Tuberculosis infection prevention and control: why we need a whole systems approach.

Infection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an on-going project entitled Umoya omuhle ("good air"), conducted in two provinces of South Africa, that adopts an interdisciplinary, 'whole systems' approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis (Mtb) through improved IPC. We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines, health facility space, infrastructure, organisation of care, and management culture. Methods drawn from epidemiology, anthropology, and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs, as well as opportunities to address the problem holistically. A 'whole systems' approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission

Organisational Culture and Mask-Wearing Practices for Tuberculosis Infection Prevention and Control among Health Care Workers in Primary Care Facilities in the Western Cape, South Africa: A Qualitative Study

Background: Although many healthcare workers (HCWs) are aware of the protective role that mask-wearing has in reducing transmission of tuberculosis (TB) and other airborne diseases, studies on infection prevention and control (IPC) for TB in South Africa indicate that mask-wearing is often poorly implemented. Mask-wearing practices are influenced by aspects of the environment and organisational culture within which HCWs work. Methods: We draw on 23 interviews and four focus group discussions conducted with 44 HCWs in six primary care facilities in the Western Cape Province of South Africa. Three key dimensions of organisational culture were used to guide a thematic analysis of HCWs’ perceptions of masks and mask-wearing practices in the context of TB infection prevention and control. Results: First, HCW accounts address both the physical experience of wearing masks, as well as how mask-wearing is perceived in social interactions, reflecting visual manifestations of organisational culture in clinics. Second, HCWs expressed shared ways of thinking in their normalisation of TB as an inevitable risk that is inherent to their work and their localization of TB risk in specific areas of the clinic. Third, deeper assumptions about mask-wearing as an individual choice rather than a collective responsibility were embedded in power and accountability relationships among HCWs and clinic managers. These features of organisational culture are underpinned by broader systemic shortcomings, including limited availability of masks, poorly enforced protocols, and a general lack of role modelling around mask-wearing. HCW mask-wearing was thus shaped not only by individual knowledge and motivation but also by the embodied social dimensions of mask-wearing, the perceptions that TB risk was normal and localizable, and a shared underlying tendency to assume that mask-wearing, ultimately, was a matter of individual choice and responsibility. Conclusions: Organisational culture has an important, and under-researched, impact on HCW mask-wearing and other PPE and IPC practices. Consistent mask-wearing might become a more routine feature of IPC in health facilities if facility managers more actively promote engagement with TB-IPC guidelines and develop a sense of collective involvement and ownership of TB-IPC in facilities

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries

In Caenorhabditis elegans Nanoparticle-Bio-Interactions Become Transparent: Silica-Nanoparticles Induce Reproductive Senescence

While expectations and applications of nanotechnologies grow exponentially, little is known about interactions of engineered nanoparticles with multicellular organisms. Here we propose the transparent roundworm Caenorhabditis elegans as a simple but anatomically and biologically well defined animal model that allows for whole organism analyses of nanoparticle-bio-interactions. Microscopic techniques showed that fluorescently labelled nanoparticles are efficiently taken up by the worms during feeding, and translocate to primary organs such as epithelial cells of the intestine, as well as secondary organs belonging to the reproductive tract. The life span of nanoparticle-fed Caenorhabditis elegans remained unchanged, whereas a reduction of progeny production was observed in silica-nanoparticle exposed worms versus untreated controls. This reduction was accompanied by a significant increase of the ‘bag of worms’ phenotype that is characterized by failed egg-laying and usually occurs in aged wild type worms. Experimental exclusion of developmental defects suggests that silica-nanoparticles induce an age-related degeneration of reproductive organs, and thus set a research platform for both, detailed elucidation of molecular mechanisms and high throughput screening of different nanomaterials by analyses of progeny production

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study

BACKGROUND : In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. METHODS : Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. FINDINGS : Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87–94) for rpoB (rifampicin resistance), 86% (74–93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39–68) for pncA (pyrazinamide resistance), 85% (77–91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81–92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. INTERPRETATION : Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation.The Bill & Melinda Gates Foundation, the United States Agency for International Development, and the TB Alliance.www.thelancet.com/infectionhttp://www.thelancet.com/infectionam2018Medical Microbiolog

Containing Arsenic-Enriched Groundwater Tracing Lead Isotopic Compositions Of Common Arsenical Pesticides In A Coastal Maine Watershed Containing Arsenic-Enriched Ground Water

Arsenical pesticides and herbicides were extensively used on apple, blueberry, and potato crops in New England during the first half of the twentieth century. Lead arsenate was the most heavily used arsenical pesticide until it was officially banned. Lead arsenate, calcium arsenate, and sodium arsenate have similar Pb isotope compositions: 208Pb/207Pb = 2.3839-2.4722, and 206Pb/207Pb = 1.1035-1.2010. Other arsenical pesticides such as copper acetoarsenite (Paris green), methyl arsonic acid and methane arsonic acid, as well as arsanilic acid are widely variable in isotope composition. Although a complete understanding of the effects of historical use of arsenical pesticides is not available, initial studies indicate that arsenic and lead concentrations in stream sediments in New England are higher in agricultural areas that intensely used arsenical pesticides than in other areas. The Pb isotope compositions of pesticides partially overlap values of stream sediments from areas with the most extensive agricultural use. The lingering effects of arsenical pesticide use were tested in a detailed geochemical and isotopic study of soil profiles from a watershed containing arsenic-enriched ground water in coastal Maine. Acid-leach compositions of the soils represent lead adsorbed to mineral surfaces or held in soluble minerals (Fe- and Mn-hydroxides, carbonate, and some micaceous minerals), whereas residue compositions likely reflect bedrock compositions. The soil profiles contain labile Pb (acid-leach) showing a moderate range in 206Pb/207Pb (1.1870-1.2069), and 208Pb/207Pb (2.4519-2.4876). Isotope values vary as a function of depth: the lowest Pb isotope ratios (e.g., 208Pb/206Pb) representing labile lead are in the uppermost soil horizons. Lead contents decrease with depth in the soil profiles. Arsenic contents show no clear trend with depth. A multi-component mixing scheme that included lead from the local parent rock (Penobscot Formation), lead derived from combustion of fossil fuels, and possibly lead from other anthropogenic sources (e.g., pesticides), could account for Pb isotope variations in the soil profiles. In agricultural regions, our preliminary data show that the extensive use of arsenical pesticides and herbicides can be a significant anthropogenic source of arsenic and lead to stream sediments and soils

Crater lake evolution at Santa Ana Volcano (El Salvador) following the 2005 eruption

The crater lake at Santa Ana Volcano (El Salvador) was monitored during 1992–1993 and 2002–2007. Crater lake chemistry was generally similar until the 2005 eruption. Acidification of the hydrothermal system by condensing magmatic gases yielded fluids that sustained a cool acid sulfate-chloride lake roughly 200 m in diameter (temperature = 16–28 °C, pH = 0.7–2.0, SO42− = 4500–14,000 mg/L, Cl− = 1100–9200 mg/L, total dissolved solids [TDS] = 7000–25,000 mg/L). The phreatomagmatic eruption Volcanic Explosivity Index (VEI) 3 of October 2005 modified the summit crater morphology, leading to physical, thermal, and chemical changes in the lake over the next few years. The lake became hotter and more acidic, with variable chemistry and color (temperature = 24–66 °C, pH = 0.4–1.3, SO42− = 2500–9800 mg/L, Cl− = 3200–22,000 mg/L, TDS = 10,000–36,000 mg/L, turquoise-gray-yellow color). The SO42−/Cl− ratio dropped below 1, indicating an increase in the rate of volcanic gas input and coincident S depletion by abundant precipitation of native sulfur and secondary S-bearing minerals (alunite, gypsum, iron sulfides, and anhydrite). An increase in rare earth element (REE) concentrations in lake waters indicated leaching of the newly intruded magma. The eruption likely enhanced permeability in the edifice, further increasing the amount of available fresh wall rock to react with acidic fluids, and the concentration of rock-forming elements in the lake increased fivefold to a maximum of 90 g rock dissolved per kg water. The magma continued to degas through the lake bottom at the drowned eruptive vent, providing a large, direct gas input into the lake. Direct gas discharge into the lake led to sulfur saturation and formation of hollow sulfur spherules by percolation of gas bubbles through the molten sulfur bottom layer. Increased heat input into the lake (8–830 MW, equivalent SO2 flux of 16–1600 t/d) led to enhanced evaporation and highly variable lake mass. Consequently, on three occasions during 2006 and 2007, the lake area diminished to 70% of its former size