Complete genome sequences of paired isogenic Burkholderia pseudomallei isolated from a Thai pediatric patient with a urinary tract infection.

Burkholderia pseudomallei is the causative agent of melioidosis, the disease endemic in Southeast Asia and northern Australia. We report complete genome sequences of paired isogenic B. pseudomallei isolated from a 12-year-old Thai male presenting with acute urinary tract infection before (SCBP001) and after (SCBP007) a decrease in susceptibility to ceftazidime.

Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand.

This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron variant. We enrolled 97 children and 57 adolescents. At 3 months, 30 children (31%) and 34 adolescents (60%) reported at least one long COVID symptom, with respiratory symptoms prevailing (25% children and 32% adolescents). The median time from infection to vaccination was 3 months in adolescents and 7 months in children. At 1 month following vaccination, in children who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 86.2% inhibition (71.1-91.8) and 79.2% inhibition (61.5-88.9), respectively (p = 0.26). Among adolescents who received one-dose and two-dose BNT162b2 vaccines, the median (IQR) sVNT against Omicron was 64.4% inhibition (46.8-88.8) and 68.8% inhibition (65.0-91.2) (p = 0.64). Adolescents had a higher prevalence of long COVID than children. Immunogenicity against the Omicron variant after vaccination was high and did not vary between one or two doses of the vaccine in either children or adolescents.

Good performance of syphilis rapid diagnostic test kits among young key populations in Thailand.

BACKGROUND: The prevalence of syphilis is increasing among adolescents and young adults (AYAs) globally. Use of syphilis rapid diagnostic treponemal tests (RDTs) may improve test coverage and same-day treatment. This study aims to determine sensitivity and specificity of two syphilis RDTs. METHODS: A cross-sectional study was conducted in men who have sex with men and transgender women aged 15-24 years attending a sexual health clinic in Bangkok. Syphilis RDTs used were Determine Syphilis TP and Bioline Syphilis 3.0, using whole blood from finger pricks and venipuncture. Treponemal pallidum electrochemiluminescence assay was used as standard reference. RESULTS: From February to July 2022, 200 AYAs with a mean age 21.1 (SD2.1) years were enrolled, including 50 (25.0%) living with HIV. Prevalence of syphilis was 10.5% (95%CI 6.6-15.6), which was higher among AYAs living with HIV (22.0%) compared with AYAs unaffected by HIV (6.7%). Sensitivities of Determine Syphilis TP and Bioline Syphilis 3.0 were 85.7% (95%CI 63.7-97.0) and 66.7% (95%CI 43.0-85.4), respectively. Specificity of both RDTs was 100% (95%CI 98.0-100.0). Performance of RDTs was similar for both specimens. CONCLUSIONS: Syphilis RDTs have high sensitivity and specificity in diagnosing syphilis. It should be considered for use in sexual health clinics with high syphilis prevalence to initiate treatment promptly.

A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines.

BACKGROUND: Immunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed. OBJECTIVE: To evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults. METHODS: A double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x1010 viral particles) or low dose (LD, 2.5x1010 viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms. RESULTS: From July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD. CONCLUSION: Half-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings.

Pediatric and Neonatal Invasive Candidiasis: Species Distribution and Mortality Rate in a Thai Tertiary Care Hospital.

