Masters Degrees (Medical Virology)
Permanent URI for this collection
Browse
Browsing Masters Degrees (Medical Virology) by browse.metadata.advisor "Dempers, Johan"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- ItemProfiling cardiovascular viral pathogens in cases of sudden and unexpected death in infants (SUDI) at the Tygerberg Medico-legal Mortuary and the role of myocarditis as a possible cause of death(Stellenbosch : Stellenbosch University., 2020-03) Venter, Michaela Lucienne; De Beer, Corena; Dempers, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH ABSTRACT: Introduction: Sudden unexpected death in infancy (SUDI) is a heterogeneous group in which pathological changes, when observed, can either be an adequate or non-conclusive cause of death (COD). A non-conclusive COD is referred to as Sudden Infant Death Syndrome (SIDS), which is postulated to be the result of multiple risk factors including infection. Viral heart infections, resulting in myocarditis, reportedly contribute to SUDI cases. Numerous viruses have been associated with myocarditis, with few ever having been investigated in a South African context. Aim: The study aimed to investigate the presence of three specific viruses in the heart of SUDI cases admitted to the Tygerberg Medico-legal Mortuary over a one-year period. Methodology: Swab samples of the left ventricle of the heart were collected from SUDI cases admitted to the Tygerberg Medico-legal Mortuary over the period of one year. Concurrently, swabs and tissue were retrieved for microbiological and histological analysis, respectively. Conventional qualitative polymerase chain reaction assays were used to detect three deoxyribonucleic acid viruses, namely human adenovirus (HAdV), human bocavirus (HBoV) and parvovirus B19 (PVB19), possibly linked to myocarditis. Clinical history, sociodemographic information and the final COD were collected from case files. All viral results were compared to the histology of the tissue. Associations were investigated between sociodemographic information and viral presence through statistical analysis in order to identify significant risk factors. Results: Heart swabs were collected from 173 SUDI case, consisting of 93 males and 80 females and a mean age of 12.1 ± 9.8 weeks. Over half of the SUDI cases occurred in the cold seasons. The majority of the cases were assigned Infection as a COD, with just under half assigned as SIDS. Only one virus, HBoV, was detected in the heart tissue with implications of myocarditis histologically observed in one of the viral positive SUDI cases. Bacterial presence was also confirmed in only one case. All viral infections were observed in the cold seasons. Risk factors were highlighted between variable associations. Significant associations were observed between prematurity, room ventilation, birthweight and the COD. Significant associations were also observed between microbiology results, histology and the temperature on the day of death. Conclusion: The study expanded the knowledge regarding myocardial infections contributing to SUDI in the study population, as well as significant risk factors. Viral detection in the myocardium, supported by histological evidence, provided an improved way of classifying COD as infection.
- ItemProfiling Enterovirus and Parvovirus B19 in sudden and unexpected death in infancy (SUDI) at the Tygerberg Medico-legal Mortuary and the role of myocarditis as a possible cause of death(Stellenbosch : Stellenbosch University, 2018-03) Saayman, Jamie Ester; De Beer, Corena; Dempers, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH SUMMARY: Background: Sudden infant death syndrome (SIDS) remains one of the leading causes of death among infants. The Triple-Risk Model has contributed to identifying modifiable risk factors that may lead to a reduction of SIDS occurrences. Cardiovascular infection contributes significantly to mortality and morbidity in children and adults. Acute myocarditis affects infants more severely than adults and has a known association with Coxsackie-B, Adeno-, parvo- B19, Epstein Barr-, Cytomegalo-, Human herpes-6 viruses. These viruses have been explored in sudden unexpected death in infancy (SUDI) and shown some association between SIDS and myocardial infection. Aim: This study aimed to describe two cardiovascular viruses in SUDI cases and to determine the association of myocarditis to these deaths. Methodology: Heart swab and tissue samples were prospectively collected from SUDI cases at the Tygerberg Medico-legal Mortuary over a one year period. The samples were collected in parallel with routine heart swabs for microbiology analysis and peripheral blood for HIV screening. The SUDI samples were additionally screened for enterovirus and parvovirus B19 by polymerase chain reaction assays. The heart tissue was processed for histological analysis. Sociodemographic information, medical history and final cause of death were obtained during the initial interview with family / caregiver(s) and from case files respectively, and potential risk factors in the SUDI population were identified from the data by statistical analysis. Results: Heart swab and tissue samples were collected from 168 and 161 SUDI cases respectively. The SUDI population consisted of 81 males and 87 females. Majority of deaths (64%) were in infants younger than 14 weeks and 67% occurred during the colder months of the year. In more than half of the cases an infectious cause of death was confirmed, while in 40% death was attributed to SIDS. There was a higher frequency of death among black infants, which is consistent with the literature, however it is not clinically relevant as it is not a representation of the general population profile in the Western Cape. The heart tissue for histology was within normal limits in all but 10 of 161 SUDI cases examined for morphological change associated with viral myocarditis, and 1 of these 10 cases was diagnosed as myocarditis as the final cause of death. The only significant risk factor identified in this population was ethnicity, but the finding was not clinically relevant. Conclusion: The results obtained from this study support the Triple-Risk Model of SIDS. The high proportion of deaths that remained unexplained (i.e. SIDS) emphasizes the need to introduce additional testing, such as molecular based tests which provide significant value when establishing a final cause of death. SIDS research in South Africa is limited and would be valuable in the forensic environment.
