Fig. 2.1 Risk of tuberculous infection due to contact with an active case, by type of case (Sm+, positive on direct smear of sputum microscopy for acid-fast bacilli; Sm- ,negative on direct smear but positive on culture for M. tuberculosis) and nature of contact (Close, living in the same household as the source case; Casual, acquainted but not liing with the source case). (Source: S. Grzybowski et al., Bull. Int. Union Tuberc., 1975, 50, 90-106.)
The likelihood of infection with tuberculosis, given contact with an infectious case, is a function of the duration and intensity of the contact. Thus, individuals living in the same household (and particularly those sharing the same bedroom) with an infectious case have the greatest risk of becoming infected. The likelihood of infection from casual contact is substantially less (Fig. 2.1). Given contact with an infectious case, on average, approximately one in six persons will become infected. It is much more likely that a contact will remain uninfected than that such a person will become infected after contact with a single infectious case.
Once infected, the likelihood of developing disease is not different, whatever the source. Some studies [2] have suggested that individuals infected by smear-positive source cases are more likely to develop disease. This conclusion is probably incorrect, resulting from the determination of the proportion of infected contacts arising from remote infection based upon population surveys of tuberculin sensitivity which underestimates the prevalence of remote infection among the subset of the population having contact with a case of tuberculosis (and particularly that group whose contact is with a smear-negative, culture-positive case). The likelihood of developing disease is greatest immediately following infection and declines exponentially from that point [8,9]. The incidence of clinically significant disease within the first year after infection is approximately 1.5%. Within the first 5 years after infection (during the steep slope of the decline) the cumulative risk of disease is between 5 and 10% the remainder of the lifetime risk (under stable social and immunological conditions) is probably around 5%. Thus, under usual conditions and on average, the total lifetime cumulative risk of developing disease after becoming infected by contact with an infectious case, is perhaps 15% (about one in six persons). Where repeated contacts with infectious cases are likely, the probability of developing disease may be higher.
Wallgren [10], using the tuberculin skin test to determine the point at which individuals became infected, calculated what he called a 'timetable' of tuberculosis. The type of tuberculosis and the site in the body that was affected bore a striking relationship to the time since the infection occurred. This continues to be true, for example, in Tanzania where the type of tuberculosis varies markedly with age, as Wallgren observed (Fig. 2.2). The first event to occur following infection (within 12 weeks after contact with the infectious case) is the conversion of the tuberculin skin test. In most individuals, systemic response to the infection includes a
Fig. 2.2 Distribution of types of tuberculosis cases (sm+, positive for acid-fast bacilli on direct smear microscopy of sputum; sm-, negative on direct smear, ep, extrapulmonary) in Kilimanjaro Region, Tanzania in 1989 by age group.
slight rise in temperature, possibly accompanied by flu-like symptoms. Subsequently, the tuberculin skin test demonstrates significant induration for many years, although in some individuals, it may become insignificant or absent in old age [11]. A minority of people who become infected with tuberculosis develop primary disease. Usually, disease is localized in the lung and the regional lymph nodes within the chest, resolving without treatment, leaving a very small calcified scar in the pulmonary parenchyma along with calcification of the hilar lymph node. The appearance of a healed primary complex on chest radiograph has the same significance in terms of probability of subsequent active disease as does a significant tuberculin skin reaction, as both merely reflect previous primary infection. In a small proportion of patients with primary tuberculosis, complications many occur. These include local extension and cavitation (progressive primary tuberculosis), dissemination throughout the body (miliary tuberculosis, often accompanied by tuberculous meningitis), and local complications, the most common of which is obstruction of the right middle lobe bronchus leading to an obstructive pneumonia with subsequent localized bronchiectasis.
Tuberculous pleurisy occurs, on average, 6 months following primary infection [12]. It is usually a self-limited condition and often resolves spontaneously. In such cases, the likelihood of subsequent relapse (usually in the form of pulmonary tuberculosis) is approximately one in three. A number of hypersensitivity reactions to the tubercle bacillus accompanying primary infection are known to occur, such as dactylitis, erythema nodo-sum and phlyctenular conjunctivitis. Where tuberculosis is common, tuberculous lymphadenitis (scrofula) is the most common form of extrapulmonary disease. It occurs quite early following infection and is most common in groups in which recent infection with tuberculosis is common (thus young people).
Post-primary pulmonary tuberculosis is the most common form of tuberculosis and occurs most frequently within 5 years of primary infection. Approximately 85% of such cases may be bacteriologically confirmed by sputum culture. Usually more than one-half of these are positive for acid-fast bacilli on direct microscopy of sputum specimens (and are termed smear-positive).
Skeletal tuberculosis may occur at any point in the timetable and has three forms: spondylitis, arthritis and isolated osteomyelitis [13]. Spondylitis most frequently involves the lower intervertebral discs. Tuberculous arthritis most commonly involves the hips, the knees, the shoulders and the elbows, in that order of frequency. A high proportion of patients with tuberculous arthritis have evidence of tuberculosis on the chest radiograph. Abdominal tuberculosis [14, 15] occurs in several clinical types. The most common, tuberculous peritonitis, presents with the picture of hepatic failure, abdominal mass or acute abdomen. Ileocecal tuberculosis has all the clinical appearances of Crohn's disease. Anorectal tuberculosis is most frequently a companion of pulmonary tuberculosis and in
