The challenge of extra-pulmonary TB

The twin challenges in tackling EPTB are lack of awareness, even among physicians, and lack of accurate diagnostic and treatment criteria

Updated - May 16, 2024 09:51 am IST

Published - May 15, 2024 02:29 am IST

A tuberculosis patient receives medicines from a nurse at a TB hospital in Guwahati. File

A tuberculosis patient receives medicines from a nurse at a TB hospital in Guwahati. File | Photo Credit: AP

While the most common form of tuberculosis (TB), which is pulmonary TB, infects the lungs, some 20% of TB infections develop in the lymph nodes, brain, gut, eyes, or other organs. Some of these organs have immune privileges in the body. This means that extra-pulmonary infections can persist even after the TB infection in the lungs is resolved. Just as we have an undercount of the people infected with TB, the public health challenge of extra-pulmonary TB (EPTB) may be larger than our current estimates.

The World Health Organization (WHO) reports over 10 million new cases of TB every year and India alone accounts for 27% of the global TB burden. However, the burden of EPTB is hard to estimate. EPTB is often stain negative, which means it is not detectable on regular TB stain tests. The infection may surface in any part of the body and present itself like other non-TB conditions. Many cases of EPTB may not have a corresponding lung infection. So, EPTB’s true prevalence in society remains hidden.

As the burden of pulmonary TB is greatest, it makes epidemiological sense to focus our efforts on its elimination. The lungs are the primary source of infection spread and reducing this burden will impact all forms of the disease. However, given the scale of TB, variants like EPTB end up affecting a large number of people. EPTB’s under diagnosis results in irreparable damage to the infected organs, leading to vision loss or even blindness, for example. It is therefore important to address TB in all its complexity.

Knowledge gap

The twin challenges in tackling EPTB are lack of awareness, even among physicians, and lack of accurate diagnostic and treatment criteria. The mycobacterium that causes TB was first isolated in the eye just a year after Robert Koch identified the organism. Yet, many who treat the disease (and some who treat the eyes) are ignorant of this association. This situation is true with most of the other organs that host a TB infection as well. Even for those who are aware, it is challenging to reach an accurate diagnosis and put patients on the right therapy for treatment.

As TB can be present in multiple organs, the lack of formal and functioning protocols to exchange information between doctors in multiple specialities leads to silos of knowledge. In 2014, a group of experts from different health institutions across the country, the WHO, and the Cochrane Infectious Disease Group came together to formulate INDEX-TB, a set of guidelines for EPTB management in India. The group also released a set of clinical practice points for 10 organs, but good quality evidence was available only for five of them. This work has remained dormant. More needs to be done to foster and build a common approach to EPTB management, especially in a high TB burden country like India.

Armed with guidelines and practice points, our hospital systems need to generate better data on EPTB. Our current source of EPTB numbers are the TB departments of large public hospitals. However, specialist departments for each organ are the primary centres for EPTB management. Their data practices are diverse and do not become part of our aggregate numbers for EPTB prevalence. These departments must capture patient data and be ready to share it with the National TB Control Programme. Their action may help reinvigorate Ni-kshay, the national patient management portal for TB control, which has incomplete and missing data on TB patients insofar as EPTB patient data are concerned.

Research priority

Key aspects of EPTB, including the mechanisms of infection spread and the TB bacterium’s interactions with our organs, remain under-explored. A troubling aspect of EPTB infection is the prolonged presence of disease markers even after the infection is resolved with treatment. Some EPTB patients who complete anti-TB therapy may still find themselves affected by the disease. In the eye, for example, an autoimmune response to antigens triggered by the original infection can lead to a persistent intraocular inflammation even after appropriate anti-TB therapy. Similarly, there might be other immunological mechanisms lurking in other organs affected by EPTB that may prolong the disease, even after the bacteria have been cleared from that organ. This phenomenon causes a lot of misery to persons with EPTB and is an active area of research.

A concerted effort by different EPTB specialities, and advanced immunological tools such as single-cell RNA sequencing, might be able to uncover the immune mechanisms for the disease. Unless we understand these mechanisms, physicians will continue to treat EPTB with long duration anti-TB therapy (sometimes for even two years or more), assuming that the infection is persisting in the organ. This not only fails to resolve the disease, but also exposes the patient to the toxicity of anti-TB therapy.

Diagnosis and treatment protocols for all organs affected by EPTB do not exist. We will need high-quality data through clinical trials to formulate them. Similarly, INDEX-TB guidelines were formulated over a decade ago and need to be updated with the latest data and experience. They also need to be multidisciplinary and benefit from inputs from a variety of specialised areas of health care.

Nearly one in five TB patients have EPTB. Most of them go undiagnosed, and the few who are diagnosed cannot benefit from care unless they visit a few specialist health facilities. It is time we bring EPTB out of the shadows.

Tejah Balantrapu is Associate Director, Science, Health Data, and Story-telling, LV Prasad Eye Institute; Soumyava Basu is Head, Uveitis Services, LV Prasad Eye Institute

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