Multimorbidities and Tuberculosis: A Multidisciplinary, Integrated Care Model Is the Way Forward

In spite of the intensified efforts at global, regional, and national levels, tuberculosis (TB) continues to be the major infectious cause of death worldwide. Active TB is found to be associated with a breakdown of the immune surveillance. This may lead to a situation where TB becomes associated with many noncommunicable diseases (NCDs) as well as certain communicable diseases. It has been recognized that TB coexists with many NCDs, especially in high-burden regions of the world.[1] The most commonly encountered multimorbidities in TB patients include diabetes mellitus (DM), malnutrition, anemia, HIV, tobacco smoking, alcohol use, depression, and chronic lung diseases. Both pulmonary TB (PTB) and extra-PTB (EPTB) may cluster with the various comorbidities. Major comorbidities associated with active TB and the key clinical and molecular pathways have implications for the overall disease control policies. Hence, it is imperative that all these comorbidities in the TB population need to be identified to improve the co-management of TB and other coexisting illnesses. Synergies between TB and NCDs that could be explored in public health efforts include joint health promotion strategies, reciprocal screening programs, and coordinated integrated treatments.[2] TUBERCULOSIS AND DIABETES In general, DM triples the risk of TB.[3] The association between DM and TB has been recognized for the past several years. However, the actual relevance of the dual epidemic of TB and DM became well established only during the past 10–15 years. DM-TB patients are found to have worse anti-TB treatment outcomes versus non-DM-TB patients. DM is rapidly increasing globally including the South East Asian countries due to the shifting socioeconomic and lifestyle factors.[4] Any further increase in the number of DM-TB patients may hamper the progress that has already been achieved in the global fight against the disease. Several studies to date have convincingly shown that DM-TB patients have severe symptom burden and may pose diagnostic challenges and poor treatment outcomes. Some studies have shown that DM patients are at increased risk for latent tuberculosis infection (LTBI) and progression to overt disease. The various mechanistic pathways of the dual DM-TB epidemics leading to altered disease behavior of DM-TB patients are getting elucidated. All these stress the need for bidirectional screening for DM-TB in this population.[5] It also calls for an emphasis on a wide range of overlapping diseases, especially in resource-poor countries. There is an urgent need for integration of existing TB services with the various coexisting comorbidities at the same time monitoring some of the vertical elements to ensure the key aspects such as the supply of anti-TB drugs, monitoring, evaluation, and national level surveillance. TUBERCULOSIS AND HIV The interrelationship between TB and HIV/AIDS is well established. People living with HIV are about 29 times more vulnerable to develop TB.[6] We have well-established management strategies for the twin epidemic of TB-HIV and are followed globally. The regional response plans for TB HIV 2017–2021 lay down strategies for enhanced action in this regard.[7] TUBERCULOSIS AND TOBACCO SMOKING The WHO estimates that there is a high burden of tobacco use in the South East Asia regions. It is shown that smokers are twice as likely to be infected with Mycobacterium tuberculosis and progression to active disease. Smoking negatively impacts every stage of TB disease. It is also found to increase the risk of LTBI, delay culture conversion, prolong sputum smear positivity, cavitary disease, delayed treatment, treatment default, and poor treatment outcomes. Smokers are twice as likely to die of TB compared to nonsmokers.[8,9] Tobacco smoking significantly increases the risk of TB recurrence/relapse and mortality during treatment among TB patients. All these highlight the need to address tobacco smoking to improve the treatment outcome. CHRONIC LUNG DISEASES Chronic lung diseases, especially chronic obstructive pulmonary disease (COPD) and chronic asthma, may also have to be addressed along with anti-tobacco measures.[9] Several studies have shown that COPD and asthma are two commonly encountered respiratory comorbidities in TB patients.[10-12] It is also to be noted that TB per se may lead to COPD.[13,14] The TB and Tobacco Regional Response Plan for South East Asia 2017–2022 advocates a three-pronged strategy to tackle the issue.[15] TUBERCULOSIS AND NUTRITION Malnourishment increases the risk of TB and TB can lead to malnourishment.[16-18] Malnutrition is highly prevalent in people with TB. Nutritional assessment, counseling, and appropriate improvement of the nutritional status are important. Undernutrition and underlying food insecurity are among the most important determinants of the burden of TB. The burden of TB provides a useful barometer as an indicator of disease and the socioeconomic inequality and deprivation.[19] TUBERCULOSIS–DEPRESSION Depression is a comorbid condition that occurs in TB patients making the TB management challenging.[20,21] The mechanistic link between TB and depression has been extensively studied. It is seen that the inflammation generated by TB infection may enhance the risk of depression. At the same time, depression may compromise the host immunity by enhancing the risk of TB infection. DM, an established risk factor of TB, is usually comorbid with depression.[22-27] The co-occurrence of these 2 conditions in TB creates a complex clinical scenario which is a difficult task to manage. Furthermore, TB depression patients may have several pharmacological interactions, especially Isoniazid (INH) and rifampicin interacting with many antidepressants and psychotropics.[28-31] Apart from those already discussed, TB can also be associated with other conditions such as cardiovascular diseases (coronary artery disease and hypertension), anemia, hypothyroidism, alcoholism and substance abuse, chronic liver disease, and chronic kidney disease.[32-35] In this issue of the journal PULMON, Dr. Akhilesh Kunoor et al. have attempted to look at the frequency of the commonly encountered comorbidities in TB patients reporting to a tertiary care center. It is a retrospective, descriptive study analyzing the distribution of the various comorbidities in TB patients (PTB and EPTB). They have found diabetes and chronic lung diseases as the most common comorbid conditions, followed by cardiovascular diseases including hypertension. They have also shown the impact of those comorbidities in the overall treatment outcome. In spite of certain limitations of the study, like the retrospective, hospital record-based data, the authors merit appreciation as they were able to reproduce results comparable with other studies. They also succeeded in conveying the message for the early identification of the coexisting comorbid illnesses for a better overall management of TB. Every practicing clinician caring TB patients should be aware of the ramifications of the various comorbidities for a successful treatment outcome. This is of paramount importance to achieve success in our fight against TB. As per the WHO to achieve a proper TB control, the rate of patients who reach a cured rate must be no <85%. Several factors such as socioeconomic barriers, clinical characteristics, and drug resistance may account for the failure to achieve this target. Various studies have shown that the presence of polymorbidities in TB patients is associated with poor clinical outcomes. The co-occurrence of many of the comorbid conditions will render the overall management difficult, calling for a focused multidisciplinary collaboration and integrated TB treatment strategies. Co-management of comorbidities in TB patients has become an integral component of the overall TB control program. An integrative care model could serve as a cost-efficient strategy to coordinate the TB comorbidity control program. This team-based integrated approach may deliver good results in the control of many coexisting medical conditions such as diabetes mellitus (DM), coronary heart disease, hypertension, c/c respiratory diseases, depression, tobacco use as well as improving the various symptoms including depression, treatment adherence, and overall well-being.