Human Influenza Resulting from Aerosol Inhalation

Alford, Robert H.; Kasel, Julius A.; Gerone, Peter J.; Knight, Vernon

doi:10.3181/00379727-122-31255

Cited by 324 publications

(294 citation statements)

References 5 publications

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“…The FID 50 of ARdelivered virus was 1.9 pfu for PN99 virus and 4 pfu for TH16 virus, similar to the reported 50% human infectious dose of aerosols 1-3 μm in size, which ranges from 0.6 to 3 50% tissue culture infectious dose (TCID 50 ) (20). A recently developed nose-only influenza aerosol system generates particles in the same size range as our system, but characterization of infectivity, transmission, and deposition in ferrets was not reported (21,22).…”

Section: Discussionsupporting

confidence: 75%

“…Ferrets, 6-to 11-mo-old (Triple F Farms) and serologically negative against currently circulating influenza viruses and H5N1 viruses, were used in this study and were housed in cages within a Duo-Flo Bioclean mobile clean room (Lab Products). Ferrets were sedated as described (10) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) ), and high (60-87 FID 50 ). To determine the dose at which the ferrets inoculated with PN99 virus become contagious, two naïve ferrets for each transmission experiment were placed either in the same cage as inoculated ferrets or in an adjacent cage with a perforated adjoining wall, to assess contact or respiratory droplet transmission, respectively, as described (8).…”

Section: Methodsmentioning

confidence: 99%

“…Serial dilutions of virus were administered either IN or by AR to two to five ferrets each until an end point was reached, and no virus shedding was detected in nasal washes. Once the 50% ferret infectious dose (FID 50 ) values were determined retrospectively for each inoculation, doses were grouped into dose categories as follows: for IN doses, low (1.8-2.3 FID 50 ), intermediate (23 FID 50 ), and high (100-227 FID 50 ); and for ARpresented doses, low (1.5-2.2 FID 50 ), intermediate (15)(16)(17)(18)(19)(20)(21)(22) ), and high (395-526 FID 50 ). At each dose, transmission was assessed by placing two naïve ferrets in contact with inoculated animals, either in the same cage for contact transmission or in an adjacent cage with a perforated side wall for respiratory droplet transmission.…”

Section: Comparison Of Aerosol and Intranasal H3n2 Virus Inoculations Inmentioning

confidence: 99%

“…Serial dilutions of virus were administered to two to six ferrets each IN or by AR to assess infectivity, and disease progression was evaluated at all doses. Inoculations were grouped into dose categories: for IN doses, low (1.2 FID 50 ); intermediate (12 FID 50 ); and high (62-115 FID 50 ); for AR-presented doses, low (1.5-1.8 FID 50 ); intermediate (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) ), and high (60-87 FID 50 ). Additionally, a 100 FID 50 IN dose or 66-87 FID 50 AR-presented dose was administered to three ferrets each, and at 3 dpi virus titers in tissues were determined.…”

Section: Comparison Of Aerosol and Intranasal H5n1 Virus Inoculations Inmentioning

confidence: 99%

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Influenza virus aerosol exposure and analytical system for ferrets

