Advancing One human-animal-environment Health for global health security: what does the evidence say?

In this Series paper, we review the contributions of One Health approaches (ie, at the human-animal-environment interface) to improve global health security across a range of health hazards and we summarise contemporary evidence of incremental benefits of a One Health approach. We assessed how One Health approaches were reported to the Food and Agricultural Organization of the UN, the World Organisation for Animal Health (WOAH, formerly OIE), and WHO, within the monitoring and assessment frameworks, including WHO International Health Regulations (2005) and WOAH Performance of Veterinary Services. We reviewed One Health theoretical foundations, methods, and case studies. Examples from joint health services and infrastructure, surveillance-response systems, surveillance of antimicrobial resistance, food safety and security, environmental hazards, water and sanitation, and zoonoses control clearly show incremental benefits of One Health approaches. One Health approaches appear to be most effective and sustainable in the prevention, preparedness, and early detection and investigation of evolving risks and hazards; the evidence base for their application is strongest in the control of endemic and neglected tropical diseases. For benefits to be maximised and extended, improved One Health operationalisation is needed by strengthening multisectoral coordination mechanisms at national, regional, and global levels.

Case-Control Study of Risk Factors for Acquired Hepatitis E Virus Infections in Blood Donors, United Kingdom, 2018-2019.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in England. Substantial yearly increases of autochthonous infections were observed during 2003-2016 and again during 2017-2019. Previous studies associated acute HEV cases with consumption of processed pork products, we investigated risk factors for autochthonous HEV infections in the blood donor population in England. Study participants were 117 HEV RNA-positive blood donors and 564 HEV RNA-negative blood donors. No persons with positive results were vegetarian; 97.4% of persons with positive results reported eating pork products. Consuming bacon (OR 3.0, 95% CI 1.7-5.5; p<0.0001), cured pork meats (OR 3.5, 95% CI 2.2-5.4; p<0.0001), and pigs' liver (OR 2.9, 95% CI 1.0-8.3; p = 0.04) were significantly associated with HEV infection. Our findings confirm previous links to pork products and suggest that appropriate animal husbandry is essential to reduce the risk for HEV infection.

Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes.

The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment.

Human-to-Human Transmission of Monkeypox Virus, United Kingdom, October 2018.

In September 2018, monkeypox virus was transmitted from a patient to a healthcare worker in the United Kingdom. Transmission was probably through contact with contaminated bedding. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Of 134 potential contacts, 4 became ill; all patients survived.

Epidemiology of Hepatitis E in England and Wales: A 10-Year Retrospective Surveillance Study, 2008-2017.

Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as "G3 abcdhij") is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.

Cat-to-Human Transmission of Mycobacterium bovis, United Kingdom.

Human infection with Mycobacterium bovis is reported infrequently in the United Kingdom. Most cases involve previous consumption of unpasteurized milk. We report a rare occurrence of 2 incidents of cat-to-human transmission of M. bovis during a cluster of infection in cats.

Two cases of monkeypox imported to the United Kingdom, September 2018.

In early September 2018, two cases of monkeypox were reported in the United Kingdom (UK), diagnosed on 7 September in Cornwall (South West England) and 11 September in Blackpool (North West England). The cases were epidemiologically unconnected and had recently travelled to the UK from Nigeria, where monkeypox is currently circulating. We describe the epidemiology and the public health response for the first diagnosed cases outside the African continent since 2003.

West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach.

This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections.

Virology, serology, and demography of hepatitis E viremic blood donors in South East England.

BACKGROUND: Hepatitis E virus (HEV) Genotype 3 (G3) in England comprises two principal phylogenetic groups (Group 1 and Group 2) and can be transmitted by transfusion. Unselected screening identified 79 viremic donors; 76 participated in a follow-up study. STUDY DESIGN AND METHODS: Viral RNA dynamics, phylogenetics, and seroconversion were characterized in the donors. Detailed demographic, travel, clinical, and lifestyle questionnaires were undertaken. RESULTS: The majority of viremic individuals (57/79) were seronegative at time of donation but all seroconverted. Viremia was short-lived, with a median of 6.5 weeks to confirmed viral clearance. All infections were acquired in the United Kingdom and were G3, with Group 2 viruses predominating (43/54; 80%). Infection was associated with some clinical symptoms both at and after donation (8/77; 10%). Viral loads and symptoms were more pronounced in Group 1 infections. There was no serologic evidence of reinfection. Donors were more commonly male (p = 0.002); both male and female donors were older than comparator donors. Animal contact was unlikely to be the source of infection. Consumption of chicken and pig meat was common to all infected donors; processed pig meat was most commonly purchased from one particular retail chain. CONCLUSION: Viremic donors represent primary infection in older members of the community and reflect a widespread zoonotic in the United Kingdom. The two phylogenetic groups of HEV G3 display different pathogenicity and the more common Group 2 appears less adapted to humans. There are no objective demographic criteria that can identify donors at enhanced HEV risk.

Prevalence of Hepatitis E Virus Infection in Pigs at the Time of Slaughter, United Kingdom, 2013.

Since 2010, reports of infection with hepatitis E virus (HEV) have increased in England and Wales. Despite mounting evidence regarding the zoonotic potential of porcine HEV, there are limited data on its prevalence in pigs in the United Kingdom. We investigated antibody prevalence, active infection, and virus variation in serum and cecal content samples from 629 pigs at slaughter. Prevalence of antibodies to HEV was 92.8% (584/629), and HEV RNA was detected in 15% of cecal contents (93/629), 3% of plasma samples (22/629), and 2% of both (14/629). However, although HEV is prevalent in pigs in the United Kingdom and viremic pigs are entering the food chain, most (22/23) viral sequences clustered separately from the dominant type seen in humans. Thus, pigs raised in the United Kingdom are unlikely to be the main source of human HEV infections in the United Kingdom. Further research is needed to identify the source of these infections.

Public Health Investigation of Two Outbreaks of Shiga Toxin-Producing Escherichia coli O157 Associated with Consumption of Watercress.

An increase in the number of cases of Shiga toxin-producing Escherichia coli (STEC) O157 phage type 2 (PT2) in England in September 2013 was epidemiologically linked to watercress consumption. Whole-genome sequencing (WGS) identified a phylogenetically related cluster of 22 cases (outbreak 1). The isolates comprising this cluster were not closely related to any other United Kingdom strain in the Public Health England WGS database, suggesting a possible imported source. A second outbreak of STEC O157 PT2 (outbreak 2) was identified epidemiologically following the detection of outbreak 1. Isolates associated with outbreak 2 were phylogenetically distinct from those in outbreak 1. Epidemiologically unrelated isolates on the same branch as the outbreak 2 cluster included those from human cases in England with domestically acquired infection and United Kingdom domestic cattle. Environmental sampling using PCR resulted in the isolation of STEC O157 PT2 from irrigation water at one implicated watercress farm, and WGS showed this isolate belonged to the same phylogenetic cluster as outbreak 2 isolates. Cattle were in close proximity to the watercress bed and were potentially the source of the second outbreak. Transfer of STEC from the field to the watercress bed may have occurred through wildlife entering the watercress farm or via runoff water. During this complex outbreak investigation, epidemiological studies, comprehensive testing of environmental samples, and the use of novel molecular methods proved invaluable in demonstrating that two simultaneous outbreaks of STEC O157 PT2 were both linked to the consumption of watercress but were associated with different sources of contamination.

Indigenous hepatitis E in England and wales from 2003 to 2012: evidence of an emerging novel phylotype of viruses.

BACKGROUND: Enhanced surveillance and molecular characterisation studies of hepatitis E virus (HEV) in England and Wales have been undertaken since 2003. The dynamics of hepatitis E have changed recently with an increase in the number of indigenous cases and an observed viral shift. METHODS: HEV antibody and RNA data were analysed to ascertain the annual number of acute infections, the HEV genotype disposition and viral phylogeny. These data were investigated in the context of collected travel history and demographic data. RESULTS: In total, 2713 acute hepatitis E cases were diagnosed, of which 1376 were indigenous infections. Travel associated cases remained steady and mainly associated with Genotype 1 infections. In contrast, major fluctuations were noted in indigenously-acquired cases with a dramatic year on year increase during 2010-2012. Molecular characterisation demonstrated indigenous infections to cluster into two distinct phylogenetic groups with the emergence of a novel group of Genotype 3 viruses coinciding with the recent increase in cases. CONCLUSIONS: HEV infection rates are dynamic in England and Wales, influenced by changing trends in indigenously-acquired cases. The recent increase in indigenous cases and the emergence of indigenous viruses not commonly circulating prior to 2010 suggest that the risk of acquiring HEV has changed.

Guidance for contact tracing of cases of Lassa fever, Ebola or Marburg haemorrhagic fever on an airplane: results of a European expert consultation.

BACKGROUND: Travel from countries where viral haemorrhagic fevers (VHF) are endemic has increased significantly over the past decades. In several reported VHF events on airplanes, passenger trace back was initiated but the scale of the trace back differed considerably. The absence of guidance documents to help the decision on necessity and scale of the trace back contributed to this variation.This article outlines the recommendations of an expert panel on Lassa fever, Ebola and Marburg haemorrhagic fever to the wider scientific community in order to advise the relevant stakeholders in the decision and scale of a possible passenger trace back. METHOD: The evidence was collected through review of published literature and through the views of an expert panel. The guidance was agreed by consensus. RESULTS: Only a few events of VHF cases during air travel are reported in literature, with no documented infection in followed up contacts, so that no evidence of transmission of VHF during air travel exists to date. Based on this and the expert opinion, it was recommended that passenger trace back was undertaken only if: the index case had symptoms during the flight; the flight was within 21 days after detection of the event; and for Lassa fever if exposure of body fluid has been reported. The trace back should only be done after confirmation of the index case. Passengers and crew with direct contact, seat neighbours (+/- 1 seat), crew and cleaning personal of the section of the index case should be included in the trace back. CONCLUSION: No evidence has been found for the transmission of VHF in airplanes. This information should be taken into account, when a trace back decision has to be taken, because such a measure produces an enormous work load. The procedure suggested by the expert group can guide decisions made in future events, where a patient with suspected VHF infection travelled on a plane. However, the actual decision on start and scale of a trace back always lies in the hands of the responsible people taking all relevant information into account.

Hepatitis E outbreak on cruise ship.

In 2008, acute hepatitis E infection was confirmed in 4 passengers returning to the United Kingdom after a world cruise. Epidemiologic investigation showed that of 789 persons who provided blood samples, 195 (25%) were seropositive, 33 (4%) had immunoglobulin [Ig] M levels consistent with recent acute infection (11 of these persons were symptomatic), and 162 (21%) had IgG only, consistent with past infection. Passenger mean age was 68 years. Most (426/789, 54%) passengers were female, yet most with acute infection (25/33, 76%) were male. Sequencing of RNA from 3 case-patients identified hepatitis E virus genotype 3, closely homologous to genotype 3 viruses from Europe. Significant association with acute infection was found for being male, drinking alcohol, and consuming shellfish while on board (odds ratio 4.27, 95% confidence interval 1.23-26.94, p = 0.019). This was probably a common-source foodborne outbreak.

Safe management of mass fatalities following chemical, biological, and radiological incidents.

Contaminated mass fatalities following the release of chemical, biological, or radiological agents pose a potential major health hazard. A United Kingdom government investigation has identified a number of areas of risk. This paper presents an outline of the findings of the study and describes specific pathways for the management of contaminated and non-contaminated fatalities. Factors determining the choice between cremation and burial are discussed. Effective decontamination remains a neglected area of study for both fatalities and casualties.

Identifying potential emerging threats through epidemic intelligence activities-looking for the needle in the haystack?

BACKGROUND: Epidemic intelligence (EI) for emerging infections is the process of identifying key information on emerging infectious diseases and specific incidents. Automated web-based infectious disease surveillance technologies are available; however, human input is still needed to review, validate, and interpret these sources. In this study, entries captured by Public Health England's (PHE) manual event-based EI system were examined to inform future intelligence gathering activities. METHODS: A descriptive analysis of unique events captured in a database between 2013 and 2017 was conducted. The top five diseases in terms of the number of entries were described in depth to determine the effectiveness of PHE's EI surveillance system compared to other sources. RESULTS: Between 2013 and 2017, a total of 22 847 unique entries were added to the database. The top three initial and definitive information sources varied considerably by disease. Ebola entries dominated the database, making up 23.7% of the total, followed by Zika (11.8%), Middle East respiratory syndrome (6.7%), cholera (5.5%), and yellow fever and undiagnosed morbidity (both 3.3%). Initial reports of major outbreaks due to the top five disease agents were picked up through the manual system prior to being publicly reported by official sources. CONCLUSIONS: PHE's manual EI process quickly and accurately detected global public health threats at the earliest stages and allowed for monitoring of events as they evolved.

The Epidemiology of Q Fever in England and Wales 2000-2015.

Between 2000 and 2015, 904 cases of acute Q fever were reported in England and Wales. The case dataset had a male to female ratio of 2.5:1, and a median age of 45 years. Two outbreaks were recognised during this time period, and the incidence of sporadic cases was highest across the southwest of England, and Wales. There are limitations in the surveillance system for Q fever, including possible geographical differences in reporting and limited epidemiological data collection. The surveillance system needs to be strengthened in order to improve the quality and completeness of the epidemiological dataset. The authors conclude with recommendations on how to achieve this.

Control of arbovirus infections by a coordinated response: West Nile Virus in England and Wales.

Although there is no recognized transmission of human arboviral infections in the UK, concerns about the possible spread of West Nile virus (WNV) have precipitated coordinated activities around both surveillance and response. The Department of Health has chaired a UK WNV task force since the end of 2000. This is a multidisciplinary group of senior representatives from Agencies and Government Departments involved in human and animal health, entomology and academic departments. Activities include surveillance for WNV infections in humans, and in dead birds, mosquitoes and horses. All have been negative for WNV. A WNV contingency plan was produced in 2004, and this could be used as a generic plan for an effective and coordinated response in the event of the emergence of a new vector-borne zoonotic infection.

Impact of the HIV epidemic in sub-Saharan Africa on the pattern of HIV in the UK.

OBJECTIVE: To describe the epidemiology of HIV infection acquired in Africa and among African communities in the United Kingdom. DESIGN: Descriptive analysis using national HIV and AIDS surveillance data, routine voluntary confidential HIV reporting and unlinked anonymous seroprevalence surveys in the United Kingdom to the end of December 2001. RESULTS: Of all reported HIV infections diagnosed in the United Kingdom by the end of 2001, 21% (9993 of 48,226) were probably acquired in Africa and 90% of these infections were heterosexually acquired. Numbers of diagnoses of HIV infection acquired in Africa have been increasing rapidly, with rises in infections from southeastern and southern Africa predominating recently. Among those living with diagnosed HIV infection in 2000, 23% (4883 of 21,291) were described as black African, 81% of whom lived in London. The proportion living in London has declined over successive prevalence surveys. CONCLUSIONS: Infections acquired in Africa and among Africans are making an increasing contribution to HIV infection in the United Kingdom. Migration, diagnosis of long-standing infection and incident cases are all potential influences, but they are difficult to measure. Improvement in early diagnosis of HIV continues to be an important component of intervention to prevent onward vertical and sexual transmission and to promote access to treatment and care.

Inter- and intra-genic intersubtype HIV-1 recombination in rural and semi-urban Uganda.

OBJECTIVE: To investigate the number and variety of viruses with discrepant subtypes between env and gag and within gag in two cohorts in Uganda. METHODS: Sequences were generated from PCR products amplified directly (without cloning) from patient blood and compared in the v3/v4 region of env and the p17 and p24 regions of gag to reference subtype strains by phylogenetic analysis. Gag sequences with a discrepant subtype between p17 and p24 were analysed further to indicate approximate sites of recombination. RESULTS: Envelope subtypes D and A were predominant, but subtypes B, C and G were also found. From analysis of three short regions of the HIV genome we found 15 different combinations of subtype assortment, including 11 different recombinant permutations. Approximately 30% of viruses (29/104) in this part of Uganda appear to be recombinants between the env and gag genes and 10% (11/104) are recombinant within the gag gene. There was no clear pattern of crossover points within the gag gene. There seems to be no evidence of new circulating recombinant forms. CONCLUSION: Both inter-genic and intra-genic inter-subtype recombination appear to be a relatively common occurrence in this geographical region where two subtypes of virus co-circulate. These results have implications for cross-clade vaccine design.