A Natural History Study of Timothy Syndrome.

Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C . Timothy syndrome patients were first identified as having a cardiac presentation of Long QT and syndactyly of the fingers and/or toes, and an identical variant in CACNA1C , Gly406Arg. However, since this original identification, more individuals harboring diverse variants in CACNA1C have been identified and have presented with various cardiac and extra-cardiac symptoms. Furthermore, it has remained underexplored whether individuals harboring canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) have additional symptoms. Here, we describe the first Natural History Study for Timothy syndrome, providing a thorough resource describing the current understanding of disease manifestation in Timothy syndrome patients. Parents of Timothy syndrome children were queried regarding a wide-ranging set of symptoms and features via a survey. Importantly, we find that in addition to cardiac concerns, Timothy syndrome patients commonly share extra-cardiac features including neurodevelopmental impairments, hypoglycemia, and respiratory problems. Our work expands the current understanding of the disorder to better inform the care of Timothy syndrome patients.

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer.

Importance: Head and neck squamous cell carcinoma is a highly lethal cancer that is often associated with human papillomavirus (HPV). Recent studies have shown promise in the use of HPV DNA detection in salivary rinses and plasma as a factor associated with a future diagnosis of HPV-positive oropharynx cancer (HPVOPC). However, the use of plasma and salivary HPV DNA detection in defining risk for recurrence in the context of a prospective, phase 3, clinical trial coupled with standardized clinical surveillance has not been reported. Objective: To identify patients with low-risk HPVOPC at risk for recurrence by detection of HPV16 DNA in plasma and salivary rinses. Design, Setting, and Participants: In this cohort study, 233 low-risk patients were recruited from 32 head and neck treatment centers in Ireland (1 [3.1%]), the Netherlands (1 [3.1%]), and the UK (30 [93.8%]) as part of the DE-ESCALATE HPV trial, an open-label, phase 3 randomized clinical trial examining treatment with cetuximab vs cisplatin for HPVOPC. Patients were assayed for the presence of HPV16 DNA in plasma and salivary rinse via a quantitative polymerase chain reaction-based assay. Main Outcomes and Measures: Assay results were associated with risk of recurrence and lead time from HPV16 DNA detection to recurrence. Results: Of 233 patients, 45 (19.3%) were women, and the mean (SD) age was 57.01 (8.45) years. A total 1040 salivary or blood samples were collected during the course of the study. With a median follow-up of 760 days, the sensitivity and specificity of combined plasma and salivary rinse HPV DNA assays for detecting recurrence were 65% and 87%, respectively. There was a median lead time of positive test to event/recurrence date of 19 days (range, 0-536 days) and mean (SD) of 122 (169.8) days. Conclusion and Relevance: The results of this cohort study suggest that in the setting of a randomized, prospective, phase 3 trial for low-risk patients with HPVOPC, posttreatment presence of HPV DNA in plasma and salivary rinses is associated with recurrence; a lead time between test positivity and clinical recurrence offers a potential opportunity for earlier detection of recurrence.

An HIV Diagnostic Testing Algorithm Using the cobas HIV-1/HIV-2 Qualitative Assay for HIV Type Differentiation and Confirmation.

Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) diagnostic testing algorithms recommended by the Centers for Disease Control involve up to three tests and rely mostly on detection of viral antigen and host antibody responses. HIV-1 p24 antigen/HIV-1/HIV-2 antibody-reactive specimens are confirmed with an immunochromatographic HIV-1/HIV-2 antibody differentiation assay, and negative or indeterminate results from the differentiation assay are resolved by an HIV-1-specific nucleic acid amplification test (NAT). The performance of a proposed alternative algorithm using the cobas HIV-1/HIV-2 qualitative NAT as the differentiation assay was evaluated in subjects known to be infected with HIV-1 (n = 876) or HIV-2 (n = 139), at low (n = 6,017) or high (n = 1,020) risk of HIV-1 infection, or at high-risk for HIV-2 infection (n = 498) (study A). The performance of the cobas HIV-1/HIV-2 qualitative test was also evaluated by comparison to an HIV-1 or HIV-2 alternative NAT (study B). The HIV-1 and HIV-2 overall percent agreements (OPA) in study A ranged from 95% to 100% in all groups. The positive percent agreements (PPA) for HIV-1 and HIV-2 were 100% (876/876) and 99.4% (167/168), respectively, for known positive groups. The negative percent agreement in the HIV low-risk group was 100% for both HIV-1 and HIV-2. In study B, the HIV-1 and HIV-2 OPA ranged from 99% to 100% in all groups evaluated (n = 183 to 1,030), and the PPA for HIV-1 and HIV-2 were 100% and 99.5%, respectively, for known positive groups. The cobas HIV-1/HIV-2 qualitative assay can discriminate between HIV-1 and HIV-2 based on HIV RNA and can be included in an alternative diagnostic algorithm for HIV.

Clinical performance of the GenMark Dx ePlex respiratory pathogen panels for upper and lower respiratory tract infections.

The GenMark Dx ePlex Respiratory Pathogen Panel (RP) is a multiplexed nucleic acid test for the qualitative detection of common viral and a few bacterial causes of respiratory tract infections. The ePlex RP has received FDA clearance for nasopharyngeal swab (NPS) specimens collected in viral transport media. In this study, we evaluated the performance of the ePlex RP panel in comparison to the NxTAG Respiratory Pathogen Panel (NxTAG-RPP) from Luminex in use in our laboratory, not only for NPS but also for bronchoalveolar lavage specimens (BAL). We also evaluated the impact of implementing the ePlex RP on the test turn-around time (TAT). The newest panel from GenMark Dx, the ePlex Respiratory Pathogen Panel 2 (RP2), which added the SARS-CoV-2 target to the RP was also evaluated for NPS. Verification of the performance of the ePlex RP for both NPS and BAL showed 93.3 % and 84.9 % total agreement with the NxTAG-RPP respectively. An overall comparison of the TAT after implementing the ePlex RP as compared to the NxTAG-RPP assay showed an average decrease of almost seven-fold.

Outcomes of transplant recipients treated with cidofovir for resistant or refractory cytomegalovirus infection.

BACKGROUND: Treatment of ganciclovir-resistant (GCV-R)/refractory cytomegalovirus (CMV) infections in blood/marrow transplant (BMT) and solid organ transplant (SOT) recipients remains suboptimal. Cidofovir (CDV), a nucleotide analogue with anti-CMV activity, is nephrotoxic and oculotoxic. METHODS: We retrospectively evaluated the outcomes of SOT and BMT patients with GCV-R/refractory CMV treated with CDV between 1/1/2008 and 12/31/2017. DATA COLLECTED: baseline demographics, CMV serostatus, clinical and virologic presentations and outcomes, UL97 and UL54 genotype mutations, drug toxicities, and cause of death. Descriptive statistics were used. RESULTS: 16 patients received CDV for treatment of CMV: six BMT and 10 SOT. Seven (47%) of the patients had high-risk donor/recipient serostatus: six (60%) SOT were D+/R-; one (16.7%) BMT was D-/R+. Median time to CMV DNAemia was 131 days post-transplant (IQR, 37.5-230.3). Proven tissue invasive disease was present in three patients (18.8%). Twelve (75%) had genotype testing; 10 (83.3%) of those had antiviral resistance mutations. While on CDV, six (37.5%) developed nephrotoxicity, and four (25%) developed uveitis (two had both uveitis and nephrotoxicity). Eight (50%) had failure to clear CMV DNAemia despite CDV treatment. Eight (50%) of the patients died; median time to death, after initiation of CDV, was 33.5 days [IQR22-988]. CONCLUSIONS: In the absence of good therapeutic alternatives, CDV is used in GCV-R/refractory CMV infection. However, it is associated with a substantial risk of toxicity and failure to clear CMV DNAemia, highlighting the need for development of newer and less toxic therapies. The high mortality in this group of patients underscores the severity of illness in this population.

Routine HIV Test Results in 6 US Clinical Laboratories Using the Recommended Laboratory HIV Testing Algorithm With Geenius HIV 1/2 Supplemental Assay.

BACKGROUND: Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. METHODS: We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. RESULTS: Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. CONCLUSIONS: Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

Cytomegalovirus in Adult Allogeneic Blood and Marrow Transplant Patients Before or Around the Period of Neutrophil Recovery: A Single-Center, Retrospective, Descriptive Study.