Gustin

Belser

Wadford

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

108

178

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Understanding the transmission ability of newly emerging influenza viruses is central to the development of public health preparedness and prevention strategies. Animals are used to model influenza virus infection and transmission, but the routinely used intranasal inoculation of a liquid virus suspension does not reflect natural infection. We report the development of an inoculation method that delivers an influenza virus aerosol inoculum to ferrets and the characterization of size distribution and viable virus present in aerosols shed from infected ferrets during normal breathing and sneezing. By comparing virus deposition, infectivity, virulence, and transmissibility among animals inoculated intranasally or by aerosols with a human (H3N2) or avian (H5N1) influenza virus, we demonstrate that aerosol inoculations more closely resemble a natural, airborne influenza virus infection and that viable virus is measurable in droplets and droplet nuclei exhaled by infected ferrets. These methods will provide improved risk assessment of emerging influenza viruses that pose a threat to public health.I nfluenza viruses cause outbreaks of highly contagious respiratory illness among humans, and most likely have done so since ancient times (1). Despite frequent influenza epidemics and occasional pandemics occurring in more recent times, the relative contribution of the various modes of influenza virus transmission among humans remains poorly understood. Although seasonal and pandemic influenza viruses readily achieve sustained transmission in susceptible humans, avian influenza H5N1 viruses have not, despite having caused hundreds of human infections, primarily resulting from exposure to infected poultry (2). Furthermore, recent reports indicate reduced secondary attack rates in some community settings for the pandemic 2009 H1N1 virus compared with seasonal and previous pandemic strains (3,4). This notable diversity in the transmissibility of influenza viruses suggests possible differences in the predominant routes of transmission used by different strains under different conditions. There are three modes of transmission: (i) contact transmission, including direct and indirect contact with contaminated surfaces; (ii) droplet transmission, occurring when large (≥5 μm) particles contact a person's conjunctiva or respiratory mucosa; and (iii) droplet nuclei transmission (also referred to as "airborne" or "aerosol" transmission), occurring when small (<5 μm) particles that are capable of prolonged suspension in the air are inhaled. The relative predominance of these different modes of influenza virus transmission in different settings remains controversial and is a major public health question that needs to be addressed. Mammalian models of influenza transmission have been developed to better understand the process of transmission and to rapidly identify the emerging influenza viruses with transmissibility properties that may confer pandemic potential (5-8).The ferret has become widely recognized as an excellent model of influen...

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Section: Discussionsupporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: Comparison Of Aerosol and Intranasal H3n2 Virus Inoculations Inmentioning

confidence: 99%

Section: Comparison Of Aerosol and Intranasal H5n1 Virus Inoculations Inmentioning

confidence: 99%

See 2 more Smart Citations

Influenza virus aerosol exposure and analytical system for ferrets

Gustin

Belser

Wadford

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

108

178

View full text Add to dashboard Cite

show abstract

“…person to person) as compared with aerosol transmission. Infection by Influenza via aerosol transmission is far more efficient than person to person contact, taking an estimated 27,000 times fewer virions to induce productive infection leading to disease [2,4]. Considering that the virus is routinely aerosolized during even seasonal Influenza outbreaks, this fact requires us to take into account the possibility of genetically modified Influenza virus being released in an aerosol fashion -a method of delivery that would very likely be completely undetectable at the time of occurrence.…”

Section: Reviewmentioning

confidence: 99%

What the Novel H1N1 Influenza Outbreak Can Teach us about Influenza as a Bioterrorism Weapon

Morrow¹

2011

J Bioterror Biodef

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While we often see Influenza infections as part of our daily lives during winter in the United States, it is a virus with significant potential for manipulation into an agent that may be used in the framework of Bioterrorism. The Novel H1N1 outbreak of 2009 highlighted what our response is to such an unsuspected outbreak both on a national and global scale. The responses to this outbreak allowed us to avert significant damage from the Pandemic, but retrospective analysis suggests that if the outbreak had been more virulent, greater impact would have been felt on a global scale. This short review attempts to briefly summarize our response to the Novel H1N1 outbreak in the United States and to apply the knowledge gleaned from this analysis to a hypothetical Bioterrorism attack that employs a modified Influenza virus, an event that is unlikely but not impossible.

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Effect of Lack of Gravity on Airborne Infection During Space Flight

Knight¹

1970

JAMA

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Human Influenza Resulting from Aerosol Inhalation

Cited by 324 publications

References 5 publications

Influenza virus aerosol exposure and analytical system for ferrets

Influenza virus aerosol exposure and analytical system for ferrets

What the Novel H1N1 Influenza Outbreak Can Teach us about Influenza as a Bioterrorism Weapon

Effect of Lack of Gravity on Airborne Infection During Space Flight

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