Transplacental Chikungunya Virus Antibody Kinetics, Thailand

Antibodies to chikungunya virus were detected by hemagglutination-inhibition assay in 33.6% of 2,000 infants' cord sera at delivery. Follow-up of 24 seropositive infants showed that the half-life of antibody persistence was 35.5 days. Chikungunya virus infection is common in Thailand, and routine use of diagnostic assays is needed

Clinical epidemiology, risk factors and treatment outcomes of extended-spectrum beta-lactamase producing Enterobacteriaceae bacteremia among children in a Tertiary Care Hospital, Bangkok, Thailand

Abstract Objective Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae infection is an emerging problem in paediatric populations leading to increased mortality. The purpose of this study was to determine the prevalence, risk factors and clinical outcomes of ESBL-producing Enterobacteriaceae in paediatric blood stream infections (BSIs). A retrospective review of paediatric patients diagnosed with Enterobacteriaceae bacteremia was performed at Phramongkutklao Hospital from 2010 to 2017. Results Among 97 non-duplicated blood isolates, the prevalence of ESBL-producing Enterobacteriaceae was 53.6% (28.9% Escherichia coli and 25.8% Klebsiella spp. isolates). The study indicated that the prevalence of ESBL infection was higher among patients with chronic illness, especially hematologic malignancies, than among patients without underlying disease (P = 0.01). No differences were observed in the prior use of any antibiotics, the use of extended-spectrum cephalosporin, neutropaenia or the presence of an indwelling central venous catheter. Mortality in the ESBL group was significantly higher than that in the non-ESBL group, with observed mortalities of 38.9% and 13.3%, respectively (P < 0.05). In conclusion, BSIs with ESBL-producing Enterobacteriaceae tended to increase infection rates and impact survival rates among paediatric patients

Bridging the immunogenicity of a tetravalent dengue vaccine (TAK-003) from children and adolescents to adults

Abstract Immunobridging is an important methodology that can be used to extrapolate vaccine efficacy estimates to populations not evaluated in clinical studies, and that has been successfully used in developing many vaccines. Dengue, caused by a mosquito-transmitted flavivirus endemic to many tropical and subtropical regions, is traditionally thought of as a pediatric disease but is now a global threat to both children and adults. We bridged immunogenicity data from a phase 3 efficacy study of a tetravalent dengue vaccine (TAK-003), performed in children and adolescents living in endemic areas, with an immunogenicity study in adults in non-endemic areas. Neutralizing antibody responses were comparable in both studies following receipt of a two-dose TAK-003 schedule (months 0 and 3). Similar immune responses were observed across exploratory assessments of additional humoral responses. These data support the potential for clinical efficacy of TAK-003 in adults

Influenza vaccine effectiveness in the tropics: moderate protection in a case test-negative analysis of a hospital-based surveillance population in Bangkok between August 2009 and January 2013.

Influenza in the tropics occurs year round with peaks that correspond variably to temperate regions. However, data on influenza vaccine effectiveness (VE) in the tropics is sparse. We report on the effectiveness of influenza vaccine to prevent medically attended laboratory confirmed influenza from sentinel surveillance conducted at a Thai military medical facility in Bangkok, Thailand from August 2009 to January 2013. Patients ≥6 months old presenting with influenza-like illness underwent combined nasal/throat swabs which were tested by influenza RT-PCR. A case test-negative study design was used to evaluate VE. Of 2999 samples available for analysis,1059 (35.3%) were PCR-positive (cases) and 1940 (64.6%) were PCR-negative (test-negative controls). Five hundred and seven (16.9%) of these patients reported being vaccinated within the previous 12 months. Periods of high and low influenza activity were defined based on publicly available Thai Ministry of Public Health data. Overall VE adjusted for age and epiweek was found to be 50.1% (95%CI: 35.0, 61.9%). The May to April adjusted VE for year 2010, 2011 and 2012 was 57.7% (95%CI: 33.7, 73.8%), 57.1% (95% CI: 35.2, 68.3%) and 37.6% (95% CI: 3.5, 62.9%).During high influenza activity in years with the same vaccine formulation, the adjusted VE was 54.9% (95%CI: 38.9, 66.9%). VE appeared to be much higher during high versus low influenza activity periods. The adjusted point estimate for VE was highest in the 18-49 year age group (76.6%) followed by 6-23 months (58.1%) and 2-17 years (52.5%). Adjusted estimates were not done for those ≥50 years of age due to small numbers. VE in patients with underlying disease was 75.5% compared to 48.0% in those without. Our findings demonstrate moderate protection by influenza vaccination and support the utility of influenza vaccination in the tropics including in very young children and those with underlying disease

Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions

Three phase II randomized trials evaluated the safety/immunogenicity of two formulations of live-attenuated tetravalent dengue virus (TDEN) vaccine in dengue-endemic (Puerto Rico, Thailand) and non-endemic (US) regions (NCT00350337/NCT00370682/NCT00468858). We describe cell-mediated immune (CMI) responses; safety and humoral responses were reported previously. Participants received two doses of vaccine or control (placebo or the precursor live-attenuated TDEN vaccine) 6 months apart. Selected US participants received a booster 5–12 months post-dose 2. Evaluated subsets of the per-protocol cohorts included 75 primarily dengue virus (DENV)-unprimed US adults, 69 primarily flavivirus-primed Thai adults, and 100 DENV-primed or DENV-unprimed Puerto Rican adults/adolescents/children. T-cell responses were quantified using intracellular cytokine staining (ICS; DENV-infected cell-lysate or DENV-1/DENV-2 peptide-pool stimulation) or IFN-γ ELISPOT (DENV-2 peptide-pool stimulation). Memory B-cell responses were quantified using B-cell ELISPOT. Across populations and age strata, DENV serotype-specific CD4+ T-cell responses were slightly to moderately increased (medians ≤0.18% [ICS]), DENV-2–biased, and variable for both formulations. Responses in unprimed subjects were primarily detected post-dose 1. Response magnitudes in primed subjects were similar between doses. Multifunctional CD8+ T-cell responses were detected after peptide-pool stimulation. T-cell responses were mostly directed to DENV nonstructural proteins 3 and 5. Memory B-cell responses were tetravalent, of low-to-moderate magnitudes (medians ≤0.25%), and mainly observed post-dose 2 in unprimed subjects and post-dose 1 in primed subjects. A third dose did not boost CMI responses. In conclusion, both formulations of the live-attenuated TDEN vaccine candidate were poorly to moderately immunogenic with respect to B-cell and T-cell responses, irrespective of the priming status of the participants. Abbreviation ATP: according-to-protocol; ICS: Intracellular Cytokine Staining; NS3: Nonstructural protein 3; ELISPOT: Enzyme-Linked ImmunoSpot; JEV: Japanese encephalitis virus; PBMC: peripheral blood mononuclear cell

Data from: Clinical and laboratory predictors of influenza infection among individuals with influenza-like illness presenting to an urban Thai hospital over a five-year period

Early diagnosis of influenza infection maximizes the effectiveness of antiviral medicines. Here, we assess the ability for clinical characteristics and rapid influenza tests to predict PCR-confirmed influenza infection in a sentinel, cross-sectional study for influenza-like illness (ILI) in Thailand. Participants meeting criteria for acute ILI (fever > 38°C and cough or sore throat) were recruited from inpatient and outpatient departments in Bangkok, Thailand, from 2009-2014. The primary endpoint for the study was the occurrence of virologically-confirmed influenza infection (based upon detection of viral RNA by RT-PCR) among individuals presenting for care with ILI. Nasal and throat swabs were tested by rapid influenza test (QuickVue) and by RT-PCR. Vaccine effectiveness (VE) was calculated using the case test-negative method. Classification and Regression Tree (CART) analysis was used to predict influenza RT-PCR positivity based upon symptoms reported. We enrolled 4572 individuals with ILI; 32.7% had detectable influenza RNA by RT-PCR. Influenza cases were attributable to influenza B (38.6%), A(H1N1)pdm09 (35.1%), and A(H3N2) (26.3%) viruses. VE was highest against influenza A(H1N1)pdm09 virus and among adults. The most important symptoms for predicting influenza PCR-positivity among patients with ILI were cough, runny nose, chills, and body aches. The accuracy of the CART predictive model was 72.8%, with an NPV of 78.1% and a PPV of 59.7%. During epidemic periods, PPV improved to 68.5%. The PPV of the QuickVue assay relative to RT-PCR was 93.0% overall, with peak performance during epidemic periods and in the absence of oseltamivir treatment. Clinical criteria demonstrated poor predictive capability outside of epidemic periods while rapid tests were reasonably accurate and may provide an acceptable alternative to RT-PCR testing in resource-limited areas

Infectious Causes of Encephalitis and Meningoencephalitis in Thailand, 2003–2005

Acute encephalitis is a severe neurologic syndrome. Determining etiology from among ≈100 possible agents is difficult. To identify infectious etiologies of encephalitis in Thailand, we conducted surveillance in 7 hospitals during July 2003–August 2005 and selected patients with acute onset of brain dysfunction with fever or hypothermia and with abnormalities seen on neuroimages or electroencephalograms or with cerebrospinal fluid pleocytosis. Blood and cerebrospinal fluid were tested for >30 pathogens. Among 149 case-patients, median age was 12 (range 0–83) years, 84 (56%) were male, and 15 (10%) died. Etiology was confirmed or probable for 54 (36%) and possible or unknown for 95 (64%). Among confirmed or probable etiologies, the leading pathogens were Japanese encephalitis virus, enteroviruses, and Orientia tsutsugamushi. No samples were positive for chikungunya, Nipah, or West Nile viruses; Bartonella henselae; or malaria parasites. Although a broad range of infectious agents was identified, the etiology of most cases remains unknown