Mycobacterial Infection



Mycobacterial Infection


Tariq Muzzafar, MBBS





Key Facts


Clinical Issues



  • High index of suspicion essential for diagnosis


  • Definitive diagnosis by histology and culture of LN


  • Molecular methods enable quicker identification of organism


  • FNA is as useful as excisional LN biopsy in HIV(±) patients


Microscopic Pathology



  • Granulomas, classically with necrotic center (caseation)


  • Concentric layers of epithelioid cells, Langhans giant cells, lymphocytes, and plasma cells


  • Fibrosis, hyalinization, calcification present in healing phase


  • In LN biopsy specimen, AFB identified by Ziehl-Neelsen, Kinyoun, Fite-Faraco stains


  • Auramine-rhodamine stain with fluorescent microscopy more sensitive for detection


Top Differential Diagnoses



  • M. avium-intracellulare lymphadenitis


  • Histoplasma lymphadenitis


  • Kikuchi-Fujimoto lymphadenitis


  • Cat scratch lymphadenitis


  • Sarcoidosis lymphadenopathy


Reporting Considerations



  • Suspected or confirmed cases of TB should be reported to local public health department



    • Identify adult source case and contacts for follow-up






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.)


TERMINOLOGY



Abbreviations



  • Acid-fast bacilli (AFB)


  • Tuberculosis (TB)



Definitions



  • Lymphadenitis caused by infection with Mycobacterium tuberculosis


ETIOLOGY/PATHOGENESIS


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


CLINICAL ISSUES


Epidemiology



  • 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


Presentation



  • 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



Treatment

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mycobacterial Infection

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