Search

Background: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants., Methodology/principal Findings: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers., Conclusions/significance: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Myocarditis and pericarditis cases following Coronavirus 2019 (COVID-19) vaccination were reported worldwide. In Thailand, COVID-19 vaccines were approved for emergency use. Adverse event following immunization (AEFI) surveillance has been strengthened to ensure the safety of the vaccines. This study aimed to describe the characteristics of myocarditis and pericarditis, and identify the factors associated with myocarditis and pericarditis following COVID-19 vaccination in Thailand., Method: We carried out a descriptive study of reports of myocarditis and pericarditis to Thailand's National AEFI Program (AEFI-DDC) between 1 March and 31 December 2021. An unpaired case-control study was conducted to determine the factors associated with myocarditis and pericarditis after the CoronaVac, ChAdOx1-nCoV, BBIBP-CorV, BNT162b2, and mRNA-1273 vaccines. The cases consisted of COVID-19 vaccine recipients who met the definition of confirmed, probable, or suspected cases of myocarditis or pericarditis within 30 days of vaccination. The controls were people who underwent COVID-19 vaccination between 1 March and 31 December 2021, with no adverse reactions documented after vaccination., Results: Among the 31,125 events recorded in the AEFI-DDC after 104.63 million vaccinations, 204 cases of myocarditis and pericarditis were identified. The majority of them were male (69%). The median age was 15 years (interquartile range (IQR): 13-17). The incidence was highest following the BNT162b2 vaccination (0.97 cases per 100,000 doses administered). Ten deaths were reported in this study; no deaths were reported among children who received the mRNA vaccine. Compared with the age-specific incidence of myocarditis and pericarditis in Thailand before the introduction of the COVID-19 vaccination, the incidence of myocarditis and pericarditis after the BNT162b2 vaccine was greater in the 12-17 and 18-20 age groups in both males and females. It was higher after the second dose in 12- to 17-year-olds (2.68 cases per 100,000 doses administered) and highest after the second dose in male 12- to 17-year-olds (4.43 cases per 100,000 doses administered). Young age and a mRNA-based vaccination were associated with myocarditis and pericarditis following administration of the COVID-19 vaccine after multivariate analysis., Conclusions: Myocarditis and pericarditis following vaccination against COVID-19 were uncommon and mild, and were most likely to affect male adolescents. The COVID-19 vaccine offers the recipients enormous benefits. The balance between the risks and advantages of the vaccine and consistent monitoring of AEFI are essential for management of the disease and identification of AEFI.

Background: Immunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand., Methods: We conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site., Results: Overall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores ≤2, indicating slight or no disability)., Conclusions: Immunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs., Competing Interests: The authors have declared that no competing interests exist.

Information is limited regarding differential serological responses after acute Zika virus (ZIKV) infections and prevalence of cross-reactivity with anti-dengue virus (DENV) assays comparing children and adults. Early convalescent sera from a cohort of suspected mild DENV cases between December 2016 and September 2018 at Bamrasnaradura Infectious Diseases Institute in Thailand were tested for nonstructural protein 1 (NS1)-based anti-ZIKV IgM and IgG ELISAs (Euroimmun), and in-house anti-DENV IgM- and IgG-capture ELISAs. ZIKV cases were identified by positive real-time reverse transcriptase-polymerase chain reaction on urine. Sera from 26 (10 children and 16 adults) ZIKV and 227 (153 children and 74 adults) non-ZIKA cases collected at the median duration of 18 days (interquartile range [IQR] 18,19) post-onset of symptoms were tested. Comparing pediatric ZIKV to adult ZIKV cases, the mean anti-ZIKV IgM ratio was higher (2.12 versus 1.27 units, respectively; P = 0.07), whereas mean anti-ZIKV IgG ratio was lower (3.13 versus 4.24 units, respectively; P = 0.03). Sensitivity of anti-ZIKV IgM and specificity of anti-ZIKV IgG in pediatric ZIKV were higher than in adult ZIKV cases (80.0% versus 43.7% and 79.1% versus 43.2%, respectively). No cross-reactivity with anti-DENV IgM- and IgG-capture ELISA were reported in pediatric ZIKV cases in our study, whereas 25% and 12.5% were found in adult ZIKV cases, respectively. Age-related ZIKV serological differences have been observed. Positive NS1-based anti-ZIKV IgM and IgG ELISA at the early convalescent phase could be useful for ZIKV diagnosis in children, even in a dengue endemic setting.

Acute Zika virus (ZIKV) infection may mimic dengue virus (DENV) infection. We aimed to study the clinical difference of ZIKV disease among suspected non-severe DENV patients comparing children and adults. Patients with acute illness suspected of DENV disease plus no evidence of plasma leakage at the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, were enrolled from December 2016 to September 2018. Clinical data including DENV rapid diagnostic test (RDT) results were collected. Zika virus diagnosis was confirmed by real-time reverse transcription PCR on urine. Of 291 (180 pediatric and 111 adult) cases enrolled, 27 (10 pediatric and 17 adult) confirmed ZIKV cases were found. Rash was more frequent among pediatric ZIKV than pediatric non-ZIKV cases (100% versus 60%, P = 0.01). Rash, arthralgia, and conjunctivitis were more frequent among adult ZIKV than adult non-ZIKV cases (100% versus 29.8%, 64.7% versus 26.6%, 52.9% versus 9.7%, all P < 0.01, respectively). The median (interquartile range [IQR]) duration of rash was 4.5 (3.0, 7.25) days and 6.0 (4.5, 7.0) days in pediatric and adults ZIKV cases, respectively. Pediatric ZIKV cases had more fever (100% versus 58.5%, P = 0.03) but less arthralgia (20% versus 64.7%, P = 0.04) and less conjunctivitis (10% versus 52.9%, P = 0.04) than adult ZIKV cases. No ZIKV cases with DENV RDTs performed around day 3 of illness were positive for dengue nonstructural protein 1 (NS1) antigen. In dengue-endemic settings, rash and fever in children, and rash, arthralgia, and conjunctivitis in adults, particularly if rash persists for ≥ 3 days, plus negative dengue NS1 Ag during early febrile phase should prompt ZIKV diagnostic testing.

Objective: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV)., Design: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV., Methods: Two hundred and eighty-five children (ages 2-14 years at baseline; Mage = 6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups [above (n = 145) and below average (n = 140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e. complete blood count [CBC])., Results: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87 and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions between mental health problems and both CD4 cell count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression., Conclusion: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also suggest that interactions between HIV disease and mental health problems are early antecedents to neurocognitive difficulties in later childhood among youth with pHIV.

Background: Children with perinatal HIV (pHIV) may display distinct long-term cognitive phenotypes. We used group-based trajectory modeling to identify clusters of children with pHIV after similar developmental trajectories and predictors of belonging to select cognitive trajectory groups., Methods: Participants included children, 4-17 years of age, with pHIV in Thailand and Cambodia. Cognitive measures included translated versions of Intelligence Quotient tests, Color Trails Tests and Beery-Buktenica Developmental Test of Visual-Motor Integration conducted semiannually over 3-6 years. The best fit of trajectory groups was determined using maximum likelihood estimation. Multivariate logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group., Results: Group-based trajectory analyses revealed a 3-cluster classification for each cognitive test, labeled as high, medium and low scoring groups. Most trajectory group scores remained stable across age. Verbal IQ declined in all 3 trajectory groups and the high scoring group for Children's Color Trails Test 1 and 2 showed an increase in scores across age. Children in the lowest scoring trajectory group were more likely to present at an older age and report lower household income., Conclusions: Group-based trajectory modeling succinctly classifies cohort heterogeneity in cognitive outcomes in pHIV. Most trajectories remained stable across age suggesting that cognitive potential is likely determined at an early age with the exception of a small subgroup of children who displayed developmental gains in select cognitive domains and may represent those with better cognitive reserve. Poverty and longer duration of untreated HIV may predispose children with pHIV to suboptimal cognitive development.

Objectives: Psychosocial challenges associated with perinatally acquired HIV (PHIV) infection are well known, yet many children infected with HIV since birth demonstrate positive outcomes, referred to as resilience. The purpose of this study was to evaluate emotional-behavioral development and identify salient predictors of resilience among long-term survivors of PHIV., Design: Prospective investigation of children with PHIV compared with demographically similar perinatally HIV-exposed but uninfected (PHEU) and HIV-unexposed, uninfected (HUU) children, all from Thailand and Cambodia., Methods: The Child Behavior Checklist (CBCL; parent version) was administered at baseline and annual follow-up visits (median follow-up of 3 years) to children age 6-14. Resilience was defined as consistent CBCL scores on the Internalizing, Externalizing or Total Problem T scales within normative ranges (T-scores <60) at every time point. Generalized estimating equations examined CBCL scores over time and logistic models examined demographic, socioeconomic, and cultural predictors of resilience., Results: Participants included 448 children (236 PHIV, 98 PHEU, 114 HUU), with median (interquartile range) age at first evaluation of 7 (6-9) years. Children with PHIV exhibited similar rates of resilience as PHEU and HUU on the Externalizing and Total Problems scales. Resilience on the Internalizing scale was more likely in PHEU (71%) compared with PHIV (59%) or HUU (56%), P = 0.049. Factors associated with resilience in adjusted models included: HIV-exposed but uninfected status, higher household income, Cambodian nationality, female sex, and caregiver type., Conclusion: Despite biopsychosocial risks, resilience is observed among PHIV and PHEU children. Further study is needed to understand mechanisms underlying associated factors and intervention priorities.

Background: Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited., Methodology: This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir or raltegravir., Results: Fifty-four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n = 44) and toxicity to second-line regimens (n = 10). At switching to third-line ARV, the median age (interquartile range) was 14.3 (12.4-15.4) years. Genotypes at time of second-line failure (n = 44) were M184V (77%), ≥4 thymidine analogue mutations (25%), non-nucleoside reverse transcriptase inhibitor-resistant associated mutation (RAM) (80%), ETR-RAM score ≥4 (14%), any lopinavir-RAM (59%) and ≥1 major DRV-RAM (41%). The third-line regimens had a median of 4 (min-max, 4-6) drugs and included ETR/DRV/r (43%), DRV/r (33%), ETR (17%), tipranavir/ritonavir (2%) or raltegravir/DRV/r/ (4%). The median CD4 (interquartile range) increased from 16% (12-21) at third-line switch to 21% (18-25) and 410 (172-682) to 607 (428-742) cells/mm at 48 weeks (P < 0.001). HIV RNA declined from 3.9 (2.9-4.9) to 1.6 (1.6-3.0) log10 copies/mL (P < 0.001) and 33/50 (66%) had levels <50 copies/mL at 48 weeks. Seventeen (31%) had HIV-RNA ≥1000 copies/mL; about half due to poor adherence; genotyping in 13 of these adolescents revealed ETR-RAM score ≥4 in 2 (15%) and ≥1 major DRV-RAM in 7 (54%)., Conclusions: Third-line ARV therapy was well tolerated and resulted in virologic suppression in 70% of adolescents at 1 year. Poor adherence and limited ARV options are major problems in the long-term management of adolescents with HIV.

Background: Clinical practice guidelines for influenza have been implemented to maximise the appropriate use of empirical oseltamivir; however, good predictive values are required., Methods: Between October 2011 and September 2013, children aged < 15 years who presented at the Bamrasnaradura Infectious Diseases Institute with an influenza-like illness plus either (i) pneumonia or (ii) being in a higher risk group for influenza complications were prospectively enrolled. Respiratory specimens were taken for real-time polymerase chain reaction testing (RT-PCR). Clinical characteristics, laboratory data and oseltamivir therapy were recorded., Results: 85 cases were enrolled. Of these, the proportions of those with pneumonia, who were aged < 2 years and who had underlying diseases were 74.1%, 56.5% and 38.8%, respectively. RT-PCR detected respiratory syncytial virusamong (35.3%), influenza (22.3by%), adenovirus (14.1%), human metapneumovirus (5.9%), para-influenza (3.5%) and no viruses (25.9 %). Pneumonia (OR 0.16, 95% CI 0.05-0.50) and having two clinical criteria (OR 0.24, 95% CI 0.08-0.76) were significantly negative predictors of influenza. Having cluster transmissions (OR 5.18, 95% CI 1.38-19.37) and a monocyte proportion >7% (OR 3.58, 95% CI 1.15-11.17) were significantly positive predictors of influenza. The mean (SD) percentage of influenza-like illness during the study period was 7.04 (2.02)., Conclusions: Clinical criteria guidelines yielded a low predictive value (22.3%) for influenza in children. Seasonality, cluster transmission, white blood cell and differential counts may be helpful in diagnosing influenza. Nonetheless, empirical oseltamivir should not be delayed for those in need.

Background: Monocytes play a central role in HIV neuropathogenesis, but there are limited data on monocyte subsets and markers of monocyte activation in perinatally HIV-infected children., Objective: To determine the relationship between monocyte subsets, the sCD163 monocyte activation marker, and neuropsychological performance among perinatally HIV-infected children initiating antiretroviral therapy (ART)., Methods: ART-naïve children from the PREDICT study were categorised into two groups: those on ART for ≥24 weeks (ART group, n =201) and those untreated (no ART group, n =79). This analysis used data from the baseline and week 144 including sCD163 and frequencies of activated monocytes (CD14+/CD16+/HLA-DR+), perivascular monocytes (CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+), and neuropsychological testing scores: Verbal and Performance Intelligence Quotient (VIQ and PIQ), Beery Visuomotor Integration (VMI) and Children's Color Trails 2 (CT2)., Results: Baseline demographic and HIV disease parameters were similar between groups. The median age was 6 years, CD4 was 20% (620 cells/mm 3 ), and HIV RNA was 4.8 log 10 . By week 144, the ART vs the no ART group had significantly higher CD4 (938 vs 552 cells/mm 3 ) and lower HIV RNA (1.6 vs 4.38 log 10 copies/mL, P <0.05). sCD163 declined in the ART vs no ART group (median changes -2533 vs -159 ng/mL, P <0.0001). Frequencies of all monocyte subsets declined in the treated but not the untreated group ( P <0.05). Higher CD14+/CD16+/HLA-DR+ percentage was associated with higher VIQ, Beery VMI and CT2 scores. Higher percentages of CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+ were associated with higher CT2 and VIQ, respectively., Conclusion: ART significantly reduced sCD163 levels and frequencies of activated and perivascular monocytes. Higher frequencies of these cells correlated with better neuropsychological performance suggesting a protective role of monocyte-macrophage immune activation in perinatal HIV infection in terms of neuropsychological function.

There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1-12 years (N=207) were randomized to immediate-ART or deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000 copies/mL after ≥6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log(10)copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF (p=0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56; 95%CI 1.78-11.69), reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42-20.73), and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64; 95%CI 1.96-38.04). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF.

Background: This study assesses the relationships between lymphocyte and monocyte subsets and intelligence quotient (IQ) scores in antiretroviral therapy (ART)-naive, HIV-infected Thai children without advanced HIV disease., Findings: Sixty-seven ART-naive Thai children with CD4 between 15-24% underwent cognitive testing by Weschler intelligence scale and had 13 cell subsets performed by flow cytometry including naive, memory and activated subsets of CD4+ and CD8+ T cells, activated and perivascular monocytes and B cells. Regression modelling with log10 cell count and cell percentage transformation was performed.Median age (IQR) was 9 (7-10) years, 33% were male, CDC stages N:A:B were 1:67:31%, median CD4% and count (IQR) were 21 (18-24)%, 597 (424-801) cells/mm3 and HIV RNA (IQR) was 4.6 (4.1-4.9) log10 copies/ml. Most (82%) lived at home, 45% had a biological parent as their primary caregiver, and 26 (49%) had low family income. The mean (SD) scores were 75 (13) for full scale IQ (FIQ), 73 (12) for verbal IQ (VIQ) and 80 (14) for performance IQ (PIQ). Adjusted multivariate regression analysis showed significant negative associations between B cell counts and FIQ, VIQ and PIQ (p < 0.01 for all); similar associations were found for B cell percentages (p < 0.05 for all)., Conclusions: High B cell counts and percentages were strongly associated with poorer FIQ, VIQ and PIQ scores. Prospective, long-term assessment of cell subsets and determination of relevant B cell subpopulations could help further elucidate associations between lymphocyte subsets and neurocognitive development.

Human immunodeficiency virus (HIV)-negative children born to HIV-infected mothers may exhibit differences in neurodevelopment (ND) compared to age- and gender-matched controls whose lives have not been affected by HIV. This could occur due to exposure to HIV and antiretroviral agents in utero and perinatally, or differences in the environment in which they grow up. This study assessed neurodevelopmental outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children enrolled as controls in a multicenter ND study from Thailand and Cambodia. One hundred sixty HEU and 167 HUU children completed a neurodevelopmental assessment using the Beery Visual Motor Integration (VMI) test, Color Trails, Perdue Pegboard, and Child Behavior Checklist (CBCL). Thai children (n = 202) also completed the Wechsler Intelligence Scale (IQ) and Stanford-Binet II memory tests. In analyses adjusted for caregiver education, parent as caregiver, household income, age, and ethnicity, statistically significant lower scores were seen on verbal IQ (VIQ), full-scale IQ (FSIQ), and Binet Bead Memory among HEU compared to HUU. The mean (95% CI) differences were -6.13 (-10.3 to -1.96), p = 0.004; -4.57 (-8.80 to -0.35), p = 0.03; and -3.72 (-6.57 to -0.88), p = 0.01 for VIQ, FSIQ, and Binet Bead Memory, respectively. We observed no significant differences in performance IQ, other Binet memory domains, Color Trail, Perdue Pegboard, Beery VMI, or CBCL test scores. We conclude that HEU children evidence reductions in some neurodevelopmental outcomes compared to HUU; however, these differences are small and it remains unclear to what extent they have immediate and long-term clinical significance.

Background: We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes., Methods: Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319)., Results: At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist., Conclusions: In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.

Human leukocyte antigen (HLA)-B*5701 allele is associated with abacavir hypersensitivity. Limited data among Asians showed lower rates of HLA-B*5701 compared with Caucasians. In 296 children with HIV in Thailand and Cambodia, the prevalence of HLA-B*5701 was 4.0% (95% confidence interval: 1.6-8.0%) among Thai and 3.4% (95% confidence interval: 0.9-8.5%) among Cambodian children. HLA-B*5701 carriage is not uncommon among Thai and Cambodian children; it is close to the prevalence found in European and higher than the prevalence found in East Asian and African studies.

Background: The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival., Methods: In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 1-12 years who were infected with HIV and had CD4 percentages of 15-24%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091., Findings: Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 6·4 years (IQR 3·9-8·4). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (16-22%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 98·7% (95% CI 94·7-99·7; 148 of 150 patients) compared with 97·9% (93·7-99·3; 146 of 149 patients) in the early treatment group (p=0·6)., Interpretation: AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Anemia is common in HIV-infected children and iron deficiency is thought to be a common cause. This study investigates the prevalence of anemia, thalassemia, and underlying iron status in Thai and Cambodian children without advanced HIV disease to determine the necessity of routine iron supplementation. Antiretroviral (ARV)-naive HIV-infected Asian children aged 1-12 years, with CD4 15-24%, CDC A or B, and hemoglobin (Hb) ≥7.5 g/dl were eligible for the study. Iron studies, serum ferritin, Hb typing, and C-reactive protein were assessed. Anemia was defined as Hb <11.0 g/dl in children <5 years of age or <11.5 g/dl in children 5-12 years. We enrolled 299 children; 57.9% were female and the mean (SD) age was 6.3 (2.9) years. The mean (SD) CD4% and HIV-RNA were 20% (4.6) and 4.6 (0.6) log(10) copies/ml, respectively. The mean (SD) Hb and serum ferritin were 11.2 (1.1) g/dl and 78.3 (76.4) μg/liter, respectively. The overall iron deficiency anemia (IDA) prevalence was 2.7%. One hundred and forty-eight (50%) children had anemia, mostly of a mild degree. Of these, 69 (46.6%) had the thalassemia trait, 62 (41.8%) had anemia of chronic disease (ACD), 9 (6.1%) had thalassemia diseases, 3 (2.0%) had iron deficiency anemia, and 5 (3.4%) had IDA and the thalassemia trait. The thalassemia trait was not associated with increased serum ferritin levels. Mild anemia is common in ARV-naïve Thai and Cambodian children without advanced HIV. However, IDA prevalence is low; with the majority of cases caused by ACD. A routine prescription of iron supplement in anemic HIV-infected children without laboratory confirmation of IDA should be discouraged, especially in regions with a high prevalence of thalassemia and low prevalence of IDA.

There are limited data on quality of life (QOL) 1 in untreated HIV-infected children who do not have severe HIV symptoms. Moreover, such data do not exist for Asian children. Poor QOL could be a factor in deciding if antiretroviral therapy (ART) should be initiated. Thai and Cambodian children (n=294), aged 1-11 years, naïve to ART, with mild to moderate HIV symptoms and CD4 15-24% were enrolled. Their caregivers completed the Pediatric AIDS Clinical Trials Group QOL questionnaire prior to ART commencement. Six QOL domains were assessed using transformed scores that ranged from 0 to 100. Higher QOL scores indicated better health. Mean age was 6.1 (SD 2.8) years, mean CD4 was 723 (SD 369) cells/mm(3), 57% was female, and%CDC N:A:B was 2:63:35%. One-third knew their HIV diagnosis. Mean (SD) scores were 69.9 (17.6) for health perception, 64.5 (16.2) for physical resilience, 84.2 (15.6) for physical functioning, 77.9 (16.3) for psychosocial well-being, 74.7 (28.7) for social and role functioning, 90.0 (12.1) for health care utilization, and 87.4 (11.3) for symptoms domains. Children with CD4 counts above the 2008 World Health Organization (WHO) ART-initiation criteria (n=53) had higher scores in health perception and health care utilization than those with lower CD4 values. Younger children had poorer QOL than older children despite having similar mean CD4%. In conclusion, untreated Asian children without severe HIV symptoms had relatively low QOL scores compared to published reports in Western countries. Therapy initiation criteria by the WHO identified children with lower QOL scores to start ART; however, children who did not fit ART-initiation criteria and those who were younger also displayed poor QOL. QOL assessment should be considered in untreated children to inform decisions about when to initiate ART.

Background: Dyslipidaemia is a common complication among HIV-infected children after antiretroviral therapy (ART); however, HIV itself can cause abnormal lipid metabolism. There is limited information of lipid profiles among Asian HIV-infected children naive to ART., Methods: A total of 274 HIV-infected ART-naive Thai and Cambodian children aged 1-12 years with CD4% between 15% and 24% were included. Patients were fasted for ≥4 h before blood was drawn. Abnormal lipid levels were defined as triglyceride (TG)>130 mg/dl, total cholesterol (TC)>200 mg/dl, low-density lipoprotein (LDL)>130 mg/dl and high-density lipoprotein (HDL)≤40 mg/dl., Results: The mean (±SD) was 76.6 (33.8) months for age and -1.3 (1.0) for weight Z-score. Mean (±SD) CD4% was 19.9 (4.8) % and HIV RNA was 4.6 (0.6) log(10) copies/ml. The median (±SD) fasting time was 13.0 (2.7) h. Mean (±SD) for lipids were 116 (62) mg/dl for TG, 139 (29) mg/dl for TC, 73 (29) mg/dl for LDL and 45 (19) mg/dl for HDL. Overall 63.9% had dyslipidaemia with hypertriglyceridaemia and hypo-HDL being the most common (28% and 45%, respectively), while 2% had hypercholesterolaemia or hyper-LDL. After adjusting for age, having HIV RNA>5 log(10) copies/ml was associated with hypo-HDL with ORs of 8.1 (95% CI 2.7-24.3)., Conclusions: Up to two-thirds of ART-naive, HIV-infected Asian children with mild-to-moderate immune suppression had dyslipidaemia. Low HDL was the most common and was associated with high HIV viraemia. The long-term consequence of low HDL deserves further investigation in children.

Background: There are limited data on the immune profiles of HIV-positive children compared with healthy controls, and no such data for Asian children., Objectives: To immunophenotype HIV-positive Asian children, including long-term nonprogressors (LTNPs), compared with age-matched healthy controls., Methods: We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15% to 24% CD4(+) T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n = 50), defined as children ≥8 years old with CD4(+) T-cell counts ≥350 cells/mm(3), were compared with data from age-matched non-LTNPs (n = 17) and controls (n = 53)., Results: Compared with controls, HIV-positive children had lower values (cell count per mm(3) and percent distribution) for T(H) cells and higher values for cytotoxic T cells, with reductions in populations of naive T(H) and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated T(H) and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of T(H) and cytotoxic T cells, naive and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated T(H) and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male., Conclusion: Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for T(H) cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated T(H), and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: As increasing numbers of children initiate antiretroviral treatment (ART), a systematic process is needed to measure and improve pediatric HIV care quality., Methods: Pediatric HIVQUAL-T, a model for performance measurement and quality improvement (QI), was adapted from the U.S. HIVQUAL model by incorporating Thai national guidelines as standards. In each of five pilot-site hospitals in Thailand in 2005-2007, clinical data abstracted from patient records were used to identify priority areas for QI. Improvement strategies were designed by clinic teams in different care system areas, and indicators were remeasured in 2006 and 2007., Results: At the five hospitals, 1119 HIV-infected children younger than 15 years of age received care in 2005, 1183 in 2006, and 1,341 in 2007--of whom 460, 435, and 418, respectively, were selected for chart abstraction. Of the eligible children, > or = 95% received clinical monitoring, annual CD4 count monitoring, ART, and adherence and growth assessments; 60%-90% received Pneumocystis jiroveci pneumonia (PCP) prophylaxis, tuberculosis (TB) screening, oral health assessments, and HIV disclosure. Indicators with a score < or = 40% in 2005 but with significant improvement (p < .05) in 2006-2007 following QI activities were Mycobacterium avium complex (MAC) prophylaxis, and cytomegalovirus (CMV) retinitis and immunization screenings., Conclusions: Despite the promulgation of national guidelines, performance rates of some pediatric HIV indicators needed improvement. The pediatric HIVQUAL-T model facilitates use of hospital data for pediatric HIV care improvement and indicates that the U.S. HIVQUAL model is adaptable to developing countries.

The pneumococcal conjugate vaccines (PCVs) have demonstrated good safety profile and efficacy against invasive pneumococcal diseases (IPD) caused by the serotypes included in the vaccines. The PCV also benefit to the unvaccinated children and adults from herd immunity. With the widespread use of the vaccine, emerging of non vaccine serotypes has been documented. The IPD burden in Thailand was found to be lower than that found in the western countries but the data in high risk population has been lacking. The PCV has been available in Thailand since 2006 as an optional vaccine, out of National Vaccine Program, with the uptake of less than 5% in children under 5 years of age. The serotypes distribution in Thailand has not changed significantly. In the year 2000-2005, compared with year 2006-2009, the most common serotypes in children < 5 years have been similar; comprising of 6B, 23F, 14, and 19F, however 19A has become more prevalence (6.2%) in the years 2006-2009. With the new breakpoint of penicillin susceptibility for non-meningeal strains, most penumococcal isolates in Thailand were susceptible to penicillin. To project the benefit for widespread use of PCV in Thailand the cost benefit analyses including the different types of PCV, the various dosing schedule, the benefit from herd immunity and the disadvantage of serotype replacement are needed.

We evaluated the validity of CD4 count against CD4% criteria of 2008 World Health Organization guideline for initiating antiretroviral therapy using the data of 446 human immunodeficiency virus-infected Asian children aged 1 to 12 years who were screened to the Pediatric Randomized of Early versus Deferred Initiation in Cambodia and Thailand study. The overall sensitivity and specificity were 34% and 98%, respectively. Using the current CD4 count criteria would globally result in 66% missed opportunity to initiate treatment in a timely fashion. Raising CD4 count thresholds should be considered to increase its sensitivity and reduce missed opportunity.

To determine the incidence and spectrum of malignancies in human immunodeficiency virus-infected children, we surveyed 48 hospitals in Thailand between 1996 and 2000. There were 23 children (14 boys and 9 girls; average age at diagnosis of malignancy, 4.2 years), and the incidence rate was 0.6 per 1000 person-years. The most common malignancy was lymphoma (87.0%). The prognosis was poor.

Background: On March 11, 2003, a World Health Organization (WHO) physician was admitted to Bamrasnaradura Institute, after alerting the world to the dangers of severe acute respiratory syndrome (SARS) in Vietnam and developing a fever himself. Specimens from the first day of his admission were among the first to demonstrate the novel coronavirus, by culture, reverse transcription-polymerase chain reaction (RT-PCR), and rising of specific antibody, but proper protective measures remained unknown. The authors instituted airborne, droplet and contact precautions from the time of admission, and reviewed the efficacy of these measures., Material and Method: A specific unit was set up to care for the physician, beginning by roping off an isolated room and using a window fan to create negative pressure, and later by constructing a glass-walled antechamber, designated changing and decontamination areas, and adding high-efficiency particulate air (HEPA) filters. The use of personal protective equipment (PPE) was consistently enforced by nurse managers for all the staff and visitors, including a minimum of N95 respirators, goggles or face shields, double gowns, double gloves, full head and shoe covering, and full Powered Air Purifying Respirator (PAPR) for intubation. To assess the adherence to PPE and the possibility of transmission to exposed staff a structured questionnaire was administered and serum samples tested for SARS coronavirus by enzyme-linked immunosorbent assay (ELISA). Exposure was defined as presence on the SARS ward or contact with laboratory specimens, and close contact was presence in the patient's room., Results: The WHO physician died from respiratory failure on day 19. 112 of 129 exposed staff completed questionnaires, and the 70 who entered the patient's room reported a mean of 42 minutes of exposure (range 6 minutes-23.5 hours). 100% reported consistent handwashing after exposure, 95% consistently used a fit-tested N95 or greater respirator, and 80% were fully compliant with strict institutional PPE protocol. No staff developed an illness consistent with SARS. Serum samples from 35 close contacts obtained after day 28 had a negative result for SARS coronavirus antibody., Conclusions: Hospitalization of one of the earliest SARS patients with documented coronavirus shedding provided multiple opportunities for spread to the hospital staff, but strict enforcement of conservative infection control recommendations throughout the hospitalization was associated with no transmission.

Blood cultures of children treated at King Chulalongkorn Memorial Hospital from 1986 to 2000 were retrospectively reviewed and 19 specimens were positive for Salmonella typhi. Of 14 patients whose medical records were available, the age range was between 2 years and 15 years with a male to female ratio of 1.8:1. Major presentations were prolonged fever with a mean duration of 7 days and gastrointestinal manifestations including abdominal pain (71%), hepatomegaly (64%), anorexia (57%), vomiting (57%), and diarrhea (50%). Most cases had normal hematocrit values with white blood cell counts of 5,000-9,000 cells/mm3 and the percentage of neutrophils was 60-89. Complications were abnormal urine sediments (3) including a case of typhoid nephritis, severe enteritis (2) and acute hemolysis (1). Most isolates were susceptible to cotrimoxazole, ampicillin and ceftriaxone by the disk diffusion susceptibility test. Defervescence was seen within 3-14 days after antibiotic therapy. There was no mortality.

We report a 14-year-old girl who presented with signs of appendicitis and had her appendix removed. She subsequently proved to have mesenteric adenitis owing to Salmonella typhi which responded to treatment with ceftriaxone.

We report a child with typhoid glomerulonephritis who presented with fever, gastrointestinal symptoms, edema, hypertension and abnormal urine findings including microscopic hematuria and proteinuria. Salmonella typhi resistant to ampicillin and cotrimoxazole was isolated from a blood culture. Renal biopsy was not performed. The child successfully treated with ceftriaxone.