Evaluation of the implementation of the Xpert® MTB/RIF assay in Fiji

Setting: All Xpert ® MTB/RIF tests performed in the three TB (tuberculosis) treatment centres in Fiji from June 2012 to February 2013

Regional destination attributes that attract domestic tourists: the role of man-made venues for leisure and recreation

Publishe

On the Effects of Droplet Loading on the Structure of Spray Jets

This paper uses advanced laser diagnostics to investigate the effects of droplet loading on the structure and mixing patterns of sprays in a non-reacting, turbulent jet. A nozzle designed at University of Sydney with the objective of studying spray flames has been used for producing a two phase flow in a co-flowing air stream with well defined boundary conditions. Varying the quantity of liquid injective will vary the number density of the droplets in the flow. The co-flowing air stream is seeded with a fixed concentration of nitric oxide, NO which will act as a conserved scalar. Laser induced fluorescence of NO is exploited to provide a direct quantitative measure of the mixture fraction. Radial profiles of the mean and the rms of mixture fraction has been collected at various axial positions in jets with different spray loadings. It is found that mixture fraction profiles are different from those measured in turbulent gaseous jets and increasing the droplet loading increases the mixture fraction of the jet due to evaporating droplets

E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer.

PURPOSE: Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC). METHODS: Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO bid) on days 3 and 10 (PIE) in a 3-week cycle. RESULTS: We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade ≥3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1-78.9, 95 % CI 57.1-80.4 %) for arm A and 57.6 % (90 % CI 46.7-67.9, 95 % CI 44.8-69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4-7.5 months) and 11.9 months (95 % CI 9.6-13.7 months) for arm A and 6.0 months (95 % CI 5.4-7.0 months) and 11.0 months (95 % CI 8.6-13.1 months) for arm B. CONCLUSION: Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC

Therapeutic efficacy of favipiravir against Bourbon virus in mice

Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV

Test Characteristics of Urinary Lipoarabinomannan and Predictors of Mortality among Hospitalized HIV-Infected Tuberculosis Suspects in Tanzania.

Tuberculosis is the most common cause of death among patients with HIV infection living in tuberculosis endemic countries, but many cases are not diagnosed pre-mortem. We assessed the test characteristics of urinary lipoarabinomannan (LAM) and predictors of mortality among HIV-associated tuberculosis suspects in Tanzania. We prospectively enrolled hospitalized HIV-infected patients in Dar es Salaam, with ≥2 weeks of cough or fever, or weight loss. Subjects gave 2 mLs of urine to test for LAM using a commercially available ELISA, ≥2 sputum specimens for concentrated AFB smear and solid media culture, and 40 mLs of blood for culture. Among 212 evaluable subjects, 143 (68%) were female; mean age was 36 years; and the median CD4 count 86 cells/mm(3). 69 subjects (33%) had culture confirmation of tuberculosis and 65 (31%) were LAM positive. For 69 cases of sputum or blood culture-confirmed tuberculosis, LAM sensitivity was 65% and specificity 86% compared to 36% and 98% for sputum smear. LAM test characteristics were not different in patients with bacteremia but showed higher sensitivity and lower specificity with decreasing CD4 cell count. Two month mortality was 64 (53%) of 121 with outcomes available. In multivariate analysis there was significant association of mortality with absence of anti-retroviral therapy (p = 0.004) and a trend toward association with a positive urine LAM (p = 0.16). Among culture-negative patients mortality was 9 (75%) of 12 in LAM positive patients and 27 (38%) of 71 in LAM negative patients (p = 0.02). Urine LAM is more sensitive than sputum smear and has utility for the rapid diagnosis of culture-confirmed tuberculosis in this high-risk population. Mortality data raise the possibility that urine LAM may also be a marker for culture-negative tuberculosis

Aid to conflict-affected countries : lessons for donors

The first section looks at the implications of conflict for aid effectiveness and selectivity. We argue that, while aid is generally effective in promoting growth and by implication reducing poverty, it is more effective in promoting growth in post-conflict countries. We then consider the implications of these findings for donor selectivity models and for assessment of donor performance in allocating development aid among recipient countries. We argue that, while further research on aid effectiveness in post-conflict scenarios is needed, existing selectivity models should be augmented with, inter alia, post-conflict variables, and donors should be evaluated on the basis, inter alia, of the share of their aid budgets allocated to countries experiencing post-conflict episodes. We also argue for aid delivered in the form of projects to countries with weak institutions in early post-conflict years. The second section focuses on policies for donors operating in conflict-affected countries. We set out five of the most important principles: (1) focus on broad-based recovery from war; (2) to achieve a broad-based recovery, get involved before the conflict ends; (3) focus on poverty, but avoid &lsquo;wish lists&rsquo;; (4) help to reduce insecurity so aid can contribute more effectively to growth and poverty reduction; and (5) in economic reform, focus on improving public expenditure management and revenue mobilisation. The third section concludes by emphasising the fact that there is no hard or fast dividing line between &lsquo;war&rsquo; and &lsquo;peace&rsquo; and that it may take many years for a society to become truly &lsquo;post&rsquo;-conflict&rsquo;. Donors, therefore, need to prepare for the long haul.<br /

Rapid Urine LAM Testing Improves Diagnosis of Expectorated Smear-Negative Pulmonary Tuberculosis in an HIV-endemic Region

We sought to determine if urine lipoarabinomannan (LAM) would improve diagnosis of pulmonary TB. We enrolled consecutive adults presenting with ≥2 TB-related symptoms, obtained one induced sputum sample for smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing (DetermineTM TB LAM, Alere). We used culture-confirmed pulmonary TB as the gold standard, and compared accuracy with area under receiver operating characteristic curves (AUROC). Among 90 participants, 82 of 88 tested (93%) were HIV-infected with a median CD4 168/mm3 (IQR 89–256/mm3). Diagnostic sensitivities of urine LAM and sputum AFB were 42.1% (95% CI 29.1–55.9%) and 21.1% (95% CI 11.4–33.9%), and increased to 52.6% (95% CI 39.0–66.0%) when combined. Sensitivity of LAM increased significantly among participants with a lower Karnofsky Performance score, anemia, hypoalbuminemia, and higher C-reactive protein. Combining LAM with AFB had an AUROC = 0.68 (95% CI 0.59–0.77), significantly better than AFB alone (AUROC=0.58; 95% CI 0.51–0.64). The combination of LAM and AFB was significantly better than AFB alone among patients with Karnofsky Performance score ≤90, hemoglobin ≤10 g/dL, albumin ≤25 g/L, C-reactive protein ≥25 mg/L, or CD4 <200/mm3. Urine LAM testing may be most beneficial among patients with functional impairment, elevated inflammatory markers, or greater immunosuppression