Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired

MINING SPATIOTEMPORAL PATTERNS OF THE ELDER’S DAILY MOVEMENT

With rapid developments in wearable device technology, a vast amount of spatiotemporal data, such as people’s movement and physical activities, are generated. Information derived from the data reveals important knowledge that can contribute a long-term care and psychological assessment of the elders’ living condition especially in long-term care institutions. This study aims to develop a method to investigate the spatial-temporal movement patterns of the elders with their outdoor trajectory information. To achieve the goal, GPS based location data of the elderly subjects from long-term care institutions are collected and analysed with geographic information system (GIS). A GIS statistical model is developed to mine the elderly subjects’ spatiotemporal patterns with the location data and represent their daily movement pattern at particular time. The proposed method first finds the meaningful trajectory and extracts the frequent patterns from the time-stamp location data. Then, a density-based clustering method is used to identify the major moving range and the gather/stay hotspot in both spatial and temporal dimensions. The preliminary results indicate that the major moving area of the elderly people encompasses their dorm and has a short moving distance who often stay in the same site. Subjects’ outdoor appearance are corresponded to their life routine. The results can be useful for understanding elders’ social network construction, risky area identification and medical care monitoring

Characterizing the spatial distribution of coral reefs in the South-Central Coast region of Viet Nam using Planetscope imagery

This study aims to understand the spatial distribution of coral reefs in the central region of Viet Nam. We classified live coral cover in Son Tra Peninsula (ST) and Cu Lao Cham Island (CLC) in the South-Central Coast Region of Viet Nam using the Maximum Likelihood Classifier on 3 m Planetscope imagery. Confusion matrices and the accuracy of the classifier were assessed using field data (1,543 and 1,560 photographs in ST and CLC, respectively). The results showed that the reef’s width ranged from 30 to 300 m across the study site, and we were able to detect live coral cover across a depth gradient of 2 to 6 m below the sea surface. The overall accuracies of the classifier (the Kappa coefficient) were 76.78% (0.76) and 78.08% (0.78) for ST and CLC, respectively. We found that 60.25% of coral reefs in ST were unhealthy and the live coral cover was less than 50%, while 25.75% and 11.46% of those in CLC were in good and excellent conditions, respectively. This study demonstrates the feasibility of utilizing Planetscope imagery to monitor shallow coral reefs of small islands at a high spatial resolution of 3 m. The results of this study provide valuable information for coral reef protection and conservation

Implementation of C-reactive protein point of care testing to improve antibiotic targeting in respiratory illness in Vietnamese primary care (ICAT): a study protocol for a cluster randomised controlled trial

Introduction C-reactive protein (CRP), a biomarker of infection, has been used widely in high-income settings to guide antibiotic treatment in patients presenting with respiratory illnesses in primary care. Recent trials in low- and middle-income countries showed that CRP testing could safely reduce antibiotic use in patients with non-severe acute respiratory infections (ARIs) and fever in primary care. The studies, however, were conducted in a research-oriented context, with research staff closely monitoring healthcare behaviour thus potentially influencing healthcare workers’ prescribing practices. For policy-makers to consider wide-scale roll-out, a pragmatic implementation study of the impact of CRP point of care (POC) testing in routine care is needed. Methods and analysis A pragmatic, cluster-randomised controlled trial, with two study arms, consisting of 24 commune health centres (CHC) in the intervention arm (provision of CRP tests with additional healthcare worker guidance) and 24 facilities acting as controls (routine care). Comparison between the treatment arms will be through logistic regression, with the treatment assignment as a fixed effect, and the CHC as a random effect. With 48 clusters, an average of 10 consultations per facility per week will result in approximately 520 over 1 year, and 24 960 in total (12 480 per arm). We will be able to detect a reduction of 12% to 23% or more in immediate antibiotic prescription as a result of the CRP POC intervention. The primary endpoint is the proportion of patient consultations for ARI resulting in immediate antibiotic prescription. Secondary endpoints include the proportion of all patients receiving an antibiotic prescription regardless of ARI diagnosis, frequency of re-consultation, subsequent antibiotic use when antibiotics are not prescribed, referral and hospitalisation. Ethics and dissemination The study protocol was approved by the Oxford University Tropical Research Ethics Committee (OxTREC, Reference: 53–18), and the ethical committee of the National Hospital for Tropical Diseases in Vietnam (Reference:07/HDDD-NDTW/2019). Results from this study will be disseminated via meetings with stakeholders, conferences and publications in peer-reviewed journals. Authorship and reporting of this work will follow international guidelines. Trial registration details NCT03855215; Pre-results

A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis

BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .)