Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam.

SETTING: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. OBJECTIVES: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010-2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010-2012. DESIGN: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. RESULTS: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. CONCLUSION: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection-currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation

Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam

<p>Abstract</p> <p>Background</p> <p>Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.</p> <p>This study investigate if educating primary health center (PHC) staff or introducing rapid diagnostic tests (RDTs) improve diagnostic resolution and accuracy for acute undifferentiated fever (AUF) and reduce prescription of antibiotics and costs for patients.</p> <p>Methods</p> <p>In a PHC randomized intervention study in southern Vietnam, the presumptive diagnoses for AUF patients were recorded and confirmed by serology on paired (acute and convalescence) sera. After one year, PHCs were randomized to four intervention arms: training on infectious diseases (A), the provision of RDTs (B), the combination (AB) and control (C). The intervention lasted from 2002 until 2006.</p> <p>Results</p> <p>The frequency of the non-etiologic diagnosis "undifferentiated fever" decreased in group AB, and - with some delay- also in group B. The diagnosis "dengue" increased in group AB, but only temporarily, although dengue was the most common cause of fever. A correct diagnosis for dengue initially increased in groups AB and B but only for AB this was sustained. Antibiotics prescriptions increased in group C. During intervention it initially declined in AB with a tendency to increase afterwards; in B it gradually declined. There was a substantial increase of patients' costs in B.</p> <p>Conclusions</p> <p>The introduction of RDTs for infectious diseases such as dengue, through free market principles, does improve the quality of the diagnosis and decreases the prescription of antibiotics at the PHC level. However, the effect is more sustainable in combination with training; without it RDTs lead to an excess of costs.</p

Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms

Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver

Genomic-Assisted Enhancement in Stress Tolerance for Productivity Improvement in Sorghum

Sorghum [Sorghum bicolor (L.) Moench], the fifth most important cereal crop in the world after wheat, rice, maize, and barley, is a multipurpose crop widely grown for food, feed, fodder, forage, and fuel, vital to the food security of many of the world’s poorest people living in fragile agroecological zones. Globally, sorghum is grown on ~42 million hectares area in ~100 countries of Africa, Asia, Oceania, and the Americas. Sorghum grain is used mostly as food (~55%), in the form of flat breads and porridges in Asia and Africa, and as feed (~33%) in the Americas. Stover of sorghum is an increasingly important source of dry season fodder for livestock, especially in South Asia. In India, area under sorghum cultivation has been drastically come down to less than one third in the last six decades but with a limited reduction in total production suggesting the high-yield potential of this crop. Sorghum productivity is far lower compared to its genetic potential owing to a limited exploitation of genetic and genomic resources developed in the recent past. Sorghum production is challenged by various abiotic and biotic stresses leading to a significant reduction in yield. Advances in modern genetics and genomics resources and tools could potentially help to further strengthen sorghum production by accelerating the rate of genetic gains and expediting the breeding cycle to develop cultivars with enhanced yield stability under stress. This chapter reviews the advances made in generating the genetic and genomics resources in sorghum and their interventions in improving the yield stability under abiotic and biotic stresses to improve the productivity of this climate-smart cereal

Effect of two alternative methods of pooling sputum prior to testing for tuberculosis with genexpert MTB/RIF

Background: Pooling sputum specimens is one potential strategy for reducing the cost of using Xpert MTB/RIF, a rapid polymerase chain reaction (PCR)-based test, for the diagnosis of pulmonary tuberculosis. We sought to compare the sensitivity of two alternative method of pooling. Methods: Patients referred for assessment for TB, whose initial sputum was Xpert MTB positive, were recruited and their sputum specimens were pooled for analysis with sputum specimens that were Xpert MTB negative. Two alternative pooling strategies were employed: one in which the concentration of sample reagent (buffer) was maintained at 2:1 (standard), in accordance with the manufacturer's instructions, and another in which the concentration of sample reagent was reduced to 1:1. Results: We tested 101 Xpert MTB positive sputum specimens. Among these, 96% of valid test results (95% confidence interval (CI) 89-99%) were positive using the "standard buffer method". Using the "reduced buffer pooling" method 94% of valid test results (95% CI 87-98%) were positive. McNemar's test for the difference in paired proportions did not reach statistical significance (P = 0.56). Conclusion: We have confirmed that pooling of two sputum specimens for testing in a single cartridge is a valid method of reducing the number of cartridges required when using Xpert MTB to detect pulmonary tuberculosis. Two alternative pooling strategies tested here yielded similar results. Trial registration: The present study was conducted within the Active Casefinding in Tuberculosis (ACT3) Trial. The ACT3 Trial had been registered with Australian and New Zealand Clinical Trials Register on 8th April, 2014

The role of animals as a source of antimicrobial resistant nontyphoidal Salmonella causing invasive and non-invasive human disease in Vietnam

Background Nontyphoidal Salmonella (NTS) are associated with both diarrhea and bacteremia. Antimicrobial resistance (AMR) is common in NTS in low-middle income countries, but the major source(s) of AMR NTS in humans are not known. Here, we aimed to assess the role of animals as a source of AMR in human NTS infections in Vietnam. We retrospectively combined and analyzed 672 NTS human and animal isolates from four studies in southern Vietnam and compared serovars, sequence types (ST), and AMR profiles. We generated a population structure of circulating organisms and aimed to attribute sources of AMR in NTS causing invasive and noninvasive disease in humans using Bayesian multinomial mixture models. Results Among 672 NTS isolates, 148 (22%) originated from human blood, 211 (31%) from human stool, and 313 (47%) from animal stool. The distribution of serovars, STs, and AMR profiles differed among sources; serovars Enteritidis, Typhimurium, and Weltevreden were the most common in human blood, human stool, and animals, respectively. We identified an association between the source of NTS and AMR profile; the majority of AMR isolates were isolated from human blood (p < 0.001). Modelling by ST-AMR profile found chickens and pigs were likely the major sources of AMR NTS in human blood and stool, respectively; but unsampled sources were found to be a major contributor. Conclusions Antimicrobial use in food animals is hypothesized to play role in the emergence of AMR in human pathogens. Our cross-sectional population-based approach suggests a significant overlap between AMR in NTS in animals and humans, but animal NTS does explain the full extent of AMR in human NTS infections in Vietnam