Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study,Peru

Background

Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households'' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs.

Methods and Findings

From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household''s annual income. In poorer households, costs were lower but constituted a higher proportion of the household''s annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1–2.6], p = 0.01). The adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18% (95% CI = 6.9%–28%), similar to that of MDR TB (20% [95% CI = 14%–25%]). Sensitivity analyses demonstrated that existing catastrophic costs thresholds (≥10% or ≥15% of household annual income) were not associated with adverse outcome in our setting. Study limitations included not measuring certain “dis-saving” variables (including selling household items) and gathering only 6 mo of costs-specific follow-up data for MDR TB patients.

Conclusions

Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring higher relative costs was associated with adverse TB outcome. The population attributable fraction indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse outcomes. Thus TB is a socioeconomic as well as infectious problem, and TB control interventions should address both the economic and clinical aspects of this disease. Please see later in the article for the Editors'' Summary     

Identification of a Napin-Like Peptide from Eugenia malaccensis L. Seeds with Inhibitory Activity Toward Staphylococcus aureus and Salmonella Enteritidis

This study aimed to purify and characterize peptides from the seeds of Eugenia malaccensis, L. (jambo) with inhibitory activity against the foodborne pathogens Staphylococcus aureus and Salmonella Enteritidis. Crude extract (CE), precipitate fraction 30–60 % and molecules between 3.5 and 10 kDa obtained from precipitate fraction 30–60 % (Em2) showed inhibitory activity against the tested bacterial strains. The highest antibacterial activity was observed for Em2 against S. aureus. The major peak eluted at approximately 30 % in an acetonitrile gradient in reverse-phase chromatography of Em2 (Em2-F1 to Em2-F19), and it showed the highest antibacterial activity, which was twofold higher against S. aureus than against S. Enteritidis. MALDI-ToF spectra of Em2-F18 revealed a molecular mass of 1,231.1 Da and the amino acid sequence showed high identity to the napin family. These findings report for the first time a napin-like peptide from E. malaccensis L. seeds with potential to be applied as a new anti-Staphylococcus molecule.     

Ultrastructure and Immunofluorescence of the midgut of Bombus morio (Hymenoptera: Apidae: Bombini)

Bumblebees are widely distributed across the world and have great economic and ecological importance as pollinators in the forest as well as in agriculture. The insect midgut consists of three cell types, which play various important roles in digestion, absorption, and hormone production. The present study characterized the anterior and posterior midgut regions of the bumblebee, Bombus morio. The digestive, regenerative and endocrine cells in the midgut showed regional differences in their number, nuclear size, as well as the size of the striated border. Ultrastructurally, the digestive cells contained many mitochondria and long microvilli; however, in the anterior midgut region, these cells showed dilated basal labyrinths with a few openings for the hemocoel, whereas the labyrinths of the basal posterior region remained inverse characteristics. Thus, the characterization of the midgut of B. morio supported an ecto-endoperitrophic circulation, contributing to a better understanding of the digestive process in this bee.     

Do alien and native tree species from Central Argentina differ in their water transport strategy?

In this study we assessed the water transport strategies and the abundance of alien and native tree species at a regional scale in Córdoba Mountains, Central Argentina. The aims of this study were: (i) to analyse whether alien and native tree species show divergent water transport strategies; and (ii) to explore whether species abundances of alien and natives are associated with specific trait attributes. Eight alien species and 12 native species were recorded in 50 complete vascular plant vegetation relevés. Water transport strategies were assessed through the following functional traits: minimum leaf water potential, potential water content of wood, effective leaf area, leaf area per sapwood area and wood density. Also, resource use strategies were assessed throughout the measurement of specific leaf area. We found that alien species had a higher efficiency in water transport (i.e. higher minimum leaf water potential and lower wood density values) and faster resource acquisition and use (higher specific leaf area values) than native species. We did not find evidence suggesting that the relative abundance of species was associated to water transport strategies and faster resource acquisition and use. Alien species seem to differ from natives in specific functional attributes that are absent in the resident community and might allow aliens to use more resources and at a higher rate than native species. Finally, our results show the potential of a trait‐based predictive framework for alien species, and the possible effects on ecosystem functions.     

Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema

We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×10⁵), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-β levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.     

Brazilian Multicentre Study on Preterm Birth (EMIP): Prevalence and Factors Associated with Spontaneous Preterm Birth

BackgroundPreterm birth rate is increasing and is currently a worldwide concern. The purpose of this study was to estimate the prevalence of preterm birth in a sample of health facilities in Brazil and to identify the main risk factors associated with spontaneous preterm births.ConclusionsThe preterm birth rate in these health facilities in Brazil is high and spontaneous preterm births account for two thirds of them. A better understanding of the factors associated with spontaneous preterm birth is of utmost importance for planning effective measures to reduce the burden of its increasing rates.     

Detection of the Influenza A(H1N1)pdm09 Virus Carrying the K-15E,P83S and Q293H Mutations in Patients Who Have Undergone Bone Marrow Transplant

The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.     

The Gastroprotective Effect of Menthol: Involvement of Anti-Apoptotic,Antioxidant and Anti-Inflammatory Activities

The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg) or menthol (50 mg/kg) and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70) and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO) was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms.