High-Contact Object and Surface Contamination in a Household of Persons with Monkeypox Virus Infection - Utah, June 2022.

In May 2022, the Salt Lake County Health Department reported two real-time polymerase chain reaction (PCR)-confirmed travel-associated cases of monkeypox to the Utah Department of Health and Human Services (UDHHS). The two persons with monkeypox (patients A and B) lived together without other housemates. Both persons experienced prodromal symptoms (e.g., fatigue and body aches). Eight days after symptom onset, patient A experienced penile lesions; lesions spread to the lips, hands, legs, chest, and scalp by day 10. Patient B experienced prodromal symptoms 8 days after illness onset of patient A; patient B experienced a lesion on the foot which spread to the leg and finger by day 11. Although both patients had lesions in multiple anatomic areas, the overall number of lesions was small, and lesions varied in presentation from "pimple-like" or ulcerated, to characteristically well-circumscribed and centrally umbilicated. Both patients had mild illness. The time from symptom onset to resolution was approximately 30 days for patient A and approximately 22 days for patient B.

COVID-19 Testing to Sustain In-Person Instruction and Extracurricular Activities in High Schools - Utah, November 2020-March 2021.

Cessation of kindergarten through grade 12 in-person instruction and extracurricular activities, which has often occurred during the COVID-19 pandemic, can have negative social, emotional, and educational consequences for children (1,2). Although preventive measures such as masking, physical distancing, hand hygiene, and improved ventilation are commonly used in schools to reduce transmission of SARS-CoV-2, the virus that causes COVID-19, and support in-person instruction (3-6), routine school-based COVID-19 testing has not been as widely implemented. In addition to these types of standard preventive measures, Utah health and school partners implemented two high school testing programs to sustain extracurricular activities and in-person instruction and help identify SARS-CoV-2 infections: 1) Test to Play,* in which testing every 14 days was mandated for participation in extracurricular activities; and 2) Test to Stay,† which involved school-wide testing to continue in-person instruction as an alternative to transitioning to remote instruction if a school crossed a defined outbreak threshold (3). During November 30, 2020-March 20, 2021, among 59,552 students tested through these programs, 1,886 (3.2%) received a positive result. Test to Play was implemented at 127 (66%) of Utah's 193 public high schools and facilitated completion of approximately 95% of scheduled high school extracurricular winter athletics competition events.§ Test to Stay was conducted at 13 high schools, saving an estimated 109,752 in-person instruction student-days.¶ School-based COVID-19 testing should be considered as part of a comprehensive prevention strategy to help identify SARS-CoV-2 infections in schools and sustain in-person instruction and extracurricular activities.

Previous Infection and Effectiveness of COVID-19 Vaccination in Middle- and High-School Students.

BACKGROUND AND OBJECTIVES: Understanding the real-world impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mitigation measures, particularly vaccination, in children and adolescents in congregate settings remains important. We evaluated protection against SARS-CoV-2 infection using school-based testing data. METHODS: Using data from Utah middle- and high-school students participating in school-wide antigen testing in January 2022 during omicron (BA.1) variant predominance, log binomial models were fit to estimate the protection of previous SARS-CoV-2 infection and coronavirus disease 2019 vaccination against SARS-CoV-2 infection. RESULTS: Among 17 910 students, median age was 16 years (range: 12-19), 16.7% had documented previous SARS-CoV-2 infection; 55.6% received 2 vaccine doses with 211 median days since the second dose; and 8.6% of students aged 16 to 19 years received 3 vaccine doses with 21 median days since the third dose. Protection from previous infection alone was 35.9% (95% confidence interval [CI]: 12.9%-52.8%) and 23.8% (95% CI: 2.1%-40.7%) for students aged 12 to 15 and 16 to 19 years, respectively. Protection from 2-dose hybrid immunity (previous SARS-CoV-2 infection and vaccination) with <180 days since the second dose was 58.7% (95% CI: 33.2%-74.4%) for students aged 12 to 15 and 54.7% (95% CI: 31.0%-70.3%) for students aged 16 to 19 years. Protection was highest (70.0%, 95% CI: 42.3%-84.5%) among students with 3-dose hybrid immunity, although confidence intervals overlap with 2-dose vaccination. CONCLUSIONS: The estimated protection against infection was strongest for those with hybrid immunity from previous infection and recent vaccination with a third dose.

Risk Factors for Klebsiella Infections among Hospitalized Patients with Preexisting Colonization.

Klebsiella commonly colonizes the intestinal tract of hospitalized patients and is a leading cause of health care-associated infections. Colonization is associated with subsequent infection, but the factors determining this progression are unclear. A cohort study was performed, in which intensive care and hematology/oncology patients with Klebsiella colonization based on rectal swab culture were enrolled and monitored for infection for 90 days after a positive swab. Electronic medical records were analyzed for patient factors associated with subsequent infection, and variables of potential significance in a bivariable analysis were used to build a final multivariable model. Concordance between colonizing and infecting isolates was assessed by wzi capsular gene sequencing. Among 2,087 hospitalizations from 1,978 colonized patients, 90 cases of infection (4.3%) were identified. The mean time to infection was 20.6 ± 24.69 (range, 0 to 91; median, 11.5) days. Of 86 typed cases, 68 unique wzi types were identified, and 69 cases (80.2%) were colonized with an isolate of the same type prior to infection. Based on multivariable modeling, overall comorbidities, depression, and low albumin levels at the time of rectal swab collection were independently associated with subsequent Klebsiella infection (i.e., cases). Despite the high diversity of colonizing strains of Klebsiella, there is high concordance with subsequent infecting isolates, and progression to infection is relatively quick. Readily accessible data from the medical record could be used by clinicians to identify colonized patients at an increased risk of subsequent Klebsiella infection. IMPORTANCE Klebsiella is a leading cause of health care-associated infections. Patients who are intestinally colonized with Klebsiella are at a significantly increased risk of subsequent infection, but only a subset of colonized patients progress to disease. Colonization offers a potential window of opportunity to intervene and prevent these infections, if the patients at greatest risk could be identified. To identify patient factors associated with infection in colonized patients, we studied 1,978 colonized patients. We found that patients with a higher burden of underlying disease in general, depression in particular, and low albumin levels in a blood test were more likely to develop infection. However, these variables did not completely predict infection, suggesting that other host and microbial factors may also be important. The clinical variables associated with infection are readily available in the medical record and could serve as the foundation for developing an integrated risk assessment of Klebsiella infection in hospitalized patients.

Adapting Rapid Diagnostic Tests to Detect Historical Dengue Virus Infections.

The only licensed dengue vaccine, Dengvaxia®, increases risk of severe dengue when given to individuals without prior dengue virus (DENV) infection but is protective against future disease in those with prior DENV immunity. The World Health Organization has recommended using rapid diagnostic tests (RDT) to determine history of prior DENV infection and suitability for vaccination. Dengue experts recommend that these assays be highly specific (≥98%) to avoid erroneously vaccinating individuals without prior DENV infection, as well as be sensitive enough (≥95%) to detect individuals with a single prior DENV infection. We evaluated one existing and two newly developed anti-flavivirus RDTs using samples collected >6 months post-infection from individuals in non-endemic and DENV and ZIKV endemic areas. We first evaluated the IgG component of the SD BIOLINE Dengue IgG/IgM RDT, which was developed to assist in confirming acute/recent DENV infections (n=93 samples). When evaluated following the manufacturer's instructions, the SD BIOLINE Dengue RDT had 100% specificity for both non-endemic and endemic samples but low sensitivity for detecting DENV seropositivity (0% non-endemic, 41% endemic). Sensitivity increased (53% non-endemic, 98% endemic) when tests were allowed to run beyond manufacturer recommendations (0.5 up to 3 hours), but specificity decreased in endemic samples (36%). When tests were evaluated using a quantitative reader, optimal specificity could be achieved (≥98%) while still retaining sensitivity at earlier timepoints in non-endemic (44-88%) and endemic samples (31-55%). We next evaluated novel dengue and Zika RDTs developed by Excivion to detect prior DENV or ZIKV infections and reduce cross-flavivirus reactivity (n=207 samples). When evaluated visually, the Excivion Dengue RDT had sensitivity and specificity values of 79%, but when evaluated with a quantitative reader, optimal specificity could be achieved (≥98%) while still maintaining moderate sensitivity (48-75%). The Excivion Zika RDT had high specificity (>98%) and sensitivity (>93%) when evaluated quantitatively, suggesting it may be used alongside dengue RDTs to minimize misclassification due to cross-reactivity. Our findings demonstrate the potential of RDTs to be used for dengue pre-vaccination screening to reduce vaccine-induced priming for severe dengue and show how assay design adaptations as well quantitative evaluation can further improve RDTs for this purpose.

Epidemiological and Microbiome Associations Between Klebsiella pneumoniae and Vancomycin-Resistant Enterococcus Colonization in Intensive Care Unit Patients.

BACKGROUND: Prior colonization by Klebsiella pneumoniae and vancomycin-resistant Enterococci (VRE) is associated with subsequent infection, particularly in intensive care unit (ICU) populations. Screening for VRE colonization, but not K. pneumoniae, is routinely performed in some health care systems. Identification of patient factors associated with K. pneumoniae colonization could enable infection prevention. METHODS: ICU patients were screened for VRE and K. pneumoniae by rectal swab culture over 2 time periods: July-October 2014 (n = 1209) and January-May 2016 (n = 1243). Patient demographics, baseline laboratory data, comorbidities, and outcomes were analyzed. 16S rRNA gene-based analysis was performed on a subset of patients (n = 248) to identify microbiota characteristics associated with VRE and K. pneumoniae colonization. RESULTS: K. pneumoniae colonization (17.3% of patients in the 2014 cohort, 7.3% in 2016) was significantly associated with VRE colonization in multivariable analysis (P = .03 in 2016; P = .08 in 2014). VRE colonization was associated with poor underlying health, whereas K. pneumoniae colonization was associated with advanced age. The most prevalent operational taxonomic units were Escherichia coli /Shigella spp., Klebsiella, and Enterococcus, consistent with high rates of detectable K. pneumoniae and VRE by culture. Microbial community structure in noncolonized patients was significantly different from those with VRE, K. pneumoniae, or both, attributable to differences in the relative abundance of Klebsiella and Enterococcus. CONCLUSIONS: K. pneumoniae co-colonizes with VRE and is a predominant taxon in ICU patients, but colonization was not associated with significant comorbidities. Screening for K. pneumoniae and VRE simultaneously could be an efficient approach for novel infection prevention strategies.

Iron Acquisition and Siderophore Release by Carbapenem-Resistant Sequence Type 258 Klebsiella pneumoniae.

Klebsiella pneumoniae is rapidly acquiring resistance to all known antibiotics, including carbapenems. Multilocus sequence type ST258 (sequence type 258), carrying a gene encoding the K. pneumoniae carbapenemase (blaKPC) on a transmissible plasmid, is the most prevalent carbapenem-resistant Enterobacteriaceae (CRE) in the United States and has disseminated worldwide. Previously, whole-genome sequencing identified core genome single nucleotide variants that divide ST258 into two distinct clades, ST258a and ST258b. Furthermore, a subset of ST258b strains have a 347-base deletion within the enterobactin (Ent) exporter gene entS Despite the predicted inability of these strains to secrete the siderophore Ent, this clade is prevalent among clinical isolates, indicating that a full-length entS gene is not necessary for infection. To compare the transcriptional responses of ST258 subtypes to iron limitation, we performed transcriptome sequencing (RNA-Seq) in minimal medium alone or supplemented with iron or human serum and measured gene expression patterns. Iron limitation induced differential expression of distinct iron acquisition pathways when comparing ST258a and ST258b strains, including the upregulation of the hemin transport operon in entS partial deletion isolates. To measure how K. pneumoniae strains vary in iron chelation and siderophore production, we performed in vitro chrome azurol S (CAS) and Arnow assays as well as mass spectrometry. We determined that both ST258a and ST258b strains grow under iron-depleted conditions, can utilize hemin for growth, and secrete Ent, despite the partial entS deletion in a subset of ST258b strains. All carbapenem-resistant (CR) K. pneumoniae strains tested were susceptible to growth inhibition by the Ent-sequestering innate immune protein lipocalin 2.IMPORTANCE Carbapenem-resistant Enterobacteriaceae, including K. pneumoniae, are a major health care concern worldwide because they cause a wide range of infection and are resistant to all or nearly all antibiotics. To cause infection, these bacteria must acquire iron, and a major mechanism of acquiring iron is by secreting a molecule called enterobactin that strips iron from host proteins. However, a subset of carbapenem-resistant K. pneumoniae strains that lack a portion of the entS gene that is required for enterobactin secretion was recently discovered. To understand how these mutant strains obtain iron, we studied their transcriptional responses, bacterial growth, and enterobactin secretion under iron-limited conditions. We found that strains both with mutated and intact entS genes grow under iron-limiting conditions, secrete enterobactin, and utilize an alternate iron source, hemin, for growth. Our data indicate that carbapenem-resistant K. pneumoniae can use varied methods for iron uptake during infection.