Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules

<p>Abstract</p> <p>Background</p> <p>Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa. Isoniazid prophylaxis can reduce tuberculosis incidence in this population. However, for the treatment to be effective, adherence to the medication must be optimized. We investigated adherence to isoniazid prophylaxis administered daily, compared to three times a week, and predictors of adherence amongst HIV-infected children.</p> <p>Methods</p> <p>We investigated adherence to study medication in a two centre, randomized trial comparing daily to three times a week dosing of isoniazid. The study was conducted at two tertiary paediatric care centres in Cape Town, South Africa. Over a 5 year period, we followed 324 HIV-infected children aged ≥ 8 weeks. Adherence information based on pill counts was available for 276 children. Percentage adherence was calculated by counting the number of pills returned. Adherence ≥ 90% was considered to be optimal. Analysis was done using summary and repeated measures, comparing adherence to the two dosing schedules. Mean percentage adherence (per child during follow-up time) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90% in each group. For repeated measures, percentage adherence (per child per visit) was dichotomized at 90%. A logistic regression model with generalized estimating equations, to account for within-individual correlation, was used to evaluate the impact of the dosing schedule. Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants.</p> <p>Results</p> <p>The overall adherence to isoniazid was excellent, with a mean adherence of 94.7% (95% confidence interval [CI] 93.5-95.9); similar mean adherence was achieved by the group taking daily medication (93.8%; 95% CI 92.1-95.6) and by the three times a week group (95.5%; 95% CI 93.8-97.2). Two-hundred and seventeen (78.6%) children achieved a mean adherence of ≥ 90%. Adherence was similar for daily and three times a week dosing schedules in univariate (odds ratio [OR] 0.88; 95% CI 0.66-1.17; <it>P </it>= 0.38) and multivariate (adjusted OR 0.85; 95% CI 0.64-1.11; <it>P </it>= 0.23) models. Children from overcrowded homes were less adherent (adjusted OR 0.71; 95% CI 0.54-0.95; <it>P </it>= 0.02). Age at study visit was predictive of adherence, with better adherence achieved in children older than 4 years (adjusted OR 1.96; 95% CI 1.16-3.32; <it>P </it>= 0.01).</p> <p>Conclusion</p> <p>Adherence to isoniazid was excellent regardless of the dosing schedule used. Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing, without compromising adherence or efficacy.</p> <p>Trial registration</p> <p>Clinical Trials NCT00330304</p

Incidence and severity of childhood pneumonia in the first year of life in a South African birth cohort: the Drakenstein Child Health Study

Background Childhood pneumonia causes substantial mortality and morbidity. Accurate measurements of pneumonia incidence are scarce in low-income and middle-income countries, particularly after implementation of pneumococcal conjugate vaccine. We aimed to assess the incidence, severity, and risk factors for pneumonia in the fi rst year of life in children enrolled in a South African birth cohort. Methods This birth cohort study is being done at two sites in Paarl, a periurban area of South Africa. We enrolled pregnant women (>18 years) and followed up mother–infant pairs to 1 year of age. We obtained data for risk factors and respiratory symptoms. Children received 13-valent pneumococcal conjugate vaccine according to national immunisation schedules. We established pneumonia surveillance systems and documented episodes of ambulatory pneumonia and pneumonia warranting hospital admission. We calculated incidence rate ratios for pneumonia with mixed-eff ects Poisson regression. Findings Between May 29, 2012 and May 31, 2014, we enrolled 697 infants who accrued 513 child-years of follow-up. We recorded 141 pneumonia episodes, with an incidence of 0·27 episodes per child-year (95% CI 0·23–0·32). 32 (23%) pneumonia cases were severe pneumonia, with an incidence of 0·06 episodes per child-year (95% CI 0·04–0·08). Two (1%) of 141 pneumonia episodes led to death from pneumonia. Maternal HIV, maternal smoking, male sex, and malnutrition were associated with an increased incidence of pneumonia. Interpretation Pneumonia incidence was high in the fi rst year of life, despite a strong immunisation programme including 13-valent pneumococcal conjugate vaccine. Incidence was associated with pneumonia risk factors that are amenable to interventions. Prevention of childhood pneumonia through public health interventions to address these risk factors should be strengthened. Funding Bill & Melinda Gates Foundation, South African Thoracic Society, Federation of Infectious Diseases Societies of South Africa, and University of Cape Town

The status of alien bamboos in South Africa

CITATION: Canavan, S. et al. 2021. The status of alien bamboos in South Africa. South African Journal of Botany, 138:33-40. doi:10.1016/j.sajb.2020.11.027.The original publication is available at https://www.sciencedirect.com/journal/south-african-journal-of-botanyThe growing interest in commercial cultivation of bamboos (Poaceae subfamily Bambusoideae) has led to the introduction of new alien species into South Africa. The rate at which bamboos are being planted in South Africa is a cause for concern because of the impacts of bamboo invasions in other parts of the world. To understand the risks associated with new introductions and new plantings, we assess the outcomes of past introductions of bamboos into South Africa. To this end we: (1) produce an inventory of alien bamboo taxa; (2) assess the distribution of bamboos; (3) determine the rate of spread of bamboo at a site with a high density of naturalised stands; and (4) evaluate the current regulatory status of alien bamboos in South Africa. We used a combination of expert opinion, literature, historical records of populations, and public participation to produce a species list and locate populations of alien bamboos. We also attempted to confirm species identities using DNA barcoding. We found that 28 currently-accepted species of bamboo have been recorded in South Africa. However, we have little confidence in this estimate, as 20 of the species could not be confirmed or identified as present in the country. Bamboos are an inherently challenging group to identify using vegetative material, and DNA barcoding was inconclusive. The distribution of bamboos across the country varied with the type or lineage (e.g. herbaceous, tropical or temperate) and the source of information (e.g. herbarium records, in-field observation or public contribution). Although alien bamboos are naturalised at several sites, we found no large invasive stands nor evidence of widespread negative environmental impacts. Nonetheless, we recommend caution regarding future introductions of bamboos for commercial cultivation, as the nature of the plantings will likely differ from the historical situation in both the location, configuration, and the scale of cultivation, and as new species are likely to be introduced. We propose several changes to the current listing of bamboo taxa in national legislation pertaining to alien and invasive species.https://www.sciencedirect.com/science/article/pii/S0254629920311868?via%3DihubPublisher’s versio

Displaying desire and distinction in housing

The article discusses the significance of cultural capital for the understanding of the field of housing in contemporary Britain. It explores the relationship between housing and the position of individuals in social space mapped out by means of a multiple correspondence analysis. It considers the material aspects of housing and the changing contexts that are linked to the creation and display of desire for social position and distinction expressed in talk about home decoration as personal expression and individuals' ideas of a `dream house'. It is based on an empirical investigation of taste and lifestyle using nationally representative survey data and qualitative interviews. The article shows both that personal resources and the imagination of home are linked to levels of cultural capital, and that rich methods of investigation are required to grasp the significance of these normally invisible assets to broaden the academic understanding of the field of housing in contemporary culture

Unresolved native range taxonomy complicates inferences in invasion ecology : Acacia dealbata Link as an example

CITATION: Hirsch, H. et al. 2017. Unresolved native range taxonomy complicates inferences in invasion ecology : acacia dealbata Link as an example. Biological Invasions, 19(6):1715-1722. doi:10.1007/s10530-017-1381-9The original publication is available at https://www.springer.com/journal/10530Elaborate and expensive endeavours are underway worldwide to understand and manage biological invasions. However, the success of such efforts can be jeopardised due to taxonomic uncertainty. We highlight how unresolved native range taxonomy can complicate inferences in invasion ecology using the invasive tree Acacia dealbata in South Africa as an example. Acacia dealbata is thought to comprise two subspecies based on morphological characteristics and environmental requirements within its native range in Australia: ssp. dealbata and spp. subalpina. Biological control is the most promising option for managing invasive A. dealbata populations in South Africa, but it remains unknown which genetic/taxonomic entities are present in the country. Resolving this question is crucial for selecting appropriate biological control agents and for identifying areas with the highest invasion risk. We used species distribution models (SDMs) and phylogeographic approaches to address this issue. The ability of subspecies-specific and overall species SDMs to predict occurrences in South Africa was also explored. Furthermore, as non-overlapping bioclimatic niches between the two taxonomic entities may translate into evolutionary distinctiveness, we also tested genetic distances between the entities using DNA sequencing data and network analysis. Both approaches were unable to differentiate the two putative subspecies of A. dealbata. However, the SDM approach revealed a potential niche shift in the non-native range, and DNA sequencing results suggested repeated introductions of different native provenances into South Africa. Our findings provide important information for ongoing biological control attempts and highlight the importance of resolving taxonomic uncertainties in invasion ecology.Publisher’s versio

Pancreatic Epithelial IL17/IL17RA Signaling Drives B7-H4 Expression to Promote Tumorigenesis

IL17 is required for the initiation and progression of pancreatic cancer, particularly in the context of inflammation, as previously shown by genetic and pharmacological approaches. However, the cellular compartment and downstream molecular mediators of IL17-mediated pancreatic tumorigenesis have not been fully identified. This study examined the cellular compartment required by generating transgenic animals with IL17 receptor A (IL17RA), which was genetically deleted from either the pancreatic epithelial compartment or the hematopoietic compartment via generation of IL17RA-deficient (IL17-RA-/-) bone marrow chimeras, in the context of embryonically activated or inducible Kras. Deletion of IL17RA from the pancreatic epithelial compartment, but not from hematopoietic compartment, resulted in delayed initiation and progression of premalignant lesions and increased infiltration of CD8+ cytotoxic T cells to the tumor microenvironment. Absence of IL17RA in the pancreatic compartment affected transcriptional profiles of epithelial cells, modulating stemness, and immunological pathways. B7-H4, a known inhibitor of T-cell activation encoded by the gene Vtcn1, was the checkpoint molecule most upregulated via IL17 early during pancreatic tumorigenesis, and its genetic deletion delayed the development of pancreatic premalignant lesions and reduced immunosuppression. Thus, our data reveal that pancreatic epithelial IL17RA promotes pancreatic tumorigenesis by reprogramming the immune pancreatic landscape, which is partially orchestrated by regulation of B7-H4. Our findings provide the foundation of the mechanisms triggered by IL17 to mediate pancreatic tumorigenesis and reveal the avenues for early pancreatic cancer immune interception. See related Spotlight by Lee and Pasca di Magliano, p. 1130

A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection

Abstract Background Autosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced. Case presentation Two half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.1128-1G>A, in the proband and his mother and was later confirmed in his half-brother. Conclusions Children with BCG vaccine complications in SSA should be referred for further investigation and particular consideration of MSMD

Ecological disequilibrium drives insect pest and pathogen accumulation in non-native trees

CITATION: Crous, C. J., et al. 2017. Ecological disequilibrium drives insect pest and pathogen accumulation in non-native trees. AoB PLANTS, 9(1):1-16, doi:10.1093/aobpla/plw081.The original publication is available at https://academic.oup.com/aobplaNon-native trees have become dominant components of many landscapes, including urban ecosystems, commercial forestry plantations, fruit orchards and as invasives in natural ecosystems. Often, these trees have been separated from their natural enemies (i.e. insects and pathogens) leading to ecological disequilibrium, that is, the immediate breakdown of historically co-evolved interactions once introduced into novel environments. Long-established, non-native tree plantations provide useful experiments to explore the dimensions of such ecological disequilibria. We quantify the status quo of non-native insect pests and pathogens catching up with their tree hosts (planted Acacia, Eucalyptus and Pinus species) in South Africa, and examine which native South African enemy species utilize these trees as hosts. Interestingly, pines, with no confamilial relatives in South Africa and the longest residence time (almost two centuries), have acquired only one highly polyphagous native pathogen. This is in contrast to acacias and eucalypts, both with many native and confamilial relatives in South Africa that have acquired more native pathogens. These patterns support the known role of phylogenetic relatedness of non-native and native floras in influencing the likelihood of pathogen shifts between them. This relationship, however, does not seem to hold for native insects. Native insects appear far more likely to expand their feeding habits onto non-native tree hosts than are native pathogens, although they are generally less damaging. The ecological disequilibrium conditions of non-native trees are deeply rooted in the eco-evolutionary experience of the host plant, co-evolved natural enemies and native organisms from the introduced range. We should expect considerable spatial and temporal variation in ecological disequilibrium conditions among non-native taxa, which can be significantly influenced by biosecurity and management practices.https://academic.oup.com/aobpla/article/9/1/plw081/2737455Publisher's versio