Impact of interventions for tuberculosis prevention and care in South Africa - a systematic review of mathematical modelling studies.

BACKGROUND: Substantial additional efforts are needed to prevent, find and successfully treat tuberculosis (TB) in South Africa (SA). In thepast decade, an increasing body of mathematical modelling research has investigated the population-level impact of TB prevention and careinterventions. To date, this evidence has not been assessed in the SA context. OBJECTIVE: To systematically review mathematical modelling studies that estimated the impact of interventions towards the World HealthOrganization's End TB Strategy targets for TB incidence, TB deaths and catastrophic costs due to TB in SA. METHODS: We searched the PubMed, Web of Science and Scopus databases for studies that used transmission-dynamic models of TB in SAand reported on at least one of the End TB Strategy targets at population level. We described study populations, type of interventions andtheir target groups, and estimates of impact and other key findings. For studies of country-level interventions, we estimated average annualpercentage declines (AAPDs) in TB incidence and mortality attributable to the intervention. RESULTS: We identified 29 studies that met our inclusion criteria, of which 7 modelled TB preventive interventions (vaccination,antiretroviral treatment (ART) for HIV, TB preventive treatment (TPT)), 12 considered interventions along the care cascade for TB(screening/case finding, reducing initial loss to follow-up, diagnostic and treatment interventions), and 10 modelled combinationsof preventive and care-cascade interventions. Only one study focused on reducing catastrophic costs due to TB. The highest impactof a single intervention was estimated in studies of TB vaccination, TPT among people living with HIV, and scale-up of ART. Forpreventive interventions, AAPDs for TB incidence varied between 0.06% and 7.07%, and for care-cascade interventions between 0.05%and 3.27%. CONCLUSION: We describe a body of mathematical modelling research with a focus on TB prevention and care in SA. We found higherestimates of impact reported in studies of preventive interventions, highlighting the need to invest in TB prevention in SA. However, studyheterogeneity and inconsistent baseline scenarios limit the ability to compare impact estimates between studies. Combinations, rather thansingle interventions, are likely needed to reach the End TB Strategy targets in SA.

Prevalence of overweight and obesity among African primary school learners: a systematic review and meta-analysis.

INTRODUCTION: The increasing trend in the global prevalence of childhood overweight and obesity presents a major public health challenge. This study reports the results of a systematic review and meta-analysis to estimate the prevalence of overweight and obesity among primary school learners residing in Africa according to the different body mass index criteria and population level characteristics. METHODS: A search of multiple databases was conducted to identify relevant research articles published between January 1980 and February 2017. Random effects models were used to pool prevalence data within and across population level characteristics after variance stabilization through arcsine transformation (PROSPERO registration number CRD42016035248). RESULTS: Data from 45 studies across 15 African countries, and comprising 92,379 and 89,468 participants for overweight and obesity estimates were included. Estimated overweight and obesity prevalence differed significantly across criteria: 10.5% [95% confidence interval, CI: 7.1-14.3] and 6.1% [3.4-9.7] by World Health Organization; 9.5% [6.5-13.0] and 4.0% [2.5-5.9] by International Obesity Task Force; and 11.5% [9.6-13.4] and 6.9% [5.0-9.0] by Centre for Diseases Control, respectively (p = 0.0027 for overweight; p < 0.0001 for obesity). Estimates were mostly higher in urban, and private schools, but generally similar by gender, major geographic regions, publication year and sample size. Substantial heterogeneity in the estimates across and within criteria were not always explained by major study characteristics. CONCLUSION: Overweight and obesity are prevalent among African primary school learners, particularly those attending urban, and private schools. The results from this meta-analysis could be helpful in making informed decisions on childhood obesity prevention efforts in African countries.

A validated patient-specific FSI model for vascular access in haemodialysis.

The flow rate inside arteriovenous fistulas is many times higher than physiological flow and is accompanied by high wall shear stress resulting in low patency rates. A fluid-structure interaction finite element model is developed to analyse the blood flow and vessel mechanics to elucidate the mechanisms that can lead to failure. The simulations are validated against flow measurements obtained from magnetic resonance imaging data.

Using formative research to develop a nutrition education resource aimed at assisting low-income households in South Africa adopt a healthier diet.

As part of a comprehensive programme to prevent non-communicable disease in South Africa, there is a need to develop public education campaigns on healthy eating. Urban populations of lower socioeconomic status are a priority target population. This study involved formative research to guide the development of a nutrition resource appropriate to the budgetary constraints and information needs of poor households in the major urban centres of South Africa. Twenty-two focus groups were convened to explore the target audience's knowledge, beliefs, attitudes and practices as they related to healthy eating and their views about the proposed nutrition resource (N = 167). A brief questionnaire assessed eating and cooking practices among focus group participants. Key informant interviews with eight dieticians/nutritionists working with this population added to the focus group findings. The research identified important issues to take into account in the development of the resource. These included the need to: directly address prevalent misconceptions about healthy eating and unhealthy eating practices; increase self-efficacy regarding the purchasing and preparation of healthy food; represent diverse cultural traditions and consider the issues of affordability and availability of food ingredients. This study demonstrates the value of using formative research in the design of nutrition-related communication in a multicultural, poor, urban South African setting.

High-dimensional nested analysis of variance to assess the effect of production season, quality grade and steam pasteurization on the phenolic composition of fermented rooibos herbal tea.

A nested analysis of variance combined with simultaneous component analysis, ASCA, was proposed to model high-dimensional chromatographic data. The data were obtained from an experiment designed to investigate the effect of production season, quality grade and post-production processing (steam pasteurization) on the phenolic content of the infusion of the popular herbal tea, rooibos, at 'cup-of-tea' strength. Specifically, a four-way analysis of variance where the experimental design involves nesting in two of the three crossed factors was considered. For the purpose of the study, batches of fermented rooibos plant material were sampled from each of four quality grades during three production seasons (2009, 2010 and 2011) and a sub-sample of each batch was steam-pasteurized. The phenolic content of each rooibos infusion was characterized by high performance liquid chromatography (HPLC)-diode array detection (DAD). In contrast to previous studies, the complete HPLC-DAD signals were used in the chemometric analysis in order to take into account the entire phenolic profile. All factors had a significant effect on the phenolic content of a 'cup-of-tea' strength rooibos infusion. In particular, infusions prepared from the grade A (highest quality) samples contained a higher content of almost all phenolic compounds than the lower quality plant material. The variations of the content of isoorientin and orientin in the different quality grade infusions over production seasons are larger than the variations in the content of aspalathin and quercetin-3-O-robinobioside. Ferulic acid can be used as an indicator of the quality of rooibos tea as its content generally decreases with increasing tea quality. Steam pasteurization decreased the content of the majority of phenolic compounds in a 'cup-of-tea' strength rooibos infusion.

Parasites of domestic and wild animals in South Africa. XLVII. Ticks of tortoises and other reptiles.

A total of 586 reptiles, belonging to 35 species and five subspecies, were examined in surveys aimed at determining the species spectrum and geographic distribution of ticks that infest them. Of these reptiles 509 were tortoises, 28 monitor or other lizards, and 49 snakes. Nine ixodid tick species, of which seven belonged to the genus Amblyomma, and one argasid tick, Ornithodoros compactus were recovered. Seven of the ten tick species are parasites of reptiles. Amongst these seven species Amblyomma marmoreum was most prevalent and numerous on leopard tortoises, Geochelone pardalis; Amblyomma nuttalliwas present only on Bell's hinged tortoises, Kinixys belliana; and most Amblyomma sylvaticum were collected from angulate tortoises, Chersina angulata. Amblyomma exornatum (formerly Aponomma exornatum) was only recovered from monitor lizards, Varanus spp.; most Amblyomma latum (formerly Aponomma latum) were from snakes; and a single nymph of Amblyomma transversale (formerly Aponomma transversale) was collected from a southern African python, Python natalensis. All 30 Namaqualand speckled padloper tortoises, Homopus signatus signatus, examined were infested with O. compactus. The seasonal occurrence of A. sylvaticum and the geographic distribution of this tick and of A. marmoreum, A. nuttalli, A. exornatum, A. latum and O. compactus are illustrated.

Determination of anthocyanins in wine by direct injection liquid chromatography-diode array detection-mass spectrometry and classification of wines using discriminant analysis.

A rapid HPLC-diode array detection (DAD) method was developed for the routine analysis of 16 anthocyanins in wine. Direct injection of filtered wine samples followed by selective detection at 520 nm allowed quantitation of these compounds in red wines. The method was linear for malvidin-3-glucoside over the range 5-250ppm, and the limit of detection for this compound was 0.18 ppm. A volatile mobile phase is used, which enables hyphenation to mass spectrometry (MS). With HPLC-MS, a total of 44 pigments could be identified in South African wines. Obtained mass spectra are discussed for a series of representative wine constituents and results are compared with literature references. An attempt was made to differentiate between different cultivars according to the anthocyanin content using stepwise forward linear discriminant analysis (LDA).

Determinants of growth failure in 12-24-month-old children in a high-density urban slum community in East London, South Africa.

OBJECTIVE: The study's main objectives were the identification of determinants of growth failure in 12-24-month-old children from an urban slum community attending a day hospital as well as the identification of focus areas for intervention. DESIGN: The research was executed as a case-control study with a one-to-two design. A hypothetical causal model was developed for the undernutrition situation in Duncan Village. A questionnaire to assess the direct and underlying causes of growth failure in the study population was developed from this model. SUBJECTS: One-hundred and fifty children were selected for the study, with 100 children in the control group and 50 children in the growth-failure group. Each child in the growth-failure group was matched with two children in the control group based on age and sex. The children were chosen according to anthropometric indices and p-albumin levels. SETTING: The research was conducted at a primary health care centre in Duncan Village, an overpopulated urban slum area in East London, a small city on the east coast of South Africa. RESULTS: No significant differences were found between the two groups for the occurrence of disease and infection. Dietary intake seemed to be generally poor in all the children. No significant differences were found between the two groups for the indicators of household food security, health service utilization and environmental conditions. The most important underlying determinants of growth failure that were identified in the study population seem to be related to the caring capacity, and the resultant caring behaviours of mothers. The risk for growth failure is increased when a child has a mother who is not the head of the household (relative risk) (RR=4.3), who is not involved with the discipline of her children (RR=2.2), who is not the guardian of the child (RR=8), who was not born in Duncan Village or in a city (RR=2.16), who is not able to write (RR=2.7) or read Xhosa (RR=2.53), who has a school education of

Methylphenidate affects striatal dopamine differently in an animal model for attention-deficit/hyperactivity disorder--the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit/hyperactivity disorder (ADHD) because it has behavioural characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to those of ADHD. ADHD children have been shown to have reduced striatal activation in certain tasks. SHR have reduced striatal dopamine release in response to electrical stimulation. The present study set out to investigate possible long-term effects of methylphenidate treatment on dopaminergic function in striatal slices of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. Methylphenidate treatment (3 mg/kg daily for 14 days) did not normalize the decreased electrically-stimulated release of [(3)H]dopamine from SHR caudate-putamen slices nor did it affect postsynaptic D(2) receptor function. However, the second electrical stimulus caused a relatively greater release of [(3)H]dopamine from caudate-putamen slices of methylphenidate-treated SHR than from vehicle-treated SHR, suggesting that presynaptic mechanisms controlling dopamine release had been altered. Interestingly, [(3)H]dopamine release from WKY caudate-putamen slices in response to D(2) autoreceptor blockade by the antagonist, sulpiride, was selectively increased by methylphenidate treatment. This effect was not seen in SHR possibly because D(2) autoreceptor function had already been up-regulated. The results show that methylphenidate is unable to enhance D(2) autoreceptor function in SHR.

Clinical value of using an automated sperm morphology analyzer (IVOS).

OBJECTIVE: To determine the clinical value of automated normal sperm morphology outcomes. DESIGN: Prospective clinical study. SETTING: Clinical and research assisted reproduction laboratory. PATIENT(S): Two hundred seven GIFT cycles. INTERVENTION(S): The wife was induced to superovulate, laparoscopically aspirated, and the gametes were transferred laparoscopically. The husband's sperm morphology was evaluated with use of a sperm morphology analyzer using the strict criteria classification system. MAIN OUTCOME MEASURE(S): Normal sperm morphology, IVF, and pregnancy outcomes. RESULT(S): The logistic regression model showed that normal sperm morphology was significantly associated with fertilization in vitro, as dependent (age) and independent variables. Analyzing the fertilization rates across the 5% normal sperm morphology cutoff point, a fertilization rate of 39.39% (< or = 5%) compared with 62.92% (>5%) was obtained. The logistic regression model showed that normal sperm morphology was also a significant predictor of pregnancy when allowing for the number of oocytes transferred and female age. Analyzing the pregnancy rates across the 5% normal sperm morphology cutoff point, pregnancy rates of 15.15% (< or = 5%) and 37.36% (>5%) were obtained. CONCLUSION(S): Normal sperm morphology as evaluated by the automated semen analyzer (IVOS) was shown to adhere to the same fertility cutoff point (5%), as determined by the manual evaluation of sperm morphology. Automated normal sperm morphology outcomes also were found to be significant predictors of IVF and pregnancy in a GIFT program.

Normal sperm morphology and chromatin packaging: comparison between aniline blue and chromomycin A3 staining.

The successful implementation of ICSI has provided a unique means of allowing couples suffering from severe male infertility to achieve their reproductive goals. However, despite the great therapeutic advantages of the technique, ICSI often provides solutions to clinicians in the absence of an aetiological or pathophysiological diagnosis. The development of a sequential diagnostic schedule for patients consulting for fertility disturbances would be an ideal method of approach. Since sperm morphology recorded by strict criteria has often been correlated with fertilization failure, the present study aimed to evaluate the relationship between normal morphology and chromatin staining among fertile and subfertile men. Both chromomycin A3 (CMA3) and acidic aniline blue (AAB) were employed to record chromatin packaging quality among 58 men visiting the andrology laboratory. Intra- and interassay variations were initially recorded for fertile sperm donors. The coefficients of variation (CV) for all intra- and inter-assay assessments were < 12%. Chromatin packaging was significantly and negatively correlated with normal sperm morphology, namely r = 0.40 (P = 0.001) and r = 0.33 (P = 0.001) for CMA3 and AAB, respectively. Receiver operator characteristics illustrated sensitivity and specificity values of 75% and 82% for CMA3 and 60% and 91% for AAB, respectively. Significantly different CMA3 and AAB staining was recorded among men with severe teratozoospermia (< 4% normal forms) when compared with normozoospermic men (> 14% normal forms), namely 49% vs. 29% for CMA3 and 51% vs. 26% for AAB staining, respectively. Chromatin packaging assessments should be a valuable addition to the sequential diagnostic programme in an assisted reproduction arena.

Differences between electrically-, ritalin- and D-amphetamine-stimulated release of [3H]dopamine from brain slices suggest impaired vesicular storage of dopamine in an animal model of Attention-Deficit Hyperactivity Disorder.

The spontaneously hypertensive rat (SHR) has behavioural characteristics which make it a suitable animal model for Attention-Deficit Hyperactivity Disorder (ADHD). The drugs of choice in the treatment of ADHD are methylphenidate and D-amphetamine. Using an in vitro superfusion system, we showed that both drugs released [3H]dopamine (DA) (and metabolites) from prefrontal cortex, nucleus accumbens and caudate-putamen slices, but methylphenidate was from 7- to 17-fold less potent than D-amphetamine. The similarity in the drug effects on SHR and WKY [3H]DA release is in accordance with the fact that there is no 'paradoxical effect' of psychomotor stimulants on ADHD behaviour. Methylphenidate released significantly less [3H]DA from nucleus accumbens slices obtained from SHR than from their normotensive Wistar-Kyoto (WKY) controls. Electrical stimulation released less [3H]DA from prefrontal cortex and caudate-putamen slices of SHR, while D-amphetamine, in contrast to methylphenidate, released more [3H]DA from prefrontal cortex, nucleus accumbens and caudate-putamen slices of SHR compared to WKY. Inhibition of the DA uptake carrier by low concentrations of methylphenidate increased the electrically-stimulated release of [3H]DA to the same extent in SHR and WKY tissue, suggesting that the DA transporter was not responsible for the differences between SHR and WKY. The present results suggest that SHR may have impaired vesicular storage of DA causing leakage of DA into the cytoplasm, since SHR released less [3H]DA from vesicular stores in response to methylphenidate or electrical stimulation and released more [3H]DA from cytoplasmic stores via the uptake carrier in response to D-amphetamine. Methylphenidate might be the drug of choice in the treatment of ADHD because it releases DA from vesicular stores only and is less potent than D-amphetamine, thus making it possible to adjust the dose and thereby 'normalise' reduced DA function more precisely than is possible with D-amphetamine. There was no difference between SHR and WKY with respect to D-amphetamine-stimulated release of [14C]acetylcholine (ACh) or methylphenidate-induced inhibition of the electrically-stimulated release of [14C]ACh from nucleus accumbens or caudate-putamen slices, suggesting that there is no major change in cholinergic transmission in SHR.

Significance of antisperm antibodies in female serum in a gamete intrafallopian transfer program.

The influence of antisperm antibodies in the female serum on fertilization and pregnancy rate in patients undergoing GIFT was assessed. A study group of 52 couples (69 cycles) with significant levels of antisperm antibodies in the female serum were compared to a control group of 749 couples (1185 cycles). Maternal serum or donor serum was used as growth medium supplement. The TAT test was performed for the detection of antisperm antibodies in the serum. Antisperm-antibody presence in female serum was associated with similar fertilization and pregnancy rates in a GIFT program compared to the control group. The type of serum used as growth medium supplement did not affect statistically the fertilization or pregnancy rate.

Comparison of two staining and evaluation methods used for computerized human sperm morphology evaluations.

The purpose of the study was to analyse the agreement between computer analysed (Hamilton Thorne, IVOS Dimensions Version 3) normal sperm morphology and values obtained from 97 slides stained according to the Papanicolaou and Diff-Quik method. Liquefied semen samples were washed once by centrifugation and air dried smears on slides were made, which were stained according to the Papanicolaou and Diff-Quik method and analysed by computer. The paired t-test was used to assess whether any bias existed between the two methods. The limits of agreement were calculated using the Bland and Altman approach and a modification of this approach (mean-dependent limits). A significant bias of 1.6% was obtained in favour of higher normal sperm morphology percentages when using the Diff-Quik method. The standard limits of agreement were -13.4% to 16.6%, whereas the mean-dependent limits of agreement were 1.6% [5.8 + 0.6 (mean percentage normal morphology)]. Statistically, the Diff-Quik and Papanicolaou staining methods produce different normal sperm morphology profiles. These inherent differences may, therefore, require the establishment of new normal sperm morphology thresholds for male fertility, based on clinical data, when using the Diff-Quik staining method in conjunction with computerized analysis.

Effects of different staining and washing procedures on the results of human sperm morphology evaluation by manual and computerised methods.

The purpose of this study was to investigate the effect of different staining and washing procedures on the results of human sperm morphology evaluation by manual and computerised methods. Furthermore, it was intended to find the staining and washing combination which would provide optimal readability for computer-assisted sperm morphology evaluations. In phase one, four staining methods were evaluated for smears prepared from the resulting samples following a two times washing procedure. In phase two, 20 semen samples were used to compare the Diff-Quik and Papanicolaou staining methods, following one and two washes. All manual readings, of Papanicolaou and Diff-Quik stained smears, were comparable with each other, with means between 7.3% and 7.9% normal spermatozoa. All the manual readings were also comparable to the computer readings of the Diff-Quik slides following one and two washes with means of 9.0% and 5.9%, respectively. However, due to the higher computer readings found for the Papanicolaou stained smears, with means of 13.9% and 13.5% following one and two washes, respectively, a statistically significantly difference between overall computer and manual readings was found (Wilks' Lamda, P = 0.0002). Taking all data into consideration, it could be concluded that the one wash Diff-Quik stained smears was the optimal preparation method for computerised sperm morphology evaluation, comparing favourably with manual evaluations.

Slide preparation and staining procedures for reliable results using computerized morphology.

The purpose of this study was to standardize slide preparation and staining procedures to improve the efficiency and effectivity of the IVOS system on normal sperm morphology readings with regard to the strict criteria. Semen samples from patients attending the Reproductive Biology Unit, Tygerberg Hospital, were used. In experiment 1, five different Diff-Quik staining procedures, including the standard procedure, were evaluated on each of 22 patients and the effect of slide preparation within 1 h or more than 5 h after collection and the effect of immediate fixation versus fixation after 24 h were observed. In experiment 2, the manual evaluation time per slide (n = 20) by two technicians was compared with the time taken by computer. In experiment 1 the median % normal for the 5 different staining procedures was 6, 6.5, 9.5, 8.5, and 5.5%. No significant difference was found between the different staining procedures (p = .60, nonparametric Friedman test). In experiment 2 the mean time for manual assessment by two technicians was 3 min:6 s and 3 min:53 s per slide as compared to 4 min:39 s by computer. For experiment 1, slides can be prepared immediately or after 5 h. Fixation time also does not interfere with the computer's ability to identify normal forms. For experiment 2, the IVOS system is competitive regarding assessment time. Standardization of optimum staining procedures is important to ensure repeatability and comparability. Therefore, slides should be prepared immediately after liquefaction and fixed immediately after air drying.

A comparative study using prepared and unprepared frozen semen for donor insemination.

The aim of this study was to compare the efficacy of pericervical insemination with unprepared semen With that of intrauterine insemination with prepared donor semen in a prospective, randomized, crossover clinical trial. Fifty-four subsequent patients who qualified for therapeutic donor insemination were randomized to receive alternately either an intrauterine insemination with thawed frozen donor semen, prepared by double wash and swim-up, or pericervical insemination with unprepared thawed frozen donor semen in subsequent treatment cycles, with each patient serving as her own control. Eleven pregnancies ensued from 54 cycles of intrauterine insemination (20.4% per cycle), and 2 pregnancies ensued from 58 cycles of pericervical insemination (3.4% per cycle, p = .005). Five pregnancies ensued during the first treatment cycle (13.2%), 4 during the second treatment cycle (17.4%), 2 during the third (13.2%), 1 during the fourth (7.1%), and 1 after the fourth treatment cycle (4.8%). The significantly better pregnancy rate from intrauterine insemination with prepared semen supports this treatment option. The decrease in pregnancy rate after the fourth treatment cycle confirms the need for alternative therapy after 4 failed cycles of therapeutic donor insemination.

Altered dopaminergic function in the prefrontal cortex, nucleus accumbens and caudate-putamen of an animal model of attention-deficit hyperactivity disorder--the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for Attention-Deficit Hyperactivity Disorder (ADHD). The behavioural problems of ADHD have been suggested to be secondary to altered reinforcement mechanisms resulting from dysfunction of the mesolimbic and mesocortical dopaminergic systems. The present study therefore investigated whether there are regional differences in dopamine (DA) and acetylcholine (ACh) release and DA D2-receptor function in SHR compared to their normotensive Wistar-Kyoto (WKY) controls. The DA D2-receptor agonist, quinpirole, caused significantly greater inhibition of DA release from caudate-putamen but not from nucleus accumbens or prefrontal cortex slices of SHR relative to WKY. DA D2-receptor blockade by the antagonist, sulpiride, caused a significantly greater increase in DA release from nucleus accumbens slices of SHR compared to WKY suggesting increased efficacy of DA autoreceptors at low endogenous agonist concentrations in the nucleus accumbens of SHR. The electrically-stimulated release of DA was significantly lower in caudate-putamen and prefrontal cortex slices of SHR than in slices of WKY. This could be attributed to increased autoreceptor-mediated inhibition of DA release in caudate-putamen slices but not in the prefrontal cortex. No difference was observed between SHR and WKY with respect to DA D2-receptor-mediated inhibition of ACh release from caudate-putamen or nucleus accumbens slices, suggesting that postsynaptic DA D2-receptor function is not altered in SHR relative to WKY.