Before any further discussions concerning home care or pandemic preparedness and the bolstering of medical surge capability, it is necessary to carefully review how Influenza is transmitted from animals to humans, and from humans to humans.
The study of the medical effects of any virus requires closely examining infected human cases and infected human tissue cultures in the laboratory. Unfortunately, in many cases, it is also necessary to develop a laboratory animal model of the infection. Animals like humans, show different susceptibilities to different viruses. Therefore, it is necessary to search for an animal species that can be infected by the virus being studied. Usually, the selection of special laboratory mice and rats fulfill this role. These animals are easy to keep and study, and they can show where a virus will replicate in a mammalian body. They can also help us understand how well various vaccines and antiviral drugs work. Such experiments are conducted with utmost consideration and follow strict protocols for how the animals are housed and fed, as well as their compassionate care. Occasionally, an animal species is found where the virus being studied causes signs and symptoms that very closely match what is observed when humans are infected with the virus. This then becomes the preferred animal model for the disease.
For Influenza, a small mammal called the ferret serves as the model for human infection. These highly intelligent animals make delightful, interesting pets, and they have greatly advanced our knowledge of Influenza transmission. Ferrets and humans share similar lung structures and function, and human and avian influenza viruses exhibit similar patterns of binding to the sialic acids (the receptor for influenza viruses), which are distributed throughout the respiratory tract in both species. Ferrets show the same clinical signs as humans when experimentally infected in the laboratory, including a nasal discharge and sneezing. Like humans, they run a fever starting a day after infection. Human and avian influenza viruses replicate well in the respiratory tract of ferrets without prior adaptation, and the spread of the virus through the body after infection with High-Pathogenic Avian Influenza viruses is like that seen in the human cases that have been described.
Ferrets have demonstrated Influenza virus spread by direct contact (i.e. by housing an infected and an uninfected ferret together) or by the spread of respiratory droplets in the absence of direct contact (i.e. separating infected and uninfected ferrets with a perforated wall that only allows an air exchange.1
The H1N1 virus that caused the great 1918 pandemic was by itself highly dangerous, but as discussed previously, much of the mortality associated with this event was due to a secondary bacterial pneumonia that developed after the Influenza virus had damaged the respiratory tract. Ferrets show this same pattern, corroborating the historical human data showing that cases of pneumonia are increased during some pandemic influenza outbreaks.
Based on ferret and human data, it is acknowledged that the Influenza virus may be transmitted to humans in three ways: by direct contact with infected individuals; by contact with contaminated objects and then touching the face, eyes, or mouth (doorknobs, elevator buttons, work surfaces, dust, children’s toys, light switches, etc.); and finally, by the inhalation of virus laden aerosols. The relative importance of each one of these during a human pandemic spread is ill defined, but in a healthcare setting, all routes of infection must be guarded against.
Numerous scientists have emphasized that droplet transmission is an important mode by which influenza virus infection is acquired and there is over 50-years of data on the behavior of small particle aerosols and the viability of infectious viruses in such aerosols. Yet the previous 2006 DHHS Pandemic Influenza Plan, recommended the use of simple surgical masks as part of the personal protective equipment (PPE) for routine patient care. This recommendation was wrong inside a healthcare setting with an environment of dehumidified air, low ambient ultraviolet light, and high concentrations of virus in the environment.2,3,4,5,6,7 It took until 2017 for the DHHS to update its Pandemic Plan to fully recommend and stockpile high-efficiency particulate air (HEPA) filtered N95 masks for which they use the term “respirators”.
The new interim guidance document says the use of N-95 “respirators” (designed to stop 95% of small airborne particles) is “prudent” for medical workers providing direct care for patients with confirmed or suspected pandemic flu and is recommended in caring for those with secondary pneumonia. It also says respirator use is “prudent” for support workers in direct contact with patients. The 2017 pandemic plan also advises healthcare facilities to expect and plan for shortages of N-95 respirators and similar protective equipment in the event of a pandemic. This is because the majority of these are now made overseas with a lengthy supply chain vulnerable to pandemic disruption.
These new recommendations reflect an increased concern about the possibility of airborne transmission of flu viruses. Yet the DHHS 2017 update says the CDC has found no new scientific evidence on this question. DHHS says the new guidance “augments and supersedes” previous advice. While it discusses the use of N-95 HEPA (High Efficiency Particulate Air) respirators for other direct care activities involving patients with confirmed or suspected pandemic influenza, it provides little guidance about the home health care activities that it promotes during a pandemic. There is a disconnect here. If it is prudent for healthcare workers to be wearing N-95 respirators, then that should be the baseline for protection for anyone in contact with an influenza patient. This should include home caregivers.
Irrespective, repeated experimental data now shows that even the current 2017 DHHS guidelines are inadequate for complete protection against Influenza infection in healthcare settings featuring low-humidity, controlled environmental conditions found in hospitals. This is because a patient’s coughing and sneezing can produce both large and small particle aerosols. If this aerosol has droplets in the 1 to 5-micron mass-median-diameter size-range it will have the same physical behavior as a gas. Consequently, infected mucous droplets in this size range can remain suspended in the air and some strains of the influenza virus can remain viable and infectious for at least 2-hours in the floating aerosol. 8,9
It has been known for some time that a variety of respiratory viruses (including Influenza A virus strains), can cause documented human eye infections.10,11 While rare, sporadic reports of eye-related symptoms following H5N1 and the 2009 H1N1 Influenza strains have been documented. The dangerous Influenza A viruses of the H7 subtype have resulted in over 100 cases of human infection since 2002, and these frequently cause eye inflammation in infected individuals along with severe respiratory disease and death.12 Eye exposure as a route for Influenza virus entry into the body has been confirmed by documented accidental laboratory exposures (e.g., by liquid Influenza virus tissue culture fluid being splashed or infected ferrets sneezing into a scientist’s face and eyes) and occupational exposures (e.g., by direct ocular exposure to infected poultry or eye abrasions from contaminated dust during chicken culling operations).
A large body of evidence now makes it clear that the human eye is a target for the entry of some Influenza A virus strains into the human respiratory tract. In the eye, both the transparent clear part of the eye (the cornea), the inner lining of the eyelids, and the white part of the eye (the conjunctival epithelial cells) contain the sialic acids molecules that serve as the receptors for the H protein of the Influenza virus.12,13 When the human eye contacts a suspended large and small small-particle Influenza-laden aerosols from an infected patient’s cough or sneeze, a surface tension effect can draw the viral particles to the moist epithelial cells on the ocular surface where they adhere. Once adherent, the nasolacrimal drainage system of the eye, will drain the attached viruses from the surface of the eye through the tear ducts and into the inside cavity of the nose within 30-minutes. Surprisingly, even the deeper structures of the human eye have been shown to support Influenza virus replication.
Experiments reveal that ocular-only exposure to virus-containing aerosols constitutes a valid exposure route for a potentially fatal respiratory infection, even for viruses that do not demonstrate an ocular viral tropism. Ferrets inoculated solely by the ocular aerosol route with avian (H7N7, H7N9) or human (H1N1, H3N2) strains were able to transmit these Influenza viruses to uninfected animals by direct-contact or respiratory-droplets. This underscores the public health implications of human ocular exposure in clinical or occupational health care settings. These experiments have shown that eye exposure alone to Influenza A virus strains are sufficient to cause a lethal infection in the surrogate ferret model.
Therefore, respiratory protection alone will not fully protect against influenza virus exposure, infection and severe disease.
Under Federal Respiratory Protection Standards 29 CFR 1910.134 and Personal Protective Equipment Standard 29 CFR 1910.132, any medical surge capability must also focus on the safety of the medical surge providers and staff.
The demonstrated vulnerability of the human eye as a point of infection with some strains of the Influenza Group A virus, indicates that without recommending full eye covering, the current 2017 DHHS/CDC guidelines being promoted for healthcare workers are inadequate to afford complete 100% protection during a global Influenza pandemic, Therefore its recommendations might not be in compliance with Federal law. In addition, the DHHS guidelines being given to home caregivers are also inadequate to prevent infection,
As was seen in the 2014 Ebola debacle in the United States, it is essential for DHHS and the Public Health authorities to keep up to date with the latest peer-reviewed research before making national guidelines. Apparently, this is being done very slowly for Influenza.
In a global Influenza pandemic, U.S. healthcare workers must be assured that the protective measures and personal protective equipment that they use, will prevent them from contracting the disease. The infection of even a few volunteer workers with Influenza could have a domino effect on the rest of the volunteer workforce and an existing surge personnel capability could vanish overnight because of illness and fear of infection.14
Adding eye goggles to the protective ensemble would be one solution, but this would require additional training in decontamination when doffing PPE. This is because the outer surface of the goggles should be considered to be contaminated with live Influenza virus. Therefore ideally, full airway protection requires not only HEPA filtered air, but also full-face protection and this must be combined with alcohol-based wipe disinfection of both the protection device and the hands after use.
In this respect, a significant number of full-face respirators are manufactured by a variety of companies. Their cost range is between $120 to $420. However, they require a precise donning and doffing procedure and some may require submersion for complete decontamination. Some models are bulky, heavy, and require fit testing to ensure a good face seal. Some require OSHA-mandated respiratory medical clearance for institutional use.
Hence, there is an urgent need for an affordable, simple, negative pressure, air purifying respirator that is lightweight, easy to don and doff, and able to reliably achieve a face-seal without qualitative fit testing. Searching the internet for concept ideas, we came across a design called the “social gas mask”.15 We were immediately attracted to the design and in Figure 22, we have made suggested improvements for use of this basic concept by both healthcare workers and by the minimally-trained general public during a severe 1918-type Influenza pandemic. Such a design would be comfortable, low profile, and compatible with wearing corrective eyeglasses or contact lenses. Because this could be used by the public, a suitable modified design would feature dual self-sterilizing filter units based on low-voltage U.V. LEDs embedded into the inside of an insertable, replaceable HEPA filter cartridge. These inexpensive 3-volt Ultraviolet (UV) Light Emitting Diodes (LED) would supply a wavelength sufficient to create nucleic acid dimer formation to sterilize any viral agent trapped in the HEPA material of the filter cartridge. Minimal training could ensure that the wearer properly decontaminates both the respirator and their hands when doffing.
The most critical component of this respirator concept would be the novel use of a soft polymer “pleated accordion cup” which would act to seal the HEPA filters to the mouth and nose using only the mild outside pressure provided by the chin extension and the top polymer retaining band. Such a product could be extremely useful during the projected “Vaccine Gap” between an initial severe Influenza outbreak and general vaccine availability for the public. A “just-in-time” manufacturing capability could be pre-arranged as part of the Strategic National Stockpile. It is likely that such a reusable “Integral Pandemic Respirator” could be mass produced for the same price as a single course of generic Tamiflu ($155.86). Unlike Tamiflu, the respirator can be used for long periods of time (days) and if hermetically-sealed packaging is used in conjunction with oxygen absorbing packets, it could feature an extended shelf life.
The Problem of Circulating Banknotes
The successful control of any viral disease outbreak requires knowledge of the different circumstances or agents that could promote its transmission among hosts. In this respect, there is one final aspect of general pandemic preparedness that must be addressed. This concerns the survival of the Influenza virus on common circulating banknotes.
In a series of experiments, banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and the virus survival time was tested after different periods. Influenza A viruses tested by cell culture methods, survived up to 3-days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17-days) in the laboratory.16 When the nasopharyngeal secretions of naturally infected children were used, the Influenza virus survived on banknotes for at least 48-hours in one-third of the cases.
The unexpected stability of the Influenza virus in this non-biological environment suggests that this possibility for environmental contamination should be considered in the setting of pandemic preparedness. Banknotes might be a significant factor in Influenza transmission, but our research indicates that no federal agency has yet addressed this concern. This potential mode for transmission might be negated by the simple exposure of banknotes to sunlight, by dunking in methanol, or by impregnating bank notes with an inorganic antiviral substance at the time of their manufacture.
- Sutton, et.al. Airborne Transmission of Highly Pathogenic H7N1 Influenza Virus in Ferrets Virol. June 2014 vol. 88 no. 12 6623-6635. Posted online 2 April 2014, doi:10.1128/JVI.02765-1
- Moser, M. R., T. R. Bender, H. S. Margolis, G. R. Noble, A. P. Kendal, and D. G. Ritter. 1979. Outbreak of influenza aboard a commercial airliner. Am. J. Epidemiol. 110:1-6
- Raymond Tellier, Perspective; Emerg. Inf. Dis. Volume 12, Number 11, November 2006 Samira Mubareka, et.al., Transmission of Influenza Virus via Aerosols and Fomites in the Guinea Pig Model J Infect Dis (2009) 199 (6): 858-865. 15 March 2009.
- Belser, et.al, The ferret as a model organism to study influenza A virus infection. Disease Models & Mechanisms, 2011, 4: 575-579; doi: 10.1242/dmm.007823
- Noti JD, et al. Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room. Clin Infect Dis 2012 Jun; 54(11):1569-1577.
- Cowling BJ. Airborne transmission of influenza: implication for control in healthcare and community settings. (Editorial) Clin Infect Dis 2012 (early online publication). Clin Infect Dis. 2012 Jun;54(11):1578-80. doi: 10.1093/cid/cis240. PMID: 22460979
- N. Nikitin, O. Karpova, et.al., Influenza Virus Aerosols in the Air and Their Infectiousness. Advances in Virology. Volume 2014 (2014), Article ID 859090, http://dx.doi.org/10.1155/2014/859090
- J.R.Brown, et.al. Influenza virus survival in aerosols and estimates of viable virus loss resultingfrom aerosolization and air-sampling Journal of Hospital Infection. Volume 91, Issue 3, November 2015, Pages 278-281 https://doi.org/10.1016/j.jhin.2015.08.004
- Belser, et.al. Ocular Tropism of Respiratory Viruses Microbiol. Mol. Biol. Rev. March 2013 vol. 77 no. 1 144-156. doi: 10.1128/MMBR.00058-12
- J. Belser, D. Wadford, Terrence M. Tumpey, Ocular Infection of Mice with Influenza A (H7) Viruses: a Site of Primary Replication and Spread to the Respiratory Tract, J. Virol. July 2009 vol. 83 no. 14 7075-7084. posted online 20 May 2009, doi: 10.1128/JVI.0053509
- J. Belser, Hui Zeng, T. Tumpey, et.al. Ocular Tropism of Influenza A Viruses: Identification of H7 Subtype-Specific Host Responses in Human Respiratory and Ocular Cells. J. Virol. October 2011 vol. 85 no. 19 10117-10125. posted online 20 July 2011, doi: 10.1128/JVI.05101-11
- J. Belser, Terrence Tumpey, et.al. Pathogenesis, Transmissibility, and Ocular Tropism of a Highly Pathogenic Avian Influenza A (H7N3) Virus Associated with Human Conjunctivitis. J. Virol. May 2013 vol. 87 no. 10 5746-5754 Accepted manuscript posted online 13 March 2013, doi: 10.1128/JVI.00154-13
- J, Belser, et.al. Influenza Virus Infectivity and Virulence following Ocular-Only Aerosol Inoculation of Ferrets. J. Virol. September 2014 vol. 88 no. 17 9647-9654 posted online June 2014, doi: 10.1128/JVI.01067
- Rossow, C., W. Fales, et.al. Healthcare Providers: Will They Come to Work During an Influenza Pandemic? Disaster Management and Human Health Risk III, WIT Transactions on the Built Environment, Vol 133, 2013, ISSN: 1743-3509, ISBN: 978-1-84564-738.
- The Social Gas Mask; Designer: Zlil Lazarovich http://www.yankodesign.com/2014/07/11/the-social-gas-mask/
- Y. Thomas, G. Vogel, L. Kaiser., Survival of Influenza Virus on Banknotes Appl. Environ. Microbiol. May 2008 vol. 74 no. 10 3002-3007. posted online 21 March 2008, doi: 10.1128/AEM.00076-08