USSR as a whole for the period of 1970--1976 were analyzed. The mathematical parameters of the monthyly distribution of morbidity rate under the influence of long-term factors for each union republic were determined. In analyzing actual morbidity rates for definite years these data may help determine to what extent such rates are influenced by incidental factors. Mathematical analysis allowed to divide the territory of the USSR into 5 groups of areas with different patterns of the seasonal distribution of typhoid cases: the RSFSR, the Ukrainian SSR and the Moldavian SSR, the Byelorussian SSR and the Soviet Baltic republics, the Transcaucasian republics, the republics of Central Asia and the Kazakh SSR. April was found to be the optimum time for the immunoprophylaxis of typhoid fever throughout the whole territory of the USSR in the presence of epidemiological indications.
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.
A review of 130 children cases of typhoid fever in Saigon (Vietnam). Leuco-neutropenia is far from regular but thrombopenia is frequent. The typhoid bacillus is generally cultivated from blood during the first two weeks of the evolution. There is evidence in most S. typhi strains of a plasmid resistance for streptomycine, chloramphenicol, tetracycline and sulfamides. Strains of the various other enterobacteria of the intestinal flora are generally resistant for many more antibiotics than S. typhi.
Results of determination of the quantitative content of immunoglobulins (IgA, IgG and IgM) demonstrated chronic typhoid carrier state to be a dynamic process characterized by high IgA and IgG indices which began to form as early as the acute period. A complex of clinico-laboratory indices permitted to detect the latent phase of the carrier state among the persons who sustained typhoid fever within the range of 30%; this confirmed the statement of a number of investigators put forward earlier that the true number of carriers was much greater than that recorded.
Two clinical trials were conducted to compare the efficacy of 3 antimicrobial agents often recommended for the treatment of typhoid fever. Chloramphenicol was more effective than parenteral ampicillin or oral co-trimoxazole (trimethaprim/sulphamethoxazole) in reducing the duration of fever. Oral chloramphenicol was more effective than parenteral chloramphenicol probably because oral doses resulted in higher blood concentrations of the drug. However, parenteral chloramphenicol was given during the initial period of acute illness, without loss of efficacy.
A typhoid fever epidemic broke out in Baden-Württemberg during October and December 1974, 436 cases could be analyzed statistically. The interval between the date of earliest symptoms and the registration at the health-office was 18 days. This was the double respectively the triple of previous typhoid outbreaks. This interval results from a prolonged stay at home and a hospitalisation time with an average of 5 days from the hospitalisation to the registration. The interval between hospitalisation and the definitive diagnosis was 19 hours. The analysis of the age and sex incidence shows a high percentage of 15 to 30 years old women, which is due to the occupational exposition. The low morbidity of the 50 to 65 years old men points at a pre-exposition during World War II.
Adenosine deaminase activity has been measured in the peripheral lymphocytes of 12 patients suffering from typhoid fever. The mean activity was found to be significantly higher (P less than 0,001) when compared with normal controls.
Semiquantitative estimates of circulating endotoxin were performed by the limulus test in patients suffering from typhoid fever and other salmonelloses. The test was positive in a large number of cases. However, no clearcut correlation was found between existence of endotoxemia, as such, and pyrexia. A correlation with recent bacteremia was found for highest levels of endotoxin activity. In minor salmonelloses a striking prevalence of positive cases was observed in the age group under one year. These findings were discussed in relation to the diagnostic and pathogenetic facets of the problem.
Thyroid status was estimated serially by measuring triiodothyronine (T3), thyroxine (T4) and thyrotrophin (hTSH) in 20 patients suffering from meningococcal meningitis, typhoid fever and other acute febrile illnesses. Significantly low T3 and only slightly increased T4 were observed in all the patients. hTSH was normal in all of these. A significant reciprocal relationship was found between the degree of fever and fall in T3 concentrations. T3 tended to rise in patients who recovered but in those who deteriorated or died, T3 remained persistently low.
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The recovery of Salmonella typhi from blood, rectal swab, urine, bone-marrow, and rose spots was compared in 62 patients with typhoid fever, most of whom had received some antibiotic therapy before presentation. S. typhi was isolated from culture of bone-marrow in 56 patients (90%); in contrast, S. typhi was recovered from blood in only 25 (40%), from stool in 23 (37%), and urine in 4 (7%). S. typhi was isolated from 24 (63%) of 38 patients who had rose-spot cultures. If culture sites had been limited to blood, stool, and urine, the bacteriological diagnosis would have been missed in 24 patients.
A case is described of a 15-year-old girl who developed Landry-Guillain-Barré-Strohl Syndrome (LGBSS) on the ninth day of typhoid fever. In the absence of other known cause or association of LGBSS Salmonella typhi is believed to be aetiologically related. The patient recovered uneventfully from her neurological illness in about ten weeks from onset of symptoms.