Novel bioparticle vaccines against Chlamydia trachomatis

Chlamydia trachomatis, a sexually transmitted obligate intracellular bacterium, presents a significant global public health concern due to its high prevalence. Although C. trachomatis infection often remains undetected, it can lead to serious complications such as pelvic inflammatory disease, infertility, ectopic pregnancy, miscarriage, and even blindness. While antibiotics are effective against acute infection, they are believed to increase the risk of reinfection. Despite advances in understanding C. trachomatis-caused infectious diseases, a prophylactic vaccine against the bacterium is yet to be developed. The challenges lie in the safety risks associated with using weakened live vaccines and the limited efficacy of current alternative vaccination strategies. Protective immunity against C. trachomatis, like other intracellular pathogens, relies on both humoral and cellular immune responses, targeting the extracellular and intracellular stages of the bacterium, respectively. Many studies have focused on inducing protective CD4+ (Th1) T cell-mediated and humoral responses, but efforts to activate CD8+ T cells, responsible for monitoring and eliminating intracellular infections, are still in the early stages. Therefore, the development of innovative C. trachomatis vaccines, capable of inducing potent humoral and cellular (CD4+ and CD8+ T cell) responses, requires a complementary interdisciplinary approach with experts from various fields. The main objective of this thesis was to create and evaluate novel C. trachomatis bioparticle vaccines, using bacterial outer membrane vesicles (OMVs) and protein bodies (PBs) as delivery platforms. Several vaccine candidates based on LPS-detoxified Salmonella OMVs and E. coli PBs have been generated. Preclinical testing in a mouse model has shown that the OMV/PB-based vaccines are safe and immunogenic, inducing specific humoral and cellular immune responses against C. trachomatis antigens in both systemic and mucosal compartments. Currently, the protective efficacy of the most promising vaccine is being evaluated and compared to other vectored vaccines using a genital mouse challenge model

Developing University Students’ Statistical Reasoning via a Research-informed Course

Statistical reasoning (SR) is an essential skill for students in studying statistics. This study aims to develop SR for university students through an appropriately designed course in statistics. Employing a quasi-experimental design, this study evaluated students' SR changes as they participated in a research-informed statistics course, designed to integrate statistical reasoning. The results showed that the course helps students improve their SR, with their scores increased by 23% from the pre-test to the post-test. Specifically, the SR scores on measures of central tendency of the experimental class increased by 8%; while the SR scores on the measures of variability of the experimental class increased by 34%. Suggestions about curriculum and teaching are included, such as offering opportunities for statistical investigations with real data; going deeper into building and understanding formulas; and training lecturers to teach statistics using approaches that are different from traditional teaching methods, as well as evaluating students' statistical learning with reliable tools

Antibacterial, antioxidant and cytotoxic activities of different fractions of acetone extract from flowers of Dipterocarpus intricatus Dyer (Dipterocarpaceae)

This study has shown for the first time the antimicrobial, antioxidant and cytotoxicity of 3 fractions of acetone extract, including hexane, chloroform and ethyl acetate from flowers of Dipterocarpus intricatus. Antibacterial test using disc diffusion method showed that the chloroform and ethyl acetate fractions inhibited the growth of all the tested bacteria, including Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus and Staphylococcus aureus while the hexane fraction showed the antibacterial activity against B. cereus and S. enteritidis. Antioxidant activity and cancer cell resistance of those extracts were conducted using DPPH and MTT methods respectively. As a result, the DPPH radical scavenging activity of the hexane, chloroform and ethyl acetate fractions were determined with the IC50 values of 0.508, 0.22 and 0.075 mg/mL respectively while the cytotoxicity to HepG2 cell line of those fractions was 163.3 ppm, 106.7 ppm and 459.3 ppm. These results suggested the potential application of these fractions isolated from D. intricatus flowers as the natural antimicrobial, antioxidant and cytotoxic agents for medicine

Planning for Developing Students’ Statistical Literacy: A Research-Informed Framework Development

Teachers’ planning as a research area still receives little attention. This study focuses on developing a research-informed framework to assess teachers’ statistics lesson plans. Using a design-based research approach, we developed a framework that includes (a) two criteria related to learning intentions (clear and comprehensive), (b) four criteria related to task features (statistical literacy, statistical investigation, real data, multiple representations), and (c) one related to constructivist lessons. Then, the team provided professional development on statistical literacy and ways to elicit and develop it in the classroom. After that, the teachers discussed the framework and used it to revise their lesson plans. Also, teachers provided feedback to revise the framework. We discuss how the framework can offer a tool for researchers to examine teacher planning competence and teachers to reflect on their practice

Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease.

BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford

Kinetics of neutralizing antibodies against Omicron variant in Vietnamese healthcare workers after primary immunization with ChAdOx1-S and booster immunization with BNT162b2

We studied the development and persistence of neutralizing antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs, including group 1 (G1, N = 21) and group 2 (G2; N = 26) without and with breakthrough Delta variant infection before booster immunization, respectively). The study participants had completed primary immunization with ChAdOx1-S and booster vaccination with BNT162b2. Neutralizing antibodies were measured using a surrogate virus neutralization assay. Of the 21 study participants in G1, neutralizing antibodies against ancestral strain, Delta variant, BA.1, and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralizing antibodies to the study viruses at week 2 post booster dose. Of the 26 study participants in G2, neutralizing antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralizing antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralizing activities against ancestral strain and Delta variant compared with those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasize the importance of the first booster dose in producing cross-neutralizing antibodies against Omicron variant. A second booster to maintain long-term vaccine effectiveness against the currently circulating variants merits further research

Urinary catecholamine excretion, cardiovascular variability, and outcomes in tetanus

Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system. The clinical syndrome of autonomic nervous system dysfunction (ANSD) seen in severe tetanus is characterized principally by changes in heart rate and blood pressure which have been linked to increased circulating catecholamines. Previous studies have described varying relationships between catecholamines and signs of ANSD in tetanus, but are limited by confounders and assays used. In this study, we aimed to perform detailed characterization of the relationship between catecholamines (adrenaline and noradrenaline), cardiovascular parameters (heart rate and blood pressure) and clinical outcomes (ANSD, mechanical ventilation required, and length of intensive care unit stay) in adults with tetanus, as well as examine whether intrathecal antitoxin administration affected subsequent catecholamine excretion. Noradrenaline and adrenaline were measured by ELISA from 24-h urine collections taken on day 5 of hospitalization in 272 patients enrolled in a 2 × 2 factorial-blinded randomized controlled trial in a Vietnamese hospital. Catecholamine results measured from 263 patients were available for analysis. After adjustment for potential confounders (i.e., age, sex, intervention treatment, and medications), there were indications of non-linear relationships between urinary catecholamines and heart rate. Adrenaline and noradrenaline were associated with subsequent development of ANSD, and length of ICU stay

Wearable devices for remote monitoring of hospitalized patients with COVID-19 in Vietnam

Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments

Spatiotemporal evolution of SARS-CoV-2 Alpha and Delta variants during large nationwide outbreak of COVID-19, Vietnam, 2021

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions

An Outbreak of Severe Infections with Community-Acquired MRSA Carrying the Panton-Valentine Leukocidin Following Vaccination

Background: Infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging worldwide. We investigated an outbreak of severe CA-MRSA infections in children following out-patient vaccination. Methods and Findings: We carried out a field investigation after adverse events following immunization (AEFI) were reported. We reviewed the clinical data from all cases. S. aureus recovered from skin infections and from nasal and throat swabs were analyzed by pulse-field gel electrophoresis, multi locus sequence typing, PCR and microarray. In May 2006, nine children presented with AEFI, ranging from fatal toxic shock syndrome, necrotizing soft tissue infection, purulent abscesses, to fever with rash. All had received a vaccination injection in different health centres in one District of Ho Chi Minh City. Eight children had been vaccinated by the same health care worker (HCW). Deficiencies in vaccine quality, storage practices, or preparation and delivery were not found. Infection control practices were insufficient. CA-MRSA was cultured in four children and from nasal and throat swabs from the HCW. Strains from children and HCW were indistinguishable. All carried the Panton-Valentine leukocidine (PVL), the staphylococcal enterotoxin B gene, the gene complex for staphylococcal-cassette-chromosome mec type V, and were sequence type 59. Strain HCM3A is epidemiologically unrelated to a strain of ST59 prevalent in the USA, althoughthey belong to the same lineage. Conclusions. We describe an outbreak of infections with CA-MRSA in children, transmitted by an asymptomatic colonized HCW during immunization injection. Consistent adherence to injection practice guidelines is needed to prevent CA-MRSA transmission in both in- and outpatient settings