Latent TB
Diagnosis & Screening (WHO 2020+, USPSTF 2023,
ATS/CDC)
1) Terminology ที่ต้องเข้าใจ (High-yield)
|
Term ใหม่ |
Term เดิม |
ความหมาย |
|
Tuberculosis infection (TBI) |
Latent TB |
ติดเชื้อ TB
แต่ไม่มีอาการและไม่แพร่เชื้อ |
|
Tuberculosis disease |
Active TB |
มีอาการ +
แพร่เชื้อได้ |
Key concept:
TBI = มี viable M. tuberculosis ถูก immune system ควบคุม (not dormant 100%)
2) Natural history & clinical significance
- ส่วนใหญ่ร่างกาย “contain” เชื้อ → asymptomatic,
noninfectious
- แต่เชื้อยังมีชีวิต → เสี่ยง reactivation (TB disease)
- Lifetime
risk โดยรวม ~5–10%
- Risk สูงสุด: 2 ปีแรกหลังติดเชื้อ
- Treatment
TBI ลด risk progression ได้ ~90%
Public health impact:
- ลด future transmission
- ลด burden ของ TB disease
3) Indications for TBI testing (ใคร
“ควรตรวจ” เท่านั้น)
⚠️ No role for general
population screening
หลักการ:
Test only if result will change management (test-to-treat
strategy)
3.1 กลุ่มเสี่ยงติดเชื้อใหม่ (Risk of
new infection)
High priority
- Close
contact TB case (household, enclosed ≥4 hr/week)
- Health
care workers with exposure
- Recent
exposure to untreated pulmonary TB
- Congregate
settings:
- Prisons
- Homeless
shelters
- Long-term
care facilities
แนวทาง contact:
- Test ทันที + repeat 8–10 weeks after last exposure (window
period)
3.2 กลุ่มเสี่ยง progression เป็น TB disease (สำคัญมากในคลินิก)
High-risk (≥6× risk) → ต้อง test เสมอ
- HIV
infection
- Solid
organ transplant
- TNF-α inhibitors / biologics /
JAK inhibitors
- Hematologic
malignancy
- Chemotherapy
- Fibronodular
scar on CXR (old TB)
- Severe
immunosuppression
Moderate-risk (3–6× risk)
- Diabetes
mellitus
- Chronic
steroid use
- CKD
- Solid
tumors (lung, H&N)
→ Test เฉพาะถ้ามี epidemiologic risk (เช่น มาจากประเทศ endemic)
Slightly increased risk (1.5–3×)
- Underweight
- Smoking
- Small
granuloma on CXR
→
Individualized testing
4) Epidemiologic risk (สำคัญในบริบทเอเชีย/ไทย)
ควรพิจารณา TBI testing:
- Born/resided
in high TB incidence countries (เช่น Southeast Asia)
- Migrants
from endemic areas
- Refugees
- Injection
drug users
- Homeless
(ตรงกับบริบทประเทศไทยซึ่งเป็น TB-endemic
setting)
5) Special populations (High-yield exam + practice)
5.1 HIV infection
- Screen
all newly diagnosed HIV (TST or IGRA)
- Repeat
if initial CD4 <200 (false negative risk)
- Annual
screening if ongoing exposure risk
- In
high TB prevalence: may treat TBI even if test negative (after excluding
active TB)
5.2 Malignancy
Routine TBI testing recommended:
- Hematologic
malignancy (IRR ~26)
- Head
& neck cancer
- Lung
cancer
Risk stratify in other solid tumors
5.3 Health care workers (practical policy)
- Baseline
screening (IGRA or TST)
- No
routine annual screening if low-incidence setting + no exposure
- Repeat
testing only after exposure
- Serial
screening: high-risk units (ER, pulmonology, TB clinic)
(เหมาะกับแพทย์ฉุกเฉินตาม guideline)
6) Diagnostic principle of TBI (Core concept)
ไม่มี test ใด “confirm
TBI” ได้ 100%
Diagnosis =
Positive immune test (TST/IGRA) + Exclude active TB disease
7) Tests for TBI
7.1 Two main tests
|
Test |
Mechanism |
Key features |
|
TST (Mantoux) |
Delayed-type hypersensitivity |
Cheap, less specific |
|
IGRA (QFT, T-SPOT) |
IFN-γ response to TB antigens |
More specific |
ทั้งสอง:
- Detect
cell-mediated immunity
- Cannot
differentiate active vs latent TB
- Low
predictive value (≈90% positive will NOT develop
TB)
8) IGRA vs TST (Clinical decision)
8.1 IGRA preferred when:
- Prior
BCG vaccination (เช่น ไทย)
- Unlikely
to return for TST reading
- Higher
specificity needed
- History
of NTM infection
- Adult
migrants from endemic countries
(Practical: IGRA มักเหมาะในประเทศไทย)
8.2 TST preferred when:
- Resource-limited
settings
- Serial
testing (conversion monitoring)
- Cost
concern
- Occupational
screening programs
9) Predictive value (Clinical reality)
- Positive
IGRA → higher
specificity than TST
- Positive
predictive value still very low (~0.5–2%)
- Negative
test → low future TB
risk
- Risk
stratification > test result alone
10) Dual testing (Advanced clinical use)
When useful:
- Immunocompromised
patients (increase sensitivity)
- Discordant
results
- Low
pretest probability + positive test
- High-risk
+ negative first test
Interpretation:
- Both
positive → highest
risk
- Both
negative → lowest risk
- Discordant
→ intermediate risk
11) Serial testing & conversion
Definition
- IGRA:
negative → positive =
conversion
- TST:
increase ≥10 mm (or ≥6 mm increase in some
protocols)
Key concept:
Conversion = new infection →
high priority for treatment
12) Excluding active TB (CRITICAL before TBI treatment)
⚠️ ห้ามเริ่ม TBI
treatment ก่อน exclude TB disease
(เสี่ยง drug resistance จาก inadvertent
monotherapy)
12.1 Mandatory evaluation
- History
(cough >2 weeks, fever, night sweats, weight loss)
- Physical
examination
- Chest
X-ray (CXR)
12.2 Indications for sputum testing
ทำ AFB smear + culture + NAAT หาก:
- TB
symptoms
- Abnormal
CXR
- Immunocompromised
- Suspicious
radiographic lesion
Specimen:
- 3
sputum samples
- ≥8
hr apart
- Include
early morning sample
13) Chest X-ray interpretation in TBI
Typical findings:
- Normal
CXR (≈85% in TBI)
- Old
healed TB:
- Fibronodular
scar
- Calcified
granuloma
- Upper
lobe fibrosis
Clinical implication:
“Inactive TB” on CXR = higher risk of reactivation → treat TBI
14) False-positive & false-negative considerations
False positive TST:
- BCG
vaccination (very common in Asia)
- NTM
infection
→ Prefer
IGRA
False negative:
- Immunosuppression
- HIV
(low CD4)
- Recent
infection (window period)
- Severe
illness
15) Special technical notes (Exam pearls)
- COVID
vaccine: defer TBI testing ~4 weeks if not urgent
- Prior
TST does NOT significantly boost IGRA (clinically acceptable)
- NTM
infection → IGRA
preferred
16) Age & risk-benefit of TBI treatment (clinical
decision)
INH hepatotoxicity risk:
- 65
yr: >5%
- 50–65
yr: 2–5%
- <50
yr: <2%
Clinical implication:
In older adults →
prefer shorter rifamycin-based regimens (4R, 3HP)
17) WHO 2020/2024 key recommendations (Global practice)
- Either
TST or IGRA acceptable
- No
clear superiority for predicting progression
- Choose
based on:
- Cost
- Availability
- Infrastructure
- Local
epidemiology
Resource-limited settings:
- TST
often more practical
18) Next-generation diagnostic tools (Emerging)
WHO-endorsed TB antigen skin tests:
- Cy-TB
- C-TST
- Diaskintest
Advantages:
- TST
simplicity + IGRA specificity
(Currently limited availability)
19) Clinical algorithm (Practical for physicians)
Step 1: Identify risk group
- Contact?
- Immunocompromised?
- Migrant
from endemic area?
- HCW
exposure?
Step 2: Test (IGRA preferred in BCG-vaccinated adults)
Step 3: If positive →
Exclude active TB
- Symptoms
screen
- CXR
- Sputum
if indicated
Step 4: Diagnose TBI → consider preventive therapy
|
Ultra–high yield summary (สำหรับใช้งานจริงในคลินิก)
|
Treatment of Latent Tuberculosis Infection
1) Core clinical concept (ต้องเข้าใจก่อนรักษา)
- TBI
(Latent TB) = มี immune evidence (TST/IGRA+) แต่ไม่มีอาการและไม่แพร่เชื้อ
- เชื้อยัง viable →
เสี่ยง reactivation TB
- การรักษา TBI ลด risk progression → TB disease ได้สูงสุด
~90%
- Priority
ของ TB control:
1.
Treat active TB (อันดับแรก)
2.
Identify & treat TBI (อันดับสอง
โดยเฉพาะ high-risk)
2) Whom to treat (ใคร “ควรรักษา” TBI)
หลักการสำคัญ:
“Test only if you intend to treat”
ไม่ควรรักษา:
- ไม่มี exposure risk
- ไม่มี risk progression
- Low
pretest probability (risk > benefit)
2.1 กลุ่มที่ควรรักษาแน่นอน (High
priority)
A. Recent exposure
- Close
contact active pulmonary TB
- Recent
TST/IGRA conversion (<2 years)
- Household
contact TB
B. High risk progression (ต้องรักษาแม้ asymptomatic)
- HIV
infection (แต่หัวข้อนี้เป็นอีก guideline)
- Immunosuppressive
therapy (biologics, TNF-α
inhibitors)
- Solid
organ transplant
- Hematologic
malignancy
- Fibronodular
scar on CXR (old healed TB)
- CKD,
dialysis
- Planned
long-term immunosuppression
(สำคัญในเวชปฏิบัติจริง)
2.2 Moderate-risk (พิจารณาเป็นรายบุคคล)
- Diabetes
mellitus
- Steroid
use
- Malnutrition
- Smokers
- Migrants
from TB-endemic countries (เช่น Southeast Asia)
(บริบทประเทศไทย → prevalence
TBI สูง → threshold รักษาต่ำกว่า low-incidence
countries)
3) Mandatory BEFORE starting TBI treatment (Critical
safety step)
3.1 Exclude active TB disease (ห้ามพลาด)
ต้องทำทุกเคส:
- History:
cough, fever, night sweats, weight loss
- Physical
exam (LN, systemic signs)
- Chest
X-ray (mandatory)
เหตุผล:
ป้องกัน inadvertent monotherapy → drug resistance TB
3.2 เมื่อใดต้องส่ง sputum
- TB
symptoms
- Abnormal
CXR
- Radiographic
progression
- Immunocompromised
- Suspicion
culture-negative TB disease
ส่ง:
- AFB
smear + culture + NAAT
4) Baseline assessment before regimen selection
ควรประเมิน:
- Liver
disease / alcohol use
- Neuropathy
risk
- Drug-drug
interactions
- Cardiac
disease (rifamycin interactions)
- Age
(hepatotoxicity ↑ with
age)
- Concomitant
hepatotoxic drugs
4.1 Indications for baseline LFT
ควรตรวจ baseline LFT ใน:
- Alcohol
use
- Chronic
liver disease / hepatitis
- IVDU
- On
hepatotoxic drugs
- History
elevated transaminases
- Symptoms
of liver disease
- (Many
experts: age ≥35 yr)
Relative contraindication:
- Active
hepatitis
- End-stage
liver disease
5) Regimen selection (High-yield clinical decision)
Key principle (CDC/NTCA 2020):
Rifamycin-based regimens preferred over INH monotherapy
เหตุผล:
- Better
adherence
- Shorter
duration
- Lower
hepatotoxicity
- Similar
efficacy
6) Preferred regimens for TBI (Adults without HIV)
6.1 First-line: Rifamycin-based regimens (Preferred)
1) 4R — Rifampin daily 4 months
- Duration:
4 months
- Efficacy
≈
INH 9 months
- Higher
completion rate (≈79% vs 63%)
- Lower
hepatotoxicity
- Cost-effective
- Practical
in real-world settings
👉 Often best regimen in
adults (especially >50 yr)
2) 3HP — INH + Rifapentine weekly × 3 months
- Weekly
dosing (12 doses)
- DOT
preferred (but self-admin possible)
- Noninferior
to 9H
- Completion
rate high (~82–87%)
Indications (trial population):
- Recent
converters
- Close
contacts
- Fibrotic
CXR
- High-risk
populations
Key adverse effects:
- Hypersensitivity
/ flu-like syndrome (~3–4%)
- Rare
hypotension/syncope (0.3%)
3) 3HR — INH + Rifampin daily 3 months
- Alternative
regimen
- Limited
data but comparable efficacy
- Useful
when shorter regimen needed
7) Alternative regimen (when rifamycin contraindicated)
7.1 INH monotherapy (6H or 9H)
- Efficacy:
60–90%
- Optimal
duration: 9 months (9H)
- 6H
less effective but acceptable
ข้อเสีย:
- Hepatotoxicity
higher
- Poor
adherence (long duration)
ใช้เมื่อ:
- Drug
interactions with rifamycins
- Rifamycin
intolerance
- Hypersensitivity
8) Regimens that should NOT be used
❌ Rifampin + Pyrazinamide
(RIF+PZA)
→ Severe hepatotoxicity
(historically abandoned)
9) Special clinical considerations in regimen choice
9.1 Drug-drug interactions (สำคัญมาก)
Rifampin/Rifapentine interactions:
- Warfarin
- OCP/hormonal
contraceptives
- Antiepileptics
- Antidepressants
- Methadone
/ buprenorphine
- Antiarrhythmics
- Antiretrovirals
(ต้อง review medication list ทุกเคส)
9.2 Age consideration
- INH
hepatotoxicity ↑
markedly with age
- 50–65
yr → prefer 4R over
INH
- Older
adults tolerate rifamycin better (generally)
10) Pyridoxine (Vitamin B6) supplementation
ให้ร่วมกับ INH ในผู้มี risk
neuropathy:
- Diabetes
- CKD
/ uremia
- Alcoholism
- Malnutrition
- HIV
- Pregnancy
- Seizure
disorders
- Elderly
Dose:
- Daily
INH: 25–50 mg/day
- Weekly
3HP: 50 mg weekly
11) Monitoring during TBI treatment (Practical clinic
schedule)
11.1 Clinical follow-up
- Monthly
visit (minimum)
- Assess:
- Hepatitis
symptoms
- Rash
- Neuropathy
- Adherence
11.2 Laboratory monitoring
Routine LFT not required in all
But monthly LFT if:
- Baseline
abnormal LFT
- Liver
disease
- Alcohol
use
- High-risk
patients
12) Hepatotoxicity management (High-yield)
Stop INH or rifamycin if:
- Symptomatic
+ AST/ALT >3× ULN
- Asymptomatic
+ AST/ALT >5× ULN
Symptoms of hepatitis to educate patient:
- Anorexia
- Nausea/vomiting
- Dark
urine
- Jaundice
- RUQ
pain
- Fatigue
>3 days
13) Adherence (Major determinant of real-world efficacy)
Challenges:
- Long
duration (especially INH)
- Pill
burden
- Asymptomatic
disease → low
motivation
Strategies:
- Shorter
regimens (4R, 3HP)
- DOT
(especially 3HP)
- Patient
education
- Reminder
systems
14) Treatment interruption (Practical rule)
- <2
months interruption →
resume regimen
- 2
months interruption →
restart from beginning (consider)
- Early
interruption = higher risk failure
15) Special scenario: Drug-resistant TB exposure
15.1 INH-resistant contact
→ 4R
(rifampin 4 months)
15.2 Rifampin-resistant contact
→ INH 9
months
15.3 MDR-TB contact (FQ susceptible)
→
Levofloxacin 6 months
(≈59%
reduction TB incidence)
Monitoring:
- QTc
baseline + follow-up
- Cardiac
risk assessment
16) Post-treatment follow-up
- No
test to confirm eradication
- TST/IGRA
remains positive (do NOT repeat)
- Re-testing
has no clinical value
- If
TB symptoms develop →
re-evaluate (CXR + workup)
Protection duration:
- 12–19+
years (observational data)
- Depends
on reinfection risk (endemic settings)
17) High-yield clinical pearls (สำหรับแพทย์ใช้งานจริง)
- Always
exclude active TB before TBI treatment
- Rifamycin
regimens (4R, 3HP) = first-line in most adults
- INH
only if rifamycin contraindicated
- Educate
patient about hepatitis symptoms EVERY visit
- Do
NOT repeat IGRA/TST after positive test
- Monthly
follow-up is mandatory
- Shorter
regimens → better
adherence & outcomes
18) Ultra–concise order set (copy ใช้ในคลินิก)
Diagnosis: Tuberculosis Infection (IGRA/TST positive,
no active TB)
Before treatment:
- Symptom
screen TB
- CXR
- ±
Sputum if indicated
- Baseline
LFT (risk-based)
- Medication
review (DDI)
Preferred regimen:
- 4R
(Rifampin 4 months)
or - 3HP
(INH + Rifapentine weekly × 12 doses)
Add:
- Pyridoxine
if INH-containing regimen
- Monthly
follow-up (AE + adherence monitoring)
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