Prevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program – Vietnam

Background

An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm³ for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam.

Methods

Serum samples were collected and stored during 2009–2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm³ were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines.

Results

Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm³ were available for CrAg testing. Median CD4 count was 40 (range 0–99) cells/mm³. Nine (4%; 95% CI 2–7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3–11%) than in North Vietnam (2%; 95% CI 0–6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190, $137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively.

Conclusion

CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care.     

Protocorm-like body formation,stem elongation,and enhanced growth of Anthurium andraeanum ‘Tropical’ plantlet on medium containing silver nanoparticles

In Vitro Cellular & Developmental Biology - Plant - In this study, a new method for shoot regeneration via protocorm-like bodies (PLBs) is described. Shoot proliferation using stem elongation...     

Reprogrammed lung epithelial cells by decrease of miR-451a in extracellular vesicles contribute to aggravation of pulmonary fibrosis

Cell Biology and Toxicology - Extracellular vesicles (EVs) play novel roles in homeostasis through cell-to-cell communication in human airways via transferring miRNAs. However, the contribution of...     

Four New Stilbene Derivatives Isolated from Gnetum latifolium var. funiculare Markgr. and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells

Gnetum latifolium var. funiculare Markgr. is a medicinal plant and widely distributed in mountainous areas of Vietnam. Phytochemical investigation on the trunks of this plant afforded eight stilbene derivatives ( 1 – 8 ) including for new compounds ( 1 – 4 ). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Among the isolates, compounds 1 – 3 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with the IC₅₀ values ranging from 46.81 to 68.10 μM, compounds 4 and 6 showed weak effects with the IC₅₀ values of 96.57 and 79.46 μM, respectively, compared to that of the positive control compound, dexamethasone (IC₅₀ 14.20 μM).     

Morphologies of Fibronectin Fibrils Formed under Shear Conditions and Their Cellular Adhesiveness Properties

Fibrillar fibronectin (FFN) is a biological active form of FN which formlinear and branched meshwork around cells and support cellular activities. Previous studies have demonstrated that shear stress can induce cell-free FN fibrillogenesis. In this study, we further examined the effect of shear stress conditions onmorphology of formed FFN and preliminarily looked for relationship betweenFFN’s morphology and cell adhesion. Plasma FN at 50 µg/ml was perfusedthrough channel slides at shear rates of 500 s^-1 or 4000 s^-1. Our results showedthat there were four FFN structures formed: (1) FN nodules, (2) fibril in differentsizes (3) with or without nodule attachment, and (4) fibrillar matrix. At 4000 s^-1,FFN fibrils was formed within the first 10 min and reached the highest surfacecoverage only after 20 min. In contrast, FFN formation was significant moreslowly at 500 s^-1 at which only FN nodules and small fibrils were formed. Platelets bound on thin layer of FN and rarely found on large FN fibrils. In contrast,fibroblast stretched their shape on platform of FFN matrix and bound activelyto all types of FFNs. Taken together, our data suggests a morphological dependentbiological activity of FFN.     

Small-molecule inhibitors of histone deacetylase improve CRISPR-based adenine base editing

CRISPR-based base editors (BEs) are widely used to induce nucleotide substitutions in living cells and organisms without causing the damaging DNA double-strand breaks and DNA donor templates. Cytosine BEs that induce C:G to T:A conversion and adenine BEs that induce A:T to G:C conversion have been developed. Various attempts have been made to increase the efficiency of both BEs; however, their activities need to be improved for further applications. Here, we describe a fluorescent reporter-based drug screening platform to identify novel chemicals with the goal of improving adenine base editing efficiency. The reporter system revealed that histone deacetylase inhibitors, particularly romidepsin, enhanced base editing efficiencies by up to 4.9-fold by increasing the expression levels of proteins and target accessibility. The results support the use of romidepsin as a viable option to improve base editing efficiency in biomedical research and therapeutic genome engineering.     

On the distribution of the number of internal equilibria in random evolutionary games

Journal of Mathematical Biology - The analysis of equilibrium points is of great importance in evolutionary game theory with numerous practical ramifications in ecology, population genetics, social...     

Protective and enhancing HLA alleles, HLA-DRB1*0901 and HLA-A*24, for severe forms of dengue virus infection, dengue hemorrhagic fever and dengue shock syndrome

Background

Dengue virus (DV) infection is one of the most important mosquito-borne diseases in the tropics. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. Protective and/or pathogenic T cell immunity is supposed to be important in the pathogenesis of DHF and DSS.

Methodology/Principal Findings

To identify HLA alleles controlling T cell immunity against dengue virus (DV), we performed a hospital-based case control study at Children''s Hospital No.2, Ho Chi Minh City (HCMC), and Vinh Long Province Hospital (VL) in Southern Vietnam from 2002 to 2005. A total of 211 and 418 patients with DHF and DSS, respectively, diagnosed according to the World Health Organization (WHO) criteria, were analyzed for their characteristic HLA-A, -B and -DRB1 alleles. Four hundred fifty healthy children (250 from HCMC and 200 from VL) of the same Kinh ethnicity were also analyzed as population background. In HLA class I, frequency of the HLA-A*24 showed increased tendency in both DHF and DSS patients, which reproduced a previous study. The frequency of A*24 with histidine at codon 70 (A*2402/03/10), based on main anchor binding site specificity analysis in DSS and DHF patients, was significantly higher than that in the population background groups (HCMC 02-03 DSS: OR = 1.89, P = 0.008, DHF: OR = 1.75, P = 0.033; VL 02-03 DSS: OR = 1.70, P = 0.03, DHF: OR = 1.46, P = 0.38; VL 04-05 DSS: OR = 2.09, P = 0.0075, DHF: OR = 2.02, P = 0.038). In HLA class II, the HLA-DRB1*0901 frequency was significantly decreased in secondary infection of DSS in VL 04-05 (OR = 0.35, P = 0.0025, Pc = 0.03). Moreover, the frequency of HLA-DRB1*0901 in particular was significantly decreased in DSS when compared with DHF in DEN-2 infection (P = 0.02).

Conclusion

This study improves our understanding of the risk of HLA-class I for severe outcome of DV infection in the light of peptide anchor binding site and provides novel evidence that HLA-class II may control disease severity (DHF to DSS) in DV infection.