IgG Avidity Research Articles

Kan Örneğinden Aktif Toksoplazmozis Moleküler Tespiti ve Genotiplemesi

Toxoplasma gondii, which is an obligate intracellular protozoan, and its primer infection during pregnancy can cause several problems. This study presents a case report of a woman who delivered a baby with multi-organ failure and was diagnosed with congenital toxoplasmosis. During the gestation period, there was no history of febrile, enlargement of lymph nodes, or common cold symptoms, but there was a history of miscarriage. The serology test of anti-Toxoplasma immunoglobulin (Ig)G and IgM were reactive. The IgG avidity test was 90%, and positive SAG2. The sequencing and analysis of polymerase chain reaction product assumed to have the Type I T. gondii, which must be confirmed using other loci apart from SAG2. This case report aims to raise awareness of the risk of congenital toxoplasmosis in asymptomatic mothers with a history of miscarriage. Routine and serial screening for the disease is recommended in high-risk pregnant women to prevent congenital transmission.

Serologic evaluation of cytomegalovirus (CMV), Toxoplasma gondii and Brucella in schizophrenia patients.

Infectious agents are considered as a possible cause of schizophrenia. The aim of this study was to evaluate the serum levels of cytomegalovirus (CMV), Toxoplasma gondii and Brucella antibodies in schizophrenia patients compared with the control group. This cross-sectional study was performed on 75 patients with schizophrenia who were clinically diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by two independent psychiatrists. As the controls, 75 sex and age-matched individuals were selected from orthopedic and surgical wards, who were admitted because of trauma. Anti-Toxoplasma gondii IgG antibody was detected by Abbott's company diagnostic kit. To detect anti-Brucella IgG antibodies, the enzyme-linked immunosorbent assay (ELISA) test with Vircell diagnostic kit was used. Quantitative luminescence (CLIA) method using Abbott diagnostic kit was also used to detect anti-cytomegalovirus IgG antibody (CMV IgG avidity). There was not any clinically significant differences in the mean value of Toxoplasma, CMV and Brucella IgG antibodies between schizophrenia and control group. However, considering cut-off point for these tests and further analysis with non-parametric tests showed clinically significant difference between two groups at cut-off point 1.1 for anti-Brucella IgG antibody which indicated more positive samples in schizophrenia group (24 out of 75) than control group (12 out of 75) with a p-value less than 0.05 (0.046). The results of the present study showed no association between toxoplasmosis infection and CMV and schizophrenia. However, there might be a positive correlation between anti-Brucella IgG antibody and schizophrenia.

Rubella virus IgM and IgG antibodies with avidity in pregnant women and outcomes at a tertiary facility in Ghana.

Congenital rubella syndrome (CRS) is a recognised cause of childhood deafness and blindness caused by the transplacental transmission of rubella virus during pregnancy. Women in the reproductive age group, and by extension their unborn babies may therefore be at increased risk. The prevalence of Rubella virus specific IgM and IgG antibodies, including IgG avidity, was determined in pregnant women attending the antenatal clinic at a Teaching Hospital in Ghana. One hundred and forty-five women in their second and third trimesters of pregnancy from the outpatient clinic were recruited over a period of 2 months after written informed consent was obtained. Study participants completed a questionnaire and venous blood drawn for IgM, IgG, and avidity testing using SERION ELISA (SERION® Immunologics, Würzburg, Germany). Babies of mothers with positive or indeterminate IgM and low avidity IgG antibodies were offered specialist cardiological, ophthalmological or hearing assessment during follow up. One hundred and twenty-eight (88.3%) had only IgG antibodies, 5 (3.4%) had IgM and IgG antibodies, while 12 (8.3%) had no antibodies. No patient had IgM antibodies alone. Ten women (6.9%) had indeterminate levels of IgM antibodies. Majority of the women had high avidity IgG antibodies, while 5 (3.4%) had low avidity antibodies. No patient had IgM with low avidity antibodies. There was no statistical association between socio-demographic factors and the presence of IgM, IgG (low or high avidity) antibodies. Of all the children followed, none had the clinical definition of CRS. Consistent with the World Health Organization elimination strategy for measles and rubella viruses, non-immune women in the reproductive age group should be vaccinated. The immunization programme should be expanded to include teenagers and adults. Though Congenital Rubella Syndrome was not detected, the risk still remains.

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 <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 <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.

Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

Multiplexed evaluation of immunity against SARS-CoV-2 variants using surface enhanced fluorescence from a nanostructured plasmonic chip

Generated by the immune system post-infection or through vaccination, the effectiveness of antibodies against emerging SARS-CoV-2 variants is crucial for protecting individuals from the COVID-19 pandemic. Herein, a platform for the multiplexed evaluation of SARS-CoV-2 neutralizing antibodies against various variants was designed on the basis of near-infrared (NIR) surface enhanced fluorescence by nano-plasmonic gold chip (pGOLD). Antibody level across variants (Wild-type, Alpha, Beta, Delta, Omicron) was confirmed by the sera from recovered-individuals who were unvaccinated and had infected with Wild-type, Delta, Omicron variants. However, the neutralizing activity against Omicron variant was markedly decreased for individuals infected by Wild-type (~ 5.6-fold) and Delta variant (~ 19.1-fold). To the opposite, neutralizing antibody from individuals recovered from Omicron variant infection showed weak binding strength against non-Omicron variants. Antibody evolution over time was studied with individuals 196–530 days post Wild-type infection. Decreasing IgG antibody titer accompanied by increasing IgG binding avidity with elongated post-infection period were observed for the sera from Wild-type recovered-individuals with different post-infection times, suggesting that after the primary infection, a great number of antibodies were generated and then gradually decreased, while the antibody matured over time. By comparing the IgG level of individuals vaccinated for 27–51 days with individual post-infection, we found that ca. 1 month after two doses of vaccination, the antibody level was comparable to that of 500 days post-infection, and vaccination could enhance IgG avidity more efficiently. This work demonstrated a platform for the multiplexed, high-throughput and rapid screening of acquired immunity against SARS-CoV-2 variants, providing a new approach for the analysis of vaccine effectiveness, immunity against emerging variants, and related serological study.Graphical

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

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.

Investigation of Toxoplasma gondii Seropositivity in Pregnant Women in Kastamonu Province, Turkey

Toxoplasma gondii (T. gondii) is a protozoan parasite that infects most warm-blooded animal species and causes toxoplasmosis. Especially infections that occur during pregnancy can lead to serious clinical symptoms. This study retrospectively revealed the T. gondii seroprevalence of pregnant women in Kastamonu province, Turkey. Anti-T. gondii IgM and IgG positivity of 1.294 pregnant women between the ages of 15-44 years who applied to the Obstetrics and Gynecology Outpatients of Kastamonu Training and Research Hospital from January 2018 to January 2022 were investigated retrospectively. The IgG avidity test was performed for both anti-T. gondii IgM and IgG positivity. Anti-T. gondii IgM and IgG seropositivity were determined as 1.1% (n=14) and 20.3% (n=263), respectively. Anti-T. gondii IgM and IgG positivity were detected together in 11 pregnant women. IgG avidity test results of only six pregnant women could be reached, two pregnant had high IgG avidity, and four pregnant had low IgG avidity. Anti-T. gondii IgG positivity rate increased with increasing age (p=0.039). The number of seronegative pregnant women was considered high in Kastamonu. It is significant for expectant mothers to know about prevention methods in order not to acquire toxoplasmosis.

Screening for the Detection of Toxoplasma gondii IgG, IgM and IgA in Females of Reproductive Age from Western Romania.

Toxoplasma gondii, a zoonotic protozoan parasite, has the capacity to infect the fetus if the pregnant woman primarily acquires the infection during pregnancy. We evaluated the prevalence of T. gondii IgG, IgM and IgA antibodies in women of reproductive age residing in Western Romania. We also assessed the value of adding a T. gondii IgA test to the serologic panel for the diagnosis of toxoplasmosis, including the detection of a recently acquired infection. Serologic testing to demonstrate the presence of T. gondii IgG antibodies was conducted in 1317 females aged 15-45 years. T. gondii IgM and IgA antibody tests were performed in those with detectable IgG antibodies and IgG avidity test was performed if IgM and/or IgA screening test results were positive. T. gondii IgG were detected in 607 (46.09%; 95%CI: 43.41-48.79) of 1317 study participants and IgG seroprevalence tended to increase with age from 35.44% (95%CI: 29.89-41.30) in age group 15-24 years to 62.85% (95%CI: 56.57-68.82) in age group 35-45 years, showing a significant age-associated increase (p &lt; 0.001). Of the 607 persons with detectable T. gondii IgG antibodies, T. gondii IgM antibodies were demonstrated in 8.90% (95%CI: 6.88-11.43), T. gondii IgA in 1.65% (95%CI: 0.90-3.01) and both T. gondii IgM and IgA in 0.99% (95%CI: 0.45-2.14). The prevalence of IgA antibodies tended to decrease with increasing avidity, from 75% (95%CI: 19.41-99.37) in samples with low avidity to 11.76% (95%CI: 4.44-23.87) in those with high avidity (p = 0.01). Of the study participants who were positive for both T. gondii IgM and IgA antibodies, 66.67% had low or equivocal IgG avidity test results compared to 6.25% who tested positive for IgM, were negative for IgA and in whom low or equivocal IgG avidity test results were noted (p = 0.001). This study indicates that in Western Romania, T. gondii IgG seroprevalence is high in females of reproductive age and T. gondii IgA antibodies may be rarely detected during a serologic screening. However, in individuals with demonstrable T. gondii IgG and IgM antibodies, testing for T. gondii IgA may improve the rate for the detection of a recently acquired toxoplasmosis.

Maternal Serological Screening for Congenital Toxoplasmosis During Pregnancy and Evaluating the Pregnant Women’s Knowledge on Toxoplasmosis in Qazvin, Iran

Background: The present study was designed to determine the prevalence of Toxoplasma gondii seronegative pregnant women, estimate the frequency of fetuses at risk of congenital toxoplasmosis in the study area, and also to investigate the awareness of the studied mothers about T. gondii disease.Methods: A total of 740 pregnant women referred to two health centers in Qazvin province were surveyed voluntarily for anti-T. gondii IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA). IgG avidity test was used as a confirmatory test for samples showing positive or borderline results for IgM antibodies. Data on socioeconomic, demographic, and knowledge of participants about toxoplasmosis were collected using questionnaires and through face-to-face interviews. Multivariable logistic regression modeling was used to identify the potential predictor variables for T. gondii infection. Results: Overall, 21.2% (157/740) and 0.27% (2/740) of pregnant women were positive for T. gondii IgG and IgM antibodies, respectively. Only 1.7% (13/740) of expectant mothers had prior information on toxoplasmosis. Among socioeconomic and demographic variables, contact with soil was the merely cause of a significant association with T. gondii infection. Other variables including age, occupation, education level, residential area, source of drinking water, abortion history, number of childbirth, consumption of raw/undercooked meat, having home cat and and consumption of raw vegetables failed to establish significant associations. Conclusion: Our results clarified that the prevalence of T. gondii has remarkably reduced in the study area. This finding indicates a low risk of congenital toxoplasmosis in this region.

Adjuvants to increase immunogenicity of SARS-CoV-2 RBD and support maternal-fetal transference of antibodies in mice.

Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women-to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.

Quality of antibody responses by adults and young children to 13-valent pneumococcal conjugate vaccination and Streptococcus pneumoniae colonisation

Childhood pneumococcal conjugate vaccine (PCV) protects against invasive pneumococcal disease caused by vaccine-serotype (VT) Streptococcus pneumoniae by generating opsonophagocytic anti-capsular antibodies, but how vaccination protects against and reduces VT carriage is less well understood. Using serological samples from PCV-vaccinated Malawian individuals and a UK human challenge model, we explored whether antibody quality (IgG subclass, opsonophagocytic killing, and avidity) is associated with protection from carriage. Following experimental challenge of adults with S. pneumoniae serotype 6B, 3/21 PCV13-vaccinees were colonised with pneumococcus compared to 12/24 hepatitis A-vaccinated controls; PCV13-vaccination induced serotype-specific IgG, IgG1, and IgG2, and strong opsonophagocytic responses. However, there was no clear relationship between antibody quality and protection from carriage or carriage intensity after vaccination. Similarly, among PCV13-vaccinated Malawian infants there was no relationship between serotype-specific antibody titre or quality and carriage through exposure to circulating serotypes. Although opsonophagocytic responses were low in infants, antibody titre and avidity to circulating serotypes 19F and 6A were maintained or increased with age. These data suggest a complex relationship between antibody-mediated immunity and pneumococcal carriage, and that PCV13-driven antibody quality may mature with age and exposure.

Investigation of Toxoplasma Gondii, Rubella virus and Cytomegalovirus Infections in Pregnancy, Retrospective Evaluation of Avidity Tests and Perinatal Follow-up Results

Aim: In this study, it was aimed to investigate Toxoplasma Gondii, Rubella virus and Cytomegalovirus (CMV) IgM and IgG results, the avidity tests and perinatal follow-up results retrospectively. Material and Method: Test results of pregnant women who applied to Gynecology and Obstetrics Polyclinics in 2017-2018 were analyzed retrospectively.When IgM result was positive for any of these infections, IgG avidity indices, ultrasound (USG) findings, prenatal screening results, amniocentesis results, week of gestation that IgM positivity was observed, and if any treatments applied for these infections, were examined from the file records of pregnant women. Results: It was observed that 24.1% of 6719 patients were Toxoplasma IgG, 98.9% were Rubella IgG and 98.7% were CMV IgG positive. When the IgM positivity was examined, it was seen that this rate was 0.46% (n=31) for Toxoplasma, 0.16% (n=11) for Rubella and 0.7% (n=47) for CMV. There was only 9 low avidity test results for Toxoplasma Gondii. But there was no evidence of perinatal infection associated with these infectious agents . Conclusion: In conclusion, screening for toxoplasma, rubella and CMV infections during pregnancy is still a controversial subject and there is no national screening programme in Turkey. Knowing the seroprevalence is of great importance in establishing national screening strategies and providing consultancy to pregnant women about protection from these infections. From this point of view our study is valuable in that it contributes to these data as the first study conducted in Balıkesir region on this subject

Occurrence of Seropositivity of Toxoplasma gondii, Cytomegalovirus, and Rubella Infections in Pregnant Women

Aim: To assess the seropositivity for Toxoplasma gondii, Rubella virus, and Cytomegalovirus among pregnant females in Hyderabad, Sindh, Pakistan Methodology: A prospective study was undertaken at the Department of Gynecology and Obstetrics, Bahria University of Health Sciences, Karachi, Pakistan between March 2020 to June 2021. All women with confirmed pregnancies were eligible to participate in the study. Women with ectopic pregnancy or women who were not receiving prenatal care at our center were excluded. All participants underwent assessment for antibody Titres for Toxoplasmosis, Rubella, and CMV. Blood specimens of participating women were obtained in aseptic conditions for laboratory investigations. The IgM and IgG antibodies for Toxoplasma gondii, Rubella, and CMV along with IgG antibodies for CMV and Toxoplasma gondii were assessed comprehensively. Seropositivity was stratified with respect to age groups. Results: A total of 336 women with a mean age of 26.88 ± 3.77 years were included. The rate of seropositivity for anti-Toxoplasma IgM, anti-Rubella IgM, and anti-CMV IgM was 1.2%, 0.6%, and 2.7%, consecutively. A total of four (1.2%) cases were positive for anti-Toxoplasma IgM. 126(37.5%) women were positive for Anti-Toxoplasma IgG. For the three positive cases of both IgM and IgG, avidity test showed high avidity. Overall, one case for toxoplasma gondii was detected. Two women were positive for anti-Rubella IgM only (positive cases). Overall, 291 (86.6%) individuals were positive for Rubella IgG. Overall, two cases of Rubella were detected in our study. All nine positive cases of anti-CMV IgM antibodies were also positive for anti-CMV IgG. For these nine cases, anti-CMV IgG avidity was reported which turned out to be intermediary or high. Overall, we did not detect a case of CMV in our study. Conclusion: We found high levels of IgG antibodies for Rubella and CMV, indicating past infection/immunity. The present study highlighted the seroprevalence rate of Toxoplasma gondii, CMV, and Rubella in a cohort of pregnant women from Sindh. However, this rate could be under-reported as many women do not avail of antenatal services during pregnancy, especially from rural Sindh, Pakistan. Nevertheless, this study adds to the current literature. Furthermore, it is recommended to regularly screen pregnant females for these infections. Keywords: Cytomegalovirus, rubella, seroprevalence, torch infections, toxoplasma gondii

Contribution of Serum Cytomegalovirus PCR to Diagnosis of Early CMV Primary Infection in Pregnant Women.

(1) Background: What is the role of serum CMV PCR in the diagnosis of recent primary infection (PI) in pregnant women when IgG avidity is uninformative? (2) Methods: Retrospective cohort study to compare serum versus whole blood CMV PCR. (a) Qualitative assessment: CMV PCR was performed on 123 serum samples and 74 whole blood samples collected from 132 pregnant women with recent CMV PI. PCR positivity rate was used to calculate sensitivity in serum and whole blood. (b) Quantitative assessment: CMV PCR was performed on 72 paired samples of serum and whole blood collected on the same day from 57 patients. (3) Results: In pregnant women, PCR positivity rate was 89% for serum samples versus 100% in whole blood in the case of very recent PI (<15 days), but only 27% in serum versus 68% in whole blood for PI occurring from 6 weeks to 3 months before. Comparing CMV viral loads between serum and whole blood, we determined the limit of CMV DNA detection in serum as 3 log copies/mL (whole blood equivalent). (4) Conclusions: Serum CMV PCR is reliable in confirming PI in cases when only IgM is detected. It is therefore a valuable tool in introducing valaciclovir treatment as early as possible to prevent mother-to-child CMV transmission.

Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)—therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)—and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6–23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration < 65 µg/dL) and 40% had anaemia before receiving zinc supplementation. aAfter receiving the TZ, MNP or PZ regimen, the plasma anti-E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02428647 (NCT02428647, 29/04/2015).

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii.

In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected with Toxoplasma gondii, with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti-T. gondii total IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence of T. gondii soluble antigen (STAg) the amount of CD4+ T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4+ CD25HighFOXP3+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti-T. gondii antibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses against T. gondii.

Seroprevalence, risk factors, and serological cross-reactivity for diagnosis of Toxoplasma gondii and Neospora caninum infections in goats in India

Toxoplasma gondii and Neospora caninum are genetically related cyst-forming protozoan parasites that cause reproductive failures in ruminants. Given the limited information on the epidemiology of these infections in goats in India, the study aimed to estimate the seroprevalence, assess antibody cross-reactivity for diagnosis, and identify associated risk factors. A total of 695 sera were evaluated for antibodies to T. gondii and N. caninum infections using Modified Agglutination Test (MAT for Toxoplasma)/Neospora agglutination test (NAT), Enzyme-linked immunosorbent assay (ELISA), and Indirect Fluorescent Antibody Test (IFAT for tachyzoite and bradyzoite stages). The seroprevalence rate of T. gondii and N. caninum infections was 56.9% and 10.9%, respectively. Inter-rater agreement (kappa value - κ) was calculated to assess agreements between various diagnostic assays, using the IFAT as the gold standard (for detecting both infections), the agreements for MAT/NAT (κ = 0.97) and the ELISA (κ = 0.95) were excellent. The acute infection among seropositive goats were determined using serological (IgG avidity test - measures the binding strength between IgG antibodies and parasite antigens) and molecular diagnoses (PCR for repetitive DNA sequences – Toxoplasma B1 gene: 131 bp and Neospora NC5 gene: 328 bp). Among seropositive goats ≥80% had high IgG avidity and <10% of animals had low IgG avidity antibodies for both infections. Most low IgG avidity goats were PCR positive for the TgB1 gene (94.4%) or Nc5 gene (85.7%). In the serological assays, we used different dilutions of test serum to rule out the cross-reactivity owing to similar antigenic makeup between these two parasites. When the serological cross-reactivity was analyzed using invasion assay at a serum titer of ≥200, more than 90% T. gondii positive sera showed host cell invasion of N. caninum and vice versa. Largely, the serological results indicate that cut-off serum dilution of ≥1:200 for ELISA and IFAT and ≥1:25 for MAT/NAT avoids serological cross-reactivity between T. gondii and N. caninum. Further, the Univariate and multivariate analyses showed that adult animals (>2 years), reservoir hosts, and extensive rearing systems are common risk factors for these infections. However, the history of abortion was identified as a significant risk factor for T. gondii infection. This study revealed that T. gondii and N. caninum infections are highly prevalent in this region and the use of an appropriate cut-off serum dilution is necessary to avoid cross-reactivity between these closely related parasites.

Durability of Immune Response After COVID-19 Booster Vaccination and Association With COVID-19 Omicron Infection

The BNT162b2 two-dose vaccine (BioNTech/Pfizer) has high effectiveness that wanes within several months. The third dose is effective in mounting a significant immune response, but its durability is unknown. To compare antibody waning after second and third doses and estimate the association of antibody kinetics with susceptibility to infection with the Omicron variant of SARS-CoV-2. In a prospective longitudinal cohort study in a tertiary medical center in Israel, health care workers who received the BNT162b2 vaccine were followed up monthly for IgG and neutralizing antibody levels. Linear mixed models were used to compare antibody titer waning of second and third doses and to assess whether antibody dynamics were associated with Omicron transmission. Avidity, T cell activation, and microneutralization of sera against different variants of concern were assessed for a subgroup. Vaccination with a booster dose of the BNT162b2 vaccine. The primary outcome was the rate of antibody titer change over time, and the secondary outcome was SARS-CoV-2 Omicron variant infection, as confirmed by reverse transcriptase-polymerase chain reaction. Overall, 4868 health care workers (mean [SD] age, 46.9 [13.7] years; 3558 [73.1%] women) and 3972 health care workers (mean [SD] age, 48.5 [14.1] years; 996 [74.9%] women) were followed up for 5 months after their second and third vaccine doses, respectively. Waning of IgG levels was slower after the third compared with the second dose (1.32%/d [95% CI, 1,29%/d to 1.36%/d] vs 2.26% [95% CI, 2.13%/d 2.38%/d]), as was waning of neutralizing antibody levels (1.32%/d [95% CI, 1.21%/d to 1.43%/d] vs 3.34%/d [95% CI, 3.11%/d to 3.58%/d]). Among 2865 health care workers assessed for Omicron incidence during an additional 2 months of follow-up, lower IgG peak (ratio of means 0.86 [95% CI, 0.80-0.91]) was associated with Omicron infection, and among participants aged 65 years and older, faster waning of IgG and neutralizing antibodies (ratio of mean rates, 1.40; [95% CI, 1.13-1.68] and 3.58 [95% CI, 1.92-6.67], respectively) were associated with Omicron infection. No waning in IgG avidity was observed 112 days after the third dose. Live neutralization of Omicron was lower compared with previous strains, with a geometric mean titer at the peak of 111 (95% CI, 75-166), compared with 942 (95% CI, 585-1518) for WT, 410 (95% CI, 266-634) for Delta; it demonstrated similar waning to 26 (95% CI, 16-42) within 4 months. Among 77 participants tested for T cell activity, mean (SD) T cell activity decreased from 98 (5.4) T cells/106 peripheral blood mononuclear cells to 59 (9.3) T cells/106 peripheral blood mononuclear cells. This study found that the third vaccine dose was associated with greater durability than the second dose; however, Omicron was associated with greater resistance to neutralization than wild type and Delta variants of concern. Humoral response dynamics were associated with susceptibility to Omicron infection.