The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt-Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP(D) type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrP(D) T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (p(GM)) or the white matter (p(WM)) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of p(GM)- and p(WM)-CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of p(WM)- and p(GM)-CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in p(GM)-CJD, but were ubiquitous in p(WM)-CJD. Typing of resPrP(D) T1 showed an unglycosylated fragment of ~ 20 kDa (T1(20)) in p(GM)-CJD and sCJDMM1 patients, while a doublet of ~ 21-20 kDa (T1(21-20)) was a molecular signature of p(WM)-CJD in subcortical regions. In addition, conformational characteristics of p(WM)-CJD resPrP(D) T1 differed from those of p(GM)-CJD and sCJDMM1. Inoculation of p(WM)-CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with p(WM)-CJD. Furthermore, T1(20) of p(WM)-CJD, but not T1(21), was propagated in mice. These data suggest that T1(21) and T1(20) of p(WM)-CJD, and T1(20) of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T1(20) of the novel p(GM)-CJD subtype.

BACKGROUND: The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network's (NHSN's) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs). METHODS: The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units. RESULTS: The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs. CONCLUSIONS: NHSN's initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions.

OBJECTIVES: Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in mid-to-late life. sCJD in early adulthood is extremely uncommon. The purpose of this report is to raise awareness of young cases of sCJD that are not associated with a genetic mutation or acquired prion disease risk factors. METHODS: We describe the clinical presentation, diagnostic work-up, and post-mortem examination of a 22-year-old man with sCJD. RESULTS: The patient presented with a rapidly progressive neurocognitive disorder consisting of early and prominent psychiatric symptoms. Cerebrospinal (CSF) real time quaking induced conversion (RT-QuIC) was indeterminate, and brain magnetic resonance imaging (MRI) was suggestive of prion disease. Neuropathologic examination and the absence of a genetic mutation and acquired prion disease risk factors resulted in a final diagnosis of sCJD. DISCUSSION: Although extremely rare, sCJD can occur in young people and should be considered in the setting of rapidly progressive neuropsychiatric conditions. Post-mortem examination is required to diagnose the type of prion disease and remains important to surveil for known and potentially novel acquired prion diseases.

BACKGROUND: Leading Change is one of five Executive Core Qualifications (ECQs) used in developing leaders in the federal government. Leadership development programs that incorporate multirater feedback and executive coaching are valuable in developing competencies to lead change. METHODS: We examined the extent by which coaching influenced Leading Change competencies and identified effective tools and resources used to enhance the leadership capacity of first- and midlevel leaders at Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis Prevention. Data included qualitative data collected via semi-structured interviews that focused on leadership changes made by leaders in the Coaching and Leadership Initiative (CaLI), a leadership development program for Team Leads and Branch Chiefs. FINDINGS: Ninety-six participants completed leadership coaching; 94 (98%) of whom completed one or more interviews. Of those 94 respondents, 74 (79%) reported improvements in their ability to lead change in 3 of 4 leading change competencies: creativity and innovation, flexibility, and resilience. All respondents indicated tools and resources that were effective in leading change: 49 (52%) participated in instructor-led activities during their CaLI experience; 33 (35%) experiential activities; 94 (100%) developmental relationships, assessment, and feedback; and 25 (27%) self-development. CONCLUSIONS/APPLICATION TO PRACTICE: First- and midlevel leaders in a public health agency benefitted from using leadership coaching in developing competencies to lead organizational change. Leadership development programs might benefit from examining Leading Change competencies and including instructor-led and experiential activities as an additional component of a comprehensive leadership development program.

This case study is part of a series centered on the Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN) health care-associated infection (HAI) surveillance definitions. The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions among infection preventionists and to promote accurate determination of HAI events. These cases reflect some of the complex patient scenarios that infection preventionists have encountered in their daily surveillance of HAIs using NHSN definitions. Objectives have been previously published.(1).

CONTEXT: Public health managers' leadership skills can be improved through multirater feedback and coaching. OBJECTIVE: To explore to what extent participation in a coaching intervention influences leadership behaviors of first- and second-level leaders in a federal public health agency. DESIGN: Team leads and branch chiefs in the Centers for Disease Control and Prevention's (CDC's) National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) were invited to participate in the Coaching and Leadership Initiative (CaLI), which incorporates the US Office of Personnel Management (OPM) Leadership 360 assessment, 6 coaching sessions, and 2 in-depth interviews. SETTING: NCHHSTP is one of 16 CDC national centers, institute, and offices. PARTICIPANTS: Staff serving as team leads or branch chiefs. MAIN OUTCOME MEASURES: Two in-depth interviews explored CaLI's influence on leadership behaviors regarding the government-wide Leading People executive core qualification. RESULTS: A total of 103 (93%) CaLI participants completed the OPM 360 feedback, 82 (80%) completed leadership coaching; 71 of 82 (87%) completed phase 1 interview, and 46 of 71 (65%) completed phase 2 interview. Eighty unique participants completed 1 or more interviews; all indicated that CaLI helped provide new perspectives, practices, and approaches that led to better communication and relationships, different approaches to conflict resolution, and awareness of individual leadership practices. Of the 71 participants who completed phase 1 evaluation, 66 (93%) said they made changes in developing others, 56 (79%) completed conflict management and team building, and 16 (23%) completed leveraging diversity. Of the 46 participants who completed both phase 1 and phase 2 interviews and among those who made changes post-CaLI, 23 of 26 (88%) sustained those leadership changes in developing others, 21 of 27 (78%) in team building; 24 of 34 (71%) in conflict management; and 5 of 10 (50%) in leveraging diversity. CONCLUSIONS: This study demonstrates the benefits and effectiveness of using multirater feedback and leadership coaching for first- and midlevel public health leaders.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive traumatic brain injury (TBI). CTE is generally found in athletes participating in contact sports and military personnel exposed to explosive blasts but can also affect civilians. Clinically and pathologically, CTE overlaps with post-traumatic stress disorder (PTSD), a term mostly used in a clinical context. The histopathology of CTE is defined by the deposition of hyperphosphorylated tau protein in neurons and astrocytes preferentially with perivascular distribution and at the depths of the cortical sulci. In addition to hyperphosphorylated tau, other pathologic proteins are deposited in CTE, including amyloid beta (Abeta), transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) and alpha-synuclein. However, the coexistence of prion disease in CTE has not been observed. We report three cases of histopathologically validated CTE with co-existing sporadic prion disease. Two were identified in a cohort of 55 pathologically verified cases of CTE submitted to the CTE Center of Boston University. One was identified among brain tissues submitted to the National Prion Disease Pathology Surveillance Center of Case Western Reserve University. The histopathological phenotype and properties of the abnormal, disease-related prion protein (PrP(D)) of the three CTE cases were examined using lesion profile, immunohistochemistry, electrophoresis and conformational tests. Subjects with sporadic Creutzfeldt-Jakob disease (sCJD) matched for age, PrP genotype and PrP(D) type were used as controls. The histopathology phenotype and PrP(D) properties of the three CTE subjects showed no significant differences from their respective sCJD controls suggesting that recurring neurotrauma or coexisting CTE pathology did not detectably impact the prion disease phenotype and PrP(D) conformational characteristics. Based on the reported incidence of sporadic prion disease, the detection of two cases with sCJD in the CTE Center series of 55 CTE cases by chance alone would be highly unlikely (p = 8.93*10(- 6)). Nevertheless, examination of a larger cohort of CTE is required to conclusively determine whether the risk of CJD is significantly increased in patients with CTE.

Background: The yeasts species determination is fundamental not only for an accurate diagnosis but also for establishing a suitable patient treatment. We performed a concordance study of five methodologies for the species identification of oral isolates of Candida in Colombia. Methods: Sixty-seven Candida isolates were tested by; API(R) 20C-AUX, Vitek(R)2 Compact, Vitek(R)MS, Microflex(R) and a molecular test (panfungal PCR and sequencing). The commercial cost and processing time of the samples was done by graphical analysis. Results: Panfungal PCR differentiated 12 species of Candida, Vitek(R)MS and Microflex(R) methods identified 9 species, and API(R) 20C-AUX and Vitek(R)2 Compact methods identified 8 species each. Weighted Kappa (wK) showed a high agreement between Panfungal PCR, Vitek(R)MS, Microflex(R) and API(R) 20C-AUX (wK 0.62-0.93). The wK that involved the Vitek(R)2 Compact method presented moderate or good concordances compared with the other methods (wK 0.56-0.73). Methodologies based on MALDI TOF MS required 4 minutes to generate results and the Microflex(R) method had the lowest selling price. Conclusion: The methods evaluated showed high concordance in their results, being higher for the molecular methods and the methodologies based on MALDI TOF. The latter are faster and cheaper, presenting as promising alternatives for the routine identification of yeast species of the genus Candida.

The presence of pathology related to the deposition of amyloid-beta (Abeta) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP(Sc)), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP(Sc) with the exception of iCJD harboring the "MMi" phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Abeta pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients' younger age CAA was more severe in iCJD than sCJD, while Abeta diffuse plaques, in absence of Abeta CP, populated one third of sCJD. Abeta pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD.In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Abeta phenotypes indicating that the occurrence of Abeta pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Abeta phenotype in iCJD since it is observed in nearly 90% of all iCJD with Abeta pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Abeta pathology of other factors, including GH deficiency, cannot be discounted, our findings increase the mounting evidence that this pathology is acquired by a mechanism resembling that of prion diseases.

Screening pregnant women for HIV and syphilis is a critical component of national programming to achieve elimination of mother to child transmission (EMTCT) for the two diseases. Many countries have well-resourced programmes for HIV screening in pregnant women and key populations (men who have sex with men and sex workers), but screening for syphilis in these same risk groups is seldom centralised and often falls within the responsibilities but outside the priorities of reproductive health, antenatal care and sexually transmitted infection (STI) control programmes. The tragedy of babies avoiding HIV and dying of syphilis and the lack of progress in Africa in congenital syphilis elimination despite tremendous successes in EMTCT for HIV has once again reminded us of the need to re-examine this situation.1,2 | In this issue, Obure et al describes a comparative analysis of costs of single versus dual rapid diagnostic tests for HIV and syphilis in the cities of Bogota and Cali in Columbia.3 The authors report higher costs associated with the use of rapid dual HIV/syphilis tests compared to single rapid HIV and syphilis tests. At baseline, the Columbia purchase price of the rapid dual test kits was more expensive than the single test kits; US$3.62 for the dual test versus US$2.26 for the two single tests (US$1.03 for single HIV and US$1.23 for syphilis). A comprehensive diagnostic brief of rapid dual tests has recently cited the average cost of US$1.50 per test kit.4 Pan American Health Organisation’s (PAHO) Strategic Fund is offering the same rapid dual test kits for US$1.50 per test.

BACKGROUND: Maintaining population-based registries requires adequate and sustained resources; however, to date there has been no systematic evaluation to identify the resource needs for cancer registration in most countries, including Colombia. A systematic assessment of the costs can quantify the funding required and identify processes to improve efficiency of cancer registries. METHODS: The Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool) was tailored specifically for the Colombian registries and was used to collect resource use data from five regional population-based cancer registries: Barranquilla, Bucaramanga, Cali, Manizales, and Pasto. The registries provided cost data for the year 2013 and cancer cases corresponding to the year 2010. RESULTS: We identified an almost threefold variation in the average cost per case (77,932 to 214,082 Colombian pesos or US $41 to US $113 in 2013) across the registries, but there were also substantial differences in data collection approaches, types of data collected, and activities performed. Cost per inhabitant varied between 95 and 415 Colombian pesos (US $0.05 to US $0.22). Between 20% and 45% of the total cost was due to fixed cost activities. CONCLUSIONS: The detailed economic information presented in this study constitutes a valuable source of activity-based cost data that registries can use to compare operations, assess key factors that lead to differences in cost per case, and identify potential approaches to improve efficiencies. Furthermore, the knowledge gained from studying the Colombian registries can help inform the planning and operations of other registries in the region.

BACKGROUND: The key aims of this study were to identify sources of support for cancer registry activities, to quantify resource use and estimate costs to operate registries in low- and middle-income countries (LMIC) at different stages of development across three continents. METHODS: Using the Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool), cost and resource use data were collected from eight population-based cancer registries, including one in a low-income country (Uganda [Kampala)]), two in lower to middle-income countries (Kenya [Nairobi] and India [Mumbai]), and five in an upper to middle-income country (Colombia [Pasto, Barranquilla, Bucaramanga, Manizales and Cali cancer registries]). RESULTS: Host institution contributions accounted for 30%-70% of total investment in cancer registry activities. Cancer registration involves substantial fixed cost and labor. Labor accounts for more than 50% of all expenditures across all registries. The cost per cancer case registered in low-income and lower-middle-income countries ranged from US $3.77 to US $15.62 (United States dollars). In Colombia, an upper to middle-income country, the cost per case registered ranged from US $41.28 to US $113.39. Registries serving large populations (over 15 million inhabitants) had a lower cost per inhabitant (less than US $0.01 in Mumbai, India) than registries serving small populations (under 500,000 inhabitants) [US $0.22] in Pasto, Colombia. CONCLUSION: This study estimates the total cost and resources used for cancer registration across several countries in the limited-resource setting, and provides cancer registration stakeholders and registries with opportunities to identify cost savings and efficiency improvements. Our results suggest that cancer registration involve substantial fixed costs and labor, and that partnership with other institutions is critical for the operation and sustainability of cancer registries in limited resource settings. Although we included registries from a variety of limited-resource areas, information from eight registries in four countries may not be large enough to capture all the potential differences among the registries in limited-resource settings.

OBJECTIVE To determine the typical microbial bioburden (overall bacterial and multidrug-resistant organisms [MDROs]) on high-touch healthcare environmental surfaces after routine or terminal cleaning. DESIGN Prospective 2.5-year microbiological survey of large surface areas (>1,000 cm2). SETTING MDRO contact-precaution rooms from 9 acute-care hospitals and 2 long-term care facilities in 4 states. PARTICIPANTS Samples from 166 rooms (113 routine cleaned and 53 terminal cleaned rooms). METHODS Using a standard sponge-wipe sampling protocol, 2 composite samples were collected from each room; a third sample was collected from each Clostridium difficile room. Composite 1 included the TV remote, telephone, call button, and bed rails. Composite 2 included the room door handle, IV pole, and overbed table. Composite 3 included toileting surfaces. Total bacteria and MDROs (ie, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci [VRE], Acinetobacter baumannii, Klebsiella pneumoniae, and C. difficile) were quantified, confirmed, and tested for drug resistance. RESULTS The mean microbial bioburden and range from routine cleaned room composites were higher (2,700 colony-forming units [CFU]/100 cm2; ≤1-130,000 CFU/100 cm2) than from terminal cleaned room composites (353 CFU/100 cm2; ≤1-4,300 CFU/100 cm2). MDROs were recovered from 34% of routine cleaned room composites (range ≤1-13,000 CFU/100 cm2) and 17% of terminal cleaned room composites (≤1-524 CFU/100 cm2). MDROs were recovered from 40% of rooms; VRE was the most common (19%). CONCLUSIONS This multicenter bioburden summary provides a first step to determining microbial bioburden on healthcare surfaces, which may help provide a basis for developing standards to evaluate cleaning and disinfection as well as a framework for studies using an evidentiary hierarchy for environmental infection control. Infect Control Hosp Epidemiol 2016;1-7.

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

INTRODUCTION: The present study compares the clinical, pathological and molecular features of a United States (US) case of growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those of two earlier referred US cases of GH-CJD and one case of dura mater (d)-associated CJD (dCJD). All iatrogenic CJD (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) of the prion protein (PrP) gene and had scrapie prion protein (PrP(Sc)) type 1 (iCJDMM1). RESULTS: The index subject presented with ataxia, weight loss and changes in the sleep pattern about 38 years after the midpoint of GH treatment. Autopsy examination revealed a neuropathological phenotype reminiscent of both sCJDMV2-K (a sporadic CJD subtype in subjects methionine/valine heterozygous at codon 129 with PrP(Sc) type 2 and the presence of kuru plaques) and variant CJD (vCJD). The two earlier cases of GH-CJDMM1 and the one of dCJDMM1 were associated with neuropathological phenotypes that differed from that of the index case mainly because they lacked PrP plaques. The phenotype of the earlier GH-CJDMM1 cases shared several, but not all, characteristics with sCJDMM1, whereas dCJDMM1 was phenotypically indistinguishable from sCJDMM1. Two distinct groups of dCJDMM1 have also been described in Japan based on clinical features, the presence or absence of PrP plaques and distinct PK-resistant PrP(Sc) (resPrP(Sc)) electrophoretic mobilities. The resPrP(Sc) electrophoretic mobility was, however, identical in our GH-CJDMM1 and dCJDMM1 cases, and matched that of sCJDMM1. CONCLUSIONS: Our study shows that receipt of prion-contaminated GH can lead to a prion disease with molecular features (129MM and PrP(Sc) type 2) and phenotypic characteristics that differ from those of sporadic prion disease (sCJDMM1), a difference that may reflect adaptation of "heterologous" prion strains to the 129MM background.

The occurrence of sporadic prion disease among adolescents is extremely rare. A prion disease was confirmed in an adolescent with disease onset at 13 years of age. Genetic, neuropathologic, and biochemical analyses of the patient's autopsy brain tissue were consistent with sporadic fatal insomnia, a type of sporadic prion disease. There was no evidence of an environmental source of infection, and this patient represents the youngest documented case of sporadic prion disease. Although rare, a prion disease diagnosis should not be discounted in adolescents exhibiting neurologic signs. Brain tissue testing is necessary for disease confirmation and is particularly beneficial in cases with an unusual clinical presentation.

OBJECTIVE: The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV). METHODS: Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics. RESULTS: Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3,129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with "variably protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in the PrP gene coding region. INTERPRETATION: Because all 3,129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Straussler-Scheinker disease.

OBJECTIVE: We investigated a cluster of cases of bloodstream infection (BSI) due to the mold Phialemonium at a hemodialysis center in Illinois and conducted a cohort study to identify risk factors. DESIGN: Environmental assessment and cohort study. SETTING: A hemodialysis center in a tertiary care hospital. METHODS: A case patient was defined as a person who underwent dialysis at the center and had a blood sample that tested positive for Phialemonium curvatum on culture. We reviewed microbiology and medical records and tested water, surface, and dialysate samples by culture. Molds isolated from environmental and clinical specimens were identified by their morphological features and confirmed by sequencing DNA. RESULTS: We identified 2 case patients with BSI due to P. curvatum. Both became febrile and hypotensive while undergoing dialysis on the same machine at the same treatment station, although on different days. Dialysis machines were equipped with waste handling option ports that are used to discard dialyzer priming fluid. We isolated P. curvatum from the product water (ie, water used for dialysis purposes) at 2 of 19 treatment stations, one of which was the implicated station. CONCLUSION: The source of P. curvatum was likely the water distribution system. To our knowledge, this is the first report of patients acquiring a mold BSI from contaminated product water. The route of exposure in these cases of BSI due to P. curvatum may be related to the malfunction and improper maintenance of the waste handling option ports. Waste handling option ports have been previously implicated as the source of bacterial BSI due to the backflow of waste fluid into a patient's blood line. No additional cases of infection were noted after remediation of the water distribution system and after discontinuing use of waste handling option ports at the facility.