RESURGENCE OF TUBERCULOSIS DOTS FAILURE OR THOUGHT FAILURE!

RESURGENCE OF TUBERCULOSIS

DOTS FAILURE OR THOUGHT FAILURE!

The World Health Organization (WHO) declared tuberculosis (TB) a global public health emergency in 1993 and since then intensified its efforts to control the disease worldwide¹. Revised National Tuberculosis Control Programme (RNTCP) and directly observed treatment short course (DOTS) were introduced in the country after a pilot study in 1997. The programme was introduced in a phased manner covering the whole population of the country by 2006.It enjoyed the back up of infrastructure of health care system, a new hierarchal human resource chain and huge external funding. The concept of daily, directly observed therapy, incorporating a full six months of Rifampicin has been adopted by the majority of countries worldwide as a major part of Stop TB Strategy². Lower rates of cure in National TB Control program (NTP) highlight the operational challenges of delivering a daily regimen over an extended period of  time^{2, 3}. India implemented the Revised National TB Control Program (RNTCP) as a national government run system that used a thrice weekly regimen administered by DOT⁴. Cure rates in India have been comparable with countries using daily dosing. TB mortality has dropped significantly, and the prevalence of TB has declined slightly over the last two decades⁴. The therapeutic regimens given under direct observation as recommended by WHO have been shown to be highly effective for both preventing and treating TB ⁵. It was propagated with much fanfare and enthusiasm and even the protagonists became ardent believers by the course of time. It took 30 years for the national tuberculosis control program to be declared a failure, but it took only 10 years or less to say that RNTCP is not achieving the desired result. Now the revised program is being re-revised citing examples of multidrug resistance and extensive drug resistance.

Directly observed therapy short course (DOTS) is the internationally recommended strategy to ensure cure of tuberculosis. It has become the standard for the diagnosis, treatment and monitoring of tuberculosis worldwide and has been implemented in 182 of 211 countries, covering more than 77% of world's population^6,7 in response to the growing threat of this disease. 

In India, under the Revised National Tuberculosis Control Program (RNTCP), the percentage of smear-positive re-treatment cases out of all smear-positive cases is 24%⁸. The causes of re-treatment include relapse, failure, and default in treatment. RNTCP does not follow up the patients for any period of time after successful completion of treatment to determine whether they relapse. Due to the fact that India has the maximum number of cases and highest burden of TB in the world, an effective TB control program in India is essential. It also will have global implications in the international TB control effort. There is no statistically significant difference between the two treatment groups in terms of cure or treatment completion. Hill categorically admits that superiority of DOTS over unsupervised therapy for routine TB care has not yet been shown in an evidence-based fashion⁹. His contention is that it is not better in suboptimal settings and indicates that the program quality must be strong enough to yield its optimal benefits.  Of the new smear-positive patients registered under Category 1, the default and failure rates were 12% and 5%, respectively, reported by Chandrasekaran in 2006 and 16% and 4%, respectively, reported by Thomas¹⁰. Mehra recorded a failure rate of 3.4%¹¹. The distribution of default and failure cases in Category 2 patients was 22% and 14%, respectively, in the study by Mukherjee¹².  Hill in his review of studies from around the world, calculated an average failure rate to be 2.4% ±2.2% for 21 culture-based studies and 2.5% ±1.7% for nine smear-based studies⁹. Nevertheless, high relapse rate of 11-13% has been reported in patients treated by DOT under RNTCP from several different locations in India over the last many years ^{10, 13, 14}.

Most authorities are convinced that DOTS improves treatment effectiveness, drug resistance rates, and overall TB control. It is a fact that the intermittent regimen used under the program is equally effective under direct observation as compared to the daily regimen, and choosing a daily regimen does not undermine the successes of the program ^{15, 16}. There are no good quality studies that may cast light over the preferences, adherence, and felt problems of the clients of the RNTCP. Without understanding the wishes and the problems seen from the patients, it may be difficult to modify a strategy so strongly advocated by the WHO and many other international organizations working with TB. Role of HIV, Multi Drug Resistant (MDR) TB, re-infection with a different strain of Mycobacterium tuberculosis and outcomes in the pediatric age group, also need to be investigated for relapse. However, based on the above evidences and in the interest of having uniformity of care across all healthcare sectors it is decided to introduce daily regimen under RNTCP. It is argued that this will help to achieve universal access to quality TB care and prevent development of drug resistance. When such a decision is taken and program is being reintroduced, it will be better to take stock of what went wrong in the previous programs. It will help the program managers to take corrective steps so that the new program will not have the same fate after a few years.

The three main causes of failure of TB treatment relate to the actions of doctors in prescribing incorrect regimes, problems with the drugs being delivered (either the quantity or the quality), and the patients failing to take sufficient quantity of the drugs.

I.                   Doctors – Not adhering to guidelines or following inappropriate guidelines.

II.                Drugs –Poor quality, irregular supply and wrong delivery (dose/combination). In some case drugs are unsuitable due to the presence of drug resistance.

III.             Patients –Lack of information, Lack of money for treatment and/or transport, fear of actual or presumed side effects, lack of commitment to a long course of drugs and other co morbidity.

Apart from the above we have to consider few other reasons for the program failure. This is because system did not correct certain inherent causes of failure of the previous program (NTP).

1)      Administrative failure

The initial enthusiasm once the program was launched faded away too quickly. There was lack of commitment on the part of administrators. Most of the program managers and contractual staff were committed and RNTCP gained a lot of ground among common man due to their hard work. Most of the medical college faculty who were suspicious initially cooperated and it was bringing good result. This was mainly due to the concerted effort of program managers, District TB officers, medical college core committee members and contractual staff. But after few years these staff were shuffled and their grievances were never attended. Contractual staff on meager wages struggled to get that amount released in time. District program managers of NHM were responsible for dealing finances. Since they have many other programs to look after, due importance to TB program was never given. Once commitment is lost and enthusiastic workers left for greener pastures we can imagine the fate of the program.

Treatment adherence is a critical determinant of treatment outcomes. Poor outcome and emergence of drug resistance are mainly due to irregular and incomplete treatment. The DOTS strategy has been the backbone of TB programs for the last decade. In certain places, strict adherence to the program by healthcare worker has resulted in cost-effective and sustainable control of TB epidemics. However, accumulating evidence has pointed to the effectiveness of a wide variety of approaches including community and family-centered DOTS, which is more achievable for most developing healthcare systems and produce comparable outcomes to healthcare worker supervised DOTS.

However in a larger perspective, treatment support system developed with mutual trust and respect between the patient, family, providers, treatment supporters and the health system. This will promptly identify and address all possible factors that could lead to treatment interruptions. This includes not only medical factors such as co-morbidities, adverse drug reactions and emergencies, but also take care of various social, vocational, nutritional, economic and psychological stress experienced by the patient throughout the course of treatment. Regular and effective supervision by the health supervisors at various levels and close monitoring of the progress made by the patient on treatment are critical components to ensure high standards of care. Capacity building among health care workers and engaging local community based organizations, self-help groups and patient support groups could prove to be effective interventions to promote treatment adherence ^{17, 18}. Supervision and support should be individualized and should include a range of recommended interventions including patient counseling and education. An important element of the patient centered strategy is to assess and promote adherence to the treatment regimen, and, to address poor adherence when it occurs. These measures should be tailored based on the patient's clinical and social history. It also should be mutually acceptable to the patient and the provider.

2)      Role of private practitioners

India continues to have high TB incidence, and, the mortality due to TB is still unacceptably high. The challenges of TB control in India are magnified by the existence of parallel systems for TB diagnosis and treatment – the public and the private. Each system takes care of approximately half of the TB cases¹⁹.The methods and standards vary greatly depending on whether public or private care is accessed and furthermore what type of private care is sought, from super-specialty tertiary institutions to non-qualified providers ²⁰. RNTCP was implemented through the existing health care system, the pivotal role being played by district TB centers. There were additional staff supplement with adequate materials and funds. Every peripheral health center is empowered to take up the challenge of diagnosing, treating and monitoring TB patients. Since medical colleges are the opinion leaders in health care and trains new generation of doctors and paramedics there was an attempt to bring all medical colleges in the loop and hence task force is being organized in public and private medical education institutions. At the same time we are all aware that 50-60% of health care delivery in the country is through private practitioners. They work in institutions as well as individually. RNTCP, to a large extent, failed to bring these practitioners in to its fold. There were many concerns for them which were not addressed properly. Hence treatment of tuberculosis through private practitioners remained largely out of the program. Many institutions do not want to join a Govt. run program for fear of auditing. But most important of all is the fear of exposing their know how in treating tuberculosis. I know many practitioners using non rifampicin containing regimen, non-pyrazinamide containing regimen and levofloxacin based first line treatment. Many have more concern on liver dysfunction, peripheral neuropathy etc. and hence load the patient with two or more vitamins. This will all lead to non-compliance. Once therapeutic response is poor these patients are referred to the program. This previous treatment history is also poorly documented and may be a source of bias. It has been recorded that patients turn up at RNTCP after seeking medical care from many providers in the private sector. It might be true that many TB patients may see an advantage in not reporting previous treatment, in order to escape with a lighter 6-month treatment instead of a more punishing 8-month treatment regimen. When drug resistance is being reported from many parts of the country, these same practitioners started blaming the program.

3)      Availability of drugs in the open market

When the Govt. is committed to provide good quality anti TB drugs to patients in the country, why the drugs were made available in the open market? When these potent drugs are freely available, there is a chance to misuse these drugs to the extent of treating with inadequate regimen, inadequate dosing etc. This will lead on to failure and development of resistance. If it was banned when RNTCP was expanded to cover the whole nation, all the patients (suspected or diagnosed) will be brought to the single window of DOTS. This will ensure uniform treatment, treatment completion and follow up.

4)      Overemphasis on sputum microscopy and neglecting clinical and radiological evidence.

In NTP the main disadvantage being pointed out is overemphasis on radiology. X ray being highly sensitive but poorly specific, leads to more of false positives. When we turned to RNTCP the emphasis shifted to sputum microscopy. This is a highly specific test even though sensitivity is poor. So we have a proportion of false negatives in the society. Actually the planners should have developed a more realistic diagnostic test combining both. In the recent guidelines a new entity is included as clinically diagnosed TB which is diagnosed through clinical and radiological methods. Overdependence of sputum microscopy led to a peculiar situation in which clinicians failed to use their clinical judgment but blindly followed sputum microscopy result. Even after improvement in staining and detection, the sputum pick up remained as low as 60%. So 40% of TB cases roam around without being detected. When these patients are reported as negative after repeated sputum examination, there is hesitancy in starting anti-TB drugs. This leads to delay in starting treatment and progression of disease.

Conclusion

Urgent efforts are necessary for the control of tuberculosis in the country. Both intermittent and daily regimens are proved to be effective in treating tuberculosis. What is most essential is to ensure adherence to the program both from patient’s side and provider side. It is important to take stock of the factors leading to failure of previous programs and to take appropriate measures so that what is implemented now remains the standard of care for TB in years to come.

References

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2.      World Health Organization, Stop TB Strategy, 2013; Geneva 2013.

3.      World Health Organization, Global Tuberculosis Report 2012; Geneva 2012.

4.      Revised National TB Control Program 2013; tbcindia.nic.in

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10.  Thomas A, Gopi PG, Santha T, Chandrasekaran V, Subramani R, Selvakumar N, et al. Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS program in South India. Int J Tuberc Lung Dis. 2005; 9(5):556–61.

11.  Mehra RK, Dhingra VK, Nish A, Vashist RP. Study of relapse and failure cases of CAT I retreated with CAT II under RNTCP–an eleven year follow up. Indian J Tuberc. 2008; 55:188–91.

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13.  G S Azhar. DOTS for TB relapse in India: A systematic review. Lung India. 2012; 29(2): 147–53

14.  Dave P, Rade K, Modi B, SolankiR,Patel P, Shah A, Vadera B. Assessment of Long-term Outcome among New Smear Positive Pulmonary TB Patients Treated with Intermittent Regimen under RNTCP – A Retrospective Cohort Study. Natl J Community Med 2013; 4(2):189-94.

15.  Alvarez TA et al. Prevalence of drug-resistant Mycobacterium tuberculosis in patients under intermittent or daily treatment. J Bras Pneumol. 2009; 35(6):555-60.

16.  Wells AW et al. Implications of the current tuberculosis treatment landscape for future regimen change. Int J Tuberc Lung Dis. 2011; 15(6):746–53.

17.  Volmink J, Garner P - Directly observed therapy for treating tuberculosis (Review) - The Cochrane Library - 2009, Issue 1, http://www.thecochranelibrary.com

18.  Munro SA, Lewin SA, Smith H, Engel ME, Fretheim A, et al. Patient adherence to Tuberculosis treatment: A systematic review of qualitative research. PLoS Med 2007; 4(7): e238.

19.  Satyanarayana S, Nair SA, Chadha SS, Shivashankar R, Sharma G, et al. () From Where Are Tuberculosis Patients Accessing Treatment in India? Results from a Cross-Sectional Community Based Survey of 30 Districts.PLoS ONE 2011; 6(9): e24160.

20.  Anurag Bhargava et al., Mismanagement of Tuberculosis in India: Causes, Consequences, and the Way forward. Hypothesis 2011, 9(1): e7.