Use of proxy indicators for automated surveillance of severe acute respiratory infection, the Netherlands, 2017 to 2023: a proof-of-concept study.

BackgroundEffective pandemic preparedness requires robust severe acute respiratory infection (SARI) surveillance. However, identifying SARI patients based on symptoms is time-consuming. Using the number of reverse transcription (RT)-PCR tests or contact and droplet precaution labels as a proxy for SARI could accurately reflect the epidemiology of patients presenting with SARI.AimWe aimed to compare the number of RT-PCR tests, contact and droplet precaution labels and SARI-related International Classification of Disease (ICD)-10 codes and evaluate their use as surveillance indicators.MethodsPatients from all age groups hospitalised at Leiden University Medical Center between 1 January 2017 up to and including 30 April 2023 were eligible for inclusion. We used a clinical data collection tool to extract data from electronic medical records. For each surveillance indicator, we plotted the absolute count for each week, the incidence proportion per week and the correlation between the three surveillance indicators.ResultsWe included 117,404 hospital admissions. The three surveillance indicators generally followed a similar pattern before and during the COVID-19 pandemic. The correlation was highest between contact and droplet precaution labels and ICD-10 diagnostic codes (Pearson correlation coefficient: 0.84). There was a strong increase in the number of RT-PCR tests after the start of the COVID-19 pandemic.DiscussionAll three surveillance indicators have advantages and disadvantages. ICD-10 diagnostic codes are suitable but are subject to reporting delays. Contact and droplet precaution labels are a feasible option for automated SARI surveillance, since these reflect trends in SARI incidence and may be available real-time.

Substantial impact of the COVID-19 pandemic on the reported number of diagnosed chronic hepatitis C virus infections in the Netherlands, 2019-2021.

BACKGROUND: The COVID-19 pandemic has widespread consequences for health facilities, social contacts, and health-seeking behaviour, affecting the incidence, diagnosis and reporting of other infectious diseases. We examined trends in reported chronic hepatitis C virus (HCV) infections and associated transmission routes in the Netherlands to identify the potential impact of COVID-19 on access to healthcare (testing) services. METHODS: We analysed notification data of patients with chronic HCV reported to the National Notifiable Disease Surveillance System from January 2019 until December 2021 in the Netherlands. Rates of newly reported chronic cases per 100,000 population with 95% confidence intervals (CI) were calculated, and we compared proportional changes in transmission routes for chronic HCV between 2019, 2020 and 2021. RESULTS: During the study period, a total of 1,521 chronic HCV infections were reported, 72% males, median age 52 years, and an overall rate of 8.8 (95%CI 8.4-9.2) per 100,000 population. We observed an overall decline (-41.9%) in the number of reported chronic HCV in 2020 compared to 2019, with the sharpest decline in men who have sex with men (MSM)-related transmission (-57.9% in 2020, p = 0.005). CONCLUSIONS: Reported cases of chronic HCV strongly declined during the COVID-19 pandemic when healthcare services were scaled down. Between February and June 2021, reported chronic HCV cases increased again, indicating a recovery of healthcare services. MSM showed the largest decline compared to other groups. Further research is needed to fully understand the impact of access to healthcare, health seeking behaviour, and (sexual) transmission risks of HCV during the COVID-19 pandemic.

Diagnostic accuracy of SARS-CoV-2 rapid antigen self-tests in asymptomatic individuals in the omicron period: a cross-sectional study.

OBJECTIVES: To assess the performances of three commonly used antigen rapid diagnostic tests used as self-tests in asymptomatic individuals in the Omicron period. METHODS: We performed a cross-sectional diagnostic test accuracy study in the Omicron period in three public health service COVID-19 test sites in the Netherlands, including 3600 asymptomatic individuals aged ≥ 16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex [Flowflex], MP Biomedicals (MPBio), or Siemens-Healthineers CLINITEST [CLINITEST]) to perform unsupervised at home. Diagnostic accuracies of each self-test were calculated. RESULTS: Overall sensitivities were 27.5% (95% CI, 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for CLINITEST. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. Specificities were >99% for all tests in most analyses. DISCUSSION: The sensitivities of three commonly used SARS-CoV-2 antigen rapid diagnostic tests when used as self-tests in asymptomatic individuals in the Omicron period were very low. Antigen rapid diagnostic test self-testing in asymptomatic individuals may only detect a minority of infections at that point in time. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield, and individuals should be advised to re-test when symptoms develop.