BACKGROUND: Invasive candidiasis (IC) is a serious infection among children with underlying medical conditions. A shift from C. albicans to non-albicans Candida has been observed worldwide. This study aims to identify species of Candida and factors associated with the overall 30-day mortality rate. METHODS: A retrospective chart review was conducted among children with culture-confirmed IC from birth to 15 years of age at King Chulalongkorn Memorial Hospital, Thailand. Multivariate Cox regression analysis was performed to determine associated factors with 30-day mortality. RESULTS: From 2003 to 2019, 102 episodes of IC in pediatric group with a median age of 16 months (interquartile range 4-65) and 12 episodes of IC in neonatal group with a median age of 18 days (interquartile range 12-22). The species distribution were Candida albicans (35%), Candida parapsilosis (26%), Candida tropicalis (22%), Candida glabrata (6%) and other/unspecified species (11%). Antifungal treatment was given in 88% (67% Amphotericin B deoxycholate, 28% Fluconazole). Overall 30-day mortality rates were 28.5% [95% confidence interval (CI) 20.8%-38.4%] and 8.3% (95% CI 1.2%-46.1%) in pediatrics and neonates, respectively. Mortality rate among the neutropenic group was significantly higher than non-neutropenic group (46.4% vs. 20.6%, P = 0.005). Factors associated with 30-day mortality in pediatric IC were shock [adjusted hazard ratio (aHR) 4.2; 95% CI 1.8-9.4], thrombocytopenia (aHR 7.7; 95% CI 1.8-33.9) and no antifungal treatment (aHR 4.6; 95% CI 1.7-12.1). CONCLUSIONS: Two-third of children with IC were diagnosed with non-albicans Candida. Children with high mortality rate included those with neutropenia, presented with shock or thrombocytopenia, such that the proper empiric antifungal treatment is recommended.

High prescribing rates of third-generation cephalosporins in children hospitalized with acute lower respiratory infections at a university hospital.

OBJECTIVE: Antibiotics are frequently prescribed for the treatment of acute lower respiratory infections (ALRI) in children ≤5 years of age, even though viral aetiologies are the most common. The aim of this study was to describe antibiotic prescribing rates and patterns in children ≤5 years of age hospitalized with ALRI. METHODS: A retrospective study was conducted involving patients aged 1 month to 5 years hospitalized with ALRI at a university hospital. Patient demographics, ALRI diagnosis, microbiological data, antibiotics prescribed, and treatment outcomes were recorded and analysed. RESULTS: A total of 1283 patients were enrolled. Their median age was 1.6 years (interquartile range 0.8-2.8 years). Thirty-six percent had a co-morbidity. The diagnosis at discharge was viral ALRI in 81% and bacterial pneumonia in 19%. The mortality rate was 0.4%. The overall antibiotic prescribing rate was 46% (95% confidence interval 43-49%). Antibiotic prescribing rates were higher among children with co-morbidities (65% vs 35%, p < 0.001) and older children (57% for >2-5 years vs 39% for ≤2 years, p < 0.001). Parenteral third-generation cephalosporins were prescribed in up to 68% of all prescriptions. CONCLUSIONS: Nearly-half of hospitalized children with ALRI were prescribed antibiotics. The majority of prescribed antibiotics were third-generation cephalosporins. An antimicrobial stewardship programme and antibiotic guidelines should be implemented to promote the judicious use of antibiotics.

Antibody responses to SARS-CoV-2 in patients with differing severities of coronavirus disease 2019.

BACKGROUND: A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination. AIM: To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. METHODS: Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed. RESULTS: A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8-93.6) and 84.8% (95% CI: 76.2-91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003). CONCLUSION: The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection.

Efficacy of chlorhexidine patches on central line-associated bloodstream infections in children.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are important hospital-acquired infections. Chlorhexidine-impregnated dressings (also known as chlorhexidine patches, CHG patches) are reported to decrease CLABSIs in adults. This study aims to determine the efficacy of CHG patches in reducing CLABSIs in children. METHODS: An open-label randomized controlled trial was conducted in children aged 2 months to 18 years, requiring a short-term catheter. Patients were randomized into two groups, allocated to receive CHG patches or standard transparent dressings. Care of the catheter was in accordance with Asia Pacific Society of Infection Control (APSIC) recommendations. Central-line-associated bloodstream infections were defined using National Healthcare Safety Network surveillance criteria. RESULTS: From April 2017 to April 2018, 192 children were enrolled. There were 108 CHG patch catheters and 101 standard dressing catheters, contributing to 3,113 catheter days. The median duration of catheter dwelling was 13 days, with an interquartile range (IQR) of 8-20 days. Half were placed at the jugular vein and 22% at the femoral vein. There were 23 CLABSI events. Incidence rates for CHG patches and standard dressings were 7.98 (95% confidence interval (CI), 4.25-13.65) and 6.74 (95% CI, 3.23-12.39) per 1,000 catheter days, respectively (incidence rate ratio 1.18; 95% CI, 0.52-2.70). The CLABSI pathogens were 15 Gram-negative bacteria, six Gram-positive bacteria, and two Candida organisms. Catheter colonization of CHG patches and standard dressings were 2.02 (95% CI, 0.42-5.91) and 3.07 (95% CI, 1.00-7.16) per 1,000 catheter days, respectively. Only local adverse effects occurred in 6.8% of the participants. CONCLUSIONS: In our setting, there was no difference in CLABSI rates when the chlorhexidine patch dressings were compared with the standard transparent dressings. Strengthening of CLABSI prevention bundles is mandatory.

Optimizing Vancomycin Use Through 2-Point AUC-Based Therapeutic Drug Monitoring in Pediatric Patients.

The 24-hour vancomycin area under the serum concentration-time curve (AUC24 ) divided by the minimum inhibitory concentration (MIC) (AUC24 /MIC) is more closely related to patient outcomes than serum trough concentrations (Ctrough ). Two-point simplified equations for calculating AUC based on serum peak concentrations (Cpeak ) and Ctrough , named equation A (EqA) and equation B (EqB), have recently been adopted into clinical use for adult pediatric patients. We aimed to find the agreement between predicted AUC24 using the reference method (ref) relative to EqA and EqB and the correlation between Ctrough and AUC24 . From June to December 2018, 43 pediatric patients with normal renal function, receiving 15 mg/kg of vancomycin intravenously every 6 hours, were enrolled. The pediatric patients' median age was 2.2 years (range 0.1-15.3). At steady state, vancomycin Cpeak and Ctrough were measured at 2 hours after infusion completion and within 30 minutes before the next dosing, respectively. AUC24 was estimated using ref, EqA, and EqB. From Bland-Altman analysis, the 2 AUC24 s estimated by ref and EqA showed less bias than those estimated by ref and EqB (bias 1.3 and -72.1 mg⋅h/L, respectively). Ctrough and AUC24 using either ref or EqA were correlated more closely (r2 = 0.94) than with EqB (r2 = 0.86). Assuming a vancomycin MIC of 1 mg/L, an AUC24 ≥400 mg⋅h/L was targeted. Regardless of the method used, AUC24 ≥400 mg⋅h/L was never seen with Ctrough <8 mg/L but was always seen with Ctrough >10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC24 estimation. Ctrough >10 mg/L correlated highly to AUC24 ≥400 mg⋅h/L.

Novel mutations in Thai patients with glanzmann thrombasthenia.

OBJECTIVES: Glanzmann thrombasthenia (GT) is an autosomal recessive platelet disorder, caused by defects of the platelet integrin αIIbß3 (GPIIb/IIIa) resulting from pathogenic mutations in either ITGA2B or ITGB3. It is characterized by spontaneous mucocutaneous bleeding. The molecular features of GT in Thailand have not been identified. This study aimed to determine the clinical and molecular features of unrelated Thai patients with GT. METHODS: Four patients with clinically suspected GT were recruited at the Division of Pediatric Hematology/Oncology, King Chulalongkorn Memorial Hospital. The diagnosis was based on clinical and hematological parameters as well as genetic analysis. Whole exome sequencing (WES) was performed in all cases. RESULTS: Of the four patients studied, the median age at first suspicion of GT was 2.5 years. All presented with severe bleeding symptoms (WHO bleeding scale 3). Flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression. By WES, we successfully identified seven mutant alleles in ITGA2B. One alteration, the c.2915dup (p.Leu973Alafs*63), was detected in two unrelated families. One patient was homozygous for the c.617T>A (p.Val206Asp). Of the five different mutations, three have never been previously described. These include a missense, c.617T>A (p.Val206Asp), a deletion, c.1524_1533del (p.Gln508Hisfs*3), and a nonsense, c.2344C>T (p.Arg782Ter). CONCLUSION: This study reported three novel mutations expanding the genotypic spectrum of ITGA2B causing GT.