Serological Screening Research Articles

Equine piroplasmosis: Case descriptions and overview of the epidemiological situation in Europe with focus on Germany

Equine piroplasmosis (EP) is caused by Babesia (B.) caballi and Theileria (T.) equi and is transmitted by hard ticks. Predominantly, the Mediterranean region is known as being endemic for both pathogens in Europe. However, autochthonous infections in central European countries such as Germany can no longer be ruled out due to individual case reports in horses without any stays abroad as well as the geographical expansion of the habitats of different tick species. The case reports presented underline the risk of infection for horses travelling to endemic areas and in horses imported from such areas to non-endemic countries. Clinical signs are often unspecific and include fever, icterus, lethargy, inappetence, weight loss, and reduced performance. Mild to severe anemia is the most common hematologic abnormality, but thrombocytopenia has also been described. Direct (polymerase chain reaction, microscopical analysis of blood smears) and indirect detection methods (detection of antibodies) are available for the diagnosis of pathogen contact and/or infection. Imidocarb-dipropionate is recommended as treatment of choice against EP. Infections with B. caballi can be cleared, while infections with T. equi often result in a life-long carrier status despite treatment. Prevention is limited to controlling or avoiding tick contact. Aside from potentially severe and life-threatening clinical signs, equine piroplasmosis has a significant economic impact on the international trade of horses worldwide. EP is classified as a notifiable disease according to WOAH guidelines, which recommend serological screening for B. caballi and T. equi according to the respective national guidelines when travelling across borders. To date, EP is not classified as a notifiable nor reportable disease in Germany.

Development of a seroepidemiological tool for bat-borne and shrew-borne hantaviruses and its application using samples from Zambia.

Rodent-borne orthohantaviruses are the causative agents of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Apart from the classic rodent-borne hantaviruses, numerous species of hantaviruses have been identified in shrews and bats; however, their antigenicity and pathogenicity are unknown. This study focused on developing a serological method to detect antibodies against bat- and shrew-borne hantaviruses. Five bat-borne (Brno, Dakrong, Quezon, Robina, and Xuan Song) and 6 shrew-borne (Asama, Altai, Cao Bang, Nova, Seewis, and Thottapalayam) viruses were selected based on the phylogenetic differences in their N proteins. The recombinant N (rN) proteins of these viruses were expressed as antigens in Vero E6 and 293T cell lines using the pCAGGS/MCS vector. Antisera against the Nus-tagged rN fusion proteins of these viruses (mouse anti-Brno, Dakrong, Quezon, Robina, Xuan Song, Asama, Cao Bang, and Nova, while rabbit anti-Altai, Seewis and Thottapalayam) were also generated. Antigenic cross-reactivity was examined in antisera and rN-expressing Vero E6 cells. The rN proteins of almost all the tested viruses, except for the Quezon and Robina viruses, showed independent antigenicity. For serological screening of bat samples, 5 rNs of the bat-borne viruses were expressed together in a single transfection protocol. Similarly, 6 rNs of shrew-borne viruses were expressed. Reactivities of the mixed antigen system were also examined across the singly transfected Vero cell lines to ensure that all antigens were expressed. Using these antigens, bat serum samples collected from Zambia were screened using the indirect immunofluorescence antibody test (IFAT). Selected positive samples were individually tested for the respective antigens by IFAT and western blot assays using rN-expressing 293T cell lysates. Of the 1,764 bat serum samples tested, 11.4% and 17.4% were positive for bat and shrew mixed antigens, respectively. These samples showed positive reactions to the Brno, Dakrong, Quezon, Xuan Son, Robina, Asama, Altai, Cao Bang, or Thottapalayam virus antigens. These observations suggest that the mixed-antigen screening system is useful for serological screening For Orthohantavirus infections and that bats in Zambia are likely exposed to not only bat-borne hantaviruses but also to shrew-borne hantaviruses.

Suboptimal Vaccination Coverage and Serological Screening in Western Australian Children With Inflammatory Bowel Disease Receiving Immunosuppressive Therapy: An Opportunity for Improvement

Suboptimal Vaccination Coverage and Serological Screening in Western Australian Children With Inflammatory Bowel Disease Receiving Immunosuppressive Therapy: An Opportunity for Improvement

Poor semen quality is associated with impaired antioxidant response and acute phase proteins and is likely mediated by high cortisol levels in Brucella-seropositive dromedary camel bulls

Brucellosis in dromedary camel bulls leads to either temporary or permanent loss of fertility. Camel brucellosis is associated with both orchitis and epididymitis. However, the clinical signs of camel brucellosis are not clear as those in cattle. Therefore, this study aimed to diagnose camel brucellosis based on a serological screening using Rose Bengal plate test (RBPT) followed by competitive ELISA. To understand the impact of brucellosis on camel bull fertility, this study aimed to examine the semen characteristics, evaluate the testicular histopathology, examine hormonal profile, antioxidants and acute phase proteins (APP). A total of 150 mature bulls were used in this study. Blood samples were collected for serological, hormonal, and biochemical analysis. This study revealed that 6.6% and 7.3% of the examined bulls were Brucella-seropositive using RBPT and competitive ELISA, respectively. The Brucella-seropositive dromedary bulls showed poor semen quality, pathological changes orchitis, and lower testosterone. Moreover, our findings showed a higher cortisol level, and significant impairments in the measured APP and antioxidants in Brucella-seropositive bulls. In conclusion, the Brucella-seropositive dromedary bulls showed lower fertility due to poor semen quality and lower testosterone levels. Such lower fertility is likely mediated by high cortisol levels, and impaired APP and antioxidants’ defense response.

RVSV-ZEBOV vaccination in people with pre-existing immunity to Ebolavirus: an open-label safety and immunogenicity study in Guinean communities affected by Ebola virus disease (l’essai proches)

BackgroundZaire Ebolavirus disease (EVD) outbreaks can be controlled using rVSV-ZEBOV vaccination and other public health measures. People in high-risk areas may have pre-existing antibodies from asymptomatic Ebolavirus exposure that might affect response to rVSV-ZEBOV. Therefore, we assessed the impact pre-existing immunity had on post-vaccination IgG titre, virus neutralisation, and reactogenicity following vaccination.MethodsIn this prospective cohort study, 2115 consenting close contacts (“proches”) of EVD survivors were recruited. Proches were vaccinated with rVSV-ZEBOV and followed up for 28 days for safety and immunogenicity. Anti-GP IgG titre at baseline and day 28 was assessed by ELISA. Samples from a representative subset were evaluated using live virus neutralisation.ResultsTen percent were seropositive at baseline. At day 28, IgG in baseline seronegative (GMT 0.106 IU/ml, 95% CI: 0.100 to 0.113) and seropositive (GMT 0.237 IU/ml, 0.210 to 0.267) participants significantly increased from baseline (both p < 0.0001). There was strong correlation between antibody titres and virus neutralisation in day 28 samples (Spearman’s rho 0.75). Vaccinees with baseline IgG antibodies against Zaire Ebolavirus had similar safety profiles to those without detectable antibodies (63.6% vs 66.1% adults experienced any adverse event; 49.1% vs 60.9% in children), with almost all adverse events graded as mild. No serious adverse events were attributed to vaccination. No EVD survivors tested positive for Ebolavirus by RT-PCR.ConclusionsThese data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection whose state does not blunt rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required.

Evaluation of the clinical utility of NIPT-plus and analysis of adverse pregnancy outcomes.

To evaluate the performance of NIPT-plus in detecting fetal aneuploidies and CNVs and analyze the factors influencing adverse pregnancy outcomes. The retrospectively analyzed 8726 pregnant women who underwent NIPT-plus for fetal screening were classified into low- (who tested voluntarily) and high-risk (women with advanced age, abnormal ultrasound, abnormal serological screening, or a combination of indications) groups. Basic maternal information, prenatal findings, and pregnancy outcomes were recorded. NIPT-plus performance was assessed for various chromosomal abnormalities and the association between the fetal fraction and adverse pregnancy outcomes. Thirty-six (0.4%) patients had failed tests; 144 (1.65%) positive cases were detected, of which, 107 (74.31%) opted for invasive testing, and 51 were verified as true positives. The total positive predictive value was 45.45% and 48.65% in the low- and high-risk groups, respectively, and the difference was not significant. Among the subsequent cases with abnormal ultrasound monitoring, two false-negative cases were identified, and pathogenic CNV diagnosis was confirmed through amniocentesis, resulting in pregnancy termination. Fetal fraction was not associated with an increased adverse pregnancy outcome risk; however, ethnic differences may affect pregnancy outcomes. NIPT-plus technology use is no longer restricted to high-risk pregnant women, and it may produce false-positive results. The stakeholders should be aware of this limitation. The uncertainties and potential risks of the test results should be explained to the test takers to enable informed decision making and to minimize unnecessary anxiety and concerns. Ethnicity may influence adverse pregnancy outcomes in local multiracial settings.

Clinical application of chromosome microarray analysis and karyotyping in prenatal diagnosis in Northwest China.

Karyotyping and chromosome microarray analysis (CMA) are the two main prenatal diagnostic techniques currently used for genetic testing. We aimed to evaluate the value of chromosomal karyotyping and CMA for different prenatal indications. A total of 2084 amniocentesis samples from pregnant women who underwent prenatal diagnosis from 16 to 22 + 6weeks of gestation between January 2021 and December 2022 were retrospectively collected. The pregnant women were classified according to different prenatal diagnostic indications and underwent CMA and karyotype analysis. Clinical data were collected, and the results of the CMA and karyotype analysis were statistically analyzed to compare the effects of the two diagnostic techniques. The total detection rate of abnormal chromosomes was significantly higher using CMA than karyotype analysis. The detection rate of abnormal chromosomes using CMA was significantly higher than that using karyotyping for ultrasound abnormalities, high-risk serologic screening, adverse pregnancy history, positive noninvasive prenatal test (NIPT) screening, and ultrasound abnormalities combined with adverse pregnancy history indications. Among the fetuses with inconsistent results between the two testing methods, 144 had an abnormal CMA but a normal karyotype, with the highest percentage of pregnant women with ultrasound abnormalities at 38.89% (56/144). CMA had the highest detection rate for structural abnormalities combined with soft-index abnormalities among all ultrasound abnormalities. The highest detection rate of copy number variants in the group of structural abnormalities in a single system was in the genitourinary system (3/29, 10.34%). CMA can improve the detection rate of chromosomal abnormalities in patients with ultrasound abnormalities, high-risk serologic screening, adverse maternal history, positive NIPT screening, and ultrasound abnormalities combined with adverse maternal history and can increase the detection rate of chromosomal abnormalities in karyotypic normality by 6.91% (144/2,084), this result is higher than similar studies. However, karyotype analysis remains advantageous over CMA regarding balanced chromosomal rearrangement and detection of low-level chimeras, and the combination of the two methods is more helpful in improving the detection rate of prenatal chromosomal abnormalities.

Seroprevalence and Distribution of Toxoplasma gondii Infections among Patients in the West Bank, Palestine (2017-2021).

Toxoplasmosis is a zoonotic disease caused by the obligate intracellular protozoan Toxoplasma gondii. The current study assessed the seroepidemiological status and risk factors of T. gondii in the West Bank, Palestine. We conducted a retrospective study among 1,475 patients referred for serological examination for toxoplasmosis between 2017 and 2021 at the Central Public Health Laboratory. The overall prevalences of anti-T. gondii IgG and IgM antibodies were 1.0% [18.9-23.0%] and 1.0% [0.5-1.6%], respectively. Multifactorial analysis showed that age and sex were significantly associated with the presence of IgG antibodies. The prevalence of IgG antibodies was highest in 2018 and decreased significantly each year until 2021. Routine serological screening in women of childbearing age and pregnant women is recommended.

Serologic screening and molecular surveillance of Kaposi sarcoma herpesvirus (KSHV)/human herpesvirus-8 (HHV-8) infections for early recognition and effective treatment of KSHV-associated inflammatory cytokine syndrome (KICS) in solid organ transplant recipients

Kaposi sarcoma herpesvirus/human herpesvirus-8 (HHV-8) neoplastic and non-neoplastic disease in solid organ transplant (SOT) recipients can be life-threatening. We evaluated the seroprevalence of HHV-8 infection among donors (D) and recipients (R), the incidence of HHV-8 transmission/reactivation, and the clinical characteristics, management, and outcomes of HHV-8-related diseases, including Kaposi sarcoma herpesvirus-associated inflammatory cytokine syndrome (KICS), in consecutive SOT patients from 2011 to 2023. HHV-8 seroprevalence was 3.3% in 1349 donors and 8.4% in 1856 recipients screened (p<0.0001). Among the D+/R- group (n=49), 13 patients developed HHV-8-related diseases: 7 liver recipients had KICS, and 1 lung recipient had Kaposi sarcoma (KS) with subsequent KICS. Four KICS patients treated with rituximab survived, while the 3 patients not treated with rituximab died. Within the D-/R- group, out of 5 (0.3%) patients with non-donor-derived primary HHV-8 infection, 3 liver recipients developed KICS. In the R+ patients (n=155), 3 developed KS. In our cohort, 25/944 (2.6%) liver transplant recipients had a primary HHV-8 infection, and 10 of them (40%) developed KICS; 40% (4/10) of HHV-8 seropositive heart transplant recipients developed reactivation and 2 of them (50%) had fatal KS. Serologic screening and molecular surveillance of D+/R- patient groups facilitate early recognition and effective therapy of KICS.

Evaluation of the Vitros® Anti-T. cruzi Assay for its incorporation into the Trypanosoma cruzi Infection Diagnostic Algorithm

Background and objectiveSerological screening for Chagas disease (CD) in Latin American adults living in Europe is a cost-effective strategy for transmission prevention. The World Health Organization recommends two different serological tests including native and recombinant antigens for IgG detection. In Spain, most commercialized native tests require manual processing. We aimed to evaluate the sensitivity and specificity of the automated Vitros® Anti-T. cruzi native antigen-based test. MethodsA total of 556 serum samples were tested using two different tests: 1) our reference assay, a chemiluminescence immunoassay employing a recombinant multi-antigen protein (Liaison® XL Murex Chagas); 2) a chemiluminescence immunoassay with native antigen (Vitros® Anti-T. cruzi assay). Additionally, 180 samples were also processed by a manual indirect immunofluorescent assay (Chagas IFA). Sensibility, specificity and kappa index were calculated. ResultsVitros® showed a kappa index of 0.94 (IC 95%: 0.86-1.03) compared to Liaison® XL with a sensitivity of 93.6% and specificity of 99.5%. Compared to IFA, Vitros® showed a kappa index of 0.61 (IC 95%: 0.47-0.76), sensitivity of 97.5% and specificity of 70.37%. Discrepant results were obtained mainly in treated patients. ConclusionsThe Vitros® Anti-T. cruzi assay showed potential for implementation as an automated serological screening test, enhancing the diagnostic process in high-throughput microbiology laboratories.

Characterization of anti-AAV2 neutralizing antibody levels in sheep prior to and following intravitreal AAV2.7m8 injection

Gene augmentation therapy is a promising treatment for incurable, blinding inherited retinal diseases, and intravitreal delivery is being studied as a safe alternative to subretinal injections. Adeno-Associated Viruses (AAV) are commonly-used vectors for ocular gene augmentation therapy. Naturally occurring pre-operative exposure and infection with AAV could result in presence of neutralizing antibodies (NAB’s) in patients’ serum, and may affect the safety and efficacy of treatment. Our aim was to characterize the humoral response against AAV pre- and post-intravitreal delivery of AAV2.7m8 vectors in a naturally-occurring sheep model of CNGA3 achromatopsia. Serial serum neutralization assays were performed to screen sheep for pre-exiting anti-AAV2 NAB’s, and to assess the effect of intravitreal AAV2.7m8 injection on post-operative NAB titers and intraocular inflammation in sheep. The effect of viral dose and transgene type were also assessed. Serological screening revealed pre-operative seropositivity in 21.4% of animals, with age being a risk factor for the presence of anti-AAV2 NAB’s. NAB titers increased following intravitreal AAV administration in the majority of sheep. There was no significant difference in the degree of post-operative serum neutralization between pre-operatively seronegative sheep and those with pre-existing antibodies. However, only sheep with pre-existing antibodies presented with signs of post-operative inflammation. We conclude that pre-existing anti-AAV2 NAB’s do not affect the level of post-operative NAB titers; however, they increase the risk of post-operative ocular inflammation. Our results could have implications for the management of AAV-mediated ocular gene therapies, a technology being increasingly studied and used in patients.

Autochthonous dengue outbreak in Lombardy, Italy: enhanced surveillance and vector control measures

Abstract Description of the problem On 18 August 2023, the first autochthonous case of dengue was registered in Lombardy, in a person living in a village in Lodi province. The case, a man with no history of travels prior to symptoms onset, developed flu-like symptoms on 3 August. After initial suspicion of WNV infection, he was confirmed to have a DENV-1 infection. Following the notification, measures to control the spread of the disease were activated, including alert of healthcare professionals, vector control activities, entomological monitoring and active case finding among household contacts and people living close to the case. Moreover, a serological screening was proposed to population of the entire municipality, along with a survey collecting data about travels abroad and symptoms. Results Forty-one confirmed and six probable autochthonous cases were identified. The last case developed symptoms on 20 October. Among confirmed cases, 24 were identified after admission to Emergency Department, 16 through community screening and one at the time of blood donation. 38/41 confirmed cases were symptomatic, with fever, rash and retro-orbital pain being the most common symptoms. Mean age was 55,5 years (3-88), while male: female ratio was 2:1. Hospitalisation was required for 7/41 cases. Community screening was offered from 25 August to 8 October and 416 individuals participated. Among them 10 tested positive for DENV IgG and 27 for DENV IgM (16 were subsequently confirmed as DENV cases, 6 remained probable and 5 were ruled out as non-cases). The primary case of the outbreak was not identified. Vector control activities and entomological monitoring were conducted on 21 August within 200-m radius area around the residence and places visited by index case. Subsequent interventions were conducted in all public areas and sensitive sites of the municipality. Lessons Enhancement of surveillance through community screening allowed identification of several additional autochthonous cases. Key messages • Strengthening of surveillance, vector control activities and entomological monitoring is crucial to prevent and control future outbreaks in non-endemic areas with stable presence of Aedes mosquitoes. • To minimize the risk of introduction and spread of dengue virus in non-endemic areas, it is essential to raise awareness among travellers and general population about preventive and control measures.

Application of Genetic Origin Analysis of Copy Number Variations in Non-Invasive Prenatal Testing.

This study aimed to assess the application of origin analysis of copy number variations (CNVs) in non-invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT. We enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV-Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell-free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked. A total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)-CNVs and 44 cases of F-CNVs. The occurrence of M/F-CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)-F-CNVs was high in cases where serological screening indicated intermediate, high-risk, or abnormal US findings (p<0.05). In the M/F-CNV group, most of the P/LP-CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5Mb in size, and nine (13.85%) were between 5 and 10Mb. In the F-CNV group, foetal P/LP-CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP-F-CNV fragments. The prenatal diagnostic rate and positive predictive value in the F-CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p<0.05). Genetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

Safety of Hepatitis B Virus Screening in Blood Donors from the Hospital Foundation of Hematology and Hemotherapy of the State of Amazonas (HEMOAM) in the Brazilian Amazon

Background: Hepatitis B is an infectious disease of worldwide importance and of great interest to transfusion medicine. The Amazon region has areas of high endemicity, outlining a worrying scenario for transfusion and epidemiological safety. Objective: To analyze the profiles of serological and molecular markers for HBV of blood donors from HEMOAM. Methods: Blood donors with different patterns of reactivity in serological and molecular screening for HBV were tested for viral load by the qPCR method at the reference center for liver diseases in the state of Amazonas. Results: A total of 230,591 donors were tested, with 3104 (1.34%) found reactive for HBV and 2790 (89.9%) found reactive for isolated anti-HBc. Viral load was not detected in 100% of donors reactive only to HBsAg, while 100% of donors with positive anti-HBc and positive HBsAg or HBV NAT demonstrated a detectable viral load. We also detected one case of occult hepatitis B (0.03%) only with reactive HBV NAT and five donors (0.2%) with positive anti-HBc and HBV NAT. Conclusions: With this result, the great importance of the anti-HBc test for the unsuitability of blood donors was verified, as well as the fundamental introduction of the HBV NAT test in screening for hepatitis B in Brazilian blood banks, as this was the only way to detect the viral infection burden in asymptomatic donors who previously would not be treated, which contributed to the maintenance of the endemicity of hepatitis B in the Brazilian Amazon.

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundThere is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.MethodsAutoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.ResultsDuring the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.ConclusionsIndividuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

Assessment of genetic diversity, tissue tropism, and antigenic properties of Grimsö betacoronavirus in Swedish bank voles (Clethrionomys glareolus)

Zoonotic coronaviruses can transmit over species barriers and infect humans. To understand the zoonotic potential of a betacoronavirus, Grimsö virus (GRIV), we investigated the geographic distribution and tissue tropism of GRIV in Swedish bank voles (Clethrionomys glareolus), and the antigenicity of the nucleocapsid (N) protein. We screened the lung tissues from animals collected in the southern Sweden by RT-PCR with primers targeting the spike gene. Seven out of 74 animals were found to be positive. They are genetically close to GRIV from Grimsö, central Sweden. Positive rodents were studied for the tissue distribution of GRIV and GRIV RNA was mainly found in the respiratory tract. After three attempts of virus isolation were failed, we successfully established a Vero E6 cell line that stably expressed GRIV N protein, which has no cross-reactivity with patient serum containing antibodies against SARS-CoV-2, or with MERS-CoV. However, a low level of cross-reactivity to common cold coronaviruses was found, likely HCoV-OC43 or HCoV-HKU1, probably due to shared linear epitopes. With the high prevalence and the suggested respiratory transmission route, GRIV may have a high potential for spillover and cross-species transmission, and future serological screening of GRIV infections in domestic animals or humans will be needed.

Evaluation of different standard and modified two-tier testing strategies for the laboratory diagnosis of lyme borreliosis in a European setting

BackgroundDiagnosis of Lyme borreliosis (LB) relies on clinical symptoms and detection of Borrelia-specific antibodies. Guidelines recommend a two-tier testing (TTT) strategy for disseminated LB: serological screening with a sensitive enzyme immunoassay (EIA) and confirmation with a specific immunoblot. Searching for the most sensitive and specific approach, this retrospective study evaluated standard (STTT) and modified (MTTT) strategies using a well-defined study population.MethodsCases included patients with active Lyme neuroborreliosis (LNB; n = 29) or Lyme arthritis (LA; n = 17). Controls comprised patients treated for LNB (n = 36) or LA (n = 8), healthy individuals who were either untreated (n = 75) or treated for LB (n = 15) in the past, and patients with potentially cross-reactive diseases (n = 16). Sera were subjected to three EIAs and two immunoblots. Reactive screening results were confirmed by immunoblot (STTT) or EIA (MTTT). Solitary IgM results in the screening assay and effects of antibiotic treatment on isotype-specific seropositivity rates were also assessed.ResultsSensitivities of STTT strategies ranged from 90%–97% for LNB and were 100% for LA. MTTT strategies were 100% sensitive. Specificities ranged from 89%–95% for STTT and from 88%–93% for MTTT strategies. Differences between STTT and MTTT strategies were not statistically significant. Solitary IgM reactivity was common among controls. Antibiotic treatment significantly reduced IgM/IgG positivity for LNB patients; for LA patients, a decline was only observed for IgM.ConclusionIn conclusion, MTTT strategies showed a slightly higher sensitivity and similar specificity compared to STTT strategies. Since EIAs are more time- and cost-efficient, MTTT strategies seem more favorable for clinical use. IgG testing enhances specificity with minimal sensitivity loss.

Identification of High-Incidence Populations in the United States for Anti-Epstein-Barr Virus Serologic Screening for Nasopharyngeal Carcinoma.

In the United States, Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective. We obtained NPC incidence data from the Surveillance, Epidemiology, and End Results Asian and Pacific Islander datasets. We estimated the number needed to screen (NNS), mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI. Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median incremental cost-effectiveness ratio/gross domestic product, 0.82) and among men in intermediate-incidence populations. Nearly half of NPC in the United States arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women aged 35 to 65 years of Chinese, Sāmoan, or Southeast Asian ethnicity, or men aged 35 to 60 years of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective. These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.

Seroprevalence of Neonatal Herpes Simplex Virus Infection at A Tertiary Teaching Hospital in Malaysia

INTRODUCTION: Neonatal herpes simplex virus (HSV) infection is generally infrequent, despite being a life-threatening illness. Knowledge of its prevalence is limited in Malaysia since most cases are asymptomatic infections and only limited routine neonatal HSV screening is conducted. This study therefore provides a comprehensive investigation of the seroprevalence of HSV-1 and HSV-2 in neonates. MATERIALS AND METHODS: Serological screening for HSV-1 IgG and HSV-2 IgG antibody tests using the Electrochemiluminescence assay was performed on serum samples of 215 neonates delivered from January until December 2022 at Hospital Universiti Sains Malaysia. RESULTS: Of the neonates, 54.4% were found to be HSV-1 positive, while 4.2% were HSV-2 positive. All the HSV-2 neonates were co-infected with HSV-1. Newborns aged 0–10 days were the most infected group by HSV-1 (92.3%) and HSV-2 (55.6%). The most reported clinical presentation was small gestational age (SGA) (60%). Microcephaly and macrocephaly were observed in one neonate each. The clinical presentations of reactive HSV-1 and HSV-2 cases revealed the presence of fever with rash in both cases. CONCLUSION: The high seroprevalence of HSV-1 is alarming. It is hoped that these data will support the advocacy of screening women for HSV before or during pregnancy as a precautionary approach to reducing the risk of vertical transmission.

Clinical strategy study on prenatal screening and diagnostic model for Down syndrome

Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged < 35 years who underwent only one screening for foetal Down syndrome (DS), the detection rate, false positive rate and positive predictive value of NIPS for foetuses with DS were superior to those of the other four serological screening methods. Although applying NIPS as first-line screening method yields the highest efficacy and benefits, it currently lacks cost-effectiveness when compared to serological screening and sequential NIPS screening strategies.