Submitted:
21 October 2026
Posted:
22 October 2026
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Abstract
Background/Objectives: The transport of patients with high-consequence infectious diseases (HCIDs) links biosafety science and emergency medicine. The 2026 Bundibugyo virus disease epidemic and the multinational Andes virus outbreak associated with an expedition cruise ship have renewed attention on how such patients are moved safely between the community, hospitals and high-level isolation units. This narrative review synthesises the international literature on biocontainment transport and integrates it into an operational framework for emergency medical systems. Methods: A structured search of PubMed/MEDLINE and Scopus (to 10 October 2026), complemented by guidance from the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention and national authorities, was conducted and reported according to the SANRA scale. Evidence was organised across seven operational domains and combined with the operational experience of the Italian Red Cross biocontainment transport service. Results: Of 2432 records identified, 1485 unique records were screened. The literature is dominated by aeromedical case reports, technical evaluations and expert consensus, with few comparative studies. Recurrent findings concern device integrity and air quality within transport isolators, the risk of self-contamination during doffing, heat strain and communication limits imposed by personal protective equipment, decontamination of vehicles and isolators, the maintenance of team readiness during periods of low activity, and the psychological burden on patients and staff. These findings are integrated into a framework comprising a four-link containment chain, a seven-phase operational workflow, a three-tier complexity classification and a role-based responsibility matrix. Conclusions: Biocontainment transport is better understood as an integrated emergency system than as a device-centred intervention. The proposed framework is a structured, consensus-based reference for planning, training and quality assurance; its components require prospective evaluation.
Keywords:
biocontainment
; high-consequence infectious diseases
; patient transport
; emergency medical ser-vices
; high-level containment transport
; personal protective equipment
; decontamination
; Ebola
; Andes virus
; narrative review
1. Introduction
High-consequence infectious diseases (HCIDs) are acute infections that are transmissible from person to person, cause severe illness with high case-fatality rates, and require enhanced infection prevention and control measures and specialised clinical care [1,2]. The group includes filovirus diseases (Ebola and Marburg), Lassa fever, Crimean-Congo haemorrhagic fever, Andes virus infection and emerging respiratory pathogens with pandemic potential [2,3]. Effective countermeasures are available only for a minority of these pathogens: no licensed vaccine or specific antiviral treatment is available for Bundibugyo virus [4], and no specific treatment is available for Andes virus infection, whose management remains largely supportive [3,5]. For these reasons, containment remains the cornerstone of safe clinical care.
Two events in 2026 have brought HCID transport back to the centre of preparedness planning. In May 2026 the World Health Organization (WHO) declared the Bundibugyo virus disease epidemic in the Democratic Republic of the Congo and Uganda a Public Health Emergency of International Concern [6,7]; health care workers were among the earliest cases [8], and imported cases were reported in Europe [9]. In the same weeks, an outbreak of Andes virus—the only hantavirus with documented person-to-person transmission—was linked to the expedition cruise ship MV Hondius, with 13 cases among passengers and crew of 23 nationalities and a coordinated international response that required medical evacuation, repatriation, isolation and quarantine across several countries [10,11,12]. Both events required the safe movement of patients between the community, ports, airports, hospitals and high-level isolation units (HLIUs).
The containment of patients with dangerous infections has a long history. Flexible-film isolators were developed from gnotobiotic research and, in their negative-pressure version, used in hospitals for patients with dangerous infections in the 1970s [13,14,15]; dedicated containment care units originated alongside the biosafety level (BSL) 4 laboratories of the US Army Medical Research Institute of Infectious Diseases in the late 1960s [16,17]; and containment aircraft transit isolators and aeromedical isolation teams were developed to move patients without interrupting the containment chain [18,19]. The 2014–2016 West African Ebola epidemic, and later the COVID-19 pandemic, prompted European and North American health systems to expand and formalise high-level containment transport (HLCT) [20,21,22].
Published reviews have focused mainly on aeromedical evacuation [20,21], whereas ground transport—the most frequent modality in daily practice—has received less attention [23,24]. Surveys have documented heterogeneous national arrangements, with only a minority of European isolation centres reporting both national and local guidelines for HCID patient transport [24]. Most of the available evidence consists of case reports, technical evaluations and expert consensus, and no single source addresses devices, procedures, team governance and human factors together.
In Italy, the Public Health Unit of the Italian Red Cross (CRI) has operated a biocontainment transport service since 2006 under an agreement with the Ministry of Health; according to the service's activity records (unpublished data), between December 2020 and March 2022 it performed 1585 transports, covering 188,305 km and involving 2326 patients, during the COVID-19 pandemic. This experience generated operational procedures that have been only partially described in the literature [23].
The aim of this narrative review is therefore twofold: (i) to synthesise the international literature and guidance on the biocontainment transport of HCID patients across its main operational domains, and (ii) to integrate this evidence with the operational experience of the CRI service into a structured framework for emergency medical systems. The framework is presented as a consensus-based reference to support planning, training and quality assurance; it is not an empirical evaluation of transport outcomes.
2. Methods
This narrative review was prepared according to the Scale for the Assessment of Narrative Review Articles (SANRA) [25]. A structured literature search was conducted in PubMed/MEDLINE and Scopus from database inception to 10 October 2026. Search strings combined terms for HCIDs and high-level containment (e.g., "biocontainment", "high-level isolation", "Ebola", "Marburg", "Lassa", "viral haemorrhagic fever", "hantavirus") with terms for patient transport and emergency medical services (e.g., "patient transport", "ambulance", "prehospital", "aeromedical", "transport isolator"). Six additional domain-specific searches addressed personal protective equipment (PPE), decontamination, the psychological impact on staff, governance, training and networks, isolation transport of COVID-19 patients, and person-to-person transmission of Andes virus. The complete search strings are reported in Supplementary Table S1. In Scopus, results were limited to English and Italian at the search stage; for PubMed records, the same language restriction was applied during screening.
Grey literature was retrieved from the websites of WHO, the European Centre for Disease Prevention and Control (ECDC), the US Centers for Disease Control and Prevention (CDC), the National Emerging Special Pathogens Training and Education Center (NETEC), the UK Health Security Agency and the Italian Ministry of Health, and reference lists of included articles were hand-searched. Records were eligible if they addressed the transport or prehospital management of patients with suspected or confirmed HCIDs, or the use of high-level containment transport devices, and were relevant to at least one domain of the framework: biosafety and devices; PPE; decontamination; operational workflow; complexity stratification and team composition; governance, training and networks; and human factors. Primary studies, reviews, case reports and series, technical evaluations and guidance documents were considered. Laboratory, molecular and veterinary studies without operational content, hospital infection control studies unrelated to these domains, and conference abstracts were excluded.
The searches identified 2432 records (PubMed, n = 1004; Scopus, n = 1428). After removal of 947 duplicates, 1485 unique records were screened on title and abstract; 1283 were excluded (1212 not relevant, 57 for language, 14 further duplicates or superseded versions), and 202 were assessed for their contribution to each domain. When several sources reported overlapping evidence, the most recent, most comprehensive or highest-level source (systematic reviews and guidance documents over single reports) was retained. In total, 100 sources identified through the database searches and 17 guidance documents, standards and other sources are cited in this review. Titles and abstracts were screened by one author (F.D.), supported by a preliminary AI-assisted classification that was verified record by record. The evidence was synthesised narratively by domain. Where published evidence was unavailable, operational content is explicitly identified as derived from the authors' field experience within the CRI biocontainment transport programme. All outputs were checked against the original sources and revised by the authors, who take full responsibility for the selection, synthesis and interpretation of the evidence.
3. Biosafety Framework and the Containment Chain
Biological agents are classified into four risk groups according to their infectivity, pathogenicity, transmissibility and the availability of prophylaxis or treatment, and laboratory work is matched to four corresponding containment levels [26,27,28]. HCID pathogens belong mainly to risk group 4 (e.g., Ebola, Marburg and Lassa viruses) and, for selected respiratory pathogens, to risk group 3 [26]. Translating these principles to patient care requires attention to the actual routes of transmission. Early analyses of viral haemorrhagic fevers identified parenteral inoculation of staff as the main danger and indicated that fomites and droplets must also be considered, whereas the role of small-particle aerosols remained debated [29]. Consensus recommendations of the European Network for Infectious Diseases (EUNID) built on this evidence to define infection control requirements for the clinical management of highly infectious diseases, including invasive procedures [2]. For Andes virus, viral RNA is consistently detectable in blood during the acute phase and infectious virus has been recovered from several body fluids, including saliva, gingival crevicular fluid, nasopharyngeal secretions and urine [30], supporting contact, droplet and airborne precautions during close patient contact. Current recommendations for Andes virus combine an airborne infection isolation room with gown, gloves, eye protection and an N95 or higher-level respirator, within a layered, risk-based approach that reflects the uncertainty about the timing and route of infectiousness [3].
Compared with a fixed HLIU, the mobile environment adds vibration, acceleration, confined space, variable climate, prolonged task duration and limited access to the patient. Within the framework proposed here, safety during transport is conceptualised as a containment chain of four interdependent links: (1) PPE; (2) the physical containment envelope of the transport isolator or vehicle compartment; (3) negative pressure with high-efficiency particulate air (HEPA) filtration; and (4) structured decontamination. By analogy with the chain of survival, the failure of any single link can compromise the integrity of the whole system. This conceptual model reflects the authors' operational consensus; the evidence relating to each link is reviewed in the following sections.
4. Transport Platforms and Device Architecture
The single-patient stretcher isolator is the primary physical barrier between the patient and the environment. Italian technical requirements for the transport of patients infected with risk group 4 agents specify, among other features, assembly within minutes, a sealed envelope, a negative pressure gradient greater than 6 Pa with respect to the external environment, HEPA filtration of at least class H13 according to EN 1822, battery autonomy of at least 10 hours and an airflow of 35–40 m³/h [31,32]. Air enters through a pre-filter at the foot of the isolator and is exhausted through the HEPA filter at the head end, so that small breaches of the envelope result in inward rather than outward airflow. Experimental studies of flexible-film negative-pressure isolators confirmed a high degree of containment and protection of staff when operated correctly [14,15]. The CRI service uses a stretcher isolator of this type (Isoark N36, Beth-El Industries, Israel), whose care protocols during road transfer have been described previously [23].
The technical literature identifies several vulnerabilities of transport devices. During a ground transport exercise of approximately 257 miles, carbon dioxide and humidity accumulated inside a stretcher isolator, reaching steady-state CO₂ concentrations of about 3000–4400 ppm; when failure of the blower unit was simulated, CO₂ exceeded 10,000 ppm within 8 minutes [33]. These data support systematic verification of the blower, filters and battery before departure and continuous monitoring of the patient during transport. In the aeromedical setting, a standard isolation unit lost leak tightness after a simulated explosive cabin decompression because the envelope ruptured from over-expansion [34]. In ground ambulances, an Ebola infection in a driver in Sierra Leone was attributed to body fluids leaking from the patient compartment into the cab [35]; an assessment of 14 vehicles found that the wall separating the two compartments often lacked a waterproof seal, that bulk body fluids were not removed before disinfection and that pressure from chlorine sprayers may have pushed fluids into the cab [35]. In the United States, the patient compartment of the ambulance was stripped of non-essential items and lined with a continuous envelope of plastic sheeting, and the cab was sealed from the patient compartment [36]. Conversely, a negative-pressure containment pod with filtration installed in the patient module of an ambulance reduced aerosol concentrations in the workspace [37].
Portable isolation units with the clinical team outside the envelope, widely used during the COVID-19 pandemic, enable long-distance transport but limit access to the patient. In a series of 13 long-distance aeromedical transports of COVID-19 patients in a portable isolation unit, the main limitations were restricted access, reduced manual dexterity through porthole gloves and line disconnections during loading; one patient experienced endotracheal tube displacement [38]. Reduced dexterity when working through containment systems has also been documented experimentally [39]. The 2025 national exercise of the US Portable Biocontainment Unit showed that paediatric transport requires specific planning, as children reported anxiety related to noise, vibration, movement and the appearance of staff in PPE, as well as communication difficulties [40].
Beyond single-patient isolators, the framework includes multi-patient systems: modified minibuses or coaches with an internal envelope and one or more HEPA-filtered negative-pressure units, used to move groups of ambulatory patients who do not require vital support, and portable isolation chambers for intra-hospital settings without fixed isolation rooms. Collective transport of critically ill patients has also been performed by air: a risk analysis based on failure modes, effects and criticality analysis allowed six flights carrying 36 critically ill COVID-19 patients without reported harm to patients or staff [41]. Finally, interoperability between devices—through connecting sleeves and transfer ports—allows a patient to be moved from a transport isolator to a fixed isolation room without interrupting the containment chain; where transfer ports are not available, the isolator is introduced into the receiving room before the patient is transferred.
5. Personal Protective Equipment
PPE is the link of the containment chain that depends most directly on human performance. A Cochrane review of PPE for highly infectious diseases found low- to very-low-certainty evidence that covering more of the body improves protection, usually at the cost of more difficult donning and doffing and lower comfort; double gloving, following structured doffing guidance, spoken instructions during doffing and glove disinfection before removal may reduce contamination [42]. A series of rapid reviews, with certainty of evidence assessed using GRADE, informed the WHO infection prevention and control guideline for Ebola and Marburg disease [1,43]. Heat stress imposed by PPE in hot environments is itself a safety risk [44], and a literature review of physiological strain in HCID care identified heat strain and dehydration as an occupational health concern that can impair performance [45]. These data support the principle, adopted in the framework, that PPE selection must balance biological protection, chemical resistance to the selected decontaminant and ergonomic compatibility with the wearer's role [46,47].
Doffing is the most critical phase. In a simulation study, all health care workers wearing Ebola-level PPE made at least one protocol deviation during doffing, and some deviations were committed by the doffing assistants or trained observers themselves [48]. Using surrogate viruses, a structured doffing protocol supervised by a trained monitor protected against self-contamination with enveloped virus, while contamination with a non-enveloped surrogate persisted on inner gloves when alcohol-based hand rub was used for glove hygiene [49]. In a randomised trial, an intervention package combined with teamwork training significantly reduced self-contamination and improved teamwork scores [50]. Consensus documents have translated these findings into unified PPE ensembles and core principles applicable across protocols [46,47].
Several aspects are specific to transport. Prolonged transports require a prospective plan for PPE changes, because comfort decreases and the risk of inadvertent self-contamination increases over time [44,45]. Powered air-purifying respirators reduce speech intelligibility, mainly because of fan noise: in a pilot study only 67% of spoken words were correctly identified, and one model scored below the 70% benchmark used for respirator certification [51]. PPE impairs communication among staff, between staff and patients and between patients and their families, and closed-loop communication has been adopted to mitigate these barriers [52]; in the framework, laryngophones or in-ear radio systems are positioned so as not to interfere with the doffing sequence. In a randomised manikin trial, the quality of cardiopulmonary resuscitation was not affected by chemical-biological-radiological-nuclear PPE, whereas tourniquet application, decompression of tension pneumothorax and peripheral venous and intraosseous access took significantly longer [53]; reduced dexterity is a recognised limitation of both PPE and isolator glove ports [38,39]. For outer gloves, the framework distinguishes between operators who handle isolator zippers, for whom cut-resistant neoprene gloves are preferred, and clinicians who need tactile sensitivity, who use nitrile gloves; because the acceptable quality level of gloves is self-declared by manufacturers in Europe, it should be considered in procurement. Driver PPE must remain compatible with safe vehicle operation: sealed boots impair pedal control and fogging of eye protection reduces visual acuity, so individual fitting trials are recommended. For Andes virus, recommendations on respiratory protection changed during the 2026 outbreak—from medical masks to FFP2 or N95 respirators for passengers and crew—exposing the absence of clear guidance for outbreaks with person-to-person transmission [3,54].
6. Decontamination
In the framework, decontamination is a multi-stage process performed at defined time points—on departure from the point of origin, on arrival at the destination and on return to base—and subdivided into technical decontamination (chemical inactivation at a safe distance), remediation and physical cleaning. Disinfectant selection must consider both virucidal efficacy and compatibility with materials. Sodium hypochlorite is effective but corrosive; in a contact-kill assay against Ebola virus on aircraft-relevant materials, an aircraft cleaning product performed similarly to hypochlorite without its corrosive properties [55]. Standard operating procedures for disinfecting aircraft after a suspected highly infectious disease case have been defined [56], and an aerosol-based protocol has recently been proposed to reconcile antimicrobial efficacy with material compatibility in areas that are inaccessible to manual disinfection [57]. Laboratory evidence on hygiene and virucidal interventions has also been summarised for the two pathogens of the 2026 events, Bundibugyo virus and Andes virus [58].
Volumetric methods complement surface disinfection. Hydrogen peroxide vapour was used for the terminal decontamination of the isolators and rooms of a UK HLIU after an Ebola case and allowed the unit to return to service more quickly than formaldehyde [59]. For a portable isolation unit, fumigation with hydrogen peroxide achieved complete inactivation of biological indicators but only limited inactivation of a viral surrogate suspended in organic liquids, which led to a combined protocol of fumigation, surface wiping and a second fumigation [60]. These findings, together with the observation that high-pressure spraying of chlorine in an ambulance whose bulk fluids had not been removed may have spread contamination [35], support the sequence used in the framework, in which gross contamination is removed at low pressure before volumetric and surface decontamination. In Europe, protocols for the disinfection of ambulances and equipment were available in about 70% of isolation centres in 2009 [24]. The framework includes the preferred organisational model of a decontamination unit with unidirectional personnel flow, negative pressure, doffing stations and waste collection, and the minimum requirement of an improvised station with contained waste collection under field conditions.
Finally, the framework proposes monitoring of decontaminant consumption per transport as an indirect quality indicator: a sudden reduction in consumption at constant activity should prompt a procedural review by the coordinator, because it may signal the omission of decontamination steps. This indicator derives from the authors' operational experience and has not been formally validated.
7. Operational Workflow
Reviews of aeromedical HLCT have organised best practices into pre-flight, in-flight and post-flight phases [20,21], and similar structures are described for ground transport by emergency medical services (EMS), whose experience in the United States emphasised ambulance preparation, PPE selection and environmental decontamination [36]. National and regional systems have formalised these elements in concepts of operations [61], dedicated transport teams [62], combined land–air evacuation pathways [63], military aeromedical capabilities [64,65,66] and guidance from public health agencies [67,68,69]. In Italy, it has been recommended that HCID transports be performed by specialised teams linked to HLIUs rather than by routine EMS ambulances, using vehicles with controlled ventilation, negative pressure, HEPA filtration, intercom systems and separation of the driver from the patient, and combining domestic aeromedical flights with special ambulances over long distances; PPE alone is not sufficient without extensive training and dedicated areas for ambulance decontamination [70]. Since 2005 the Italian Air Force has maintained a rapid-response aeromedical isolation team at Pratica di Mare, using aircraft transit isolators and staffed by teams of at least three physicians (team leader, infectious disease specialist and anaesthesiologist) and six nurses, in formal collaboration with the Spallanzani Institute [65]; its first operational flight, in 2006, transported a patient with multidrug-resistant tuberculosis [64,66]. Comparisons of guidelines in Western countries [71] and European surveys [22,24] show considerable variability in equipment, staffing and procedures.
The framework structures each mission into seven sequential phases: pre-alert/alert, materials preparation, initial briefing, transport, decontamination, materials restoration and debriefing. During pre-alert, the coordinator collects structured information on the patient (weight, mobility, confirmed or suspected diagnosis, current vital support, monitoring needs and clinical complexity) and on logistics (origin and destination, access routes, vertical mobility constraints and manoeuvring space for the isolator). Materials preparation includes isolator assembly and a pre-transport checklist covering the integrity of the envelope and zipper, the closure of access ports and cable glands, the integrity of glove ports, the installation and locking of the HEPA filter, the battery charge and the negative-pressure function. In the CRI protocol, negative pressure is measured at three points (head, centre and feet) with a differential manometer and compared with the device reference value: a progressive decline over successive transports suggests filter saturation, whereas an abrupt decline suggests an acute structural or mechanical failure. The air-quality data described above [33] support including ventilation and blower function in this check.
The initial briefing consolidates information among team members and external agencies. Transport execution comprises patient preparation, loading, monitoring during transport and handover at destination, with specific adaptations for mechanical ventilation and multiple infusions. Debriefing after each mission supports procedural review and, after high-intensity operations, psychological defusing facilitated by a trained mental health professional (Section 10).
Large-scale operations add a coordination dimension. During the first COVID-19 wave, a regional medical evacuation operation in Lombardy transferred 121 intensive care patients, mostly by air, to other Italian regions and to Germany, with outcomes comparable to those of patients who remained in regional intensive care units and one life-threatening event during transport [72]. Aeromedical evacuation to the Spallanzani Institute in Rome was used for patients with COVID-19 and complex coinfections [73]. A global tabletop exercise on long-range air transport of patients with viral haemorrhagic fever found that many countries rely on the same organisations for this capability, which may become a bottleneck when several countries request evacuation simultaneously [74]. A review of EMS in the United States identified non-standardised licensing, inconsistent medical direction and difficulties in implementing PPE as vulnerabilities to HCIDs [75].
8. Complexity Stratification and Team Composition
During the COVID-19 pandemic, the heterogeneity of patients—from ambulatory, mildly symptomatic individuals to mechanically ventilated patients—required a scalable approach to device selection and staffing. The framework uses a classification algorithm based on parameters that can be assessed quickly by the coordinator: mobility status, presence of monitoring devices, need for oxygen therapy and flow rate, need for mechanical ventilation or supraglottic airway management, and type of transfer (intra-hospital, extra-hospital or aeromedical). Three complexity levels are defined (Table 1). This classification is based on expert consensus within the CRI service and has not been validated against clinical outcomes.
High-complexity transports are supported by a growing clinical literature. Invasive organ support has been provided within isolator tents in a UK HLIU without additional risk to staff [76]. For hantavirus cardiopulmonary syndrome, for which no cure exists, extracorporeal membrane oxygenation (ECMO) has improved survival and early recognition is essential during critical care transport [5]; prone positioning has been used during transfer as a bridge to ECMO [77], and imported Andes virus infection in Europe required prolonged ECMO together with infection control measures for persistent viral shedding [78]. For aeromedical evacuation, patients should be stabilised before departure, and procedures that may be needed in flight—such as intubation and the placement of intravenous lines and urinary catheters—should preferably be performed in the departure hospital, also because of hypoxia and gas expansion at altitude [65]. Reports of tube displacement and line disconnection in portable isolation units [38] and the use of formal risk analysis for collective transport [41] indicate that high-complexity transports require dedicated critical care staff and pre-planned procedures for airway and vascular access management inside the envelope.
The type of transfer further modulates complexity. Intra-hospital transfers focus on maintaining clean pathways. Extra-hospital transfers introduce distance-dependent requirements—short-range (within the area of the originating facility), medium-range (within the province) and long-range (inter-provincial or inter-regional)—concerning reserve PPE, en-route decontamination capacity and planned stops. Aeromedical transfers add requirements related to cabin pressure, gas expansion within devices [34] and aviation certification.
9. Governance, Networks and Competency Maintenance
The framework assigns accountability for each operational domain through a responsibility matrix rather than a purely hierarchical structure (Table 2). Five functional roles are identified: biocontainment technician (device logistics and decontamination), team leader (operational coordination and quality supervision within the vehicle), coordinator (overall transport management and resource planning, external to direct intervention), physician (clinical decision-making) and nurse (clinical patient management in support of, or in the absence of, the physician). The clinical component is activated according to the complexity level, so that clinical care never compromises the integrity of the containment chain.
Comparable governance tools have been described in fixed facilities: the incident command system has been adapted to the activation of hospital biocontainment units [79], and HLIU frameworks developed by European consensus define organisational and infection control requirements [2,80]. At the system level, the US National Special Pathogen System of Care stratifies facilities by capability [81], the German STAKOB network links public health competence centres and treatment centres [82], and global analyses have mapped HLIU capabilities and gaps [83,84]. In Italy, the Spallanzani Institute has described its response model for viral haemorrhagic fevers [85], and new biocontainment capacity has been developed at regional level [86]. Transport services need to be integrated into these networks, with shared protocols for handover and for compatible devices [61,62].
Competency maintenance is a continuing governance responsibility, particularly for teams with low operational frequency, in whom procedural drift—the progressive, unconscious omission of critical steps—may occur. A 12-year analysis in an HCID hospital found a bimodal pattern of occupational exposure, with the highest exposure density among staff with less than two years of experience and a renewed increase among staff with more than ten years, which the authors linked to complacency and burnout [87]. Among US critical care air transport clinicians, those without recent operational experience were no more likely to pass revalidation than first-time students [88]. Readiness checklists used during periods of inactivity identified staffing and waste management as the greatest threats to activation [89], and staffing and just-in-time training remain common challenges across HLIUs [90]. Interventions supported by the literature include simulation-based mastery learning for PPE [91], safety officers who monitor staff safety during care and transport [92], supervision of PPE practices with real-time feedback [93], buddy systems with frequent training [94] and the explicit adoption of high-reliability principles [95]. Scheduled full-scale exercises with complete PPE and representative isolators are therefore the primary mitigation strategy in the framework, complemented by indirect indicators such as decontaminant consumption (Section 6).
10. Human Factors: Patient and Operator Dimensions
For conscious patients, the transport isolator imposes physical confinement, a muffled acoustic environment and reduced physical contact with caregivers. Patients treated for Ebola in a biocontainment unit described feelings of lack of control, social and emotional isolation and loneliness, to which staff PPE contributed [96]. Children in the US Portable Biocontainment Unit reported anxiety related to noise, vibration and the appearance of staff in PPE, and communication difficulties were common [40]. During aeromedical evacuation in an aircraft transit isolator, the predicted incidence of motion sickness was about 2% for a 6-hour flight, supporting individual rather than routine prophylaxis [97]. Confinement within the isolator is itself recognised as a psychological stressor during aeromedical evacuation [65]. Telemedicine platforms have been developed to support communication with isolated patients [98]. In the framework, a clear pre-transport explanation of the device and of each phase is the primary non-pharmacological intervention; synchronised team behaviour and calm, professional communication reassure the patient, and light procedural sedation may be considered by the physician when these measures are insufficient.
For staff, systematic reviews and meta-analyses consistently show a psychological burden among health care workers involved in epidemic and pandemic responses. Compared with lower-risk colleagues, staff in direct contact with affected patients had higher odds of acute or post-traumatic stress and psychological distress [99]; frequent symptoms included concern about transmitting infection to family members, perceived stress, sleep difficulties and burnout [100]. Workers in a US biocontainment unit reported isolation, changes in home life and episodes of discrimination, and many used behavioural health counselling [101]. Psychological stress was also reported among health care professionals caring for Ebola patients in Europe [102]; the experience of Red Cross nurses deployed to an Ebola treatment centre highlighted the need for preparation and support before, during and after deployment [103]; and among EMS providers, whose perceived danger decreased with adequate education and transparent communication from their organisation [104]. During the 2026 Bundibugyo virus disease response, a minimum package of mental health and psychosocial support has been proposed, spanning preparation before deployment, protection and support during the response, confidential follow-up afterwards and continuous learning, and including psychological first aid, peer support, supportive supervision and referral pathways; robust comparative evidence of effectiveness, however, remains scarce [105].
Evidence on interventions remains limited. A Cochrane mixed-methods review of interventions to support the resilience and mental health of frontline workers found limited evidence on the effectiveness of such interventions [106], and a systematic review of early interventions identified psychological first aid, eye movement desensitisation and reprocessing, and trauma risk management as the approaches with the most consistent support [107]. In the framework, structured debriefing after each mission and psychological defusing after high-intensity events, facilitated by trained professionals, are used as organisational tools for early identification of stress and referral to occupational mental health services, rather than as treatments. Coordinators and team leaders share responsibility for recognising early signs of stress. These elements are derived from field experience and require formal evaluation with validated instruments.
11. The Integrated Operational Framework
Table 3 summarises the framework by domain, together with the main supporting evidence and the level of evidence on which each component rests. The framework combines four elements: the four-link containment chain; the seven-phase operational workflow with its pre-transport checklist; the three-tier complexity classification that links patient characteristics to devices and team composition; and the responsibility matrix that defines accountability across domains. Human factors and competency maintenance are treated as structural components rather than ancillary considerations. Most components rest on regulatory requirements, technical evaluations and expert consensus; only a few are supported by comparative studies.
12. Discussion
This review shows that the literature on biocontainment transport is fragmented and largely descriptive. Aeromedical evacuation is better documented than ground transport, and evidence on devices, PPE and decontamination comes mainly from technical evaluations and simulation studies, while governance and human factors are addressed mostly by qualitative studies and expert consensus. The contribution of the proposed framework lies not in new devices or techniques but in the explicit integration of these domains, which may help emergency medical systems to plan, train and audit HCID transport. Its novelty is therefore modest, and its value should be judged by its usefulness as a structured reference rather than as evidence of effectiveness.
The 2026 events illustrate why each domain matters. A systematic review of health care-associated Andes virus exposures found that infections among health care personnel occurred when transmission-based precautions were delayed or breached, with none or inadequate PPE in the reports describing such infections [108]; household and nosocomial transmission had already been documented in Chile [109]. During the 2026 outbreak, a health care worker not directly involved in patient care had a transient low-positive PCR result without seroconversion, suggesting that asymptomatic infection after indirect exposure may occur [110]. In Spain, the response relied on the network of high-level isolation and treatment units built after the 2014 Ebola epidemic [111]; in Italy, regional public health services implemented rapid surveillance of high-risk contacts [112]; and reports from the multinational response described challenges for prehospital care, health care facilities and public health systems [113]. A rapid assessment by the European Society of Clinical Microbiology and Infectious Diseases recommended standard and contact precautions for health care workers caring for suspected cases, noting that airborne precautions with N95 or FFP2 respirators would have been reasonable, and highlighted that, in maritime settings, the land-based location of advanced critical care leaves a narrow window within which a critically ill patient can be transferred safely [114]. Earlier reports of nosocomial Crimean-Congo haemorrhagic fever after aeromedical evacuation [115] and of Lassa fever without transmission to health care workers under standard precautions [116] show that the risk depends strongly on clinical procedures and on the consistent application of precautions.
During the COVID-19 programme of the CRI service, personnel involved in biocontainment transport were included in an occupational health surveillance programme. Within this framework, no documented occupational infections attributable to biocontainment transport, and no confirmed patient-to-staff transmission events during transport, were identified. This observation is reported only as operational context and should not be interpreted as an estimate of risk: surveillance was not designed as a study, the number of exposed staff and the sensitivity of surveillance for asymptomatic infection were not formally assessed, the period largely coincided with the vaccination of health care workers against SARS-CoV-2, and SARS-CoV-2 is a risk group 3 pathogen, so the observation cannot be extrapolated to risk group 4 agents. Structured symptom-monitoring tools for staff, such as those developed for biocontainment units [117], could support a prospective assessment.
The framework may be transferable to other settings, including systems with limited resources, where the classification algorithm and responsibility matrix could help to allocate scarce biocontainment assets, and to other high-risk transport scenarios, such as chemical or radiological emergencies, in which a containment chain and clear team governance are equally required. Its transferability, however, has not been tested.
This review has limitations. As a narrative review, it is exposed to selection bias despite the structured search, and the synthesis is qualitative; screening was performed by a single author, supported by an AI-assisted preliminary classification, rather than by two independent reviewers. Only two databases and two languages were searched, and part of the relevant experience is reported in grey literature or not published. Many sources are case reports, simulation studies or expert opinion, so the certainty of the evidence is generally low. The operational components derive from a single organisation, the CRI, and some elements—particularly the coordinator role—may require adaptation to other institutional settings. The psychological content has not been assessed with validated instruments. Finally, the framework has not been prospectively validated.
Future work should include a prospective study of the CRI transport dataset, with ethical approval and appropriate statistical analysis, to describe activity, complexity and adverse events; validation of the complexity classification against clinical outcomes; evaluation of decontamination adherence and of the decontaminant-consumption indicator; and assessment of the psychological impact on transport staff with validated instruments, such as the Impact of Event Scale-Revised or the Maslach Burnout Inventory.
13. Conclusions
The transport of HCID patients is a critical and still poorly evidenced interface between biosafety and emergency medicine. The available literature supports attention to device integrity and air quality, safe doffing and the physiological limits of PPE, validated decontamination, the maintenance of team readiness and the psychological needs of patients and staff. The integrated framework proposed here—containment chain, operational workflow, complexity classification and responsibility matrix—organises these elements into a structured reference for emergency medical systems. Because it rests mainly on technical evidence and expert consensus, its components should be evaluated prospectively.
Supplementary Materials
The following supporting information can be downloaded at the website of this paper posted on Preprints.org, Table S1: Search strategies for PubMed and Scopus; Figure S1: Flow of record identification and selection.
Author Contributions
Conceptualisation, F.D. and U.A.; methodology, F.D.; formal analysis, F.D.; investigation, F.D., M.G.B., E.F. and U.A.; resources, F.D.; data curation, F.D.; writing—original draft preparation, F.D.; writing—review and editing, F.D., M.G.B., E.F. and U.A.; visualisation, F.D.; supervision, U.A.; project administration, F.D. and U.A. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Not applicable. This review is based on published literature and guidance documents and did not involve the collection of data from human participants.
Informed Consent Statement
Not applicable.
Data Availability Statement
No new data were created or analysed in this study. The search strategies are provided in the Supplementary Materials.
Acknowledgments
The authors thank all Italian Red Cross personnel—biocontainment technicians, nurses, physicians, drivers and coordinators—whose work in the biocontainment transport service informed the operational framework described in this review. During the preparation of this manuscript, the authors used AI for language editing of the text. The authors have reviewed and edited the output and take full responsibility for the content of this publication.
Conflicts of Interest
The authors declare no conflicts of interest.
Abbreviations
The following abbreviations are used in this manuscript:
| ATI | Aircraft transit isolator |
| BSL | Biosafety level |
| CDC | Centers for Disease Control and Prevention |
| CRI | Italian Red Cross (Croce Rossa Italiana) |
| ECDC | European Centre for Disease Prevention and Control |
| ECMO | Extracorporeal membrane oxygenation |
| EMS | Emergency medical services |
| EUNID | European Network for Infectious Diseases |
| HCID | High-consequence infectious disease |
| HCPS | Hantavirus cardiopulmonary syndrome |
| HEPA | High-efficiency particulate air |
| HLCT | High-level containment transport |
| HLIU | High-level isolation unit |
| NETEC | National Emerging Special Pathogens Training and Education Center |
| PPE | Personal protective equipment |
| SANRA | Scale for the Assessment of Narrative Review Articles |
| SGA | Supraglottic airway |
| WHO | World Health Organization |
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Table 1.
Transport complexity classification, clinical characteristics, recommended device and team composition (framework based on expert consensus).
Table 1.
Transport complexity classification, clinical characteristics, recommended device and team composition (framework based on expert consensus).
| Complexity | Clinical characteristics | Device | Team composition |
| Low | Ambulatory patient; no vital support; no monitoring | Stretcher isolator or biocontainment minibus | Minimum 2 (driver, operator); optimal 3 (dedicated driver, 2 operators) |
| Medium | Monitored patient; oxygen therapy <10 L/min; not intubated | Stretcher isolator on ambulance | Minimum 3 (driver, operator, nurse); optimal 4 (driver, operator, nurse, physician) |
| High | Intubated or SGA patient; mechanical ventilation; multiple infusion pumps; continuous monitoring | Stretcher isolator on dedicated biocontainment ambulance | Minimum 3 (driver, operator, physician); optimal 4 (driver, operator, critical care physician, nurse) |
SGA, supraglottic airway.
Table 2.
Responsibility matrix for biocontainment transport team roles across operational domains.
| Role | Pre-transport health assessment | Logistical assessment | Patient transfer | Decontamination | Clinical management during transport | Technical isolator management |
| Biocontainment technician | E | E | CC | E | ||
| Team leader | CC | C | C | CC | C | CC |
| Coordinator | E | V | E | |||
| Physician | E | CC | CC | E | CC | |
| Nurse | CC | CC | CC | CC | CC |
E, executes; V, verifies; C, coordinates; CC, collaborates.
Table 3.
Integrated operational framework: components, supporting evidence and level of evidence.
| Domain | Framework component | Main supporting evidence | Level of evidence |
| Biosafety and containment chain | Four-link containment chain (PPE, envelope, negative pressure with HEPA filtration, decontamination) | Risk group classification [26,27]; transmission routes [29,30]; EUNID consensus [2] | Regulatory standards; expert consensus |
| Devices | Isolator requirements; pre-transport verification of negative pressure, filter, blower and battery; interoperability | National requirements [31]; isolator containment [15]; air quality [33]; decompression [34]; ambulance compartment [35,37]; portable units [38,40] | Regulatory standards; technical evaluations; case reports |
| PPE | Role-specific PPE; supervised doffing; planned PPE changes; communication aids | Cochrane review [42]; WHO evidence synthesis [43]; doffing studies [48,49,50]; heat strain [44,45]; communication [51,52] | Systematic reviews (low certainty); simulation studies |
| Decontamination | Three time points; sequence of gross removal, volumetric and surface decontamination; consumption indicator | Disinfectant efficacy [55,58]; aircraft [56,57]; hydrogen peroxide vapour [59,60] | Laboratory and technical studies; indicator based on expert consensus |
| Operational workflow | Seven phases; structured pre-alert; checklist; debriefing | Aeromedical reviews [20,21]; EMS experience [36]; concepts of operations [61,62] | Reviews of case reports; expert consensus |
| Complexity and team | Three-tier classification linking patient status to device and team | Critical care in isolators [76]; HCPS transport [5,77,78]; risk analysis [41] | Case reports; expert consensus (not validated) |
| Governance and competency | Responsibility matrix; coordinator role; exercises; readiness monitoring | Incident command [79]; networks [81,82]; experience and revalidation [87,88]; readiness [89]; training [50,91] | Observational studies; expert consensus |
| Human factors | Pre-transport communication; debriefing and defusing; referral pathways | Patient experience [40,96]; staff burden [99,100,101]; interventions [106,107] | Systematic reviews; qualitative studies; expert consensus |
EUNID, European Network for Infectious Diseases; HCPS, hantavirus cardiopulmonary syndrome; HEPA, high-efficiency particulate air; PPE, personal protective equipment.
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