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.

Nutritional Status Link with Polioseronegativity Among Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Background: Malnutrition is identified as a risk-factor for insufficient polioseroconversion in the context of a vaccine-derived polio virus (VDPV) outbreak prone region. To assess the prevalence of malnutrition and its link to poliovirus insufficient immunity, a cross-sectional household survey was conducted in the regions of Haut- Lomami and Tanganyika, DRC. Methods: In March 2018, we included 968 healthy children aged 6 to 59 months from eight out of 27 districts. Selection of study locations within these districts was done using a stratified random sampling method, where villages were chosen based on habitat characteristics identified from satellite images. Consent was obtained verbally in the preferred language of the participant (French or Swahili) by interviewers who received specific training for this task. Furthermore, participants contributed a dried blood spot sample, collected via finger prick. To assess malnutrition, we measured height and weight, applying WHO criteria to determine rates of underweight, wasting, and stunting. The assessment of immunity to poliovirus types 1, 2, and 3 through the detection of neutralizing antibodies was carried out at the CDC in Atlanta, USA. Results: Of the study population, we found 24.7% underweight, 54.8% stunted, and 15.4% wasted. With IC95%, underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.96; [1.52-2.54]) were significantly associated with seronegativity to polioserotype 1. Underweight (OR=1.64; [1.20-2.24]) and the non-administration of vitamin A (OR=1.55; [1.20-2.01]) were significantly associated with seronegativity to polioserotype 2. Underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.80. [1.38-2.35]) were significantly associated with seronegativity to polioserotype 3. Underweight (OR=1.68; IC95% [1.10-2.57]) and the non-administration of vitamin A (OR=1.82; IC95% [1.30-2.55]) were significantly associated with seronegativity to all polioserotypes. Conclusion: This study reveals a significant association between underweight and polioseronegativity in children. In order to reduce vaccine failures in high-risk areas, an integrated approach by vaccination and nutrition programs should be adopted.

Prediction Model with Validation for Polioseronegativity in Malnourished Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Background: Malnutrition is identified as a risk factor for insufficient polio seroconversion in the context of a vaccine-derived poliovirus (VDPV) outbreak-prone region. In the Democratic Republic of Congo (DRC), underweight decreased from 31% (in 2001) to 26% (in 2018). Since 2004, VDPV serotype 2 outbreaks (cVDPV2) have been documented and were geographically limited around the Haut-Lomami and Tanganyika Provinces. Methods: To develop and validate a predictive model for poliomyelitis vaccine response in malnourished infants, a cross-sectional household study was carried out in the Haut-Lomami and Tanganyika provinces. Healthy children aged 6 to 59 months (n=968) were enrolled from eight health zones (HZ) out of 27, in March 2018. We performed a bivariate and multivariate logistics analysis. Final models were selected using a stepwise Wald method, and variables were selected based on the criterion p < 0.05. The association between nutritional variables, explaining polio seronegativity for the three serotypes, was assessed using the receiver operating characteristic curve (ROC curve). Results: Factors significantly associated with seronegativity to the three polio serotypes were underweight, non-administration of vitamin A, and the age group of 12 to 59 months. The sensitivity was 10.5%, and its specificity was 96.4% while the positive predictive values (PPV) and negative (PNV) were 62.7% and 65.3%, respectively. We found a convergence of the curves of the initial sample and two split samples. Based on the comparison of the overlapping confidence intervals of the ROC curve, we concluded that our prediction model is valid. Conclusion: This study proposed the first tool which variables are easy to collect by any health worker in charge of vaccination or in charge of nutrition. It will bring on top, the collaboration between the Immunization and the Nutritional programs in DRC integration policy, and its replicability in other low- and middle-income countries with endemic poliovirus.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in HIV Seronegative Patients: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum infection is a rare disorder with poor outcome. Although cases of patients with human immunodeficiency virus (HIV) infection have been well documented, little study has reported in the setting of HIV seronegative. In this study, we report a case of HLH secondary to histoplasmosis in an immunocompetent patient in China and review all cases on this situation. The objective was to summary their epidemiology, clinical characteristics, diagnostic approaches, and therapeutic response. A 46-year-old male cooker presented fever, fatigue, anorexia, and weight loss. Bone marrow examination suggest fungus organism and hemophagocytosis, and further, bone marrow culture confirmed Histoplasma capsulatum, as the etiology of HLH. The patient was successfully treated. We reviewed a total of the 13 cases (including our patient) of HLH with histoplasmosis in intact immunology patients. Twelve of the 13 patients are from endemic areas, and nine of the 12 cases are from emerging endemic areas, India and China. Three patients had sojourn history may related to the disease onset. Twelve of the 13 cases fulfilled HLH-2004 criteria. The diagnosis of Histoplasma capsulatum infection was established by histological examination (13 of 13), culture (4 of 13), molecular method (2 of 13), and antigen or serological assays (2 of 13). Amphotericin B, posaconazole, and itraconazole show favorable activity against the fungus, seven patients used specific treatment for HLH. For analysis of outcomes, two of the 13 patients died. Our present case report and literature review show that disseminated Histoplasma capsulatum infection with HLH in the immunocompetent population becomes increasingly common in emerging endemic areas and have high mortality. It is necessary for clinicians to improve the awareness of disease diagnosis due to the atypical population and disease presentation. Timely diagnosis and early use of antifungal agents will lead to favorable prognosis.

Primary Kaposi's Sarcoma of the Nasal Cavity: Clinical Experience and Review of the Literature.

Kaposi's sarcoma (KS) is a vascular sarcoma derived from vascular endothelial cells and presents with multiple lesions. It mainly appears on the skin and oral mucosa, usually in the face, oral mucosa, and genitals. Very few cases of primary lesions in the nasal cavity have been reported. It is often difficult to diagnose only by imaging examination. Here, we describe a case of KS in a patient who was human immunodeficiency virus (HIV)-negative, in which the primary sites were the nasal mucosa and nasal septum. A diagnosis was made according to the patient's clinical presentation, physical examination, laboratory examination, imaging examination, and histopathological results. We used surgical resection combined with chemotherapy, with 6 months' postoperative follow-up without recurrence. We reviewed the relevant literature to identify similar cases and summarize the findings reported on this rare manifestation of KS. We recommend that, where possible, antiviral therapy such as interferon, and regular review should continue, to improve the survival rate and patients' quality of life.

Helios expressing regulatory T cells are correlated with decreased IL-2 producing CD8 T cells and antibody diversity in Mozambican individuals living chronically with HIV-1.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation but may also suppress beneficial HIV-1 specific immune responses. We aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response in Mozambican people living chronically with HIV-1 (PLWH-C). RESULTS: In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2+CD4 T cells (r = 0.647; p = 0.032) and IL-2+IFNγ+CD8 T cells (r = 0.551; p = 0.014), while the proportions of Helios+Tregs correlated inversely with levels of IL-2+CD8 T cells (r = - 0.541; p = 0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38+HLA-DR+CD8 T cells (r = 0.620; p = 0.012), viral load (r = 0.452; p = 0.040) and inversely with absolute CD4 T cells count (r = - 0.481; p = 0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of Helios+Tregs (r = - 0.45; p = 0.02). CONCLUSION: Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.

HIV knowledge and its correlation with the Undetectable = Untransmittable slogan in Brazil

ABSTRACT Knowledge about HIV transmission and prevention is a necessary step for adopting preventive behaviors. We assessed HIV knowledge and its correlation with the perceived accuracy of the "Undetectable = Untransmittable" (U=U) slogan in an online sample with 401 adult Brazilians. Overall, 28% of participants showed high HIV knowledge level. The perceived accuracy of the U=U slogan significantly correlated with HIV knowledge. Younger participants, those reporting lower income or lower education, or who had never tested for HIV showed poorer HIV knowledge. Filling gaps of knowledge among specific populations is urgent in order to increase preventive behaviors and decrease HIV stigma.

Efficacy and safety of BNT162b2 vaccination in patients with solid cancer receiving anticancer therapy - a single centre prospective study.

AIM: Patients with cancer are at an increased risk for severe coronavirus disease of 2019, thus data on the safety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted this prospective study of patients with cancer vaccinated with BNT162b2 and monitored for antibody response and safety. The aim was to evaluate the rate of seropositivity and define predictors for non-reactive immune response. Furthermore, we evaluated the frequency and the severity of adverse events. METHODS: The study included patients with solid tumours undergoing anticancer treatment and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralising antibodies were measured 2-4 weeks after each vaccine dose. RESULTS: The analysis included 129 patients, of which 70.5% patients were metastatic. Patients were treated with chemotherapy (55%), immunotherapy (34.1%), biological agents (24.8%), hormonal treatment (8.5%) and radiotherapy (4.6%), that were given either alone or in combinations. The seropositivity rate among patients with cancer and controls was 32.4% versus 59.8% (p < 0.0001) after the first dose and 84.1% versus 98.9% (p < 0.0001) after the second dose, respectively. Median RBD-IgG titre was lower among patients than controls (p < 0.0001). Patients who were seronegative after the second dose had significantly more comorbidities than that with patients with seropositivity (77.8% vs 41.1%, respectively, p = 0.0042). CONCLUSION: Adequate antibody response after BNT162b2 vaccination was achieved after two doses but not after one dose, in patients with cancer vaccinated during anticancer therapy.

Seroprevalence against the measles virus after vaccination or natural infection in an adult population in Madinah, Saudi Arabia.

Background: Over the past few years, measles cases have increased worldwide, despite the availability of a safe and highly effective vaccine. Numerous countries have eliminated measles or have made substantial advancements toward elimination.Materials and Methods: This study investigated the seroprevalence of anti-measles antibodies and vaccination status among 362 men and 81 women in Madinah. All participants were vaccinated or acquired immunity naturally due to infection. We aimed to examine the persistence of anti-measles IgG antibodies, which were qualitatively and quantitatively determined using ELISA.Results: We showed that measles seropositivity (92%, n = 408) was significantly more frequent than negative (5.4%, n = 14) and equivocal results (2.5%, n = 11). Among men, 92.8% were seropositive for the anti-measles IgG antibody, whereas 88.9% of women were seropositive. In addition, a significant relationship was observed between age and measles seropositivity, with a significant positive correlation between age and anti-measles antibody concentration as assessed by Spearman's correlation analysis (r = 0.405, p < .001).Conclusion: Based on these results, observing the serological status of the population 20-38 y after vaccination may be necessary to minimize the proportion of individuals who may be vulnerable to contracting measles. Despite the efficacy of the measles, mumps, and rubella vaccine and the positive global impact associated with the use of this vaccine, including a general decline in measles cases, attention must still be paid to the issue of measles risk, and seronegative individuals should be identified and advised to receive a booster dose of the vaccine.

Cellular Immunity in COVID-19 Convalescents with PCR-Confirmed Infection but with Undetectable SARS-CoV-2-Specific IgG.

We investigated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a group of convalescent, potential blood donors in Germany who had PCR-confirmed SARS-CoV-2 infection. Sixty days after onset of symptoms, 13/78 (17%) study participants had borderline or negative results to an ELISA detecting IgG against the S1 protein of SARS-CoV-2. We analyzed participants with PCR-confirmed infection who had strong antibody responses (ratio >3) as positive controls and participants without symptoms of SARS-CoV-2 infection and without household contact with infected patients as negative controls. Using interferon-γ ELISpot, we observed that 78% of PCR-positive volunteers with undetectable antibodies showed T cell immunity against SARS-CoV-2. We observed a similar frequency (80%) of T-cell immunity in convalescent donors with strong antibody responses but did not detect immunity in negative controls. We concluded that, in convalescent patients with undetectable SARS-CoV-2 IgG, immunity may be mediated through T cells.

Hepatitis B virus infection confirmation and infection status identification in blood donors without serological markers / 中国输血杂志

【Objective】 To confirm Hepatitis B virus (HBV) infections and identify infection status by excluding false positive in blood donors reactive to nucleic acid testing (NAT) but without serological markers (Seroneg-NAT). 【Methods】 Seroneg-NAT yields were selected among blood donors in Dalian Blood Center from November 1, 2010 to February 28, 2021, and their HBV DNA was further confirmed with TaqMan HBV DNA quantification or virions concentration by polyethylene glycol (PEG) precipitation combined with in-house nested PCR targeting the S, BCP, PreS/S and Precore/core regions of the viral genome, and follow-up test was carried out, including blood routine screening and HBsAg, anti-HBs and anti-HBc testing. HBV infection was confirmed by HBV DNA yielding and anti-HBs/anti-HBc seroconversion in follow-up testing, and HBV DNA was further sequenced if necessary. 【Results】 During the period of 10 years and 4 months, 0.03% (126/466 911) Seroneg-NAT yields were selected, of which 46.8% (59/126) were HBV DNA+ and 53.2% (67/126) were unconfirmed. Among 126 Seroneg-NAT yields, 40.5% (51/126) were involved in follow-up test, of which 28 were HBV DNA+ and 23 were unconfirmed. HBV infections were confirmed in 48% (60/126) of Seroneg-NAT yields. Of follow-up donors, 54.9% (28/51) were identified as early infection before seroconversion, 2.0% (1/51) seronegative occult HBV infection (OBI), and 37.3% (19/51) NAT false positive. There were still 5.9% (3/51) classified as the indetermination. 【Conclusion】 Nearly half Seroneg-NAT yields in Dalian blood donors were infected with HBV and more than 50% were early infections before seroconversion. The majority of HBV DNA unconfirmed without serological markers were false positives.

A cross-sectional study of association of serostatus and extra-articular manifestations in patients with rheumatoid arthritis in a teaching hospital.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, which mistakenly attacks the joints and induces the inflammatory changes that thicken the joints (the synovium) resulting in swelling and pain in and around the joints. It causes pain, joint deformity, and also affects the quality of life. The joint is affected symmetrically. It also can affect body systems, such as the cardiovascular, respiratory systems, or other systems, which manifest as extra-articular manifestations. Extra-articular manifestations of RA are documented less in India hence this study was undertaken to correlate RA with extra-articular manifestations as well as its relationship with serostatus in patients with extra-articular manifestations. MATERIALS AND METHODS: Sixty patients (age between 18-60 years) attending Medicine/Rheumatology outpatient department were included in the study (12 months) who fulfilled the 2010 RA classification criteria laid down by American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) for RA. All the subjects underwent a thorough history, clinical examination, and laboratory investigations. The relevant data were analyzed with appropriate statistical methods after 12 months' duration. RESULTS: Nearly 68.33% of the subjects were found to have extra-articular manifestations mostly in the age group of 31-40 years with prevalence higher in the female. In the seropositive patients, early morning stiffness (EMS) constitutes 63.82% of the total extra-articular manifestations in the patients followed by anemia (38.29%) and peripheral neuropathy (34.04%). On the other hand, in the seronegative cases, EMS (61.53%) followed by anemia (23.07), peripheral neuropathy (15.38%), and keratoconjunctivitis sicca (15.38%). Extra-articular manifestations in seropositive patients have a statistically significant relationship with the increase in the duration of the disease. CONCLUSION: Extra-articular manifestations need to be looked carefully as it is associated with more severe disease. Seropositivity and extra-articular manifestations both usually indicate that the RA is more severe and may affect the quality of life.

Cryptococcal Meningitis: A Rare Complication in HIV-Negative Patients with Nephrotic Syndrome in A Chinese Teaching Hospital.

Cryptococcal meningitis (CM) is a rare complication in HIV-negative patients with nephrotic syndrome (NS), and knowledge about the clinical profile of NS with CM is limited. We performed a retrospective study of all patients with CM-NS admitted to the Jiangxi Chest Hospital (JCH) between 2011 and 2019 and systematically reviewed cases of CM-NS reported in the Chinese language. Among a total of 226 CM patients referred to the JCH, seven had NS (3.1%); these patients were combined with 22 CM-NS cases reported in the Chinese language for analysis. Headache, fever, nausea, and meningeal irritation were the most common initial symptoms, and the median time from symptom onset to CM diagnostic confirmation was 30 days. One patient initially tested negative for CM but was later confirmed to be positive. Among the 29 analysed patients, 41.4% (12/29) were misdiagnosed with other complications, including four patients from the JCH (4/7, 57.1%) and eight patients from published reports (8/22, 36.3%). The overall mortality rate was 17.2% (5/29); among these patients, 60% (3/5) were misdiagnosed. Induction treatment with amphotericin B plus 5-fluorocytosine (9/29) or amphotericin B plus fluconazole (7/29) successfully cleared the infection. Fluconazole may be a suitable alternative if 5-fluorocytosine is not readily available or not tolerated, and repetitive testing is important to reach a conclusive diagnosis in NS patients suspected of having CM.

Neurologic Presentation of Probable Seronegative Paraneoplastic Encephalitis in a Woman With an Ovarian Teratoma.

We describe a case of probable autoimmune encephalitis developed as a result of paraneoplastic syndrome in a woman with an ovarian teratoma. Patients may present with psychiatric and neurological symptoms, which are caused by anti-N-methyl-D-aspartate (anti-NMDA) receptor antibodies produced in response to a teratoma that crosses the blood-brain barrier and damages brain tissue in the limbic area, causing encephalitis. Our patient presented with seizures, myoclonus, and memory problems. This is a relatively newly discovered and rare problem; however, it can be quite debilitating if left untreated. This diagnosis may be often missed due to the absence of highly sensitive tests. Autoimmune encephalitis has to be on the list of differential diagnoses for patients with new-onset psychiatric or neurological symptoms.

Association of time-to-treatment with outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients.

BACKGROUND: The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and the clinical outcomes in HIV-negative patients with PCP who presented with hypoxemic respiratory failure. METHODS: A retrospective observational study was performed involving 51 HIV-negative patients with PCP who presented in respiratory failure and were admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between the time to anti-PCP treatment and in-hospital mortality. RESULTS: All patients were treated with appropriate anti-PCP treatment, primarily involving trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0-97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to confirmation of the microbiological diagnosis. However, the hospital mortality rates were not associated with increasing quartiles of time until anti-PCP treatment (P = 0.818, test for trend). In addition, hospital mortality of patients received early empiric treatment was not better than those of patients received definitive treatment after microbiologic diagnosis (48.4% vs. 40.0%, P = 0.765). In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01-1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34-72.65) were independently associated with increased mortality. CONCLUSIONS: There was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP who presented in hypoxemic respiratory failure.

Congenital cytomegalovirus infection in Central Germany: an underestimated risk.

PURPOSE: This is the first study to determine the cytomegalovirus (CMV) seronegativity rate for women of childbearing age in Saxony-Anhalt and to determine the prevalence of clinically relevant congenital CMV (cCMV) infection in Central Germany, because there are no valid data available. METHODS: The retrospective study was undertaken between January 2005 and December 2015. For the first time in Germany, the following seven data sources were used to analyze the prevalence of clinically relevant cCMV infection and the rate of CMV seronegative women of childbearing age: CMV Screening in maternity unit, University Women's Hospital, Social Paediatrics Centre (SPC), Malformation Monitoring Centre (MMC), Newborn Hearing Screening (NHS), Neonatal Intensive Care Unit (NICU), and In-house Doctor Department. Key parameters were anti-CMV IgG and IgM, CMV PCR of urine, and clinically relevant symptoms caused by CMV. RESULTS: Between 46 and 52% of women of childbearing age were CMV seronegative. The prevalence of clinically relevant cCMV infection was between 0.008 and 0.04%. CONCLUSIONS: The CMV seronegativity rate of women of childbearing age was confirmed to be in the middle range of estimated data from other sources in Germany. Data from the NICU, SPC, NHS, and MMC show the prevalence of clinically relevant cCMV infection. The risk of all cCMV infections is underestimated. Thus, the true prevalence of clinically relevant and subclinical cCMV infections is >0.04%.

Highly Human Immunodeficiency Virus-Exposed Seronegative Men Have Lower Mucosal Innate Immune Reactivity.

Risk of HIV acquisition varies, and some individuals are highly HIV-1-exposed, yet, persistently seronegative (HESN). The immunologic mechanisms contributing to this phenomenon are an area of intense interest. As immune activation and inflammation facilitate disease progression in HIV-1-infected persons and gastrointestinal-associated lymphoid tissue is a highly susceptible site for transmission, we hypothesized that reduced gut mucosal immune reactivity may contribute to reduced HIV-1 susceptibility in HESN men with a history of numerous rectal sexual exposures. To test this, we used ex vivo mucosal explants from freshly acquired colorectal biopsies from healthy control and HESN subjects who were stimulated with specific innate immune ligands and inactivated whole pathogens. Immune reactivity was then assessed via cytokine arrays and proteomic analysis. Mucosal immune cell compositions were quantified via immunohistochemistry. We found that explants from HESN subjects produced less proinflammatory cytokines compared with controls following innate immune stimulation; while noninflammatory cytokines were similar between groups. Proteomic analysis identified several immune response proteins to be differentially expressed between HIV-1-stimulated HESN and control explants. Immunohistochemical examination of colorectal mucosa showed similar amounts of T cells, macrophages, and dendritic cells between groups. The results of this pilot study suggest that mucosal innate immune reactivity is dampened in HESN versus control groups, despite presence of similar densities of immune cells in the colorectal mucosa. This observed modulation of the rectal mucosal immune response may contribute to lower risk of mucosal HIV-1 transmission in these individuals.

Comparing the rubella seronegativity in pregnant women who received one dose of rubella vaccine at different ages in Taiwan.

INTRODUCTION: Vaccination is the best strategy to prevent rubella and congenital rubella. The aim of our study was to assess the immunity to rubella and determine rubella virus antibody titers in pregnant women who were offered a single dose of rubella vaccine at different ages of their lives. METHODS: A total 15,067 rubella IgG antibody test results for Taiwanese pregnant women who received routine prenatal checkup at Fooyin University Hospital from 1999 to 2014 were analyzed in this study. The women were divided into five birth cohorts in order to compare their rubella seronegativities and antibody titers according to the different period of rubella vaccination policy in Taiwan. RESULTS: The total rubella seronegativity rate was 11.2% (95% CI: 10.7-11.7%) and the mean rubella antibody titers was 51.0IU/mL (SD=54.7IU/mL). The junior school cohort has the lowest rubella seronegativity of 7.6% (95% CI: 6.9-8.2%). The seronegativities were significantly high in the preschool cohort and in the 15-month-old cohort, 14.9% (95% CI: 13.2-16.6%) and 14.8% (95% CI: 11.5-18.1%), respectively. The OR values were 2.1 (95% CI: 1.8-2.5, p<0.001) in the preschool cohort and 2.2 (95% CI: 1.6-2.8, p<0.001) in the 15-month-old cohort, respectively, against the junior school cohort. Women in the 15-month-old cohort have lowest average rubella IgG titer, 25.4IU/mL. CONCLUSION: The total rubella seronegativity rate was 11.2% in all native pregnant women. Women who received one dose rubella vaccine at preschool and 15-month-old have highest seronegativities. The 15-month-old cohort has the lowest average rubella IgG titer. We recommend a revised catch-up immunization policy to women who received one dose rubella vaccine at a younger age.

Rubella seronegativity in antenatal screening - Is it influenced by the introduction of universal childhood rubella immunization?

OBJECTIVE: This study examined the impact of rubella immunization, implemented in Hong Kong in phases since 1978, on antenatal rubella serological status in Chinese women. METHODS: In a retrospective cohort study, the incidence of antenatal rubella seronegative status in our parturients managed from 1998 to 2013 was analyzed by their year-of-birth as follows: <1965 (no childhood immunization), 1965-1982 (single dose at Primary 6), and ≥1983 (two doses at age 12 months and 12 years), adjusting for other factors including age, parity, body mass index, place-of-birth status and hepatitis B surface antigen (HBsAg) status. FINDINGS: Rubella seronegativity decreased from 12.9%, 10.5%, to 9.8% respectively, and correlated inversely (P<0.001) with year-of-birth cohorts. Despite similar demographic profiles, this correlation was found only in Hong-Kong-born women (from 12.6%, 7.5% to 6.5% respectively), who also had significant lower incidences of rubella seronegativity (OR 0.73, 0.31 and 0.29 respectively) and HBsAg seropositivity (OR 1.09, 0.63 and 0.48 respectively) than China-born women. On regression analysis, rubella seronegativity was actually significantly increased following the implementation of immunization (aOR 1.20) while it was the reverse for non-residents (aOR 0.61). CONCLUSION: Although rubella seronegativity decreased with immunization, the effect was less than expected when adjusted for other risk factors.