Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool

New and emerging infections with blood-borne pathogens pose an ongoing threat to the safety of blood transfusions and transplants. Bioarchives of stored blood donor samples represent a valuable pathogen screening resource for both ensuring safety of blood transfusions and for wider public health infectious disease surveillance. Large scale testing of donors enables early detection of pathogen spread and extent of population exposure. We have implemented two complementary systems for the bioarchiving of blood donor samples in England for these purposes. The CODONET bioarchive collects samples from geographically targeted regions of potential pathogen emergence. Consenting donors provide detailed information to allow for risk assessment and, importantly, to distinguish imported from autochthonously acquired infection. Separately, the blood donor surveillance archive (BDSA) stores 100 or 200 pools of 24 randomly selected, fully anonymised donation samples from donors in England every 2 weeks, allowing large-scale continuous sampling. This enables rapid evaluation of the presence of blood-borne pathogens in donor populations and a large-scale epidemiological tool to detect pathogen emergence in real-time. Combined, these bioarchives allow for proactive assessment of donation transmission risk, and as targeted population-wide archives, contribute to public health surveillance of emerging pathogens and pandemic spread.

Thanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis, health outcomes have improved. This paper evaluates the health system costs and the health-related quality of life implications of these guidelines. A sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015. Data for patients aged ≥16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months. Patient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS) and the EuroQoL; healthcare costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life Years (QALYs) were calculated from the EQ-5D utility scores. Cost-utility analysis was performed using the NHS and Social Care perspective. A total of 49 patients were included; 35 were treated within 48 hours, 'early' (median (IQR) 8.25 [3.7-20.5]) and 14 were treated after 48 hours 'delayed' (median (IQR) 93.9 [66.7-100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0-3) compared with 4 (29%) in the delayed group. According to GOS, 10 (29%) had a good recovery in the early treatment group, but only 1 (7%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p<0.000). After adjusting for age and symptom duration at admission, early treatment incurred a lower average cost at discharge, £23,086 (95% CI: £15,186 to £30,987) vs £42,405 (95% CI: £25,457 to £59,354) [p<0.04]. A -£20,218 (95% CI: -£52,173 to £11,783) cost difference was observed at the 12- month follow-up post discharge. This study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment.

Scrub typhus and other doxycycline-treatable infections are significant contributors of acute encephalitis syndrome (AES) in India. Limited surveillance in South India has hindered their recognition and the inclusion of doxycycline in treatment protocols. We aimed to systematically investigate infectious aetiologies of AES in children from Karnataka, India, and develop clinical prediction models for diagnosing scrub typhus and guiding clinical decisions for doxycycline therapy. This multicentre, prospective study enrolled children aged >28 days to 18 years with AES presenting to three tertiary care hospitals in Bengaluru, India. Primary outcomes were microbiological diagnosis of AES and clinical prediction models for diagnosing scrub typhus and identifying patients with doxycycline-treatable causes. Models were developed using multivariable logistic regression, internally validated, and simplified into point-scoring systems. Model performance was evaluated using c-statistics, calibration slopes, and calibration-in-the-large, adhering to TRIPOD guidelines. Between February 2020 and February 2023, 714 children were screened, of whom 587 were included. Of these, 315 (54%) had a microbiological diagnosis. Scrub typhus accounted for 138/315 (44%), and doxycycline-treatable causes were diagnosed in 193/315 (61%) of these cases. Key predictors associated with both scrub typhus and doxycycline-treatable causes were age, illness duration, lymphadenopathy, oedema, hepatomegaly, lymphocyte count, platelet count, and serum albumin levels. Adjusted c-statistics were 0.83 (95% CI: 0.78-0.87) for the scrub typhus model and 0.75 (95% CI: 0.7-0.81) for the doxycycline model, with calibration slopes of 0.85 (0.82-0.88) and 0.83 (0.78-0.87), respectively. CITL values were -0.03 (-0.06-0) and 0.05 (0.02-0.09). Points-based scores predicted probabilities ranging from 5% to 99.8% (scrub typhus model) and 20%-99% (doxycycline-treatable model). Scrub typhus was the most common microbiological diagnosis, and most patients had a doxycycline-treatable cause, underscoring the need to prioritise doxycycline in empirical treatment protocols in South India. The models demonstrated strong performance; however external validation is necessary for broader applicability. DBT/Wellcome Trust India Alliance FellowshipIA/CPHE/18/1/503960.

Norovirus is one of the most important etiological agents of gastroenteritis (GE) and food-borne diarrhea in all age groups worldwide. Here we report five draft genomes of norovirus isolated from stool samples collected from under-five children presenting with GE in Malawi from 2012 to 2024.

Scientific meetings and conferences are crucial in knowledge dissemination, fostering collaborations, professional development and inspiring innovative research. However, their traditional structure and organization have remained largely unchanged, perpetuating barriers that continue to exclude scientists from historically marginalized backgrounds. In response, the Microbiology Society has begun its journey to address these longstanding challenges, redesigning its meetings to create a more inclusive culture and a welcoming environment for all participants.

ObjectivesTo evaluate the effectiveness of localised Tier 3 restrictions, implemented in England in December 2020, on reducing COVID-19 hospitalisations compared with less stringent Tier 2 measures and the variations by neighbourhood deprivation and the prevalence of Alpha (B.1.1.7) variant, the primary variant of concern then, to measure hospital services’ burden and inequalities across different communities.DesignObservational study using a synthetic control method, comparing weekly hospitalisation rates in Tier 3 areas to a synthetic control from Tier 2 areas.SettingEngland between 4 October 2020 and 21 February 2021.Participants23 million people under Tier 3 restrictions, compared with a synthetic control group derived from 29 million people under Tier 2 restrictions.InterventionsTier 3 restrictions in designated areas were implemented from 7 December 2020, imposing stricter limits on gatherings and hospitality than Tier 2, followed by a national lockdown on 6 January 2021.Primary and secondary outcome measuresWeekly COVID-19-related hospitalisations for neighbourhoods in England over 11 weeks following the interventions.ResultsImplementing Tier 3 restrictions were associated with a 17% average reduction in hospitalisations compared with Tier 2 areas (95% CI 13% to 21%; 8158 (6286 to 9981) in total). The effects were similar across different levels of neighbourhood deprivation and prevalence of the Alpha variant.ConclusionsRegionally targeted Tier 3 restrictions in England had a moderate but significant effect on reducing hospitalisations. The impact did not exacerbate socioeconomic inequalities during the pandemic. Our findings suggest that regionally targeted restrictions can be effective in managing infectious diseases.

Abstract Rotavirus is the leading cause of severe diarrhea among children under five worldwide, especially in low- and middle-income countries (LMICs). Although vaccination is the best strategy for preventing rotavirus infection, obstacles leading to poor vaccine effectiveness undermine its impact in LMICs. This study aimed to evaluate the impact and cost-effectiveness of the current two-dose Rotarix vaccine schedule in Malawi compared to two alternative vaccine delivery schedules and a next-generation neonatal vaccine (RV3-BB) from 2025-2034. The cost-effectiveness of rotavirus vaccine strategies in Malawi was evaluated from both the government and societal perspectives using estimates of moderate-to-severe and non-severe rotavirus cases derived from a mathematical model of rotavirus transmission dynamics and published estimates of health-seeking behaviors and costs as inputs. A probabilistic sensitivity analysis was performed to evaluate the robustness of our results to parameter uncertainty. Over a ten-year time horizon, the current two-dose strategy was predicted to avert over 1.5 million cases and 90,000 disability-adjusted life-years (DALYs) and cost $104.87 per DALY averted compared to no vaccination from the government perspective. Adding a third dose at 14 weeks could avert about 1 million more cases and cost $5 million more than the current strategy. The neonatal RV3-BB vaccine could avert 1.1 million cases and 41,000 DALYs due to rotavirus and save about $3.7 million compared to the current strategy. The current rotavirus vaccine program in Malawi is cost-effective and saves lives compared to no vaccination. However, adding a third dose is likely to be cost-effective at a willingness to pay (WTP) of $138.38 per DALY averted, while switching to the neonatal RV3-BB vaccine when available is likely to be cost-effective at a WTP above $45.89 per DALY averted.

Abstract Background Gastrointestinal (GI) infections exert a significant public health burden on healthcare services in the United Kingdom (UK). The literature suggests an association between ethnicity and health; however, we do not know the extent of inequalities in GI infection/disease in the UK. This systematic review aimed to identify studies that ascertain differences in the incidence or prevalence of GI infections between UK ethnic groups and explore possible explanations for heterogeneity observed within the literature. Methods MEDLINE, CINAHL Plus, Web of Science (Science Social Science Citation Index), and grey literature were searched from 1980 to 21st June 2023 for studies reporting an association between ethnicity and GI infections in UK population samples. Two reviewers independently screened the studies and conducted quality appraisals; data extraction was undertaken by one reviewer and verified by another reviewer. A narrative synthesis was undertaken and a harvest plot supported the textual synthesis to investigate potential sources of heterogeneity in effect estimates by GI pathogen and ethnic group. Results The searches identified 10028 studies, of which 16 met the inclusion criteria. 15 out of 47 effect estimates from a total of 16 studies found that GI infection risk was greater in Black and Ethnic Minority Groups, mainly of Asian ethnicity, compared to the majority White population. 13 studies reported a higher risk in ethnic minorities of Asian ethnicity, while one study described a higher risk in the Non-White ethnic group. One single study on STEC reported a higher risk of GI infection in the White population compared to the Non-White population, while another single study on norovirus found no significant difference by ethnic group. Conclusions This systematic review demonstrates that ethnic minority groups in the UK have a higher risk of GI infections than the general or White population. Key messages • There is a clear need to elucidate further the high incidence of GI infections in UK Indian, Pakistani, and Bangladeshi communities. • Tackling ethnic inequalities requires a concerted approach and translating evidence into policy.

Background Antimicrobial resistance (AMR) poses a significant global health challenge, resulting in over 1.27 million deaths in 2019 and projected to cause up to 10 million deaths annually in the future. To address this issue, the healthcare sector requires rapid and accurate bacterial identification, which is currently not readily available for effective antimicrobial stewardship. In a UK national first, we implemented 16S ribosomal RNA (rRNA) sequencing using Oxford Nanopore Technology (ONT) in an NHS setting to enhance diagnostic capabilities, aiming to reduce antibiotic misuse and improve patient outcomes. Methods We implemented 16S rRNA sequencing via ONT, running samples from seven NHS hospitals across Cheshire and Merseyside. We focused on samples from sterile sites, such as “pus”, “fluid”, and “tissue”, typically collected from critical care units. The assay was validated against traditional methods including Sanger sequencing and MALDI-TOF, with a turnaround time of 24-72 hours. Clinical impact was measured by analysing changes in antibiotic regimens and patient outcomes based on 16S assay results over a period of several months post-launch. Findings ONT 16S rRNA sequencing significantly impacted antibiotic treatment in 34.2% of cases, reducing patient stays and outperforming traditional methods by detecting additional bacterial organisms and identifying bacteria missed by reference labs. It provided species-level identification and confirmed non-infectious conditions in 5.4% of cases, aiding alternative treatment decisions. Its speed, cost-effectiveness, and minimal training requirements contributed to its successful integration into clinical practice. Interpretation The integration of ONT 16S sequencing into routine NHS diagnostics has significantly improved antimicrobial stewardship by offering a faster, more sensitive, and accurate bacterial identification method. Earlier use of this assay in cases where routine cultures are likely to fail could enhance patient outcomes further by enabling timely, targeted antibiotic therapies, reducing hospital stays, and curbing unnecessary antibiotic use.

Ebola virus disease poses a recurring risk to human health. We conducted a systematic review (PROSPERO CRD42023393345) of Ebola virus disease transmission models and parameters published from database inception to July 7, 2023, from PubMed and Web of Science. Two people screened each abstract and full text. Papers were extracted with a bespoke Access database, 10% were double extracted. We extracted 1280 parameters and 295 models from 522 papers. Basic reproduction number estimates were highly variable, as were effective reproduction numbers, likely reflecting spatiotemporal variability in interventions. Random-effect estimates were 15·4 days (95% CI 13·2-17·5) for the serial interval, 8·5 days (7·7-9·2) for the incubation period, 9·3 days (8·5-10·1) for the symptom-onset-to-death delay, and 13·0 days (10·4-15·7) for symptom-onset-to-recovery. Common effect estimates were similar, albeit with narrower CIs. Case-fatality ratio estimates were generally high but highly variable, which could reflect heterogeneity in underlying risk factors. Although a substantial body of literature exists on Ebola virus disease models and epidemiological parameter estimates, many of these studies focus on the west African Ebola epidemic and are primarily associated with Zaire Ebola virus, which leaves a key gap in our knowledge regarding other Ebola virus species and outbreak contexts.