Tanusha Singh

Challenges facing sterilization and depyrogenation of nanoparticles: Effects on structural stability and biomedical applications

This review outlines and compares techniques that are currently available for the sterilization of nanoparticles and addresses the topic of endotoxin contamination. Several techniques are available for the removal of microbial contamination from nanoparticles developed for use in nanomedicine applications. These techniques include filtration, autoclaving and irradiation, as well as formaldehyde, ethylene oxide and gas plasma treatments. Of these sterilization methodologies, filtration may potentially remove microbial contamination without altering the physicochemical properties of the carrier nanoparticles, nor affecting their toxicity and functionality. However, no single process may be applied to all nanoparticle preparations and, therefore, it is recommended that each nanoparticle-drug system be validated on a case-by-case basis. From the clinical editor: This comprehensive review covers the currently available methods for removal of microbial contaminations from nanoparticles for nanomedicine applications. The review highlights the pros and cons of each available method. Authors conclude that there is no single best method and recommend a customized approach for each nanoparticle system.

Work-related allergic respiratory disease and asthma in spice mill workers is associated with inhalant chili pepper and garlic exposures

Objective The aim of the study was to determine the prevalence and risk factors for allergic respiratory disease in spice mill workers. Methods A cross-sectional study of 150 workers used European Community Respiratory Health Survey questionnaires, Phadiatop, serum specific IgE (garlic, chili pepper), spirometry and fractional exhaled nitric oxide (FeNO). Personal air samples (n=62) collected from eight-hour shifts were analysed for inhalable particulate mass. Novel immunological assays quantified airborne garlic and chili pepper allergen concentrations. Results Mean dust particulate mass (geometric mean (GM)=2.06 mg/m3), chili pepper (GM=0.44 µg/m3) and garlic allergen (GM=0.24 µg/m3) were highest in blending and were highly correlated. Workers’ mean age was 33 years, 71% were men, 46% current smokers and 45% atopic. Spice-dust-related asthma-like symptoms (17%) were common, as was garlic sensitisation (19%), with 13% being monosensitised and 6% cosensitised to chili pepper. Airflow reversibility and FeNO>50 ppb was present in 4% and 8% of workers respectively. Spice-dust-related ocular-nasal (OR 2.40, CI 1.09 to 5.27) and asthma-like (OR 4.15, CI 1.09 to 15.72) symptoms were strongly associated with airborne garlic in the highly exposed (>0.235 µg/m3) workers. Workers monosensitised to garlic were more likely to be exposed to higher airborne chili pepper (>0.92 µg/m3) (OR 11.52, CI 1.17 to 113.11) than garlic allergens (OR 5.08, CI 1.17 to 22.08) in this mill. Probable asthma was also more strongly associated with chili pepper than with garlic sensitisation. Conclusions Exposure to inhalable spice dust (GM >2.06 mg/m3) containing garlic (GM>0.24 µg/m³) and chili pepper (GM >0.44 µg/m3) allergens increase the risk of allergic respiratory disease and asthma.

Workplace Determinants of Endotoxin Exposure in Dental Healthcare Facilities in South Africa

OBJECTIVES Aerosols generated during dental procedures have been reported to contain endotoxin as a result of bacterial contamination of dental unit water lines. This study investigated the determinants of airborne endotoxin exposure in dental healthcare settings. METHODS The study population included dental personnel (n = 454) from five academic dental institutions in South Africa. Personal air samples (n = 413) in various dental jobs and water samples (n = 403) from dental handpieces and basin taps were collected. The chromogenic-1000 limulus amebocyte lysate assay was used to determine endotoxin levels. Exposure metrics were developed on the basis of individually measured exposures and average levels within each job category. Analysis of variance and multivariate linear regression models were constructed to ascertain the determinants of exposure in the dental group. RESULTS There was a 2-fold variation in personal airborne endotoxin from the least exposed (administration) to the most exposed (laboratory) jobs (geometric mean levels: 2.38 versus 5.63 EU m(-3)). Three percent of personal samples were above DECOS recommended exposure limit (50 EU m(-3)). In the univariate linear models, the age of the dental units explained the most variability observed in the personal air samples (R(2) = 0.20, P < 0.001), followed by the season of the year (R(2) = 0.11, P < 0.001). Other variables such as institution and total number of dental units per institution also explained a modest degree of variability. A multivariate model explaining the greatest variability (adjusted R(2) = 0.40, P < 0.001) included: the age of institution buildings, total number of dental units per institution, ambient temperature, ambient air velocity, endotoxin levels in water, job category (staff versus students), dental unit model type and age of dental unit. CONCLUSIONS Apart from job type, dental unit characteristics are important predictors of airborne endotoxin levels in this setting.

Risk factors associated with asthma phenotypes in dental healthcare workers

BACKGROUND Exposure in the dental environment can increase the risk of respiratory disease in dental healthcare workers (HCWs). This study investigated the prevalence of asthma phenotypes in dental HCWs and associated risk factors. METHODS A cross-sectional study of 454 dental HCWs in five dental institutions in South Africa was conducted. A self-administered questionnaire elicited the health and employment history of subjects. Sera was analyzed for atopic status and latex sensitization. Pre- and post-bronchodilator spirometry was performed. RESULTS The prevalence of atopic asthma was 6.9%, non-atopic asthma 5.9% and work-exacerbated asthma (WEA) 4.0%. Atopy and work-related ocular-nasal symptoms were strong predictors of WEA (OR: 3.4; 95% CI: 1.07-10.8; OR: 6.7, 95% CI: 2.4-19.1), respectively. Regular use of personal protective equipment (PPE) was associated with a protective affect (OR: 0.23, 95% CI: 0.1-0.7) among non-atopic asthmatics, while glove use and respiratory protection was protective among atopic asthmatics (OR: 0.39, 95% CI: 0.17-0.89). CONCLUSION Identification of risk factors associated with specific asthma phenotypes in dental HCWs can be used to focus preventive strategies for asthmatics.

Allergenicity of latex rubber products used in South African dental schools

BACKGROUND Latex sensitisation is recognised as a health problem among health care workers (HCWs) using latex products. The aim of this study was to quantify specific latex allergens in latex devices used in South African academic dental schools. The current study also compared the total protein content and the levels of specific allergens in these products. METHODS Fourteen latex examination gloves (powdered and non-powdered) and five dental rubber dams, representing 6 brands, from five dental academic institutions were analysed for latex allergens and total protein. Total protein content was determined using the BioRad DC protein assay kit and natural rubber allergen levels using a capture enyme-linked immunosorbent assay (ELISA) specific for Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02. RESULTS Hev b 6.02 was found in higher concentrations than other natural rubber latex (NRL) allergens in the products analysed. Hev b 5 content ranged from 0 to 9.2 microg/g and Hev b 6.02 from 0.09 to 61.5 microg/g of sample. Hev b 1 levels were below the detection limit (DL) for 79% of the samples (15/19). Dental dams showed higher allergen levels (median 80.91 microg/g) than latex gloves (median 11.34 microg/g). Powdered rubber samples also showed higher allergen levels (median 40.54 microg/g) than non-powdered samples (median 5.31 microg/g). A statistically significant correlation was observed between total protein and total allergen (r=0.74, p<0.001) concentrations. CONCLUSION NRL allergen concentrations differ significantly by product and brand. This study has demonstrated that NRL allergens in latex-containing products used in South African dental institutions are present at sufficiently high levels to pose an allergic health risk.

Environmental factors associated with baseline and serial changes in fractional exhaled nitric oxide (FeNO) in spice mill workers

Background This study evaluated the determinants of high fractional exhaled nitric oxide (FeNO; >50 ppb) and serial changes in FeNO over a 24-hour period in spice mill workers at risk of work-related allergic respiratory disease and asthma. Methods A cross-sectional study of 150 workers used European Community Respiratory Health Survey (ECRHS) questionnaires, Phadiatop, serum-specific IgE (garlic, chilli pepper, wheat; Phadia, ImmunoCAP), spirometry and FeNO. A hand-held portable nitric oxide sampling device (NIOX MINO, Aerocrine AB) measured FeNO before and after the 8-hour shift and after 24 hours from baseline. Results The mean age of workers was 33 years; 71% were male, 46% current smokers and 45% atopic. Among workers with garlic sensitisation, 13% were monosensitised and 6% were co-sensitised to chilli pepper. Baseline preshift FeNO geometric mean (GM=14.9 ppb) was similar to the mean change across shift (GM=15.4 ppb) and across the 24-hour period (GM=15.8 ppb). In multivariate linear models, smoking (β=−0.507) and atopy (β=0.433) were strongly associated with FeNO. High FeNO (>50 ppb) was significantly associated with asthma-like symptoms due to spice dust (OR=5.38, CI 1.01 to 28.95). Sensitisation to chilli pepper was more strongly correlated with FeNO (r=0.32) and FeNO>50 ppb (OR=17.04, p=0.005) than garlic. FeNO increase (>12%) across 24 hours demonstrated a strong association with elevated exposures to spice dust particulate (OR=3.77, CI 1.01 to 14.24). Conclusions This study suggests that chilli pepper sensitisation is associated with high FeNO (>50 ppb), more strongly compared with garlic, despite the low prevalence of sensitisation to chilli. Elevated inhalant spice dust particulate is associated with a delayed elevation of FeNO across the 24-hour period.

Relationship between Pesticide Metabolites, Cytokine Patterns, and Asthma-Related Outcomes in Rural Women Workers

The objective of this study was to investigate the relationship between exposure to organophosphate (OP) and pyrethroid (PYR) pesticides with serum cytokine patterns and asthma-related outcomes among rural women workers. A cross-sectional study was conducted among rural women (n = 211), including those working and living on farms and nearby town dwellers. Pesticide exposure was assessed using urinary metabolite concentrations of OP and PYR pesticides. Health outcome assessment was ascertained through the European Community Respiratory Health Survey (ECRHS) questionnaire, fractional exhaled nitric oxide (FeNO), and serum cytokines associated with asthma. The prevalence of doctor-diagnosed asthma was 11%, adult-onset asthma 9%, and current asthma 6%. In this population, the proportion of T helper type 2 (Th2) cytokines (interleukin (IL)-4, IL-5, and IL-13) detectable in subjects was between 18% and 40%, while the proportion of non-Th2 cytokines (IL-6, IL-8, IL-10, IL-17, and interferon gamma) was between 35% and 71%. Most Th2 and non-Th2 cytokines were positively associated with either OP or PYR metabolites. Non-Th2 cytokines showed much stronger associations with OP metabolites (Dimethyl phosphate OR = 4.23; 95% CI: 1.54–11.65) than Th2 cytokines (Dimethyl phosphate OR = 1.69; 95% CI: 0.83–3.46). This study suggests that exposure to most OP and some PYR pesticides may be associated with asthma-related cytokines, with non-Th2 cytokines demonstrating consistently stronger relationships.

High concentrations of natural rubber latex allergens in gloves used by laboratory health personnel in South Africa

Introduction. Gloves made of natural rubber latex (NRL) are commonly used by healthcare workers because of their good qualities. However, allergic reactions to latex allergens are still commonly reported. Objective. To measure the concentrations of Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02 allergens in gloves used by a large laboratory service in South Africa. Methods. NRL gloves as well as non-latex gloves supplied by various suppliers that were used by the laboratory personnel during the period June 2009 - May 2010 were obtained from various suppliers on the vendor list. Proteins were extracted from the gloves and Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02 allergens were quantified using the FITkit assay. Results. Twenty NRL gloves from 13 different brands were analysed. Only four (20%) of the 20 NRL gloves analysed had a total allergen content <0.15 µg/g, the suggested threshold limit for low allergenicity for the sum of these four allergens. Conclusion. This study demonstrated that a very low proportion of gloves tested had a total allergen content below the threshold for low allergenicity.

Staphylococcus aureus and Escherichia coli levels on the hands of theatre staff in three hospitals in Johannesburg, South Africa, before and after handwashing

BACKGROUND Hand hygiene is a fundamental component of infection control. Hand contamination with Staphylococcus aureus and Escherichia coli may contribute to infections. OBJECTIVES To assess the effectiveness of different handwashing methods in reducing the levels of bacterial flora, especially S. aureus and E. coli, on the hands of theatre staff. METHODS A cross-sectional study was conducted among 70 staff in surgical theatres of three randomly chosen hospitals in Johannesburg, South Africa. Samples were taken before and after handwashing using the modified glove juice method and the fingernail press technique. Standard microbiological techniques were used to identify bacteria. Descriptive statistics and non-parametric analysis were used to compare the differences between hospitals and to determine the effects of handwashing on microbial flora and skin irritation. RESULTS S. aureus organisms were isolated in the prewash samples of 29 (41%) and in the postwash samples of 20 (29%) workers. Of the 29 with positive prewash cultures, 19 (65.5%) showed decreased postwash counts, while 10 (34.5%) showed no change or increased counts. Four workers with a negative prewash count had a positive postwash count. No statistical differences were found between postwash counts categorised by the type of cleansing formula used and the washing technique. E. coli organisms were identified in the prewash count of the fingertip press of one worker. CONCLUSIONS Almost half of the theatre staff carried S. aureus isolates on their hands prior to handwashing and approximately one-third after handwashing. Closer monitoring of handwashing techniques should be introduced.

1204 Occupational exposure assessment to bioaerosols in poultry farming activities

Introduction Poultry farm workers are exposed to various hazardous biological agents in organic dust. Particulate dust, endotoxins and (1–3) β-d-glucans) in poultry dust have been implicated in adverse respiratory effects including work-related asthma. Method The study was conducted at various sites of a South African poultry farm consisting of broilers, rearing, laying, hatchery and catching processes. Personal inhalable samples were collected from 298 workers using filtration technique at a flow rate of 2 l/min for the entire work shift. Filter extracts were analysed for (1–3) β-d-glucan and endotoxin using the endpoint Glucatell and Limulus amebocyte lysate test (LAL) assays, respectively. Total inhalable dust concentration was also determined. Data were analysed using STATA 12. Results Dust particulate levels had an overall geometric mean (GM) of 11.04 mg/m3 and differed by farm process The mean dust particulate concentration was highest in the rearing department (GM=54.04 mg/m3, GSD=3.74) followed by hatchery (GM=36.25 mg/m3, GSD=3.46). The automated egg laying farms recorded elevated concentrations of dust particulate (GM=35.23 mg/m3), endotoxin (GM=880 EU/m3) and (1–3) β-d-glucan (GM=136 ng/m3) levels compared to the manual laying system (GM=3.95 mg/m3; GM=680 EU/m3; GM=97 ng/m3). Large broilers had relatively higher total dust particulate and endotoxin concentrations while small broilers had higher (1–3) β-d-glucan levels. The catching crew were found to have the highest concentrations of (1–3) β-d-glucan (GM=644 ng/m3, GSD=1.89) and endotoxin levels (GM=23902 EU/m3, GSD=9.64). Discussion This exposure characterisation study revealed that total inhalable dust, endotoxin and (1–3) β-d-glucans were very high and significantly variable between the five main poultry farming processes. Workers in all processes were exposed to endotoxin levels above the recommended OEL of 90 EU/m3. Inhalable dust particulate was also above the 10 mg/m3 OEL for total inhalable dust in the hatchery, rearing and automated laying farms. Poultry catchers appear to be at greatest risk of developing adverse respiratory health effects due to endotoxins and (1–3) β-d-glucans.