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PubMed2004

The death of Alexander the Great: malaria or typhoid fever?

Alexander the Great had a profound effect on world history. His conquests covered the entire known world at the time, and he was responsible for the spread of Greek culture throughout the ancient world. In Babylon in 323 BC, Alexander died when he was nearly 33 years old. Possible explanations for his death have included alcoholic liver disease and strychnine poisoning, but little data support either condition as the cause of his death. Alexander most likely died from malaria or typhoid fever, which were rampant in ancient Babylon. The description of his final illness from the royal diaries is consistent with typhoid fever or malaria but is most characteristic of typhoid fever.

Ancient Lands↗

PubMedDate not supplied

Typhoid fever and HIV infection: a rare disease association in industrialized countries.

Typhoid fever is still a global health problem, mainly in tropical and subtropical areas of the world and in developing countries, where relatively elevated morbidity and mortality rates still are present, mostly because of persisting poor hygienic conditions. In the majority of Mediterranean regions, including Italy, the disease is constantly present, though with a low prevalence rate, as a result of an endemic persistence of Salmonella typhi infection.1-4 On the other hand, in industrialized countries, most cases of S. typhi infection are related to foreign travel or prior residence in endemic countries.4-6 In the United States, 2445 cases of typhoid fever have been reported in the decade 1985 to 1994, and the annual number of cases remained relatively stable over time: over 70% of episodes were acquired in endemic countries (mostly Mexico and India).6 The persisting morbidity of S. typhi also may be supported by the increasing resistance rate of this pathogen against a number of commonly used antimicrobial compounds. For instance, 6% of 331 evaluable S. typhi strains were resistant to ampicillin, chloramphenicol, and cotrimoxazole, and 22% of isolates were resistant to at least one of these three agents in a recent survey performed in the United States.6 The spread of antibiotic resistance among S. typhi isolates is emerging in many countries, and multidrug-resistant strains have been isolated, as well as isolates with poor susceptibility to fluoroquinolones,3-5,7-9 so that in vitro susceptibility should be determined for all cultured strains, and antimicrobial treatment should be adjusted accordingly. Nevertheless, fluoroquinolones (e.g., ciprofloxacin and pefloxacin) or third-generation cephalosporins, still represent the best choice for empirical treatment,2,4,6-8,10 and mortality remains rare in Western countries (less than 1% of episodes), although it is expected to be greater in developing areas of the world. The aim of this report is to describe two cases of typhoid fever that occurred in patients with human immunodeficiency virus (HIV) infection, a rarely reported disease association in industrialized countries.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Unlocking the genome of the human typhoid bacillus.

Molecular studies are shedding new light on the pathogenesis of human typhoid fever, which is still a very common disease in developing countries. For example, the total genome DNA sequence has recently been determined for a multiple-drug-resistant Salmonella typhi, the serotype that is the cause of typhoid fever. The genome sequence showed many distinguishing features, including clusters of S typhi specific genes and a large number--over 200--of pseudogenes. This information, together with other molecular studies, has provided vital clues in several important areas of typhoid biology. We have new insights into the mechanisms underpinning the human host specificity of S typhi, and have exploitable new routes to improved diagnostics and a better understanding of the epidemiology of the disease.

Anti-Bacterial Agents↗

PubMed2002

Detection of Salmonella typhi by polymerase chain reaction: implications in diagnosis of typhoid fever.

The present study was conducted to detect Salmonella typhi by polymerase chain reaction (PCR) in a clinical setting. A group of 40 clinically suspected cases of typhoid fever, lasting for about 3-11 days, with or without chills and rigors and hepatosplenomegaly were selected. Of these, 20 were culture positive and the remaining 20 were found to be negative by conventional blood culture technique. Primary PCR was followed by nested PCR using two sets of primers corresponding to flagellar gene of S. typhi strain. Two bands of about 458 and 343 bp were detected in 20 blood culture positive cases and 12 of the 20 culture negative ones. In the simulated group of samples, no amplification was detected. Our results suggest that PCR-based diagnosis is particularly useful for all clinically suspected cases of typhoid fever. The sensitivity of PCR and its potential use in routine diagnosis and epidemiological studies of typhoid fever can be exploited to complement studies by including bone marrow culture, faeces and bile samples.

Humans↗

PubMed2006

Risk factors for typhoid fever in a slum in Dhaka, Bangladesh.

We systematically investigated risk factors for typhoid fever in Kamalapur, a poor urban area of Bangladesh, to inform targeted public health measures for its control. We interviewed patients with typhoid fever and two age-matched controls per case about exposures during the 14 days before the onset of illness. The municipal water supply was used by all 41 cases and 81of 82 controls. In multivariate analysis, drinking unboiled water at home was a significant risk factor [adjusted odds ratio (aOR) 12.1, 95% CI 2.2-65.6]. Twenty-three (56%) cases and 21 (26%) controls reported that water from the primary source was foul-smelling (aOR 7.4, 95% CI 2.1-25.4). Eating papaya was associated with illness (aOR 5.2, 95% CI 1.2-22.2). Using a latrine for defecation was significantly protective (aOR 0.1, 95% CI 0.02-0.9). Improved chlorination of the municipal water supply or disinfecting drinking water at the household level may dramatically reduce the risk of typhoid fever in Kamalapur. The protective effect of using latrines, particularly among young children, should be investigated further.

Adolescent↗

PubMed2007

Optimizing typhoid fever case definitions by combining serological tests in a large population study in Hechi City, China.

Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO>or=80 & TH>A), a positive Tubex test (>or=4) and a positive Typhidot-M test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.

Adolescent↗

PubMed1997

Typhoid fever in Ujung Pandang, Indonesia--high-risk groups and high-risk behaviours.

We performed a hospital-based case-control study to identify high risk groups and routes of transmission of typhoid fever in the city of Ujung Pandang on the island of Sulawesi, Indonesia. The annual incidence of this disease in southern Sulawesi is estimated at 3.1/1000 and the case fatality at 5.1% Cases were 50 patients over 13 years of age admitted to Stella Maris Hospital with a diagnosis of typhoid fever between June and September 1991. Diagnosis was made on clinical grounds and in 90% of cases confirmed by a Widal test. Controls were 42 patients admitted for non-infectious disorders during the same period and individually matched by age and sex. Controls did not have a history of typhoid fever. Interviews took place in hospital. Analysis was by unconditional logistic regression. High-risk groups consisted of those who were single, unemployed and those who had a university education. Median age of cases was 22 years. Consumption of food from warungs (food stalls in the street) was strongly associated with risk (OR = 45). Both cases and controls washed hands after use of the toilet and before meals, but cases used soap significantly less often (OR = 30). The results of this study can be used to take preventive measures against this severe disease of educated and single young adults by targetting them for IEC-activities emphasizing the importance of thorough hand-washing and the need to take care in the selection of street-foods.

Adolescent↗

PubMed1984

Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone.

We compared high-dose dexamethasone (initial dose, 3 mg per kilogram of body weight) with placebo in a randomized, double-blind trial involving 38 patients with culture-positive, specifically defined severe typhoid fever. The patients in the two treatment groups ranged in age from 5 to 54 and were comparable at the outset. All patients received chloramphenicol. The case-fatality rate of 10 per cent (2 of 20 patients) in the dexamethasone group was significantly lower than the fatality rate of 55.6 per cent (10 of 18) in the placebo group (P = 0.003). There was no significant difference in the incidence of complications among the survivors in either group. Delirium, obtundation, and stupor were grave prognostic signs that were useful for predicting which patients were at high risk of dying before they became comatose or went into shock. Dexamethasone is unnecessary for most patients with typhoid but is recommended for all patients with suspected typhoid fever who are delirious, obtunded, stuporous, comatose, or in shock.

Adolescent↗

PubMed1998

Treatment with ciprofloxacin in children with typhoid fever.

We investigated the use, treatment results and safety of ciprofloxacin in the treatment of childhood typhoid and paratyphoid infections in an industrialized country. The study was retrospective, and the material consisted of children admitted to Hvidovre or Glostrup University Hospitals from 1991 to 1995, and treated with ciprofloxacin for a culture proven diagnosis of typhoid fever. 21 children were included, 18 had positive cultures for Salmonella typhi and 3 had positive cultures for S. paratyphi A. All isolates were fully susceptible to ciprofloxacin. The median duration of treatment was 10 d, median oral dose was 24 mg/kg/d and the median intravenous dose was 15 mg/kg/d. Within 4 d after start of treatment all subjects had a normal body temperature. No subjects had clinical or microbiological relapse and all stool cultures after end of treatment were negative. Adverse events were rare, but in 2 children a transient limb/ataxia or a period of confusion were recorded. Both children recovered within a few days without sequelae. We conclude that ciprofloxacin was effective and well tolerated for treatment of typhoid fever in children. The few adverse events that were recorded left no permanent sequelae, and were likely to be caused by the disease itself.

