Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand.

BACKGROUND: Early diagnosis of neonatal sepsis is essential to prevent severe complications and avoid unnecessary use of antibiotics. The mortality of neonatal sepsis is over 18%in many countries. This study aimed to develop a predictive model for the diagnosis of bacterial late-onset neonatal sepsis. METHODS: A case-control study was conducted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand. Data were derived from the medical records of 52 sepsis cases and 156 non-sepsis controls. Only proven bacterial neonatal sepsis cases were included in the sepsis group. The non-sepsis group consisted of neonates without any infection. Potential predictors consisted of risk factors, clinical conditions, laboratory data, and treatment modalities. The model was developed based on multiple logistic regression analysis. RESULTS: The incidence of late proven neonatal sepsis was 1.46%. The model had 6 significant variables: poor feeding, abnormal heart rate (outside the range 100-180 x/min), abnormal temperature (outside the range 36o-37.9 °C), abnormal oxygen saturation, abnormal leucocytes (according to Manroe's criteria by age), and abnormal pH (outside the range 7.27-7.45). The area below the Receiver Operating Characteristics (ROC) curve was 95.5%. The score had a sensitivity of 88.5% and specificity of 90.4%. CONCLUSION: A predictive model and a scoring system were developed for proven bacterial late-onset neonatal sepsis. This simpler tool is expected to somewhat replace microbiological culture, especially in resource-limited settings.

Monoclonal antibody-based capture ELISA in the diagnosis of previous dengue infection.

BACKGROUND: Dengue is an important mosquito-borne disease. There is currently only one licensed vaccine for dengue prevention. The vaccine provides higher efficacy in pre-vaccination dengue-seropositive persons but a higher risk of subsequent more severe dengue in dengue-seronegative persons. It is recommended that the dengue vaccine may be given in dengue-seropositive individuals or as mass vaccination without individual pre-vaccination screening in areas where the dengue seroprevalence is > 80% in children aged 9 years. We evaluated a dengue specific immunoglobulin G monoclonal antibody-based capture enzyme-linked immunosorbent assay (MAb-ELISA) in the diagnosis of previous dengue infection using serum samples from the cohort study in Ratchaburi Province, Thailand. METHODS: The MAb-ELISA was compared to 70% plaque reduction neutralization test (PRNT70) in 453 serum samples from children aged 3-11 years in Ratchaburi Province, Thailand. RESULTS: The sensitivity and specificity of MAb-ELISA at the positive to negative (P/N) ratio cut-off level of > 3 were both 0.91 in the diagnosis of previous dengue infection, compared to PRNT70. The false positivity was mainly in Japanese encephalitis (JE) seropositive subjects. CONCLUSIONS: This research provides evidence that MAb-ELISA is useful for dengue seroprevalence study and dengue pre-vaccination screening. JE seropositivity was the major cause of false positive result in the study population.

Vaccine for prevention of mild and moderate-to-severe influenza in children.

BACKGROUND: Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages. METHODS: In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group). RESULTS: In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%). CONCLUSIONS: The QIV was efficacious in preventing influenza in children. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).

Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial.

BACKGROUND: Roughly half the world's population live in dengue-endemic countries, but no vaccine is licensed. We investigated the efficacy of a recombinant, live, attenuated tetravalent dengue vaccine. METHODS: In this observer-masked, randomised, controlled, monocentre, phase 2b, proof-of-concept trial, healthy Thai schoolchildren aged 4-11 years were randomly assigned (2:1) to receive three injections of dengue vaccine or control (rabies vaccine or placebo) at months 0, 6, and 12. Randomisation was by computer-generated permuted blocks of six and participants were assigned with an interactive response system. Participants were actively followed up until month 25. All acute febrile illnesses were investigated. Dengue viraemia was confirmed by serotype-specific RT-PCR and non-structural protein 1 ELISA. The primary objective was to assess protective efficacy against virologically confirmed, symptomatic dengue, irrespective of severity or serotype, occurring 1 month or longer after the third injection (per-protocol analysis). This trial is registered at ClinicalTrials.gov, NCT00842530. FINDINGS: 4002 participants were assigned to vaccine (n=2669) or control (n=1333). 3673 were included in the primary analysis (2452 vaccine, 1221 control). 134 cases of virologically confirmed dengue occurred during the study. Efficacy was 30·2% (95% CI -13·4 to 56·6), and differed by serotype. Dengue vaccine was well tolerated, with no safety signals after 2 years of follow-up after the first dose. INTERPRETATION: These data show for the first time that a safe vaccine against dengue is possible. Ongoing large-scale phase 3 studies in various epidemiological settings will provide pivotal data for the CYD dengue vaccine candidate. FUNDING: Sanofi Pasteur.

Differences in clinical features between children and adults with dengue hemorrhagic fever/dengue shock syndrome.

This retrospective study was conducted to assess the differences in clinical features between children and adults with dengue hemorrhagic fever/ dengue shock syndrome (DHF/DSS) admitted to Ratchaburi Hospital, Ratchaburi Province, Thailand. A total of 273 patients with DHF/DSS admitted to Ratchaburi Hospital during January 2007 to May 2008 were included in the study. The median age (range) of studied subjects was 16 years (6 months to 62 years) and the ratio of adults to children was 1.6:1. Forty-eight percent of subjects were 16-30 years old. The common signs, symptoms and clinical features were: nausea/vomiting (74.0%), a positive tourniquet test (73.0%), anorexia (67.0%), hemoconcentration (58.0%), headache (54.0%), abdominal tenderness (43.0%), myalgia (39.0%) and pleural effusion (20.0%). Children had anorexia, a positive tourniquet test, abdominal tenderness and a convalescent rash more frequently than adults. Children also had significantly more prominent plasma leakage as shown by lower serum albumin and sodium and a higher prevalence of pleural effusion, ascites and shock. Although not statistically significant, the prevalence of bleeding in children was higher than in adults but more adults needed blood transfusion. This study provides additional insight into the clinical picture of DHF/DSS in adults and children and may be beneficial for clinicians caring for these adults and children.

Antibody persistence upto 5 years after primary immunization and booster with an inactivated chromatographically purified Vero cell-derived Japanese encephalitis vaccine in Thai children.

Japanese encephalitis is the main cause of viral encephalitis in Asia. In a previous single-arm vaccine trial, an inactivated chromatographically purified Japanese encephalitis Vero cell vaccine (CVI-JE; JEVACTM) was safe and immunogenic in 152 Thai children aged 1-3 years receiving a 2-dose primary immunization and booster dose 1 year later. We conducted a 5-year follow-up assessment of the persistence of the immune response the 144 children remaining in this cohort after first booster dose. Immunity was assessed by 50% plaque reduction neutralization test annually for up to 5 years post-booster. Seroprotection rates (95%CI) decreased from 100% (97.1-100) at 1 year post-booster to 93% (85.0-98.3) at 5 years post-booster. No serious vaccine-related adverse events or Japanese encephalitis infections were reported. A 2-dose primary immunization and booster 1 year later with CVI-JE provided long-lasting immunity in the majority of children.

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015.

BACKGROUND: To determine the seroprevalence and transmission dynamics of dengue virus (DENV), age-stratified longitudinal serological surveys were conducted in Bangphae district, Ratchaburi province, Thailand, for 3 years between April 2012 and April 2015. METHODOLOGY: The surveys enrolled 2012 healthy children and adults between 1 and 55 years-of-age, and a longitudinal serosurvey of six repeated bleeds of the same cohort of individuals was conducted every 8 months for the first 2 years (M0, M8, M16) and every half a year (M24, M30, M36) for the rest of the study period. All samples were tested using in-house indirect sandwich dengue IgG ELISA to determine DENV antibody titer, and 640 paired samples which showed rising of DENV IgG titers in paired serum were further tested using in-house neutralization assay, Plaque Reduction Neutralization Test (PRNT50). PRINCIPAL FINDINGS: When compared against the gold standard based on the results of PRNT50, sensitivity and specificity of indirect ELISA were found to be both about 85%. The overall DENV IgG positivity determined by ELISA was 74.3% in 2012 and increased to 79.4% by the final sample collection in 2015. In our study sample, more than 98% of subjects older than 25 years were found to be seropositive. Among 518 IgG negative subjects at enrollment, the seroconversion rates were measured in paired bleeds; the rates (between successive visits, approximately 6 months) ranged between 4.8% (between M16 and M24) and 14.7% (between M0 and M8). The dominant serotype of primary DENV infection cases based on seroconversion was identified from the PRNT results and it was DENV-2. CONCLUSIONS: Our study documented high levels of seroprevalence and rate of transmission. Given the importance of the serostatus and disease burden in consideration for dengue vaccine introduction, our data could be used in decision-making on implementation of various dengue control and preventive measures.

Antibody responses against heterologous A/H5N1 strains for an MF59-adjuvanted cell culture-derived A/H5N1 (aH5N1c) influenza vaccine in healthy pediatric subjects.

BACKGROUND: Vaccines are the main prophylactic measure against pandemic influenza. Adjuvanted, cell culture-derived vaccines, which are not subject to limitations of egg-based vaccine production, have the potential to elicit an antibody response against heterologous strains and may be beneficial in the event of an A/H5N1 pandemic. METHODS: A prespecified exploratory analysis of data from a phase 2, randomized, controlled, observer-blind multicenter trial (NCT01776554) to evaluate the immunogenicity of a MF59-adjuvanted, cell culture-based A/H5N1 influenza vaccine (aH5N1c), containing 7.5 µg hemagglutinin antigen per dose, in subjects 6 months through 17 years of age was conducted. Geometric mean titers (GMT) were determined using hemagglutination inhibition (HI) and microneutralization (MN) assays, and proportions of patients achieving seroconversion, HI and MN titers ≥ 1:40, and a 4-fold increase in MN titers against 5 heterologous strains (influenza A/H5N1 Anhui/2005, Egypt/2010, Hubei/2010, Indonesia/2005, and Vietnam/1203/2004) three weeks after administration of the second dose were assessed. RESULTS: After the second dose, HI GMTs against heterologous strains increased between 8- and 40-fold, and MN GMTs increased 13- to 160-fold on Day 43 vs Day 1. On Day 43, 32-72% of subjects had HI titers ≥ 1:40 and achieved seroconversion against the heterologous strains. Using the MN assay, 84-100% of subjects had MN titers ≥ 1:40 and 83-100% achieved an at least 4-fold increase in MN titers against the heterologous strains. The highest responses were consistently against A/H5N1 Egypt/2010. CONCLUSIONS: When given to children aged 6 months through 17 years, aH5N1c resulted in increased immunogenicity from baseline against all 5 heterologous A/H5N1 strains tested, demonstrating the potential of an MF59-adjuvanted, cell-derived A/H5N1 vaccine to provide cross-protection against other A/H5N1 strains (NCT01776554).

Knowledge, attitude, and practices toward COVID-19 among the international travelers in Thailand.

BACKGROUND: International travel is among the leading impactful factors of COVID-19 transmission; thus, adequate knowledge, good attitude and good preventive practices toward COVID-19 for international travelers are particularly essential for successful pandemic control. METHODS: A cross-sectional, questionnaire-based study was conducted to determine knowledge, attitude and practices (KAP) of international travelers (both Thai and non-Thai) and expatriates in Thailand. The data were collected at the Thai Travel Clinic, Bangkok, Thailand and via online platforms during May to October 2020. The independent T-test, Chi-square test and multiple regression analysis (MRA) were applied to determine factors influencing the KAP. RESULTS: Of 399 travelers, 46.6% were male, 72.1% had a Bachelor's degree or higher, and the mean age was 35.6 ± 9.6 years. Due to unexpected travel restrictions and lock down, 77.9% of participants were Thai and the respective major purpose of travel was business/work. Travel cancellation/postponement was reported at 73.9%. While sufficient knowledge (≥ 60% correct answers) was reported in 77.9% of participants, a low percentage of correct answers was found in the questions regarding disease transmission. The travelers reported a neutral attitude and an overall moderate concern regarding the COVID-19 situation. Adequate preventive practices were determined by the average practice score 3.54 ± 0.38 (0 = never and 4 = always). The MRA revealed that the factors influencing good practices were travelers who: i) enrolled from outside the hospital (online platform); ii) received pretravel advice at hospital; iii) were female; iv) participated before the declaration of the end of the outbreak; v) were aged 40-49 years, and vi) visited friends and relatives. CONCLUSIONS: The majority of travelers in this study had sufficient knowledge, a neutral attitude and adequate preventive practices toward COVID-19. The factors influencing good practices included pretravel advice, sex, age and the point in the timeline of the outbreak. In order to better control the COVID-19 pandemic situation, pretravel counselling and advice should be promoted as a means to improve knowledge, particularly in disease transmission, increase awareness and emphasize appropriate preventive measures toward COVID-19 among international travelers. Furthermore, preventive practices should be bolstered at all times regardless of the outbreak situation.

Clinical and epidemiologic characteristics associated with dengue fever in 2011-2016 in Bang Phae district, Ratchaburi province, Thailand.

BACKGROUND: Dengue is a major public health problem in Thailand, but data are often focused on certain dengue-endemic areas. Methods: To better understand dengue epidemiology and clinical characteristics in Thailand, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-localized febrile illness at Bang Phae Community Hospital in Ratchaburi province, Thailand from October 2011 to September 2016. RESULTS: Among 951 febrile episodes, 130 were dengue-confirmed. Individuals aged 10-14 years were mostly affected, followed by those 15-19 years-of-age, with about 15% of dengue-confirmed cases from adults 25 years and older. There were annual peaks of dengue occurrence between June-November. Most prevalent serotype in circulation was DENV-2 in 2012, DENV-3 in 2014, and DENV-4 & -3 in 2015. Among dengue cases, 65% were accurately detected using the dengue NS1 RDT. Detection rate was similar between secondary and primary dengue cases where 66% of secondary vs. 60% of primary dengue cases had positive results on the NS1 RDT. Among dengue cases, 66% were clinically diagnosed with suspected dengue or DHF, prior to lab confirmation. Dengue was positively associated with rash, headache, hematemesis and alterations to consciousness, when compared to non-dengue. Dengue patients were 10.6 times more likely to be hospitalized, compared to non-dengue cases. Among dengue cases, 95 were secondary and 35 were primary infections. There were 8 suspected DHF cases and all were identified to be secondary dengue. Secondary dengue cases were 3.5 times more likely to be hospitalized compared to primary dengue cases. Although the majority of our dengue-positive patients were secondary dengue cases, with few patients showing manifestations of DHF, our dengue cases were mostly mild disease. Even among children < 10 years-of-age, 61% had secondary infection and the rate of secondary infection increased with age. CONCLUSION: While the majority of dengue-confirmed cases were children, almost three-quarters of dengue-confirmed cases in this study were secondary dengue. Our study results consistent with previous data from the country confirm the hyperendemic transmission of DENV in Thailand, even in the non-epidemic years. With various interventions becoming available for dengue prevention and control, including dengue vaccines, decision-making on future implementation strategies should be based on such burden of disease data.

Social factors related to quality of life among HIV infected children in ubon Ratchathani Province, Thailand.

A cross-sectional study was conducted to determine the social factors and quality of life of HIV infected children attending the Pediatric Infectious Disease Clinic, Sappasithiprasong Hospital, Ubon Ratchathani Province, Thailand. Data were collected during October-November 2008, by interviewing caretakers and their children using a structured questionnaire. The children's families were in need of improved social support (84.5%), since community resources provided limited support, such as clothes, food, financial support, consultation, and information. The HIV infected children's quality of life needed improvement (78.7%). The factors associated with quality of life included having others as main caretakers (OR 4.64, 95% CI 1.45-14.78), parental death (OR 4.19, 95% CI 1.55-11.31), age of caregivers above 45 years old (OR 9.52, 95% CI 2.62-34.53), and family income less than THB 5,000 per month (OR 5.25, 95% CI 1.14-23.39). However, on multivariate analysis, only age of caregiver was a significant predictor for quality of life of the child. Children who were cared for by caregivers aged 45 years or above had a better quality of life than those whose caregivers were 20-45 years old (OR 6.32, 95% CI 1.12-35.62). Therefore, to improve quality of life among HIV infected children, age of caregiver is an important factor to be considered. Government and non-government organizations should focus on supporting caregivers in terms of food, financial, and emotional support based on resources available in the community.

A three-year clinical study on immunogenicity, safety, and booster response of purified chick embryo cell rabies vaccine administered intramuscularly or intradermally to 12- to 18-month-old Thai children, concomitantly with Japanese encephalitis vaccine.

After concomitant administration of purified chick embryo cell rabies vaccine and Japanese encephalitis vaccine to toddlers, adequate rabies and Japanese encephalitis virus neutralizing antibodies concentrations were demonstrated by day 49, 7 days after a booster at 1 year, and in the majorly at 3 years postvaccination. The inclusion of rabies vaccine in the expanded program on immunization should be considered in rabies endemic countries.

Safety, Tolerability and Immunogenicity of an MF59-adjuvanted, Cell Culture-derived, A/H5N1, Subunit Influenza Virus Vaccine: Results From a Dose-finding Clinical Trial in Healthy Pediatric Subjects.

BACKGROUND: A/H5N1 influenza virus has significant pandemic potential, and vaccination is the main prophylactic measure. This phase 2, randomized, observer-blind, multicenter study evaluated the safety and immunogenicity of two MF59-adjuvanted, cell culture-derived H5N1 (aH5N1c) vaccine formulations in healthy pediatric subjects 6 months to 17 years old. METHODS: Subjects (N = 662) received 2 aH5N1c doses 3 weeks apart, containing either 7.5 µg (full dose) or 3.75 µg (half dose) hemagglutinin antigen per dose. Local reactions and adverse events (AEs) were assessed by age. Antibody responses were measured by hemagglutination inhibition assay and assessed as geometric mean titers, geometric mean ratios (GMRs) and percentages of subjects achieving titers ≥1:40 and seroconversion (NCT01776554). RESULTS: No vaccine-related serious AEs occurred. Incidence of solicited local reactions and systemic AEs were similar across vaccine groups. Tenderness and irritability in <6-year olds, and injection site pain, myalgia and fatigue in 6-17-year olds were the most commonly reported reactions in both full- and half-dose recipients. Frequencies of AEs were lower after the second dose than the first dose in all vaccine and age groups. Three weeks after the administration of a second dose, both full- and half-dose formulations met the Center for Biologics Evaluation Research and Review (United States) and Committee for Medicinal Products for Human Use (EU) licensure criteria for titers ≥1:40 (full dose 96% subjects; half dose 86%), seroconversion (full dose 96% subjects; half dose 86%), and GMR (full dose GMR 262; half dose 84). Antibody responses were highest in 6-35-month olds. CONCLUSIONS: In pediatric subjects, both aH5N1c vaccine formulations were well tolerated and highly immunogenic, meeting both US and EU licensure criteria for pandemic influenza vaccines.

Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly.

BACKGROUND: A/H5N1 influenza viruses have high pandemic potential; consequently, vaccines need to be produced rapidly. MF59® adjuvant reduces the antigen required per dose, allowing for dose sparing and more rapid vaccine availability. METHODS: Two multicenter, phase II trials were conducted to evaluate the safety and immunogenicity of an MF59-adjuvanted, cell culture-derived, A/H5N1 vaccine (aH5N1c) among 979 adult (18-64 years old) and 1393 elderly (≥65 years old) subjects. Participants were equally randomized to receive 2 full-dose (7.5 µg of hemagglutinin antigen per dose) or 2 half-dose aH5N1c vaccinations 3 weeks apart. Outcomes were based on Center for Biologics Evaluation Research and Review (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria (titers ≥1:40 and seroconversions on day 43). Solicited reactions and adverse events were assessed (www.clinicaltrials.gov: NCT01776541 and NCT01766921). RESULTS: CBER and CHMP criteria were met by both age groups. CBER criteria for hemagglutination titers were met for the full-dose formulation. Solicited reaction frequencies tended to be higher in the full-dose group and were of mild to moderate intensity. No vaccine-related serious adverse events occurred. CONCLUSIONS: In adult and elderly participants, the full-dose aH5N1c vaccine formulation was well tolerated and met US and European licensure criteria for pandemic vaccines.

Age-specific prevalence of dengue antibodies in Bangkok infants and children.

Seroprevalence of dengue antibodies were determined in healthy children in Bangkok. At 9, 12, and 18 months of age 23%, 9%, and 17% of children respectively had neutralizing antibodies against one or more serotypes. DEN1 was the most prevalent, followed by DEN3, DEN2, and DEN4. Twelve children had serologic evidence of dengue infection. The nadir of dengue antibodies in children was at 12 months of age. In highly endemic areas, dengue vaccination could be needed at an early age.

MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial.

BACKGROUND: Co-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women. METHODS: In this phase IIIb study (NCT01755689), 1300 healthy 9-25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6. Immunogenicity, safety and reactogenicity were evaluated. RESULTS: Immunogenicity of MenACWY-TT and AS04-HPV16/18 when co-administered was non-inferior to that of the 2 vaccines given separately. Co-administration of MenACWY-TT, AS04-HPV16/18 and Tdap was non-inferior to MenACWY-TT administered alone or to Tdap co-administered with AS04-HPV16/18 in terms of immunogenicity for all vaccine components, except pertussis antigens. Post-vaccination, ≥89.5% of participants reached antibody levels above the pre-specified threshold for all antigens. No safety concerns were identified. CONCLUSION: Our data support co-administration of MenACWY-TT with Tdap and AS04-HPV16/18 vaccines in adolescents.

Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell vaccine: a systematic literature review and meta-analysis.

INTRODUCTION: Fifteen million people each year receive post-exposure prophylaxis (PEP) to prevent rabies, yet the disease remains neglected and highly under-reported. AREAS COVERED: In this systematic literature review, we assessed the immunogenicity, efficacy, and safety of a purified chick embryo cell-culture rabies vaccine (PCECV) for PEP against rabies by intramuscular (IM) or intradermal (ID) administration. We performed meta-analyses to compare immunogenicity according to the route of vaccine administration, study population, and PEP regimen, such as number of doses, and concomitant rabies immunoglobulin. EXPERT COMMENTARY: There were 54 estimates of immune responses to vaccination, which showed that in the overall population, after starting PEP with PCECV by the IM or ID route (≥2.5 IU per dose), almost all individuals had rabies virus neutralizing antibody (RVNA) titers above the World Health Organization (WHO) recommended serological threshold for an adequate immune response to vaccination (RVNA ≥0.5 IU/ml by day 14). In the overall population, PCECV had an acceptable safety profile. However, given that there are 59,000 human rabies deaths reported annually, the challenge is to improve access to PCECV for PEP against human rabies.

Immunogenicity and safety of inactivated chromatographically purified Vero cell-derived Japanese encephalitis vaccine in Thai children.

Inactivated mouse-brain-derived Japanese encephalitis vaccine has a worrisome safety profile and the live attenuated vaccine is unsuitable in immunodeficiency. This study aimed to evaluate the immunogenicity and safety of an inactivated chromatographically purified Vero-cell-derived JE vaccine (CVI-JE, Beijing P-3 strain) in children. 152 healthy Thai children, with an average (SD) age of 14.4 (3.8) months, received 3 doses of CVI-JE on days 0, 7-28, and one year. Homologous JE neutralizing antibody titers (NT) were measured. All subjects had seroprotection [geometric mean titer (GMT) 150] 28 days' post 2nd vaccination. The seroprotection rates at 1 year after primary series and and 1 month after the booster were 89.3% (GMT 49) and 100% (GMT 621), respectively. Local and systemic reactions-fever (17.6%), vomiting (8%), and poor appetite (5.3%)-were noted within 28 days' post-vaccination. All these symptoms were self-limited. CONCLUSIONS: CVI-JE is safe, immunogenic, and provided high NT.

Shortening intradermal rabies post-exposure prophylaxis regimens to 1 week: Results from a phase III clinical trial in children, adolescents and adults.

BACKGROUND: This phase III clinical trial compared the immunogenicity and safety of a purified chick-embryo cell rabies vaccine (PCECV) administered according to a shortened post-exposure prophylaxis (PEP) 4-site/1-week intradermal regimen, compared with the currently recommended 2-site/Thai Red Cross (TRC) regimen. METHODOLOGY/PRINCIPAL FINDINGS: This controlled, open-label, multi-center study (NCT02177032) enrolled healthy individuals ≥1 year of age, randomized into 4 groups to receive intradermal PCECV according to one of the 2 regimens, with or without human rabies immunoglobulin (HRIG) administration at first visit (in adults only). Rabies virus neutralizing antibody (RVNA) concentrations and percentages of participants with RVNA concentrations ≥0.5 IU/mL (considered as adequate concentrations following PEP) were assessed up to day (D) 365 post-first vaccination. Non-inferiority of the 4-site/1-week regimen to the 2-site/TRC regimen was demonstrated if at D49, the lower limit of the 95% confidence interval (CI) for the difference between groups in the percentage of participants with adequate RVNA concentrations was >-5%. Of the 443 participants receiving the 4-site/1-week regimen, 88 adults received HRIG; 442 participants received the 2-site/TRC regimen (88 with HRIG). All participants achieved adequate RVNA concentrations by D14. At D49, the difference in percentage of participants with adequate RVNA concentrations between the 4-site/1-week and the 2-site/TRC groups was -1 (95%CI: -2.4-0.0); thus, non-inferiority was concluded. RVNA geometric mean concentrations were 18 IU/mL in 4-site/1-week groups and 12 IU/mL in 2-site/TRC groups at D14, and subsequently declined in all groups. RVNA concentrations were consistently lower in adults with HRIG administration than in those without. The 2 regimens had similar safety profiles. Of the 15 serious adverse events reported in 4-site/1-week groups and 19 in 2-site/TRC groups, none were vaccination-related. SIGNIFICANCE: The data suggest that the 4-site/1-week regimen might be an alternative to current recommendations, with potential benefits in terms of improved cost-efficiency and compliance to vaccination.

Health problems among Thai tourists returning from India.

BACKGROUND: The number of Thai tourists visiting India is increasing each year. Most studies investigating health problems among international travellers to India have focused on travellers from Europe or North America, and the applicability of these studies to Asian travellers is unknown. METHODS: This cross-sectional study used data collected from Thai tourists who had recently completed a trip to India. A questionnaire on demographic data, travel characteristics, pre-travel health preparation, and health problems during the trip to India was administered. All participants were also invited to answer a follow-up questionnaire 15 days after their arrival. RESULTS: The study included 1,304 Thai tourists returning from India between October 2014 and March 2015. Sixty-two percent were female. Overall median age was 49 years, and the median length of stay was 10.6 days. Most were package tourists, and 52% (675) reported health problems during their trip. Common health problems were cough, runny nose, and sore throat (31.1%), followed by musculoskeletal problems (21.7%), fever (12.7%), diarrhea (9.8%) and skin problems (6.6%). Other reported problems were related to the eyes/ears (2.1%), animal exposure (1.9%) and accidents (0.8%). We found that several factors may be associated with the incidence of health problems among these tourists, including travelling style and travel health preparation. In the follow-up questionnaire, 16.8% of the participants reported new or additional symptoms that developed after their return to Thailand. Respiratory symptoms were still the most common health problems during this 15-day period. CONCLUSIONS: Over half (52%) of Thai tourists experienced health problems during their trip to India. The most common health problem was not travellers' diarrhoea, as would be expected from published studies. Rather, respiratory and musculoskeletal problems were common symptoms. This information will be useful in pre-travel assessment and care. Our findings may indicate that health risks among travellers vary by nationality.