What are the risk factors for developing Tuberculosis (TB)?

Risk Factors for Tuberculosis

Tuberculosis risk is driven by a combination of immunologic, social, and epidemiologic factors, with HIV infection representing the single highest-risk condition (35-162 cases per 1000 person-years), followed by silicosis, recent TB infection, and chronic renal failure requiring hemodialysis. 1, 2

Highest-Risk Immunocompromised Conditions

HIV infection poses the greatest individual risk for TB progression, with annual rates of 35-162 cases per 1000 person-years compared to 1.1 per 1000 in the general population. 1, 2 Among HIV-infected persons with positive tuberculin tests, the annual risk reaches 45 cases per 1000 person-years. 1

• HIV-coinfected injection drug users face even more extreme risk at 76 cases per 1000 person-years, reflecting combined immunosuppression and increased transmission. 1, 2
• Silicosis carries approximately 30-fold increased risk (68 cases per 1000 person-years), making it the second-highest medical risk factor after HIV. 1, 2
• Chronic renal failure with hemodialysis increases risk 10-25 times above the general population. 1, 2
• Solid organ transplant recipients have 15-fold increased risk, while stem cell transplant recipients face 8-12-fold increased risk. 2

Recent TB Infection and Prior Disease

The highest risk period occurs within the first year after initial infection (12.9 cases per 1000 person-years), declining substantially to 1.6 cases per 1000 person-years for infections 1-7 years past. 1, 2

• Radiographic fibrotic lesions consistent with prior healed TB carry 2.0-13.6 cases per 1000 person-years. 1, 2
• Close contacts of newly diagnosed infectious TB cases require screening with a ≥5 mm tuberculin test threshold. 2, 3

Diabetes Mellitus

Diabetic patients have 2-4-fold increased TB risk, with even higher risk in those with insulin-dependent or poorly controlled diabetes. 1, 2 This represents a critical risk factor given diabetes prevalence in developed countries. 2

Immunosuppressive Medications

Prednisone ≥15 mg/day for 2-4 weeks represents the threshold dose that suppresses tuberculin reactivity and predisposes to TB reactivation. 1, 2 This is the lower limit that could predispose persons to develop TB, with higher doses and longer duration conferring greater risk. 1

• TNF-α antagonists (infliximab, etanercept, adalimumab) carry 5-7-fold increased TB risk, requiring mandatory screening for latent TB before initiation. 2
• Prolonged corticosteroid therapy and other immunosuppressive agents increase reactivation risk, though exact thresholds remain incompletely defined. 1

Malnutrition and Weight Loss

Being >15% underweight carries 2.6 cases per 1000 person-years—more than double the risk of normal weight individuals (1.1 cases per 1000 person-years). 1, 2 A dose-response relationship exists:

• Underweight by 10-14%: 2.0 cases per 1000 person-years 1, 2
• Underweight by 5-9%: 2.2 cases per 1000 person-years 1
• Overweight by >5%: 0.7 cases per 1000 person-years (protective effect) 1, 2

Clinical conditions causing malabsorption or preventing adequate nutrition increase risk, including gastrectomy, jejunoileal bypass, chronic peptic ulcer disease, chronic malabsorption syndromes, and carcinomas of the oropharynx and upper GI tract. 1, 3

Injection Drug Use

HIV-seronegative injection drug users have 10 cases per 1000 person-years, reflecting increased transmission, more recent infection, and immunologic effects of drug use itself. 1, 2 This risk increases dramatically with HIV coinfection to 76 cases per 1000 person-years. 1, 2

Additional Medical Conditions

• Carcinoma of the head or neck increases risk through mechanisms affecting nutrition and immunity. 1
• Lymphoma and leukemia are associated with active TB due to underlying immunosuppression. 1
• Cardiac transplantation increases risk through required immunosuppression. 1

Social Determinants and Environmental Factors

TB remains inextricably linked with poverty, with modeling studies demonstrating that reducing extreme poverty and expanding social protection could reduce TB incidence by up to 84.3%. 1

• Poor housing and environmental conditions, food insecurity, malnutrition, alcohol consumption, smoking, and incarceration predispose people to developing TB. 1
• Low socioeconomic status increases risk across multiple indicators (crowding, education, income, poverty, unemployment), with crowding having the greatest impact. 1
• Inadequate healthcare access, especially for poor and low-wage workers without paid sick days or insurance, increases vulnerability. 1

Epidemiologic and High-Risk Populations

Foreign-born persons from high-prevalence countries represent a major risk group, accounting for 94% of TB cases among Asians and 74% among Hispanics in the United States. 1

• Residents of congregate settings (homeless shelters, correctional facilities, nursing homes) face ongoing transmission risk. 1, 2
• Healthcare workers with TB exposure have elevated risk, though this may be attributable to other factors such as foreign birth. 1
• Urban areas with populations >500,000 account for >75% of TB cases. 1

Age-Related Considerations

Children younger than 5 years with positive tuberculin tests are at high risk for progression to active disease with potential for disseminated TB, including life-threatening tuberculous meningitis or miliary TB. 1, 2

• Adolescents and young adults have increased risk for developing active TB. 1
• Adults older than 65 years have the highest incidence (8.4 cases/100,000 population). 1

Substance Use

• Alcohol use increases risk, though difficult to isolate from other confounding factors given multiple co-occurring risk factors in this population. 1, 2
• Smoking increases TB risk, with a dose-effect relationship demonstrated. 1, 4

Critical Clinical Pitfall

The presence of multiple risk factors compounds TB risk exponentially rather than additively. 2 Clinicians must recognize that patients with combinations of risk factors (e.g., HIV-infected injection drug user with malnutrition) face dramatically elevated risk requiring heightened surveillance and lower thresholds for screening and treatment of latent TB infection. 1, 2

Male sex confers approximately double the risk of women in mid- and older-adult age groups, with men accounting for 61.3% of reported TB cases. 1, 4