Occurrence of antibiotics in Lettuce (Lactuca sativa L.) and Radish (Raphanus sativus L.) following organic soil fertilisation under plot-scale conditions: Crop and human health implications.

Recent studies have demonstrated the crop uptake of antibiotics (ABs) from soils treated with AB-carrying fertilisers. However, there is a lack of plot-scale studies linking their effects at the agronomic and metabolomic/transcriptomic level to their impact on human health. This paper assesses the plant uptake of 23 ABs following two productive cycles of lettuce and radish cropped with sewage sludge, pig slurry, the organic fraction of municipal solid waste, or chemical fertilisation under plot-scale conditions (32 plots spanning 3-10 m2 each). AB uptake by plants depended on both the vegetable and the AB class and was higher in radish than in lettuce edible parts. Levels ranged from undetectable to up to 76 ng/g (fresh weight). Repetitive organic fertilisation resulted in an increase in the concentration of ABs in lettuce leaves, but not in radish roots. Significant metabolomic and transcriptomic changes were observed following soil fertilisation. Nevertheless, a human health risk assessment indicates that the occurrence of ABs in lettuce or radish edible parts does not pose any risk. To our knowledge, this is the first holistic plot-scale study demonstrating that the use of organic fertilisers containing ABs is safe for crop security and human health.

Presumptive treatment of multidrug-resistant tuberculosis in household contacts.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a growing global health threat that often requires presumptive treatment in the absence of drug susceptibility testing (DST) results. OBJECTIVE: To compare two approaches to the treatment of MDR-TB contacts with no DST results who develop TB disease. DESIGN: We conducted a retrospective cohort study of adults treated for TB disease who were contacts of patients living with MDR-TB. Subjects had been treated according to one of two presumptive treatment strategies: 1) regimens containing exclusively first-line drugs, and 2) regimens that included both first- and second-line drugs that were adjusted if and when DST results became available. The primary endpoint was a composite of death and treatment failure. RESULTS: Household contacts of MDR-TB patients who developed TB disease and were treated with first-line regimens were significantly more likely to experience unfavorable end-of-treatment outcomes than those treated with presumptive MDR-TB regimens (RR 2.88, 95%CI 1.24-6.68). CONCLUSION: Household contacts of MDR-TB patients who develop TB disease but have no DST results should receive regimens containing second-line drugs selected based on the infecting strain of the index patient. Regimens containing only first-line anti-tuberculosis drugs significantly increase the risk of unfavorable outcomes.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.

Recurrent arrival of oil to Galician coast: the final step of the Prestige deep oil spill.

Yearly monitoring in one of the most affected coastal zones by the Prestige oil spill, namely Nemiña and O Rostro beaches (NW Spain), has been carried out since 2004. Topographic data of beaches revealed seasonal altimetric changes up to 4m that would prevent the on shore persistence of oil. However, surficial and subsurficial oil was detected in the intertidal area of both beaches in all campaigns. The hydrocarbon analysis confirmed that this oil corresponded to the Prestige oil, even nine years after the accident. Tar balls were highly biodegraded suggesting that the oil was accumulated on the subtidal sediments for a long time and transported to the coast by the action of waves. The present work provides new evidence of the long term persistence of deep oil spills from wrecks in marine areas where the hydrodynamic conditions play a twofold key role, in determining the exposed coastal area to recurrent contamination and in burying and resurfacing the oil in the intertidal zone.

Predictors of sputum culture conversion among patients treated for multidrug-resistant tuberculosis.

OBJECTIVE: To identify predictors of initial sputum culture conversion, estimate the usefulness of persistent positive cultures at different time points in predicting treatment failure, and evaluate different definitions of culture conversion for predicting failure among patients with multidrug-resistant tuberculosis (MDR-TB) in five countries, 2000-2004. METHODS: Predictors of time to conversion were identified using multivariate Cox proportional hazards regression modeling. Receiver operating characteristic curves were plotted to visualize the effect of using different definitions of 'culture conversion' on the balance between sensitivity and specificity. RESULTS: Overall, 1209/1416 (85%) of patients with baseline positive cultures converted in a median of 3.0 months (interquartile range 2.0-5.0). Independent predictors of less likely conversion included baseline positive smear (hazard ratio [HR] 0.60, 95%CI 0.53-0.68), resistance to pyrazinamide (HR 0.82, 95%CI 0.70-0.96), fluoroquinolones (FQs; HR 0.65, 95%CI 0.51-0.83) or thioamide (HR 0.83, 95%CI 0.71-0.96), previous use of FQs (HR 0.71, 95%CI 0.60-0.83), poor outcome of previous anti-tuberculosis treatment (HR 0.69, 95%CI 0.54-0.88) and alcoholism (HR 0.74, 95%CI 0.63-0.87). The maximum combined sensitivity (84%) and specificity (94%) in predicting treatment failure was based on lack of culture conversion at month 9 of treatment, assuming conversion is defined as five consecutive negative cultures. CONCLUSION: Patients with identified risk factors were less likely to achieve sputum culture conversion during MDR-TB treatment.

Programmatic management of multidrug-resistant tuberculosis: models from three countries.

BACKGROUND: Although multidrug-resistant tuberculosis (MDR-TB) is a major global health problem, there is a gap in programmatic treatment implementation. METHODS: This study describes MDR-TB treatment models in three countries--Peru, Russia and Lesotho-- using qualitative data collected over a 13-year period. RESULTS: A program analysis is presented for each country focusing on baseline medical care, initial implementation and program evolution. A pattern analysis revealed six overarching themes common to all three programs: 1) importance of baseline assessments, 2) early identification of key collaborators, 3) identification of initial locus of care, 4) minimization of patient-incurred costs, 5) targeted interventions for vulnerable populations and 6) importance of technical assistance and funding. Site commonalities and differences in each of these areas were analyzed. CONCLUSIONS: It is recommended that all programs providing MDR-TB treatment address these six areas during program development and implementation.

Accumulation trends of petroleum hydrocarbons in commercial shellfish from the Galician coast (NW Spain) affected by the Prestige oil spill.

Aliphatic and aromatic hydrocarbons were determined in three species of commercial shellfish, namely razor shells (Ensis arcuatus and Ensis siliqua), goose barnacle (Pollicipes cornucopia) and sea urchin (Paracentrotus lividus), living in different habitats and exhibiting different feeding behaviors. The samples were collected monthly, from January 2003 to October 2004, in three stations of the Galicia coast (NW Spain), following the Prestige oil spill, with the aim of assessing their response to the spill and, therefore, their suitability for monitoring purposes. The aliphatic fractions were mostly dominated by biogenic hydrocarbons, reflecting the diet composition of the organisms and their low metabolic capacity. The presence of oil was assessed by the determination of chemical markers. The analysis of the aromatic fractions revealed the occurrence of 3-6 ring parent and alkylated PAHs, consistent with a mixed petrogenic-pyrolytic origin, with the common feature of the predominance of chrysene in all samples collected after the spill. However, the distributions exhibited both temporal and interspecies variations. The PAH concentrations (Sigma13) increased significantly after the spill and decreased 6-7 months later close to background levels for the region. One year after the accident, the median values were: 58 microg/kg for razor shells, 26 microg/kg for barnacles, and 25 microg/kg for sea urchins. The temporal evolution of the PAH concentrations along the survey period was used to estimate loss rates for bioavailable PAHs in barnacles and sea urchins after the spill. Half-life values were in the order of 30 and 60 d, respectively. The results of the study demonstrate that barnacles can be suitable species for oil spill monitoring.

Assessment of in vivo effects of the prestige fuel oil spill on the mediterranean mussel immune system.

A laboratory experiment was carried out to study immune function alteration of the mussel Mytilus galloprovincialis when exposed to the Prestige oil spilled in November 2002 on the northwestern Spanish coast. Mussels were maintained for 4 months in tanks with flowing seawater and with 1, 2, and 0 kg (controls) Prestige fuel oil. Polycyclic aromatic hydrocarbon concentrations, which were determined in gills and digestive glands, were higher in digestive glands. The methylphenantrene and dibenzothiophene profiles confirmed the real exposure of mussels to the fuel oil. Immune data analysis revealed that no differences between fuel-treated and control animals were found in the cellular immune parameters measured (hemocyte viability, phagocytic activity, nitric oxide production, and chemiluminescence emission). In addition, histologic observations did not reveal tissue lesions in any of the samples, probably because of the short time of fuel-oil exposure. In contrast, significant differences were found in serum protein concentration and lysozyme activity between the fuel-treated mussels and controls. However, these humoral immune parameters were dependant on numerous environmental and physiologic factors, so it was difficult to ascertain the real effect of the fuel oil on their variability. Because hemocytes are the primary line of defense of bivalve mollusks, the results obtained in the present study suggest that the mussel immune system was not significantly affected by exposure to the Prestige fuel oil.

Fingerprinting petroleum hydrocarbons in plankton and surface sediments during the spring and early summer blooms in the Galician coast (NW Spain) after the Prestige oil spill.

Plankton samples (20-350 microm and >350 microm) collected at three transects along the Galician coast (NW Spain) were analysed for individual aliphatic and aromatic hydrocarbons by GC-MS. Sample collection was performed in April-July 2003, after the Prestige oil spill (November 2002), to determine whether the hydrocarbons released into the water column as a consequence of the spill were accumulated by the planktonic communities during the subsequent spring and early summer blooms. Surface sediments were also collected to assess the presence of the spilled oil, removed from the water column by downward particle transport. Plankton concentrations of PAHs (Sigma14 parent components) were in the range of 25-898 ng g(-1)dw, the highest values being close to coastal urban areas. However, the individual distributions were highly dominated by alkyl naphthalenes and phenanthrenes, paralleling those in the water dissolved fraction. The detailed study of petrogenic molecular markers (e.g. steranes and triterpanes, and methyl phenanthrenes and dibenzothiophenes) showed the occurrence of background petrogenic pollution but not related with the Prestige oil, with the possible exception of the station off Costa da Morte in May 2003, heavily oiled after the accident. The dominant northerly wind conditions during the spring and early summer 2003, which prevented the arrival of fresh oil spilled from the wreck, together with the heavy nature of the fuel oil, which was barely dispersed in seawater, and the large variability of planktonic cycles, could be the factors hiding the acute accumulation of the spilled hydrocarbons. Then, with the above exception, the concentrations of PAHs found in the collected samples, mostly deriving from chronic pollution, can be considered as the reference values for the region.

Spatial and temporal trends of petroleum hydrocarbons in wild mussels from the Galician coast (NW Spain) affected by the Prestige oil spill.

Polycyclic aromatic hydrocarbons (PAHs) were determined in tissues of wild mussels (Mytilus galloprovincialis) from the Galicia coast (NW Spain) in order to assess the extent of the environmental impact caused by the Prestige oil spill (November 13, 2002). Three sampling campaigns were carried out in February, June and November 2003 at 24 stations along the Galicia coast, from La Guardia (Pontevedra) to Ribadeo (Lugo). The spatial distribution of PAHs found in the first sampling period, clearly revealed the central area (Costa da Morte) as the most affected by the oil spill. In these stations, concentrations up to 7780 microg/kg dw of the sum of 13 parent PAHs were found 2-3 months after the spill. Molecular parameters within the aliphatic and aromatic fractions confirmed the presence of the Prestige oil in these samples. The levels markedly decreased at most of the stations in the second sampling and recovered to levels found before the spill in November 2003, 1 year after the accident (29-279 microg/kg dw, av. 133+/-83 microg/kg dw). However, a certain increase was observed in some sites which could be related to the remobilization of oil residues from still unclean intertidal spots or sediments due to the winter marine weather conditions.

Retreatment management strategies when first-line tuberculosis therapy fails.

SETTING: Public ambulatory centers in northern Lima, Peru. OBJECTIVE: To compare two retreatment strategies in Category I failures. DESIGN: Retrospective cohort study of Category I failures enrolled between February 1997 and October 2001. Strategy A was a nationwide approach, applying a Category II regimen; if that regimen failed, a standardized regimen including second-line drugs was used. Strategy B was a pilot protocol designed to diagnose and treat multidrug-resistant tuberculosis (MDR-TB); this strategy included drug susceptibility testing (DST) and eliminated the Category II regimen. RESULTS: Of 125 patients that Category I failed to cure, 73 entered Strategy A and 52 entered Strategy B. Almost 90% of those with DST results had MDR-TB. Strategy B was three times more likely than Strategy A to cure patients (79% vs. 38%, RR = 2.9, 95% CI 1.7-5.1) and five times more likely to cure patients than the Category II regimen alone (79% vs. 15%, RR 5.2, 95% CI 3.0-9.2). Strategy B also significantly reduced delays to MDR-TB diagnosis and to the initiation of MDR-TB therapy. CONCLUSIONS: Under program conditions, a retreatment strategy based on DST and eliminating the Category II regimen can improve clinical outcomes among Category I treatment failures found to have active, infectious MDR-TB.

Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.

SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.

Evaluation of acute toxicity and genotoxicity of liquid products from pyrolysis of Eucalyptus grandis wood.

Slow pyrolysis of Eucalyptus grandis wood was performed in an oven laboratory, and smoke was trapped and condensed to yield liquid products. Polycyclic aromatic hydrocarbons (PAHs) and phenolic fractions were isolated from the former liquid products using adsorption column chromatography (ACC) and identified by GC/MS. Concentrations of PAH and phenolic fractions in total pyrolysis liquids were respectively 48.9 microg/g and 8.59% (w/w). Acute toxicity of total samples of pyrolysis liquids and the phenolic fraction was evaluated by means of two bioassays, namely, 24-h immobilization bioassay with Daphnia magna and Microtox bioassays, the latter employing the luminescent bacteria Photobacterium phosphoreum. Total pyrolysis liquids and the PAH fraction were evaluated for genotoxicity by the Microtox bioassay conducted using rehydrated freeze-dried dark mutant of the luminescent bacteria Vibrio fisheri strain M169. Total pyrolysis liquids and the phenolic fraction, respectively, in concentrations of 170 and 68 mg/L were able to immobilize 50% (EC(50)) of the D. magna population following 24-h exposure. Concentrations of 19 and 6 mg/L, respectively, for total pyrolysis liquids and phenolic fraction were the effective concentrations that resulted in a 50% (EC(50)) reduction in light produced by bacteria in the Microtox bioassay. Accordingly, the Microtox bioassay was more sensitive to toxic effects of both kind of samples than the D. magna bioassay, particularly for the phenolic fraction. Regarding to the genotoxicity evaluation, the results achieved by Microtox bioassay showed that total pyrolysis liquids had no genotoxic effects with and without exogenous metabolic activation using rat liver homogenate (S9). However, the PAH fraction showed toxic effects with rat liver activation and had a dose-response number (DRN) equal to 1.6, being in this way suspected genotoxic. The lowest detected concentration (LDC) of the PAH fraction able to cause genotoxic effects was 375 microg/L.