CHARACTERIZATION OF CLINICAL AND BIOLOGIC MANIFESTATIONS OF CHIKUNGUNYA AMONG CHILDREN IN AN URBAN AREA, THAILAND: A RETROSPECTIVE COHORT STUDY.

Chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, has reemerged in Southeast Asia since 2019. A retrospective review of CHIKV cases was conducted. Children commonly presented with high-grade fever, rash, arthralgia, and lymphopenia. Neurological manifestations or shock occurred in 20% of hospitalized children. These findings indicate the need for increased vigilance for CHIKV alongside dengue in travelers from Southeast Asia with suspected mosquito-borne viral infections.

Challenges towards an AIDS-free generation in Africa and Asia.

PURPOSE OF REVIEW: To review the latest data on prevention of HIV vertical transmission in Asia and Africa and discuss strategic directions to achieve an AIDS free generation by 2030. RECENT FINDINGS: Progress in vertical transmission elimination efforts in Africa and Asia have stalled in the last decade, with 130 000 new infections in 2022. Main causes of vertical transmissions vary; in Asia-Pacific due to its low-burden, thus low testing coverage, but high overall vertical transmission rates, in South and East Africa due to new HIV infections during pregnancy and breast/chestfeeding, whereas in Western and Central Africa due to low antiretroviral therapy (ART) coverage. Long-acting injectable ART and neutralizing antibodies for treatment and prevention show promise in supporting efforts to further reduce vertical transmissions. Integrated and more accessible pre- and postnatal care is needed to achieve an AIDS-free generation. SUMMARY: Much can be implemented to address existing HIV service gaps; including strengthening of HIV prevention services for youth and women of childbearing age and pregnant people, early detection and treatment, and the delivery of integrated services that can reach and retain pregnant and postpartum people living with HIV in care.

Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium.

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms.

INTRODUCTION: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg. METHODS: Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C 24 ) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C 24 concentration. RESULTS: From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C 24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL. CONCLUSIONS: Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.

Predicting oxygen needs in COVID-19 patients using chest radiography multi-region radiomics.

The objective is to evaluate the performance of blood test results, radiomics, and a combination of the two data types on the prediction of the 24-h oxygenation support need for the Coronavirus disease 2019 (COVID-19) patients. In this retrospective cohort study, COVID-19 patients with confirmed real-time reverse transcription-polymerase chain reaction assay (RT-PCR) test results between February 2020 and August 2021 were investigated. Initial blood cell counts, chest radiograph, and the status of oxygenation support used within 24 h were collected (n = 290; mean age, 45 ± 19 years; 125 men). Radiomics features from six lung zones were extracted. Logistic regression and random forest models were developed using the clinical-only, radiomics-only, and combined data. Ten repeats of fivefold cross-validation with bootstrapping were used to identify the input features and models with the highest area under the receiver operating characteristic curve (AUC). Higher AUCs were achieved when using only radiomics features compared to using only clinical features (0.94 ± 0.03 vs. 0.88 ± 0.04). The best combined model using both radiomics and clinical features achieved highest in the cross-validation (0.95 ± 0.02) and test sets (0.96 ± 0.02). In comparison, the best clinical-only model yielded AUCs of 0.88 ± 0.04 in cross-validation and 0.89 ± 0.03 in test set. Both radiomics and clinical data can be used to predict 24-h oxygenation support need for COVID-19 patients with AUC > 0.88. Moreover, the combination of both data types further improved the performance.

High mortality in adolescents and young adults with perinatally-acquired HIV in Thailand during the transition to adulthood.

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.

Phase II prefusion non-stabilised Covid-19 mRNA vaccine randomised study.

ChulaCov19 mRNA vaccine demonstrated promising phase 1 results. Healthy adults aged 18-59 years were double-blind randomised 4:1 to receive two intramuscular doses of ChulaCov19 50 µg or placebo. Primary endpoints were safety and microneutralization antibody against-wild-type (Micro-VNT50) at day 50. One hundred fifty adults with median (IQR) age 37 (30-46) years were randomised. ChulaCov19 was well tolerated, and most adverse events were mild to moderate and temporary. Geometric mean titres (GMT) of neutralizing titre against wild-type for ChulaCov19 on day 50 were 1367 IU/mL. T-cell IFN-γ-ELISpot showed the highest responses at one week (Day29) after dose 2 then gradually declined. ChulaCov19 50 µg is well tolerated and elicited high neutralizing antibodies and strong T-cell responses in healthy adults.Trial registration number: ClinicalTrials.gov Identifier NCT04566276, 28/09/2020.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines.

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.

Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

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.

Hybrid immunity from SARS-CoV-2 infection and mRNA BNT162b2 vaccine among Thai school-aged children.

Objective: To compare the immune response of hybrid immunity - arising from SARS-CoV-2 infection and mRNA BNT162b2 vaccination - to that of 2-doses of vaccine. Methods: In a subanalysis of BNT162b2 vaccine trial in 5 to 11-year-old children, There were 179 children who had hybrid immunity compared with 134 children with solely 2-dose vaccine. The immunological outcome was a surrogate virus neutralization test (sVNT) against the Omicron strain, BA.1, (%inhibition). An sVNT level ≥68 % inhibition was considered as protective immune response. Results: From February to April 2022, 179 children had COVID-19 natural infection resulting in hybrid immunity included: Group1;prior vaccination(n = 17), Group2;after the first dose(n = 61), and Group3;after the second dose(n = 97). The proportion of children with protective immune response was higher in Group 3 and Group 1 - 61.9 % and 58.8 %, compared to 36.1 % and 34.3 % in Group 2 and comparator group (2 doses of vaccine), respectively. The geometric mean % inhibition of sVNT was higher in Group 1 (68.5, 95 %CI 55.5-84.6) and Group 3 (63.5, 95 %CI 55.5-72.6), followed by comparator group (49.6, 95 %CI 44.8-54.9) and Group 2 (42.1, 95 %CI 34.6-51.3), p < 0.001. Conclusions: Immune response that arises from BNT162b2 vaccine after natural infection and infection after 2 doses of BNT162b2 was higher than infection after partially-vaccinated children.

Global COVID-19 Vaccination in Infants and Children: Effectiveness, Safety, and Challenges.

COVID-19 Vaccines, which include mRNA and inactivated vaccines, have been proven effective and safe for infants and children aged more than six months in reducing the severity of the disease, hospitalization, multisystem inflammatory syndrome in children, and death. Nonetheless, the real-world effectiveness of these vaccines in preventing infection is generally lower than in clinical trials due to the emergence of variants of concern, especially the Omicron strains. Despite the availability of vaccines for children, their uptake remains low globally, particularly among parents who are hesitant to vaccinate their children. This review article aims to provide a comprehensive overview of COVID-19 vaccine safety and efficacy from clinical trials and the current COVID-19 vaccine recommendations for infants and children aged 6 months to < 12 years for 2023-2024, discuss the progress made in vaccine implementation and real-world effectiveness, and address the knowledge gap and future directions.

The changing characteristics of a cohort of children and adolescents living with HIV at antiretroviral therapy initiation in Asia.

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.

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial.

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124-159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir. FUNDING: Penta Foundation, ViiV Healthcare, and UK Medical Research Council.

Immunogenicity of BNT162b2 in children 6 months to under 5 years of age with previous SARS-CoV-2 infection, in the era of Omicron predominance.

Background: Children 6 months to < 5 years old are recommended to receive 3-dose regimen of BNT162b2. Children previously infected with Omicron variant of SARS-CoV-2 develop immunity from natural infection, therefore may require fewer doses of vaccine. Objective: To compare immunogenicity of 1- or 2-dose BNT162b2 in healthy children post COVID-19 with 3-dose BNT162b2 in COVID-naïve children. Methods: Children aged 6 months to < 5 years who developed COVID-19 during the Omicron-predominant period were enrolled; Group A 3-6 months(N = 40) and Group B > 6 months(N = 40) prior to vaccination. Participants in Group A and B received 2-dose BNT162b2 intramuscularly 1 month apart. COVID-naïve children were enrolled as a control group (N = 40) and received 3-dose BNT162b2 at month 0,1,3. Neutralizing antibody against Omicron variant(BA.2.75 and BA.4/5) was determined by pseudovirus assays(pVNT) as reported by neutralization dilution for 50%inhibition (ID50) at 28 days after the 1st and 2nd dose. Results: From October-November 2022, 120 children with a median age of 2.8 years (IQR 1.6-4.0) were enrolled. The median duration since COVID-19 to vaccination was 4.4 months(IQR 3.8-5.4) in Group A and 7.9 months(7.0-8.5) in Group B. In Group A, the geometric means(GMs) of pVNT-BA.2.75 ID50 were 553 (95%CI 338-906) and 753(516-1098) after 1 and 2 doses, respectively, and the GMs of pVNT-BA.4/5 ID50 were 1936(1402-2673) and 1885(1414-2512), respectively. In Group B, the GMs of pVNT-BA.2.75 ID50 were 1383(1100-1742) and 1419 (1104-1823), and the GMs of pVNT-BA.4/5 ID50 were 2627(2048-3367) and 2056(1546-2735), respectively. Meanwhile in COVID-naïve group, the GMs of pVNT-BA.2.75 and pVNT-BA.4/5 ID50 were 158(98-255) and 59(31-114) after the 3rd dose, respectively. The geometric mean ratio(GMR) of pVNT-BA.2.75 ID50 after 1 dose in Group A and B compared with after 3 doses in COVID-naïve group were 3.50 (1.93-6.34) and 8.74 (4.79-15.95), respectively. The GMR of pVNT-BA.2.75 ID50 after 1 dose in Group B compared with Group A was 2.50 (1.45-4.31). Conclusions: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.

Outcomes among Thai children with risk conditions hospitalized for pneumococcal disease (invasive or non-bacteraemic pneumonia): A multi-centre, observational study.

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.

A Three-Year Follow-Up of Bone Density Among Thai Adolescents With Perinatally Acquired HIV After Completion of Vitamin D and Calcium Supplementation.

PURPOSE: To determine changes in bone mineral density (BMD) and bone metabolism-related biomarkers among Thai adolescents with perinatally acquired HIV infection (PHIVA) at 3 years following completion of vitamin D and calcium (VitD/Cal) supplementation. METHODS: An observational follow-up study was conducted among PHIVA who received 48-week VitD/Cal supplementation (either high-dose [3,200 IU/1,200 mg daily] or standard-dose [400 IU/1,200 mg daily]). Lumbar spine BMD (LSBMD) was assessed by dual-energy x-ray absorptiometry. Serum 25-hydroxyvitamin D, intact parathyroid hormone, and bone turnover markers were measured. Changes in LSBMD z-scores and other bone parameters at 3 years after stopping VitD/Cal supplementation compared with baseline or week 48 of supplementation were assessed among participants previously receiving high-dose and standard-dose VitD/Cal supplementation. RESULTS: Of 114 enrolled PHIVA, 46% and 54% had previously received high-dose and standard-dose VitD/Cal supplementation, respectively. The median age was 20 years; 53% were male. At 3 years after completion of VitD/Cal supplementation, we observed a significant decline in 25-hydroxyvitamin D and increase in intact parathyroid hormone but no significant rebounds of C-terminal telopeptides of collagen type I and procollagen type I amino-terminal propeptides and no significant changes in LSBMD z-scores among PHIVA in both treatment groups, compared with the measurements at week 48 of supplementation. Notably, LSBMD z-scores at 3 years after stopping VitD/Cal supplements were not significantly altered from baseline evaluations in both PHIVA groups. DISCUSSION: Three years after completion of high-dose or standard-dose VitD/Cal supplementation, LSBMD z-scores of our Thai PHIVA were not significantly changed from baseline and week 48 of supplementation. VitD/Cal supplementation of PHIVA during periods of peak bone mass accrual may have sustained and long-term skeletal benefits.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women.

INTRODUCTION: Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdapchem) shown effective for maternal immunization. METHODS: This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or tetanus, reduced-dose diphtheria combined with ap1gen (Tdap1gen), or combined with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.5 µg pertactin (Boostrix™, Tdap8chem). Blood was collected at Day 0 and Day 28 post-vaccination. The non-inferiority of the study vaccines was assessed based on anti-PT IgG antibody levels on Day 28 pooled with results from a similarly structured previous trial in non-pregnant women. RESULTS: 400 healthy pregnant women received one dose of vaccine. Combined with data from 250 non-pregnant women, all study vaccines containing PTgen were non-inferior to comparator vaccine (Tdap8chem). Both ap1gen and TdaP5gen vaccines could be considered to have superior immunogenicity to Tdap8chem. Local and systemic solicited reactions were similar among all vaccine groups. CONCLUSIONS: Vaccine formulations containing PTgen were safe and immunogenic in pregnant women. The ap1gen vaccine, with the lowest cost and reactogenicity, may be suitable for use in pregnant women when diphtheria and tetanus toxoids are not needed. This study is registered in the Thai Clinical Trial Registry (www. CLINICALTRIALS: in.th), number TCTR20180725004.

Evaluation of Clinical Case Definitions for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Young Children.

BACKGROUND: Various case definitions of respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) are currently proposed. We assessed the performance of 3 clinical case definitions against the World Health Organization definition recommended in 2015 (WHO 2015). METHODS: In this prospective cohort study conducted in 8 countries, 2401 children were followed up for 2 years from birth. Suspected LRTIs were detected via active and passive surveillance, followed by in-person clinical evaluation including single timepoint respiratory rate and oxygen saturation (by pulse oximetry) assessment, and nasopharyngeal sampling for RSV testing by polymerase chain reaction. Agreement between case definitions was evaluated using Cohen's κ statistics. RESULTS: Of 1652 suspected LRTIs, 227 met the WHO 2015 criteria for RSV-LRTI; 73 were classified as severe. All alternative definitions were highly concordant with the WHO 2015 definition for RSV-LRTI (κ: 0.95-1.00), but less concordant for severe RSV-LRTI (κ: 0.47-0.82). Tachypnea was present for 196/226 (86.7%) WHO 2015 RSV-LRTIs and 168/243 (69.1%) LRTI/bronchiolitis/pneumonia cases, clinically diagnosed by nonstudy physicians. Low oxygen saturation levels were observed in only 55/226 (24.3%) WHO 2015 RSV-LRTIs. CONCLUSIONS: Three case definitions for RSV-LRTI showed high concordance with the WHO 2015 definition, while agreement was lower for severe RSV-LRTI. In contrast to increased respiratory rate, low oxygen saturation was not a consistent finding in RSV-LRTIs and severe RSV-LRTIs. This study demonstrates that current definitions are highly concordant for RSV-LRTIs, but a standard definition is still needed for severe RSV-LRTI. CLINICAL TRIAL REGISTRATION: NCT01995175.