Adolescent↗

PubMed1988

Typhoid fever in hospitalized children in Kelantan, Malaysia.

A retrospective study of 137 patients with blood culture-positive typhoid fever admitted to the paediatric unit of the Hospital Universiti Sains Malaysia was carried out to study epidemiological, clinical, laboratory and treatment aspects of typhoid fever in Kelantanese children in hospital. The male:female ratio was 1:1.1. School-children were the most affected. Cases were seen throughout the year. The five most frequently presenting features were fever, hepatomegaly, diarrhoea, vomiting and cough. Rose spots were seen in only two patients. Complications included gastritis, bronchitis, ileus, psychosis, encephalopathy, gastro-intestinal bleeding and myocarditis. Relative bradycardia was not seen. Blood and stool cultures were positive in the 1st, 2nd and 3rd weeks of illness. There was no significant difference between percentages of elevated O and H titres, whether done during or after the 1st week of illness. A four-fold rise in (O) titres occurred in 50% of cases tested. We would miss 50% of typhoid fever cases if a titre (O) equal to more than 1/160 were relied upon for diagnosis. Altogether, 46% of patients had leucopenia. Chloramphenicol was the most commonly used antibiotic. There were two deaths.

Child↗

PubMed1991

Hepatic dysfunction in paediatric typhoidal salmonellosis.

Although hepatic dysfunction has been described among adults with typhoid, there are few reports of significant hepatic functional impairment in children with typhoid. Of 435 children with culture-proven typhoid seen at the Aga Khan University Hospital, hepatomegaly was noted in 125 (29%) and isolated right hypochondrial tenderness in three (7%). Liver function tests performed on 156 of these children were normal in 121 (78%) and showed significant hepatic dysfunction in 35 (22%). Patients with significant hepatic dysfunction were more toxic (p less than 0.001) at presentation and had higher mortality (p less than 0.002) than those with normal liver function. Two children presented with a picture of fulminant hepatic failure with fatal outcome.

Child↗

PubMed2000

Typhoid fever, ciprofloxacin and growth in young children.

Typhoid fever remains a significant public health problem in Southern Asia, particularly with the emergence of multi-resistant strains of Salmonella typhi in the late 1980s. Use of ciprofloxacin in children, although discouraged, is increasing and we aimed to assess whether its use affects growth or the prevalence of joint symptomology. Children under 6 years of age diagnosed as typhoid fever on the basis of a positive Widal test were recruited in the outpatient department of a paediatric teaching hospital after treatment had been initiated. During 6 months follow-up, prevalences of arthritis/arthralgia and ponderal, linear and knemometric growth were recorded. Seventy-five children were recruited (mean age 32 months, mean weight-for-height Z-score--1.3, mean height-for-age Z-score 1.4) and 29 (39%) of them received ciprofloxacin. No significant adverse effects on ponderal, linear or knemometric growth, or on the incidence of arthritis/arthralgia were found to be associated with the use of ciprofloxacin. Knemometric and ponderal catch-up growth was demonstrable 30 days after diagnosis but linear growth was still declining 3 months after diagnosis with catch-up growth demonstrable only after 6 months. We conclude that ciprofloxacin is commonly used in typhoid fever and has no adverse effects on growth or joint symptomology.

Anti-Infective Agents↗

PubMed2004

Diagnostic methods for typhoid fever in Nigeria.

In this study, 65 patients are screened for Salmonella typhi by conventional culture and the Widal test. In addition, the patients undergo full blood count are screened for malaria parasites. Of the 65 patients, 50 report febrile conditions, while the remaining 15 are used as a control population. In the febrile group, 13 (26%) were positive for S. typhi, while in the control group only one (7%) was positive for S. typhi. Overall, 36 (64.3%) patients had malaria parasites. Patients with a higher O antibody titre (> or = 1 in 80) by Widal test were found to have consumed both tap water and pure water. More females (10/14; mean age: 33) had typhoid fever as a result of S. typhi infection, the majority of which were isolated from stool samples (57%). Nine of the isolates were also positive for malaria parasites, seven of which were in the trophozoite stage. Plasmodium falciparum was the predominant parasite (78%), the remainder being P. malariae. The majority of patients (12/14) with typhoid fever had normal PCV values. In conclusion, it is recommended that tests for the diagnosis of typhoid fever in Nigeria should include malaria parasites, S. typhi culture from faecal samples, and the Widal test.

