Mycobacterial Infection

Mycobacterial Infection

Tariq Muzzafar, MBBS

Scanning electron micrograph demonstrates M. tuberculosis; the bacterium ranges from 2-4 µm long and 0.2-0.5 µm wide. (Courtesy J. Carr, CDC Public Health Image Library, #9997.

Thin-section transmission electron micrograph demonstrates M. tuberculosis bacilli. (Courtesy CDC Public Health Image Library, #8433.)



Infectious Agents

  • M. tuberculosis

Immunocompetent Patients

  • Reactivation of disease at site seeded during primary infection by hematogenous route

  • As compared to adults, young children more commonly have

    • Disseminated disease

    • Severe illness even with low bacterial loads

  • Deficient immune responses implicated

  • Infection of tonsils, adenoids, and Waldeyer ring can occur

  • Abdominal involvement may occur via ingestion of milk or sputum infected with M. tuberculosis

Immunocompromised Patients

  • Reactivation of latent infection

  • Part of generalized infection, miliary dissemination

    • Greater mycobacterial load than immunocompetent patients

  • Laryngeal involvement very infectious: Special precautions needed



  • Incidence

    • Childhood tuberculosis represents

      • 15-40% of all cases in low- and middle-income countries

      • 2-7% of all cases in industrialized countries

    • Associated with lower socioeconomic status and overcrowding

    • Represents ˜ 40% of peripheral lymphadenopathy in developing world

    • Prevalence of TB lymphadenitis in children ≤ 14 years in rural India: 4.4/1,000

    • In industrialized countries, most cases occur in immigrants and travelers to endemic areas

      • Immigrant populations mostly originate from Southeast Asia and Africa

    • Lymphadenitis is most common form of extrapulmonary tuberculosis

    • Risk of infection higher in following settings

    • Lower socioeconomic status, overcrowding leading to close contact with index case

    • Orphanages and refugee camps

    • Immunosuppression: HIV (most important), malignancies, chemotherapy, corticosteroids

  • Age

    • Incidence

    • Decreases from birth to 8 years of age

    • Increases again in late adolescence and early adult life

  • Gender

    • M:F = 1:2

  • Ethnicity

    • Asian Pacific Islanders more susceptible


  • Characteristically, multiple lymph nodes (LNs) involved

  • Usually unilateral; can be bilateral

  • Superficial LN involvement

    • Most common form of extrapulmonary TB in children

    • Anterior and posterior cervical (most common)

    • Supraclavicular, submandibular, preauricular, submental also involved

    • Classified as nonsevere disease if

    • No spread to or compression of adjacent neural, vascular, lymphatic, or bony tissues

    • Isolated sinus or fistula formation from node present, and no involvement of other organs

  • Inguinal, epitrochlear, axillary involvement rare

  • Isolated intraabdominal LNs can be involved

    • Periportal, peripancreatic, and mesenteric

    • Classified as nonsevere if only enlarged abdominal nodes present

    • Due to hematogenous or retrograde lymphatic spread from lung, or ingestion of sputum or milk infected with M. tuberculosis

  • Generalized lymphadenopathy and hepatosplenomegaly may occur

    • Due to lymphohematogenous spread

  • Typical course

    • Lymph nodes usually enlarge gradually in the early stages

    • Systemic signs and symptoms absent

    • Low-grade fever may be present

    • Without treatment, caseation necrosis, rupture of capsule, involvement of adjacent LNs and overlying skin, sinus tract

  • Occasional cases

    • Lymphadenitis acute with rapid enlargement

    • High fever, tenderness, fluctuation, overlying cellulitis

  • Parabronchial and paratracheal involvement can lead to airway compromise

  • LN on physical examination

    • Firm, rubbery, discrete, and nontender; may be matted

    • Nodes may feel fixed to underlying or overlying tissues

    • May be swollen and tender due to secondary bacterial infection

Laboratory Tests

  • Tuberculin skin test (TST)

    • May be negative with culture documented disease in

    • 10% of immunocompetent children; may become positive subsequently

    • Disseminated disease

    • HIV-positive patients

  • Interferon-Y release assays (IGRA)

    • Measure in vitro T-cell interferon-Y release in response to 2 unique antigens

      • Sensitivity similar to TST; specificity higher

      • Negative in prior Bacillus Calmette-Guérin vaccination and in sensitization to nontuberculous mycobacteria

    • 2 widely studied tests

      • Enzyme-linked immunospot (ELISpot) (T-SPOT.TB; Oxford Immunotec; Oxford, UK)

      • Enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold; Cellestis; Chadstone, VIC; Australia)

    • TST and IGRA cannot distinguish between infection, active disease, and past disease

    • IGRA not recommended to replace TST in low- and middle-income countries

  • Direct staining

    • Carbolfuchsin stains (Ziehl-Neelsen stain; Kinyoun stain) highlight AFB

      • AFB are bright red against blue or green background, depending on counterstain

      • Must be scanned under oil-immersion

      • Time consuming due to limited size of field viewed at 1 time

      • < 2% of children below 10 years positive in newly diagnosed TB

      • Negative smears do not rule out diagnosis

    • Fluorochrome stain (auramine O, ± rhodamine)

    • Scanning is quicker since slides can be scanned at 25x objective

    • Confirmation may require 40x objective

    • Bacteria bright yellow (auramine) or orange-red (rhodamine) against dark background

  • Microbiological culture

    • General comments

      • Only ˜ 30% of children confirmed bacteriologically

      • 5% of children < 10 years positive in newly diagnosed TB

    • Löwenstein-Jensen (LJ) medium

      • Less sensitive

      • Recommended only for chromogenic studies and biochemical tests

    • Middlebrook 7H10 and 7H11 agar medium used for isolation and susceptibility testing

    • Automated radiometric detection systems: BACTEC 460 (BD Diagnostic Systems; Sparks, MD; USA)

    • Automated nonradiometric detection systems

    • MGIT 960 (BD Diagnostic Systems)

    • MB/BacT System (BioMerieux; Durham, NC; USA)

    • BACTEC MYCO/F lytic blood culture bottle (BD Diagnostic Systems)

    • ESP Culture System II (TREK Diagnostic Systems, Inc.; Cleveland, OH; USA)

  • Gas-liquid and high-performance liquid chromatography

    • Useful in culture confirmation

  • Molecular diagnosis (nucleic acid amplification)

    • Quicker and accurate identification compared to traditional methods; specificity > 97%

    • Negative result does not rule out diagnosis

    • AFB microscopy negative cases

      • Real-time polymerase chain reaction assay useful

      • Xpert-MTB/RIF (Cepheid, Sunnyvale, California, USA) assay recommended by WHO

      • Detects 81-bp-core region of RNA-polymerase β-subunit gene flanked by M. tuberculosis-specific DNA sequences

      • Can test for rifampicin resistance simultaneously

      • Initial diagnostic test in cases with suspected multidrug-resistant (MDR) TB or HIV-associated TB

    • AFB microscopy positive cases

    • Molecular line probe assays preferred

    • GenoType-MTBDRplus (Hain Lifesciences, Nehren, Germany) assay recommended by WHO

    • Can test for rifampin and isoniazid resistance simultaneously

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mycobacterial Infection
Premium Wordpress Themes by UFO Themes
%d bloggers like this: