4.　From Infection to Contagiousness

Tuberculosis disease may occur directly after infection or, more commonly, it may develop after a period of quiescence, through reactivation of the quiescent micro organisms.　The transition from infection to disease has been described in detail in contacts of tuberculosis cases, prior to the development of chemotherapy²⁶, in "controls" in trials of preventive chemotherapy of primary infection²⁷, and in "controls" in trials of vaccination of adolescents with Bacille Calmette Guerin (BCG)²⁸.　The site and type of disease varies with the time that has elapsed since infection has occured²⁷.　This variation is probably influenced by the state of the immune system at the time the disease occurs²⁹.　The variation with immune status is best illustrated in individuals infected with the Human Immuno Deficiency Virus (HIV).　In such individuals, the lifetime probability of progression from infection to disease increases from one in six to ten, to one in two to three³⁰ and is only limited by the reduced life expectancy of the HIV-infected individual.

The most frequent site of involvement of tuberculosis is the lung which is essentially the only contagious form of the disease.

　

5.　From Contagious to No longer contagious

The clinical course of tuberculosis, in the absence of specific treatment, has been characterized from several sources: a series of reports from the era prior to the introduction of chemotherapy^{31 32} and a report from India, indicating the outcome of patients in the absence of chemotherapy³³.　From these studies, it has been shown (figure 2) that over five years following the diagnosis of tuberculosis, approximately half the patients will die, one-third will become quiescent (bacteriologically negative) and slightly less than one-fifth will remain alive and bacteriologically positive.　Whether the patient is dead or becomes bacteriologically negative, the patient is no longer contagious.　Thus, it is the period of bacteriological positivity which is the determining factor of contagiousness.　

The type of tuberculosis with the most adverse outcome is disseminated tuberculosis, often associated with tuberculous meningitis, in which there is a high fatality rate, even when chemotherapy is given³⁴; this form of tuberculosis is not usually contagious but is rather a marker of recent infection.　Tuberculosis with extensive involvement of the lungs (far advanced disease) which is also associated with the highest bacterial population and therefore the greatest contagious potential, has a higher than average fatality rate as well^{35 36} whether or not chemotherapy is given.　Other forms of tuberculosis, which are less contagious, have a much better prognosis.

While response to treatment does not vary in those with Human Immune Deficiency Virus (HIV) infection, survival is markedly reduced and continuous reduction occurs after completion of treatment³⁷.　Within eighteen months of diagnosis, survival is reduced to nearly fifty per cent.

　

6.　From No longer contagious to Contagious again

An individual who has had tuberculosis which was bacteriologically active but which has become no longer active (has been cured either with or without chemotherapy) can become again contagious.　This may occur: a) if the micro organisms from the disease become active again or b) if the individual becomes infected with an entirely new strain of organisms after exposure to another source case.

The probability of the former occurring, when the individual has never previously been treated, has been shown to decline over time from 4.4% annually for the first five years to 1.6% annually for the next five years³⁸.　Subsequent probability of the disease becoming active again is approximately 0.5% per annum, continuing throughout the lifetime of the individual³⁹.　It is greater in those with larger residual scars⁴⁰ and markedly reduced in those who have had adequate chemotherapy for either treatment of their previous disease or for prevention of reactivation.

The probability of becoming reinfected is related to the likelihood and nature of exposure but is reduced by an immunological protection afforded by the initial infection^{8 41 42}.　Studies utilizing molecular genetic techniques⁴³ have demonstrated, however, that a substantial proportion of such cases (as many as 40% in some studies) may occur in this way.

　

B.　Measuring tuberculosis

　

1.　Counting deaths

In the past, mortality rates have been used to measure the problem of tuberculosis.　Mortality rates are available for whole populations from as far back as the mid 19^th century and for selected locations (large cities) from the 18^th century⁴⁴.　The introduction of chemotherapy for the treatment of tuberculosis has disrupted the constant relation between cases and deaths⁴⁵ and has rendered mortality an unreliable index of the tuberculosis problem since the 1950s.

　

Test characteristics

A review of 394 deaths related to tuberculosis was made in Norway⁴⁶.　All deaths were reviewed by a panel of experts to determine those whose deaths were due to tuberculosis.　In this study, the efficiency of officially reported mortality statistics was: sensitivity 69%, specificity 87%, positive predictive value 70% and negative predictive value 87%.　Another study in Canada³⁸ found 153 cases who had died while on treatment for tuberculosis.　Among these deaths, only 30 (20%) were due to tuberculosis.　Another 28 died of tuberculosis (48% of deaths due to tuberculosis) in the same period but were diagnosed only after death and were not included in the official Vital Statistics.

　

2.　Identifying cases

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