Pharmacist: TB-Comorbidities and special situations

Several medical conditions are risk factors for TB and poor TB treatment outcomes. Similarly, TB can complicate the course of some diseases. Therefore, it is important to identify these comorbidities in people diagnosed with TB to ensure early diagnosis and improved outcomes. When these conditions are highly prevalent in the general population, they can significantly contribute to the TB burden. Consequently, reducing the prevalence of these conditions can help prevent TB.

TB shares underlying social determinants with many of these conditions. Addressing the social determinants of health is a shared responsibility across disease programmes and other stakeholders within and beyond the health sector. 

Figure: Various comorbid and special situation related with tuberculosis

The primary impact of HIV on TB is that the risk of developing TB becomes higher in patients with HIV. Overall, HIV-infected persons have an approximately 8-times greater risk of TB than persons without HIV infection. 

Screen TB PLHIV patients for symptoms of TB and HIV

Figure: Screening steps for TB - HIV patients

Treatment for TB HIV Patients​

• All TB patients who have been diagnosed and registered under NTEP should be referred for screening for HIV.
• Referral of TB patients for screening for HIV and its recording & reporting is the responsibility of the Peripheral Health Institutions(PHI) where TB treatment is initiated.
• TB patients diagnosed with HIV will receive the same duration of TB treatment with daily regimen as non-HIV TB patients.
• TB patients must be referred to the nearest ART(Anti - Retroviral Treatment) centre for management of HIV.

As a consequence of urbanization as well as social and economic development, there has been a rapidly growing epidemic of Diabetes Mellitus(DM). India has the second largest number of diabetic people in the world.

Screen TB patients for symptoms of diabetes

Figure: Screening steps for TB - Diabetic Patients

Treatment for TB Diabetes Patients​

• All TB patients who have been diagnosed and registered under NTEP will be referred for screening for Diabetes.
• Referral of TB patients for screening for DM and its recording & reporting is the responsibility of the Peripheral Health Institutions(PHI) where TB treatment is initiated.
• TB patients diagnosed with diabetes will receive the same duration of TB treatment with daily regimen as non-diabetic TB patients.
• TB patients must be referred to the nearest healthcare facility for management of DM.
• Regular monitoring of blood sugar levels is advised.

Malnutrition refers to deficiencies, excesses or imbalances in a person’s intake of energy and/or nutrients. The term malnutrition covers 2 broad groups of conditions.

• One is ‘undernutrition’—which includes stunting(low height for age), wasting(low weight for height), underweight(low weight for age) and micronutrient deficiencies or insufficiencies(a lack of important vitamins and minerals).
• The other is overweight, obesity and diet-related non communicable diseases (such as heart disease, stroke, diabetes, and cancer).

Screen TB Malnutrition patients for nutritional needs

Figure: Screening Steps for TB - Malnutrition patients

Treatment for TB Malnutrition Patients

Cases of TB with SAM and moderate undernutrition should be referred to the nearest health facility of NTEP for further management. Special focus should be given to the following categories:

• Children below five years
• School-age children and adolescents(Up to age 18 years)
• Adults, including pregnant and lactating women, with active TB and SAM

About 10% TB deaths globally have been attributed to alcohol as a risk factor(WHO, Global TB Report 2017). Alcohol abuse is associated with threefold increase in risk of contracting tuberculosis.

Side effects of anti TB drugs in this situation might get aggravated.

Figure: Impact of Alcoholism on TB patients

Treatment for Alcoholic TB Patients:

• Patients with TB and a history of alcohol use should be referred to the nearest health facility of NTEP to manage TB and alcoholism.
• While registering as a TB case, the status of alcohol use should be recorded in the patient records. If the TB patient is an alcohol user, he/she should be counselled to quit it. If the patient doesn't quit alcohol, s/he may be referred to the nearest alcohol de-addiction facility.
• The patient should be assessed at every follow-up visit for TB and the status of use of alcohol.
• At the end of treatment, his/her status of alcohol use should be recorded on the treatment card. If the patient has not quit alcohol, he/she should be referred to the nearest alcohol de-addiction facility and Alcohol Anonymous wherever available.

Almost 38% of TB deaths are associated with the use of tobacco. The prevalence of TB is three times higher among ever-smokers as compared to that of never-smokers. Mortality from TB is three to four times higher among ever-smokers as compared to never-smokers. Smoking contributes to 50% of male deaths in the 25-69 age group from TB in India.

Figure: Impact of Tobacco on TB patients

Treatment for TB - Tobacco Patients:

• While registering as a TB case, the status of tobacco use is recorded on the TB treatment card.
• If the TB patient is a smoker or tobacco user, he/she is counselled to quit tobacco use. The patient is assessed at every visit for follow up for TB and the status of tobacco use.
• At the end of treatment, his/her status of tobacco use is recorded in the treatment card. If the patient has not quit tobacco use, he/she will be referred to the nearest Tobacco Cessation Clinic(TCC) or Quit Line or M-Cessation Initiative.

Silicosis is a progressive and disabling interstitial lung disease caused by inhalation and deposition in the lungs of particles of free silica.

Mutual Risk of TB and Silicosis

• TB is a clinical complication of silicosis, called silico-tuberculosis. Silica-exposed workers with or without silicosis are at increased risk for TB. There is also an increased risk of extrapulmonary TB in individuals exposed to silica.
• The risk of a patient with silicosis developing TB is 2.8 – 3.9 times higher than a healthy individual.
• The risk of TB relapse in patients with silicosis is approximately 1.5 times higher than in patients without silicosis.

The presence of silica particles in the lung and silicosis may:

• Facilitate initiation of TB infection and progression to active TB
• Exacerbate the course and outcome of TB, including prognosis and survival

Diagnosis

The diagnosis of silicosis is made based on a history of exposure to silica accompanied by a clinical and radiological profile consistent with the disease.

Under the Integrated Management Algorithm for TB disease and TB infection released by the National TB Elimination Programme (NTEP), patients with silicosis are first screened according to the four-symptom complex to rule out/in active TB and tested for TB accordingly. 

If active TB is ruled out >> Refer for Tuberculin Skin Test (TST)/ Interferon Gamma Release Assay (IGRA) >> Positive test >> Evaluate with Chest X-ray (CXR) >> Commence TB Preventive Therapy (TPT) irrespective of CXR results.

CXR often indicates TB in silicosis patients earlier than the clinical symptoms, and regular radiographic screening is required for early TB detection. Radiographic comparison of serial films is done with particular attention to:

• Rapid appearance of new opacities, symmetric nodules or consolidation and the finding of pleural effusion or excavations.
• Cavitation is the strongest indicator of probable silico-tuberculosis.

Other diagnostic tools that can help in diagnosis are:

• Chest Computed Tomography (CT) scan
• Bronchoscopy with bronchoalveolar lavage in conjunction with transbronchial biopsy
• Spirometry

Treatment and Follow-up

To keep the disease from getting worse, all silicosis patients need to eliminate any more exposure to silica. Supportive measures include the use of cough medicines, bronchodilators, oxygen therapy and pulmonary rehabilitation.

TB treatment in patients with silicosis is challenging, perhaps due to impairment of macrophage function by free silica and/or poor drug penetration into fibrotic nodules. Usual anti-TB drugs with directly observed therapy are recommended but for an extended duration of at least 8 months, to reduce the chances of relapse.

Follow-up of patients with silicosis and TB follow the same schedule as is in prevailing guidelines.

Prevention

TB prevention in silicosis patients is essential and includes:

• Active surveillance of vulnerable groups including workers
• Adoption of measures to reduce exposure to silica dust
• Patients with silicosis are eligible for TPT after ruling out active TB

NTEP is in the process of engaging with the Ministry of Labour and Mining to identify high priority districts with stone crushing units/ mining industry. Specific guidelines will be developed to support persons with an occupational risk for TB and provide access, diagnosis and treatment services from the programme.

Resources

• NTEP at a Glance; Comprehensive Clinical Management Protocol of Tuberculosis, 2022.
• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Silico-tuberculosis, Silicosis and Other Respiratory Morbidities Among Sandstone Mine-workers in Rajasthan - A Cross-sectional Study, Saranya Rajavel et al., 2020.
• Mini-review: Silico-tuberculosis; Massimiliano Lanzafame et al, 2021.
• Immunity to the Dual Threat of Silica Exposure and Mycobacterium tuberculosis, Petr Konečný et al., 2019.

Assessment

​

Relationship between Cancer and Tuberculosis (TB)

TB and malignancy may be related in the following four ways:

1. TB as a marker for occult cancer: Occult cancer may lead to locally-reduced infection barriers and/or generalised immunosuppression, rendering a cancer patient susceptible to TB infection/ reactivation.
2. TB as a risk factor for cancer: TB may increase the risk of cancer locally and systemically through chronic inflammation, fibrosis and production of carcinogenic molecules.
3. Shared risk factors for TB and some cancers: Shared risk factors such as smoking, alcoholism, Chronic Obstructive Pulmonary Disease (COPD) and immunosuppression, including HIV, may lead to both TB and cancer, affecting both prevalent and subsequent cancer risk.
4. Treatment of cancer-fueling TB: Many cancers are treated with immunosuppressants or steroids. These drugs might induce immunosuppression in the patients undergoing treatment for cancer and hence, a flare-up of TB.

Mutual Risk of Cancer and TB

• TB patients are 2-11 times more likely than non-TB patients to develop lung cancer, according to studies.
• After cancer diagnosis, the incidence of TB also increases, both in the short term and long-term.
• All types of cancer increase the risk of the development of active TB, but with varying degrees. Haematologic cancer patients had the highest rates of active TB, followed by head and neck cancers, lung cancer and breast cancer patients.

There is intrinsic immunosuppression due to the cancer itself, immunosuppressive effects of chemotherapy, or other host factors (e.g., smoking, malnutrition) that may increase the susceptibility to both cancer and TB. Thus, there is increased incidence of TB in cancer patients, and vice-versa.

Diagnosis of TB in Cancer Patients: Under the Integrated Management Algorithm for TB disease and TB infection released by the National TB Elimination Programme (NTEP), cancer patients are first screened according to the four-symptom complex to rule out/in active TB and all presumptive TB cases need to undergo testing for TB.

Co-existence of TB and cancer poses a diagnostic challenge since clinical and radiological presentations between TB and cancers are similar, hence the need for bidirectional screening. E.g., if biopsy specimens reveal infiltration by malignant cells, still send sample for microbiological confirmation of M. tuberculosis. Thus, allowing for accurate diagnosis and initiation of anti-TB treatment instead of attributing clinical deterioration to chemotherapy complications and progression of underlying malignancy.

Diagnosis of lung cancer in TB patients is usually done in consultation with a clinical specialist and can include examination of induced sputum specimens for malignant cells, as well as use of other diagnostic tools such as Computed Tomography (CT) scans, bronchoscopy, Positron Emission Tomography (PET) scans, Magnetic Resonance Imaging (MRI), histopathology and the use of biological markers.

Treatment

TB treatment in cancer patients uses the standard DS-TB/DR-TB regimens and course, except that the treating physician should assess the drug interactions between anti-TB and anti-cancer drugs. For cancer treatment, drugs may have to be modified to accommodate anti-TB treatment and to aid better prognosis of the TB outcome. However, all decisions must be taken by a competent specialist after examining the individual case.

Curative resection, chemotherapy and radiation therapy are the mainstay treatment options for cancer in TB patients. Co-existence of TB in cancer patients necessitates anti-TB treatment with extended duration, if required. Follow-up during and after treatment also follows prevailing guidelines.

Prevention

Under the NTEP, TB prevention in cancer patients is essential and includes:

• Regular screening for signs and symptoms of TB infection among all patients on immunosuppressive therapy and anti-Tumour Necrosis Factor (TNF) medicines.
• Education and referral of patients who do not have TB symptoms for TB infection testing/assessment of their eligibility for TPT.

Resources

• NTEP at a Glance; Comprehensive Clinical Management Protocol of Tuberculosis, 2022.
• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Tuberculosis and Risk of Cancer: A Danish Nationwide Cohort Study, D. F. Simonsen et al., International Journal of Tuberculosis and Lung Diseases, The Union, 2014.
• Increased Risk of Active Tuberculosis after Cancer Diagnosis, Dennis F. Simonsen et al., Journal of Infection, 2017.
• Pulmonary Tuberculosis as Differential Diagnosis of Lung Cancer; MLB Bhatt et al., South Asian Journal of Cancer, 2012.

Assessment

The presence of tuberculosis disease during pregnancy, delivery, and postpartum is known to result in unfavourable outcomes for both pregnant women and their infants. These outcomes include a roughly two-fold increased risk of preterm birth, low birth weight, intrauterine growth restriction, and a six-fold increase in perinatal death.

Screen TB patients in Pregnancy & Lactating Patients

Figure: Screening Steps in special situation - Pregnancy and Lactating TB Patients

Treatment for TB - Pregnant & Lactating Patients

• Cases of pregnant/lactating women with active TB should be referred to the nearest health facility of NTEP for further management.
• They should be continued on iron and folic acid and other vitamins and minerals to complement their maternal micronutrient needs.
• In situations when calcium intake is low, calcium supplementation is recommended as part of antenatal care.

Tuberculosis and COVID-19 are infectious diseases which primarily attack the lungs. They present with similar symptoms of cough, fever and difficulty in breathing, although TB disease has a longer incubation period and a slower onset of disease.

Screen patients for symptoms of TB and COVID-19

Figure: Screening steps for TB - COVID 19 Patients

Management of TB & COVID-19 Patients

People with TB are likely to be at increased risk of COVID-19 infection, illness and death. So, TB patients should take precautions as advised by health authorities to be protected from COVID-19 and continue their TB treatment as prescribed.

Prevention: While both TB and COVID-19 are spread by close contact between people, the exact mode of transmission differs. Thus, the patient should be explained the following measures to control disease spread.

• Apart from that keeping rooms well ventilated, avoiding crowds and Respiratory precautions are thus important in the control of COVID-19 and TB Disease