Global Public Health · Supplementary · from Global Public Health

Case 2: Tuberculosis Control in Resource-Limited Setting

Patient Presentation

Demographics: 34-year-old male mineworker, Lesotho

Chief Complaint: "Cough for three months with blood in the sputum and weight loss."

History of Present Illness: The patient presents to the district hospital outpatient department with a 3-month history of productive cough, initially mucoid but now with intermittent hemoptysis (blood-streaked sputum, approximately 2-3 tablespoons per day for the past 2 weeks). He reports progressive weight loss of approximately 10 kg over 3 months, drenching night sweats requiring sheet changes, low-grade fevers, and decreased appetite.

He works as a gold mineworker in South Africa and returns to Lesotho periodically. His work involves underground drilling with significant silica dust exposure over 8 years. He reports that two coworkers from his shift have been diagnosed with tuberculosis in the past year. He was tested for TB 6 months ago at the mine clinic (sputum smear negative) and was told he was fine.

He lives in a small two-room house with his wife, three children (ages 4, 8, 11), his mother (age 62), and his brother. The house has poor ventilation with only one small window per room. He was diagnosed with HIV 3 years ago during routine mine health screening but has been poorly adherent to antiretroviral therapy (ART), taking his medications intermittently.

Past Medical History:

• HIV infection (diagnosed 3 years ago)
• Silicosis (early stage, diagnosed at mine health screening)
• Previous TB treatment 5 years ago (completed 6-month course, declared cured)
• Intermittent ART adherence

Medications:

• Tenofovir/lamivudine/dolutegravir (TLD) fixed-dose combination — intermittent adherence
• Co-trimoxazole 960 mg daily — not taking consistently

Social History:

• Gold mineworker for 8 years (silica exposure)
• Alcohol: Heavy use (traditional beer and spirits, estimated 30+ units/week)
• Smoking: 10 cigarettes/day for 12 years
• Lives in overcrowded, poorly ventilated home
• Low income, household food insecurity
• Cross-border migrant worker (Lesotho-South Africa)

Family History:

• Father: Died of "chest disease" at age 48 (likely TB, unconfirmed)
• Mother: Cough for 1 month (not yet evaluated)

Physical Examination

• Vital Signs: BP 100/64 mmHg, HR 104 bpm, RR 22, Temp 38.4°C, SpO2 92% RA, BMI 17.2 (underweight)
• General: Cachectic male, chronically ill-appearing, temporal wasting, oral thrush
• HEENT: Oral candidiasis (white plaques on palate and tongue), poor dentition, no lymphadenopathy
• Respiratory: Decreased breath sounds right upper lobe, bronchial breathing right apex, coarse crackles bilaterally (right > left), dullness to percussion right upper zone
• Cardiovascular: Tachycardic, regular, no murmurs
• Abdomen: Scaphoid, mildly tender in right upper quadrant, liver palpable 3 cm below costal margin, no splenomegaly
• Extremities: Finger clubbing bilaterally, no edema
• Skin: Generalized pallor, no Kaposi lesions
• Lymph nodes: Bilateral axillary lymphadenopathy (< 2 cm, firm, mobile)

Workup and Results

Laboratory Studies:

Imaging/Additional Studies:

• Chest X-ray: Right upper lobe cavity (3.5 cm), bilateral upper lobe infiltrates with fibrotic changes, right hilar lymphadenopathy, volume loss right upper lobe; additionally, fine nodular pattern in bilateral lower zones consistent with silicosis
• Audiometry: Normal baseline (pre-aminoglycoside if needed)
• ECG: Sinus tachycardia, normal QTc (412 ms)
• Visual acuity: 20/20 bilaterally (baseline before ethambutol)

Clinical Image

Diagram showing the integrated approach to multidrug-resistant TB management in a resource-limited setting: drug susceptibility-guided regimen selection, HIV co-management, infection prevention and control measures, contact tracing strategy, and the social determinants of TB (mining, migration, poverty, overcrowding). Source: Educational illustration.

Diagnosis

Multidrug-Resistant Pulmonary Tuberculosis (MDR-TB: Rifampicin + Isoniazid Resistant) with Cavitary Disease, HIV Co-infection with Virological Failure (Advanced Immunosuppression, CD4 89), Occupational Silicosis, and Malnutrition

Key Diagnostic Criteria:

• Xpert MTB/RIF Ultra: MTB detected with rifampicin resistance
• Line probe assay confirming dual resistance to rifampicin (rpoB S531L) and isoniazid (katG) = MDR-TB by definition
• Fluoroquinolone and aminoglycoside sensitive on second-line LPA (not pre-XDR or XDR)
• High bacillary load (smear 3+, Xpert "HIGH") with cavitary disease indicating high infectiousness
• HIV co-infection with advanced immunosuppression (CD4 89) and virological failure on first-line ART
• Positive urine TB-LAM indicating disseminated TB risk in severely immunocompromised patient
• Previous TB treatment (possible acquired resistance) with ongoing risk factors (silicosis, HIV, mining exposure)

Treatment Plan

1. MDR-TB treatment (WHO shorter all-oral regimen, 9-11 months — eligible as fluoroquinolone-sensitive, no prior second-line drug exposure):

• Intensive phase (4-6 months): Bedaquiline 400 mg daily x 2 weeks then 200 mg 3x/week + Levofloxacin 750-1000 mg daily + Linezolid 600 mg daily + Ethionamide 500 mg daily + Clofazimine 100 mg daily + Pyrazinamide 1500 mg daily + Ethambutol 1200 mg daily
• Continuation phase (5 months): Levofloxacin + Clofazimine + Pyrazinamide + Ethambutol
• Intensive phase extended to 6 months if sputum culture positive at month 4
• Monitor sputum cultures monthly until conversion, then at months 5, 8, and end of treatment

1. Linezolid monitoring (most toxic drug in regimen):

• Monthly CBC (myelosuppression: anemia, thrombocytopenia, neutropenia)
• Monthly visual acuity and color vision testing (optic neuritis — irreversible)
• Peripheral neuropathy assessment at each visit
• Pyridoxine (vitamin B6) 100 mg daily for neuropathy prevention
• Reduce to 300 mg daily or discontinue if toxicity develops

1. Bedaquiline monitoring:

• ECG at baseline, 2 weeks, monthly (QTc prolongation risk)
• Hold if QTc > 500 ms; hepatic function monitoring monthly

1. HIV management:

• Restart ART with adherence support 2 weeks after MDR-TB treatment initiation (delay reduces IRIS risk)
• Switch to dolutegravir-based regimen with adherence assessment; if virological failure confirmed despite good adherence, perform genotypic resistance testing
• Co-trimoxazole prophylaxis (CD4 < 200)
• Monitor for immune reconstitution inflammatory syndrome (IRIS) — heightened risk with CD4 89

1. Nutritional support:

• Nutritional assessment and supplementation (ready-to-use therapeutic food, RUTF)
• Pyridoxine 100 mg daily, multivitamins, folate
• Food support for the household (food insecurity drives non-adherence)

1. Infection prevention and control:

• Patient to wear surgical mask when outside isolation
• Household infection control: open windows, improve ventilation, reduce overcrowding
• Sputum culture conversion documented before de-isolation

PUBLIC HEALTH INTERVENTIONS:

1. Contact investigation (critical):

• Screen all 7 household contacts: symptom screening, chest X-ray, sputum collection for any symptomatic contacts
• Children < 5 years (the 4-year-old): initiate preventive therapy (levofloxacin-based regimen for MDR-TB contacts) regardless of symptoms after excluding active TB
• Mother (coughing for 1 month): urgent sputum testing with Xpert MTB/RIF Ultra
• HIV testing for all household contacts
• Mine coworker notification through occupational health services

1. Cross-border coordination:

• Notify both Lesotho and South Africa national TB programs (cross-border referral)
• Ensure treatment continuity if patient returns to South Africa through bilateral health agreements

1. Adherence support:

• Video-observed therapy (VOT) or community health worker-supported DOT
• Treatment supporter identified (wife)
• Alcohol cessation counseling (alcohol increases hepatotoxicity risk and non-adherence)
• Smoking cessation
• Monthly multidisciplinary team review (clinician, nurse, social worker, counselor)

1. Occupational health:

• Report to mining company occupational health department
• Silicosis surveillance and worker compensation claim
• Advocate for improved mine ventilation and dust suppression

Key Learning Points

• Xpert MTB/RIF Ultra has transformed TB diagnosis by providing simultaneous detection of M. tuberculosis and rifampicin resistance within 2 hours at point of care; it should be the initial diagnostic test for all presumptive TB cases, especially in HIV-positive individuals and high-MDR-TB-burden settings
• The WHO shorter all-oral MDR-TB regimen (9-11 months with bedaquiline, linezolid, levofloxacin, clofazimine) has replaced injectable-based regimens and significantly improves outcomes and tolerability; eligibility depends on fluoroquinolone sensitivity and no prior second-line drug use
• TB-HIV co-management requires careful timing of ART initiation (2-8 weeks after TB treatment), monitoring for IRIS, and attention to drug-drug interactions; in severely immunocompromised patients (CD4 < 50), ART should start within 2 weeks
• Silicosis is the strongest occupational risk factor for TB (30-fold increased risk) and is endemic among gold miners in southern Africa; the silicosis-TB-HIV syndemic is a major public health challenge requiring intersectoral collaboration between health and mining sectors
• Contact investigation for MDR-TB must include MDR-TB-specific preventive therapy for close contacts, particularly children under 5; this is a critical and often neglected component of MDR-TB control programs

All cases for this lecture as Markdown