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2004 - TB as example of airborne infection

Drs. Eric Leung, CC Leung, TB & Chest, Department of Health

Droplet and droplet nucleus
The notion of airborne transmission of infectious disease and the concept of droplet nucleus were first developed by William F Wells, a Harvard sanitary engineer, in his 1934 paper I "On airborne infection II: droplet and droplet nuclei". The size of the droplets created by an air current sweeping on the surface of a liquid is determined primarily by the velocity of air and the surface tension of the liquid. As air velocity increases, the size of the droplets decreases until about IOOm/s,the diameter of the droplets approaches 10 microns. In sneezing and coughing, the peak airflow in bronchi approaches 300m/s, the droplet ejected should be less than 10 microns in diameter.

The fate of the respiratory droplet particles depends on their sizes. Large droplets and mucoid matter rapidly fall to the ground where they become entrapped. These particles - even if made airborne again by agitation - are highly unlikely to transverse the airway when inhaled. By contrast, the smaller particles will undergo rapid evaporation to produce the droplet nuclei. The droplet nuclei settle at a rate of O.2mm per second, even the gentlest of air current will keep them airborne for long period.

It was Richard L Riley, a student of Dr Wells, who demonstrated that TB is unequivocally airborne. The study was carried out in a Veterans Administration Hospital in Baltimore. 2,3A six-bed hospital ward was renovated so that the exhaust air passed through guinea pig exposure chambers located in a penthouse above the ward.Hundreds of guinea pigs breathed air from the ward, essentially served as a quantitative air sampler. All animals were tuberculin skin tested at monthly interval. The converters were replaced by fresh animals. The infected animals were sacrificed and autopsied. The characteristic lesion was a single pulmonary tubercle, assumed to have developed from a single infectious droplet nucleus.

Over the 4-years period, 134 guinea pigs were infected. Since each guinea pig breathes about 240 ft3 of air per month, over 48 months the colony breathed collectively about 1,500,000 fr3of air. In this volume of air, there were 134 infectious doses of tuberculosis, then there was one infectious dose in about 11,000 ft3 of air. This was the first calculation of infectiousness of the airborne particle in the literature. This figure is consistent with the estimated average amount of air breathed by a student nurse working in a TB ward in the pre-chemotherapy era, before converting the tuberculin skin test positive.3

Since then, other well documented outbreaks such as the outbreak of TB abroad the naval vessel "Richard R Byrd", 4 and the spread of TB by wound irrigation 5 provide evidence of airborne transmission between people and added further insight into the relative importance of airborne transmission and direct contact.

Mathematical model of airborne infection
In 1978, Riley and Wells 6 derived a steady-state mathematical model for assessing the infectiousness of airborne transmission. Since the number of infectious nuclei
required to infect a person is generally unknown, Wells defined a "quantum" of infection as an infectious dose, which could be one or more infectious particles.

q =quanta of airborne infection produced by an infectious person
J =number of infectors
Q =infection free ventilation (outdoor or disinfected air)
Jq/Q =equilibrium concentration of quanta in room air
p = pulmonary ventilation rate per susceptible
t =duration of exposure to infection
pt =the volume of potentially infected air breathed

Number of quanta breathed by a susceptible person
= concentration in the air (Jq/Q) x volume of air breathed (pt)
= Jqpt/Q

Assuming that infection is a randomly occurring event*, the probability that a susceptible person will escape infection by time t is approximately given by e,JqptlQ

The probability that the susceptible person will breathe one or more quanta and become an infected case by time t is therefore given by I _ e,JqptlQ

And the number of new infected cases C by time t is given by:

C=S(I-e,JqptlQ)w,here S is the number of susceptible persons initially.

(*An Poisson process with the probability distribution in form of Pk(t)= (At)k/ kLe-A\ where Pk(t) is the probability of exactly k events occurring by time t, and A is a constant).

In the literature, there were several outbreaks of TB in which contact tracing were done and the environment conditions were carefully documented to permit estimation of the infectiousness of the airborne transmission.

Catching the droplet nuclei -from conceptual thinking to quantitative measurement

In 2004, Fennelly et al 12reported a new method to directly study the concentration and size distribution of the infectious aerosols by using of an air sampler in a small chamber. For the first time, the size of the air borne infectious particle generated by cough from TB patients can be directly measured. They were found to be in respirable size range. Large differences between patients with potential infectiousness were noted, as was a relatively brisk response to therapy.

The elusive pathway: the aerobiologic pathway for the transmission of communicable respiratory disease

With the emergence of SARS and avian flu, the transmission pathways of these novel
agents have generated renewal of interest in airborne transmission. 13A recent study
has shown that the SARS virus can be spread by airborne route. 14Another study
detected the presence of airborne rhinovirus by air sampling in an office environment.
15These studies highlighted the importance of deciphering the aerobiology of airborne transmission.

Whether the infective agent can be spread by respiratory droplet or a droplet nucleus depends on several factors:

1. The source of aerosol generation. Whether it is from the respiratory tract in which a fine droplet nucleus can be generated or from indirect aerosolization from environmentally contaminated source such as fomite or sewage.
2. The length of time a particle resides in the air which depends on the physical characteristic such as size, composition and environmental factors. The length of time that the particle remains infectious which depends on the initial metabolic state, genetic characteristic and environmental factors.
3. The portion of the respiratory tract of the susceptible host in which the inhaled particle is deposited i.e. nasopharyngeal, tracheobronchial or alveolus.

The infective agent can be classified as obligate, preferential, or opportunistic, on the basis of the agent's capacity to be transmitted and to induce disease through fine- particle aerosols and other routes.

1. An obligate airborne transmission is an infection that, under natural conditions is initiated only through aerosol deposited in the distal lung. The best known obligate airborne organism is TB.
2. Preferential airborne transmission are agents that can naturally initiate infection through multiple routes but are predominantly transmitted by aerosol through distal airway such as measles or smallpox.
3. Disease with opportunistic infections are infections that naturally cause disease through other routes (e.g., the gastrointestinal tract) but that can also initiate infection through the distal lung and may use fine-particle aerosols as an efficient means of propagating in favourable environments.

Prevention of airborne transmission (with TB as an example)

CDC guidelines published in 1994 16 aims at a hierarchy of controls:
1. Administrative controls include efforts to reduce any delay in diagnosis and policies to ensure more extensive and rapid respiratory isolation.
2. Engineering controls include ventilation, HEPA filter and ultraviolet (UV) light.
3. Personal controls include masks and personal respirators, BCG (bacille Calmette-Guerin) vaccination, tuberculin skin testing and preventive therapy with isoniazid.

1. Administrative controls with early diagnosis, prompt isolation and early treatment will decrease the bacillary load at the source.

2. a) Ventilation rate:

The rate of exchange of contaminated air with clean air within a room is referred to as the ventilation rate, expressed as the number of air changes per hour (ACPH). A ventilation rate of I ACPH means that the ventilation system delivers a volume of air equal to the room volume each hour. One ACPH will reduce the concentration of a given contaminant within in a room by 67% in I hour, whereas a ventilation rate of 6 ACPH will reduce the contaminant concentration by more than 99% in the same period.

2. b)High efficiency particulate aerosol (HEPA) filtration unit

HEPA filter provides a minimum particulate removal of 99.97% for thermally generated smoke particles or equivalent with a diameter of 0.3 micron. It works by the process diffusion, interception and inertial impaction. However the filter acts as a resistive load, requires regular maintenance and should be regarded as high-grade biohazard when disposed.

2. c)Ultraviolet Germicidal Irradiation

In experimental study, with a room of 200 fe and 10ft ceiling, installing a 30 W UV lamp is equivalent to adding 20 AC/hr. 17
UV light is attractive for TB control because the fixtures are relatively cheap, and the maintenance and energy costs are also low. It appears to be particularly useful in settings where there is high risk of exposure to unrecognised cases, such as shelters for the homeless and emergency departments. It may also be a useful adjunct in high- risk areas of the hospital such as bronchoscopy suites and autopsy rooms.
Direct exposure to UV light can result in keratoconjunctivitis (so-called welder's eye), and prolonged direct exposure is associated with skin cancer. Because of fear of these potential complications, the use of UV light has been limited to date. However, these complications are easily prevented by installing the fixtures within ventilation systems (duct irradiation), or by using wall- or ceiling-mounted fixtures with baffles to block rays directed downward so that only the air in the upper room is irradiated (upper room irradiation).

3. Personal Respiratory Protective Device

For air purifying respirators, it removes the contaminants by filtration, adsorption or chemical reaction.

It can be classified into positive pressure such as powered air purifying respirators (PAPR) and negative pressure respirator such as N95 respirator.

In 1995, National Institute of Occupational Safety and Health (NIOSH) set up a new system of classification •
• It identifies three main class of respirator N, P, R; (N stands for "not resistant to oil," P for "oil proof' and R for "oil resistant.")
• "N" class intended for protection against non-oil based aerosol.
• "R" and "P" for use against oil based aerosol, which degrade filter material quickly.
• The filter efficiencies is rated with 0.3 urn mass median aerodynamic diameter particle (MMAD) into 3 grades: 99.97% (HEPA filter), 99% and 95%. •
• N95 keeps out 95 percent of particles that have a diameter of 0.3 microns. •
• CDC (MMWRI994) recommends N-95 respirator for HCW.

Please note that NIOSH only certifies the efficiency of a respirator, it tests only the filter and not overall efficiency of both the filtering face piece and face mask leakage. Fit test should be done to decrease the leakage.

1. Wells WF et al. On airborne infection II. Droplets and droplet nuceli. Am J Hyg 1934;20:611-618.
2. Riley RL et al. Air Hygiene in tuberculosis: quantitative studies of infectivity and control in a pilot ward. Am Rev Tuberc and Pulm Dis 1957;75:420-431.
3. Riley RL. The J. Burns Amberson Lecture: Aerial dissemination of pulmonary tuberculosis. Am Rev Tuber and Pulm Dis 1957;76:931-941.
4. Houk V et al. The epidemiology of tuberculosis in a closed environment. Arc Environ Health 1968;16:26-52.
5. Hutton MD et al. Nosocomial transmission of tuberculosis associated with a draining abscess. J Infect Dis 1990; 161:286-295.
6. Riley et al. Airborne spread of measles in a suburban elementary school. Am J Epidemiology 1978;107:421-432.
7. Riley RL et al. Airborne Infection. New York, Macmillan, 1961.
8. Riley RL et al. Infectiousness of air from a tuberculosis wardnultraviolet irradiation of infected air: Comparative infectiousness of different patients. Am Rev Respir Dis 1962;85:511-525.
9. Nardell EA et al. Airborne infection Theoretical limits of protection achievable by Building Ventilation. Am Rev Respir Dis 1991;144:302-306.
10. Catanzaro A et al. Nosocomial tuberculosis. Am Rev Respir Dis 1982;123:559-562.
11. Templeton GL et al. The risk of transmission of mycobacterium tuberculosis at bedside and during autopsy. Ann Intern Med 1995;122:922-925.
12. Fennelly KP et al. Isolation of viable airborne Mycobacterium Tuberculosis; a new method to study transmission. Am J Respir Crit Care Med 2004;169:604-609.
13. Roy CJ et al. Airborne transmission of Communicable Infection - the elusive pathway. N Engl J Med 2004;350: 1710-1712.
14. Yu TS et al. Evidence of Airborne Transmission of the Severe Acute Respiratory Syndrome Virus. N Engl J Med 2004;350: 1731-1739.
15. Theodore AM et al. Detection of Airborne Rhinovirus and its Relation to Outdoor Air Supply in Office Environments. Am J Respir Crit Care Med 2004; 169(II): 1187-1190.
16. Centers for Disease Control. Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health- Care Facilities, 1994. MMWR 1994;43:1-132.
17. Riley RL et al. Clearing the air: the theory and application of ultraviolet air disinfection. Am Rev Respir Dis 1989;139:1286-1294.