recent infection has been identifed, intenventon with chemotherapy is ethically mandatory, making further study of the natural history impossibie.

　

3.　Host immunity

The function of the immune defense system is vitally important in reducing the probability of the transition from infection to disease and is the key predictor of this transition.　It may also be the determining factor in the relation between desease and time since infection.　The level of cell-mediated immunity in patients with HIV infection, measured by the CD4 count, is highly correlated with the probability of this transition¹²⁴ and has been shown to correlate with the clinical pattern of tuberculosis disease²⁹.　The CD4 count is a relatively crude measure of immune status; more precise measures have not yet been developed.

　

4.　Bacterial load

The bacterial load in cases of tuberculosis is important in determining the clinical course and transmission potential.　The patients with the highest bacterial load are much more likely to have higher concentrations of bacteria in expectorated sputum and are therefore much more contagious than other patients²³.　Such patients are also likely to have a less favorable clinieal course with a significantly higher fatality rate³⁵.　In additon, they are more likely to become again contagious after becoming non contagious⁴⁰.

Bacterial load can be crudely estimated by grade of positivity of sputum smears.　More precise measures are the colony-forming units whose trend has been shown to relate to the outcome of chemotherapy in studies of early bactericidal activity¹²⁵.　The trend in bacteriological conversion is related to bacterial load and has also been shown to accurately predict clinical course¹²⁶.

　

F.　Evaluation of interventions

　

The epidemiology of tuberculosis includes an evaluation of the situation of tuberculosis as well as measures to control it¹.

　

1.　Objectives of intervention

The aims of the fight against tuberculosis are¹²⁷:

-　for individual patients: to cure their disease, to quickly restore their capacity for activities of daily living and to preserve their position in their family and community;

-　for a community: to decrease the spread of tuberculous infection and, by this means, to hasten the disappearance of this disease from society.

　

2.　Outcome of treatment

The outcome of treatment of sputum smear positive pulmonary tuberculosis should be routinely evaluated wherever tuberculosis patients are treated.　The following definitions are officially recommended¹²⁸:

-　smear negative (cured): smear negative at one month prior to the completion of chemotherapy and on at least one previous occasion;

-　smear not done (treatment completed): completed treatment but smear results not available on at least two occasions prior to the completion of treatment;

-　smear positive (failure): smears remaining or becoming again smear positive at five months or later during treatment;

-　died: death from any cause while on treatment;

-　defaulted: failed to collect medication for more that two consecutive months after the date of the last attendance during the course of treatment or, at the time of evaluation (15 months after the close of the quarter in which the patient was initially registered) is still on treatment;

-　transferred out: treatment results unavailable on a patient who was transferred to another centre to continue treatment.

The various outcomes are, to a large extent, intermediate endpoints, are designed for routine monitoring and their definitions are consequently of limited value for scientific usage.　For example, the definition of death in this circumstance does not accurately reflect fatality as the death is more likely from causes other than tuberculosis.　In addition, the definition of smear positive as a treatment result may be in error due to the fact that some patients may remain smear positive while being culture negative, due to the continued excretion of dead bacilli^{129 130}.　The use of cultures, where reliably available, can bring more precision to the definitions of smear negative (cured) and smear not done (treatment completed).

In spite of these deficiencies, it is important to use the internationally recommended definitions for purposes of comparison.　Moreover, it is possible, within these definitions, to create subsets with more precise characterization.

Another outcome of treatment, not routinely monitored, is that of relapse after treatment.　This occurs when a case who, having previously been treated, was declared cured prior to becoming once again sputum smear positive¹³¹.　Such a patient would require a second positive sputum smear to confirm the first smear in order to be classified a relapse.　The defnition can be extended, for scientific purposes, to include cases positive on cuture, although negative on smear.

　

3.　Impact of chemotherapy

Chemotherapy immediately reduces fatality from tuberculosis, no matter what the quality of the treatment¹³².　Tuberculosis mortality rates began a steep decline with the advent of the first chemotherapy agent (streptomycin) in virtually every country in Europe and North Ameriea.

When chemotherapy is well applied, the prevalence of tuberculosis is rapidly reduced while the incidence is more slowly reduced¹³³ due to the continuing

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