Comparison of ADAMTS13 and Von Willebrand factor levels and activities, and plasminogen levels, in plasma products currently available for the treatment of thrombotic thrombocytopenic purpura in South Africa.

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) results from a deficiency in the Von Willebrand factor (VWF) cleaving protease, ADAMTS13. Treatment involves plasma exchange (PEX) therapy with either fresh frozen plasma (FFP), cryosupernatant (CSP) or solvent/detergent-treated plasma (SDP), available in South Africa as Bioplasma FDP. The aim of the study was to generate in vitro data on these products, and to explore possible differences between the products that may offer treatment advantages. METHODS: Twenty samples per product (FFP, CSP and Bioplasma FDP) were analysed for levels and activities of ADAMTS13 and VWF. Plasminogen levels, a proposed physiological back-up system for ADAMTS13, were also determined. FFP and CSP samples were subanalysed according to ABO blood group. Samples were analysed by means of commercially available ELISA assays. RESULTS: All samples had normal/high ADAMTS13 activity (Median activity for SDP = 94.0%, CSP = 80.5%, FFP = 122.0%) and plasminogen levels. The VWF content was mostly normal for Bioplasma FDP, typically deficient for CSP and mostly deficient for FFP, which was an unexpected finding. Depending on the parameter, Bioplasma FDP was the most standardised, with coefficients of variation (CV) from 14.1% to 27.3%, while FFP showed great inter-individual variation (CV 24.6% to 208.6%). Statistically significant differences were found across products (P ≤ 0.0095), and ABO blood groups (P = 0.0001). CONCLUSION: All three products can be used for the treatment of TTP. The choice of product depends on the need for additional viral safety, costs, product availability and the perceived impact of within-product variations.

[Erythroderma revealing IPEX syndrome]. / Érythrodermie révélatrice d'un syndrome IPEX.

BACKGROUND: Primary immunodeficiencies are rare and frequently life-threatening conditions in the first year of life. They may present with isolated skin manifestations and the absence of other clinical signs may delay diagnosis and management of the disease. Herein we describe a case of IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome) that illustrates this situation. PATIENTS AND METHODS: A 2.5-month-old boy was seen with a psoriasiform eruption. Despite applications of topical steroids, skin lesions progressed to severe exfoliative ichtyosiform erythroderma. A skin biopsy showed keratinocyte necrosis with a dense, epidermotropic, lymphocytic CD8+ infiltrate. The infant presented increased serum IgE and eosinophilia. He developed an enteropathy with severe and profuse diarrhea, septicemia and hypovolemic shock that led to sudden cardiac arrest. DNA analysis revealed a mutation in the FOXP3 gene, confirming IPEX syndrome. A favorable outcome was achieved following allogeneic bone marrow transplant. DISCUSSION: IPEX syndrome is characterized by early secretory enteropathy with profuse diarrhea, dermatitis and diabetes mellitus. Onset usually occurs within the first weeks or months of life, and the natural course of the disease is often lethal. Cutaneous manifestations appear to be mostly eczematiform, psoriasiform or ichthyosiform. These may be the first sign of the disease and a common inflammatory skin disorder may be wrongly diagnosed. The severity of the lesions and their limited response to topical steroids should alert the clinician. CONCLUSION: The early onset of severe cutaneous manifestations with persistent lesions and poor response to topical steroids should lead to an early skin biopsy. If histopathological changes show a cytotoxic lymphocytic infiltrate with keratinocyte necrosis, a diagnosis of primary immunodeficiency must be considered enabling rapid intitation of specific management.

Magnetotactic bacteria used to generate electricity based on Faraday's law of electromagnetic induction.

Magnetotactic bacteria (MTB) have the unique ability to produce magnetic particles surrounded by a biomembrane to form the magnetosome organelle. Therefore, MTB have novel physical and magnetic properties and have consequently been used in several biotechnological applications. The magnetic properties of these micro-organisms and their magnetosomes have, however, never been used for the generation of electricity as described in this letter. Comparisons were made between, firstly, the electricity generated from purified magnetosomes, MTB culture (bacterial cells with magnetosomes) and sterile, liquid growth medium (control). Secondly, the electricity generated by a dilution series of purified magnetosomes were compared. A statistically significant difference was found between the voltage measured from the purified magnetosomes (highest voltage), MTB culture (lower voltage) and liquid growth medium (lowest voltage). In the dilution series, the voltage measured increased as the magnetosome concentration increased, but only up to an optimum concentration (0·0376 mg ml-1 ). In this study, we have demonstrated that a significantly higher voltage than that of the control could be measured when MTB or purified magnetosomes were pumped through a solenoid by applying Faraday's law of electromagnetic induction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides proof-of-concept of electromagnetic induction using magnetosomes or magnetotactic bacteria in an experimental setup based on the law of Faraday. The concept of using these bacteria or their biomineralized magnetic nanoparticles as a biological alternative in low voltage electricity generation has the potential to be further explored and developed.

