Case report: Infectious cerebral vasculitis due to rickettsiosis.

Rickettsiosis is a widespread infection throughout the world and in Africa, it covers a wide range of infectious diseases caused by Rickettsia species. Rickettsial infections, with the exception of Q fever, typically present with fever, rash, and vasculitis. The central nervous system (CNS) can be affected by all rickettsial diseases and is an important target for several of them. Clinical manifestations are suggestive of rickettsial infection, but serology and skin biopsy provide confirmation. Although the presence of abnormal neuroimaging is rare, its presence is associated with a worse clinical prognosis. Computed tomography (CT) and magnetic resonance imaging (MRI) scans mainly show signs of vasculitis, which may be reversible if appropriate treatment is initiated early in the course of the disease. We present here a case of infectious cerebral vasculitis due to rickettsiosis with some MRI features.

Moleculargenetic and in Addition Partly Discrepant Infection Serological Malaria Testing in Two Blood Donors.

Introduction: According to the guidelines (GL) valid in Germany, persons born or raised in a malaria-endemic area or had continuously stayed in a malaria-endemic area for more than 6 months may only be admitted donating blood if, among other things, validated and quality-assured laboratory diagnostics show that there is no evidence of infectivity. In a statement of the Working Group "Blood" of the Federal Ministry of Health (WGB), a reduction of the deferral period from 4 to 3 years and an antibody test after the deferral period are recommended. Methods: In accordance with the GL, nucleic acid testing (NAT) by means of PCR is carried out at our institution after a retention period of 4 years. In addition to the validated molecular biological testing, an infection serological examination was performed. Case Presentation: In the present cases, Plasmodia genome was detected in the respective single PCR in two blood donors originating from malaria-endemic areas after the expiry of the deferral period. However, one donor tested negative for antibodies against Plasmodia. Discussion/Conclusion: This observation is discussed in the context of a recommendation of the WGB. The question is addressed whether PCR testing is dispensable or whether a combination of infection serological testing and NAT should be favored.

Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1.

This study is to probe into the meaning of serum miR-532-5p in nontraumatic osteonecrosis of the femoral head (ONFH), and a molecular mechanism of miR-532-5p in the development of nontraumatic ONFH. This study enrolled 96 patients diagnosed with nontraumatic ONFH and 96 patients with femoral neck fracture. The levels of miR-532-5p, ABL1, MMP-3, MMP-13, and cleaved-caspase3 were determined. Radiographic progression was assessed by ARCO staging system. Visual analog scale (VAS) and Harris hip score (HHS) were employed for evaluation of the symptomatic severity of nontraumatic ONFH. Cell viability and apoptosis in chondrocytes isolated from clinical samples were investigated with CCK-8 and flow cytometry. The levels of lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) were determined. miR-532-5p was downregulated in tissues and serum of patients with nontraumatic ONFH, negatively related with ARCO staging and VAS, and positively correlated with HHS. Cell apoptosis, LDH, MDA, and ROS strengthened, while cell viability, ΔΨm, and SOD reduced in chondrocytes of nontraumatic ONFH patients. ABL1 was upregulated in cartilage tissues from nontraumatic ONFH patients. miR-532-5p targeted ABL1, and overexpressed miR-532-5p alleviated nontraumatic ONFH-induced oxidative stress damage of chondrocytes by restraining ABL1. miR-532-5p ameliorated oxidative stress injury in nontraumatic ONFH by inhibiting ABL1.

[Use of LDBIO Diagnostics® TOXOPLASMA ICT IGG-IGM in association with Siemens Atellica® IM in toxoplasmosis serological screening]. / Place du test rapide LDBIO Diagnostics® TOXOPLASMA ICT IGG-IGM en complément de la sérologie Siemens Atellica® IM dans la stratégie diagnostique de la toxoplasmose.

According to French recommendations for serological screening of toxoplasmosis, some profiles must be confirmed by additional methods, extending the time taken to produce results. Thus, the Laborizon Bretagne technical platform in Nantes studied the place of the LDBIO Diagnostics® TOXOPLASMA ICT IGG-IGM (ICT) test in addition to Siemens Atellica® serology. IgG-/IgM+ and equivocal or weak positive IgG/IgM- (IgGEq/IgM-) profiles on Atellica® will be confirmed by ICT, Alinity® Abbott and Platelia® Biorad. Among the 66 IgGEq/IgM- profiles, the concordance is perfect between ICT and complementary techniques: 21 weak positives were confirmed positive, 8 equivocal were considered negative and 37 were confirmed positive. Concerning the 76 IgG-/IgM+ profiles, 68 are negative and 7 are positive by complementary techniques and ICT. One discordance was observed. The Atellica®/ICT combination allows excellent discrimination of IgG-/IgM+ and IgGEq/IgM serological profiles with consistent diagnostic orientation in 99.3% of cases. Only 1 sample was found to be discordant but required monitoring at 15 days. The observed performances are compatible with routine use. This test simplifies the analytical process, improves the time to obtain results, while guaranteeing an excellent level of quality.

Cervids as Sentinels for Rickettsia spp. in Portugal.

Cervids are highly exposed to ticks, however, their role in the life cycle of these rickettsiae has not been fully elucidated. Given the expanding distribution and growing population of deer species in Portugal, coupled with their direct and indirect interactions with humans during hunting, it becomes crucial to explore their role as sentinels and potential reservoirs of Rickettsia. The present investigation aimed to detect and evaluate exposure to Rickettsia in free-living deer from Portugal. Blood samples (n = 77) were collected from hunted game animals (red deer and fallow deer) from different areas throughout Portugal (Idanha-a-Nova, Monte Fidalgo, Montalvão and Arraiolos) and sera were tested by immunofluorescence assay, to detect antibodies. Additionally, blood DNA samples were screened for SFGR by nested-polymerase chain reaction targeting a fragment of the outer membrane protein B (ompB) gene, as well as for Anaplasma and Ehrlichia spp. targeting the 16S rRNA gene. Thirty-five per cent (25 deer and two fallow deer) tested positive (sera with a titer ≥1:64) for IgG antibodies against Rickettsia conorii. No rickettsial DNA was detected by PCR for the ompB gene, and all DNA samples tested negative for Anaplasma and Ehrlichia. As far as we know, this study is the first screening of cervid species in Portugal for Rickettsia antibodies. The findings suggest that these animals serve as useful sentinel indicators for the circulation of rickettsiae, offering a complementary perspective to studies focused on ticks. The increasing numbers of hunted deer in Portugal and the potential zoonotic features of Rickettsia spp. highlight the importance of continued surveillance directed at tick-borne diseases, especially those involving wild animals.

SARS-CoV-2 seroprevalence in Nova Scotia blood donors.

Background: SARS-CoV-2 seroprevalence monitors cumulative infection rates irrespective of case testing protocols. We aimed to describe Nova Scotia blood donor seroprevalence in relation to public health policy and reported data over the course of the COVID-19 pandemic (May 2020 to August 2022). Methods: Monthly random Nova Scotia blood donation samples (24,258 in total) were tested for SARS-CoV-2 infection antibodies (anti-nucleocapsid) from May 2020 to August 2022, and vaccination antibodies (anti-spike) from January 2021 to August 2022. Multivariable logistic regression for infection antibodies and vaccination antibodies separately with month, age, sex, and racialization identified independent predictors. The provincial nucleic acid amplification test (NAAT)-positive case rate over the pandemic was calculated from publicly available data. Results: Anti-N seroprevalence was 3.8% in January 2022, increasing to 50.8% in August 2022. The general population COVID-19 case rate was 3.5% in January 2022, increasing to 12.5% in August 2022. The percentage of NAAT-positive samples in public health laboratories increased from 1% in November 2021 to a peak of 30.7% in April 2022 with decreasing numbers of tests performed. Higher proportions of younger donors as well as Black, Indigenous, and racialized blood donors were more likely to have infection antibodies (p < 0.01). Vaccination antibodies increased to 100% over 2021, initially in older donors (60+ years), and followed by progressively younger age groups. Conclusions: SARS-CoV-2 infection rates were relatively low in Nova Scotia until the more contagious Omicron variant dominated, after which about half of Nova Scotia donors had been infected despite most adults being vaccinated (although severity was much lower in vaccinated individuals). Most COVID-19 cases were detected by NAAT until Omicron arrived. When NAAT testing priorities focused on high-risk individuals, infection rates were better reflected by seroprevalence.

Historique: La séroprévalence du SRAS-CoV-2 permet de surveiller les taux d'infection cumulatifs, quels que soient les protocoles de dépistage des cas. Les chercheurs voulaient décrire la séroprévalence chez les donneurs de sang néo-écossais par rapport aux politiques sanitaires et aux données déclarées tout au long de la pandémie de COVID-19 (mai 2020 à août 2022). Méthodologie: Les chercheurs ont mesuré les anticorps à l'infection par le SRAS-CoV-2 (antinucléocapsidiques) de manière aléatoire tous les mois dans des échantillons de dons de sang de la Nouvelle-Écosse (pour un total de 24 258) entre mai 2020 et août 2022, de même que les anticorps aux vaccins (antispiculaires) (entre janvier 2021 et août 2022). La régression logistique multivariable effectuée séparément pour les anticorps contre l'infection et les anticorps aux vaccins, par rapport au mois, à l'âge, au genre et à la race, ont permis d'établir les prédicteurs indépendants. Les chercheurs ont calculé le taux de cas provinciaux positifs aux tests d'amplification des acides nucléiques (TAAN) à partir des données publiques tout au long de la pandémie. Résultats: La séroprévalence anti-N, qui s'élevait à 3,8 % en janvier 2022, était passée à 50,8 % en août 2022. Le taux de cas de COVID-19 dans la population générale se situait à 3,5 % en janvier 2022 et était monté à 12,5 % en août 2022. Le pourcentage d'échantillons positifs au TAAN dans les laboratoires de santé publique est passé de 1 % en novembre 2021 à un pic de 30,7 % en avril 2022, conjointement à une diminution du nombre de tests effectués. De plus fortes proportions de donneurs plus jeunes et de donneurs noirs, autochtones et racisés étaient susceptibles de posséder des anticorps contre l'infection (p < 0,01). Les anticorps attribuables à la vaccination ont atteint 100 % en 2021, d'abord chez les donneurs plus âgés (de plus de 60 ans), puis dans les tranches d'âges progressivement plus jeunes. Conclusions: Les taux d'infection par le SRAS-CoV-2 sont demeurés relativement faibles en Nouvelle-Écosse jusqu'à la domination du variant Omicron plus contagieux, puis environ la moitié des donneurs néo-écossais ont été infectés, même si la plupart des adultes étaient vaccinés (la gravité de la maladie était toutefois beaucoup plus faible chez les personnes vaccinées). La plupart des cas de COVID-19 ont été dépistés par TAAN jusqu'à l'apparition du variant Omicron. Lorsque les priorités de dépistage par TAAN ont été limitées aux personnes à haut risque, les taux d'infection étaient mieux reflétés par la séroprévalence.

Concurrent infection of dengue virus with malaria parasites among outpatients attending healthcare facilities in Benin city, Nigeria.

Background: Dengue virus (DENV) and malaria parasites (MP) are among the common febrile diseases affecting the tropics and subtropics of the world. Both are mosquito-borne pathogens affecting humans and other animals. Methods: Blood samples were collected from 280 consented out-patients attending the selected hospitals and were analyzed. Malaria parasites were detected using microscopy and Malaria Ag Pf/Pan Rapid Test Device. Dengue virus was detected by serology and heminested reverse transcriptase PCR (hnRT-PCR) to target the flavivirus polymerase (NS5) gene. Results: Malaria parasites recorded a total positivity of 151 patients (53.9%) using microscopy, while DENV antibodies (DENV IgM and DENV IgG) were positive in 16 (5.7%) and 39 (13.9%) patients, respectively. There was a concurrent infection between MP/DENV IgM in 13 (4.6%) patients and MP/DENV IgG in 27 (9.6%) patients. Molecular identification revealed DENV serotype 2 in circulation. Conclusion: This study documents molecular evidence of dengue virus coexisting with malaria parasites in the study population, hence the need for efficient surveillance and control system.

Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots.

Background: In the earliest days of COVID-19 pandemic, the collection of dried blood spots (DBS) enabled public health laboratories to undertake population-scale seroprevalence studies to estimate rates of SARS-CoV-2 exposure. With SARS-CoV-2 seropositivity levels now estimated to exceed 94% in the United States, attention has turned to using DBS to assess functional (neutralizing) antibodies within cohorts of interest. Methods: Contrived DBS eluates from convalescent, fully vaccinated and pre-COVID-19 serum samples were evaluated in SARS-CoV-2 plaque reduction neutralization titer (PRNT) assays, a SARS-CoV-2 specific 8-plex microsphere immunoassay, a cell-based pseudovirus assay, and two different spike-ACE2 inhibition assays, an in-house Luminex-based RBD-ACE2 inhibition assay and a commercial real-time PCR-based inhibition assay (NAB-Sure™). Results: DBS eluates from convalescent individuals were compatible with the spike-ACE2 inhibition assays, but not cell-based pseudovirus assays or PRNT. However, the insensitivity of cell-based pseudovirus assays was overcome with DBS eluates from vaccinated individuals with high SARS-CoV-2 antibody titers. Conclusion: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.

Assessment of the effect of long-term serum storage for retrospective serologic diagnosis of canine monocytic ehrlichiosis (Ehrlichia canis).

There is currently sparse information on the possible effect of long-term storage of serum specimens for the retrospective serodiagnosis of canine monocytic ehrlichiosis (CME). The aim of this study was to assess the agreement between the original serologic outcome and the results of a repeat indirect fluorescent antibody (IFA) assay for the detection of IgG antibodies against E. canis. A secondary aim was to compare the diagnostic performance of two commercially available point-of-care (POC) immunochromatographic (IC) assays. Archived serum samples originally tested as positive (n=66) or negative (n=19) for E. canis IgG antibodies and kept frozen at -20°C for a median of 22 years, were retrospectively examined by IFA and by two POC IC assays. Cohen's Kappa coefficient (0.748, p < 0.0001), indicated a substantial agreement between the original and repeat serologic testing results. An almost identical high sensitivity and moderate specificity were established for the two POC IC assays. Canine serum specimens on long-term storage may still be of value for seroepidemiologic surveys investigating the exposure to E. canis.

Inferring COVID-19 testing and vaccination behavior from New Jersey testing data.

Characterizing the relationship between disease testing behaviors and infectious disease dynamics is of great importance for public health. Tests for both current and past infection can influence disease-related behaviors at the individual level, while population-level knowledge of an epidemic's course may feed back to affect one's likelihood of taking a test. The COVID-19 pandemic has generated testing data on an unprecedented scale for tests detecting both current infection (PCR, antigen) and past infection (serology); this opens the way to characterizing the complex relationship between testing behavior and infection dynamics. Leveraging a rich database of individualized COVID-19 testing histories in New Jersey, we analyze the behavioral relationships between PCR and serology tests, infection, and vaccination. We quantify interactions between individuals' test-taking tendencies and their past testing and infection histories, finding that PCR tests were disproportionately taken by people currently infected, and serology tests were disproportionately taken by people with past infection or vaccination. The effects of previous positive test results on testing behavior are less consistent, as individuals with past PCR positives were more likely to take subsequent PCR and serology tests at some periods of the epidemic time course and less likely at others. Lastly, we fit a model to the titer values collected from serology tests to infer vaccination trends, finding a marked decrease in vaccination rates among individuals who had previously received a positive PCR test. These results exemplify the utility of individualized testing histories in uncovering hidden behavioral variables affecting testing and vaccination.

A panel of recombinant Leishmania donovani cell surface and secreted proteins identifies LdBPK_323600.1 as a serological marker of symptomatic infection.

Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE: Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans.

Chlamydia trachomatis seroassays used in epidemiologic research: a narrative review and practical considerations.

Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the "state of the science" for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.

Serological follow-up after syphilis diagnosis in Israel.

The global incidence of syphilis is increasing. Continuity of care challenges the control of sexually transmitted diseases. In this study, we assessed the follow-up and serological decline differences between community- and hospital-diagnosed patients in Israel. A historical cohort study was conducted using the Israel National Syphilis Center (NSC) repository. Patients with a positive non-specific Venereal Disease Research Laboratory (VDRL) test between 2011 and 2020 were included. Rates of serological follow-up and serological titre decreases were compared between hospital- and community-diagnosed patients. The study included 4,445 patients, 2,596 (58.4%) were diagnosed in community clinics and 1,849 (41.6%) in hospitals. Of community-diagnosed patients, 1,957 (75.4%) performed follow-up testing, compared with 834 (51.2%) hospital-diagnosed patients (p < 0.001). On multivariate analysis, the odds ratio of serology follow-up among community-diagnosed patients was 2.8 (95 per cent confidence interval (95% CI): 2.2-3.5) that of hospital-diagnosed patients. There were 1,397 (71.4%) community-diagnosed patients with serological titre decrease, compared with 626 (74.9%) hospital-diagnosed patients (p = 0.03). On multivariate analysis, this difference diminished. Serological follow-up testing is suboptimal and was performed more often among patients initially diagnosed in the community compared to hospitals. Continuity of care should be improved to promote successful patient care and prevent disease spread.

Navigating the Diagnostic Challenges of Mycoplasma and Legionella Coinfection Through Serological Testing.

Diagnosing community-acquired pneumonia (CAP) is increasingly challenging, especially with the emergence of atypical pathogens such as Mycoplasma pneumoniae and Legionella pneumophila. This report presents the case of a 60-year-old male exhibiting lethargy and decreased oral intake, with a medical history marked by chronic kidney disease and benign prostate hyperplasia. Despite a positive Legionella urine antigen, the clinical and radiological profile did not align with Legionella pneumonia. Elevated M. pneumoniae IgM antibody titers further complicated the diagnostic scenario. We explore the complexities of distinguishing coinfection from primary infection, highlight the limitations of serological testing, and promote a comprehensive diagnostic strategy customized to individual patient circumstances. This case emphasizes the importance of comprehensive assessment strategies to understand atypical pneumonia presentations, particularly within complex clinical scenarios.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. OBJECTIVE: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. METHODS: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). RESULTS: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. CONCLUSIONS: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.

Measles in Czech population with varying vaccination rates in 2018-2019: clinical and laboratory differences between vaccinated and unvaccinated individuals and their relevance to clinical practice.

BACKGROUND AND OBJECTIVES: In a highly vaccinated population, an increasing number of previously vaccinated measles cases can be expected. The aim of this study was to assess the effect of vaccination on the clinical course and immune response in relation to the current measles case definition. METHODS: The presence of fever, catarrhal symptoms, exanthema and complications, and specific IgM and IgG positivity were assessed in all 230 patients and compared in 193 patients with known vaccination status, divided into measles-containing vaccine (MCV) groups: MCV0 (85 patients), MCV1 (25 patients) and MCV2 (83 patients). RESULTS: Statistically significant differences between groups were found for catarrhal symptoms.Conjunctivitis and rhinitis were significantly less frequent in the MCV2 group (47% and 54%) compared to MCV0 (80% and 80%), p < 0.001 and p = 0.002 respectively. Typical exanthema was present in 74 (87%) MCV0 and 56 (67%) MCV2 patients, p = 0.005. Complications were most common in the MCV0 group (29%). ECDC clinical case criteria were met in 81 (95%) MCV0, 18 (72%) MCV1 and 59 (71%) MCV2 patients, p < 0.001. IgM were positive in 64 (83%) MCV0, 14 (74%) MCV1 and 36 (67%) MCV2 patients, differences were not statistically significant. There were highly significant differences in IgG between MCV0 and both vaccinated groups (p < 0.001). CONCLUSIONS: A redefinition of the clinical case classification is essential to better capture modified measles and to raise awareness among healthcare workers of the differences in measles in vaccinated patients.

Detection of intrathecal IgG antibody for varicella and measles diagnosis by evaluation and comparison of a commercial IgG chemiluminescent immunoassay with two ELISAs.

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.