Microscope image of a Mycobacterium, a member of the family that causes tuberculosis. Photo: NIAID/Wikimedia Commons
March 24 is observed as World TB day to draw attention to a disease with records of its impact stretching into antiquity. Tuberculosis is caused by the bacillus, Mycobacterium tuberculosis, which spreads when an infected person expels the bacteria through the mouth or nose. Despite advances in treatment, TB kills nearly 1.6 million people every year across the world. About 10 million new cases of TB infection are reported every year, with a majority of the cases in South and South East Asia and Africa. India alone accounts for over 25% of the TB burden. The disease has shown no real signs of slowing down despite researchers, governments and international bodies working aggressively to manage it.
TB is typically a lung (pulmonary) disease. Indeed, TB in the lung is the most common cause of both morbidity and mortality. It is also the primary source of infection spread and is therefore of great public health importance. Not surprisingly, most TB research as well as government policy is focused on the prevention and control of pulmonary TB.
However, pulmonary TB is not the only form of TB. When the bacillus affects other parts of the body it is called extrapulmonary TB (EPTB). In fact, EPTB can infect virtually every other organ in the body. EPTB accounts for 15-20% of all reported TB cases, which may increase up to 50% in patients with HIV. These infections are caused by Mycobacterium tuberculosis entering the bloodstream from the lungs and spreading to different parts of the body.
The bacteria may lie dormant in these organs, or incite an inflammatory response that manifests as disease specific to the organ. So, TB in the brain will cause neurological symptoms, gastrointestinal symptoms in the gut, or ocular symptoms in the eye. The most common extra-pulmonary organs affected by TB though, are the lymph nodes (roughly a third of all EPTB cases). Lymph nodes are parts of our adaptive immune system that inspect and filter out pathogens from the body. These nodes are present across the body and infection of the lymph nodes typically causes swelling and pain in the part where these are located.
The diverse scope of active infection makes the diagnosis and treatment of EPTB pose several challenges to the treating clinicians. The clinical presentations of EPTB are generally non-specific and may mimic other infectious and non-infectious conditions. Secondly, in patients with EPTB, the bacteria may not be as easy to detect in the tissues as it is in the sputum samples of patients with lung TB.
Finally, more than half of the patients with EPTB may not have associated lung disease. Thus, many cases of EPTB remain undiagnosed or are diagnosed late, causing irreparable damage to the organs. A good example is TB of the eye which is commonly misdiagnosed as another form of uveitis (an inflammation in the eye) leading to prolonged vision loss for the patient. Concerted efforts are needed not only to develop accurate diagnostic and treatment criteria, but also to increase awareness about EPTB among physicians who may be treating EPTB cases in their clinics without adequate knowledge of the condition or the protocols to follow.
The challenge is to bring together physicians from different specialties such as neurology, gastroenterology or ophthalmology to the same table to discuss EPTB as a single entity. Specialists tend to remain restricted to their own specialties and rarely get a chance to interact with each other. This means that each specialty remains oblivious to the insights gained into the diagnosis and management of EPTB by another specialty.
The Central TB Division of the government of India decided to meet this challenge in 2014, when it brought together TB experts from 10 different medical specialties to formulate guidelines for EPTB, under the guidance of professor S.K. Sharma, then head of internal medicine at the All India Institute of Medical Sciences, New Delhi. The group was supported by the Cochrane South Asia and Cochrane Infectious Disease groups (a UK-based organisation for evidence-based research) to formulate guidelines for EPTB in India. At the end of the exercise that lasted nearly two years, the group produced select recommendations for only five of the ten organ systems that were investigated. These were called the INDEX-TB (Indian Extrapulmonary TB) guidelines, and were endorsed by the World Health Organisation (WHO). In addition to the guidelines, the group also released clinical practice points for each of the 10 organ systems. While the INDEX-TB guidelines managed to bring different medical specialties on a common platform and highlight the cause of EPTB, much more needs to be done by the central TB division and other inter-governmental agencies like the WHO.
A good start would be to collect data from different medical specialties on their departmental record of the prevalence of EPTB in the community, rather than from TB departments in large hospitals. The government of India runs Ni-Kshay, a web-enabled patient management system for TB control under the National Tuberculosis Elimination Programme. This allows health professionals from both public and private sectors to register TB cases under their care, and access other TB-related facilities. However, this programme is plagued by incomplete information and many TB patients are not notified in the Ni-Kshay database. This problem is further exacerbated by the fact that there are many more patients who remain undiagnosed and even unaware of EPTB.
Hence, there is a need to proactively screen patients presenting with different extrapulmonary symptoms in both public and private health care for evidence of EPTB. We also need to generate high-quality data through clinical trials for formulating guidelines for the diagnosis and treatment of all forms of EPTB. The mechanisms of the spread of TB bacteria from the lungs to other parts of the body, and how these bacteria interact with specific organs in the body are all still poorly understood.
Together, these efforts may well uncover that EPTB is a larger public health problem than it is currently believed to be. It will go a long way in identifying patients with EPTB across the country and giving them access to appropriate care.
Soumyava Basu, head of uveitis services at the LV Prasad Eye Institute, Hyderabad.