Detection of RNA viruses in sudden infant death (SID)

Abstract

Continuing previous work, reverse transcriptase polymerase chain reaction approaches for the detection of RNA viruses (influenza A+B, parainfluenza virus 3, respiratory syncytial virus) were developed. A total of 118 infant deaths, including 13 cases of non-natural death (nND), 78 cases of natural death (ND) without morphological signs of interstitial pneumonia (IP), 27 cases showing IP (ND+IP), were investigated using frozen lung tissue ( N=100) and paraffin-embedded material ( N=18). In five of the autopsy cases (ND+IP) the influenza B virus genome could be detected and the other types of viruses were completely negative. Together with previous results (detection of adenoviruses and cytomegaloviruses) in the same groups, the frequency of virus detection in the cases with IP was 48% compared with 14% in the ND without IP and 7% in the nND. Significant differences in the frequency of virus detection were also obtained when the cases were divided in SIDS and non-SIDS. The results obtained indicate an association between IP and some viruses and support the hypothesis that respiratory virus infections could act as trigger in sudden infant death.

On the Question of the Diagnosis of Sudden Infant Death Syndrome

“…При этом речь идет как о вирусных [66,75], так и о бактериальных инфекциях [76]. По мнению авто-ров [66], анализировавших медицинскую документацию и протоколы аутопсии детей первого года жизни, вне-запно умерших на дому, основными причинами СВСМ в 66,7% являются оппортунистические инфекции с хро-ническим течением (цитомегаловирусная инфекция) и в 33,3% -ОРВИ (чаще грипп) на фоне фетопатий и выраженного иммунодефицита.…”

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

“…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.…”

“…The significance of detecting viruses has largely remained undetermined in the context of SIDS [10,11,24,27]. Controversy exists and the same viruses are circulating at similar or higher frequencies in babies that died from accidents, and are also similar to those viruses circulating in living babies and infants in the general population causing self-limiting infections [27,28].…”

Diagnosis of Influenza from Respiratory Autopsy Tissues

“…Detection of influenza RNA in frozen postmortem specimens is relatively straightforward, 26 and has even been used in the detection and sequencing of the 1918 influenza virus genes from human bodies frozen in the permafrost. 27 Molecular analyses on formalin-fixed tissues, particularly those that require RNA, can be quite difficult because formalin fixation strongly cross-links nucleic acids, and the embedding process can introduce ribonucleases, resulting in significant RNA degradation and smaller amplifiable fragments.…”

“…28,29 Most research that demonstrates evidence of the influenza virus in formalinfixed or formalin-fixed, paraffin-embedded (FFPE) tissues from fatal human seasonal influenza cases has used assays such as immunohistochemistry (IHC), 30 in situ hybridization, 31 or conventional RT-PCR. 26,[32][33][34][35][36] However, because of the amplicon size limitations presented by FFPE tissues, rRT-PCR methods for detection of pathogens are the most ideal. Although recent reports containing limited details of the detection of influenza by conventional RT-PCR 37 and rRT-PCR 38 -40 in FFPE tissues have been published, there are no detailed reports describing routine methods to extract RNA from and performance of rRT-PCR to detect influenza A, its H1 and H3 subtypes, and influenza B in FFPE autopsy tissues.…”