In which regions and high‑risk populations is tuberculosis most prevalent, and what are the recommended screening and preventive therapy strategies?

Tuberculosis Prevalence and Screening Strategies

Tuberculosis is most prevalent in Sub-Saharan Africa (356 cases per 100,000 population) and South-East Asia (44% of global cases), with priority screening recommended for HIV-infected persons, recent immigrants from high-burden countries, prisoners, homeless individuals, healthcare workers, and persons with immunosuppressive conditions. 1, 2, 3

Geographic Distribution of High TB Burden

Regions with Highest Incidence

• Sub-Saharan Africa has the highest TB incidence rate at 356 new cases per 100,000 population annually, driven primarily by the HIV epidemic 2, 3, 4
• South-East Asia accounts for 44% of global TB cases, with India alone representing 26% of the worldwide burden 5
• Western Pacific region contributes 18% of global cases, with China (8.4%), Indonesia (8.5%), and the Philippines (6.0%) being major contributors 5
• Former Soviet Union countries have estimated incidence rates exceeding 100 new cases per 100,000 population 2

Country-Specific High-Burden Nations

Eight countries account for two-thirds of global TB cases: India (26%), Indonesia (8.5%), China (8.4%), Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%), and South Africa (3.6%) 5

Priority High-Risk Populations Requiring Systematic Screening (Tier 1)

Highest Priority Groups

• HIV-infected persons have a risk of TB progression of 35-162 cases per 1,000 person-years and face 50 times higher risk than the general population, with TST considered positive at ≥5mm induration 1, 6
• Close contacts of active pulmonary TB cases, especially children under 4 years old, require immediate screening with TST positive at ≥5mm 1, 7
• Prisoners and incarcerated populations have substantially elevated TB rates and should be screened with TST positive at ≥10mm 6, 1
• Recently arrived refugees and legal immigrants with class B1/B2 TB notification status, particularly those from countries with incidence >100 per 100,000 within the past 5 years 6, 1

Medical Conditions Requiring Screening

• Patients initiating anti-TNF therapy require pre-treatment screening algorithms, as they have 5-7 times higher risk than the general population 1, 6
• Dialysis patients and those preparing for organ/hematological transplantation, with transplant recipients having 15-fold increased risk 1, 6
• Patients with silicosis require systematic testing and 12 months of treatment if positive 1, 6
• Immunosuppressed patients on ≥15mg/day prednisone for ≥1 month, with TST positive at ≥5mm 1, 7
• Persons with fibrotic chest radiograph changes consistent with prior TB, requiring 12 months of isoniazid or 4 months of isoniazid plus rifampin 1, 7

Secondary High-Risk Groups (Tier 2)

Congregate Settings and Vulnerable Populations

• Healthcare workers in endemic areas or those exposed to TB patients, with TST positive at ≥10mm 6, 1
• Homeless persons living in shelters have elevated transmission risk due to crowded conditions 6, 1
• Illicit drug users, particularly injection drug users who may also have HIV co-infection, with TST positive at ≥10mm 1, 7
• Immigrants reporting for adjustment of status from high-burden countries 6

Additional Medical Risk Factors

• Diabetes mellitus patients have 2-4 times increased TB risk, with TST positive at ≥10mm 1, 7
• Chronic renal failure and glomerular disease patients have the highest risk with standardized incidence ratio of 23.36 1
• Hematologic malignancies (leukemias, lymphomas) and head/neck or lung carcinomas 1, 7
• Patients with >10% weight loss below ideal body weight, with TST positive at ≥10mm 1, 7
• Untreated hepatitis C patients have adjusted hazard ratio of 2.9 for active TB 1
• Rheumatoid arthritis patients have standardized incidence ratio of 10.9 versus general population 1

Recommended Screening Strategies

Initial Screening Algorithm

• All individuals must first be screened for TB symptoms including cough, hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, and fatigue—presence of any symptom warrants immediate further evaluation 1, 8
• Chest radiography is mandatory before any LTBI treatment to exclude active TB disease, even in asymptomatic individuals 1, 8
• The combination of symptom screening plus chest radiography offers the highest sensitivity and negative predictive value to rule out active TB 1

Testing Methodology

• Either TST or IGRA can be used in high-income countries with TB incidence <100 per 100,000, but IGRA is preferred in BCG-vaccinated individuals to avoid false-positive results 1
• Two-step TST is required at baseline if no testing was performed in the preceding year 1
• TST interpretation uses three cutoff levels: ≥5mm for highest risk groups (HIV, immunosuppressed, recent contacts, fibrotic lesions), ≥10mm for moderate risk groups (immigrants, healthcare workers, prisoners, diabetes, chronic renal failure), and ≥15mm for persons with no risk factors 1, 7

Special Population Considerations

• Migrant farm workers should be screened annually, with emphasis on homebase site screening where access and follow-up are more reliable 6
• Children under 4 years old who are close contacts of infectious persons require preventive therapy even if initial TST is negative, with repeat testing at 12 weeks 6, 7
• Tuberculin-negative children and adolescents exposed within the past 3 months should receive preventive therapy until repeat testing 12 weeks after contact 7

Preventive Therapy Strategies

Treatment Regimens for LTBI

• Preferred regimens include 3-month weekly rifapentine plus isoniazid or 3-4 month daily isoniazid plus rifampicin 8
• Minimum 12 months of therapy is required for HIV-infected persons and those with fibrotic pulmonary lesions or silicosis 7, 6
• Directly observed therapy twice weekly (isoniazid 15mg/kg up to 900mg) should be used when necessary to facilitate supervision and ensure completion 6

Monitoring and Safety

• Liver function tests should be monitored every 2-4 weeks during treatment, especially for pregnant women and persons with liver disease history 8
• Patients should receive pyridoxine (vitamin B6) with isoniazid to prevent peripheral neuropathy, particularly HIV-infected persons 8
• Only 60.5% of patients complete preventive therapy in meta-analyses, making compliance the crucial determinant of success 6

Critical Pitfalls to Avoid

Testing and Treatment Errors

• Do not perform routine testing in low-risk populations without risk factors, as this diverts resources and increases false-positive results 1
• Do not test unless prepared to treat—testing should only be conducted when a plan exists to complete treatment in LTBI-positive persons 1
• BCG vaccination does not contraindicate TST, but may affect interpretation; IGRA should be used when available in BCG-vaccinated individuals 1
• Do not perform routine anergy testing in HIV-positive or immunosuppressed persons 1
• Single-drug therapy must never be used for active TB disease, as this leads to drug resistance 8

Programmatic Challenges

• ACF programs improve access but create expectations for follow-up care that weak health systems cannot deliver, leading to patient disengagement 9
• Out-of-pocket costs and repeated clinic visits undermine screening effectiveness even when diagnosis is free 9
• Stigma and discrimination cause community members to refuse screening, contact tracing, and treatment, particularly where HIV and TB stigma compound each other 9
• Health workers require protection and support, as they fear infection and face difficult working conditions in poorly resourced systems 9