Convergence of non-communicable diseases and tuberculosis

When Mycobacterium tuberculosis (MTB) enters the body, it typically starts by infecting respiratory epithelial cells or mucosal tissues, eventually reaching the alveoli. Here, it faces two primary fates: it can be engulfed by immune cells like macrophages and dendritic cells (DCs) through phagocytosis, or it can directly infect alveolar epithelial cells, leading to the potential spread of tuberculosis (TB) throughout the body. The host's response to this invasion often involves the formation of granulomas, which effectively contain the bacteria, limiting its proliferation and the progression of the disease. However, while granulomas manage to control MTB, they also provide a sanctuary where the bacteria can lie dormant, creating a state of latent TB that poses a risk of reactivation. MTB employs clever survival strategies, such as evading phagolysosomal fusion to bypass the immune response, and it modulates the function of DCs by altering their secretion of inflammatory factors. Early immune responses involve neutrophils and NK cells, with the latter enhancing macrophage activity to inhibit MTB growth through cytokine secretion.[1]

See also: https://tbreadingnotes.blogspot.com/2024/08/management-of-drug-resistant.html

The interaction between TB and diabetes mellitus (DM) adds another layer of complexity to this infectious scenario. In diabetic patients, hyperglycemia leads to abnormal activation of neutrophils, which in turn cause tissue and organ damage through the release of reactive oxygen species (ROS) and pro-inflammatory cytokines. This high blood sugar environment also impairs adaptive immunity by reducing the number of lymphocytes in germinal centers and glycosylating immunoglobulins, thus compromising their functionality. Patients with TB-DM face increased challenges, including higher rates of treatment failure and mortality, a greater propensity to develop drug resistance, and an elevated risk of transmitting the disease. Interestingly, while successful TB treatment can normalize glucose tolerance, latent MTB infection might predispose individuals to diabetes later in life by possibly affecting insulin resistance. Moreover, MTB's ability to utilize cholesterol within host cells not only aids its survival but also suggests that lipid-controlling drugs might have anti-TB potential, offering a novel therapeutic avenue.[1]

See also: https://tbreadingnotes.blogspot.com/2024/08/the-impact-of-new-tuberculosis.html

In 2016, the global landscape of tuberculosis (TB) was marked by 10.4 million new cases and 1.7 million deaths, with over 85% of these occurring in low- and middle-income countries (LMICs). None of these countries are projected to meet the 2030 Sustainable Development Goals related to TB, which aim to reduce TB deaths by 90% and TB incidence by 80% from 2015 levels. The chronic nature of TB has been identified as a risk factor for non-communicable diseases (NCDs), particularly because TB can alter metabolic parameters like blood glucose levels. During active TB infection, there's a noted increase in blood glucose, potentially leading to hyperglycemia, which might be due to the acute stress response involving pro-inflammatory cytokines and regulatory hormones. Treatment for TB can reverse this trend by lowering blood glucose levels, but the relationship is bidirectional and complex, with pre-existing hyperglycemia possibly exacerbating into diabetes mellitus (DM) due to TB's effects on insulin sensitivity and pro-inflammatory responses in adipose tissue.[2]

The link between TB and metabolic conditions extends beyond glucose metabolism. TB can induce epigenetic changes that might increase the risk of hyperglycemia or DM, although empirical evidence on this post-TB risk is scarce. Elevated levels of heme oxygenase-1, seen in TB patients, are associated with both inflammation and an increased risk of DM. The complexity of this relationship necessitates prospective studies to measure how metabolic parameters change after TB treatment, to discern the true incidence of DM and other metabolic disorders. However, such studies must carefully manage control groups and account for potential reverse causality, where TB might unmask a pre-existing predisposition to DM, thus complicating the interpretation of post-TB DM incidence.[2]

Moreover, the impact of TB on respiratory health is profound, with projections indicating that by 2030, chronic obstructive pulmonary disease (COPD) will surpass lower respiratory tract infections to become the third leading cause of death globally. This trend is fueled by increasing air pollution and tobacco use, alongside TB's contribution to the burden of chronic lung disease (CLD). In regions like South Africa, previous pulmonary TB significantly increases the risk of chronic bronchitis, with the effects sometimes being more severe than those from smoking. The aftermath of TB includes lung damage like cavitation, bronchiectasis, and fibrosis, which can lead to chronic respiratory issues. TB also intertwines with cardiovascular health; for instance, patients with repeated TB treatment have an increased risk of acute coronary syndrome and ischemic stroke. The inflammatory response from TB can contribute to cardiovascular diseases through mechanisms like plaque formation or rupture, and alterations in lipid profiles, where TB patients often show lower levels of cholesterol, potentially affecting immune function and cardiovascular health. The challenge lies in distinguishing whether these cardiovascular outcomes are direct results of TB or exacerbated by pre-existing risk factors.[2]

See also: https://tbreadingnotes.blogspot.com/2024/08/multidrug-resistant-tuberculosis.html

References:
1. Zhao, L., Fan, K., Sun, X., Li, W., Qin, F., Shi, L., Gao, F. and Zheng, C., 2024. Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus. Frontiers in Immunology, 14, p.1305325.

2. Magee, M.J., Salindri, A.D., Gujral, U.P., Auld, S.C., Bao, J., Haw, J.S., Lin, H.H. and Kornfeld, H., 2018. Convergence of non-communicable diseases and tuberculosis: a two-way street?. The International Journal of Tuberculosis and Lung Disease, 22(11), pp.1258-1268. https://doi.org/10.5588/ijtld.18.0045