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Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from patients having acute diarrhoeal disease.

BACKGROUND: Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearance of multiple drug resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from faecal samples of patients with acute diarrhoeal disease attending the outpatient and inpatient departments of a hospital in Saudi Arabia during the years 1999 to 2002. METHODS: Non-typhoidal Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacin were determined by the agar dilution method. RESULTS: During the study period, 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1 were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulfamethoxazole in 18.5% of the strains. Nalidixic acid resistance was encountered in 9.9% and ciprofloxacin resistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.5% in 2002 (P=0.0007) and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002 (P=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal Salmonella isolated during 2002. The MIC was >256 microg/mL to nalidixic acid and 8 to 16 microg/mL to ciprofloxacin. CONCLUSION: The increasing rates of antimicrobial resistance encountered among non-typhoidal Salmonella necessitate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increase in resistance and should be restricted.

Acute Disease↗

Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from patients having acute diarrhoeal disease.

BACKGROUND: Non-typhoidal Salmonella are one of the key etiological agents of diarrhoeal disease. The appearance of multiple drug resistance along with resistance to quinolones in this bacterium poses a serious therapeutic problem. We determined the prevalence of nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from faecal samples of patients with acute diarrhoeal disease attending the outpatient and inpatient department of a hospital in Saudi Arabia during the years 1999 to 2002. METHODS: Non-typhoidal Salmonella were isolated from faecal samples. Antimicrobial susceptibility was tested by the disc diffusion test. MICs to nalidixic acid and ciprofloxacin were determined by the agar dilution method. RESULTS: During the study period, 524 strains of non-typhoidal Salmonella were isolated. Strains belonging to serogroup C1 were the commonest (41.4%) followed by serogroups B and D (15.6% and 14.5%, respectively). Resistance to ampicillin was observed in 22.9% and to trimethoprim/sulfamethoxazole in 18.5% of the strains. Nalidixic acid resistance was encountered in 9.9% and ciprofloxacin resistance in 2.3% of the strains. Resistance to nalidixic acid significantly increased from 0.1% in 1999 to 5.5% in 2002 (P=0.0007) and ciprofloxacin resistance increased significantly from 0.1% in 1999 to 0.9% in 2002 (P=0.0001). MICs to nalidixic acid and ciprofloxacin were determined among 29 nalidixic acid-resistant strains of non-typhoidal Salmonella isolated during 2002. The MIC was >256 microg/mL to nalidixic acid and 8 to 16 microg/mL to ciprofloxacin. CONCLUSION: The increasing rates of antimicrobial resistance encountered among non-typhoidal Salmonella necessitate the judicious use of these drugs in humans. Moreover, these findings support the concern that the use of quinolones in animal feed may lead to an increase in resistance and should be restricted.

Acute Disease↗

Typhoid vaccines.

Typhoid fever continues to be a major public health problem in developing countries with about 33 million cases per year. Protective efficacy of traditional acetone/phenol killed vaccines is similar to newer typhoid vaccines (Ty21A and Vi antigen vaccine) but side effects of these newer vaccines are considerably less. Though the mortality is low, typhoid fever causes considerable morbidity and loss of working days. Problems during treatment are increasing due to emergence and spread of multidrug resistant S. typhi. Hence to decrease the incidence of typhoid fever in addition to ensuring safe water supply and excreta disposal a typhoid vaccine needs to be introduced in the National Immunization Schedule.

Administration, Oral↗

Outbreak of typhoid fever in vaccinated members of the French Armed Forces in the Ivory Coast.

In 2001, an outbreak of typhoid fever occurred among the members of the French Armed Forces. All had received a typhoid vaccination as per the immunization schedule practiced in the Armed Forces (every 5 years). A retrospective cohort study was conducted in 94 personnel. The objectives were to confirm the diagnosis, determine the source of contamination and identify the factors associated with defective vaccinal efficacy. Twenty-four cases were clinically identified. A cucumber salad was identified as the contaminating dish (Risk Ratio = 3.6; 95%CI 1.5-8.9). Only one factor was related to defective vaccinal efficacy; the risk of typhoid fever was two-fold higher in people vaccinated more than 3 years previously (Risk Ratio = 2.2; 95%CI, 1.1-4.2). Compliance with food hygiene rules could have prevented 24 cases of typhoid fever. Nevertheless, repeat vaccination against typhoid fever is now conducted every 3 years in the French Forces, in compliance with the manufacturers' recommendations.

Adult↗

Vi-negative strains of Salmonella typhosa: attempts to induce W-V reversion and the use of non-Vi strains in evaluating typhoid vaccines.

