•IgA in breast milk was not associated with reduced RV3-BB vaccine take in Indonesia.•IgG titre in cord blood was associated with lower vaccine immunogenicity after one, not three doses of ...vaccine.•RV3-BB vaccine appears to be able to be given with breast-feeding in high rotavirus disease burden settings.
Placental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia.
196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0–5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68). Rotavirus specific IgA and NA in colostrum and breast milk, rotavirus specific cord IgG, Serum IgA and stool excretion were measured.
There was little evidence of an association between IgA in colostrum or breast milk and cumulative vaccine take after three doses in the neonatal or infant groups. In the neonatal group, there was a negative association between IgG titre in cord blood and cumulative vaccine take (odds ratio OR 0.96; 95% confidence interval CI 0.92–1.00; p = 0.03) and serum IgA response (OR 0.94; 95%CI 0.89–0.99; p = 0.02) after one dose of vaccine, which were not evident after three doses in the neonatal or infant groups.
Amongst Indonesian infants we did not find an association between IgA in colostrum or breast milk and vaccine take after 3 doses of RV3-BB vaccine. Maternal rotavirus antibodies in breast milk appear to have minimal impact on RV3-BB vaccine take when administered with a short delay in breast-feeding in settings with a high rotavirus disease burden.
Severe diarrhea from rotavirus remains an important cause of illness in infants. In this trial, investigators in Indonesia assessed the potential benefit of a neonatal rotavirus vaccine.
Abstract
Background
Histo-blood group antigen (HBGA) status may affect vaccine efficacy due to rotavirus strains binding to HBGAs in a P genotype–dependent manner. This study aimed to determine if ...HBGA status affected vaccine take of the G3P6 neonatal vaccine RV3-BB.
Methods
DNA was extracted from stool samples collected in a subset (n = 164) of the RV3-BB phase IIb trial in Indonesian infants. FUT2 and FUT3 genes were amplified and sequenced, with any single-nucleotide polymorphisms analyzed to infer Lewis and secretor status. Measures of positive cumulative vaccine take were defined as serum immune response (immunoglobulin A or serum-neutralizing antibody) and/or stool excretion of RV3-BB virus. Participants were stratified by HBGA status and measures of vaccine take.
Results
In 147 of 164 participants, Lewis and secretor phenotype were determined. Positive vaccine take was recorded for 144 (97.9%) of 147 participants with the combined phenotype determined. Cumulative vaccine take was not significantly associated with secretor status (relative risk, 1.00 95% CI, .94–1.06; P = .97) or Lewis phenotype (relative risk, 1.03 95% CI, .94–1.14; P = .33), nor was a difference observed when analyzed by each component of vaccine take.
Conclusions
The RV3-BB vaccine produced positive cumulative vaccine take, irrespective of HBGA status in Indonesian infants.
Population differences in histo-blood group antigen status may contribute to the varying performance of oral rotavirus vaccines. This study revealed that the RV3-BB vaccine produced positive cumulative vaccine take, irrespective of histo-blood group antigen status in Indonesian infants.
Background Systemic lupus erythematosus (SLE) is a complex disease with various manifestations. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities which plays ...an important role in immune regulation and inflammation. Serum level of IL-6 may be used as a parameter of disease activity, especially in pediatric SLE patients with mild disease activity or total remission with conflicting clinical manifestations and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores.
Objective To identify the characteristics of serum IL-6 concentration in pediatric SLE with mild disease activities and total remission.
Methods This case-control study was performed at the allergy-immunology outpatient clinic, Department of Child Health Dr. Cipto Mangunkusumo Hospital, Jakarta and Dr. Sardjito Hospital, Yogyakarta. Serum IL-6 concentration and disease activity were assessed in all pediatric SLE patients aged 1-18 years old. Disease activity was assessed with SLEDAI scores and serum level of IL-6 was measured by enzyme-linked immunosorbent assay.
Results Among 60 subjects included in this study, 30 subjects with mild activities were in the case group and 30 subjects with total remissions were in the control group. There was no difference in serum IL-6 concentration between the case and control group (OR 0.483; 95%CI 0.041to 5.628; P=0.500). In this study, 2 subjects with urinary tract infection had high serum IL-6 concentrations.
Conclusion There is no difference in serum IL-6 concentration between pediatric SLE patients with mild disease activities compared to total remissions.
Patients with Systemic Lupus Erythematosus (SLE) are susceptible to infection due to defects in their immune system. Corticosteroids and immunosuppressant drugs used as SLE therapy also contribute to ...infection. This study aimed is to determine predictors of infection in pediatric patients with SLE. This retrospective cohort study was conducted at Dr. Sardjito Hospital, a referral hospital in Yogyakarta, Indonesia between 2013 and 2019. Logistic regression analysis was performed to identify predictor variables for the occurrence of infection. A total of 109 SLE patients were included in this study. The incidence of infection in children with SLE was 27.5%. The most common types of infection in hospitalized SLE patients were urinary tract infections (41%), skin and soft tissue infections (20.5%), and pneumonia (20.5%). Multivariate regression analysis showed that the use of methylprednisolone pulse dose (RR 3.204; 95% CI 1.234-8.318) was a predictor of infection. Clinician should closely observe SLE patients with predictors for infection.
Antimicrobial resistance has become a global health emergency and is contributed to by inappropriate antibiotic use in community clinical settings. The aim of this study was to evaluate the ...antimicrobial use pattern in infants from birth until 18 months of age in Indonesia.
A post-hoc analysis was conducted in 1621 participants from the RV3BB Phase IIb trial conducted in Indonesia from January 2013 through July 2016. Any health events were documented in the trial as adverse events. Concomitant medication surveillance recorded all medications, including antibiotics during the 18 months of follow-up. Information included the frequency, duration of usage, formulation, classes, and their indications, including prophylactic antibiotic and perinatal use.
Of 1621 participants, 551 (33.99%) received at least one antibiotic for treatment of infections during the 18 months observation period. Additionally, during the perinatal period, prophylactic antibiotics were used in 1244 (76.74%) participants and antibiotics consumed in 235 mothers of participants (14.50%). A total of 956 antibiotic consumptions were recorded for 18 months follow up, 67 (7.01%) as part of antimicrobial combinations. The average duration of antibiotic course was 4.92 days. Penicillin and sulfonamides were the most common antibiotic classes consumed (38.81% and 24.48%, respectively).
Despite the low community consumption rate, the overuse of antibiotic in URTIs and non-bloody diarrhea in our setting represents a major opportunity for antimicrobial stewardship, particularly in early life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rational medication use for treatment is mandatory, particularly in children as they are vulnerable to possible hazards of drugs. Understanding the medication use pattern is of importance to identify ...the problems of drug therapy and to improve the appropriate use of medication among this population.
A post-hoc study of the RV3-BB Phase IIb trial to children aged 0-18 months which was conducted in Indonesia during January 2013 to July 2016. Any concomitant medication use and health events among 1621 trial participants during the 18 months of follow-up were documented. Information on medication use included the frequency, formulation, indication, duration of usage, number of regimens, medication types, and therapeutic classes.
The majority of participants (N = 1333/1621; 82.2%) used at least one non-antibiotic medication for treatment during the 18-month observation period. A total of 7586 medication uses were recorded, mostly in oral formulation (90.5%). Of all illnesses recorded, 24.7% were treated with a single drug regimen of non-antibiotic medication. The most common therapeutic classes used were analgesics/antipyretics (30.1%), antihistamines for systemic use (17.4%), cough and cold preparations (13.5%), vitamins (8.6%), and antidiarrheals (6.6%). The main medication types used were paracetamol (29.9%), chlorpheniramine (16.8%), guaifenesin (8.9%), zinc (4.6%), and ambroxol (4.1%). Respiratory system disorder was the most common reason for medication use (51.9%), followed by gastrointestinal disorders (19.2%), pyrexia (16.9%), and skin disorders (7.0%).
A large number of children were exposed to at least one medication during their early life, including those where evidence of efficacy and safety in a pediatric population is lacking. This supports the need for further research on pediatric drug therapy to improve the appropriate use of medication in this population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Both OPV and rotavirus vaccines contain live, attenuated strains that replicate in the gut.•OPV and rotavirus vaccine co-administration has been associated with lower rotavirus immune ...responses.•RV3-BB is a novel human neonatal rotavirus vaccine that provides protection from rotavirus disease from birth.•OPV and RV3-BB co-administration did not reduce immunogenicity of either vaccine.•These findings support the use of RV3-BB where either OPV or IPV is used in the routine schedule.
The RV3-BB human neonatal rotavirus vaccine was developed to provide protection from severe rotavirus disease from birth. The aim of this study was to investigate the potential for mutual interference in the immunogenicity of oral polio vaccine (OPV) and RV3-BB.
A randomized, placebo-controlled trial involving 1649 participants was conducted from January 2013 to July 2016 in Central Java and Yogyakarta, Indonesia. Participants received three doses of oral RV3-BB, with the first dose given at 0–5 days (neonatal schedule) or ~8 weeks (infant schedule), or placebo. Two sub-studies assessed the immunogenicity of RV3-BB when co-administered with either trivalent OPV (OPV group, n = 282) or inactivated polio vaccine (IPV group, n = 333). Serum samples were tested for antibodies to poliovirus strains 1, 2 and 3 by neutralization assays following doses 1 and 4 of OPV.
Sero-protective rates to poliovirus type 1, 2 or 3 were similar (range 0.96–1.00) after four doses of OPV co-administered with RV3-BB compared with placebo. Serum IgA responses to RV3-BB were similar when co-administered with either OPV or IPV (difference in proportions OPV vs IPV: sIgA responses; neonatal schedule 0.01, 95% CI −0.12 to 0.14; p = 0.847; infant schedule −0.10, 95% CI −0.21 to −0.001; p = 0.046: sIgA GMT ratio: neonatal schedule 1.23, 95% CI 0.71–2.14, p = 0.463 or infant schedule 1.20, 95% CI 0.74–1.96, p = 0.448).
The co-administration of OPV with RV3-BB rotavirus vaccine in a birth dose strategy did not reduce the immunogenicity of either vaccine. These findings support the use of a neonatal RV3-BB vaccine where either OPV or IPV is used in the routine vaccination schedule.
Background The use of long-term oral glucocorticoid therapy, specifically in the treatment of systemic lupus erythematosus (SLE), has increased in the past two decades. Chronic glucocorticoid use may ...lead to a linear growth disturbances.
Objective To determine the association between linear growth and systemic glucocorticoid therapy in pediatric SLE patients.
Methods This retrospective cohort study used medical record data of pediatric SLE patients. All subjects received systemic glucocorticoids. The linear growth parameters recorded in this study were height-for-age z-score (HAZ) and height velocity at 0, 6, and 12 months of treatment. We recorded potential risk factors of linear growth disturbance, such as pubertal status, sex, SLE severity, pulse methylprednisolone use, daily glucocorticoid dose, and nutritional status.
Results Of 42 patients with SLE, 83.3% were female, with a mean age of 13 years at diagnosis. Eighteen subjects (42.9%) experienced abnormal height velocity. There was a significant reduction in HAZ between 0, 6, and 12 months of treatment (P=0.016). Between 0 and 6 months of treatment, there was a mean HAZ decrease of 0.11 (P=0.015). There was a trend towards a risk for decreased HAZ at 6 and 12 months of treatment with pulse methylprednisolone (RR 1.25 and 1.27, respectively), as well as for abnormal height velocity (RR 1.73), but they did not reach statistical significance.
Conclusion There is a reduction in linear growth in the first 12 months of systemic glucocorticoid therapy in children with SLE. Administration of systemic glucocorticoid significantly reduced HAZ in the first six months of therapy.
Background Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (CKD) in children. Delayed diagnosis of CAKUT due to lack of universal ...screening (such as prenatal ultrasound screening or postnatal ultrasound screening in neonates with risk of CAKUT) has led to more cases of advanced CKD in children. CKD has high morbidity and mortality, and early detection is required to prevent the progression of CKD.
Objective To determine the factors that predict the development of advanced CKD in children with CAKUT.
Methods This retrospective cohort study included children with CAKUT at Dr. Sardjito Hospital, Yogyakarta, Indonesia from January 2016 to February 2021. Patients who were diagnosed with CAKUT were followed up to 5 years or until the onset of advanced CKD. Advanced CKD was defined as a decreased estimated glomerular filtration rate (eGFR) of less than 30mL/min/1.73m2 based on the revised Schwartz formula. CKD progression-free survival was determined with Kaplan-Meier and Cox regression analyses.
Results Among 62 subjects with CAKUT, 7 (11.3%) subjects progressed to advanced CKD. The mean time of advanced CKD progression was 52.2 (95%CI 46.9 to 57.5) months. The overall incidence rate was 22 per 1,000 person-years. Based on Kaplan-Meier analysis, children with eGFR <60 mL/min/1.73m2 at the time of diagnosis had more rapid progression to advanced CKD than patients with eGFR ?60 mL/min/1.73m2 40.2 (95%CI 33.4 to 46.6) months vs. 58.2 95%CI 46.9 to 57.5) months; P=0.02, respectively.
Conclusion Reduced eGFR at the time of diagnosis showed rapid progression to advanced CKD.
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