Edaravone N-benzyl pyridinium derivatives: BACE-1 inhibition, kinetics and in silico binding pose determination.

BACE-1 plays a pivotal role in the production of ß-amyloid (Aß) peptides, implicated in Alzheimer's Disease (AD) pathology. We previously described edaravone N-benzyl pyridinium derivatives (EBPDs) that exhibited multifunctional activity against multiple AD targets. In this study we explored the EBPDs BACE-1 inhibitory activity to potentially enhance the compounds therapeutic profile. The EBPDs exhibited moderate BACE-1 inhibitory activity (IC50 = 44.10 µM - 123.70 µM) and obtained IC50 values between 2.0 and 5.8-fold greater than resveratrol, a known BACE-1 inhibitor (IC50 = 253.20 µM), in this assay. Compound 3 was the most potent inhibitor with an IC50 of 44.10 µM and a Ki of 19.96 µM and a mixed-type mode of inhibition that favored binding in a competitive manner. Molecular docking identified crucial interactions with BACE-1 active site residues, supported by 100 ns MD simulations. The study highlighted the EBPDs therapeutic potential as BACE-1 inhibitors and multifunctional anti-AD therapeutic agents.

First line of defence: Eucalyptus leaf waxes influence infection by an aggressive fungal leaf pathogen.

Leaf epicuticular waxes provide important anatomical and chemical defences against fungi that infect leaves. In this study we analysed the leaf wax composition of Eucalyptus grandis × Eucalyptus urophylla hybrids with contrasting susceptibilities to Teratosphaeria leaf blight (TLB) caused by Teratosphaeria destructans, one of the most important foliar diseases of Eucalyptus. The Eucalyptus cuticular wax was extracted from non-inoculated and inoculated genotypes with different levels of susceptibility to TLB and analysed by gas chromatography-mass spectrometry. The results showed that a triterpenoid, cycloartenol (CAS), was abundant in a resistant genotype and that hexanedioic acid content increased in the resistant genotypes in response to T. destructans infection. In contrast, palmitic acid was significantly more abundant in the inoculated highly susceptible genotype. In-vitro and in-planta T. destructans spore germination assays with pure compounds, showed that CAS and hexanedioic acid significantly inhibited spore germination. Application of these two compounds to the leaves of a susceptible host also significantly increased resistance to infection. In contrast, palmitic acid promoted spore germination and, when applied to the leaves of a resistant genotype, increased colonization by the pathogen. This is the first study providing insights into differences in the leaf wax composition of hosts with different levels of susceptibility to T. destructans. It also showed that leaf wax compounds can modulate spore germination and, ultimately, host resistance to infection.

Tissue ontogeny and chemical composition influence bacterial biodiversity in the wood and shoot tip of Populus nigra.

Plant-microbe interactions significantly influence plant growth dynamics and adaptability. This study explores the impact of metabolites on microbial biodiversity in shoot tips and wood of Populus nigra under greenhouse conditions, using high-throughput sequencing and metabolite profiling. Branches from P. nigra were harvested, rooted, and transplanted into pots for growth. After 3 months, tissue samples from shoot tips and wood were collected, and metabolites extracted and analysed using GC-MS and LC-MS. Genomic DNA was extracted and subjected to high-throughput sequencing for bacterial biodiversity profiling. Both datasets were analysed using bioinformatic and statistical pipelines. Metabolite profiling indicated that shoot tips had a higher relative abundance of primary and secondary metabolites, including sugars, fatty acids, organic acids, phenolic acid derivatives and salicinoids, while wood was enriched in flavonoids. Bacterial biodiversity also differed significantly between these tissues, with Clostridiales, Bacteroidales and Bacillales dominating in shoot tips, associated with rapid growth and anaerobic fermentation, while wood tissues were characterized by diazotrophs from Rhizobiales, Sphingomonadales and Frankiales. PCoA clustering confirmed tissue-specific microbial differences. Functional analysis revealed an enrichment of fundamental cellular processes in shoot tips, while wood exhibited pathways related to degradation and mortality. Metabolite profiling revealed significant variations in primary and secondary metabolites, highlighting their influence on microbial biodiversity across plant tissues. The dominance of specific bacterial orders and distinct functional pathways in each tissue suggests a tailored microbial response to the unique environments of shoot tips and wood.

Use of the passive lower lingual arch in the management of anterior mandibular crowding in the mixed dentition.

Leeway space preservation in the mixed dentition is a well-documented method of space management. In the mandibular arch it may be saved for utilisation in the correction of minor anterior crowding by the placement of a passive lower lingual arch (LLA) during the transition from the mixed dentition to the permanent dentition.

The thrombin generation capability of the Chacma baboon (Papio ursinus): implications for haemostatic disease models.

Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated intravascular coagulation, and their potential treatment with novel drugs. Thrombin generation is vital for these models, and an important potential therapeutic target. We investigated the thrombin generation profile of the Chacma baboon (Papio ursinus - a common pre-clinical model) including the effects of sex and ABO blood group. Thrombin generation curves, lag times, peak heights, times-to-peak, velocity indexes and Endogenous Thrombin Potentials (ETPs) of 40 adult Chacma baboons were assessed and compared with normal human plasma, using a low concentration of tissue factor (1 pM) and phospholipids. Reference intervals were calculated, and results compared between O and non-O ABO blood groups, and between males and females. Lag times of all baboons fell within the human reference interval. Most animals (n = 32; 80%) had times-to-peak above, and velocity indexes and peak heights markedly below (n = 27; 68%) the human range. However, 97.5% of baboons had an ETP above the human reference interval, indicating greater overall thrombin generation. ABO blood group had no effect, but males (n = 14; 35%) had less potent thrombin generation than females (n = 26; 65%), with significantly longer lag times (p = 0.0475), lower peak thrombin concentrations (p = 0.0203), and lower ETPs (p = 0.0238). Chacma baboons have greater overall endogenous thrombin generation potentials than humans, which is even more prominent in females. This should be considered when designing future baboon model experiments involving the haemostatic system, or when evaluating novel therapies in these animals.

Estimating the changing burden of disease attributable to alcohol use in South Africa for 2000, 2006 and 2012.

BACKGROUND: Alcohol use was one of the leading contributors to South Africa (SA)'s disease burden in 2000, accounting for 7% of deaths and disability-adjusted life years (DALYs) in the first South African Comparative Risk Assessment Study (SACRA1). Since then, patterns of alcohol use have changed, as has the epidemiological evidence pertaining to the role of alcohol as a risk factor for infectious diseases, most notably HIV/AIDS and tuberculosis (TB). OBJECTIVES: To estimate the burden of disease attributable to alcohol use by sex and age group in SA in 2000, 2006 and 2012. METHODS: The analysis follows the World Health Organization (WHO)'s comparative risk assessment methodology. Population attributable fractions (PAFs) were calculated from modelled exposure estimated from a systematic assessment and synthesis of 17 nationally representative surveys and relative risks based on the global review by the International Model of Alcohol Harms and Policies. PAFs were applied to the burden of disease estimates from the revised second South African National Burden of Disease Study (SANBD2) to calculate the alcohol-attributable burden for deaths and DALYs for 2000, 2006 and 2012. We quantified the uncertainty by observing the posterior distribution of the estimated prevalence of drinkers and mean use among adult drinkers (≥15 years old) in a Bayesian model. We assumed no uncertainty in the outcome measures. RESULTS: The alcohol-attributable disease burden decreased from 2000 to 2012 after peaking in 2006, owing to shifts in the disease burden, particularly infectious disease and injuries, and changes in drinking patterns. In 2012, alcohol-attributable harm accounted for an estimated 7.1% (95% uncertainty interval (UI) 6.6 - 7.6) of all deaths and 5.6% (95% UI 5.3 - 6.0) of all DALYs. Attributable deaths were split three ways fairly evenly across major disease categories: infectious diseases (36.4%), non-communicable diseases (32.4%) and injuries (31.2%). Top rankings for alcohol-attributable DALYs for specific causes were TB (22.6%), HIV/AIDS (16.0%), road traffic injuries (15.9%), interpersonal violence (12.8%), cardiovascular disease (11.1%), cancer and cirrhosis (both 4%). Alcohol remains an important contributor to the overall disease burden, ranking fifth in terms of deaths and DALYs. CONCLUSION: Although reducing overall alcohol use will decrease the burden of disease at a societal level, alcohol harm reduction strategies in SA should prioritise evidence-based interventions to change drinking patterns. Frequent heavy episodic (i.e. binge) drinking accounts for the unusually large share of injuries and infectious diseases in the alcohol-attributable burden of disease profile. Interventions should focus on the distal causes of heavy drinking by focusing on strategies recommended by the WHO's SAFER initiative.

Estimating the changing burden of disease attributable to high fasting plasma glucose in South Africa for 2000, 2006 and 2012.

BACKGROUND: Worldwide, higher-than-optimal fasting plasma glucose (FPG) is among the leading modifiable risk factors associated with all- cause mortality and disability-adjusted life years (DALYs) due to the direct sequelae of diabetes and the increased risk for cardiovascular and chronic kidney disease. OBJECTIVES: To report deaths and DALYs of health outcomes attributable to high FPG by age and sex for South Africa (SA) for 2000, 2006 and 2012. METHODS: Comparative risk assessment methodology was used to estimate the burden attributable to high FPG. A meta-regression analysis was performed using data from national and small-area studies to estimate the population distribution of FPG and diabetes prevalence. Attributable fractions were calculated for selected health outcomes and applied to local burden estimates from the second South African National Burden of Disease Study (SANBD2). Age-standardised rates were calculated using World Health Organization world standard population weights. RESULTS: We estimated a 5% increase in mean FPG from 5.31 (95% confidence interval (CI) 5.18 - 5.43) mmol/L to 5.57 (95% CI 5.41 - 5.72) mmol/L and a 75% increase in diabetes prevalence from 7.3% (95% CI 6.7 - 8.3) to 12.8% (95% CI 11.9 - 14.0) between 2000 and 2012. The age-standardised attributable death rate increased from 153.7 (95% CI 126.9 - 192.7) per 100 000 population in 2000 to 203.5 (95% CI 172.2 - 240.8) per 100 000 population in 2012, i.e. a 32.4% increase. During the same period, age-standardised attributable DALY rates increased by 43.8%, from 3 000 (95% CI 2 564 - 3 602) per 100 000 population in 2000 to 4 312 (95% CI 3 798 - 4 916) per 100 000 population in 2012. In each year, females had similar attributable death rates to males but higher DALY rates. A notable exception was tuberculosis, with an age-standardised attributable death rate in males double that in females in 2000 (14.3 v. 7.0 per 100 000 population) and 2.2 times higher in 2012 (18.4 v. 8.5 per 100 000 population). Similarly, attributable DALY rates were higher in males, 1.7 times higher in 2000 (323 v. 186 per 100 000 population) and 1.6 times higher in 2012 (502 v. 321 per 100 000 population). Between 2000 and 2012, the age-standardised death rate for chronic kidney disease increased by 98.3% (from 11.7 to 23.1 per 100 000 population) and the DALY rate increased by 116.9% (from 266 to 578 per 100 000 population). CONCLUSION: High FPG is emerging as a public health crisis, with an attributable burden doubling between 2000 and 2012. The consequences are costly in terms of quality of life, ability to earn an income, and the economic and emotional burden on individuals and their families. Urgent action is needed to curb the increase and reduce the burden associated with this risk factor. National data on FPG distribution are scant, and efforts are warranted to ensure adequate monitoring of the effectiveness of the interventions.

Estimating the changing burden of disease attributable to high body mass index in South Africa for 2000, 2006 and 2012.

BACKGROUND: A high body mass index (BMI) is associated with several cardiovascular diseases, diabetes and chronic kidney disease, cancers, and other selected health conditions. OBJECTIVES: To quantify the deaths and disability-adjusted life years (DALYs) attributed to high BMI in persons aged ≥20 years in South Africa (SA) for 2000, 2006 and 2012. METHODS: The comparative risk assessment (CRA) methodology was followed. Meta-regressions of the BMI mean and standard deviation from nine national surveys spanning 1998 - 2017 were conducted to provide estimates by age and sex for adults aged ≥20 years. Population attributable fractions were calculated for selected health outcomes using relative risks identified by the Global Burden of Disease Study (2017), and applied to deaths and DALY estimates from the second South African National Burden of Disease Study to estimate the burden attributed to high BMI in a customised Microsoft Excel workbook. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. BMI was assumed to follow a log-normal distribution, and the theoretical minimum value of BMI below which no risk was estimated was assumed to follow a uniform distribution from 20 kg/m2 to 25 kg/m2. RESULTS: Between 2000 and 2012, mean BMI increased by 6% from 27.7 kg/m2 (95% confidence interval (CI) 27.6 - 27.9) to 29.4 kg/m2 (95% CI 29.3 - 29.5) for females, and by 3% from 23.9 kg/m2 (95% CI 23.7 - 24.1) to 24.6 kg/m2 (95% CI 24.5 - 24.8) for males. In 2012, high BMI caused 58 757 deaths (95% uncertainty interval (UI) 46 740 - 67 590) or 11.1% (95% UI 8.8 - 12.8) of all deaths, and 1.42 million DALYs (95% UI 1.15 - 1.61) or 6.9% (95% UI 5.6 - 7.8) of all DALYs. Over the study period, the burden in females was ~1.5 - 1.8 times higher than that in males. Type 2 diabetes mellitus became the leading cause of death attributable to high BMI in 2012 (n=12 382 deaths), followed by hypertensive heart disease (n=12 146), haemorrhagic stroke (n=9 141), ischaemic heart disease (n=7 499) and ischaemic stroke (n=4 044). The age-standardised attributable DALY rate per 100 000 population for males increased by 6.6% from 3 777 (95% UI 2 639 - 4 869) in 2000 to 4 026 (95% UI 2 831 - 5 115) in 2012, while it increased by 7.8% for females from 6 042 (95% UI 5 064 - 6 702) to 6 513 (95% UI 5 597 - 7 033). CONCLUSION: Average BMI increased between 2000 and 2012 and accounted for a growing proportion of total deaths and DALYs. There is a need to develop, implement and evaluate comprehensive interventions to achieve lasting change in the determinants and impact of overweight and obesity, particularly among women.

Estimating the burden of disease attributable to a diet low in fruit and vegetables in South Africa for 2000, 2006 and 2012.

BACKGROUND: Low intake of fruit and vegetables is associated with an increased risk of various non-communicable diseases, including major causes of death and disability such as cardiovascular disease, diabetes mellitus and cancers. Diets low in fruit and vegetables are prevalent in the South African (SA) population, and average intake is well below the internationally recommended threshold. OBJECTIVES: To estimate the burden of disease attributable to a diet low in fruit and vegetables by sex and age group in SA for the years 2000, 2006 and 2012. METHODS: We followed World Health Organization and Global Burden of Disease Study comparative risk assessment methodology. Population attributable fractions - calculated from fruit and vegetable intake estimated from national and local surveys and relative risks for health outcomes based on the current literature - were applied to the burden estimates from the second South African National Burden of Disease Study (SANBD2). Outcome measures included deaths and disability-adjusted life years (DALYs) lost from ischaemic heart disease, stroke, type 2 diabetes, and five categories of cancers. RESULTS: Between 2000 and 2012, the average intake of fruit of the SA adult population (≥25 years) declined by 7%, from 48.5 g/d (95% uncertainty interval (UI) 46.6 - 50.5) to 45.2 g/d (95% UI 42.7 - 47.6). Vegetable intake declined by 25%, from 146.9 g/d (95% UI 142.3 - 151.8) to 110.5 g/d (95% UI 105.9 - 115.0). In 2012, these consumption patterns are estimated to have caused 26 423 deaths (95% UI 24 368 - 28 006), amounting to 5.0% (95% UI 4.6 - 5.3%) of all deaths in SA, and the loss of 514 823 (95% UI 473 508 - 544 803) healthy life years or 2.5% (95% UI 2.3 - 2.6%) of all DALYs. Cardiovascular disease comprised the largest proportion of the attributable burden, with 83% of deaths and 84% of DALYs. Age-standardised death rates were higher for males (145.1 deaths per 100 000; 95% UI 127.9 - 156.2) than for females (108.0 deaths per 100 000; 95% UI 96.2 - 118.1); in both sexes, rates were lower than those observed in 2000 (-9% and -12%, respectively). CONCLUSION: Despite the overall reduction in standardised death rates observed since 2000, the absolute burden of disease attributable to inadequate intake of fruit and vegetables in SA remains of significant concern. Effective interventions supported by legislation and policy are needed to reverse the declining trends in consumption observed in most age categories and to curb the associated burden.

Prophylaxis is the new standard of care in patients with haemophilia.

Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with >2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this 'In Practice' article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.

Estimating the changing disease burden attributable to smoking in South Africa for 2000, 2006 and 2012.

BACKGROUND: Ongoing quantification of the disease burden attributable to smoking is important to monitor and strengthen tobacco control policies. OBJECTIVES: To estimate the attributable burden due to smoking in South Africa for 2000, 2006 and 2012. METHODS: We estimated attributable burden due to smoking for selected causes of death in South African (SA) adults aged ≥35 years for 2000, 2006 and 2012. We combined smoking prevalence results from 15 national surveys (1998 - 2017) and smoking impact ratios using national mortality rates. Relative risks between smoking and select causes of death were derived from local and international data. RESULTS: Smoking prevalence declined from 25.0% in 1998 (40.5% in males, 10.9% in females) to 19.4% in 2012 (31.9% in males, 7.9% in females), but plateaued after 2010. In 2012 tobacco smoking caused an estimated 31 078 deaths (23 444 in males and 7 634 in females), accounting for 6.9% of total deaths of all ages (17.3% of deaths in adults aged ≥35 years), a 10.5% decline overall since 2000 (7% in males; 18% in females). Age-standardised mortality rates (and disability-adjusted life years (DALYs)) similarly declined in all population groups but remained high in the coloured population. Chronic obstructive pulmonary disease accounted for most tobacco-attributed deaths (6 373), followed by lung cancer (4 923), ischaemic heart disease (4 216), tuberculosis (2 326) and lower respiratory infections (1 950). The distribution of major causes of smoking-attributable deaths shows a middle- to high-income pattern in whites and Asians, and a middle- to low-income pattern in coloureds and black Africans. The role of infectious lung disease (TB and LRIs) has been underappreciated. These diseases comprised 21.0% of deaths among black Africans compared with only 4.3% among whites. It is concerning that smoking rates have plateaued since 2010. CONCLUSION: The gains achieved in reducing smoking prevalence in SA have been eroded since 2010. An increase in excise taxes is the most effective measure for reducing smoking prevalence. The advent of serious respiratory pandemics such as COVID-19 has increased the urgency of considering the role that smoking cessation/abstinence can play in the prevention of, and post-hospital recovery from, any condition.

Overview.

BACKGROUND: South Africa (SA) faces multiple health challenges. Quantifying the contribution of modifiable risk factors can be used to identify and prioritise areas of concern for population health and opportunities for health promotion and disease prevention interventions. OBJECTIVE: To estimate the attributable burden of 18 modifiable risk factors for 2000, 2006 and 2012. METHODS: Comparative risk assessment (CRA), a standardised and systematic approach, was used to estimate the attributable burden of 18 risk factors. Risk exposure estimates were sourced from local data, and meta-regressions were used to model the parameters, depending on the availability of data. Risk-outcome pairs meeting the criteria for convincing or probable evidence were assessed using relative risks against a theoretical minimum risk exposure level to calculate either a potential impact fraction or population attributable fraction (PAF). Relative risks were sourced from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study as well as published cohort and intervention studies. Attributable burden was calculated for each risk factor for 2000, 2006 and 2012 by applying the PAF to estimates of deaths and years of life lost from the Second South African National Burden of Disease Study (SANBD2). Uncertainty analyses were performed using Monte Carlo simulation, and age-standardised rates were calculated using the World Health Organization standard population. RESULTS: Unsafe sex was the leading risk factor across all years, accounting for one in four DALYs (26.6%) of the estimated 20.6 million DALYs in 2012. The top five leading risk factors for males and females remained the same between 2000 and 2012. For males, the leading risks were (in order of descending rank): unsafe sex; alcohol consumption; interpersonal violence; tobacco smoking; and high systolic blood pressure; while for females the leading risks were unsafe sex; interpersonal violence; high systolic blood pressure; high body mass index; and high fasting plasma glucose. Since 2000, the attributable age-standardised death rates decreased for most risk factors. The largest decrease was for household air pollution (-41.8%). However, there was a notable increase in the age-standardised death rate for high fasting plasma glucose (44.1%), followed by ambient air pollution (7%). CONCLUSION: This study reflects the continued dominance of unsafe sex and interpersonal violence during the study period, as well as the combined effects of poverty and underdevelopment with the emergence of cardiometabolic-related risk factors and ambient air pollution as key modifiable risk factors in SA. Despite reductions in the attributable burden of many risk factors, the study reveals significant scope for health promotion and disease prevention initiatives and provides an important tool for policy makers to influence policy and programme interventions in the country.

The effects of streptokinase in a Chacma baboon (Papio ursinus) model of acquired thrombotic thrombocytopenic purpura.

TTP is a life-threatening disorder with limited pharmaceutical treatment options. Recently, the potential of streptokinase in the treatment of acquired TTP was demonstrated in humans in vitro, and in vivo in a mouse model. We aimed to determine the in vitro and in vivo effects of streptokinase in an established Papio ursinus model of acquired TTP. In vitro: VWF activities & multimer patterns and thromboelastograms were assessed with increasing concentrations of streptokinase. In vivo: After induction of TTP, escalating streptokinase doses (ranging from 50,000 to 900,000 IU) were administered, and the effects of streptokinase assessed on peripheral blood counts, fibrinolysis, VWF activities & multimer patterns and thromboelastograms. In an extension of the study, high-dose streptokinase (1,500,000-3,000,000 IU) was administered to another baboon. After spiking, fibrinolysis with loss of large VWF multimers was observed at [2200 IU/mL]-roughly equivalent to 1,500,000 IU. However, administration of escalating intravenous streptokinase doses had no in vivo effect on the TTP phenotype, and in vivo increases in plasmin activity were mild when compared with baseline, even at high doses. Minimal effect on VWF multimer patterns was observed but only at doses ≥ 1500,000 IU. Streptokinase is not effective in resolving TTP in a Papio ursinus model of TTP, possibly due to limited activation of the baboon fibrinolytic system. Modifications to this model, the use of alternative higher animal models, or alternative thrombolytics, should be considered to establish proof-of-concept.

Heparin-induced thrombocytopenia: An update for the COVID-19 era.

The increased use of heparin during the current COVID-19 pandemic has highlighted the risk of a rare but potentially serious complication of heparin therapy, viz. heparin-induced thrombocytopenia (HIT). This is a short review on the pharmacology of heparin and its derivatives, and the pathophysiology of HIT. Guidance on laboratory testing for and clinical management of HIT is presented in accordance with international guidelines. There are important similarities and differences between HIT and the new entity of vaccine-induced immune thrombotic thrombocytopenia, also known as thrombosis with thrombocytopenia syndrome, which clinicians need to be aware of.

Clinical determinants of migraine preventive treatment: contribution of SMILE, an observational survey of primary care migraine management in France.

METHODS: SMILE was an observational study carried out in France among office-based general practitioners (GPs) and neurologists from November 2005 to July 2006 to assess the determinants of prescription of migraine preventive therapy in primary care medicine. A total of 1467 GPs and 83 neurologists were included, treating 5417 and 248 migraine sufferers, respectively. RESULTS: The main factors leading physicians to deem a patient eligible for preventive treatment were perceived medication overuse and frequency of headaches, and secondarily, severity of headaches and functional impact. On the other hand, patient satisfaction with the acute treatment of attacks and triptan use, and secondarily, a long migraine history were found to influence patient eligibility negatively. DISCUSSION/CONCLUSION: Noticeably, psychiatric disorders (anxiety, stress) did not appear, aside from somatic factors, among the determinants that significantly influence physicians' judgment about the option of establishing a preventive treatment. However, they are important features of migraine condition and should be listed among the factors guiding choices about migraine preventive therapy.

First Report of Aster Yellows Phytoplasma in Grapevines in South Africa.

For many years phytoplasma diseases have caused serious losses in most of the major grape-growing regions of the world, except South Africa, where a mixed phytoplasma infection was first reported in 2006 (1). During the early growing season of 2006, symptoms consistent with phytoplasma disease were observed in vineyards in the Olifants River Valley. Symptoms included yellowing of leaves, incomplete lignification of shoots, shortening of internodes, and the abortion of growth tips and immature bunches. Symptomatic shoots and leaves from grapevine cultivars (Merlot, Shiraz, Cabernet Sauvignon, Ruby Cabernet, Pinotage, Corinth, Chardonnay, Columbar, Chenin blanc, Sauvignon blanc, Sultana, and Regal) were collected during the early growing season (November) of 2006, 2007, and 2008. Total DNA was extracted from 32 of these samples (from single plants in the same vineyards over the 3 years) with the Invisorb Spin Plant Mini Kit (Invitek, Berlin, Germany) and tested by nested PCR using two universal primer pairs, P1/P7 and R16F2n/R16R2 (3). The first round of PCR of the 2006 samples yielded 1.8-kb fragments for 17 of the samples, while the nested PCR yielded an additional seven positive samples, confirming the necessity of nested PCR for reliable diagnosis. A similar trend was observed in the 2007 and 2008 PCR test results. All asymptomatic plants, which were included as negative controls, and water controls were negative by nested PCR. Twenty-four 1,245-bp amplicons, generated by nested PCR, were excised from gels, purified with a NucleoSpin Extract II Kit (Macherey-Nagel, Düren, Germany) and directly sequenced. Sequence data was compiled with the BioEdit Version 7.0.4.1 sequence alignment editor software (2), aligned using ClustalW Version 1.4 (4), and a consensus sequence was generated (GenBank Accession No. GQ365729). A BLAST search of the NCBI GenBank database using the individual sequences revealed high sequence identities (≥99%) with the aster yellows phytoplasma group (16SrI) and specifically with the subgroup 16SrI-B. In a comparison of the sequences of the 1.2-kb PCR fragments of 24 local samples with each other, sequence identities of ~99% were observed. These results clearly illustrate that all vines screened were infected with the same phytoplasma. Single nucleotide differences observed between different isolates may indicate the presence of closely related sequence variants of this phytoplasma. Aster yellows occurs worldwide and has been reported to infect grapevine-South Africa can now be added to this list. During the three seasons of our study, the area in which symptomatic vineyards were observed increased significantly, indicating spread by a biological vector. Moreover, infected vineyards were noticed in two other South African grape-growing regions. In contrast to the previous report, which reported a mixed infection of phytoplasmas of groups 16SrXII-A and 16SrII-B (1), PCR screening and sequencing of more than 40 individual samples from these areas confirmed these all to be infected with aster yellows phytoplasma only. To our knowledge, this is the first report of the detection and identification of an aster yellows phytoplasma causing grapevine yellows disease in South Africa. References: (1) S. Botti and A. Bertaccini. Plant Dis. 90:1360, 2006. (2) T. A. Hall. Nucleic Acids. Symp. Ser. 41:95, 1999. (3) I.-M. Lee et al. Phytopathology 83:834, 1993. (4) J. D. Thompson et al. Nucleic Acids Res. 22:4673, 1994.

[Management of stroke in sub-Saharan Africa: current issues]. / Prise en charge des accidents vasculaires cérébraux en Afrique subsaharienne.

In sub-Saharan Africa, stroke is likely to present an increasingly important public health problem with a larger relative share of overall morbidity and mortality. Overall, sub-Saharan Health Care is characterized by a lack of human resources, lack of facilities for special investigations, and especially an absence of specific programs addressing the prevention of cardiovascular conditions. Current data on the epidemiology of stroke in sub-Saharan Africa, although sparse and fragmentary, indicate a comparatively high incidence of cerebral hemorrhage associated with high blood pressure, while ischemic stroke in black Africans still appears to be related primarily to small artery disease, HIV infection, and sickle cell disease. With urbanization, the role of large-vessel atherosclerosis is increasing. It is thus essential to coordinate government funding, health care professionals and development agencies to address this rising health problem. Access to health care needs to be better structured, and screening programs should be developed in order to identify and treat vascular risk factors. Improved training of health care professionals is also required in the areas of prevention, diagnosis and management of stroke. Implementation of best-practice recommendations for the management of stroke adapted to the specificities and resources of African countries would help rationalize the scarce resources currently available.