National Tuberculosis Seminar, Hanoi, Vietnam, February,1997
Problems of Diagnosis of Tuberculosis in NTP
Toru Mori, M.D. (Research Institute of Tuberculosis)
1. Smear positive TB as a top priority in CF
There may be nobody to doubt the significance of smear positive tuberculosis as a top priority in case-finding and treatment of tuberculosis.
It is epidemiologilly important as a virtually sole type of disease transmitting infection. At the same time, it is an important target for medical, curative service, because of its serious symptoms and its severe prognosis. Also, there are some other reasons to enhance its relevance as a target of control activity. It is rather easy to detect with a use of simple instrument and technique. It is clinically severe enough to drive patients to take action seeking for its cure.
All these factors altogether make a rationale for the case finding on passive mode.
Of cause beside these above, the concept of the passive case-finding of smear positive tuberculosis should be supported by other factors, such as the availability of PHC faceless with such capacity and people's motivation for its use, or avoidance of excessive case load due to active case finding scheme.
2. Quality of Smear examinations in TB Diagnosis
Needless to say, the above principle has been accepted worldwide. But we have to remember that the preassumption is that the smear examination is accurate enough to believe. If not so, the situation can be a disaster. It is not only essential in the diagnosis of tuberculosis, but also in the monitoring of treatment Therefore, the quality assurance of the smear examination is very important and this is one of our subjects in this workshop.
Generally, the accuracy or quality of the diagnosis is measured with two basic parameters, i.e., sensitivity and specificity. Sensitivity is a measure to indicate to which extent the diagnosis is free from false negative cases, or how many true cases can be diagnosed. Specificity is a measure to indicate to which extent the diagnosis is free from false positive cases. Today we have no time to go further into this matter, but it is important to be always aware of the needs of quality assurance of the laboratory works.
One point I would like to raise is one of the operational ways to assuring quality of diagnosis, that is a principle of three examinations of smear in diagnosing a patient. Here is a study on the effectiveness of such practice. In this study a total of 194 patients with X-ray shadow suggesting tuberculosis were examined consecutively 8 times with both smear and culture. 53 were positive for smear, and 68 for culture. For smear positive cases, there were 36 cases proven positive on the first examination. By adding another examination, case yield is increased by 9, so that with 2 times of examinations, 85% of the ultimately detected cases could be picked up, and after 3 times the additional gain is small. Thus, multiple test can increase sensitivity of a test. At the same time we have to have 2 positives tests out of three examinations in order to diagnosed a case, which is for the sake of better specificity.
3. Diagnosing and Treating Smear negative TB
As you have seen in the above study, culture examination added another 22 cases as cases of bacteriologically confirmed tuberculosis.
If we admit a smear negative and culture positive case in the case definition of tuberculosis, then the culture examination can increase the specifity.
The same is true also for X-ray diagnosis of tuberculosis. Then the problem is significance of including such cases in the target of treatment of tuberculosis.
These means of examination do exist already in reality, but in order to make argument straightforward, I will start the discussion from basic points. The first point is a technical limitations of these high techniques. Culture examination may give more false positive cases, because of e.g., contamination with environmental mycobacteria. Far more serious problems is concerning X-ray diagnosis, i.e., to tell whether the shadow is active, or requiring treatment, or inactive. There have been many studies to show the very wide variation of the reading results between different readers, even in case of well trained ones. Among others, the problem of diagnosis of activity based on only one film remains.
In our experiment of test reading of Xray films of various types and staages of tuberculosis patients by many expert readers, there are some cases which are diagnosed as "active" by one third of the reader, as "intermediate" and "healed" , each by another one third.
Still it is assumed that there could be some consensus on the definition of the activity of the shadow, so that such finding as newly appearing infiltrations that is resistant to general antibiotics therapy, or cavity in the patients never treated for tuberculosis, etc. could be diagnosed as active TB. In Japan, about 55 of the newly notified tuberculosis cases are those diagnosed in that way. Recently, in one Health Centre paris of Xray films were collected, i.e. pretreatment and posttreatment films, and were reviewed by comparison. It was revealed that in about one third of the pairs there was no change in the shadow suggesting the lesion had been inactive from the beginning. If this is a nationwide phenomenon, then in Japan about 17% of tuberculosis cases are overdiagnosis cases. In order to avoid this kind of disaster as much as possible, again the quality assurance of diagnosis is necessary which is far more formidable task than for the bacteriology laboratory procedure.
