Bone health and vitamin D status among perinatally HIV-infected Asian children and adolescents with virological suppression

Background: Pathogenesis of reduced bone mass and its relationships with hypovitaminosis D in HIV-infected populations are largely unknown. The goals of this dissertation were to determine the prevalence of low bone mass and its pathogenesis, along with the prevalence of hypovitaminosis D and its effects on bone turnover and bone density among HIV-infected Asian adolescents. Methods: A multicenter, cross-sectional study was conducted at four pediatric HIV centers in Thailand and Indonesia. Perinatally HIV-infected adolescents aged 10-18 years receiving antiretroviral therapy with virologic suppression (HIV RNA 65 pg/ml were defined as hypovitaminosis D and hyperparathyroidism, respectively. Results: Of 396 participants, 57% were female and median age (IQR) was 15.0 (13.3-16.9) years. The prevalence of lumbar spine BMD and BMAD Z-scores <=-2 were 16.4% and 8.3%, respectively. Z-scores were lower with older age, female sex, body mass index <5th percentile, protease inhibitor exposure and CD4+ <15% before ART initiation. Increased bone turnover markers were inversely associated with BMD/BMAD Z-scores. Among 394 adolescents who had 25-OHD results, the prevalence of hypovitaminosis D, hyperparathyroidism, and both conditions were 21% (95%CI: 17-25%), 17% (95%CI: 13-20%) and 5% (95%CI: 3-7%), respectively. Adolescents with hypovitaminosis D and secondary hyperparathyroidism had the highest median bone resorption (CTX: 1610 vs. 1270 ng/l; P=0.04) and bone formation (PINP: 572 vs. 330 μg/l; P=0.02) markers, and the greatest proportion of low BMD (42 vs. 15%; P=0.01) compared to the rest of the cohort. Conclusion: Low bone mass was not uncommon in our adolescents. Bone turnover dysregulation was associated with reduced bone mass. Hypovitaminosis D complicated with secondary hyperparathyroidism was associated with increased bone turnover and bone demineralization. Monitoring of bone mass and vitamin D status may be important for this population

Characteristics of Respiratory Syncytial Virus Infection in Hospitalized Children Before and During the COVID-19 Pandemic in Thailand

Objectives This study compared the epidemiological and clinical manifestations of patients hospitalized with respiratory syncytial virus (RSV) infection before and during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary care hospital in Chiang Mai Province, Thailand. Methods This retrospective observational study utilized data from all cases of laboratory-confirmed RSV infection at Maharaj Nakorn Chiang Mai Hospital from January 2016 to December 2021. Differences in the clinical presentation of RSV infection before (2016 to 2019) and during (2020 to 2021) the COVID-19 pandemic were analyzed and compared. Results In total, 358 patients hospitalized with RSV infections were reported from January 2016 to December 2021. During the COVID-19 pandemic, only 74 cases of hospitalized RSV infection were reported. Compared to pre-pandemic levels, the clinical presentations of RSV infection showed statistically significant decreases in fever on admission (p=0.004), productive cough (p=0.004), sputum (p=0.003), nausea (p=0.03), cyanosis (p=0.004), pallor (p<0.001), diarrhea (p<0.001), and chest pain (p<0.001). Furthermore, vigilant measures to prevent the spread of COVID-19, including lockdowns, also interrupted the RSV season in Thailand from 2020 to 2021. Conclusions The incidence of RSV infection was affected by the COVID-19 pandemic in Chiang Mai Province, Thailand, which also changed the clinical presentation and seasonal pattern of RSV infection in children

Successful treatment of a child with vascular pythiosis

<p>Abstract</p> <p>Background</p> <p>Human pythiosis is an emerging and life-threatening infectious disease caused by <it>Pythium insidiosum</it>. It occurs primarily in tropical, subtropical and temperate areas of the world, including Thailand. The aim of this report is to present the first pediatric case of typical vascular pythiosis.</p> <p>Case Presentation</p> <p>A 10-year-old boy with underlying β-thalassemia presented with gangrenous ulcers and claudication of the right leg which were unresponsive to antibiotic therapy for 6 weeks. Computerized tomography angiography indicated chronic arterial occlusion involving the right distal external iliac artery and its branches. High-above-knee amputation was urgently done to remove infected arteries and tissues, and to stop disease progression. Antibody to <it>P. insidiosum </it>was detected in a serum sample by the immunoblot and the immunochromatography tests. Fungal culture followed by nucleic sequence analysis was positive for <it>P. insidiosum </it>in the resected iliac arterial tissue. Immunotherapeutic vaccine and antifungal agents were administered. The patient remained well and was discharged after 2 months hospitalization without recurrence of the disease. At the time of this communication he has been symptom-free for 2 years.</p> <p>Conclusions</p> <p>The child presented with the classical manifestations of vascular pythiosis as seen in adult cases. However, because pediatricians were unfamiliar with the disease, diagnosis and surgical treatment were delayed. Both early diagnosis and appropriate surgical and medical treatments are crucial for good prognosis.</p

Optimizing Clinical Trial Design to Maximize Evidence Generation in Pediatric HIV.

For HIV-infected children, formulation development, pharmacokinetic (PK) data, and evaluation of early toxicity are critical for licensing new antiretroviral drugs; direct evidence of efficacy in children may not be needed if acceptable safety and PK parameters are demonstrated in children. However, it is important to address questions where adult trial data cannot be extrapolated to children. In this fast-moving area, interventions need to be tailored to resource-limited settings where most HIV-infected children live and take account of decreasing numbers of younger HIV-infected children after successful prevention of mother-to-child HIV transmission. Innovative randomized controlled trial (RCT) designs enable several questions relevant to children's treatment and care to be answered within the same study. We reflect on key considerations, and, with examples, discuss the relative merits of different RCT designs for addressing multiple scientific questions including parallel multi-arm RCTs, factorial RCTs, and cross-over RCTs. We discuss inclusion of several populations (eg, untreated and pretreated children; children and adults) in "basket" trials; incorporation of secondary randomizations after enrollment and use of nested substudies (particularly PK and formulation acceptability) within large RCTs. We review the literature on trial designs across other disease areas in pediatrics and rare diseases and discuss their relevance for addressing questions relevant to HIV-infected children; we provide an example of a Bayesian trial design in prevention of mother-to-child HIV transmission and consider this approach for future pediatric trials. Finally, we discuss the relevance of these approaches to other areas, in particular, childhood tuberculosis and hepatitis

Immune reconstitution inflammatory syndrome from Penicillium marneffei in an HIV-infected child: a case report and review of literature

<p>Abstract</p> <p>Backgrounds</p> <p>Disseminated <it>Penicillium marneffei </it>infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unmasking type of IRIS caused by disseminated <it>P. marneffei </it>infection after ART initiation.</p> <p>Case presentation</p> <p>A 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4⁺cell count was 7.2% or 39 cells/mm³. On admission, her repeated CD4⁺cell count was 11% or 51 cells/mm³and her plasma HIV-RNA level was < 50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture, and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without evidence of recurrence of disease.</p> <p>Conclusions</p> <p>IRIS from <it>P. marneffei </it>in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.</p

Metabolic syndrome, biochemical markers, and body composition in youth living with perinatal HIV infection on antiretroviral treatment.

People living with HIV who are on antiretroviral treatment are at increased risk of developing premature cardiovascular disease. Children with perinatal HIV infection (PHIV) have survived through their adolescence and are entering adulthood. We determined the prevalence of metabolic syndrome, abnormal biochemical markers, and characterized body composition parameters in youth living with perinatal HIV infection. This cross-sectional study was conducted at the Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand from December 2017 to February 2018. PHIV-youths between 15 <25 years of age who were receiving ART were enrolled. Data collection included ART-related history, blood pressure, and anthropometric measurements. Body composition including android, gynoid fat mass, and total body fat were measured by dual-energy X-ray absorptiometry. Fasting blood was drawn to test for lipid profile, glucose, and high sensitivity c-reactive protein (hsCRP). One hundred and twenty PHIV-youths (48% female) were enrolled. Their mean age and the median duration on ART were 20.3 (SD2.6) and 14.1 (IQR 10.4-14.9) years, respectively; 76 (63%) were on first-line non-nucleoside reverse transcriptase inhibitors-based regimens. Thirty-three (28%), 74 (62%), and 13 (11%) of PHIV-youths were underweight (BMI < 18.5 kg/m2), normal (BMI 18.5-24.9 kg/m2), and overweight (BMI ≥ 25.0 kg/m2), respectively. The prevalence of metabolic syndrome was 10.6% (95%CI 5.0-16.0). Seventy-six of 113 (67.3%) of PHIV-youths had lipid alteration; the most prevalent types being low HDL (46.9%) and increased triglycerides (27.4%). Overall 43 (35.9%) had increased hsCRP (16.7% with immediate and 19.2% with high risk for CVD). Females had significantly higher percentage of android and gynoid fat, but lower Android to gynoid ratio (AGR) compared to males. There were 77%, 31%, and 21% of PHIV-youths in the overweight, normal weight, and underweight group with AGR in tertile 3, respectively. In conclusion, we documented presence of metabolic syndrome in 10.6% of PHIV-youths on ART. Increase AGR representing abdominal obesity was detected even in youths with normal BMI or underweight

Epidemiology and associated factors for hospitalization related respiratory syncytial virus infection among children less than 5 years of age in Northern Thailand

Background: Respiratory syncytial virus (RSV) is often the main problem in young children that require hospitalization. The objective of this study was to identify factors associated with RSV-related hospitalizations in young children less than five years old. Methodology: A retrospective study was conducted for acute respiratory tract infection (ARTI) at a tertiary care hospital from January 2017 to December 2021 by using binary logistic regression analysis to detect the associated factors with RSV-related hospitalizations in children. Results: RSV-related hospitalization was detected in 293 of 410 (71.46 %) cases of RSV infection, most of which appeared in the rainy months of August to November. The most common symptoms and signs were 81.5 % rhinorrhea, 70.7 % cough, 68.5 % sore throat, 68.3 % sputum production, and 66.8 % fever. Factors associated with RSV-related hospitalization were age less than or equal to 2 years (aOR = 4.62, 95 % CI = 1.86–11.44), preterm birth (aOR = 2.61, 95 % CI = 1.05–6.10), patients with underlying disease (aOR = 3.06, 95 % CI = 1.21–10.34), and the presenting symptoms with sputum production (aOR = 16.49, 95 % CI = 3.80–71.55). Laboratory blood tests, low levels of hematocrit (aOR = 9.61, 95 % CI = 1.09–84.49) was the associated factor for hospitalization with RSV infection (p < 0.05). Conclusions: Factors associated with RSV-related hospitalizations in children were age less than or equal to two years, preterm birth, underlying disease, symptoms of sputum production. The low level of hematocrit was also associated with RSV-related hospitalizations in these children

Predominance of ON1 and BA9 genotypes of human respiratory syncytial virus in children with acute respiratory infection in Chiang Mai, Thailand, 2020–2021

Background: Human respiratory syncytial virus (hRSV) is an important cause of acute respiratory infection, especially in children. Few studies have investigated molecular epidemiology of hRSV infection in Thailand. The aims of this study were to investigate the prevalence and genotype diversity of hRSV in children with acute respiratory infection (ARI) in Thailand. Methods: A total of 383 nasopharyngeal swabs collected from children with ARI from October 2020 to September 2021 were screened for hRSV and nucleotide sequences of the hypervariable region 2 (HVR2) of G gene of the detected hRSV were analysed. Results: Of 383 nasopharyngeal swabs, 104 (27.2 %) were positive for hRSV, of which 51 (49.0 %), 43 (41.3 %), and 10 (9.6 %) were hRSV-A, hRSV-B, and untypeable strains, respectively. All hRSV-A and hRSV-B were ON1 genotype and BA9 genotype, respectively. Most of the hRSV strains were detected in the cool months, November 2020 to February 2021. Phylogenetic analysis of the HVR2 sequence of G gene revealed three clusters of hRSV-A (ON1 genotype) and two clusters of hRSV-B (BA9 genotype). The hRSV-A strains in cluster 1 and 3 were closely related to the hRSV-A reference strains reported previously from other regions of Thailand whereas those in cluster 2 were closely related to the hRSV-A reference strains reported previously from Europe and Africa. For the hRSV-B strains, both clusters 1 and 2 were closely related to the hRSV-B reference strains reported previously from Europe, Australia, and Taiwan. The predicted N- and O-linked glycosylation sites were found along the length of HVR2 of G protein, mostly in the hRSV-B strains. Conclusions: The ON1 and BA9 were the only two hRSV genotypes that were co-predominant and solely detected in this study. The findings indicated that the ON1 and BA9 are the only two hRSV genotypes currently circulating in children with ARI in northern Thailand

Comparison of antibody responses following natural infection with Severe Acute Respiratory Syndrome Coronavirus 2 or receipt of CoronaVac or ChAdOx1 (AZD1222) vaccination in Chiang Mai, Thailand

Background: In Thailand, early vaccination initiatives for SARS-CoV-2 relied on CoronaVac (Sinovac Life Sciences) and ChAdOx1 (Oxford–AstraZeneca) vaccines. However, the data of immunogenicity of these two vaccines in Thai populations is limited. This real time, head-to-head comparative study was conducted to investigate antibody (Ab) responses to SARS-CoV-2 following infection or receipt of either CoronaVac or ChAdOx1 vaccination in Chiang Mai, Thailand. Methods: Sera was collected within two months from participants having a history of documented SARS-CoV-2 infection or at one month after the second dose of CoronaVac vaccine. Sera from participants with a history of receiving one dose of ChAdOx1 vaccination was collected twice, at one month following each vaccine dose. Neutralizing antibodies (NAbs) were assessed using the surrogate neutralization test and anti-spike protein antibodies were assessed using an in-house enzyme-linked immunosorbent assay. Results: The prevalence of NAbs against SARS-CoV-2 was 92.1 %, 95.7 %, 64.1 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. The inhibition rate in individuals receiving two doses of ChAdOx1 vaccine (90.8%) was significantly higher than individuals who had recovered from natural infection (71.7%) or individuals who had received two doses of CoronaVac vaccine (66.7%). The prevalence of anti-spike Abs was 97.4 %, 97.8 %, 97.4 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. Significantly higher levels of anti-spike Abs were observed in the ChAdOx1 group after two doses of vaccination (1975 AU/mL) compared to those who had recovered from natural infection (468.5 AU/mL) and individuals who had received CoronaVac (554.4 AU/mL). Neutralizing activity had a statistically significant positive correlation with levels of anti-spike Abs. Conclusions: ChAdOx1 vaccine may provide superior immunogenicity than CoronaVac and natural infection

Nonalcoholic fatty liver disease and hepatic fibrosis among perinatally HIV-monoinfected Asian adolescents receiving antiretroviral therapy.

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance