Latent TB deserves more attention

Dr Amitava Acharyya, CNS Correspondent, India
Tuberculosis (TB) remains a major infectious disease globally. After initial contact with viable TB bacilli, hosts who fail to clear all Mycobacterium TB (M.TB) can progress to the status of latent TB infection (LTBI) and have a life-time risk of 5%–15% to further progress into active disease.

The main aim of LTBI treatment is to prevent progression of latent stage of TB to active TB, and this treatment is usually practised in low TB-burden countries, especially among specific high-risk populations, including people living with human immunodeficiency virus (HIV), adult and child contacts of pulmonary TB cases, patients who initiate anti-tumour necrosis factor treatment, patients who receive dialysis, patients preparing for organ or hematological transplant, and patients with silicosis. A new study conducted by Dr Leonardo Martinez, a research fellow at Stanford University School of Medicine, USA, has found that the chances of onset of latent TB infection are higher among people with diabetes or with uncontrolled blood sugar levels, as compared to normoglycemic people. This concept can reflect the enormous load of future TB management in Sikkim, is the least populous and landlocked state in north east India. Most of the state’s population resides in rural areas. It is heartening that Sikkim has received many prestigious awards in last two decades on account of its economic growth, cleanliness, primary education, women empowerment and several health related indicators.  But when it comes to multi drug resistant TB (MDR-TB) and presumptive type 2 diabetes mellitus (T2DM) patients (RBS≥140 mg/dl) then Sikkim becomes a high risk zone.

Data shows Sikkim to be the next big concern on India’s TB scenario, with 11% of the new TB cases in the state found to be multi-drug-resistant. This figure is almost same as that of Mumbai, which is called the country’s TB capital,. The MDR-TB occurrence in new TB cases is near about 2% in rest of India.  Another data of National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) found that this state has a very high percentage of presumptive T2DM patients.

It is interesting to note that both diseases have a ‘pre –disease state’.  In T2DM, the pre-diabetes conditions are called as IFG and IGT. Various studies on T2DM & TB have proved that hyperglycemic patients have a greater chance to develop latent TB infection. In the case of TB, the pre-disease state is the latent TB state, where patients do not show any clinical signs and symptoms of TB, but some dormant TB bacteria are present in the body that can become active in future under conducive circumstances.

In a webinar organised by CNS, Dr Anil Kapur, Managing Director of World Diabetes Foundation said that, “There is clear evidence that diabetes increases the risk of active TB, latent TB and also of MDR-TB, and this is directly related to worsening of glucose control. Even a fasting blood glucose level of 130, which is not extremely bad diabetes control level, is finding extremely high rates of latent TB infection. The prevalence rate of active TB disease in people with diabetes varies with background TB incidence. In high TB burden countries it can be 5 to 14 times higher than in the general population. A study done in Indonesia found the rates of TB in people with diabetes to be 14.7 times higher than in the general population, in India it is in the range of about 7 to 8 times. The prevalence of diabetes among TB cases is about 2 to 3 times higher than in the general population”.

The following facts about TB and T2DM make the allied management of the two diseases very difficult and critical:

(i) Recurrence of TB and mortality are much higher in co-morbid diabetes patients, even after being successfully treated for it

(ii) Research shows that among people who are being treated for TB, those with diabetes remain contagious for a longer time than those who do not have diabetes

(iii) TB itself is responsible for temporarily increasing blood sugar levels, a condition known as impaired glucose tolerance, which is a risk factor for developing diabetes

(iv) Anti-tubercular drugs like Rifampicin can make it more difficult to control diabetes

(v) Oral Hypoglycaemic Agents (OHA) had been found to decrease the effectiveness of anti tubercular drugs.

There has been one hypothetical biological plausibility of T2DM and TB.  It starts after the inhalation of M.TB bacilli stored in alveolar macrophages in the lung. Failure of clearance of M.TB in alveolar macrophages may lead to bacterial replication and further spreading. It was seen that mice with DM had a delayed and impaired innate immune response to the invasion of M.TB. Similar evidence for impaired innate response was also found in T2DM patients.

Some researchers from Mexico lead by Dr Martin Castellanos Joya, a National TB Programme expert, have developed a bi-directional integrated screening and management model for diabetes and TB in primary care settings. As Sikkim has a huge burden of diabetes and TB, it is high time for policy makers to implement an integrated bi-directional screening for diabetes and TB on a pilot basis in Sikkim.

The tuberculin sensitivity test (TST) or Mantoux test, is a cost effective test for detecting latent TB among T2DM and normal individuals. If the area of skin where you received the PPD injection is not swollen, or is only slightly swollen 48 to 72 hours after the injection, the test results are negative. The amount of swelling may be different for children, people with HIV, the elderly, and others at high risk. A negative test result means that most likely one is infected with the TB bacteria. A small reaction, called an induration or hard bump, at the site of the test (5 to 9 mm of swelling) signifies a positive result for TB, which could be latent or active. So a a positive result should be followed by more tests to find whether the TB is latent or active.

The preventive treatment of LTBI is of great importance for the elimination of TB worldwide, as envisaged in the sustainable development goal 3 of ending TB by 2030.

Dr Amitava Acharyya, Citizen News Service - CNS
November 6, 2017