BACKGROUND: Few reports exist on pre-engraftment cytomegalovirus (CMV) DNAemia in allogeneic blood or marrow transplant (allo BMT) recipients. We describe this clinical entity, its management, and the potential effect of 3 different quantitative CMV deoxyribonucleic acid (DNA) tests used during the 6-year study period. METHODS: We performed a retrospective, single-center study of allo BMT recipients from 2010 to 2015 who developed CMV DNAemia before neutrophil recovery (absolute neutrophil count [ANC] <1000 cells/mm3, "pre-engraftment CMV") or who became neutropenic concomitant with detectable CMV DNA ("peri-engraftment CMV"). Clinical data were collected from the electronic medical record. RESULTS: Among 1151 adult allo BMT patients, 73 developed CMV DNAemia before engraftment or while neutropenic after initial engraftment. Most patients were eventually treated (valganciclovir or ganciclovir, N = 68; foscarnet, N = 1); 4 were not treated. First CMV detection occurred at median day +12 (range, 0-48), but treatment was not started until median day +33 (range, 4-105) at median ANC of 760 cells/mm3. Six patients had peak viral loads >5000 IU/mL; none had tissue-invasive disease. One developed ganciclovir resistance. No significant differences were observed upon stratification by quantitative CMV DNA test. CONCLUSIONS: Cytomegalovirus DNA was detected in 6.3% of pre- and peri-engraftment allo-HSCT patients. Ganciclovir derivatives were commonly used for treatment despite risk of neutropenia. Treatment was typically deferred until CMV DNA and ANC rose. With rare exceptions, this treatment strategy did not appear to have adverse clinical consequences with respect to acute CMV. Different CMV DNA quantification tests used performed similarly from a clinical perspective despite different analytical performance characteristics.

Optimization and evaluation of a novel real-time RT-PCR test for detection of parechovirus in cerebrospinal fluid.

Human parechovirus (HPeV) infections cause a broad array of clinical manifestations ranging from gastrointestinal or respiratory illness to central nervous system (CNS) diseases. Though nucleic acid amplification tests (NAATs) for detection of HPeVs have been described, a need exists for sensitive and specific NAATs with internal control (IC). This study describes optimization and evaluation of a novel, real-time reverse transcription PCR (RT-PCR) test for detection of HPeV from CSF using EliTech HPeV Research-Use-Only detection reagent, MS2 IC and quantified HPeV control. Four RT-PCR kits were compared to select an enzyme with optimal amplification efficiency. The optimal RT-PCR enzyme volume and the best approach to add MS2 to the easyMAG extraction platform were investigated. Following assay optimization, performance characteristics were determined. SuperScript was the most efficient one-step RT-PCR kit, with 0.5 µl/reaction of enzyme being most cost-effective. Adding MS2 to samples post-lysis was better than pre-lysis. The limit of detection of the new test was 570 copies/mL. Commercially-available HPeV 1-6 were detectable, and no cross-reactivity with other CNS pathogens was observed. This test was accurate and reproducible for detection of HPeV and IC. It demonstrated good performance characteristics and is a useful addition to a suite of molecular assays for detection of viral pathogens in CSF.

Diagnosis and monitoring of HCV infection using the cobas® HCV test for use on the cobas® 6800/8800 systems.

BACKGROUND AND OBJECTIVES: Accurate, sensitive, and specific tests for detection and monitoring of hepatitis C virus (HCV) RNA concentrations are essential for diagnosis and management of HCV infections. We evaluated the next-generation reverse-transcription real-time PCR test, cobas® HCV test for use with the cobas® 6800/8800 systems ("cobas HCV") by determining its analytical performance characteristics and clinical utility for the diagnosis and therapeutic monitoring of chronic HCV infections. METHODS: The limit of detection (LOD), linearity, precision, specificity, matrix equivalence of plasma and serum, and quantitative agreement with the COBAS® AmpliPrep/COBAS® TaqMan® HCV Test version 2.0 ("CAP/CTM HCV v2") were evaluated. Clinical utility for the diagnosis of chronic HCV infection was demonstrated by testing plasma from HCV seropositive individuals and comparing results to a nucleic acid amplification test (NAAT) approved for use in the diagnosis of chronic hepatitis C. Clinical specificity was investigated by testing plasma from HCV antibody negative subjects with non-HCV related liver diseases. Utility for monitoring treatment response was defined by testing plasma collected during treatment of HCV genotypes (GT) 1, 2, and 3 and determining positive predictive value (PPV), negative predictive value (NPV) and the odds ratio (OR) for predicting cure (sustained virologic response 12 weeks after treatment cessation, "SVR12"). RESULTS: The cobas HCV test demonstrated an LOD of at least 15 IU/mL and measurable range from 15 to at least 1.0E + 08 IU/mL (1.2-8.0 log10 IU/mL) for GT 1-6, with high accuracy (≤0.16 log10 difference) and precision (standard deviation 0.04-0.14 log10) throughout the linear range. Paired plasma and serum samples showed highly correlated performance (R2 = 0.97). Quantification was 100% specific for HCV in analytical studies. Correlation with CAP/CTM HCV v2 was high in patient samples (mean titer difference: 0.05 log10 with a 95% CI: 0.03-0.06 log10). For the diagnosis of chronic HCV, positive and negative percent agreement between cobas HCV and the comparator NAAT were 98.8-100% on the cobas 6800 and 8800 systems. Clinical specificity of cobas HCV using samples from HCV antibody negative subjects with non-HCV related liver diseases was 99.6% and 100% on cobas 6800 and 8800 systems. In therapeutic monitoring and SVR12 prediction during experimental treatment for chronic HCV GT 1 infections, undetectable HCV RNA by cobas HCV at different on-treatment weeks had a PPV 76.8%-79.4%, NPV 29.9%-100%, and OR 1.64-47.52. During therapy of HCV GT 2 and GT 3, treatment week 4 and 12 results were: PPV, 84.7% and 75.3%; NPV, 47.8% and 50.0%; OR, 5.09 and 3.05. CONCLUSIONS: The cobas HCV test is highly sensitive, specific, and accurate HCV RNA test for GT 1-6. It demonstrates excellent correlation with the FDA-approved CAP/CTM HCV v2 test. It is useful clinically for detection of active HCV infection in individuals that have had a positive anti-HCV antibody test result and in monitoring treatment response.

Comparison of Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected Participants Enrolled in a Multinational Clinical Trial: HPTN 052.

OBJECTIVE: Data comparing hepatitis B virus (HBV) infection in HIV-infected [HIV(+)], and HIV-uninfected [HIV(-)] individuals recruited into the same study are limited. HBV infection status and chronic hepatitis B (cHB) were characterized in a multinational clinical trial: HIV Prevention Trials Network (HPTN 052). METHOD: HBV infection status at enrollment was compared between HIV(+) (N = 1241) and HIV(-) (N = 1232) from 7 HBV-endemic countries. Hepatitis B e antigen and plasma HBV DNA were determined in cHB. Median CD4, median plasma HIV RNA, and prevalence of transaminase elevation were compared in HIV(+) with and without cHB. Significance was assessed with χ, Fisher exact, and median tests. RESULTS: Among all participants, 33.6% had HBV exposure without cHB (8.9% isolated HBV core antibody, "HBcAb"; 24.7% HBcAb and anti-HB surface antibody positive, "recovered"), 4.3% had cHB, 8.9% were vaccinated, and 53.5% were uninfected. Data were similar among HIV(+) and HIV(-) except for isolated HBcAb, which was more prevalent in HIV(+) than HIV(-) [10.1% vs. 7.7%, P = 0.046]. Median HBV DNA trended higher in HIV(+) than in HIV(-). In HIV(+) with cHB versus those without cHB, transaminase elevations were more prevalent (alanine aminotransferase ≤ grade 2, 12% vs. 5.2%, P = 0.037; aspartate aminotransferase ≤ grade 2, 26% vs. 6.0%, P < 0.001), CD4 trended lower, and HIV RNA was similar. CONCLUSIONS: HBV infection status did not differ by HIV infection status. HIV co-infection was associated with isolated HBcAb and a trend of increased HBV DNA. In HIV, cHB was associated with mild transaminase elevations and a trend toward lower CD4.

The effect of a genetic variant on quantitative real-time PCR in a case of disseminated adenovirus infection.

A patient developed disseminated adenovirus infection following bone marrow transplant. TaqMan real-time PCR showed reduced maximum fluorescence in the amplification curve from all plasma samples. Sequencing revealed three single nucleotide mismatches between the TaqMan probe and probe binding region. Real-time PCR with probe matching the isolate sequence showed normal amplification and a higher copy number result.

Chronic Hepatitis B, C, and D.

Chronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.

Outcomes in Transplant Recipients Treated With Foscarnet for Ganciclovir-Resistant or Refractory Cytomegalovirus Infection.

BACKGROUND: Antiviral-resistant or refractory cytomegalovirus (CMV) infection is challenging, and salvage therapies, foscarnet, and cidofovir, have significant toxicities. Several investigational anti-CMV agents are under development, but more information is needed on outcomes of current treatments to facilitate clinical trial design for new drugs. METHODS: Records of solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients at a single center over a 10-year period were reviewed retrospectively to characterize those who had received foscarnet treatment for ganciclovir-resistant or refractory CMV infection. Data were collected on virologic responses, mortality, and nephrotoxicity. RESULTS: Of 39 patients (22 SOT, 17 HCT), 15 had documented ganciclovir resistance mutations and 11 (28%) of 39 had tissue-invasive CMV. Median duration of foscarnet was 32 days. Virologic failure occurred in 13 (33%) of 39 and relapses of viremia occurred in 31%. Mortality was 12 (31%) of 39 and was higher in HCT than SOT (P = 0.001), although ganciclovir resistance was more common in SOT (P = 0.003). Doses of ganciclovir or valganciclovir were low in 10 (26%) of 39 at some time before switching to foscarnet. Renal dysfunction occurred in 20 (51%) of 39 by end of treatment and in 7 (28%) of 25 after 6 months. CONCLUSIONS: Outcomes of existing treatment for ganciclovir-resistant or refractory CMV are suboptimal, in terms of virologic clearance, renal dysfunction, and mortality. These data should provide background information for future clinical trials of newer antiviral agents.

Hepatitis E Virus Infection Among Solid Organ Transplant Recipients at a North American Transplant Center.

Background. Autochthonous hepatitis E virus (HEV) infection has been reported in over 200 solid organ transplant (SOT) recipients since 2006, yet little is known about the burden of HEV among SOT recipients in North America. We performed a retrospective, cross-sectional study to investigate the prevalence and risk factors associated with HEV infection among SOT recipients at our institution. Methods. Children and adults (n = 311) who received allografts between 1988 and 2012 at the Johns Hopkins Hospital were assessed for evidence of HEV infection by testing posttransplantation serum samples for HEV antibody by enzyme immunoassay and HEV RNA by reverse transcription quantitative polymerase chain reaction. Individuals with evidence of posttransplant HEV infection (presence of anti-HEV immunoglobulin [Ig]M antibody, anti-HEV IgG seroconversion, or HEV RNA) were compared with individuals without evidence of infection and assessed for risk factors associated with infection. Results. Twelve individuals (4%) developed posttransplant HEV infection. Posttransplant HEV infection was associated with an increased risk for graft rejection (odds ratio, 14.2; P = .03). No individuals developed chronic infection. Conclusions. Solid organ transplant recipients in the United States are at risk for posttransplant HEV infection. Further studies are needed to characterize environmental risk factors and the risk of HEV infection after SOT in North America.

The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases.

Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of detecting EBV DNA in the plasma and peripheral blood mononuclear cells (PBMCs) of 2146 patients who had blood specimens sent to the Johns Hopkins Hospital clinical laboratory for viral quantitative real-time polymerase chain reaction assay over a 5-year period. Within this largely immunocompromised and hospitalized cohort, 535 patients (25%) had EBV detected in plasma or PBMCs. When EBV was detected in the absence of an EBV(+)disease (n = 402), it was present only in PBMCs in 69% of cases. Immunocompromised patients were less likely to have EBV in plasma than in PBMCs in the absence of EBV(+)disease. In patients with active, systemic EBV(+)diseases (n = 105), EBV was detected in plasma in 99% of cases but detected in PBMCs in only 54%. Across a range of copy number cutoffs, EBV in plasma had higher specificity and sensitivity for EBV(+)disease as compared with EBV in PBMCs. EBV copy number in plasma distinguished untreated, EBV(+)lymphoma from EBV(+)lymphoma in remission and EBV(-)lymphoma, and also distinguished untreated, EBV(+)posttransplantation lymphoproliferative disorder (PTLD) from EBV(+)PTLD in remission and EBV(-)PTLD. EBV copy number quantification is a useful diagnostic marker across the spectrum of EBV(+)diseases, even among immunocompromised patients, with plasma specimens more indicative of EBV(+)disease than PBMCs.

A Polymerase Chain Reaction-Based Algorithm to Detect and Prevent Transmission of Adenoviral Conjunctivitis in Hospital Employees.

PURPOSE: To devise and implement a practice algorithm that would enable rapid detection and appropriate furlough of hospital employees with adenoviral conjunctivitis in order to prevent healthcare-associated epidemic keratoconjunctivitis. DESIGN: Evaluation of an ongoing quality assurance/improvement initiative. METHODS: Employees of Johns Hopkins Hospital with signs and symptoms of adenoviral conjunctivitis underwent evaluation by nurse practitioners in Occupational Health and rapid diagnostic testing by real-time polymerase chain reaction (PCR). Sequencing was used to determine serotype when adenovirus was detected. Signs, symptoms, diagnosis, and disposition of employees with eye complaints as well as PCR and serotype results were recorded. RESULTS: Over a 36-month period approximately 18% of initial employee visits were due to unique, eye-related complaints. Viral conjunctivitis was suspected in 542 of 858 employees with eye complaints (62%); adenovirus was detected by PCR in 44 of 542 suspected viral conjunctivitis cases (8%) or 44 of 858 employees with any eye concern (5%). Fourteen of the 44 employees had adenoviral serotypes and clinical presentation consistent with epidemic keratoconjunctivitis (type 37 [n = 6], 8 [n = 4], 4 [n = 3], 19 [n = 1]). Other serotypes found in individuals with less severe conjunctivitis were 3 (n = 5), 4 (n = 5), 56 (n = 4), 1 (n = 2), 42 (n = 1), and 7 (n = 1). No healthcare-associated adenoviral conjunctivitis outbreaks occurred after algorithm implementation, and fewer employees required furlough than had clinical diagnosis alone been used. CONCLUSIONS: The algorithm is an effective infection prevention tool that minimizes productivity loss compared to clinical diagnosis and allows for determination of prevalence and serotype characterization of adenoviral conjunctivitis in hospital employees.

Clinical diagnosis of influenza in the ED.

BACKGROUND: Timely and accurate diagnosis of influenza remains a challenge but is critical for patients who may benefit from antiviral therapy. This study determined the test characteristics of provider diagnosis of influenza, final ED electronic medical record (EMR) diagnosis of influenza, and influenza-like illness (ILI) in patients recommended to receive antiviral treatment according to Centers for Disease Control and Prevention (CDC) guidelines. In addition, we evaluated the compliance with CDC antiviral guidelines. METHODS: A prospective cohort of adults presenting to a tertiary care ED with an acute respiratory illness who met CDC criteria for recommended antiviral treatment were enrolled and tested for influenza. A clinical diagnosis of influenza was assessed by asking the clinician: "Do you think this patient has influenza?" Influenza-like illness was defined according to current CDC criteria. RESULTS: In this cohort of 270 subjects, 42 (16%; 95% confidence interval [CI], 11%-20%) had influenza. Clinician diagnosis had a sensitivity of 36% (95% CI, 22%-52%) and specificity of 78% (95% CI, 72%-83%); EMR final ED diagnosis had a sensitivity of 26% (95% CI, 14%-42%) and specificity of 97% (95% CI, 94%-99%); ILI had a sensitivity of 31% (95% CI, 18%-47%) and specificity of 88% (95% CI, 83%-92%). Only 15 influenza-positive patients (36%) received antiviral treatment. CONCLUSION: Clinician diagnosis, final ED EMR diagnosis, and ILI have low sensitivity for diagnosing influenza, and there is overall poor compliance with CDC antiviral treatment recommendations. Improved methods of influenza diagnosis are needed to help guide management in the clinical setting.