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BackgroundChallenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers.MethodsOne hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained.ResultsThe standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08).ConclusionThe high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.

Ischaemic heart disease (IHD) remains a major cause of morbidity/mortality globally, firmly established in Westernized or 'developed' countries and rising in prevalence in developing nations. Thus, cardioprotective therapies to limit myocardial damage with associated ischaemia-reperfusion (I-R), during infarction or surgical ischaemia, is a very important, although still elusive, clinical goal. The opioid receptor system, encompassing the δ (vas deferens), κ (ketocyclazocine) and μ (morphine) opioid receptors and their endogenous opioid ligands (endorphins, dynorphins, enkephalins), appears as a logical candidate for such exploitation. This regulatory system may orchestrate organism and organ responses to stress, induces mammalian hibernation and associated metabolic protection, triggers powerful adaptive stress resistance in response to ischaemia/hypoxia (preconditioning), and mediates cardiac benefit stemming from physical activity. In addition to direct myocardial actions, central opioid receptor signalling may also enhance the ability of the heart to withstand I-R injury. The δ-and κ-opioid receptors are strongly implicated in cardioprotection across models and species (including anti-infarct and anti-arrhythmic actions), with mixed evidence for μ opioid receptor-dependent protection in animal and human tissues. A small number of clinical trials have provided evidence of cardiac benefit from morphine or remifentanil in cardiopulmonary bypass or coronary angioplasty patients, although further trials of subtype-specific opioid receptor agonists are needed. The precise roles and utility of this GPCR family in healthy and diseased human myocardium, and in mediating central and peripheral survival responses, warrant further investigation, as do the putative negative influences of ageing, IHD co-morbidities, and relevant drugs on opioid receptor signalling and protective responses.

BackgroundXpert MTB/RIF was introduced as a screening test for all presumptive tuberculosis cases in primary health services in Cape Town, South Africa.Study AimTo compare multidrug-resistant tuberculosis (MDR-TB) treatment commencement times in MDRTBPlus Line Probe Assay and Xpert MTB/RIF-based algorithms in a routine operational setting.MethodsThe study was undertaken in 10 of 29 high tuberculosis burden primary health facilities, selected through stratified random sampling. An observational study was undertaken as facilities transitioned to the Xpert MTB/RIF-based algorithm. MDR-TB diagnostic data were collected from electronic laboratory records and treatment data from clinical records and registers. Kaplan Meier time-to-event analysis was used to compare treatment commencement time, laboratory turnaround time and action delay between algorithms. A facility-level paired analysis was done: the median time-to-event was estimated per facility in each algorithm and mean differences between algorithms compared using a paired t-test. Cox proportional hazards regression was used to assess the effect of patient-level variables on treatment commencement time. The difference between algorithms was compared using the hazard ratio.ResultsThe median treatment commencement time in the Xpert MTB/RIF-based algorithm was 17 days (95% CI 13 to 22 days), with a median laboratory turnaround time (to result available in the laboratory) of <1 day (95% CI<1 to 1 day). There was a decrease of 25 days (95% CI 17 to 32 days, p<0.001) in median MDR-TB treatment commencement time in the Xpert MTB/RIF-based algorithm. We found no significant effect on treatment commencement times for the patient-level variables assessed.ConclusionMDR-TB treatment commencement time was significantly reduced in the Xpert MTB/RIF-based algorithm. Changes in the health system may have contributed. However, an unacceptable level of delay remains. Health system and patient factors contributing to delay need to be evaluated and addressed to optimise test benefits.

AimsTo determine the prevalence of and risk factors for diabetes mellitus and examine its diagnosis and management in the study communities.MethodsThis is a population-based cross-sectional study among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Diabetes is defined as a random blood glucose concentration (RBG) ⩾ 11.1 mmol/L, or RBG < 11.1 mmol/L but with a self-reported prior diabetes diagnosis. For individuals with a prior diagnosis of diabetes, RBG < 7.8 mmol/L was considered to be an acceptable level of glycaemia.ResultsAmong 45,767 Zambian and 12,496 WC participants the age-standardised prevalence of diabetes was 3.5% and 7.2% respectively. The highest risk groups identified were those of older age and those with obesity. Of those identified to have diabetes, 34.5% in Zambia and 12.7% in WC were previously unaware of their diagnosis. Among Zambian participants with diabetes, this proportion was lower among individuals with better education or with higher household socio-economic position. Of all those with previously diagnosed diabetes, 66.0% in Zambia and 59.4% in WC were not on any diabetes treatment, and 34.4% in Zambia and 32.7% in WC had a RBG concentration beyond the recommended level, ⩾7.8 mmol/L.ConclusionsThe diabetes risk factor profile for our study communities is similar to that seen in high-income populations. A high proportion of individuals with diabetes are not on diabetes treatment and of those on treatment a high proportion have high glycaemic concentrations. Such data may assist in healthcare planning to ensure timely diagnosis and management of diabetes.

BackgroundAlthough new molecular diagnostic tests such as GenoType MTBDRplus and Xpert® MTB/RIF have reduced multidrug-resistant tuberculosis (MDR-TB) treatment initiation times, patients’ experiences of diagnosis and treatment initiation are not known. This study aimed to explore and compare MDR-TB patients’ experiences of their diagnostic and treatment initiation pathway in GenoType MTBDRplus and Xpert® MTB/RIF-based diagnostic algorithms.MethodsThe study was undertaken in Cape Town, South Africa where primary health-care services provided free TB diagnosis and treatment. A smear, culture and GenoType MTBDRplus diagnostic algorithm was used in 2010, with Xpert® MTB/RIF phased in from 2011–2013. Participants diagnosed in each algorithm at four facilities were purposively sampled, stratifying by age, gender and MDR-TB risk profiles. We conducted in-depth qualitative interviews using a semi-structured interview guide. Through constant comparative analysis we induced common and divergent themes related to symptom recognition, health-care access, testing for MDR-TB and treatment initiation within and between groups. Data were triangulated with clinical information and health visit data from a structured questionnaire.ResultsWe identified both enablers and barriers to early MDR-TB diagnosis and treatment. Half the patients had previously been treated for TB; most recognised recurring symptoms and reported early health-seeking. Those who attributed symptoms to other causes delayed health-seeking. Perceptions of poor public sector services were prevalent and may have contributed both to deferred health-seeking and to patient’s use of the private sector, contributing to delays. However, once on treatment, most patients expressed satisfaction with public sector care. Two patients in the Xpert® MTB/RIF-based algorithm exemplified its potential to reduce delays, commencing MDR-TB treatment within a week of their first health contact. However, most patients in both algorithms experienced substantial delays. Avoidable health system delays resulted from providers not testing for TB at initial health contact, non-adherence to testing algorithms, results not being available and failure to promptly recall patients with positive results.ConclusionWhilst the introduction of rapid tests such as Xpert® MTB/RIF can expedite MDR-TB diagnosis and treatment initiation, the full benefits are unlikely to be realised without reducing delays in health-seeking and addressing the structural barriers present in the health-care system.

SUMMARYObesity with associated metabolic disturbances worsens ischaemic heart disease outcomes, and rodent studies confirm that obesity with insulin-resistance impairs myocardial resistance to ischemia-reperfusion (I-R) injury. However, the effects of obesity per se are unclear, with some evidence for paradoxic cardioprotection (particularly in older subjects). We tested the impact of dietary obesity on I-R tolerance and reperfusion injury salvage kinase (RISK) signalling in hearts from middle-aged (10 months old) insulin-insensitive rats. Hearts from Wistar rats on either a 32-week control (CD) or high carbohydrate obesogenic (OB) diet were assessed for I-R resistance in vivo (45 minutes left anterior descending artery occlusion and 120 minutes reperfusion) and ex vivo (25 minutes ischemia and 60 minutes reperfusion). Expression and δ-opioid receptor (δ-OR) phospho-regulation of pro-survival (Akt/PKB, Erk1/2, eNOS) and pro-injury (GSK3β) enzymes were also examined. OB rats were heavier (764±25 versus 657±22 g for CD; P<0.05), hyperleptinaemic (11.1±0.7 versus 5.0±0.7 for CD; P<0.01) and comparably insulin-insensitive (HOMA-IR of 63.2±3.3 versus 63.2±1.6 for CD). In vivo infarction was more than halved in OB (20±3%) versus CD rats (45±6% P<0.05), as was post-ischaemic lactate dehydrogenase efflux (0.4±0.3 mU/ml versus 5.6±0.5 mU/ml; P<0.02) and ex vivo contractile dysfunction (62±2% versus 44±6% recovery of ventricular force; P<0.05). OB hearts exhibited up to 60% higher Akt expression, with increased phosphorylation of eNOS (+100%), GSK3β (+45%) and Erk1/2 (+15%). Pre-ischaemic δ-OR agonism with BW373U86 improved recoveries in CD hearts in association with phosphorylation of Akt (+40%), eNOS (+75%) and GSK3β (+30%), yet failed to further enhance RISK-NOS activation or I-R outcomes in OB hearts. In summary, dietary obesity in the context of age-related insulin-insensitivity paradoxically improves myocardial I-R tolerance, in association with moderate hyperleptinaemic and enhanced RISK expression and phospho-regulation. However, OB hearts are resistant to further RISK modulation and cardioprotection via acute δ-OR agonism.

Sheep from a Merino selection experiment at the Tygerhoek research farm in the Southern Cape provided material for this study. The selection lines involved included a line selected for clean fleece weight, a "Wet and Dry" line, a fine wool line and an unselected Control line. Rectal faeces samples were obtained from individual animals at 13 to 16 months of age, after drenching was withheld for at least 10 weeks. Nematode eggs in these samples were counted. Fitting the appropriate fixed effects, the heritability of untransformed, cube root transformed and log transformed faecal nematode egg count (FEC) was obtained from single-trait analyses. The effects of sex and birth year were involved in a significant interaction. Means for FEC were generally higher in ram progeny than in ewes, but the magnitude of the sex difference was not consistent. Multiple lambs had a slightly lower mean for FEC than singles, while FEC was unaffected by dam age. The heritability of FEC was estimated at between 0.14 for untransformed data and 0.18 for log transformed FEC. Genetic correlations of log transformed FEC with two-tooth staple strength (-0.49) and coefficient of variation of fibre diameter (0.30) were favourable. Clean fleece weight was unfavourably related to FEC on a genetic level (0.19). Selection for resistance to parasitic nematodes after natural challenge should thus be feasible in the Merino lines studied.