The Relationship Between Blood Sample Volume and Diagnostic Sensitivity of Blood Culture for Typhoid and Paratyphoid Fever: A Systematic Review and Meta-Analysis
Antillon M., Saad NJ., Baker S., Pollard AJ., Pitzer VE.
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 &lt; .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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The relationship between the blood sample volume and culture sensitivity should be accounted for in incidence and next-generation diagnostic studies.</jats:p> </jats:sec>