Rabies and the pandemic: lessons for One Health

This article examines the impact of coronavirus disease 2019 (COVID-19) on dog-mediated rabies, a neglected tropical disease that remains endemic in >65 countries. A globally agreed strategy for rabies elimination is underpinned by a One Health approach, coordinating human and animal health sectors and engaging communities. We present data on the scale and nature of COVID-19 disruption to rabies control programmes and the wider learning for One Health implementation. We argue that the global shift in health priorities caused by the pandemic, and consequent side-lining of animal health, will have broader ramifications for One Health implementation and preparedness for future emergent zoonoses

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes. METHODS AND ANALYSIS: We will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes. ETHICS AND DISSEMINATION: The study has been approved by the North West-Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination

United against rabies forum:The one health concept at work

Human deaths from rabies are preventable and can be eliminated by applying a systematic One Health approach. However, this ancient disease still threatens the lives of millions of people in up to 150 countries and kills an estimated 59, 000 people every year. Rabies today is largely a disease of poverty, almost always linked to dog bites, with most deaths occurring in neglected communities in Africa and Asia. The disease places an immense economic burden on its victims, a cost that far outweighs the investment needed to control it. A global framework for rabies elimination in humans is set out in Zero by 30: The Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. Despite the existence of proven control strategies and agreement on the path to eliminating human rabies deaths, mortality numbers from rabies remain high, and COVID-19 has set back efforts even further. But COVID-19 has also highlighted the value of a One Health approach to zoonotic disease and pandemic prevention. Rabies control programs offer a practical route to building One Health capacities that can also address other zoonotic threats, including those with pandemic potential. The United Against Rabies Forum aims to accelerate progress on rabies elimination while applying a One Health approach. The Forum promotes cross-sector collaboration among stakeholders and supports countries in their rabies elimination efforts. Increased political engagement and resource mobilization, both internationally and nationally, will be needed to achieve global rabies goals and can also make One Health implementation a reality

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study

© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and sequelae in UK adults to improve the management of patients and assist in health service planning. Methods: We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission. Findings: 1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3–7), increasing to 9 days (6–12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year. Interpretation: Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services. Funding: Meningitis Research Foundation and UK National Institute for Health Research

The impact of the first year of the COVID-19 pandemic on canine rabies control efforts: a mixed-methods study of observations about the present and lessons for the future

Achieving zero human deaths from dog-mediated rabies has been set as a global target for 2030. However, the COVID-19 pandemic has disrupted essential health services across the world, with disproportionate impacts on Neglected Tropical Diseases. Through a mixed-method study using stakeholder questionnaires and in-depth interviews, we examined the scale and nature of disruption from the first year of the pandemic to rabies control programs, and reflected on lessons for the future. Study participants included practitioners and policymakers working in government, academia, international organizations, and the pharmaceutical industry across 48 countries, mainly in Africa and Asia. Mass dog vaccination, essential to rabies control, was most heavily impacted and in 2020, was carried out as planned in just 5% of surveyed countries. Access to post-exposure prophylaxis (PEP) also decreased due to fear of COVID-19 infection and difficulties in reaching health care centers. Dog vaccination and PEP delivery suffered from disruptions to the importation and distribution of vaccines. School closures affected rabies awareness activities and, when public events moved online, they could not reach the most disadvantaged groups. Surveillance, already weak, was severely disrupted by movement restrictions which, together with reduced demand for PEP, exacerbated under-reporting. Participants reported growing complaints around free-roaming dogs, with numbers likely to have increased in some settings. In some countries, dog rabies outbreaks and human rabies cases were already ascribed to the pandemic, but further impacts are likely still to be realized. Meanwhile, decreased demand for PEP from COVID-19 constraints could lead to reduced procurement in future. In the wake of post-COVID-19 demands on health services, there is an opportunity for veterinary services to show leadership in progressing the Zero by 30 agenda, particularly in scaling up mass dog vaccination within and across countries, as well as potential to make better use of community-based vaccinators. Countries must further secure stable procurement of dog and human vaccines, classifying them as essential goods prioritized for import and where needed, through sharing of stocks. Dedicated telemedicine services also show promise, for example through fostering participatory disease surveillance, including Integrated Bite Case Management, and delivering up-to-date instructions on the closest sources of PEP

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: epidemiological results

Objectives To estimate the incidence of gastroenteritis in individuals in care homes. Design Prospective cohort study. Setting Five participating care homes in North West England, UK. Participants Residents and staff present at the five study care homes between 15 August 2017 and 30 May 2019 (n=268). Outcome measures We calculated incidence rates for all gastroenteritis cases per 1000 person-years at risk and per 1000 bed-days at risk. We also calculated the incidence rate of gastroenteritis outbreaks per 100 care homes per year. Results In total 45 cases were reported during the surveillance period, equating to 133.7 cases per 1000 person-years at risk. In residents the incidence rate was 0.62 cases per 1000 bed-days. We observed seven outbreaks in all care homes included in surveillance, a rate of 76.4 outbreaks per 100 care homes per year. 15 stool samples were tested; three were positive for norovirus, no other pathogens were detected. Conclusions We found that surveillance of infectious gastroenteritis disease in care homes based on outbreaks, the current general approach, detected a majority of cases of gastroenteritis. However, if policymakers are to estimate the burden of infectious gastroenteritis in this setting using only routine outbreak surveillance data and not accounting for non-outbreak cases, this study implies that the total burden will be underestimated. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made

Sporadic cryptosporidiosis case-control study with genotyping

Risk factors for Cryptosporidiosis in United Kingdom

Insect bite prevention.

Protection from the bites of arthropod (insect and acarine) vectors of disease is the first line of defense against disease transmission and should be advised in all cases when traveling abroad. Details are described of the main approaches for the prevention of bites, including topical or skin repellents, impregnated clothing, bed nets, and spatial or aerial repellents and aerosols. The bionomics of the main arthropod vectors of disease are described along with photographic plates and tabulated advice to give the traveler. An in-depth treatment of the different protection methodologies provides an up-to-date overview of the technologies involved

Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT)Research in context

Summary: Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference −0.6%, 95% CI −3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme