Theel, Elitza S.

Diagnostic testing for Lyme disease (LD) remains dependent on detection of antibodies to LD Borrelia using serologic assays, in adherence to the standard two-tiered testing (STTT) algorithm. We present the first analytic evaluation of the automated Borrelia B31 ViraChip IgM and IgG microarray immunoblot (MIB) assays (Viramed Biotech AG, Planegg, Germany) in comparison to two different, semiautomated blot assays for LD, including the Borrelia B31 ViraStripe IgM and IgG line immunoassays (LIAs) (Viramed) and the MarDx Borrelia burgdorferi IgM and IgG Western blot (WB) assays (Trinity Biotech, Carlsbad, CA), using prospectively collected sera ( n = 411) and archived, clinically characterized samples ( n = 91).

Abstract Background Toxoplasmosis is routinely diagnosed through detection of Toxoplasma gondii–specific antibodies. However, the imperfect specificity of T. gondii serologic assays is a well-recognized limitation. The new BioPlex 2200 (Bio-Rad Laboratories) T. gondii, rubella, and cytomegalovirus (ToRC) IgM multiplex flow immunoassay (MFI) received FDA clearance in May 2017. We evaluated the clinical performance of the new T. gondii IgM and existing IgG portion of this MFI. Methods Three hundred prospectively collected consecutive, residual sera, submitted for T. gondii serologic testing as part of routine clinical care, and an archived set of 52 residual sera previously positive for anti–T. gondii IgM and IgG with the predicate ADVIA Centaur Toxoplasma IgM and IgG assays (Siemens) were evaluated. Performance of the BioPlex 2200 T. gondii IgM and IgG MFIs was assessed by calculating positive (PPA) and negative percent agreement (NPA) compared to the Centaur tests. Results Among prospective specimens, the BioPlex 2200 T. gondii IgM and IgG MFIs demonstrated a PPA of 0% (0/7) and 82.3% (28/34) and NPA of 99.3% (288/290) and 95.8% (251/262), respectively, with the Centaur assays. Chart review of the 7 Centaur T. gondii IgM-positive samples revealed that these were likely falsely positive. Among archived samples, the BioPlex 2200 T. gondii IgM and IgG MFIs showed PPAs of 90.4% (47/52) and 100% (52/52), respectively. Conclusions The BioPlex 2200 T. gondii IgM and IgG MFIs demonstrated excellent concordance with the Centaur assays. The T. gondii IgM MFI may provide higher specificity in low-prevalence populations.

Abstract Background Current American College of Gastroenterology (ACG) guidelines suggest that Helicobacter pylori serologic testing may be helpful to rule out H. pylori in areas with low disease prevalence. However, even in low prevalence regions, the positive predictive value of a positive serologic result remains low. Additionally, both the ACG and the American Gastroenterological Association recommend that this noninvasive testing be avoided entirely for patients 55 years and older. Methods The objective of this multicenter retrospective study was to assess H. pylori seroprevalence rates among symptomatic patients and serologic test utilization at the local, state, and national level. Submitted specimens were presumed to be collected from patients with upper gastrointestinal symptoms suspicious for an H. pylori etiology. Results for H. pylori IgG serologic tests performed between 2005 and 2014 were collected from 5 medical centers. Data were evaluated in the context of professional practice guidelines, with a focus on patients ages 55 years and older. Results Nationwide seropositivity among symptomatic individuals is approximately 25%, and 4 of 5 centers reported decreasing seropositivity rates over this 10-year period. State-specific seropositivity among symptomatic patients ranged from 12.4% in the state of Washington to 33.9% in Mississippi. Conclusions We demonstrate that for 48 states >25% of all H. pylori serologic testing was performed in individuals ≥55 years. Despite recommendations to avoid serologic evaluation for H. pylori infection, this study indicates that serology continues to be used at high rates across age-groups.

ABSTRACT The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI; n = 39) or active TB infection ( n = 3), and in health care workers (HCWs; n = 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients [ R ] > 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.

Abstract The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

ABSTRACT Rapid and accurate laboratory tests are important for the timely diagnosis and treatment of central nervous system infections. The FilmArray meningitis/encephalitis (ME) panel (BioFire Diagnostics, Salt Lake City, UT) is an FDA-cleared, multiplex molecular panel that allows the detection of 14 pathogens (bacterial [ n = 6], viral [ n = 7], and fungal [ n = 1] pathogens) from cerebrospinal fluid (CSF). In this study, we evaluated the performance characteristics of the FilmArray ME panel using clinical, residual CSF samples ( n = 291) that tested positive by a routine method(s) (e.g., bacterial culture, individual real-time PCR assay) for a pathogen represented on the ME panel. Of note, a subset ( n = 76) of the CSF specimens was collected during the prevaccine era and had been characterized as positive for a bacterial pathogen. The FilmArray ME panel demonstrated an overall percent positive agreement (PPA) of 97.5% (78/80) for bacterial pathogens, 90.1% (145/161) for viruses, and 52% (26/50) for Cryptococcus neoformans/C. gattii . Despite the low overall agreement (52%) between the ME panel and antigen testing for detection of C. neoformans/C. gattii , the percent positive agreement of the FilmArray assay for C. neoformans/C. gattii was 92.3% (12/13) when the results were compared directly to the results of routine fungal smear or culture. The FilmArray ME panel offers a rapid (∼60-min), syndrome-based approach for the detection of select meningitis and encephalitis pathogens.

ABSTRACT Since the emergence and dissemination of Zika virus (ZIKV) in late 2015, our understanding of the biology, transmission, clinical disease, and potential sequelae associated with infection has markedly expanded. Over the past 2 years, the number of diagnostic assays for ZIKV has increased from none in 2015 to 5 serological assays and 14 molecular assays in 2017, all with emergency use authorization granted through the U.S. Food and Drug Administration. Here we provide an update on ZIKV, addressing what we have collectively learned since the outbreak began, including a summary of currently available diagnostic assays for this virus.

Abstract Bannwarth syndrome (BWS), an infrequent manifestation of neuroinvasive Lyme disease (LD) characterized by radiculopathy, neuropathy, and lymphocytic pleocytosis, is more commonly documented in Europe than North America. Here, we describe a cluster of 5 neuroinvasive LD cases with BWS in the upper Midwest United States between July and August 2017.

Direct detection of Zika virus (ZIKV) nucleic acid with nucleic acid tests is definitive laboratory evidence of infection. Initial studies suggest that the ZIKV viremic period is limited, leading the Centers for Disease Control and Prevention to recommend that nucleic acid tests be utilized only up to 14 days postsymptom onset in serum and urine. The host immune response to flaviviruses, including to ZIKV, primarily targets the viral envelope (E) protein, which has three main domains (ED I–III). Recent studies suggest that neutralizing antibodies against the EDIII domain are relatively specific and potentially able to discriminate between ZIKV and dengue virus, which share 29% amino acid homology at that region. Comparatively, neutralizing antibodies to EDI and EDII, with amino acid homologies of 35 and 51% between these two viruses, respectively, are highly cross-reactive and likely responsible for the nonspecific reactions observed in the respective serologic assays. The current article describes the humoral immune response to ZIKV, reviews serologic assays for detection of antibodies to ZIKV, discusses performance characteristics of commercially available tests, and summarizes the strengths and limitations of currently available serologic methods. Assays examined in the review include the Centers for Disease Control and Prevention Zika IgM antibody capture ELISA, InBios ZIKV Detect IgM Capture ELISA, DiaSorin, LIAISON XL Zika Capture IgM Assay, Euroimmun anti-ZIKV IgM ELISA, and plaque reduction neutralization tests. Despite the availability of multiple diagnostic tests, there remains a need for modified and novel testing strategies, including the potential use of multiple enzyme immunoassays either in parallel or sequentially and IgG in addition to IgM determination.