WGS identified a highly diverse group of C. difficile isolates among children with CDI, including those with HCFA CDI. Clostridium difficile transmission among symptomatic children was very uncommon. Among putatively transmitted cases, investigation of shared healthcare exposures often did not identify a potential transmission source.
Background Clostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood. Methods In this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9–12 months underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, antitoxin IgG and NAb were measured in cord blood from 50 mothers unrelated to study infants. Results Among 32 infants, 16 (50%) were colonized with TCD; 12 were first colonized >1 month before serology measurements. A variety of sequence types were identified, and there was evidence of putative in-home (enrolled siblings) and outpatient clinic transmission. Infants first colonized with TCD >1 month prior had significantly greater serum antitoxin IgA and IgG against toxins A (P = .02 for both) and B (P = .009 and .008, respectively) compared with non–TCD-colonized infants, and greater IgG compared with unrelated cord blood (P = .005). Five of 12 (42%) colonized infants had detectable NAb titers compared with zero non–TCD-colonized infants (P = .02). Breastfeeding was not associated with differences in serological measurements. Conclusions TCD colonization is associated with a humoral immune response against toxins A and B, with evidence of toxin B neutralization in vitro. The extent and duration of protection against CDI later in life afforded by natural C. difficile immunization events require further investigation.
Background Clostridium difficile colonization is common in children. PCR does not distinguish infection (CDI) from colonization. Toxin enzyme immunoassay (EIA) and PCR cycle threshold (Ct) may predict CDI in PCR+ adults, but assay performance in children is poorly understood.MethodsStools from children aged 2–21 years with laboratory-identified (labID) CDI (tcdB PCR+; GeneXpert) underwent: toxin EIA (QUIK CHEK Complete [QCC] and Immunocard [IC]); cell culture cytotoxicity neutralization assay (CCCNA); and C. difficile stool culture (Cx). Children were determined to have clinical CDI (cCDI) by chart review and/or parent communication if all were noted: at least three unformed stools (Bristol type 5–7) in 24 hours; response to CDI treatment within 5 days; and no other likely diarrheal etiology. EIA and PCR Ct performance were measured for various reference standards (RefStd) based on stool assay results and/or cCDI classification.ResultsA total of 253 PCR+ stools were included. All stools underwent QCC; 218 (86%) were quantity sufficient for IC. Discordant EIA results occurred in 19/218 (8.7%) stools. Table 1 lists EIA sensitivity (Sn), EIA specificity (Sp), and median PCR Ct for each RefStd. Figure 1 shows the receiver operating characteristic (ROC) curve for PCR Ct to identify PCR+/CCCNA+/cCDI+ children (area under curve = 0.76). The difference between sensitivity (71%) and specificity (72%) was minimized at Ct < 23.5.ConclusionOnly a minority of PCR+ children meets strict clinical and laboratory CDI criteria. More stringent CDI definitions are associated with increasing toxin EIA Sn and lower PCR Ct (i.e., greater stool C. difficile inoculum). However, both toxin EIA and PCR Ct perform suboptimally as stand-alone tests to distinguish CDI from colonization in PCR+ children.Table 1: Toxin EIA and PCR Ct PerformanceRefStd (n for QCC)QCC EIA (n = 253)IC EIA (n = 218)Median PCR Ct(Ref+/Ref−)SnSpSnSpPCR+ only (253)0.360.3424.3PCR+ / Cx+ (211)0.410.930.390.9423.7 / 29.1**PCR+ / CCCNA+ (128)0.690.990.650.9922.2 / 28.5**PCR+ / cCDI+ (103)0.460.710.470.7423.6 / 25.2*PCR+ / Cx+ / cCDI+ (89)0.510.730.510.7623.2 / 26.1*PCR+ / CCCNA+ / cCDI+ (63)0.730.770.720.8021.8 / 26.3**Ref+ vs. Ref- (Wilcoxon rank-sum): *P < 0.05; **P < 0.0001.Figure 1.ROC Curve of PCR Ct to Identify PCR+ / CCCNA+ / cCDI+ Children.Disclosures L. Kociolek, Alere/Techlab: Investigator, Research support.
Systems thinking principles are increasingly recognized as an important part of public health research and practice. However, the extent to which systems thinking is being integrated into public health practice, and its impact on health outcomes, is largely unknown. This is in part due to the paucity of options for measuring systems thinking at the organizational level and in the context of public health practice. Building on existing frameworks of public health competencies, infrastructure, and systems thinking principles, this article proposes a conceptual model and corresponding indicators for measuring organizational systems thinking and application within state public health departments. We describe our process for developing this model and indicators, drawing from both research and practice‐based evidence on systems thinking, and offer a set of indicators for measuring organizational‐level systems thinking in the context of public health practice.
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