The silent superbug
11 April 2016
Totally drug resistant TB is the lethal superbug that could haunt India’s future.
In 2015, the World Health Organisation (WHO) stated that approximately a quarter of the total global burden of tuberculosis was shouldered by India. Before that, in 2006, after looking at the available public health sector data, WHO declared that there were 110-132 cases of ‘multi-drug resistant’ tuberculosis (MDR-TB) in India. Though there have been efforts to control this epidemic, in the past decades, new cases of MDR-TB and ‘extensively drug-resistant’ tuberculosis (XDR-TB) have emerged.
Recent international media attention has been centred on a new and deadlier strain of tuberculosis, categorised as ‘totally drug resistant’ tuberculosis (TDR-TB). In 2009, 15 tuberculosis patients in Iran were reported to be resistant to all anti-TB drugs tested. Then, in December 2011, a team of doctors in Mumbai reported four patients with TDR-TB. A few weeks later, the Times of India reported another eight cases in Mumbai. The discovery of TDR-TB has created a lot of speculation within the Indian healthcare system and is a strong contender for the title of the next ‘superbug’ that could haunt Southasia.
Tuberculosis is a chronic disease caused by the bacteria Mycobacterium tuberculosis. It spreads from person to person through air. When infected, TB usually affects the lungs, but it can also affect other parts of the body, such as the brain, intestines, kidneys, and even the spine. Symptoms of TB manifest differently, depending on where the TB bacteria is growing in the body. In pulmonary TB, symptoms range from a chronic cough, pain in the chest, fatigue, coughing up of blood, weight loss, fever and night-sweats.
In developing countries, the disease has a large footprint in terms of morbidity and mortality. Over 95 percent of TB deaths occur in low- and middle-income countries, according to figures released by WHO in 2015. Among women aged between 15 and 44, it is one of the top five causes of mortality. Once the standardised short-course treatment was adopted widely in the 1980s, TB specialists had hoped that the disease burden would decline globally. Their hopes were only partially realised. While there definitely was an overall decline in most developed countries, this was not replicated in developing countries, such as India.
In 2012, WHO defined multi-drug resistant tuberculosis, or MDR-TB, as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs. MDR-TB first emerged in the early 1990’s in Mumbai. The government failed to take action until 1995 by arguing that the disease would be too expensive and technically difficult to treat. But over time, TB has slowly escalated to the top of the country’s healthcare agenda.
In 2011, 77 countries worldwide had already reported cases of XDR-TB. Both treatment and management of such cases are well beyond the capacity of any developing country and in particular India which has a small health budget – 1.2 percent of the GDP in 2015. The fifth ‘TB Joint Monitoring Mission 2015’ draft report observed that the implementation of the National Strategic Plan (NSP) for the five-year period 2012-2017 was not on track because of budget cuts. Resource-planning under the NSP is critically under-funded by the government, with annual budget allocations not matching requirements. The report stated that the approximate shortfall in the NSP budget would be INR 1500 crore (USD 226 million) less than the minimum required budget estimate of INR 4500 crore (USD 677 million), if this trend continues.
Officially, India represented 20 percent of the world MDR-TB burden in 2006. This was an underestimate because it only represented public healthcare data and did not take into account patients from the private sector. Due to the missing private sector data, the full extent of the problem has not yet been captured. In addition, due to mismanagement of MDR-TB by the Indian healthcare system, an estimated one out of ten cases has led to the development of extensively-drug resistance (XDR-TB); that is, resistant to at least three to six drugs used to treat TB.
The first case of XDR-TB was reported by PD Hinduja Hospital and Research Centre in 2006, which caused concern among healthcare officials. Although the situation seemed to be under control, it wasn’t until 2012 when the first TDR-TB case was reported by Dr Zarir F Udwadia, chest physician and head of the laboratory in PD Hinduja Hospital and Research Centre. The laboratory, where the strain was isolated, is a reputed myco-bacterial laboratory, accredited for drug susceptibility testing (DST) by the Revised National TB Control programme. In 2014, Dr Udwadia stated that since the initial detection of TDR-TB in four patients, they had detected 11 more patients with the same resistance pattern in a paper co-authored with Dr Deepesh Vendoti for the Journal of Epidemiology and Community Health
TB management in India has been haphazard at best. Development of TDR-TB in the country can be attributed to diverse factors such as injudicious diagnostic and treatment techniques by healthcare authorities – both from the private and public sectors, improper drug dosages, lack of an adequate infection control and poor laboratory infrastructure, among others.
The disease is more present in communities living in overcrowded areas, where poor ventilation, poor sanitation and compromised water supply systems all increase the risk of TB transmission. Poverty also results in poor nutrition, which is associated with lowered immune function. Stigma, economic barriers, lack of awareness and inadequate social support and difficulties in transporting patients to health facilities, may hinder early diagnosis and also complicate treatment outcomes. Finally, TB’s association with HIV poses societal hurdles in reporting such co-infection cases and its subsequent treatment.
In 1961, the National TB Programme (NTP) was implemented by the Indian government. Due to the lack of funding available, the programme suffered from limited supply of required drugs, diagnostics and treatment. Then in 1993, as a part of a globally coordinated response to TB, the DOTS (directly observed treatment short course) programme was implemented in the country that focussed on the diagnosis and treatment of pulmonary TB by testing sputum samples and supervised treatment for six to eight months. As part of the programme, the patients are asked to come by on specified days to take medications under observation. Due to the emphasis on early case detection, DOTS does not work for every patient and must be adapted on a per patient basis. In 2008, due to increasing resistance, DOTS-plus was implemented. The success of this follow-up programme, to stem the further increase in XDR-TB and TDR-TB, is questionable. The problem of DOTS is its biomedical approach, which does not take into account the social-cultural aspects of TB. Questions as to why people develop TB in the first place are not addressed and aspects such as poverty, malnourishment, psychological problems and stigma, which make it difficult to access healthcare providers, are not taken into account. Furthermore, the monitoring of TB cases at the national level has been patchy, which makes it difficult to obtain reliable data.
Slum areas and other poor communities, in Indian cities and villages, are usually catered to by private allopathic practitioners along with alternative and traditional healers. But such physicians are also largely unequipped to deal with drug resistant TB since they have limited knowledge about the diagnosis and treatment of the disease itself. A Mumbai study that was conducted in 2010 by Dr Udwadia showed that only six of 106 private practitioners who were working around the Dharavi area were able to prescribe correctly for a hypothetical patient with MDR-TB. The results of the research was published in the Clinical Infectious Diseases journal in 2012, which stated that the majority of the prescriptions were inappropriate and could have easily contributed to the increase in MDR-TB, XDR-TB and even TDR-TB.
According to the study, 60 to 80 percent of patients first approach a private practitioner and go to a public sector doctor only after realising that their health is deteriorating because of improper treatment. Previously, the public sector would not take the initiative and approach patients or private practitioners and would wait for the patients to come voluntarily. Soon, government doctors noticed that this intermittent waiting period led to the build-up of resistance due to improper management by the private sector and made it harder to combat the drug resistant TB once the patient arrived at a government medical facility.
This realisation prompted the government to try a more active approach by including the private sector and forming a public-private mix (PPM) programme in order to tackle this health crisis more competently and holistically. However, the PPM programme has been challenging for many reasons. The primary problem is identifying reliable private practitioners who will follow guidelines and provide the much-required last mile connectivity for TB treatment.
Moreover, differences in perspectives among private and public actors can also create problems. In 2014, Nora Engel, a PhD researcher in the field of TB management who works as an assistant professor of Global Health at the Maastricht University, Netherlands, published a paper that summarised study results that shows that ‘problem definitions’ and ‘differing control practices’, including supervision, standardisation and problems of culture clash can hinder the success of PPM programmes. Nevertheless, the public sector will not be able to deal with the increase in drug-resistant TB effectively without the involvement of the private sector, since this is where most of the patients initially turn to. It has become crucial to bridge the different organisational practices which hinder the diagnosis of TB and the delivery of treatment.
Efficacy may also be improved by studying why poor patients choose to pay for inadequate treatment provided the private sector rather than approach public sector clinics, where the treatment is free and better regulated. Understanding this hesitation to approach government facilities and filling the gaps in TB awareness and treatment is the key to improving the situation.
In January 2012, the four patients of TDR-TB, reported in Mumbai, were resistant to all first-line and second-line drugs. Unfortunately both the WHO and the Indian government have not officially acknowledged the category and the emergence of TDR-TB, which has complicated the situation even more. While the reasons for the government’s refusal to acknowledge the problem is understandable, the hesitance of the WHO is more mystifying. WHO held a consultation in 2012 about the case definition on TDR-TB – a meet that official government representatives from India failed to attend. Even though, after this consultation, WHO noted that “reports of tuberculosis (TB) patients with severe patterns of drug resistance are increasing and present clinicians with a formidable challenge”, it concluded that there was not enough evidence to create a new category of resistance. WHO cited “technical difficulties with drug susceptibility testing (DST)” which was used to identify these TDR-TB strains as the reason.
However, this does not change the fact that in 2012, all four patients in Mumbai were tested thoroughly and have shown to be fully resistant to all available drugs. A TDR-TB definition needs to be acknowledged in order for new medication and treatments to be developed for those that are resistant. It is mostly an unacknowledged truth that although only 12 patients were reported in 2012, many more have probably gone unnoticed due to a lack of monitoring and surveillance within the healthcare system.
The Government of India and WHO should learn from their mistakes for being hesitant in acknowledging the emergence of MDR-TB in the early 1990s and face this new emerging TDR-TB strain before an outbreak occurs. The government needs to invest more in health infrastructure, new diagnostics and treatment facilities. The recent cuts of 20 percent in an already small national health budget are very worrisome and may result in additional funding problems in TB-management. As noted earlier, India needs to also actively invest and work on the long neglected social determinants of health causing the TB epidemic by providing nutrition, proper housing, employment and a higher quality of healthcare.
Most patients with TDR-TB die. Prevention, as always, is the first line of defence. It is important to frame the TB epidemic not just as a natural disaster caused by a bacterial infection, but to acknowledge the social-ecological aspects and tailor solutions accordingly. These include adopting policies, laws and incentives that support responsible choices among the public through the PPM programme and encourage private practitioners to foster accountability and to closely monitor what is happening within their private practices. The stigma and psychological aspects of the disease need to be actively addressed.
In addition, interventions in the form of social protection and urban planning are required to lessen susceptibility to TB in low-income communities and overall TB control, along with strengthening infrastructure in under-funded public health facilities. Management of TB can easily be aligned with Sustainable Developmental Goals. We need to stop viewing and acting only from a biomedical perspective. Instead of relying on pills and vaccines as the main method of intervention, we should see the problem for what it actually is and act upon it.
~ Sona Geworgjan is currently pursuing an MSc in Global Health at Maastricht University, Netherlands.
~ Cristina Valencia is a fellow at the European Programme for Intervention Epidemiology Training, part of the European Center for disease prevention and Control (ECDC).