Infectious Disease Transmission by Arline Travel

Improvements in aviation technology have led to considerable growth of domestic and international flights...


Introduction
Following the Wright brothers' first powered flights in 1903, technological advancements in aeronautics have enabled aircraft to overcome distances that would have taken many months or weeks to complete by terrestrial modes in a matter of hours by air [1]. Commercial aircraft carry over 3 billion passengers annually [2] and provide transport not only for cargo and people but also infectious disease. Smallpox, measles, tuberculosis, SARS and seasonal influenza are documented to have been transmitted during commercial flights [3]. Infections may be spread within aircrafts through close contact and by mean of large droplets; airborne spread through small-particle aerosols (as in the case of Severe Acute Respiratory Syndrome [SARS]), through contaminated food or infectious disease vectors (insects, rodents or parasites). Perhaps the greatest concern for global health is the ability of a person with a contagious illness to travel virtually to any part of the world within 24 hours and spread disease across considerable distances [4]. Infected passengers can arrive at their destination during an asymptomatic incubation period and transmit disease without detection [5]. The first decade of the 21 st century witnessed the emergence and worldwide spread of two major global epidemics: SARS in 2003 a H1N1 Influenza Virus pandemic of 2009 [6] and most recently the global SARS-CoV-2 pandemic [7]. In all three cases diseases rapidly spread across the globe in a matter of weeks to months, a process linked directly to long-distance traffic routes Despite many respiratory pathogens being primarily transmitted through direct contact and large droplet spread, few such as Mycoplasma pneumoniae, Influenza Virus, and Measles Virus may also be transmitted through airborne routes [9]. Opportunities for disease spread associated with commercial flight are considerable and include contact with contaminated fomites (counter tops, seats, trays, handrails, toilets, etc.), from close-quarters movement of the passengers while boarding, seating proximity during the flight, or in waiting areas or lines before boarding or after deplaning [10]. Increases in arthropod-borne viruses (Arboviruses) spread have been, in part, attributed to increased air travel harboring mosquito vectors which carry West Nile, Japanese Encephalitis, Venezuelan Equine Encephalitis, Rift Valley Fever, Dengue, Yellow Fever, Chikungunya, and Zika [11]. However, most commonly reported diseases transmitted on aircraft have been spread by the fecal-oral route via contaminated food. A total of 41 in-flight foodborne outbreaks resulting in 11 deaths were documented between 1947 and 1999 [12]. The most commonly implicated culprits are salmonellae, shigellae, and Vibrio cholerae. Although incidence of transmission of infectious diseases by contagious co-passengers remains relatively uncommon [13], International Health Protection Authorities are encouraged to join forces and focus on the problem of epidemic spread via civil aviation because contamination of aircraft by infected passengers is an alarming, documented reality and cause of concern in the absence of World Health Organization (WHO) guidelines for disinfection of pathogenic agents on aircraft [14].

Air Travel
Air travel appears to have been a dream of the earliest human civilizations as evidenced by the commonly represented winged human archetypes in art and paintings and myths of human flight (notably Icarus) provide evidence of an ancient aspiration to effortlessly cover vast distances with the ease. Early attempts to imitate the natural flight of birds were constrained by limits of human anatomy and physiology. Designs of failed attempts revealed an incomplete understanding of aerodynamics and ineffective power to weight ratios that kept early attempts at flight grounded. Not until the Wright brothers combined their mechanical expertise with an engine capable of delivering sufficient power to provide necessary aerodynamic lift did humans finally launch the era of air travel. The first flights at Kitty Hawk in North Carolina (USA) laid the foundation for technological developments which led to considerable improvements in aerospace engineering and eventually ventures into space. Along the way, air travel presented challenges to the first aeronautic explorers; drafty, unheated, unpressurized flights required flyers to dress warmly to combat cold and carry oxygen to survive the hypoxic atmosphere of high altitudes [1].
Modern commercial passenger cabins, however, are regulated by an environmental system that controls pressurization, temperature, ventilation, and air filtration [12] and provide a comfortable flying experience for the masses. The comforts of modern air travel support a global air transportation network with over three billion passengers travelling between more than 4000 airports on more than 50 million flights a year. This unprecedented mobility effectively connects all corners of the populated globe via airways transporting goods, cargo, and people but also plays an important role in worldwide spread of infectious diseases [15][16][17][18][19] Modern airports, all fewer than 18 hours apart, serve not only as nodes of transport but also transit points for the worldwide spread of disease [20]. Peoples. Yersinia pestis, the bacterium responsible for the plague, for example, was able to thrive and prolong its European spread into the 14 th and 15 th century due to dispersion of asymptomatic carriers trying to escape the foci of disease and unwittingly transmitting the contagion to naïve populations. Likewise, Spanish explorers introduced smallpox chickenpox, and measles to Native American populations who had no immunity against these pathogens with catastrophic consequences. Exposure to these never-before seen infections contributed considerably to the downfall of ancient empires of the New World brought to ruin by a combination of conventional and biological warfare. The conquering Europeans, in return, acquired Treponema pallidum, the spirochete that causes the sexually transmitted disease syphilis, and spread the infection throughout the Old World over subsequent centuries causing disfiguring morbidity and death among rulers and peasants alike.

Historical Spread of Infectious Disease by Intercontinental Travel
Prior to the advent of industrialization, intercontinental voyages required months at sea. Travelers displaying disease symptoms that could not be addressed by the modest medical means available during a voyage were often dispatched overboard without reaching their destination. This selected for the spread of infectious diseases that could remain asymptomatic for longer times. Ignorance of the germ theory made it impossible to recognize the cause of disease contagion, this assisted infectious agents overcoming long journeys, in some cases, without the realization of the ignorant hosts. Technological advances shortened travel times and brought about the advent of epidemics spreading faster such as the 1918-1920 influenza pandemic which infected 500 million people worldwide with an estimated 50 to 100 million deaths [21].
Faster transit times allowed infected passengers to traverse vaster distances spreading contagion not only to fellow travelers before any symptoms appeared but also at their port of arrival. Perhaps not coincidentally, onset of flu symptoms is more rapid than that of the diseases that had spread by mean of transatlantic voyage across the Atlantic during the previous centuries such as the 8 documented cholera pandemics [22].

Commercial Flight Travel Conditions
Modern airliners provide a unique environment where susceptible passengers are exposed to each other for prolonged Though the external air supply at altitude is assumed to be sterile, these filters ensure the removal of dust, vapors, bacteria, and fungi.
HEPA filters also effectively capture viral particles spread by droplet nuclei [24,27]. Modern aircraft are equipped with environmental control systems that produce laminar (side to side) circulation of cabin air [12]. Air enters the cabin from overhead, circulates across the aircraft and exits the cabin near the floor. Longitudinal (front to back) airflow is limited, effectively giving rise to sections of air flow in the cabin which prevent spread of airborne particles [12].
Despite these controls, passengers remain vulnerable to airborne transmission as evidenced by multiple documented cases of incabin spread of infectious disease.

Measles, An Example of Transmission by Direct Contact
During typical flight conditions, passengers are exposed to the greatest risk of disease transmission because of high-person density and close proximity [12]. This greatly facilitates disease spread of, for example, measles, because transmission can occur during the earliest (prodromal) stages of illness when a passenger might be unaware of their condition. Measles is a highly contagious viral infection transmitted by direct contact via infectious droplets [28] that has been nearly eradicated from the United States as a result of aggressive vaccination campaigns [12]. However, cases continued to be reported as a result of infected individuals traveling into the US from countries where measles has remained endemic and as a result of failure to adhere to preventive recommendations [29]. Seven cases of secondary measles linked to an index case as a result of in-transit exposure were reported in 1982. In one such case a passenger spread the virus in the flight cabin while five other individuals were infected at a common departure gate [30]. That same year, two passengers were infected by a separate index passenger on a flight from Venezuela to Miami and 8 cases of in-flight transmitted measles were reported during a flight from New York to Tel Aviv in 1994. Between 1996 and 2000, 30% of measles cases imported into the US were estimated to be from people who travelled while experiencing symptoms of the disease.
In June 2005, an unvaccinated traveler was identified as the source of a measles outbreak in Brazil [28]. The index case was originally exposed to measles in the Maldives and during subsequent flights transmitted the disease to two secondary cases, both of whom were unvaccinated [28].

Tuberculosis Spread Through Small Droplets
Tuberculosis (TB) is a significant cause of mortality and morbidity with millions of new cases reported each year [31]. WHO guidelines indicate that sitting within two rows of an infectious passenger on flights lasting more than 8 hours is sufficient for TB transmission [32]. The United States Centers for Disease Control and Prevention (CDC) conducted investigations of seven index cases that had flown between 1992 and 1994 [9]. Transmission was detected in 2 crew members who had worked in close proximity with an index case for at least 12 hours and 4 passengers who were seated in the same cabin section as another index case on a flight lasting longer than 8 hours [9]. These findings support the conclusion that transmission of Mycobacterium tuberculosis on flights is similar to exposure during other activities where prolonged contact with potentially infectious individuals occurs.
Though awareness and screening programs have raised awareness of the risk of transmission, TB remains a public health concern and recently made news in Ireland where 24 commercial flights associated with infectious cases of TB were reported between 2011 and 2014 [33]. The disease is believed to be transmitted by aerosolized droplets, but airborne or small droplet transmission is thought to explain the distribution of SARS on commercial airlines [12]. Of the thousands of SARS cases documented during the outbreak in 2003, one reported the introduction of SARS into Vietnam by a businessman flying from China via Hong Kong SAR [31]. Dissemination of the infection led to SARS cases reported in Singapore, Beijing, Canada, Germany, France and other countries with in-flight transmission being the most likely cause of spread [37].  infectious for long periods. As an example, ASFV infectivity persists more than 1000 days in frozen meat [44]. This long ASFV persistence explains that the introduction of contaminated pork meat or other swine products from international transports has been hypothesized to be the way of introduction in Europe; specifically, to Portugal in 1957, to Cuba in 1971, to Brazil in 1978, Belgium in 1985 and, as recently as 2007 to Georgia [46]. These examples illustrate how long-distance air travel can infect individuals at far distances by not only carrying infected passengers but also by transporting infected food products.

Asymptomatic Carriers
In January of 2010 Haiti experienced a 7. Nepal where a cholera outbreak was ongoing. Evidently, they were not sufficiently symptomatic to rouse suspicion and were able to board a plane and reach their destination functioning as a vector for disease spread across the globe. This example also reinforces an often-overlooked notion that diseases such as cholera may be harbored in a nearly or fully asymptomatic carrier state by some individuals facilitating dissemination, especially via air travel.
The SARS-CoV-2 is also likely to have spread sizably as a result of asymptomatic carriers through air travel. This is perhaps best illustrated by a study that followed a group of 24 asymptomatic tourists exposed to a hotel manager (who later tested positive for COVID-19) flying from Tel Aviv, Israel to Frankfurt, Germany in March 2020 [49]. While none of the travelers displayed any symptoms or received a diagnosis of COVID-19 before embarking

Vector Borne Disease Transmission
In addition to human passengers, animals regularly transported on aircraft may harbor infectious diseases or carry infected vectors such as mosquitoes, fleas, ticks and other arthropods. As many as 87 cases of "airport malaria", caused primarily by the protozoan parasite Plasmodium falciparum, occurring in and around airports among people who have not travelled to endemic areas evidence that malaria-carrying mosquitoes are transported by aircraft [50,51]. Dengue, Chikungunya and yellow fever, viruses also spread by mosquitoes have also been recognized to be transmitted via aircraft [50,52]. Serotype analysis of thousands of dengue cases in Europe and the US point to successive imports of Asian strains coinciding with increased air travel from the 1960s onwards [52].

Chikungunya virus first appeared on the Kenyan coast in 2004
and subsequently emerged in succession on small islands in the Western Indian Ocean [53]. A massive epidemic followed, affecting an estimated 6.9 million in India that swept eastward to Southeast Asia, with cases documented as far as Italy in 2007 [52].  [56] have been proven to be effective in the healthcare setting, their use is not well studied in disease control aboard aircraft. Nevertheless, a mask could be made available for passengers suspected of having infectious diseases such as SARS or COVID-19 and procedures should be in place in the event of the necessity for isolation. Notification of risk exposure is warranted for passengers and crew who have been exposed to infectious disease aboard commercial aircraft. This is typically limited to flights lasting longer than 8 hours and is dependent upon the design of the aircraft, flight origin and destination, and health department recommendations.

Risk Assessment
Risk assessment is complicated by multiple factors that affect transmission of infectious disease in aircrafts. Investigations of tuberculosis spread on flights provide data that suggest that risk of disease transmission to other passengers is proportional to proximity and length of exposure [9]. However, confounding these criteria are studies that report variations such as one outbreak of SARS were passengers seated as far as seven rows from the source were affected [10,56]. Further complicating risk determination is the role cabin ventilation plays in disease transmission. Proper ventilation in confined spaces reduces the concentration of airborne contagion logarithmically [57,58]. The laminar flow within the cabin prevents longitudinal spread and combined with frequent air exchange through HEPA filtration limits transmission of contagion from one cabin section to another [12]. However, when ventilation system is not operating optimally, chance of transmission can increase. In-flight passenger movement also affects the risk of disease transmission. The movement of fellow passengers, crew, and that of an index patient can modify exposure risks and influence the risk distribution for transmission events [59]. Combining epidemiological data with mathematical models of proximity and ventilation may assist demonstrating the interrelationship of these factors and how they affect disease transmission [12]. Thus far, such models have demonstrated that the risk of in-flight tuberculosis transmission is reduced by half when ventilation rate is doubled and exponentially reduced when passengers are seated 15 seats from the infectious source [60].

Aircraft Maintenance
In addition to preventive measures which include public health education, screening, and response policy, commercial airlines have implemented on-ground and in-flight control measures to reduce the risk of transmission. Every aircraft undergoes cleaning based on standard cleaning procedures prior to the next departure [14].
Neither aircraft manufacturers nor the WHO have provided standard recommendations for cleaning aircraft [32] or safe disinfection.
The absence of standard guidelines leaves room for adaptation of best practices, conclusions from new findings, real-life experiences, and circumstances to best deal with life-threatening diseases [14].

Conclusion
Continued growth of global air travel is intrinsically and unescapably linked to an increased risk of infectious disease spread and therefore a contributing factor towards the emergence and dispersal of pandemic disease. It is impossible to predict what infectious agent will cause the next pandemic, but it is likely that air travel will contribute to its spread. Social mitigation strategies are

Conflict of Interest
The authors have no conflict of interest to declare.