Quantitation of Bacteria in Blood of Typhoid Fever Patients and Relationship between Counts and Clinical Features, Transmissibility, and Antibiotic Resistance

Abstract

Salmonella typhi was isolated from 369 andSalmonella paratyphi A was isolated from 6 of 515 Vietnamese patients with suspected enteric fever. Compared with conventional broth culture of blood, direct plating of the buffy coat had a diagnostic sensitivity of 99.5% (95% confidence interval [CI], 97.1 to 100%). Blood bacterial counts were estimated by the pour plate method. The median S. typhi count in blood was 1 CFU/ml (range, <0.3 to 387 CFU/ml), of which a mean of 63% (95% CI, 58 to 67%) were intracellular. The mean number of bacteria per infected leukocyte was 1.3 (interquartile range [IQR], 0.7 to 2.4) CFU/cell (n = 81). Children (<15 years old;n = 115) had higher median blood bacterial counts than adults (n = 262): 1.5 (range, <0.3 to 387) versus 0.6 (range, <0.3 to 17.7) CFU/ml (P = 0.008), and patients who excreted S. typhi in feces had higher bacteremias than those who did not: a median of 3 (range, <0.3 to 32) versus 1 (range, <0.3 to 68) CFU/ml (P = 0.02). Blood bacterial counts declined with increasing duration of illness (P = 0.002) and were higher in infections caused by multidrug-resistant S. typhi (1.3 [range, <0.3 to 387] CFU/ml; n = 313) than in infections caused by antibiotic-sensitive S. typhi (0.5 [range, <0.3 to 32] CFU/ml; n = 62) (P = 0.006). In a multivariate analysis this proved to be an independent association, suggesting a relationship between antibiotic resistance and virulence in S. typhi.

Searching for the elusive typhoid diagnostic

“…They were able to amplify fliC from all culture-positive and negative blood samples tested but reported a higher gene copy number in culture positives (1,000 -45,000), compared to negatives (<1000). However, this real-time PCR data is somewhat contradictory with the microbiological data, which demonstrates that bacteria/ml of blood is generally low with the majority of patients having <1 organism/ml of blood [21]. It is somewhat surprising that typhoid patients may have between a 1,000 to 45,000 times more dead bacteria than live bacteria in the blood.…”

“…This situation may be exacerbated as many patients reach microbiological facilities at a later stage of infection or may be "self treated" with antimicrobials. Thus, there are a number of characteristics of the pathogenesis of typhoid that impinge on diagnostics [21,22]. An obvious caveat is the low number of bacteria in the blood and other tissues.…”

Human IgG isotypes and activating Fcγ receptors in the interaction of Salmonella enterica serovar Typhimurium with phagocytic cells

“…One of the ways that S. enterica spreads within the host is through the bloodstream. 12,25,55,56 Improvements in bacterial uptake could reduce the levels of bacteria in the circulating blood and hence possibly limit the spread of the bacteria in vivo and prevent or stop bacteraemia in septicaemic infections. Studies on the distribution of IgG antibody subclasses in human immune serum in areas of endemic typhoid fever have shown that the dominating IgG antibody subclass is IgG2.…”

Typhoid fever in children in Africa

“…Among studies which considered the unselected group, only 2 ⁄ 6 report prevalences >1%, with 5.51% prevalence in Dhaka, Bangladesh and 6.1% in Malaysia (Choo et al 1993;Sinha et al 1999;Feng 2000;Brooks et al 2005;Siddiqui et al 2006). In studies on selected populations, the reported prevalence was between 8.6% and 71.5% (Wain et al 1998;Vollaard et al 2004). The high figures in this group may be attributed to highly restricted inclusion criteria.…”