Under-detection of blood culture-positive enteric fever cases: The impact of missing data and methods for adjusting incidence estimates.

BACKGROUND: In surveillance for typhoid fever, under-detection of cases occurs when patients with fever do not seek medical care, or seek medical care but do not receive a blood test. Missing data may result in incorrect estimates of disease incidence. METHODS: We used data from an ongoing randomised clinical trial of typhoid conjugate vaccine among children in Nepal to determine if eligible patients attending our fever clinics who did not have blood taken for culture had a lower risk of disease than those who had blood drawn. We assessed clinical and demographic predictors of having blood taken for culture, and predictors of culture-positive results. Missing blood culture data were imputed using multiple imputations. RESULTS: During the first year of surveillance, 2392 fever presentations were recorded and 1615 (68%) of these had blood cultures. Children were more likely to have blood taken for culture if they were older, had fever for longer, a current temperature ≥38 degrees, or if typhoid or a urinary tract infection were suspected. Based on imputation models, those with blood cultures were 1.87 times more likely to have blood culture-positive fever than those with missing data. CONCLUSION: Clinical opinion on the cause of the fever may play a large part in the decision to offer blood culture, regardless of study protocol. Crude typhoid incidence estimates should be adjusted for the proportion of cases that go undetected due to missing blood cultures while adjusting for the lower likelihood of culture-positivity in the group with missing data.

Cardiac Involvement in Travelers with Enteric Fever.

Data regarding cardiac involvement in enteric fever among travelers are scarce. In this retrospective study, 59 patients were hospitalized with enteric fever during 2004-2017 and 28 had cardiac workups. Among those, four had evidence of cardiac involvement, including clinical myocarditis, electrocardiogram changes, or troponin elevation. Cardiac involvement was higher among patients infected with Salmonella Typhi than with Salmonella Paratyphi A (P = 0.08), with a significant relative risk of 6 (95% CI: 1.15-31.22, P = 0.03). Time from symptoms onset to effective treatment was longer for patients with cardiac involvement (13 versus 7.15 days, P < 0.05). It seems that cardiac involvement in enteric fever is not uncommon in travelers. Such involvement seems to be more common in patients with delay of effective treatment to the second week of illness. Although fatal or complicated cases are rare in travelers, the cardiac complication may be an important contributor to morbidity and mortality in this group.

The Relationship Between Blood Sample Volume and Diagnostic Sensitivity of Blood Culture for Typhoid and Paratyphoid Fever: A Systematic Review and Meta-Analysis.

Background: Blood culture is the standard diagnostic method for typhoid and paratyphoid (enteric) fever in surveillance studies and clinical trials, but sensitivity is widely acknowledged to be suboptimal. We conducted a systematic review and meta-analysis to examine sources of heterogeneity across studies and quantified the effect of blood volume. Methods: We searched the literature to identify all studies that performed blood culture alongside bone marrow culture (a gold standard) to detect cases of enteric fever. We performed a meta-regression analysis to quantify the relationship between blood sample volume and diagnostic sensitivity. Furthermore, we evaluated the impact of patient age, antimicrobial use, and symptom duration on sensitivity. Results: We estimated blood culture diagnostic sensitivity was 0.59 (95% confidence interval [CI], 0.54-0.64) with significant between-study heterogeneity (I2, 76% [95% CI, 68%-82%]; P < .01). Sensitivity ranged from 0.51 (95% CI, 0.44-0.57) for a 2-mL blood specimen to 0.65 (95% CI, 0.58-0.70) for a 10-mL blood specimen, indicative of a relationship between specimen volume and sensitivity. Subgroup analysis showed significant heterogeneity by patient age and a weak trend towards higher sensitivity among more recent studies. Sensitivity was 34% lower (95% CI, 4%-54%) among patients with prior antimicrobial use and 31% lower after the first week of symptoms (95% CI, 19%-41%). There was no evidence of confounding by patient age, antimicrobial use, symptom duration, or study date on the relationship between specimen volume and sensitivity. Conclusions: The relationship between the blood sample volume and culture sensitivity should be accounted for in incidence and next-generation diagnostic studies.

[Epidemiological characteristics and molecular typing of typhoid and paratyphoid in China, 2009-2013].

Objective: To understand the epidemiological and molecular characteristics of typhoid and paratyphoid in China from 2009 to 2013, and provide evidence for the prevention and control of typhoid and paratyphoid, the development and improvement of surveillance strategies. Methods: Epidemiological analysis was conducted on the incidence data of typhoid and paratyphoid, and related public health emergencies in China during 2009-2013. Pathogen isolation and culture, serologic test were conducted for the typhoid and paratyphoid cases from 13 national surveillance sites. The isolates were subjected to antimicrobial susceptibility testing. Pulsed-field gel electrophoresis (PFGE) was performed for the molecular typing of these isolates. Results: The average incidence of typhoid and paratyphoid in China during this period was 1.03/100 000. The reported case number and incidence decreased with year. The provinces reporting high case numbers were Yunnan, Guizhou, Guangxi, Hunan, Zhejiang, Guangdong and Xinjiang. The incidence of age group 0-4 years was highest. The proportion of farmers and children outside child care settings showed an increasing tendency over time. The annual incidence peak was during July-August. Twenty five outbreaks occurred during 2009-2013. The results of pathogen isolation and culture showed that the positive rate was 3.00% (940/31 322), among the positive isolates, the proportion of Salmonella paratyphi A accounted for higher proportion (68.19%, 641/940) compared with Salmonella typhi (31.60%, 297/940). The drug resistances of Salmonella typhi and Salmonella paratyphi varied, but their resistances to nalidixic acid were highest (50.22% and 85.33%) respectively. A certain amount of Salmonella typhi isolates showed the resistance to the 3rd generation cephalosporins. PFGE analysis showed divergent patterns of Salmonella typhi compared with limited patterns of Salmonella paratyphi A. Conclusion: The epidemic level of typhoid and paratyphoid in China was relatively low, but the outbreak occurred occasionally. It is necessary to enhance the laboratory-based surveillance, particularly the capability of etiological diagnosis, outbreak investigation, response and antibiotic resistance monitoring, and conduct risk factor investigation in provinces with high incidences in recent years.

Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever.

BACKGROUND: Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. OBJECTIVES: To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. SELECTION CRITERIA: We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. MAIN RESULTS: Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub-Saharan Africa. All of the RDTs were designed to detect S.Typhi infection only.Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot-M, and TyphiRapid-Tr02) in 22 studies; and the Test-It Typhoid immunochromatographic lateral flow assay, and its earlier prototypes (dipstick, latex agglutination) developed by the Royal Tropical Institute, Amsterdam (KIT) in nine studies. Meta-analyses showed an average sensitivity of 78% (95% confidence interval (CI) 71% to 85%) and specificity of 87% (95% CI 82% to 91%) for TUBEX; and an average sensitivity of 69% (95% CI 59% to 78%) and specificity of 90% (95% CI 78% to 93%) for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% (95% CI 73% to 91%) and specificity was 79% (95% CI 70% to 87%). When we based the analysis on the 13 studies of the Typhidot test that either reported indeterminate test results or where the test format means there are no indeterminate results, the average sensitivity was 78% (95% CI 65% to 87%) and specificity was 77% (95% CI 66% to 86%). We did not identify any difference in either sensitivity or specificity between TUBEX, Typhidot, and Test-it Typhoid tests when based on comparison to the 13 Typhidot studies where indeterminate results are either reported or not applicable. If TUBEX and Test-it Typhoid are compared to all Typhidot studies, the sensitivity of Typhidot was higher than Test-it Typhoid (15% (95% CI 2% to 28%), but other comparisons did not show a difference at the 95% level of CIs.In a hypothetical cohort of 1000 patients presenting with fever where 30% (300 patients) have enteric fever, on average Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results will miss the diagnosis in 66 patients with enteric fever, TUBEX will miss 66, and Test-It Typhoid and prototype (KIT) tests will miss 93. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests.The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. AUTHORS' CONCLUSIONS: In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed.

[Drug tolerance and PFGE molecular typing of Salmonella paratyphi A isolated in Dengfeng, Henan province, 2009-2015].

OBJECTIVE: To investigate the drug tolerance and PFGE patterns of Salmonella(S.)paratyphi A strains isolated from sentinel hospitals in Dengfeng, Henan province, during 2009-2015. METHODS: Venous blood samples were collected from paratyphoid patients and cultured in double phase blood culture bottle. Suspicious strains were identified and used for Salomonella. O antigen and H1/2 phase flagellum-induced serum agglutination test with API20E biochemical systems and SSI Salmonella typing sera. According to Salmonella molecular typing and K-B drug susceptibility testing method published by PulseNet China bacterial infectious disease monitoring network and USA Clinical and Laboratory Standards Institute, we analyzed the drug susceptibility and PFGE molecule characteristics of S. paratyphi A strains isolated from the patients. RESULTS: A total of 126 strains of S. paratyphi A were isolated from 248 blood samples, the antigen modes of them were 1, 2, 12:a:-. The resistance rate of 126 strains of S. paratyphi A was 83.3% to ampicillin; 29.4% to ceftazidime, 31.2% to cefotaxime, 17.5% to cefepime; 62.6% to nalidixic acid; 19.3% to ciprofloxacin, 26.4% to norfloxacin; 22.8% to gentamicin, 47.9% to streptomycin; 19.2% to chloramphenicol, 24.2% to methicillin benzyl ammonium, 58.6% to compound sulfamethoxazole and 46.7% to tetracycline. The 126 strains of S. paratyphi A had different levels of resistance to 8 kinds of antibiotics, 109 strains were multidrug resistant(86.5%), 9 strains were resistant to 2-3 kinds of antibiotics(7.1%), 76 strains were resistant to 5-8 kinds of antibiotics(60.3%), 17 strains were resistant to 9-10 kinds of antibiotics(13.5%), 7 strains were resistant to 11-12 kinds of antibiotics(5.6%). The 126 strains of S. paratyphi A were divided into 14 molecular patterns by digestion with XbaⅠand pulsed field gel electrophoresis. The antibiotics resistance to third generation cephalosporin(CAZ, CTX), one generation and three generation of quinolones(NAL, CIP, NOR)and aminoglycosides antibiotics(STR)showed an upward trend. Each pattern contained 1-98 strains with similarity ranged from 64.10% to 100.00%. PTYA 1, 6, 9 and 10 were the main PFGE belt types. CONCLUSION: The drug resistance of clinical isolates of S. paratyphi A was serious in Dengfeng, Henan province, PFGE patterns showed a diversity, but predominant patterns could also be found. The PFGE patterns of some strains had clustering and were related with their antidrug spectrums.

Development and Evaluation of a Blood Culture PCR Assay for Rapid Detection of Salmonella Paratyphi A in Clinical Samples.

BACKGROUND: Enteric fever remains an important cause of morbidity in many low-income countries and Salmonella Paratyphi A has emerged as the aetiological agent in an increasing proportion of cases. Lack of adequate diagnostics hinders early diagnosis and prompt treatment of both typhoid and paratyphoid but development of assays to identify paratyphoid has been particularly neglected. Here we describe the development of a rapid and sensitive blood culture PCR method for detection of Salmonella Paratyphi A from blood, potentially allowing for appropriate diagnosis and antimicrobial treatment to be initiated on the same day. METHODS: Venous blood samples from volunteers experimentally challenged orally with Salmonella Paratyphi A, who subsequently developed paratyphoid, were taken on the day of diagnosis; 10 ml for quantitative blood culture and automated blood culture, and 5 ml for blood culture PCR. In the latter assay, bacteria were grown in tryptone soy broth containing 2.4% ox bile and micrococcal nuclease for 5 hours (37°C) before bacterial DNA was isolated for PCR detection targeting the fliC-a gene of Salmonella Paratyphi A. RESULTS: An optimized broth containing 2.4% ox bile and micrococcal nuclease, as well as a PCR test was developed for a blood culture PCR assay of Salmonella Paratyphi A. The volunteers diagnosed with paratyphoid had a median bacterial burden of 1 (range 0.1-6.9) CFU/ml blood. All the blood culture PCR positive cases where a positive bacterial growth was shown by quantitative blood culture had a bacterial burden of ≥ 0.3 CFU/ ml blood. The blood culture PCR assay identified an equal number of positive cases as automated blood culture at higher bacterial loads (≥0.3 CFU/ml blood), but utilized only half the volume of specimens. CONCLUSIONS: The blood culture PCR method for detection of Salmonella Paratyphi A can be completed within 9 hours and offers the potential for same-day diagnosis of enteric fever. Using 5 ml blood, it exhibited a lower limit of detection equal to 0.3 CFU/ml blood, and it performed at least as well as automated blood culture at higher bacterial loads (≥0.3 CFU/ml blood) of clinical specimens despite using half the volume of blood. The findings warrant its further study in endemic populations with a potential use as a novel diagnostic which fills the present gap of paratyphoid diagnostics.

Detection of Typhoidal and Paratyphoidal Salmonella in Blood by Real-time Polymerase Chain Reaction.

BACKGROUND: The gold standard for diagnosis of enteric fever caused by Salmonella Typhi or Salmonella Paratyphi A or B is bone marrow culture. However, because bone marrow aspiration is highly invasive, many hospitals and large health centers perform blood culture instead. As blood culture has several limitations, there is a need for novel typhoid diagnostics with improved sensitivity and more rapid time to detection. METHODS: We developed a clyA-based real-time polymerase chain reaction (qPCR) method to detect Salmonella Typhi and Salmonella Paratyphi A simultaneously in blood. The sensitivity and specificity of this probeset was first evaluated in vitro in the laboratory and then in a typhoid-endemic population, in Karachi, Pakistan, and in healthy US volunteers. RESULTS: We optimized a DNA extraction and real-time PCR-based method that could reliably detect 1 colony-forming unit/mL of Salmonella Typhi. The probe set was able to detect clinical Salmonella Typhi and Salmonella Paratyphi A strains and also diarrheagenic Escherichia coli, but not invasive E. coli or other invasive bacteria. In the field, the clyA qPCR diagnostic was 40% as sensitive as blood culture. However, when qPCR-positive specimens were considered to be true positives, blood culture only exhibited 28.57% sensitivity. Specificity was ≥90% for all comparisons and in the healthy US volunteers. qPCR was significantly faster than blood culture in terms of detection of typhoid and paratyphoid. CONCLUSIONS: Based on lessons learned, we recommend that future field trials of this and other novel diagnostics that detect typhoidal and nontyphoidal Salmonella employ multiple methodologies to define a "positive" sample.

O:2-CRM(197) conjugates against Salmonella Paratyphi A.

Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

Serologic evidence for effective production of cytolysin A in Salmonella enterica serovars typhi and paratyphi A during human infection.

ClyASTy and ClyASPaA are closely related pore-forming cytolysins of Salmonella enterica serovars Typhi and Paratyphi A whose expression is strongly repressed under standard in vitro growth conditions. We show here that human infections by these pathogens cause a specific antibody response to ClyA, indicating effective toxin production during infection.

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.

Determination of diagnostic Widal titres in Kumasi, Ghana.

