Post-mortem diagnosis, of cytomegalovirus and varicella zoster virus co-infection by combined histology and tissue molecular biology, in a sudden unexplained infant death

Abstract

Background: An autopsy case of a two-month-old male infant who suddenly and unexpectedly died during his sleep, eight days after the onset of benign varicella.

Objectives: To describe post-mortem combined histological and tissue molecular biological techniques for the diagnosis of cytomegalovirus and varicella zoster virus co-infection as a cause of death.

Study design: Real-time quantitative PCR and RT-PCR assays for Herpesviruses, respiratory viruses, Adenovirus, Enterovirus and Parvovirus B19 were performed on multi-organ frozen samples and paraffin-embedded tissues in combination with histology.

Results: Cytomegalovirus and varicella zoster virus were detected by molecular biology with highest viral loads detected in the lungs (4.6×10(7) and 1.9×10(5) genome copies per million of cells, respectively). Pulmonary extensive necrotizing inflammation and immunohistochemistry correlated to virological data. Virological molecular biology was negative on paraffin-embedded tissues.

Conclusions: This case shows that thorough quantitative virological investigations on frozen tissues must be performed in combination with histology and immunohistochemistry for the determination of the cause of a sudden unexplained infant death.

Keywords: Cytomegalovirus; Histopathology; Real-time PCR assay; Sudden unexpected infant death; Varicella zoster virus; Virology.

Fig. 1

Pulmonary (A and C) and renal (B and D) histological and immunohistochemical features. (A) Hematoxylin eosin-stained pulmonary sections showing necrotizing inflammation (×200). (B) Hematoxylin eosin-stained renal inflammation with moderate mononuclear cell infiltrates (×200). (C) A CMV cell inclusion detected in lung by anti-CMV anti-body (brown stained cell; ×200). (D) Numerous CMV inclusions detected in renal tubular cells by anti-CMV antibody (brown stained cells; ×200).

Fig. 2

CMV and VZV loads, normalized per million of cells, assessed in multi-organ frozen tissues sampled during the autopsy.