Avidity Assay Research Articles

Measles immunity status in Iranian infants and children and outbreak concerns: Time for reconsidering the vaccination schedule?

Introduction: Measles vaccination has greatly reduced the disease burden worldwide, but challenges remain due to variations in vaccine effectiveness across age groups. This study aimed to assess the serological profile of measles antibodies across different age groups, evaluate the impact of maternal immunity on antibody levels in infants under 12 months, and assess measles immunity in vaccinated individuals. Material and methods: This cross-sectional study was conducted from June 2022 to January 2023 at the Children’s Medical Center, a referral hospital in Iran. Serum samples were tested for measles-specific IgG and IgM antibodies using a commercial enzyme-linked immunosorbent assay (ELSA). An avidity assay was performed to assess measles virus-specific IgG antibodies on the samples that were positive and borderline for the measles IgG ELISA. Results: The study included 969 participants across various age groups. Among them, 23% (221 out of 953) tested positive for measles IgM ELISA, and 52% (504 out of 969) for measles IgG ELISA. Regarding the avidity assay for measles virus-specific IgG, the majority (418 out of 573, 73%) showed high-avidity antibodies. Measles-specific IgG levels varied significantly across different age groups, with infants below 6 months old showing a mean IgG level of 477 mIU/mL, declining to 230 mIU/mL between 6 and 12 months, and increasing significantly to 683 mIU/mL in the 12 to 18 month age group, reaching a peak at 938 mIU/mL among children aged 18–72 months. Conclusion: The increasing IgM positivity among young Iranians suggests a rising risk of measles outbreaks, possibly due to vaccination gaps. Inadequate antibody levels in infants raise concerns about vaccination effectiveness. Considering declining maternal antibodies, vaccinating infants at 6–9 months could be beneficial. Boosters for adolescents and women may further mitigate outbreak risks.

COMPARISON SEROPREVALENCE OF TOXOPLASMA GONDII, RUBELLA, AND CYTOMEGALOVIRUS IN MUŞ PROVINCE BEFORE AND DURING THE COVID-19 PANDEMİC

The aim of this study is to determine the seroprevalence of Toxoplasma gondii (T. gondii), rubella and cytomegalovirus (CMV) and the primary infection rates of these agents with avidity test in pregnant women in Muş province. Additionally, the effect of prevention and protection measures implemented during the Covid-19 pandemic on the prevalence of T. gondii, rubella and CMV in pregnant women was also investigated. Between 2018 and 2021, IgG and IgM antibodies in the serum samples of pregnant women who applied to the Department of Gynecology and Obstetrics polyclinic of Muş State Hospital were examined by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA). High and low avidity assays were examined by enzyme linked fluorescence assay (ELFA). Low seroprevalence of T. gondii IgG antibody (28%) and the detection of low avidity detection in 38 of 102 pregnant women indicate that this parasite may be a risk for intrauterine life. Rubella IgG (89%) and CMV IgG (99%) antibodies were found to carry a low risk due to their high seroprevalence and avidity. It was determined that Covid-19 prevention and protection measures caused a significant decrease in the prevalence of rubella and CMV, but had no effect on the prevalence of T.gondii.

Comparative functional characterization and in vitro immunological cross-reactivity studies on Daboia russelii and Craspedocephalus malabaricus venom.

Snake venom is a complex mixture of organic and inorganic constituents, including proteins and peptides. Several studies showed that antivenom efficacy differs due to intra- and inter-species venom variation. In the current study, comparative functional characterization of major enzymatic proteins present in Craspedocephalus malabaricus and Daboia russelii venom was investigated through various in vitro and immunological cross-reactivity assays. The enzymatic assays revealed that hyaluronidase and phospholipase A2 activities were markedly higher in D. russelii. By contrast, fibrinogenolytic, fibrin clotting and L-amino acid oxidase activities were higher in C. malabaricus venom. ELISA results suggested that all the antivenoms had lower binding potential towards C. malabaricus venom. For D. russelii venom, the endpoint titration value was observed at 1:72 900 for all the antivenoms. In the case of C. malabaricus venom, the endpoint titration value was 1:2700, except for Biological E (1:8100). All these results, along with the avidity assays, indicate the strength of venom-antivenom interactions. Similarly, the western blot results suggest that all the antivenoms showed varied efficacies in binding and detecting the venom antigenic epitopes in both species. The results highlight the need for species-specific antivenom to better manage snakebite victims.

An Assessment of Trends in HIV-1 Prevalence and Incidence and Spatio-Temporal Analyses of HIV-1 Recent Infection Among MSM During the Surveillance Period Between 2018 and 2022 in Sichuan, China.

Men who have sex with men (MSM) is one main type of high-risk activities facilitating HIV-1 transmission in Sichuan province. Previous works on HIV-1 incidence and prevalence among MSM only concentrated before 2018, the situation after that is unknown. In addition, the distribution of hot-spots related to current HIV-1 epidemic is also rarely known among MSM in Sichuan. To update trends of HIV-1 prevalence and incidence and to visualize hot-spots of ongoing transmission in Sichuan province during surveillance period among MSM between 2018 and 2022. Limiting Antigen Avidity assay was performed to detect recent infection within new HIV-1 diagnoses founded during surveillance period among MSM. The HIV-1 prevalence and incidence were calculated according to an extrapolation method proposed by publications and guidelines. Trend tests were performed using χ2 tests with linear-by-linear association. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spots of HIV-1 recent infections among MSM. Between 2018 and 2022, 16,697 individuals participated in HIV-1 MSM sentinel surveillance program, of which 449 samples (98.25%) were tested with LAg-Avidity EIA, and 230 samples were classified as recent infection. Respectively, the overall prevalence and incidence were 2.74% and 3.69% (95% CI: 3.21, 4.16) and both had significant declining trends (p < 0.001). Luzhou city had a highest HIV-1 incidence (10.74%, 95% CI: 8.39, 13.10) over the study period and was recognized as a hot-spot for recent HIV-1 infection among MSM. During the surveillance period, both HIV-1 prevalence and incidence were declining. However, Luzhou city had an unusually high HIV-1 incidence and became an emerging hot-spot of recent HIV-1 infection among MSM. This finding suggested focused attention, cross-regional intervention strategies, and prevention programs are urgently required to curb the spread of ongoing transmission.

Congenital cytomegalovirus infection in newborns suspected of congenital rubella syndrome in Iran: a cross-sectional study

BackgroundFollowing rubella virus control, the most important cause of congenital infections is human cytomegalovirus (HCMV). Congenital CMV (cCMV) may happen both in primary and non-primary maternal infections. The present study aimed to screen cCMV in symptomatic newborns suspected of congenital rubella syndrome (CRS) in Iran.MethodsOut of 1629 collected infants' serum samples suspected of CRS but negative for rubella IgM, 524 samples were selected regarding cCMV complications. These samples were divided into two age groups: 1- one month and younger, 2- older than 1 month up to one year. Anti-HCMV IgM detection was performed on these serums. Then HCMV IgG avidity assay and HCMV DNA detection were carried out on all samples with positive and borderline results in IgM detection.ResultsHerein, 3.67% of symptomatic infants aged one month and younger had positive and borderline HCMV IgM, 12.5% of which had a low avidity index (AI). HCMV IgM detection rate among symptomatic infants older than one month to one year was 14.5%. Identified genotypes in this study were gB-1(63.63%), gB2 (18.18%), and gB3 (18.18%), respectively.ConclusionsThis comprehensive study was performed on serum samples of symptomatic infants clinically suspected of cCMV from all over Iran. There was a good correlation between serology findings and PCR.

Evaluation of different cut-off points for IgG avidity and IgM in the diagnosis of acute toxoplasmosis in pregnant women participating in a congenital toxoplasmosis screening program.

The main social impact of toxoplasmosis stems from its ability to be vertically transmitted. Postnatally acquired infection is generally asymptomatic in approximately 70-90% of cases, making diagnosis often dependent on laboratory tests using serological methods to search for anti-T. gondii antibodies. This study aimed to investigate the ability of the VIDAS TOXO IgG avidity and VIDAS TOXO IgM assays to confirm recent toxoplasmosis. In total, 341 pregnant women with suspected acute toxoplasmosis were systematically monitored in the Program for Control of Congenital Toxoplasmosis in Minas Gerais State, Brazil. We conducted an observational analytical-descriptive cross-sectional study and grouped according to clinical and laboratory criteria as having acute or chronic toxoplasmosis. The VIDAS TOXO IgG avidity and VIDAS TOXO IgM assays were evaluated to investigate the capacity to identify acute infection. IgG avidity showed good performance in identifying acute toxoplasmosis when the IgG avidity index was lower than or equal to 0.1. Values greater than or equal to 3.16 according to the TOXO IgM kit were associated with a greater chance of acute infection. These results may contribute to a more adequate diagnosis of acute gestational toxoplasmosis and, consequently, the avoidance of inadequate or unnecessary treatments.

Measles IgG Avidity Assay.

Measles IgG avidity assays determine the overall strength of molecular binding between measles-specific IgG antibodies and measles virus antigens. Avidity results can distinguish recent from distant measles virus infections. Individuals who are immunologically naïve to measles virus develop low-avidity antibodies upon measles virus infection or first-time vaccination. Within 4-6months, antibodies mature to high avidity. Measles avidity assays are most useful in the context of measles elimination. In such settings, avidity and epidemiological and clinical information are used to classify measles breakthrough infections for control and surveillance purposes and to assist in case confirmation when other laboratory results are inconclusive or nonexistent. We present a highly accurate end-titer measles avidity assay that delivers results based on IgG quality (avidity) that are independent of IgG concentration.

Optimal, Off-the-Shelf, CAR-iNKT Cell Platform-Based Immunotherapy for Multiple Myeloma

Autologous CAR-T cell immunotherapy targeting BCMA confers significantly improved progression free survival as compared to standard-of-care in relapsed/refractory multiple myeloma. However, despite &amp;gt;50% complete remission rates, patients continue to relapse. Of note, in current licenced BCMA CAR-T products, 4-1BB comprises the co-stimulatory domain of a 2 nd generation CAR. Expression of CD1d by myeloma plasma cells (PC) lends itself to immunotherapy with the CD1d-restricted, glycolipid-reactive iNKT cells which can be deployed ‘off-the-shelf’ without causing aGVHD. We hypothesised that ‘off-the-shelf’ anti-BCMA CAR-iNKT would be an alternative platform for the treatment of MM. We sought to identify the CAR design that would function optimally in conjunction with iNKT cells. To this end, we designed several different second (28z, 4-1BBz, OX40z) and third (28z-4-1BBz, 28z-OX40z) generation BCMA CARs and tested their anti-myeloma activity. Lentiviral transduction efficiency of iNKT cells was comparable for all five CARs and all five CAR-iNKT were able to kill two BCMA-expressing but not BCMA knock out myeloma cell lines in short- and long-term cytotoxicity assays. The level of cytotoxicity varied with donor, timing of the assay and cell lines, with the only consistent pattern seen with the 3 rdgeneration CD28-4-1BB CAR. This showed the least reactivity at low E:T ratios in both 4 and 16hrs assays for both donors tested. Testing cytotoxicity against primary myeloma PC (n=3) showed that the 3 rd gen CARs were less active than the three 2 nd gen counterparts. Short term proliferation assays using Incucyte Zoom demonstrated a higher proliferative potential of CD28z CAR-iNKT cells with CD28z-4-1BBz CAR showing the least proliferation. In a longer term 35-day assay, following stimulation with the iNKT cell ligand aGalCer, we found that CD28z CAR-iNKT cells showed the highest expansion. To further probe functional differences between the five CARs, we tested the corresponding CAR-iNKT cells in acoustic force avidity assays. These highlighted CD28z CAR-iNKT cells as having the highest avidity amongst CAR-iNKT cells with untransduced iNKT cells the lowest (Fig. 1A ). Using confocal microscopy, we explored how these differences in avidity impacted the ability of CAR-iNKT cells to shape the immune synapse (IS) and engage the cytolytic apparatus. We found that while conjugates of untransduced iNKT cells with myeloma cells all fell in the distal centrosome group, of the five CARs, CD28z and 4-1BBz CAR-iNKT conjugates recorded the highest and the lowest respectively proximal and docked conjugates, i.e., those signifying imminent or active discharge of the cytolytic granules. To delve further into the mechanism(s) of higher avidity and ability to established IS by CD28z CAR-iNKT, we compared the transcriptomes of CD28z vs 4-1BBz CAR-iNKT from three donors. We found 64 genes differentially expressed (14 up- and 50 down-regulated in CD28z CAR-iNKT, padj&amp;lt;0.05). Amongst the upregulated genes we identified, currently investigating genes that encode proteins that were previously implicated in the strength and duration of IS. To investigate the in vivo correlates of these functional assays, we deployed a xenograft myeloma model using MM1.S luciferase-expressing cells (Fig. 1B ). All five CAR iNKT cells were i.v transferred to myeloma-bearing mice at the limiting dose of 10 6 CAR+ cells/mouse and disease burden was monitored by bioluminescence. In line with the functional assays, we found that mice receiving CD28z CAR-iNKT cells demonstrated the lowest disease burden and survived the longest (p&amp;lt;0.01). While disease burden and survival of animals receiving CD28z-4-1BBz CAR-iNKT was the same as controls, 4-1BBz CAR-iNKT-treated mice showed significantly higher disease burden and shortened survival as compared to CD28z CAR-iNKT. Further disease burden assessment by flow-cytometry at sacrifice showed that CD28z CAR-iNKT-treated animals had the lowest (p&amp;lt;0.01) frequency of myeloma cells in their peripheral blood, bone marrow and spleen. Finally, in ongoing xenograft assays, we find that compared to 10 6 28z BCMA CAR-iNKT and 5x10 6 untransduced iNKT, 5x10 6 28z BCMA CAR-iNKT cells maintain better disease control (p=0.008, day7). We conclude that CD28z by enhancing effector-target avidity and strength of IS constitutes the optimal CAR design for clinical development of CAR-iNKT therapy of multiple myeloma.

Comparison of two serological screening strategies for cytomegalovirus primary infection in the first trimester of pregnancy

IntroductionCMV serology screening in the first trimester pregnancy is based on IgG and IgM testing followed by IgG avidity in cases with positive IgM. However, the sensitivity of this strategy to diagnose maternal primary infection has been questioned. The objective of the study was to compare this strategy 1 with a strategy 2 consisting of running avidity test on all samples with positive IgG (ignoring IgM results) using fully automated current generation CMV IgG, IgM and IgG avidity assays. Population and methods1516 consecutive pregnant women between 12 and 14 weeks were screened in one maternity. Strategy 1 was done prospectively with LIAISON® CMV IgG II and LIAISON® CMV IgM II, followed by LIAISON® CMV IgG Avidity II and VIDAS® CMV IgG avidity II testing in cases with positive or equivocal IgM. Strategy 2 was done retrospectively on the same population and consisted of running avidity with the LIAISON® CMV IgG Avidity II in all samples with positive IgG. ResultsThe sensitivity to diagnose a confirmed or a possible maternal primary infection in the first trimester was 91.6 % and 83 % for strategy 1 and 2 respectively (p > 0.99). Strategy 1 missed one possible primary infection and strategy 2 missed 2 confirmed primary infection. Inconclusive results happened in 0 and 0.7 % of samples with strategy 1 and 2 respectively. ConclusionThis study suggests that strategy 1 has better sensitivity and practicability than strategy 2. However, to achieve a good performance with strategy 1, using highly sensitive IgM assay is mandatory.

Evaluation of the accuracy of the Asanté assay as a point-of-care rapid test for HIV-1 recent infections using serum bank specimens from blood donors in South Africa, July 2018 - August 2021.

Point-of-care (POC) rapid recency testing can be used as a cost-effective tool to identify recently infected individuals (i.e. infected within the last 12 months) in near-real time, support epidemic control and identify hotspots for transmission as part of recent infection surveillance. To evaluate the performance of the Asanté (HIV-1) rapid recency assay as a POC rapid test among blood donors in South Africa (SA). The study was a cross-sectional and validity study of the Asanté HIV-1 Rapid Recency Assay performed on 715 consecutively archived plasma donor specimens from the SA National Blood Services to determine their recency and established HIV infection status. ELISA and rapid assays for HIV antibody detection were used as the reference-testing standard for confirming an infection, while the Maxim HIV-1 limiting antigen (LAg) avidity assay was used as a reference for comparing HIV recency status. Validity tests (sensitivity, specificity, negative and positive predictive values) and Cohen-Kappa tests of the agreement were conducted to compare the Asanté HIV-1 rapid recency assay results with the reference tests. Of the 715 studied blood samples, 63.1% (n=451/715) were confirmed to be HIV-positive based on the reference standard. The sensitivity and specificity of the Asanté HIV-1 rapid recency assay in diagnosing established HIV infection compared to the ELISA were 98.4% (95% CI 96.7 - 99.3) and 99.6% (95% CI 97.6 - 100), respectively. Compared with HIV rapid assay, the sensitivity and specificity of the Asanté HIV-1 rapid recency assay was 98.7% (95% CI 97.0 - 99.4) and 99.2% (95% CI 97.1 - 100), respectively. Of the 451 HIV-positive blood samples, 43% were confirmed as recent HIV infections by the Maxim HIV-1 LAg avidity assay. There was high agreement between the Asanté HIV-1 rapid recency assay and the Maxim HIV-1 LAg avidity assay (94.1%, k=0.879, p<0.0001). The sensitivity and specificity of the Asante HIV-1 assay was 89.4% (95% CI 84.0 - 93.0) and 97.7% (95% CI 94.8 - 99.0), respectively. The Asanté HIV-1 rapid recency assay test results demonstrated high accuracy (>90%) compared with the HIV ELISA and rapid assays for determining established infection and the Maxim HIV-1 LAg avidity assay for classifying recent HIV-1 infections. The assay's sensitivity for established infections was below the World Health Organization criteria (<99%) for POC devices. The Asanté HIV-1 rapid recency assay can be used to distinguish between recent and long-term infections, but may not be considered a POC test for determining HIV infection.

Population-based study of the durability of humoral immunity after SARS-CoV-2 infection.

SARS-CoV-2 antibody quantity and quality are key markers of humoral immunity. However, there is substantial uncertainty about their durability. We investigated levels and temporal change of SARS-CoV-2 antibody quantity and quality. We analyzed sera (8 binding, 4 avidity assays for spike-(S-)protein and nucleocapsid-(N-)protein; neutralization) from 211 seropositive unvaccinated participants, from the population-based longitudinal TiKoCo study, at three time points within one year after infection with the ancestral SARS-CoV-2 virus. We found a significant decline of neutralization titers and binding antibody levels in most assays (linear mixed regression model, p<0.01). S-specific serum avidity increased markedly over time, in contrast to N-specific. Binding antibody levels were higher in older versus younger participants - a difference that disappeared for the asymptomatic-infected. We found stronger antibody decline in men versus women and lower binding and avidity levels in current versus never-smokers. Our comprehensive longitudinal analyses across 13 antibody assays suggest decreased neutralization-based protection and prolonged affinity maturation within one year after infection.

Identification of ADA as a Biomarker for Atypical Epstein Barr Virus Infection in Children.

This study aims to explore the ability of adenosine deaminase (ADA) to discriminate atypical Epstein Barr virus (EBV) infection in children from acute febrile illness. All children admitted to the Children's Hospital of Soochow University between 2018 and 2019, who were acute febrile patients and subjected to the plasma EBV-DNA polymerase chain reaction (PCR) and indirect immunofluorescence (IIF) assay for EBV-specific antibodies assays. The diagnostic value of each detection index was compared by the area under the ROC curve. In children with atypical Epstein Barr virus infection, the sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 62.87%, 100.00%,100.00%, 61.73% and 0.63 for EBV-DNA PCR assay, 80.84%, 100.00%, 100.00%, 75.76% and 0.81 for VCA-IgG avidity and 89.22%, 87.00%, 91.98%, 82.86% and 0.76 for ADA. VCA-IgG avidity (AUC=0.904, P<0.01) and ADA (AUC=0.881, P<0.01) assays had the great diagnostic efficiency. In addition, the sensitivity, specificity and AUC were 92.75%,91.43% and 0.921(95%CI: 0.856-0.985) for ADA in the course≤3 days group, respectively. ADA has a good diagnostic value in the early stage of atypical EBV infection, and is not affected by primary EBV infection and reactivation. SCHLüSSELWöRTER: Adenosine deaminase, Epstein -Barr virus, Biomarker, children.

Antibody response in children with multisystem inflammatory syndrome related to COVID-19 (MIS-C) compared to children with uncomplicated COVID-19.

To comprehensively analyze the quality of the antibody response between children with Multisystem inflammatory syndrome (MIS-C) and age-matched controls at one month after SARS-CoV-2 exposure, and infected in the same time-period. Serum from 20 MIS-C children at admission, and 14 control children were analyzed. Antigen specific antibody isotypes and subclasses directed against various antigens of SARS-CoV-2 as well as against human common coronavirus (HCoVs) and commensal or pathogenic microorganisms were assessed by a bead-based multiplexed serological assay and by ELISA. The functionality of these antibodies was also assessed using a plaque reduction neutralization test, a RBD-specific avidity assay, a complement deposition assay and an antibody-dependent neutrophil phagocytosis (ADNP) assay. Children with MIS-C developed a stronger IgA antibody response in comparison to children with uncomplicated COVID-19, while IgG and IgM responses are largely similar in both groups. We found a typical class-switched antibody profile with high level of IgG and IgA titers and a measurable low IgM due to relatively recent SARS-CoV-2 infection (one month). SARS-CoV-2-specific IgG antibodies of MIS-C children had higher functional properties (higher neutralization activity, avidity and complement binding) as compared to children with uncomplicated COVID-19. There was no difference in the response to common endemic coronaviruses between both groups. However, MIS-C children had a moderate increase against mucosal commensal and pathogenic strains, reflecting a potential association between a disruption of the mucosal barrier with the disease. Even if it is still unclear why some children develop a MIS-C, we show here that MIS-C children produce higher titers of IgA antibodies, and IgG antibodies with higher functionality, which could reflect the local gastro-intestinal mucosal inflammation potentially induced by a sustained SARS-CoV-2 gut infection leading to continuous release of SARS-CoV-2 antigens.

Demographic Characteristics and Hot-Spot Areas of Recent Infections Among New HIV Diagnoses in Sichuan, China, Between 2018 and 2020.

Sichuan Province is severely affected by the HIV epidemic in China. Little is known about the characteristics of recent infections among new HIV diagnoses, which is critical to prevention strategies, evaluation of the HIV epidemic and health resource allocation. Meanwhile, individuals at primary stages of infection are related to the hot-spot areas of ongoing transmission in new HIV diagnoses, which is also rarely known. This article aimed to report the proportion of recent infections among new HIV diagnoses, and to reveal demographic characteristics associated with HIV recent infections, and finally, to indicate the hot-spot areas of ongoing transmission in Sichuan province between 2018 and 2020. Limiting Antigen (LAg)-Avidity assay was performed to detect recent infection within new HIV diagnoses reported in odd months between 2018 and 2020. Results were reclassified according to the data on CD4 cell count, antiretroviral treatment and the existence of an AIDS-defining illness. Logistic regression was used to determine characteristics associated with HIV recent infections. The spatial analysis was conducted with ArcGIS 10.7 to figure hot-spot areas of HIV recent infections. 42,089 newly diagnosed HIV-1 cases were tested using the LAg-Avidity EIA. In total, 5848 (13.89%) of those were classified as HIV recent infections. Female, age between 18-25 years and men who had sex with men were related to higher proportion of HIV recent infections. Logistic regression revealed that MSM aged between 18-25 years were more likely to be classified as recent infection. Spatial analysis demonstrated significant clustering in Chengdu, Yibin, Luzhou city between 2018 and 2020. Hot spots were mainly clustered in the center of Sichuan in 2018, but gradually spread to southwest and northwest between 2019 and 2020. Enhanced preventive measures among relevant risk groups and areas where the potential HIV-1 transmission is ongoing is urgently needed to curb further spread.

Method variation of cytomegalovirus IGM assays in EQA

Cytomegalovirus (CMV) is a common virus that infects people of all ages. Correctly diagnosing a primary CMV infection in pregnant women is critical to avoid congenital anomalies. CMV IgM specificity is poor in detecting primary infections due to vial reactivation or persistence following primary infection. Algorithms using CMV IgM and IgG avidity can be useful. We sought to review the performance of CMV IgM and IgG avidity assays in the RCPAQAP CMV External Quality Assurance (EQA) Program. Data sourced from an expected IgM positive consenting donor sample was assessed using RCPAQAP software. The same sample was included in four surveys over three years. Variation in the quantitative IgM data across methods was consistently noted (e.g., Roche vs Diasorin). There were also similar differences in the qualitative interpretations between the ‘negative’ and ‘positive’ groups (21 vs 92, respectively). While 120 sites reported for IgM, only 34 of these measured IgG avidity which more than 95% reported as ‘high’. In a clinical setting, access to both results may be of benefit. While the study was limited, further investigation of discrepancies between CMV methods when interpreting results should be considered. The inclusion of IgG avidity is recommended.

Evaluation of Toxoplasma gondii IgG avidity assays through a comparison of IgM serostatus

Primary Toxoplasma gondii (T. gondii) infection during pregnancy could result in congenital disease with severe clinical complications. IgM antibodies are one of the indices of primary infection. The IgG avidity index (AI) is also known to remain low for at least 3 months after primary infection. Here, we evaluated and compared the performance of T. gondii IgG avidity assays as confirmed by T. gondii IgM serostatus and number of days post-exposure. Four assays preferentially used in Japan were employed to measure the T. gondii IgG AI. Results for the T. gondii IgG AI showed good concordance, particularly in cases with a low IgG AI. This study confirms that the combination of T. gondii IgM and IgG AI tests is a reliable and suitable method for identifying T. gondii primary infections. Our study proposes the necessity of measuring the T. gondii IgG AI as an additional indicator of T. gondii primary infection.

Facilitating Next-Generation Pre-Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project.

Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases.

Sero-detection of Epstein-Barr virus and Cytomegalovirus Antibodies among patients with Systemic lupus Erythematous in Sudan

Infection by Cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been implicated in the pathogenesis of Systemic lupus Erythematous (SLE). The current study aimed to determine the frequency of EBV and CMV IgG among Sudanese patients with SLE. A case-control analytical study was conducted on 82 participants in Khartoum State during the period from 2017 to 2018. Serum from patients with SLE (n=62), and controls participants (n=20) were tested for IgG antibodies against EBV and CMV using the Avidity ELISA assay. Pretested questionnaire data were analyzed by SPSS software V.20 (IBM, Chicago,IL). Means and proportions of the demographic were calculated for SLE seropositive groups. Chi-square test and binary logistic regression analysis were used for SLE as a dependent factor while IgG seropositive groups of EBV and CMV as the independent variable and, SLE variables as dependent variables. Odds ratio (OR) with a 95% confidence interval was calculated and statistical significance was defined as a P value below 0.05. Eighty-two females with SLE volunteered to participate in this study, including 62 cases with systemic lupus erythematosus and 20 control participants. Average age means ± SD (34±1.4) for cases and (34±1.6) for controls. Original tribes in Sudan were screened Avidity assay for Western State 37(45.1%), Northern State 29(35.4%), Central State 17(20.7%), and Southern State1 (1.2%) respectively. Seropositivity of IgG by Avidity assay revealed high score for CMV 60 (96.8%) among cases vs 19(95%) among controls, (OR 1.579, CI -95% (0.136-18.4), P &lt;0.05). Seropositivity for both EBV and Co-infection was 58 (98.3%) vs 16 (80.0%) among cases and controls, respectively (OR 3.625, CI -95% (0.227-2.708), P &lt;0.05). Patients with SLE in Sudan have a high rate of infections by EBV and CMV as evidenced by the IgG avidity test indicating association.

HIV Incidence, Recent HIV Infection, and Associated Factors, Kenya, 2007-2018.

Nationally representative surveys provide an opportunity to assess trends in recent human immunodeficiency virus (HIV) infection based on assays for recent HIV infection. We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012, and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (<12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design. Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 [95% confidence interval (CI) 0.057-0.23], representing 35,900 (95% CI 16,300-55,600) new infections per year in Kenya among persons aged 15-64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 [adjusted odds ratio (aOR) = 0.31, p < .001]. Compared to no HIV infection, being aged 25-34 versus 35-64 years (aOR = 4.2, 95% CI 1.4-13), having more lifetime sex partners (aOR = 5.2, 95% CI 1.6-17 for 2-3 partners and aOR = 8.6, 95% CI 2.8-26 for ≥4 partners vs. 0-1 partners), and never having tested for HIV (aOR = 4.1, 95% CI 1.5-11) were independently associated with recent HIV infection. Although HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.

Maternal Cytomegalovirus Antibodies during Early and Late (Persistent) Phases after Primary Cytomegalovirus Infection during Pregnancy: An Observational Study

Background: We analyzed both early and late (persistent) phases of each cytomegalovirus (CMV) antibody in mothers with primary CMV infection during pregnancy and subsequent congenital CMV infection for a long period from late pregnancy to after delivery using our stored serum samples. Methods: We used stored serum samples obtained during pregnancy to after delivery from mothers with CMV immunoglobulin (Ig) G seroconversion and subsequent infant congenital CMV infection. CMV antibodies, including CMV IgG titer, IgM titer, and IgG avidity, were assessed using the Denka IgG assay, Denka IgM assay Ver.1 and Ver.2, and Enzygnost IgG assay and Denka IgG avidity assay, respectively. We analyzed the dynamics of each CMV antibody for a long period from late pregnancy to after delivery and correlations of each antibody, calculating Pearson’s correlation coefficients (R2). Results: We used 67 serum samples obtained from 12 included participants between 2013 and 2018. CMV IgG increased until 61 weeks and did not change significantly after. CMV IgM decreased until 52 weeks and did not change significantly after that in both assays. CMV IgG avidity increased until 64 weeks and did not change significantly after that in both assays. In CMV IgM, a strong positive correlation was found (R2 = 0.9326) between the two different IgM assays. Serum results of the late phase (after 60 weeks) were subsumed into the area of high CMV IgG avidity and low CMV IgM titer, which probably was equivalent to the persistent IgM. Conclusions: CMV antibodies in mothers during the late phase of primary infection were in high IgG avidity and low IgM titer, which probably was equivalent to the persistent IgM.