Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Sudden Unexpected Death in Infancy (SUDI) refers to any such sudden demise in a child. If the child dies while asleep within the first year of life, and if no conclusive cause of death can be ascertained by means of complete autopsy and investigation into the circumstances surrounding death, including visit of the death scene, such a case is classified as one of Sudden Infant Death Syndrome (SIDS). By South African law, a full medico-legal autopsy is mandated in cases where the cause of death is not evident – including cases of possible SIDS. There can be little doubt that viral infection can be a cause of death in cases of supposed SUDI. At the Tygerberg medico-legal (forensic) laboratory, the evaluation of lung tissue for the presence of fatal viral lung infections forms part of the institutional protocol for the examination of SUDI cases. Lung samples of these SUDI cases are routinely tested for the presence of Cytomegalovirus (CMV), adenovirus and respiratory syncytial virus (RSV) by means of shell vial cultures. In a retrospective pilot study of 366 SUDI case files from Tygerberg Hospital, Western Cape, from 2004 – 2006, it was evident that in only 13.9% of possible SIDS cases, positive results for one or more of the aforementioned viruses were obtained. We hypothesise that the current method of virus detection, together with other factors such as the interval between death and post mortem examination, transport time of the specimens to the laboratory etc. might not be optimal to give a realistic picture of death in infancy caused by viral pulmonary infection. As other test modalities exist for the diagnosis of pulmonary viral infections, these methods were compared in terms of positive yield and association with viral pneumonitis, keeping the cost and time needed for each assay in mind. A total of 82 samples were collected over an 8 month period and routine shell vial cultures were done, followed by real-time Polymerase Chain Reaction (PCR) and immunohistochemical (IHC) staining of the lung sections with consensus pathology opinion. As expected, the real-time PCR method was much more better suited for identifying positive samples than shell vials (35% vs. 3.7% respectively). IHC staining also aided the pathologist in diagnosing viral infections microscopically. We expect the findings to be instrumental in streamlining not only our institutional SIDS investigation protocol, but also the development of a standardised national SIDS investigation protocol. / AFRIKAANSE OPSOMMING: “Sudden Unexpected Death in Infancy” (SUDI) verwys na enige skielike sterfte van ‘n kind. Indien die kind sterf tydens sy/haar slaap periode en geen oortuigende oorsaak van dood bepaal kan word deur middel van ’n volledige nadoodse ondersoek en ondersoek na die omstandighede tydens die dood, insluitend ’n besoek aan die doodstoneel nie, word so ’n geval as Wiegiedood (SIDS) geklassifiseer. SuidAfrikaanse wetgewing vereis ’n volledige medies-geregtelike nadoodse ondersoek in gevalle waar die oorsaak van dood onbekend is – insluitend gevalle van moontlike Wiegiedood. Daar is min twyfel dat virusinfeksie ‘n oorsaak van, of bydraende faktor tot dood kan wees in gevalle van moontlike SUDI. By die Tygerberg forensiese laboratorium vorm die evaluasie van long weefsel vir die teenwoordigheid van dodelike virusinfeksies deel van die institusionele protokol vir die ondersoek van SUDI gevalle. Long monsters van hierdie SUDI gevalle ondergaan roetine toetse vir die teenwoordigheid van sitomegaalvirus, respiratoriese sinsitialevirus en adenovirus deur middel van selkulture (“shell vial cultures”). In ‘n retrospektiewe steekproef van 366 SUDI gevalle by Tygerberg Hospitaal, Wes-Kaap van 2004 – 2006, is bevind dat in slegs 13.9% van moontlike SUDI gevalle die teenwoordigheid van een of meer van bogenoemde virusse bevestig kon word. Ons hipotese is dat hierdie metode van virus deteksie, tesame met ander faktore soos die tydsinterval tussen dood en nadoodse ondersoek, tyd om monsters na die laboratorium te vervoer ens. moontlik nie optimaal is om ‘n realistiese beeld van dood in babas as gevolg van pulmonale virusinfeksie te gee nie. Aangesien ander toets modaliteite bestaan vir die diagnose van pulmonale virusinfeksies, is hierdie metodes vergelyk in terme van positiewe opbrengs en assosiasie met virale pneumonitis, teen ’n agtergrond van die koste en tyd benodig per toets. ’n Totaal van 82 monsters is oor ‘n 8 maande periode versamel en roetine selkulture is gedoen, gevolg deur “real-time” Polimerase Ketting Reaksie (PKR), asook immunohistochemiese (IHC) kleuring van long snitte met patologiese verslae. Soos vermoed, is gevind dat die real-time PKR metode baie meer akkuraat is om positiewe monsters te identifiseer as roetine selkulture (35% vs 3.7% onderskeidelik). IHC kleuring het ook mikroskopiese diagnose van virale infeksies deur die patoloog vergemaklik. Ons verwag dat hierdie bevindinge grootliks kan bydra in die vaartbelyning van ons institusionele SIDS ondersoek protokol, asook in die ontwikkeling van ’n gestandaardiseerde nasionale SIDS ondersoek protokol.

I och för sig är idag ett uttryck vars betydelse inte helt lätt låter sig härledas från de inbördes orden. En sökning i Språkbankens historiska korpusar ger vid handen meningar som […] lifwet är aldrig wigtigt i och för sig sielft, aldrig såsom ändamål, blott såsom medel till sedlighet (Stockholmsposten år 1820), där användningen verkar skilja sig från hur vi idag använder uttrycket. Metoden semi-automatic uniqueness differentiation (SUDi) är en nyligen framtagen metod för polysemidisambiguering. SUDi är framtagen för att utföra undersökningar av synkront material, och har tidigare inte används i en diakron undersökning. Det huvudsakliga syftet med föreliggande undersökning är att med hjälp av SUDi finna empiriskt stöd för hypotesen att i och för sig idag är polysemt med hur det en gång har använts. Undersökningen syftar dock även till att evaluera hur väl SUDi lämpar sig för en diakron undersökning som denna. De två tidsperioderna som undersöks är år 1820–1839 samt år 2000–2013. Valet av perioden 1820–1839 motiveras av att träffarna på uttrycket först vid den här perioden är tillräckligt många till antalet, samt att texten uttrycken förekommer i håller tillräckligt hög kvalitet. Materialet består totalt av 200 meningar, 100 stycken från vardera tidsperioden, och utgörs av tidningstext. Uppsatsens teoretiska ramverk är konstruktionsgrammatiken. Metoden SUDi består av fem steg: (i) använd en korpus för att samla in exempel på formen som tros vara polysem, (ii) sortera intuitivt in exemplen i två filer, (iii) kör filerna genom ett annoteringsprogram som märker upp texterna med språkvetenskaplig information och producerar xml-filer av de annoterade texterna, (iv) kör xml-filerna genom Uneek, ett webbaserat verktyg som utför komparativa analyser av annoterad text, och presenterar vilka drag som är unika för vardera texten och vilka drag de har gemensamt, (v) tolka resultatet. Resultatet visar att i och för sig i det moderna materialet och i och för sig i det äldre materialet högst troligt är polysema. Ett par av de för det äldre uttrycket unika dragen som visade sig utgöra empiriskt stöd för polysemi är att själv kan stå omedelbart efter i och för sig i satsen, samt att i och för sig kan ingå i en participfras med betrakta. Vad beträffar metodens lämplighet för diakron undersökning påträffades tre problem: flera av skillnaderna Uneek tar fram i själva verket skillnader mellan de två språkskedena generellt, det krävs en del extra manuellt arbete som är tidskrävande, och delar av valideringen blir problematisk eftersom en nutida forskares språkliga intuition inte med tillfredsställande säkerhet kan bedöma meningars acceptans i tidigare skeden av historien. Trots dessa problem bedöms metoden, med viss anpassning, vara användbar även för diakrona undersökningar.

