Analysis of time to regulatory and ethical approval of SATVI TB vaccine trials in South Africa

Background. Tuberculosis (TB) vaccine trials in South Africa must be approved by the Medicines Control Council (MCC) and by a human research ethics committee (HREC). Delays in regulatory and ethical approval may affect operational and budget planning and clinical development of the product. Aim. Our aim was to analyse the time to regulatory and ethical approval for TB vaccine trials conducted by the South African Tuberculosis Vaccine Initiative (SATVI) and to evaluate factors that influence time to final approval. Method. Sixteen new TB vaccine clinical trials conducted by SATVI between 2004 and 2012 on infants, children, and adults were included. The period between submission and final approval was determined for protocols submitted to the MCC and the University of Cape Town HREC. Results. Median approval time following first submission to the MCC was 122 days (IQR 112 - 168; range 71 - 350), and for protocol amendments 103 days (interquartile range (IQR) 76 - 141; range 23 - 191; n=30). Median time following first submission for HREC approval was 60 days (IQR 33 - 81; range 18 - 125), and for amendments 6 days (IQR 4 - 13; range 1 - 37; n=30). There was no significant difference in approval time by trial phase, year of submission, revisions required, study population, sample size, or whether a clinical research organisation (CRO) was used. Conclusion. The time needed for regulatory and ethics approval was highly variable, but MCC approval for first submissions took twice as long as HREC approval and was the primary determinant of time to final approval. National regulatory capacity should be strengthened to facilitate the conduct of new TB vaccine trials in this country with its high burden of TB

Traditional uses and local perspectives on baobab (Adansonia digitata) population structure by selected ethnic groups in northern Namibia

The aim of this study was to document local traditional uses on Adansonia digitata (baobab) among the Herero, Ovambo, San and Masubiya ethnic groups in northern Namibia. Data was collected by oral interviews using a semi-structured questionnaire. A total of 64 respondents were interviewed. Indigenous knowledge on baobab is transferred from older generations to younger generations through word of mouth. The information that was captured includes local traditional use and benefits of baobab, use value, and perceptions on baobab population dynamics. Findings from the current study revealed that baobab uses go beyond provision of food, medicine and spiritual needs in Namibia. It is also used as feed for chicken. The bark was also recorded to be useful as fodder during drought. The fruit is the most used part of the baobab, but the use value of bark was generally high among all ethnic groups. The study revealed that the Ovambo people use more baobab products than the Herero, San and Masubiya communities. Destructive uses of seeds were identified as a factor contributing to the lack of regeneration of baobab. It is recommended that destructive uses of baobab, especially use of seeds, need to be regulated to sustainable levels for conservation of baobab in Namibia. Furthermore, the benefits from the baobab tree need to be promoted in order to fully utilize its potential in improving livelihoods of rural communities in Namibia.http://www.elsevier.com/locate/sajb2018-11-01hj2018Plant Production and Soil Scienc

Risky behaviour and psychosocial correlates in adolescents - is there a link with tuberculosis?

Reasons for the increase in incidence of Tuberculosis (TB) in late adolescence are poorly understood. One hypothesis is that psychological and behavioural variables associated with adolescence may increase risk of developing TB. The study aimed to determine whether psychosocial and behavioural variables affect incidence of TB disease in adolescents. Methods: A case control study design was used in adolescents who were participants in a TB epidemiological study. Cases were adolescents diagnosed with TB disease. Approximately half of the controls had no TB disease but a positive TST indicative of latent TB. Half had neither TB disease nor latent TB. A self-administered questionnaire was completed by participants. The questionnaire consisted of a combination of standardised psychosocial instruments. Results: Of 292 participants, 62 were cases, 112 had latent TB and 118 neither TB disease nor latent TB. There were no significant differences in instrument scores between cases and controls. There was a trend for certain adverse life events to be more common in the TB-disease group. Conclusion: In adolescents, a trend for association between TB incidence and psychosocial and behavioural variables was not statistically significant. Given the trend, research with larger samples, and more comprehensive assessment of the relationship between stressors and TB, is warranted

Disturbance impacts on the persistence niche of key species in the Baikiaea–Guibourtia–Pterocarpus woodlands of north-western Zimbabwe

Please read abstract in the article.http://www.tandfonline.com/loi/tsfs20hj2023Plant Production and Soil Scienc

Extracellular Vesicles Secreted in Response to Cytokine Exposure Increase Mitochondrial Oxygen Consumption in Recipient Cells

Extracellular vesicles (EVs) are small, membrane-bound nanoparticles released from most, if not all cells, and can carry functionally active cargo (proteins, nucleic acids) which can be taken up by neighboring cells and mediate physiologically relevant effects. In this capacity, EVs are being regarded as novel cell-to-cell communicators, which may play important roles in the progression of neurodegenerative diseases, like Alzheimer’s disease (AD). Aside from the canonical physical hallmarks of this disease [amyloid β (Aβ) plaques, neurofibrillary tangles, and widespread cell death], AD is characterized by chronic neuroinflammation and mitochondrial dysfunction. In the current study, we sought to better understand the role of tumor necrosis factor-alpha (TNF-α), known to be involved in inflammation, in mediating alterations in mitochondrial function and EV secretion. Using an immortalized hippocampal cell line, we observed significant reductions in several parameters of mitochondrial oxygen consumption after a 24-h exposure period to TNF-α. In addition, after TNF-α exposure we also observed significant upregulation of two microRNAs (miRNAs; miR-34a and miR-146a) associated with mitochondrial dysfunction in secreted EVs. Despite this, when naïve cells are exposed to EVs isolated from TNF-α treated cells, mitochondrial respiration, proton leak, and reactive oxygen species (ROS) production are all significantly increased. Collectively these data indicate that a potent proinflammatory cytokine, TNF-α, induces significant mitochondrial dysfunction in a neuronal cell type, in part via the secretion of EVs, which significantly alter mitochondrial activity in recipient cells

Evolving Identification of Blood Cells Associated with Clinically Isolated Syndrome: Importance of Time since Clinical Presentation and Diagnostic MRI

It is not clear how the profile of immune cells in peripheral blood differs between patients with clinically isolated syndrome (CIS) and healthy controls (HC). This study aimed to identify a CIS peripheral blood signature that may provide clues for potential immunomodulatory approaches early in disease. Peripheral blood mononuclear cells (PBMCs) were collected from 18 people with CIS, 19 HC and 13 individuals with other demyelinating conditions (ODC) including multiple sclerosis (MS). Individuals with CIS separated into two groups, namely those with early (≤14 days post-diagnostic magnetic resonance imaging (MRI); n = 6) and late (≥27 days; n = 12) blood sampling. Transitional B cells were increased in the blood of CIS patients independently of when blood was taken. However, there were two time-dependent effects found in the late CIS group relative to HC, including decreased CD56bright NK cells, which correlated significantly with time since MRI, and increased CD141+ myeloid dendritic cell (mDC2) frequencies. Higher CD1c+ B cells and lower non-classical monocyte frequencies were characteristic of more recent demyelinating disease activity (ODC and early CIS). Analysing cell populations by time since symptoms (subjective) and diagnostic MRI (objective) may contribute to understanding CIS

Access to chloroquine in patients with rheumatic and musculoskeletal diseases attending rheumatology outpatient clinics during the COVID-19 pandemic

Herbal medicines made from the bark of the Cinchona tree, and later quinine, have been widely used for centuries to treat medical conditions such as tropical malaria. More recently, chloroquine (CQ) and its synthetic derivatives have been used as antimalarials and to treat systemic lupus erythematosus, rheumatoid arthritis, and in the past 14 months or so, COVID-19 pneumonia. Anecdotal evidence and the erratic covering through social media of its potential efficacy in the treatment of COVID-19 pneumonia have resulted in the widespread off-label use of CQ in South Africa and worldwide. This study aimed to show that access to CQ as a chronic medication for rheumatic and musculoskeletal diseases was limited during the COVID-19 pandemic, and that this resulted in an increased incidence of flares in these patients, affecting their morbidity and potentially leading to mortality

Analysis of time to regulatory and ethical approval of SATVI TB vaccine trials in South Africa

Background. Tuberculosis (TB) vaccine trials in South Africa must be approved by the Medicines Control Council (MCC) and by a human research ethics committee (HREC). Delays in regulatory and ethical approval may affect operational and budget planning and clinical development of the product. Aim. Our aim was to analyse the time to regulatory and ethical approval for TB vaccine trials conducted by the South African Tuberculosis Vaccine Initiative (SATVI) and to evaluate factors that influence time to final approval. Method. Sixteen new TB vaccine clinical trials conducted by SATVI between 2004 and 2012 on infants, children, and adults were included. The period between submission and final approval was determined for protocols submitted to the MCC and the University of Cape Town HREC. Results. Median approval time following first submission to the MCC was 122 days (IQR 112 - 168; range 71 - 350), and for protocol amendments 103 days (interquartile range (IQR) 76 - 141; range 23 - 191; n=30). Median time following first submission for HREC approval was 60 days (IQR 33 - 81; range 18 - 125), and for amendments 6 days (IQR 4 - 13; range 1 - 37; n=30). There was no significant difference in approval time by trial phase, year of submission, revisions required, study population, sample size, or whether a clinical research organisation (CRO) was used. Conclusion. The time needed for regulatory and ethics approval was highly variable, but MCC approval for first submissions took twice as long as HREC approval and was the primary determinant of time to final approval. National regulatory capacity should be strengthened to facilitate the conduct of new TB vaccine trials in this country with its high burden of TB

Sudanian versus Zambezian woodlands of Africa : composition, ecology, biogeography and use

The Sudanian woodlands (SW) and Zambezian woodlands (ZW) of Africa cover two extensive vegetation zones in Africa. The main question is how similar or different are their woodlands. This paper aims to synthesize available information on woodlands of the Sudanian (SR) and Zambezian (ZR) regions in terms of: i) their floristics and ecology, ii) main drivers of change, iii) their socio-economic relevance to local populations, and iv) how resource use affects the main drivers. This synthesis deals with 141 publications, including 94% research articles and books on Sudanian and Zambezian woodlands of Africa. Google Scholar's search engine were used. Inclusion criteria comprised the geographical focus (Sudanian and Zambezian regions), the ecosystem type (woodland), and the type of information reported in the studies (ecology, socio-economic and biogeography aspects). The overall results were categorized as addressing either ecological or socio-economic aspects of woodlands. The SW and ZW share a number of families, genera and species. The ZR counts at least 8500 plant species, of which 54% are endemic, while there are possibly no more than 2750 plant species in the SR. Three distinct woodland types are ecologically important and clearly differentiated in the ZW. However, combined effect of the wide tolerances of the species and the gradual change in the climate in the SZ, makes it difficult to recognize distinct woodland systems. The presence of great rifts and swells in the Zambezian part of Africa, explain in part the difference in the vegetation composition and the high diversity and plant endemism in the Zambezian zones. In both Regions, use of woodland and the associated ecological impacts are quite similar. Both biogeography and land use change explain the vegetation differences between the two regions. Knowledge of factors underlying vegetation adaptations and change provide a basis for sustainable resource use through integrated multiple-use systems.The University of Pretoria Postdoctoral Fellowship Programhttps://www.elsevier.com/locate/actoec2021-08-01hj2021Plant Production and Soil Scienc

Tree species composition and diversity in Miombo woodlands between co‐managed and government‐managed regimes, Malawi

Comparative information on the composition and diversity in tree species associations in Miombo woodland is limited. This study assessed how tree species associations across forest reserves of Miombo woodland in Malawi varied in composition and diversity concerning site factors and resource use disturbances under co‐management versus government management. Eighty nested circular plots, randomly selected in ArcGIS, were sampled to record stem diameter at breast height (DBH) of tree species: 0.04 ha for stems 5–29.9 cm DBH and 0.16 ha for stems ≥30 cm DBH. The recorded 109 tree species grouped into communities and 14 sub‐communities, using stem counts by species in TWINSPAN analysis. Sub‐divisions to level 5 showed eigenvalues ≥0.3, symbolising the stability of sub‐divisions. North/South sub‐divisions related to site factors; historical/current resource use influenced differences at levels 3–5. Species importance differed, indicating few important species in each sub‐community. Brachystegia and Julbernardia species showed importance across sub‐communities while Uapaca sansibarica in government management. Disturbances stimulated high species diversity. Recommendations include the need for a policy review towards group‐felling mature stands to stimulate regeneration and selective thinning of suppressed stems in stand development stages to maintain species diversity, productive recovery, diverse resource use value, and monitoring of harvesting impacts.Appendix A. Tree species names, families, species codes, and the number of stems per species recorded in each sampled forest reserve (FR) under co‐management (CM) and government management (GM) in Miombo woodland in Malawi.The African Forest Forum and Malawi Government.https://wileyonlinelibrary.com/journal/aje2021-11-07hj2021Plant Production and Soil Scienc