Impact of molecular ciprofloxacin resistance testing in management of gonorrhoea in a large urban clinic.

OBJECTIVES: Antibiotic resistance in gonorrhoea is of significant public health concern with the emergence of resistance to last-line therapies such as ceftriaxone. Despite around half of Neisseria gonorrhoeae isolates tested in the UK being susceptible to ciprofloxacin, very little ciprofloxacin is used in clinical practice. Testing for the S91F mutation associated with ciprofloxacin resistance is now available in CE-marked assays and may reduce the requirement for ceftriaxone, but many patients are treated empirically, or as sexual contacts, which may limit any benefit. We describe the real-world impact of such testing on antimicrobial use and clinical outcomes in people found to have gonorrhoea in a large urban UK sexual health clinic. METHODS: Molecular ciprofloxacin resistance testing (ResistancePlus GC assay (SpeeDx)) was undertaken as an additional test after initial diagnosis (m2000 Realtime CT/NG assay (Abbott Molecular)) in those not already known to have had antimicrobial treatment. Data from a 6-month period (from March to September 2022) were analysed to determine treatment choice and treatment outcome. RESULTS: A total of 998 clinical samples tested positive for N. gonorrhoeae in 682 episodes of infection. Of the 560 (56%) samples eligible for resistance testing, 269 (48.0%) were reported as wild-type, 180 (32.1%) were predicted to be resistant, 63 (11.3%) had an indeterminate resistance profile, and in 48 (8.6%) samples, N. gonorrhoeae was not detected. Ciprofloxacin was prescribed in 172 (75%) of 228 episodes in which the wild-type strain was detected. Four (2%) of those treated with ciprofloxacin had a positive test-of-cure sample by NAAT, with no reinfection risk. All four had ciprofloxacin-susceptible infection by phenotypic antimicrobial susceptibility testing. CONCLUSIONS: In routine practice in a large UK clinic, molecular ciprofloxacin resistance testing led to a significant shift in antibiotic use, reducing use of ceftriaxone. Testing can be targeted to reduce unnecessary additional testing. Longer term impact on antimicrobial resistance requires ongoing surveillance.

Impact of the COVID-19 Pandemic on HIV Test Uptake Among People Who Inject Drugs in the Context of an HIV Outbreak.

Glasgow, Scotland's largest city, has been experiencing an HIV outbreak among people who inject drugs (PWID) since 2015. A key focus of the public health response has been to increase HIV testing among those at risk of infection. Our aim was to assess the impact of COVID-19 on HIV testing among PWID in Glasgow. HIV test uptake in the last 12 months was quantified among: (1) PWID recruited in six Needle Exchange Surveillance Initiative (NESI) surveys (n = 6110); linked laboratory data for (2) people prescribed opioid agonist therapy (OAT) (n = 14,527) and (3) people hospitalised for an injecting-related hospital admission (IRHA) (n = 12,621) across four time periods: pre-outbreak (2010-2014); early-outbreak (2015-2016); ongoing-outbreak (2017-2019); and COVID-19 (2020-June 21). From the pre to ongoing period, HIV testing increased: the highest among people recruited in NESI (from 28% to 56%) and on OAT (from 17% to 54%) while the lowest was among people with an IRHA (from 15% to 42%). From the ongoing to the COVID-19 period, HIV testing decreased markedly among people prescribed OAT, from 54% to 37% (aOR 0.50, 95% CI 0.48-0.53), but increased marginally among people with an IRHA from 42% to 47% (aOR 1.19, 95% CI 1.08-1.31). In conclusion, progress in increasing testing in response to the HIV outbreak has been eroded by COVID-19. Adoption of a linked data approach could be warranted in other settings to inform efforts to eliminate HIV transmission.

SARS-CoV-2 Evolution and Patient Immunological History Shape the Breadth and Potency of Antibody-Mediated Immunity.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralization responses against SARS-CoV-2Wuhan, SARS-CoV-2α, SARS-CoV-2δ, and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2α, or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.

Neutralizing antibodies provide protection against viruses and are generated because of vaccination or prior infections. The main target of anti-SARS-CoV-2 neutralizing antibodies is a protein called spike, which decorates the viral particle and mediates viral entry into cells. As SARS-CoV-2 evolves, mutations accumulate in the spike protein, allowing the virus to escape antibody-mediated immunity and decreasing vaccine effectiveness. Multiple SARS-CoV-2 variants have appeared since the start of the COVID-19 pandemic, causing various waves of infection through the population and infecting­in some cases­people that had been previously infected or vaccinated. Because the antibody response is highly specific, individuals infected with different variants are likely to have different repertoires of neutralizing antibodies. We studied the breadth and potency of the antibody-mediated response against different SARS-CoV-2 variants using sera from vaccinated people as well as from people infected with different variants. We show that potency of the antibody response against different SARS-CoV-2 variants depends on the particular variant that infected each person, the exposure type (infection or vaccination) and the number and order of exposures. Our study provides insight into the interplay between virus evolution and immunity, as well as important information for the development of better vaccination strategies.

Genomic epidemiology of SARS-CoV-2 in a university outbreak setting and implications for public health planning.

Whole genome sequencing of SARS-CoV-2 has occurred at an unprecedented scale, and can be exploited for characterising outbreak risks at the fine-scale needed to inform control strategies. One setting at continued risk of COVID-19 outbreaks are higher education institutions, associated with student movements at the start of term, close living conditions within residential halls, and high social contact rates. Here we analysed SARS-CoV-2 whole genome sequences in combination with epidemiological data to investigate a large cluster of student cases associated with University of Glasgow accommodation in autumn 2020, Scotland. We identified 519 student cases of SARS-CoV-2 infection associated with this large cluster through contact tracing data, with 30% sequencing coverage for further analysis. We estimated at least 11 independent introductions of SARS-CoV-2 into the student population, with four comprising the majority of detected cases and consistent with separate outbreaks. These four outbreaks were curtailed within a week following implementation of control measures. The impact of student infections on the local community was short-term despite an underlying increase in community infections. Our study highlights the need for context-specific information in the formation of public health policy for higher educational settings.

Examining the impact of the first wave of COVID-19 and associated control measures on interventions to prevent blood-borne viruses among people who inject drugs in Scotland: an interrupted time series study.

BACKGROUND: COVID-19 has likely affected the delivery of interventions to prevent blood-borne viruses (BBVs) among people who inject drugs (PWID). We examined the impact of the first wave of COVID-19 in Scotland on: 1) needle and syringe provision (NSP), 2) opioid agonist therapy (OAT) and 3) BBV testing. METHODS: An interrupted time series study design; 23rd March 2020 (date of the first 'lockdown') was chosen as the key date. RESULTS: The number of HIV tests and HCV tests in drug services/prisons, and the number of needles/syringes (N/S) distributed decreased by 94% (RR=0.062, 95% CI 0.041-0.094, p < 0.001), 95% (RR=0.049, 95% CI 0.034-0.069, p < 0.001) and 18% (RR = 0.816, 95% CI 0.750-0.887, p < 0.001), respectively, immediately after lockdown. Post-lockdown, an increasing trend was observed relating to the number of N/S distributed (0.6%; RR = 1.006, 95% CI 1.001-1.012, p = 0.015), HIV tests (12.1%; RR = 1.121, 95% CI 1.092-1.152, p < 0.001) and HCV tests (13.2%; RR = 1.132, 95 CI 1.106-1.158, p < 0.001). Trends relating to the total amount of methadone prescribed remained stable, but a decreasing trend in the number of prescriptions (2.4%; RR = 0.976, 95% CI 0.959-0.993, p = 0.006) and an increasing trend in the quantity prescribed per prescription (2.8%; RR = 1.028, 95% CI 1.013-1.042, p < 0.001) was observed post-lockdown. CONCLUSIONS: COVID-19 impacted the delivery of BBV prevention services for PWID in Scotland. While there is evidence of service recovery; further effort is likely required to return some intervention coverage to pre-pandemic levels in the context of subsequent waves of COVID-19.

Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs.

BACKGROUND & AIMS: Scale-up of highly effective direct-acting antivirals (DAAs) for HCV among people who inject drugs (PWID) in Scotland has led to a reduction in the prevalence of viraemia in this population. However, the extent of reinfection among those treated with DAAs remains uncertain. We estimated HCV reinfection rates among PWID in Scotland by treatment setting, pre- and post-introduction of DAAs, and the potential number of undiagnosed reinfections resulting from incomplete follow-up testing. METHODS: Through linkage of national clinical and laboratory HCV data, a retrospective cohort of PWID who commenced treatment between 2000-2018 and achieved a sustained virological response (SVR) were followed up for reinfection to December 2019. Reinfection was defined as a positive HCV antigen or RNA test. RESULTS: Of 5,686 SVRs among 5,592 PWID, 4,126 (73%) had an HCV RNA or antigen test post-SVR. Of those retested, we identified 361 reinfections (3.9/100 person-years [PY]). The reinfection rate increased from 1.5/100 PY among PWID treated in 2000-2009 to 8.8/100 PY in 2017-2018. The highest reinfection rates were observed among those treated in prison (14.3/100 PY) and community settings (9.5/100 PY). Among those treated in the DAA era (2015-2018), 68% were tested within the first year post-SVR but only 30% in the second year; while 169 reinfections were diagnosed in follow-up, an estimated 200 reinfections (54% of the estimated total) had gone undetected. CONCLUSIONS: HCV reinfection rates among PWID in Scotland have risen alongside the scale-up of DAAs and broadened access to treatment for those at highest risk, through delivery in community drug services. Promotion of HCV testing post-SVR among PWID is essential to ensure those reinfected are identified and retreated promptly. LAY SUMMARY: Increased rates of hepatitis C reinfection in Scotland were observed following the rapid scale-up of highly effective direct-acting antiviral (DAA) treatments among people who inject drugs. This demonstrates that community-based treatment pathways are reaching high-risk groups, regarded vital in efforts to eliminate the virus. However, we estimate that less than half of reinfections have been detected in the DAA era because of inadequate levels of retesting beyond the first year following successful treatment. Sustained efforts that involve high coverage of harm reduction measures and high uptake of annual testing are required to ensure prompt diagnosis and treatment of those reinfected if the goals of elimination are to be met.

The uptake of foil from needle and syringe provision services and its role in smoking or snorting heroin among people who inject drugs in Scotland.

BACKGROUND: In the UK, legislation was implemented in 2014 allowing needle and syringe provision (NSP) services to offer foil to people who inject drugs (PWID) to encourage smoking rather than injecting. This paper aims to examine the association between foil uptake and smoking or snorting heroin among PWID. This is the first large scale national study to examine foil uptake and smoking or snorting heroin among PWID post legislative change. METHOD: Data from 1453 PWID interviewed via Scotland's Needle Exchange Surveillance Initiative in 2017-2018 were analysed using multivariate logistic regression. RESULTS: Overall, 36% of PWID had obtained foil from NSP services in the past six months. The odds of smoking or snorting heroin were higher among those who had obtained foil (Adjusted Odds Ratio (AOR) 3.79 (95% CI 2.98-4.82) p<0.001) compared to those who had not. Smoking or snorting heroin was associated with lower odds of injecting four or more times daily (AOR 0.60 (95% CI 0.40-0.90) p = 0.012) and injecting into the groin or neck (AOR 0.57 (95% CI 0.46-0.71) p<0.001) but increased odds of having had a skin and soft tissue infection (SSTI) (AOR 1.49 (95% CI 1.17-1.89) p = 0.001) and having experienced an overdose (AOR 1.58 (95% CI 1.18-2.10) p = 0.002) both in the past year. CONCLUSION: The promotion of smoking drugs via foil provision from NSP services may contribute to the package of harm reduction measures for PWID alongside the provision of injecting equipment. We found that those in receipt of foil were more likely to smoke or snort heroin, and that smoking or snorting heroin was associated with a lower likelihood of some risky injecting behaviours, namely frequent injecting and injecting into the groin or neck. But it remains uncertain if the provision of foil can lead to a reduction in health harms, such as SSTI and overdose. Future research is needed to understand PWID motivations for smoking drugs, obtaining foil from NSP services, and its uses particularly among polydrug users.

Evaluation of the scale-up of HIV testing among people who inject drugs in Scotland in the context of an ongoing HIV outbreak.

BACKGROUND: A large outbreak of HIV among people who inject drugs (PWID) has been ongoing in Glasgow city centre (GCC), Scotland since early 2015. The outbreak is associated with high levels of homelessness, cocaine injecting and injecting in public places. A key component of the public health response was the scale-up of HIV testing in a range of services engaged with PWID. Our aims were to: 1) evaluate the extent of and change in HIV testing over the course of the outbreak and 2) examine factors associated with reporting an HIV test. METHODS: Self-report of an HIV test in the last 12 months was collected for 15,081 PWID interviewed in six national cross-sectional bio-behavioural surveys during 2008-2018. Multi-variate logistic regression was undertaken to determine trends in HIV testing by region of recruitment (GCC; rest of Glasgow; other Scottish city centres (SCC); and rest of Scotland) and outbreak period (pre: 2008-14; early: 2015-16; ongoing: 2017-18). RESULTS: HIV testing increased across all regions and was most pronounced in GCC comparing the ongoing (67%) to the pre-outbreak period (33%) (aOR=4.68, 95% CI 3.23 to 6.77, p<0.001). However, compared to other SCCs pre-outbreak (with 46% reporting testing), those recruited in GCC had a lower odds of HIV testing early outbreak (aOR=0.37, 95% CI 0.27 to 0.54, p<0.001) and more modest increased odds in the ongoing outbreak period (aOR=1.41, 95% CI 0.97 to 2.05, p=0.069). Among PWID recruited in the whole of Glasgow in the ongoing phase, reporting an HIV test was associated with injecting cocaine or in public places (aOR=2.20, 95% CI 1.53 to 3.17, p<0.001), receipt of methadone (aOR=1.48, 95% CI 1.01 to 2.17, p=0.042) and incarceration in the last year (aOR=1.72, 95% CI 1.18 to 2.51, p=0.004). CONCLUSIONS: Relatively low levels of HIV testing pre- and early-outbreak likely hindered efforts to control the spread of infection among PWID in Glasgow. Uptake has since increased with expansion of testing across multiple settings, particularly among those at high risk of infection. Further effort is needed to ensure the vast majority of PWID are regularly tested, not just in the epicentre of the outbreak but in other areas with low population prevalence of infection.

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services: real-world data.

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). DESIGN, SETTING AND PARTICIPANTS: Natural experiment, evaluated using data from national biennial surveys of PWID and national clinical data. Services providing injecting equipment (2010-18) and HCV treatment clinics (2017-18) across Scotland. A total of 12 492 PWID who completed a questionnaire and provided a blood spot (tested for HCV-antibodies and RNA); 4105 individuals who initiated HCV treatment. INTERVENTION AND COMPARATOR, MEASUREMENTS: The intervention was rapid DAA scale-up among PWID, which occurred in Tayside. The comparator was GGC/RoS. Trends in HCV viraemia and uptake of HCV therapy over time; sustained viral response (SVR) rates to therapy by region and treatment setting. FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population.

Severe Acute Respiratory Syndrome Coronavirus 2 Serosurveillance in a Patient Population Reveals Differences in Virus Exposure and Antibody-Mediated Immunity According to Host Demography and Healthcare Setting.

Identifying drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient serum samples showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralization assays showed that highly neutralizing antibodies developed in about half of individuals who tested positive with enzyme-linked immunosorbent assay, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, male patients, and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralization activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves.

High willingness to use drug consumption rooms among people who inject drugs in Scotland: findings from a national bio-behavioural survey among people who inject drugs.

BACKGROUND: To address rising drug-related harms (including significant transmission of HIV) among people who inject drugs (PWID) in Glasgow, officials have proposed the introduction of the UK's first drug consumption room (DCR) in Glasgow city centre. Using a nationally representative sample, this study aimed to determine willingness to use a DCR among PWID nationally, in Glasgow city centre (the proposed DCR location), other Scottish city centres (excluding Glasgow) and the rest of Scotland (excluding city centres). METHODS: Bio-behavioural survey, of 1469 current PWID (injected in last 6 months) across Scotland during 2017-18. Willingness to use DCRs was examined by drug-related risk behaviours and harms overall in Scotland, and then stratified by Glasgow city centre (n = 219), other Scottish city centres (n = 226) and the rest of Scotland (n = 1024). RESULTS: The majority of PWID overall in Scotland (75%) were willing to use a DCR; willingness was higher among those recruited in Glasgow city centre (83%) and other Scottish city centres (83%), compared to the rest of Scotland (72%) (p < 0.001). Willingness was greater among PWID who reported (compared to those who did not report) injecting heroin (76%, p = 0.002), cocaine injecting (79%, p = 0.014), homelessness (86%, p < 0.001), public injecting (87%, p < 0.001) and an overdose (80%, p = 0.026). Willingness was found to be associated with a cumulative multiple risk variable: increased from 66% among those with a score of zero to 85% with a score of at least three (p < 0.001). CONCLUSIONS: The vast majority of PWID at greatest risk of drug-related harm in Glasgow and elsewhere in Scotland would be willing to use a DCR, supporting proposals for the introduction of DCRs nationally.

Performance characteristics of the SpeeDx PlexPCR VHS assay for the molecular detection of herpes simplex virus, varicella zoster virus, and Treponema pallidum in lesion swabs.

This study compares the performance of a commercial polymerase chain reaction (PCR) assay for detection of herpes simplex virus (HSV) 1 and 2, varicella zoster virus (VZV), and Treponema pallidum with laboratory-developed assays. A panel of 250 samples, previously tested using in-house assays, was tested on the PlexPCR® VHS assay. The panel consisted of 202 positive specimens [HSV-1 (n=51); HSV-2 (n=51); VZV (n=51); T. pallidum (n=49)] and 48 negative specimens. Genital samples had been previously tested for HSV-1/2 and T. pallidum and nongenital or unspecified samples for HSV-1/2 and VZV. The overall agreement between the PlexPCR® VHS and in-house assays was 97%. Negative agreement was ≥99%, and positive agreement for individual targets was 96% (47/49) for T. pallidum, 98% for HSV-1 and HSV-2 (50/51), and 100% (51/51) for VZV. Adoption of this assay would allow greater availability of molecular syphilis detection and enhance the diagnostic yield of samples collected from cutaneous/mucocutaneous lesions.

Evaluation of dried blood spot testing using the Abbott Alinity i.

BACKGROUND: The West of Scotland Specialist Virology Centre currently uses the Abbott Architect for DBS serology. The new Abbott Alinity i will replace the Architect in our laboratory. In this study, mock and stored patient DBS samples were tested on both platforms and results compared. STUDY DESIGN: Mock DBS were made from whole blood where patient results were known (38 negative samples and 141 positive samples; 39 HIV Antigen/Antibody (Ag/Ab), 35 HCV IgG antibody (HCVG), 34 HBV core IgG (HBCG) and 33 HBsAg). Mock DBS were tested on both Abbott platforms. Stored patient DBS samples (132 negative and 263 positive: 9 HIVAg/Ab, 10 HBsAg, 52 HBCG and 60 HCVG) previously tested on the Architect were retested on the Alinity i. RESULTS: Mock DBS showed good correlation between the Architect and Alinity i for the HIV Ag/Ab,HBCG and HCVG assays. A poorer correlation occurred with HBsAg, the Alinity i reported HBsAg positives at a lower value compared to the Architect. The coefficient of variation for intra-assay variation was 1.69 % (HIVAg/Ab), 3.25 % (HCVG), 1.68 % (HBsAg) and 1.95 % (HBCG). The sensitivity and specificity was determined based on results from the mock and patient samples. At S/Co cut-off 1.0 both HIV and HBsAg had a sensitivity of 100 %. A cut-off 0.8 gave a sensitivity of 95.83 % (95 % CI 89.67%-98.85%) for HCVG and 0.3 gave a sensitivity of 98.8 % (CI 93.69%-99.97%) for HBCG. DISCUSSION: The alinity i compared well against the architect and can be used to test DBS samples.

Investigating utilising the Alinity m platform to detect hepatitis C virus RNA in dried blood spot samples.

BACKGROUND: Elimination of Hepatitis C virus (HCV) relies on increasing HCV diagnostic rates in hard to reach populations. Dried blood spot (DBS) samples are a convenient sample type for HCV testing, as they can be collected in non-traditional settings such as drug services and prison settings, increasing access to HCV testing. OBJECTIVES: Herein we investigate an off-label DBS protocol for use on the Abbott Alinity m platform. STUDY DESIGN: A dilution series of HCV RNA positive blood was used to determine the analytical sensitivity of the test. We assess the sensitivity and specificity of HCV RNA detection in 50 mock DBS specimens compared to associated plasma viral load, and re-test 66 clinical DBS, previously tested on the m2000 to determine the clinical sensitivity and specificity of the assay. RESULTS: The dilution panel suggested that the Alinity m DBS assay is one log more sensitive than our current DBS HCV RNA assay. Mock DBS demonstrated 100% specificity, and 100% sensitivity for samples with plasma HCV RNA viral loads > 2.7 log10 IU/mL, however four samples with viral loads between 1.3 and 2.4 log10 IU/mL were not detected. The clinical sensitivity and specificity of previously tested DBS was 94% and 100% respectively, with two samples reported as low level RNA positive on the m2000 testing negative on Alinty m. CONCLUSIONS: The data suggests that DBS can be used as an off-label specimen type on the Alinity m HCV assay. Allowing continuous, random access testing of DBS simultaneously alongside other Alintiy m assays, potentially improving test turn-around times.

Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019.

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study.

OBJECTIVE: Population-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis of population-based data from Scotland. DESIGN: Through analysis of national surveillance data (involving linkage of HCV diagnosis and clinical databases to hospital and deaths registers), we determined i) the scale-up in the number of patients treated and achieving a sustained viral response (SVR), and ii) the change in the trend of new presentations with HCV-related DC, with the introduction of DAAs. RESULTS: Approximately 11 000 patients had been treated in Scotland over the 8-year period 2010/11 to 2017/18. The scale-up in the number of patients achieving SVR between the pre-DAA and DAA eras was 2.3-fold overall and 5.9-fold among those with compensated cirrhosis (the group at immediate risk of developing DC). In the pre-DAA era, the annual number of HCV-related DC presentations increased 4.6-fold between 2000 (30) and 2014 (142). In the DAA era, presentations decreased by 51% to 69 in 2018 (and by 67% among those with chronic infection at presentation), representing a significant change in trend (rate ratio 0.88, 95% CI 0.85 to 0.90). With the introduction of DAAs, an estimated 330 DC cases had been averted during 2015-18. CONCLUSIONS: National scale-up in interferon-free DAA treatment is associated with the rapid downturn in presentations of HCV-related DC at the population-level. Major progress in averting HCV-related DC in the short-term is feasible, and thus other countries should strive to achieve the same.