Rajen N. Naidoo

Manganese and lead in children's blood and airborne particulate matter in Durban, South Africa.

Despite the toxicity and widespread use of manganese (Mn) and lead (Pb) as additives to motor fuels and for other purposes, information regarding human exposure in Africa is very limited. This study investigates the environmental exposures of Mn and Pb in Durban, South Africa, a region that has utilized both metals in gasoline. Airborne metals were sampled as PM(2.5) and PM(10) at three sites, and blood samples were obtained from a population-based sample of 408 school children attending seven schools. In PM(2.5), Mn and Pb concentrations averaged 17±27 ng m(-3) and 77±91 ng m(-3), respectively; Mn concentrations in PM(10) were higher (49±44 ng m(-3)). In blood, Mn concentrations averaged 10.1±3.4 μg L(-1) and 8% of children exceeded 15 μg L(-1), the normal range. Mn concentrations fit a lognormal distribution. Heavier and Indian children had elevated levels. Pb in blood averaged 5.3±2.1 μg dL(-1), and 3.4% of children exceeded 10 μg dL(-1), the guideline level. Pb levels were best fit by a mixed (extreme value) distribution, and boys and children living in industrialized areas of Durban had elevated levels. Although airborne Mn and Pb concentrations were correlated, blood levels were not. A trend analysis shows dramatic decreases of Pb levels in air and childrens blood in South Africa, although a sizable fraction of children still exceeds guideline levels. The studys findings suggest that while vehicle exhaust may contribute to exposures of both metals, other sources currently dominate Pb exposures.

Pesticide safety training and practices in women working in small-scale agriculture in South Africa

Objectives Unregulated use of pesticides continues in developing countries in the presence of illiteracy and limited safety training and practices. This paper describes training and safety practices when mixing and spraying pesticides, and acetylcholinesterase levels among women farmers in KwaZulu-Natal, South Africa. Methods A cross-sectional study conducted in women working in small-scale agriculture in rural KwaZulu-Natal, South Africa in 2006 assessed pesticide training and safety practices using a questionnaire survey and measured acetylcholinesterase levels in 803 women. Three components of safety behaviour were identified through principle component analysis and described. Results The mean age of participants was 41.8 years (range 18–82 years) with a mean of 6.9 years (range 1–12 years) of education among school attendees. Among the 803 women included, 366 (45.6%) were the primary sprayers on their farm. Only 16.4% of the sprayers had ever attended a pesticide training course and only 18.0% reported ever reading pesticide labels. Of the women using some form of protective equipment, 56.7% and 54.9% reported doing so when mixing and spraying pesticides, respectively. The mean acetylcholinesterase level corrected for haemoglobin among study participants was 28.9 U/g Hb (95% CI 28.4 to 29.4). Conclusion Women working in small-scale agriculture in rural KwaZulu-Natal with limited access to pesticide training observe few safety practices when mixing and spraying pesticides.

Occupational exposures and chronic obstructive pulmonary disease: a hospital based case–control study

Background Occupational exposures are associated with chronic obstructive pulmonary disease (COPD). This study investigated this association among a population with a high prevalence of tuberculosis and smoking. Methods Cases (n=110) diagnosed by pulmonologists were selected from specialist respiratory clinics. Frequency sex- and age-matched controls (n=102) were selected from other clinics at the same institutions. Lifetime occupational exposure histories were obtained through interviews. Exposure variables derived from the ALOHA Job Exposure Matrix (JEM) were used to complement the self-reporting variables. ORs were calculated from logistic regression models, adjusting for smoking and past history of tuberculosis. Percentage population attributable risk (PAR%) was also calculated. Results The adjusted ORs for COPD from the JEM-derived high cumulative biological dust exposure, high cumulative mineral dust exposure and high cumulative gas and fumes exposure were 2.1 (95% CI 1.1 to 4.2), 1.1 (95% CI 0.6 to 2.4) and 1.8 (95% CI 0.8 to 3.9), respectively. Self-reported occupational exposures were associated with higher risks, with adjusted ORs for high dust exposure-years and high chemical, gas and fumes exposure-years of 5.9 (95% CI 2.6 to 13.2) and 3.6 (95% CI 1.6 to 7.9), respectively. Among ever smokers, there was an increased risk for COPD, with ORs ranging from 5.0 to 5.5. Tuberculosis was a strong risk factor, with an OR ranging from 7.7 to 8.1. The PAR% was 25% for self-reported high exposures, but lower when the JEM variables were used. Conclusions Lifetime occupational exposures contribute to the risk of COPD, adjusted for smoking. These risks are present in populations with a high burden of tuberculosis, which is considered an important causative factor.

Agricultural Activities, Pesticide Use and Occupational Hazards among Women Working in Small Scale Farming in Northern KwaZulu-Natal, South Africa

Abstract South Mricas land policies have increased womens participation in agriculture, but limited information exists about their agricultural activities. We surveyed 911 women working on the Makhatini Flats in Northern KwaZulu-Natal in 2006, gathering data on demographics, agricultural activities, crop production and pesticide use in both irrigated and Dryland areas. Average age of participants was 41.9, with Drylands women slightly older. Education levels were low among both groups, but lowest in the Drylands. Drylands women were more likely to engage in reported agricultural activities, including pesticide spraYing. Use of World Health Organization class I and II pesticides was reported in both areas. Farm ownership, age <30 years, and being a sprayer were associated with knowledge of the names of pesticides utilized. This analysis suggests that women on the Drylands face greater risk of adverse ergonomic health outcomes and women from both areas are equally at risk for adverse pesticiderelated health outcomes.

The relationship between asthma and ambient air pollutants among primary school students in Durban, South Africa

We examined the prevalence of asthma among students in Grades 3 and 6 at a primary school located in the highly industrialised South Durban Industrial Basin. After baseline interviews and methacholine challenge testing (MCT), students completed bihourly symptom logs during an 18-day study period. Continuous measurements of ambient contaminants at the school included sulphur dioxide (SO2), oxides of nitrogen (NOx), and respirable particulate matter less than 10 µm (PM10). Generalised estimating equations were used to examine associations between lagged fluctuations in ambient air pollutant concentrations and daily reported symptoms. Among the 248 participants, 52% had asthma of any severity; including 11% with moderate to severe persistent asthma. On MCT, 21% of the children had marked (PC20 ≤ 2 mg/ml), 29% had probable, and 19% had possible airway hyperreactivity. Concentrations of air pollutants at the school during the study period fell below international and South African standards and guidelines. Increased lower respiratory symptoms (cough, wheezing, chest tightness or heaviness, and shortness of breath) were strongly and consistently associated with prior day fluctuations in ambient levels of both SO2 and PM10 in both single-pollutant and two-pollutant models. We note the important role of local stakeholders in implementing and conducting this study.

GSTM1 and GSTP1 gene variants and the effect of air pollutants on lung function measures in South African children

BACKGROUND Several genes are associated with an increased susceptibility to asthma, which may be exacerbated by ambient air pollution. These genes include GSTM1 (glutathione-S-transferase M1 gene) and GSTP1 (glutathione-S-transferase P1 gene), which may modulate the response to epithelial oxidative changes caused by air pollutant exposure. This study evaluated fluctuations in the forced expiratory volume in one second (FEV(1)) in relation to lagged daily averages of ambient air pollutants (SO(2), NO(2), NO, and PM(10)) while considering genotype as an effect modifier. METHODS A longitudinal cohort of 129 schoolchildren of African descent from Durban, South Africa was assessed. GSTM1 (null vs. present genotype) and GSTP1 (Ile105Val; AA → AG/GG) genotypes were determined using standard techniques. SO(2), NO(2), NO, and PM(10) were measured continuously over a year using validated methods. The outcome was intraday variability in FEV(1) . Data were collected daily over a 3-week period in each of four seasons (2004-2005). RESULTS Among the children tested, 27% had the GSTM1 null genotype and 81% carried the GSTP1 G allele. Approximately 26 out 104 children (25%) showed evidence of bronchial hyperreactivity, 13% reported having symptoms in keeping with persistent asthma, and a further 25% reported symptoms of mild intermittent asthma. PM(10) and SO(2) levels were moderately high relative to international guidelines. Neither GSTM1 nor GSTP1 genotypes alone were significantly associated with FEV(1) intraday variability. In models not including genotype, FEV(1) variability was statistically significantly associated only with NO(2) for 5-day lags (% change in intraday variability in FEV1 per interquartile range = 1.59, CI 0.58, 2.61). The GSTP1 genotype modified the effect of 3 days prior 24-hr average PM(10) and increased FEV(1) variability. A similar pattern was observed for lagged 3 day SO(2) exposure (P interaction < 0.05). Adverse effects of these pollutants were limited to individuals carrying the G allele for this polymorphism. CONCLUSION Among this indigenous South African children cohort, the GSTP1 genotype modified the effects of ambient exposures to PM(10) and SO(2) and lung function. A plausible mechanism for these observed effects is decreased capacity to mount an effective response to oxidative stress associated with the GSTP1 AG + GG genotype.

Estimation of respirable dust exposure among coal miners in South Africa

The use of retrospective occupational hygiene data for epidemiologic studies is useful in determining exposure-outcome relationships, but the potential for exposure misclassification is high. Although dust sampling in the South African coal industry has been a legal requirement for several decades, these historical data are not readily adequate for estimating past exposures. This study describes the respirable coal mine dust levels in three South African coal mines over time. Each of the participating mining operations had well-documented dust sampling information that was used to describe historical trends in dust exposure. Investigator-collected personal dust samples were taken using standardized techniques from the face, backbye (underground jobs not at the coal face), and surface from 50 miners at each mine, repeated over three sampling cycles. Job histories and exposure information was obtained from a sample of 684 current miners and 188 ex-miners. Linear models were developed to estimate the exposure levels associated with work in each mine, exposure zone, and over time using a combination of operator-collected historical data and investigator-collected samples. The estimated levels were then combined with work history information to calculate cumulative exposure metrics for the miner cohort. The mean historical and investigator-collected respirable dust levels were within international norms and South African standards. Silica content of the dust samples was also below the 5% regulatory action level. Mean respirable dust concentrations at the face, based on investigator-collected samples, were 0.9 mg/m3, 1.3 mg/m3, and 1.9 mg/m3 at Mines 1, 2, and 3, respectively. The operator-collected samples showed considerable variability across exposure zones, mines, and time, with the annual means at the face ranging from 0.4 mg/m3 to 2.9 mg/m3. Statistically significant findings were found between operator- and investigator-collected dust samples. Model-based arithmetic mean dust estimates at the face were 1.2 mg/m3, 2.0 mg/m3, and 0.9 mg/m3 for Mines 1, 2, and 3, respectively. Using these levels, the mean cumulative exposure for the cohort was 56.8 mg-years/m3. Current miners had a mean cumulative exposure of 66.5 mg-years/m3, compared with ex-miners of 26.8 mg-years/m3. Improvements in dust management or the use of different sampling equipment could account for the significant differences seen between operator- and investigator-collected data. Regression modeling for estimating mean dust levels over time using combined historical and investigator-collected data seems a reasonable method and useful in constructing models to describe cumulative exposures in a cohort of current and ex-miners.

Respirable coal dust exposure and respiratory symptoms in South-African coal miners: A comparison of current and ex-miners

Objectives: Dose–response associations between respirable dust exposure and respiratory symptoms and between symptoms and spirometry outcomes among currently employed and formerly employed South-African coal miners were investigated. Methods: Work histories, interviews, and spirometry and cumulative exposure were assessed among 684 current and 212 ex-miners. Results: Lower prevalences of symptoms were found among employed compared with ex-miners. Associations with increasing exposure for symptoms of phlegm and past history of tuberculosis were observed, whereas other symptom prevalences were higher in the higher exposure categories. Symptomatic ex-miners exhibited lower lung function compared to the nonsymptomatic. Conclusions: Compared with published data, symptoms rates were low in current miners but high in ex-miners. Although explanations could include the low prevalence of smoking and/or reporting/selection bias, a “survivor” and/or a “hire” effect is more likely, resulting in an underestimation of the dust-related effect.

Oxidative stress and air pollution exposure during pregnancy A molecular assessment

Chronic air pollution exposure during pregnancy can cause oxidative stress leading to adverse birth outcomes. The aim of this study was to assess and compare oxidative stress response in peripheral lymphocytes isolated from pregnant women from a highly industrialized locale (south Durban (SD); n = 50) and a control with lower air pollutant levels (north Durban (ND); n = 50). Oxidative stress response was measured by quantifying malondialdehyde (MDA) levels and a SuperArray gene panel. Mitochondrial function (adenosine triphosphate (ATP) levels and mitochondrial depolarization), DNA integrity (comet assay and mitochondrial DNA (mtDNA) viability) and DNA repair (OGG1) were assessed. Antioxidant response was assessed by quantification of glutathione (GSH) and SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2) and uncoupling protein 2 (UCP2) protein and messenger RNA (mRNA) expression. Levels of MDA (p = 0.9), mitochondrial depolarization (p = 0.88), ATP (1.89-fold), SOD2 (1.23-fold) and UCP2 (1.58-fold) gene expression were elevated in the SD group with significantly higher UCP2 protein levels (p = 0.05) and longer comet tail length (p = 0.0004). The expression of Nrf2 protein (p = 0.03) and mRNA levels (−1.37-fold), GSH concentration (p < 0.0001), mtDNA amplification (−2.04-fold) and OGG1 mRNA (−2.78-fold) activity were decreased in the SD group. Of the 84 oxidative stress-related genes evaluated, 26 were differentially regulated. Pregnant women exposed to higher air pollutant levels showed increased markers for oxidative stress and compromised DNA integrity and repair.

Occupational Exposures and Chronic Obstructive Pulmonary Disease: Incontrovertible Evidence for Causality?

addition and of great pathogenetic concern, a hereditary (i.e., gene-determined) component is believed to contribute importantly to the clinical occurrence of each condition. However, the culprit genes, so far at least, have eluded identification. Thousands of patients with heart disease, cancer, and chronic obstructive pulmonary disease, along with suitable numbers of healthy control subjects, have had genome-wide association studies, and more and more people are having genomic analyses; yet all that has turned up are some low-risk genetic variants that both alone and in combination fall far short of accounting for the putative hereditary link with the disease. Much of importance seems to be missing. Useful offshoots of pharmacogenomics, how variations in the human genome affect the response to medications, are beginning to show up in everyday medicine. The Food and Drug Administration now requires genetic information in the labeling of warfarin, clopidogrel, and several other commonly used drugs. Moreover, tumor biomarkers are being increasingly used to optimize choice of chemotherapeutic regimens in various malignancies, including non–small-cell cancer of the lung (7). Detection of cancers bearing the gene encoding mutated epidermal growth factor receptor or the EML/ALK4 translocation and treatment with specifically addressed chemotherapeutic agents has led to significantly prolonged therapeutic responses, which do not occur in patients without the biomarker. Recent observations suggest that some of the individualized clinical advantages resulting from the detection of tell-tale biomarkers and treatment with tailored agents might be lost or attenuated (8); it turns out that renal cell cancers, and probably other malignancies, contain multiple markers or mutations that may not show up in a single biopsy specimen, thereby confusing the personalized “genomics landscape.” (Sometimes people equate genetic testing with genomic analysis, but the two are very different. Separate tests are now available to determine if a person carries one of the more than 1,000 known genes linked to human diseases, nearly all of which are infrequent and seldom encountered in medical practice, and which for the most part were not discovered by genomic analysis.) The enormously complicated and high-priced steps leading to full realization of the seemingly vast clinical potential inherent in the human genome were cataloged in the 2007 Health and Human Services document already cited (3). The summary account of the recent NHLBI-sponsored conference, “New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care,” added a few more charges (9). Both reports stress that implementation stretches considerably beyond simply learning more than we know now about how and which genes regulate human disease; neither proffered a timetable nor budget.