Adult↗

PubMed1960

Studies on infection and immunity in experimental typhoid fever. II. Susceptibility of recovered animals to re-exposure.

Chimpanzees recovered from typhoid fever induced by ingestion of large numbers of phage-type T S. typhosa were rechallenged approximately a year and a half later with a like number of a phage-type E(1) strain. Control animals exhibited febrile responses, bacteriemia, and other significant laboratory and clinical findings, including increases in C-reactive protein levels and sedimentation rates. All of the previously infected and recovered chimpanzees were negative with respect to the aforementioned observations, and appeared to have resisted significant re-infection. On the other hand, recovery from typhoid fever induced by smaller numbers of S. typhosa failed to protect completely against rechallenge with larger numbers of these organisms. These findings indicate that chimpanzees recovered from typhoid fever may be protected against re-infection, even though the re-infecting organism is of a different phage type. Differences in the magnitude of the original and subsequent infecting inocula appear to influence the response to rechallenge.

Animals↗

PubMed2000

Azithromycin versus ceftriaxone for the treatment of uncomplicated typhoid fever in children.

A total of 108 children aged 4-17 years were randomized to receive 7 days of azithromycin (10 mg/kg/day; maximum, 500 mg/day) or ceftriaxone (75 mg/kg/day; maximum, 2.5 g/day), to assess the efficacy of the agents for the treatment of uncomplicated typhoid fever. Salmonella typhi was isolated from the initial cultures of blood samples from 64 patients. A total of 31 (91%) of the 34 patients treated with azithromycin and 29 (97%) of the 30 patients treated with ceftriaxone were cured (P>.05). All 64 isolates were susceptible to azithromycin and ceftriaxone. Of the patients treated with ceftriaxone, 4 subsequently had relapse of their infection. No serious side effects occurred in any study subject. Oral azithromycin administered once daily appears to be effective for the treatment of uncomplicated typhoid fever in children. If these results are confirmed, the agent could be a convenient alternative for the treatment of typhoid fever, especially in individuals in developing countries where medical resources are scarce.

Adolescent↗

PubMed2003

Sexual transmission of typhoid fever: a multistate outbreak among men who have sex with men.

In August 2000, the Ohio Department of Health reported a cluster of men with typhoid fever who denied having traveled abroad. To determine the cause and the extent of the outbreak, an epidemiological investigation was initiated in which 7 persons in Ohio, Kentucky, and Indiana with culture-confirmed Salmonella enterica serotype Typhi infection and 2 persons with probable typhoid fever were evaluated; all were men, and all but one reported having had sex with 1 asymptomatic male S. Typhi carrier. We document sexual transmission of typhoid fever, which may be acquired by means of oral and anal sex, as well as via food and drink.

Disease Outbreaks↗

PubMed2005

Host susceptibility and clinical outcomes in toll-like receptor 5-deficient patients with typhoid fever in Vietnam.

Toll-like receptor 5 (TLR5) mediates innate immune responses to bacterial pathogens by binding to flagellin. A polymorphism in the TLR5 gene introduces a premature stop codon (TLR5(392STOP)) that is associated with susceptibility to legionnaires disease. Here we investigated whether TLR5(392STOP) was associated with typhoid fever. The frequency of TLR5(392STOP) was not significantly different in 565 patients with typhoid fever and 281 ethnically matched control subjects. Furthermore, TLR5 deficiency had no measurable effect on a number of clinical parameters associated with typhoid fever, including fever clearance time, pathogen burden, disease severity, or age at acquisition of disease. TLR5 may not play an important role in TLR-stimulated innate immune responses to human infection with Salmonella enterica serovar Typhi. Initiation of these responses may rely on other TLRs that recognize different bacterial ligands.

Adolescent↗

PubMed2005

Enteric (typhoid) fever in travelers.

The incidence of enteric (typhoid) fever in travelers is estimated to be approximately 3-30 cases per 100,000 travelers to developing countries. Recently, it is become clear that travelers who are visiting friends and relatives, especially travelers to the Indian subcontinent, seem to be the most vulnerable to enteric fever and require special attention for prevention. Recent concerns are the increasing incidence of paratyphoid fever in Asia, which is not covered by available typhoid vaccines, and the emergence of infections caused by antibiotic-resistant strains (including strains resistant to fluoroquinolones). Typhoid vaccination is recommended for most travelers to moderate- to high-risk countries. Because of the nonspecific clinical presentation of enteric fever, a high index of suspicion is important in febrile travelers who have traveled to areas of endemicity.

Bacterial Vaccines↗