On 2015 Jun 23, Prof.Dr.Jogenananda Pramanik commented:

Delayed diagnosis of MDR-TB and TB with co-infection of HIV – A major concern!

Tuberculosis (TB) is emerging as an dreaded communicable disease in Malaysia, with the death rate even higher than that of dengue (Ministry of Health, Malay Mail, 2014). Besides being a deadly disease, TB is also an expensive disease which is adding additional economic burden to the health system of the country. Delayed diagnosis of tuberculosis (TB) may lead to an increased period of infectivity in the community, a delay in treatment and a severe form of the disease like MDR-TB and TB with HIV co-infection.(1-7) We appreciate the insightful attempts of Chang CT1, Esterman A.(1) in analyzing the delay in diagnosis of tuberculosis in two perspectives: (A) period between the onset of TB symptoms to any first medical consultation (patients' delay); and (B) period between the first medical consultation to the diagnosis of TB (diagnosis delay). Moreover, we would like to emphasize that there is a need to reduce the time lag between the first inoculations of patient’s sample in solid or liquid culture media till appearance of macroscopically detectable AFB colonies. One of the priorities in the control of tuberculosis is to cure patients with the disease, given that the most effective way to prevent transmission and avoid the appearance of drug-resistant strains is to detect cases of tuberculosis early and treat them appropriately. As a routine practice, all patients suspected of having PTB should submit at least two sputum specimens for microscopic examination in a quality-assured laboratory. These techniques while remaining an important baseline modality of investigations currently, they lack the desired sensitivity or are time consuming. Hence, Nucleic Acid Amplification Tests for the detection of Mycobacterium tuberculosis are useful tools for rapid diagnosis of TB, both pulmonary and extra-pulmonary. These tests are also useful for the rapid screening of patients suspected of MDR-TB. Nucleic Acid Amplification Tests (NAAT) provide rapid results within 24 - 48 hours and has greater PPV (>95%) with AFB smear positive specimens. They have the ability to confirm rapidly the presence of Mycobacterium in 50 - 80% AFB smear negative, culture positive specimens. However, Molecular assays may supplement but cannot replace conventional methods for culture and sensitivity. Moreover their high cost and requirement for sophisticated laboratory infrastructure limit their use in routine diagnosis. Laboratories with advanced infrastructure are limited in most of the peripheral diagnostic laboratories in Malaysia(6-7).

To balance the lack of sophisticated laboratory infrastructure for performing TB identification and drug sensitivity tests to exclude MDR-TB cases with speed and accuracy, there is an urgent need of inexpensive, non-invasive, robust diagnostic and culture sensitivity test. To achieve this goal an attempt was made to incorporate thyroxine hormone in solid and liquid media for culture of AFB in vitro (8-12) Presently, we planned to evaluate the effectiveness of this thyroxine supplemented culture media for culture of AFB from clinical samples in vitro and also to standardize use of this method in comparison to routine AFB culture procedure. This study may prove to be a useful technique for rapid culture isolation of AFB in vitro.

References:

1.Chang CT1, Esterman A.Diagnostic delay among pulmonary tuberculosis patients in Sarawak, Malaysia: a cross-sectional study. Rural Remote Health. 2007 Apr-Jun;7(2):667. Epub 2007 May 11. 2. Alison Rodger, Shabbar Jaffar, Stuar Paynter et al., Delay in the diagnosis of pulmonary tuberculosis, London, 1998-2000: analysis of surveillance data: BMJ 2003; 326 doi: http://dx.doi.org/10.1136/bmj.326.7395.909 (Published 26 April 2003)<br> 3. Zahar JR, Azoulay E, Klement E et al., Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure. Intensive Care Med 2001; 27: 513–520 4. Wares D.. Delay in diagnosis of tuberculosis: of remaining concern in England and Wales. J Public Health Med 1999; 21: 355–356 5. Aldhubhani AH1, lzham MI, Pazilah I, Anaam MS (2013)Effect of delay in diagnosis on the rate of tuberculosis among close contacts of tuberculosis patients. East Mediterr Health J. 2013 Oct;19(10):837-42. 6. Ying Li1†, John Ehiri2†, Shenglan Tang et al., 3(2013)Research article Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis:BMC Medicine 2013, 11:156 doi:10.1186/1741-7015-11-156 7. Timothy William123, Uma Parameswaran12, Wai Khew Lee4 et al., Pulmonary tuberculosis in outpatients in Sabah, Malaysia: advanced disease but low incidence of HIV co-infection: BMC Infectious Diseases 2015, 15:32 doi:10.1186/s12879-015-0758-6 8. Pramanik J, Lodam AN, Reddy MVR, Narang P and Harinath BC. Increased yield of excretory-secretory antigen with thyroxine supplementation in in vitro culture of tubercle bacilli. Ind. J. tub. 1997; 44: 185-190. 9. Pramanik J, Lodam AN, Badole CM, Reddy MVR, Patond KR and Harinath BC. Detection of tubercular antibody and antigen in sera of bone and joint tuberculosis. Ind. J. Clin. Biochem. 2000; 15 (1): 22–28. 10. Lodam AN, Pramanik J, Reddy MVR and Harinath BC. Diagnostic potential of fractionated Mycobacterium tuberculosis H37Ra excretory-secretory (EST-DE1) antigen in pulmonary tuberculosis. Ind. J. Clin. Biochem. 1997; 12 (1): 71-77. 11. Pramanik.J. BMJ.2003.http://www.bmj.com/rapid-response/2011/10/30/delays-diagnosis-tuberculosislet-us-use-thyroxine-supplemented-culture-med: Delays in diagnosis of tuberculosis? Let us use thyroxin supplemented culture medium for early lab-diagnosis. 12. Pramanik.J. BMJ: 2004.http://www.bmj.com/rapid-response/2011/10/30/early-diagnosis-tuberculosis-reported-third-world-country Early diagnosis of tuberculosis-reported from third world country:A research letter from India.

On 2015 Jun 23, Prof.Dr.Jogenananda Pramanik commented:

Delayed diagnosis of MDR-TB and TB with co-infection of HIV – A major concern!

Tuberculosis (TB) is emerging as an dreaded communicable disease in Malaysia, with the death rate even higher than that of dengue (Ministry of Health, Malay Mail, 2014). Besides being a deadly disease, TB is also an expensive disease which is adding additional economic burden to the health system of the country. Delayed diagnosis of tuberculosis (TB) may lead to an increased period of infectivity in the community, a delay in treatment and a severe form of the disease like MDR-TB and TB with HIV co-infection.(1-7) We appreciate the insightful attempts of Chang CT1, Esterman A.(1) in analyzing the delay in diagnosis of tuberculosis in two perspectives: (A) period between the onset of TB symptoms to any first medical consultation (patients' delay); and (B) period between the first medical consultation to the diagnosis of TB (diagnosis delay). Moreover, we would like to emphasize that there is a need to reduce the time lag between the first inoculations of patient’s sample in solid or liquid culture media till appearance of macroscopically detectable AFB colonies. One of the priorities in the control of tuberculosis is to cure patients with the disease, given that the most effective way to prevent transmission and avoid the appearance of drug-resistant strains is to detect cases of tuberculosis early and treat them appropriately. As a routine practice, all patients suspected of having PTB should submit at least two sputum specimens for microscopic examination in a quality-assured laboratory. These techniques while remaining an important baseline modality of investigations currently, they lack the desired sensitivity or are time consuming. Hence, Nucleic Acid Amplification Tests for the detection of Mycobacterium tuberculosis are useful tools for rapid diagnosis of TB, both pulmonary and extra-pulmonary. These tests are also useful for the rapid screening of patients suspected of MDR-TB. Nucleic Acid Amplification Tests (NAAT) provide rapid results within 24 - 48 hours and has greater PPV (>95%) with AFB smear positive specimens. They have the ability to confirm rapidly the presence of Mycobacterium in 50 - 80% AFB smear negative, culture positive specimens. However, Molecular assays may supplement but cannot replace conventional methods for culture and sensitivity. Moreover their high cost and requirement for sophisticated laboratory infrastructure limit their use in routine diagnosis. Laboratories with advanced infrastructure are limited in most of the peripheral diagnostic laboratories in Malaysia(6-7).

To balance the lack of sophisticated laboratory infrastructure for performing TB identification and drug sensitivity tests to exclude MDR-TB cases with speed and accuracy, there is an urgent need of inexpensive, non-invasive, robust diagnostic and culture sensitivity test. To achieve this goal an attempt was made to incorporate thyroxine hormone in solid and liquid media for culture of AFB in vitro (8-12) Presently, we planned to evaluate the effectiveness of this thyroxine supplemented culture media for culture of AFB from clinical samples in vitro and also to standardize use of this method in comparison to routine AFB culture procedure. This study may prove to be a useful technique for rapid culture isolation of AFB in vitro.

References:

1.Chang CT1, Esterman A.Diagnostic delay among pulmonary tuberculosis patients in Sarawak, Malaysia: a cross-sectional study. Rural Remote Health. 2007 Apr-Jun;7(2):667. Epub 2007 May 11. 2. Alison Rodger, Shabbar Jaffar, Stuar Paynter et al., Delay in the diagnosis of pulmonary tuberculosis, London, 1998-2000: analysis of surveillance data: BMJ 2003; 326 doi: http://dx.doi.org/10.1136/bmj.326.7395.909 (Published 26 April 2003)<br> 3. Zahar JR, Azoulay E, Klement E et al., Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure. Intensive Care Med 2001; 27: 513–520 4. Wares D.. Delay in diagnosis of tuberculosis: of remaining concern in England and Wales. J Public Health Med 1999; 21: 355–356 5. Aldhubhani AH1, lzham MI, Pazilah I, Anaam MS (2013)Effect of delay in diagnosis on the rate of tuberculosis among close contacts of tuberculosis patients. East Mediterr Health J. 2013 Oct;19(10):837-42. 6. Ying Li1†, John Ehiri2†, Shenglan Tang et al., 3(2013)Research article Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis:BMC Medicine 2013, 11:156 doi:10.1186/1741-7015-11-156 7. Timothy William123, Uma Parameswaran12, Wai Khew Lee4 et al., Pulmonary tuberculosis in outpatients in Sabah, Malaysia: advanced disease but low incidence of HIV co-infection: BMC Infectious Diseases 2015, 15:32 doi:10.1186/s12879-015-0758-6 8. Pramanik J, Lodam AN, Reddy MVR, Narang P and Harinath BC. Increased yield of excretory-secretory antigen with thyroxine supplementation in in vitro culture of tubercle bacilli. Ind. J. tub. 1997; 44: 185-190. 9. Pramanik J, Lodam AN, Badole CM, Reddy MVR, Patond KR and Harinath BC. Detection of tubercular antibody and antigen in sera of bone and joint tuberculosis. Ind. J. Clin. Biochem. 2000; 15 (1): 22–28. 10. Lodam AN, Pramanik J, Reddy MVR and Harinath BC. Diagnostic potential of fractionated Mycobacterium tuberculosis H37Ra excretory-secretory (EST-DE1) antigen in pulmonary tuberculosis. Ind. J. Clin. Biochem. 1997; 12 (1): 71-77. 11. Pramanik.J. BMJ.2003.http://www.bmj.com/rapid-response/2011/10/30/delays-diagnosis-tuberculosislet-us-use-thyroxine-supplemented-culture-med: Delays in diagnosis of tuberculosis? Let us use thyroxin supplemented culture medium for early lab-diagnosis. 12. Pramanik.J. BMJ: 2004.http://www.bmj.com/rapid-response/2011/10/30/early-diagnosis-tuberculosis-reported-third-world-country Early diagnosis of tuberculosis-reported from third world country:A research letter from India.