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EDITORIAL
Year : 2017  |  Volume : 34  |  Issue : 1  |  Page : 1-2  

Rapid diagnosis and shorter regimen for multidrug-resistant tuberculosis: A priority to improve treatment outcome


1 Department of Pulmonary Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
2 Department of Internal Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India

Date of Web Publication30-Dec-2016

Correspondence Address:
Rajendra Prasad
Department of Pulmonary Medicine, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-2113.197118

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How to cite this article:
Prasad R, Gupta N, Banka A. Rapid diagnosis and shorter regimen for multidrug-resistant tuberculosis: A priority to improve treatment outcome. Lung India 2017;34:1-2

How to cite this URL:
Prasad R, Gupta N, Banka A. Rapid diagnosis and shorter regimen for multidrug-resistant tuberculosis: A priority to improve treatment outcome. Lung India [serial online] 2017 [cited 2017 May 1];34:1-2. Available from: http://www.lungindia.com/text.asp?2017/34/1/1/197118



Tuberculosis (TB) occurs worldwide and remains an important cause of morbidity and mortality in many countries. There were an estimated 9.6 million new cases of TB-causing death to 1.5 million people globally in 2014. In India, there were estimated 2.2 million (23% of total cases globally) new cases causing death to 0.25 million people in 2014.[1] It is a cause for concern, and a real paradox as pathogenesis, transmission, diagnosis, treatment, and prevention are well known for TB.

Ideally, good chemotherapy should achieve 100% sputum conversion provided correct regimens are prescribed and taken. There will be hardly any relapse if duration of treatment has been sufficient and there will be no emergence of drug resistance. The Global Tuberculosis Report 2015 estimated that 3.3% of newly diagnosed and 20% of previously treated TB cases had multidrug resistant-TB (MDR-TB). It has been estimated that 480,000 MDR-TB cases emerged and 190,000 deaths occurred due to MDR-TB globally. In India, estimates showed that the prevalence of MDR-TB among new and previously treated patients was 2.2% and 15%, respectively. It has been estimated that 99,000 cases of MDR-TB emerge every year, of which 71,000 were among notified cases of TB in 2014. Of 71,000 MDR-TB cases, only 25248 were diagnosed, 24,073 were started on treatment and treatment success rate was only 46% in India.[1],[2] The possible reasons for poor treatment outcomes of MDR-TB cases are due to lengthy, expensive, and toxic regimens leading to poor compliance.[3],[4],[5],[6]

Early suspicion, diagnosis and appropriate treatment of MDR-TB are essential to prevent morbidity, mortality, and transmission of MDR-TB. The WHO recently announced new recommendation to speed up the diagnosis through the novel diagnostic test like GenXpert MTB/RIF which can diagnose rifampicin resistance in <2 h as a surrogate marker for the diagnosis of MDR-TB [7] and 2nd line probe assays recommended by WHO recently to identify genetic mutation in multidrug resistance/rifampicin resistance strains to detect resistance to fluoroquinolones and 2nd line injectable anti-TB drugs.[8] To improve treatment outcome of MDR-TB, a shorter and economical 9–12 months treatment regimen for MDR-TB cases has been recommended by WHO recently.[9] The new shorter regimen can be completed in less than half the time required by the current standard treatment of the MDR-TB. The current standard treatment regimen of MDR-TB lasts 24 months and yields low cure rate of about 48%.[1] Given that patients have to take second line anti-TB drugs fraught with lot of adverse drug reactions for a prolonged period, compliance is often quite poor. Many patients are either lost to follow-up, or their treatment is interrupted. The new shorter treatment regimen can be completed within 12 months. It is less expensive, can improve outcomes by better adherence to treatment and a reduction in loss to follow-up. The shorter MDR regimen is suitable for patients suffering from uncomplicated MDR-TB which is not resistant to 2nd line anti-TB drugs. Programmatic studies evaluating the shorter MDR regimen have been carried out in the countries across the world involving more than 1200 patients showed the cure rate of 82% and overall success rate of 84.5%.[9],[10],[11],[12],[13] They also showed that shorter MDR treatment regimen given in patients who met specific inclusion criteria had a statistically significant higher likelihood of treatment success than those who received a longer conventional regimen of 18–24 months.

Several studies are also underway to assess the efficacy of new drug combinations for MDR-TB treatment in India. One study is recruiting patients on the usual 24-month treatment along with those who are being put on the new drug, bedaquiline. Another cohort of patients is likely to be part of a clinical study to assess the Bangladesh regimen. Yet another short regimen is being developed by Global Alliance for TB drug development called PaMZ comprising of PA 824 (Pa), moxifloxacin (M), and pyrazinamide (Z).[14] The therapy is intended for patients with drug-sensitive TB and as well as MDR-TB. Phase 2b clinical studies showed the potential of PaMZ to treat drug-sensitive TB and some cases of MDR-TB in 4–6 months, irrespective of their HIV status.[15] The global phase-3 clinical study named Shortening Treatment by Advancing Novel Drugs in patients who are currently considered to have either drug-sensitive or MDR-TB is under way. Enrolment for the global Phase 3 clinical study of PaMZ is already underway. It expects to enroll 1500 patients across 15 countries.[16] Patients from five states of India (Maharashtra, Delhi, Gujarat, Tamil Nadu, and West Bengal) are also expected to be enrolled for this study. Although this study has suspended participant recruitment currently, if found successful in Phase 3 trial; the PaMZ regimen would eliminate the need for injectable drugs and reduce the cost of MDR-TB treatment in patients who are sensitive to these drugs. There is an urgent need for evaluating shortened treatment regimens for MDR-TB in different settings.

Given the significant burden of MDR-TB in India coupled with high treatment default rates and poor treatment success, it is vital for India to evaluate the shorter regimens in various settings and add to the evidence base for the impact of these regimens on reducing TB-related mortality and morbidity. Decision makers/Government of India need to adopt shorter and new MDR-TB regimen to fulfill the goal of end TB strategy by 2030[17] as envisaged in sustainable development goals.

 
   References Top

1.
World Health Organization. Global Tuberculosis Report 2015. Report No. WHO/HTM/2015.08. Geneva: World Health Organization; 2015.  Back to cited text no. 1
    
2.
Prasad R, Gupta N, Singh M. Multidrug resistant tuberculosis: Trends and control. Indian J Chest Dis Allied Sci 2014;56:237-46.  Back to cited text no. 2
    
3.
World Health Organization. Companion Handbook to the WHO Guidelines for the Programmatic Management of Drug Resistant Tuberculosis. WHO/HTM/TB/2014.11. Geneva: World Health Organization; 2014.  Back to cited text no. 3
    
4.
Central TB Division. Guidelines on programmatic management of drug resistant TB (PMDT) in India. New Delhi: Directorate of General Health Services, Ministry of Health and Family Welfare, Government of India; 2012.  Back to cited text no. 4
    
5.
Prasad R, Srivastava DK. Multidrug and extensively drug resistant TB (M/XDR TB) management: Current issues. Clin Epidemiol Glob health 2013;1:124-8.  Back to cited text no. 5
    
6.
Prasad R. Multidrug and extensively drug-resistant tuberculosis management: Evidences and controversies. Lung India 2012;29:154-9.  Back to cited text no. 6
  Medknow Journal  
7.
World Health Organization. Automated Real-time Nucleic Acid Amplifi cation Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF System Policy Statement. WHO/HTM/TB/2011.4. Geneva: World Health Organization; 2011.  Back to cited text no. 7
    
8.
World Health Organization. The Use of Molecular Line Probe Assays for the Detection of Resistance to Second-line Anti-tuberculosis Drugs. WHO/HTM/TB/2016.07. Geneva: World Health Organization; 2016.  Back to cited text no. 8
    
9.
World Health Organization. WHO Treatment Guidelines for Drug-resistant Tuberculosis 2016 Update. WHO/HTM/TB/2016.04. Geneva: World Health Organization; 2016.  Back to cited text no. 9
    
10.
Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 2010;182:684-92.  Back to cited text no. 10
    
11.
Kuaban C, Noeske J, Rieder HL, Aït-Khaled N, Abena Foe JL, Trébucq A. High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon. Int J Tuberc Lung Dis 2015;19:517-24.  Back to cited text no. 11
    
12.
Piubello A, Harouna SH, Souleymane MB, Boukary I, Morou S, Daouda M, et al. High cure rate with standardised short-course multidrug-resistant tuberculosis treatment in Niger: No relapses. Int J Tuberc Lung Dis 2014;18:1188-94.  Back to cited text no. 12
    
13.
Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bauer M, Bayona JN, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: An individual patient data meta-analysis of 9,153 patients. PLoS Med 2012;9:e1001300.  Back to cited text no. 13
    
14.
Available from: http://www.tballiance.org/portfolio/regimen/pamz. [Last accessed on 2016 Oct 10].  Back to cited text no. 14
    
15.
Dawson R, Diacon AH, Everitt D, van Niekerk C, Donald PR, Burger DA, et al. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: A phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis. Lancet 2015;385:1738-47.  Back to cited text no. 15
    
16.
Available from: https://www.clinicaltrials.gov/ct2/show/NCT02342886. [Last accessed on 2016 Oct 10].  Back to cited text no. 16
    
17.
The End TB Strategy WHO. WHO/HTM/TB/2015.19. Available from: http://www.who.int/tb/End_TB_brochure.pdf?ua=1. [Last accessed on 2016 Oct 10].  Back to cited text no. 17
    




 

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