Virological investigations in sudden unexpected deaths in infancy (SUDI)

Abstract

Previous studies have implicated viral infections in the pathogenesis of sudden unexpected death in infancy (SUDI), and routine virological investigations are recommended by current SUDI autopsy protocols. The aim of this study is to determine the role of post-mortem virology in establishing a cause of death. A retrospective review of 546 SUDI autopsies was carried out as part of a larger series of >1,500 consecutive paediatric autopsies performed over a 10-year period, 1996-2005, in a single specialist centre. Virological tests were performed as part of the post-mortem examination in 490 (90%) of the 546 SUDI autopsies, comprising 4,639 individual virological tests, of which 79% were performed on lung tissue samples. Diagnostic methods included immunofluorescence assays (using a routine respiratory virus panel; 98% of cases), cell culture (61%), rapid culture techniques such as the DEAFF test for CMV (55%), PCR (13%), electron microscopy (10%), and others. Virus was identified in only 18 cases (4%), viz. five cases of enterovirus, four of RSV, three of HSV and CMV, and one each of adenovirus, influenza virus and HIV. In seven of the 18 cases the death was classified as due to viral infection, whilst of the remaining 11 cases, death was due to bacterial infection in five, a non-infective cause in one and unexplained in five. Virus was identified in 33% of deaths due to probable viral infections, but also in 6% of SUDI due to bacterial infections, and in 2% of SUDI due to known non-infective causes and unexplained SUDI. When predominantly using immunofluorescence, virus is identified in only a small proportion of SUDI autopsies, resulting in a contribution to the final cause of death in <2% of SUDI post-mortem examinations. Routine post-mortem virological analysis by means of an immunofluorescence respiratory virus panel appears to be of limited benefit in SUDI for the purposes of determining cause of death. Application of a broader panel using more sensitive detection techniques may reveal more viruses, although their contribution to the final cause of death requires further exploration.

Review of immunological and virological aspects as contributory factors in Sudden Unexpected Death in Infancy (SUDI)

“…A rise in SIDS cases has been documented in certain populations where infections are frequent, including during colder climates and annual influenza outbreaks [21,22,23].…”

“…Some viruses isolated from SUDI cases include human enterovirus [10,23], HAdV [10,23,24], Epstein-Barr virus (EBV) [10,11], parvovirus B19 [10], human herpes simplex virus (HSV) [10,11], CMV [11,23,24], human rhinovirus (HRV) [24], influenza virus [23,24], RSV [23,25], HPIV [25] and rotavirus [26], isolated from myocardial, lung, bowel and liver specimens [10,23,24]. At Tygerberg FPS Mortuary myocardial and bowel specimens from SUDI cases are not considered for routine viral investigation and HRV, EBV, parvovirus B19, HSV, human enterovirus and rotavirus do not grow in shell-vial cultures.…”

“…Exposure to cigarette smoke, poor nutrition, a mild viral infection, excessive heat while sleeping in the prone position, an immature immune system due to a critical period in development and other medical conditions all pose enough risk factors to fit the triple-risk model for SIDS [15,23,33,34]. Since SIDS is documented to be higher in the two to four month age group, this could represent a critical developmental period that coincides with a loss of immune protection due to of waning maternally transferred antibodies [5,42].…”

“…Extended death to post-mortem intervals may affect virus viability and viral NA integrity, which could result in reduced viral detection during culture attempts and molecular assays [23]. There is currently no defined window period to ensure the successful detection of viruses in molecular or culture assays, but Rambaud et al [12] showed that a post-mortem interval of up to four days still yielded significant bacterial and viral isolates in 85% of SUDI cases using molecular detection methods.…”

“…This approach gave rise to the triple-risk model, where the risk is highest when an underlying vulnerability in homeostatic control and an exogenous stressor coincide at a critical developmental stage [23,32,33,34]. The most likely environmental or exogenous trigger is a viral infection and the proposed underlying vulnerabilities include immune deficiencies and poor control or over-expression of inflammatory mediators [15,23,33].…”