Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.

/pdf/superspreading-and-the-effect-of-individual-variation-on-1hf80n09pb.pdf

Superspreading and the effect of individual variation on disease emergence

Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities

Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm3) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as "speech superemitters," consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.

/pdf/aerosol-emission-and-superemission-during-human-speech-426opv4edj.pdf

Aerosol emission and superemission during human speech increase with voice loudness

Over the past few years, prompted by pandemic preparedness initiatives, the debate over the modes of transmission of influenza has been rekindled and several reviews have appeared. Arguments supporting an important role for aerosol transmission that were reviewed included prolonged survival of the virus in aerosol suspensions, demonstration of the low infectious dose required for aerosol transmission in human volunteers, and clinical and epidemiological observations were disentanglements of large droplets and aerosol transmission was possible. Since these reviews were published, several new studies have been done and generated new data. These include direct demonstration of the presence of influenza viruses in aerosolized droplets from the tidal breathing of infected persons and in the air of an emergency department; the establishment of the guinea pig model for influenza transmission, where it was shown that aerosol transmission is important and probably modulated by temperature and humidity; the demonstration of some genetic determinants of airborne transmission of influenza viruses as assessed using the ferret model; and mathematical modelling studies that strongly support the aerosol route. These recent results and their implication for infection control of influenza are discussed in this review.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2009.0302.focus

Aerosol transmission of influenza A virus: a review of new studies

The role of particle size in aerosolised pathogen transmission: A review

Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These “exhaled bioaerosols” may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these “high-producer” individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 ± 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension.

https://www.princeton.edu/%7Estonelab/Publications/pdfs/From%20Howard/ScienceNaturePNAS/PNAS/EdwardsInhaling%20to%20Mitigate%20Exhaled%20Bioaerosols.pdf

Inhaling to mitigate exhaled bioaerosols

Aerosolized food products can be of sufficient size to deposit in the mouth without easily entering into the respiratory tract and of small enough size so as to allow for suspension in air. An apparatus (110) incorporating an aerosol generating device and food products can allow for the aerosolization of the food products and the delivery thereof in a matter suitable for inhalation or deposition and subsequent ingestion. The food delivery apparatus (110) represents a novel means of delivering food to the mouths of humans and animals. Indeed, the apparatus (110) of the invention is designed to produce, transport, and direct aerosolized food particles of sufficient size to deposit in the mouth without substantial exposure or entry into the respiratory tract and of small enough size so as to allow for suspension in air.

Delivering aerosolizable food products

Methods and devices to determine rate of particle production and the size range for the particles produced for an individual are described herein. The device (10) contains a mouthpiece (12) , a filter (14) , a low resistance one-way valve (16) , a particle counter (20) and a computer (30) . Optionally, the device also contains a gas flow meter (22) . The data obtained using the device can be used to determine if a formulation for reducing particle exhalation should be administered to an individual. This device is particularly useful prior to and/or following entry in a cleanroom to ensure that the cleanroom standards are maintained.

Method and device for decreasing contamination

Formulations have been developed for pulmonary delivery to treat or reduce the infectivity of diseases such as viral infections, especially tuberculosis, SARS, influenza and respiratory synticial virus in humans and hoof and mouth disease in animals, or to reduce the symptoms of allergy or other pulmonary disease. Formulations for pulmonary administration include a material that significantly alters physical properties such as surface tension and surface elasticity of lung mucus lining fluid, which may be isotonic saline and, optionally, a carrier. The formulation may be administered as a liquid solution, suspension, aerosol, or powder where the particles consist basically of an osmotically active solute. Drugs, especially antivirals or antibiotics, may optionally be included with the formulation. These may be administered with or incorporated into the formulation.

Jonathan Man

Papers

Inhaling to mitigate exhaled bioaerosols

Delivering aerosolizable food products

Method and device for decreasing contamination

Formulations decreasing particle exhalation

Recent Advances Related to the Systemic Delivery of Therapeutic Molecules by Inhalation