Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England

The term “high-consequence infectious disease” (HCID) was originally defined in England in 2016 and subsequently adopted by the public health agencies of the other UK nations (Northern Ireland, Scotland, and Wales). Since that time, the term has been used increasingly in guidance and policy documents of the United Kingdom and other countries.¹ The United Kingdom defines HCID as an “acute infectious disease [that] typically has a high case fatality rate, may not have effective prophylaxis or treatment, [is] often difficult to recognise and detect rapidly, [has the] ability to spread in the community and within healthcare settings, [and] requires an enhanced individual, population and system response to ensure it is managed effectively, efficiently and safely.”² In England, HCID status is used to determine the appropriate clinical and public health response pathways for the infectious disease. However, HCID status has no standing in UK law and does not by itself affect the classification of the causative pathogen in terms of the pathogen hazard group, management of clinical or laboratory waste, or transport requirements for biological samples and waste (these are governed by separate UK laws and regulations pertaining to specific pathogens, some of which cause HCIDs).

The HCID definition was developed by the HCID program, a joint initiative between the National Health Service (NHS) England and Public Health England (now UK Health Security Agency; UKHSA) that operated between 2016 and 2018. The program aimed to describe and improve end-to-end pathways and processes for HCID cases, encompassing both clinical and public health management of suspected and confirmed cases, as well as the management of contacts of cases. After defining HCID, the program developed 2 lists of diseases:² airborne HCIDs (A-HCIDs) and contact HCIDs (C-HCIDs). The lists of A-HCIDs and C-HCIDs (Box) are maintained by UKHSA and are agreed upon by the public health agencies of the 4 UK nations, sometimes supported by recommendations and advice from specialist committees that advise the UK Department of Health and Social Care. From a practical perspective, these lists ensure that all stakeholders know which diseases require care in an HCID center and which do not. The lists also inform clinicians about what diseases to expect, so they can prepare appropriately before seeing a particular disease for the first time.

A-HCIDs include diseases where the causative pathogen is known to be transmitted, or highly likely to be transmitted, between humans in community settings by exposure to respiratory secretions—including droplets, droplet nuclei, or aerosols—excreted by infected humans. The term “airborne” refers here to the specific, standardized infection prevention and control (IPC) measures used for these diseases, which may be more than what is required for a particular disease (eg, aerosol IPC precautions applied for a disease that spreads predominantly via exposure to nonaerosolized respiratory secretions). It does not mean that all A-HCIDs are commonly spread by exposure to aerosolized, infectious respiratory particles, and some A-HCIDs may be transmitted more commonly by direct physical contact in some outbreaks, such as the mpox (monkeypox) virus being transmitted by direct contact during sex. This “1-size” approach to IPC for all A-HCIDs balances the potential for an overly cautious approach for some HCIDs with the benefits of training in, and the application of, a single, unified method, such as using 1 type of personal protective equipment (PPE) ensemble for all HCIDs.⁴

Established pandemics are deliberately excluded from the remit of the public health and clinical HCID systems and plans. This is because a pandemic necessarily requires its own specific response system that is much larger and more complicated than the systems designed for occasional cases or small clusters/outbreaks of HCIDs. It is possible, however, that a novel disease may be classified as an HCID soon after it has emerged and before it reaches pandemic status. This was the case for COVID-19, which was temporarily assigned A-HCID status in the United Kingdom in January 2020 as a precautionary measure when information about the disease was limited. HCID status was removed in March 2020, following a scheduled review of international data that had accumulated, which showed that COVID-19 did not meet the HCID framework criteria. Additionally, it was clear by this point that a much larger pandemic response was needed and, accordingly, the UK government launched its COVID-19 pandemic response plan shortly after the WHO March 11, 2020, declaration of a COVID-19 pandemic.⁵ Notably, the same level of IPC precautions as those used in HCID systems could be recommended in a pandemic response plan, if they are thought to be required and are feasible.

Essentially, C-HCIDs are viral hemorrhagic fevers (VHFs) where human-to-human transmission is known to occur. This includes Lassa fever (LF), Ebola virus disease (EVD), Marburg virus disease, and Crimean-Congo hemorrhagic fever (CCHF), as well as other VHFs that may be less well known but still exhibit human-to-human spread. VHFs that may cause severe and fatal disease but do not transmit between humans, such as dengue fever, yellow fever, and Rift Valley fever, are not C-HCIDs. Human-to-human transmission of C-HCIDs occurs by exposure to infected blood, body tissues, or body fluids; there is no evidence that “natural” transmission of C-HCIDs has occurred by inhaling infectious respiratory secretions from an infected person. Regardless, IPC measures for confirmed C-HCID cases include airborne precautions in addition to contact precautions; this is because some medical procedures could result in the aerosolization or emission of infectious particles, and risk tolerance is typically very low when trying to avoid potential exposures to HCID pathogens.

The A-HCID concept and clinical management system is relatively new, but the NHS in the United Kingdom has been safely managing confirmed cases of C-HCIDs—albeit under the name of VHFs—using a high-level isolation unit (HLIU) patient isolator system since 1976. As of July 2024, this cohort includes 16 cases of LF, 4 cases of EVD, and 3 cases of CCHF (NHSE England Contact HCID Network internal data). However, the unprecedented 2014-2016 EVD epidemics in some western African countries, along with the emergence of Middle East respiratory syndrome in 2012 and avian influenza A (H7N9) in 2013, triggered a review of existing plans, processes, and capabilities, which were coordinated by England’s HCID program.

While the program did not significantly change clinical provision for managing confirmed C-HCID cases, which had already been enhanced in 2014-2015 in light of the unprecedented EVD outbreaks in West Africa, improvements to C-HCID pathways and IPC measures were made, for both suspected and confirmed C-HCID case management. Additionally, the network of 4 NHS trusts that might provide care to patients with confirmed C-HCIDs, including 2 hospitals with HLIUs and patient-isolators, became a formal C-HCID network.

Perhaps more significantly, it was recognized that an equivalent network of specialist centers did not exist for treating confirmed cases of A-HCIDs, which arguably are, and will continue to be, the greater HCID threat for most high-income countries including the United Kingdom. One of the major outcomes of the program was NHS England’s commissioning of A-HCID treatment centers, including pediatric service provision, across 7 NHS hospital trusts in England that already had existing infectious disease services.

The C-HCID and A-HCID networks continue to grow, gaining and sharing experiences of safe and effective case management, while adapting to an evolving HCID and emerging infection landscape. To this extent and following a recent review, more A-HCID treatment centers are being commissioned in 2023-2024, along with an additional pediatric C-HCID treatment center that will serve London and the South of England.

An additional benefit of the HCID program was the strengthening of working relationships and coordination between clinical and public health specialists involved in preparing for, and responding to, HCID incidents in the United Kingdom. A proposed network of centers to assess and manage suspected HCID cases was considered neither appropriate nor achievable; instead, all NHS hospitals with emergency departments in England are expected to be able to safely isolate, assess, and care for suspected HCID cases. This arrangement reflects, in part, knowledge that people with travel-associated infections and previous HCID patients in the United Kingdom tend to present unwell to their nearest hospital, and patients may reside anywhere in the United Kingdom. Additionally, HCIDs remain rare in the United Kingdom and moving patients long distances to specialist HCID assessment centers could affect the safe and urgent management of more common and sometimes serious infections, and place additional stresses and strains on NHS resources.

NHS England, UKHSA, and the HCID networks continue to help hospitals in England prepare for and respond to suspected HCID cases, focusing on case recognition, rapid diagnosis, safe isolation and care, and timely transfer of the patient to an HCID treatment center within 24 to 48 hours of laboratory confirmation. All UK healthcare providers assessing and managing patients for whom C-HCID diagnosis is being considered are expected to adhere to the national guidance and algorithm published by the Advisory Committee on Dangerous Pathogens (ACDP).⁶ UKHSA provides broad guidance on all HCIDs,² including A-HCIDs, along with more detailed guidance collections for specific HCIDs, such as Middle East respiratory syndrome and mpox.^7,8

The decision to recommend admission of a confirmed case to A-HCID or C-HCID treatment centers considers the clinical status and medical needs of the patient, estimation of their current state of infectiousness, and what is known about the natural history of the particular HCID. There is a lower threshold to recommend admission of patients with mild illness when little is known about the disease, or progression to severe disease is common and unpredictable. Recovered, noninfectious cases who are diagnosed retrospectively (eg, by serological testing or molecular testing of a sample obtained previously) are not admitted to an HCID center. All patients with active HCIDs and in need of hospital-level medical care (ie, they have moderate to severe illness) in England must be admitted or transferred to an HCID treatment center. For patients with C-HCIDs, this rule applies to all 4 nations of the United Kingdom. Pediatric patients needing admission are typically accompanied by an exposed or infected parent or caregiver.

It is worth noting that there is no legal mandate to hospitalize newly diagnosed, infectious HCID patients in the United Kingdom. A public health authority may request a judge or magistrate to issue an isolation-in-hospital order under public health legislation⁹ if a patient requires isolation in hospital to prevent transmission of their infection to others and the patient has refused admission. It is possible for selected HCID patients to self-isolate in their place of residence with monitoring and review by public health and clinical teams, if this can be achieved safely and has been agreed upon by UKHSA; however, the default position is to recommend admission to an HCID center and there must be a clear rationale if an alternative plan is to be approved. One example of an alternative plan might be home-based isolation with public health and clinical monitoring for a family cluster of asymptomatic, infected children and parents/caregivers, any of whom could be admitted rapidly to a nearby HCID center if they were to become unwell.

In this case study, we describe separately the structure, functions, operational principles, and experiences of the C-HCID and A-HCID networks that manage confirmed HCID cases. We also discuss current and future limitations and challenges in managing HCID cases in England, as well as efforts being made to address them, including preparing for less likely but important case/cluster scenarios and achieving additional surge capacity.

England’s C-HCID network receives patients from all UK nations, because only England has the necessary facilities to manage C-HCID cases in the United Kingdom. The network consists of 2 adult HLIUs: the Royal Free Hospital HLIU in London and the Royal Victoria Infirmary Newcastle upon Tyne. Two additional surge centers in Liverpool and Sheffield could help manage adult cases in the unlikely event that capacity at the 2 HLIUs (in London and Newcastle upon Tyne) is exceeded. To date, the Royal Free Hospital HLIU in London is the only HLIU that has received patients with confirmed C-HCIDs for ongoing specialist care and isolation and, as such, it is the United Kingdom’s principal adult HLIU. In addition to being commissioned to provide care to adults, the HLIU at the Royal Victoria Infirmary in Newcastle is currently the only pediatric HLIU in the United Kingdom. It should be noted that in the United Kingdom, the term “HLIU” is only used to describe the specialist units commissioned to receive, isolate, and provide care to patients with C-HCIDs; these units are separate from, and in addition to, the commissioned C-HCID surge and A-HCID treatment service provisions.

Effective biocontainment and the safe care of adult cases in the 2 HLIUs is achieved primarily by using Trexler flexible-film patient isolators (2 available within each HLIU). Currently, infants and individuals under 16 years of age with C-HCIDs will receive care in Newcastle using a PPE-based model, rather than being placed in Trexler isolators. This is because the Trexler isolators have no sides to the beds, which are required for safe care of smaller children, and the sleeves of the half-suits to access the patient for care are too widely spaced for smaller children. Additionally, there is concern about the ability to safely contain a child, who might be scared and anxious, within an isolator. All 4 adult centers (2 HLIUs and 2 surge centers) are prepared to implement a PPE-delivered model of care on temporarily converted hospital wards, in the unlikely event that the 4 HLIU Trexler isolators cannot be used or they are all occupied.

Laboratory diagnosis of C-HCIDs takes place at the UKHSA’s Rare and Imported Pathogens Laboratory in Porton Down. Once confirmed, NHS England activates the C-HCID network and an urgent virtual meeting is convened to discuss all relevant issues: the diagnosis, exposure history, clinical details, current clinical status and infectious status, the need for hospital-based care, prognosis (and end-of-life care if relevant), expectation of any associated cases, security and confidentiality aspects, patient compliance with isolation, operational readiness of all centers, agreed location of care for the patient if transfer is indicated, and the mechanism of safe transfer.

For adults, the default location for transfer is the Royal Free HLIU in London, which has more extensive experience in case management and the most developed and dedicated infrastructure. As of July 2024, the Royal Free team has provided Trexler isolator-based care to 12 patients with LF, 4 patients with EVD, and 2 patients with CCHF, initially at Coppetts Wood Fever Hospital in North London, and since 2008, at the Royal Free Hospital. Some UK-diagnosed patients were not transferred to the HLIU, because some had recovered by the time the diagnosis was made and others died prior to transfer. For infants and children, the default receiving center is the Royal Victoria Infirmary in Newcastle, as it is currently the only pediatric HLIU in England. The Newcastle pediatric HLIU has not managed any confirmed pediatric cases to date, but the team has experience managing suspected C-HCID cases using the PPE-based model of care.

The 2 HLIUs and the 2 surge centers follow the same operational tenets: they have a trained cadre of clinical and support staff, provide high-level isolation of patients to achieve pathogen containment, implement appropriate waste management systems, and have safe and appropriate laboratory facilities for doing routine clinical tests. The overall approach is to have a safer system of working that is appropriate to the HCID risk. While the teams provide C-HCID patients with the best care possible, the primary consideration in all aspects of clinical care and clinical decisionmaking is to protect staff, other patients and visitors, and the wider population from pathogen exposure and subsequent infection. The safe management of patients in C-HCID centers is consistent and compliant with the principles, practices, and requirements described in the ACDP guidance on management of patients with VHFs caused by ACDP hazard group 4 viruses.⁵

Patients with confirmed C-HCIDs can be transferred to a C-HCID treatment center by 1 of 3 methods: using the Royal Air Force (RAF) Air Transport Isolator (ATI) (Figures 1A and 1B),¹⁰ using an EpiShuttle (EpiGuard, Oslo, Norway)¹¹ portable isolator transported in an ambulance staffed by NHS Hazardous Area Response Team (HART) paramedics (Figure 1C), and using an open trolley/gurney in an ambulance with HART paramedics wearing HCID PPE ensembles (Figure 1D). This latter option is the most likely method for transferring pediatric patients, particularly if they are not invasively ventilated. The choice of transfer method considers the clinical status of the patient, their age, and logistical considerations, and it includes a risk assessment. The ATI can be transported in a fixed-wing RAF aircraft or by road in the RAF’s specially adapted, large ambulance (“jumbulance”); the ATI and the RAF’s specialist medical transfer capability are described in more detail elsewhere.¹⁰ If a patient arrives at a center via EpiShuttle or open trolley/gurney, they may be transferred through the hospital and into a Trexler isolator using an ATI that is kept at the hospital; this is to ensure end-to-end containment (Figure 1B) of infection risk and prevent potential contamination of the HLIU room where the Trexler isolator is located and any other parts of the hospital that the patient passes on their way to the HLIU.

At the Royal Free Hospital HLIU, all Category A waste is rendered noninfectious using large-capacity autoclaves located within the HLIU, allowing it to be managed subsequently as normal clinical waste. The other centers have pathways in place to temporarily store and then safely move Category A waste to offsite licensed processors where it can be made safe for disposal. The Royal Free also has a dedicated high-containment laboratory within its HLIU suite (Figure 2), where a substantial panel of hematology, biochemistry, and microbiology tests can be performed, using a mixture of automated analyzers and traditional laboratory techniques. This includes the ability to perform rapid blood gas analysis, thromboelastography, bacterial cultures, and microscopy.¹² The other C-HCID centers have approved processes in place for performing a more limited panel of essential tests safely via their local laboratory infrastructures. None of the centers have assays that are used for detecting or monitoring levels of C-HCID viruses during illness; those assays are performed by UKHSA’s Rare and Imported Pathogens Laboratory using high-containment laboratories in Porton Down and London, with results typically available in 12 to 24 hours.

The Trexler flexible-film isolators (Figure 3) were introduced in 1976, initially to manage any smallpox cases that might occur in the posteradication era. The design of the isolator was informed by positive pressure flexible-film isolators used in veterinary science, with the human isolators being much larger. Operating in positive pressure mode, they were used to protect severely immunocompromised hematology patients from infections, and in negative pressure mode, they were used to manage patients with highly infectious diseases. Temperature-controlled air filtered by a high-efficiency particulate air (HEPA) filter is diffused into the plastic ceiling of the isolator and mechanically extracted, with an overall negative balance. The removed air passes through HEPA filters and the isolators are located within secure rooms that are themselves under negative pressure (−40 Pa and at least 12 air changes per hour) and have HEPA filtration of removed air before it is discharged into the atmosphere. Other rooms within the contaminated zone of the HLIU are also under negative pressure, and a 1-way system operates in the unit with separate entrances and shower-out exits. Floors are color-coded to demarcate clean and contaminated zones and are lined to make them impermeable to fluids. Access to the unit is restricted to approved staff only, and interlocking doors are used on anterooms. Visitors are not allowed to enter patient care areas, but they can see the patient in the isolator through large windows and communicate via intercoms, mobile phones, or wireless tablet devices. Intercoms are also used for communication between staff in the isolator room and staff at the clean nurses’ station, and the patient-allocated electronic tablet device may be used by staff to take photographs (eg, of a wound or skin rash) for the patient’s electronic medical record.

One key benefit of the Trexler isolators is the total containment of a pathogen around the infectious patient, so that staff do not need to wear HCID PPE ensembles for long periods and can avoid cumulative exposure risks associated with the frequent use and removal of PPE. Another significant benefit is that it is much easier to train multidisciplinary staff in the use of the Trexler isolator, compared with training, assisting, and supervising staff when PPE care models are used. Staff can easily have close, protected, physical contact with the patient by using 5 half-suits that are part of the head- and side-walls of the isolator, which are made of flexible, transparent plastic (Figure 4). Each half-suit comes with an air-cooling vest to prevent the user from overheating and to prevent condensation forming on the visor. Additional single arms—like those found in laboratory gloveboxes—are available at various points around the isolator, their locations informed by case management experience gained over the years.

Staff with recent experience caring for patients in the Trexler isolators agree that the main limitations of the isolator model are confinement of the patient within a relatively small space, which can be challenging or unpleasant for some patients and is considered unsuitable for young children, and the lack of scalability for larger outbreaks (there are 4 single-occupancy Trexler isolator beds in the United Kingdom). Further comparisons of the benefits and drawbacks of isolator- and PPE-based care models are described in the Table. Regardless, for the usual C-HCID case scenarios seen in the United Kingdom over the last 50 years—1 confirmed adult case every few years—the isolator approach has proven to be highly effective, popular with those who have provided care, and generally well tolerated by (adult) patients.

IPC measures required for HCID are arguably more demanding than those required for other, more common, infectious diseases. Furthermore, the IPC requirements for C-HCIDs in the United Kingdom are even more stringent than those required for A-HCIDs. A single, PPE-based IPC system for both A-HCID and C-HCID (ie, without the use of a patient isolator) may have the benefit of staff having to train in a single IPC system, but it could also result in an IPC system that is suboptimal for C-HCID patients and cumbersome and excessive for typical A-HCID patients. While chemical disinfection of appropriate PPE suits prior to and during doffing PPE (ie, “wet doffing”) might reduce the risk of pathogen exposure during doffing, it adds a layer of operational complexity, as well as additional and significant resource costs. It also complicates the training and retraining of large numbers of multidisciplinary staff, and it is harder to provide additional staff with “just-in-time” training when more complex PPE suits and wet doffing are used.

