Neonatal Multisystem Inflammatory Syndrome (MIS-N): The First Case Report in Thailand

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

Metabolic Disorders in HIV-Infected Adolescents Receiving Protease Inhibitors

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

Immunogenicity of a Two-Dose Human Papillomavirus Vaccine Schedule in HIV-Infected Adolescents with Immune Reconstitution

HIV-infected patients are at increased risk of human papillomavirus (HPV) acquisition and HPV-associated diseases. This study set out to determine whether a two-dose (2D) HPV vaccination schedule was sufficient in HIV-infected adolescents with immune reconstitution (IR) following antiretroviral treatment. Participants aged 9–15 years who had CD4 cell counts > 500 cells/mm3 and HIV-1 RNA p = 0.946), respectively, and the anti-HPV-18 GMTs were 2039.3 (1432.2–2903.8) and 2859.8 (1810.0–4518.4) in the 2D and 3D (p = 0.313) groups, respectively. In females, the anti-HPV-16 GMTs were 15,758.7 (8868.0–28,003.4) and 26,241.6 (16,972.7–40,572.3) in the 2D and 3D groups (p = 0.197), respectively, and the anti-HPV-18 GMTs were 5971.4 (3026.8–11,780.6) and 9993.1 (5950.8–16,781.1) in the 2D and 3D groups (p = 0.271), respectively. In summary, a 2D schedule is as immunogenic in young adolescents with IR as a 3D schedule in older subjects and those without IR

A pilot program of HIV pre-exposure prophylaxis in Thai youth.

IntroductionThere are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents.MethodsThis 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.ResultsOf 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.ConclusionsDaily 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

Elevated Inflammatory Mediators in Adults with Oculorespiratory Syndrome following Influenza Immunization: a Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network Study

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

Immunogenicity and reactogenicity of heterologous COVID-19 vaccination in pregnant women

This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18–45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0–35.5) years and gestational age of 23.5 (IQR 18.0–30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery (r = 0.719, P < .001) and inversely correlated with elapsed time after the second vaccination (r = −0.366, P < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings