Tuberculosis in India.

Tuberculosis in India: Issues like MDR, Childhood TB:
 

India still has 24 per cent of world’s TB cases, WHO data shows India has the most number of TB cases among the six countries that account for 60 per cent of total cases worldwide. Continuing the fight to eradicate tuberculosis from India, which has 24 per cent of the world’s total number of TB cases, the Indian Society for Clinical Research or ISCR called for a comprehensive research in multi-drug resistant TB. Reports show that the disease kills 480,000 to 500,000 Indians every year, making it a big challenge for India to achieve its goal of being TB free by 2025. According to the World Health Organisation, it is the world’s top infectious disease killer and 5000 people die because of it every day. It ranks among the top 10 global causes of death, and in 2015 alone; a million children below the age of 14 years worldwide were diagnosed with TB and 1, 70,000 of them died. 10-15 per cent of TB patients are under the age of 14.

In 2012, India’s golden jubilee year of TB control, the World Health Organization (WHO) named India the worst performer among developing nations, with 17 per cent of the global population carrying 26 per cent of the global TB burden. Tuberculosis is very much in the news, but for all the wrong reasons(So might be important for UPSC) —. a shortage of drugs; increasing multi-drug and extensive drug resistance (MDR, XDR), making treatment both cumbersome and expensive; total drug resistance (TDR) as a veritable death warrant; popularly used serological tests for diagnosis being declared worse than useless, and a government order for mandatory case notification. Private practitioners are legally authorized to treat TB, but without quality check mechanisms.

So what is the problem here ??

History of TB prevention in India

1962 – National TB Control Project withMain intervention –BCG

1978 - The Expanded Programme on Immunization took over BCG vaccination.

1979 -preliminary results of a 15-year-long BCG trial showed no protection against infection by TB bacilli. The disappointing results were much debated, and ignored by the then TB control leadership.

1999 -the final results, which were published in the Indian Journal of Medical Research, confirmed that the TB control project had lost the tool of primary prevention.

1997 - The Revised National TB Control Programme (RNTCP) that came into being has to its credit some enviable accomplishments.

What Is RNTCP??

Objective:

1. To achieve cure rate of at least 85%

2. Detection of at least 70% of TB cases in population

It is a centrally sponsored scheme with assistance from World Bank, USAAID and other international institutions

1993 - It is implemented through DOTS (Directly Observed Short Course)

So what is DOTS?

DOTS use health care workers to supervise the administration of TB Therapy with objectives

1.      Sustained political and financial commitment

2.      Diagnosis by quality ensured sputum-smear microscopy test

3.      Standard short course anti TB treatment given under direct and supportive observation

4.      Regular and uninterrupted supply of anti TB drugs

5.      Standardized treatment and reporting

2006 – RNTCP Country wide coverage and achieved 86 per cent treatment success rate in recent years

2007- RNTCP achieved the global target of 70 per cent case detection (53 cases per 100,000 populations per year).

2012 -WHO’s Annual Report on TB confirmed India’s failure. DOTS saves lives from TB mortality, but has failed to control TB.

So what went wrong??

The Revised National TB Control Programme (RNTCP) achieved country-wide coverage in March 2006 and achieved 86 per cent treatment success rate in recent years. More than 15,000 suspects are examined for the disease every day and about 3,500 patients are started on treatment. And to its credit, for the very first time in 2007, RNTCP achieved the global target of 70 per cent case detection (53 cases per 100,000 population per year). (data just to know the gravity of issue)

Despite these impressive achievements, India has the highest TB burden in the world — 3.5 million active TB cases. The number of new active TB cases detected every year is over two million; it was 2.2 million in 2011. And the disease kills two people every three minutes. Incidentally, the incidence and prevalence figures are not a true indicator of the ground reality — the number of patients treated by the private sector is not known.

But why is India continuing to record the most number of TB patients in the world every year? A closer inspection reveals that the programme is far from perfect and may require a thorough re-examination of both design and implementation. The massive country-wide drug stock-out crisis that played out recently is, but, just one of the malaises that the programme faces.

Issues in RNTCP

1. The national TB control programme (RNTCP) uses a passive system for diagnosing TB patients. The design of the system is such that it waits for patients to walk into the centres to get tested. It is well known that patients walk into these centres quite late in the day. And in the process, they end up infecting many people. That a single active TB patient who is not on treatment is capable of infecting 10 or more people in a year shows how badly our RNTCP programme is in need of a reorientation. It has to necessarily shift gears and seriously consider changing its strategy from the current passive case-detection system to an active mode of detecting cases.

2.For those with extra-pulmonary TB, a sputum test will not help in diagnosis. RNTCP is not interested in them as they do not spread TB bacilli. So, the project illustrates incomplete health care and inadequate public health.

3.“Control” is a defined term in epidemiology — the disease burden should be reduced to a pre-stated level, within a stipulated period of time, and proven to be due to intervention and because of a “secular trend.” As socio-economic status increases, TB should decline even without specific interventions — that is a “secular trend.” RNTCP has not set control targets in terms of a time frame and disease burden. It is not measuring a secular trend. Thus, the “control” in RNTCP is not epidemiologically sound.

4.The Centre, in line with WHO recommendations, had sent an advisory approximately four months ago, to discontinue serological (or blood-based) tests to diagnose TB, as its results aren't accurate. But serological tests continue to be used in labs across the country, for economic reasons, say several studies done by TB experts. It doesn't have the stigma and low-margins of a sputum-smear microscopy — the basic TB test. And it is as expensive as a liquid culture test.

4.Private practitioners are legally authorised to treat TB, but without quality check mechanisms. They often bypass the prescribed treatment protocol, while MDR, XDR and TDR result from non-protocol drug treatment.They also encourage serological tests which are banned .

5.In young children, infection can rapidly lead to disease, called childhood TB, which can be serious and life-threatening. BCG fails to protect against infection by TB bacilli, but protects against infection progressing to childhood TB. Thus, universal neonatal BCG vaccination saves thousands of lives and huge costs for diagnosis and treatment. Childhood TB is not infectious; so, treating childhood TB has no role in TB control.

6.Historically, though, there has been less investment in TB medicines, because a majority of the affected were poor, and therefore, there was little market incentive for the industry to invest in this area.

CHILDHOOD TB

According to WHO, the risk of developing the disease is “much greater” in infants and those below five years who have been infected than those above the age of five. In infected children below five years, if the disease does develop, it usually does so “within two years of infection.” But in the case of infants, the disease can set in within a matter of 6-8 weeks of infection.

How far we are from even contemplating a radical change in our case-detection approach can be assessed by looking at how the WHO-recommended, RNTCP-approved contact screening of children below five years in households where an adult has been recently diagnosed with active pulmonary TB (sputum smear positive) is carried out. Children below five years from such households are most vulnerable to getting infected and probably developing active TB. 

As a preamble, one has to only examine the differences between the WHO guidelines and the RNTCP guidelines to understand the extent of disconnect. While the WHO recommends contact screening in children below five years, RNTCP has it as below six years! 

·       Screening children would help in diagnosing those who have already developed the disease (active TB) as well as those who have been infected but yet to develop the disease. 

·         While treatment for those who have developed the disease would be through the routine multi-drug regimen Children who have been infected but have not yet developed the disease are ideal candidates for a preventive therapy.

·         Contact screening of young children combined with chemoprophylaxis (preventive drug therapy) would go a long way in breaking the TB transmission cycle and reducing the case load by preventing the number of people who would become TB patients.

·         Contact screening does not require much additional resources and can be implemented through the existing system if compliance is ensured through adequate monitoring and supervision.

Reality in India:

·         As per 2008 survey, Only 14 per cent of children aged 6-14 years were screened for TB and only 19 per cent (16 of 84 children) of children below six years were initiated on preventive therapy. There was no difference between urban and rural areas in terms of preventive therapy initiation. It has not been prioritized by RNTCP. No reporting of this activity is required.

·         Health care workers (HCW) in rural areas were themselves less aware of contact screening and preventive therapy in young children. Awareness level among HCWs that immediate family members are more susceptible to infection was “significantly lower” in rural areas. Only one-third of parents in rural areas were aware of contact screening and the need for preventive therapy in children below five years.

·         The DOTS TB treatment card of the adult (index patient) has no provision for documenting the details of contact screening, preventive therapy, follow-up and treatment completion.

As a follow up some improvements like all the health workers — medical officers to DOTS workers — were provided basic training on all aspects of contact screening and preventive therapy. And a separate preventive therapy register and card were also introduced in line with the WHO recommendations. After this , 2013 study in same area reveals that the results were quite dramatic. The health workers were able to identify 82 per cent of child contacts. Sixty-one per cent (53 children below six years) were screened for TB disease and put on preventive treatment. Of the 53 children, 74 per cent (39 children) completed the treatment. This is a huge improvement compared to just 19 per cent children who were even initiated on treatment in 2008.

Issues in diagnosing TB in Children

It’s a fact that diagnosing TB in children under five years is a challenging task. As WHO’s “Roadmap for childhood Tuberculosis,” has pointed out, there are no “effective diagnostic tests.” Unexplained loss of more than five per cent of the highest weight recorded in the past three months, or fever and/or cough for more than two weeks make TB more likely, especially when the child has been in contact with an infectious pulmonary TB patient in the same household. Yet, diagnosis cannot be made on the basis of clinical symptoms alone.

·         Young children will not be able to produce sputum. This is largely because their cough reflex is not fully developed; they tend to swallow the sputum. Sputum is the most basic and important sample for diagnosing pulmonary TB disease.

·         Even when a sputum sample does become available, it may contain only a few TB bacteria.So it is hard to see a few bacteria under microscopy.So, paediatric TB is called ‘pauci-bacillary disease’ (fewer bacilli).The sensitivity of diagnosis — by smear microscopy and culture — depends on the amount of bacteria present in the sample.

·         But even in the absence of sputum sample for micro-bacterial confirmation, much information can be gained from tuberculin skin test (TST) and X-ray results. Though infected, TST can be negative in infants because their immune system is not mature. This is where chest X-rays come in handy.

·         “Positive chest X-rays (e.g. enlarged lymph nodes inside the chest) are also indicative of TB. But X-rays can be abnormal due to many diseases (e.g. bacterial or viral pneumonia, asthma).If X-rays are abnormal, that pushes the diagnosis towards active TB, not latent TB. But X-ray results need to be used along with other tests. A positive TST and suggestive X-ray, plus history of close contact with a TB case in the house, and symptoms (e.g. not gaining weight, fever) are most likely to point to TB diagnosis.” 

The recently updated national guidelines on paediatric tuberculosis lay great emphasis on bacteriological confirmation using sputum samples even when chest X-ray is suggestive and TST is positive, and the child has received a complete course of antibiotic treatment. 

“In cases where sputum is not available for examination or sputum microscopy fails to demonstrate, alternative specimens (gastric lavage, induced sputum, broncho-alveolar lavage) should be collected, depending upon the feasibility, under the supervision of a paediatrician'.

Facilities to collect sputum using the two different lavage methods from those under five years are available only in the tertiary centres in the urban areas. So what percentage of children from the rural areas would end up getting correctly diagnosed and treated? Incidentally, RNTCP aims to achieve “universal access” to quality assured TB diagnosis and treatment during 2012-2017. 

That’s a very tall order considering that even tuberculin is often not available in peripheral health facilities.

Multi Drug Resistance 

Under RNTCP, the DOTS (directly observed treatment, short course) strategy was adapted. Covering the whole of the country, diagnosis is primarily done by collecting sputum from the patient and examining it under microscope after making a smear. 

This facility is being provided by specially trained laboratory technicians posted in peripheral hospitals at the 20-30,000 population level. If a patient diagnosed with TB, drugs are made available on the doorstep by a DOTS provider who keeps track of the patient. 

The DOTS provider is a minimally trained person, who can be either a health staff member or a responsible villager. This treatment is thus under direct supervision. Four drugs are commonly used, Rifampicin, Isoniazid, Ethambutol and Pyrazinamide, in different combinations for six months. In some cases, injectible drug Streptomycin is used. The patient is followed up with sputum examination periodically to trace the progression of the disease. All these services, including the drugs, are provided free of cost. 

Multidrug resistant TB (MDR TB) is caused by bacteria that do not respond to at least Isoniazid and Rifampicin, the most powerful, first line anti-TB drugs. Drug-resistant TB occurs when drugs are not properly taken, like incomplete treatment, wrong dosage, wrong length of treatment, wrong combination, unavailability of drugs or poor quality drugs. 

•            MDR TB diagnosis and treatment is difficult. First of all, the diagnosis needs culture and drug susceptibility testing entailing extensive laboratory work. There are only a few laboratories where this test can be done in India. 
•      Once the problem is diagnosed as MDR TB, the second line drugs, which are 300 times costlier than the first line drugs, are prescribed. These are ofloxacin/levofloxacin, ethionamide, cycloserine, pyrazinamide, ethambutol and kanamycin. These drugs are used for 24 months in different combinations and have severe adverse events. 

Steps to prevent MDR

•   Take drug as prescribed — Adequate counseling to patient at the start of treatment on dosage
•   Continuous supply of quality drugs
•   Periodic follow-up to check for compliance and any adverse reactions
•   Take your drugs timely
•   Do not miss dose
•   Report any untoward incidents
•   Complete treatment

In recent years, the government has made a conscious effort to scale up DOTS Plus services i.e. a specialized strategy that focuses on drug resistant TB and is now available across 35 States in India.

Introduction of newer diagnostic tests such as Xpert MTB/RIF which can detect MDR-TB from the sample as well as resistance to rifampicin, a surrogate marker for MDR-TB, in less than two hours has become important to rapidly diagnose MDR-TB.

Earlier Solid culture method resultcan be obtained only after 4 months ,Liquid Culture method result in two months ,Line Probe Assay test single MDR sample result obtained  in two days ,Now Gene Xpert result can be obtained with in two hours.

Issues in Xpert MTB/RIF

·         Need for a constant supply of electricity

·         The high cost of the instrument and cartridges.

·         waste management of cartridges and

·         Its utility in extra-pulmonary and smear negative samples has been questionably low. 

In 2012 Government has declared tuberculosis (TB) a notifiable disease. The announcement signifies that with immediate effect, all private doctors, caregivers and clinics treating a patient suffering from TB will have to report every single case of the air-borne disease to the government.

This might help in reducing MDR TB cases and early detection and prevention .The 12th five year Plan for TB control added, "All diagnosed TB cases will be notified irrespective of their treatment or registration status."