ClassTR: Classifying Within-Host Heterogeneity Based on Tandem Repeats with Application to Mycobacterium tuberculosis Infections.

Genomic tools have revealed genetically diverse pathogens within some hosts. Within-host pathogen diversity, which we refer to as "complex infection", is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis. Complex infection arises through two mechanisms: within-host mutation (which results in clonal heterogeneity) and reinfection (which results in mixed infections). Estimates of the frequency of within-host mutation and reinfection in populations are critical for understanding the natural history of disease. These estimates influence projections of disease trends and effects of interventions. The genotyping technique MLVA (multiple loci variable-number tandem repeats analysis) can identify complex infections, but the current method to distinguish clonal heterogeneity from mixed infections is based on a rather simple rule. Here we describe ClassTR, a method which leverages MLVA information from isolates collected in a population to distinguish mixed infections from clonal heterogeneity. We formulate the resolution of complex infections into their constituent strains as an optimization problem, and show its NP-completeness. We solve it efficiently by using mixed integer linear programming and graph decomposition. Once the complex infections are resolved into their constituent strains, ClassTR probabilistically classifies isolates as clonally heterogeneous or mixed by using a model of tandem repeat evolution. We first compare ClassTR with the standard rule-based classification on 100 simulated datasets. ClassTR outperforms the standard method, improving classification accuracy from 48% to 80%. We then apply ClassTR to a sample of 436 strains collected from tuberculosis patients in a South African community, of which 92 had complex infections. We find that ClassTR assigns an alternate classification to 18 of the 92 complex infections, suggesting important differences in practice. By explicitly modeling tandem repeat evolution, ClassTR helps to improve our understanding of the mechanisms driving within-host diversity of pathogens like Mycobacterium tuberculosis

Common laboratory investigations in obstetrics and gynaecology

No Abstract

Synergies, tensions and challenges in HIV prevention, treatment and cure research: exploratory conversations with HIV experts in South Africa

Background: The ethical concerns associated with HIV prevention and treatment research have been widely explored in South Africa over the past 3 decades. However, HIV cure research is relatively new to the region and significant ethical and social challenges are anticipated. There has been no published empirical enquiry in Africa into key informant perspectives on HIV cure research. Consequently, this study was conducted to gain preliminary data from South African HIV clinicians, researchers and activists. Methods: In-depth interviews were conducted on a purposive sample of fourteen key informants in South Africa. Audiotaped interviews were transcribed verbatim with concurrent thematic analysis. The perspectives of HIV clinicians, researchers and activists were captured. Analyst triangulation occurred as the data were analysed by three authors independently. Results: The rapid evolution of HIV cure research agendas was prominent with participants expressing some concern that the global North was driving the cure agenda. Participants described a symbiotic relationship between cure, treatment and prevention research necessitating collaboration. Assessing and managing knowledge and expectations around HIV cure research emerged as a central theme related to challenges to constructing ‘cure’ - how patients understand the idea of cure is important in explaining the complexity of cure research especially in the South African context where understanding of science is often challenging. Managing expectations and avoiding curative misconception will have implications for consent processes. Unique strategies in cure research could include treatment interruption, which has the potential to create therapeutic and ethical conflict and will be perceived as a significant risk. Ethical challenges in cure research will impact on informed consent and community engagement. Conclusions: It was encouraging to note the desire for synergy amongst researchers and clinicians working in the fields of prevention, treatment and cure. Translation of complex HIV cure science into lay language is critical. Moving forward, RECs must be adequately constituted with scientific expertise and community representation when reviewing cure protocols. It is hoped that knowledge and resource sharing in the context of collaboration between research scientists working in cure and those working in treatment and prevention will accelerate progress towards cur

Cobalt removal from wastewater using pine sawdust

Agricultural wastes can cause environmental problems if not well managed, but there is a lot of potential to use these wastes as raw material in other processes. In this investigation, pine sawdust was evaluated as an adsorbent in the treatment of wastewater containing cobalt ions. A two-level three-factor full-factorial experimental design with centre points was used to study the interactive effect of the operating parameters in order to achieve the best conditions for the batch adsorption of cobalt ions. A response surface analysis was also conducted to further understand the interactions amongst the factors such as adsorbent dose, solution pH and initial concentration. In addition, adsorption isotherms, namely the Freundlich and Langmuir, were used to characterize the removal of cobalt from the wastewater. It was observed that the combined effect of low adsorbent dose, high pH and high initial concentration of wastewater resulted in the highest adsorption capacity. The Freundlich isotherm provided a better fit to the experimental data than the Langmuir isotherm. Moreover, pine sawdust showed adsorption capabilities for cobalt, and hence it could be an option in the quest to use waste to treat wastewater

Pituitary function tests in black patients with pseudocyesis

Pituitary function was evaluated in a group of 10 patients with pseudocyesis. One patient was postmenopausal; the remainder demonstrated normal basal prolactin, luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels and also normal pituitary-adrenal, pituitary-thyroid axes. Oestradiol deficiency was present in 6 patients, while 2 patients demonstrated elevated serum progesterone values, suggestive of a luteal phase. Gonadotrophin-releasing hormone administration resulted in exaggerated stimulation of LH and FSH in 4 and 2 patients, respectively. Impaired growth hormone (GH) secretion was present in 6 patients after insulin-induced hypoglycaemia and L-dopa administration. GH impairment is probably a consequence of the oestrogen deficiency that commonly occurs in this condition. It thus appears that there are aberrations in specific pituitary hormone responses after provocation in pseudocyesis

Asthma control - Practical suggestions for practicing doctors in family practice

Many surveys of asthma care suggest that only 5% of asthmatics are meeting the ‘Goals of asthma management' as set out in the Global Initiative for Asthma (GINA) guidelines. Despite the availability of useful asthma therapies and treatment strategies, the morbidity from asthma has remained significant. This review includes practical suggestions on optimal asthma control for the family practitioner. South African Family Practice Vol. 50 (2) 2008: pp. 26-3

The value of pimecrolimus in improving quality of life of children with severe eczema – an open non-randomised study

Background: Atopic eczema is a common skin condition. It has the potential to severely impair quality of life in affected children. Pimecrolimus is currently registered for mild-moderate eczema but in clinical practice children with more severe disease are often treated with this therapy in an attempt to find a safe addition to long-term topical corticosteroid usage. The aim of this study was to test the value of pimecrolimus in improving quality of life in children with severe atopic eczema.Methods: This a single site, phase 4, non-randomised, open label trial of pimecrolimus use in children aged 4 months to 12 years living withmoderate to very severe atopic eczema. The study was conducted at Steve Biko Academic Hospital. Patients with unsatisfactorily controlled disease despite conventional topical therapy, adequate use of emollients, allergen avoidance and non-pharmacological skin hygiene were enrolled. A ParentIndex Quality of Life Questionnaire was completed by parents before and three months after using pimecrolimus.Results: A total of 24 patients were recruited, 20 of whom completed the study. Ninety per cent of patients had co-morbid asthma and allergicrhinitis. The Parent Index Quality of Life demonstrated a mean 33% score improvement after the use of pimecrolimus. There was an attendant reduction in cost of therapy to these patients.Conclusions: Pimecrolimus usage should be extended to patients with more severe atopic eczema as the improvement in quality of life is important and demonstrable.Keywords: severe eczema; topical steroids; calcineurin inhibitors; pimecrolimus; quality of lif

Second-stage primary Caesarean deliveries: Are maternal complications increased?

Background: Second-stage Caesarean sections (CSs) are known to be associated with increased complications but most reports originate fromtertiary hospitals, which attend to high-risk patients. Complication rates may differ in district hospitals, which attend to low-risk patients.Methods: This was a retrospective study carried out at a district maternity unit in Durban. The hospital records of all CSs over an eight-month periodwere reviewed and obstetric and neonatal complications of second-stage CSs were compared with a group of first-stage CSs performed during thestudy period.Results: There were 4 654 deliveries, including 1 257 CSs, in the study period. The CS rate was 27.2%. Of 617 (8.5%) emergency CSs, 53 wereperformed in the second stage of labour.The maternal and neonatal complication rates were low and no statistical differences were found between the patients who had second-stage orthose who had first-stage CSs, except for increased blood loss, blood-stained urine, prolonged operative times and postoperative fever for secondstageCSs.Conclusions: Second-stage CSs performed in a district hospital are associated with increased maternal complication rates but not with neonatalcomplications

Consent for critical care research after death from COVID-19: Arguments for a waiver

Pandemics challenge clinicians and scientists in many ways, especially when the virus is novel and disease expression becomes variable or unpredictable. Under such circumstances, research becomes critical to inform clinical care and protect future patients. Given that severely ill patients admitted to intensive care units are at high risk of mortality, establishing the cause of death at a histopathological level could prove invaluable in contributing to the understanding of COVID-19. Postmortem examination including autopsies would be optimal. However, in the context of high contagion and limited personal protective equipment, full autopsies are not being conducted in South Africa (SA). A compromise would require tissue biopsies and samples to be taken immediately after death to obtain diagnostic information, which could potentially guide care of future patients, or generate hypotheses for finding needed solutions. In the absence of an advance written directive (including a will or medical record) providing consent for postmortem research, proxy consent is the next best option. However, obtaining consent from distraught family members, under circumstances of legally mandated lockdown when strict infection control measures limit visitors in hospitals, is challenging. Their extreme vulnerability and emotional distress make full understanding of the rationale and consent process difficult either before or upon death of a family member. While it is morally distressing to convey a message of death telephonically, it is inhumane to request consent for urgent research in the same conversation. Careful balancing of the principles of autonomy, non-maleficence and justice becomes an ethical imperative. Under such circumstances, a waiver of consent, preferably followed by deferred proxy consent, granted by a research ethics committee in keeping with national ethics guidance and legislation, would fulfil the basic premise of care and research: first do no harm. This article examines the SA research ethics framework, guidance and legislation to justify support for a waiver of consent followed by deferred proxy consent, when possible, in urgent research after death to inform current and future care to contain the pandemic in the public interest