Human adenovirus infections in pediatric population - An update on clinico-pathologic correlation

Abstract

Human adenoviruses can cause infections at any age but most commonly in pediatric population, especially in young children and infants. By the time of 10 years old, most children have had at least one episode of adenovirus infection. Adenoviruses can cause many symptoms similar to common cold, including rhinorrhea, fever, cough, and sore throat. Lower respiratory infections such as bronchitis, bronchiolitis, and pneumonia can be severe and even fatal. Other diseases such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, and meningoencephalitis can also be associated with adenovirus infections. A variety of recent advancement of structural and molecular biology methods have revamped the taxonomy of adenoviruses and furthered our understanding of the diversity of related clinical diseases. Because of the wide spectrum and complexity of diseases associated with human adenovirus infections, the scope of this review is limited to basic virology and epidemiology of adenoviruses with a main focus on the clinico-pathologic correlation. Clinical manifestations and pathology of any infectious disease are always related; therefore, it is logical to review clinico-pathologic correlation within the specific disease entity caused by adenoviruses to better understand this common viral infection in pediatric population.

Keywords: Clinico–pathologic correlation; Epidemiology; Human adenoviruses; Pediatric infections.

Fig. 1

(A) Transmission electron micrograph with an ultra-thin section of an adenovirus-infected cell showing adenoviruses replicate in the nucleus of cells and form intranuclear paracrystalline arrays of 70–90 nm adenovirus particles. (B) Structure of adenovirus virion. Non-enveloped capsid with an icosahedral symmetry and nucleocapsid containing a double-stranded linear DNA genome. The icosahedral shell is composed of 240 capsomeres of hexon trimers (12 per triangular facet of the icosahedron), 12 pentameric penton capsomeres at each vertex, and 12 fibers extending from the pentons.

Fig. 2

Tropism of human adenoviruses with associated clinical diseases in various organ systems. The numbers indicate HAdV types; the numbers in red are the more common types.

Fig. 3

(A) Adenoviral encephalitis with characteristic smudge cells in infected neurons (arrow). (B) Immunostaining showing HAdV antigens within neurons (arrows) and neuronal processes (arrow heads). (C) Chemosis and diffuse erythema of the bulbar and palpebral conjunctiva in a child with epidemic keratoconjunctivitis. (D) Cytology of conjunctival scraping showing Cowdry type A intranuclear inclusion (arrows) of early HAdV infections in epidemic keratoconjunctivitis. (E) Necrotizing bronchitis in a fatal case of infant showing extensive denudation of the surface epithelium, edematous lamina propria, necrosis, and mononuclear inflammatory cells infiltrate. (F) Immunostaining of HAdV antigens in the denudated surface epithelium and necrotic areas in the same patient with necrotizing bronchitis. (G) Adenoviral necrotizing pneumonia with abundant smudge cells, fibrinous exudate, mixed inflammatory cells, and karyorrhectic debris in alveoli. (H) Immunostaining showing abundant HAdV antigens in smudge cells and lung parenchyma with necrotizing inflammation. (I) Basophilic intranuclear inclusions (arrow) and smudge cells (arrow heads) in surface intestinal epithelium in a child with intussusception. (J) Immunostaining showing abundant HAdV antigens in intestinal epithelial cells in the same child with intussusception. (K) Hyperplasia of submucosal lymphoid follicles (arrows) in an infant with intussusception. (L) Scattered immunostaining of HAdV antigens in the submucosal lymphoid follicle in the same infant with intussusception. (M) Adenoviral hepatitis with focal necrotizing inflammation showing karyorrhectic debris, smudge cells, and large basophilic intranuclear inclusions (arrow) in hepatocytes. (N) Immunostaining showing abundant HAdV antigens in necrotic foci in the liver. (O) Higher-power magnification of adenoviral necrotizing nephritis showing characteristic smudge cells (arrows) and eosinophilic necrotic material (arrow heads) in HAdV infected renal tubular cells. (P) Lymph node biopsy from a hemophagocytic lymphohistiocytosis patient showing effacement of nodal structure and increased number of histiocytes with hemophagocytosis (arrows). Hematoxylin and Eosin stain, A, E, G, I, K, M, O, P. Original magnifications: ×400 (A); ×100 (E, G); ×200 (I, M, P); ×50 (K); ×630 (O). Immunoalkaline phosphatase with napthol fast red substrate and hematoxylin counterstain, B, F, H, J, L, N. Original magnifications: ×400 (B); ×100 (F, H); ×200 (J, L, N). Papanicolaou stain, D. Original magnification: ×1,000.