Tully, Joseph G. (Walter Reed Army Institute of Research, Washington, D.C.) and Julius A. Currie. Vi-negative strains of Salmonella typhosa: attempts to induce W-V reversion and the use of non-Vi strains in evaluating typhoid vaccines. J. Bacteriol. 84:747-753. 1962.-Repeated attempts have been made to detect reversion of several W-form Salmonella typhosa strains to Vi antigen-containing cultures. Passage of the O-901, H-901, and Ty2W cultures through various mouse strains did not result in the recovery of V-form typhoid bacilli. Rabbits immunized repeatedly with non-Vi strains of typhoid bacilli, or with W cultures successively passed through mice, did not respond with Vi antibody formation. Attempts also were made to detect reversion of non-Vi strains passed in broth and plate cultures to which heat-killed Vi antigen-containing strains had been added. No evidence was obtained that the selection of Vi-containing cultures had been enhanced. The non-Vi typhoid strains employed in this study thus appeared to be stable W-form cultures. Viable-cell vaccines and acetone-killed and dried (AKD) vaccines of V- and W-form S. typhosa were compared in active mouse protection tests against intraperitoneal and intracerebral challenges with V- and W-form typhoid strains. Only Vi-containing cultures effectively protected mice against virulent V-form challenges, regardless of the route utilized. Greater quantities of both viable-cell and AKD vaccines prepared from non-Vi strains were required for protection against V- as well as W-form S. typhosa challenges.

Animals↗

Reactive arthritis associated with typhoid vaccination in travelers: report of two cases with negative HLA-B27.

As international travel to developing countries increases, more people seek medical advice concerning food and water-borne diseases, including typhoid fever. Prevention of typhoid fever in high-risk groups (travelers to endemic areas, laboratory workers and household contacts of typhoid carriers) should rely primarily on prevention of exposure. However, immunization is an important adjunct. The decision to immunize against typhoid fever should be individualized, taking into account the benefits versus the risk of possible adverse reactions. Cases of reactive arthritis have been associated with the heat-phenol inactivated 'whole cell' parenteral vaccine, but to our knowledge reactive arthritis has not been previously reported with the oral form (Ty21a). This is a report of HLA-B27 negative reactive arthritis occurring in two travelers after the administration of oral Ty21a typhoid vaccine.

Adult↗

New and improved vaccines. Promising weapons against varicella, hepatitis A, and typhoid fever.

The initial motives behind development of vaccines were to protect against life-threatening infections (eg, rabies, diphtheria), to eradicate sweeping outbreaks of serious diseases (eg, paralytic poliomyelitis, smallpox), and to prevent diseases in a vulnerable population by the immunization of surrogates (eg, rubella immunization to prevent congenital rubella syndrome). Now a fourth motive emerges: prevention of less serious infections to improve quality of life. The advantages of new vaccines and immunization programs should no longer be measured exclusively in terms of the number of lives saved but should take into account direct and indirect cost savings and overall benefit to individual and societal health and well-being. Although varicella and hepatitis A infections can be life-threatening, most cases are self-limited and have no significant sequelae. Immunization is more likely to improve quality of life than to save lives. Vaccination against typhoid remains a potentially lifesaving act in developing nations, but even the newer typhoid vaccines were developed primarily to reduce the frequency and severity of adverse reactions to immunization rather than to improve the protective efficacy of the original heat-phenol inactivated vaccine. Varicella virus vaccine, hepatitis A virus vaccines, and the typhoid polysaccharide Vi capsular vaccine represent important additions to immunization agents. These vaccines are immunogenic, clinically effective, and generally safe, with infrequent and usually mild adverse reactions. Their favorable benefit-risk ratio should encourage their appropriate use. The Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians have already recommended varicella vaccine for universal immunization of children. Formal recommendations that hepatitis A vaccine also be routinely used for all children may be forthcoming in the next few years; in the meantime, persons at high risk should be immunized. Typhoid vaccination will likely continue to be used selectively for those who have significant contact with the organism or those who travel to typhoid-endemic countries.

Adolescent↗

A CONTROLED FIELD TRIAL OF THE EFFECTIVENESS OF ACETONE-DRIED AND INACTIVATED AND HEAT-PHENOL-INACTIVATED TYPHOID VACCINES IN YUGOSLAVIA.

In 1954-60 a Yugoslav Typhoid Commission showed in the first controlled field trial of typhoid vaccines, carried out in Osijek, Yugoslavia, that heat-phenol-inactivated typhoid vaccine gave a relatively high and long-lasting immunity. However, this liquid vaccine preparation was unstable and laboratory potency tests were inconclusive, and it was therefore decided that stable, dried, heat-killed, phenol-preserved vaccine be tested together with an acetone-inactivated and -dried vaccine in controlled field trials, supported in part by the World Health Organization, in Yugoslavia and British Guiana.This is report on the controlled trials organized in two Yugoslav towns, Bitola and Pristina. Three comparable groups were formed by random allocation of vaccines among 45 497 volunteers in the two towns. In each town one group received heat-phenol vaccine, the second group acetone-dried vaccine and the third (control) group tetanus toxoid. Two doses were given four weeks apart in the spring of 1960 and the vaccinated persons were followed up for 2 1/2 years. The effectiveness of the vaccines was measured by comparing typhoid morbidity rates in the three groups. It was found during an outbreak of typhoid fever in Pristina two years after primary vaccination that both the acetone-dried and the heat-phenol vaccines were effective, the former being superior.

Accident Prevention↗

The role of epidemiology in the introduction of vi polysaccharide typhoid fever vaccines in Asia.

Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction.

Asia↗

Controlled field trials of paratyphoid B vaccine and evaluation of the effectiveness of a single administration of typhoid vaccine.

In 1963 and 1964 field trials were organized in the USSR for the purpose of evaluating the effectiveness of paratyphoid B vaccine. An opportunity was thereby afforded to assess the effectiveness of a single administration of typhoid vaccine, used as the preparation administered to the paratyphoid control group of 89 046 persons. Similarly, the control group used for assessing the effectiveness of the typhoid vaccine was the group of 86 620 persons inoculated with the paratyphoid vaccine.It was established that it is, in principle, possible to immunize people effectively against paratyphoid B by administering heat-killed paratyphoid B vaccine prepared from an aerated broth culture. It was found that the protective effect of the vaccine depends upon the size of the dose and the number of times it is administered. A protective effect was produced when a dose of 6 x 10(8) organisms was administered to persons from 7 to 16 years of age. Two inoculations of the paratyphoid B vaccine ensured protection over the 30 months that the observations lasted, whereas a single administration only conferred protection for up to one year.It was also confirmed that it is possible to obtain a protective effect with a single administration of a heat-killed typhoid vaccine prepared from an aerated broth culture. A single administration of the typhoid vaccine had a less marked protective effect (index of effectiveness 58%) than 2 administrations, a fall in the level of the protection conferred occurring during the year after immunization. The frequency and intensity of general and local reactions were identical for equal doses of typhoid and paratyphoid B vaccine.

Adolescent↗

Controlled field trial with dried sorbed paratyphoid B and typhoid vaccines.

In 1968-70 a field trial was arranged in the USSR to evaluate the effectiveness of dried sorbed paratyphoid B and typhoid vaccines when administered in two doses separated by an interval of 20-30 days.TWO GROUPS OF SCHOOLCHILDREN WERE UNDER OBSERVATION: a group inoculated with paratyphoid B vaccine (75 805 children) and a group inoculated with typhoid vaccine (76 314 children). The persons who were inoculated with the paratyphoid B vaccine formed the control group used in evaluating the effectiveness of the typhoid vaccine, and those inoculated with the typhoid vaccine formed the control group for the evaluation of the paratyphoid vaccine.Two doses of dried sorbed paratyphoid B vaccine made from Salmonella paratyphi B, strain No. 42, containing 5 x 10(8) microbial cells per injection, protected about 70% of those inoculated. Two doses of dried sorbed typhoid vaccine made from S. typhi, strain Ty 2 4446, also with 5 x 10(8) cells per injection, protected about 80% of those inoculated.At least 21 months of protection (the period of observation) were obtained following immunization with dried sorbed preparations made from heat-killed aerated broth cultures.Both types of vaccine produced the same frequency and intensity of general and local reactions; these were moderate. The general and local reactions to a second injection were substantially less marked than those to the first.

Child↗

Multi-drug resistant typhoid fever in hospitalised children. Clinical, bacteriological and epidemiological profiles.

A total of 592 children with clinical diagnosis of typhoid fever admitted to the Dr B. C. Roy Memorial Hospital for Children, Calcutta, India during the period between February 1990 and January 1992, were screened for Salmonella typhi by blood culture. S. typhi was isolated from 221 (37.3%) cases. The majority of the strains (92.3%) showed multi-drug resistant (MDR). They were resistant to chloramphenicol, ampicillin, tetracycline and trimethoprim-sulphamethoxazole. However, all the strains were uniformly (100%) susceptible to gentamicin, amikacin, furazolidone, norfloxacin and ciprofloxacin. Minimum inhibitory concentration of the antimicrobial agents against the resistant strains of S. typhi ranged between 200 and > 1600 micrograms/ml. Phage type 0 was most frequently encountered. The rate of isolation of S. typhi was more or less the same in all the pediatric age groups. The majority of the cases came from lower socio-economic classes with poor personal hygiene. Fever was the main presenting feature in all the cases. Other associated features of the MDR typhoid fever cases, who were uncomplicated during admission, were headache (36.0%), chill and rigor (23.2%), diarrhea (37.2%), anorexia (26.2%), vomiting (23.8%), cough (18.0%) and abdominal pain (19.8%). Hepatosplenomegaly was present in 42.4% cases. However, complications were less frequently encountered among the MDR typhoid fever cases who were uncomplicated during admission and treated as in-patients. Fourteen bacteriologically-confirmed MDR typhoid fever cases had jaundice and another 18 cases had an abnormal state of consciousness during admission. Four (2.0%) bacteriologically-confirmed MDR typhoid fever patients died during the period of observation.

Age Distribution↗

Early diagnosis of typhoid fever by an enzyme immunoassay using Salmonella typhi outer membrane protein preparations.

An enzyme immunoassay (EIA) for detection of serum antibodies in patients with typhoid fever was developed using Salmonella typhi outer membrane protein (OMP) preparations as antigen. Acute phase (first week) sera from adult typhoid fever patients were tested as well as sera from the following control groups: adult travellers with diarrhea caused by enterotoxigenic Escherichia coli, children infected with Campylobacter jejuni, healthy Mexican adult blood donors, and adults with septicemia caused by other organisms. At a 1:3,125 serum dilution, the mean absorbance values were 1.41 in the typhoid fever patients, and 0.57, 0.55, 0.51 and 0.52 in the respective control groups. Inhibition EIA studies using OMP preparations or lipopolysaccharide (LPS) as free antigen indicated that proteins can play an important role in the detection of antibodies in early typhoid fever. This EIA may be useful for the diagnosis of typhoid fever since results were obtained within about five hours and in an endemic area antibodies against Salmonella typhi OMP preparations appear early in the course of the disease.

Adolescent↗

Typhoid colonic perforation in childhood: a ten-year experience.

BACKGROUND: Intestinal perforation resulting from a complication of typhoid fever has always been of concern because of its high morbidity and mortality rates. Most perforations occur in the terminal ileum. METHODS: Between May 1995 and June 2005, 24 children with typhoid colonic perforations receiving operations were retrospectively reviewed. The patients were 5 months to 86 months of age (mean: 25.1+/-17.5 months). Surgical management consisted of primary closure of the perforation with ileostomy (70.8%), wedge resection and simple closure (20.8%), and partial colectomy with colostomy (4.2%). For the 11 patients with solitary cecal perforation, 6 received simple closure with ileostomy (group I), and wedge resection and simple closure was performed in the remaining 5 patients (group C). After operation, total parenteral nutrition (TPN) was instituted in each patient. RESULTS: Solitary cecal perforation is the most common type (45.8%). The length of hospital stay (LOS) varied from 12 days to 73 days, and the mean duration was 24.5+/-14.7 days. The LOS showed no significant difference with regard to the location and the number of perforations. No mortality was noted in the entire series, but 19 patients had one or more complications, which may have prolonged the LOS; anemia and wound infections were the two most common problems. Group C had the shorter LOS (16.4+/-3.4 days, versus 40.2+/-22.6 days for group I) and fewer complications (0.6+/-0.5, versus 3.25+/-1.7 for group I). Any readmission for secondary operation to restore intestinal continuity in group C was therefore avoided. CONCLUSIONS: To understand thoroughly the clinical course of typhoid fever is important. The typically high rate of complications after intestinal perforation secondary to typhoid fever may be reduced if operation is undertaken earlier. Solitary cecal perforation can be managed safely with wedge resection and simple closure without bowel exterioration. Routine usage of TPN may reduce the mortality associated with complications resulting from typhoid perforations.

Age Factors↗

Re-evaluation of the Widal agglutination test in response to the changing pattern of typhoid fever in the highlands of Papua New Guinea.

In 1992 it was decided to re-evaluate the Widal slide agglutination test as a rapid diagnostic test for typhoid fever in Papua New Guinea. This was in response to an apparent increase in the number of false positive Widal slide agglutinations occurring using an O cut-off titre greater than or equal to 40 which was previously shown to be appropriate in 1987. The results of the re-evaluation indicated that the Widal test using a diagnostic cut-off titre of > or = 40 lacked specificity and was no longer appropriate for this population. A new O antibody titre of > or = 160 was recommended as a diagnostic titre for typhoid fever in PNG. The fall in the specificity of the Widal slide agglutination test over the five-year period between the initial assessment and the re-evaluation is due to an increase in general population antibody levels caused by the changing pattern of typhoid in the community. Before 1987 typhoid fever occurred as sporadic, isolated outbreaks and most people living in the highlands of PNG were immunologically naive. By 1992 typhoid fever had become a well-established endemic disease and many more people had been exposed to Salmonella typhi and as a result developed antibodies. We have been able to demonstrate clearly a remarkable change in the immune status of the community, in which the proportion of healthy individuals with a Widal tube O agglutination titre of 40 or more rose from 0 to 56% in the short span of five years.(ABSTRACT TRUNCATED AT 250 WORDS)

Agglutination Tests↗

Serodiagnosis of typhoid fever in paediatric patients by anti-LPS ELISA.

Enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis showed that up to 50% of the anti-typhoid antibody in sera from blood culture positive paediatric typhoid fever patients is directed against lipopolysaccharide (LPS) antigen. Anti-Salmonella typhi LPS ELISA was therefore compared to Widal agglutination for serodiagnosis of typhoid fever in paediatric patients. Sera from 38 paediatric control individuals were ELISA negative for anti-S. typhi LPS IgG; all but 2 of these specimens were negative for anti-S. typhi LPS IgM. Paediatric patients hospitalized with signs and symptoms of typhoid fever were separated into 4 groups and tested by ELISA with the following results: 46 patients negative by both culture and Widal agglutination tests, 48% positive for anti-S. typhi LPS IgG and 35% for anti-S. typhi LPS IgM; 22 negative by culture but with positive Widal titres, 82% and 68% positive respectively; 28 culture positive for S. typhi, 93% and 82% respectively; and 12 culture positive for Salmonella other than S. typhi, 92% and 92% respectively. These data suggest that anti-S. typhi LPS ELISA is a suitable assay for diagnosis of typhoid fever in children.

Adolescent↗

Diagnosis of typhoid fever in Nigeria: misuse of the Widal test.

In the last 2 years, there has been public panic across Nigeria about an epidemic of a 'killer' febrile disease, purportedly typhoid fever. The evidence for this epidemic is reviewed in the light of appropriate diagnosis of typhoid fever. All the patients were diagnosed as typhoid fever, primarily based on Widal test results. Investigations in the hospital of 15 patients confirmed malaria in 70% who, though failing to respond to chloroquine, promptly responded to treatment with Fansidar (sulfadoxine + pyrimethamine). Fever in the remaining 30%, without evidence of malaria and who failed to respond to chloroquine, Fansidar and antibacterials including chloramphenicol, remitted spontaneously. The merits and limitations of the Widal test are discussed. It is concluded that diagnosis of typhoid fever by the Widal test alone is prone to error, and that any claims of a typhoid fever epidemic in Nigeria remain mere conjecture. Misuse of the Widal test and, subsequently, misuse of the antibiotic chloramphenicol, should be very strongly condemned.

Adult↗

Colonoscopic manifestations of typhoid fever with lower gastrointestinal bleeding.

BACKGROUND: Intestinal bleeding in patients with typhoid fever usually occurs in the ileum. However, endoscopic findings in such patients are not well established. We examined the colonoscopic manifestations of intestinal lesions with bleeding in patients with typhoid fever. PATIENTS AND METHODS: The colonoscopic findings of seven patients who presented with haematochezia due to typhoid fever were reviewed retrospectively. Typhoid fever was diagnosed when the Salmonella typhi was isolated or when the Widal test showed strongly positive reactions. RESULTS: Clinical data and colonoscopic findings were reviewed in seven patients (four men and three women with an average age of 42 years). The most commonly involved area was the terminal ileum (100%), followed by the ileocecal valve (57%), the ascending colon (43%), and the transverse colon (29%). Left colon was intact in all cases. The most common colonoscopic finding was multiple variable-sized punched-out ulcers with slightly elevated margin, as found in five patients. In two patients, only several oedematous hyperaemic mucosal patches with haemorrhagic spots or shallow erosions were seen. Active bleeding was noticed only in one patient, who received endoscopic haemostasis twice. The remaining six patients were treated by conservative treatment including antibiotic therapy. There was no complication during or after the colonoscopic examination. CONCLUSIONS: Intestinal bleeding in typhoid fever usually occurs from the ulcers in the ileum or proximal colon, and the most common colonoscopic manifestations are multiple variable-sized punched-out ulcerations.

Adult↗