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Few national programs and research cohorts within low- and middle-income countries (LMICs) document transition-related processes and outcomes for adolescents and young adults living with HIV (AYLH) transitioning to adulthood. Between 2017-2020, The Global fRAmework of Data collection Used for Adolescent HIV Transition Evaluation (GRADUATE) project convened a collaborative advisory group to identify key variables and definitions capturing the process, predictors, and outcomes across the transition period. In total, 114 variables identified as essential to measuring AYLH transition-related data were identified and formatted into a GRADUATE Data Exchange Standard (DES), which was added to and harmonized with the existing International epidemiology Databases to Evaluate AIDS (IeDEA) DES. In 2019, the GRADUATE DES was pilot tested at four IeDEA facilities in Malawi, South Africa, and Thailand through a cross-sectional study. Upon comparing the variables to routine medical records, available data were too limited to adequately capture transition-related processes and outcomes. However, additional data collection using GRADUATE tools was feasible and improved completeness. Of the 100 (52% female) AYLH included in the pilot study, 71% had transitioned/transferred to adult care, with 42% transitioning from an adolescent-specific model of care within an integrated family clinic to having their clinic visits scheduled on a different day of the week while 58% transferred from a pediatric facility to one offering adult HIV care. While almost all (94%) had a transition-related discussion with their healthcare providers prior to the transition, we found that 69% (95% CI 49-85%) were somewhat or very satisfied/comfortable with the post-transfer clinic and the staff. Utilization of the GRADUATE DES better characterized AYLH transitioning to adulthood across LMICs, and optimally measured transition preparation activities and outcomes. Utilization of the GRADUATE DES in other settings could facilitate comparisons and identify gaps in the care of transitioning adolescents that need to be addressed.
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OBJECTIVES: To develop a pragmatic twice daily lamivudine dosing strategy for preterm infants from 24 to 37 completed weeks of gestation. METHODS: Data were combined from eight pharmacokinetic studies in neonates and infants receiving lamivudine oral solution. A population pharmacokinetic model was developed using non-linear mixed effects regression. Different lamivudine dosing strategies, stratified by gestational age at birth (GA) bands, were simulated in a virtual population of preterm infants, aimed at maintaining lamivudine drug exposures (AUC0-12) within a reference target range of 2.95 to 13.25 µg·h/mL, prior to switching to WHO-weight band doses when ≥4 weeks of age and weighing ≥3 kg. RESULTS: A total of 154 infants (59% female) contributed 858 lamivudine plasma concentrations. Median (range) GA at birth was 38 (27-41) weeks. At the time of first pharmacokinetic sampling infants were older with median postnatal age (PNA) of 6.3 (0.52-26.6) weeks. Lamivudine concentrations were described by a one-compartment model, with CL/F and V/F allometrically scaled to weight. Maturation of CL/F was described using an Emax model based on PNA. CL/F was also adjusted on GA to allow extrapolation for extreme prematurity. Simulations predicted an optimal lamivudine dosing for infants GA ≥24 to <30 weeks of 2 mg/kg twice daily from birth until weighing 3 kg; and for GA ≥30 to <37 weeks, 2 mg/kg twice daily for the first 4 weeks of life, followed by 4 mg/kg twice daily until weighing 3 kg. CONCLUSIONS: Model-based predictions support twice daily pragmatic GA band dosing of lamivudine for preterm infants, but clinical validation is warranted.
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OBJECTIVES: Impact of frailty towards immunogenicity and reactogenicity of BNT162b2 boosters administered via intramuscular or intradermal routes in a Thai geriatric population DESIGN: Prospective, randomized, open-labeled. SETTING: Siriraj Hospital, Thailand. PARTICIPANTS: Geriatric adults aged ≥65 years. INTERVENTION: 10 µg intradermal or 30 µg intramuscular BNT162b2 (Pfizer-BioNTech). MEASUREMENTS: Anti-SARS-CoV-2 receptor binding domain IgG, neutralizing antibodies (NAb), and interferon-gamma producing cells against Wuhan and Omicron BA.4/5. Analyses were stratified based on participants' Clinical Frailty Scale. RESULTS: A total of 139 participants were included in the analysis. Two-four weeks post-booster administration, NAb titers against Wuhan but not Omicron BA.4/5 were significantly lower among frail participants than non-frail participants who received intramuscular administration. Spike-specific T cell responses were similar for frail and non-frail participants, regardless of administration route. Frail participants who received intradermal BNT162b2 had fewer local adverse events (AEs), but higher systemic AEs than non-frail participants. CONCLUSION: Similar immune responses across vaccine routes warrants further evaluation of intradermal BNT162b2 in frail geriatric populations. Frail participants may be more sensitive to reporting systemic AEs. REGISTRATION OF CLINICAL TRIALS: The parent study was registered under the Thai Clinical Trials Registry (TCTR20220112002).
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BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , Aged , Aged, 80 and over , Female , Humans , Male , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunology , ChAdOx1 nCoV-19 , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Frail Elderly , Immunization, Secondary , Injections, Intramuscular , Prospective Studies , Southeast Asian People , ThailandABSTRACT
Our multicenter, medical chart review, cost-of-illness study used a micro-costing approach to evaluate the economic burden associated with varicella in Bangkok, Thailand, from a societal perspective. We reviewed medical charts of adults and children with a primary diagnosis of varicella (2014-2018) from 4 hospitals in Bangkok. Reported healthcare resource utilization and missed school or workdays were extracted from medical charts. Mean direct, indirect, and total costs per patient were estimated for overall, adult, and pediatric patients (2020 USD). Of the 200 children and 60 adults, 99.6%, 5.4%, and 5.4% had a varicella-related outpatient visit, emergency department visit, and hospitalization, respectively. The mean direct medical cost was 33 USD for pediatric and adult patients. The mean cost of outpatient visits (8 vs 13 USD, P<0.001) and medications (7 vs 9 USD, P<0.001) was significantly lower among pediatric patients. Forty-eight children reported a mean of 5.8 school days lost, and 32 adult patients reported a mean of 7.4 workdays lost. The mean total cost per varicella patient was 89 USD, with the mean total cost higher for adult than pediatric patients (145 vs 72 USD, P<0.001). Indirect cost accounted for 63% of the total cost per patient (54% for pediatric patients and 77% for adult patients). There is a substantial economic burden associated with patients seeking varicella-related healthcare in Thailand, including considerable indirect costs.
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Transitioning from pediatric to adult care remains a challenge for adolescents and young adults with perinatally-acquired HIV (AYA-PHIV). We assessed treatment outcomes and mortality among Thai AYA-PHIV. The study included AYA-PHIV who reached age 18-24 years who started antiretroviral treatment during childhood at five pediatric HIV clinics across Thailand. From November 2020-July 2021, data were gathered from a cohort database, medical records, and the Thai National AIDS Program. Of 811 eligible AYA-PHIV, 93% were alive; median age 22.3 years (IQR 20.6-23.7), treatment duration 16.1 years (IQR 13.4-18.0). Current HIV care was provided in adults (71%) and pediatric clinics (29%). Treatment regimens included non-nucleoside reverse transcriptase inhibitors (55%), protease inhibitors (36%), and integrase inhibitors (8%); 78% had HIV RNA <200 copies/ml. Of the 7.0% who died, median age at death was 20.8 years (IQR 20.6-22.1); 88% were AIDS-related death. Mortality after age 18 was 1.76 per 100-person years (95% confidence interval 1.36-2.28). Those with CD4 <200 cell/mm3 at age 15 had higher risk of mortality (adjusted hazard ratio 6.16, 95% CI 2.37-16.02). In conclusion, the high mortality among Thai AYA-PHIV indicated the need for better systems to support AYA-PHIV during the transition to adulthood.
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HIV Infections , Humans , Thailand/epidemiology , Female , Male , HIV Infections/mortality , HIV Infections/drug therapy , Young Adult , Adolescent , Infectious Disease Transmission, Vertical/prevention & control , Transition to Adult Care , Anti-HIV Agents/therapeutic use , AdultABSTRACT
OBJECTIVES: We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS and Low-IS). METHODS: Patients aged 12-18 years diagnosed with SLE were enrolled. High-IS was defined as >7.5 mg/day prednisolone or with other immunosuppressant, while Low-IS was defined as only ≤7.5 mg/day of prednisolone and no immunosuppressant. Two doses of BNT162b2 vaccination were given 4 weeks apart, followed by a booster (third) dose at 4-6 months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) against Wuhan and Omicron variants, and cellular immune response by IFN-γ-ELISpot assay were evaluated following vaccination. Adverse events (AEs) and SLE flare were monitored. RESULTS: A total of 73 participants were enrolled, 40 and 33 in the High-IS and Low-IS group, respectively. At 4 weeks following the 2nd dose, overall anti-RBD IgG seropositivity was 97.3%, with no difference between the groups (p = .498). AdoSLE on High-IS had lower anti-RBD IgG (p < .001), Wuhan NT (p < .001), and IFN-γ-ELISpot (p = .022) than those on Low-IS. A 3rd dose induced significantly higher antibody responses than after the 2nd dose (p < .001) in both groups and established seroconversion against Omicron variants, with persistent lower antibody levels in High-IS group. SELENA-SLEDAI scores within 12 weeks after 2-dose vaccination was higher than before vaccination (3.1 vs 2.5; p < .036); however, the occurrence of disease flare by SELENA-SLEDAI flare index was not different after vaccination compared to before vaccination, consistent across groups. Non-severe AEs occurred similarly in both groups. CONCLUSION: AdoSLE on High-IS induced lower SARS-CoV-2 vaccine immune responses than Low-IS. Vaccination can increase disease activity and requires close monitoring for disease flare.
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Lupus Erythematosus, Systemic , Humans , Adolescent , Lupus Erythematosus, Systemic/drug therapy , BNT162 Vaccine , COVID-19 Vaccines/adverse effects , Symptom Flare Up , Prednisolone , Immunosuppressive Agents/adverse effects , Immunoglobulin G , Antibodies, Viral , Vaccination , Immunogenicity, VaccineABSTRACT
INTRODUCTION: There are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents. METHODS: This pilot study enrolled Thai adolescents 14-20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots. RESULTS: Of the 61 enrolled adolescents, median age 18.1 (IQR: 14.8-20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6-1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5-58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4-56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions. CONCLUSIONS: Daily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents , HIV Infections , Organophosphates , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , Adolescent , Young Adult , Adult , Female , HIV Infections/prevention & control , HIV Infections/drug therapy , Pilot Projects , Homosexuality, Male , Thailand/epidemiology , Emtricitabine/therapeutic useABSTRACT
INTRODUCTION: Human Immunodeficiency Virus (HIV) prevalence among young gender-diverse (a wide range of gender identities for people whose gender identity is different from the sex that they were assigned at birth) individuals is high but testing coverage among this key population remains low. We aim to evaluate strategies for outreach, HIV testing, and linkage to proper management in young men-who-have-had-sex-with-men (MSM, homosexual male) and transgender women (TGW) in Bangkok, Thailand. METHODS: The "YM2M outreach program" consisted of two strategies: 1) online platforms (OP) and 2) physical outreach activities (POA). Participant questionnaires were completed on a voluntary basis during outreach activities during 2018-2021. Demographic and behavioral characteristics were assessed for association with HIV positivity. RESULTS: A total of 3,972 homosexual male and TGW participated in the YM2M program: 2,973 by OP and 999 by POA. Of 2,230 participants who reported gender identity, 603/1,392 (43.3%) of OP and 252/985 (25.6%) of POA were gender diverse. Of 631 (21.2%) participants in OP and 970 (97.1%) in POA who underwent testing, 286 (45.3%) in OP and 41 (4.2%) in POA were HIV-positive. The venue reporting highest HIV yield was the Mor-Lam (11.5%). Among those with an HIV-positive test, 175 (61.2%) from OP and 23 (51.1%) from POA were successfully linked to HIV care. The independent factors associated with HIV positive in OP were being youth (adjusted odd ratio (aOR), 0.37; 95%CI 0.16-0.81; P = 0.01) and suspected or confirmed STI (aOR 15.39; 95%CI 7.17-33.03, P<0.01); while those in in POA at Mor-Lam were being gender diverse (aOR, 8.43; 95%CI 1.94-36.62; P<0.01) and reactive syphilis test (aOR, 5.40;95%CI 2.45-11.88; P<0.01). Linkage to pre-exposure prophylaxis (PrEP) among HIV-negative participants was low, 4.9% and 2.6% in OP and POA participants, respectively. CONCLUSIONS: While uptake of HIV testing was higher in POA while OP was more effective in identifying undiagnosed people living with HIV/AIDS and linking them to care. Neither strategy was considered effective in linkage to PrEP.
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HIV Infections , HIV Seropositivity , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Transgender Persons , Adolescent , Female , Humans , Male , Gender Identity , HIV , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/drug therapy , Homosexuality, Male , Sexual Behavior , Thailand/epidemiologyABSTRACT
INTRODUCTION: Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. METHODS: This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. RESULTS: Anti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5gen group at birth (118.8 [95% CI 93.9-150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (2.6 [1.7-4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. CONCLUSIONS: BioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.
Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines , Tetanus , Whooping Cough , Infant , Infant, Newborn , Cricetinae , Animals , Humans , Female , Pregnancy , Whooping Cough/prevention & control , CHO Cells , Antibodies, Bacterial , Cricetulus , Pertussis Vaccine , Vaccination , Vaccines, Synthetic , Tetanus Toxoid , Antibodies, Neutralizing , Mothers , Postpartum PeriodABSTRACT
BACKGROUND: Females with perinatal HIV (PHIV) infection are at elevated risk for anogenital high-risk human papillomavirus (HR-HPV) infection. Limited data are available around the effect of the HPV vaccination after initiation of sexual activity among PHIV youth. This study aims to assess the impact of a bivalent HPV vaccination on the persistence of anogenital HR-HPV among sexually active female PHIV youth and matched HIV-negative controls aged 12-24years in Thailand and Vietnam. METHODS: During a 3-year study, prevalent, incident, and persistent HR-HPV infection were assessed at annual visits. A subset of participants received a bivalent HPV vaccine. Samples were taken for HPV testing from the vagina, cervix, and anus. HR-HPV persistence was defined as the detection of the same genotype(s) at any anogenital compartment over≥two consecutive visits. RESULTS: Of the 93 PHIV and 99 HIV-negative female youth enrolled in this study, 25 (27%) PHIV and 22 (22%) HIV-negative youth received a HPV vaccine. Persistent infection with any HR-HPV type was significantly lower among PHIV youth who received the vaccine compared to those who did not (33%vs 61%, P =0.02); a difference was not observed among HIV-negative youth (35%vs 50%, P =0.82). PHIV infection (adjusted prevalence ratio [aPR] 2.31, 95% CI 1.45-3.67) and not receiving a HPV vaccine (aPR, 1.19, 95%CI 1.06-1.33) were associated with persistent anogenital HR-HPV infection. CONCLUSIONS: Bivalent HPV vaccination after initiation of sexual activity was associated with reduced persistence of anogenital HR-HPV infection in Southeast Asian PHIV female youth, which may be related to vaccine cross-protection. Primary and catch-up HPV vaccinations should be prioritised for children and youth with HIV.
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HIV Infections , Papillomavirus Infections , Papillomavirus Vaccines , Sexually Transmitted Diseases , Child , Pregnancy , Adolescent , Humans , Female , HIV , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Papillomavirus Infections/complications , HIV Infections/complications , Sexually Transmitted Diseases/complications , Vaccination , Prevalence , Papillomavirus Vaccines/therapeutic use , Human Papillomavirus VirusesABSTRACT
Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.
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The authors wish to make the following corrections to this published paper [...].
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Despite improvements in HIV testing and earlier antiretroviral therapy (ART) initiation in children living with HIV through the years, a considerable proportion start treatment with advanced disease. We studied characteristics of children and adolescents living with HIV and their level of immunodeficiency at ART initiation using data from a multi-country Asian cohort. We included children and adolescents who were ART-naïve and <18 years of age at ART initiation from 2011 to 2020 at 17 HIV clinics in six countries. Incidence rates of opportunistic infections (OIs) in the first two years of triple-drug ART (≥3 antiretrovirals) was also reported. Competing risk regression analysis was performed to identify factors associated with first occurrence of OI. In 2,027 children and adolescents (54% males), median age at ART initiation increased from 4.5 years in 2011-2013 to 6.7 in 2017-2020, median CD4 count doubled from 237 cells/µl to 466 cells/µl, and proportion of children who initiated ART as severely immunodeficient decreased from 70% to 45%. During follow-up, 275 (14%) children who received triple-drug ART as first treatment and had at least one clinic visit, developed at least one OI in the first two years of treatment (9.40 per 100 person-years). The incidence rate of any first OI declined from 12.52 to 7.58 per 100 person-years during 2011-2013 and 2017-2020. Lower hazard of OIs were found in those with age at first ART 2-14 years, current CD4 ≥200 cells/µl, and receiving ART between 2017 and 2020. The analysis demonstrated increasing number of children and adolescents starting ART with high CD4 count at ART start. The rate of first OI markedly decreased in children who started ART in more recent years. There remains a clear need for improvement in HIV control strategies in children, by promoting earlier diagnosis and timely treatment.
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HIV Infections , Opportunistic Infections , Adolescent , Child , Child, Preschool , Female , Humans , Male , Ambulatory Care , Anti-Retroviral Agents/therapeutic use , Asia/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiologyABSTRACT
BACKGROUND: Measuring the maximum occipitofrontal circumference only once at birth or within 24 h after birth may lead to misclassifications of microcephaly. This study compared the head circumference (HC) of newborns at birth or within 24 h after birth to their third day of life (DOL3) as well as evaluated maternal- and infant-specific factors associated with increased HC by DOL3. METHODS: This prospective study included 1131 live births between February and May 2019 with a gestational age > 27 weeks. All newborns had their HC measured at birth or within 24 h after birth as well as on DOL3 before discharge. HC measurements were performed by trained personnel using non-elastic tape measures. The World Health Organization (WHO) and Fenton Growth Charts were used as reference ranges for interpretation of full-term and preterm neonates, respectively. RESULTS: Paired sample t-test analyses found a statistically significant increase in HC measured on the DOL3 compared with HCs of the same newborns at birth or within 24 h of birth. The mean HC increase was 0.17 cm (95% confidence interval [0.13, 0.21], P < 0.001). The mean ± standard deviation HC within 24 h of birth and at DOL3 were 33.58 ± 1.53 cm and 33.75 ± 1.37 cm, respectively. Thirty-two newborns had HCs less than the third percentile (< P3) at birth, 25 of which had HC ≥ P3 at DOL3. After adjusting for mode of and presentation at delivery, newborns whose mothers experienced labor pains (ß = 0.31, P < 0.001) and were either symmetrically (ß = 0.59, P = 0.002) or asymmetrically small-for-gestational age (SGA; ß = 0.37, P = 0.03) had significantly increased HC at DOL3. On average, newborns whose mothers experienced labor pain had 0.31 cm increases in HC at DOL3. Symmetrical SGA newborns also had an average 0.59 cm increase in HC at DOL3. Parity and gestational age were not associated with changes in HC. CONCLUSIONS: Serial HC measurements on DOL3 or before newborns' discharge is crucial to classifying congenital microcephaly.
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Microcephaly , Pregnancy , Infant , Female , Humans , Infant, Newborn , Microcephaly/diagnosis , Prospective Studies , Cephalometry , Gestational Age , Infant, Small for Gestational AgeABSTRACT
Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31â¯785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16â¯639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.
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COVID-19 , Adolescent , Humans , Child , Male , Infant , Child, Preschool , Female , COVID-19/epidemiology , SARS-CoV-2 , Pandemics , OxygenABSTRACT
OBJECTIVE: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children. METHODS: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-µg) or half-dose (5-µg) BNT162b2 vaccines as follows: CoronaVac/10-µg-BNT162b2 (Group 1), CoronaVac/5-µg-BNT162b2 (Group 2), 10-µg-BNT162b2/10-µg-BNT162b2 (Group 3), or 10-µg-BNT162b2/5-µg-BNT162b2 (Group 4). A subset of participants from each arm received 10-µg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported. RESULTS: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter. CONCLUSION: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.
Subject(s)
COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , Child , Child, Preschool , Female , Humans , Male , Antibodies, Neutralizing , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Prospective Studies , SARS-CoV-2 , Southeast Asian People , VaccinationABSTRACT
COVID-19 vaccines have been introduced in children and adolescents in many countries. However, high levels of community transmission and infection-derived immunity make the decision to introduce COVID-19 vaccination of children in countries yet to do so particularly challenging. For example, other vaccine preventable diseases, including measles and polio, generally have far higher childhood morbidity and mortality in low-income and middle-income countries (LMICs) than COVID-19, and coverage with these vaccines has declined during the pandemic. Many countries are yet to introduce pneumococcal conjugate and rotavirus vaccines for children, which prevent common causes of childhood death, or human papillomavirus vaccine for adolescents. The Pfizer and Moderna COVID-19 vaccines that have been widely tested in children and adolescents have a positive risk-benefit profile. However, the benefit is less compared with other life-saving vaccines in this age group, particularly in LMICs and settings with widespread infection-derived immunity. The resources required for rollout may also pose a considerable challenge in LMICs. In this paper, we describe COVID-19 in children, with a focus on LMICs, and summarise the published literature on safety, efficacy and effectiveness of COVID-19 vaccination in children and adolescents. We highlight the complexity of decision-making regarding COVID-19 vaccination of children now that most of this low-risk population benefit from infection-derived immunity. We emphasise that at-risk groups should be prioritised for COVID-19 vaccination; and that if COVID-19 vaccines are introduced for children, the opportunity should be taken to improve coverage of routine childhood vaccines and preventative healthcare. Additionally, we highlight the paucity of epidemiological data in LMICs, and that for future epidemics, measures need to be taken to ensure equitable access to safe and efficacious vaccines before exposure to infection.
Subject(s)
COVID-19 , Adolescent , Humans , Child , COVID-19 Vaccines , Vaccination , 2019-nCoV Vaccine mRNA-1273 , PandemicsABSTRACT
Objective: To describe the risk condition status and clinical outcomes among Thai children hospitalized with pneumococcal disease. Methods: In this retrospective analysis, children with invasive pneumococcal disease (IPD) or x-ray-confirmed non-bacteraemic pneumococcal pneumonia (NBPP) were identified from nine hospitals in Thailand between 2010 and 2019. Data on risk factors and outcomes were extracted from medical records. Results: In total, 413 cases were identified: 319 IPD and 94 NBPP. Overall, 133 (32.2%) patients were admitted to intensive care units and 11/406 (2.7%) died. Twenty-seven percent of IPD cases had at-risk conditions and 15% had high-risk conditions. Most IPD cases (32.9%) occurred in children aged 2-4 years, and most NBPP cases (28.7%) occurred in infants aged 0-11 months. Of 51 Streptococcus pneumoniae isolates collected, 41 (80%) were pneumococcal 13-valent conjugate vaccine serotypes. Only 5.1% of children had received a pneumococcal vaccine. Conclusions: Most children with IPD and NBPP did not have high-risk or at-risk conditions, while 42% had at-risk or high-risk conditions for pneumococcal disease. Very few children in the cohort had received any type of pneumococcal vaccine. Increasing the availability of pneumococcal conjugate vaccines should be considered to reduce the burden of pneumococcal disease among children in Thailand.