Head-to-head comparison of the accuracy of saliva and nasal rapid antigen SARS-CoV-2 self-testing: cross-sectional study.

BACKGROUND: The diagnostic accuracy of unsupervised self-testing with rapid antigen diagnostic tests (Ag-RDTs) is mostly unknown. We studied the diagnostic accuracy of a self-performed SARS-CoV-2 saliva and nasal Ag-RDT in the general population. METHODS: This large cross-sectional study consecutively included unselected individuals aged ≥ 16 years presenting for SARS-CoV-2 testing at three public health service test sites. Participants underwent molecular test sampling and received two self-tests (the Hangzhou AllTest Biotech saliva self-test and the SD Biosensor nasal self-test by Roche Diagnostics) to perform themselves at home. Diagnostic accuracy of both self-tests was assessed with molecular testing as reference. RESULTS: Out of 2819 participants, 6.5% had a positive molecular test. Overall sensitivities were 46.7% (39.3-54.2%) for the saliva Ag-RDT and 68.9% (61.6-75.6%) for the nasal Ag-RDT. With a viral load cut-off (≥ 5.2 log10 SARS-CoV-2 E-gene copies/mL) as a proxy of infectiousness, these sensitivities increased to 54.9% (46.4-63.3%) and 83.9% (76.9-89.5%), respectively. For the nasal Ag-RDT, sensitivities were 78.5% (71.1-84.8%) and 22.6% (9.6-41.1%) in those symptomatic and asymptomatic at the time of sampling, which increased to 90.4% (83.8-94.9%) and 38.9% (17.3-64.3%) after applying the viral load cut-off. In those with and without prior SARS-CoV-2 infection, sensitivities were 36.8% (16.3-61.6%) and 72.7% (65.1-79.4%). Specificities were > 99% and > 99%, positive predictive values > 70% and > 90%, and negative predictive values > 95% and > 95%, for the saliva and nasal Ag-RDT, respectively, in most analyses. Most participants considered the self-performing and result interpretation (very) easy for both self-tests. CONCLUSIONS: The Hangzhou AllTest Biotech saliva self Ag-RDT is not reliable for SARS-CoV-2 detection, overall, and in all studied subgroups. The SD Biosensor nasal self Ag-RDT had high sensitivity in individuals with symptoms and in those without prior SARS-CoV-2 infection but low sensitivity in asymptomatic individuals and those with a prior SARS-CoV-2 infection which warrants further investigation.

Diagnostic accuracy of covid-19 rapid antigen tests with unsupervised self-sampling in people with symptoms in the omicron period: cross sectional study.

OBJECTIVE: To assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period. DESIGN: Prospective cross sectional diagnostic test accuracy study. SETTING: Three public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022. PARTICIPANTS: 6497 people with covid-19 symptoms aged ≥16 years presenting for testing. INTERVENTIONS: Participants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers). MAIN OUTCOME MEASURES: The main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard. RESULTS: During phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ2 test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively). CONCLUSIONS: Sensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well.

Detection of SARS-CoV-2 infection in the general population by three prevailing rapid antigen tests: cross-sectional diagnostic accuracy study.

BACKGROUND: Rapid antigen diagnostic tests (Ag-RDTs) are the most widely used point-of-care tests for detecting SARS-CoV-2 infection. Since the accuracy may have altered by changes in SARS-CoV-2 epidemiology, indications for testing, sampling and testing procedures, and roll-out of COVID-19 vaccination, we evaluated the performance of three prevailing SARS-CoV-2 Ag-RDTs. METHODS: In this cross-sectional study, we consecutively enrolled individuals aged >16 years presenting for SARS-CoV-2 testing at three Dutch public health service COVID-19 test sites. In the first phase, participants underwent either BD-Veritor System (Becton Dickinson), PanBio (Abbott), or SD-Biosensor (Roche Diagnostics) testing with routine sampling procedures. In a subsequent phase, participants underwent SD-Biosensor testing with a less invasive sampling method (combined oropharyngeal-nasal [OP-N] swab). Diagnostic accuracies were assessed against molecular testing. RESULTS: Six thousand nine hundred fifty-five of 7005 participants (99%) with results from both an Ag-RDT and a molecular reference test were analysed. SARS-CoV-2 prevalence and overall sensitivities were 13% (188/1441) and 69% (129/188, 95% CI 62-75) for BD-Veritor, 8% (173/2056) and 69% (119/173, 61-76) for PanBio, and 12% (215/1769) and 74% (160/215, 68-80) for SD-Biosensor with routine sampling and 10% (164/1689) and 75% (123/164, 68-81) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72-83% and 54-56%, respectively. Above a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities were 86% (125/146, 79-91) for BD-Veritor, 89% (108/121, 82-94) for PanBio, and 88% (160/182, 82-92) for SD-Biosensor with routine sampling and 84% (118/141, 77-89) with OP-N sampling. Specificities were >99% for all tests in most analyses. Sixty-one per cent of false-negative Ag-RDT participants returned for testing within 14 days (median: 3 days, interquartile range 3) of whom 90% tested positive. CONCLUSIONS: Overall sensitivities of three SARS-CoV-2 Ag-RDTs were 69-75%, increasing to ≥86% above a viral load cut-off. The decreased sensitivity among asymptomatic participants and high positivity rate during follow-up in false-negative Ag-RDT participants emphasise the need for education of the public about the importance of re-testing after an initial negative Ag-RDT should symptoms develop. For SD-Biosensor, the diagnostic accuracy with OP-N and deep nasopharyngeal sampling was similar; adopting the more convenient sampling method might reduce the threshold for professional testing.

Shorter serial intervals in SARS-CoV-2 cases with Omicron BA.1 variant compared with Delta variant, the Netherlands, 13 to 26 December 2021.

The SARS-CoV-2 Omicron variant has a growth advantage over the Delta variant because of higher transmissibility, immune evasion or shorter serial interval. Using S gene target failure (SGTF) as indication for Omicron BA.1, we identified 908 SGTF and 1,621 non-SGTF serial intervals in the same period. Within households, the mean serial interval for SGTF cases was 0.2-0.6 days shorter than for non-SGTF cases. This suggests that the growth advantage of Omicron is partly due to a shorter serial interval.

Outbreaks of mumps genotype G viruses in the Netherlands between October 2019 and March 2020: clusters associated with multiple introductions.

BACKGROUND: From October 2019-March 2020, several clusters of mumps cases were identified in the Netherlands. Our objective was to describe cluster-associated mumps virus transmission using epidemiological and molecular information in order to help future mumps outbreak investigation and control efforts. METHODS: An epidemiological cluster includes ≥ 2 mumps cases with at least an epidemiological-link to a laboratory-confirmed mumps case. A molecular group includes ≥ 2 mumps cases with identical mumps virus sequences. Cases with symptom onset date between 1 October 2019 and 31 March 2020 reported through the National Notifiable Diseases Surveillance System were included. We described epidemiological and clinical characteristics of mumps cases. Sequence data was obtained from selected regions of mumps virus genomes (2270 nucleotides). Associations between epidemiological and molecular information were investigated. RESULTS: In total, 102 mumps cases were notified (90% laboratory-confirmed, 10% epidemiologically-linked). 71 out of 102 cases were identified as part of an epidemiological cluster and/or molecular group. Twenty-one (30%) of 71 cases were identified solely from epidemiological information, 25 (35%) solely from molecular surveillance, and 25 (35%) using both. Fourteen epidemiological clusters were identified containing a total of 46 (range: 2-12, median: 3) cases. Complete sequence data was obtained from 50 mumps genotype G viruses. Twelve molecular groups were identified containing 43 (range: 2-13) cases, dispersed geographically and timewise. Combined information grouped seven epidemiological clusters into two distinct molecular groups. The first lasting for 14 weeks, the other for 6. Additionally, one molecular group was detected, linked by geography and time but without an epidemiological-link. CONCLUSIONS: Combined epidemiological and molecular information indicated ongoing mumps virus transmission from multiple introductions for extended time periods. Sequence analysis provided valuable insights into epidemiological clustering. If combined information is available in a timely manner, this would improve outbreak detection, generate further insight into mumps transmission, and guide necessary control measures.

Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study.

OBJECTIVE: To assess the diagnostic test accuracy of two rapid antigen tests in asymptomatic and presymptomatic close contacts of people with SARS-CoV-2 infection on day 5 after exposure. DESIGN: Prospective cross sectional study. SETTING: Four public health service covid-19 test sites in the Netherlands. PARTICIPANTS: 4274 consecutively included close contacts (identified through test-and-trace programme or contact tracing app) aged 16 years or older and asymptomatic for covid-19 when requesting a test. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of Veritor System (Beckton Dickinson) and Biosensor (Roche Diagnostics) rapid antigen tests, with reverse-transcriptase polymerase chain reaction (RT-PCR) testing as reference standard. The viral load cut-off above which 95% of people with a positive RT-PCR test result were virus culture positive was used as a proxy of infectiousness. RESULTS: Of 2678 participants tested with Veritor, 233 (8.7%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 149 were also detected by the rapid antigen test (sensitivity 63.9%, 95% confidence interval 57.4% to 70.1%). Of 1596 participants tested with Biosensor, 132 (8.3%) had a RT-PCR confirmed SARS-CoV-2 infection of whom 83 were detected by the rapid antigen test (sensitivity 62.9%, 54.0% to 71.1%). In those who were still asymptomatic at the time of sampling, sensitivity was 58.7% (51.1% to 66.0%) for Veritor (n=2317) and 59.4% (49.2% to 69.1%) for Biosensor (n=1414), and in those who developed symptoms were 84.2% (68.7% to 94.0%; n=219) for Veritor and 73.3% (54.1% to 87.7%; n=158) for Biosensor. When a viral load cut-off was applied for infectiouness (≥5.2 log10 SARS-CoV-2 E gene copies/mL), the overall sensitivity was 90.1% (84.2% to 94.4%) for Veritor and 86.8% (78.1% to 93.0%) for Biosensor, and 88.1% (80.5% to 93.5%) for Veritor and 85.1% (74.3% to 92.6%) for Biosensor, among those who remained asymptomatic throughout. Specificities were >99%, and positive and negative predictive values were >90% and >95%, for both rapid antigen tests in all analyses. CONCLUSIONS: The sensitivities of both rapid antigen tests in asymptomatic and presymptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 60%, increasing to more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

An efficient molecular approach to distinguish chains of measles virus transmission in the elimination phase.

Measles viruses continue to spread globally, despite the availability of a safe and effective vaccine. Molecular surveillance of measles virus has become an essential tool to demonstrate whether cascades of infections in a certain region or country are the result of endemic spread or the repeatedly introduction of the virus in contained outbreaks. Currently, molecular surveillance of measles viruses worldwide is mainly based on 450 nucleotides of the C-terminal region of the nucleoprotein (N450). However, as a result of the disappearance of particular measles virus clades over the past decades, this gene segment does not provide sufficient resolution anymore to answer these questions. To increase the molecular resolution, sequence data were collected from three regions of the measles virus genome, the partial non-coding region between the M and F gene (M-F NCR4465-4754), partial H gene (H8022-8621) and the partial L gene (L10724-11438) for measles viruses detected in 2018 and 2019 in the Netherlands. Analysis of obtained sequence data indicated that sequencing of these three regions resulted in an increase in molecular resolution for measles virus genotype B3 and D8 viruses, two of the four global genotypes currently predominant in the European region. Furthermore, this improved resolution was sufficient to support an epidemiology characterized by repeat introduction of measles virus rather than endemic virus spread. In conclusion, sequencing of the M-F NCR4465-4754, H8022-8621 and L10724-11438 regions of the measles virus is an efficient and useful approach for molecular surveillance of measles viruses.

Immunogenicity, duration of protection, effectiveness and safety of rubella containing vaccines: A systematic literature review and meta-analysis.

BACKGROUND: Rubella containing vaccines (RCV) prevent rubella virus infection and subsequent congenital rubella syndrome (CRS). To update the evidence on immunogenicity, duration of protection, effectiveness and safety of RCV, we conducted a systematic literature review. METHODS: We searched EMBASE and SCOPUS, using keywords for rubella vaccine in combination with immunogenicity (seroconversion and seropositivity), duration of protection, efficacy/effectiveness, and safety. Original research papers involving at least one dose of RCV (at any age), published between 1-1-2010 and 17-5-2019 were included. Where appropriate, meta-analyses were performed. Quality of included studies was assessed using GRADE methodology. RESULTS: We included 36 papers (32 randomized controlled trials (RCTs) and 4 observational studies) on immunogenicity (RA27/3 strain) in children and adolescent girls, 14 papers (5 RCTs and 9 observational studies) on duration of protection, one paper on vaccine effectiveness (VE) (BRDII strain), and 74 studies on safety, including three on safety in pregnancy. Meta-analysis of immunogenicity data showed 99% seroconversion (95% CI: 98-99%) after a single dose of RCV in children, independent of co-administration with other vaccines. Seroconversion after RCV1 below 9 months of age (BRDII strain, at 8 months) was 93% (95% CI: 92-95%). For duration of protection, the included studies showed a seropositivity of 88%-100% measured 1-20 years after one or two RCV doses. The single study on VE of BRDII strain, reported 100% VE after one and two doses. Among 34,332 individuals participating in the RCTs, 140 severe adverse events (SAEs) were reported as possibly related to RCV. Among the case reports on SAEs, the association with RCV was confirmed in one report (on fulminant encephalitis). Among 3,000 pregnant women who were inadvertently vaccinated, no SAEs were reported. CONCLUSIONS: One and two doses of RCV are highly immunogenic for a long period of time, effective in preventing rubella and CRS, and safe.

Molecular epidemiology of mumps viruses in the Netherlands, 2017-2019.

Mumps cases continue to occur, also in countries with a relatively high vaccination rate. The last major outbreaks of mumps in the Netherlands were in 2009-2012 and thereafter, only small clusters and single cases were reported. Molecular epidemiology can provide insights in the circulation of mumps viruses. The aims of the present study were to analyze the molecular epidemiology of mumps viruses in the Netherlands in 2017-2019 and to compare the phylogenetic trees built from sequence data of near complete mumps virus genomes or from the SH gene and non-coding regions (SH+NCRs). To this end, Sanger sequence data from SH+NCRs were analyzed from 82 mumps genotype G viruses. In addition, near complete genomes were obtained from 10 mumps virus isolates using next-generation sequencing. Analysis of SH+NCRs sequences of mumps genotype G viruses revealed the presence of two major genetic lineages in the Netherlands, which was confirmed by analysis of near complete genomes. Comparison of phylogenetic trees built with SH+NCRs or near complete genomes indicated that the topology was similar, while somewhat longer branches were present in the phylogenetic tree with near complete genomes. These results confirm that analysis of SH + NCRs sequence data is a useful approach for molecular surveillance. Furthermore, data from recent mumps genotype G viruses might indicate (intermittent) circulation of mumps genotype G viruses in the Netherlands in 2017-2019.

A Third Dose of Measles-Mumps-Rubella Vaccine to Improve Immunity Against Mumps in Young Adults.

BACKGROUND: Waning of vaccine-induced immunity is considered to play a central role in the reemergence of mumps among vaccinated young adults. The aim of the present study was to investigate antibody responses and safety of a third dose of measles-mumps-rubella vaccine (MMR-3) in 150 young adults. Antibody levels were related to a surrogate of protection based on preoutbreak serum antibody levels in 31 persons with and 715 without serological evidence of mumps. METHODS: Mumps virus-specific immunoglobulin G (IgG) antibody responses and mumps virus-neutralizing antibody responses (based on the focus-reduction neutralizing test) against both the Jeryl Lynn mumps virus vaccine strain (hereafter, the "vaccine strain") and the MuVi/Utrecht.NLD/40.10 outbreak strain (hereafter, the "outbreak strain") were determined, and vaccine safety was evaluated. RESULTS: Four weeks following MMR-3 receipt, levels of IgG, anti-vaccine strain, and anti-outbreak strain antibodies increased by a factor of 1.65, 1.34, and 1.35, respectively. Although antibody levels decreased 1 year later, they were still above the baseline level by a factor of 1.37, 1.15, and 1.27, respectively. Based on the surrogate protective antibody cutoff, significantly more participants were protected against mumps virus infection up to 1 year after vaccination (ie, they had antibody levels above the presumed threshold for herd immunity). CONCLUSIONS: MMR-3 receipt increased antibody levels that may protect against mumps virus infection for longer than previously assumed and is expected to be a good and safe intervention for controlling a mumps outbreak. CLINICAL TRIALS REGISTRATION: 2016-001104-36; NTR5911.

Seroepidemiology of Measles, Mumps and Rubella on Bonaire, St. Eustatius and Saba: The First Population-Based Serosurveillance Study in Caribbean Netherlands.

The National Immunization Program (NIP) on Bonaire, St. Eustatius and Saba (i.e., Caribbean Netherlands (CN)) includes the measles-mumps-rubella (MMR) vaccine since 1988/89. Seroepidemiological data is an important tool to evaluate the NIP, hence a cross-sectional representative population-based serosurveillance study was conducted for the first time in CN in mid-2017. Participants (n = 1829, aged 0-90 years) donated a blood sample and completed a health-related questionnaire. MMR-specific IgG antibodies were determined using a bead-based multiplex immunoassay and risk factors were analyzed using logistic regression models. Overall seroprevalence was high for measles (94%), but lower for mumps and rubella (both 85%). In NIP eligibles, including women of childbearing age, rubella seroprevalence (88%) exceeded the threshold for protection (85%); however, for measles (89%) this protective level (95%) was not met. MMR seropositivity was lowest in children who became CN resident at 11-17 years of age (especially for measles (72%)), mostly originating from Latin America and other non-Western countries. Interestingly, rubella seroprevalence was lowest in non-NIP eligible adults from Dutch overseas territories and Suriname (75%). Taken together, MMR immunity is generally good in CN, nonetheless some risk groups were identified. Additionally, we found evidence for a unique island epidemiology. In light of recent regional measles outbreaks, disease monitoring remains of utmost importance.

Hepatitis B and C prevalence and incidence in key population groups with multiple risk factors in the EU/EEA: a systematic review.

BackgroundPeople living with HIV (PLHIV) and people in prison are population groups with a potentially high risk and/or prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.AimWe conducted a systematic review in order to find prevalence and incidence estimates in these populations in the European Union/European Economic Area (EU/EEA).MethodsOriginal research articles published between January 2005 and February 2017 were retrieved from PubMed and Embase in February 2017.ResultsFifty-two articles were included, providing 97 estimates of HBV/HCV infection prevalence or incidence. Estimates of HBV infection prevalence ranged between 2.9% and43.4% in PLHIV and 0.0% and 25.2% in people in prison. Estimates of HCV infection prevalence ranged from 2.9% to 43.4% in PLHIV and 0.0% to 25.2% in people in prison. Incidence estimates ranged between 0.0 and 2.5 cases per 100 person-years for HBV infection in PLHIV. No such data was available for people in prison. HCV infection incidence ranged between 0.3 and 0.9 cases per 100 person-years in PLHIV and between 1 and 1.2 cases per 100 person-years in people in prison. Prevalence estimates were generally higher than in the general population, especially for HCV infection and among groups with multiple risk factors.ConclusionsPLHIV, people in prison and groups with multiple risk factors, have a high prevalence of HBV and HCV and may be at ongoing risk of infection. These groups should be among the populations prioritised and targeted for active case finding and prevention programmes in the EU/EEA.

Hepatitis B and C testing strategies in healthcare and community settings in the EU/EEA: A systematic review.

An estimated 9 million individuals are chronically infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) across the European Union/European Economic Area (EU/EEA), many of which are yet to be diagnosed. We performed a systematic review to identify interventions effective at improving testing offer and uptake in the EU/EEA. Original research articles published between 1 January 2008 and 1 September 2017 were retrieved from PubMed and EMBASE. Search strings combined terms for HBV/HCV, intervention, testing and geographic terms (EU/EEA). Out of 8331 records retrieved, 93 studies were selected. Included studies reported on testing initiatives in primary health care (9), hospital (12), other healthcare settings (31) and community settings (41). Testing initiatives targeted population groups such as migrants, drug users, prisoners, pregnant women and the general population. Testing targeted to populations at higher risk yielded high coverage rates in many settings. Implementation of novel testing approaches, including dried blood spot (DBS) testing, was associated with increased coverage in several settings including drug services, pharmacies and STI clinics. Community-based testing services were effective in reaching populations at higher risk for infection, vulnerable and hard-to-reach populations. In conclusion, our review identified several successful testing approaches implemented in healthcare and community settings, including testing approaches targeting groups at higher risk, community-based testing services and DBS testing. Combining a diverse set of testing opportunities within national testing strategies may lead to higher impact both in terms of testing coverage and in terms of reduction, on the undiagnosed fraction.

Oral fluid: Non-invasive alternative for parvovirus B19 diagnosis?

BACKGROUND: Infections with parvovirus B19 (B19V) have been associated with a wide range of disease manifestations of which erythema infectiosum (fifth disease) in children is most common. Clinical signs following infection of children with B19V can be similar to measles and rubella. Laboratory detection of B19V infections is based on detection of B19V-specific IgM antibodies by enzyme immunoassay (IgM-EIA) and/or B19V DNA by quantitative PCR (qPCR) on blood samples. The need for invasive sampling can be a barrier for public health diagnostics. OBJECTIVES: To evaluate the use of a dual target B19V-qPCR directed against the NS1 and VP2 of B19V on oral fluid samples as a non-invasive alternative for laboratory diagnosis of B19V infections in children below 12 years of age with exanthema. STUDY DESIGN: Oral fluid and serum samples were collected from 116 children with exanthema. All serum samples were tested by IgM-EIA/IgG-EIA, while all oral fluid and 56 serum samples were tested by B19V-qPCR. RESULTS: B19V-specific IgM antibodies were detected in 25 of 116 children in the study. B19V DNA was detected in oral fluid in 17 of the 25 children who were IgM positive, as well as two children who were IgM-equivocal or negative. The child with the equivocal IgM had a high quantity of B19V DNA in oral fluid (7 log IU/ml), compatible with an acute B19V infection. The IgM-negative child was IgG-positive and 4 log IU/ml B19V DNA was detected in the oral fluid sample, suggesting an acute infection and a falsely negative IgM. Sample size calculations indicated that oral fluid samples for qPCR should be collected from 2 to 3 children during outbreaks of exanthema to achieve similar sensitivity as IgM-EIA for one child (≥0.9) to confirm or exclude B19V. CONCLUSIONS: Results indicate that oral fluid samples are a suitable public health alternative for detection of B19V infections, potentially lowering the barriers for sampling.

Optimizing molecular surveillance of mumps genotype G viruses.

Mumps viruses continue to cause sporadic cases and outbreaks in countries with a high vaccination coverage for mumps. Molecular surveillance of mumps viruses can be supportive to elucidate the origin and transmission routes of mumps virus in case of an outbreak. Currently, molecular surveillance is worldwide primarily focused on sequencing of the small hydrophobic (SH) gene. However, few studies have already shown that additional genes or regions contribute to the resolution of the sequence data in such a way that mumps cases that seem to be linked to the same source on basis of the SH sequence, appear to be linked to another source or chain of transmission. Notably, this sequence information was recently extracted from the hemagglutinin-neuraminidase (HN) and fusion (F) genes (total 3364 nucleotides), or from the sum of the three non-coding regions (NCRs; total 1954 nt) between the nucleocapsid protein, phosphoprotein, matrix protein and F protein, but also from the complete genome. Here, sequence data from NCRs were compared with that of the HN and F gene, using mumps genotype G viruses detected in the Netherlands between 2010 and 2018. Results of this study indicate that NCRs sequence data provided similar or slightly better sequence resolution compared to the HN and F genes for most viruses. For molecular surveillance of currently circulating mumps genotype G viruses is sequencing of SH in combination with NCRs currently a useful approach.

Cost-effectiveness of screening for chronic hepatitis B and C among migrant populations in a low endemic country.

BACKGROUND: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective. METHODS: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed. RESULTS: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections. CONCLUSIONS: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants.