Severe acute respiratory syndrome coronavirus 2 infection rate among pediatric patients with respiratory symptoms.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) in children has been increasing worldwide since the onset of the pandemic. This study examined the risk factors and characteristics of COVID-19 among pediatric patients compared to other respiratory viral infections. METHODS: This was a prospective cross-sectional study. Patients aged 0-18 years presenting with respiratory symptoms from October 2020 to December 2021 were included. Demographic and clinical data were reviewed. RESULTS: In total, 738 pediatric patients were enrolled. Of these, 48.5% had COVID-19, and 41.3% were infected with another respiratory virus. The COVID-19 incidence increased from 0.5% during the original strain outbreak (October 2020 to March 2021) to 56.5% and 73.4% during the alpha (April to June 2021) and delta (July to December 2021) periods, respectively. Children aged 6-18 years, being female, obesity, exposure to household members with COVID-19, and the delta period were risk factors for COVID-19. Being aged 1-5 years, obesity, shortness of breath, productive cough, and chest pain were associated with COVID-19 pneumonia. Children aged 5-18 years, underlying neurological disease, a history of COVID-19 pneumonia, and the delta period were associated with long COVID. CONCLUSIONS: Pediatric COVID-19 patients presenting with respiratory symptoms who are obese or have been exposed to household members with COVID-19 should be tested for COVID-19. COVID-19 patients who are obese, younger than five years old, or who present with shortness of breath, productive cough, or chest pain should be evaluated for pneumonia. COVID-19 patients with a history of COVID-19 pneumonia or underlying neurological disease should receive follow-up for long COVID.

Bloodstream bacterial infections in thalassemic pediatric and adolescent patients after hematopoietic stem cell transplantation.

BACKGROUND: Thalassemic patients usually require regular blood transfusions; however, HSCT can provide a cure. Incidence of IBI in pediatric patients post-HSCT is still scant. OBJECTIVES: This study aimed to explore whether thalassemic patients had a different incidence of post-HSCT IBI compared with patients with other underlying diseases. Factors associated with IBI in the pediatric population undergoing HSCT were also investigated. METHODS: In this retrospective cohort study, clinical data of pediatric patients who underwent HSCT during the period from 2011 to 2016 were reviewed and analyzed. The primary outcome was incidence of IBI within 1-year post-HSCT. RESULTS: Of 123 patients, 53 were thalassemic. IBI was diagnosed in 23 patients within 1 year after HSCT (incidence: 19.5 episodes/1000 patients/month). The IBI incidence was lower in thalassemic patients than in patients with other underlying diseases (6.9 vs. 31.6 episodes/1000 patients/month). Having thalassemia as an underlying disease was the only factor associated with lower IBI in pediatric post-HSCT patients (hazard ratio: 0.245; 95% confidence interval, 0.080-0.748). In post-HSCT thalassemic patients, IBI mostly occurred within 100 days after HSCT, and most of these cases had catheter-related blood stream infection. The risk of IBI tended higher for haploidentical HSCT, but this difference was not statistically significantly different. CONCLUSION: The IBI incidence after HSCT was lower in thalassemic patients than in those with other underlying diseases. Catheter-related blood stream infection was the major IBI in these patients. IBI was not a major complication in thalassemic pediatric patients undergoing HSCT.

Pediatric drug utilization evaluation of cefepime and piperacillin/tazobactam.

BACKGROUND: Drug utilization evaluation (DUE) is a systematic, criteria-based assessment of medicine that aims to optimize the appropriateness of antibiotic prescription. This study aimed to evaluate the performance of the DUE on prescriptions of two commonly used antibiotics in a pediatric population, cefepime and piperacillin/tazobactam, in a tertiary care hospital. METHODS: This quasi-experimental study was conducted at the Department of Pediatrics, Ramathibodi Hospital, between March 2020 and August 2021. All hospitalized children aged 1 month to 20 years who received at least one dose of cefepime or piperacillin/tazobactam were enrolled. Before implementing the DUE, cefepime and piperacillin/tazobactam prescriptions were retrospectively evaluated using the DUE criteria. During the 6 month DUE implementation period, physicians voluntarily chose to use DUE to assess the prescriptions' appropriateness. Demographic data, antibiotic use, and clinical data were recorded. RESULTS: There were 304 prescriptions of cefepime and piperacillin/tazobactam, with 108 empirical prescriptions (72 patients) in the DUE group and 158 prescriptions (138 patients) in the non-DUE group. The appropriateness of empirical prescriptions of cefepime and piperacillin/tazobactam was significantly higher in the DUE group (93.5% vs. 83.5%; P = 0.003). Drug utilization evaluation was significantly associated with appropriate empirical prescriptions (adjusted OR 5.32: 95% CI 1.80-15.73; P = 0.003). Prescriptions in critical care wards and urinary tract infections (UTIs) were associated with not fulfilling the DUE criteria for appropriateness. CONCLUSIONS: Drug utilization evaluation could improve the appropriateness of empirical use of cefepime and piperacillin/tazobactam in pediatric patients. Patients in critical care units and with UTIs appeared to be associated with inappropriate empirical treatment.

Handshake stewardship reduces carbapenem prescription in a pediatric critical care setting.

BACKGROUND: Intensive care unit (ICU) settings typically have a high-volume prescription of carbapenems. Antimicrobial stewardship programs (ASPs) aim to promote appropriate antibiotic use. Handshake stewardship (HS) is adapted from ASPs but focuses on direct feedback to physicians who prescribed antibiotics regarding the appropriateness of antibiotic prescription. This study aimed to evaluate the impact and acceptability of HS on carbapenem consumption in pediatric critical care settings. METHODS: This study was conducted over 18 months spanning pre-and post-implementation of HS. Carbapenem prescriptions were automatically discontinued during the pre-implementation period after 72 h if no indications existed. During the post-implementation, HS was performed by direct feedback to ICU physicians regarding the appropriateness of carbapenem prescriptions within 24 h. The primary outcome was the carbapenem consumption rate, defined as days of therapy (DOT)/1,000 patient-ICU days. Secondary outcomes were the acceptability of HS, length of critical care stay (LOCS), 30-day infection-related mortality rate, and the rate of carbapenem-resistant Enterobacteriaceae (CRE). RESULTS: There were 212 carbapenem prescriptions (163 patients) and 174 carbapenem prescriptions (110 patients) in the pre-and post-implementation periods, respectively. Carbapenem consumption decreased significantly from 667 to 369 DOT/1,000 patient-ICU days, with a median difference of 292 DOT/1,000 patient-ICU days (P < 0.001; 95% confidence interval: 175-408) after HS implementation. The acceptability of the HS was 95.4%. The LOCS, 30-day infection-related mortality, and CRE rate were not significantly different between pre-and post-implementation periods. CONCLUSIONS: Handshake stewardship significantly reduced carbapenem prescription in critically ill pediatric patients without negatively affecting patient outcomes.

Immunogenicity of varicella zoster vaccine in pediatric liver transplantation.

BACKGROUND: Pediatric liver transplant (LT) candidates often miss complete varicella-zoster virus (VZV) vaccination before LT. We aimed to evaluate the immunogenicity of two doses of VZV vaccines in pediatric LT candidates younger than 2 years and persistence of its immunogenicity after LT. METHODS: Patients aged 9-24 months were enrolled before LT. The first dose of VZV vaccine was given at 9 months, and the second dose was given at between 1 to 3 months later, and at least 4 weeks before LT. Varicella-zoster IgG (VZG) was used to detect immunoglobulin G antibodies to VZV and was reported as a test value (TV). A test value ≥ 0.9 was considered as seropositive. TV was measured at enrollment, 1 month after the first and the second dose of VZV vaccine, before LT, and 3 and 6 months after LT. RESULTS: Fourteen children were enrolled in this prospective cohort study. The median age at the first and the second dose of VZV vaccine was 11.5 months (IQR 9-12) and 13 months (IQR 12-33), respectively. The seroconversion rate was 66.7% (8/12) and 70% (7/10) after the first and second VZV vaccine doses, respectively. Seven of nine patients who underwent LT had two doses of VZV vaccine. Six patients were seropositive before LT, which persisted at 3 to 6 months after LT. Of two patients who received only one dose, TV was not detected after LT. CONCLUSIONS: The two doses of VZV vaccine appeared to be more immunogenic than one dose in pediatric LT candidates aged less than 2 years.

Association between adenovirus infection and mortality outcome among pediatric patients after hematopoietic stem cell transplant.

BACKGROUND: Adenovirus can cause severe diseases in post-hematopoietic stem cell transplant (HSCT) patients. Because these patients also have many other factors contributing to mortality, it remains controversial whether adenovirus infection itself contributes to increased mortality in these patients. OBJECTIVE: To determine if adenovirus infection contributes to mortality in pediatric post-HSCT patients. METHODS: This retrospective cohort study was performed in post HSCT patients, aged 0-18 years old, admitted at Ramathibodi Hospital from 2016 to 2020. Adenovirus infection was defined as the detection of adenovirus in blood or urine by polymerase chain reaction. Multivariate cox regression was used to identify factors associated with death. RESULTS: The incidence of overall adenovirus infection (viremia or viruria) in this cohort was 20.8% (26 out of 125 enrolled patients). From the multivariate cox regression analysis, overall adenovirus infection was not significantly associated with death (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 0.96-6.06; p = .060). However, presence of viremia (HR: 3.90; 95% CI: 1.40-10.86; p = .009), having maximal serum viral load > 10 000 copies/ml (HR: 3.70; 95% CI: 1.20-11.38; p = .023), presence of end-organ diseases (HR: 3.44; 95% CI: 1.18-10.01; p = .023) were associated with mortality. Underlying diseases requiring long-term immunosuppressive drugs before HSCT, invasive fungal disease, invasive bacterial infection, cytomegalovirus infection, and longer engraftment time were also associated with mortality. CONCLUSION: Overall adenovirus infection does not appear to play a significant role in mortality in pediatric post-HSCT patients. However, more invasive forms of adenovirus infection were associated with mortality in these patients.

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) recipients require hepatitis B (HBV) revaccination. Hepatitis B surface antibody (anti-HBs) seroconversion rates after revaccination range from 64% to 79% in these patients. The seroconversion rate and factors associated with non-seroconversion have not been clearly elucidated in pediatric and young adult recipients after HSCT. OBJECTIVES: To evaluate anti-HBs seroconversion rates in pediatric and young adult patients revaccinated after HSCT, and to identify factors associated with non-seroconversion. METHOD: The current study was prospective and cross-sectional. Post-HSCT recipients aged ≤25 years who had completed a course of three HBV revaccinations were recruited, and their anti-HBs titers were assessed. Non-seroconverted patients were administered a fourth vaccination. Those who subsequently remained seronegative were administered two additional vaccinations. Those who remained seronegative after all six vaccinations were defined as non-responders. RESULTS: A total of 118 patients were enrolled. The HBV-containing vaccines used included DTaP-IPV-HBV-Hib, DTwP-HBV-Hib, and monovalent vaccines. The anti-HBs seroconversion rate after three revaccinations was 82% (95% confidence interval [CI], 73.7-89.2). One patient (0.8%) was classified as non-responder. Factors associated with non-seroconversion after three revaccinations included cytomegalovirus (CMV) reactivation (odds ratio [OR] 10.63, 95% CI 1.16-97.00), anti-HBs seronegativity before HSCT (OR 7.01, 95% CI 1.55-31.78) and three DTwP-HBV-Hib revaccinations (OR 11.71, 95% CI 1.43-96.26). CONCLUSION: In the current study the anti-HBs seroconversion rate after three HBV revaccinations was excellent. CMV reactivation, anti-HBs seronegativity before HSCT, and three DTwP-HBV-Hib revaccinations were associated with non-seroconversion, but the non-responder rate was low.

B cell subset alteration and the expression of tissue homing molecules in dengue infected patients.

BACKGROUND: B cells play an essential role during dengue viral infection. While a major expansion of antibody secreting cells (ASCs) was observed, the importance of these increased frequencies of ASCs remains unclear. The alteration of B cell subsets may result from the expression of tissue specific homing molecules leading to their mobilization and distribution to different target organs during acute dengue viral infection. METHODS: In this study, whole blood samples were obtained from thirty pediatric dengue-infected patients and ten healthy children and then stained with fluorochrome-conjugated monoclonal antibodies against CD3, CD14, CD19, CD20, CD21, CD27, CD38, CD45, CD138 and homing molecules of interest before analyzed by polychromatic flow cytometry. B cell subsets were characterized throughout acute infection period. RESULTS: Data shows that there were no detectable differences in frequencies of resting, activated and tissue memory cells, whereas the frequency of ASCs was significantly increased and associated with the lower frequency of naïve cells. These results were found from patients with both dengue fever and dengue hemorrhagic fever, suggesting that such change or alteration of B cells was not associated with disease severity. Moreover, several homing molecules (e.g., CXCR3 and CCR2) were found in ASCs, indicating that ASCs may distribute to inflamed tissues and various organs. CONCLUSIONS: Findings from this study provide insight into B cell subset distribution. Furthermore, organ mobilization according to homing molecule expression on different B cell subsets during the course of dengue viral infection also suggests they are distributed to inflamed tissues and various organs.

Viral-specific T-cell response in hemorrhagic cystitis after haploidentical donor stem cell transplantation.

Viral hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) can be devastating. Standard treatment modalities have not been well established, but immune reconstitution may be necessary for sustained viral clearance. We studied five pediatric patients who developed viral HC after haplo-identical HSCT. All patients developed virus-specific CD4- and CD8-positive T cells, and the emergence of these viral-specific T cells was temporally associated with successful viral clearance.

Pediatric extended spectrum ß-lactamase infection: Community-acquired infection and treatment options.

BACKGROUND: Infection caused by extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in pediatric patients has been increasing and spreading to the community, compromising the options for effective antibiotics. This retrospective study was conducted to identify which antibiotics ESBL-producing Enterobacteriaceae remain susceptible to. In addition, the prevalence of community-acquired infection caused by these organisms, and the possibility of association between these organisms and septic shock, were explored. METHODS: Antibiotic susceptibility of ESBL-producing and non-ESBL-producing Escherichia coli and Klebsiella pneumoniae strains isolated from pediatric patients were reviewed to determine the rates of susceptibility to various antibiotics. A chart review was performed to clarify the prevalence of community-acquired infection and the severity. RESULTS: Of 849 strains analyzed, 40% were ESBL positive. Apart from cephalosporins, ESBL-producing strains were also less likely to be susceptible to other antibiotics, such as quinolones, gentamicin, netilmicin, and cotrimoxazole, more than 90% of which were still susceptible to amikacin, carbapenems, colistin, and tigecycline. Around 20% of community-acquired infections in the present study were caused by ESBL-producing strains. ESBL-producing strains found in the community were more likely to be susceptible to gentamicin, netilmicin, and cefepime than those found in hospital. Infection caused by ESBL-producing strains was not significantly associated with septic shock. CONCLUSION: The increase in infection caused by ESBL-producing Enterobacteriaceae limits the availability of effective antibiotics. Given that carbapenems are necessary for treating serious infections, amikacin, cefepime, and piperacillin/tazobactam are possible options for consolidative therapy or for non-serious infection.

Economic and Clinical Outcomes of Pediatric Patients Under Two With Respiratory Syncytial Virus Infection in Thailand: A Real-world Retrospective Cohort Study.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of acute respiratory tract infection in children, including in Thailand. We conducted this study to evaluate the economic and clinical outcomes of patients <2 years old with RSV infection at a tertiary teaching hospital in Thailand. METHODS: This was a retrospective cohort study during 2014-2021. To be eligible, patients had to report at least 1 positive RSV test and were <2 years old. Descriptive statistics were used to describe baseline characteristics, healthcare resource utilization, direct medical costs (1 US dollars [USD] = 31.98 Thai Baht) and clinical outcomes. RESULTS: Among 1370 RSV-positive patients, 49.9% of the patients (n = 683) were hospitalized at or within 3 days of RSV diagnosis with a median length of stay of 6 days (interquartile range [IQR]: 4-9 days), 38.8% were diagnosed with RSV-related respiratory complications (n = 532) and 1.5% died during the hospitalization episode (n = 20). A total of 22.5% of hospitalized patients (n = 154) received critical care during the hospitalization episode. The median cost of each RSV episode was USD539 (IQR: USD167-USD2106) and was higher among hospitalized patients (median: USD2112; IQR: USD1379-USD3182) compared with nonhospitalized patients (median: USD167; IQR: USD112-USD276). CONCLUSIONS: RSV infection represents a potentially important contributor to healthcare resource use and medical costs among children <2 years old in Thailand. Coupled with epidemiologic data, findings from our study will be useful to illustrate the overall economic burden associated with RSV infection among children in Thailand.

Immunogenicity of Hepatitis B Vaccine in Pediatric Systemic Lupus Erythematosus Patients.

BACKGROUND: Pediatric patients with systemic lupus erythematosus (SLE) are at increased infectious risk caused by underlying immunologic dysregulation and immunosuppressive therapy. Hepatitis B virus (HBV) could be reactivated during the immunosuppressive treatment in patients with past HBV infections. Information on immunogenicity after hepatitis B (HB) immunization and reimmunization are still scarce. METHODS: SLE patients 5-18 years of age who had completed a primary HB immunization were enrolled. Anti-HBs levels at enrollment and after each vaccine dose were determined. Patients with anti-HBs levels < 10 mIU/mL were administered 1 booster dose. After 1 booster dose, patients with negative anti-HBs levels were administered 2 more booster doses. RESULTS: Ninety-three SLE patients were enrolled. The prevalence of seroprotection assessed by anti-HBs > 10 mIU/mL after completion of a primary HB immunization was 25.8% (95% CI: 17.2-34.4). Lupus nephritis was associated with unprotective anti-HBs levels [odds ratio (OR): 4.341; 95% CI: 1.044-18.040]. The anti-HBs seroconversion was 72.3% (95% CI: 61.5-83.0) after 1 booster dose and increased up to 93.4% (95% CI: 86.9-98.4) after 3 booster doses. SLE Disease Activity Index-2000 score ≥ 4 (OR: 4.625; 95% CI: 1.45-14.80) was significantly associated with nonseroconversion after the first booster dose. Hypocomplementemia before the first and second booster doses (OR: 27; 95% CI: 1.26-578.35) was significantly associated with nonseroconversion after 3 booster doses. CONCLUSIONS: All pediatric SLE patients should be evaluated for HBV serological status before immunosuppressive treatment. SLE patients with SLE Disease Activity Index-2000 score > 4 should need 3 booster doses if their anti-HBs level was < 10 mIU/mL.

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.

Immunogenicity and reactogenicity of fractional, heterologous primary COVID-19 vaccination schedules with BNT162b2 boosters in 5-11-year-old Thai children: A multicenter, prospective, double-blind, randomized control trial.

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.

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.

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases.

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12-18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7-16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7-74.2) and 233.6 (95% CI 79-690.6); adolescents with cancer 62.3 (95% CI 29.2-133.1) and 214.9(95% CI 34.2-1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4-84.8) and 849.8 (95% CI 393.4-1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3-98.8) and 3240.3 (95% CI 2699-3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3-98.9) and 3818.5 (95% CI 3490.4-4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8-62.4) and 178.7 (95% CI 91.2-350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4-92.8) and 1037.1 (95% CI 933.3-1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required.

Good recovery of immunization stress-related responses presenting as a cluster of stroke-like events following CoronaVac and ChAdOx1 vaccinations.

BACKGROUND: Immunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand. METHODS: We conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site. RESULTS: Overall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores ≤2, indicating slight or no disability). CONCLUSIONS: Immunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.

Increase in invasive Streptococcus pneumoniae infections in children with sickle cell disease since pneumococcal conjugate vaccine licensure.

Invasive pneumococcal disease (IPD) in children with sickle cell disease has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine usage. We report 10 IPD cases since pneumococcal protein-conjugate vaccine licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in sickle cell disease.

Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains.

RATIONALE: Mycoplasma pneumoniae was recently discovered to produce an ADP-ribosylating and vacuolating cytotoxin, designated CARDS toxin, which is hypothesized to be a primary pathogenic mechanism responsible for M. pneumoniae-induced pulmonary inflammation. It is unknown if cytotoxin production varies with M. pneumoniae strain or if variation in cytotoxin production affects pulmonary disease severity. OBJECTIVES: To examine the production of CARDS toxin by various strains of M. pneumoniae and compare the disease manifestations elicited by these strains in an experimental model of M. pneumoniae respiratory infection. METHODS: BALB/c mice were inoculated once intranasally with SP4 broth (negative control) or three different M. pneumoniae strains: M129-B7, M129-B9, or S1. Mice were assessed at 1, 2, 4, 7, 10, and 14 days after inoculation. Outcome variables included comparisons among M. pneumoniae strains relative to bronchoalveolar lavage (BAL) M. pneumoniae quantitative culture, CARDS toxin-based PCR, and CARDS toxin protein determinations, as well as cytokine and chemokine concentrations. Graded lung histopathologic score (HPS) was also assessed. MEASUREMENTS AND MAIN RESULTS: CARDS toxin concentrations were significantly increased in mice inoculated with strain S1 compared with mice inoculated with M129-B7 or M129-B9 strains. Quantitative M. pneumoniae culture and polymerase chain reaction were also significantly greater in mice infected with S1 strain compared with the other two strains, as were lung HPS and concentrations of IFN-γ, IL-12, IL-1α, macrophage inflammatory protein-1α, and keratinocyte-derived chemokine. In addition, a significant positive correlation was found between CARDS toxin concentration and lung HPS. CONCLUSIONS: CARDS toxin concentrations in BAL are directly linked to the ability of specific M. pneumoniae strains to colonize, replicate, and persist, and elicit lung histopathology. This variation among strains may predict the range in severity of pulmonary disease observed among patients.

Invasive Fungal Disease Among Pediatric and Adolescent Patients Undergoing Itraconazole Prophylaxis After Hematopoietic Stem Cell Transplantation.

BACKGROUND: Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Itraconazole has been used for prevention of IFD, but data related to incidence and associated factors of IFD in pediatric and adolescent patients on itraconazole prophylaxis remain scarce. OBJECTIVES: To identify incidence and risk factors associated with IFD among pediatric and adolescent patients receiving itraconazole prophylaxis after HSCT. METHODS: Patients younger than 21 years who received itraconazole prophylaxis after HSCT from January 2007 to December 2016 were retrospectively enrolled. Incidence of IFD within 1 year and associated factors were analyzed. RESULTS: All patients received itraconazole during the pre-engraftment period. Of 170 patients, 29 had IFD, with an incidence of 17.1% at 1 year. IFD at 1 year was significantly associated with increased mortality. Of 29 patients with IFD, only 9 developed IFD while on itraconazole prophylaxis (5.3%), all of whom had invasive pulmonary aspergillosis. No invasive candidiasis occurred during itraconazole prophylaxis. Prolonged neutropenia (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.02-1.13), graft-versus-host disease within 100 days after transplantation (HR = 3.17; 95% CI, 1.17-8.57), and using etoposide in preconditioning regimens (HR = 21.60; 95% CI, 2.44-190.95) were significantly associated with IFD at 1 year. No patients had to discontinue itraconazole because of its adverse effects. CONCLUSIONS: Itraconazole proffered good efficacy for prevention of candidiasis during the pre-engraftment period. Most IFD episodes occurred after the engraftment period when itraconazole had been discontinued. During this period, patients with risk factors require appropriate fungal prophylaxis.