The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus–virus ...interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract
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.
Our study provides a comprehensive evaluation of in whom, and when, seasonal coronavirus infections occur. We compare infection patterns across coronavirus types, evaluate evidence of interactions with other respiratory viruses, and discuss implications for newly emerged coronavirus disease 2019.
The early diagnosis of active hepatitis C virus (HCV) infection remains a significant barrier to the treatment of the disease and to preventing the associated significant morbidity and mortality ...seen, worldwide. Current testing is delayed due to the high cost, long turnaround times and high expertise needed in centralised diagnostic laboratories. Here we demonstrate a user-friendly, low-cost pan-genotypic assay, based upon reverse transcriptase loop mediated isothermal amplification (RT-LAMP). We developed a prototype device for point-of-care use, comprising a LAMP amplification chamber and lateral flow nucleic acid detection strips, giving a visually-read, user-friendly result in <40 min. The developed assay fulfils the current guidelines recommended by World Health Organisation and is manufactured at minimal cost using simple, portable equipment. Further development of the diagnostic test will facilitate linkage between disease diagnosis and treatment, greatly improving patient care pathways and reducing loss to follow-up, so assisting in the global elimination strategy.
•Rapid simultaneous PCR diagnosis of viral gastroenteritis is advantageous.•Many difficulties encountered when attempting to multiplex the assays.•Development of a single multiplex assay for the ...detection of viral gastroenteritis from stool samples.•The multiplex developed is sensitive, specific, robust and reproducible.
Viral gastroenteritis is a major health problem with significant morbidity and economic consequences. Viral gastroenteritis is caused by a number of viruses, including norovirus, rotavirus, adenovirus, astrovirus, and sapovirus. Conventional diagnosis is based on direct antigen detection and electron microscopy, however enzyme immunoassay’s are insensitive and not available for all relevant pathogens, and electron microscope (EM) is no longer routinely carried out in most laboratories. Most laboratories now offer norovirus real-time PCR testing however the availability of other assays is variable. Commercial methods for the detection of inflectional intestinal disease (IID) are available but these can be expensive and are not commonly used. This paper describes the development of a single multiplex assay for the simultaneous detection of adenovirus, astrovirus, rotavirus and sapovirus from stool samples. The multiplex was evaluated by assessing endpoint sensitivity, specificity, panel of clinical samples, quality control (QC) panel and the robustness and reproducibility of the multiplex.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such ...pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Respiratory illness can cause significant morbidity.•Gargle samples are easy to take and sample the same area as a throat swab.•Assessed utility of gargles for the molecular detection of respiratory ...infections.•Data suggests that gargle samples are a more sensitive sample type than THS.•Recommend other testing sites consider gargle samples for respiratory diagnosis.
Respiratory illness causes significant morbidity especially in children, the elderly and the immunocompromised. The sample type taken and the quality of that sample are of great significance in providing an accurate diagnosis. Gargle samples are easy to take and sample the same area as a throat swab (THS). In this study, we assessed the utility of gargle samples for the molecular detection of common respiratory infections. Paired gargle and THS samples collected on the same day from the same patient were compared. We also included in our analysis paired THS and gargle samples that were collected within three days of each other as these samples are likely to have been taken during the same illness. Overall the data suggests that gargle samples are a more sensitive sample type than THS samples as overall the diagnostic yield was higher in the gargle samples and the Ct value of the gargle samples was stronger for the majority of samples in comparison to THS samples. Similar data was seen in the paired samples collected within one to three days of each other, as although the diagnostic yield between the sample types was similar (similar discrepant results), the majority of gargles had stronger Ct values than THS samples. This paper highlights the usefulness of gargle samples as non-invasive sensitive respiratory sample in comparison to THS samples. We recommend that other testing sites should consider using gargle samples for respiratory diagnosis as it will bring benefits in terms of sensitivity and sampling ease of use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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
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.
Molecular ciprofloxacin resistance testing (
GC assay (SpeeDx)) was undertaken as an additional test after initial diagnosis (
2000 Realti
e 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.
A total of 998 clinical samples tested positive for
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,
.
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.
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.
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.
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.
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.
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.
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.
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•HCV reinfection rates increased in the early phase of treatment scale-up with direct-acting antivirals among PWID in Scotland.•Community-based treatment pathways are reaching groups at high risk of reinfection, regarded vital for elimination.•Low levels of retesting for HCV were observed beyond the first year following successful treatment.•Considerable numbers of HCV reinfections may have gone undetected in the early phase of treatment scale-up.•Concerted effort to ensure prompt diagnosis of reinfection needs to be integral to national strategies for PWID.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Dried blood spots (DBS) can be used for blood-borne virus testing.•DBS testing was compared on both the Abbott Architect and the Abbott Alinity i.•Good correlation between Abbott Architect and ...Abbott Alinity i for DBS samples.•Manufacturer’s cut-off set for plasma can be used for HIV and HBsAg.•Alteration in manufacturer’s cut-off suggested for HCV antibody and HBV core IgG.
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.
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.
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.
The alinity i compared well against the architect and can be used to test DBS samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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