Diffusive gradient in thin-films (DGT) as risk assessment and management tools in the Central Witwatersrand Goldfield, South Africa

Diffusive gradient in thin-films (DGT) technology was used to monitor bio-available metals and the tool was developed for risk-based pollution assessment and liability apportionment in the Witwatersrand Goldfields, South Africa, where there is widespread mine-related pollution. DGT technology is a passive sampling technique whereby metal species are selectively diffused from polluted water through a diffusion layer and trapped by an inner chelating resin, giving rise to time-weighted average concentrations.The results show that the concentrations of most hazardous metals recorded from grab samples are higher than values recorded from DGT samplers, resulting in inaccurate input information to risk assessors, the public and decision makers. DGT samplers deployed along upper, middle and lower reaches of Elsburgspruit, a stream southeast of Johannesburg, provided data which could assist in evaluating the source and evolution of metals along the stream length. DGT samplers deployed in 5 augers at different depths around a tailings dam showed that liming and trenching fails to contain deep seepage of trace metals. The results highlight the potential of using DGT samplers as a monitoring tool for providing accurate metal pollution information, assessing source and evolution of metals in streams or rivers for apportionment of liabilities, and evaluating the success of current contaminant containment methods.Keywords: Diffusive gradient in thin-films, binding gel, hydrogel, grab samples, diffusive boundary laye

Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

BACKGROUND: Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. METHODS: LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. RESULTS: 32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and < 50 cells/μl, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls. CONCLUSIONS: Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection

Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>The development and evaluation of rapid and accurate new diagnostic tools is essential to improve tuberculosis (TB) control in developing countries. In a previous study, the first release of a urine LAM-ELISA by Chemogen (Portland, USA) has been evaluated with a promising sensitivity and specificity for the diagnosis of pulmonary TB. In the present study, the now commercially available assay has been clinically assessed regarding its diagnostic value alone and in combination with clinical co-factors.</p> <p>Methods</p> <p>The test was applied to two urine samples from 291 consecutively enrolled Tanzanian patients with suspected pulmonary tuberculosis. The participants were subsequently assigned to classification groups according to microbiological, clinical and radiological findings at recruitment and during a maximum follow up period of 56 days.</p> <p>Results</p> <p>Only 35 out of 69 pulmonary TB cases -confirmed by smear microscopy and/or solid culture and/or liquid culture- showed at least one positive LAM-ELISA result (sensitivity 50.7%). The sensitivity was noticeably higher in females (66.7%) and in HIV positive participants (62.0%). The specificity amounted to 87.8% and was determined in participants with negative results in all microbiological tests and with sustained recovery under antibiotic treatment at day 56. Correlation with urinalysis revealed that proteinuria was significantly and positively associated with LAM-positivity (<it>P </it>= 0.026).</p> <p>Conclusion</p> <p>This commercially available generation of LAM-ELISA does not appear to be useful as an independent diagnostic test for pulmonary tuberculosis. The question whether the assay is suitable as a supplemental device in the diagnosis of HIV-associated TB, requires further investigations.</p

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type

A Threshold Value for the Time Delay to TB Diagnosis

The original publication is available at http:/www.plosone.orgIncludes bibliographyBackgound. In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. Methodology/Principal Findings. This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. Conclusions/Significance. The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. © 2007 Uys et al.Publishers' Versio

The effect of household heads training about the use of treated bed nets on the burden of malaria and anaemia in under-five children: a cluster randomized trial in Ethiopia

<p>Abstract</p> <p>Background</p> <p>Long-lasting insecticide-treated bed nets (LLITN) have demonstrated a significant effect in reducing malaria-related morbidity and mortality. However, barriers on the utilization of LLITN have hampered the desired outcomes. The aim of this study was to assess the effect of community empowerment on the burden of malaria and anaemia in under-five children in Ethiopia.</p> <p>Methods</p> <p>A cluster randomized trial was done in 22 (11 intervention and 11 control) villages in south-west Ethiopia. The intervention consisted of tailored training of household heads about the proper use of LLITN and community network system. The burden of malaria and anaemia in under-five children was determined through mass blood investigation at baseline, six and 12 months of the project period. Cases of malaria and anaemia were treated based on the national protocol. The burden of malaria and anaemia between the intervention and control villages was compared using the complex logistic regression model by taking into account the clustering effect. Eight Focus group discussions were conducted to complement the quantitative findings.</p> <p>Results</p> <p>A total of 2,105 household heads received the intervention and the prevalence of malaria and anaemia was assessed among 2410, 2037 and 2612 under-five children at baseline, six and 12 months of the project period respectively. During the high transmission/epidemic season, children in the intervention arm were less likely to have malaria as compared to children in the control arm (OR = 0.42; 95%CI: 0.32, 0.57). Symptomatic malaria also steadily declined in the intervention villages compared to the control villages in the follow up periods. Children in the intervention arm were less likely to be anaemic compared to those in the control arm both at the high (OR = 0.84; 95%CI: 0.71, 0.99)) and low (OR = 0.73; 95%CI: 0.60, 0.89) transmission seasons.</p> <p>Conclusion</p> <p>Training of household heads on the utilization of LLITN significantly reduces the burden of malaria in under-five children. The Ministry of Health of Ethiopia in collaboration with other partners should design similar strategies in high-risk areas to control malaria in Ethiopia.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12610000035022.aspx">ACTRN12610000035022</a></p

Incidence, prevalence and mortality rates of malaria in Ethiopia from 1990 to 2015: analysis of the global burden of diseases 2015

Background: In Ethiopia there is no complete registration system to measure disease burden and risk factors accurately. In this study, the 2015 Global Burden of Diseases, Injuries and Risk factors (GBD) data were used to analyse the incidence, prevalence and mortality rates of malaria in Ethiopia over the last 25 years. Methods: GBD 2015 used verbal autopsy (VA) surveys, reports, and published scientific articles to estimate the burden of malaria in Ethiopia. Age and gender-specific causes of death for malaria were estimated using Cause of Death Ensemble Modelling (CODEm). Results: The number of new cases of malaria declined from 2.8 million (95% uncertainty interval (UI): 1.4-4.5million) in 1990 to 621,345 (95% UI: 462,230-797,442) in 2015. Malaria caused an estimated 30,323.9 deaths (95% UI: 11,533.3-61,215.3) in 1990 and 1,561.7 deaths (95% UI: 752.8-2,660.5) in 2015, a 94.8% reduction over the 25 years. Age-standardized mortality rate of malaria has declined by 96.5% between 1990 and 2015 with an annual rate of change (ARC) of 13.4%. Age-standardized malaria incidence rate among all ages and gender declined by 88.7% between 1990 and 2015. The number of disability-adjusted life years lost (DALY) due to malaria decreased from 2.2 million (95% UI: 0.76-4.7 million) in 1990 to 0.18 million (95% UI: 0.12-0.26 million) in 2015, with a total reduction 91.7%. Similarly, age-standardized DALY rate declined by 94.8% during the same period. Conclusions: Ethiopia has achieved a 50% reduction target of malaria of the Millennium Development Goals (MDGs). The country should strengthen its malaria control and treatment strategies to achieve the Sustainable Development Goals (SDG)

Clinicopathological Significance and Prognostic Value of DNA Methyltransferase 1, 3a, and 3b Expressions in Sporadic Epithelial Ovarian Cancer

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients