There were limitations in our approach to describe the distribution of XDR-TB. We did not explore the reliability of microbiological methods in various laboratories. The microbiological diagnosis of XDR-TB data included here remain not validated by reference laboratories. National Institute for Tuberculosis Research (NITR) in Chennai is RNTCP's Supranational Reference Centre (designated by WHO) and it participates in international external quality assessment for microscopy, culture and DST22
. In turn, NITR monitors the quality of laboratories in the country on behalf of RNTCP. Two laboratories that reported XDR-TB (New Delhi TB Centre and Christian Medical College at Vellore) are accredited by RNTCP for culture and DST. The Vellore laboratory was the nodal centre for the in-country external quality assessment scheme of the Indian Association of Medical Microbiologists22
. Hinduja Hospital, Mumbai, is accredited by College of American Pathologists13
These reports have originated from 10 tertiary care centres in nine cities, distributed widely in the country. Therefore, the data have no representative value for epidemiological assessment. Many hospitals that diagnose and treat TB may use the recommended sputum smear-examination and/or chest X-ray without culturing the bacterium. Many laboratories with culture facilities for M. tuberculosis may not conduct DST even for first line anti-TB drugs to diagnose MDR-TB. When MDR organisms are detected, DST for second line drugs is unlikely to be conducted, being cumbersome and expensive. Thus the true prevalence of XDR-TB remains unknown.
The diagnosis of XDR-TB has enormous implications both for the individual and the community. The choice of anti-TB drugs is limited and the ones available are too expensive and too reactogenic24
. Treatment outcome is mostly disappointing and case-fatality rate (CFR) is very high - in one report the CFR was 51 per cent within a month of diagnosis25
. When transmitted to new hosts the organisms will remain XDR, hence progressive primary TB and eventual secondary TB (after the period of latent infection), if occur, will inevitably be due to XDR-TB. Therefore, there is an urgent need to prevent secondary transmission at all costs, barring the curtailment of human rights beyond ethical limits. The tension between individual freedom of movement in society and public health need for its restriction has to be addressed and resolved. These considerations call for urgent national policy and guidelines and innovative design for early diagnosis and case management of XDR-TB.
A national registry of XDR-TB will allow every institution to report cases as soon as they are detected. The bacilli isolated from each case should be collected and verified in a reference laboratory. Therefore, a number of reference laboratories should be established and networked so that the facility is readily accessible. A treatment protocol should be designed and applied under RNTCP supervision on every diagnosed case of XDR-TB. While on treatment, precautions necessary to prevent transmission to members of family and to healthcare workers in contact should be applied. The elements of such precautions need to be urgently defined. There is also an urgent need for effective infection-control measures within clinics and hospitals. Prevention of transmission through reducing the airborne shedding and inhalation inoculation can be achieved by measures to reduce aerosol production and circulation in room air. This must be implemented in every hospital co-ordinated by hospital infection control committees. There has been a report of death of a healthcare worker with XDR-TB, most likely hospital-acquired26
In order to inhibit the development of MDR and XDR-TB, better diagnostic algorithm needs to be designed and popularized27,28
. Based on carefully crafted clinical criteria every case of suspected pulmonary TB should have at least one sputum culture for M. tuberculosis
in order to substantially improve the diagnostic sensitivity and to allow DST well ahead of clinical treatment failure in case the organism is MDR27,28
. This will require massive expansion of laboratory capacity throughout the country29
. Every MDR isolate should be further screened for XDR organisms in reference laboratories. The currently recommended sputum smears for detection of acid fast bacilli (AFB) by Zeihl-Neilsen staining should be supplemented with a more sensitive method using fluorescent microscopy29
Treatment of TB by community-based medical practitioners often do not conform the recommended regimen; also many patients interrupt or discontinue treatment. This sets the stage for emergence of MDR- and XDR-TB in India30
. Many patients with MDR-TB have been documented to have non-standard treatment regimens in the past18
or had repeatedly defaulted on treatment. Such patients should be identified, counselled and restrained with assistance from family and employers - balancing rights of the individual and safety of society.
Although HIV infection does not by itself increase the probability of developing anti TB drug resistance, the co-morbidity with MDR- or XDR-TB is life threatening to HIV positive people. One study9
had looked at the prevalence of XDR-TB in HIV infected patients and found that among 54 patients, 12 (22%) had MDR-TB and among them 4 (33.3%) had XDR-TB. All four died within 3 months of diagnosis.
Addressing XDR-TB in India will be a formidable challenge. The strategy of RNTCP has been to minimize the development of MDR-TB by standardized drug regimens and consequently reduce the emergence of XDR bacilli. We suspect that the major cause of emergence of XDR-TB is the widespread practice of non-standard drug regimens in the private sector healthcare settings. Guidelines to fully integrate DOTS and DOTS-Plus (diagnosis and treatment of MDR-TB) have already been brought out by RNTCP30
. The target is to detect and treat at least 30,000 cases of MDR-TB annually, free of charge, from 2012-2013 onwards31
. Unless TB treatment in private sector is effectively regulated, the problems of MDR- and XDR-TB will remain largely unrecognized.
In conclusion, reports from just nine cities across India document the presence of XDR-TB in India. There is an urgent need for country-wide surveillance of MDR- and XDR-TB. Massive expansion of quality-assured mycobacteriology laboratories and strict guidelines and protocols are essential for diagnosis and treatment of XDR-TB. Practical and effective infection-containment measures and facilities for intensive counselling of TB patients need to be established. Educating professionals on these elements and school and college students and the public on prevention of TB must also become part of national TB control efforts.
XDR-TB in India
This write up on extensively drug resistant tuberculosis in India - a review by Drs Joy Sarojini Michael and T. Jacob John is an interesting attempt to focus on a problem which generates very diverse actions among people, scientific leaders, clinicians and public health personnel. As these reports are based on various tertiary care hospitals, these cannot be extrapolated to estimate the burden of the drug resistance in the community. Secondly, there are very few accredited laboratories for second line of TB drugs in India and as such there can be problems about the interpretation and credibility of the profiles reported by many investigators. Nevertheless, one cannot ignore that the problem needs to be addressed by giving it due importance. However, this should not lead to scare as a very small proportion of MDR isolates has been generally found to be XDR. Many Institutions of Government of India including those of ICMR have been working hard to provide the services and augment the capabilities to accurately diagnose the resistance. Several international agencies are also playing their part. I am sure the infrastructure to accurately diagnose different types of the resistance to second line drugs and management of drug resistant cases will be strengthened over a period of time. Till then the readers should read these reports with caution knowing fully well the limitations but get ready to improve as per the needs to do better.
Chairman, Editorial Board, IJMR, Director-General, I.C.M.R. & Secretary, Department of Health Research, Government of India, New Delhi 110 029, India