scholarly journals Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hygon Mutavhatsindi ◽  
Gian D. van der Spuy ◽  
Stephanus T. Malherbe ◽  
Jayne S. Sutherland ◽  
Annemieke Geluk ◽  
...  
Keyword(s):  
Point Of Care ◽  
Diagnostic Techniques ◽  
World Health ◽  
Hiv Positive ◽  
Prior History ◽  
Study Cohort ◽  
Serum Samples ◽  
Point Of Care Test ◽  
History Of ◽  
Triage Test

The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis (TB) is a priority in the global effort to combat this disease, particularly in resource-constrained settings. Previous studies have identified host biomarker signatures which showed potential, but there is a need to validate and refine these for development as a test. We recruited 1,403 adults presenting with symptoms suggestive of pulmonary TB at primary healthcare clinics in six countries from West, East and Southern Africa. Of the study cohort, 326 were diagnosed with TB and 787 with other respiratory diseases, from whom we randomly selected 1005 participants. Using Luminex® technology, we measured the levels of 20 host biomarkers in serum samples which we used to evaluate the diagnostic accuracy of previously identified and novel bio-signatures. Our previously identified seven-marker bio-signature did not perform well (sensitivity: 89%, specificity: 60%). We also identified an optimal, two-marker bio-signature with a sensitivity of 94% and specificity of 69% in patients with no history of previous TB. This signature performed slightly better than C-reactive protein (CRP) alone. The cut-off value for a positive diagnosis differed for human immuno-deficiency virus (HIV)-positive and -negative individuals. Notably, we also found that no signature was able to diagnose TB adequately in patients with a prior history of the disease. We have identified a two-marker, pan-African bio-signature which is more robust than CRP alone and meets the World Health Organization (WHO) target product profile requirements for a triage test in both HIV-negative and HIV-positive individuals. This signature could be incorporated into a point-of-care device, greatly reducing the necessity for expensive confirmatory diagnostics and potentially reducing the number of cases currently lost to follow-up. It might also potentially be useful with individuals unable to provide sputum or with paucibacillary disease. We suggest that the performance of TB diagnostic signatures can be improved by incorporating the HIV-status of the patient. We further suggest that only patients who have never had TB be subjected to a triage test and that those with a history of previous TB be evaluated using more direct diagnostic techniques.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.

scholarly journals Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Flaminia Olearo ◽  
Huyen Nguyen ◽  
Fabrice Bonnet ◽  
Sabine Yerly ◽  
Gilles Wandeler ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Antiviral Treatment ◽  
Composite Endpoint ◽  
Hiv Treatment ◽  
Hiv Positive ◽  
Prior History ◽  
History Of ◽  
The Impact ◽  
Hiv 1

Abstract Objective The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. Method This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. Results We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154–441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2–79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4–21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35–4.59 and HR 1.66; 95% CI, 0.81–3.43, respectively). Conclusions In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.

scholarly journals Detecting tuberculosis: rapid tools but slow progress

2019 ◽  
Vol 9 (3) ◽  
pp. 80-83
Author(s):  
K. England ◽  
T. Masini ◽  
E. Fajardo
Keyword(s):  
Point Of Care ◽  
Scale Up ◽  
Critical Issue ◽  
World Health ◽  
High Turnover ◽  
Low Resource Settings ◽  
Laboratory Staff ◽  
Low Resource ◽  
Point Of Care Test ◽  
Health Organization

The World Health Organization (WHO) currently recommends Xpert® MTB/RIF as the initial test for all people with presumptive tuberculosis (TB). A number of challenges have been reported, however, in using this technology, particularly in low-resource settings. Here we examine these challenges, and provide our perspective of the barriers to Xpert scale-up as assessed through a survey in 16 TB burden countries in which the Médecins Sans Frontières is present. We observed that the key barriers to scale-up include a lack of policy adoption and implementation of WHO recommendations for the use of Xpert, resulting from high costs, poor sensitisation of clinical staff and a high turnover of trained laboratory staff; insufficient service and maintenance provision provided by the manufacturer; and inadequate resources for sustainability and expansion. Funding is a critical issue as countries begin to transition out of support from the Global Fund. While it is clear that there is still an urgent need for research into and development of a rapid, affordable point-of-care test for TB that is truly adapted for use in low-resource settings, countries in the meantime need to develop functional and sustainable Xpert networks in order to close the existing diagnostic gap.

Ki-1 Positive Anaplastic Large Cell Lymphoma Due to Immune Deficiency.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4709-4709
Author(s):  
Monique Chang ◽  
Jennifer Kujawa ◽  
Michael Garrison ◽  
Alexander Hindenburg
Keyword(s):  
Immune Deficiency ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Case Reports ◽  
Large Cell ◽  
Hiv Positive ◽  
Prior History ◽  
Lymphoid Malignancy ◽  
History Of ◽  
Large Cell Lymphoma

Abstract Cases of Ki-1 positive anaplastic large cell lymphoma (ALCL), including ALK (t 2,5) positive and negative expression, have largely been associated with immunosuppressed transplant recipients, human immunodeficiency virus (HIV) positive patients and patients with a prior history of a lymphoproliferative disorder. We reviewed the literature and found cases of secondary Ki-1 positive ALCL in immunocompromised patients including patients with a prior history of lymphoid malignancy. Some of these latter cases may have been diagnosed initially as Hodgkin’s disease and later reclassified as Ki-1 positive ALCL. In post-transplant and HIV positive patients, severe and prolonged immunosuppression likely led to the development of Ki-1 positive ALCL. We postulate that although rare, the occurrence of Ki-1 positive ALCL in patients previously treated for a lymphoid malignancy is possible due to a pre-existing immune deficiency state. We report a case of ALK- ALCL occurring 10 years following treatment of HCL with persistent depressed T4/T8 ratio one year after achieving a complete remission of the ALCL. Secondary Cases of Ki-1 Anaplastic Large Cell Lymphoma Cases of Post-transplant Ki-1 Positive Anaplastic Large Cell Lymphoma Allograft # of Case Reports ALK (t 2,5) Renal 16 12 unknown, 4 positive Cardiac 3     1 negative, 2 positive Liver 1 1 positive Cases of Ki-1 Positive Anaplastic Large Cell Lymphoma in Patients With HIV or Treated with Immunosuppressants for Non-Malignant Disorders Cause of Immune Deficiency # of Case Reports ALK (t 2,5) HIV + 10 10 unknown Immunosuppressive tx for Evan’s syndrome 1 negative Azathioprine for Crohn’s Dz. 1 unknown Cases of Secondary Ki-1 Positive Anaplastic Large Cell Lymphoma in Patients Treated for Malignancy Primary Malignancy # of Case Reports ALK (t 2,5) Hodgkin’s Disease 3 3 unknown Hairy Cell Leukemia 2 1 unknown, 1 negative Mycosis Fungoides 2 2 unknown

scholarly journals Accuracy of Rapid Point-of-Care Antibody Test in patients with suspected or confirmed COVID-19

2020 ◽  
Author(s):  
Rama Vancheeswaran ◽  
Merlin L Willcox ◽  
Beth Stuart ◽  
Matthew Knight ◽  
Hala Kandil ◽  
...  
Keyword(s):  
Point Of Care ◽  
Antibody Test ◽  
Reference Laboratory ◽  
List Type ◽  
Reference Standard ◽  
Point Of Care Test ◽  
History Of ◽  
Antibody Tests ◽  
Composite Reference Standard ◽  
Rapid Antibody

AbstractObjectivesTo assess the real-world diagnostic accuracy of the Livzon point-of-care rapid test for antibodies to SARS-COV-2DesignProspective cohort studySettingDistrict general hospital in EnglandParticipants173 Patients and 224 hospital staff with a history of COVID-19 symptoms, and who underwent PCR and/or reference antibody testing for COVID-19.InterventionsThe Livzon point-of-care (POC) lateral flow immunoassay rapid antibody test (IgM and IgG) was conducted at least 7 days after onset of symptoms and compared to the composite reference standard of PCR for SARS-COV-2 plus reference laboratory testing for antibodies to SARS-COV-2. The SARS-CoV-2 RT-PCR was tested using the available molecular technology during the study time (PHE laboratories, GeneXpert® system Xpert, Xpress SARS-CoV-2 and Source bioscience laboratory). All molecular platforms/assays were PHE/NHSE approved. The reference antibody test was the Elecsys Anti-SARS-CoV-2 assay (Roche diagnostics GmBH).Main outcome measuresSensitivity and specificity of the rapid antibody testResultsThe reference antibody test was positive in 190/268 (70.9%) of participants with a history of symptoms suggestive of COVID-19; in the majority (n=312) the POC test was taken 35 days or more after onset of symptoms. The POC antibody test had an overall sensitivity of 90.1% (292/328, 95% CI 86.3 – 93.1) and specificity of 100% (68/68, 95% CI 94.7 - 100) for confirming prior SARS-CoV-2 infection when compared to the composite reference standard. Sensitivity was 97.8% (89/92, 95% CI 92.3% to 99.7%) in participants who had been admitted to hospital and 84.4% (124/147, 95% CI 77.5% to 89.8%) in those with milder illness who had never been seen in hospital.ConclusionsThe Livzon point-of-care antibody test had comparable sensitivity and specificity to the reference laboratory antibody test, so could be used in clinical settings to support decision-making about patients presenting with more than 10 days of symptoms of COVID-19.What is already known on this topic-Presence of IgG and IgM antibodies to SARS-COV-2 indicates that the person was infected at least 7 days previously and is usually no longer infectious.-Rapid point-of-care tests for antibodies to SARS-COV-2 are widely available, cheap and easy to use-Preliminary evaluations suggested that rapid antibody tests may have insufficient accuracy to be useful for testing individual patients.What this study adds-The rapid point-of-care test for antibodies to SARS-COV-2 was 90.1% sensitive and 100% specific compared to reference standards for prior infection with COVID-19.-This is comparable to reference antibody tests-The point-of-care test evaluated in this study could be used to support clinical decision-making in real time, for patients presenting with symptoms of possible COVID-19 with at least 10 days of symptoms.

scholarly journals Need for Intrapartum Antibiotic Prophylaxis in Women with Prior History of Group B Streptococcus Carriage

2021 ◽  
Vol 5 (2) ◽  
Keyword(s):  
Antibiotic Prophylaxis ◽  
Point Of Care ◽  
Neonatal Infection ◽  
University Hospital ◽  
Prior History ◽  
Point Of Care Testing ◽  
Benzyl Penicillin ◽  
Intrapartum Antibiotic Prophylaxis ◽  
History Of ◽  
Intrapartum Antibiotic

The incidence of early onset neonatal GBS(EOGBS) disease in the UK and Ireland is 0.57/1000 births. Intrapartum antibiotic prophylaxis (IAP) reduces the risk. Previous colonisation is associated with 50% carriage in the current pregnancy. In these women, RCOG recommends IAP with a history of neonatal infection, otherwise offering the option of screening at 35-37 weeks. In Ireland, there is no national consensus on IAP in prior GBS colonisation. Currently at University Hospital Waterford (UHW), all women with prior GBS colonisation receive IAP. Studies examining the use of point-of-care testing have shown reduction in the use of IAP and EOGBS rates. We aimed to examine the screening and IAP administration in maternal prior GBS colonisation and the incidence of GBS in this cohort in UHW. Data was collected retrospectively from laboratory, medical records and electronic patient manager systems. Women who received IAP between 1stJuly 2020 and 31stDecember 2020 were identified. Women who received IAP for current and prior GBS colonisation were included. Women who received IAP for preterm labour, preterm prelabour rupture of membranes and pyrexia in labour were excluded. Ninety-two women with current or prior GBS colonisation received IAP, of which only 15(16.30%) were current and 77(83.69%) were prior GBS colonisation. In women with prior GBS colonisation, 49(63.63%) were screened, 3/49(6.12%) were positive, 28 were not screened. Seventy-eight (84.78%) received benzyl-penicillin. Six (6.52%) received clindamycin. Twenty-two (23.91%) babies were admitted to the Neonatal Unit, however, only one cultured positive for gram-positive cocci. The incidence of EOGBS in this cohort is low. A risk-based approach or point-of-care testing should be considered to reduce unnecessary IAP administration.

Evaluation of the Alere Pima™ for CD4+ T lymphocytes counts in HIV-positive outpatients in Southern Brazil

2014 ◽  
Vol 25 (13) ◽  
pp. 956-959 ◽  
Author(s):  
L Rathunde ◽  
GMB Kussen ◽  
MP Beltrame ◽  
LM Dalla Costa ◽  
SM Raboni
Keyword(s):  
Flow Cytometry ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Predictive Value ◽  
Opportunistic Infections ◽  
Point Of Care ◽  
High Sensitivity ◽  
Hiv Positive ◽  
Point Of Care Test ◽  
Patients At Risk

CD4 + lymphocyte counts are routinely ordered during the early phases of antiretroviral therapy and for prophylaxis of opportunistic infections in HIV-positive patients. Flow cytometry is the standard methodology for CD4 counts in Brazilian reference laboratories. However, these laboratories are located in large cities, frequently distant from patients, thus limiting patient access and delaying results. We compared a point-of-care test with flow cytometry determination of CD4+ T lymphocyte counts in HIV patients. We analysed 107 consecutive samples by both methods. Overall, the point-of-care test performed well, with excellent agreement between it and the standard method. Test results were concordant for patients with CD4+ T lymphocyte values above and below 200 cells/mm 3. The performance characteristics obtained were sensitivity 94% (95% CI 89.5–98.5%), specificity 93% (95% CI 88.2–97.8%), positive predictive value 86% (95% CI 79.4–92.6%), and negative predictive value 97% (95% CI 94–100%). The high sensitivity and specificity of the point-of-care test methodology suggest its utility as an alternative method for rapid measurement of CD4+ T lymphocytes in patients with limited access to reference laboratories, enabling prompt therapeutic intervention for patients at risk of progression to AIDS.

scholarly journals Subclinical imaging changes in cerebral cavernous angiomas during prospective surveillance

2020 ◽  
pp. 1-8
Author(s):  
Julián Carrión-Penagos ◽  
Hussein A. Zeineddine ◽  
Sean P. Polster ◽  
Romuald Girard ◽  
Seán B. Lyne ◽  
...  
Keyword(s):  
Surgical Intervention ◽  
Maximum Diameter ◽  
Prior History ◽  
Study Cohort ◽  
Prospective Surveillance ◽  
Cavernous Angiomas ◽  
Surrogate Outcome ◽  
Institutional Review ◽  
History Of

OBJECTIVEThe purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease.METHODSOne hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board–approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed.RESULTSThere were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC.CONCLUSIONSRates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.

scholarly journals The Use of Antigenic SARS-CoV-2 Point-of-Care Test: The Italian Pediatric Real-Life Experience

2021 ◽  
pp. 000992282110539
Author(s):  
Federica Ferrari ◽  
Fortunata Civitelli ◽  
Francesca Ardenti Morini ◽  
Federico Angelo Carmelo Buonaiuto ◽  
Gianluca Frega ◽  
...  
Keyword(s):  
Life Experience ◽  
Close Contact ◽  
Point Of Care ◽  
Pediatric Population ◽  
Real Life ◽  
Gastrointestinal Symptoms ◽  
Point Of Care Test ◽  
Large Numbers ◽  
History Of ◽  
Acute Rhinitis

In Italy, during the second epidemic wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapid antigenic (Ag) test at point-of-care (POCT) station were employed to quickly evaluate large numbers of swabs. We collected data of all children who underwent the Ag test in our hospital. All positive patients were recalled to perform reverse transcription polymerase chain reaction. A total of 2133 tests were collected over 1 month. Clinical data of 1941 children (median age = 3.7 years) were analyzed: 1343 (69.2%) patients complained of symptoms, 594 (30.6%) had a history of close contact with SARS-CoV-2-positive individuals. Among symptoms reported, acute rhinitis was the most frequent (67.9%), followed by cough (42.6%) and fever (31.5%). Among all tests, 95.8% resulted negative, 4.2% positive: 37/89 were confirmed. In confirmed cases, fever (56.2% vs 32.2%; P = .041) and gastrointestinal symptoms (18.8% vs 6.25%; P = .041) were significantly more frequent compared with negative children. The use of POCT for Ag test seems appropriate for SARS-CoV-2 screening in the pediatric population. In children, fever and gastrointestinal symptoms may constitute red flags of SARS-CoV-2.

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