Doctor of Public Health / For many years the major cause of infant mortality in NSW has been the result of Sudden Infant Death Syndrome (SIDS). Statistics show the area defined as 'Western Sydney' is no exception, and in 2002, a report prepared by the Epidemiology, Indicators, Evaluation and Research Unit (EIRE) in Western Sydney presented data indicating SIDS rates in the area were higher than the state average. In particular, two Local Government Areas (LGAs) had clusters of SIDS deaths. Previous Australian research identified a higher risk of SIDS and other causes of infant mortality in Aboriginal and Torres Strait Islander populations. The areas of Western Sydney where SIDS rates were higher than expected were home to Aboriginal, Torres Strait Islander and Pacific Island residents. The number of SIDS deaths in Aboriginal infants did not explain the higher than expected rate of SIDS in the areas under investigation. Studies undertaken in New Zealand and the Pacific Islands have identified higher than expected risk of SIDS in Maori and Pacific Island communities in those countries, although this has never been studied in Pacific Island residents living in Australia. The reasons for these communities exhibiting a higher than normal SIDS rate is not completely understood, but can be partially explained by behavioural practices which are known to impact adversely on the risk of SIDS. This study sought to investigate the level of knowledge concerning the prevention of sudden and unexpected death in infants (SUDI) in three key groups of infant caregivers: general practitioners, nurses and parents living or working in the area geographically defined by Sydney West Area Health Service (WSAHS). In addition, the study sought to identify any variation in knowledge of SIDS reduction strategies in the three groups under study, and to investigate factors influencing knowledge and practice in these participants. The study findings were then used as a basis on which to develop strategies and recommendations to enhance the delivery of safe sleeping messages through the health care system. Using a combination of qualitative and quantitative methods, this cross-sectional study highlights a number of issues around infant care practices and the major influences on new parents living in a multicultural community. Results of the study showed there is a large variation in knowledge around safe sleeping practices (including SIDS reduction strategies) in all the groups studied. Although educational campaigns are conducted regularly, many general practitioners and parents are confused about the key SIDS reduction messages and still place infants in sleeping positions considered unsafe. While nurses and midwives were aware of the SIDS reduction strategies, they still occasionally used infant sleeping positions considered unsafe. General practitioners born overseas in a country where English is not the first language were less likely to be familiar with safe sleeping messages, including SIDS reduction strategies. Families from a Culturally and Linguistically Diverse (CALD) background were less likely to have seen SIDS information in their own language than families who spoke English, and as a result were more likely to use traditional methods of infant care, including co-sleeping with siblings and parents and side or tummy sleeping. CALD parents were more likely to rely on herbal remedies and friends and family for assistance, than English speaking parents who accessed health professionals as the first point of call when infants were unwell. The study identified a relatively recent practice, which until reported in this study, has not been documented in the literature. The practice of draping infant prams with blankets originated from the Cancer Council of Australia guidelines which recommend covering a pram with a light muslin wrap to protect infants’ skin from the sun. It appears parents have misinterpreted this message and are covering infant prams with blankets to encourage sleep, even when sun exposure is not an issue. Research suggests that poor air quality around the head of an infant may affect an infant’s arousal response. While no research has been conducted on the air quality around an infants head when covered by a heavy blanket in a pram, it is possible based on research into air quality around infants, that that this practice may increase the risk of sudden and unexpected death in an infant. In conclusion, this study found that multiple changes to the SIDS reduction messages since the initial ‘Reduce the Risks’ Campaign have led to confusion about ways of preventing SIDS in GPs, nurses and parents in Western Sydney. The study makes seven recommendations aimed at improving knowledge of safe sleeping practices in these groups, and optimizing health outcomes for infants using a collaborative approach to service delivery and future initiatives.

Thesis (MScMedSc)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background: Sudden infant death syndrome (SIDS) is considered the second most frequent cause of infant mortality worldwide. Research specifically pertaining to SIDS is limited in the South African setting. Identifiable causes for sudden infant death remain challenging despite full medico-legal investigations inclusive of autopsy, scene visit and ancillary studies. Viral infections could contribute to some sudden unexpected death in infancy (SUDI) cases, especially since a multitude of respiratory viruses have been detected from autopsy specimens. The specific contribution of viruses in the events preceding death, including the subsequent involvement of the immature immune response in infants, still warrants deciphering. Infancy is characterised by marked vulnerability to infections due to immaturities of their immune systems that may only resolve as infants grow older when these sudden deaths rarely still occur. In South Africa there is a lack of a standard protocol for investigations into the causes of SIDS, including the lack of standard guidelines as to which specimens should be taken, which viruses should be investigated and which laboratory assays should be utilised. Objectives: In this prospective descriptive study we aimed to investigate the prevalence of viruses in SUDI and SIDS cases at Tygerberg Forensic Pathology Service (FPS) Mortuary over a one year period. The primary aim was to explore possible respiratory viral infections in SUDI and SIDS cases and to determine the usefulness of molecular techniques to detect viruses from SUDI cases. To determine the significance of viruses, we assessed signs of infection from lung histology. The secondary objectives included collecting demographic data to investigate possible risk factors for SUDI and to look for possible similarities between viruses confirmed in living hospitalised infants at Tygerberg, during the study period compared to viruses detected from SUDI cases. Methods: Between May 2012 and May 2013 samples were collected from 148 SUDI cases presenting at Tygerberg FPS Mortuary. As part of the mandatory routine investigations into SUDI, shell vial culture (SVC) results were collected from lung and liver tissue specimens and bacterial culture results were collected from left and right lung and heart swabs at autopsy. To investigate the possibility of viruses implicated in some of the infant deaths we used the Seeplex® RV15 Ace detection multiplex polymerase chain reaction (PCR) assay to establish the frequency of 13 ribonucleic acid (RNA) respiratory viruses (influenza A and B, human parainfluenza 1-4, human coronavirus [OC43, 229E/NL63], human rhinovirus A, B and C, respiratory syncytial virus A and B, human enterovirus and human metapneumovirus) from RNA extracted from tracheal and lower left and right lung lobe swabs. Tissue from the lower left and right lung lobes were also assessed for histology signs of infection. Results: During our study we confirmed multiple known demographic risk factors for SIDS, such as the age peak around 1-3 months, the male predominance, bed-sharing, sleeping in the prone position, heavy wrapping in warm blankets, prenatal smoke exposure, and socio-economic factors. With the Seeplex® RV15 Ace detection assay between one and three viruses were detected in 59.5% (88/148) of cases. Of the 88 cases that had viruses detected, 75% (66/88) had one virus and 25% (22/88) had co-detections of two to three viruses. The most common viruses detected were HRV in 77% (68/88) of cases, RSV in 18% (16/88) of cases and HCoV in 14% (12/88) of cases. Many of the viruses we detected from our cases are included in the SVC test that forms part of the medico-legal laboratory investigation for all SUDI cases at Tygerberg FPS Mortuary. SVCs were positive in 9.5% (14/148) of all cases only. We showed that the SVC method is potentially missing most of the 13 respiratory viruses we investigated that could contribute to death in some of the SUDI cases. Conclusion: In some cases that had a Cause of Death Classification - SIDS, the PCR viruses detected cannot be ignored, especially when it is supported by histological evidence of infection. We thus propose that the use of PCR could alter a Cause of Death Classification from SIDS to Infection in some of these cases. Further research is needed to determine the significance of detecting viruses from SUDI cases wherein no significant histological evidence of infection was observed. This questions whether PCR may be too sensitive and is detecting past and latent viral infections that do not play any role in the cause of death. The histological picture also requires further characterisation to determine if it accurately predicts infections or lethal events and can truly support virology findings, especially in young infants whose immune systems are still maturing. Without determining the true prevalence of viruses in SUDI cases and the viral-specific immune response, the contribution of virus-specific infections to this syndrome will remain largely undetermined. / AFRIKAANSE OPSOMMING: Agtergrond: Wiegiedood (“SIDS/SUDI”) word beskou as die tweede mees algemene oorsaak van sterftes in kinders jonger as een jaar wêreldwyd. Toegewyde SIDS-spesifieke navorsing in die Suid-Afrikaanse samelewing is beperk. Dit bly steeds „n uitdaging om oorsake te probeer identifiseer vir hierdie onverwagte sterftes in kinders (SUDI) ten spyte van volledige medies-geregtelike ondersoeke, insluitende die lykskouing, ondersoek van die doodstoneel en aanvullende ondersoeke. Virusinfeksies kan aansienlik bydra tot sommige onverwagte sterftes in kinders, aangesien verskeie respiratoriese virusse alreeds aangetoon is in monsters verkry tydens outopsies. Die spesifieke rol wat virusse speel in die prosesse wat die dood voorafgaan, asook die bydraende rol van „n onder-ontwikkelde immuunrespons in babas, regverdig verdere ondersoek. Die eerste jaar van lewe word gekenmerk deur verhoogde vatbaarheid vir infeksies weens die ontwikkelende immuunstelsels soos wat babas ouer word, en die voorkoms van SUDI neem stelselmatig af met „n toename in ouderdom. In Suid-Afrika bestaan daar tans geen standaard protokol vir die ondersoek van wiegiedood nie en daar is ook nie standaard riglyne oor die tipe monsters wat geneem moet word, watter virusse ondersoek moet word en watter laboratorium toetse uitgevoer moet word nie. Doelstellings: In hierdie prospektiewe beskrywende studie is gepoog om die virusse wat in gevalle van wiegiedood of SUDI voorkom te ondersoek. Die studie is uitgevoer by die Tygerberg Geregtelike Patologie Dienste lykshuis oor 'n tydperk van een jaar. Molekulêre tegnieke om virusse aan te toon in hierdie gevalle is gebruik om spesifieke virusinfeksies te ondersoek. Die resultate is met histologiese tekens van infeksie in longweefsel gekorreleer. Demografiese data is verder versamel om moontlike risikofaktore vir wiegiedood te ondersoek. Dit is verder vergelyk met virusse wat met dieselfde diagnostiese tegnieke in babas geïdentifiseer is wat tydens die studieperiode in Tygerberg Hospitaal opgeneem was met lugweginfeksies. Metodes: Monsters van 148 SUDI gevalle wat by die Tygerberg lykshuis opgeneem is, is versamel tussen Mei 2012 en Mei 2013. As deel van die roetine ondersoeke in SUDI gevalle, was selkultuur resultate verkry van long en lewer weefsel, asook bakteriële kulture van deppers wat van beide longe en hart geneem was tydens die lykskouings. „n Seeplex® RV15 Ace polimerase kettingreaksie (PKR) toets is gebruik om die teenwoordigheid van virusse te ondersoek wat moontlik by die babasterftes betrokke kon wees. Trageale- en longdeppers wat tydens die lykskouings versamel was, was getoets vir 13 ribonukleïensure (RNS) respiratoriese virusse (influenza A and B, human parainfluenza 1-4, human coronavirus [OC43, 229E/NL63], human rhinovirus A, B and C, respiratory syncytial virus A and B, human enterovirus and human metapneumovirus). Resultate: Ons studie het verskeie bekende demografiese risikofaktore vir SUDI bevestig, byvoorbeeld „n ouderdomspiek tussen een en drie maande ouderdom, manlike predominansie, deel van „n bed met ander persone, slaap posisie op die maag, styf toedraai in warm komberse, blootstelling aan sigaretrook voor geboorte en sosio-ekonomiese faktore. Die Seeplex® RV15 Ace toets het tussen een en drie virusse geïdentifiseer in 59.5% (88/148) van die gevalle. Uit die 88 gevalle waarin virusse opgespoor was, was selgs een virus in 75% (66/88) van gevalle gevind en twee en drie virusse in 25% (22/88). Die mees algemene virusse was HRV in 77% (68/88) van gevalle, RSV in 18% (16/88) van gevalle en HCoV in 14% (12/88) van gevalle. Baie van die virusse wat tydens hierdie studie ondersoek was, was ingesluit in die roetine selkultuur toets wat deel vorm van die standaard medies-geregtelike laboratoriumondersoeke in alle SUDI gevalle by die Tygerberg lykshuis, alhoewel die selkulture positief was in slegs 9.5% (14/148) van gevalle. Ons het gevind dat baie respiratoriese virusse potensieel gemisdiagnoseer word wat „n rol kon speel in of bydra tot die dood van sommige SUDI gevalle. Gevolgtrekking: In sommige gevalle waarin SIDS geklassifiseer is as die oorsaak van dood, kan die virusse wat met PKR toetse opgespoor is nie geïgnoreer word nie, veral waar die bevinding ondersteun word deur histologiese bewyse van infeksie. Ons stel dus voor dat die gebruik van PKR toetse die oorsaak van dood klassifikasie kan verander van SIDS na Infeksie in sommige van hierdie gevalle. Verdere navorsing is nodig om die waarde van gelyktydige opsporing van virusse in SUDI gevalle te bepaal wanneer daar geen noemenswaardige histologiese bewyse van infeksie gevind word nie. Dit bevraagteken of die PKR toets dalk te sensitief is en gevolglik vorige en latente virusinfeksies identifiseer wat nie noodwendig 'n rol in die oorsaak van dood speel nie. Die diagnostiese en kliniese waarde van die histologiese beeld in terme van die rol van virusinfeksies as bydraende oorsaak van dood moet verder ondersoek word, veral in jong kinders wie se immuunstelsels nog nie volledig ontwikkel is nie. Indien die werklike voorkoms van virusse in SUDI gevalle en die virus-spesifieke immuunrespons nie bepaal word nie, sal die rol van virus-spesifieke infeksies in hierdie sindroom grootliks onbekend bly. / Harry Crossley Foundation / Poliomyelitis Research Foundation (PRF) / National Health Laboratory Services Research Trust