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Infectious bronchitis is a highly contagious viral disease that represents an economic threat for poultry despite the wide use of vaccination. To characterize the virus circulating in Peru, we analyzed 200 samples, including nasopharyngeal swabs and multiple tissues collected from animals suspected of being infected with infectious bronchitis virus (IBV) between January and August in 2015. All animals had at least one positive sample for IBV by RT-PCR. Out of these positive samples, eighteen (18) were selected for viral isolation and a partial S1 sequencing. Phylogenetic analysis showed that sixteen isolates clustered with members of GI-16 lineage, also known as Q1, with nucleotide homology ranging from 93% to 98%. The two remaining isolates grouped with members of the GI-1 lineage. Our study reveals circulation of GI-16 lineage during this period in poultry systems in Peru, along with GI-1 lineage (vaccine-derived). Moreover, those IBV GI-16 isolates showed unique nucleotide and amino acid changes compared to their closest relatives. Altogether, these findings reveal the circulation of GI-16 lineage while describing changes at key regions of the S protein that might be of relevance for vaccine evasion. These results highlight the importance of genetic surveillance for improving vaccination strategies against infectious bronchitis.

The application of pig slurry as fertilizer in agriculture provides nutrients, but it can also contain veterinary medicines, including antibiotic residues (ABs), which can have an ecotoxicological impact on agroecosystems. Furthermore, uptake, translocation, and accumulation of ABs in crops can mobilize them throughout the food chain. This greenhouse study aims to assess AB uptake from soil fertilized with pig slurry and its phenotypical effects on Lactuca sativa L. The plants were cropped in loamy clay soil dosed at 140 kg total N/ha and containing antibiotics (lincomycin, sulfadiazine, oxytetracycline, and enrofloxacin) at different concentration levels (0, 0.05, 0.5, 5, 50, and 500 mg/kg fresh weight, fw). Whereas sulfadiazine (11.8 ng/g fw) was detected in lettuce leaves at the intermediate doses (0.5 mg/kg), lincomycin and its transformation products (hydroxy/sulfate) were only detected at the 50 mg/kg fw dose. In addition, increased AB doses in the pig slurry resulted in decreased lettuce fresh weight and lipid and carbohydrate content and became lethal to lettuce at the highest AB concentrations (500 mg/kg fw). Nevertheless, even at higher doses, the AB content in lettuce following pig-slurry fertilization did not pose any direct significant human health risk (total hazard quotient<0.01). However, the promotion of antimicrobial resistance in humans due to the intake of these vegetables cannot be ruled out., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions., (Copyright © 2021 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

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 m 2 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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Before 2021, the combination of bortezomib, cyclophosphamide, and dexamethasone (VCd) was one of the most used upfront therapy for systemic immunoglobulin light chain (AL) amyloidosis. Recently, daratumumab in combination with VCd resulted in improved outcomes compared to VCd. However, it's still unclear the role of cyclophosphamide in this combination., Materials and Methods: We conducted this retrospective single-institutional study to compare the outcomes of upfront bortezomib and dexamethasone with or without cyclophosphamide (VD vs. VCd)., Results: Of 136 total patients, 62 received VD and 74 received VCd. The median age was 64 and the median number of organs involved was 2. Hematologic response was achieved among 73.4% patients in the VD arm and 85.9% in the VCd arm at 3 months (P = .15). Best organ response was not different between 2 arms (34.1% vs. 52.9% for VD and VCd arms, respectively; P = .28). After a median follow-up of 24.4 months, 2-year OS for VD and VCd arm was 70.6% and 84.6% respectively. The median overall survival was 70 months for VD arm and not reached for VCd arm (P = .30). There was no statistically significant difference in median time to next therapy (9.3 vs. 13.5 months for VD and VCd arms, respectively. P = .99)., Conclusion: the addition of cyclophosphamide to VD was not associated with improved outcomes of patients with AL amyloidosis in this retrospective study., (Copyright © 2022. Published by Elsevier Inc.)

The aim of this study was to establish the diagnoses of patients with disseminated eczema and analyze the allergens involved in disseminated eczema due to allergic contact dermatitis. We analyzed the data from patients with a diagnosis of disseminated / generalized eczema who had undergone anamnesis, physical examination and patch tests in a Contact Dermatitis consultation from 2003 to 2019. Allergic contact dermatitis was the most frequent diagnosis, folowed by atopic dermatitis, asteatotic eczema, and gravitational eczema. The allergens most frequently involved in allergic contact dermatitis were isothiazolinones, topical medications, paraphenylenediamine, and fragrances. Allergic contact dermatitis caused almost half of the cases of disseminated eczema. It would be therefore advisable for patients with disseminated eczema to be assessed at a Contact Dermatitis unit and undergo patch tests.

Background: Cutaneous, superficial and or suprafascial leiomyoma are divided into three variants: piloleiomyomas (PL), angioleiomyomas (AL) and genital leiomyomas (GL) that include the vulvar, scrotal and areolar forms. This study set out to establish the clinical and histological characteristics and incidence of each variant, and any likely associations with internal neoplasms., Methods: A review was carried out of 255 cases of cutaneous leiomyomas diagnosed between 1982 and 2018 at the Pathology departments of three hospitals (Navarra and Alicante). Demographic, clinical, histological and immunohistochemical variables were described and compared., Results: The incidence of PL in Navarra was 4.3 cases per million inhabitants a year, with another 20 cases of AL and 1.4 cases of GL. Cutaneous forms make up approximately 3.5% of the total leiomyomas. The population with PL suffered more frequently from breast cancer (OR?=?4.8; CI 95%: 1.3-17.4; p?=?0.006). Nipple leiomyomas are small, accompanied by localised pain, and are predominantly fascicular or solid, with very infrequent effect on the subcutaneous cellular tissue and scarce atypia. This makes for a contrast with the other GLs, which are medium sized and infrequently painful, predominantly nodular, and frequent effect on the subcutaneous tissue and atypia., Conclusions: The information provided here about the clinical and histological characteristics of the different varieties of leiomyomas indicate that there is a need to reconsider the classification of nipple leiomyomas outside the group of GLs. An association between PL and breast carcinoma was detected, which needs to be confirmed in future studies so as to determine if this leiomyoma is a risk marker for breast cancer.

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions., (Copyright © 2021 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cultivation practice using organic amendments is plausible to ensure global food security. However, plant abiotic stress due to the presence of metals and organic microcontaminants (OMCs) in fertilization products cannot be overlooked. In this study, we monitored lettuce metabolism and phenotypic response following the application of either sewage sludge (SS), the organic fraction of municipal solid waste, swine manure (SM), chemical fertilizers (CF), or no amendment (C) in a greenhouse facility. The experimental set-up consisted of five treatments with five replicates (25 experimental units randomly distributed). All fertilizers were supplied at the equivalent agronomic total nitrogen dose, but the occurrence of trace metals and/or OMCs was greater in the SS and SM than the rest. Non-target metabolomic analysis (high-resolution mass spectrometry coupled with partial least squares regression) identified more than 300 plant metabolites (amino acids, organic acids, sugar alcohols, and sugars), 55 of which showed significant changes in their relative abundances depending on the type of amendment. Functional analysis indicated that the use of CF or SS increased the levels of metabolites involved in carbohydrate and nitrogen metabolism. Therefore, although SS and SM fertilizers had a greater presence of heavy metals and/or OMCs, our results indicate that they did not induce measurable adverse effects in the lettuce phenotype or metabolism. Metabolic changes between fertilizers (CF and SS vs. C and SM) were mainly due to nitrogen availability.

Understanding factors affecting ME availability for productive processes is an important step in optimal feed formulation. This study compared a modelling methodology with the comparative slaughter technique (CST) to estimate energy partitioning to heat production and energy retention (RE) and to investigate differences in heat dissipation. At hatch, 50 broilers were randomly allocated in one of 4 pens equipped with a precision feeding station. From day 14 to day 45, they were either fed with a low-ME (3,111 kcal/kg ME) or a high-ME (3,383 kcal/kg ME) diet. At day 19, birds were assigned to pair-feeding in groups of 6 with lead birds eating ad libitum (100%) and follow birds eating at either 50, 60, 70, 80, or 90% of the paired lead's cumulative feed intake. Heat production and RE were estimated by CST and with a nonlinear mixed model explaining daily ME intake (MEI) as a function of metabolic BW and average daily gain (ADG). The energy partitioning model predicted MEI = (145.10 + u) BW 0.83  + 1.09 × BW -0.18  × ADG 1.19  + ε. The model underestimated heat production by 13.4% and overestimated RE by 22.8% compared with the CST. The model was not able to distinguish between net energy for gain values of the diets (1,448 ± 18.5 kcal/kg vs. 1,493 ± 18.0 kcal/kg for the low-ME and high-ME diet, respectively), whereas the CST found a 148 kcal/kg difference between the low-ME and high-ME diets (1,101 ± 22.5 kcal/kg vs. 1,249 ± 22.0 kcal/kg, respectively). The estimates of the net energy for gain values of the 2 diets decreased with increasing feed restriction. The heat increment of feeding did not differ between birds fed with the low- or high-ME diet (26% of MEI). Additional measurements on heat dissipation, physical activity, and immune status indicated that the energetic content of the diet and feed restriction affect some parameters (shank temperature, feeding station visits) but not others (leukocyte counts, heterophil to lymphocyte ratio, and immune cell function)., (Copyright © 2020. Published by Elsevier Inc.)

Background: To describe the dermoscopic features in superficial basal cell carcinoma that are associated with a poor therapeutic response to imiquimod treatment., Method: Clinical and dermatoscopic photographs of 56 superficial basal cell carcinomas of different patients were compared retrospectively, assessed in our office for five years and treated with topic 5% imiquimod five days a week for six weeks. The different dermatoscopic signs of the lesions were identified and the association of each of them with the response to treatment was assessed., Results: A total response to treatment was achieved by 69.5% of the lesions of patients treated with imiquimod. Dermatoscopy of responding lesions showed a higher frequency of lesions with in focus gray dots (43.6%) and multiple erosions of less than 2 mm (61.5%), without observing statistically significant differences. Within the group with poor response to treatment, a greater number of lesions were found with the presence of arborizing telangiectasias (58.8%), blue-gray ovoid nests (41.1%), ulceration (58.8%), shiny white-red structureless areas (82.2%) and chrysalis (41.2%). The areas in blue-white veil areas (23.5%) and rainbow pattern (23.5%) were only observed in non-responding lesions. Both groups were similar regarding age, sex, diameter of lesions and frequency of some dermatoscopic signs: fine short telangiectasias, gray blue globules, arc-leaf areas and cart-wheel structures., Conclusion: The study identified dermatoscopic criteria that are significantly associated with a worse response to treatment with imiquimod. In contrast, we found no dermatoscopic signs that correlate specifically to a complete response to treatment.

Antibiotic exposure during neonatal development may result in transient or persistent alterations of key microbes that are vital for normal development of local and systemic immunity, potentially impairing immune competence later in life. To further elucidate the relationship between antibiotic exposure and immune development, newborn pigs were exposed to a therapeutic pediatric dose (30 mg/kg/day) of amoxicillin (AB) or placebo (PL) from post-natal day (PND) 0-14. Subsequently, immune cell phenotype, microbial composition, and immune response to an intraperitoneal (IP) challenge with Salmonella enterica serovar Typhimurium were evaluated. AB exposure caused significant changes in fecal microbial composition on PND 3 ( P = 0.025). This stemmed from a 2-fold increase in Enterobacteriaceae with live cecal coliforms on PND 7 indicating at 10-fold increase ( P = 0.036). Alterations in microbial composition were transient, and successional patterns were normalizing by PND 14 ( P = 0.693). Differences in PBMC (peripheral blood mononuclear cell) immune cell subtypes were detected, with the percentage of CD3 + CD4 + T cells among the broader T cell population (CD3 + CD4 + /CD3 + ) being significantly higher ( P = 0.031) in AB pigs and the numbers of CD4+CD45RA+ (naïve) T cells per liter of blood were lower on PND 21 in AB pigs ( P = 0.036). Meanwhile, PBMCs from AB pigs produced significantly more IFNγ upon stimulation with a T-cell mitogen on PND 21 and 49 ( P = 0.021). When AB pigs were challenged with heat-killed Salmonella (IP) on PND 49, IFNγ gene expression in peripheral blood was upregulated compared to those treated with PL ( P = 0.043). Additionally, AB pigs showed stronger activation among neutrophils infiltrating the peritoneal cavity after in vivo immune challenge, based on higher levels of NF-κB nuclear translocation ( P = 0.001). Overall, our results indicate that early life treatment with a therapeutically relevant dose of a commonly prescribed antibiotic has a programming effect on the immune system. Despite antibiotics only causing a transient disruption in gut-associated microbial communities, implications were long-term, with antibiotic treated pigs mounting an upregulated response to an immune challenge. This research adds to the growing body of evidence indicating adverse immune outcomes of early life antibiotic exposures.

Water deficit stress (WDS)-tolerance in grain amaranths ( Amaranthus hypochondriacus , A. cruentus and A. caudatus ), and A. hybridus , their presumed shared ancestor, was examined. A. hypochondriacus was the most WDS-tolerant species, a trait that correlated with an enhanced osmotic adjustment (OA), a stronger expression of abscisic acid (ABA) marker genes and a more robust sugar starvation response (SSR). Superior OA was supported by higher basal hexose (Hex) levels and high Hex/sucrose (Suc) ratios in A. hypochondriacus roots, which were further increased during WDS. This coincided with increased invertase, amylase and sucrose synthase activities and a strong depletion of the starch reserves in leaves and roots. The OA was complemented by the higher accumulation of proline, raffinose, and other probable raffinose-family oligosaccharides of unknown structure in leaves and/or roots. The latter coincided with a stronger expression of Galactinol synthase 1 and Raffinose synthase in leaves. Increased SnRK1 activity and expression levels of the class II AhTPS9 and AhTPS11 trehalose phosphate synthase genes, recognized as part of the SSR network in Arabidopsis, were induced in roots of stressed A. hypochondriacus . It is concluded that these physiological modifications improved WDS in A. hypochondriacus by raising its water use efficiency.

Social concern has raised during the last years due to the development of antibiotic resistance hotspots in different environmental compartments, including the edible parts of crops. To assess the influence of the water quality used for watering, we collected samples from soil, roots, leaves and beans from the legume plant Vicia faba (broad beans) in three agricultural peri-urban plots (Barcelona, NE Spain), irrigated with either groundwater, river water, or reclaimed water. Antibiotic resistance genes (ARGs) sul1, tetM, qnrS1, bla CTX-M-32, bla OXA-58 , mecA, and bla TEM were quantified by real-time PCR, along with 16S rDNA and intl1 sequences, as proxies for bacterial abundance and integron prevalence, respectively. Microbiome composition of all samples were analyzed by high-throughput DNA sequencing. Results show a gradient of bacterial species diversity and of ARG prevalence from highly diverse soil samples to microbially-poor beans and leaves, in which Rhizobiales essentially displaced all other groups, and that presented very small loads of ARGs and integron sequences. The data suggest that the microbiome and the associated resistome were likely influenced by agricultural practices and water quality, and that future irrigation water legal standards should consider the specific Physiology of the different crop plants., (Copyright © 2018 Elsevier Inc. All rights reserved.)

While the presence of antibiotic resistance genes (ARGs) in agricultural soils and products has been firmly established, their distribution among the different plant parts and the contribution of agricultural practices, including irrigation with reclaimed water, have not been adequately addressed yet. To this end, we analyzed the levels of seven ARGs (sul1, bla TEM , bla CTX-M-32 , mecA, qnrS1, tetM, bla OXA-58 ), plus the integrase gene intl1, in soils, roots, leaves, and fruits from two commercial tomato fields irrigated with either unpolluted groundwater or from a channel impacted by treated wastewater, using culture-independent, quantitative real-time PCR methods. ARGs and intl1 sequences were found in leaves and fruits at levels representing from 1 to 10% of those found in roots or soil. The relative abundance of intl1 sequences correlated with tetM, bla TEM , and sul1 levels, suggesting a high horizontal mobility potential for these ARGs. High-throughput 16S rDNA sequencing revealed microbiome differences both between sample types (soil plus roots versus leaves plus fruits) and sampling zones, and a correlation between the prevalence of Pseudomonadaceae and the levels of different ARGs, particularly in fruits and leaves. We concluded that both microbiome composition and ARGs levels in plants parts, including fruits, were likely influenced by agricultural practices., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa., Methods: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa., Findings: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040., Interpretation: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis., Funding: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Primary health care (PHC) has been recognized as a core component of effective health systems since the early part of the twentieth century. However, despite notable progress, there remains a large gap between what individuals and communities need, and the quality and effectiveness of care delivered. The Primary Health Care Performance Initiative (PHCPI) was established by an international consortium to catalyze improvements in PHC delivery and outcomes in low- and middle-income countries through better measurement and sharing of effective models and practices. PHCPI has developed a framework to illustrate the relationship between key financing, workforce, and supply inputs, and core primary health care functions of first-contact accessibility, comprehensiveness, coordination, continuity, and person-centeredness. The framework provides guidance for more effective assessment of current strengths and gaps in PHC delivery through a core set of 25 key indicators ("Vital Signs"). Emerging best practices that foster high-performing PHC system development are being codified and shared around low- and high-income countries. These measurement and improvement approaches provide countries and implementers with tools to assess the current state of their PHC delivery system and to identify where cross-country learning can accelerate improvements in PHC quality and effectiveness.

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests., Competing Interests: can be found alongside this article at erj.ersjournals.com, (The content of this work is copyright the authors or their employers. Design and branding are copyright ©ERS 2016.)

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.

Background: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined., Methods: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens., Results: Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome., Conclusions: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance., (Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen., Methods and Findings: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse., Conclusions: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.

SUMOylation is an important post-translational modification conserved in eukaryotic organisms. In Trypanosoma brucei, SUMO (Small Ubiquitin-like MOdifier) is essential in procyclic and bloodstream forms. Furthermore, SUMO has been linked to the antigenic variation process, as a highly SUMOylated focus was recently identified within chromatin-associated proteins of the active variant surface glycoprotein expression site. We aimed to establish a reliable strategy to identify SUMO conjugates in T. brucei. We expressed various tagged variants of SUMO from the endogenous locus. His-HA-TbSUMO was useful to validate the tag functionality but SUMO conjugates were not enriched enough over contaminants after affinity purification. A Lys-deficient SUMO version, created to reduce contaminants by Lys-C digestion, was able to overcome this issue but did not allow mapping many SUMOylation sites. This cell line was in turn useful to demonstrate that polySUMO chains are not essential for parasite viability. Finally, a His-HA-TbSUMO(T106K) version allowed the purification of SUMO conjugates and, after digestion with Lys-C, the enrichment for diGly-Lys peptides using specific antibodies. This site-specific proteomic strategy led us to identify 45 SUMOylated proteins and 53 acceptor sites unambiguously. SUMOylated proteins belong mainly to nuclear processes, such as DNA replication and repair, transcription, rRNA biogenesis and chromatin remodelling, among others., (© 2015 John Wiley & Sons Ltd.)

Determination of the dissolved-bioavailable fraction of methylmercury (MeHg) and its degradation pathways in freshwaters deserve attention, to further our understanding of the potential risk and toxicity of MeHg. Since the photodegradation of MeHg is the most important known abiotic process able to demethylate MeHg, this study investigated the role of sunlight on MeHg bioavailability in freshwater environments. Experiments to calculate photodegradation rate constants of MeHg in different types of freshwater in combination with experiments to distinguish the labile fraction of MeHg after being exposed to sunlight were performed. The ability of diffusive gradients in thin films based on polyacrylamide (P-DGT) to assess DGT-labile MeHg during photodegradation was successfully tested. First order photodegradation rate constants (kpd) of bioavailable MeHg determined in five different types of waters with different amount of dissolved organic matter (DOM), were in the range 0.073-0.254 h(-1), confirming previous findings that once there is DOM in solution, which would favour the photodegradation process, the kpd is mainly affected by light attenuation. Simulated sunlight seems not to alter the lability of MeHg, although photodegradation processes may decrease the concentrations of MeHg, contributing to reduce the amount of bioavailable MeHg (i.e. MeHg uptake by DGT). However, the quality of DOM, rather than the quantity, plays an important role in the bioavailability of MeHg in freshwater., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens.

Rationale: For treatment of multidrug-resistant tuberculosis, World Health Organization (WHO) guidelines recommend four likely effective drugs plus pyrazinamide (PZA), irrespective of the likely effectiveness of PZA in an individual patient. Whether this regimen should be supplemented in the absence of likely PZA effectiveness is an open question., Objectives: The objectives of this study were to examine (1) whether individuals receiving four likely effective drugs (based on documented susceptibility or no prior exposure) experienced higher mortality during the intensive phase of treatment than those receiving five likely effective drugs and (2) whether the WHO-recommended regimen (four likely effective drugs plus PZA) may be compromised in individuals in whom PZA is not likely effective., Methods: Among 668 patients, we compared the hazard of death across regimen groups characterized by the number of likely effective drugs and whether pyrazinamide was one of the likely effective drugs., Measurements and Main Results: Relative to five likely effective drugs, regimens of four likely effective drugs and the WHO-recommended regimen used in individuals in whom PZA was not likely effective were associated with higher mortality rates (respectively, adjusted hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.35-6.09 and adjusted HR, 2.76; 95% CI, 0.92-8.27). The mortality rate for a regimen of five likely effective drugs with likely effective PZA was similar to that for the regimen of five likely effective drugs without PZA (HR, 1.00; 95% CI, 0.12-8.00)., Conclusions: Mortality may be reduced by the inclusion of five likely effective drugs, including an injectable, during the intensive phase of treatment. If PZA is unlikely to be effective in an individual patient, these results suggest adding a different, likely effective drug.

Background: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis., Methods: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling., Findings: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0·0001). Furthermore, conversion status at 6 months (adjusted OR 14·07 [95% CI 10·05-19·71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4·12 [95% CI 2·25-7·54]) or who had unknown HIV infection (3·59 [1·96-6·58]), but not in those who were HIV positive (0·38 [0·12-1·18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27·3% [95% confidence limit 16·6-41·4]) and high specificity (89·8% [82·3-94·4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91·8% [85·9-95·4]), but moderate specificity (57·8% [42·5-71·6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment., Interpretation: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis., Funding: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Interest in identifying pools of antibacterial-resistance genes has grown over the last decade, with veterinary antibiotics (VAs) receiving particular attention. In this paper, a mesoscale study aimed at evaluating the vertical transport of common VAs-namely, fluoroquinolones, tetracyclines, sulfonamides, and lincosamides in agricultural soil subjected to drip irrigation-was performed under greenhouse conditions. Accordingly, leachates of cropped and uncropped soil, amended with swine-slurry leading to 19-38 μg kg(-1) (dry mass) antibiotics in the soil, were analyzed over the course of the productive cycle of a lettuce (42 days) with three sampling campaigns (N = 24). High lincomycin (LCM) concentrations (30-39 μg L(-1)) were detected in the leachates collected from the swine-slurry-amended soil. The highest LCM mass recovered in the leachates (30.1 ± 1.63 %) was obtained from cropped experimental units. In addition, the LCM leaching constant and its leaching potential as obtained from the first-order model were higher in the leachates from the cropped experimental units. Lower concentrations of sulfadimethoxine were also detected in leachates and in soil. Enrofloxacin and oxytetracycline occurred only in soil, which is consistent with high soil interaction.

Background: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance., Methods: To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC., Results: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance., Conclusions: Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting)., Setting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert., Results: 1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62-0.72]) and culture (5 vs. 8 days, 0.68 [0.65-0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047)., Conclusions: The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system., Trial Registration: ClinicalTrials.gov NCT01201941.

We conducted a case-control study to examine associations between parasite infection, including protozoa infection, and tuberculosis (TB) in children in Lima, Peru. We enrolled 189 matched-pairs. In multivariable conditional logistic regression analyses, Blastocystis hominis infection (rate ratio = 0.30, 95% confidence interval = 0.14-0.64, P = 0.002) was strongly associated with a lower risk of TB. We observed a statistically significant inverse linear dose-response relationship between Blastocystis hominis infection and TB. These findings should be confirmed in future prospective studies.

We estimated the proportion of household contacts whose drug-susceptibility test results matched those of the purported source patient with multidrug-resistant tuberculosis. Ninety-nine (88.4%) contacts had isolates resistant to isoniazid and rifampin, and 41 (36.6%) contacts had isolates with results that also matched the purported source for ethambutol, streptomycin, and pyrazinamide.

Allogeneic hematopoietic cell transplantation offers improved survival in patients with ALL, but with regimens containing TBI, the nonrelapse mortality is 20-40%. Efforts to lessen transplant toxicities by reducing conditioning regimen intensity have led to increased relapse risk. Therefore, there is a need for less toxic regimens that maintain an anti-leukemia effect. We report here a retrospective review of 65 patients with ALL in first remission receiving grafts from allogeneic donors after fludarabine 40 mg/m(2)/day for 4 days and i.v. BU targeted to a median daily area under the concentration-time curve below 6000 μmoles min/L. At 2 years after transplantation, OS was 65% (95% confidence interval (CI): 52-77%), relapse-free survival was 61% (95% CI: 48-73%), cumulative incidence of relapse was 26% (95% CI: 17-39%) and cumulative incidence of nonrelapse mortality was 14% (95% CI: 8-26%). Age over 35 years, Ph chromosome positivity and minimal residual disease at transplant did not adversely affect outcomes. Pharmacokinetically targeted BU and fludarabine can provide intensive pre-transplant conditioning for adults with ALL in first remission, with promising relapse-free and OS rates.

We conducted a case-control study among children in Lima, Peru to identify factors associated with tuberculosis disease. Known close contact with someone with tuberculosis disease, prior hospitalization, and history of anemia were associated with a higher tuberculosis disease rate. Consumption of fruits/vegetables ≥5 days/week was associated with a lower rate. Isoniazid uptake was low among children with a known contact.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach in patients with multiple myeloma, but its use for consolidation of first remission has not yet been fully explored. Twenty-two myeloma patients with very good partial response (VGPR) or CR received allogeneic peripheral blood grafts as consolidation from HLA-matched donors between 2007 and 2012. Conditioning regimens were fludarabine (30 mg/m(2) i.v. if with bortezomib and 40 mg/m(2) i.v. when without bortezomib, × 4 days) plus melphalan (70 mg/m(2) intravenously × 2 days) with (n=13) or without (n=9) bortezomib (1.3 mg/m(2)). The cumulative incidence of grades II - IV acute GVHD at day 100 was 45% (95% CI: 24-65%) and moderate-to-severe chronic GVHD at 2 years was 46% (95% CI: 19-69%). With a median follow-up of 18 (range, 2-61) months, the 2-year PFS estimate is 74.8% (95% CI: 45-90%), which compares favorably with the 52% (95% CI: 35-66%) after autologous HCT for similar patients (a median follow-up of 30 (range, 9-55) months). We are conducting a phase 2 study to assess the efficacy of allogeneic HCT as post-remission therapy.

The use of reclaimed water for agricultural irrigation has emerged as a new strategy for coping with water scarcity in semiarid countries. However, the incorporation of the organic microcontaminants in such water into the diet through crop uptake poses a potential risk to human health. This paper aims to assess the presence of organic microcontaminants in different crops irrigated with groundwater and reclaimed water (secondary or tertiary effluents) in a greenhouse experiment. The determination of microcontaminants in water and vegetation samples was performed by solid-phase extraction and matrix solid-phase dispersion procedure with GC-MS/MS, respectively. The presence of nitrates in the groundwater used for irrigation increased biomass production by a higher proportion than the harvest index. The concentration of microcontaminants in lettuce, carrots, and green beans ranged from less than the limit of quantitation to 571 ng g(-1) (fresh weight). Tributyl phosphate and butylated hydroxyanisole exhibited the highest concentration levels in crops. The concentration and frequency of detection of microcontaminants were lower in green bean pods than in green bean roots and leaves. Although the concentrations were generally low, the simultaneous presence of a variety of microcontaminants should be taken into consideration when assessing the risk to human health.

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., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy., Methods: We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis., Results: Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2-53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17-0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17-50.60]; P = .004)., Conclusions: Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease.

Background: The tuberculosis burden in children exposed at home to multidrug-resistant tuberculosis (MDR-TB) is unquantified. With limited access to MDR-TB treatment, likely millions of children share the experience of chronic exposure to an infectious patient., Methods: We conducted a retrospective cohort study of child and adult household contacts of patients treated for MDR-TB in Lima, Peru, in 1996 to 2003. The primary outcome was TB disease. We estimated prevalence of TB disease when the index case began MDR-TB treatment and incidence of TB disease over the subsequent 4 years., Results: Among 1299 child contacts, 67 were treated for TB. TB prevalence was 1771 (confidence interval [CI]: 1052-2489) per 100,000 children. In 4362 child-years of follow-up, TB incidence rates per 100,000 child-years were: 2079 (CI: 1302-2855) in year 1; 315 (CI: 6-624) in year 2; 634 (CI: 195-1072) in year 3; and 530 (CI: 66-994) in year 4. TB disease rates in children aged >1 year were not significantly different from those observed in adults. Children accounted for 20% of TB cases. Seven (87.5%) of 8 children tested had MDR-TB. Child contacts had TB disease rates approximately 30 times higher than children in the general population., Conclusions: Children were at high risk for TB disease when the index case started MDR-TB treatment and during the following year. These results highlight the need for implementing contact investigations and establishing systems for prompt referral and treatment of pediatric household contacts of MDR-TB patients, regardless of the age of the child.