Typhoid and Paratyphoid Fever: A 10-Year Retrospective Study of 41 Cases in a Parisian Hospital

BACKGROUND: Enteric fever remains a major cause of fever in travelers. We evaluated new trends in enteric fever. METHODS: We reviewed the epidemiological, clinical, biological, bacteriological data, and outcome of all cases of typhoid and paratyphoid fever seen in our department over the last decade. The inclusion criteria were the presence of signs compatible with enteric fever and isolation of Salmonella typhi or Salmonella paratyphi A, B, or C from blood or stool cultures or any other site. RESULTS: Among the 41 patients, 38 (93%) had travel-associated enteric fever. The main geographic source of contamination was the Indian subcontinent. One patient had been vaccinated with parenteral Vi vaccine 1 year previously. Fever and headaches were the only signs which were present in more than 80% of patients. The Widal test at inclusion was positive in 27%, and a second serological test was found to be positive in 50% of evaluated cases. Blood cultures and stool cultures were positive in 34 cases and 10 cases, respectively. Salmonellae spp were isolated in both hemocultures and stool cultures in 4 cases and in urine in 1 case. Two strains of S. typhi were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. One strain of S. typhi and one of S. paratyphi B were nalidixic acid resistant. All evaluable patients were cured with the exception of 2 patients (1 failure, 1 relapse). We observed 3 toxic reactions. No patients died. CONCLUSION: The diagnosis and outcome of enteric fever are hampered by the lack of specificity of clinical and biological signs, the increasing rates of antimicrobial resistance, and the occurrence of toxic reactions during treatment.     

In vitro sensitivity of enteric bacteria to epicillin,chloramphenicol, ampicillin and furazolidone

Summary

Strains of Salmonella typhi (148) and Salmonella paratyphi A (27) isolated from the blood of patients with clinical features of enteric fever were tested in vitro for their sensitivity to epicillin, ampicillin, chloramphenicol and furazolidone. Results from both the disc and tube dilution methods showed that greater percentages of the two strains were sensitive to epicillin than to the other antibiotics.     

Ceftriaxone versus chloramphenicol in the treatment of enteric fever

Fifty-five patients with culture-proven Salmonella typhi and paratyphi enteric fever were assigned to one of two therapeutic regimens. Group I received ceftriaxone 60-80 mg/kg/day intramuscularly for 5-7 days, those in group II received chloramphenicol 50-80 mg/kg/day orally in 4 divided doses for 12-14 days. both groups were comparable as regards age, sex, severity and duration of symptoms prior to admission. A significant reduction in the mean number of days taken for patients to become afebrile, disappearance of clinical signs and symptoms, duration of therapy and hospital stay were observed in patients receiving ceftriaxone as compared to those receiving chloramphenicol. None of the patients receiving ceftriaxone relapsed, while three patients receiving chloramphenicol relapsed. No major reactions were seen with either drug.     

Salmonella typhi infection in adults is not limited to travellers returning from the tropics

We reviewed the case notes of 23 adult patients infected with Salmonella typhi and admitted to the infectious disease unit, Auckland Hospital between January 1977 and December 1984. Fifteen had typhoid fever and eight were chronic carriers of S typhi. All isolates were sensitive to amoxycillin, chloramphenicol and cotrimoxazole. Ten of those with typhoid fever had recently been in tropical countries, predominantly Pacific Islands. The remaining five all lived in South Auckland and had not travelled out of New Zealand: we suspect that contaminated shellfish collected from the Manukau Harbour in South Auckland were the source. Typhoid fever should be suspected in young travellers returning to New Zealand with fever, diarrhoea, abdominal pain and headache. Similarly this diagnosis should be suspected in Polynesians and Maoris from South Auckland who have not travelled. All but one patient with typhoid fever responded clinically to the initial regimen which was usually oral amoxycillin given for a median 18 days. One other patient relapsed. Cholescystectomy and subsequent oral antibacterials eradicated S typhi from five biliary carriers with abnormal gallbladders. Prolonged high dose oral amoxycillin alone was effective in one of two carrier patients with normal gallbladders. The role of the Department of Health in identifying carriers of S typhi remains important.     

Ciprofloxacin versus chloramphenicol in the treatment of salmonella infection

Strains of Salmonella typhi resistant to chloramphenicol and ampicillin have been isolated in several countries. This study compares treatment of Salmonella infection using ciprofloxacin (500 mg twice daily) for 10 days with chloramphenicol (50 mg/kg per day divided into four doses) for 14 days. The pathogen eradication rates for patients receiving ciprofloxacin was 18/20 (90%), compared with 25/28 (89%) for those who received chloramphenicol. Signs and symptoms in patients receiving chloramphenicol lasted longer and sometimes twice as long as patients treated with ciprofloxacin. In this study, ciprofloxacin was superior to cloramphenicol in the treatment of S. typhi infection and also had fewer side-effects and the convenience of a twice-a-day dosing     

Imported typhoid fever in Switzerland, 1993 to 2004

Background.  In industrialized countries, typhoid fever occurs mainly in returned travelers. To determine the need for preventive strategies, eg, for vaccination, continuous monitoring is needed to assess where the risk for travelers is highest.
Methods.  To investigate where the risk for travelers to acquire typhoid fever is highest, 208 patients with typhoid fever and recent travel were matched with travelers' statistics collected by the Swiss Federal Office of Statistics.
Results.  At the beginning of the study period, up to 30 infections with Salmonella typhi were recorded per year in Switzerland. Since 2001, less than 15 confirmed cases per year occurred. A majority of the 208 (88.5%) typhoid cases were associated with recent travel. Countries with highest risk were Pakistan (24 per 100,000), Cambodia (20 per 100,000), Nepal (14 per 100,000), India (12 per 100,000), and Sri Lanka (9 per 100,000).
Conclusions.  We found that over a 12-year period (1993–2004), the travel-associated risk of typhoid fever is highest for destinations in the Indian subcontinent. All other regions showed a decline, most markedly in southern Europe. Our results suggest that typhoid fever vaccination should be recommended for all travelers to countries in South Asia. Otherwise, vaccination of tourists to frequently visited low- and intermediate-risk areas is not necessary, unless there are behavioral risk factors.     

伤寒、甲、乙、丙型副伤寒沙门菌多重荧光PCR方法的评估及临床应用

目的建立和评估多重荧光PCR方法快速鉴定伤寒、甲、乙、丙型副伤寒沙门菌的方法,并应用于临床血培养样品的检测。方法收集留取医院的可疑伤寒患者的血培养标本,用多重实时荧光PCR法和传统分离培养法同时进行分离鉴定,分析比较双盲实验结果,评价多重实时荧光PCR方法的灵敏度、特异度等检测性能指标。结果共检测临床样本538例,多重荧光PCR法检出阳性218例,比传统培养法多检出6例;阴性320例,与传统培养法一致。以传统检测方法为金标准,多重荧光PCR方法的灵敏度为100%,特异度为98.2%。结论建立的多重荧光PCR检测方法操作简便,可快速、特异、灵敏地检测出伤寒、甲、乙、丙型副伤寒沙门菌,可以应用于临床标本的早期快速分型诊断,提升重大传染病的应急处置能力和监测能力。     

77例耐氯霉素伤寒杆菌药敏试验的探讨

目的：探讨耐氯霉素伤寒杆菌与常用的治疗伤寒药物之间的关系。方法：收集经血培养或大便培养证实为伤寒杆菌的菌株,用氯霉素,卡那霉素,四环素,氨苄西林等作药物敏感试验。结果：１０１株伤寒杆菌中,有７７株对氯霉素或≥２种药物不敏感,其中对≥３种药物达７２株次。结论：耐氯霉素伤寒杆菌对常用治疗药物耐药性大,对氨基糖苷类抗生素较敏感。     

In vitro and clinical evaluation of ofloxacin in urinary tract infection and enteric fever

During 1984 to 1988, 35 patients with urinary tract infection (UTI) and 37 patients with enteric fever were treated successfully with 400 mg ofloxacin twice a day for 7 to 10 days. Clinical cure or improvement was observed in 31 of the 35 patients with UTI; 32 patients were bacteriologically assessed and eradication was achieved in all of them. Ofloxacin was particularly effective in the treatment of enteric fever in 35 patients; eradication was achieved in all of them; 34 patients were clinically cured within 4 days, however, one patient with bacteraemia due to Salmonella paratyphi A subsequently died, due to his underlying disorder. The MIC90 of the Enterobacteriaceae including Salmonella was less than 0.12 micrograms/ml. Interestingly, beta-lactamase-producing strains of Salmonella and other Enterobacteriaceae in the present study were 28% and 29%, respectively. Ofloxacin therefore offers an effective b.i.d. dosage schedule for enteric fever and UTI due to beta-lactamase-producing bacteria.     

New generation typhoid vaccines: an effective preventive strategy to control typhoid fever in developing countries

Typhoid fever is a serious systemic infection, caused by the enteric pathogen Salmonella enterica serovar Typhi, a highly virulent and invasive enteric bacterium. This disease occurs in all parts of world where water supplies and sanitation are substandard. These pathogens then travel to food, drinks and water through house-flies and other vectors. Globally, an estimated 12-33 million cases of enteric fever occur with 216,00-600,000 deaths per year, almost exclusively in the developing countries. Health surveys conducted by the Health Ministry of India in the community development areas indicated a morbidity rate varying from 102-2219/100,000 population in different parts of the country. A limited study in an urban slum showed 1% of children up to 17 years of age suffer from typhoid fever annually. The continued high burden of typhoid fever and the alarming spread of antibiotic resistant strains led the World Health Organization (WHO), almost ten years ago, to recommend immunization using the two new-generation vaccines in school- aged children in areas where typhoid fever posed a significant problem and where antibiotic resistant strains were prevalent. Morbidity and mortality due to high incidence of typhoid fever favors the introduction of typhoid vaccine in routine immunization in India. This vaccine should be given at the age of 2 years with Vi antigen vaccine and at least one more dose be given at 5 years of age.     

Comparative in vitro activity of enoxacin and other fluoroquinolones against multi-resistant strains of Salmonella typhi.

The in vitro activities of enoxacin, lomefloxacin, norfloxacin, ofloxacin, and pefloxacin against 274 strains of Salmonella typhi isolated from suspected typhoid fever patients (137 multi-resistant strains and 137 strains sensitive to chloramphenicol, ampicillin and/or co-trimoxazole) were determined using disk diffusion and agar dilution techniques. In vitro, enoxacin was active against all tested strains with a MIC90 and inhibition zone size against multi-resistant strains of 0.12 mg/l and 34 mm diameter, respectively. Similar results were found with the other fluoroquinolones. Enoxacin and other fluoroquinolones may be the therapy of choice in cases of typhoid fever caused by organisms resistant to the standard therapy, chloramphenicol.     

伤寒疫苗的现状及展望

伤寒仍是发展中国家的主要公共卫生问题,控制伤寒的最有效措施是接种疫苗.此文介绍了早期伤寒疫苗和现行伤寒疫苗的的安全性和有效性,讨论了伤寒Vi多糖结合疫苗的研发现状及应用前景.     

巢式聚合酶链反应快速检测血液标本中

目的建立一种检测血液中伤寒沙门菌的方法.方法根据伤寒沙门菌特异鞭毛基因设计两对引物,通过巢式聚合酶链反应(PCR)扩增伤寒沙门菌DNA片断,扩增产物通过凝胶电泳进行分析.结果用伤寒沙门菌DNA系列稀释液进行试验,巢式PCR能够检出10个伤寒沙门菌.36份培养阳性标本,33份PCR阳性;6份培养阴性但临床高度可疑的伤寒病人标本PCR阳性10份其它原因引起发热的临床标本均为阴性.结论巢式PCR能够快速、特异、准确地检出血液中的伤寒沙门菌.     

Emergence of multidrug-resistant Salmonella enterica serovar Typhi associated with a class 1 integron carrying the dfrA7 gene cassette in Nepal

A total of 121 Salmonella enterica serovars Typhi and Paratyphi A isolated from enteric fever patients at a university hospital in Nepal between February 2004 and January 2006 were tested for their antimicrobial susceptibility. The occurrence and cassette content of integrons as well as the molecular mechanisms of resistance among the multidrug-resistant (MDR) S. Typhi were evaluated. Thirty-nine percent of the isolates were susceptible to all the antimicrobial agents tested. Seven of the S. Typhi strains were MDR. None of the 121 S. enterica isolates were resistant to ciprofloxacin, cefazolin, rifampicin or kanamycin. All MDR S. Typhi isolates contained a class 1 integron with a single cassette, dfrA7, conferring resistance to trimethoprim. Pulsed-field gel electrophoresis (PFGE) of XbaI-generated genomic restriction fragments yielded 12 different patterns. Five of the seven MDR isolates containing class 1 integrons had an identical PFGE pattern. Resistance to sulfamethoxazole, streptomycin, ampicillin, tetracycline and chloramphenicol was mediated by sul1, strA-strB, blaTEM-like, tetB and catA genes, respectively. To the best of our knowledge, this is the first report of integron-associated multidrug resistance as well as the first molecular characterisation of the mechanism of resistance of S. Typhi isolated from Nepal. This study indicates the spread of integron-associated multidrug resistance in S. Typhi in Nepal.     

甲型副伤寒沙门氏菌主动外排多重耐药基因与表达研究

目的 调查临床分离甲型副伤寒沙门氏菌对常用抗生素的耐药情况与多重耐药主动外排基因acrB的检测、序列分析及其表达水平。方法 用琼脂二倍稀释法测定7种抗生素对甲型副伤寒沙门氏菌的抗菌活性。以基因库序列为参考设计引物PCR扩增acrB、测序并用RT-PCR方法检测其表达。结果 12株甲型副伤寒沙门氏菌对氧氟沙星、环丙沙星、头孢噻肟、哌拉西林、氯霉素、四环素、庆大霉素的耐药率除氯霉素为0外。其余均为8．33％。对三类不同种类抗菌药物多种耐药者l株。所有细菌均检测到多重耐药外排基因acrB．测序结果与参考沙门氏菌序列(No．AL627267)比较，有l处碱基差异。与大肠埃希氏菌(No．ECU00734)比较，碱基同源性为84．4l％(70／449)，提示其碱基序列同源性均极高。分别选取对两类抗菌药物耐药及敏感甲型副伤寒沙门氏菌各一株进行RT-PCR检测，结果 两株细菌均检测到多重耐药外排基因acrB的表达。结论甲型副伤寒沙门氏菌对喹诺酮类、第三代头孢菌素类等药物耐药率低，但有多重耐药。甲型副伤寒沙门氏菌中均存在acrAB主动外排系统。与大肠埃希氏菌同源性高，可检测到其表达。主动外排机制可能是甲型副伤寒沙门氏菌形成多重耐药的主要原因之一。     

Epidemiology of typhoid fever in Mauritius

BACKGROUND: The epidemiology of typhoid fever in Mauritius was studied to determine whether there was any need for tourists visiting Mauritius to be vaccinated against the disease, and where Mauritians with typhoid fever had been infected. Data on antibiotic susceptibility of Salmonella typhi isolates from Mauritius were also analyzed. METHODS: Since 1997 every time S. typhi is isolated from blood cultures at our laboratory, an epidemiologic inquiry is conducted to determine the likely origin of the infection and the outcome of treatment, and the information collected is recorded. Results of antibiotic susceptibility testing are also noted. Data recorded on cases between 1997 and 2004 were reviewed and analyzed. RESULTS: S. typhi was isolated on 25 occasions during the 8-year period. The infection was likely to have been acquired in Mauritius in only 6 cases (24%). Another 6 cases (24%) occurred in expatriate workers from the Indian subcontinent. Of the 13 Mauritians (52%) who probably acquired the infection abroad, 11 had a history of recent travel to India. Thirteen of 14 S. typhi isolates from cases acquired in India were resistant to nalidixic acid. Of the 6 cases acquired in Mauritius, 4 occurred in children under 12 years and 1 was caused by a multiply resistant strain. Twenty-two patients made an uneventful recovery. One death was indirectly caused by typhoid fever, and there was 1 case each of intestinal perforation and relapse. CONCLUSIONS: In Mauritius typhoid fever is mainly an imported disease, but indigenous cases of the illness occur rarely and sporadically. Travelers to Mauritius need not be vaccinated against typhoid fever as the risk of acquiring the disease in the country is negligible. Mauritians traveling to India must be made aware of the risk of typhoid fever and of preventive measures. Ceftriaxone should be used as the initial first-line treatment of infection acquired in India.     

A cost-effectiveness analysis of typhoid fever vaccines in US military personnel

Typhoid fever has been a problem for military personnel throughout history. A cost-effectiveness analysis of typhoid fever vaccines from the perspective of the US military was performed. Currently 3 vaccine preparations are available in the US: an oral live Type 21A whole cell vaccine; a single-dose parenteral, cell subunit vaccine; and a 2-dose parenteral heat-phenol killed, whole cell vaccine. This analysis assumed all vaccinees were US military personnel. Two pharmacoeconomic models were developed, one for personnel who have not yet been deployed, and the other for personnel who are deployed to an area endemic for typhoid fever. Drug acquisition, administration, adverse effect and lost work costs, as well as the costs associated with typhoid fever, were included in this analysis. Unique military issues, typhoid fever attack rates, vaccine efficacy, and compliance with each vaccine's dosage regimen were included in this analysis. A sensitivity analysis was performed to test the robustness of the models. Typhoid fever immunisation is not cost-effective for US military personnel unless they are considered imminently deployable or are deployed. The most cost-effective vaccine for US military personnel is the single-dose, cell subunit parenteral vaccine.     

The comparison of cultures,widal agglutination test and polymerase chain reaction as a diagnostic tool in typhoid fever

Typhoid fever caused by Salmonella typhi, paratyphi A and B, is an important cause of morbidity and mortality in many developing countries. A rapid and sensitive method for the detection of S. typhi is essential for early diagnosis of typhoid fever and effective therapy. In this study 45 febrile patients who were suspected to have enteric fever were enrolled, and the results of blood cultures, widal agglutination tests and Polymerase Chain Reaction in these cases were evaluated. Group I consisted of 11 patients with diseases other than salmonella infections, group II represented 6 patients with positive cultures, and group III represented 28 patients with negative blood cultures negative but who were clinically suspected cases that had a medical history of using variable antimicrobial agents. Two positive PCR results were present; one of them was in culture positive group (16,6%) and the other was in culture negative group (3,5%). In our study widal agglutination tests and cultures were found not to be helpful in differential dignosis. Although PCR based detection of S. typhi is reported to be a sensitive and specific test for the diagnosis of enteric fever, in our study the benefit of this method in the diagnosis of especially patients who were treated with antimicrobial therapy was not clearly determined. Other methods to increase sensitiviy and specificity to levels such as those of real time PCR should be developed and large-scaled studies should be done in endemic and non-epidemic regions.     

Patient Compliance in the Use of Vivotif Berna® Vaccine, Typhoid Vaccine, Live Oral Ty21a

Background: Several live attenuated vaccines against bacterial enteric pathogens have recently been licensed. These include the Salmonella typhi Ty21a typhoid vaccine (Vivotif Berna® Vaccine) and Vibrio cholerae CVD103-HgR cholera vaccine (Mutacol Berna® Vaccine). They comprise a unique class of biologics in which patient compliance is required for their optimal use. This is of particular importance in the case of the Ty21a vaccine strain of which multiple doses are required. Furthermore, exposure to heat, concomitant use with antibiotics or antimalarial drugs, and timing of vaccination with respect to food intake can affect vaccine potency and/or efficacy. This study was conducted to determine the level of compliance among adult North American travelers and to evaluate compliance errors with respect to potential vaccine efficacy.
Methods: Questionnaires were provided to 1091 travelers at twelve travel clinics in the United States and Canada. The patients were requested to complete forms which asked questions relating to vaccine storage and usage, and to return them to the travel clinic. A total of 762 completed questionnaires were returned.
Results: Few compliance errors were made regarding proper storage of the vaccine. The most common compliance errors involved not taking all four capsules on alternate days (10%) and not taking all four doses of vaccine prior to departure (6%).
Conclusions: Pretravel counselling was effective in obtaining a high compliance rate among adult travelers in the use of Vivotif Berna® Vaccine. The majority of compliance errors reported would not be expected to negatively impact upon vaccine efficacy.