Access to COVID-19 testing by individuals with housing insecurity during the early days of the COVID-19 pandemic in the United States: a scoping review.

Introduction: The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pandemic as they faced increased risk of infection and difficulty in accessing testing and medical care. Individuals experiencing housing insecurity are a particularly vulnerable population given the additional barriers they face. In this scoping review, we identify some of the barriers this high-risk group experienced during the early days of the pandemic and assess novel solutions to overcome these barriers. Methods: A scoping review was performed following PRISMA-Sc guidelines looking for studies focusing on COVID-19 testing among individuals experiencing housing insecurity. Barriers as well as solutions to barriers were identified as applicable and summarized using qualitative methods, highlighting particular ways that proved effective in facilitating access to testing access and delivery. Results: Ultimately, 42 studies were included in the scoping review, with 143 barriers grouped into four categories: lack of cultural understanding, systemic racism, and stigma; medical care cost, insurance, and logistics; immigration policies, language, and fear of deportation; and other. Out of these 42 studies, 30 of these studies also suggested solutions to address them. Conclusion: A paucity of studies have analyzed COVID-19 testing barriers among those experiencing housing insecurity, and this is even more pronounced in terms of solutions to address those barriers. Expanding resources and supporting investigators within this space is necessary to ensure equitable healthcare delivery.

RADx-UP Testing Core: Access to COVID-19 Diagnostics in Community-Engaged Research with Underserved Populations.

Research on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding initiative, the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program, was developed to address the research gap in understanding the adoption of COVID-19 testing in underserved populations. This program is the single largest investment in health disparities and community-engaged research in the history of the NIH. The RADx-UP Testing Core (TC) provides community-based investigators with essential scientific expertise and guidance on COVID-19 diagnostics. This commentary describes the first 2 years of the TC's experience, highlighting the challenges faced and insights gained to safely and effectively deploy large-scale diagnostics for community-initiated research in underserved populations during a pandemic. The success of RADx-UP shows that community-based research to increase access and uptake of testing among underserved populations can be accomplished during a pandemic with tools, resources, and multidisciplinary expertise provided by a centralized testing-specific coordinating center. We developed adaptive tools to support individual testing strategies and frameworks for these diverse studies and ensured continuous monitoring of testing strategies and use of study data. In a rapidly evolving setting of tremendous uncertainty, the TC provided essential and real-time technical expertise to support safe, effective, and adaptive testing. The lessons learned go beyond this pandemic and can serve as a framework for rapid deployment of testing in response to future crises, especially when populations are affected inequitably.

The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria.

The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, polymerase chain reaction, amplicon/metagenomic sequencing, in situ hybridization), imaging (positron emission computed tomography with 18F-fluorodeoxyglucose, cardiac computed tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of "typical" microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the Duke-ISCVID Criteria available online as a "Living Document."

Application of Nuclear Magnetic Resonance to Detect Toxigenic Clostridium difficile from Stool Specimens: A Proof of Concept.

We evaluated the performance of an early prototype core molecular mirroring nuclear magnetic resonance detection platform (Mentor-100) to detect toxigenic Clostridium difficile from stool. This technology uses customized nanoparticles bound to target specific oligonucleotide probes that form binaries in the presence of nucleic acid from the target microorganism. Liquid patient stool specimens were seeded with C. difficile or other Clostridium species to determine the analytical sensitivity and specificity. Samples underwent nucleic acid extraction and target amplification with probes conjugated with iron nanoparticles. Signal from nuclear magnetic resonance spin-spin relaxation time was measured to detect the presence or absence of toxigenic C. difficile. The limit of detection was <180 colony forming units per reaction of toxigenic C. difficile. No cross-reactivity was observed with nontoxigenic C. difficile, Clostridium sordellii, Clostridium perfringens, Bacillus subtilis, or Paenibacillus polymyxa at 108 colony forming units/mL. Correlation studies using frozen stool samples yielded a sensitivity of 88.4% (61 of 69) and a specificity of 87.0% (40 of 46) as compared with a commercial PCR assay for C. difficile. The area under the curve in the receiver operating characteristic curve analysis was 0.922. The prototype molecular mirroring platform showed promising performance for pathogen detection from clinical specimens. The platform design has the potential to offer a novel, low-cost alternative to currently available nucleic acid-based tests.

The Suspected Infected Prosthetic Joint: Clinical Acumen and Added Value of Laboratory Investigations.

Consensus definitions have emerged for the discrimination between infected and uninfected prosthetic joints but diagnostic uncertainty often occurs. We examined the accuracy of orthopaedic surgeons' assessments to diagnose the infected prosthetic hip or knee and elucidated the added value of laboratory parameters. A prospective cohort study of patients undergoing revision arthroplasty of hip or knee was conducted over a one-year period. Orthopaedic surgeons' determinations prior to arthroplasty were recorded. A reference diagnostic standard was determined retrospectively by independent review from 3 infectious diseases physicians. Patients were followed up to 12 months. For 198 patients enrolled, 228 surgical encounters (110 knee, 118 hip) were classified by independent reviewers as 176 uninfected and 52 infected. Orthopaedic surgeons' preoperative diagnoses of infection had high diagnostic accuracy (sensitivity 89%, specificity 99%, PPV 98%, NPV 97%). Addition of intraoperative findings and histopathology improved their diagnostic accuracy. Addition of culture and PCR results improved sensitivity of diagnostic determinations but not specificity. We provide evidence that clinical acumen has high diagnostic accuracy using routine preoperative parameters. Histopathology from intraoperative specimens would improve surgeons' diagnostic accuracy but culture and PCR from intraoperative specimens could create greater diagnostic uncertainty. This study is critical to further our understanding of the added value, if any, of laboratory testing to support clinical decision making for the suspected infected joint and allow us to identify diagnostic gaps for emerging technologies to fill that will improve our ability to diagnose the infected prosthetic joint.

Balancing Enthusiasm for Innovative Technologies with Optimizing Value: An Approach to Adopt New Laboratory Tests for Infectious Diseases Using Bloodstream Infections as Exemplar.

A number of exciting new technologies have emerged to detect infectious diseases with greater accuracy and provide faster times to result in hopes of improving the provision of care and patient outcomes. However, the challenge in evaluating new methods lies not in the technical performance of tests but in (1) defining the specific advantages of new methods over the present gold standards in a practicable way and (2) understanding how advanced technologies will prompt changes in medical and public health decisions. With rising costs to deliver care, enthusiasm for innovative technologies should be balanced with a comprehensive understanding of clinical and laboratory ecosystems and how such factors influence the success or failure of test implementation. Selecting bloodstream infections as an exemplar, we provide a 6-step model for test adoption that will help clinicians and laboratorians better define the value of a new technology specific to their clinical practices.

Survey of physicians' perspectives and knowledge about diagnostic tests for bloodstream infections.

BACKGROUND: Physicians rely on blood culture to diagnose bloodstream infections (BSI) despite its limitations. As new technologies emerge for rapid BSI diagnosis, optimization of their application to patient care requires an understanding of clinicians' perspectives on BSI diagnosis and how a rapid test would influence medical decisions. METHODS: We administered a 26-question survey to practitioners in infectious diseases/microbiology, critical care, internal medicine, and hematology/oncology services in USA and Germany about current standards in diagnosing and treating BSI and a hypothetical rapid BSI test. RESULTS: Responses from 242 providers had roughly equal representation across specialties. For suspected BSI patients, 78% of practitioners would administer empiric broad spectrum antibiotics although they estimated, on average, that 31% of patients received incorrect antibiotics while awaiting blood culture results. The ability of blood culture to rule in or rule out infection was very/extremely acceptable in 67% and 36%, respectively. Given rapid test results, 60-87% of practitioners would narrow the spectrum of antimicrobial therapy depending on the microorganism detected, with significantly higher percentages when resistance determinants were also tested. Over half of respondents felt a rapid test would be very/extremely influential on clinical practice. CONCLUSIONS: Limitations of blood culture were perceived as a barrier to patient care. A rapid test to diagnose BSI would impact clinical practice, but the extent of impact may be limited by prevailing attitudes and practices. Opportunities exist for interventions to influence practitioners' behaviors in BSI management particularly with emergence of newer diagnostic tests.

Mycobacterium chelonae-abscessus complex associated with sinopulmonary disease, Northeastern USA.

Members of the Mycobacterium chelonae-abscessus complex represent Mycobacterium species that cause invasive infections in immunocompetent and immunocompromised hosts. We report the detection of a new pathogen that had been misidentified as M. chelonae with an atypical antimicrobial drug susceptibility profile. The discovery prompted a multicenter investigation of 26 patients. Almost all patients were from the northeastern United States, and most had underlying sinus or pulmonary disease. Infected patients had clinical features similar to those with M. abscessus infections. Taxonomically, the new pathogen shared molecular identity with members of the M. chelonae-abscessus complex. Multilocus DNA target sequencing, DNA-DNA hybridization, and deep multilocus sequencing (43 full-length genes) support a new taxon for these microorganisms. Because most isolates originated in Pennsylvania, we propose the name M. franklinii sp. nov. This investigation underscores the need for accurate identification of Mycobacterium spp. to detect new pathogens implicated in human disease.

Isolation and characterization of "Pseudomonas andersonii" from four cases of pulmonary granulomas and emended species description.

"Pseudomonas andersonii" is a Gram-negative bacillus initially isolated from a granulomatous lung lesion. Novel species status has not been validated for this single strain. We report four additional cases of pulmonary granuloma involving P. andersonii and further characterize the organism. These patients had pulmonary nodules that were surgically resected and which grew P. andersonii on routine culture. Mycobacterium avium complex was concomitantly isolated in two cases, and fungal structures were identified histopathologically in two other cases. The five P. andersonii strains described to date were similar in growth characteristics, biochemical reactions, matrix-assisted laser desorption ionization-time of flight mass spectrometry protein profiles, and susceptibility to antimicrobial agents. Their 16S rRNA genes were 99.9 to 100% identical but less than 95.0% similar to those of all other known bacteria. The gyrA genes of these strains were 99.5 to 100% identical. These shared features illustrate P. andersonii as a unique and distinct bacterium and support the novel species status of the organism.

Physician use of parasite tests in the United States from 1997 to 2006 and in a Utah Cryptosporidium outbreak in 2007.

Parasitic infection is uncommon in the United States, but surveys suggest that physicians test when the presence of parasites is unlikely and fail to order appropriate testing when suspicion is high. Numerous studies confirm that immunoassays are more sensitive for Giardia and Cryptosporidium detection, but our experience was that physicians preferentially used ovum and parasite examination (O&P). We conducted a retrospective study of fecal parasite testing at a referral laboratory nationally (1997 to 2006) and during a Cryptosporidium outbreak (Utah, 2007) to correlate physician use of O&P and enzyme immunoassays (EIAs) with the yield of parasites detected. Nationally, of 170,671 episodes, 76.0% (n = 129,732) included O&P, 27.9% (n = 47,666) included Giardia EIA, and 5.7% (n = 9,754) included Cryptosporidium EIA. Most pathogens were Giardia or Cryptosporidium. More episodes were positive when EIA was performed (n = 1,860/54,483 [3.4%]) than when O&P only was performed (n = 1,667/116,188 [1.4%]; P < 0.001), and EIA was more sensitive than O&P. However, more O&P results were positive among patients with both O&P and EIA performed (2.5%) than among those with O&P only performed (1.4%; P < 0.001), suggesting that patients tested by O&P only may have been at lower risk. During the first 10 weeks of the outbreak, physicians also preferentially used O&P over EIA, but no Cryptosporidium cases were detected by O&P. We conclude that clinicians frequently use O&P testing when test performance and epidemiology support the use of immunoassays or no testing. We recommend that stool O&P be limited to patients with negative immunoassay results and persistent symptoms or individuals at increased risk for non-Giardia, non-Cryptosporidium infection. An evidence-based algorithm for the evaluation of patients with suspected intestinal parasitic infection is proposed.

A review of sentinel laboratory performance: identification and notification of bioterrorism agents.

CONTEXT: The anthrax incident of 2001 in the United States prompted the College of American Pathologists (CAP), the Association of Public Health Laboratories, and the Centers for Disease Control and Prevention to develop exercises for Laboratory Response Network (LRN) sentinel laboratories. OBJECTIVE: To provide an overview of the results of the CAP bioterrorism Laboratory Preparedness Survey (LPS, 2007) and Laboratory Preparedness Exercise (LPX, 2008) and assist LRN sentinel laboratories and public health agencies in planning for bioterrorism events. DESIGN: Bioterrorism agents and nonbiothreat mimic organisms were provided in 2 mailings per year (2007 and 2008, 20 total challenges). Within each mailing, 2 to 3 agents were category A or category B bioterrorism agents (total of 10 categoric challenges). Some category A/B isolates were modified/vaccine strains. The total number of laboratories participating in these exercises ranged from 1316 to 1381. Isolate characteristics used to identify the organisms were compiled along with the participants' reporting actions. Educational commentary was provided with each exercise. RESULTS: Acceptable identification responses were as follows: Bacillus anthracis, 90% (2007) and 99.9% (2008); Yersinia pestis, 83.8% (2007) and 87.6% (2008); and Francisella tularensis subsp Holarctica, 86.6% (2007) and 91.6% (2008). The time interval between specimen receipt and notification of results to an LRN reference laboratory decreased from more than 10 days in 2007 to 3 or 4 days in 2008 for some challenges. CONCLUSIONS: The bioterrorism challenge program (LPS, LPX) provides important comparative data from more than 1300 sentinel laboratories that can be used by individual laboratories to evaluate their identification and LRN reporting performance.

Mycobacterium neoaurum and Mycobacterium bacteremicum sp. nov. as causes of mycobacteremia.

Reference isolates of Mycobacterium neoaurum, Mycobacterium aurum, and the nonvalidated species "Mycobacterium lacticola" were the focus of two recent molecular taxonomic studies. On the basis of this grouping, we identified 46 clinical pigmented, rapidly growing mycobacterial isolates. By 16S rRNA gene sequencing, only two major taxa were identified: M. neoaurum and a previously uncharacterized "M. neoaurum-like" group. The M. neoaurum-like group exhibited only 99.7% identity to M. neoaurum by 16S rRNA gene sequencing and 96.5% identity to M. neoaurum by rpoB sequencing and was named M. bacteremicum. No clinical isolates of M. aurum or M. lacticola were identified. Of isolates with known sources, 4/8 (50%) of M. bacteremicum isolates and 22/34 (65%) of M. neoaurum isolates were recovered from blood, and 35% of these were known to be from patients with catheter-related sepsis. MIC and clinical data on these 46 isolates of M. neoaurum and M. bacteremicum along with a review of 16 previously reported cases of infection with the M. neoaurum-M. lacticola group demonstrated that the isolates were highly susceptible to all drugs tested except clarithromycin, and most clinical cases were successfully treated. The clarithromycin resistance suggested the presence of an inducible erm gene reported in other species of rapidly growing mycobacteria. Sequencing studies are currently required to identify these two species. Strain ATCC 25791 (originally submitted as an example of Mycobacterium aurum) is proposed to be the type strain of M. bacteremicum.

Identifying respiratory viruses in nasal mucus from children.

Large amounts of respiratory viruses are shed in nasal secretions by children. Nasal mucus was compared with nasopharyngeal swabs as a source for respiratory virus testing. Multiplex reverse transcription-polymerase chain reaction detected virus in nasal mucus specimens in 73% (11/15) of positive cases, demonstrating the potential utility of less invasive specimens when a highly sensitive method is used for respiratory virus detection.

Comparison of 10 indirect fluorescent antibodies to detect and type influenza A specimens.

CONTEXT: Management of influenza infections relies on rapid, accurate, and sensitive diagnostic techniques. Influenza A (IA) strain typing has become more important since the emergence of highly pathogenic avian and novel influenza strains and the high frequency of oseltamivir resistance in circulating H1N1 isolates. OBJECTIVE: To analyze the performance of indirect fluorescent antibody testing for subtyping a broad range of IA strains. DESIGN: Ten indirect fluorescent antibody reagents were used to detect and type 100 archived IA respiratory specimens from 1986 through 1995 and 2006 through 2007 and a reassortant, nonpathogenic H5N1 sample. Both direct specimen and cultured isolates were tested. Reverse transcription-polymerase chain reaction was used to confirm indirect fluorescent antibody results. Three H1N1-, 2 H3N2-, and 1 H1-H2-H3-H5-specific antibodies (Chemicon Diagnostics), an IA pool reagent (Trinity Biotech), and H1, H3, and H1-H3-specific antibodies (Centers for Disease Control and Prevention) were used. RESULTS: Reverse transcription-polymerase chain reaction confirmed all 100 isolates as IA and identified 71 as H1, 22 as H3, and 7 as non-H1-H3. Sensitivity of direct specimen testing ranged was 18.3% to 57.7% for the H1 reagents, 36.4% to 50.0% for the H3 reagents, and 40.0% to 53.8% for the pool reagents. Subtyping was more sensitive on cultured isolates than direct specimens. Specificity for all antibodies was 89.7% to 100%. The H5N1 sample was positive by direct testing and culture (reverse transcription-polymerase chain reaction, Centers for Disease Control and Prevention H5N1 pool, Chemicon H1-H2-H3-H5). No cross-reactivity was observed when the 10 antibodies were tested against other common respiratory viruses. CONCLUSIONS: When positive, IA subtyping antibodies can serve as a useful diagnostic tool when multiple influenza virus subtypes are cocirculating with different susceptibility patterns.

Limited utility of culture for Mycoplasma pneumoniae and Chlamydophila pneumoniae for diagnosis of respiratory tract infections.

We assessed the utility of culture for Mycoplasma pneumoniae and Chlamydophila pneumoniae to diagnose respiratory tract infections. Compared to PCR and IgM serology, culture was less sensitive and had extremely low yield. Culture is not recommended for these pathogens, and this method should be eliminated from routine practice.

Simultaneous sequence analysis of the 16S rRNA and rpoB genes by use of RipSeq software to identify Mycobacterium species.

The 16S rRNA gene is commonly used to identify Mycobacterium spp., but alternative DNA targets can provide better resolution to the species level. We evaluated a novel system that enables simultaneous amplification, sequencing, and analysis of two different DNA targets in a single tube to identify clinical isolates of Mycobacterium spp. For 139 clinical isolates, we found that the 16S rRNA gene alone identified 67 (48%) isolates as single species, 68 (49%) isolates to the complex or group level, and 4 (3%) isolates to the genus level only. The rpoB gene alone identified 117 (84%) isolates as single species, 10 (7%) isolates to the complex or group level, and 12 (8%) isolates to the genus level only. Combining the separate analyses for sequencing of two gene targets, 119 (86%) isolates were identified as single species and 10 (7%) isolates were identified to the complex or group level. Seven (5%) isolates were identified as novel species within established groups, and 3 (2%) were identified to the genus level only. Dual-locus identification identified 110 (79%) isolates as single species and 22 (16%) isolates to the complex or group level. Six (4%) were identified as novel species within established groups, and 1 (1%) was identified to the genus level only. Identifications were more accurate when both the 16S rRNA and rpoB genes were screened, and reliance on a single gene target was suboptimal. RipSeq dual-locus software provides an accurate alternative method for laboratories using two different gene targets for microorganism identification.

Performance of diagnostic tests to detect respiratory viruses in older adults.

The performance of 4 laboratory methods for diagnosis of viral respiratory tract infections (RTI) in older adults was evaluated. Seventy-four nasopharyngeal (NP) swab specimens were obtained from 60 patients with RTI at a long-term care facility over 2 respiratory seasons. Sixteen specimens were positive for a respiratory virus by at least 1 method. Multiplex reverse transcriptase polymerase chain reaction (RT-PCR) by the Luminex xTAG Respiratory Viral Panel (RVP) detected 16 (100%) of the positive specimens, RVP of 24-h culture supernatant detected 8 (50%), direct fluorescent antibody testing detected 4 (25%), rapid culture detected 2 (12.5%), and rapid antigen testing detected none. For a comparison group, RVP was performed on NP swabs from 20 outpatient children with RTI. The mean fluorescence intensity by RVP was significantly lower for positive adult patients than pediatric patients (P = 0.0373). Our data suggest that older adult patients shed lower titers of viruses, necessitating a highly sensitive assay such as RT-PCR to reliably detect respiratory viral pathogens.