Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

BACKGROUND Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients. METHODS We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization. RESULTS A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08). CONCLUSIONS Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.)

Promocijas darbs

Darbā ir apkopota literatūra par furāna un tiofēna karbonilgrupas atvasinājumu, silatrānu un germatrānu iegūšanas metodēm. Tika sintezēti aminosililgrupu saturoši furfurola dietilacetāli, silīciju un germāniju saturoši furāna un tiofēna karbonilsavienojumi, veiktas karbonilgrupas reakcijas un iegūti jauni furil(tienil)nitroni, -aldimīni, -laktoni, -metilēn-bis-indoli, -ketoksīmi, -O-alkil- ketoksīmi, -1,5-benzodiazepīni. Sintezēti silatrāni un bis-germatrāni. Sintezēto savienojumu struktūras pierādītas ar spektrometriskajām metodēm, izpētīta un salīdzināta iegūto vielu bioloģiskā aktivitāte. Perspektīvākajām savienojumu klasēm noteikta spēja inhibēt angioģenēzi un matricas metaloproteināzes.Synthesis of furane and thiophene carbonyl group containing derivatives, silatranes and germatranes have been reviewed. Were synthesized aminosilyl group containing furfurol diethylacetals, silicon and germanium containing furane and thiophene carbonyl compounds, performed carbonyl group reactions and obtained new furyl(thienyl)nitrones, -aldimines, -lactones, -methylene-bis-indoles, -ketoximes, -O-alkylketoximes, -1,5-benzodiazepines. Were synthesized silatranes and bis-germatranes. Structure of the synthesized compounds demonstrated by spectrometrical methods and studied and compared the biological activity of substances. For the most promising compounds a certain ability to inhibit angiogenesis and matrix metalloproteinase was determine

Aquatic emergency preparedness and response system in Viet Nam

Viet Nam is one of the top worldwide producers of aquaculture products which accounts for about 22 percent of total agricultural GDP of Viet Nam. Recently, diseases have become the biggest challenge for global aquaculture development therefore the Vietnamese government has paid close attention to develop an effective aquatic emergency preparedness and response system to timely deal with disease introduction and outbreaks. The Department of Animal Health (DAH), under the Ministry of Agriculture and Rural Development (MARD), which is the competent authority of aquatic animal health management. To monitor transboundary diseases (especially the OIE-listed diseases), the current Vietnamese regulations only allow import of aquatic animals and its products which are certified as disease-free by competent authority of exporting country, and export aquatic animals and its products complying with importing conditions of importing country. Regional Animal Health Offices (belong to DAH) shall carry out sampling for testing pathogens and isolation for imported aquatic animals and its products as regulated in Circular 26/2016/TT-BNNPTNT dated 30 June 2016 before granting permit to import or export. For domestic transportation of aquatic animals, provincial sub DAH is responsible for monitoring infectious pathogens to certify disease-free status of aquatic animals before issuing health certificate for movement. In addition, a reporting and response system to aquatic animal diseases was established in the country from farm level to central level (DAH). Early detection and warning of diseases is critical for disease prevention and control, thus since 2014, the DAH has implemented national surveillance programs focusing on dangerous diseases in the key farming species (brackish-water shrimps, pangasius catfish) according to Circular 04/2016/TT-BNNPTNT dated 10 May 2016 of MARD and support exportation of aquatic animals and its products complying with international regulations and importing countries based on OIE recommendations and Circular 14/2016/TT-BNNPTNT dated 2 June 2016

Reference Ranges for Bone Mineral Density and Prevalence of Osteoporosis in Vietnamese Men and Women

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis.</p> <p>Methods</p> <p>This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (<it>SD</it>). Based on the two parameters, we computed T-scores (denoted by <it>T</it>_VN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (<it>T</it>_DXA), which is based on the US White population (NHANES III). We then compared the concordance between <it>T</it>_VNand <it>T</it>_DXAin the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria.</p> <p>Results</p> <p>In post-menopausal women, the prevalence of osteoporosis based on femoral neck <it>T</it>_VNwas 29%, but when the diagnosis was based on <it>T</it>_DXA, the prevalence was 44%. In men aged 50+ years, the <it>T</it>_VN-based prevalence of osteoporosis was 10%, which was lower than <it>T</it>_DXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by <it>T</it>_DXA, 35% were actually osteopenia by <it>T</it>_VN. The kappa-statistic was 0.54 for women and 0.41 for men.</p> <p>Conclusion</p> <p>These data suggest that the <it>T-</it>scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.</p

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Background Meta-analysis of patients with isoniazid-resistant tuberculosis given standard first-line anti-tuberculosis treatment indicated an increased risk of multi-drug resistant tuberculosis (MDR-TB) emerging (8%), compared to drug-sensitive tuberculosis (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with pre-existing isoniazid resistant disease with first-line anti-tuberculosis therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug-susceptibility testing was performed by Microscopic observation drug-susceptibility assay (MODS), Mycobacterial Growth Indicator Tube (MGIT) and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was five or fewer single nucleotide polymorphisms (SNPs) whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results 239 patients with isoniazid-resistant pulmonary tuberculosis were recruited. Fourteen (14/239, 5.9%) patients were diagnosed with a second episode of tuberculosis that was multi-drug resistant. Six (6/239, 2.5%) were identified as having evolved MDR-TB de novo and six as having been re-infected with a different strain. In two cases the genomic distance was between 5-10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment

Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity by inhibiting telomeric repeat binding factor 2 (TRF2), telomerase, topoisomerase I and II alpha (Top1/2a), and ataxia telangiectasia mutated (ATM) kinase activities. Importantly, these KML001-induced telomeric DNA damage and T cell senescent phenotype and machineries recapitulated our findings in patients with clinical HCV or HIV infection in that their T cells were also senescent with short telomeres and thus more vulnerable to KML001-induced apoptosis. These results shed new insights on the T cell aging network that is critical and essential in protecting chromosomal telomeres from unwanted DNA damage and securing T cell survival during cell crisis upon genomic insult

The impact of environmental and climatic variation on the spatiotemporal trends of hospitalized pediatric diarrhea in Ho Chi Minh City, Vietnam.

It is predicted that the integration of climate-based early warning systems into existing action plans will facilitate the timely provision of interventions to diarrheal disease epidemics in resource-poor settings. Diarrhea remains a considerable public health problem in Ho Chi Minh City (HCMC), Vietnam and we aimed to quantify variation in the impact of environmental conditions on diarrheal disease risk across the city. Using all inpatient diarrheal admissions data from three large hospitals within HCMC, we developed a mixed effects regression model to differentiate district-level variation in risk due to environmental conditions from the overarching seasonality of diarrheal disease hospitalization in HCMC. We identified considerable spatial heterogeneity in the risk of all-cause diarrhea across districts of HCMC with low elevation and differential responses to flooding, air temperature, and humidity driving further spatial heterogeneity in diarrheal disease risk. The incorporation of these results into predictive forecasting algorithms will provide a powerful resource to aid diarrheal disease prevention and control practices in HCMC and other similar settings

Effectiveness of cervical pessary compared to cervical cerclage with or without vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and a short cervix : Study protocol for a two-by-two factorial randomised clinical trial

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