Outcomes among Thai children with risk conditions hospitalized for pneumococcal disease (invasive or non-bacteraemic pneumonia): A multi-centre, observational study.

Objective: To describe the risk condition status and clinical outcomes among Thai children hospitalized with pneumococcal disease. Methods: In this retrospective analysis, children with invasive pneumococcal disease (IPD) or x-ray-confirmed non-bacteraemic pneumococcal pneumonia (NBPP) were identified from nine hospitals in Thailand between 2010 and 2019. Data on risk factors and outcomes were extracted from medical records. Results: In total, 413 cases were identified: 319 IPD and 94 NBPP. Overall, 133 (32.2%) patients were admitted to intensive care units and 11/406 (2.7%) died. Twenty-seven percent of IPD cases had at-risk conditions and 15% had high-risk conditions. Most IPD cases (32.9%) occurred in children aged 2-4 years, and most NBPP cases (28.7%) occurred in infants aged 0-11 months. Of 51 Streptococcus pneumoniae isolates collected, 41 (80%) were pneumococcal 13-valent conjugate vaccine serotypes. Only 5.1% of children had received a pneumococcal vaccine. Conclusions: Most children with IPD and NBPP did not have high-risk or at-risk conditions, while 42% had at-risk or high-risk conditions for pneumococcal disease. Very few children in the cohort had received any type of pneumococcal vaccine. Increasing the availability of pneumococcal conjugate vaccines should be considered to reduce the burden of pneumococcal disease among children in Thailand.

Mitochondrial genome diversity of Balamuthia mandrillaris revealed by a fatal case of granulomatous amoebic encephalitis.

Introduction: Balamuthia (B.) mandrillaris is a free-living amoeba that can cause rare yet fatal granulomatous amoebic encephalitis (GAE). However, efficacious treatment for GAE is currently unavailable, especially when genomic studies on B. mandrillaris are limited. Methods: In this study, B. mandrillaris strain KM-20 was isolated from the brain tissue of a GAE patient, and its mitochondrial genome was de novo assembled using high-coverage Nanopore long reads and Illumina short reads. Results and Discussion: Phylogenetic and comparative analyses revealed a range of diversification in the mitochondrial genome of KM-20 and nine other B. mandrillaris strains. According to the mitochondrial genome alignment, one of the most variable regions was observed in the ribosomal protein S3 (rps3), which was caused by an array of novel protein tandem repeats. The repeating units in the rps3 protein tandem region present significant copy number variations (CNVs) among B. mandrillaris strains and suggest KM-20 as the most divergent strain for its highly variable sequence and highest copy number in rps3. Moreover, mitochondrial heteroplasmy was observed in strain V039, and two genotypes of rps3 are caused by the CNVs in the tandem repeats. Taken together, the copy number and sequence variations of the protein tandem repeats enable rps3 to be a perfect target for clinical genotyping assay for B. mandrillaris. The mitochondrial genome diversity of B. mandrillaris paves the way to investigate the phylogeny and diversification of pathogenic amoebae.

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases.

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12-18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7-16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7-74.2) and 233.6 (95% CI 79-690.6); adolescents with cancer 62.3 (95% CI 29.2-133.1) and 214.9(95% CI 34.2-1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4-84.8) and 849.8 (95% CI 393.4-1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3-98.8) and 3240.3 (95% CI 2699-3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3-98.9) and 3818.5 (95% CI 3490.4-4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8-62.4) and 178.7 (95% CI 91.2-350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4-92.8) and 1037.1 (95% CI 933.3-1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required.

HBV Seroprotection and Anamnestic Response to Booster Vaccination in Pediatric Cancer Survivors.

Hepatitis B is a major global health concern and can be prevented in the era of vaccination. Impaired immunological memory to primary immunization is a common chemotherapy-related complication among cancer survivors. The study aimed to determine protective immunity against hepatitis B virus (HBV) and anamnestic response to booster vaccination. In all, 107 pediatric cancer survivors previously immunized with primary hepatitis B vaccination were enrolled. A hepatitis B booster dose was administered to those with suboptimal seroprotection (anti-HBs < 10 mIU/mL) and 2 additional doses were subsequently administered at 1 and 6 months to those whose anti-HBs remained low. Clinical and serologic parameters were analyzed. Sero-protective rate against HBV (anti-HBs ≥ 10 mIU/mL) among survivors was 20.6% with geometric mean titer (GMT) of 95.7 ± 265.6 mIU/mL. Anamnestic response was 61% after a booster vaccine among those with suboptimal seroprotection and 100% after 2 additional booster doses among those whose anti-HBs remained low. GMTs among those survivors after the First and third booster vaccines were 320.0 ± 412.4 mIU/mL and 826.5 ± 343.8 mIU/mL, respectively. Age at diagnosis was a significant independent risk factor for adequate seroprotection (adjusted OR = 0.84, 95%CI: 0.71-0.99) with a P-value of .034. No associated risk factors to predict optimal anamnestic response to booster vaccination were identified. Loss of immunological memory to primary hepatitis B immunization is an inevitable complication among most pediatric cancer survivors; therefore, assessing adequate seroprotection is essentially required. For those with limited accessibility to serologic tests, completion of full 3-booster-dose series is alternative and highly recommended.

Standardization and Evaluation of an Anti-ZIKV IgM ELISA Assay for the Serological Diagnosis of Zika Virus Infection.

Here, we describe the development of the in-house anti-Zika virus (ZIKV) IgM antibody capture ELISA (in-house ZIKV IgM ELISA) for the detection and diagnosis of acute ZIKV infections. We compared the in-house ZIKV IgM ELISA assay performance against two commercial kits, Euroimmun ZIKV IgM and InBios 2.0 ZIKV IgM ELISA. We tested the assays' ability to detect anti-ZIKV IgM using a well-defined serum sample panel. This panel included 80 ZIKV negative samples (20 negative, 20 found to be primary dengue virus [DENV][ infections, 20 secondary DENV infections, and 20 Japanese encephalitis virus [JEV] infections) and 67 ZIKV reverse transcriptase-polymerase chain reaction-positive acute serum samples. The OD values were calculated to enzyme immunoassay (EIA) unts by comparing them to weak positive controls. The results demonstrated the high sensitivity (88.06%) and specificity (90.00%) of our in-house ZIKV IgM ELISA and its 89.12% overall percentage agreement. The kappa values were deemed to be within excellent range and comparable to the InBios ZIKV IgM ELISA. Some cross-reactivity was observed among secondary DENV and JEV samples, and to a much lower extent, among primary DENV samples. These data indicate that our in-house ZIKV IgM ELISA is a reliable assay for the detection of anti-ZIKV IgM antibodies in serum.

Clinical Characteristics and Predictive Factors of Invasive Fungal Disease in Pediatric Oncology Patients with Febrile Neutropenia in a Country with Limited Resources.

BACKGROUND: The most common complication among pediatric oncology patients is febrile neutropenia (FN). Invasive fungal disease (IFD) is suspected when fever persists >4-7 days after empirical antibiotics. Its clinical characteristics and predictive factors associated with IFD among pediatric oncology patients with FN were thus explored. METHODS: Pediatric oncology patients with FN between January 1, 2012 and December 31, 2016 were enrolled in this study. Clinical characteristics, including laboratory investigations, treatment modalities, and final outcomes of IFD were retrospectively reviewed and analyzed. RESULTS: In all, 73 patients with 180 episodes of confirmed diagnosis of FN were studied. Median age at diagnosis was 6.2 years, with equal sex distribution. The most common diagnosis was acute lymphoblastic leukemia (n=91, 51%), followed by acute myeloid leukemia (n=47, 26%), Burkitt's lymphoma (n=7, 4%) and neuroblastoma (n=7, 4%). Median absolute neutrophil count at FN diagnosis was 0 (0-806) cells/mm3. IFD was diagnosed for 25 (14%) episodes. Mortality rates for FN and IFD were 4% and 20%, respectively. Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results, and prolonged broad-spectrum antibiotic administration were factors associated with IFD (P<0.05). Prolonged duration between initiation of fever and antifungal administration for nearly 10 days was an independent factor in prediction of IFD occurrence (P=0.014). CONCLUSION: Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results and prolonged broad-spectrum antibiotic administration were factors associated with IFD. Duration between initiation of fever and antifungal administration of nearly 10 days were considered a risk factors of IFD among patients with FN. IRB REFERENCE NUMBER: IRBRTA 825/2560.

Serum Lactate: A Predictor of Septic Shock in Childhood Cancers with Febrile Neutropenia.

Early recognition and management are the key elements to prevent febrile neutropenia associated mortality. The prospective observational study aimed to investigate prognostic accuracy of serum lactate to predict septic shock within 48 hours among hemodynamically stable children with febrile neutropenia. In all, 99 pediatric oncology patients who developed febrile neutropenia were enrolled in the study. Clinical information during 48 hours and serum lactate at the time of enrollment were analyzed. Among 99 participating patients, 10 developed septic shock and 4 of those expired. No significant difference was found of patients' baseline characteristics and basic laboratory parameters between patients with and without septic shock. Serum lactate was significantly elevated among patients developing septic shock (P-value < .001) and those who expired (P-value .002). Receiver operating characteristic (ROC) curve was created to identify the best cutoff value for initial serum lactate associated with the development of septic shock within 48 hours. Baseline serum lactate more than 2.5 mmol/L showed the largest area under the ROC curve to predict the septic shock development within 48 hours (ROC area, 0.90; 95% confidence interval [CI], 0.81-0.98), with sensitivity, specificity, negative predictive value, and accuracy of 80.0%, 92.1%, 97.6%, and 90.9%, respectively. Serum lactate level determined early at the time of febrile neutropenia was an effective surrogate marker for developing septic shock within 48 hours among hemodynamically stable, pediatric oncology patients. The level more than 2.5 mmol/L was the best threshold to start preemptive aggressive hemodynamic monitoring and prompt treatment to ensure adequate tissue perfusion.

Complete Coding Sequences of 22 East/Central/South African Genotype Chikungunya Virus Isolates from Thailand (2018 to 2019).

The coding-complete genome sequences of 22 chikungunya virus strains collected from the 2018-2019 outbreak in Thailand are reported. All sequences belong to the East/Central/South African (ECSA) genotype and contain two mutations, E1:K211E and E2:V264A, which were previously shown to be associated with increased viral infectivity, dissemination, and transmission in Aedes aegypti.

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

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.

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.

Serosurveillance of varicella and hepatitis B infection after reported cases in medical students and the relationship between past varicella disease history and immunity status.

OBJECTIVE: To identify seroprevalence of varicella and the relationship with their histories of experiences of varicella diseases and to provide appropriate immunization against varicella, mumps, measles, rubella and hepatitis B to medical students. MATERIAL AND METHOD: All of the medical students were eligible for participation after informed consents. Immunization history against varicella, mumps, measles, rubella (MMR) and hepatitis B were obtained from a questionnaire. A blood sample was obtained from each student for IgG antibody against VZV by ELISA. Medical students with an uncertain history or no documentation of hepatitis B vaccination were tested for HBsAg and anti-HBcIgG by ELISA. RESULTS: There were 383 medical students enrolled. The mean age at enrollment was 21.6 years (median 21.4 years; range 18-25.8 years). Of 383 medical students, 372 (97.2%) had documents of receiving MMR immunizations. The blood samples were obtained from 374 of 383 (97.6%) medical students to identify the immunity against varicella zoster virus (VZV) and the seroprevalence rate was 92%. Using VZVIgG antibody detection as a standard test, history of experience of varicella disease provided positive predictive value of 99.3% (148/149). Of 383 medical students, 277 (72.3%) were tested for hepatitis B markers and 243 (87.7%) students showed negative results. The prevalence of HBsAg carriers was 0.01% (4/383). CONCLUSION: Suboptimal immunities against vaccine preventable diseases could be demonstrated in the medical students including varicella and hepatitis B. New recommendations of immunizations against varicella, MMR and hepatitis B viruses for a particular group of the population were provided.

Invasive pneumococcal disease in Phramongkutklao Hospital 2004-2008: clinical data, serotype distribution and antimicrobial resistance patterns.

OBJECTIVE: To describe the clinical course, serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease (IPD) cases in a public hospital. MATERIAL AND METHOD: Retrospective review of IPD cases occurring from January 2004 through December 2008 was performed. Antibiotic susceptibility testing and serotyping were performed for available isolates. RESULTS: Fifty one IPD cases occurred during the study period, of which 47 had medical records available for review. The majority of cases occurred among children under 5 years of age (23.4%) and adults over 60 years of age (36.1%). Underlying diseases were identified in 72.3% of patients. Fifty-three percent of cases were associated with pneumonia, while 17% had meningitis, and 15% had isolated bacteremia. Serotype could be determined for 15 (31.9%) isolates, and 6B was most common. Based on current antibiotic susceptibility breakpoints for meningitis, 4 of the 7 available isolates from meningitis cases were penicillin resistant and one had reduced susceptibility to cefotaxime. Among non-meningitis isolates, 96.7% were penicillin susceptible and 3.3% had intermediate susceptibility to penicillin. Overall case fatality proportion was 19%. CONCLUSION: At this tertiary care hospital in Bangkok, IPD has disproportionately affected young children and the elderly. High rates of penicillin resistance among meningitis cases, the most severe form of IPD, underscore the need of appropriate treatment strategies and vaccine usage.

Cerebrospinal fluid lymphocytosis in an infant with acute Streptococcus pnuemoniae meningitis: a case report.

A 10 month-old female infant presented with one day of high fever with drowsiness and seizures. Physical examination showed meningeal irritation and mild cyanosis. The cerebrospinal fluid (CSF) profile revealed opening pressure of 27 cmH2O, closing pressure of 17 cmH2O, red blood cells 310 cells/microL, white blood cells 100 cells/microL of which 90 percents were lymphocytes, protein 391 mg/dl, sugar 0 mg/dL and blood sugar 74 mg/dl. Numerous gram positive diplococci were found on CSF Gram-stained smear. Bacterial meningitis was diagnosed and cefotaxime 300 mg/kg/day plus vancomycin 60 mg/kg/ day were given empirically. The patient developed hypotension, poor tissue perfusion, dyspnea and disseminated intravascular coagulopathy (DIC). She expired 10 hours after hospitalization. The CSF and blood culture grew out Streptococcus pneumoniae serotype 6B with the minimal inhibitory concentration (MIC) of 0.5 and 1.5 microg/mL for penicillin and cefotaxime respectively. Atypical characteristics of CSF in bacterial meningitis may cause delay in empirical antimicrobial therapy. Gram-stained smear of CSF is helpful for rapid diagnosis and proper management.

Perception of medical personnel on informed consent for research participation in Phramongkutklao Hospital and Phramongkutklao College of Medicine.

OBJECTIVE: To evaluate the perception of medical personnel and medical cadets toward informed consent obtained from potential research participants. MATERIAL AND METHOD: The authors conducted a study using self-administered questionnaires which included questions about perception on informed consent regarding its objectives, investigator's role, vulnerable subjects, family involvement and children's assent. The answer for each question was graded into 5 scales. RESULTS: A selection of 380, 30.5%, 37.6% and 31.8% of 669 were attending staff residents, and medical cadets, respectively. A total of 85.5% agreed that informed consent in therapeutic trials should be obtained by their own doctors. A total of 75.3% agreed that the primary objective of informed consent was to protect investigators from lawsuits. A total of 60.8% agreed that participant spouses had to be involved in the informed consent process. A total of 79.5% agreed that permission from children was necessary in research conducted in children. CONCLUSION: The role of investigators in therapeutic clinical trial, primary objectives of informed consent, and role of spouse were misunderstood among medical personnel and medical cadets. Education on research ethics should concentrate on these issues.