A TB infection control program should be based on control measures that address the most important factors involved in TB transmission: the concentration of droplet nuclei in the air and the rate at which droplet nuclei are inhaled by susceptible persons. The concentration of infectious droplet nuclei in the air can be reduced by environmental controls. These controls include diluting and removing contaminated air by general ventilation and air cleaning by air filtration (e.g., through HEPA filters) or UVGI.

In general ventilation systems, uncontaminated supply air mixes with contaminated room air (dilution), which is subsequently removed from the room by the exhaust system (removal). Two types of general ventilation systems can be used for dilution and removal of contaminated air: single-pass systems and recirculating systems. In single-pass systems the supply air is uncontaminated fresh outside air, and after it passes through the ventilated area, 100% of that air is exhausted to the outside. In a recirculating system, a small portion of the exhaust air is discharged to the outside and is replaced with fresh outside air, which mixes with the portion of exhaust air that was not discharged to the outside. The resulting mixture, which can contain a large proportion of contaminated air, is then recirculated. The rate at which airborne particles are removed from an enclosed space (e.g., a room) by ventilation is usually expressed as the number of air changes per hour (ACH), which is the ratio between the volume of air entering the room per hour and the room volume. A minimum of 6 ACH is recommended for TB isolation rooms and treatment rooms (26-28). Where feasible, this airflow rate should be increased to 12 ACH or more, and in areas where the nature of work is exceptionally hazardous, such as autopsy rooms, airflow rates of 15-25 ACH have been recommended (29,30).

HEPA filtration units or UVGI can be used as a supplement to ventilation control measures in settings where adequate airflow cannot be provided with the general ventilation system alone (13). HEPA filters have a demonstrated and documented minimum removal efficiency of 99.97% of particles whose diameter is > 0.3 µm (droplet nuclei are an estimated 1 to 5 µm in size [13], but they can have an aerodynamic diameter of less than 1 µm [31]). They can be used in fixed or portable HEPA recirculation systems that can achieve 12 ACH or more (13). UVGI can kill or inactivate tubercle bacilli under experimental conditions (32), especially where air mixing is accomplished mainly by convection (13). The effect of UVGI in a room without supplemental ventilation (33) and in another with a ventilation rate of 6 ACH (34) is estimated at 10 and 39 ACH, respectively. Greater rates of ventilation may decrease the killing of bacteria (34), but the optimal relationship between ventilation and UVGI is not known. However, general ventilation plus UVGI has a disinfection rate of 45 ACH if properly installed (34).

Personal protective devices are recommended when engineering controls are not likely to protect against inhaling infectious airborne droplet nuclei (e.g., in TB isolation rooms, treatment rooms in which cough-inducing or aerosol-generating procedures are performed, and ambulances during the transport of infectious TB patients) (13). The respiratory protective devices used in these settings should have a filter efficiency >95% with an obtainable face-seal leakage not greater than 10% (13). The efficiency of standard cup-shaped surgical masks in preventing the inhalation of droplet nuclei with a diameter of 1 to 5 µm is less than 50% (11) with a face-seal leakage of 0% to 20% (35). Since 1990, the use of particulate respirators including HEPA masks tested to filter 99.97% of 0.3 mm particles with a face-seal leakage less than 2% has been recommended (13).

Because of the very high costs of HEPA masks, the breathing difficulties they may cause, and the odd appearance of people wearing them, which may have a psychological impact on patients, the recommendation for personal respiratory devices is the most controversial aspect of existing TB guidelines. Reported cases of TB and skin-test conversions among health-care workers have led many to conclude that HEPA respirators are justified. On the other hand, many believe that less stringent personal protective devices, such as dust/mist respirators, may provide sufficient protection, with less discomfort and lower cost (31). New certification rules (42 CFR 84) have been recently approved that allow the use of dust/mist respirators, in addition to HEPA respirators, in TB control settings (36).

In the case of an airborne infection outbreak in a single room (e.g., a hospital room) of volume V, where a certain number I₀ > 1 of infective persons and S₀ of susceptible persons are present at initial time t = 0, the number of susceptible persons can be expressed as a function of the time interval from the beginning of the exposure (the time of exposure t, measured in minutes), the rate at which quanta are produced by the infective persons (the infection rate q), and the number of effective or equivalent air changes (AC) in the unit time (the disinfection rate C) (24).

The following assumptions (4,24,25) are taken into consideration: differences in susceptibility are neglected; the rate at which of infection are added to the air by infectious persons is considered constant; the latent period of the disease is longer than the time scale of the model, and the number of infective persons in the room is constant; droplet nuclei are instantaneously and evenly distributed in the room; droplet nuclei are assumed to be removed by fresh air ventilation of the room and ultraviolet irradiation at a constant rate; fresh air is at the same temperature and pressure as the air already present in the room; and the number of infected persons is proportional to the number of encounters between susceptible persons and quanta of infection, (and the encounter rate is proportional to both the number of susceptible persons and quanta of infection in the room [law of mass action]).

If the constant of proportionality between the number of infected persons and the number of susceptible persons times the number of quanta of infection Q is the ratio between the pulmonary ventilation p (we assume p = 0.01 m³/min) and the volume V of the room, the following equations can be derived:

• 1.

with the initial conditions

• 2.

The solution of equation 1 - equation 2 is

• 3.

• 4.

The percentage of PPD conversion among health-care workers is the following:

• 5.

• 6.

In this article, we simulate the adoption of various environmental control strategies (e.g., HEPA filtration devices or UVGI combined with ventilation) by giving suitable values to the parameter C. Also, we simulate the adoption of personal protective devices (e.g., surgical masks, dust/mist respirators, and HEPA masks) by scaling the rate at which quanta of infection are breathed (pulmonary ventilation p), which depends both on the mask's filter efficiency and face-seal leakage. If the masks adopted have a filter efficiency of X% and a face-seal leakage of Y%, then we can describe the effective filter efficiency of the mask as Z%, with Z = (X-XY/100). The scaling factor for p, therefore, is (100-Z)%.

For example, dust/mist respirators should have a filter efficiency X% equal to 95% and a face-seal leakage Y% not greater than 10%; then, their effective filter efficiency is Z = X-XY/100 = 85.5%, and the scaling factor for p is (100-Z)% = 14.5%. We derive a scaling factor of 60% and 3% for surgical and HEPA masks, respectively (13). Moreover, we assume C = 6 ACH (0.1 AC/min) for general ventilation alone, and C = 18 ACH (0.3 AC/min) or C = 45 ACH (0.75 AC/min) when HEPA filtration or UVGI is adopted in combination with ventilation (34).

We consider two types of nosocomial exposure to TB infection: exposure during high-risk procedures and exposure during normal working conditions on a ward where a source of TB infection is present. Using data from published TB outbreaks among health-care workers and assuming the use of different environmental control strategies (general ventilation, HEPA filtration, UVGI) and respiratory protective devices (surgical masks, dust/mist respirators, HEPA masks), we derive the percentage of PPD conversions that can occur.

High-Risk Procedures

We use data from four published TB outbreaks during which health-care workers were infected while performing bronchoscopy (7), jet irrigation of a thigh abscess (9), autopsy (10), and intubation (8) (Table 1). The values for q vary from six (7) to 514 (8) quanta per minute (qpm), indicating a high level of infectiveness of the index case in each outbreak. The patient with the highest rate of quanta production was considered a dangerous disseminator of TB (8).

Table 2 shows the percentage of PPD conversions that can occur during four procedures (bronchoscopy, abscess irrigation, autopsy, intubation) if different environmental control strategies were adopted, with and without the adoption of surgical masks, dust/mist respirators, or HEPA masks.

Figure 1

Figure 1. Percentage of PPD conversions predicted to occur as a function of time of exposure t during bronchoscopy, if different environmental control strategies were adopted, no personal protective devices were used, and...

The percentage of PPD conversions that can occur as a function of the time of exposure t during the least risky procedure -- bronchoscopy -- if different environmental control strategies were adopted, no personal protective devices were used, and the time of exposure varied from 50 to 400 minutes is shown in Figure 1.

Normal Working Conditions

We consider an MDR-TB outbreak that occurred on an HIV ward (21). During the initial period, the percentage of PPD conversions among health-care workers was 28%. Inadequate TB control programs or facilities (delays in TB diagnosis and in determining drug susceptibility and inadequate patient isolation precautions) facilitated the transmission. Administrative measures similar to those subsequently recommended (37) were implemented on the HIV ward, and early follow-up period showed a decrease in PPD conversions among healthcare workers (18%), who were required to wear surgical masks.

The actual time of exposure during the initial period is not available. Assuming that the ratio between the time of exposure t_in and the time span T_in=150 days of the initial period (January-May 1990) is equal to the ratio between the time of exposure t_ef=135 days (average between 139 and 129 days) and the time span T_ef=270 days of the early follow-up period (June 1990-February 1991), we assume that t_in=T_in x t_ef/T_ef ≈75 days. The remaining data are summarized in Table 3.

We calculate the rate of infection in the initial period to be q = 0.006; and after administrative control measures were implemented, it decreased to q = 0.003 in the early follow-up period. Administrative control measures decreased the rate of infection by 50%, thus confirming their key role in preventing TB transmission.

Figure 2

Figure 2. Percentage of PPD conversions predicted to occur on the HIV ward during the initial period, if different environmental control strategies were adopted and with and without the adoption of surgical masks...

Figure 2 shows the percentage of PPD conversions predicted to occur during the initial period with the use of different environmental control strategies and respiratory devices.

Our mathematical model indicates that a certain number of persons exposed to a source of TB infection will be infected in spite of all precautions. Nevertheless, if the infection rate is known, this number can be kept low by increasing the disinfection rate and decreasing the time of exposure.

We have evaluated the probability of acquiring TB infection under various exposure conditions and found that the efficacy of environmental control strategies depends on the duration of exposure and the infection rate. In particular, if the recommended levels of airflow are the only means of reducing the concentration of droplet nuclei in a room, they can neither eliminate TB contagion nor provide tolerable value for the risk of contagion. If HEPA filtration or UVGI is combined with general ventilation, protection against TB transmission is ensured at low infection rates, especially for brief exposures. As the infection rate increases, higher disinfection rates appear less and less effective in reducing the risk for transmission, and in situations of very intensive exposure, not even HEPA filtration or UVGI combined with general ventilation can keep the risk for transmission low enough. In these circumstances, respiratory protective devices may be used to protect health-care workers from inhaling droplet nuclei. The adoption of HEPA masks would provide nearly complete protection, even for long exposures, if used together with HEPA filtration or UVGI. Nevertheless, the efficacy of these control measures decreases as the infectivity of the source case increases; therefore, the only control measures that significantly reduce the infection rate are administrative.