key: cord-1030447-jh7x0s1f authors: Rafferty, A. C.; Bofkin, K.; Hughes, W.; Souter, S.; Hosegood, I.; Hall, R. N.; Furuya-Kanamori, L.; Liu, B.; Regan, T.; Drane, M.; Halder, M.; Kelaher, C.; Kirk, M. title: Does 2x2 airplane passenger contact tracing for infectious respiratory pathogens work? A systematic review of the evidence. date: 2022-02-09 journal: nan DOI: 10.1101/2022.02.09.22270715 sha: f743ccbe96e2e84b543d75b1feef51b0b28982ee doc_id: 1030447 cord_uid: jh7x0s1f We critically appraise the literature regarding in-flight transmission of a range of respiratory infections to provide an evidence base for public health policies for contact tracing passengers, given the limited pathogen-specific data for SARS-CoV-2 currently available. Using PubMed, Web of Science, and other databases including preprints, we systematically reviewed evidence of in-flight transmission of infectious respiratory illnesses. A meta-analysis was conducted where total numbers of persons on board a specific flight was known, to calculate a pooled Attack Rate (AR) for a range of pathogens. The quality of the evidence provided was assessed using a bias assessment tool developed for in-flight transmission investigations. We identified 103 publications detailing 165 flight investigations. Overall, 43.7% (72/165) of investigations provided evidence for in-flight transmission. H1N1 influenza A virus had the highest reported pooled attack rate per 100 persons (AR= 1.17), followed by SARS-CoV-2 (AR=0.54) and SARS-CoV (AR = 0.32), Mycobacterium tuberculosis (AR= 0.25), and measles virus (AR= 0.09). There was high heterogeneity in estimates between studies, except for TB. Of the 72 investigations that provided evidence for in-flight transmission, 27 investigations were assessed as having a high level of evidence, 23 as medium, and 22 as low. One third of the investigations that reported on proximity of cases showed transmission occurring beyond the 2x2 seating area. We suggest that for emerging pathogens, in the absence of pathogen-specific evidence, the 2x2 system should not be used for contact tracing. Instead, alternate contact tracing protocols and close contact definitions for enclosed areas, such as the same cabin on an aircraft or other forms of transport, should be considered as part of a whole of journey approach. 3 46 reported on proximity of cases showed transmission occurring beyond the 2x2 seating area. 47 We suggest that for emerging pathogens, in the absence of pathogen-specific evidence, the 48 2x2 system should not be used for contact tracing. Instead, alternate contact tracing 49 protocols and close contact definitions for enclosed areas, such as the same cabin on an 50 aircraft or other forms of transport, should be considered as part of a whole of journey 51 approach. . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. 54 International travel has played a major role in the rapid global spread of SARS-CoV-2, the 55 pathogen responsible for COVID-19. [1] [2] [3] The initial response to the pandemic involved 56 restrictions on international travel, which has impacted airlines, commercial aviation, 57 tourism and associated industries. The air travel industry has progressively put in place a 58 variety of interventions to prevent infections occurring before, during and after flying. These 59 interventions include: pre-testing of passengers, physical distancing, enhanced hygiene and 60 cleaning within the aircraft, having passengers and crew wearing masks, leaving middle 61 seats free, and regular screening and testing of crew. [4] 62 Transmission of infectious respiratory pathogens in an aircraft setting is complex. Some of is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint 134 We modified the bias assessment tool for tuberculosis investigations (changing timeframes 135 from weeks to months) to account for the difference in transmission dynamics and the 136 timeframe for contact tracing appropriate for this pathogen (Appendix 2). Tuberculosis 137 studies were also complicated by the extended latency period and corresponding delays in is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. 150 Respiratory pathogens included in our review included SARS-CoV (n=5) [ is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint We evaluated that 46 investigations had a high level of evidence, 71 had medium, and 48 had a low level of evidence demonstrating in-flight transmission. The median evidence score of 5 (range: -1-9). Eight investigations achieved the highest score of 9, with four of these being investigations for SARS-CoV-2. These are detailed in Appendix 3. Of the 72 investigations providing evidence for in-flight transmission, 27 were assessed as having a high level of evidence, 23 as medium, and 22 as low. Breakdown by pathogen is detailed in Table 2 . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint We found strong evidence for in-flight transmission of a range of respiratory pathogens, particularly for SARS-CoV-2. We found that 48.7% (94/193) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint our review. [63] Treatment and post exposure measures are also applicable to Mycobacterium tuberculosis, with a similarly low attack rate (AR= 0.25). Due to the rapid spread of SARS-CoV-2 in 2020, investigations into in-flight transmission were likely to be more robust as a result of higher public awareness and intense public health response and a vaccine naïve population during the period included in this review. However, this also increases the potential for publication and confirmation bias. Just under half of the investigations that reported on proximity showed transmission occurring beyond the 2x2 area. However, this does not mean that public health agencies should not use the 2x2 area for contact tracing. We suggest that, where circumstances require, public health agencies may wish 7to extend tracing beyond the 2x2 zone. These circumstances could include flights in regions with a pathogen elimination strategy, where a novel or highly infectious pathogen has emerged, or where there are multiple infectious passengers on the flight. In these scenarios, public health agencies could use alternate contact tracing protocols and definitions of close contacts for enclosed areas, such as the same cabin on an aircraft or other forms of transport. This is particularly true for highly infectious variants of SARS-CoV-2, such as the Delta variant. [121] We observed considerable heterogeneity in attack rates between studies included in the meta-analysis. This is likely due to the stochastic nature of outbreaks, differences in outbreak investigation and logistical challenges presented by contact tracing on domestic and international flights. In addition, it is likely that the many instances where infectious cases transmitted to one or fewer persons were not published. Our review does not indicate how commonly cases did not transmit outside the 2x2 zone, but does indicate that it occurs . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint from time to time. In addition, many published reports of investigations involved multiple infectious cases on the same flight, which would lead to a higher infection pressure. We recommend that where public health investigators are alerted to infectious cases is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint instances where flight contact tracing was undertaken as part of outbreak investigations but never published. Our review included investigations into SARS-CoV-2 prior to roll-out of vaccines in countries, widespread immunity due to either natural infection or vaccination, and the emergence of variants of concern with known increases in transmissibility and reduction in incubation period. As such, some of our findings may not be applicable to the current circulating strains of SARS-CoV-2 and public health control measures in place at the time of publication, but our findings do highlight that the 2x2 system of contact tracing itself is not specific enough for contact tracing management of SARS-CoV-2 in all circumstances. We assessed the level of evidence using a bias and assessment tool that we adapted from Leitmeyer et al. [6] This allowed us to assess each investigation to determine the evidence level. We used the tool to assess the methods used in each investigation, which identified a high degree of heterogeneity. The methodological issues identified highlight the weakness of many investigations within this review, contributing to the overall median rating of medium evidence level in this review. The high proportion of investigations with low and medium evidence scores is attributable to the majority of investigations using the narrow 2x2 contact tracing strategies, the time between flight and commencement of contact tracing (often attributed to delays in clinical presentation and subsequent diagnosis), and the incomplete nature of contact tracing. All of these factors would lead to potentially missed secondary cases, introducing bias into the studies. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint unit to undertake a thorough contact tracing investigation to determine if in-flight transmission has occurred is limited due to multiple jurisdictions, international travel and lack of contact details for passengers who are in transit. This is highlighted in a number of multi-national investigations included in this review, where the same flights or cases were reported by different jurisdictions, such as a MERS virus outbreak that was investigated in the UK and the US [24, 25] and an international flight with a H1N1 investigation that was investigated by multiple jurisdictions. [86, 90] Asymptomatic infections may also be underreported as testing may only be conducted on symptomatic individuals. For SARS-CoV-2, many countries, including Australia and New Zealand, have required all incoming passengers to undertake mandatory quarantine in hotels or other purpose-built facilities where they are routinely tested therefore providing opportunities for more complete follow-up. [123] Case studies of in-flight outbreaks detail secondary cases that are identified with an epidemiological link and investigated further. As case studies do not assist in quantifying the risk of in-flight transmission, they should not solely be relied on as an evidence base, but rather provide an exploratory tool to prompt further study. The relevance of case studies decreases after the initial stages of pathogen emergence once robust epidemiological is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint wider contact tracing strategies depending on their local disease control priorities and resource constraints. Investigations using routine surveillance data are only appropriate for notifiable diseases resulting in health outcomes that require presentation to medical services. Otherwise, investigations are likely underreporting the occurrence of potential in-flight transmission. However, for the pathogen SARS-CoV-2, some countries have high levels of testing, including asymptomatic testing, meaning that there is high ascertainment of cases. Therefore, the use of surveillance systems may be adequate to evaluate potential in-flight transmission events for SARS-CoV-2 but is limited for other pathogens. In particular, the use of 2x2 contact tracing may reinforce the belief that it is effective if no tracing and testing occurs outside this zone. Surveillance systems are likely to underrepresent cases for notifiable diseases that are less common, cause mild illness, have no treatment, are relatively rare, or do not require a laboratory test for treatment and management. Retrospective analysis of surveillance data is not recommended as an investigative approach for public health action due to potential underreporting, inherent in surveillance systems, and lack of timeliness. In our review, we determined that air travel related transmission of pathogens responsible for many respiratory illnesses occurred outside of the standard 2x2 area for contact tracing. However, we have found overall that this evidence was only of a medium level of quality and raises questions about reliance upon a single 2x2 contact metric. In contrast, our findings indicate that in certain circumstances, a whole-of-flight or whole-of-journey approach may be necessary for contact tracing persons infected with emerging pathogens . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. The entire air travel process, from travel to an airport to departing the terminal at the end destination, needs to be considered in terms of infection control and interaction during public health investigations. This style of multilayered, approach has been recommended by the International Civil Aviation Organisation and IATA, and should be considered by public health authorities when investigating infectious respiratory diseases in the context of flight [124] . This multilayered approach will help protect public health and enable containment of infectious respiratory pathogens as international travel resumes. We acknowledge and thank our Australian and New Zealand health department and airline colleagues for their assistance with this review and participating in discussion regarding inflight transmission. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint . 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(2) [81] -- (1) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Bae, 2020 (1) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted February 9, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted February 9, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 9, 2022. ; https://doi.org/10.1101/2022.02.09.22270715 doi: medRxiv preprint