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Background A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. Methods A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PTgen and 1 μg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 μg PTgen and 5 μg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PTgen and 5 μg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PTchem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. Results Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81–98) for ap1gen, 88% (95% CI 76–95) for Tdap1gen, 80% (95% CI 66–90) for Tdap2gen, 94% (95% CI 83–99) for TdaP5gen, and 78% (95% CI 64–88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. Conclusions All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. Clinical Trial Registration: Thai Clinical Trial Registry, TCTR20180321004.

BACKGROUND Prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of ASP de-escalation recommendations in children who received meropenem. METHODS A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary-care teaching hospital. The ASP team gave recommendation between 72 and 120 h after initiating meropenem therapy. Acceptance of de-escalation recommendations among primary physicians was evaluated within 24 h of recommendation. Outcomes included clinical success rate on the 7th day and incidence rate of acquisition of carbapenem-resistant gram-negative bacteria (CR-GNB) within 30 days. RESULTS From March to December 2019, 217 children with a median (interquartile range) age of 2.1 (0.6, 9.5) years received meropenem. The ASP team gave recommendations in 127 (58.5%) of cases for continuation of meropenem therapy and 90 (41.5%) of cases for de-escalation. The overall acceptance of ASP de-escalation recommendations was 57.8% (95%CI: 46.9-68.1%). Clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (P = 0.06). The incidence rate of acquisition of CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (P = 0.03). CONCLUSIONS About half of the recommendations to de-escalate meropenem prescriptions were accepted through the ASP intervention. Carbapenem-resistant gram-negative bacteria acquisitions was less likely in the de-escalation group. A robust de-escalation strategy 72 h following carbapenem initiation should be encouraged to combat multidrug-resistant organisms.

Prevention of emerging infections in children is a dynamic arena where substantial medical advances have enabled intervention and prevention of infection outbreaks. This article discusses 5 infections causing significant morbidity and mortality across Asia, Latin America, and Africa. Avian influenza and the Middle East respiratory syndrome are highly contagious zoonoses spread through aerosol and droplets, affecting predominantly Asia. Dengue infection and chikungunya are endemic mosquito-borne viruses in tropical regions across Asia, Latin America, and Africa. Ebola is a highly contagious virus spread through human-to-human contact. The latest information in clinical manifestations, infection, prevention control, chemoprophylaxis, vaccination, and public health measures is reviewed.

Objectives The World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). Methods Children aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. Results From November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). Conclusions The 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.

Background Population pharmacokinetic analysis in critically ill infants remains a challenge for lack of information. Objectives To determine the population pharmacokinetic parameters of meropenem and evaluate the covariates affecting population pharmacokinetic parameters. Methods A prospective study was conducted on 35 patients. A total of 160 blood samples were collected and determined free of drug concentrations of meropenem. Population pharmacokinetic data were analyzed using NONMEM software. Internal validation methods, including bootstrapping and prediction-corrected visual predictive checks, were applied to evaluate the robustness and predictive power of the final model. Results A one-compartment model with first-order elimination showed the best fit to the data. The typical clearance (CL) values and volume of distribution (Vd) were 1.33 L/h and 2.27 L, respectively. Weight and creatinine clearance were influential covariates for CL, while weight was a significant covariate for Vd of meropenem. The model evaluation results suggested robustness and good predictability of the final model. The standard dosage regimens of meropenem achieved 40% f T>MIC but not enough if a more aggressive target of 80% f T>MIC at MIC value of ≥ 16 µg/mL is desired. Conclusions This population pharmacokinetic model could be used for suggesting individualized meropenem dosage regimens in critically ill infants.

Objectives: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. Methods: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. Results: Ninety patients with a median age (IQR) of 48 months (16–127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6–66.6) versus 6.0 mg/L (4.2–8.6) (P < 0.01). The EI group had a trend of higher proportion of patients who achieved 50% fT>4xMIC (72.7% versus 30.0%; P = 0.06). Conclusions: PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period.

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.

Objectives Febrile neutropenia (FN) is severe and potentially life-threatening in oncologic patients. The objective of this study is to define the factors associated with severe adverse outcomes of pediatric FN. Methods A retrospective and prospective descriptive study performed in pediatric patients diagnosed with FN at King Chulalongkorn Memorial Hospital from January 2013 to December 2017. Severe adverse events defined as the presence in one of these following oxygen therapies, mechanical ventilator, shock, admission to ICU, renal dysfunction, and liver dysfunction. Results The study included 267 patients with 563 febrile neutropenia episodes. The median (range) age was 5.1 years (1 month-15 year). Among 563 febrile neutropenia episodes, 115 episodes (20%) developed severe adverse events. The FN patients were classified into low and high-risk groups, 91% of patients with severe adverse events and all 21 patients who died were in high risk group. The overall mortality rate was 3.1%. Factors associated with severe adverse events were fungal infection (aOR 6.51, 95%CI 2.29-18.56), central venous catheter insertion (aOR 4.28, 95% CI 2.51-7.29), CPG defined high risk (aOR 3.35, 95%CI 1.56-7.17), viral infection (aOR 2.72, 95%CI 1.05-7.06), lower respiratory tract infection (aOR 2.52, 95%CI 1.09-5.82) and treatment not according to CPG (aOR 2.47, 95% CI 1.51-4.03). Conclusions Fungal and viral infection, central venous catheter insertion, lower respiratory tract infection, CPG defined high risk and treatment not according to CPG were associated factors of increased risk for severe adverse events. Our current institutional CPG for FN in children was applicable and improved clinical outcomes for this group of patients. .

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.

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) young children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among PHIV and PHEU children aged 18-60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers’ symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare prevalence of behavioral problems between groups of participants. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers’ depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to presence of child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.

BACKGROUND The World Health Organization has set a goal to eliminate mother-to-child transmission of syphilis to a target of

Background: Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection. Methods: Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies. Results: The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 [1-4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 [0-4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay. Conclusions: These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.

To compare the unbound plasma meropenem concentrations at mid-dosing intervals (CA prospective observational study was conducted in children aged 1 month to 18 years receiving meropenem every 8 hours by either EI or IB. Meropenem CTDM data from 72 patients with a median age (interquartile range [IQR]) of 12 months (3-37) were used. Meropenem dose was 120 and 60 mg/kg/day in EI and IB groups, respectively. Geometric mean (95% confidence interval [CI]) CA meropenem dose of 20 mg/kg/dose given by IB should not be used in critically ill children, even if they are not suspected of having a central nervous system infection. A dose of 40 mg/kg/dose given by EI resulted in higher C

Antimicrobial resistance is a global health threat and there is an urgent need to manage antibiotic use to slow its development. However, antimicrobial stewardship interventions in low- and middle-income countries (LMIC) have been limited in terms of their resourcing, feasibility and effectiveness in the face of greater challenges in child mortality. We sought to gather together examples of antibiotic use problems faced by clinicians in LMIC, many of which are unique to these settings, and real-world antimicrobial stewardship solutions identified, with the goal of learning broader lessons that might be applicable across LMIC.

Infection prevention challenges are ubiquitous in healthcare, but some are unique to or more prevalent in low-and middle-income country settings. Despite limited resources, innovative and committed paediatric healthcare providers and infection preventionists have found creative solutions to address the very real and pressing risks their patients face every day. We gathered examples of infection prevention and control challenges faced by clinicians in resource-limited healthcare facilities, and the real-world infection prevention and control solutions they implemented, with the goal of learning broader lessons applicable to low-and middle-income countrie.

Introduction Efavirenz (EFV) is commonly used for first‐line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48‐week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV‐ to RPV‐based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV. Methods We conducted an open‐label, single‐arm, multi‐centre study in Thailand in virologically suppressed adolescents aged 12–18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018. Results One hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4–17.0), median CD4 count was 664 cells/mm3 (29.9%); 58% were receiving tenofovir‐DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV‐associated mutations (K101E and Y181C) and a lamivudine‐associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV‐related symptoms, depression score or health‐related QOL were observed over time; however, there was significant improvement in performance‐based assessments of executive function at week 24. Conclusions A high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.

Contains fulltext : 283099.pdf (Publisher’s version ) (Open Access) BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and

Contains fulltext : 282959.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to

Combination antiretroviral drug regimens are increasingly preferred for neonatal postexposure prophylaxis (PEP) among HIV-exposed infants with high-risk of transmission. We evaluated the adverse events associated with the use of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) for neonatal PEP during the first 6 weeks of life.A prospective cohort of non-breast-fed HIV-exposed infants was conducted at 5 clinical sites in Thailand. Study population included 100 high-risk HIV-exposed infants (maternal HIV RNA50 copies/mL prior to delivery or received antiretroviral therapy less than 12 weeks) and 100 low-risk HIV-exposed neonates. High-risk infants received ZDV/3TC/NVP for 6 weeks whereas low-risk HIV-exposed neonates received a 4-week regimen of ZDV. Complete blood count, aspartate transaminase and alanine transaminase were assessed at birth, 1, 2 and 4 months of life.From October 2015 to November 2017, 200 infants were enrolled, of which 18.5% had low birth weight2500 g. The proportion of infants with anemia grade 2 or higher at 1 and 2 months of life between ZDV/3TC/NVP and ZDV prophylaxis was 48.5% vs 32.3% (P=0.02); nevertheless, severe anemia (grade 3) was not significantly different; 9.2% vs 10.2% (P=0.81), respectively. At 1 month old, infants on ZDV/3TC/NVP prophylaxis had significantly higher grade 2 anemia versus infants on ZDV alone (33.0% vs 13.4%; P=0.001); however, no difference was observed at 2 months old. No differences in neutropenia or hepatotoxicity between infant prophylactic regimens were observed.Triple antiretroviral neonatal PEP with ZDV/3TC/NVP for 6 weeks in high-risk HIV-exposed infants did not significantly increase the risk of short-term toxicity compared with ZDV-monotherapy prophylaxis.

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 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.

Triple-drug infant antiretroviral prophylaxis containing nevirapine (NVP) is increasingly used to prevent HIV transmission among neonates at high risk of HIV infection. Our aim was to describe NVP concentration from birth through the first month of life.High-risk HIV-exposed neonates were enrolled in a prospective cohort in Thailand. High-risk neonates defined as maternal HIV RNA50 copies/mL before delivery or mother received antiretroviral treatment for12 weeks before delivery. Neonates received zidovudine (4 mg/kg) and lamivudine (2 mg/kg) twice daily, plus NVP (4 mg/kg) once daily (no lead-in) from birth to 6 weeks of life. Infant plasma samples were collected at 1, 2, 14 or 2, 7, 28 days of life. NVP trough concentrations (C24) were estimated using a population pharmacokinetic model and target C24 was ≥0.1 mg/L. "Washout" efavirenz (EFV) concentrations were assessed in infants whose mother received EFV-based antiretroviral treatment.A total of 48 infants were included: 25 (52%) were male and 12 (25%) were preterm (gestational age 34-37 weeks). Median (interquartile range) predicted NVP C24 were 1.34 mg/L (1.13-1.84), 2.24 (2.00-2.59), 2.78 (2.61-3.12), 2.20 (1.86-2.44) and 0.81 (0.58-0.98) on days 1, 2, 7, 14 and 28 of life, respectively. NVP C24 was not significantly different between term and preterm infants. All infants maintained NVP C24 ≥0.1 mg/L. EFV via placental transfer remained detectable in infants up to 7 days of life.NVP 4 mg/kg daily from birth provided adequate prophylactic concentrations during the first month of life in high-risk HIV-exposed neonates.

Background Diagnosing tuberculosis (TB) in children is challenging due to its paucibacillary nature. Loop-mediated isothermal amplification (TB-LAMP) is a simple, rapid, and specific point-of-care molecular diagnostic test. However, evaluation of its performance remains limited in children. This study aimed to evaluate the diagnostic performance of Eiken TB-LAMP among children with presumed tuberculosis disease. Methods Pulmonary and extrapulmonary specimens were collected from children under 18 years with presumed TB. Each specimen was tested by using TB-LAMP, acid-fast bacilli (AFB) smear microscopy, and one of the two molecular assays (polymerase chain reaction [PCR] or Xpert MTB/RIF). Sensitivity and specificity were estimated compared to mycobacterial culture as reference standard. Results From January 2020 to January 2021, 75 participants with presumed TB were enrolled with median age of 7 years (IQR 2-12). Seventeen specimens from 16 (21.3%) children had bacteriologically confirmed TB: 10 pulmonary and 7 extrapulmonary specimens. Overall sensitivity and specificity of TB-LAMP was 76.5% (95% CI 50.1%-93.2%) and 100% (95% CI 94.3%-100%), respectively. It had significantly higher sensitivity than AFB (52.9%, 95% CI 27.8%-77.0%) and similar to other molecular assays; PCR 82.4% (95% CI 56.6%-96.2%), Xpert MTB/RIF 70.0% (95% CI 34.8%-93.3%). Sensitivity of TB-LAMP for pulmonary, lymph node tissue, and extrapulmonary fluid was 80% (95% CI 44.4%-97.5%), 100% (95% CI 39.8-100), and 33.3% (95% CI 0.8-90.6), respectively. TB-LAMP detected all smear-positive (N = 9) and 50% of smear-negative (N = 8) specimens. Conclusions TB-LAMP had higher sensitivity than AFB microscopy and accuracy similar to other molecular assays in both pulmonary and extrapulmonary specimens. These findings support using TB-LAMP as a point-of-care test in children.

Thailand has implemented single-dose mumps-containing vaccines since 1997 and two doses since 2010. This study aimed to describe the seroprevalence of mumps among children who received one- or two-dose mumps vaccines. A cross-sectional study of 145 children (aged 3-9 years) and 422 adolescents (10-18 years) was conducted. Mumps IgG seropositivity was defined as ≥ 22 RU/mL by EUROIMMUN ELISA method. The mumps seroprevalence was higher in children (82.1%, 95% CI 74.8-87.9) compared to adolescents (41.7%, 95% CI 37.0-46.6) who had received at least one dose of the mumps vaccine. Among those receiving 2 doses of mumps vaccine at ≥ 5 years after their last mumps vaccination, only 51.3% had maintained IgG ≥ 22 RU/ml. There was a reverse correlation between mumps IgG titer and the time interval from the second dose of mumps vaccine (R = -0.44, p 0.001). A booster dose of MMR vaccine in young adults may be needed.

Rubella is generally a mild disease, but infection during pregnancy can cause congenital rubella syndrome. Thailand has implemented a two-dose MMR vaccination policy since 2010. This study aimed to describe the seroprevalence rate of rubella among children and adolescents in Thailand. We conducted a cross-sectional study of 132 healthy children (aged 3-9 years) who had received 2 doses of rubella vaccine and 424 adolescents (aged 10-18 years) who were expected to receive at least 1 dose of rubella vaccine. Stored serum samples from healthy children and recently drawn serum samples from adolescents were tested for rubella IgG antibody using a commercial enzyme-linked immunosorbent assay (ELISA) kit (EUROIMMUN). Seroprotection was defined as a rubella IgG level ≥ 10 IU/mL. The rubella seroprevalence rate among children and adolescents who had 2 documented doses of MMR was 97.0% (95 %CI 92.5-99.2%) and 85.4% (95% CI 78.8-90.6%, p

Background: \ud While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens.\ud \ud Methods: \ud Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children

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.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.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).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.

Introduction Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre‐exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP. Methods This open‐label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once‐daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once‐daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir‐diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self‐reported adherence of >50%. Lumbar spine (L2‐L4) BMD (LSBMD) was evaluated by dual‐energy X‐ray absorptiometry scan zero and six months after PrEP initiation. Results From March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry, median (IQR) LSBMD z‐score was −0.8 (−1.5 to −0.3), 17% had low LSBMD (Z‐score 3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (−0.1 to 0.03), p = 0.04. Conclusions Increases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long‐term follow‐up should be considered to explore long‐term outcomes.

Background: Social network strategies (SNS) assumes that people in the same social share similar HIV risk. Methods: This study evaluated SNS to promote HIV testing of young men who have sex with men (YMSM) and transgender women (YTGW) aged 15–24 years. “Recruiters” referred their ‘network members’ (NMs) to clinic. NMs were provided HIV testing. Proportions of first-time HIV testers and number of NMs were analyzed. Results: Between April 2021 to March 2022, 83 recruiters referred 202 NMs. Median age of NMs was 19 years (IQR 17-20), 62% were YMSM. One-hundred-and-twenty-four NMs (61%) were first-time HIV testers. YTGW recruited more NMs per recruiter (5.4 vs 1.4, p = 0.002). HIV prevalence was 3.0% (95% CI 1.1-6.4). Thirty-one-point-three percent of NMs at HIV risk initiated oral HIV preexposure prophylaxis. Conclusions: SNS is a good strategy to reach adolescents at risk of HIV infection. More than half of NMs were first-time HIV testers.

Background World Health Organization changed the recommendation for pre-exposure rabies prophylaxis from 3-dose to 2-dose regimen in 2018. Given limited data of 2-dose regimens in pediatric population, this study aimed to compare the immunogenicity between 2-dose and 3-dose pre-exposure rabies immunization. Methods This study was conducted among healthy children aged 2–12 years. They were randomized to 2-dose vaccination (2D) on days 0 and 28 or 3-dose vaccination (3D) on days 0, 7, and 28. Purified Vero cell rabies vaccine (PVRV-Verorab™) was administered intramuscularly. Rabies virus neutralizing antibody (RVNA) titers were measured at 3 time points: 14-day after complete vaccination, 1-year pre-booster vaccination, and 7-day post-booster dose to mimic scenario of rabies exposure. RVNA titers ≥0.5 IU/ml were considered adequate antibody. T cell specific response to rabies vaccine antigen was measured using the interferon-gamma enzyme linked immunospot assay. Results From September to October 2017, 107 participants (51% males), 78 in 2D group and 29 in 3D group were enrolled. Median age was 5.8 years (IQR 4.4–7.3). All participants had RVNA titers ≥0.5 IU/ml after primary vaccination [GMT 2D: 18.6 (95%CI 15.9–21.8) and 3D: 16.3 (95%CI 13.2–20.1 IU/ml), p = 0.35]. At 1-year prior to receiving the booster, only 80% of the children in 2D group maintained RVNA titers ≥0.5 IU/ml compared to 100% of the children in 3D group (p = 0.01). However, all participants in both groups had RVNA ≥0.5 IU/ml at 7-day post booster vaccination [GMT 2D: 20.9 (95%CI 17.4–25.3) and 3D: 22.2 (95%CI 15.8–31.4) IU/ml (P = 0.75)]. The median number of IFN-γ secreting cells at 7-day post-booster dose was 98 and 128 SFCs per 106 PBMCs in the 2D and 3D groups, respectively (P = 0.30). Conclusions Two-dose primary rabies immunization provided adequate antibody at post primary vaccination and post booster. The results support 2-dose regimen of pre-exposure rabies immunization in the pediatric population.

This study aimed to determine the proportion of varicella non-immune pediatric healthcare workers (HCWs) of the Pediatrics Department of King Chulalongkorn Memorial Hospital and to determine cost-effective strategies for identifying non-immune personnel. A cross-sectional study using a self-administered questionnaire to determine HCWs' histories of chickenpox or 2-dose varicella vaccination was conducted. From a total of 699 HCWs, 653 HCWs (93%), including 145 physicians (22%), 297 nurses (46%), and 211 administrative staff (32%), responded to questionnaires. There were 475 HCWs (73%) who had a history of chickenpox, 58 (9%) who had completed the 2-dose varicella vaccine schedule, and 120 (18%) whose varicella-zoster virus (VZV) immunity status was uncertain. In total, 107 HCWs (89%) were tested for VZV IgG, 90 of whom had immunity, and 17 were determined to be non-immune. After combining history and VZV IgG test results, the prevalence of non-immune HCWs was 2.6% (95%CI 1.4-3.8), with those ≤40 years of age at higher risk of non-immunity. Implementing a strategy that involves testing of only those with an unknown VZV status and vaccination for only those determined to be non-immune costs 1,801 United States dollar (USD), less than the total cost (4,601 USD) for vaccinating all HCWs with uncertain status.

Background Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically suppressed HIV-1-infected adolescents after switching from EFV. Methods Adolescents aged 12–18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily). Intensive 24-h blood samplings at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 h were performed 4 weeks after switching. PK parameters were calculated using a non-compartmental method and compared with published data from the PAINT and pooled ECHO/THRIVE substudies. HIV RNA level was measured at weeks 12 and 24. Biochemical profiles were measured at baseline and week 24. Results From January to June 2016, 20 adolescents (12 male) were enrolled. Median (IQR) age was 16 (15–17) years and weight was 49 (42–59) kg. Mean (sd) AUC24 h, C24 h and Cmax of RPV were 2,041 (745) ng•h/ml, 69 (29) ng/ml and 143 (65) ng/ml, respectively. Median (IQR) Tmax was 5 (2–9) h. Four adolescents had C24 h Conclusions Virologically suppressed HIV-infected adolescents had adequate RPV exposure and remained virologically suppressed after switching from EFV. RPV can be used as long-term maintenance ART in HIV-infected adolescents.

Background Japanese Encephalitis chimeric virus vaccine (JE-CV) and SA14-14-2 vaccine are live-attenuated JE vaccines produced from the same virus strain. Data on interchangeability is limited. Objectives To evaluate the immunogenicity and safety of JE-CV booster after primary vaccination with SA14-14-2 vaccine. Methods This study was an open-label clinical trial in Thai children who had received a primary SA14-14-2 vaccination at 12–24 months before enrollment (ClinicalTrials.gov NCT02602652). JE-CV was administered. A 50% plaque reduction neutralization test (PRNT50) against three virus strains; JE-CV, SA-14-14-2 and wild-type JE virus was measured before and 28-days post vaccination. The laboratory was performed at PRNT50 titers ⩾10 (1/dil) were considered seroprotective against JE. Geometric mean titer (GMT) of PRNT50 was calculated. Adverse events were observed for 28 days. Results From March 2014 to June 2015, 50 children (64% male) were enrolled. Mean age and duration after primary vaccination was 26.9 (SD 4.6) and 12.8 (SD 2.7) months, respectively. The proportion of participants who had PRNT50pre and post-booster vaccination were 92% and 96% against JE-CV virus, 56% and 98% against SA-14-14-2 strain and 70% and 98% against wild-type JE virus, respectively. Solicited injection site reactions including erythema, pain and swelling occurred in 18%, 10% and 4% of subjects, respectively. Four children (8%) had fever (⩾37.7 Celsius). Eight children (16%) had adverse events, which were not related to the vaccine. Conclusions AJE-CV booster dose is highly immunogenic and safe among children who previously received SA14-14-2 vaccine.

Invasive aspergillosis (IA) is a severe infection in immunocompromised patients. Recently, serum galactomannan has been widely used for diagnosis and voriconazole as an antifungal agent. The objective of this study is to describe clinical features and survival outcomes of IA.A retrospective chart review of IA in patients younger than 18 years old at King Chulalongkorn Memorial Hospital, Thailand, was conducted. Clinical definitions were based on criteria oft he European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) 2008.Between January 2006 and December 2012, 40 cases of invasive aspergillosis were identified, classified as proven (8 patients, 20%), probable (28, 70%), and possible IA (4, 10%). Median age of patients was 10 years (range, 42 days-17 years). The most common underlying disease was hematologic malignancy (60%). The major risk factor was neutropenia (65%) with median duration of 21 days (range, 4-58 days). The most common site of infection was in the lungs (80%). The most common computed tomography chest finding was nodules (71%). An air crescent sign was seen only in 11% and a halo sign was found only in 7% of patients. Serum galactomannan was positive in 78% of patients with median value of 1.34 (range 0.5-5.6). Only seven patients (17%) had microbiological confirmation, of which were Aspergillus flavus (4 cases) and Aspergillus fumigates (3 cases). Antifungal therapy included voriconazole (23 patients, 58%), amphotericin B (12, 30%), liposomal amphotericin B (3, 8%), caspofungin (1, 2%) and itraconazole (1, 2%). Two deaths related to angioinvasive complications of aspergillosis (pulmonary hemorrhage and rupture mycotic aneurysm) were reported The 3-month and 12- month survival rates after diagnosed IA were 73.7% and 56.7%, respectively. The major cause of death was new episode of sepsis found in 11 cases (52%).The 1-year survival rate was poor; however, cause of death is related to complications of the immunocompromised state not from IA.