Communications to the Editor |

Persistent Presence of Acid-Fast Bacilli in Pulmonary Tuberculosis : Possible Implications for Developing Countries FREE TO VIEW

Neeraj Gupta, MBBS, MD
Author and Funding Information

Affiliations: Ajmer, India,  University of British Columbia Vancouver, BC

Correspondence to: Neeraj Gupta, MBBS, MD, 16, Anand Nagar, Anasagar Circular Rd, Ajmer - 305006 (RAJ.) India

Chest. 2000;118(3):880-881. doi:10.1378/chest.118.3.880-a
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To the Editor:

I went carefully through the study, “The Significance of the Persistent Presence of Acid-fast Bacilli in Sputum Smears in Pulmonary Tuberculosis” by Al-Moamary et al (September 1999).1 They have correctly pointed out the fact that while their recommendations may apply well to developed countries, it may not be the case for other developing countries, where the incidence of initial as well as acquired drug resistance is relatively high.2

In a country like India, the facility of a standard laboratory for Mycobacterium tuberculosis culture and sensitivity is far from the reach of the general population. Furthermore, the concept of directly observed treatments has not yet been applied to the wider part of the nation to ensure compliance to treatment. With this background, one can afford to go for culture and sensitivity tests only when treatment failure is suspected on the basis of smear positivity at the end of 20 weeks of treatment, as recommended by World Health Organization (WHO) criteria.3

The purpose of my communication is to share my preliminary data (unpublished) from a study of multidrug-resistant tuberculosis (MDR-TB), which is going on at Jawahar Lal Nehru Medical College, in Ajmer, India. On the basis of smear positivity at 20 weeks of treatment with first-line antituberculous drugs, sputa of 26 patients were subjected to culture and sensitivity tests for antituberculous drugs. Twenty-four patients (92%) had positive culture after 4 to 8 weeks of incubation. All of them were resistant to isoniazid and rifampicin, with variable resistance to other antituberculous drugs. Sixteen patients (67%) had moderate to advanced parenchymal disease.

On the basis of the above data (although small), I have my submission for developing countries in the same context: (1) All patients with smear-positive cultures after 20 weeks of treatment with first-line drugs should strongly be suspected as having MDR-TB and must undergo culture and sensitivity tests; and (2) There are more chances of treatment failure with more extensive parenchymal diseases in contrast to the above-mentioned study.

In the last, I have two important queries to the authors regarding the interpretation of their study results:

1. In the smear-positive/culture-positive group, the median period of persistently positive smear results was 39 weeks. This should always be a cause for concern. The cause of prolonged culture positivity in this group is not discussed! The lack of a fourth drug (ethambutol/streptomycin) in the initial intensive phase may be one of the causes, because all patients were smear positive at the outset. Transient drug resistance may be another explanation that does not influence the treatment response. It is also not clear whether these patients were fresh or defaulter; the treatment for them differs!

2. Do their results have implications for a modification in the definition of treatment failure, which the WHO defines as persistent smear positivity at ≥ 5 months after starting treatment?2 Should culture be added to the present definition to universalize the criteria?

Al-Moamary, MS, Black, W, Bessuille, E, et al (1999) The significance of persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis.Chest116,726-731
Paramasivan, CN An overview of drug resistance in India.Lung India1998;16,21-28
WHOTB: a clinical manual for Southeast Asia. Delhi, India: Lordson, 1997; 66.
To the Editor:

Dr. Gupta’s observation that our findings may not be applicable to developing countries is valid and should serve to re-emphasize a point we had tried to stress in the paper, namely, that our findings apply to a modern tuberculosis screening program in a developed country. Persistently positive smears in some developing countries, as shown by the data Dr. Gupta presented, should strongly suggest treatment failure.

As concerns Dr. Gupta’s questions, of our seven patients who had persistently positive sputum smears and cultures, two had multiple drug-resistant disease and another had resistance to isoniazid and was intolerant of rifampin. Of the four patients with a fully sensitive organism, two received only isoniazid, rifampin, and pyrazinamide as initial treatment, and the other two received four drugs initially. Both patients treated with three drugs initially had radiographic evidence of cavitation and had either two or three of six lung zones involved with disease. Whereas it is unlikely that addition of ethambutal to the initial drug regimen would have hastened smear and culture conversion, streptomycin may have. Apart from that, we have no information that would explain the persistent smear and culture positivity in these patients. We know of no evidence that transient drug resistance has any clinical relevance.

The World Health Organization (WHO) definition of treatment failure referred to is clearly an operational definition meant to be applicable to all settings, including those where cultures are not readily available. In our setting, as we have shown, most patients who met the WHO definition for treatment failure did not, in fact, have treatment failure. In Dr. Gupta’s setting, the vast majority meeting the definition would be considered treatment failures. Ideally, culture and sensitivity data are required at that point to guide therapy. The WHO definition seems realistic in a setting such as the one described by Dr. Gupta. Modifying the definition to include culture data in settings where cultures are not available would lessen the utility of the definition in such settings. The definition is clearly not appropriate in our setting, but it is not relied upon in guiding management because of routinely available culture data.




Al-Moamary, MS, Black, W, Bessuille, E, et al (1999) The significance of persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis.Chest116,726-731
Paramasivan, CN An overview of drug resistance in India.Lung India1998;16,21-28
WHOTB: a clinical manual for Southeast Asia. Delhi, India: Lordson, 1997; 66.
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