Negative Diagnostic Test Research Articles

Pseudomembranous colitis with negative Clostridium difficile PCR presenting with massive ascites: a case report and literature review

Pseudomembranous colitis (PMC) is characterized by the presence of an inflammatory pseudomembrane overlying the colonic mucosa, and is primarily caused by Clostridium difficile infection (CDI). PMC is often associated with the use of broad-spectrum antibiotics. Common symptoms include watery diarrhea, mucus in stool, abdominal cramps, and fever. We report a case of a 52-year-old female presenting with new abdominal distention, frequent bloody, mucoid, jelly-like diarrhea, and abdominal pain. Peritoneal fluid analysis showed neutrocytic ascites with low serum-ascites albumin gradient (SAAG). A diagnosis of pseudomembranous colitis was confirmed by flexible sigmoidoscopy. However, polymerase chain reaction (PCR) test for Clostridium difficile was negative. The patient was treated with metronidazole (500 mg IV q8h) and vancomycin (250 mg PO QID). Her symptoms resolved after several days of treatment with no ascites found by ultrasound. Neutrocytic ascites can be a complication of PMC. Physicians should also be aware that empirical treatment of Clostridium difficile may cause false negative diagnostic test result.

Metagenomic Analysis Reveals High Abundance of Torque Teno Mini Virus in the Respiratory Tract of Children with Acute Respiratory Illness.

Human Anelloviridae is a highly prevalent viral family, including three main genera—Alphatorquevirus (Torque teno virus, TTV), Betatorquevirus (Torque teno mini virus, TTMV), and Gammatorquevirus (Torque teno midi virus, TTMDV). To date, the characterization of Anelloviridae in the respiratory tract of children with acute respiratory infection (ARI) has been poorly reported and mainly focused on TTV. We performed a metagenomic analysis of eight respiratory samples collected from children with an ARI of unknown etiology (eight samples tested negative with a multiplex PCR assay, out of the 39 samples initially selected based on negative routine diagnostic testing). A total of 19 pediatric respiratory samples that tested positive for respiratory syncytial virus (RSV, n = 13) or influenza virus (n = 6) were also sequenced. Anelloviridae reads were detected in 16/27 samples, including 6/8 negative samples, 7/13 RSV samples and 3/6 influenza samples. For samples with a detection of at least one Anelloviridae genus, TTMV represented 87.1 (66.1–99.2)% of Anelloviridae reads, while TTV and TTMDV represented 0.8 (0.0–9.6)% and 0.7 (0.0–7.1)%, respectively (p < 0.001). Our findings highlight a high prevalence of TTMV in respiratory samples of children with an ARI of unknown etiology, as well as in samples with an RSV or influenza infection. Larger studies are needed to explore the role of TTMV in childhood respiratory diseases.

EP417: Exome sequencing unravels dual diagnoses and complex molecular etiologies in a family with prior negative diagnostic testing

Exome sequencing (ES) has recently been recommended as a first- or second-tier diagnostic test for individuals with developmental delay/intellectual disability and/or congenital anomalies, largely due to the high yield (approximately 34%) for identifying underlying genetic etiologies. Family-based testing strategies such as trio testing (proband plus parents) are typically suggested to aid in the interpretation of unclassified variants as this testing often yields many variants in each individual.

No infectious SARS-CoV-2 in breast milk from a cohort of 110 lactating women

BackgroundGenomic RNA of severe acute respiratory syndrome-associated coronavirus type 2 (SARS-CoV-2) has been detected in the breast milk of lactating women, but its pathological significance has remained uncertain due to the small size of prior studies.MethodsBreast milk from 110 lactating women was analyzed by reverse transcription-polymerase chain reaction (285 samples) and viral culture (160 samples). Those containing SARS-CoV-2 viral RNA (vRNA) were examined for the presence of subgenomic RNA (sgRNA), a putative marker of infectivity.ResultsSixty-five women had a positive SARS-CoV-2 diagnostic test, 9 had symptoms but negative diagnostic tests, and 36 symptomatic women were not tested. SARS-CoV-2 vRNA was detected in the milk of 7 (6%) women with either a confirmed infection or symptomatic illness, including 6 of 65 (9%) women with a positive SARS-CoV-2 diagnostic test. Infectious virus was not detected in any culture and none had detectable sgRNA. In control experiments, infectious SARS-CoV-2 could be cultured after addition to breastmilk despite several freeze–thaw cycles, as it occurs in the storage and usage of human milk.ConclusionsSARS-CoV-2 RNA can be found infrequently in the breastmilk after recent infection, but we found no evidence that breastmilk contains an infectious virus or that breastfeeding represents a risk factor for transmission of infection to infants.ImpactThis article goes beyond prior small studies to provide evidence that infectious SARS-CoV-2 is not present in the milk of lactating women with recent infection, even when SARS-CoV-2 RNA is detected.Recent SARS-CoV-2 infection or detection of its RNA in human milk is not a contraindication to breastfeeding.

349. Diagnostic Testing and Antibiotic Utilization in Patients with COVID-19

BackgroundPatients with COVID-19 receive high rates of antibiotic therapy, despite viral origin of infection. Reports of bacterial coinfection range from 3.5 to 8% in the early phase of infection. This study aimed to evaluate the relationship between diagnostic tests and antibiotic utilization in patients admitted with COVID-19 at the University of Maryland Medical Center to better inform future prescribing practices.MethodsRetrospective cohort study of adult patients with a positive SARS-CoV-2 PCR on admission from March 2020 through June 2020. Associations between diagnostic tests employed and antibiotic initiation and duration were explored using bivariate analysis (SPSS®). ResultsBaseline characteristics of 224 included patients are reported in Table 1. Excluding SARS-CoV-2 PCRs, most frequently performed diagnostic tests included blood cultures (65.6%), MRSA nasal surveillance (45.1%), respiratory cultures (36.2%), respiratory viral panel (RVP) (33.0%), and Legionella (28.6%) and pneumococcal (26.3%) urine antigens. Positivity of RVP, Legionella, pneumococcus, blood, and respiratory tests were low (1.3%, 0.4%, 0.9%, 1.8%, and 6.7%, respectively). A total of 62% of patients were initiated on antibacterial therapy with a median cumulative antibiotic duration of 77.9 hours (IQR 41.4, 111.8). History of chronic respiratory disease (76% vs. 58.6%; P=0.025), any degree of oxygen requirement on admission (72% vs. 42.6%; P=0.006), and performance of blood cultures (70.7% vs. 46.8%, P< 0.0001) were associated with antibiotic initiation. Positive bacterial diagnostic respiratory culture (median duration 72.8h [IQR 46.7, 96.6] vs. 97.3h [IQR 79.8, 194.1]; P=0.027) and positive blood culture (median duration 80.1h [IQR 42.1, 111.7] vs. 97.5h [IQR 71.8, 164.8]; P=0.046) were associated with longer antibiotic duration. Patients who did not have respiratory cultures performed had similar antibiotic durations as those with negative respiratory cultures.Table 1. Baseline Characteristics ConclusionDespite low coinfection rates, negative diagnostic tests did not result in shorter empiric antibacterial duration. These findings highlight the ongoing need for both diagnostic and antimicrobial stewardship in COVID-19. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

Prevention of SARS-CoV-2 transmission during a large, live, indoor gathering (SPRING): a non-inferiority, randomised, controlled trial

BackgroundMass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation.MethodsThe non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18–45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin <0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075.FindingsBetween May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09–0·40) and three of the 1947 non-attendees (0·15%; 0·03–0·45; absolute difference, 95% CI −0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint.InterpretationParticipation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2–transmission risk, provided a comprehensive preventive intervention was implemented.FundingFrench Ministry of Health.TranslationFor the French translation of the abstract see Supplementary Materials section.

Quadriceps Isometric Strength at 90° and 60° of Knee Flexion Following a Medial Meniscus Root Tear: A Case Report

Background Meniscus injury can significantly impair an individual's quality of life. Meniscus root disruption can more quickly lead to joint degradation than other types of meniscus injuries can. Existing clinical diagnostic testing specific to a meniscus root tear is insufficient. Case Presentation A 51-year-old man unknowingly tore a meniscus root repair, had negative diagnostic testing performed by his primary physical therapist, and subsequently underwent isometric quadriceps and functional testing 2 weeks after his reinjury. Differential diagnosis included bone, muscle, ligament, and general joint irritation from the injury. Outcome and Follow-Up Isometric quadriceps strength (measured as torque production) at 90° was significantly lower (8 times) than at 60° of knee flexion in the presence of a meniscus root tear. Discussion Diagnostic tests for the meniscus may not always be reliable when it comes to diagnosing a root tear. Strength testing at specific angles of knee flexion may be used as a potential clinical indicator that a root tear is present. JOSPT Cases 2021;1(4):268–272. doi:10.2519/josptcases.2021.10493

MP11-08 NEGATIVE MPMRI RULES OUT EXTRA-PROSTATIC EXTENSION IN PROSTATE CANCER BEFORE RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-08 NEGATIVE MPMRI RULES OUT EXTRA-PROSTATIC EXTENSION IN PROSTATE CANCER BEFORE RADICAL PROSTATECTOMY Eoin Dinneen, Jelena Banjeglav, Jamie Lindsay, John-Patrick Mulligan, Tom Strange, Dan Heffernan-Ho, Francesco Giganti, Briggs Tim, Senthil Nathan, Ashwin Sridhar, Jacques Grierson, Haider Aiman, Alex Freeman, Veeru Kasivisvanathan, Shaw Greg, and Shonit Punwani Eoin DinneenEoin Dinneen More articles by this author , Jelena BanjeglavJelena Banjeglav More articles by this author , Jamie LindsayJamie Lindsay More articles by this author , John-Patrick MulliganJohn-Patrick Mulligan More articles by this author , Tom StrangeTom Strange More articles by this author , Dan Heffernan-HoDan Heffernan-Ho More articles by this author , Francesco GigantiFrancesco Giganti More articles by this author , Briggs TimBriggs Tim More articles by this author , Senthil NathanSenthil Nathan More articles by this author , Ashwin SridharAshwin Sridhar More articles by this author , Jacques GriersonJacques Grierson More articles by this author , Haider AimanHaider Aiman More articles by this author , Alex FreemanAlex Freeman More articles by this author , Veeru KasivisvanathanVeeru Kasivisvanathan More articles by this author , Shaw GregShaw Greg More articles by this author , and Shonit PunwaniShonit Punwani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The accuracy of multi-parametric MRI (mpMRI) in pre-operative staging and recommending nerve-sparing in radical prostatectomy (RP) remains controversial. There is considerable heterogeneity in the performance and the reliability of mpMRI in predicting extra-prostatic extension (EPE), with reduced sensitivity identified as a key limitation in previous systematic reviews. The objective of this study was to evaluate the ability of expert genitourinary radiologists at a high-volume RP centre to predict prostate cancer EPE on a side-specific basis using a Likert scale. METHODS: We included 124 men who underwent robot-assisted RP (RARP) as part of the NeuroSAFE PROOF study at our centre (NCT03317990). Three genitourinary radiologists retrospectively reviewed mpMRI blinded to prostatectomy pathology results, assigned a Likert score of suspicion for EPE (1-5) for each side of the prostate on the basis of sequential MRI information and then after clinical information was revealed. We present the detection rates for EPE at each level of the Likert scale, test performance when Likert score is dichotomised, and the value of additional imaging and clinical information in EPE prediction. RESULTS: A total of 231 lobes from 121 men (mean age 56.9 years±7) were evaluated. 39 men (32.2%), or 43 lobes (18.6%) had EPE. 47.7% of lobes were assigned a Likert score 1-2 (i.e. had a negative diagnostic test). Detection rates of EPE increased with each increment in the Likert score assigned (Table 1, p<0.001). For detection of EPE, Likert score ≥3 had sensitivity, specificity, NPV, PPV of 90.2%, 52%, 96%, 29.1%, respectively. Kappa coefficient for agreement between radiologists on the final Likert was 0.62, 0.64, and 064 between readers 1&2, 1&3, and 2&3, respectively, indicating substantial agreement. Diagnostic accuracy improved as MRI sequences and clinical information were revealed. The AUCs for T2WI alone, +DWI, +DCE, +PSA, and +biopsy information, were 0.612 (CI; 0.55-0.674), 0.683 (CI: 0.624-0.741), 0.757 (CI: 0.704-0.810), 0.784 (CI: 0.734-0.833) and 0.813 (CI: 0.77-0.86), respectively. CONCLUSIONS: Likert score is a practical and simple system that can be used effectively by experienced readers to rule out EPE. We report high sensitivity, which is important as the clinical imperative to not miss EPE in order to provide best chance cure with RP. Diagnostic accuracy of EPE prediction using mpMRI improves with additional MRI sequences and with sight of clinical parameters, which emphasises the importance of biopsy information and the multidisciplinary team when using mpMRI for prostate cancer staging. Source of Funding: NeuroSAFE PROOF trial funded by a charitable grant from JP Moulton Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e180-e180 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eoin Dinneen More articles by this author Jelena Banjeglav More articles by this author Jamie Lindsay More articles by this author John-Patrick Mulligan More articles by this author Tom Strange More articles by this author Dan Heffernan-Ho More articles by this author Francesco Giganti More articles by this author Briggs Tim More articles by this author Senthil Nathan More articles by this author Ashwin Sridhar More articles by this author Jacques Grierson More articles by this author Haider Aiman More articles by this author Alex Freeman More articles by this author Veeru Kasivisvanathan More articles by this author Shaw Greg More articles by this author Shonit Punwani More articles by this author Expand All Advertisement Loading ...

Prevention of Sars-Cov-2 Transmission During a Large, Live, Indoor Gathering: The Noninferiority Randomised-Controlled Spring Trial

Background: Mass indoor gatherings were banned in early 2020 to prevent SARS-CoV-2 spread. We aimed to assess, under controlled conditions, whether systematic antigen-screening within 3 days, medical mask-wearing and optimized ventilation could prevent SARS-CoV-2 spread during a large, indoor gathering without physical distancing.Methods: The non-inferiority, prospective, open-label, randomized (2:1)-controlled SPRING trial was conducted on May 29, 2021 in Paris, France. Participants, 18–45 years old, had no comorbidities, COVID-19 symptoms and recent case contact, and a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated to the experimental arm (attendees) or to the control arm (non-attendees). The primary outcome measure was the number of SARS-CoV-2–positive RT-PCR on self-collected saliva 7 days (D7) post-gathering. An artificial intelligence tool analyzing anonymised, continuous video-capture data evaluated participants’ mask-wearing compliance. This trial is registered with ClinicalTrials.gov, NCT04872075.Findings: Among 6678 randomized participants (median age 28 years; 59% women), 88% of each group complied with follow-up requirements. The D7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0.20%; 95% Confidence Interval [CI], 0.09 to 0.40) and 3 of the 1,947 non-attendees (0.15%; 0.03 to 0.45) (absolute difference, 95%CI, –0.26% to +0.28%), findings that met the non-inferiority criterion (margin Interpretation: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2–transmission risk, provided a comprehensive preventive intervention was implemented.Trial Registration: This study was registered on ClinicalTrials.gov (NCT04872075).Funding: French Ministry of HealthDeclaration of Interest: All authors declare no competing interestsEthical Approval: The trial protocol was approved by the Scientific Ethics Committee of the Sud-Ouest and Outremer Regions of France and the French Data-Protection Agency

Migration-associated malaria from Africa in southern Spain

BackgroundThe western area of the province of Almeria, sited in southern Spain, has one of the highest immigrant population rates in Spain, mainly dedicated to agricultural work. In recent years, there has been a significant increase in the number of cases of imported malaria associated with migrants from countries belonging to sub-Saharan Africa. The objective of our study is to describe the epidemiological, clinical and analytical characteristics of malaria patients treated in a specialized tropical unit, paying special attention to the differences between VFR and non-VFR migrants and also to the peculiarities of microscopic malaria cases compared to submicroscopic ones.MethodsRetrospective observational study of migrants over 14 years of age with imported malaria treated from October 2004 to May 2019. Characteristics of VFR and non-VFR migrants were compared. Malaria cases were divided into microscopic malaria (MM) and submicroscopic malaria (SMM). SMM was defined as the presence of a positive malaria PCR test together with a negative direct microscopic examination and a negative rapid diagnostic test (RDT). Microscopic malaria was defined as the presence of a positive RDT and/or a positive smear examination.ResultsThree hundred thirty-six cases of malaria were diagnosed, 329 in sub-Saharan immigrants. Of these, 78.1% were VFR migrants, in whom MM predominated (85.2% of cases). In non-VFR migrants, SMM represented 72.2% of the cases. Overall, 239 (72.6%) patients presented MM and 90 (27.4%) SMM. Fever was the most frequent clinical manifestation (64.4%), mainly in the MM group (MM: 81.1% vs SMM: 20.0%; p < 0.01). The most frequent species was P. falciparum. Patients with SMM presented fewer cytopenias and a greater number of coinfections due to soil-transmitted helminths, filarial and intestinal protozoa compared to patients with MM.ConclusionsImported malaria in our area is closely related to sub-Saharan migration. VFR migrants are the main risk group, highlighting the need for actions aimed at improving disease prevention measures. On the other hand, almost a third of the cases are due to SMM. This fact could justify its systematic screening, at least for those travelers at greater risk.Graphical

MCAT Mutations Cause Nuclear LHON-like Optic Neuropathy

Pathological variants in the nuclear malonyl-CoA-acyl carrier protein transacylase (MCAT) gene, which encodes a mitochondrial protein involved in fatty-acid biogenesis, have been reported in two siblings from China affected by insidious optic nerve degeneration in childhood, leading to blindness in the first decade of life. After analysing 51 families with negative molecular diagnostic tests, from a cohort of 200 families with hereditary optic neuropathy (HON), we identified two novel MCAT mutations in a female patient who presented with acute, sudden, bilateral, yet asymmetric, central visual loss at the age of 20. This presentation is consistent with a Leber hereditary optic neuropathy (LHON)-like phenotype, whose existence and association with NDUFS2 and DNAJC30 has only recently been described. Our findings reveal a wider phenotypic presentation of MCAT mutations, and a greater genetic heterogeneity of nuclear LHON-like phenotypes. Although MCAT pathological variants are very uncommon, this gene should be investigated in HON patients, irrespective of disease presentation.

COVID-19 in patients with multiple sclerosis treated with cladribine tablets: An update

BackgroundWe previously summarized outcomes for 46 cladribine tablets (CladT)-treated patients with multiple sclerosis (MS) and confirmed or suspected COVID-19, as reported to the Merck KGaA Global Patient Safety Database. This report updates on these findings, to 15 January 2021, for a total of 272 reported cases of COVID-19 among CladT recipients. MethodsCase definitions: confirmed (COVID-19 diagnostic test was positive); suspected (no confirmatory test performed/reported). Cases fulfilling the criteria of hospitalized, medically significant, or fatal were designated as serious and outcomes were classified per usual pharmacovigilance practice. ResultsThe evaluable cohort comprised 261 patients (confirmed COVID-19, n=160; suspected, n=101); an additional 11 patients had symptoms compatible with COVID-19 but were not evaluated further given their negative diagnostic tests. Median time to onset of COVID-19 from the most recent preceding CladT treatment course was 162 days (n=139). Outcomes were: recovered/recovering, n=133 (51%); not recovered/not resolved, n=19 (7%); died, n=1 (0.4%); and not reported/missing/pending, n=108 (41%). Of the total cohort, 40 (15%) experienced serious COVID-19. ConclusionOur results suggest that CladT-treated patients with MS are generally not at greater risk of serious disease and/or a severe outcome with COVID-19 compared with the general population and other patients with MS who acquired COVID-19.

Development of a Simple Index to Measure Overuse of Diagnostic Testing at the Hospital Level Using Administrative Data.

We developed a diagnostic overuse index that identifies hospitals with high levels of diagnostic intensity by comparing negative diagnostic testing rates for common diagnoses. We prospectively identified candidate overuse metrics, each defined by the percentage of patients with a particular diagnosis who underwent a potentially unnecessary diagnostic test. We used data from seven states participating in the State Inpatient Databases. Candidate metrics were tested for temporal stability and internal consistency. Using mixed-effects ordinal regression and adjusting for regional and hospital characteristics, we compared results of our index with three Dartmouth health service area-level utilization metrics and three Medicare county-level cost metrics. The index was comprised of five metrics with good temporal stability and internal consistency. It correlated with five of the six prespecified overuse measures. Among the Dartmouth metrics, our index correlated most closely with physician reimbursement, with an odds ratio of 2.02 (95% CI, 1.11-3.66) of being in a higher tertile of the overuse index when comparing tertiles 3 and 1 of this Dartmouth metric. Among the Medicare county-level metrics, our index correlated most closely with standardized costs of procedures per capita, with an odds ratio of 2.03 (95% CI, 1.21-3.39) of being in a higher overuse index tertile when comparing tertiles 3 and 1 of this metric. We developed a novel overuse index that is preliminary in nature. This index is derived from readily available administrative data and shows some promise for measuring overuse of diagnostic testing at the hospital level.

Evidence that seasonal malaria chemoprevention with SPAQ influences blood and pre-erythrocytic stage antibody responses of Plasmodium falciparum infections in Niger

BackgroundIn endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger.MethodsThis research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes.ResultsThe analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p < 0.0001).ConclusionThe research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.

Malaria Screening Using Front-Line Loop-Mediated Isothermal Amplification.

We implemented front-line loop-mediated isothermal amplification (LAMP)-based malaria screening in our nonendemic multicenter health region to reduce reliance on microscopy without sacrificing diagnostic efficiency. We aimed to evaluate changes in test volumes, positivity rates, turnaround times, and approximate labor time savings resulting from implementation of LAMP-based malaria testing to assess the efficacy of the novel testing algorithm in our regional hub-and-spoke testing model. We reviewed data generated from institutional malaria testing between 2016 and 2019, having implemented LAMP in October 2018 as a front-line screening test for all malaria investigations from our hub facility and investigations from satellite facilities with negative rapid diagnostic tests (RDTs) and microscopy. Blood film microscopy and RDT workloads decreased substantially in the year following LAMP implementation (by 90% and 46%, respectively,) despite similar numbers of patients tested and positivity rates for malaria compared with historical data. LAMP turnaround times (TATs) were comparable to historical TATs for RDTs, and TATs for RDTs and thick films did not increase with the change in workflow. LAMP was successfully implemented in our multicenter health region malaria diagnostic algorithm, significantly reducing reliance on microscopic evaluations and RDT and providing substantial labor time savings without compromising TATs.

Correlation between Negative Rapid Influenza Diagnostic Test and Severe Disease in Hospitalized Adults with Laboratory-Confirmed Influenza Virus Infection.

.False-negative rapid influenza diagnostic test (RIDT) results could mislead physicians to exclude an influenza diagnosis. We sought to evaluate the association between negative RIDT and intensive care unit (ICU) admission. We reviewed data from hospitalized adults with laboratory-confirmed influenza virus infections in a tertiary referral hospital in Taiwan from July 2009 to February 2011. The diagnosis was documented by real-time PCR or virus culture. Of 134 hospitalized adults infected with influenza virus, 38 (28%) were admitted to the ICU. Compared with RIDT-positive patients, the percentage of ICU admission was significantly higher among RIDT-negative patients (46% versus 13%, P < 0.001). The RIDT-negative patients had higher percentages of lower respiratory symptoms and more chest radiograph infiltrates. The time interval between the RIDT and antiviral treatment was longer in RIDT-negative than RIDT-positive patients (1.94 days versus 0.03 days, P < 0.001). Among patients presenting with mild illness, only a negative RIDT and delayed antiviral treatment were associated with ICU admission after adjusting for potential confounding factors. To conclude, patients with a negative RIDT were more likely to have severe disease and a delay in initiating antiviral treatment. Our findings should help improve treatment outcomes of hospitalized patients with influenza infection.

Suboptimal Biological Sampling as a Probable Cause of False-Negative COVID-19 Diagnostic Test Results.

False-negative severe acute respiratory syndrome coronavirus 2 test results can negatively impact the clinical and public health response to coronavirus disease 2019 (COVID-19). We used droplet digital polymerase chain reaction (ddPCR) to demonstrate that human DNA levels, a stable molecular marker of sampling quality, were significantly lower in samples from 40 confirmed or suspected COVID-19 cases that yielded negative diagnostic test results (ie, suspected false-negative test results) compared with a representative pool of 87 specimens submitted for COVID-19 testing. Our results support suboptimal biological sampling as a contributor to false-negative COVID-19 test results and underscore the importance of proper training and technique in the collection of nasopharyngeal specimens.

Leukocytosis in Negative Malaria Rapid Diagnostic Test Febrile Illness Among Children Under Five Years in a District Hospital

Background: Definitive tests are not routinely available in Ghanaian district hospitals for diagnosing febrile illnesses among children under five years after excluding malaria with the rapid diagnostic test (RDT). Most of such febrile presentations are likely microbial. If an infection-induced WBC elevation is demonstrated consistently enough in such malaria-RDT negative febrile illnesses, it could become a diagnostic aid. Methods: Retrospective data from the clinical records were obtained for 432 children from 6 months to 5 years of age, who had presented with fever (temperature ≥ 37.5°C). Their respective WBC counts were also documented and statistical analysis of the data carried out. Results: A significant relationship was demonstrated between the malaria-RDT negative status and the patient’s elevated WBC count (P &lt; 0.001). Leukocytosis was absent in 58.6% of RDT-negative febrile children. Patients who tested RDT-negative were twice as likely to have elevated WBC counts (OR = 2.19) than RDT-positive patients. Conclusions: An elevated WBC count has demonstrated a potentially weak relationship with a negative malaria-RDT status among febrile children U-5 in DPH. Standing alone, however, the WBC may not be decisive for the evaluation of U-5 febrile presentations after excluding malaria.

1177 Cost Effectiveness Of Diagnostic Approaches To Sleep Apnea Evaluation During Inpatient Rehabilitation For Moderate To Severe TBI

Abstract Introduction Recent work has highlighted prevalent obstructive sleep apnea (OSA) after traumatic brain injury (TBI) when patients are vulnerable to disruption of neural repair. The recently completed clinical trial comparing screening and diagnostic tools for OSA during inpatient rehabilitation provided the opportunity to conduct economic modeling of phased approaches using actual trial findings to address one perspective (the payor) on the value of phased testing. Methods A cost-effectiveness analysis of four phased approaches to OSA diagnosis including initial utilization of portable sleep monitoring [HSAT] regardless of pre-test probability, determination of pre-test probability using two prediction models [STOPBANG, MAPI], and initial assessment using Level 1 polysomnography was conducted. The analyses were modeled assuming all participants were considered high risk thus a negative screen or portable diagnostic test would result in a participant being referred for Level 1 polysomnography. The cost aversion used in analyses were derived from a recent white paper on the economic modeling of untreated OSA. Trial data from 214 participants were used in analyses (mean age 44 [SD 18], 82% male, 75% white, with primarily motor-vehicle related injury [44%] and falls [33%] with a sample mean emergency department Glasgow Coma Scale of 8 (SD 5). Results At AHI ≥15 (33.6%), the prediction models (STOPBANG [-$5,291], MAPI [-$5,262]) resulted in greater cost savings and effectiveness relative to the HSAT approach (-$5,210) and initial use of Level 1 PSG (-$5,011). Sensitivity analyses at AHI ≥5 (70.1%) revealed the initial use of HSAT (-$6,322.85) relative to the prediction models (MAPI [-$6,249.71], STOPBANG [-$6,237) and initial assessment with Level 1 PSG (-$5,977) resulted in greater savings and cost effectiveness. Conclusion The high rates of sleep apnea after TBI highlight the importance of accurate diagnosis and treatment of this comorbid disorder. However, financial and practical barriers exist to obtaining an earlier diagnosis during inpatient rehabilitation hospitalization. Diagnostic cost savings are demonstrated across all phased approaches and OSA severity levels with the most cost-effective approach varying by incidence of OSA. Support PCORI (CER-1511-33005), GDHS (W91YTZ-13-C-0015; HT0014-19-C-0004)) for DVBIC, NIDILRR (NSDC Grant # 90DPTB00070, #90DP0084, 90DPTB0013-01-00, 90DPTB0008, 90DPT80004-02).

Rapid diagnostic tests failing to detect infections by Plasmodium falciparum encoding pfhrp2 and pfhrp3 genes in a non-endemic setting

BackgroundRapid diagnostic tests (RDTs) detecting the histidine-rich protein 2 (PfHRP2) have a central position for the management of Plasmodium falciparum infections. Yet, variable detection of certain targeted motifs, low parasitaemia, but also deletion of pfhrp2 gene or its homologue pfhrp3, may result in false-negative RDT leading to misdiagnosis and delayed treatment. This study aimed at investigating the prevalence, and understanding the possible causes, of P. falciparum RDT-negative infections at Montpellier Academic Hospital, France.MethodsThe prevalence of falsely-negative RDT results reported before and after the introduction of a loop-mediated isothermal amplification (LAMP) assay, as part as the malaria screening strategy in January 2017, was analysed. Negative P. falciparum RDT infections were screened for pfhrp2 or pfhrp3 deletion; and exons 2 were sequenced to show a putative genetic diversity impairing PfHRP2 detection.ResultsThe overall prevalence of P. falciparum negative RDTs from January 2006 to December 2018 was low (3/446). Whereas no cases were reported from 2006 to 2016 (0/373), period during which the malaria diagnostic screen was based on microscopy and RDT, prevalence increased up to 4.1% (3/73) between 2017 and 2018, when molecular detection was implemented for primary screening. Neither pfhrp2/3 deletion nor major variation in the frequency of repetitive epitopes could explain these false-negative RDT results.ConclusionThis paper demonstrates the presence of pfhrp2 and pfhrp3 genes in three P. falciparum RDT-negative infections and reviews the possible reasons for non-detection of HRP2/3 antigens in a non-endemic setting. It highlights the emergence of falsely negative rapid diagnostic tests in a non-endemic setting and draws attention on the risk of missing malaria cases with low parasitaemia infections using the RDT plus microscopy-based strategy currently recommended by French authorities. The relevance of a novel diagnostic scheme based upon a LAMP assay is discussed.