Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model.

BACKGROUND: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. METHODS: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. RESULTS: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4-37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167-379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9-15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87-5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). CONCLUSION: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored.

Short-term immune response after inactivated SARS-CoV-2 (CoronaVac®, Sinovac) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-AstraZeneca) vaccinations in health care workers.

BACKGROUND: Inactivated SARS-CoV-2 (CoronaVac®, Sinovac, or SV) and ChAdOx1 nCoV-19 (Vaxzevria®, Oxford-Astra Zeneca, or AZ) vaccines have been administered to the health care workers (HCWs). OBJECTIVE: To determine the short-term immune response after the SV and AZ vaccinations in HCWs. METHODS: In this prospective cohort study, HCWs who completed a 2-dose regimen of the SV or AZ were included. Immune response was evaluated by surrogate viral neutralization test (sVNT) and anti-SARS-CoV-2 total antibody. Blood samples were analyzed at 4 and 12 weeks after the complete vaccination. The primary outcome was the seroconversion rate at 4-weeks after complete immunization. RESULTS: Overall, 185 HCWs with a median (IQR) age of 40.5 (30.3-55.8) years (94 HCWs in the SV group and 91 in the AZ group) were included. At 4 weeks after completing the SV vaccination, 60.6% (95%CI: 50.0-70.6%) had seroconversion evaluated by sVNT (≥ 68% inhibition), comparable to the patients recovered from mild COVID-19 infection (69.0%), with a rapid reduction to 12.2% (95%CI: 6.3-20.8) at 12 weeks. In contrast, 85.7% (95%CI: 76.8-92.2%) HCWs who completed two doses of the AZ for 4 weeks had seroconversion, comparable to the COVID-19 pneumonia patients (92.5%), with a reduction to 39.2% (95%CI: 28.4-50.9%) at 12 weeks. When using the anti-SARS-CoV-2 total antibody level (≥ 132 U/ml) criteria, only 71.3% HCWs in the SV group had seroconversion, compared to 100% in the AZ group at 4 weeks. CONCLUSIONS: A rapid decline of short-term immune response in the HCWs after the SV vaccination indicates the need for a vaccine booster, particularly during the ongoing spreading of the SARS-CoV-2 variants of concern.

Prevalence of latent tuberculosis infection and feasibility of TB preventive therapy among Thai prisoners: a cross-sectional study.

BACKGROUND: Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). METHODS: A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. RESULTS: From August 2018-November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32-50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16-2.01, p = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74-5.24, p < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24-2.79, p = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. CONCLUSION: This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

Behavioral problems in perinatally HIV-infected young children with early antiretroviral therapy and HIV-exposed uninfected young children: prevalence and associated factors.

Although behavioral problems have been observed in children and adolescents with perinatally-acquired HIV infection (PHIV), behavioral information regarding younger PHIV children are scarce. This study aims to identify behavioral problems in PHIV and HIV-exposed uninfected (HEU) children and to evaluate factors associated with such problems. A prospective study of PHIV and HEU young children was conducted. Behavioral problems were assessed with the Child Behavior Checklist (CBCL) at baseline and 12 months later among children aged 18-60 months old. The Patient Health Questionnaire-9 and the Parenting Styles & Dimensions Questionnaire identified primary caregivers' symptoms of depression and parenting styles, respectively, at both visits. Chi-squared analyses were used to compare the prevalence of behavioral problems between groups. Factors associated with behavioral problems were analyzed by logistic regression. From 2016 to 2017, 121 children (41 PHIV and 80 HEU) were assessed with no significant differences in prevalence of Total, Internalizing, Externalizing, and Syndrome scales problems between PHIV and HEU at both visits (p > 0.5). Primary caregivers' depression and lower education in addition to authoritarian and permissive parenting styles were significantly related to child behavioral problems. Family-centered care for families affected by HIV, including positive parenting promotion, mental health care, and education are warranted.

Real-Life Clinical Practice of Using the Xpert MTB/RIF Assay in Thailand.

BACKGROUND: Delayed diagnosis of tuberculosis (TB) and drug-resistant TB are major challenges of TB control in Thailand. This study assessed the practicality of the Xpert MTB/RIF assay in a real-life setting with high prevalence of human immunodeficiency virus (HIV) infection and pulmonary tuberculosis (PTB). METHODS: This prospective study was conducted at 3 large tertiary care hospitals. Patients who had suspected PTB were enrolled into the study. Expectorated sputum samples were sent for staining, mycobacterial culture, and Xpert MTB/RIF. RESULTS: Four hundred ninety-four patients were enrolled. From 355 cases with final diagnosis of PTB, 263 (71.8%) had definite diagnosis and 92 cases had probable diagnosis. Among TB culture-positive cases, Xpert MTB/RIF had 100% and 81% sensitivity in sputum smear-positive and smear-negative groups, respectively. The specificity was 95.7%. The sensitivity and positive predictive value of Xpert MTB/RIF in culture-negative but clinically diagnosed PTB was 37.8% and 83.8%, respectively. Centrifugation was required in 59% cases with scanty sputum. Five cases were false-positive by Xpert MTB/RIF in patients with nontuberculous mycobacteria, old PTB scar, and immune reconstitution syndrome. Discordant rifampicin susceptibility results of Xpert MTB/RIF and mycobacteria growth indicator tube (MGIT) were confirmed by using rpoB gene sequencing, which raised the sensitivity of Xpert MTB/RIF in detecting rifampicin resistance to 93.8%. CONCLUSIONS: Xpert MTB/RIF is an effective tool in diagnosing PTB but will be more cost-effective for sputum-negative patients and in settings with high prevalence of rifampicin resistance. Early diagnosis of TB results in early treatment and implementation of strategies to limit spreading of TB. Sputum centrifugation may increase the yield of Xpert MTB/RIF.

Differences Between Men Who Have Sex with Men (MSM) with Low CD4 Cell Counts at Their First HIV Test and MSM with Higher CD4 Counts in Bangkok, Thailand.

Although HIV prevalence remains high among Bangkok's MSM early HIV testing as an entry point to ART has not been successfully implemented among in this population. Men who present late for initial HIV testing are a particular concern in the context of the Bangkok HIV epidemic, in that if long-term positives have had condomless sex during the time that they remained untreated they are likely to have been efficient transmitters of infection, to say nothing of the implications for their own health. A sequential sample of MSM who tested HIV positive, and CD4 counts, was taken at the Thai Red Cross Anonymous Clinic and two drop-in centers in Bangkok. Inclusion criteria were MSM aged >18 years, having not tested HIV positive earlier, who reported ≥1 of the following in the previous 6 months: condomless sex with a male, being a sex worker, or having a sexual transmitted infection (STI) diagnosis. Analysis was conducted by distinguishing between three groups of CD4 counts: <200, 200-500, >500 cells/µ to identify the social and behavioral characteristics of the men who presented late for HIV testing. Median CD4 was 325 cells/µ(n = 95). MSM with initial CD4< 200 cells/µ were significantly more likely to report problematic alcohol use. They were also more likely to report receptive anal sex and more likely to be engaged in sex work. MSM with CD4< 200 cells/µ were less likely to report recent HIV testing. Main barriers to HIV testing included being afraid of finding out that they were HIV positive and concerns about efficacy and side effects of HIV treatment. HIV stigma and concerns about treatment are still widespread and are potential barriers to HIV care among MSM in Bangkok. These barriers may work to keep men from finding out their positive HIV status in a timely manner. Thai MSM need to be made aware of the current availability of friendly HIV testing and ART services, and public health programs need to work to change their perceptions regarding ART itself. These same types of strategies might also work to destigmatize HIV and MSM within Thai society as a whole.

HIV disclosure and its effect on treatment outcomes in perinatal HIV-infected Thai children.

The World Health Organization guideline recommends informing children of their HIV status between the ages of 6-12 years. Primary caregivers of perinatal HIV-infected Thai children ≥6 years were interviewed in order to assess the HIV status disclosure rate. In addition, pill counts of antiretroviral therapy (ART) were performed every three months. CD4 and HIV-RNA were performed every six months. Of the 260 children/adolescents included, the median age of disclosure was 14.8 years. The disclosure rate among those from 6 to 12 years was 21% and for those greater than 12 years of age was 84%. When comparing children aged 6-12 years whose HIV status had been disclosed to them, to children whose HIV had yet to be disclosed, no difference was noted in median ART adherence by pill count, CD4 count, or proportion of HIV-RNA <50 copies/ml (p > 0.05). Factors associated with HIV disclosure were an age of ≥12 years (OR 17.8, 95% CI 8.86-35.79) and a current CD4 ≤ 30% (OR 2.09, 95% CI 1.20-3.62). In conclusion, although the majority of adolescents ≥12 years were aware of their HIV status only one-fifth of children aged 6-12 years were aware. Moreover, the child's/adolescent's disclosure status had no bearing on ART adherence by pill count or immunological and virological outcomes.

A multivariable normal tissue complication probability model for predicting radiation-induced hypothyroidism in nasopharyngeal carcinoma patients in the modern radiotherapy era.

Radiation-induced hypothyroidism (RHT) is a common long-term complication for nasopharyngeal carcinoma (NPC) survivors. A model using clinical and dosimetric factors for predicting risk of RHT could suggest a proper dose-volume parameters for the treatment planning in an individual level. We aim to develop a multivariable normal tissue complication probability (NTCP) model for RHT in NPC patients after intensity-modulated radiotherapy or volumetric modulated arc therapy. The model was developed using retrospective clinical data and dose-volume data of the thyroid and pituitary gland based on a standard backward stepwise multivariable logistic regression analysis and was then internally validated using 10-fold cross-validation. The final NTCP model consisted of age, pretreatment thyroid-stimulating hormone and mean thyroid dose. The model performance was good with an area under the receiver operating characteristic curve of 0.749 on an internal (200 patients) and 0.812 on an external (25 patients) validation. The mean thyroid dose at ≤45 Gy was suggested for treatment plan, owing to an RHT incidence of 2% versus 61% in the >45 Gy group.

Prevalence and Risk Factors of Healthcare-Associated Infections among Hospitalized Pediatric Patients: Point Prevalence Survey in Thailand 2021.

BACKGROUND: Healthcare-associated infections (HAIs) pose a grave threat to patient safety, morbidity, and mortality, contributing to antimicrobial resistance. Thus, we estimated the point prevalence, risk factors, types, and pathogens of HAIs in hospitalized pediatric patients. METHODS: A point prevalence survey (PPS) of HAIs in hospitalized pediatric patients < 18 years old was conducted from March to May 2021. Outcomes, risk factors, and types of HAIs associated with HAIs in 41 hospitals across Thailand were collected. RESULTS: The prevalence of HAIs was 3.9% (95% CI 2.9-5.0%) (56/1443). By ages < 1 month, 1 month-2 years, 2-12 years, and 12-18 years, the prevalence of HAIs was 4.2%, 3.3%, 4.1%, and 3.0%, respectively (p = 0.80). Significant independent risk factors were extended hospital length of stay (LOS) and central venous catheter (CVC) use. Compared to an LOS of <4 days, LOSs of 4-7 days, 8-14 days, and >14 days had adjusted odds ratios (aORs) of 2.65 (95% CI 1.05, 6.68), 5.19 (95% CI 2.00, 13.4), and 9.03 (95% CI 3.97, 20.5), respectively. The use of a CVC had an aOR of 2.45 (95% CI 1.06-5.66). Lower respiratory tract infection (LRTI) was the most common HAI type (46.4%: 26/56). The highest prevalence of HAIs was predominantly observed in LRTI diagnoses, with the highest among these in the <1 month age category at 2.3% (17/738). CONCLUSION: The prevalence of HAIs in hospitalized pediatric patients was 3.9%. Extended LOS and use of CVC were HAI risk factors. A strategy for reducing LOS and reviewing insertion indications or the early planned removal of a CVC was implemented. The surveillance of HAIs stands as a cornerstone and fundamental component of IPC, offering invaluable insights that enhance hospital IPC interventions aimed at preventing HAIs.

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.

Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU.

Background: A consensus on the definition of prolonged mechanical ventilation (PMV) for children does not exist. There is still lack of published work presenting the epidemiology, risk factors and outcomes at different cut-points for PMV patients. These are important for planning the goals of treatment and counseling of the prognosis for patient families. We aimed to determine the incidence, baseline characteristics, risk factors and outcomes of PMV in pediatric patients at various cut-points (>14, >21 or >30days). Methods: A retrospective cohort study among children <18-years-old who were PMV > 14 days in the PICU of King Chulalongkorn Memorial Hospital was conducted. The primary outcomes were incidence of PMV with various cut-points. We stratified patients into three groups (Group 1; PMV > 14-21, Group 2; >21-30, Group 3; >30 days) for evaluating the baseline characteristics, risk factors, and outcomes of PMV (extubation success, tracheostomy status and death). Factors associated with PMV and deaths were analyzed using univariate and multivariate logistic regression. Results: From January 2018 to August 2022, 1,050 patients were screened. Of these, 114 patients were enrolled. The incidence of PMV > 14, >21 and >30 days were 10.9%, 7.3% and 5.0% respectively. Extubation success was significantly lower in Group 3 than in Groups 1 & 2 (15.4% vs. 62.2% & 56.0%, P < 0.001). Consequently, the tracheostomy rate (63.5% vs. 16.2% & 12.0%, P < 0.001), VAP rate (98.1% vs. 59.5% & 80.0%, P < 0.001), mortality rate by disease (34.6% vs. 5.4% & 20.0%, P = 0.003), median PICU LOS (50.5 vs. 22.0 & 28.0 days, P < 0.001) and median hospital LOS (124.5 vs. 55.0 & 62.0 days, P < 0.001) were also significantly higher for Group 3 compared with Groups 1 & 2. The factor associated with PMV > 30 days was VAP (aOR: 19.53, 95% CI: 2.38-160.34, P = 0.01). Factors associated with non-surviving patients were 3rd degree PEM (aOR: 5.14, 95% CI: 1.57-16.88, P = 0.01), PIM3 score ≥14 (aOR: 6.75, 95% CI: 2.26-20.15, P < 0.001) and muscle relaxant usage (aOR: 5.58, 95% CI: 1.65-18.86, P = 0.01). Conclusion: Extubation failure, tracheostomy rate, VAP rate, mortality rate by disease, PICU LOS and hospital LOS were significantly higher for PMV >30 days. Consequently, we suggest that a 30-day duration as a cut-point for PMV in PICUs might be more appropriate.

Corrigendum: Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU.

[This corrects the article DOI: 10.3389/fped.2023.1167595.].

Prevalence of depression and anxiety in pulmonary tuberculosis patients and its association with unsuccessful treatment outcome: A prospective cohort study.

BACKGROUND: Pulmonary tuberculosis (TB) remains a major public health problem in Thailand. TB causes chronic disease which may cause physical disability, mental and socioeconomic problems in TB patients. Mental disorders may occur after TB infection or co-exist with the disease. This study assessed the prevalence of depression and anxiety among pulmonary TB patients and its association with treatment outcome. METHODS: This is a single-center prospective study. Pulmonary TB patients who were treated at a tertiary hospital, in both outpatient and in-patient settings, were enrolled into the study. Demographic data and Thai Hospital Anxiety and Depression Scale (HADS) score at baseline and at least 2 months after diagnosis were collected to evaluate the probability of depression and anxiety. Logistic regression model was used to analyze the data. Association between suspicious mental disorder and treatment outcome were evaluated at the end of each participant's treatment. RESULTS: One hundred and three participants were enrolled into the study on March 2018 to October 2019. The prevalence of probable depression and anxiety (Thai HADS score ≥11 from both test) were 7.8% and 6.8%, respectively. Unsuccessful treatment outcome rate was 10.7% (11/103). From the multivariate analysis, people previously treated/relapsed (aOR (95%CI): 7.04 (1.19-41.85), p = 0.03) and probable depression/anxiety with Thai HADS score ≥11 (10.12 (1.54-66.45), p = 0.02) were associated with unsuccessful treatment outcome. CONCLUSIONS: In this study, Thai HADS score could identify probable depression and anxiety among pulmonary TB patients, and its association with unfavorable treatment outcome. Clinicians should keep in mind that pulmonary TB can affect the mental status of the patients and therefore, should evaluate them and provide appropriate treatment.

Point prevalence survey of antibiotic use among hospitalized patients across 41 hospitals in Thailand.

Objectives: To describe the antibiotic use among hospitalized patients in Thailand. Methods: A standardized cross-sectional point prevalence survey (PPS) modified from the WHO PPS protocol was conducted in 41 selected hospitals in Thailand. All inpatients who received an antibiotic at 9 a.m. on the survey date were enrolled. The total number of inpatients on that day was the denominator. Results: Between March and May 2021, a total of 8958 inpatients were enumerated; 4745 inpatients received antibiotics on the day of the survey and there were 6619 prescriptions of antibiotics. The prevalence of antibiotic use was 53.0% (95% CI 51.1%-54.0%), ranging from 14.3% to 73.4%. The antibiotic use was highest among adults aged >65 years (57.1%; 95% CI 55.3%-58.9%). From 6619 antibiotics prescribed, 68.6% were used to treat infection, 26.7% for prophylaxis and 4.7% for other or unknown indications. Overall, the top three commonly used antibiotics were third-generation cephalosporins (1993; 30.1%), followed by first-generation cephalosporins (737; 11.1%) and carbapenems (703; 10.6%). The most frequently used antibiotics for community-acquired infections were third-generation cephalosporins (36.8%), followed by ß-lactam/ß-lactamase inhibitors (11.8%) and carbapenems (11.3%) whereas for the patients with hospital-acquired infections, the most common antibiotics used were carbapenems (32.7%), followed by ß-lactam/ß-lactamase inhibitors (15.7%), third-generation cephalosporins (11.7%) and colistin (11.7%). The first-generation cephalosporins were the most commonly used antibiotics (37.7%) for surgical prophylaxis. Seventy percent of the patients received surgical prophylaxis for more than 1 day post surgery. Conclusions: The prevalence of antibiotic use among hospitalized patients in Thailand is high and one-quarter of these antibiotics were used for prophylaxis. The majority of surgical prophylaxis was inappropriately used for a long duration post operation. Therefore, it is recommended that local guidelines should be developed and implemented.

Safety and Immunogenicity of Homologous and Heterologous Adenoviral-Vectored and mRNA COVID-19 Vaccine Regimens in Radiotherapy Patients.

Diminished immune response after vaccination occurs in cancer patients. This observational study evaluated the immune response and safety profile after COVID-19 vaccination in radiotherapy patients. The study comprised 53 cancer patients undergoing radiotherapy and voluntarily received the COVID-19 vaccine. The two regimens were homologous ChAdOx1-S recombinant (AstraZeneca, AZ), "AZ-AZ" and heterologous "AZ-mRNA". The seroconversion rate and anti-RBD immunoglobulin geometric mean titers (GMT) were assessed and compared with healthy controls. Adverse effects were assessed using a questionnaire. The seroconversion rate was 52.4% 1 month after the first dose with GMT 4.3 U/mL (95%CI 1.4-13). Following the second dose, the AZ-AZ group achieved 95% seroconversion rate with GMT = 188.4 U/mL (95%CI 67.1-529), which was significantly lower than the healthy cohort, GMT = 945 U/mL (95%CI 708-1261). Cancer patients in AZ-mRNA group achieved a 100% seroconversion rate with a high GMT = 1400.8 U/mL (95%CI 429.5-4566), which was significantly lower than the healthy cohort, GMT = 5169.9 U/mL (95%CI 3582.2-7461.5). Most adverse effects were mild. Our findings suggest that radiotherapy patients had fair immunogenicity after the first dose, but achieved a high seroconversion rate after the second dose with manageable adverse effects. However, their immunologic response was lower than in healthy individuals, indicating that other preventive strategies are needed.

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.

The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial.

OBJECTIVES: To evaluate the immunogenicity of an extended interval regimen of BNT162b2 among healthy school-age children. METHODS: A randomized-control trial conducted among healthy Thai children aged 5-11 years. Participants received two doses of BNT162b2 with an 8-week (extended dosing) vs 3-week interval. Immunogenicity was determined by neutralization test (NT) against the Omicron variant, surrogate virus NT (sVNT; BA.1, % inhibition), and pseudovirus NT (BA.2, the half-maximal inhibition dilution or ID50). The third dose was offered to participants who had sVNT <68% inhibition. The immunogenicity outcome was evaluated at 14 days after the second and third doses. RESULTS: During February to April 2022, 382 children with a median age (interquartile range) of 8.4 years (6.6-10.0) were enrolled. At 14 days, after two doses of BNT162b2, the geometric means of sVNT in 8-week vs 3-week interval groups were 49.6 (95% confidence interval [CI] 44.8-54.9) vs 16.5 (95% CI 13.0-20.9), with a geometric means ratio of 3.0 (95% CI 2.4-3.8). Among 102 participants who received the third dose at a median of 15 weeks from the second dose, the geometric means of sVNT increased to 73.3 (95% CI 69.0-77.8) and pseudovirus NT increased to 326 (95% CI 256-415). CONCLUSION: The extended 8-week interval regimen of BNT162b2 induced higher neutralizing antibodies than a standard 3-week interval regimen. The third dose induced high neutralizing antibodies against the Omicron variant.

Good performance of syphilis rapid diagnostic test kits among young key populations in Thailand.

BACKGROUND: The prevalence of syphilis is increasing among adolescents and young adults (AYAs) globally. Use of syphilis rapid diagnostic treponemal tests (RDTs) may improve test coverage and same-day treatment. This study aims to determine sensitivity and specificity of two syphilis RDTs. METHODS: A cross-sectional study was conducted in men who have sex with men and transgender women aged 15-24 years attending a sexual health clinic in Bangkok. Syphilis RDTs used were Determine Syphilis TP and Bioline Syphilis 3.0, using whole blood from finger pricks and venipuncture. Treponemal pallidum electrochemiluminescence assay was used as standard reference. RESULTS: From February to July 2022, 200 AYAs with a mean age 21.1 (SD2.1) years were enrolled, including 50 (25.0%) living with HIV. Prevalence of syphilis was 10.5% (95%CI 6.6-15.6), which was higher among AYAs living with HIV (22.0%) compared with AYAs unaffected by HIV (6.7%). Sensitivities of Determine Syphilis TP and Bioline Syphilis 3.0 were 85.7% (95%CI 63.7-97.0) and 66.7% (95%CI 43.0-85.4), respectively. Specificity of both RDTs was 100% (95%CI 98.0-100.0). Performance of RDTs was similar for both specimens. CONCLUSIONS: Syphilis RDTs have high sensitivity and specificity in diagnosing syphilis. It should be considered for use in sexual health clinics with high syphilis prevalence to initiate treatment promptly.

Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy.

We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of <-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10) copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy.

Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency.

INTRODUCTION: Human APOBEC3G is a host defense factor that potently inhibits HIV replication. We hypothesize that HIV-infected children with a genetic variant of APOBEC3G will have a more rapid disease progression. METHODS: Antiretroviral therapy (ART)-naïve children, aged 1-12 years old with CD4 15-24% and without severe HIV-related symptoms were enrolled. The children had CD4% and absolute CD4 counts every 12 weeks and HIV-RNA every 24 weeks until 144 weeks. ART was started when CD4% declined to < 15% or AIDS-related events developed.APOBEC3G genetic variants were performed by PCR-based restriction fragment length polymorphism techniques from peripheral blood mononuclear cells. Random-effect linear regression analysis was performed to correlate APOBEC3G genotypes and disease progression. RESULTS: 147 children, 35% male, with a median (IQR) age of 6.5 (4.3-8.8) years were enrolled. CDC N:A:B were 1:63:36%. Median baseline values were 20% for CD4% 605 cells/mm3 for CD4 count and 4.7 log10copies/mL for HIV-RNA.The frequencies of APOBEC3G genotypes AA (186H/H), AG (186H/R), GG (186R/R) were 86%, 12%, and 2% respectively. The APOBEC3G genotype GG was associated with a significant decline in CD4% -5.1% (-8.9 to -1.2%), p<0.001, and CD4 counts -226 (-415 to -34) cells/mm3, p<0.001 by random-effect liner regression analysis. No significant associations of APOBEC3G genotypes with HIV-RNA changes overtime (p=0.16) or progression to CDC B and C (p=0.49) were observed. CONCLUSIONS: APOBEC3G genotype GG was significantly associated with a more rapid decline in CD4. APOBEC3G's antiviral effects on HIV disease progression in children should be further explored.