Adjunctive dexamethasone for the treatment of HIV-uninfected adults with tuberculous meningitis stratified by Leukotriene A4 hydrolase genotype (LAST ACT): Study protocol for a randomised double blind placebo controlled non-inferiority trial [version 1; referees: 2 approved]

Background: Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy.  Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled,  multi-centre Phase III non-inferiority trial, comparing dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis treatment in HIV-uninfected patients with TBM stratified by LTA4H genotype. The primary endpoint will be death or new neurological event. The trial will enrol approximately 720 HIV-uninfected adults with a clinical diagnosis of TBM, from two hospitals in Ho Chi Minh City, Vietnam. 640 participants with CC or CT- LTA4H genotype will be randomised to either dexamethasone or placebo, and the remaining TT- genotype participants will be treated with standard-of-care dexamethasone. We will also perform a randomised comparison of three management strategies for anti-tuberculosis DILI. An identical ancillary study will also be perfomed in the linked randomised controlled trial of dexamethasone in HIV-infected adults with TBM (ACT HIV).  Discussion: Previous data have shown that LTA4H genotype may be a critical determinant of inflammation and consequently of adjunctive anti-inflammatory treatment response in TBM. We will stratify dexamethasone therapy according to LTA4H genotype in HIV-uninfected adults, which may indicate a role for targeted anti-inflammatory therapy according to variation in LTA4H C/T transition. A comparison of DILI management strategies may allow the safe continuation of rifampicin and isoniazid

Molecular epidemiology of Japanese encephalitis in northern Vietnam, 1964?2011: genotype replacement

Background: Japanese encephalitis virus (JEV) is an arthropod-borne virus causing serious public health issues in Asia. JEV consists of five genotypes and recent studies have shown the emergence of JEV genotype I (GI) and its replacement of genotype III (GIII). Using an archival JEV collection, we investigated the molecular evolution of JEV in Vietnam over the last 48 years (1964-2012) in humans, mosquitoes, and pigs, within the global context. Methods: The nine JEV isolates from humans, pigs, and mosquitoes sequenced in this study and 29 sequences available in GenBank were used to analyze the envelope (E) protein of the Vietnamese JEVs. A collection of 225 cerebrospinal fluid specimens from patients with suspected Japanese encephalitis (JE) was also tested and genotyped with real-time RT-PCR. Results: The 38 E genes identified with sequencing and nine Vietnamese JEV strains genotyped with real-time RT-PCR, belonging to two lineages, evolved in accordance with those in the rest of the world. The first GIII strain was detected in humans in Vietnam in 1964, and in mosquitoes in 1979, whereas GI strains were first detected in humans and mosquitoes in 1990 and 1994, respectively. After 2004, GI was the only genotype detected in Vietnam, demonstrating that the GIIII strains had been displaced by GI strains. Five haplotypes were identified in the Vietnamese JEVs, with SKSS predominant. The S123N and S123R substitutions in the E protein were already present in the Vietnamese JEVs. Conclusion: This study describes the long evolutionary history of JEV in Vietnam over 34 years, which correlates well with the global evolution of JEV. The Vietnamese GIII strains have been replaced by GI strains in mosquitoes, pigs, and humans. The predominant haplotypes of the Vietnamese strains support this genotype displacement in Vietnam. Further surveillance is required to confirm the disappearance of the GIII strains in nature and the emergence of new pathogens causing encephalitis in Vietnam, after the long-term use of JEV vaccines in that country

A hidden HIV epidemic among women in Vietnam

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic in Vietnam is still concentrated among high risk populations, including IDU and FSW. The response of the government has focused on the recognized high risk populations, mainly young male drug users. This concentration on one high risk population may leave other populations under-protected or unprepared for the risk and the consequences of HIV infection. In particular, attention to women's risks of exposure and needs for care may not receive sufficient attention as long as the perception persists that the epidemic is predominantly among young males. Without more knowledge of the epidemic among women, policy makers and planners cannot ensure that programs will also serve women's needs.</p> <p>Methods</p> <p>More than 300 documents appearing in the period 1990 to 2005 were gathered and reviewed to build an understanding of HIV infection and related risk behaviors among women and of the changes over time that may suggest needed policy changes.</p> <p>Results</p> <p>It appears that the risk of HIV transmission among women in Vietnam has been underestimated; the reported data may represent as little as 16% of the real number. Although modeling predicted that there would be 98,500 cases of HIV-infected women in 2005, only 15,633 were accounted for in reports from the health system. That could mean that in 2005, up to 83,000 women infected with HIV have not been detected by the health care system, for a number of possible reasons. For both detection and prevention, these women can be divided into sub-groups with different risk characteristics. They can be infected by sharing needles and syringes with IDU partners, or by having unsafe sex with clients, husbands or lovers. However, most new infections among women can be traced to sexual relations with young male injecting drug users engaged in extramarital sex. Each of these groups may need different interventions to increase the detection rate and thus ensure that the women receive the care they need.</p> <p>Conclusion</p> <p>Women in Vietnam are increasingly at risk of HIV transmission but that risk is under-reported and under-recognized. The reasons are that women are not getting tested, are not aware of risks, do not protect themselves and are not being protected by men. Based on this information, policy-makers and planners can develop better prevention and care programs that not only address women's needs but also reduce further spread of the infection among the general population.</p

High CO performance of graphene oxide modified with CuCl by using “ion implantation” method

Copper (I) chloride (CuCl) modified graphene oxide with different copper (Cu) content were prepared by ‘ion implantation’ method using CuCl as Cu source. The samples were characterized by x-ray Powder Diffraction-XRD, FTIR, BET, SEM, TEM, EDS and x-ray photoelectron spectroscopy-XPS. From TEM images and EDS elemental mapping, it showed the CuCl particles of 30–50 nm with high dispersion on graphene oxide surface. From XPS result, it revealed the presence of both Cu ^+ and Cu ^2+ ions but Cu ^+ ion amount was predominant. CO adsorption on CuCl modified graphene oxide with different Cu content was tested. Among tested CuCl modified GO samples, 2CuCl/GO sample exhibited the highest CO gas adsorption capacity of 2.9 mmol g ^−1 at 20 °C which was 7.5 times higher than that of pristine GO (0.38 mmol g ^−1 ). High CO adsorption performance on CuCl modified GO can be explained by the formation of π –complexation between CO molecules and Cu(I) ions. From CO adsorption on CuCl modified GO, it showed that the experimental data fit well with Langmuir- Freundlich model

Protective Efficacy of Monoclonal Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia.

Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (MAb) neutralizing alpha-hemolysin or a broadly cross-reactive MAb neutralizing Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysins HlgAB and HlgCB conferred only partial protection, whereas the combination of those two MAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 methicillin-resistant S. aureus epidemic clone

Field trial on a novel control method for the dengue vector, Aedes aegypti by the systematic use of Olyset Net and pyriproxyfen in Southern Vietnam

Abstract Background: Jars, tanks, and drums provide favorable rearing/breeding sites for Aedes aegypti in Vietnam. However, the use of insecticides to control mosquitoes at such breeding sites has not been approved in Vietnam since they are also often sources of drinking water, making larval vector control difficult. Mosquito nets pre-treated with long-lasting insecticide treated nets (LLITNs) form an effective measure for malaria control. We examined changes in the abundance of immature Aedes aegypti to evaluate the efficacy of covering ceramic jars with lids comprising one type of LLITN, Olyset W Net, in inhibiting oviposition by adult females, and to evaluate the effect of treating other breeding containers, such as flower vases, inside and around the outside of houses with a slow-release pyriproxyfen formulation to kill pupae

Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa Bloodstream Infection and Acute Pneumonia Rabbit Models.

Pseudomonas aeruginosa is a challenge for clinicians due to increasing drug resistance and dwindling treatment options. We report on the activity of MEDI3902, an antibody targeting type 3 secretion protein PcrV and Psl exopolysaccharide, in rabbit bloodstream and lung infection models. MEDI3902 prophylaxis or treatment was protective in both acute models and exhibited enhanced activity when combined with a subtherapeutic dose of meropenem. These findings further support MEDI3902 for the prevention or treatment of serious P. aeruginosa infections

The Role of Maternally Acquired Antibody in Providing Protective Immunity Against Nontyphoidal Salmonella in Urban Vietnamese Infants: A Birth Cohort Study

Background: Nontyphoidal Salmonella (NTS) organisms are a major cause of gastroenteritis and bacteremia, but little is known about maternally acquired immunity and natural exposure in infant populations residing in areas where NTS disease is highly endemic. Methods: We recruited 503 pregnant mothers and their infants (following delivery) from urban areas in Vietnam and followed infants until they were 1 year old. Exposure to the dominant NTS serovars, Salmonella enterica serovars Typhimurium and Enteritidis, were assessed using lipopolysaccharide (LPS) O antigen-specific antibodies. Antibody dynamics, the role of maternally acquired antibodies, and NTS seroincidence rates were modeled using multivariate linear risk factor models and generalized additive mixed-effect models. Results: Transplacental transfer of NTS LPS-specific maternal antibodies to infants was highly efficient. Waning of transplacentally acquired NTS LPS-specific antibodies at 4 months of age left infants susceptible to Salmonella organisms, after which they began to seroconvert. High seroincidences of S. Typhimurium and S. Enteritidis LPS were observed, and infants born with higher anti-LPS titers had greater plasma bactericidal activity and longer protection from seroconversion. Conclusions: Although Vietnamese infants have extensive exposure to NTS, maternally acquired antibodies appear to play a protective role against NTS infections during early infancy. These findings suggest that prenatal immunization may be an appropriate strategy to protect vulnerable infants from NTS disease

Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam [version 1; referees: 2 approved]

Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, viral pathogens were detected in a total count of 270/294 (91.8%, 95% CI 88.1-94.7) by the Luminex among reference assays, whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription