Sensitivity and specificity of the new Bio-Rad HIV screening test, Access HIV combo V2.

Diagnosing of human immunodeficiency virus (HIV) types 1 and 2 requires a screening with a highly sensitive and specific enzyme immunoassay and a low detection limit for the HIV-1 p24 antigen to minimize the diagnostic window. The objective of the study was to determine the sensitivity, specificity, and p24 limit of detection of the Access HIV combo V2 assay. Retrospective part of sensitivity: 452 HIV-1 positive samples from 403 chronic (9 different HIV-1 group M subtypes, 22 different HIV-1 group M CRFs, and 3 HIV-1 group O), 49 primary HIV-1 infections, 103 HIV-2 positive samples assessed at Pitié-Salpêtrière Hospital, 600 untyped HIV-1, 10 subtype-D, and 159 untyped HIV-2 samples assessed in Bio-Rad Laboratories. Prospective part of clinical specificity: all consecutive samples in two blood donor facilities and Pitié-Salpêtrière (6,570 patients) tested with Access HIV combo V2 and respectively Prism HIV O Plus (Abbott) or Architect HIV Ag/Ab Combo (Abbott) for Ag/Ab screening, and Procleix Ultrio (Gen Probe) for HIV RNA screening. Limit of detection for p24 antigen was assessed on recombinant virus-like particles (10 HIV-1 group M subtypes/CRFs, HIV-1 group O). Sensitivity [95% confidence interval (CI)] of Access HIV combo V2 was 100% (99.63-100) for HIV-1 chronic infection, 100% (98.55-100) for HIV-2 chronic infection, and 100% (93.00-100) for HIV-1 primary infection. Specificity (95% CI) was 99.98 (99.91-100). Limit of detection for p24 antigen was around 0.43 IU/mL [interquartile range (0.38-0.56)], and consistent across the 11 analyzed subtypes/CRFs. Hence, with both high sensitivity and specificity, Access HIV combo V2 is a suitable screening assay for HIV-1/2 infection. IMPORTANCE: Bio-Rad is one of the leading human immunodeficiency virus (HIV) screening test manufacturers. This laboratory released in 2021 their new version of the Access combo HIV test. However, to date, there have been no studies regarding its performance, especially its limit of detection of the diverse p24 antigen. We present the sensitivity (chronic and primary HIV-1 infection and HIV-2 chronic infection), specificity (blood donors and hospitalized patients), and raw data for the p24/seroconversion panels the manufacturer gave to the European agencies.

Fourth-Generation HIV Rapid Tests: Enhanced Sensitivity and Reduced Diagnostic Window for HIV-1 Primary Infection Screening.

As most HIV rapid tests (HRT) detect only HIV-1/2 antibodies, their performance during primary HIV infection is poor. Determine HIV Early detect (Abbott) (Determine) is the only HRT with an HIV-1 p24-antigen detection, but the impact of this addition in shortening the diagnostic window remains unclear. A total of 183 HIV-1 primary infection samples were tested using the HRTs Determine and ONE STEP anti-HIV (1&2) Test (InTec Products) (One-Step). The pre-seroconversion subgroup was defined as p24-antigen positivity without Western blot nor Liaison XL (fouth generation enzyme immunoassay with distinct signal for p24-antigen and HIV-1 antibody) HIV-1 antibodies. Global sensitivity (95% CI) was 95% (91-97) for Determine versus 80% (74%-85%) for One-Step (difference p = 1.38e-06). Pre-seroconversion subgroup sensitivity was lower, at 71.9 (54.6%-84.4%) for Determine and 9.7% (3.3%-24.9%) for One-Step. Among the 45 samples with an HIV-1 infection date, no HRT was reactive up to 2 weeks. Between 2 and 3 weeks, Determine sensitivity was 78% (45%-95%) versus 56% (27%-81%) for One-Step. From 3 weeks to 1 month Determine sensitivity was 90% (62%-98%) and One-Step 45% (21%-72%). The last negative sample occurred at 3 weeks for Determine versus 70-90 days for One-Step. HRT with p24-antigen detection significantly shortens the diagnostic window from approximatively 3 months to 1 month. HRTs should be used with caution in the first month after HIV infection.

Rapid tests should be used with caution for HIV-1 primary infection screening.

Rapid tests allow outpatient, low cost, reliable, screening for chronic HIV infection. However, data regarding their sensitivity on primary infection remain scarce. The objective of this study was to assess sensitivity of nine HIV rapid tests for primary HIV-1 infection screening. Seventy-five serum samples from patients during HIV-1 primary infection were included. Primary infection was diagnosed by a positive 4th generation ELISA and HIV-1 RNA positivity confirmed by Western blot patterns associated with HIV-1 primary infection. Early seroconversion was defined as the absence of antibodies on HIV-1 Western blot associated with HIV-1 RNA and p24-antigen positivity. An identical sensitivity (95% CI) of 76.7% (65.2-84.2%) was observed for HIV 1/2 STAT-PAK® Assay (STAT-PAK), INSTI™ HIV-1/HIV-2 antibody Test (INSTI), SURE CHECK® HIV 1/2 (SURE CHECK) and MULTISURE HIV rapid test (MULTISURE) with visual reading. Sensitivity was 74.7% (63.8-83.1%) for MULTISURE (automatic reading), 77.0% (66.3-85.1%) for FIRST RESPONSE® Test VIH 1-2.O CARTE (FIRST RESPONSE), 83.8% (73.8-90.5%) for VIKIA HIV1/2® (VIKIA), 88.0% (78.7-93.6%) for Genie™ Fast HIV 1/2 (Genie Fast), 88.6% (79.0-94.1%) for Hexagon HIV (Hexagon), and 92.8% (83.6-96.3%) for Exacto® TEST HIV Pro (Exacto). However, rapid tests performed poorly for the early seroconversion subgroup (n = 14), with sensitivities ranging from 7% (1.3-31.5%) for STAT-PAK, INSTI, SURE CHECK, MULTISURE (automatic reading), to 29% (12-55%) for FIRST RESPONSE, 31% (13-58%) for VIKIA, 43% (21-67%) for Hexagon and 57.1% (32.6-78.6%) for Exacto and Genie Fast. Overall, despite significant discrepancies in sensitivity, HIV rapid tests should be used with caution in the context of a suspected primary infection.

A novel high-performance rapid screening test for the detection of total HTLV-I and HTLV-II antibodies in HTLV-I/II infected patients.

Rapid diagnosis of human T-cell lymphotropic virus (HTLV) type-I and -II infections are essential for timely and cost-effective disease interventions. MP Diagnostics ASSURE HTLV-I/II Rapid Test was developed for the rapid detection of anti-HTLV-I/II antibodies in patients' serum, plasma, and whole blood specimens. ASSURE HTLV-I/II Rapid Test employed MP Biomedicals' proprietary HTLV-I/II Trifusion recombinant antigen conjugated with gold nanoparticles and HTLV-I / HTLV-II recombinant antigens immobilized on the nitrocellulose membrane to detect total HTLV-I and HTLV-II antibodies. The overall performance of the ASSURE HTLV-I/II Rapid Test was found to be 99.42% sensitivity (95% Confidence Interval, 98.32-99.88%) and 100% specificity (95% Confidence Interval, 99.58-100.00%) in the tested clinical samples, including a total of 518 HTLV-I/II positive specimens (396 HTLV-I infection, 97 HTLV-II infection and 25 HTLV-I/II dual infection) and 872 HTLV negative clinical specimens consisting of 691 healthy donor samples, 116 potentially cross-reactive samples, and 65 samples with interfering substances. The ASSURE HTLV-I/II Rapid Test can effectively be deployed as a screening tool in any prevalence studies, blood banks or organ transplant centres.

Are Confirmatory Assays Reliable for HIV-1/HIV-2 Infection Differentiation? A Multicenter Study.

Immunoblots remain the gold standard for HIV-1/HIV-2 infection confirmation. However, their ability to differentiate HIV-1 from HIV-2 infection on an antigenically diversified HIV-1 and HIV-2 panel remain uncommon. We performed a multicenter study on 116 serum samples accounting for most of the diversity of HIV-1 (9 different subtypes in group M, 17 circulating recombinant forms (CRFs), and 3 group O) and HIV-2 (groups A and B), evaluating seven confirmatory assays (six commercially available assays and one in-house assay) with genotyping as the reference. The assays were INNO-LIA HIV I/II score, HIV-2 blot 1.2, HIV blot 2.2, New Lav blot I and II, Geenius, and an in-house serotyping enzyme-linked immunosorbent assay (ELISA). Among the HIV-1 samples, INNO-LIA, HIV blot 2.2, New Lav blot I, Geenius, and serotyping had comparable high sensitivities, from 98% to 100%, whereas HIV-2 blot 1.2 and New Lav blot II had high rates of "undetermined" results (85% and 95%, respectively). HIV-2 blot 1.2 and New Lav blot II misclassified 7% and 5% of HIV-1 samples as HIV-2, respectively, and HIV-2 blot 1.2 had an 8% false-negative rate. Among the HIV-2 samples, INNO-LIA, New Lav blot II, HIV-2 blot 1.2, and serotyping had high sensitivities, from 96% to 100%. HIV blot 2.2 misclassified 17% of HIV-2 samples as HIV-1/HIV-2 dual infections. New Lav blot I misclassified 19% of HIV-2 samples as HIV-1 with a high (81%) undetermined rate, and Geenius misclassified 2% as HIV-1 and 7% as untypeable HIV positive. For HIV-1/HIV-2 dual infection, the results were less sensitive, with at most 87.5% for INNO-LIA and Geenius and 75% for HIV blot 2.2 and serotyping. Overall, confirmatory assays remain useful for most cases, with the exception of HIV-1/HIV-2 dual-infection suspicion.

CLIPPERS and its mimics: evaluation of new criteria for the diagnosis of CLIPPERS.

OBJECTIVE: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). METHODS: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria. RESULTS: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement ( ≥ 3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥ 30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma. CONCLUSIONS: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥ 30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.

Detection of varicella zoster virus DNA in blood from immunocompromised patients during the week preceding the onset of herpes zoster rash.

OBJECTIVE: To assess whether varicella zoster virus (VZV) DNA can be detected in blood before herpes zoster (HZ) rash onset. METHOD: Monocentric retrospective study from January 2019 to March 2023 including patients with HZ and stored blood samples performed during the week preceding the onset of HZ rash. Blood samples were retrospectively analyzed for VZV DNA by quantitative PCR. RESULTS: Among the 138 patients with HZ during the study period, stored blood samples performed during the week preceding the onset of HZ rash were available for 13 of them. Twelve (92 %) patients were immunosuppressed, mostly due to solid organ transplantation (38 %), solid malignancy (31 %) or autoimmune disease (23 %). During the week preceding HZ onset, VZV DNA was detected in blood from 10 (77 %) patients, with a median value of 3.6 log (copies/mL) (IQR 3.3-3.9). At the time of HZ onset, all VZV PCR performed in available blood samples were positive. CONCLUSION: Our findings demonstrates that VZV DNA can be commonly detected in blood from immunocompromised patients during the prodromal phase of HZ. Early screening of VZV DNA in blood from high-risk immunocompromised patients might improve HZ therapeutic management.

Prevalence and clinical relevance of VZV lung detection in intensive care unit: A retrospective cohort study.

OBJECTIVE: To assess the clinical relevance of varicella zoster virus (VZV) lung detection among patients hospitalized in intensive care unit (ICU). METHODS: We present a monocentric retrospective cohort study from 2012 to 2020. VZV genome was detected in bronchoalveolar lavage (BAL) fluid by real-time PCR. RESULTS: Twelve of 1389 (0.8%) patients exhibited VZV lung detection, corresponding to an incidence of 13.4 (95% confidence interval [CI] 5.8-21.0) per 100 person-years. Immunosuppression and prolonged ICU stay constituted the main risks factors. VZV detection was not associated with pulmonary deterioration but associated with a risk of shingles occurrence during the following days. CONCLUSION: VZV lung detection is a rare event among ICU patients, occurring mostly in immunocompromised patients with prolonged ICU stay. Due to its scarcity and the lack of association with pulmonary failure, a targeted approach to the VZV lung detection diagnosis may allow a significant cost saving without affecting the quality of patients care.

Comparison of two new HTLV-I/II screening methods, Abbott Alinity i rHTLV-I/II and Diasorin LIAISON® XL murex recHTLV-I/II, to Abbott architect rHTLVI/II assay.

BACKGROUND: Diagnosis of Human T-cell Lymphotropic Virus (HTLV) types I and II infection requires sequencial testing with firstly a screening using an Enzyme immunoassay followed by a confirmatory test. OBJECTIVES: To compare the performances of the Alinity i rHTLV-I/II (Abbott®) and LIAISON® XL murex recHTLV-I/II serological screening tests to the ARCHITECT rHTLVI/II test followed if positive by HTLV BLOT 2.4, MP Diagnostics as the reference. STUDY DESIGN: 119 serum samples from 92 known HTLV-I infected patients and 184 from uninfected patients with HTLV were analyzed in parallel with, Alinity i rHTLV-I/II, LIAISON® XL murex recHTLV-I/II and ARCHITECT rHTLVI/II. RESULTS: Alinity i rHTLV-I/II and LIAISON® XL murex recHTLV-I/II exhibited a total agreement with ARCHITECT rHTLVI/II for both positive and negative samples. Both tests are suitable alternatives for HTLV screening.

Herpesviridae lung reactivation and infection in patients with severe COVID-19 or influenza virus pneumonia: a comparative study.

BACKGROUND: Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. METHODS: Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. RESULTS: Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. CONCLUSIONS: HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

Depressive-, Cognitive- or Stroke-Related Risk Factors of Post-Stroke Depression: Which One Could Better Help Clinicians and Patients?

PURPOSE: Post-stroke depression (PSD) affects one third of stroke survivors, with multiple severe negative consequences. We aim to assess the weight of four different types of clinical risk factors for PSD. PATIENTS AND METHODS: We conducted a prospective cohort study in a stroke centre. After stroke, patients were assessed for cognitive performances, psychiatric standardized questionnaires and socio-demographic features. They were called three months after and assessed for major depressive episode using DSM criteria. RESULTS: PSD was diagnosed in 8 of the 59 (13.6%) patients enrolled in the study. After multivariate analysis, only "previous history of depressive episode" remained a significant predictive factor for PSD, the model explaining 19% of the total variance (OR=18.0; p=0.002). Patients with a previous history of depression had a 10-fold increased risk for PSD. CONCLUSION: Previous history of depression is confirmed as a strong risk factor for PDS and allow the identification of an at-risk sub-group of patients.

Triggers of ischemic stroke: a systematic review.

BACKGROUND AND PURPOSE: Several studies have suggested that exposure to "triggers," could precipitate the onset of ischemic stroke (IS). We performed a systematic review of the potential triggers of IS. METHODS: Two independent reviewers identified studies published between January 1980 and June 2010 from MEDLINE and Embase. Where appropriate, odds ratios (ORs) were combined. RESULTS: A total of 26 studies identified 12 potential triggers. Twenty-two studies used a case-control design, and hazard period durations ranged from 2 hours to 3 months. The majority of studies were dedicated to alcohol abuse (n = 10) and clinical infection (n = 12). There was a significant association between IS and alcohol abuse of > 40 to 60 g within the preceding 24 hours (OR = 2.66; 95% CI, 1.54 to 4.61) or > 150 g within the previous week (OR = 2.47; 95% CI, 1.52 to 4.02) and infection within the previous week (OR = 2.91; 95% CI, 1.41 to 6.00) or within the previous month (OR = 2.41; 95% CI, 1.78 to 3.27). Other triggers have been far less investigated. There was a significant association between IS and anger, heavy eating, negative or positive emotions, sudden posture change in response to a startling event, birthday, and psychological distress and no significant association with drug abuse or heavy physical exertion. Regarding methodological issues, patients were rarely blinded to study objectives, and interviewers were rarely blinded to patient status. CONCLUSIONS: Research on triggers of IS has been mainly focused on acute alcohol abuse and clinical infection. More research is needed on factors such as physical exertion or acute stress. Future studies should use more appropriate designs and examine different hazard periods.

Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients.

BACKGROUND: Paired associative stimulation (PAS) combining peripheral nerve and transcranial magnetic stimulation (TMS) have been proposed to induce long-term changes in excitability of the cerebral cortex and potentially optimize motor recovery in stroke patients. OBJECTIVE: This pilot study examined whether short-lasting changes in cortical excitability could be induced by a single session of PAS within the first months after stroke. METHODS: Six hemiparetic patients with a subcortical stroke were included. The single session PAS protocol was applied at 1, 5, and 12 months after stroke. During the follow-up, the clinical recovery of wrist function was assessed in parallel to the PAS study by the Fugl-Meyer motor scale and dynamometry of wrist extension. RESULTS: The PAS protocol induced a significant extensor carpi radialis motor evoked potential facilitation (mean +78.5%) on the paretic side 5 months after stroke. The facilitation was still present 12 months after stroke but on average smaller (+30 %). CONCLUSIONS: These electrophysiological findings suggest that patients with subcortical infarcts may respond to PAS in an earlier than later period after stroke. If the clinical efficacy of interventions such as PAS is confirmed, it could be proposed early as add-on therapy to optimize training-induced plasticity processes.

Does dystonic muscle activity affect sense of effort in cervical dystonia?

BACKGROUND: Focal dystonia has been associated with deficient processing of sense of effort cues. However, corresponding studies are lacking in cervical dystonia (CD). We hypothesized that dystonic muscle activity would perturb neck force control based on sense of effort cues. METHODS: Neck extension force control was investigated in 18 CD patients with different clinical features (7 with and 11 without retrocollis) and in 19 control subjects. Subjects performed force-matching and force-maintaining tasks at 5% and 20% of maximum voluntary contraction (MVC). Three task conditions were tested: i) with visual force feedback, ii) without visual feedback (requiring use of sense of effort), iii) without visual feedback, but with neck extensor muscle vibration (modifying muscle afferent cues). Trapezius muscle activity was recorded using electromyography (EMG). RESULTS: CD patients did not differ in task performance from healthy subjects when using visual feedback (ANOVA, p>0.7). In contrast, when relying on sense of effort cues (without visual feedback, 5% MVC), force control was impaired in patients without retrocollis (p = 0.006), but not in patients with retrocollis (p>0.2). Compared to controls, muscle vibration without visual feedback significantly affected performance in patients with retrocollis (p<0.001), but not in patients without retrocollis. Extensor EMG during rest, included as covariate in ANOVA, explained these group differences. CONCLUSION: This study shows that muscle afferent feedback biases sense of effort cues when controlling neck forces in patients with CD. The bias acts on peripheral or central sense of effort cues depending on whether the task involves dystonic muscles. This may explain why patients with retrocollis more accurately matched isometric neck extension forces. This highlights the need to consider clinical features (pattern of dystonic muscles) when evaluating sensorimotor integration in CD.