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Paragonimiasis is a food-born zoonotic parasitosis caused by Paragonimus spp. Six cases of reemerging paragonimiasis within the Karan hill-tribe near the Thai–Myanmar border were evaluated to review clinical manifestations, predisposing factors, and treatment regimens. All patients tested positive for paragonimiasis eggs and presented with an array of symptoms, including chronic cough, hemoptysis, peripheral eosinophilia, and thoracic radiograph abnormalities. All fully recovered after a 2- to 5-day course of 75 to 80 mg/kg/day praziquantel. We conclude that paragonimiasis should be considered during differential diagnoses to promote early treatment and to prevent misdiagnosis of reemerging or sporadic cases. This applies particularly to endemic regions and high-risk groups known to habitually consume raw or undercooked intermediate or paratenic hosts.

Cases of multisystem inflammatory syndrome in children (MIS-C-like disease), have rarely been reported in neonates. A 33-week gestational age twin B female neonate presented with respiratory distress, tachycardia, and abdominal distention at 15 days of age. Echocardiogram found reduced left ventricular ejection fraction to 33%. Cardiac enzyme levels were all elevated: creatine kinase-MB 6.1 ng/mL (normal 0–4.5 ng/mL), troponin-T 170 ng/L (normal < 14 ng/L) and NT-proBNP > 35,000 pg/mL (normal 250.0 to 3987.0 pg/mL). Multiplex PCR of nasopharyngeal swab material was negative for respiratory pathogens. Serological tests revealed negative anti-spike SARS-CoV-2 IgM but positive anti-nucleocapsid SARS-CoV-2 IgG in both the mother and the patient. The mother provided a history of COVID-19 during pregnancy at 19 weeks gestation. The patient was diagnosed with neonatal multisystem inflammatory syndrome (MIS-N) and successfully treated with intravenous immunoglobulin (two doses of 1 gm/kg/dose) and methylprednisolone (2 mg/kg/day for 5 days then tapered off). She later developed coronary vessel (LMCA and RCA) dilation. The non-identical twin A did not develop MIS-N, suggesting a role of host genetic background. Newborn infants born to SARS-CoV-2-infected mothers at any time during pregnancy should be closely monitored for MIS-N. The optimal treatment approaches to this syndrome and the prognosis require further study.

Implementing a single-dose empirical antibiotic (SDEA) strategy at the emergency department (ED) in children with suspected sepsis may improve outcomes. We aim to evaluate the outcomes of the SDEA strategy for children with suspected sepsis at the ED in a tertiary care center in Bangkok.Children who met the predefined checklist screening criteria for suspected sepsis were administered single-dose intravenous cefotaxime 100 mg/kg, or meropenem 40 mg/kg if they were immunocompromised or recently hospitalized. The medical records of children diagnosed with sepsis and septic shock caused by bacterial or organ-associated bacterial infections before and after implementation of the SDEA strategy were reviewed.A total of 126 children with sepsis before and 127 after implementation of the SDEA strategy were included in the analysis. The time from hospital arrival to antibiotic initiation was significantly reduced after implementation of the SDEA strategy: median, 241 (110-363) minutes before versus 89 (62-132) minutes after ( P0.001), with an increased number of patients starting antibiotics within 3 hours of hospital arrival: 42.1% vs 85.0% ( P0.001). Comparing before and after SDEA implementation, children receiving SDEA had a shorter median duration of antibiotic therapy: 7 (5-13.3) versus 5 (3-7) days ( P = 0.001), shorter length of hospital stay: 10 (6-16.3) versus 7 (4-11) days ( P = 0.001), and fewer intensive care unit admissions: 30 (23.8%) versus 17 (13.4%; P = 0.036); however, mortality was not different: 3 (2.4%) in both groups. In multivariate analysis, SDEA strategy was the independent factor associated with reduced intensive care unit admission or death. Adherence to SDEA was 91.4%. Single-dose empirical antibiotic was retrospectively considered not necessary for 22 children (11.9%), mostly diagnosed with viral infections afterward.Single-dose empirical antibiotic at the ED is an effective strategy to reduce the time from hospital arrival to antibiotic initiation and can help improve outcomes of sepsis in children.

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.

To maximize the potential of genomics in medicine, it is essential to establish databases of genomic variants for ethno-geographic groups that can be used for filtering and prioritizing candidate pathogenic variants. Populations with non-European ancestry are poorly represented among current genomic variant databases. Here, we report the first high-density survey of genomic variants for the Thai population, the Thai Reference Exome (T-REx) variant database. T-REx comprises exome sequencing data of 1092 unrelated Thai individuals. The targeted exome regions common among four capture platforms cover 30.04 Mbp on autosomes and chromosome X. 345 681 short variants (18.27% of which are novel) and 34 907 copy number variations were found. Principal component analysis on 38 469 single nucleotide variants present worldwide showed that the Thai population is most genetically similar to East and Southeast Asian populations. Moreover, unsupervised clustering revealed six Thai subpopulations consistent with the evidence of gene flow from neighboring populations. The prevalence of common pathogenic variants in T-REx was investigated in detail, which revealed subpopulation-specific patterns, in particular variants associated with erythrocyte disorders such as the HbE variant in HBB and the Viangchan variant in G6PD. T-REx serves as a pivotal addition to the current databases for genomic medicine.

OBJECTIVE: To implement a standardized cause of death reporting and review process to systematically disaggregate causes of HIV-related deaths in a cohort of Asian children and adolescents. DESIGN: Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study. METHODS: Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses. RESULTS: Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9–13) years; median CD4(+) cell count was 73 (16–325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4(þ) cell count and better weight-for-age z-score were protective against death. CONCLUSION: Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.

Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions.Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.

BACKGROUND: Sick neonates in TB endemic areas are at risk of nosocomial TB exposure.OBJECTIVE: To evaluate outcomes following contact investigation and isoniazid preventive treatment (IPT) in sick neonates exposed to healthcare personnel (HCP) with pulmonary TB.METHODS: Investigations were conducted following two exposure events in different neonatal intensive care units (NICUs). Details of the infants´ physical examination, chest X-ray and exposure history were recorded. Infants without TB disease were prescribed a 9-month course of IPT and followed for ≥1 year.RESULTS: Ninety infants were exposed in NICU A and 231 in NICU B (n = 321). The overall proportions of completing the 9-month IPT was 164/265 (61.8%): 40/79 (50.6%) in NICU A and 124/186 (66.7%) in NICU B (P = 0.01). The overall incidence of TB was 10.2% (24/236): 7.5% in NICU A and 11.2% in NICU B (P = 0.39). Contact investigation beginning >111 days after exposure was a risk factor for TB infection (P = 0.02).CONCLUSION: The risk of TB following nosocomial exposure in sick neonates was high, particularly when contact investigation was delayed. Our findings underscore the importance of hospital policies that promote early detection of TB in HCP, reduce transmission in NICUs, and facilitate rapid case investigation.

Introduction Early initiation of combination antiretroviral therapy (ART) with long‐term viral suppression may lead to seronegativity in grown‐up children with perinatally acquired HIV (PHIV). This study aimed to determine the frequency and associated factors of seronegativity in Thai children, adolescents and young adults with PHIV. Methods A cross‐sectional HIV serological study was performed in children, adolescents and young adults two years or older who were receiving ART with undetectable HIV‐RNA for at least one year from August 2018 to August 2019. Medical records were extracted for multivariate analysis of independent factors for seronegativity. Results and discussion Of 110 patients, 50 male, median (range) age was 18.4 (4.8 to 26.6) years, 8 (7.3%) were seronegative, and 1 (0.9 %) was inconclusive. The seronegative group had a younger median (range) age at ART initiation: 3.0 (1.0 to 12.0) versus 40.0 (2.0 to 207.0) months, p = 0.045; and shorter median (range) duration from ART initiation to viral suppression: 16.8 (7.2 to 42.0) versus 55.2 (6.0 to 214.8) months, p = 0.036. Multivariate analysis identified younger age at ART initiation (aOR 0.69, 95% CI 0.49 to 0.98, p = 0.038) and shorter time to viral suppression after ART initiation (aOR 0.94, 95% CI 0.89 to 0.99, p = 0.019) as independent factors associated with HIV seronegativity. Of the infants who initiated ART

Immunization is the most effective preventive strategy against varicella. While the Oka strain is commonly used for varicella vaccination worldwide, Korea widely uses the MAV/06 strain. A new live attenuated MAV/06 strain varicella vaccine (MG1111), which uses the new cell line Medical Research Council-5 for better viral propagation, was developed. MG1111 was approved by Korean health authorities. Here, we report the results of phase III, randomized, double–blind, multicenter study conducted in Korea and Thailand, which compared the immunogenicity and safety profiles of MG1111 versus the control vaccine, VarivaxTM. In total, 515 healthy children (12 month–12 years) were randomized 1:1 to receive either the MG1111 or control vaccine (MG1111: 258, Control: 257). The seroconversion rate (SCR) and geometric mean titer (GMT) were measured using the fluorescent antibody to membrane antigen (FAMA) test. The MG1111 group achieved a SCR of 97.9% (95% CI: 95.2–99.3) after vaccination. The lower limit of 95% CI for SCR difference (MG1111-VarivaxTM) was –4.0%, which was higher than the specified non-inferiority margin of –10%. Further, the GMT of the MG1111 increased from 2.0 to 74.2 (95% CI: 65.0–84.8) and the lower limits of the 95% CI for post–vaccination GMT ratios (MG1111/VarivaxTM) were 0.55 higher than the specified parameter of 0.5. Therefore, the MG1111 group was not statistically inferior to the control vaccine group in terms of SCR and GMT. Furthermore, the MG1111 and control vaccine groups were not significantly different in the percentage of participants showing adverse events—solicited, local, or systemic during 43-day period of observation and serious adverse events during 6 month of observation. The present results indicate that MG1111was not immunologically inferior to VarivaxTM, and safety profiles of MG1111 are similar to those of VarivaxTM.

Introduction The clinical relevance of low‐level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first‐line combination antiretroviral therapy (cART). Methods CLHIV aged 14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL

Background Bacille Calmette-Guerin (BCG) vaccination at birth may cause mild and benign local adverse effects (AE). More serious AE are rarely reported. Objective To describe clinical features and outcomes of BCG (Tokyo-172 strain)-induce diseases (BCG-ID) that required medical attention at a tertiary care center in Bangkok, Thailand. Method We retrospectively reviewed medical records from January 2007 to December 2016 that were selected by ICD-10 codes. The inclusion criteria were the patients under 3 years of age who developed lymphadenitis, osteitis, or disseminated infections of which BCG was a possible pathogen. Cases were classified into suspected (clinically compatible without laboratory confirmation), probable (suspected cases with M. tuberculosis complex identified), and confirmed BCG-ID (probable cases with molecular confirmation of M. bovis BCG strain). Results 95 children were identified; 57 (60.0%) were male, and the median age at presenting symptom was 3.5 (range: 0.6–28.7) months. Of these, 25 (26.3%) were suspected, 49 (51.6%) were probable, and 21 (22.1%) were confirmed BCG-ID. Overall, 87 (92%) children had regional lymphadenitis corresponding to the BCG site, 5 (5%) had osteitis, and 3 (3%) had disseminated BCG. Of those with lymphadenitis, average size was 2.2 (range 0.7–5) cm. in diameter and 53% (46/87) had pulmonary involvement. Five children with immunodeficiency; three had disseminated BCG and two had lymphadenitis. Eight (9.2%) patients with lymphadenitis underwent needle aspiration; 57 (65.5%) had surgical excision. All children with BCG osteitis underwent surgical intervention in combination with anti-tuberculosis treatment. One patient with osteitis experienced long-term leg length discrepancy. Conclusion Regional lymphadenitis was the most common feature of BCG-ID requiring medical attention. That none of the BCG osteitis were immunocompromised hosts suggested the potential virulence of BCG in neonates. A systematic national surveillance and reporting system is needed to develop accurate estimates of population incidence and support development of effective vaccine policy.

Summary Background Increasing evidence shows that protection induced by acellular pertussis vaccines is short-lived, requiring repeated booster vaccination to control pertussis disease. We aimed to assess the safety and immunogenicity of a recombinant acellular pertussis vaccine containing genetically inactivated pertussis toxin and filamentous haemagglutinin, as either a monovalent vaccine (aP [PTgen/FHA] ) or in combination with tetanus and reduced-dose diphtheria vaccines (TdaP [PTgen/FHA] ), versus a licensed tetanus and reduced-dose diphtheria and acellular pertussis combination vaccine (Tdap). Methods We did this phase 2/3, randomised controlled non-inferiority trial at two sites in Bangkok, Thailand. Healthy adolescents (aged 12–17 years) were randomly assigned (1:1:1), via a computer-generated randomisation list with block sizes of three, to receive one dose (0·5 mL) of aP (PTgen/FHA) , TdaP (PTgen/FHA) , or Tdap (comparator). Clinical research staff responsible for participant randomisation, vaccine preparation and administration, and accountability were aware of group allocation. However, allocation was concealed from all other site study staff, data management personnel, statisticians, laboratory staff, and study participants. The primary outcome was non-inferior immunogenicity of TdaP (PTgen/FHA) to Tdap based on seroconversion rates (a four-fold increase or more) for pertussis toxin and filamentous haemagglutinin IgG antibodies 28 days after vaccination, with a predefined 10% margin of equivalence. We did analysis by per protocol. This study is registered with the Thai Clinical Trial Registry, number TCTR20150703002. Findings Between July 6 and Aug 20, 2015, we allocated 450 participants to receive one dose of TdaP (PTgen/FHA) (n=150), aP (PTgen/FHA) (n=150), or comparator Tdap (n=150). 28 days after vaccination, seroconversion rates for anti-pertussis toxin IgG were 96·6% (95% CI 93·8–99·5; n=144) in the TdaP (PTgen/FHA) group and 55·0% (47·1–63·0; n=82) in the comparator Tdap group (difference 41·6%, 95% CI 33·1–50·1; p (PTgen/FHA) group and 54·4% (46·4–62·4; n=81) in the comparator group (difference 28·2%, 95% CI 18·1–38·2 p (PTgen/FHA) group were 96·0% (95% CI 92·8–99·1; n=142) for anti-pertussis toxin IgG and 93·2% (89·2–97·3; n=138) for anti-filamentous haemagglutinin IgG. These findings support the non-inferior immunogenicity of TdaP (PTgen/FHA) over comparator Tdap. Reactogenicity and incidence of adverse events were similar between groups. Interpretation The new TdaP (PTgen/FHA) vaccine is safe and induces higher pertussis responses 28 days after vaccination than does the available licensed Tdap booster vaccine. Results of our trial led to the licensure of new acellular pertussis vaccines containing genetically inactivated pertussis toxin in Thailand. The availability of recombinant monovalent pertussis vaccines that induce high antibody responses provides the medical community and consumers with the opportunity to vaccinate against pertussis when immunisation against diphtheria and tetanus is not required or not desired. Studies are underway to pave the way for licensure studies of this acellular pertussis vaccine in other countries. Funding BioNet-Asia.

Protease inhibitor (PI) may cause abnormal glucose metabolism, abnormal lipid metabolism, and metabolic syndrome in HIV-infected adults but less well studied in Asian adolescents. This cross-sectional study evaluated anthropometric factors, oral glucose tolerance test, and lipid profiles of perinatally HIV-infected Thai adolescents who had received PI-based antiretroviral therapy for at least 6 months. Eighty adolescents were enrolled [median (IQR) age 16.7 (14.6–18.0) years, 42 males]. Metabolic syndrome, prediabetes, and type 2 diabetes mellitus (T2DM) were found in 8 (10%), 17 (22.1%), and 3 (3.8%) adolescents, respectively. Dyslipidemia was found in 56 (70%) adolescents, with hypertriglyceridemia being the most common type. In multivariate analysis, presence of lipohypertrophy (OR: 25.7, 95% CI: 3.2–202.8;p=0.002) and longer duration of PI use (OR: 1.04, 95% CI: 1.00–1.08;p=0.023) were associated with metabolic syndrome. Obesity (OR: 7.71, 95% CI: 1.36–43.7;p=0.021), presence of lipohypertrophy (OR: 62.9, 95% CI: 4.97–795.6;p=0.001), and exposure to stavudine for ≥6 months (OR: 8.18, 95% CI: 1.37–48.7;p=0.021) were associated with prediabetes/T2DM, while exposure to tenofovir for ≥6 months reduced the risk (OR: 0.17, 95% CI: 0.04–0.78;p=0.022). Metabolic disorders were commonly found in adolescents receiving PI. Careful monitoring and early intervention to modify cardiovascular risk should be systematically implemented in this population particularly those with exposure to stavudine.

PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001–2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count

Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types.A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type).Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (β = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (β = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p 0.05).Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Objective: To evaluate the performance of interferon gamma release assays and tuberculin skin test in HIV-infected children and adolescents with immune reconstitution. Methods: A cross-sectional study was conducted in HIV-infected patients aged 5-18 years receiving antiretroviral treatment with CD4 T-lymphocytes >25% or >500 cells/mm3 for at least 6 months. QuantiFERON-TB Gold, T-SPOT.TB, and tuberculin skin test were performed in each patient. Results: A total of 50 patients were enrolled with median age of 13.7 years, CD4 counts of 753 (IQR: 587-989) cells/mm3. Among 27 patients with tuberculosis (16) or tuberculosis exposure (11), 8 (29.6%) were positive to at least one test, 2 (7.4%) were positive QuantiFERON-TB Gold, 3 (11.1%) positive T-SPOT.TB, and 7 (25.9%) had tuberculin skin test ≥5 mm. Among 23 patients without history of tuberculosis or exposure, all had negative interferon gamma release assays, while 2 (8.7%) had positive tuberculin skin test. Conclusions: All tests had low sensitivity despite immune reconstitution.

Objective: To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction ≥ 10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy without testing in children younger than 5 years.

Recent studies report delayed anti-HIV antibody clearance (seroreversion) among HIV-exposed uninfected infants that may affect diagnostic practices. We evaluated the age-specific seroreversion rates in Thailand.The medical records of HIV-exposed uninfected infants born in January 2000-December 2014 were reviewed. Anti-HIV seroreversion rates at 12, 18 and 24 months were analyzed in 3 periods according to the Thai National Guidelines of prevention of mother-to-child transmission of HIV: zidovudine with or without single dose nevirapine to all women (2000-2006), adding lamivudine plus nevirapine to zidovudine in women with CD4 count200 cells/mm (2007-2009) and zidovudine plus lamivudine plus boosted lopinavir to all women (2010-2014). In 2013, the serologic test kit was changed from third- to fourth-generation (4G) assay. All the infants were formula fed.Among 736 infants, the overall seroreversion rates at 12, 18 and 24 months of age were 59.38%, 94.57% and 100%, respectively. The seroreversion rates at 12 months of age declined from 68% in 2000-2006 and 65.9% in 2007-2009, to 42.9% in 2010-2014 (P = 0.001). Seroreversion rates at 18 months of age were more than 96.5% before 2013 and decreased to 79.1% in 2013-2014 (P = 0.001) with use of 4G. Multivariate analysis identified antepartum protease inhibitors treatment and the use of 4G testing as independent factors associated with delayed seroreversion.Anti-HIV seroreversion delay in HIV-exposed uninfected infants was associated with use of protease inhibitors and 4G HIV testing, complicating the interpretation to exclude perinatal HIV infection.

HIV infection may alter immunologic response and the establishment of immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to determine the need to revaccinate perinatally HIV-infected Thai adolescents.Cross-sectional serologic tests for HBV, including hepatitis B surface antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core antibody (anti-HBc), were performed in perinatally HIV-infected adolescents. Adolescents having anti-HBs100 mIU/mL with negative anti-HBc and immune reconstitution from highly active antiretroviral therapy (HAART) were revaccinated using regular (10 μg) 3-dose schedule given intramuscularly at 0-, 2- and 6-month intervals.Of 193 adolescents who received 3-dose infant HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile range) current age 14.5 (11.7-16.2) years, 7 (3.6%) had positive anti-HBc (indicating breakthrough infection), of which 4 (2%) had positive hepatitis B surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents had protective anti-HBs concentration10 mIU/mL. Of 164 revaccinated adolescents, 142 (86.6%) had HIV viral load40 copies/mL. Anti-HBs seroconversion rates10 mIU/mL were 58.0% (94/162) after the first dose and 97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects responded to the first dose with anti-HBs antibody ≥100 mIU/mL had a shorter median duration with CD4 count15% than their counterparts (6.2 vs. 11.1 months; P = 0.049).Only half of perinatally HIV-infected adolescents were able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination with 3-dose schedule is required in perinatally HIV-infected adolescents who did not initiate HAART at the time of infant vaccination.

Summary Background Nosocomial outbreaks of parvovirus B19 (pB19) have been reported, but they rarely occur among healthcare personnel (HCP). Susceptibility among pregnant HCP was the major concern. Methods An outbreak of pB19 among HCP is described in a paediatric ward with a cross-sectional serologic study in all HCP and patients exposed to the outbreak. Acute infection was diagnosed by polymerase chain reaction or positive anti-parvovirus B19 IgM. Findings Among 48 HCP (three pregnant) and 22 patients included in the outbreak serologic study, 11 (23%) HCP and two (9%) patients had acute infection. Of these, six HCP and no patients were symptomatic. Clinical manifestations included itchy rash (100%) and joint pain following resolution of rash (67%), with median rash duration of four days. Forty percent of HCP and 50% of patients had positive anti-parvovirus IgG, indicating previously immune status. HCP with acute infection and HCP who were susceptible without infection were younger than HCP with previous immunity (mean age 32.2 vs 40.5 years, respectively; P = 0.003). The attack rate was 38% among HCP and 18% among patients who were susceptible, respectively. The outbreak ended within two weeks following strict droplet precaution and segregation of symptomatic HCP. Conclusion Parvovirus B19 infection may cause nosocomial outbreak with high attack rate among HCP. Outbreak control with droplet precaution was highly effective.

Oculorespiratory syndrome (ORS) is an infrequent adverse event following influenza vaccination. Its clinical presentation suggests that ORS is an immune-mediated phenomenon, but studies of symptomatic individuals have been few. This study measured cytokine levels in peripheral blood samples following influenza vaccination in those with and without current ORS symptoms. Canadian adults receiving the 2010-2011 seasonal influenza vaccine were recruited and asked to promptly report any adverse effects. ORS symptoms occurring 4 to 48 h after vaccination were identified using previously published criteria. Two blood samples were collected from each subject to measure blood plasma cytokine and hemagglutination inhibition antibody (HAI) titers; visit 1 occurred during the acute disease phase or 4 to 72 h after vaccination for controls, and visit 2 occurred another 21 days postimmunization. Nine ORS cases and 35 controls were enrolled. The median age of ORS cases was 49 years, and 89% were female. Most cases had multiple symptoms, but none required medical care. HAI titers before and after vaccination were similar for the cases and controls. Blood plasma cytokine concentrations did not differ between the ORS cases and controls for most cytokines measured (interleukin 4 [IL-4], IL-5, IL-10, IL-13, IL-1α, IL-8, tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], and IL-17A). However, ORS cases had higher levels of IL-10 and IL-3 than the controls at visits 1 and 2, even after all symptoms had subsided. Persistent higher levels of IL-10 and IL-3 in ORS cases suggest that host factors may have predisposed these individuals to develop ORS following influenza vaccination. Further investigations are warranted, as they might identify subjects who are at risk for ORS prior to vaccination.

This single-group study investigated the immunogenicity and safety of a booster dose of the recently licensed live attenuated chimeric Japanese encephalitis vaccine in 50 healthy children (1-5 years old) who were primed with the live attenuated SA14-14-2 vaccine. A strong anamnestic response was induced 28 days postbooster: geometric mean titer, 9144 (95% confidence interval: 7365-11353); and seroprotection rate, 49 of 49 (100%) children.

BACKGROUND The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged

Lipodystrophy (LD) was evaluated in 205 children receiving antiretroviral therapy by a single investigator: 51 (24.9%) had LD; 46 peripheral lipoatrophy, three central lipohypertrophy and two combined type. All cases of peripheral and combined LD also had facial lipoatrophy. Serial photographs were provided by the families to confirm the severity of facial lipoatrophy. Forty-six (95.8%) children with peripheral or combined LD, and 75 (48.7%) without LD were exposed to stavudine (d4T) for a median duration of 45.9 versus 26.4 months (P = 0.005). In multivariate analysis, exposure to d4T for more than three months was the only factor associated with peripheral or combined LD (P < 0.001). Noticeable improvement of facial lipoatrophy was found in 11/48 (22.9%) children after a mean duration of 45.6 months following d4T discontinuation, mostly occurring during early adolescence.

Drug-resistant Mycobacterium tuberculosis (TB) infection represents a serious and growing problem. For patients infected or suspected of being infected with multidrug or extensively drug-resistant TB, several medications have to be given simultaneously for prolonged periods. Here, we review the literature on treatment and monitoring of adverse effects of pediatric drug-resistant TB therapy in a high resource, low TB burden setting.

This study assessed the acceptability and feasibility of Internet self-reporting for adverse events following pandemic and seasonal influenza immunization among 270 health care workers at a tertiary care children's and women's hospital in fall 2009. Participants responded to an online questionnaire 72 h after vaccine receipt. Non-responders were sent a reminder email 8-10 days after vaccine receipt, followed by a telephone call for those who did not respond online. The overall online response rate was high (88%). Participants rated the online self-report easy to use and would be willing to use it again. The high response rate and acceptability of the online report method suggest that web-based self-reporting for adverse event following immunization (AEFI) has the potential for rapid assessments of AEFI in mass or new immunization programs.

Summary Background Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) has been the most affordable regimen for the HIV-infected in developing countries. There are limited data comparing nevirapine (NVP) to efavirenz (EFV) in HIV-infected children. This study aimed to assess the efficacy and tolerability of NVP-based regimens compared to EFV-based regimens in HIV-infected children in Thailand. Methods The medical records of HIV-infected children who had received NNRTI-based regimens for more than 6 months at the Department of Pediatrics, Siriraj Hospital, Mahidol University, Thailand, were reviewed. Results Of the 139 HIV-infected children studied, 70 were male, and the median age at treatment initiation was 6.08 years (range 0.32–14.56 years); the median duration of follow-up was 36 months (range 6–66 months). The median baseline CD4 cell count was 185cells/mm 3 (range 2–3482cells/mm 3 ) and the median baseline CD4 percentage was 7.20% (range 0.11–36.57%). An NVP-based regimen was initiated in 61 (44%): 38 antiretroviral (ARV)-naive and 23 ARV-experienced. An EFV-based regimen was initiated in 78 (56%): 34 ARV-naive and 44 ARV-experienced. The CD4 cell count and percentage gains were not different between the NVP and EFV groups in both the ARV-naive and the ARV-experienced. However, ARV-naive children who received an EFV regimen had significantly lower baseline CD4 levels than those who received an NVP regimen. ARV-naive children had a better CD4 response than the ARV-experienced. The survival rates of children in the NVP groups were not different from those in the EFV groups for both the ARV-naive and the ARV-experienced. Treatment failure occurred in one ARV-naive NVP case (2.6%), two ARV-naive EFV cases (5.8%), and nine ARV-experienced NVP cases (39%) at 24 months of treatment, and 11 ARV-experienced EFV cases (25%) at 18 months of treatment. Seven (10%) children had adverse effects from treatment with NVP. The main side effects were rash and hepatitis; six had to switch to EFV. Four (5%) children had adverse effects from treatment with EFV; two had to switch to NVP. Conclusions Both NVP- and EFV-based HAART regimens were effective in children in Thailand for at least 3 years. HIV-infected Thai children generally tolerated NNRTI well.

Understanding dengue virus infection in children and the kinetics of maternal dengue neutralizing antibodies is essential for effective dengue immunization of children in endemic areas.Serum samples from 219 mother-child pairs and 140 children at 3, 6, 9, 12, 18, and 24 months of age from Bangkok, Thailand, were tested for serotype-specific dengue antibodies. Febrile episodes in the children were recorded.Antibodies were found in 97% of cord serum samples and disappeared in 27%, 80%, and 95% of the children by the age of 6, 9, and 12 months, respectively. Geometric mean titers (GMTs) of the antibodies to 4 dengue serotypes decreased to 5.4-15.5 in 6-month-old infants. Eleven of 12 children acquired dengue virus infection at 6 months of age and beyond; 1 had the infection at 3 months of age. Two exhibited undifferentiated febrile illnesses, and 10 had subclinical infections.Evidence of dengue virus infection and very low GMTs against all dengue serotypes in children at 6 months of age and beyond was demonstrated. There was no evidence that maternal antibodies were harmful to infants. Dengue virus infection rates increase from 12 months of age onward. These data provide information for supporting the optimal age at vaccination.

We assessed the pharmacokinetics of nevirapine in HIV and tuberculosis-coinfected children while they were receiving nevirapine-containing fixed-dose combination tablets with rifampicin-based tuberculosis treatment and after discontinuation. The median age (range) was 9.7 (4.4-11.7) years. The nevirapine area under the concentration versus time curve from 0 to 12 hours and trough concentration with rifampicin were 85.3 (40.5-170.7) mg.h/mL and 6.4 (3.00-13.27) mg/mL, respectively, providing adequate exposure.

When a neurologic condition develops after vaccination of a patient, the causal relationship is difficult to determine. We report an unusual case in which neurologic signs occurred in a previously healthy child after both doses of H1N1 2009 influenza vaccine, culminating in bilateral optic neuritis and disseminated encephalomyelitis. A causal association is more likely with repeated injury following influenza vaccination.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons.OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries.DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs.RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages.CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Seroprevalence of dengue antibodies were determined in healthy children in Bangkok. At 9, 12, and 18 months of age 23%, 9%, and 17% of children respectively had neutralizing antibodies against one or more serotypes. DEN1 was the most prevalent, followed by DEN3, DEN2, and DEN4. Twelve children had serologic evidence of dengue infection. The nadir of dengue antibodies in children was at 12 months of age. In highly endemic areas, dengue vaccination could be needed at an early age.

From 1992 to 1997, 140 Thai children 4-15 years of age received an investigational live attenuated tetravalent dengue vaccine (LATDV). These children were contacted 3-8 years later in 2001 to assess humoral immunity and investigate whether they were subsequently at higher risk of developing severe dengue. One hundred thirteen were successfully contacted and participated in this retrospective cohort study with two age- and address-matched controls per vaccinee. The number of vaccinated subjects with neutralizing antibodies increased compared with 3-8 years earlier, which was probably due to subsequent wild-type dengue infections. There were no excess hospitalizations for clinically suspected dengue fever (DF) or dengue hemorrhagic fever (DHF) in vaccinees (one with DF and three with DHF) compared with controls (14 with DHF). Results suggest that preexisting dengue antibodies induced by LATDV do not enhance dengue illness, and the use of the vaccine in a dengue-endemic area is safe.

We assessed the prevalence of vitamin D deficiency among 101 perinatally HIV-infected Thai adolescents receiving antiretroviral therapy. Median age was 14.3 (interquartile range 13.0-15.7) years, and 90% had a HIV RNA

SETTING Few data on drug-resistant (DR) tuberculosis (TB) in children are available in Thailand. OBJECTIVES To evaluate the rate, clinical features and risk of DR-TB in children. DESIGN Observational prospective study conducted in children diagnosed with TB at a tertiary care centre in Bangkok. RESULTS Of 230 children diagnosed with TB, the median age was 6.5 years; 63% had identified adult source cases, and only 7% had received prior isoniazid treatment for latent tuberculous infection. Of the 195 (85%) specimens submitted, 57 (25%) were positive using culture or polymerase chain reaction. Of the 53 positive specimens available for drug susceptibility testing (DST), 18 (34%) had any resistance, 13 (24.5%) were mono-resistant, 2 (3.8%) polyresistant and 3 (5.7%) were multidrug-resistant. In multivariate analysis, prior TB treatment (P < 0.001), presence of atelectasis (P = 0.039) or lobar consolidation (P = 0.012) on chest X-ray were associated with DR-TB. DR-TB required longer treatment but there were no differences in rate of cure, treatment completion or death. CONCLUSIONS The high rate of DR-TB underscores the importance of routine DST. History of treatment and drug susceptibility in source cases was useful in guiding initial treatment in children.

OBJECTIVES Data on lopinavir/ritonavir tablets administered once daily in children are limited. We compared the pharmacokinetics (PK) of lopinavir/ritonavir twice daily versus once daily in virologically suppressed, HIV-infected children, and assessed the virological outcome, at 48 weeks, in children receiving the regimen of lopinavir/ritonavir once daily. PATIENTS AND METHODS HIV-infected children receiving a twice-daily lopinavir/ritonavir-based regimen and with an HIV-1 RNA viral load (VL)

Neonatal infection due to Cryptococcus neoformans is extremely rare. We report a case of a 21-day-old neonate diagnosed with cryptococcal septicemia who was successfully treated with amphotericin B. He was born to a human immunodeficiency virus (HIV) seronegative mother. This report alerts general pediatricians and neonatologists to consider Cryptococcus neoformans infection as a possible cause of sepsis in newborn infants.