What intracytoplasmic inclusion bodies are characteristic of specific infectious agents?

Intracytoplasmic Inclusion Bodies in Infectious Diseases

Intracytoplasmic inclusion bodies serve as diagnostic hallmarks for specific infectious agents, with Donovan bodies in granuloma inguinale, RNA-containing inclusions in Kawasaki disease, chlamydial inclusions in lymphogranuloma venereum, morulae in ehrlichiosis, and coronavirus particles being the most clinically significant examples.

Bacterial Infections with Intracytoplasmic Inclusions

Granuloma Inguinale (Donovanosis)

• Donovan bodies are the pathognomonic intracytoplasmic inclusions seen in Wright or Giemsa-stained smears or biopsies of granulation tissue from anogenital ulcers caused by Calymmatobacterium granulomatis 1
• These inclusions appear within macrophages and are diagnostic when identified in the appropriate clinical context of painless or minimally painful granulomatous lesions 1

Chlamydial Infections

• Inclusion bodies in leukocytes of inguinal lymph node aspirates can be demonstrated by immunofluorescence in lymphogranuloma venereum caused by Chlamydia trachomatis serovars L1, L2, or L3 1
• These inclusions represent active chlamydial replication within host cells and are part of the diagnostic criteria for this sexually transmitted infection 1

Ehrlichiosis and Anaplasmosis

• Morulae (intracytoplasmic inclusions) in monocytes or neutrophils on Wright-stained peripheral blood smears are characteristic of ehrlichiosis and anaplasmosis 1
• Communication with the laboratory is paramount to ensure careful examination of blood smears, as these inclusions may be sparse and easily missed 1
• The presence of morulae in the appropriate clinical context (fever, headache, thrombocytopenia following tick exposure) supports early diagnosis before serologic confirmation 1

Viral Infections with Intracytoplasmic Inclusions

Kawasaki Disease (Suspected Novel RNA Virus)

• Intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells are commonly observed in autopsied cases of Kawasaki disease and appear to contain RNA, potentially linked to an unidentified causative agent 1
• These inclusions are found in multiple cell types throughout the body, not just respiratory epithelium, suggesting systemic viral dissemination 1
• The RNA-containing nature of these inclusions supports the hypothesis of a novel RNA virus entering through the upper respiratory tract 1

Coronavirus (SARS-CoV-2)

• Intracellular coronavirus particles appear as 60-140 nm round-to-ovoid structures with dark 6-12 nm internal dots (representing cross-sections through the helical nucleocapsid) contained within intracellular vacuoles 1
• These particles must be distinguished from normal subcellular organelles that can mimic coronavirus, including clathrin-coated vesicles, multivesicular bodies, vesiculating rough endoplasmic reticulum, and Golgi vesicles 1
• Critical diagnostic feature: True coronavirus inclusions show internal dots corresponding to nucleocapsid cross-sections, while mimics like multivesicular bodies lack these internal structures 1

Cytomegalovirus (CMV)

• Cytoplasmic inclusions in CMV consist of membrane-bound aggregates of mature virions with dense cores and multilayered envelopes, distinct from the nuclear inclusions that contain capsids 2
• These cytoplasmic inclusions are observed in disseminated CMV infection, particularly in kidneys, liver, lungs, and anterior pituitary 2
• The envelopment process involves successive coats derived from nuclear membrane and endoplasmic reticulum 2

Rabies Virus (Negri Bodies)

• Negri bodies are cytoplasmic inclusion bodies representing viral factories where viral RNA synthesis occurs, exhibiting liquid-liquid phase separation properties 3
• These spherical structures can fuse together and reversibly deform, behaving as membrane-less liquid organelles 3
• Negri bodies concentrate viral proteins and genomic RNA, serving as sites of active virus transcription and replication 3

Paramyxoviruses

• Parainfluenza virus type 5 forms cytoplasmic inclusion bodies that are liquid organelles disrupted by osmotic shock, containing primarily genomic RNA while viral mRNA distributes diffusely throughout cytoplasm 4
• Newcastle disease virus produces both intracytoplasmic and intranuclear inclusions consisting of twisted strands (18-20 nm diameter) resembling nucleocapsids, tagged by anti-P protein antibodies 5

Critical Diagnostic Pitfalls

Distinguishing True Viral Inclusions from Cellular Organelles

• Do not mistake clathrin-coated vesicles, multivesicular bodies, or other normal organelles for viral inclusions 1
• Expertise in virus morphology, knowledge of virus morphogenesis, and familiarity with normal subcellular structures are essential to avoid misidentification 1
• When morphological identification is equivocal, confirmatory techniques include immunoelectron microscopy, ultrastructural in situ hybridization, or correlation with immunohistochemistry on the same tissue 1

Clinical Context is Essential

• The presence of intracytoplasmic inclusions must be interpreted within the appropriate clinical, epidemiological, and laboratory context 1
• For tick-borne diseases like ehrlichiosis, treatment decisions should not be delayed while searching for morulae, as sensitivity is limited and clinical deterioration can be rapid 1
• In leptospirosis, while intracytoplasmic structures are not the primary diagnostic feature, the clinical syndrome (fever, myalgias, conjunctival suffusion, jaundice) combined with laboratory abnormalities guides diagnosis 6, 7, 8