TB preventive therapy
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Here is a comprehensive overview of TB Preventive Therapy (TPT), drawn from Murray & Nadel's Textbook of Respiratory Medicine.
TB Preventive Therapy (TPT)
Definition
Latent TB infection (LTBI) is defined by WHO as a state of persistent immune response to stimulation by M. tuberculosis antigens with no evidence of clinically manifest active TB. TPT aims to prevent progression from latent infection to active disease.
Efficacy
Large U.S. Public Health Service studies (~70,000 participants) demonstrated:
- Isoniazid reduced TB incidence by ~80% during the treatment year vs. placebo
- Overall reduction of ~60% over 10–12 years of follow-up
- Protective effect in all risk groups studied
Indications (in decreasing order of risk)
| Priority Group | Key Points |
|---|---|
| HIV-infected persons | TB risk 3–16%/year; 21× higher than HIV-negative. WHO recommends TPT for all PLHIV without active TB, regardless of TST/IGRA result. Consider 36-month course in high-incidence settings to also reduce reinfection risk. |
| Close contacts of new TB cases | 2–4% develop TB in the first year post-exposure. Children and adolescents have ~2× the adult risk. All close contacts should be treated (TST/IGRA may be falsely negative early). |
| Recent converters | TST conversion = ↑ ≥10 mm within 2 years (age <35) or ≥15 mm (age >35). Children <5 years are high priority. |
| Stable radiographic findings of prior TB | Untreated or inadequately treated prior TB. Rate of new TB: 0.4–3.5%/year. Exclude active disease before starting. |
| Other high-risk conditions | Silicosis, prolonged corticosteroids (≥15–20 mg prednisone/day >2–3 weeks), immunosuppression, hematologic malignancies, end-stage renal disease, rapid weight loss, gastrectomy, TNF-antagonist therapy. |
| Epidemiologically at-risk | TST ≥10 mm: foreign-born from high-prevalence areas, medically underserved, residents of long-term care/correctional facilities, homeless persons, migrant workers. |
Treatment Regimens
Preferred Regimens (as of February 2020 CDC/WHO guidance):
| Regimen | Duration | Frequency | Key Notes |
|---|---|---|---|
| INH + Rifapentine (3HP) | 3 months | Once weekly (12 doses) | Non-inferior to 9H. Highest completion rates. Age ≥2 years with/without HIV. Can use DOT or self-administered. |
| Rifampin (4R) | 4 months | Daily | Preferred for HIV-negative. 10 mg/kg (adults); max 600 mg. Watch for drug interactions. |
| INH + Rifampin (3HR) | 3 months | Daily | Conditionally recommended for adults and children with/without HIV. |
Alternative Regimens:
| Regimen | Duration | Frequency | Key Notes |
|---|---|---|---|
| INH (6H) | 6 months | Daily | Strongly recommended for HIV-negative; conditionally for HIV-positive. Not for immunosuppressed or fibrotic lesions. |
| INH (9H) | 9 months | Daily or twice weekly | Conditionally recommended for all ages; preferred in pregnancy with high reactivation risk. Twice-weekly must use DOT. |
Ultra-short course: WHO has approved 1HP (1 month daily INH + rifapentine) for individuals with or without HIV. In HIV-infected persons it showed similar efficacy to 9H with higher completion (97% vs. 90%).
INH doses: 5 mg/kg/day (adults, max 300 mg) or 15 mg/kg twice weekly (max 900 mg). Children: 10–20 mg/kg/day or 20–40 mg/kg twice weekly.
Monitoring and Safety
Baseline LFTs are indicated (not for everyone — only for):
- Liver disease, risk factors for chronic liver disease
- Regular alcohol use
- HIV infection
- Pregnancy or <3 months postpartum
Contraindications to TPT:
- Active, unstable liver disease
- Asymptomatic: aminotransferases >5× ULN
- Symptomatic: aminotransferases >3× ULN
Withhold treatment if aminotransferases ≥5× ULN (regardless of symptoms) or ≥3× ULN with symptoms.
Special monitoring is warranted in: age >35 years, concurrent medications (phenytoin, disulfiram, antiretrovirals), alcoholism, diabetes mellitus, renal insufficiency — due to increased risk of hepatitis and peripheral neuropathy.
Pyridoxine (vitamin B6) supplementation is recommended with isoniazid in patients at risk for neuropathy (malnutrition, alcoholism, diabetes, HIV, pregnancy).
Pregnancy: Generally defer isoniazid until after delivery, except if documented TST conversion during pregnancy or HIV-infected with positive TST — in these cases, the benefit outweighs risk.
Key Principle
Before initiating any TPT, active TB must be excluded by clinical history, physical examination, chest radiography, and microbiological testing if indicated. In persons with radiographic abnormalities where exclusion is uncertain, start multi-drug therapy (INH + rifampin + pyrazinamide ± ethambutol); if cultures are negative after 4 months, this duration is sufficient for preventive purposes.
— Murray & Nadel's Textbook of Respiratory Medicine, pp. 938, 1167–1168
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