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Immunoglobulin G (IgG) and immunoglobulin M (IgM) testing are commonly used to determine infection status. Typically, the detection of IgM indicates an acute or recent infection, while the presence of IgG alone suggests a chronic or past infection. However, relying solely on IgG and IgM antibody positivity may not be sufficient to differentiate acute from chronic infections. This limitation arises from several factors. The prolonged presence of IgM can complicate diagnostic interpretations, and false positive IgM results often arise from antibody cross-reactivity with various antigens. Additionally, IgM may remain undetectable in prematurely collected samples or in individuals who are immunocompromised, further complicating accurate diagnosis. As a result, additional diagnostic tools are required to confirm infection status. Avidity is a measure of the strength of the binding between an antigen and antibody. Avidity-based assays have been developed for various infectious agents, including toxoplasma, cytomegalovirus (CMV), SARS-CoV-2, and avian influenza, and are promising tools in clinical diagnostics. By measuring the strength of antibody binding, they offer critical insights into the maturity of the immune response. These assays are instrumental in distinguishing between acute and chronic or past infections, monitoring disease progression, and guiding treatment decisions. The development of automated platforms has optimized the testing process by enhancing efficiency and minimizing the risk of manual errors. Additionally, the recent advent of real-time biosensor immunoassays, including the label-free immunoassays (LFIA), has further amplified the capabilities of these assays. These advances have expanded the clinical applications of avidity-based assays, making them useful tools for the diagnosis and management of various infectious diseases. This review is structured around several key aspects of IgG avidity in clinical diagnosis, including: (i) a detailed exposition of the IgG affinity maturation process; (ii) a thorough discussion of the IgG avidity assays, including the recently emerged biosensor-based approaches; and (iii) an examination of the applications of IgG avidity in clinical diagnosis. This review is intended to contribute toward the development of enhanced diagnostic tools through critical assessment of the present landscape of avidity-based testing, which allows us to identify the existing knowledge gaps and highlight areas for future investigation. [ABSTRACT FROM AUTHOR]

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR­–negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.

Mongolia experienced a nationwide measles outbreak during 1 March 2015–31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months–5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15–25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to "hidden" cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required. [ABSTRACT FROM AUTHOR]

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]

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. [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.

Mongolia experienced a nationwide measles outbreak during 1 March 2015–31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months–5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15–25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to “hidden” cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required.

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 and Objective: The most important concern associated with diagnosing congenital toxoplasmosis is to determine when the mother has been infected. The importance of using serological diagnostic tests such as IgG-avidity assay which can distinguish between recent and past infections has been proven. The present study aimed to diagnose acute toxoplasmosis in the first trimester of pregnancy using IgG-avidity testing. Materials and Methods: The present descriptive cross-sectional study was conducted in Hamadan, Iran in 2019. A total of 340 blood samples were collected from pregnant women in the first trimester of pregnancy and stored at -70 °C until experimenting. The IgG antibody titer was then determined. Also, IgM and IgG-avidity titers were measured for those samples with a positive IgG titer. Results: Out of 340 pregnant women, 106 (31.2%) had a positive and 2 (0.6%) had a suspected IgM test. Of the 106 pregnant mothers with positive IgG, 6 (5.66%) had low IgG-avidity indicating recent infection of toxoplasmosis in the past 3 to 4 months. IgG-avidity titer was moderate in 10 patients (9.43%) and high in 90 patients (84.9%). Conclusion: Using the IgG-avidity test and its improved methods along with other serological and molecular methods can be effective in determining and differentiating acute toxoplasmosis in pregnant women, especially in the first trimester of pregnancy, and preventing its irreversible complications in the fetus.

Objectives: This study aimed at determining the prevalence of CMV infection among pregnant women at the end of pregnancy and CMV transmission to their newborns. Methods: This is cross sectional study, 213 pregnant women at delivery and their newborn babies from the Obstetrics and Gynecology Hospital in Duhok/Iraq were enrolled. A questionnaire was prepared to be answered by participants, including age, place of residence, educational level, and obstetric history as number of births, any bad obstetric history such as abortion, still birth, intrauterine growth retardation, congenital anomalies after birth. 3-5 ml of blood was drawn from each woman and examined by ELISA kit to check for the presence of Anti CMV IgM, IgG, then IgG avidity test for those with positive (IgG and IgM). Samples of cord blood were collected from newborns after birth and checked for the presence of CMV IgM by ELISA and CMV--DNA by conventional PCR using specific primers to diagnose congenital infection and determine the rate of viral transmission from infected women. Results: Serological examinations showed that 212 (99.5%) participants were CMV-IgG positive, 15 (7%) were positive for anti-CMV IgM and IgG antibodies, IgG avidity test for 15 women were of high avidity (>89%) which indicated non primary infections. Cord blood of newborns of those 15 women with positive IgG and IgM tested negative for Anti CMV IgM by ELISA and no CMV-DNA was detected by PCR, which revealed no transmission from those pregnant to their newborns. Conclusion: This study demonstrated high prevalence of CMV among examined pregnant women in Duhok city which makes them prone to non-primary infection. IgG avidity test is of high efficacy to interpret the detection of IgG and IgM together in pregnant women. Cord blood examination for the existence of CMV-IgM and CMV-DNA after delivery could exclude congenital infection. [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]

Background: The diagnosis of West Nile virus (WNV) is challenging due to short-term and low-level viremia, flavivirus cross-reactivity, and long immunoglobulin M (IgM) persistence., Aim: To evaluate different methods for WNV detection [reverse transcription-polymerase chain reaction (RT-PCR), IgM/IgG antibodies, IgG avidity] in serum, cerebrospinal fluid (CSF), and urine samples of patients with confirmed WNV infection., Methods: The study included patients with confirmed WNV neuroinvasive infection ( n = 62), asymptomatic WNV seropositive individuals ( n = 22), and individuals with false-positive WNV IgM antibodies ( n = 30). WNV RNA was detected using RT-PCR. A commercial ELISA was used to detect WNV IgM/IgG antibodies with confirmation of cross-reactive samples using a virus neutralization test (VNT). IgG-positive samples were tested for IgG avidity., Results: The WNV-RNA detection rates were significantly higher in the urine (54.5%)/serum (46.4%) than in CSF (32.2%). According to the sampling time, the WNV-RNA detection rates in urine collected within 7 days/8-14/≥ 15 days were 29.4/66.6/62.5% ( P = 0.042). However, these differences were not observed in the CSF. The median RT-PCR cycle threshold values were significantly lower in urine (32.5, IQR = 28-34) than in CSF (34.5, IQR = 33-36). The frequency of positive WNV IgM and IgG significantly differed according to the sampling time in serum but not in CSF. Positive IgM/IgG antibodies were detected in 84.3/9.3% of serum samples collected within 7 days, 100/71.1% of samples collected 8-14, and 100% samples collected after ≥ 15 days. Recent WNV infection was confirmed by low/borderline avidity index (AI) in 13.6% of asymptomatic individuals. A correlation between ELISA and AI was strong negative for IgM and strong positive for IgG. No significant correlation between ELISA IgG and VNT was found., Conclusion: The frequency of WNV RNA and antibody detection depends on the sampling time and type of clinical samples. IgG avidity could differentiate recent WNV infections from long-persisting IgM antibodies., Competing Interests: Conflict-of-interest statement: All authors reported no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Abstract Objective The purpose of the present study is to standardize and evaluate the use of the immunoglobulin G (IgG) antibody avidity test on blood samples from newborns collected on filter paper to perform the heel test aiming at its implementation in ongoing programs. Methods Blood samples from newborns were collected on filter paper simultaneously with the heel prick test. All samples were subjected to immunoglobulin M IgM and IgG enzyme-linked immunosorbent assays (ELISA). Peripheral blood was collected again in the traditional way and on filter paper from newborns with high IgG levels (33). Three types of techniques were performed, the standard for measuring IgG in serum, adapted for filter paper and the technique of IgG avidity in serum and on filter paper. The results of the avidity test were classified according to the Rahbari protocol. Results Among the 177 samples, 17 were collected in duplicate from the same child, 1 of peripheral blood and 1 on filter paper. In this analysis, 1 (5.88%) of the 17 samples collected in duplicate also exhibited low IgG avidity, suggesting congenital infection. In addition, the results obtained from serum and filter paper were in agreement, that is, 16 (94.12%) samples presented high avidity, with 100% agreement between the results obtained from serum and from filter paper. Conclusion The results of the present study indicate that the avidity test may be another valuable method for the diagnosis of congenital toxoplasmosis in newborns.

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]

Background: Diagnosis of prolonged febrile illness of unknown origin (FUO) is challenging even with the advances in the diagnostic techniques. As common as the infection with cytomegalovirus (CMV) is, most health care providers would not suspect CMV infection as a cause of FUO unless mononucleosis syndrome is evident. The aim of this study is to investigate the rate of CMV infection among patients with FUO and shed light on IgG avidity as a diagnostic tool. Patients and methods: Two hundred and twenty three (223) immune competent patients with FUO were included in our study. They were subjected to all routine laboratory investigations, fever agglutinins, tuberculin and abdominal ultrasound along with IgG and IgM for CMV and IgG avidity test. Results: This study shows that the 92.8% of the overall studied population were positive for CMV IgG. However, only 74(33.2%) of the studied population was found positive for IgM. Only one patient had positive IgM with negative IgG. IgG avidity was high in almost all of them. Only 3 patients showed low IgG avidity denoting that they have primary infection. Conclusion: CMV infection was found to be the cause of 33.2% of prolonged febrile illness experienced by immuncompetent adults. Only 1.8% of patients had primary CMV infection and the majority of them had detectable IgG level and were diagnosed with primary infection depending mainly on IgG avidity test. [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]

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]

[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]

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.

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR--negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.

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).

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]

Introduction: The high variability of SARS-CoV-2 serological response after COVID-19 infection hampers its use as indicator of the timing of infection. A potential alternative method is the determination of affinity maturation of SARS-CoV-2 IgG, expressed as the SARS-CoV-2 IgG avidity., Methods: SARS-CoV-2 IgG concentration and avidity were measured in sera of hospitalized COVID-19 patients sampled at two weeks and ≥12 weeks post symptom onset using an in-house developed protocol based on EUROIMMUN (anti-spike) and EDI™ (anti-nucleocapsid) SARS-CoV-2 IgG ELISA protocols., Results: We included 68 confirmed COVID-19 patients that tested positive for SARS-CoV-2 IgG in both the initial and follow-up specimen sampled at a median of 14 (range 10-18) days and 120 (range 84-189) days, respectively, post symptom onset. The median anti-spike and anti-nucleocapsid SARS-CoV-2 IgG avidity response was 40% (range 9-93%) and 72% (range 27-104%), respectively, for the first sample, and 66% (range 28-90%) and 57% (range 25-94%), respectively, for the second sample. The proportion of SARS-CoV-2 IgG avidity results ≥60% was significantly lower for anti-spike compared to anti-nucleocapsid IgG for initial samples ( p < 0.01) and vice versa for follow-up samples ( p < 0.01)., Conclusion: Anti-nucleocapsid SARS-CoV-2 IgG maturation occurs faster and avidity decreases faster than anti-spike IgG, indicating different kinetics of anti-spike and anti-nucleocapsid IgG. Further, affinity maturation after SARS-CoV-2 infection is frequently incomplete.