Our experience from the last 5 years of A-HCID and C-HCID events in the United Kingdom suggests that training HCID staff in 2 different IPC systems—the Trexler isolator system and PPE-based care in a ward setting—has not been problematic. Furthermore, training in both systems only applies to a proportion of staff within the C-HCID network, meaning those working at the 2 HLIUs where viral hemorrhagic fever cases are managed.

All liquid waste and semisolid waste produced by a patient is solidified using sodium polyacrylate crystals. All waste is removed from the isolator using a bag-and-seal system in the associated supply unit (Figure 5), which is connected to the main isolator’s large porthole once the patient has passed through the same porthole when admitted to the unit. Double-bagged waste goes into rigid clinical waste bins, which are then transferred to the HLIU autoclaves for decontamination or to the hospital’s secure Category A waste holding area when autoclaves are not available. HCID patient care can create very large volumes of infectious waste, which requires planning around procurement and storage of many rigid waste bins, as well as efficient, safe, and compliant waste management pathways.

The movement of objects into the Trexler isolator uses the same bag-and-seal system. Both inserting and removing items—including patients—requires specific training, can be time-consuming, and needs to be done with due care and attention to ensure biocontainment is maintained. Efforts are made to anticipate what may be required within the isolator; ideally, emergency equipment (eg, defibrillator) and medicines are inserted into the isolator before they are needed. Bagged biological samples from the patient, such as blood samples, exit the supply unit using the bag-and-seal system and are then placed into clean, decontaminated transport containers suitable for transporting Category A infectious substances to the laboratory. The net effect of these measures—a continuous, protective envelope around the patient and all infectious materials—means that staff in the room can wear surgical scrubs without additional PPE (other than nitrile gloves when inside a half-suit or using the side-arms), as long as the containment system is not compromised.

The Trexler isolator can be used and has been used to isolate adult patients requiring intensive care, up to the level of invasive monitoring, inotrope and pressor support, invasive mechanical ventilation, and hemofiltration. A half-suit at the head end of the isolator allows a practitioner to manage the airway, including tracheal intubation and extubation. Early placement of a central venous catheter is preferred for all HLIU patients, to reduce the number of venepuncture episodes for blood tests. Extracorporeal membrane oxygenation is not possible in the HLIU, but it is unlikely to be indicated for patients with contact HCIDs. Electrical and mechanical equipment is placed within the isolator, although some equipment may remain outside the isolator, with connecting cables or tubes passing through airtight ports in the isolator’s walls. When required, a hemofiltration machine housed within its own flexible film isolator is connected to the main isolator. Further details of the provision of adult critical care in a UK HLIU are described elsewhere.¹³ Currently, critical care provision for pediatric patients would have to be in an open, full PPE model. This service is being developed alongside an ethical framework that considers the significant risks, limitations, and outcomes.

The isolator is designed to accommodate the x-ray source assembly and extending arm of a portable x-ray machine, as well as ultrasound scanners. Patients with C-HCIDs in the United Kingdom are unable to undergo cross-sectional imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI) scans.

A portion of 1 wall of the isolator is extendable (Figure 3), creating additional space when needed for the patient to stand, sit on a portable stool, or do physiotherapy exercises. Electronic tablet devices and mobile phones are provided to the patient for communication and entertainment purposes. A disposable curtain can be drawn around the entire isolator to provide privacy when needed, and ceiling lights are adjustable and dimmable. Clinical psychologists and psychiatrists work closely with the HLIU team to provide support to HLIU patients, their families, and HLIU staff when needed.

Following successful treatment, patients are removed from the isolator following a joint risk assessment completed by the HLIU team, the C-HCID network, and UKHSA. The decision to step down from the HLIU considers the clinical and virological status of the patient, any ongoing risk of infectiousness and whether it can be managed safely elsewhere (eg, in an isolation room on a ward), and the implications of continuing isolator care, including the potential to cause psychological harm to the patient and resource use that is disproportionate to the current transmission risk. A deceased patient is placed in a body bag with absorbent materials before being removed from the isolator via the port (using a large bag-and-seal system) and placed in an approved, impermeable coffin within the HLIU. The coffin is then sealed within the HLIU, and the exterior is decontaminated before being removed by specialist, approved funeral directors.

At the end of an HLIU activation period, the isolator room is closed and sealed for decontamination and the air handling system is isolated. The Trexler isolator, the supply unit, the hemofiltration unit (if used), and all rooms within the HLIU undergo selective surface decontamination with sodium hypochlorite solution, followed by vaporized hydrogen peroxide decontamination¹⁴ provided by a specialist contractor. Environmental hydrogen peroxide levels are monitored and biological and chemical indicators are used to evaluate completeness of decontamination. All exposed reusable equipment remains in situ during decontamination. Most medical equipment survives the decontamination process and can be reused, but the functionality of equipment is always checked following decontamination. Heavily exposed equipment may be decommissioned and replaced, along with any damaged equipment. The flexible plastic isolator tent can be reused if close inspection confirms structural integrity has been maintained; if not, a new tent is commissioned and attached to the isolator framework. The flexible plastic has a lifespan and expiry dates are monitored. Regular safety checks of isolator integrity are performed when the unit is activated, and less frequently when the unit is on standby as part of HLIU readiness measures.

The UK HLIUs are maintained by specialist medical and nursing staff, along with engineers who maintain associated infrastructure, which includes air-handling and filtering systems, electrics and plumbing, security controls, and autoclaves (where present). When activated, infectious disease doctors and nurses remain present in the unit around the clock, following 12-hour shift patterns, with additional support from intensive care staff. At both HLIUs, specially trained biomedical scientists are available to perform routine laboratory tests safely, including on request and overnight. The scientists are microbiologists who have received additional training in performing hematology and biochemistry tests. The clinical lead for the activated HLIU joins national incident management team online meetings convened by UKHSA, and online C-HCID network meetings continue. Communications specialists from the hospital and UKHSA work together to provide statements and updates, while ensuring that patient confidentiality and information security requirements are respected.

HLIU preparedness and response efforts are truly multidisciplinary and include radiographers, therapists, the chaplaincy team, psychologists, administrators, pharmacists, and security staff, among others. For a critically ill patient requiring 2 to 3 weeks of care in the isolator, over 100 staff may complete shifts within the isolator room; this is in addition to other support staff elsewhere and can include staff who do not usually work on the unit, such as a cardiologist who has been asked to perform an echocardiogram. With such large numbers of staff required, and so many encounters between healthcare workers and patients, the Trexler isolator model proves its utility for the typical C-HCID patient scenario in the United Kingdom by reducing the need to provide repeated training in PPE-based care to staff from different departments and disciplines, and reducing the number of opportunities for virus exposure during doffing episodes that would be encountered with a PPE-based model.

Doctors, nurses, and other healthcare professionals who may work on the unit as part of their individual roles are provided with starter training in HCID procedures, including the safe use of PPE ensembles (used for assessment of suspected HCID cases and for an unlikely large outbreak or if the isolator envelope is breached) and familiarization with HLIU and its operating procedures. Annual training in IPC and HLIU emergencies is required for the hospital’s permanent infectious diseases and critical care staff, and just-in-time training is provided for new or temporary staff when the HLIU activates, along with refresher training for anyone who requests it.

Hospital- and national-level clinical and operational debriefs are held at the end of each HLIU activation, and a lessons identified log is completed during and following activation. Knowledge and experiences gained are shared with HCID specialists in other countries, and the UK C-HCID teams participate in international networks, such as the National Emerging Special Pathogens Training and Education Center International Partnerships and Programs. Patient-transfer simulation exercises are held annually with the RAF ATI team, and additional tabletop and simulation exercises take place when required, including with national stakeholders and with the A-HCID network when there is an opportunity for joint learning. Through extensive preparedness measures and investment in HLIUs that remain empty and ready to receive a patient, each HLIU can be ready to receive a confirmed case just 6 hours after being activated.

C-HCIDs diagnosed in the United Kingdom are usually acquired overseas. Cases of infection may occur in association with a known, new outbreak (eg, EVD) or may be sporadic and associated with travel to an area with an active, continual risk of exposure to that disease (eg, LF and CCHF). Regardless, it remains that C-HCID cases are rare in the United Kingdom and are typically found in adults; therefore, having 4 isolators across 2 adult HLIUs is proportionate to the known and currently expected threat-risk and is supported by UK experiences to date. However, this paradigm and the UK preparedness measures informed by it have been challenged in recent years.

The unprecedented and unexpected EVD epidemics in western African countries in 2014-2016 created new challenges for many countries outside Africa, including in the United Kingdom. Although the risk of a case associated with “normal” travel to or from the region remained low, the international response efforts—including the deployment of thousands of military, medical, research, and humanitarian response workers from the United Kingdom and Europe—meant that the likelihood of single cases, and possibly concurrent cases, requiring care in the United Kingdom was increased. This included the need to provide care to UK citizens diagnosed in West Africa and then medically evacuated to the United Kingdom. During this event, there were 3 such cases, all UK healthcare professionals working in Ebola treatment centers in Sierra Leone: 2 medically evacuated from Sierra Leone and 1 diagnosed after developing symptoms following their return to the United Kingdom. The 3 cases were not contemporaneous but could have been; therefore, there was assurance of the ability to activate 4 adult isolator beds and obtain additional surge capacity, should it be needed. That model continues to this day.

The expandable, nonisolator surge plan uses a PPE-delivered model of care. Existing patients on the designated infectious diseases wards in any or all of the 4 C-HCID treatment centers would be rapidly transferred to suitable alternative wards, and those wards would become C-HCID surge wards. Each ward could accommodate between 2 and 5 patients in individual, HEPA-filtered, negative pressure side rooms on a ward with strict access control, 1-way movements of staff, and dedicated PPE doffing and decontamination areas that exit separately into a clean zone. This would provide at least 8 beds nationally (including pediatric beds), in addition to the 4 adult Trexler isolator beds in London and Newcastle. The order in which surge beds are activated and patients are placed across the 4 centers would be decided by the network and would consider factors such as the case locations, number of existing cases at each center, care needs, and staff availability at each center.

The occurrence of a family cluster of LF cases in England in 2022 revealed the challenges involved in providing care to a C-HCID patient who is pregnant, postpartum, or a child or infant. There is further recognition that such patients (eg, a parent and their child) may be colocated and then must be separated for ongoing, specialist care. It is possible that several members of a family or another connected/coexposed group may develop C-HCID and require hospitalization simultaneously. Current planning assumptions and bed capacities should be able to accommodate these scenarios, again following the principle that containment of infection has primacy over all other aspects of care, while doing everything possible to minimize harms to the patients.

As of July 2024, only 1 mother who was diagnosed postpartum has required HLIU care; there has been no experience of providing antenatal care, delivery, or immediate postnatal and neonatal care in an HLIU setting, although standard operating procedures (SOPs) have been developed in Newcastle upon Tyne, which is the only HLIU that can care for both adults and children. Multidisciplinary exercises are being planned for late 2024 to test pregnancy and delivery scenarios, to determine what can and cannot be achieved, safely and practicably, in a Trexler isolator, compared with a PPE-based model. The exercises will also have to consider different models for providing ongoing care to an infected neonate, including the immediate and subsequent locations of care. For example, the Royal Free HLIU does not have an in-house pediatric HCID service, which could mean immediate temporary care at the Royal Free with a visiting pediatric C-HCID team present, followed by safe transfer of the infant to a pediatric HLIU elsewhere, or transfer of the pregnant women to the Newcastle upon Tyne HLIU, with delivery in a setting where both adult and pediatric/neonatology care is available.

As described earlier, a network of adult and pediatric NHS treatment centers was commissioned for the first time in 2018 to provide safe and effective management of airborne HCIDs in England. These A-HCID centers are run by adult and pediatric infectious diseases services and complement the C-HCID network. The airborne network is necessarily larger than the contact network, with a greater geographical spread of centers, greater pediatric service provision, and a larger number of allocated beds and isolation rooms; this reflects the greater likelihood of A-HCID cases occurring compared with C-HCID cases, and that human-to-human transmission and clusters or larger outbreaks are more likely with A-HCIDs.

There are 5 hospitals that provide care to adults and 4 hospitals that provide pediatric care, across 4 English cities: London, Sheffield, Newcastle upon Tyne, and Liverpool. All 4 C-HCID treatment centers also happen to be A-HCID treatment centers. All centers are expected to provide care, including critical care when required, to 2 to 4 patients with confirmed A-HCIDs with 6 hours’ notice, year-round and including outside normal working hours. Guy's and St Thomas' NHS Foundation Trust in London, is ready to provide extracorporeal membrane oxygenation (ECMO) to adult and pediatric A-HCID patients and previously provided this service to an adult patient with Middle East respiratory syndrome.

To be able to provide an A-HCID service, each center is required to have in place appropriate hospital estate that includes patient isolation facilities that adhere to national structural, design, ventilation, and air-handling requirements,¹⁵ along with required access control. For healthcare worker and patient safety, a unidirectional flow model is preferred where it can be achieved; where this is not possible, negative pressure isolation rooms with a single anteroom for entry, doffing PPE, and exiting are permitted.

Governance of the network is assured with regular overview by NHS England. Each center, adult and pediatric, has a lead clinician with a deputy lead or colead. NHS England appoints a lead center, and the network director is based at that center.

Safe working models are vital and each of the centers undertakes regular simulation training with varying scenarios. Regular discussions take place at the national level to update and harmonize all SOPs. As with the C-HCID network, all centers regularly review their SOPs, update them where necessary, and share their practices and learning with other centers. General operating principles apply to the entire network, but with scope for “localization” of protocols to apply the principles to a center’s existing infrastructure and workforce.

SOPs for A-HCID centers include those for the transfer of a patient into and within a center, sampling of the patient and safe transfer of samples, waste storage and waste management, patient assessment, decontamination processes, as well as deisolation and discharge criteria. Again, centers are encouraged to share any new SOPs they have developed with other centers in the network. A national coordinator was appointed in 2023 to coordinate SOPs, assessments of standards, and training materials.

Patient transfer methods are harmonized across the network and centers are encouraged to work and train with NHS transport providers, such as HART paramedics, to ensure that open trolley/gurney and EpiShuttle transfers are completed safely and efficiently. Special consideration needs to be given to pediatric transport, particularly when considering conscious, young children. An EpiShuttle transfer may not be the safest or appropriate mode of transport for a child, but this risk needs to be balanced with the safety of staff doing the transfer. Different pediatric A-HCID transport options are currently being considered at a national level in England, and a national HCID critical care transfer service is in development in 2024.

To minimize potential exposures to an HCID pathogen that could result in transmission, the general principle adopted by the A-HCID Network is to perform imaging only when it is essential to the clinical management of the patient and the imaging can be performed safely, with reasonable assurance of containment and/or removal of any HCID pathogen contamination. Where possible, imaging is performed within the patient’s isolation room by HCID-trained radiology staff wearing HCID PPE, such as a portable chest radiography. Cross-sectional imaging, such as a CT scan, can sometimes be performed, depending on the individual risk assessment and the ability to apply effective risk management practices that prevent exposure and transmission. Thoracic CT scanning is sought for all critically ill A-HCID patients. The movement of a patient between the isolation room and the radiology department must be carefully planned, with measures in place to avoid contamination of different parts of the hospital; this may include using transfer isolators within the hospital, performing imaging after all other patients have been seen, ensuring appropriate ventilation of the imaging suite, and decontaminating the imaging room before it is used for another patient.

Significant challenges for A-HCID treatment centers include the consistent application of enhanced IPC precautions needed to prevent exposure to respiratory droplets and aerosols that result in transmission. This includes the provision of enhanced PPE that is sufficiently safe, can be used by many staff following training, and is comfortable to wear for longer periods, such as when working in an intensive care isolation room. Following completion of a design and evaluation process with the UK Health and Safety Executive, the A-HCID network has selected a unified HCID powered air-purifying respirator (PAPR)-based PPE “treatment” ensemble (Figure 6A) to be used by all airborne treatment centers. This ensemble is being introduced across the A-HCID network in 2024 and supplements the existing HCID “assessment” PPE ensemble³ that is not PAPR-based, which can still be used for shorter periods of care for confirmed A-HCID cases (Figure 6B). The C-HCID network is implementing the same PAPR-based treatment PPE ensemble for its ward-based surge planning, and for the care of children with C-HCIDs (when providing care in a Trexler isolator is considered inappropriate or infeasible).

The challenges of ensuring adequate estate, storage space, PPE, and clinical expertise are ongoing. Experience has shown that the biggest challenge and pressure for A-HCID treatment centers has been staffing. Each center has developed its own model of care, agreed upon and supported by the network, which still adheres to the core HCID operating principles, and the requirements set out in the NHS England commissioning specifications. This includes the requirement to have nursing staff, buddies for donning and doffing, runners, and infectious disease doctors onsite, including outside of regular hours and solely for the care of A-HCID patients.

Many staff who provide care in A-HCID treatment centers do so on a voluntary basis, in addition to their usual work, which is a potential challenge and may not be sustainable in the long term; however, to date, there has been excellent engagement of staff at all A-HCID sites in providing care, even when the COVID-19 pandemic response made significant demands of staff in 2021 and 2022. In pediatric critical care, managing an A-HCID case has been shown to have a significant impact on the rest of the care services, including staffing and capacity of a limited national resource. This has prompted discussions regarding the development of an ethical framework. Cascade training of other staff, and mutual aid from adult and pediatric ID and critical care networks need to be continually developed to ensure resilience.

As with the C-HCID centers, the A-HCID centers are commissioned to care for a defined number of patients. Unlike the HLIUs that manage confirmed C-HCID cases, most A-HCID centers do not keep isolation beds empty and ready for immediate use for A-HCID care. Isolation rooms allocated to A-HCID care are multipurpose and activation typically requires existing occupants to be moved rapidly elsewhere, usually within the same hospital.

National A-HCID bed capacities were informed by likely scenarios, and as noted earlier, likelihoods and scenarios may change over time. The A-HCID centers have been able to accommodate additional patients in excess of commissioning expectations; however, this relies heavily on goodwill and the efforts of HCID staff, in addition to the support of the wider hospital and the ability of staff to respond in addition to doing their usual work. Future planning may need to identify HCID surge capacity beyond the HCID networks.

For the 2022 mpox outbreak, the 2 London adult A-HCID centers rapidly increased their HCID bed capacities (most UK mpox cases were in London) and other centers looked after mpox patients from outside their usual catchment areas. Within a few weeks of the mpox outbreak starting, and before A-HCID network maximal capacity was reached, efforts were made to identify and agree to additional capacity, using specialist regional infectious disease centers to provide safe care, including following the required HCID IPC standards. Undoubtedly, this response was informed by experiences from the COVID-19 response in early 2020, including when HCID bed capacity was exceeded in the A-HCID network in March 2020. Future A-HCID surge planning will consider the ability of busy, non-HCID hospitals to provide assistance and additional capacity for HCID patients, at what point they should be triggered, how to ensure HCID safe care standards are maintained, how their contributions will be recognized and financed, and what would happen if they also reached their maximal capacities.

Critical care for A-HCID patients is made more difficult by enhanced IPC requirements and, therefore, there is a lower threshold to engage critical care teams earlier. Staff–patient ratios may be higher for HCID patients, and this needs to be factored in to general staffing arrangements for the affected critical care department. All centers have specific protocols for safely managing medical emergencies, including cardiac arrest calls, affecting HCID patients. Typical critical care interventions, such as line insertions, airway management, and renal replacement therapy, as well as frequent personal care of the patient, need to be planned and performed carefully, and these can be more difficult due to HCID IPC requirements.