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

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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

Comorbidity in context: Part 1. Medical considerations around HIV and tuberculosis during the COVID-19 pandemic in South Africa

Infectious diseases pandemics have devastating health, social and economic consequences, especially in developing countries such as South Africa. Scarce medical resources must often be rationed effectively to contain the disease outbreak. In the case of COVID-19, even the best-resourced countries will have inadequate intensive care facilities for the large number of patients needing admission and ventilation. The scarcity of medical resources creates the need for national governments to establish admission criteria that are evidence-based and fair. Questions have been raised whether infection with HIV or tuberculosis (TB) may amplify the risk of adverse COVID-19 outcomes and therefore whether these conditions should be factored in when deciding on the rationing of intensive care facilities. In light of these questions, clinical evidence regarding inclusion of these infections as comorbidities relevant to intensive care unit admission triage criteria is investigated in the first of a two-part series of articles. There is currently no evidence to indicate that HIV or TB infection on their own predispose to an increased risk of infection with SARS-CoV-2 or worse outcomes for COVID-19. It is recommended that, as for other medical conditions, validated scoring systems for poor prognostic factors should be applied. A subsequent article examines the ethicolegal implications of limiting intensive care access of persons living with HIV or TB

Comorbidity in context: Part 2. Ethicolegal considerations around HIV and tuberculosis during the COVID-19 pandemic in South Africa

The COVID-19 pandemic has brought discussions around the appropriate and fair rationing of scare resources to the forefront. This is of special importance in a country such as South Africa (SA), where scarce resources interface with high levels of need. A large proportion of the SA population has risk factors associated with worse COVID-19 outcomes. Many people are also potentially medically and socially vulnerable secondary to the high levels of infection with HIV and tuberculosis (TB) in the country. This is the second of two articles. The first examined the clinical evidence regarding the inclusion of HIV and TB as comorbidities relevant to intensive care unit (ICU) admission triage criteria. Given the fact that patients with HIV or TB may potentially be excluded from admission to an ICU on the basis of an assumption of lack of clinical suitability for critical care, in this article we explore the ethicolegal implications of limiting ICU access of persons living with HIV or TB. We argue that all allocation and rationing decisions must be in terms of SA law, which prohibits unfair discrimination. In addition, ethical decision-making demands accurate and evidence-based strategies for the fair distribution of limited resources. Rationing decisions and processes should be fair and based on visible and consistent criteria that can be subjected to objective scrutiny, with the ultimate aim of ensuring accountability, equity and fairness

Re-screening for syphilis at the time of delivery in areas ofhigh prevalence

Two hundred women who were screened for syphilis at their initial antenatal visit were rescreened at the time of delivery. Umbilical cord blood specimens as well as maternal sera were tested. Twenty-two (11%) women were rapid plasma reagin (RPR)-positive at booking, while a total of 23 (12%) were RPR-positive at the time of delivery, including an additional 5 (3%) who seroconverted. Four women who were RPR-positive at initial testing had become negative by the time of delivery following treatment. Of all neonates born to seropositive women, only 1 demonstrated clinical evidence of congenital syphilis. In view of the high seroconversion rate, we recommend screening for syphilis at the initial antenatal visit and rescreening at the time ofdelivery in areas such as ours