Sugnet Gardner-Lubbe’s research while affiliated with Stellenbosch University and other places

Background Lower respiratory tract infections (LRTIs) in infants are caused by viral and bacterial infections. We investigated associations between LRTI and nasopharyngeal (NP) viruses and bacteria in South African infants. Methods In a birth cohort, LRTI cases were identified prospectively and age-matched with controls. NP swabs were tested using polymerase chain reaction and 16S RNA gene sequencing. We calculated adjusted conditional odds ratios (aORs) and used mixed-effects models to identify differentially abundant taxa and explore viral–bacterial interactions. Results A total of 888 case-control samples were tested. Respiratory syncytial virus (RSV) (aOR, 5.69 [95% confidence interval, 3.03–10.69]), human rhinovirus (HRV) (1.47 [1.03–2.09]), parainfluenza virus (3.46 [1.64–7.26]), adenovirus (1.99 [1.08–3.68]), enterovirus (2.32 [1.20–4.46]), Haemophilus influenzae (1.72 [1.25–2.37]), Klebsiella pneumoniae (2.66 [1.59–4.46]), and high-density Streptococcus pneumoniae (1.53 [1.01–2.32]) were associated with LRTI. LRTI was associated with decreased relative abundance of Dolosigranulum (q = .001), Corynebacterium (q = .091), and Neisseria (q = .004). In samples positive for RSV, Staphylococcus and Alloprevotella relative abundance was higher in controls compared to cases. In samples positive for parainfluenza virus or HRV, Haemophilus relative abundance was higher in cases. Detection of cytomegalovirus (CMV) in controls was associated with reduced Corynebacterium, Dolosigranulum, and Staphylococcus. Conclusions The associations between bacteria, viruses and LRTIs are similar to those from high-income countries. Haemophilus is a major bacterial driver of LRTIs, acting synergistically with viruses. Dolosigranulum and Corynebacterium may reduce LRTI risk, while Staphylococcus may reduce the risk of RSV-related LRTIs. CMV is associated with dysbiotic nasopharyngeal microbiota.

Introduction: Depletion of Lactobacillus species and an overgrowth of anaerobes in the vaginal tract bacterial vaginosis (BV)], is associated with non-optimal reproductive health outcomes, and increased susceptibility to sexually transmitted infections (STIs). BV is currently treated with antibiotics, although these provide suboptimal cure levels and high recurrence rates. Vaginal microbiota transplantation (VMT), the transfer of vaginal fluid from healthy donors with an optimal vaginal microbiota to a recipient with BV, has been proposed as an alternative treatment strategy. Methods: Here, we investigated knowledge and perceptions of blood donors to the concept of an optimal vaginal microbiome and VMT via the Western Cape Blood Service (WCBS) clinics in Cape Town, South Africa, by a self-administered questionnaire. Results & discussion: Analysis of responses from 106 eligible women showed that 86% (91/106) would consider donating samples. Responses significantly associated with willingness to donate vaginal samples included: (1) belief that helping others outweighs the inconvenience of donating vaginal sample (p = 1.093e-05) and (2) prior knowledge of the concept of a healthy vaginal microbiome (p = 0.001). Most potential donors (59/91; 65%) were willing to receive a VMT themselves if needed. Participants who were unwilling to donate vaginal samples (15/106; 14%) indicated that vaginal sample collection would be unpleasant and/or embarrassing. The benefits of a collaboration with WCBS for this project include the naturally altruistic nature of blood donors, the constant in-flow of donors to WCBS clinics, and the infrastructure and logistical aspects in place. Data from this observational study highlight factors affecting the willingness of blood donors to become vaginal sample donors.

Background The complexity of contexts and varied purposes for which biome donation are requested are unknown in South Africa. Objectives The aim of this study was to provide strategic data towards actualisation of whether a stool donor bank may be established as a collaborative between Western Cape Blood Services (WCBS) and the University of Cape Town (UCT). Method We designed a cross-sectional, questionnaire-based survey to determine willingness of WCBS blood donors to donate stool specimens for microbiome biobanking. The study was conducted between 01 June 2022 and 01 July 2022 at three WCBS donation centres in Cape Town, South Africa. Anonymous blood donors who met the inclusion criteria were enrolled. Anonymised demographic and interview data were analysed statistically. Results Analysis of responses from 209/231 blood donors demonstrated in a logistic regression model that compensation (p < 0.001) and ‘societal benefit outweighs inconvenience’ beliefs (p = 7.751e-05) were covariates significantly associated with willingness to donate stool. Age was borderline significant at a 5% level (p = 0.0556). Most willing stool donors indicated that donating stool samples would not affect blood donations (140/157, 90%). Factors decreasing willingness to donate were stool collection being unpleasant or embarrassing. Conclusion The survey provides strategic data for the establishment of a stool bank and provided an understanding of the underlying determinants regarding becoming potential donors. Contribution This is the first report on the perspectives of potential participants in donating samples towards a stool microbiome biobank in South Africa, a necessity for faecal microbiota transplantation (FMT).

Background Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. Methods In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Results Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03–10.69], human rhinovirus (HRV) [1.47, 1.03–2.09], parainfluenza virus [3.46, 1.64–7.26], adenovirus [1.99, 1.08–3.68], enterovirus [2.32, 1.20–4.46], Haemophilus influenzae [1.72, 1.25–2.37], Klebsiella pneumoniae [2.66, 1.59–4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01–2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. Conclusions The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. Funding National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L’Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

Canonical variate analysis (CVA) entails a two-sided eigenvalue decomposition. When the number of groups, J , is less than the number of variables, p , at most $J-1$ J - 1 eigenvalues are not exactly zero. A CVA biplot is the simultaneous display of the two entities: group means as points and variables as calibrated biplot axes. It follows that with two groups the group means can be exactly represented in a one-dimensional biplot but the individual samples are approximated. We define a criterion to measure the quality of representing the individual samples in a CVA biplot. Then, for the two-group case we propose an additional dimension for constructing an optimal two-dimensional CVA biplot. The proposed novel CVA biplot maintains the exact display of group means and biplot axes, but the individual sample points satisfy the optimality criterion in a unique simultaneous display of group means, calibrated biplot axes for the variables, and within group samples. Although our primary aim is to address two-group CVA, our proposal extends immediately to an optimal three-dimensional biplot when encountering the equally important case of comparing three groups in practice.

Grapevine bunch rot assessment has economic significance to wineries. Industrial working conditions require rapid assessment methods to meet the time constraints typically associated with grape intake at large wineries. Naturally rot-affected and healthy white wine grape bunches were collected over five vintages (2013 to 2016, 2020). Spectral data of 382 grape must samples were acquired using three different, but same-type attenuated total reflection mid-infrared (ATR-MIR) ALPHA spectrometers. The practical industrial problem of wavenumber shifts collected with different spectrometers was overcome by applying functional data analysis (FDA). FDA improved the data quality and boosted data mining efforts in the sample set. Canonical variate analysis (CVA) biplots were employed to visualise the detection and quantification of rot. When adding 90 % alpha-bags to CVA biplots minimal overlap between rot-affected (Yes) and healthy (No) samples was observed. Several bands were observed in the region 1734 cm-1 to 1722 cm-1 which correlated with the separation between rot-affected and healthy grape musts. These bands connect to the C=O stretching of the functional groups of carboxylic acids. In addition, wavenumber 1041 cm-1, presenting the functional group of ethanol, contributed to the separation between categories (severity % range). ATR-MIR could provide a sustainable alternative for rapid and automated rot assessment. However, qualitative severity quantification of rot was limited to only discriminating between healthy and severe rot (> 40 %). This study is novel in applying FDA to correct wavenumber shifts in ATR-MIR spectral data. Furthermore, visualisation of the viticultural data set using CVA biplots is a novel application of this technique.

Background Tuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management have been established. TSC is, however, also associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND) that are typically under-identified and under-treated yet associated with a profound burden of disease. The contemporary evidence base for the identification and treatment of TAND is much more limited and, to date, consensus recommendations for the diagnosis and management of TAND have also been limited and non-specific. Methods The TANDem project was launched with an international, interdisciplinary, and participatory consortium of 24 individuals, including TSC family representatives, from all World Health Organization (WHO) regions but one. One of the aims of the TANDem project was to generate consensus recommendations for the identification and treatment of TAND. At the time of this project, no internationally adopted standard methodology and methodological checklists existed for the generation of clinical practice recommendations. We therefore developed our own systematic procedure for evidence review and consensus-building to generate evidence-informed consensus recommendations of relevance to the global TSC community. Results At the heart of the consensus recommendations are ten core principles surrounded by cluster-specific recommendations for each of the seven natural TAND clusters identified in the literature (autism-like, dysregulated behavior, eat/sleep, mood/anxiety, neuropsychological, overactive/impulsive, and scholastic) and a set of wraparound psychosocial cluster recommendations. The overarching recommendation is to “screen” for TAND at least annually, to “act” using appropriate next steps for evaluation and treatment, and to “repeat” the process to ensure early identification and early intervention with the most appropriate biological, psychological, and social evidence-informed approaches to support individuals with TSC and their families. Conclusions The consensus recommendations should provide a systematic framework to approach the identification and treatment of TAND for health, educational, social care teams and families who live with TSC. To ensure global dissemination and implementation of these recommendations, partnerships with the international TSC community will be important. One of these steps will include the generation of a “TAND toolkit” of “what to seek” and “what to do” when difficulties are identified in TAND clusters.

Background: Tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) are often present but underidentified and undertreated in individuals with tuberous sclerosis complex (TSC). The clinician-completed TAND-Lifetime Checklist (TAND-L) was developed to address this identification and treatment gap. Stakeholder engagement identified the need for a TAND Checklist that can (1) be completed by caregivers or individuals with TSC and (2) quantify TAND difficulties. The aim of this study was to develop a self-report quantified TAND Checklist (TAND-SQ) and conduct feasibility and acceptability testing. Methods: This aim was addressed in three phases: (1) development of the TAND-SQ Checklist, (2) feasibility and acceptability testing of the "near-final" TAND-SQ Checklist, and (3) preparation of the final TAND-SQ Checklist. Participants included 23 technical experts from the TAND consortium in all phases and 58 lived experts (caregivers and individuals with TSC) in phase 2. All participants completed a TAND-SQ Checklist and a checklist feedback form. Results: Phase 1 additions to the TAND-SQ, when compared with the TAND-L, included four new items and a quantification rating. Phase 2 showed high ratings for the "near-final" TAND-SQ Checklist on comprehensiveness, clarity, ease of use, and overall acceptability. In phase 3, questions on strengths, strategies, and a TAND Cluster Profile were added. Conclusion: The TAND-SQ Checklist is presented here for use by individuals with TSC and their caregivers. The next steps as part of the TANDem project include internal and external validation of the checklist and linking of TAND Cluster Profiles generated from the checklist to evidence-informed consensus recommendations within a smartphone application.