Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Antillon M

PROVIDER: S-EPMC6226661 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Antillon Marina M Saad Neil J NJ Baker Stephen S Pollard Andrew J AJ Pitzer Virginia E VE

The Journal of infectious diseases 20181101 suppl_4

<h4>Background</h4>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.<h4>Methods</h4>We searched the literature to identify all studies that performed blood culture alongside bone marrow culture (a gold standard) ...[more]

PMID: 30307563

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Project description:PURPOSE OF REVIEW:Enteric fever remains a major global-health concern, estimated to be responsible for between 11.9 and 26.9 million cases annually. Long-term prevention of enteric fever will require improved access to safe drinking water combined with investment in sanitation and hygiene interventions. In the short-to-medium term, new control strategies for typhoid fever have arrived in the form of typhoid Vi-conjugate vaccines (TCVs), offering hope that disease control can be achieved in the near future. RECENT FINDINGS:The diagnosis of enteric fever is complicated by its nonspecific clinical presentation, coupled with the low sensitivity of commonly used diagnostics. Investment in diagnostics has the potential to improve management, to refine estimates of disease burden and to facilitate vaccine impact studies. A new generation of reliable, diagnostic tests is needed that are simultaneously accessible, cost-effective, sensitive, and specific. The emergence and global dissemination of multidrug-resistant, fluoroquinolone-resistant, and extensively drug-resistant (XDR) strains of Salmonella Typhi emphasizes the importance of continued surveillance and appropriate antibiotic stewardship, integrated into a global strategy to address antimicrobial resistance (AMR). Current empirical treatment guidelines are out of date and should be updated to respond to local trends in AMR, so as to guide treatment choices in the absence of robust diagnostics and laboratory facilities. In September 2017, the WHO Strategic Advisory Group of Experts (SAGE) immunization recommended the programmatic use of TCVs in high burden countries. Ongoing and future studies should aim to study the impact of these vaccines in a diverse range of setting and to support the deployment of TCVs in high-burden countries. SUMMARY:The advent of new generation TCVs offers us a practical and affordable public-health tool that - for the first time - can be integrated into routine childhood immunization programmes. In this review, we advocate for the deployment of TCVs in line with WHO recommendations, to improve child health and limit the spread of antibiotic-resistant S. Typhi.

Project description:Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs) to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12) found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX) immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively). Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0%) or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6), respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid) if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA)--such specimens might have been storage-denatured (especially the older paratyphoid samples) or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera analysis was insightful, revealing 64% of typhoid patients who had no change in antibody titer over 4-16 days, and 14% with no IgM-IgG class-switching.

Project description:BackgroundPrecise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.MethodsFrom September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 days; inpatients with suspected or confirmed enteric fever; patients with blood culture-confirmed enteric fever from the hospital laboratories not captured by inpatient or outpatient enrolment and cases from the laboratory network; and patients with non-traumatic ileal perforation under surgical care. We used a hybrid surveillance model, pairing facility-based blood culture surveillance with community surveys of health-care use. Blood cultures were performed for enrolled patients. We calculated overall and age-specific typhoid and paratyphoid incidence estimates for each study site. Adjusted estimates accounted for the sensitivity of blood culture, the proportion of eligible individuals who consented and provided blood, the probability of care-seeking at a study facility, and the influence of wealth and education on care-seeking. We additionally calculated incidence of hospitalisation due to typhoid and paratyphoid.FindingsA total of 34 747 patients were enrolled across 23 facilitates (six tertiary hospitals, surgical wards of two additional hospitals, and 15 laboratory network sites) during the study period. Of the 34 303 blood cultures performed on enrolled patients, 8705 (26%) were positive for typhoidal Salmonella. Adjusted incidence rates of enteric fever considered patients in the six tertiary hospitals. Adjusted incidence of S Typhi, expressed per 100 000 person-years, was 913 (95% CI 765-1095) in Dhaka. In Nepal, the adjusted typhoid incidence rates were 330 (230-480) in Kathmandu and 268 (202-362) in Kavrepalanchok. In Pakistan, the adjusted incidence rates per hospital site were 176 (144-216) and 103 (85-126). The adjusted incidence rates of paratyphoid (of which all included cases were due to S Paratyphi A) were 128 (107-154) in Bangladesh, 46 (34-62) and 81 (56-118) in the Nepal sites, and 23 (19-29) and 1 (1-1) in the Pakistan sites. Adjusted incidence of hospitalisation was high across sites, and overall, 2804 (32%) of 8705 patients with blood culture-confirmed enteric fever were hospitalised.InterpretationAcross diverse communities in three south Asian countries, adjusted incidence exceeded the threshold for "high burden" of enteric fever (100 per 100 000 person-years). Incidence was highest among children, although age patterns differed across sites. The substantial disease burden identified highlights the need for control measures, including improvements to water and sanitation infrastructure and the implementation of typhoid vaccines.FundingBill & Melinda Gates Foundation.

Project description:BackgroundRapid and reliable diagnostic assays for enteric (typhoid and paratyphoid) fever are urgently needed. We report the characterization of novel approach utilizing lymphocyte secretions, for diagnosing patients with enteric fever by the TPTest procedure.MethodologyTPTest detects Salmonella-specific IgA responses in lymphocyte culture supernatant. We utilized TPTest in patients with suspected enteric fever, patients with other illnesses, and healthy controls. We also evaluated simplified modifications of TPTest for adaptation in laboratories with limited facilities and equipment.Principal findingsTPTest was positive in 39 (27 typhoid and 12 paratyphoid A) patients confirmed by blood culture and was negative in 74 healthy individuals. Among 32 individuals with other illnesses, 29 were negative by TPTest. Of 204 individuals with suspected enteric fever who were negative by blood culture, 44 were positive by TPTest and the patients were clinically indistinguishable from patients with confirmed bacteremia, except they were more likely to be under 5 years of age. We evaluated simplifications in TPTest, including showing that lymphocytes could be recovered using lysis buffer or buffy coat method as opposed to centrifugation, that incubation of cells at 37°C did not require supplemental CO2, and that results were available for majority of samples within 24 hours. Positive results by TPTest are transient and revert to negative during convalescence, supporting use of the test in endemic areas. The results can also be read using immunodot blot approach as opposed to ELISA. Since no true gold standard currently exists, we used a number of definitions of true positives and negatives. TPTest had sensitivity of 100% compared to blood culture, and specificity that ranged from 78-97% (73-100, 95% CI), depending on definition of true negative.ConclusionThe TPTest is useful for identification of patients with enteric fever in an endemic area, and additional development of simplified TPTest is warranted.

Project description:The impact of temperature and rainfall on the occurrence of typhoid/paratyphoid fever are not fully understood. This study aimed to characterize the effect of daily ambient temperature and total rainfall on the incidence of typhoid/paratyphoid in a sub-tropical climate city of China and to identify the vulnerable groups for disease prevention. Daily notified typhoid/paratyphoid fever cases and meteorological data for Taizhou from 2005 to 2013 were extracted from the National Notifiable Disease Surveillance System and the Meteorological Data Sharing Service System, respectively. Distributed lag nonlinear model was used to quantify the association between daily mean temperature, total rainfall, and typhoid/paratyphoid fever. Subgroup analyses by gender, age, and occupation were conducted to identify the vulnerable groups. A total of 625 typhoid fever cases and 1,353 paratyphoid fever cases were reported during the study period. An increased risk of typhoid fever was detected with the increase of temperature (Each 2°C rise resulted in 6%, 95% [confidence interval] CI: 2-10% increase in typhoid cases), while the increased risk was associated with the higher temperature for paratyphoid (the highest cumulative risk of temperature was 33.40 [95% CI: 12.23-91.19] at 33°C). After the onset of mild precipitation, the relative risk of typhoid fever increased in a short-lasting and with a 13-26 days delay, and the risk was no significant after the continuous increase of precipitation (the highest cumulative risk of rainfall was 24.96 [95% CI: 4.54-87.21] at 100 mm). Whereas the risk of paratyphoid fever was immediate and long lasting, and increase rapidly with the increase of rainfall (each 100 mm increase was associated with 26% increase in paratyphoid fever cases). Significant temperature-typhoid/paratyphoid fever and rainfall-typhoid/paratyphoid fever associations were found in both genders and those aged 0-4 years old, 15-60 years old, farmers, and children. Characterized with a lagged, nonlinear, and cumulative effect, high temperature and rainfall could increase the risk of typhoid/paratyphoid fever in regions with a subtropical climate. Public health interventions such as early warning and community health education should be taken to prevent the increased risk of typhoid/paratyphoid fever, especially for the vulnerable groups.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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