Browsing by Author "La Grange, Heleen"

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    Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life
    (American Society for Microbiology, 2013-01) Reikie, Brian A.; Naidoo, Shalena; Ruck, Candice E.; Slogrove, Amy L.; De Beer, Corena; La Grange, Heleen; Adams, Rozanne C. M.; Ho, Kevin; Smolen, Kinga; Speert, David P.; Cotton, Mark F.; Preiser, Wolfgang; Esser, Monika; Kollmann, Tobias R.
    HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following theWHOextended program on immunization (EPI). Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.
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    Diagnostic options for investigating viral respiratory pathogens in sudden unexpected death in infancy (SUDI) cases
    (JSciMed Central, 2014) De Beer, Corena; La Grange, Heleen
    Sudden and unexpected deaths in infants have occurred for centuries. It has generally been referred to as sudden infant death syndrome (SIDS). A new concept, called sudden unexpected death in infancy (SUDI) was introduced in 1989, which is used for all unexpected deaths in infants and babies, usually during sleep, where fatal injury can be excluded. By definition, cases that remain unexplained after thorough investigation are still classified as SIDS. Many risk factors have been associated with SUDI, e.g. poor socioeconomic conditions and prenatal care, multiple pregnancies, parental drug use and smoking, gender, low birth weight, recent infection and the sleeping environment. Ultimately, SUDI is most probably a result of a combination of predisposing factors, external stresses and underlying vulnerabilities, although the exact mechanism of death remains unknown. Viral infections are common in infants and have repeatedly been implicated in SUDI. Respiratory infections occur frequently in infancy and early childhood and inflammatory changes in the respiratory tract in SUDI cases is often found. Different diagnostic approaches for investigating respiratory viruses in SUDI cases have been reported in the literature, but in the absence of standardised SUDI investigation protocols, research from different centres cannot be compared. Viral viability is compromised in post-mortem samples and results should be interpreted with care, as the mere presence of a pathogen does not confirm that to be the cause of death. It is therefore imperative to use a combination of diagnostic approaches in parallel with epidemiological and clinical information in SUDI cases.
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    Respiratory 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.