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Epidemiology of typhoid fever in Singapore.

A total of 1452 cases of typhoid fever was notified in Singapore from 1980-9. The morbidity rates of indigenous cases showed a steady decline from 5.9 per 100,000 population in 1980 to 1.2 per 100,000 population in 1989. The mean case fatality was 0.8%. Children, adolescents and young adults were most susceptible to typhoid fever. There was no significant difference in morbidity rates between the major ethnic groups. The vast majority of indigenous cases were sporadic while outbreaks accounted for almost one third of them. Food was the main vehicle of transmission. The commonest indigenous phage types were B1, D1 and A. Antimicrobial resistance was infrequently seen. The proportion of imported cases rose from 32% in 1980 to 72% in 1989. Almost half (48.5%) of all imported cases were local residents who contracted typhoid fever while travelling in endemic countries. As imported cases assume greater importance in the epidemiology of typhoid fever in Singapore, further drop in typhoid fever incidence would require reduction of travel-related cases through greater awareness of food hygiene and effective vaccination.

Adolescent↗

Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report.

We conducted a pilot study followed by a large clinical trial in Nepal of the use of the capsular polysaccharide of Salmonella typhi (Vi) as a vaccine to prevent typhoid fever. In the pilot study, involving 274 Nepalese, there were no significant side effects of the Vi vaccine; about 75 percent responded with a rise in serum antibodies of fourfold or more. In the clinical trial, residents of five villages were given intramuscular injections of either Vi or, as a control, pneumococcus vaccine dispensed in coded, randomly arranged, single-dose syringes. There were 6907 participants, of whom 6438 were members of the target population (5 to 44 years of age); each was visited every two days. Those with temperatures of 37.8 degrees C or higher for three consecutive days were examined and asked to give blood for culture. Typhoid was diagnosed as either blood culture-positive or clinically suspected on the basis of bradycardia, splenomegaly, and fever, with a negative blood culture. Seventeen months after vaccination, the codes were broken for the 71 patients meeting the criteria for either culture-positive or clinically suspected typhoid. The attack rate of typhoid was 16.2 per 1000 among the controls and 4.1 per 1000 among those immunized with Vi (P less than 0.00001). The efficacy of Vi was 72 percent in the culture-positive cases, 80 percent in the clinically suspected cases, and 75 percent in the two groups combined. These data provide evidence that Vi antibodies confer protection against typhoid. Surveillance continues to determine the duration of Vi-induced immunity.

Adolescent↗

Travel trouble: typhoid fever--A case presentation and review.

Endogenously contracted typhoid fever has decreased dramatically in the industrialized world. A practicing physician may not see a case in a lifetime, but health professionals should not allow typhoid to recede from their consciousness. Typhoid is still endemic in much of the developing world, and as travel increases, illnesses can and do skip around the world in a day. College students are at particular risk because they often travel on a low budget for extended periods, mix freely with local populations in endemic regions, and are not aware of the risks of such travel. College health professionals need to be able to recognize typhoid fever, should it present, and give advice to patients on primary prevention. The author includes a case presentation that is not completely classical for typhoid fever, as well as a state-of-the-art review, including description, epidemiology, signs and symptoms, diagnosis, treatment, and prevention. Special attention is given to the question of who should be immunized and which vaccines are effective.

Adult↗

Typhoid fever and genetic polymorphisms at the natural resistance-associated macrophage protein 1.

Control of Salmonella enterica serovar Typhimurium (S. typhimurium) infection in the mouse model of typhoid fever is critically dependent on the natural resistance-associated macrophage protein 1 (Nramp1). In this study, we examined the role of genetic polymorphisms in the human homologue, NRAMP1, in resistance to typhoid fever in southern Vietnam. Patients with blood-culture-confirmed typhoid fever and healthy control subjects were genotyped for 6 polymorphic markers within and near NRAMP1 on chromosome 2q35. Four single base-pair polymorphisms (274 C/T, 469+14 G/C, 1465-85 G/A, and D543N), a (GT)(n) repeat in the promoter region of NRAMP1 and D2S1471, and a microsatellite marker approximately 130-kb downstream of NRAMP1 were examined. The allelic and genotypic frequencies for each polymorphism were compared in case patients and control subjects. No allelic association was identified between the NRAMP1 alleles and typhoid fever susceptibility. In addition, neither homozygotes nor heterozygotes for any NRAMP1 variants were at increased risk of typhoid fever.

Alleles↗

Association between Helicobacter pylori infection and increased risk of typhoid fever.

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

Adolescent↗

Response of typhoid fever caused by chloramphenicol-susceptible and chloramphenicol-resistant strains of Salmonella typhi to treatment with trimethoprim-sulfamethoxazole.

Chloramphenicol remains the drug of choice for the treatment of typhoid fever in most areas despite the risks of relapses and toxicity. In a comparison of the efficacy of trimethoprim-sulfamethoxazole (TMP-SMZ) and chloramphenicol against typhoid fever, 60 patients in Indonesia were randomly assigned to receive either TMP-SMZ (320 mg of TMP and 1,600 mg of SMZ daily) or chloramphenicol (2 g daily) for 14 days. TMP-SMZ was significantly more effective in sterilizing the blood, but the two drugs were equally effective with regard to relapse rate, frequency of prolonged fever, and mortality. Use of TMP-SMZ in Vietnam for the treatment of typhoid fever caused by chloramphenicol-resistant Salmonella typhi showed that TMP-SMZ is as effective as ampicillin. Likewise, a review of other published reports suggests that TMP-SMZ has an overall record in the treatment of typhoid fever that is equal to or better than the records of other available drugs. TMP-SMZ has emerged as a satisfactory alternative to chloramphenicol for the treatment of typhoid fever and should be especially useful in areas where chloramphenicol-resistant S. typhi has been isolated.

Adolescent↗

Typhoid fever complicated by intestinal perforation: a persisting fatal disease requiring surgical management.

In Bangladesh, clinical records of 323 patients with typhoid fever were reviewed to study the incidence, fatality, and optimal therapy of the complication of intestinal perforation. Fifteen patients (4.6%) developed intestinal perforation. Case-fatality rates were six of nine patients treated medically and one of four patients treated surgically for whom the postoperative courses were known. A literature review of 57,864 cases of typhoid fever in developing countries in the antibiotic era revealed that perforation developed in 2.5% of patients, a percentage that was similar to the incidence of 2.8% reported in the preantibiotic era. The median of case-fatality rates in these reports was 43% and the proportion of all reported typhoid deaths attributable to perforation was 25%. The case-fatality rates for patients with perforation were 70% for 410 patients managed medically and 26% for 1,835 patients managed surgically. Although some reports were biased toward placing patients at lower risk into surgical treatment, the large number of patients treated successfully by surgery suggests real improvement in surgical techniques in countries with endemic typhoid fever. These results indicate that intestinal perforation persists as a major cause of death in cases of typhoid fever in developing countries in the antibiotic era and that surgical treatment with use of antibiotic therapy is optimal for this complication.

Adolescent↗

Typhoid hepatitis in children.

Liver involvement is commonly observed in patients with typhoid fever. However, a hepatitis-like picture with fever and jaundice is unusual and infrequently reported in the paediatric literature. Our aim was to characterize the clinical picture, biochemical features, and prognosis of typhoid hepatitis. One hundred cases of typhoid fever (age 0 to 12 years), proven by positive blood cultures to Salmonella typhi, were studied with special reference to hepatic dysfunction. Of these, eight patients were found to have hepatitis during the course of their illness. All had high fever, tender hepatomegaly, elevated serum bilirubin (in the range of 2.5-5.8 mg/dl), and elevated serum alanine transaminase levels (in the range 100-620 IU/l). All the eight patients showed complete clinical and biochemical recovery in response to appropriate antibiotics. The clinical picture of typhoid hepatitis frequently mimics acute viral hepatitis. In tropical areas, the differential diagnosis of a child presenting with fever and jaundice should include typhoid hepatitis.

Child↗

Serum adenosine deaminase in the early diagnosis of typhoid fever.

To study the usefulness of the enzyme adenosine deaminase for the early diagnosis of typhoid fever, its activity in serum was assayed in 277 children admitted to the Hospital Guillermo Grant Benavente at Concepción, Chile, from March, 1988, to December, 1990. The children were distributed into seven groups: control, N = 82; bacteremia, N = 8; acute viral respiratory infection, N = 43; febrile children with miscellaneous etiologies, N = 49; pulmonary tuberculosis, N = 3; hepatitis A virus infection, N = 30; and typhoid fever, N = 62. The medium serum adenosine deaminase values were significantly higher in children with typhoid fever (P < 0.0001) in relation to the values in the control group (122.2 +/- 40.7 vs 28.1 +/- 8.4 units/liter at 37 degrees C). This test had a sensitivity of 91.9% and a specificity of 92.5% in identifying the patient with typhoid fever when using 80 units/liter as the cutoff values. The positive predictive value of the test was 83.8% and the negative predictive value was 96%. Determination of adenosine deaminase values in serum could be helpful in the early diagnosis of typhoid fever.

Adenosine Deaminase↗

Neonatal typhoid fever.

Typhoid fever occurs in children less than 2 years of age but is thought to be a mild, often unrecognized illness. Neonatal typhoid fever is a rare but often life-threatening illness, uniformly fatal in the preantibiotic era. Vertical intrauterine transmission from a typhoid-infected mother is implicated in neonatal typhoid fever. Ten cases at a rural African hospital are presented. Three patients died with two deaths associated with empiric management inappropriate for Salmonella typhi. A second clinical presentation in the neonate is asymptomatic persistent excretion. Infants < or = 3 weeks old may also be infected from an exogenous source and have severe disease. Where typhoid is endemic S. typhi should be considered as a cause of sepsis neonatorum and appropriate antibiotics included in empiric therapy.

Anti-Bacterial Agents↗

Ofloxacin versus co-trimoxazole in the treatment of typhoid fever in children.

Ofloxacin has been successfully used in the treatment of typhoid fever and Salmonella infectious of adults for many years. However, it has rarely been tried for the typhoid fever of children. In the present study, the therapeutic efficacy of ofloxacin in the treatment of typhoid fever in children was compared to that of co-trimoxazole. Out of 41 patients with bacteriologically documented typhoid fever, those with co-trimoxazole-resistant strains received 20 mg/kg ofloxacin twice daily for 10 days, and those with co-trimoxazole-susceptible bacteria were given 60 mg/kg co-trimoxazole twice daily for 10 days. Both groups were compared according to the clinical variables (apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms) and the time when cultures became negative. All patients in both groups were cured without relapse. Apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms were obtained in a significantly shorter time with ofloxacin than with co-trimoxazole (P < 0.05). The interval between onset of therapy and the time when cultures became negative was significantly shorter in the ofloxacin group than in the co-trimoxazole group (P = 0.005). Ofloxacin seems to be a good alternative in the treatment of typhoid fever caused by co-trimoxazole resistant salmonellae in children aged less than 16 years. It is well tolerated by the patients and it causes no side effects with short-term usage.

Anti-Bacterial Agents↗

An evidence-based review of current guidelines for the public health control of typhoid in Australia: a case for simplification and resource savings.

BACKGROUND: Although an uncommon disease in Australia, public health control measures for typhoid remain important to prevent further cases, however, they are labour intensive. METHODS: We reviewed current guidelines from all Australian states and territories, England and the United States to ascertain whether recommended control measures for typhoid are supported by evidence from the medical literature or data from Victorian typhoid notifications. RESULTS: Guidelines lacked consistency and were overly complex, particularly with reference to the frequency and timing of faecal specimens required to demonstrate eradication of typhoid from cases and contacts. Data from the medical literature are limited and do not support the superiority of any one approach, or multiple approaches based on risk groups of cases or contacts. Victorian data suggest that a general approach, with a reduction in the number of specimens collected and duration of follow-up is reasonable. CONCLUSIONS: Potential exists for simplification and improved consistency between guidelines for the public health control of typhoid, with associated resource savings.

Anti-Infective Agents↗

[Studies on the clinical and bacteriological effects of ofloxacin on the typhoid patients and carriers].

Fundamental and clinical studies of OFLX were performed against the patients with typhoid fever and typhoid carriers. 1) Clinical and bacteriological effects: Eight patients with typhoid fever and 3 typhoid carriers were treated with OFLX. Daily doses of the agent were 900 mg in 5 adult patients, 600 mg in a child patient and 3 adult carriers. In one case of the remaining 2 adult patients, daily doses of the agent changed from 800 mg to 1200 mg and from 900 mg to 1200 mg in the other one. The duration of the treatment was 9, 14 or 21 days. Clinical efficacies of OFLX against the patients proved 4 cases were "excellent", 3 cases were "good" and one case was "poor". The eradication of Salmonella typhi recognized in all cases containing 3 carriers with the exception of the "poor" case. Adverse reactions were observed transiently in 3 patients, such a slight decrease of RBC count, decrease of granulocyte count and elevation of GPT value respectively. 2) Antimicrobial activity: MICs of OFLX against 40 strains of S. typhi were 0.05 micrograms/ml and 0.1 micrograms/ml. The MICs of NFLX, CPFX and T-3262 were almost the same as that of OFLX, and those of ENX, NY-198 and NA were higher than that of OFLX. The peaks of MIC of CP and ABPC, first choice drug against typhoid fever, were 1.56 micrograms/ml and 0.38 micrograms/ml respectively. 3) Serum concentration; Serum concentrations of OFLX were serially measured on 5 patients through the day. The concentrations of the drug were distributed from 0.82 micrograms/ml to 6.34 micrograms/ml at 6.30 a.m. and from 2.52 micrograms/ml to 11.2 micrograms/ml at 9:00 p.m. Those of the day time showed considerable individual differences.

Adult↗

Serological diagnosis of typhoid fever by counterimmunoelectrophoresis.

The sensitivity and specificity of counterimmunoelectrophoresis using three antigenic preparations obtained from Salmonella typhi were compared with those of the Widal test in the serological diagnosis of typhoid fever. A veronal buffer extract yielded precipitation lines against 50 (96%) out of 52 sera collected from patients with typhoid but against none out of 62 sera obtained from control subjects who did not have typhoid. Less satisfactory results were obtained by counterimmunoelectrophoresis when two other preparations, a protein extract (Barber antigen) and an ultrasonic lysate, were used as the antigens. By Widal test the rate of detection in patients' sera was 73% and the false-positive rate for control sera 16%. It is concluded that in an area where typhoid is endemic counterimmunoelectrophoresis using veronal buffer extract as the antigen is superior to the Widal test for serological diagnosis of typhoid fever. An additional advantage of counterimmunoelectrophoresis is that results may be obtained on the same day that the serum specimens are received.

Antibodies, Bacterial↗

Is travel prophylaxis worth while? Economic appraisal of prophylactic measures against malaria, hepatitis A, and typhoid in travellers.

OBJECTIVES: To estimate the costs and benefits of prophylaxis against travel acquired malaria, typhoid fever, and hepatitis A in United Kingdom residents during 1991. DESIGN: Retrospective analysis of national epidemiological and economic data. MAIN OUTCOME MEASURES: Incidence of travel associated infections in susceptible United Kingdom residents per visit; costs of prophylaxis provision from historical data; benefits to the health sector, community, and individuals in terms of avoided morbidity and mortality based on hospital and community costs of disease. RESULTS: The high incidence of imported malaria (0.70%) and the low costs of providing chemoprophylaxis resulted in a cost-benefit ratio of 0.19 for chloroquine and proguanil and 0.57 for a regimen containing mefloquine. Hepatitis A infection occurred in 0.05% of visits and the cost of prophylaxis invariably exceeded the benefits for immunoglobulin (cost-benefit ratio 5.8) and inactivated hepatitis A vaccine (cost-benefit ratio 15.8). Similarly, low incidence of typhoid (0.02%) and its high cost gave whole cell killed, polysaccharide Vi, and oral Ty 21a typhoid vaccines cost-benefit ratios of 18.1, 18.0, and 22.0 respectively. CONCLUSIONS: Fewer than one third of travellers receive vaccines but the total cost of providing typhoid and hepatitis A prophylaxis of 25.8m pounds is significantly higher than the treatment costs to the NHS (1.03m pounds) of cases avoided by prophylaxis. Neither hepatitis A prophylaxis nor typhoid prophylaxis is cost effective, but costs of treating malaria greatly exceed costs of chemoprophylaxis, which is therefore highly cost effective.

Antimalarials↗

Significance and value of the Widal test in the diagnosis of typhoid fever in an endemic area.

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.

Agglutination Tests↗

Comparison of passive haemagglutination test with Widal agglutination test for serological diagnosis of typhoid fever in an endemic area.

A passive haemagglutination test, using sheep red blood cells sensitised with Salmonella typhi lipopolysaccharide, was compared with the Widal test for the serological diagnosis of typhoid fever in an endemic area. The results obtained on sera from 152 patients with bacteriologically confirmed typhoid and 183 patients who did not have typhoid were analysed in terms of sensitivity, specificity, simplicity, and rapidity of the respective tests. The passive haemagglutination test was found to be more sensitive (80%) than the S typhi O antigen (71%) but marginally less sensitive than the H antigen (82%) of the Widal test. The false positive rate on control sera was 1.2% and 6.6%, respectively, for the Widal O and H antigens, and 1.6% for the passive haemagglutination test. Our findings indicate that the passive haemagglutination test is comparable with the Widal test for the serological diagnosis of typhoid fever in endemic areas, but is more simple, rapid, and economic. The passive haemagglutination test may be a useful alternative to the Widal test for the serological diagnosis of typhoid fever in busy microbiology laboratories in areas in which the disease is endemic.

Adolescent↗

Early diagnosis of typhoid fever by the detection of salivary IgA.

BACKGROUND: / AIMS: Current diagnostic methods for typhoid fever have low sensitivity and specificity. This study aimed to develop an enzyme linked immunosorbent assay (ELISA) with greater sensitivity and specificity. METHODS: The ELISA was developed and evaluated on patients with acute typhoid infection, febrile controls, and healthy controls. A sequential study on patients with culture confirmed typhoid was also carried out to determine the time period of maximum sensitivity. RESULTS: The ELISA detected anti-Salmonella typhi lipopolysaccharide (LPS) salivary IgA antibodies. A six month follow up study of patients with culture confirmed typhoid fever showed that the test shows maximum efficiency during the second and third weeks of fever and enables detection of the acute infection during the early phase. CONCLUSIONS: This ELISA can detect typhoid fever during the early phase of infection and is most efficient during the second and third weeks of fever, the time at which patients normally present for treatment. Because the sensitivity of the assay is subsequently greatly reduced, it will be useful for the diagnosis of acute infection.

Acute Disease↗