- ItemProfiling the approach to the investigation of viral infections in cases of Sudden Unexpected Death in Infancy (SUDI) in the Western Cape Province(Stellenbosch : University of Stellenbosch, 2011-03) Burger, Marilize Cornelle; De Beer, Corena; Dempers, Johan; University of Stellenbosch. Faculty of Health Sciences. Dept. of Pathology. Medical Virology.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.
- ItemA prospective study investigating the role of respiratory viral infections in Sudden Unexpected Death in Infancy (SUDI) at Tygerberg Medico-legal Mortuary(Stellenbosch : Stellenbosch University., 2020-03) Ferreira, Janca; De Beer, Corena; Dempers, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH ABSTRACT: Background: The current South African infant mortality rate is 22.1 per 1 000 live births with respiratory infections, pneumonia, influenza and interstitial lung infections being responsible for most infant deaths. Sudden Unexpected Death in Infancy (SUDI) includes all infant deaths between the age of 7 days and 1 year without an apparent cause before any investigation has occurred. However, cases that remain unexplained following thorough investigation are classified as Sudden Infant Death Syndrome (SIDS). SIDS is regarded as a disease in search of a cause with several interlinking risk factors. Numerous respiratory viruses have been detected from SUDI autopsy specimens, therefore, viral infections could contribute to some SUDI cases as an exogenous trigger on a vulnerable infant during a specific developmental stage. This might be due to the infants’ vulnerability to infections due to immaturities of their immune systems. Nonetheless, the exact contribution of respiratory viruses preceding death still needs further investigation. Objectives: The primary aim of this study was to investigate the role of major respiratory viruses, found in the lungs and trachea as either single or co-infections of all SUDI cases admitted to Tygerberg Medico-legal Mortuary (MLM) over a 1-year period. The secondary aim entailed collecting all the epidemiological information and other relevant laboratory data from the retrospective cases from the Tygerberg MLM (2015-2016) to assess any trends or differences between the 2 studies and to evaluate how risk factors associated with SUDI cases at the Tygerberg MLM might have differed or remained constant over 2 study periods. Finally, laboratory results from all infants aged between 7 days and 1 year admitted to Tygerberg Hospital (TBH) due to respiratory infections during the study period were retrieved in order to identify if similar single and multiple viruses were circulating in both populations. Methods: Between March 2018 and March 2019 samples were collected from 173 SUDI cases admitted to Tygerberg MLM. As part of the mandatory routine investigations into SUDI cases bacterial culture swabs were collected from the lower left and right lung lobes at autopsy to investigate the role of single and co-infections of viruses associated with SUDI. The Seegene AllplexTM RV Essential Assay one-step multiplex, real-time Polymerase Chain reaction (PCR) assay was used for the detection of 6 ribonucleic acid (RNA) respiratory viruses, Influenza A (Flu A), Influenza B (Flu B), Human Metapneumovirus (HMPV), Human Parainfluenza virus (HPIV), Respiratory syncytial virus A and B (RSVA/B) and Human Rhinovirus (HRV) from RNA extracted from lower left and right lung lobe and tracheal swabs. Tissue sections from the lower left and right lung lobes were also assessed for histology signs of infection. TIBCO Statistica® version 13.5.0 was used to identify any similarities or differences between the current prospective study and retrospective study, as well as the comparison group of infants admitted to TBH. Results: During this study multiple known demographic risk factors for SUDI, such as age (12.1 ± 9.8 weeks), male predominance, prematurity, low birthweight, cold season, bedsharing, prone sleeping position and ventilation were observed. With the AllplexTM RV Essential real-time PCR assay between 1 and 5 viruses were detected in 90.2% (156/173) of cases. RSV A/B (31.7%) and HRV (24.8%) were the most commonly detected viruses. The majority of PCR-positive cases were detected in the cold season, with a statistical significance observed for Flu A (p = 0.04), Flu B (p = 0.04), HPIV (p = 0.03) and RSV (p = 0.02) and cold season. The most frequently detected co-infection was between RSVA/B and HRV. Thirty-three cases had 2 viruses detected, 5 had 3 viruses and 1 case had 5 different viruses (Flu A - Flu B - HMPV - RSV A/B - HRV). The majority of cases had a cause of death (COD) of Infection. Furthermore, Flu A was significantly associated with the COD Infection and Flu B with SIDS. In 4 SIDS cases with positive histology, positive viral PCR results were observed leading to a change in COD to Infection. Major differences between the prospective and retrospective studies included female predominance, COD of SIDS, HRV being the most frequently detected virus and co-infection only being observed in 3 cases (Flu A - HRV, Flu B - HRV; HPIV - HRV - RSV A/B). The same viruses were circulating in SUDI cases and the comparison group. Conclusion: In cases that had a COD of SIDS, the PCR viruses detected cannot be ignored, especially when it is supported by histological signs of infection as seen during this study Therefore, the use of real-time PCR could alter a COD Classification from SIDS to Infection. However, the role of single or co-infection with respiratory viruses in SUDI cases wherein no histological sign of infection was observed requires further investigation. Future research is needed to determine the exact role of co-infections in those who succumb to SUDI, more specifically how viral interactions play a role in disease progression and severity in a vulnerable infant. Finally, research should be aimed at determining the effect of PCR-positive viral results in the absence of histology to identify the true cause of vulnerability in infants.
- ItemRespiratory infections and immune biomarkers of infection and inflammation in cases of Sudden Unexpected Death in Infancy (SUDI) at the Tygerberg Medico-legal Mortuary(Stellenbosch : Stellenbosch University, 2018-03) Matshazi, Don Makwakiwe; De Beer, Corena; Dempers, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Medical Virology.ENGLISH SUMMARY: infant death syndrome (SIDS) is the leading cause of infant death in the post-neonatal stage in developing and developed countries. A diagnosis of SIDS is made after medico-legal investigations fail to demonstrate an adequate cause of death in sudden unexpected death in infancy (SUDI) cases and SIDS is diagnosed in over 60% of SUDI cases. The peak incidence of SUDI is observed when infants are aged between two to four months. It is also at this stage that infants lose their maternally acquired immunity against infections. During medico-legal investigations in SUDI cases, viruses and bacteria have been confirmed, although none of them was consistently and exclusively associated with SUDI to date. Furthermore, viral respiratory symptoms are reported in 44% of SUDI cases, but the exact role they play in the events leading up to the death of the infant remains unknown. Viral infections can either facilitate easier bacterial colonisation of the respiratory system or induce an unregulated immune response through the release of cytokines and chemokines (immune biomarkers) that lead to formation of immune complexes in lungs and other respiratory organs. This could result in the loss of functionality and ultimately death of the infant. The role played by viruses and the interaction of the immune system in the events leading to SIDI therefore require further investigation to get a clearer understanding. Objectives: The first aim of this cross-sectional, descriptive study was to characterise the respiratory viruses observed in SUDI cases investigations at the Tygerberg Medico-Legal Mortuary using the Seeplex RV15 ACE detection multiplex PCR kit. The multiplex PCR viral detection results were compared to routine shell vial culture results to determine the superior viral detection method. The second aim was to assess 16 target immune biomarkers as indicators of infection or inflammation prior to or at the time of death of an infant. Methods: Samples were collected from 183 SUDI cases admitted to the Tygerberg Medico-Legal Mortuary between July 2015 and June 2016. Swabs collected from the trachea and left and right lungs were collected for multiplex PCR detection of 15 respiratory viruses. These viral targets were human adenovirus, human bocavirus, human coronavirus 229E/NL63, OC43, human enterovirus, influenza A and B, human metapneumovirus, human parainfluenza 1-4, respiratory syncytial virus A and B and human rhinovirus A/B/C. Serum was also collected for immune biomarker testing. Tissue from both lungs were collected for shell vial culture and blood was collected for HIV 1/2 antibody testing. Microbiology routine testing included culture of heart, left and right lung swab samples. Results: The gender distribution of infants in this study was not consistent with literature. There were 93 (50.8%) females and 90 (49.2%) males, although males have been identified as being at a greater risk of SUDI than females. However, other socio-demographic risk factors for SUDI, such as the greatest risk of death being at age two to four months were consistent with literature. The detection of viruses by multiplex PCR proved to be superior to SVC as the former detected viruses in more cases than the latter. The most commonly detected virus by multiplex PCR was human Rhinovirus A/B/C, which was detected in 65 (35.5%) of the 183 cases tested. Adenovirus was the second most frequently detected virus as it was present in 18 (12.6%) of the cases tested. Parainfluenza 3, Enterovirus and RSV B were detected in 10 (5.5%), 9 (4.9%) and 7 (3.8%) cases respectively. Human metapneumovirus was not detected at all by either assay. The serum concentrations of CRP and IL-6 were significantly elevated in the serum of SUDI cases where infection was the cause death compared to cases that were diagnosed as SIDS. However, levels of IL-18 were significantly reduced in the serum of SUDI cases where infection was the cause of death compared to cases with a final cause of death classification of SIDS. Conclusion: It is possible to change the cause of death from SIDS to infection if serum immune biomarker results and multiplex PCR are used in addition to tissue histology. The current study showed that serum CRP, IL-6 and IL-18 levels can possibly be regarded as candidates for use as indicators of infectious death and these findings need to be further investigated in larger study cohorts and over longer study periods.
- ItemRespiratory pathogens in cases of Sudden Unexpected Death in Infancy (SUDI) at Tygerberg forensic pathology service mortuary(Stellenbosch : Stellenbosch University, 2014-04) La Grange, Heleen; De Beer, Corena; Dempers, Johan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology, Medical Virology.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.