We used Bayes' theorem to calculate the probability of enteric fever in 260 patients presenting with undiagnosed fever, without recourse to blood or stool culture results. These individuals were divided into 110 patients with enteric fever (63 culture positive, 47 culture negative) and 150 patients with other causes of fever. Comparison of the frequencies of occurrence of 19 clinical and laboratory events, said to be helpful in the diagnosis of enteric fever, in the two groups revealed that only 8 events were significantly more frequent in enteric fever. These were: a positive Widal test at a screening dilution of 1:40; a peak temperature greater than = 39 degrees C; previous treatment for the fever; a white blood cell count less than 9 X 10(6)/litre; a polymorphonuclear leucocyte count less than 3.5 X 10(6)/litre; splenomegaly; fever duration greater than 7 d; and hepatomegaly. When the probability of enteric fever was determined prospectively in 110 patients, using only 6 of these discriminating events, the probability of patients with a positive prediction having enteric fever (diagnostic specificity) was 0.80 (95% confidence interval: 0.68 to 0.91) and the probability of those with a negative prediction not having enteric fever (diagnostic sensitivity) was 0.92 (0.85 to 0.99). Using all 19 events did not alter the diagnostic specificity or diagnostic sensitivity. This study shows that a small number of clinical and laboratory features can objectively discriminate enteric fever from other causes of fever in the majority of patients. Calculating the probability of enteric fever can aid in diagnosis, when culturing for salmonella is either unavailable or is negative.
A NEW antibiotic Chloromycetin has been clinically tested in the treatment of typhoid fever and has been found to exhibit significant chemotherapeutic effects. A description of the results in 10 cases is submitted as a preliminary report.
Typhoid fever (TF), a systemic prolonged febrile illness, continues to be a worldwide health problem especially in developing countries where there is poor sanitation and poor standards of personal hygiene. The worldwide incidence of TF is estimated to be approximately 16 million cases annually with 7 million cases occurring annually in SE Asia alone. More than 600,000 people die of the disease annually. The pathogenesis of TF is beginning to be understood. The clinical features and diagnosis of TF are well known. New diagnostic methods have yet to gain universal acceptance. Traditional treatment with the first-line antibiotics (i.e. chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole) though still being used in most developing countries are gradually being replaced with shorter courses of treatment with third generation cephalosporins or fluoroquinolones especially with the growing incidence of multi-drug resistant S typhi strains (MDR-ST). MDR-ST strains are particularly common in the Indian subcontinent; Pakistan and China. The presently available vaccines are far from satisfactory in terms of safety, efficacy and costs. Newer vaccines have been developed and are presently undergoing clinical trials in human volunteers.
Salmonella enterica serovar Typhi (S. typhi) is an intracellular pathogen belonging to the Enterobacteriaceae family, where biofilm (aggregation and colonization of cells) formation is one of their advantageous traits. Salmonella typhi is the causative agent of typhoid fever in the human body and is exceptionally host specific. It is transmitted through the fecal-oral route by consuming contaminated food or water. This subspecies is quite intelligent to evade the innate detection and immune response of the host body, leading to systemic dissemination. Consequently, during the period of illness, the gallbladder becomes a harbor and may develop antibiotic resistance. Afterwards, they start contributing to the continuous damage of epithelium cells and make the host asymptomatic and potential carriers of this pathogen for an extended period. Statistically, almost 5% of infected people with Salmonella typhi become chronic carriers and are ready to contribute to future transmission by biofilm formation. Biofilm development is already recognized to link with pathogenicity and plays a crucial role in persistency within the human body. This review seeks to discuss some of the crucial factors related to biofilm development and its mechanism of interaction causing pathogenicity. Understanding the connections between these things will open up a new avenue for finding therapeutic approaches to combat pathogenicity.
Typhoid fever continues to pose public health problems in Selangor where cases are found sporadically with occasional outbreaks reported. In February 2009, Hospital Tengku Ampuan Rahimah (HTAR) reported a cluster of typhoid fever among four children in the pediatric ward. We investigated the source of the outbreak, risk factors for the infection to propose control measures. We conducted a case-control study to identify the risk factors for the outbreak. A case was defined as a person with S. typhi isolated from blood, urine or stool and had visited Sungai Congkak recreational park on 27th January 2010. Controls were healthy household members of cases who have similar exposure but no isolation of S. typhi in blood, urine or stool. Cases were identified from routine surveillance system, medical record searching from the nearest clinic and contact tracing other than family members including food handlers and construction workers in the recreational park. Immediate control measures were initiated and followed up. Twelve (12) cases were identified from routine surveillance with 75 household controls. The Case-control study showed cases were 17 times more likely to be 12 years or younger (95% CI: 2.10, 137.86) and 13 times more likely to have ingested river water accidentally during swimming (95% CI: 3.07, 58.71). River water was found contaminated with sewage disposal from two public toilets which effluent grew salmonella spp. The typhoid outbreak in Sungai Congkak recreational park resulted from contaminated river water due to poor sanitation. Children who accidentally ingested river water were highly susceptible. Immediate closure and upgrading of public toilet has stopped the outbreak.
Typhoid fever being a systemic infection can present in a multitude of ways, involving various systems. Here we describe a case of typhoid fever presenting with acute cerebellar ataxia and marked thrombocytopenia. This atypical presentation is not common in typhoid fever and can lead to misdiagnosis as well as a delay in the initiation of appropriate therapy. Prompt clinical improvement and the return of platelet counts to normal were noted after the patient was started on IV Ceftriaxone.
The diagnostic value of the Widal test was assessed in an endemic area. The test was done on 300 normal individuals, 297 non-typhoidal fevers and 275 bacteriologically proven cases of typhoid. Of 300 normal individuals, 2% had an H agglutinin titre of 1/160 and 5% had an O agglutinin titre of 1/160. On the basis of these criteria a significant H and/or O agglutinin titre of 1/320 or more was observed in 93-97% of typhoid cases and in only 3% of patients with non-typhoidal fever. Of the sera from typhoid cases which gave a significant Widal reaction, the majority (79.9%) showed increases in both H and O agglutinins and 51 of 234 (21.8%) of these sera were collected in the first week of illness. The significance and implications of these findings are discussed.
Aptamers have emerged as prominent ligands in clinical diagnostics because they provide various advantages over antibodies, such as quicker generation time, reduced manufacturing costs, minimal batch-to-batch variability, greater modifiability, and improved thermal stability. In the present study, we isolated and characterized DNA aptamers that can specifically bind to the hemolysin E (HlyE) antigen of Salmonella Typhi for future development of typhoid diagnostic tests. The DNA aptamers against Salmonella Typhi HlyE were isolated using systematic evolution of ligands by exponential enrichment (SELEX), and their binding affinity and specificity were assessed utilizing enzyme-linked oligonucleotide assay (ELONA). A total of 11 distinct aptamers were identified, and the binding affinities and species selectivities of the three most probable aptamers were determined. Kd values were obtained in the nanomolar range, with the highest affinity of 83.6 nM determined for AptHlyE97. In addition, AptHlyE11, AptHlyE45 and AptHlyE97 clearly distinguished S. Typhi HlyE from other tested bacteria, such as Salmonella Paratyphi A, Salmonella Paratyphi B, Shigella flexneri, Klebsiella pneumonia and Escherichia coli, therefore displaying desirable specificity. These novel aptamers could be used as diagnostic ligands for the future development of inexpensive and effective point-of-care tests for typhoid surveillance, especially in developing countries of the tropics and subtropics.
Data are presented for 2382 children investigated for fever in a Malaysian hospital between 1984 and 1987 when Widal tests and blood cultures were a routine part of every fever screen. There were 145 children who were culture positive (TYP-CP) for Salmonella typhi, while 166 were culture negative but were diagnosed as having typhoid (TYP-CN). Analyses of the sensitivity and specificity of combinations of initial Widal titres in predicting a positive S. typhi culture in a febrile child (culture positive vs the rest) showed the best model to be an O- and/or H-titre of > or = 1 in 40 (sensitivity 89%; specificity 89%). While the negative predictive value of the model was high (99.2%) the positive predictive value remained below 50% even for very high titres of O and H (> 1 in 640), at which point the specificity was 98.5%, supporting the clinical view that a high proportion of the TYP-CN patients really were typhoid but were missed by culture. The TYP-CN patients showed a very similar clinical and age profile to TYP-CP patients. The length of history of fever did not affect the initial Widal titre in culture positive cases. The Widal test in children remains a sensitive and specific 'fever screen' for typhoid although it will not identify all cases. In children, lower cut-off points for O- and H-titres should be used than are generally recommended.
Acute suppurative thyroiditis in a 62 year old lady with enteric fever is reported. Plain radiography of the neck showed a distinct localised abscess cavity with air fluid level. A rare causative agent Salmonella typhi was isolated. Needle aspiration and antibiotics resulted in complete recovery.