Several patient, pathogen and environmental factors deter- mine whether transmission occurs (see Table 1).
Table 1. Patient, pathogen and environmental factors affecting transmission.
|Disease type||Strain variability||Indoor/outdoor|
|Smear-positive/smear-negativeCavitary/non-cavitary on CXR
Typical/atypical on CXR
|Extrapulmonary||Proximity to the source case|
|Respiratory symptoms||Duration of exposure|
Abbreviations: CXR, chest radiograph.
Table 2. Risk of infection among household (close) contacts according to bacteriologic status of index case (pulmonary TB only).
|Number and % infected contacts
by bacteriologic status of index case
|Contacts||S + C+||S-C+||S-C-||General
|Canada – Indigenous||0-19||1168||592||45||377||31||199||27||NA|
Adapted from Menzies D. Issues in the management of contacts of patients with active pulmonary tuberculosis. Can J Public Health 1997;88:197–201.
Abbreviations: S, smear; C, culture; PPD, purified protein derivative.
aTaken from the same reference (ie, a comparable reference population).
bIn this study contacts were considered infected only if tuberculin conversion and/or primary TB had been documented.
1.2.1. Patient (source) factors
With rare exceptions, transmission requires that a TB patient be able to generate an infectious aerosol. Therefore, transmission is predominantly from adolescent or adult patients with adult-type pulmonary TB — defined as upper lung-zone disease, with or without cavitation, but with no discernable adenopathy, on chest radiograph. Younger children can, on occasion, be infectious,4 but as a general rule they have few bacilli in their lung lesions, often do not produce sputum and therefore are rarely in a position to transmit.5 The ability of pulmonary TB patients to transmit can vary, depending upon a number of factors, listed in the following section. These factors affect contagiousness regardless of the patient’s human immunodeficiency virus (HIV) serostatus, although HIV-coinfected TB patients are less infectious than HIV-uninfected TB patients when they have severe immunosuppression.6
Sputum smear status
The most infectious pulmonary TB patients are those with smear-positive/culture-positive pulmonary TB, followed by those with smear-negative/culture-positive pulmonary TB, with the least infectious being those with smear-negative/culture-negative pulmonary TB.7–15 (See Table 2 for a summary of the epidemiologic studies on the risk of infection in household [close] contacts grouped according to the bacteriologic status of the source patients.) Sputum that is smear-positive contains 5,000 or more bacteria per milliliter.16 Patients with smear-positive bronchoalveolar lavage fluid are considered just as infectious as those with smear-positive sputum.16 Those with smear-positive induced sputum are usually considered just as infectious as smear-positive spontaneously expectorated sputum, though there are currently no data that prove this assertion. Using molecular epidemiologic tools alone, the relative transmission rate of smear-negative compared with smear-positive patients has been determined to be 0.17-0.22 or roughly one-fifth the likelihood of transmission.17–19 Using molecular epidemiologic tools combined with conventional epidemiologic, spatial temporal and genomic data, the relative transmission rate between these groups has been determined to be 0.10, or roughly one-tenth the likelihood of transmission.20 Higher sputum smear grades are associated with the highest relative risk of transmission.21 In addition to the greater infectiousness of smear-positive patients, the risk of disease after infection from a smear-positive case is greater than after a smear-negative case, presumably because of a higher risk of reinfection or a higher infecting dose (see the following section). A positive polymerase chain reaction (PCR) is also a risk factor for transmission.21 In the future, semiquantitative results from the real-time PCR method, Xpert MTB/RIF assay, may replace smear microscopy as an indicator of infectiousness.22,23
Disease type on plain chest radiograph
Pulmonary TB patients with cavitation on chest radiograph are considered to be more infectious than pulmonary TB patients without cavitation, after smear status has been taken into account.24–26 Smear-positive pulmonary TB patients with lung cavitation have higher semiquantitative smear results than those without cavitation.27,28 Smear-positive pulmonary TB patients with “typical” chest radiographic findings (upper lung-zone disease, with or without cavitation, and no discernable intrathoracic adenopathy) are more infectious than smear-positive pulmonary TB patients with “atypical” chest radiographic findings (all others).29
Patients with laryngeal TB are more infectious than those with pulmonary TB.30 Most patients with laryngeal TB also have far advanced pulmonary disease.31
In general, normal breathing produces few infectious particles, a bout of coughing or 5 minutes of speaking in a normal tone produce many more, and a sneeze produces the most.32,33 The likelihood that household contacts will be infected increases with the frequency of cough in the source case.13,34 When the aerial infectivity of the droplets from smear-positive patients was evaluated by artificially atomizing sputum and exposing guinea pigs to a standard dose, there was marked variability in the infectivity of aerosolized sputum, perhaps explaining the extraordinary heterogeneity of infectiousness among patients with smear-positive pulmonary TB.35–37 Thus, although patients may appear to have an equal number of bacteria in their sputum, the physical and chemical properties of their sputum, and/or cough characteristics or behavior may determine whether they produce a large or small number of droplet nuclei. Smoking can increase the risk of transmission, presumably via its effect on one or more of the aforementioned mechanisms.38 Allergy or viral upper respiratory tract infection may also increase aerosol formation, but these are not well studied.39
The number of contacts and the duration of exposure of each contact may increase as time to diagnosis increases. The longer the duration of symptoms in the source case, the greater the risk of transmission.21
Effective treatment, appropriate to drug susceptibility test results, rapidly reduces cough frequency and sputum bacterial counts13,40 (see Chapter 5: Treatment of Tuberculosis Disease and Appendix B – De-isolation Review and Recommendations). Given the frequency of drug resistance, the determination that treatment is effective in reducing the infectiousness of a given patient should reflect objective clinical, radiographic and/or microbiologic improvement, and not simply time elapsed since treatment initiation.
1.2.2. Patient (recipient) factors
On the one hand, immunocompetent persons who have been infected in the past have considerable protection against reinfection, estimated to be about 80% (see the following section on Pathogenesis). Immunocompromised persons, on the other hand, may become reinfected despite having been infected and adequately treated in the past. Observational studies suggest that Bacille Calmette-Guerin (BCG) vaccination in infancy offers some protection against infection with M. tuberculosis as detected by an interferon-gamma release assay (IGRA).41–44
1.2.3. Pathogen factors
Data are emerging to suggest that one or more virulence properties of M. tuberculosis may affect its ability to be transmitted.45 For example, one strain may be better suited than another to overcoming the innate resistance of the host. Although drug-resistant strains have shown reduced virulence in animal models,46 clinical evidence of their transmissibility is compelling47–50 and for practical purposes they should be considered just as transmissible as drug-susceptible strains. Beijing/W strains have been reported to be hypervirulent, but indices of transmission have been found to be no greater in patients with these strains than in those with other strains.51
1.2.4. Environmental factors
With rare exceptions, outdoor exposures are unlikely to result in transmission.52 Almost all transmission is understood to occur indoors. Factors in indoor transmission include the following items.
Air circulation and ventilation
Given a defined number of bacteria expelled into the air, the volume of air into which the bacteria are expelled determines the probability that a susceptible individual breathing that air will become infected. A high concentration of viable bacteria in the inhaled air of the contact is favored by small spaces, poor ventilation or recirculation of air, as well as little sunlight (ultraviolet rays). Ventilation dilutes the concentration of infectious droplet nuclei (see Chapter 14: Prevention and Control of Tuberculosis Transmission in Healthcare Settings).
Proximity to the source patient
Proximity to the source patient is also a determinant of transmission. Related to this is overcrowding: if, as a result of there being many people in a room, an individual is forced into close proximity with an infectious case, their risk of infection is likely to increase. And, of course, the number of persons exposed is increased.
Duration of exposure
In general, hours of exposure to a patient with infectious TB is an important predictor of TB infection.53 The duration of exposure associated with transmission is usually prolonged (days, months or even years), although reports have confirmed that, on rare occasions, close indoor exposures as short as a few minutes may be sufficient to infect a contact.54
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