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Acambis and Berna are developing HolaVax-Typhoid, a single-dose, live attenuated oral vaccine for the potential prophylaxis of typhoid. A phase II trial was successfully completed in January 1999, and in September 2002, Acambis announced that a bridging trial was planned for the first half of 2003 to confirm that the vaccine produced by Berna was equivalent to the typhoid vaccine that had been studied previously.
One hundred and twelve cases of typhoid fever presenting in outpatient and emergency department of Dhulikhel Hospital in Nepal were studied. In this study, it was found that 71% typhoid fever cases were less than 30 years of age group with male to female ratio of 3:1. Fever over 5 days followed by headache and chills were major presenting symptoms. Widal test and blood culture for Salmonella typhi were positive in 59% and 49% cases respectively. Two third of our study population had total leucocyte count of normal range. The fever clearance time was significantly better with ofloxacin compared to ciprofloxacin (p < 0.05) and ceftriaxone compared to chloramphenicol (p < 0.05). The release from treatment was significantly shorter with ceftriaxone compared to ofloxacin, ciprofloxacin and chloramphenicol (p < 0.01). Ceftriaxone was found to be 100% sensitive to salmonella typhi. Amoxicillin was only 52.1% sensitive to Salmonella typhi. Early diagnosis and institution of appropriate antibiotic therapy is of paramount importance in the management of typhoid patients.
Clinical and laboratory features, complications and treatment were retrospectively studied in 70 patients with bacteriologically documented typhoid fever, treated between January 1995 and June 2002 at Principal Hospital in Dakar, Senegal. Data analysis was done on a global basis as well as comparatively between the 37 children (under 15 years) and 33 adults. Mean age was 16.7 years (range, 1 to 52). The sex ratio was 1.4. Clinical manifestations included fever (97%), headache (50%), vomiting (71%), abdominal pain (54%), diarrhoea (49%), nnd splenomegaly (10%) without statistically significant difference between children and adults. Lyinphopenia was found in 51% of patients and anaemia in 78%. Coexisting illnesses Included malaria in 25.5% (mainly children) and hepatitis (transminases > 10N) in 24%. Complications included cholecystitis in 3 patients, gastrointestinal haemorrhage in 2, peritonitis in one, endocnrditis in one and osteomyelitis in one. Only one patient (HIV-positive) died. The incidence of antibiotic resistance was low, i.e., ainoxicilline: 2%, nalidixic acid: 1% and cotrimoxazole: 8.2%. No multidrug resistance was observed. This study shows that typhoid fever remains a major health problem in Dakar with slow resolution and potential complications. Amoxicililne and chloramphenicol can still be used for first-line treatment of typhoid fever. Little difference was found between children and adults.
This paper deals with two patients with typhoid fever in whom hepatic manifestations were the dominant and presenting features of the illness. The ability of typhoid hepatitis to simulate other common infectious diseases in this region is highlighted. It is recommended that typhoid hepatitis should be included in the differential diagnosis of patients presenting with fever and jaundice particularly in the tropics.
While acute confusional states are frequently encountered in typhoid fever, initial manifestation of this illness as "functional psychosis" is very rarely encountered. We describe our experience of three patients seen within a 15-month period, who initially presented as various forms of psychiatric disorders with little evidence of impairment of consciousness, well before the appearance of pyrexia which led to the correct diagnosis. The possible role of less severe or self limiting organic conditions in the genesis of "functional" psychosis in the African population is discussed. The importance of a high index of suspicion in the functional-type psychosis, that might be due to typhoid fever and the need to institute therapy for typhoid fever while investigating (the late appearing fever) in such cases are emphasized.
Fifty blood culture positive patients of typhoid fever were studied during the current outbreak of the disease for their clinical profile. In 39 (78%) cases the isolates of S. typhi were resistant to conventional drugs. Children below 2 years of age constituted 20% of the total cases and belonged exclusively to the group with multidrug resistant typhoid fever (MRTF). The clinical presentation seemed to mimic malaria, bronchopneumonia, meningitis, etc. Typhoid hepatitis was diagnosed in 2 cases with MRTF. Life threatening complications were seen in 28.2% patients and were observed exclusively in MRTF group.
Ofloxacin was used in the treatment of 20 cases of typhoid fever, 32 cases of bacillary dysentery and 50 cases of gonococcal infection. Altogether 102 cases were treated, 53 being male and 49 female. The daily dosage was 400 mg to 600 mg, divided into two times. The result showed that the clinical effective rate for typhoid fever, bacillary dysentery and gonococcal infections was 100%, 97% and 94% respectively, while the bacterial eradication rate was 100%, 100% and 94% respectively. the bacterial eradication rate was 100%, 97% and 94% respectively. The side effects were mild in degree. The authors are of the opinion that since ofloxacin can be administered orally with only two times a day, its absorption is nearly complete and the cure rate is high, it should be considered as the drug of choice in the treatment of typhoid fever, bacillary dysentery and gonorrhea, especially in the drug resistant cases. It is suggested that this drug be used more widely.
The second part of this review accounts on a patient with classic symptoms of typhoid fever. The case history is commented in the light of todays knowledge. The case was taken from the clinical notes of Schönlein one of the most famous clinicians of the first part of the 19th century. It reveals the difficulties of the physician to cope with such a disease without our present diagnostic and therapeutic possibilities. It is surprising to realize that 150 years ago therapy of typhoid fever was not substantially different from that in use up to the recent introduction of specific antibacterial therapy. Since the typical course of typhoid fever is only rarely encountered nowadays the case seems suitable to recall this clinical picture to our generation of physicians.
The experiments on rabbits immunized with a complex O. felineus antigen and spirit abdominal typhoid vaccine enriched with Vi-antigen, as well as studies on patients with chronic opisthorchiasis and bacterial carriers of S. typhi have established the presence of cross-reacting antigens in abdominal typhoid and opisthorchiasis pathogens. It is suggested that these antigens play an essential role in the development and outcome of abdominal typhoid secondary to chronic opisthorchiasis invasion.
Of the 257 typhoid enteric perforations analysed at the Departments of General and Paediatric Surgery, Ankara University Hospital, through the years 1979-1986, 74.9% were males, while the patients mean age was 35.8 years. The early signs and symptoms averaged 5.9 days. The corresponding percentages for the occurrence of abdominal pain, fever, nausea and vomiting and central nervous system disorders which constituted the clinical findings were 97.27, 51, 61.2 and 18 respectively. While the mean value for the white blood count ranged around 6600, only 61.9% of the cases had diagnostic findings in their erect abdominal roentgenograms. The standard method for the treatment of typhoid enteric perforations is still presently primary suturing of the perforated viscus and peritoneal drainage. Despite the use and misuse of a large variety of antibiotics, typhoid perforations still have a high morbidity of 74.1% and a mortality of 31.4%. Generalized peritonitis (78.4%), is considered to be to the most important cause in both situations.
Investigations with a view to the development and trial of a slide coagglutination test system for the detection of specific Salmonella typhi antigens have been made. As a result, diagnostic agents with sensitivity to group D Salmonella lipopolysaccharides and Vi-antigen, equal to 1 X 10(-5) to 1 X 10(-6) g/l, have been obtained. Specimens of saliva, urine and fecal filtrates from 61 adult patients with bacteriologically confirmed typhoid fever and 54 practically healthy persons have been studied. The coagglutination test has been positive with specimens from 90 +/- 4% of typhoid fever patients and, within the first 5 days of the disease, with those from 85 +/- 7% of such patients. The slide coagglutination test with saliva specimens has been found to be more informative than that with urine specimens. The data obtained in these investigations indicate that the slide coagglutination test is highly sensitive and specific, which offers good prospects for its use as a simple, economic and demonstrative method for the early tentative diagnosis of typhoid fever.
In 157 typhoid fever patients and 36 practically healthy persons the content of neutrophils forming complement-dependent rosettes (NEAC rosette-forming cells), as well as rosettes with sheep red blood cells (NE rosette-forming cells) and with typhoid erythrocyte diagnosticum (NS rosette-forming cells), has been studied. The data obtained in this investigation indicate that antigen-binding neutrophils play an active functional role in the pathogenesis of typhoid fever at its acute stage. The values characterizing the content of N rosette-forming cells may be used as a criterion for the evaluation of the severity of infection, as well as for the prognostication of complications and relapses.
The study of genetic factors associated to infectious diseases is a promising research field for optimizing their management and control in the future. For typhoid fever, one of our major health problems, this approach has been sporadic an fruitless for having been addressed to disease's overall susceptibility. Moreover, difficulties on recognition of clinical sub-sets have prevented definition of unambiguous clinical phenotypes appropriate for this objective. With the aim of finding the basis for phenotypes identification, or definite disease expressions, a search including foreign and national literature was carried out for the 1960-88 period. From animal experimentation, human immunogenetics, epidemiology and clinical literature, data was obtained for proposing five phenotypes: the incubation period, typhoid relapse, agglutinins response (Widal's test), response to vaccination and metabolic behaviour of certain substances, including antibiotics. That one or more of these phenotypes and their possible association with polymorphic systems might lead to populational subsets recognition in typhoid fever is suggested.
Using a capillary flocculation technique we evaluated serum samples of asymptomatic children for typhoid fever serology. Thirty one (5.16%) of the 600 serum samples tested were positive for a specificity of 95%. To evaluate the sensitivity of the test, serum samples from 36 children with proven typhoid fever and a similar number of control patients were evaluated. The sensitivity of the capillary flocculation test in this group was 100%. The test compared favorably with the Ruiz Castañeda serologic test for typhoid fever.
During a prospective study among 234 patients admitted with fever in two rural hospitals in West and Central Nigeria 38 cases of typhoid fever were found. The diagnosis was based on extensive serological testing in the Netherlands. The diazotest was introduced but appeared not helpful. The ordinary Widal test was not fully reliable. Eighty five percent of the patients responded to chloramphenicol. The course of typhoid fever in West Nigeria was more severe than in Central Nigeria. The findings are compared with those of similar studies of typhoid fever.
This paper reports on a prospective study comprising 125 consecutive adult cases of typhoid fever diagnosed on the basis of positive cultures for typhoid organisms. Salmonella typhi infection was found to be more frequent (89.6%) than S. paratyphi A & B (10.4%). Onset of the disease was usually insidious and the classical step-ladder pattern of fever was uncommon (12%). Rose spots were observed in 9.6% cases. Gut perforation was more common, while typhoid toxaemia and peripheral circulatory failure were less frequent than in most of the series reported from India. Both these variations are ascribed to the widespread use of corticosteroids in our patients. Gut perforation alone accounted for three-quarters of the deaths.
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.
S. S. Oronsay steamed into Vancouver harbour on January 14, 1970 with an epidemic of typhoid on board. After three weeks in quarantine the ship sailed, the epidemic contained. Eighty-three sick crewmen and passengers were admitted to hospital with suspected typhoid. Control measures were so successful that no cases developed during the subsequent voyage of the ship, no secondary cases developed in Vancouver and only one of the passengers who disembarked in Vancouver came down with typhoid, contracted while on board.