Three hundred and seven healthy food handlers and 34 blood-culture positive enteric fever patients were screened for Salmonellae agglutinins using the Widal test. Of the 307 healthy food handlers, only 3 (1.0%) had an anti-O titre of > or = 1/160 and 8 (2.6%) an anti-H titre of > or = 1/320 for Salmonella typhi, but the majority, 214 (69.7%) and 149 (48.5%) had titres of < 1/20 for O and H agglutinins respectively. Similar agglutinin titres were also seen for S. Paratyphi A, B, and C. In the 34 enteric fever patients, for S typhi, based on anti-O titre of > or = 1/160, 25 persons showed a significant titre, a sensitivity of 73.5%, and a specificity of 99.0%. And 21 persons showed a significant titre of > or = 1/320 for anti-H, a sensitivity of 61.8% and a specificity of 97.4%. Based on these findings, titres of > or = 1/160 and > or = 1/320 for anti-0 and anti-H respectively, were considered diagnostic for enteric fever in Kumasi, Ghana.

Antibody levels to Salmonella typhi and paratyphi in Nigerians.

OBJECTIVE: To determine the antibody titre levels to typhoid/paratyphoid fever organisms among apparently healthy volunteers. DESIGN: Cross sectional study. SETTING: General community and University Teaching Hospital. PARTICIPANTS: Volunteer sample of 323 apparently healthy individuals with body temperatures < or = 37.8 degrees C. MAIN OUTCOME MEASURES: Questionnaire administration to classify volunteers into three socio-economic status (SES). RESULTS: There were 35.29% of the apparently healthy population in Jos community with antibodies to typhoid/paratyphoid fever organisms. The presence of these antibodies were neither sex nor SES related. Normal antibody titres were up to 1:40 and 1:80 for O and H Salmonella antigens respectively. Contrary to the general belief, typhoid/paratyphoid fevers have not affected virtually everybody in Nigeria. The difference between those without previous history and those with previous history was significant (p < 0.05) with those in the former category having a higher percentage. CONCLUSION: For a single sero-diagnosis to have any diagnostic value in Jos community and its environs, only a four-fold rise to what has been found to be normal should be significant. This means that only titres of 1:160 and 1:320 and above for O and H antigens should be considered significant.

Detection of IgM antibody against region IV flagellin of Salmonella paratyphi A.

Salmonella paratyphi A is a pathogenic bacterium that causes paratyphoid fever. The current laboratory diagnostic techniques are unsatisfactory. To improve diagnosis, a plasmid (pSK-8E) encoding phase 1 flagellin gene nucleotide position 452-890 from S. paratyphi A has been constructed. The recombinant protein expressed from the plasmid has been used to develop an indirect ELISA for IgM antibody detection. Sera from patients with hemoculture positive for S. paratyphi A, S. typhi, other gram-positive and gram-negative bacteria, and dengue hemorrhagic fever as well as from healthy control subjects were tested. Sensitivity, specificity, positive and negative predictive values of the test were 56.9%, 98.8%, 90.6% and 92.1%, respectively. Since the sensitivity was low, the explanation for this result was investigated. It was found that the sensitivity of the test could be increased to 83.3% if the sera were obtained 9-12 days after onset of fever. The sera obtained earlier or later gave only 33.3% and 66.6% sensitivity, respectively. This result suggests that the IgM antibody detection assay which we have developed is a valuable tool for diagnosis of S. paratyphi A infection when the serum samples are taken at the appropriate time.

Culture of Salmonella typhi and Salmonella paratyphi from blood and bone marrow in suspected typhoid fever.

We studied the yield of blood and bone marrow (BM) cultures in 145 patients clinically suspected of typhoid fever (TF) in Indonesia. The objectives were to compare the positivity of blood culture using 3 ml versus 10 ml of blood and to examine in how far specific antibiotic treatment for TF interfered with the positivity of BM culture. Blood for culture was collected before antibiotic treatment was initiated in hospital and BM 1 to 10 days after the start of treatment. Cultures were performed with Oxgall subcultured on SS agar. Seventy-nine per cent of patients was treated for 14 days or more with oral chloramphenicol, 18% with chloramphenicol followed by ampicillin or cotrimoxazol and 3% with other antibiotics. Cultures were positive for Salmonella typhi or S-paratyphi A in 57 of the 145 patients (39.3%) when 3 ml of blood was cultured and in 58 (40%) when 10 ml of blood was cultured. BM culture was positive despite antibiotic treatment in 70 patients (48.2%); this positivity was significantly greater than that of blood cultures (p < 0.05). When we considered the positivity of BM culture in relation to the number of days on antibiotics in hospital, the yield of BM culture remained apparently unchanged during the first 5 days of treatment. This may be the consequence of slow elimination of S.typhi or S.paratyphi by the antibiotics used and could be responsible for relapses.

Randomized comparison of aztreonam and chloramphenicol in treatment of typhoid fever.

Patients with clinical typhoid fever plus a blood, bone marrow, or bile positive for Salmonella typhi or Salmonella paratyphi were included in an open clinical trial to compare the efficacy of aztreonam (6 g/day [2 g intravenously every 8 h]) given for 10 days with that of chloramphenicol (50 mg/kg of body weight per day [intravenously or orally]) administered for 14 days. A total of 44 patients, 22 in each group, were included in the study, and both groups were comparable in terms of baseline parameters. All patients randomized to receive chloramphenicol completed the 14 days of treatment, while two patients randomized to receive aztreonam developed an intestinal hemorrhage, and a third patient elected to withdraw from the trial. Defervescence occurred more quickly in the subjects receiving chloramphenicol than in those receiving aztreonam (P < 0.05). All patients in the chloramphenicol group were clinically cured during therapy, while four patients (21%) in the group receiving aztreonam were declared clinical treatment failures. None of the 19 patients receiving aztreonam, compared with 7 of 22 (32%) patients receiving chloramphenicol, had a positive blood culture after 24 h of therapy (P < 0.05). Adverse experiences were unusual and mild. In the study, aztreonam was less effective than chloramphenicol with regard to clinical effectiveness and time of defervescence but was more effective in the elimination of the infecting Salmonella organisms from the bloodstream.

The Widal test in a normal healthy population in the Sudan.

The Widal test was performed in 114 normal individuals from the Gezira area in Sudan. Salmonella typhi O agglutinins were found at a titre of 1.320 in 12 (10.5%) of them. Salmonella paratyphi A agglutinins were found at 1.160 in 5 (4.3%) and Salmonella paratyphi B "O" agglutinins were found in 6 (5.3%) at a titre of 1.160. None of these individuals had a history of typhoid fever or vaccination with TAB vaccine. The following points emerged: (i) normal healthy people in the Sudan have high antibody titres of Salmonella typhi; (ii) the Widal test in the Sudan should be interpreted against this background; (iii) previous diagnostic titre of 1.160 for S. typhi results in high false positive results; (iv) a titre above 1.320 is suggested as diagnostic for S. typhi; 1.160 for both S. partyphi B and S. paratyphi A.

Duodenal string-capsule culture compared with bone-marrow, blood, and rectal-swab cultures for diagnosing typhoid and paratyphoid fever.

The sensitivity of duodenal string-capsule culture (DSCC) was compared to that of bone-marrow-aspirate culture (BMAC), single 3-ml blood culture (BC), and rectal-swab culture (RSC) for isolating Salmonella typhi and Salmonella paratyphi type A from patients with typhoid and paratyphoid fever. In 36 of 154 patients DSCC could not be used, usually because the patient was too ill to swallow the capsule. In the remaining 118 patients DSCC was positive in 57.6%, RSC in 35.6%, BC in 54.2%, and BMAC in 85.6%. The sensitivity of DSCC was improved by an additional 4.7% if subcultured daily for seven days. The DSCC has no advantage over the combination of RSC and BC and is inferior in sensitivity to the BMAC. However, when a BMAC cannot be obtained, the addition of the DSCC to BC and RSC can be expected to improve the isolation rate by greater than 17%, to at least 85%.