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Guidelines recommend screening for Neisseria gonorrhoeaeand Chlamydia trachomatisat three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeaeand C trachomatison the incidence of these infections in MSM and transgender women taking PrEP.

IMPORTANCE: Congenital cytomegalovirus (cCMV) is the major cause of congenital nonhereditary sensorineural hearing loss in children. Currently, criteria to identify infants at increased risk for unfavorable hearing outcome are lacking. OBJECTIVE: To identify risk factors associated with cCMV-related hearing improvement, hearing deterioration, and late-onset hearing loss. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study included patients from 6 secondary and tertiary hospitals enrolled in the Flemish CMV registry (Belgium). Newborns with untreated cCMV infection with at least 4-year audiological follow-up were included. Patients who presented with other possible causes of sensorineural hearing loss were excluded. Data were collected for 15 years (January 1, 2007, to February 7, 2022) and analyzed from September 26, 2022, to January 16, 2023. MAIN OUTCOMES AND MEASURES: Primary outcome was hearing evolution (per-ear analysis; described as stable hearing, improvement, or deterioration). The association of gestational characteristics, clinical findings, timing of seroconversion, viral load, and hearing status at birth with hearing evolution was investigated using effect sizes (Cramer V, odds ratio [OR], or Hedges g). RESULTS: Of the 387 children, 205 of 385 with nonmissing data were male (53.2%), 113 (29.2%) had a symptomatic infection, and 274 (70.8%) had an asymptomatic infection. Every child was 4 years or older at final hearing evaluation. A total of 701 of 774 ears (90%) showed stable hearing (normal hearing or stable hearing loss since birth) over time. Late-onset hearing loss (normal hearing at birth followed by hearing loss) was present in 43 of 683 ears (6.3%). Among children with hearing loss present at birth, 24 of 34 ears (70.6%) had hearing deterioration, and 6 of 91 ears (6.6%) had hearing improvement. Prematurity was associated with a higher chance of hearing improvement (OR, 12.80; 95% CI, 2.03-80.68). Late-onset hearing loss was more prevalent in a first trimester infection (OR, 10.10; 95% CI, 2.90-34.48). None of the 104 ears of children with a third trimester seroconversion developed late-onset hearing loss. CONCLUSIONS AND RELEVANCE: Findings of this cohort study support that ongoing audiological follow-up for untreated children with congenital hearing loss is important, as the majority of patients had hearing deterioration. The timing of seroconversion was associated with the risk of developing late-onset hearing loss. These insights can aid in parental counseling, patient stratification, and follow-up. Future research should focus on the effect of treatment, the influence of determined risk factors, and the study of eventual new risk factors in patients at high risk to develop hearing loss.

•Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT).•IFN-γ release assays can predict protection against clinically significant CMV infections.•T-SPOT.CMV and QuantiFERON-CMV are the 2 most widely used of these assays.•These assays have only moderate agreement after allo-HSCT.

IMPORTANCE: With a prevalence between 0.2% and 6.1% of all live births, congenital cytomegalovirus (cCMV) infection is a major cause of congenital nonhereditary sensorineural hearing loss. Despite the large amount of research on cCMV-related hearing loss, it is still unclear which newborns are at risk of hearing loss. OBJECTIVE: To identify independent risk factors for cCMV-related congenital hearing loss and predictors of hearing loss severity at birth. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of newborns with cCMV infection used data included in the Flemish CMV registry that was collected from 6 secondary and tertiary hospitals in Flanders, Belgium, over 15 years (January 1, 2007, to February 7, 2022). Data were analyzed March 3 to October 19, 2022. Patients were included in the study after confirmed diagnosis of cCMV infection and known hearing status at birth. Patients who presented with other possible causes of sensorineural hearing loss were excluded. MAIN OUTCOMES AND MEASURES: Primary outcome was hearing status at birth. Clinical, neurological, and laboratory findings along with the timing of seroconversion and blood viral load were separately considered as risk factors. Binary logistic regression was performed to identify independent risk factors for congenital hearing loss in newborns with cCMV. Effect sizes were measured using Hedges g, odds ratio, or Cramer V. RESULTS: Of the 1033 newborns included in the study (553 of 1024 [54.0%] boys), 416 (40.3%) were diagnosed with symptomatic cCMV infection and 617 (59.7%) with asymptomatic cCMV infection. A total of 15.4% of the patients (n = 159) presented with congenital hearing loss; half of them (n = 80 [50.3%]) had isolated hearing loss. The regression model revealed 3 independent risk factors for congenital hearing loss: petechiae at birth (adjusted odds ratio [aOR], 6.7; 95% CI, 1.9-23.9), periventricular cysts on magnetic resonance imaging (MRI; aOR, 4.6; 95% CI, 1.5-14.1), and seroconversion in the first trimester (aOR, 3.1; 95% CI, 1.1-9.3). Lower viral loads were seen in patients with normal hearing compared with those with congenital hearing loss (median [IQR] viral load, 447.0 [39.3-2345.8] copies per milliliter of sample [copies/mL] vs 1349.5 [234.3-14 393.0] copies/mL; median difference, −397.0 [95% CI, −5058.0 to 174.0] copies/mL). CONCLUSIONS AND RELEVANCE: Findings of this cross-sectional study suggest that newborns with cCMV infection and petechiae at birth, periventricular cysts on MRI, or a seroconversion in the first trimester had a higher risk of congenital hearing loss. Clinicians may use these risk factors to counsel parents in the prenatal and postnatal periods about the risk of congenital hearing loss. Moreover, linking clinical features to hearing loss may provide new insights into the pathogenesis of cCMV-related hearing loss. The importance of viral load as a risk factor for congenital hearing loss remains unclear.

ABSTRACTIntroductionThe 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.MethodsSARS-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.ResultsWe 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).ConclusionAnti-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.

ABSTRACTBackgroundMolecular detection of SARS-CoV-2 in respiratory samples is the gold standard for COVID-19 diagnosis but it has a long turnaround time and struggles to detect low viral loads. Serology could help to diagnose suspected cases which lack molecular confirmation. Two case reports are presented as illustration.ObjectivesThe aim of this study was to evaluate the performance of several commercial assays for COVID-19 serology. We illustrated the added value of COVID-19 serology testing in suspect COVID-19 cases with negative molecular test.Study designTwenty-three sera from 7 patients with a confirmed molecular diagnosis of SARS-CoV-2 were tested using 14 commercial assays. Additionally, 10 pre-pandemic sera and 9 potentially cross-reactive sera were selected. We calculated sensitivity and specificity. Furthermore, we discuss the diagnostic relevance of COVID-19 serology in a retrospective cohort of 145 COVID-19 cases in which repetitive molecular and serological SARS-CoV-2 tests were applied.ResultsThe interpretation of the pooled sensitivity of IgM/A and IgG resulted in the highest values (range 14–71% on day 2–7; 88–94% on day 8–18). Overall, the specificity of the assays was high (range 79–100%). Among 145 retrospective cases, 3 cases (2%) remained negative after sequential molecular testing but positive on final SARS-CoV-2 serology.ConclusionSensitivity of COVID-19 serological diagnosis was variable but consistently increased at >7 days after symptom onset. Specificity was high. Our data suggest that serology can complement molecular testing for diagnosis of COVID-19, especially for patients presenting the 2ndweek after symptom onset or later.

ABSTRACTObjectives: Hepatitis E virus (HEV) genotype 3 is an emerging pathogen in developed countries. We evaluated the performance of two new serological assays for the detection of HEV, VIDAS® anti-HEV IgM and IgG.Methods: VIDAS® assays were performed on 77 clinical samples: 68 samples from patients suspected for HEV infection and 9 samples which previously tested positive for HEV IgM, IgG or HEV PCR. All samples were also tested using Wantai HEV assays. Cross-reactivity was assessed. To get a better view on the natural course of HEV infections, three clinical cases are described.Results: The concordance rate between VIDAS® and Wantai assays was good for HEV IgM (0.75,CI 0.52–0.98) and very good for HEV IgG (0.85,CI 0.72–0.98). Four samples tested borderline/positive with Wantai IgM but negative with VIDAS® IgM. All of these samples were HEV RNA negative, HEV IgG was positive in 2/4 samples. Five samples produced conflicting HEV IgG results. These tested positive with VIDAS® but negative with Wantai IgG. All five samples were HEV IgM and RNA negative. We detected no cross-reactivity. The clinical cases illustrate that HEV serology can still be negative in the very beginning of an acute infection.Conclusions: There is a good agreement between VIDAS® and Wantai anti-HEV IgM and IgG assays. Discrepant HEV IgM results probably reflect false positive Wantai IgM results (RNA-/IgG- samples) and longer-lasting positive Wantai IgM (RNA-/IgG+ samples). Discrepant HEV IgG results, could either represent resolved HEV infections (false negative Wantai IgG results) or false positive VIDAS® HEV IgG results.

ObjectivesAs Chlamydia trachomatis(CT) and Neisseria gonorrhoeae(NG) are the most commonly reported STIs in Belgium and the majority of women infected are asymptomatic, targeted screening of patients in specified risk groups is indicated. To prevent long-term complications and interrupt transmission, extragenital samples should be included. As this comes with a substantial extra cost, analysis of a pooled sample from vaginal and extragenital sites could be a solution. In this study, we evaluated the feasibility of molecular testing for CT and NG in pooled versus single-site samples in a large cohort of female sex workers.MethodsWomen were sampled from three anatomical sites: a pharyngeal, a vaginal and a rectal swab. Each sample was vortexed, and 400 µL of transport medium from each sample site was pooled into an empty tube. NAAT was performed using the Abbott RealTime CT/NG assay on the m2000sp/rt system.ResultsWe included 489 patients: 5.1% were positive for CT; 2.0% were positive for NG and 1.4% were coinfected, resulting in an overall prevalence of 6.5% (95% CI 4.5% to 9.1%) for CT and 3.5% (95% CI 2.0% to 5.5%) for NG. From the 42 patients positive on at least one non-pooled sample, only 5 gave a negative result on the pooled sample, resulting in a sensitivity of 94% (95% CI 79% to 99%) for CT and 82% (95% CI 57% to 96%) for NG. The missed pooled samples were all derived from single-site infections with low bacterial loads. The possibility of inadequate self-sampling as a cause of false negativity was excluded, as 4/5 were collected by the physician. Testing only vaginal samples would have led to missing 40% of CT infections and 60% of NG infections.ConclusionsPooling of samples is a cost-saving strategy for the detection of CT and NG in women, with minimal decrease in sensitivity. By reducing costs, more patients and more extragenital samples can be tested, resulting in higher detection rates.

ABSTRACTObjectives:The Seegene AllplexTMRespiratory panel was retrospectively challenged using a collection of quality control samples (QCMD) and clinical samples previously analysed with validated routine methods.Methods:A collection of 111 samples [43 QCMD samples, 13 bronchoalveolar lavage fluids and 55 nasopharyngeal aspirates/swabs] was tested with Seegene AllplexTM. The clinical samples were tested previously using either FTD® Respiratory Pathogens 21 qPCR assay (Fast Track Diagnostics), an in-house multiplex PCR for Bordetella, or BioGX Sample-ReadyTMAtypical pneumo panel (Becton Dickinson). Samples were stored at −80°C prior to analysis with Seegene Allplex™, nucleic acids were automatically extracted with NucliSENS Easymag (bioMérieux). Samples returning discordant results were subjected to repeat testing and/or additional testing by reference laboratories.Results:Seegene correctly identified 41/43 QCMD samples (95.4%); two samples positive for respiratory syncytial virus (RSV) and human metapneumovirus, respectively, were only correctly identified following repeat testing. In the 56 clinical samples, overall, 97 pathogens were identified: 65 pathogens (67.0%) were detected both by routine methods and Seegene, 24 pathogens (24.7%) only by routine methods, and 8 pathogens (8.2%) only by Seegene. The majority of discordant results was detected in samples with low pathogen load (22/32, 68.8%) and in samples containing multiple pathogens (25/32, 78.1%). Full agreement between methods was observed for influenza, RSV, adenovirus, Bordetella (para)pertussisand Chlamydiapneumoniae. Discordance was observed for human metapneumovirus, coronavirus OC43, bocavirus and parainfluenza virus, mainly type 4.Conclusion:Overall, the Seegene AllplexTMassay performed well for routine detection of important respiratory targets. Acceptable agreement was observed between Seegene and other routine assays.

•First report on macrolide resistance-associated mutations in M. genitaliumin FSW in Belgium.•Second report on the occurrence of macrolide resistance in this specific population worldwide.•M. genitaliumwas detected in 32/296 (10.8%) of participants.•Macrolide-resistance associated mutations (A2058G and A2059G) were found in 6.5% of isolates.•In contrast to other reports, the occurrence of macrolide resistance appears limited in this specific population.

Myocarditis is a common cause of dilated cardiomyopathy, one of the most important single causes of heart transplantation. Coxsackie B viruses (CBV) are considered to be the principal etiological agents of viral myocarditis and direct virus‐induced damage to the heart tissue has been suggested to be the main mechanism underlying myocarditis in the murine model [Horwitz et al. 2000 Nat Med 6:693–697]. We demonstrate that 2‐(3,4‐dichloro‐phenoxy)‐5‐nitrobenzonitrile (DNB), a compound that was earlier shown to exhibit broad‐spectrum anti‐picornavirus activity is also markedly active against CBV replication in primary human myocard fibroblast. To challenge the hypothesis of [Horwitz et al. 2000 Nat Med 6:693–697] we assessed whether DNB is able to prevent the development of CBV‐induced myocarditis in a murine model. Subcutaneous (s.c.) administration of DNB at 250 mg/kg/day, at multiple injection sites (m.i.s.), for a period of seven consecutive days (starting at 1 day before infection) to 4‐week old C3H‐mice resulted in a (i) 62% reduction in the number of myocarditis foci as compared to the untreated control animals (p = 1.7 × 10−10) and (ii) a concomitant reduction in viral titers in the heart. These findings indicate that selective inhibition of the replication of CBV may have a beneficial effect on the development of viral myocarditis and confirms that direct viral induced damage is the main mechanism underlying CBV‐induced myocarditis. Early diagnosis of virus‐induced myocarditis will likely be mandatory for an antiviral drug treatment regimen to achieve its greatest clinical benefit. J. Med. Virol. 72:263–267, 2004. © 2004 Wiley‐Liss, Inc.

ABSTRACTViral replication, as well as an immunopathological component, is assumed to be involved in coxsackie B virus-induced myocarditis. We evaluated the efficacy of the interferon inducer Ampligen on coxsackie B3 virus-induced myocarditis in C3H/HeNHsd mice. The efficacy of Ampligen was compared with that of the interferon inducer poly(inosinic acid)-poly(cytidylic acid) [poly(IC)], alpha interferon 2b (INTRON A), and pegylated alpha interferon 2b (PEG-INTRON-α-2b). Ampligen at 20 mg/kg of body weight/day was able to reduce the severity of virus-induced myocarditis, as assessed by morphometric analysis, by 98% (P= 3.0 × 10−8). When poly(IC) was administered at 15 mg/kg/day, it reduced the severity of virus-induced myocarditis by 93% (P= 5.6 × 10−5). Alpha interferon 2b (1 × 105U/day) and pegylated alpha interferon 2b (5 × 105U/day) were less effective and reduced the severity of virus-induced myocarditis by 66% (P= 0.0009) and 78% (P= 0.0002), respectively. The observed efficacies of Ampligen and poly(IC) were corroborated by the observation that the drugs also markedly reduced the virus titers in the heart, as detected by (i) quantitative real-time reverse transcription-PCR and (ii) titration for infectious virus content. Whereas the electrocardiograms for untreated mice with myocarditis were severely disturbed, the electrocardiographic parameters were normalized in Ampligen- and poly(IC)-treated mice. Even when start of treatment with Ampligen was delayed until day 2 postinfection, a time at which lesions had already appeared in untreated control animals, a marked protective effect on the development of viral myocarditis (as assessed at day 6 postinfection) was still noted.

There is a lack of information in the medical chemistry literature concerning the anti-influenza A activity of the drug rimantadine's 2-isomer (2-rimantadine). We now present results showing that, although 2-adamantanamine (2-amantadine) 3 is only moderately active, some 2-rimantadine analogues are effective anti-influenza A virus agents in vitro. The 2-rimantadine analogues and their spirocyclobutane and spirocyclopentane congeners were synthesized through interesting routes. The 2-rimantadine analogues were 2–4 times more potent than rimantadine 2 against influenza virus A H2N2strain; their spirocyclobutane congeners proved equally active to rimanta-dine 2. Two compounds exhibited a similar activity and one of the compounds was was fourfold more potent than rimantadine 2 against H3N2strain.

We evaluated the quantitative DiaSorin Liaison severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test in symptomatic and asymptomatic individuals consulting their general practitioners (GPs) during a period of stable intense virus circulation (213/100,000 habitants per day). Leftover reverse transcription-PCR (RT-PCR) positive (n?=?204) and negative (n?=?210) nasopharyngeal samples were randomly selected among fresh routine samples collected from patients consulting their GPs.

Introduction. Congenital cytomegalovirus (cCMV) is a common cause of neurodevelopmental delays and sensorineural hearing loss of infants, yet the prevalence of cCMV and the associated factors in Ethiopia are not studied. Hence, this study was to assess the prevalence and associated factors of cCMV in Southern Ethiopia. Methodology. A mother-newborn pair cross-sectional study was conducted at Hawassa University Comprehensive and Specialized Hospital, Ethiopia. Newborn’s saliva sample was tested for cCMV using Alethia CMV molecular assay. Mothers’ serum was tested serologically for anti-CMV IgM and IgG by EUROIMMUN ELISA. Pregnant women responded to a questionnaire about their previous and current obstetric history and sociodemographic characteristics. The chi-square (χ2) test and independent-sample t-test were used to determine the associations between infections and possible risk factors; then, potential variables were screened for multivariable analysis. Results. A total of 593 mother-newborn pairs were assessed. CMV was detected in 14 of 593 newborn saliva swabs (2.4%; 95% CI 1.2–3.7). As assessed by CMV IgM-positive results, maternal CMV seropositivity was 8.3% (49/593); thus, the rate of mother-to-child transmission of CMV was 28% (14/49) among CMV IgM-positive women. Congenital CMV infection was significantly associated with maternal exposure through nursery school children in the household, women sharing a feeding cup with children, and any of the detected curable STIs during pregnancy. Birth weight was negatively associated with CMV infection. Maternal age, gravidity, level of education, and sharing of children feeding utensils were not associated with cCMV infection. Conclusion. A high rate of cCMV infection in the absence of awareness demands further in-depth investigation in Ethiopia. Thus, policymakers must take appropriate action through the antenatal care system for prevention strategies and put in place a constant health education and awareness creation of pregnant women about the causes of infection and hygienic measures.

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