Immunogenicity and safety of heterologous versus homologous prime-boost schedules with inactivated and adenoviral vectored SARS-CoV-2 vaccines - A prospective multi-center study.

Background: During the peak of Coronavirus disease (COVID-19) pandemic in Thailand when the emergence of delta variant reduced the efficacy of inactivated vaccine, Thailand had abundance of inactivated vaccine but mRNA vaccine was not available and the supply of adenoviral-vectored vaccine was limited. The heterologous vaccination using CoronaVac and ChAdOx1-nCoV-19 vaccines was applied. We aim to compare the immunogenicity of immune response of primary vaccination with homologous ChAdOx1 nCoV-19 and heterologous vaccination with CoronaVac and ChAdOx1 nCoV-19. Methods: A total of 430 adults, scheduled to receive ChAdOx1-nCoV-19 as their second dose of primary COVID-19 vaccination, were enrolled. Participants were classified into two groups based on the first dose vaccine as CoronaVac (heterologous group) or ChAdOx1 nCoV-19 (homologous group). The primary outcome was antibodies to the SARS-CoV-2 spike protein receptor binding domain (anti-RBD) titres at 28 days after the second dose of vaccination. Secondary outcomes were anti-RBD titres at 90 days, surrogate viral neutralizing test (sVNT) at 28 and 90 days, and adverse events. Findings: In 358 participants with correct vaccine interval, the anti-RBD geometric mean titre ratio for the heterologous versus homologous group was 0.55 (95%CI; 0.44-0.067); p < 0.001 at day 28, and 0.80 (95%CI; 0.65-1.00); P = 0.05 at day 90. Median sVNT neutralizing activity was not significantly different in the heterologous versus homologous group at 28 days (93.5 vs 92.7 %); p = 0.13, but significantly higher in the heterologous group at day 90 (82.9 vs 76.4 %); p = 0.01. Interpretation: The homologous vaccination resulted in higher anti-RBD titres at 28 days after vaccination, but titres in the homologous group showed more rapid decline at 90 days. In the sVNT assay, median neutralization was similar at 28 days, but was longer-lasting and higher in the heterologous group at 90 days. Funding: This research received funding from the Royal College of Physicians of Thailand special grant 2021 for research initiative during COVID-19 pandemic.

Discovery and validation of circulating miRNAs for the clinical prognosis of severe dengue.

BACKGROUND: Early prognostic markers of severe dengue may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. METHODOLOGY: Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR method. PRINCIPAL FINDINGS: The discovery cohort (N = 19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six up-regulated candidate miRNAs were selected and further validated in the larger cohort (N = 135). MiR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (ROC-AUC = 0.83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3.30, 95% CI 1.81-6.04; p<0.001). CONCLUSION: Our study indicated that circulating miRNAs, especially miR-574-5p and miR-1246, might be a promising diagnostic and prognostic biomarker for severe dengue upon hospital admission, especially when using these biomarkers on days 1 to 2 before the onset of severe dengue complications.

Dengue pre-vaccination screening test evaluation for the use of dengue vaccine in an endemic area.

BACKGROUND: The dengue vaccine (Dengvaxia) is only recommended for individuals with prior dengue infection (PDI). This study aimed to perform a serosurvey to inform decision-making for vaccine introduction and identify appropriate target populations. We also evaluated the performance of the serological tests using plaque reduction neutralization test (PRNT) as a reference test in identifying PDI to determine suitability for pre-vaccination screening. METHODS: We enrolled 115 healthy individuals between 10 and 22 years of age living in the Ratchaburi province of Thailand. The serum samples were tested by PRNT to measure the prevalence and concentration of serotype-specific neutralizing antibodies. The performance of the IgG rapid diagnostic test (RDT, SD Bioline, Korea) and IgG enzyme-linked immunosorbent assay (ELISA, EUROIMMUN, Germany) in identifying PDI were evaluated by using PRNT as a reference method. RESULTS: Ninety-four (81.7%) individuals neutralized one or more dengue serotypes at a titer threshold greater than or equal to 10. Multitypic profiles were observed in 70.4% of the samples which increased to 91.9% in subjects aged 19-22. Among monotypic samples, the highest proportion was reactive against DENV-1 followed by DENV-2, DENV-3, and DENV-4. The highest anti-dengue antibody titers were recorded against DENV-1 and increased with age to a geometric mean NT50 titer (GMT) of 188.6 in the 19-22 age group. While both RDT and ELISA exhibited 100% specificity, RDT demonstrated low sensitivity (35%) with ELISA displaying much greater sensitivity (87%). CONCLUSIONS: Almost 80% of adolescents and youth in Ratchaburi province had already been exposed to one or more of the dengue virus serotypes. The dengue IgG RDT displayed low sensitivity and is likely not be suitable for dengue pre-vaccination screening. These results support the use of IgG ELISA test for dengue vaccination in endemic areas.

Modern biologics for rabies prophylaxis and the elimination of human cases mediated by dogs.

Introduction: Rabies is a major viral zoonosis and neglected tropical disease, with a global distribution. Humans, domestic animals, and wild mammals are susceptible to infection. Etiological agents reside in the Order Mononegavirales, Family Rhabdoviridae, Genus Lyssavirus. This acute, progressive encephalitis causes the highest case fatality of any conventional infectious disease. Tens of millions of humans become exposed annually to the bites of infected mammals, predominantly in Asia and Africa. Despite the existence of effective vaccines and immune globulins, tens of thousands of people, typically children in the developing world, succumb. Areas covered: Concentrating upon both historical and major published references from the peer-reviewed literature over the past 5 years, we describe current biologics for rabies prevention, newly recommended principles for prophylaxis, and relevant future products in the developmental pipeline. Expert opinion: Modern human rabies biologics are pure, potent, safe, and efficacious, when used in a timely and appropriate manner. Few individuals survive after clinical signs. Anti-viral compounds are not licensed. Experimental therapy, while obviously desirable, is highly controversial. Education on bite prevention and integrated risk management are critical. Access to affordable care, dose-sparing, and shortened regimens of human rabies biologics remain key.

Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis.

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.

Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective.

Regional epidemiological data and resistance profiles are essential for selecting appropriate antibiotic therapy for intra-abdominal infections (IAIs). However, such information may not be readily available in many areas of Asia and current international guidelines on antibiotic therapy for IAIs are for Western countries, with the most recent guidance for the Asian region dating from 2007. Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal Infections (ACT-cIAI) was convened to develop updated recommendations for antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is based on a thorough literature review of Asian and international publications related to clinical management, epidemiology, microbiology, and bacterial resistance patterns in cIAIs, combined with the expert consensus of the Taskforce members. The microbiological profiles of IAIs in the Asian region are outlined and compared with Western data, and the latest available data on antimicrobial resistance in key pathogens causing IAIs in Asia is presented. From this information, antimicrobial therapies suitable for treating cIAIs in patients in Asian settings are proposed in the hope that guidance relevant to Asian practices will prove beneficial to local physicians managing IAIs.

Assessment of appropriateness of restricted antibiotic use in Charoenkrung Pracharak Hospital, a tertiary care hospital in Bangkok, Thailand.

The purpose of this study was to evaluate the appropriate of restricted antibiotics at a tertiary care hospital in Bangkok, Thailand. Data from patient charts during September-November, 2009 were obtained regarding appropriate use of antibiotics following hospital antibiotic guidelines. Of 307 prescriptions reviewed, the prevalence of appropriate antibiotic use was 74.6% (229/307). Most patients were male (185/307) with a mean age of 64.2 +/- 18.0 years. There was a significant association between appropriate antibiotic use and patients having underlying disease, a previous history of recent antibiotic use, a recent hospitalization, admission to a medical unit and having a recent health-care institution acquired infection (p < 0.001). The diagnosis of pneumonia was associated with proper use of antibiotics compared with other diagnoses (OR 1.8). Admission to a medical ward was more likely to be associated with correct antibiotic use than having surgery (OR 7.8 and 0.07). Having a health-care institution acquired infection more likely to be associated with appropriate antibiotic use than having a community acquired infection (OR 5.5 and 0.13). Meropenem was more likely to be used appropriately than cefoperazone/sulbactam (OR 1.9 and 0.2). After multivariate analysis, controlling confounding factors, admission to a medical unit and having a health-care institution acquired infection were factors associated with proper use of restricted antibiotics (adjusted OR 9.0 and 7.1; 95% CI 2.27-35.73 and 2.38-20.95; p = 0.002 and p < 0.001, respectively). The prevalence of appropriate use of restricted antibiotics was high; physicians followed local hospital antibiotic guidelines. Future studies of compliance with hospital antibiotic guidelines and its impact on bacterial resistance and infection related mortality should be carried out to determine if appropriate antimicrobial use leads to improve outcomes.