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This study evaluated whether IgG avidity measured by chemiluminescent microparticle immunoassay (CMIA) compared with enzyme-linked immunosorbent assay (ELISA) was useful to detect primary T. gondii infection during pregnancy and to estimate the risk for congenital T. gondii infection. One hundred six women with positive tests for T. gondii IgG and T. gondii IgM, comprising 21 women (19.8%) with low (<30%), 6 (5.7%) with borderline (30%–35%), and 79 (74.5%) with high (>35%) IgG avidity measured by ELISA were selected. Their stored sera were used for T. gondii IgG avidity measurements by CMIA. In CMIA, 72 (67.9%) women had low (<50%), 12 (11.3%) had borderline (50%–59.9%), and 22 (20.8%) had high (≥60%) IgG avidity. The ratio of low T. gondii IgG avidity index in CMIA was more than three-fold than that in ELISA. Eighteen (85.7%) of 21 women with ELISA low avidity also had CMIA low avidity, and 26 (96.3%) of 27 women with ELISA low or borderline avidity corresponded to CMIA low or borderline avidity, whereas 21 (26.6%) of 79 women with ELISA high avidity were diagnosed with CMIA low avidity. All three cases with congenital T. gondii infection showed coincidentally low IgG avidity in both methods. A positive correlation in IgG avidity indices was found between of ELISA and CMIA. CMIA for T. gondii avidity measurements compared with ELISA was clinically useful to detect pregnant women at a high risk of developing congenital T. gondii infection. [ABSTRACT FROM AUTHOR]

Fasciola hepatica , a worldwide distributed helminth, has a robust immunoregulatory effect in the host, increasing the susceptibility to secondary infections. Foot and mouth disease (FMD) is a highly contagious acute vesicular viral disease effectively controlled by vaccination in endemic regions. Despite the evidence of immunoregulatory effects, the impact of fasciolosis on the immune response induced by FMD vaccination in cattle has never been assessed. Our objective was to evaluate whether the infection by F. hepatica in cattle influences the long-term immunity elicited by the currently used commercial FMD-inactivated vaccines. Aberdeen Angus steers negative for F. hepatica were vaccinated twice against FMD virus (FMDV) during the first 6 months of age using a commercial oil vaccine formulated with A24/Cruzeiro and O1/Campos strains. When maternal antibodies against F. hepatica were weaned (18––20 months of age) animals were divided into groups of 12 and infected or mock-infected with 500 metacercariae/animal. Individual serum samples were collected at 0-, 28-, 59-, 87- and 157-days post-infection (dpi). Indirect ELISAs were used to detect A24/Cruzeiro specific bovine IgG and IgG subtypes. The total IgG antibody levels and avidity against FMDV did not show significant differences between all the groups. The commercial vaccine induced higher IgG2 than IgG1 titers in vaccinated animals. Anti-FMDV IgG1 levels significantly decreased in the infected group at 28 dpi. In addition, the avidity of IgG1 FMDV-specific antibodies at day 28 in the infected group was reduced compared to the control. These results show that F. hepatica infection modified anamnestic responses against FMDV, reducing serum IgG1 titers and avidity. To our knowledge, this is the first report of immune-regulation of F. hepatica altering the immune response of FMD vaccines, one of the most globally used animal vaccines. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is a protozoan parasite that is widely distributed in the human population and is responsible for corresponding global morbidity. Specifically, T. gondii causes toxoplasmosis, leading to miscarriage, stillbirth, and neural disorders. This parasite attacks different human organs and glands, such as the thyroid gland, and causes various corresponding health issues. Recently, studies have established a link between T. gondii and autoimmune thyroid diseases (AITD), which contributes to preterm delivery, miscarriage, low birth weight, and death. Therefore, the aim of this study was to detect the prevalence of toxoplasmosis and its association with AITD among pregnant women. A total of 180 blood samples were collected from pregnant women and examined using an enzyme-linked immunosorbent assay (ELISA). The patients were within the age range of 15–50 years old, and lived in Duhok City, Iraq; samples and clinical information was collected from August 2021 to February 2022. The corresponding blood samples were tested for anti-Toxoplasma IgG antibody, Toxoplasma IgG avidity, FT3, FT4, and TSH hormones, and TPO, Tg, and TSHR antibodies. Overall, our results showed that out of 180 pregnant women, 110 (61.1%) were seropositive for anti-Toxoplasma IgG antibody; specifically, 25 (22.7%) and 85 (77.3%) had recent and past infections, respectively. Approximately 54.4% (98) of the pregnant women had thyroid disorders; further, 22 (12.2%), 13 (7.2%), and 8 (4.4%) women had TPO, Tg, and TSHR antibodies, respectively. A total of 43 (23.8%) patients screened positive for AITD. Out of the 110 Toxoplasma IgG–positive women, 35 (31.8%) had AITD. The older women, rural residents, restaurant food consumers, and women with cat contact had relatively high infection rates. Toxoplasma seropositive women had more elevated autoantibodies than seronegative ones. In conclusion, this study demonstrated a high rate of toxoplasmosis and a corresponding association with thyroid hormones changes and AITD in pregnant women in Duhok, Iraq. Further, it is necessary to reduce overall infection rates through effective health and educational programs. Therefore, it is essential to measure Toxoplasma antibodies, screen for thyroid hormones and autoantibodies, and encourage gynecologist visits to reduce the risks to mothers and fetuses. [ABSTRACT FROM AUTHOR]

Gaining more appreciation on the protective/damaging aspects of anti-SARS-CoV-2 immunity associated with disease severity is of great importance. This study aimed to evaluate the avidity of serum IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) in hospitalized symptomatic COVID-19 patients and asymptomatic RT-PCR-confirmed SARS-CoV-2 carriers as well as to compare antibody avidities with respect to vaccination status, vaccination dose and reinfection status. Serum levels of anti-S and anti-N IgG were determined using specific ELISA kits. Antibody avidity was determined by urea dissociation assay and expressed as avidity index (AI) value. Despite higher IgG levels in the symptomatic group, AI values of both anti-S and anti-N IgG were significantly lower in this group compared to asymptomatic individuals. In both groups, anti-S AI values were elevated in one-dose and two-dose vaccinees versus unvaccinated subjects, although significant differences were only detected in the symptomatic group. However, anti-N avidity showed no significant difference between the vaccinated and unvaccinated subgroups. Almost all vaccinated patients of different subgroups (based on vaccine type) had higher anti-S IgG avidity, while the statistical significance was detected only between those receiving Sinopharm compared to the unvaccinated subgroup. Also, statistically significant differences in antibody AIs were only found between primarily infected individuals of the two groups. Our findings indicate a key role for anti-SARS-CoV-2 IgG avidity in protection from symptomatic COVID-19 and calls for the incorporation of antibody avidity measurement into the current diagnostic tests to predict effective immunity toward SARS-CoV-2 infection or even for prognostic purposes. [ABSTRACT FROM AUTHOR]

Background/Aim Congenital human cytomegalovirus infection (cCMV) is the commonest congenital infection, and it can result in hearing loss and neurodevelopmental delay. Even if primary infections are more frequent and cause more severe congenital cCMV manifestations compared to NPIs, and despite partial protection from maternal immunity, the highest birth prevalence of cCMV is observed in seropositive women with non-primary CMV infection (NPI). Given that NPI contribute significantly to the overall burden of cCMV, their accurate diagnosis of NPI remains clinically important. Considering that the serological testing for CMV infection is not always reliable, we sought to determine whether detection of CMV DNA in pregnant women with a high IgG avidity index (AI) can help diagnose NPI. Materials and methods Human CMV serology screening (IgG, IgM, and IgG AI) was performed for confirmation of CMV infection in serum samples from mainly pregnant women with indications of CMV infection due to IgG+ and IgM+-positive samples in other laboratories. Pregnant women (or those with termination of pregnancy during the last period) with adequate IgG levels to perform IgG AI were included. Demographic data and mean gestation week at the time of screening were recorded. Serological testing was performed using CE-IVD commercial kits. CMV DNAemia detection by real time PCR (RT-PCR) was applied to confirm suspected CMV infection. Results Nine-hundred and thirty-four pregnant women CMV IgG positive with adequate IgG titers for AI testing were included in the study. The percentage of women with a high AI was 71.8% (671/934); among them, nearly 2.4% (16/671) had presence of CMV DNA. Also, 12.4% of women (116/934) had intermediate IgG AI and 15.7% of women (147/934) had low IgG AI. The presence of CMV DNA was observed in 13.8% (16/116) and 39.5% (58/147) of the groups with intermediate and low IgG AI, respectively. A high CMV IgG AI was associated with a negative CMV PCR status (p-value <.00001). Conclusions CMV DNA was present in 2.4% of seropositive women with high IgG AI, indicating active NPI and thus, harboring the risk of cCMV sequelae to the fetus. Moreover, the incidence of NPI may have been underestimated due to single timepoint testing. In order to detect CMV NPI in a seropositive woman, regular and frequent serology testing as well as detection of CMV DNAemia are required which render the whole diagnostic process impractical and not cost-effective. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii, an obligate intracellular protozoan parasite, is the causative agent of one of the most prevalent zoonoses worldwide. T. gondii infection is extremely important from a medical point of view, especially for pregnant women, newborns with congenital infections, and immunocompromised individuals. Thus, an accurate and proper diagnosis of this infection is essential. Among the available diagnostic tests, serology is commonly used. However, traditional serological techniques have certain limitations in evaluating the duration of T. gondii infection, which is problematic, especially for pregnant women. Avidity of T. gondii-specific IgG antibodies seems to be a significant tool for discrimination between recent and distant infections. This article describes the problem of diagnosis of T. gondii infection, with regard to IgG avidity tests. The IgG avidity test is a useful serological indicator of toxoplasmosis, which in many cases can confirm or exclude the active form of the disease. IgG antibodies produced in the recent primary T. gondii infection are of low avidity while IgG antibodies with high avidity are detected in the chronic phase of infection. Furthermore, this paper presents important topics of current research that concern the usage of parasite recombinant antigens that may improve the performance of IgG avidity tests. [ABSTRACT FROM AUTHOR]

In regions where the endemic measles virus has been eliminated, early detection of contagious patients is important for preventing the spread of measles and sustaining elimination. To investigate whether serological assays can be used for the estimation of highly infectious patients with measles, we performed a seroepidemiologic study of a measles outbreak in Yamagata Prefecture, Japan, in 2017. We tested plaque reduction neutralization (PRN), IgG avidity, and gelatin particle agglutination (PA) assays in 31 patients with measles, subdivided into two super-spreaders, three spreaders, and 26 non-spreaders. Simultaneously, these results were compared with the cycle threshold (Ct) of a semi-quantitative real-time reverse transcription PCR for the measles virus from throat swab specimens. In the PRN assay, one super-spreader and two spreaders lacked protective antibodies. The IgG avidity assay showed that two super-spreaders and one spreader had low avidity. The PA assay indicated that two super-spreaders and two spreaders lacked protective antibodies. Comparison of the results of the three serological assays and Ct revealed that patients whose antibody titers were judged as low in the IgG avidity and PA assays showed low Ct (i.e., high viral load), whereas non-spreaders tended to show low viral load. Our preliminary seroepidemiologic analysis of a population of 31 patients with measles suggests that PA and IgG avidity assays may be used for the identification of super-spreader/spreader candidates. However, further investigations are necessary to validate the robustness of these serological assays in detecting contagious measles cases. [ABSTRACT FROM AUTHOR]

[Display omitted] • SARS CoV-2 and Toxoplasma gondii are widespread infectious agents that can be expected to co-exist in a large number of patients. • Cytokines are important determinants of the severity of COVID-19 manifestations. • Toxoplasmosis induces immune modulation which reflects on concomitant infections when present. • The study of the effect of co-infection between these two pathogens on cytokine response and clinical outcome must be solidated by mass studies. The symptomatology of COVID-19 is dependent on the immune status and the cytokine response of the host. The cytokine level of the host is influenced by the presence of chronic persistent or latent infections with co-pathogens. Parasitic diseases are known to induce host immune-modulation which may impact the response to co-infection. Toxoplasmosis is a widespread protozoal infection that remains quiescent in its latent form to be re-activated during states of immune depression. Clinical data on the relation between toxoplasmosis and COVID-19 cytokine profile and symptomatology are still insufficient. Seventy-nine subjects were included in this study. Patients were diagnosed with COVID-19 by PCR. Serological testing for toxoplasmosis was performed by the detection of anti- Toxoplasma IgG antibodies, in addition to IgG avidity testing. IFN-γ and TNF-α levels were determined by RT-PCR. Among patients diagnosed with COVID-19, 67.1% were seronegative for anti- Toxoplasma IgG, while 32.9% were seropositive. High avidity was found in 10 cases (40% of seropositive cases), 4 of whom required ICU administration, while low avidity was found in 15 cases (60%), 7 of which were administered to the ICU. TNF-α and INF-γ levels were significantly higher in COVID-19 patients than in healthy control subjects. No significant association was found between the seroprevalence of toxoplasmosis and the presence of COVID-19 and its severity. Cytokines were significantly higher in both seropositive and seronegative COVID-19 patients than in their control counterparts. The high prevalence of toxoplasmosis merits further exploration of its relation to COVID-19 by mass studies. [ABSTRACT FROM AUTHOR]

The avidity index (AI) of IgG to the RBD of SARS-CoV-2 was determined for 71 patients with a mild (outpatient) course of COVID-19, including 39 primarily and 36 secondarily reinfected, and 92 patients with a severe (hospital) course of COVID-19, including 82 primarily and 10 secondarily infected. The AI was shown to correlate with the severity of repeated disease. In the group of outpatients with a mild course, the reinfected patients had significantly higher median AIs than those with primary infections (82.3% vs. 37.1%, p < 0.0001). At the same time, in patients with a severe course of COVID-19, reinfected patients still had low-avidity antibodies (median AI of 28.4% vs. 25% in the primarily infected, difference not significant, p > 0.05). This suggests that the presence of low-avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient's risk of developing COVID-19 in a severe form is significantly increased. Thus, patients with IgG of low avidity (AI ≤ 40%) had an 89 ± 20.5% chance of a severe course of recurrent COVID-19, whereas the detection of high-avidity antibodies (AI ≥ 50%) gave a probability of 94 ± 7.9% for a mild course of recurrent disease (p < 0.05). [ABSTRACT FROM AUTHOR]

Objective: Toxoplasmosis acquired in early pregnancy is a potentially severe complication for the fetus. Evaluating the risk of transplacental infection in pregnant women accessing the Tuscany Reference Center for Infectious Diseases in Pregnancy during the last 20 years with suspected or confirmed toxoplasmosis acquired in early pregnancy was the aim of the study.Study Design: We retrospectively enrolled all pregnant women undergoing amniocentesis for toxoplasmosis acquired in the first 16 gestational weeks in the period 1999-2019, comparing patients with certain acute infection (seroconversion occurred in pregnancy, CAIP) with those with suspected acute infection (IgG positive with low/intermediate IgG avidity index, SAIP).Results: 237 patients were enrolled, 187 (78.9%) with SAIP and 50 (21.1%) with CAIP. Specific IgM was detected in 47.5% and 76.7% (p-value 0.001), and the mean IgG avidity index was 22.7% and 7.1% (p-value < 0.001) in the SAIP and in the CAIP group, respectively. The mean delay from diagnosis to antibiotic initiation was 14.6 in SAIP and 11 days in CAIP group. Toxoplasma DNA was detected in the amniotic fluid in one case in a patient with CAIP. Excluding 24 newborns with not available data, prevalence of congenital infection was 0.47% [1/213 (95% CI 0.08%-2.61%)], 0% [0/178 (95% CI 0%-2.11%)] in SAIP and 2.8% [1/35 (95% CI 0.51%-14.53%)] in CAIP group.Conclusions: Toxoplasmosis acquired in early pregnancy has a low risk of fetal infection. Actively discussing case-by-case amniocentesis indication with patients, especially when a recent toxoplasmosis is not properly confirmed, is desirable. [ABSTRACT FROM AUTHOR]

Juvenile Idiopathic Arthritis (JIA) patients living in areas with high prevalence of tick-borne-encephalitis-virus-(TBEV)-infection are recommended for administration of inactivated TBE-vaccination. However, there are serious concerns regarding protective vaccine-induced immune responses against TBEV in immunocompromised patients. The present study aimed to analyze the humoral and cellular immune response to TBE-vaccination in previously TBE-vaccinated JIA patients compared to healthy controls (HC) including investigation of IgG-anti-TBEV avidity, neutralization capacity, cellular reactivity by IFNgamma-ELISPOT and cytokine secretion assays. Similar IgG-anti-TBEV antibody concentrations, neutralization titers and cellular reactivity were found between JIA and HC. The number and the early timing of booster vaccinations after primary vaccination had the most prominent effect on neutralizing antibodies in JIA and on IgG-anti-TBEV concentrations in both JIA and HC. Administration of booster vaccinations made it more likely for JIA patients to have IgG-anti-TBEV concentrations ≥165 VIEU/ml and avidities >60%. TNF-alpha inhibitors had a positive and MTX administration a negative effect on humoral immune responses. In conclusion, irrespective of having JIA or not, vaccinated children showed similar humoral and cellular immunity against TBEV several years after primary TBE-vaccination. However, in JIA, booster vaccinations mounted a significantly higher humoral immune response than in JIA without boosters. Our results highlight the need for timely administration of boosters particularly in JIA. Although immunosuppressive treatment at vaccinations in diagnosed JIA had a negative effect mainly on TBEV-specific cellular immunity, most JIA patients mounted a favorable humoral immune response which was maintained over time. Thus, successful TBE-vaccination seems highly feasible in JIA patients with immunosuppressive regimens. [ABSTRACT FROM AUTHOR]

Human Cytomegalovirus (HCMV) infection is associated with bad obstetric history (BOH) and adverse pregnancy outcomes (APO). Here, we characterized antiviral humoral profiles, systemic and virus specific cellular immune responses concurrently in pregnant women (n = 67) with complications including BOH and associated these signatures with pregnancy outcomes. Infection status was determined using nested blood PCR, seropositivity and IgG avidity by ELISA. Systemic and HCMV specific (pp65) cellular immune responses were evaluated by flow cytometry. Seropositivity was determined for other TORCH pathogens (n = 33) on samples with recorded pregnancy outcomes. This approach was more sensitive in detecting HCMV infection. Blood PCR positive participants, irrespective of their IgG avidity status, had higher cytotoxic potential in circulating CD8+ T cells (p < 0.05) suggesting that infection associated cellular dysfunction was uncoupled with avidity maturation of antiviral humoral responses. Also, impaired anamnestic degranulation of HCMV-pp65-specific T cells compared to HCMV blood PCR negative participants (p < 0.05) was observed. APO correlated with HCMV blood PCR positivity but not serostatus (p = 0.0039). Most HCMV IgM positive participants (5/6) were HCMV blood PCR positive with APO. None were found to be IgM positive for other TORCH pathogens. Multiple TORCH seropositivity however was significantly enriched in the APO group (p = 0.024). Generation of HCMV specific high avidity IgG antibodies had no bearing on APO (p = 0.9999). Our study highlights the utility of an integrated screening approach for antenatal HCMV infection in the context of BOH, where infection is associated with systemic and virus specific cellular immune dysfunction as well as APO. • Use of an integrated approach (PCR + Serology + Avidity) to detect HCMV infection. • Adverse pregnancy outcomes correlated with blood PCR positivity but not serostatus. • Impaired anamnestic degranulation of HCMV-pp65-specific Tcells in PCR + participants. • HCMV specific high IgG avidity has no bearing on adverse pregnancy outcomes. • Evaluation of HCMV specific PCR status and T cell immunity could improve outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]