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Here is a comprehensive, exam-ready answer on the Mantoux Test — structured for a 15-mark MD exam response.

MANTOUX TEST (Tuberculin Skin Test / PPD Test)


1. INTRODUCTION & HISTORICAL BACKGROUND

The Mantoux test (also called the Tuberculin Skin Test / TST / PPD test) is the standard intradermal test used for:
  • Detection of latent tuberculosis infection (LTBI)
  • Epidemiological surveys of TB prevalence
  • Contact tracing of TB cases
  • Screening high-risk populations
It was developed by Charles Mantoux in 1908, based on earlier work by Robert Koch with tuberculin.

2. PRINCIPLE

The Mantoux test is based on a Type IV (delayed-type) hypersensitivity reaction (cell-mediated immunity).
  • When an individual has been previously exposed to Mycobacterium tuberculosis (or BCG), sensitized CD4+ T-lymphocytes are generated
  • On intradermal injection of tuberculin (PPD), these T-cells recognize mycobacterial antigens and release cytokines (IFN-γ, IL-2)
  • This recruits macrophages and other cells → induration at the site within 48–72 hours

3. ANTIGEN USED — TUBERCULIN / PPD

FeatureDetail
Full namePurified Protein Derivative (PPD)
Prepared fromHeat-sterilized, filtered, concentrated culture filtrate of M. tuberculosis
Standard preparationPPD-S (Seibert's standard) — reference standard
Common formulationPPD-RT23 (used in India and many countries)
Dose1 TU (tuberculin unit) or 2 TU depending on preparation
Volume injected0.1 mL

4. TECHNIQUE

Materials Required

  • 1 mL tuberculin syringe with short-bevel 26–27G needle
  • PPD tuberculin (2 TU/0.1 mL of PPD-RT23 or 5 TU in some guidelines)
  • 70% alcohol swab

Site

  • Volar (flexor) surface of the left forearm — middle third (away from veins)

Method (Mantoux / Intradermal Injection)

  1. Clean the site with alcohol; allow to dry
  2. Hold the syringe at 5–15° angle to the skin, bevel upward
  3. Inject 0.1 mL intradermally (not subcutaneously)
  4. A pale wheal of 6–10 mm should appear immediately (confirms correct intradermal placement)
  5. Do NOT massage the site

Reading

  • Read at 48–72 hours (optimal: 72 hours)
  • Measure the transverse diameter of induration (not erythema) in millimeters, using a ruler or ballpoint pen technique
  • Use fingertip palpation to delineate the indurated area

5. INTERPRETATION

Standard Cut-offs (ATS/CDC Criteria)

Induration SizePositive in These Groups
≥ 5 mmHIV-positive patients; Recent close contacts of active TB; Patients on immunosuppressants; CXR showing fibrotic changes consistent with old TB; Organ transplant recipients
≥ 10 mmRecent immigrants from high-prevalence countries; IV drug users; Healthcare workers; Residents/staff of high-risk congregate settings (prisons, nursing homes); Children <4 years; Lab workers working with mycobacteria; Patients with diabetes, CRF, silicosis, malnutrition, leukemia/lymphoma
≥ 15 mmAll other persons with no risk factors
In India (high-burden country), for children: ≥10 mm is considered positive regardless of BCG vaccination.

WHO / Indian Guidelines (Children)

IndurationInterpretation
< 6 mmNegative
6–9 mmDoubtful / Inconclusive
≥ 10 mmPositive

6. POSITIVE MANTOUX TEST — SIGNIFICANCE

A positive test indicates prior exposure/sensitization to mycobacterial antigens. It does NOT by itself diagnose:
  • Active tuberculosis
  • Disease vs. latency
Further workup (CXR, sputum AFB, CBNAAT/GeneXpert, culture) is needed to confirm active disease.

7. GRADING OF REACTION

GradeInduration
Negative< 5 mm
Weakly positive5–9 mm
Positive10–14 mm
Strongly positive≥ 15 mm
Vesiculation/necrosisHighly significant — indicates high degree of sensitization

8. FALSE POSITIVE RESULTS

Causes of false positivity (positive test in absence of TB infection):
CauseMechanism
BCG vaccinationCross-reactive antigens in PPD (most common cause in India)
NTM infectionM. kansasii, M. marinum, M. szulgai may cross-react
Improper test readingMeasuring erythema instead of induration
Repeated TST (booster effect)Sensitization from prior testing
As noted in Harrison's (p. 5252), PPD does not differentiate well between M. tuberculosis and some non-tuberculous mycobacteria (NTM), and BCG can cause significant cross-reactivity.

9. FALSE NEGATIVE RESULTS

Causes of false negativity (negative test despite TB infection):

Technical Causes

  • Incorrect injection (subcutaneous instead of intradermal)
  • Improper storage/handling of PPD (exposure to light, heat)
  • Reading before 48 hours or after 72 hours
  • Insufficient dose

Patient-Related Causes (Anergy)

CauseExamples
ImmunosuppressionHIV/AIDS (most important), corticosteroids, cytotoxics
Severe/disseminated TBMiliary TB — exhaustion of immune response
MalnutritionProtein-energy malnutrition
Viral infectionsMeasles, EBV, varicella, influenza
Hematological malignanciesLeukemia, lymphoma, Hodgkin's disease
SarcoidosisImmunological anergy
Very old age / very young ageImmature or waning immunity
Recent TB (< 8–10 weeks)Pre-sensitization window period
Live virus vaccinesMMR, oral polio (within 4–6 weeks)
Key MD exam point: Advanced immunosuppression causes false-negative results in all immunologically-based TB tests including TST and IGRA (Primary Care Guidance for HIV, p. 14).

10. BOOSTER PHENOMENON

  • Some individuals with remote TB infection may show a negative TST initially (waned immunity)
  • Repeat testing 1–3 weeks later may show a positive result — this is called the booster effect
  • This is NOT a new infection — it represents recall/boosting of previously sensitized T-cells
  • Important in serial testing programs (e.g., healthcare workers) to establish baseline

11. TUBERCULIN CONVERSION

  • A person previously negative who becomes positive on repeat testing
  • Defined as: increase of ≥10 mm in induration size within a 2-year period
  • Indicates recent TB infection

12. COMPARISON: MANTOUX TEST vs. IGRA

FeatureMantoux (TST)IGRA (QuantiFERON-TB Gold / T-SPOT)
AntigenPPD (mixed mycobacterial antigens)ESAT-6, CFP-10, TB7.7 (TB-specific)
BCG cross-reactivityYesNo (preferred post-BCG)
Visit required2 (injection + reading)1 (blood draw)
Booster effectYesNo
CostCheapExpensive
Use in children <5 yrsPreferredLimited data; not routinely recommended
False negative in HIVYesYes (similar sensitivity)
Preferred inResource-limited settings, childrenBCG-vaccinated, low return probability
IGRA is preferred over TST in BCG-vaccinated patients and those unlikely to return for reading (Primary Care Guidance for HIV, p. 14).

13. CONTRAINDICATIONS

  • Absolute: Previous severe reaction to tuberculin (vesiculation, anaphylaxis)
  • Relative: Active skin disease at the injection site; severe immunosuppression (result unreliable)
Note: BCG vaccination is NOT a contraindication to TST.

14. SPECIAL SITUATIONS

SituationRecommendation
BCG vaccinatedUse IGRA; if TST done, ≥15 mm more likely true positive
HIV positiveLower threshold (≥5 mm = positive); CD4 <200 may give false negative
Children (<5 years)TST preferred over IGRA
Miliary TBMay be negative (anergy); do not rule out TB
PregnancySafe to perform TST
Previous positive TSTRe-testing generally not recommended

15. CLINICAL PHOTOGRAPH

Positive Mantoux Test showing induration of ~20mm measured with ruler on volar forearm
A positive Mantoux test on the volar forearm showing approximately 20 mm of induration and erythema, demarcated with ink for measurement.

16. USES OF MANTOUX TEST — SUMMARY

  1. Diagnosis of LTBI (most important use)
  2. Screening of contacts of active TB cases
  3. Epidemiological surveys (prevalence of TB infection)
  4. Diagnosis of TB in children (especially primary complex)
  5. Pre-treatment screening before starting anti-TNF therapy, transplant immunosuppression
  6. Assessment of cell-mediated immunity (e.g., in suspected immunodeficiency)

17. EXAM HIGH-YIELD POINTS

PointFact
Antigen usedPPD (Purified Protein Derivative)
Volume injected0.1 mL intradermally
Standard dose2 TU (PPD-RT23) or 5 TU (PPD-S)
SiteVolar surface, left forearm
Reading time48–72 hours
What is measuredInduration (not erythema)
Standard positive≥10 mm (general); ≥5 mm (HIV/immunosuppressed)
Reaction typeType IV hypersensitivity
Most common false positiveBCG vaccination
Most common false negativeHIV/AIDS (anergy)
Booster effectRecall of waned immunity on repeat testing
Conversion≥10 mm increase within 2 years

References:
  • Harrison's Principles of Internal Medicine, 21st Edition, p. 5252
  • Primary Care Guidance for Persons with HIV (CDC/GLGCA), p. 14
  • ATS/CDC/IDSA Guidelines on LTBI Diagnosis and Treatment
  • Park's Textbook of Preventive and Social Medicine
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