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) 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 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 the prevalence of behavioral problems between groups. 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 child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.
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.
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 RNA > 50 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 weight < 2500 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.
Abstract The 24‐hour vancomycin area under the serum concentration‐time curve (AUC 24 ) divided by the minimum inhibitory concentration (MIC) (AUC 24 /MIC) is more closely related to patient outcomes than serum trough concentrations (C trough ). Two‐point simplified equations for calculating AUC based on serum peak concentrations (C peak ) and C trough , 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 AUC 24 using the reference method (ref) relative to EqA and EqB and the correlation between C trough and AUC 24 . 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 C peak and C trough were measured at 2 hours after infusion completion and within 30 minutes before the next dosing, respectively. AUC 24 was estimated using ref, EqA, and EqB. From Bland‐Altman analysis, the 2 AUC 24 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). C trough and AUC 24 using either ref or EqA were correlated more closely ( r 2 = 0.94) than with EqB ( r 2 = 0.86). Assuming a vancomycin MIC of 1 mg/L, an AUC 24 ≥400 mg⋅h/L was targeted. Regardless of the method used, AUC 24 ≥400 mg⋅h/L was never seen with C trough <8 mg/L but was always seen with C trough >10 mg/L. In conclusion, EqA based on the 2 measured serum concentrations was sufficiently accurate for AUC 24 estimation. C trough >10 mg/L correlated highly to AUC 24 ≥400 mg⋅h/L.
To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR).A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns.39 NNUs from 12 countries.Any neonate admitted to one of the participating NNUs.This was an observational cohort study.The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%.AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.
To describe the clinical characteristics and outcomes of pediatric COVID-19 in Thailand, where favipiravir is the mainstay of antiviral treatment.We conducted a hospital based observational cohort study of COVID-19 among children. The study included children (age <15 years) with confirmed positive reverse transcriptase-polymerase chain reaction for SARS-CoV-2 from nasopharyngeal swab.From April to July 2021, 416 cases with a median age of 7.1 (interquartile range 2.7-11.6) years were included in the study. The spectrum of disease included 82 (20%) asymptomatic, 232 (56%) mild and 102 (24%) with pneumonia. Abnormal chest x-ray findings included ground-glass opacities (46%), focal infiltrations (27%), perihilar opacities (19%), reticular infiltrations (15%) and other non-specific findings (4%). Only 12 children (3%) required oxygen support. Favipiravir was prescribed to 129 children (31%); 102 patients with pneumonia and 27 patients at risk for disease progression. Pneumonia was more common in age <3 years compared with those aged 3-<12 years (adjusted odds ratio (aOR) 0.30, 95% CI 0.17-0.52), 12-15 years (aOR 0.40, 95% CI 0.21-0.77) and in patients with comorbidities (aOR 2.36, 95% CI 1.09-5.12).One-fourth of pediatric COVID-19 patients had pneumonia, but few required oxygen support. Off-label use of Favipiravir in pediatric COVID-19 patients in a recent outbreak in Bangkok is reported.
BackgroundChildren 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.MethodsWe 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 <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921).FindingsBetween Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir.InterpretationTwice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB.FundingPenta Foundation, ViiV Healthcare, UK Medical Research Council.
BackgroundPopulation pharmacokinetic analysis in critically ill infants remains a challenge for lack of information.ObjectivesTo determine the population pharmacokinetic parameters of meropenem and evaluate the covariates affecting population pharmacokinetic parameters.MethodsA 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.ResultsA 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.ConclusionsThis population pharmacokinetic model could be used for suggesting individualized meropenem dosage regimens in critically ill infants.
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.
Despite the BNT162b2 vaccination coverage, rapid transmission of Omicron SARS-CoV-2 has occurred, which is suspected to be due to the immune escape of the variant or waning vaccine efficacy of multiple BNT162b2 vaccination doses. Our study aims to compare immunogenicity against Omicron prior to and post a booster dose of BNT162b2 in healthy adolescents, and to evaluate their attitudes toward booster dose vaccination. A cross sectional study was conducted among healthy adolescents aged 12-17 who received two doses of BNT162b2 more than 5 months ago. Participants and their guardians performed self-reported questionnaires regarding reasons for receiving the booster. A 30 ug booster dose of BNT162b2 was offered. Immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against the Omicron variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) taken pre-booster and 14-days post-booster. From March to April 2022, 120 healthy Thai adolescents with a median age of 15 years (IQR 14-16) were enrolled. sVNT against Omicron pre- and post-booster had 11.9 (95%CI 0-23.9) and 94.3 (90.6-97.4) % inhibition. Geometric means (GMs) of anti-S-RBD IgG increased from 837 (728, 953) to 3041 (2893, 3229) BAU/mL. Major reasons to receive the booster vaccination were perceived as vaccine efficacy, reduced risk of spreading infection to family, and safe resumption of social activities. A booster dose of BNT162b2 elicits high immunogenicity against the Omicron variant. Motivation for receiving booster doses is to reduce risk of infection.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)