The Improvement of Adaptive Immune Responses towards COVID-19 Following Diphtheria-Tetanus-Pertussis and SARS-CoV-2 Vaccinations in Indonesian Children: Exploring the Roles of Heterologous Immunity.

BACKGROUND: Routine childhood vaccination, e.g., for diphtheria, tetanus, and pertussis (DTP), might provide additional protection against SARS-CoV-2 infection. This concept of heterologous immunity was explored in healthy children receiving both DTP and inactivated SARS-CoV-2 vaccines. METHODS: A cross-sectional study was performed on 154 healthy children aged 6-8 years old in Jakarta, Indonesia. Their vaccination status for the DTP (including a diphtheria-tetanus booster vaccine at 5 years old) and CoronaVac (from 6 years old) vaccines were recorded. Peripheral blood samples were collected from all participants, in which anti-diphtheria toxoid IgG and anti-SARS-CoV-2 S-RBD antibodies and T cell-derived IFN-γ were measured. RESULTS: The study participants with complete DTP vaccination had significantly higher titers of anti-diphtheria toxoid IgG than the ones without (median = 0.9349 versus 0.2113 IU/mL; p < 0.0001). Upon stratification based on DTP and CoronaVac vaccination statuses, the participants with complete DTP and CoronaVac vaccinations had the highest titer of anti-SARS-CoV-2 S-RBD antibodies (median = 1196 U/mL) and the highest concentration of SARS-CoV-2-specific T cell-derived IFN-γ (median = 560.9 mIU/mL) among all the groups. CONCLUSIONS: Healthy children aged 6-8 years old with complete DTP and CoronaVac vaccinations exhibited stronger SARS-CoV-2-specific T cell immune responses. This might suggest an additional benefit of routine childhood vaccination in generating protection against novel pathogens, presumably via heterologous immunity.

Care of children with congenital rubella syndrome (CRS) in Indonesia.

INTRODUCTION: Congenital rubella syndrome (CRS) is associated with severe birth defects, that lead to disability in later life. Hence, early detection and intervention are needed to prevent permanent disability and mortality in children with CRS. We evaluated the time to diagnosis or correction intervention related to survival rate using survival analysis. METHODOLOGY: A retrospective cohort study was conducted to evaluate the follow-up of CRS-confirmed cases from 2011-2018 at a national referral hospital in Jakarta, Indonesia. Parents of eligible children who registered in the national CRS registry as laboratory-confirmed CRS cases were contacted through phone calls or home visits and interviewed about the current situation of their child's health. We also obtained clinical data from the medical records. RESULTS: Fifty children, age 4 to 14 years, identified with laboratory-confirmed CRS were included in this study. Half (54%) of these children were female. All were born from mothers with no previous rubella vaccination history. Ophthalmic abnormalities such as congenital cataracts (88%) were the most common birth defect. Multiple congenital abnormalities including congenital heart disease, ocular abnormalities, and auditory defects were identified in 52% of the children. Based on Kaplan-Meier analysis, 50% of children were diagnosed at four months. Ophthalmic corrections such as cataract surgery were performed earlier than heart or auditory correction, with 50% of children undergoing eye correction one month after the diagnosis. CONCLUSIONS: There is a vital need to implement CRS surveillance in Indonesia to know the burden of CRS and reinforce the preventive actions, including vaccination against rubella.

Immunogenicity and Safety of Half-Dose Heterologous mRNA-1273 Booster Vaccination for Adults Primed with the CoronaVac® and ChAdOx1-S Vaccines for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection.

Diagnostic and antibiotic use practices among COVID-19 and non-COVID-19 patients in the Indonesian National Referral Hospital.

BACKGROUND: Little is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities. METHODS: We linked and analyzed routine databases of hospital admission, microbiology laboratory and drug dispensing of Indonesian National Referral Hospital from 2019 to 2020. Patients were classified as COVID-19 cases if their SARS-CoV-2 RT-PCR result were positive. Blood culture (BC) practices and time to discontinuation of parenteral antibiotics among inpatients who received a parenteral antibiotic for at least four consecutive days were used to assess diagnostic and antibiotic use practices, respectively. Fine and Grey subdistribution hazard model was used. RESULTS: Of 1,311 COVID-19 and 58,917 non-COVID-19 inpatients, 333 (25.4%) and 18,837 (32.0%) received a parenteral antibiotic for at least four consecutive days. Proportion of patients having BC taken within ±1 calendar day of parenteral antibiotics being started was higher in COVID-19 than in non-COVID-19 patients (21.0% [70/333] vs. 18.7% [3,529/18,837]; p<0.001). Cumulative incidence of having a BC taken within 28 days was higher in COVID-19 than in non-COVID-19 patients (44.7% [149/333] vs. 33.2% [6,254/18,837]; adjusted subdistribution-hazard ratio [aSHR] 1.71, 95% confidence interval [CI] 1.47-1.99, p<0.001). The median time to discontinuation of parenteral antibiotics was longer in COVID-19 than in non-COVID-19 patients (13 days vs. 8 days; aSHR 0.73, 95%Cl 0.65-0.83, p<0.001). CONCLUSIONS: Routine electronic data could be used to inform diagnostic and antibiotic use practices in LMICs. In Indonesia, the proportion of timely blood culture is low in both COVID-19 and non-COVID-19 patients, and duration of parenteral antibiotics is longer in COVID-19 patients. Improving diagnostic and antimicrobial stewardship is critically needed.

Nasopharyngeal carriage of Streptococcus pneumoniae among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction.

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged <5 years before 13-valent PCV (PCV13) introduction. Nasopharyngeal swabs were collected during visits to community integrated health service posts at one peri-urban and one rural study site. Specimens were analyzed by culture, and isolates were serotyped using sequential multiplex polymerase chain and Quellung reaction. Antibiotic susceptibility was performed by broth microdilution method. We enrolled 1,007 children in Gunungkidul District, Yogyakarta (peri-urban) and 815 in Southwest Sumba, East Nusa Tenggara (rural). Pneumococcal carriage prevalence was 30.9% in Gunungkidul and 87.6% in Southwest Sumba (combined: 56.3%). PCV13 serotypes (VT) carriage was 15.0% in Gunungkidul and 52.6% in Southwest Sumba (combined: 31.8%). Among pneumococcal isolates identified, the most common VT were 6B (16.4%), 19F (15.8%), and 3 (4.6%) in Gunungkidul (N = 323) and 6B (17.6%), 19F (11.0%), and 23F (9.3%) in Southwest Sumba (N = 784). Factors associated with pneumococcal carriage were age (1-2 years adjusted odds ratio (aOR) 1.9, 95% CI 1.4-2.5; 3-4 years aOR 1.5, 95% CI 1.1-2.1; reference <1 year), other children <5 years old in the household (aOR 1.5, 95% CI 1.1-2.0), and presence of ≥1 respiratory illness symptom (aOR 1.8, 95% CI 1.4-2.2). Overall, 61.5% of the pneumococcal isolates were non-susceptible to ≥1 antibiotic class and 13.2% were multi-drug non-susceptible (MDNS) (non-susceptible to ≥3 classes of antibiotics). Among 602 VT isolates, 73.9% were non-susceptible and 19.9% were MDNS. These findings are critical to establish a pre-PCV13 carriage prevalence and demonstrate the complexity in evaluating the impact of PCV13 introduction in Indonesia given the wide variability in the carriage prevalence as shown by the two study sites.

Emerging progressive atypical acute kidney injury in young children linked to ethylene glycol and diethylene glycol intoxication.

BACKGROUND: There had been a sudden surge of unusually severe and rapidly progressing acute kidney injury (AKI) incidence in Indonesia since August 2022 which did not correspond to the rise of COVID-19 incidence. We suspected this was related to ethylene glycol (EG) and diethylene glycol (DEG) intoxication. This study is aimed at describing the clinical and laboratory characteristics of AKI related to D(EG) intoxication in order to spread awareness of the possibility of intoxication in cases of rapidly progressing AKI with unknown etiology. METHODS: We conducted a cross-sectional study by collecting secondary data from the pediatric AKI registry at a national referral hospital in Jakarta, Indonesia. Data on children admitted from January to November 2022 with diagnosis of stage 3 AKI based on KDIGO criteria were included. Data regarding demographics, symptoms prior to anuria, laboratory results, infection panel including COVID-19 status, treatment administered, and mortality were analyzed. RESULTS: Sixteen patients tested positive for EG and DEG, all with history of consuming syrup-based medications. High anion gap metabolic acidosis was observed in majority of patients with mean pH 7.33 ± 0.07 and mean anion gap 15.6 ± 7.8 mEq/L. No patient had high osmolal gap (mean osmolal gap 3.46 ± 4.68). One deceased patient, who had kidney biopsy performed, showed severe damage and calcium oxalate crystals in the kidney tissue. Mortality was recorded in six patients (37.5%). CONCLUSION: Careful history taking of patient's clinical course, including consumption of syrup-based medications and laboratory findings, might aid clinicians to establish a working diagnosis of D(EG) intoxication without needing to wait for blood toxicology test. Early diagnosis and therapy are crucial to prevent substantial mortality.

Epidemiology of Haemophilus influenzae in children on Lombok Island, Indonesia.

The Haemophilus influenzae serotype b (Hib) conjugate vaccine routine immunization programme has been implemented for almost a decade; however, there is limited surveillance of H. influenzae carriage rates in the Indonesian population. H. influenzae was isolated from nasopharyngeal (NP) swab specimens of healthy children on Lombok Island, West Nusa Tenggara Province, Indonesia from 2018 to 2019. Serotyping was performed using quantitative polymerase chain reaction. We identified H. influenzae in 40 of the 96 (41.6 %) NP swab specimens. We identified 39 non-typeable H. influenzae (NTHi) isolates and 1 Hib isolate.

Factors associated with parental intention to vaccinate their preschool children against COVID-19: a cross-sectional survey in urban area of Jakarta, Indonesia.

Purpose: We reported a survey-based study assessing the parental intention to vaccinate children of 5 to 7 years old against coronavirus disease 2019 (COVID-19). The aim of this study is to assess factors influencing the parental intention to vaccinate their children against COVID-19. Materials and Methods: This study adopted a cross-sectional design, held at the public health center of Senen district, Jakarta, Indonesia from November 1-30, 2022. The off-line questionnaires were distributed via the school administrator to all eligible parents. Factors associated with intention to vaccinate were analyzed with the regression logistic models. Results: Of the 435 parents in this study, 215 had already vaccinated their children against COVID-19 (49.4%), and the overall intention of the participants to vaccinate was 69.7%. Factors associated with intention to vaccinate the children against COVID-19 were parental employment status, parental COVID-19 vaccine status and concern of contracting COVID-19. Parents who are employed, had completed vaccines with COVID-19 booster vaccine, and had concern of their children contracting COVID-19 were more likely to vaccinate their children (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.22-3.69; p=0.011; OR, 2.15; 95% CI, 1.21-3.83; p=0.013; OR, 2.40; 95% CI, 1.34-4.30; p=0.004, respectively). Concern on the vaccine's side effects was negatively associated with the willingness to vaccinate. Conclusion: This study showed that childhood COVID-19 vaccine only covered half of the population, with parental intentions for childhood COVID-19 vaccination being high, reaching almost two-thirds of the study participants. Factors influencing parental intentions were employment status, parental COVID-19 vaccine status, concerns about COVID-19 and concerns about vaccine side effects.

Estimating dengue transmission intensity from serological data: A comparative analysis using mixture and catalytic models.

BACKGROUND: Dengue virus (DENV) infection is a global health concern of increasing magnitude. To target intervention strategies, accurate estimates of the force of infection (FOI) are necessary. Catalytic models have been widely used to estimate DENV FOI and rely on a binary classification of serostatus as seropositive or seronegative, according to pre-defined antibody thresholds. Previous work has demonstrated the use of thresholds can cause serostatus misclassification and biased estimates. In contrast, mixture models do not rely on thresholds and use the full distribution of antibody titres. To date, there has been limited application of mixture models to estimate DENV FOI. METHODS: We compare the application of mixture models and time-constant and time-varying catalytic models to simulated data and to serological data collected in Vietnam from 2004 to 2009 (N ≥ 2178) and Indonesia in 2014 (N = 3194). RESULTS: The simulation study showed larger mean FOI estimate bias from the time-constant and time-varying catalytic models (-0.007 (95% Confidence Interval (CI): -0.069, 0.029) and -0.006 (95% CI -0.095, 0.043)) than from the mixture model (0.001 (95% CI -0.036, 0.065)). Coverage of the true FOI was > 95% for estimates from both the time-varying catalytic and mixture model, however the latter had reduced uncertainty. When applied to real data from Vietnam, the mixture model frequently produced higher FOI and seroprevalence estimates than the catalytic models. CONCLUSIONS: Our results suggest mixture models represent valid, potentially less biased, alternatives to catalytic models, which could be particularly useful when estimating FOI from data with largely overlapping antibody titre distributions.

Blood culture utilization and epidemiology of antimicrobial-resistant bloodstream infections before and during the COVID-19 pandemic in the Indonesian national referral hospital.

BACKGROUND: There is a paucity of data regarding blood culture utilization and antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs). In addition, there has been a concern for increasing AMR infections among COVID-19 cases in LMICs. Here, we investigated epidemiology of AMR bloodstream infections (BSI) before and during the COVID-19 pandemic in the Indonesian national referral hospital. METHODS: We evaluated blood culture utilization rate, and proportion and incidence rate of AMR-BSI caused by WHO-defined priority bacteria using routine hospital databases from 2019 to 2020. A patient was classified as a COVID-19 case if their SARS-CoV-2 RT-PCR result was positive. The proportion of resistance was defined as the ratio of the number of patients having a positive blood culture for a WHO global priority resistant pathogen per the total number of patients having a positive blood culture for the given pathogen. Poisson regression models were used to assess changes in rate over time. RESULTS: Of 60,228 in-hospital patients, 8,175 had at least one blood culture taken (total 17,819 blood cultures), giving a blood culture utilization rate of 30.6 per 1,000 patient-days. A total of 1,311 patients were COVID-19 cases. Blood culture utilization rate had been increasing before and during the COVID-19 pandemic (both p < 0.001), and was higher among COVID-19 cases than non-COVID-19 cases (43.5 vs. 30.2 per 1,000 patient-days, p < 0.001). The most common pathogens identified were K. pneumoniae (23.3%), Acinetobacter spp. (13.9%) and E. coli (13.1%). The proportion of resistance for each bacterial pathogen was similar between COVID-19 and non-COVID-19 cases (all p > 0.10). Incidence rate of hospital-origin AMR-BSI increased from 130.1 cases per 100,000 patient-days in 2019 to 165.5 in 2020 (incidence rate ratio 1.016 per month, 95%CI:1.016-1.017, p < 0.001), and was not associated with COVID-19 (p = 0.96). CONCLUSIONS: In our setting, AMR-BSI incidence and etiology were similar between COVID-19 and non-COVID-19 cases. Incidence rates of hospital-origin AMR-BSI increased in 2020, which was likely due to increased blood culture utilization. We recommend increasing blood culture utilization and generating AMR surveillance reports in LMICs to inform local health care providers and policy makers.

Evaluation of Pediatric COVID-19 Screening Process in a Tertiary Hospital of Indonesia.

Objectives: To identify parameters that can improve the effectiveness of COVID-19 screening in the pediatric population according to the demographic, clinical, and epidemiological characteristics of pediatric patients screened for COVID-19 at our hospital. Methods: A cross-sectional study of suspected and confirmed pediatric patients (0-18 years old) with COVID-19 using data from the electronic medical records of Dr. Cipto Mangunkusumo Central Hospital from March to December 2020. Results: From 1,018 data of suspected COVID-19 pediatric patients, there were 94 (9.2%) confirmed cases of COVID-19. The proportions of children with travel history (p=0.022), positive contact history (p < 0.001), fever ≥38°C (p=0.034), cough (p=0.038), and abdominal pain (p=0.022) were significantly higher in the confirmed COVID-19 group compared to the non-COVID-19 group. Conclusions: A majority of the confirmed COVID-19 pediatric patients have travel and positive contact history, along with symptoms of fever, cough, and abdominal pain. However, these are nonspecific symptoms that may also be misdiagnosed as other diseases. Improving access and turnaround time of the RT-PCR test is mandatory, as no specific screening variables have been identified.

Clinical Features of Multisystem Inflammatory Syndrome in Children Associated with COVID-19 in Indonesia.

BACKGROUND: While the number of cases of multisystem inflammatory syndrome in children (MIS-C) is increasing, reported cases in Asian countries are still low, particularly in Indonesia. This study aimed to describe the characteristics of patients with MIS-C in a tertiary referral hospital in Indonesia. METHODS: This is a cross-sectional study with collected data of patients with MIS-C admitted to Dr. Cipto Mangunkusumo from March 2020 to April 2021. RESULTS: The first case of MIS-C was detected 5 months after the first reported coronavirus disease 2019 case in Indonesia. Thirteen patients out of 158 positive admitted patients for COVID-19 were diagnosed with MIS-C during the study period. Of these 13 patients, 2 patients (15%) had a fatal outcome. Subjects were predominantly male, and the median age was 7.58 years (IQR 12.3) years. Most patients required mechanical ventilation (7 out of 13 patients) and intubation (8 out of 13 patients). Patients who needed intubation usually needed mechanical ventilation. All inflammatory markers, white blood cells, neutrophil counts, and all coagulation factor parameters (except for normal prothrombin time and activated partial prothrombin time) were elevated. The median time to MIS-C diagnosis was 2 days in the survivor group (n = 11) compared to 8.5 days in the non-survivor group (n = 2). Compared to the non-survivor group, those who survived spent more days in the hospital, received vasopressors earlier, and did not require mechanical ventilation as early as the non-survivors. CONCLUSIONS: Our work highlights the differences in MIS-C clinical course, treatment, and clinical outcomes between the two groups.

Prevalence, serotype and antibiotic susceptibility of Group B Streptococcus isolated from pregnant women in Jakarta, Indonesia.

Group B Streptococcus (GBS) is a bacterial pathogen which is a leading cause of neonatal infection. Currently, there are limited GBS data available from the Indonesian population. In this study, GBS colonization, serotype distribution and antimicrobial susceptibility profile of isolates were investigated among pregnant women in Jakarta, Indonesia. Demographics data, clinical characteristics and vaginal swabs were collected from 177 pregnant women (mean aged: 28.7 years old) at 29-40 weeks of gestation. Bacterial culture identification tests and latex agglutination were performed for GBS. Serotyping was done by conventional multiplex PCR and antibiotic susceptibility testing by broth microdilution. GBS colonization was found in 53 (30%) pregnant women. Serotype II was the most common serotype (30%) followed by serotype III (23%), Ia and IV (13% each), VI (8%), Ib and V (6% each), and one non-typeable strain. All isolates were susceptible to vancomycin, penicillin, ampicillin, cefotaxime, daptomycin and linezolid. The majority of GBS were resistant to tetracycline (89%) followed by clindamycin (21%), erythromycin (19%), and levofloxacin (6%). The serotype III was more resistant to erythromycin, clindamycin, and levofloxacin and these isolates were more likely to be multidrug resistant (6 out of 10) compared to other serotypes. This report provides demographics of GBS colonization and isolate characterization in pregnant women in Indonesia. The results may facilitate preventive strategies to reduce neonatal GBS infection and improve its treatment.

Mortality in children with positive SARS-CoV-2 polymerase chain reaction test: Lessons learned from a tertiary referral hospital in Indonesia.

BACKGROUND: The incidence of coronavirus disease 2019 (COVID-19) is still increasing rapidly, but little is known about the prevalence and characteristics of fatal cases in children in Indonesia. This study aimed to describe the characteristics of children with COVID-19 with fatal outcomes in a tertiary referral hospital in Indonesia. METHODS: This cross-sectional study used data collected from the medical records of patients with COVID-19 admitted to Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia from March to October 2020. RESULTS: During the study period, 490 patients were admitted and diagnosed with suspected and probable COVID-19. Of these patients, 50 (10.2%) were confirmed to have COVID-19, and 20 (40%) had a fatal outcome. The fatality rate was higher in patients aged ≥10 years, categorized with severe disease upon admission, PaO2/FiO2 ratio ≤300 mmHg and chronic underlying diseases. The most common clinical manifestations were generalized symptoms, while acute respiratory distress syndrome (8/20) and septic shock (7/20) were the two most common causes of death. Increased procalcitonin, D-dimer, lactate dehydrogenase and presepsin levels were found in all fatal cases. One patient met the criteria of multisystem inflammatory syndrome in children. CONCLUSION: Our work highlights the high mortality rate in paediatric patients with positive SARS-CoV-2 polymerase chain reaction test. These findings might be related to or co-incided with COVID-19 infection. Further studies are needed to improve understanding of the role of severe acute respiratory syndrome coronavirus-2 in elaborating the mechanisms leading to death in children with comorbidities.

Pneumococcal nasopharyngeal carriage in Indonesia infants and toddlers post-PCV13 vaccination in a 2+1 schedule: A prospective cohort study.

BACKGROUND: The PCV13 immunization demonstration program began in October 2017 in Indonesia. The aim of this study is to assess the dynamic changes of pneumococcal serotype before and after PCV13 administration, with two primary and one booster doses. METHODS: The prospective cohort study was conducted as a follow up study measuring the impact of PCV13 demonstration program by the Indonesian Ministry of Health in Lombok Island, West Nusa Tenggara, Indonesia, from March 2018 to June 2019. The subjects were two-month-old healthy infants who were brought to the primary care facility for routine vaccination and followed until 18 months of age. We use convenience sampling method. There were 115 infants in the control group and 118 infants in the vaccine group, and the PCV immunization was given on a 2+1 schedule. Nasopharyngeal (NP) swabs were collected four times during the vaccination periods by trained medical staff. Specimens were analyzed by culture methods to detect S. pneumonia colonization and multiplex polymerase chain reaction (mPCR) to determine serotype. The most frequently detected serotypes will be named as dominant serotypes. Descriptive analysis of demographic characteristics, the prevalence of overall and serotype colonization, and the distribution of serotypes were performed. The prevalence of both cohort groups were compared using chi-square test. Statistical significance was set at p < 0.05. RESULTS: Two hundred and thirty three infants age two months old were recruited, with 48.9% of the subjects were male and 51.1% of the subjects were female. Sociodemographic data in both cohort groups were relatively equal. Nasopharyngeal pneumococcal colonization before PCV13 administration occurred in 19.1% of the control and 22.9% of the vaccine group. The prevalence increased with increasing age in both groups. The prevalence of VT serotypes in control groups aged 2 months, 4 months, 12 months, and 18 months was 40.9%, 44.2%, 53.8%, and 54.3%, respectively, and in the vaccine group, 25.9%, 40.4%, 38.0%, and 22.6%, respectively. The most common VT serotypes in both groups were 6A/6B, 19F, 23F, and 14. The prevalence of VT serotypes decreased significantly compared to non-vaccine type serotypes after three doses of the PCV13 vaccine (p < 0.001). Another notable change was the decline in prevalence of serotype 6A/6B after PCV13 administration using the 2+1 schedule. CONCLUSIONS: This study shows lower prevalence of VT and 6A/6B serotypes in the nasopharynx among children who were PCV13 vaccinated compared with those who were unvaccinated. The result from this study will be the beginning of future vaccine evaluation in larger population and longer period of study.

First Pediatric Outpatient Parenteral Antibiotic Therapy Clinic in Indonesia.

Background: Infection remains a major pediatric health problem in Indonesia and usually leads to longer hospitalization due to the need for extended intravenous antibiotic administration. In developed countries, pediatric outpatient parenteral antibiotic therapy (P-OPAT) is well-established and proven to be safe and effective at reducing the length of hospital stay; however, data on low- and middle-income countries such as Indonesia remain limited. This P-OPAT service is new and the first service in Indonesia. Methods: The medical records of patients attending Indonesia's first P-OPAT clinic between April 2015 and March 2017 were retrospectively investigated. Results: During the 24-month period, 32 patients received treatment at the P-OPAT clinic, saving a total of 258 bed days. The majority of patients (n = 16; 50%) were diagnosed with urinary tract infection, followed by cellulitis (n = 4; 12.5%) and osteomyelitis (n = 4; 12.5%). Ceftriaxone was the most commonly used antibiotic (n = 16; 50%). All patients used a peripheral intravenous catheter and were sent home with this device. Twelve patients (37.5%) needed to change IV access more than once. None of the patients used elastomeric infusor device. The median duration of OPAT was 5 days (range 1-27 days). All patients were successfully treated with no recurrence after 30 days. One patient (3.1%) experienced drug-related complication and another one (3.1%) was readmitted due to an underlying medical condition. All the patients complied with P-OPAT schedules. Conclusions: P-OPAT service offers a safe and effective option for the delivery of outpatient intravenous antibiotics in selected patients even in resource-poor settings.

Absence of Evidence of Zika Virus Infection in Cord Blood and Urine from Newborns with Congenital Abnormalities, Indonesia.

Zika virus (ZIKV) has recently been confirmed as endemic in Indonesia, but no congenital anomalies (CA) related to ZIKV infection have been reported. We performed molecular and serological testing for ZIKV and other flaviviruses on cord serum and urine samples collected in October 2016 to April 2017 during a prospective, cross-sectional study of neonates in Jakarta, Indonesia. Of a total of 429 neonates, 53 had CA, including 14 with microcephaly. These 53, and 113 neonate controls without evidence of CA, were tested by ZIKV-specific real-time reverse transcription polymerase chain reaction (RT-PCR), pan-flavivirus RT-PCR, anti-ZIKV and anti-DENV IgM ELISA, and plaque reduction neutralization test. There was no evidence of ZIKV infection among neonates in either the CA or non-CA cohorts, except in three cases with low titers of anti-ZIKV neutralizing antibodies. Further routine evaluation throughout Indonesia of pregnant women and their newborns for exposure to ZIKV should be a high priority for determining risk.

The Gastroesophageal Reflux Disease Questionnaire in Adolescents: What Is the Best Cutoff Score?

BACKGROUND: A self-assessment questionnaire, the GERD-Questionnaire (GERD-Q) was used to determine the prevalence of GERD in adolescents, describe the related factors, and determine the impact on quality of life (QoL). METHODS: The incidence of GERD was evaluated using the GERD-Q in adolescents aged 12-18 years. The Pediatric Gastroesophageal Reflux Disease Symptom Questionnaire and Quality of Life Questionnaire (PGSQ-A) for adolescents were additionally administered. Some factors considered related to GERD were also evaluated. RESULTS: The 520 adolescents were included. The prevalence of suspected GERD, according to a GERD-Q cutoff score of ≥7 was 32.9%, and those drinking soda were 1.7 times more likely to have GERD (95% confidence interval, 1.3-2.2; p<0.001). However, soda consumption was not a risk factor for development of GERD symptoms. Applying a cutoff score of ≥8, only 10.9% of the participants had a positive GERD score, but the association with soda consumption persisted. The median PGSQ-A score in subjects suspected of GERD was 8 (range 0-37) on weekends and 1 (range 0-17) during weekdays (p<0.001) compared to those not suspected of GERD, with a median of 2 (range 0-27) during weekends and 0 (range 0-10) during weekdays. Heartburn, regurgitation, and extraesophageal symptoms correlated significantly with QoL (p<0.001). CONCLUSION: The prevalence of suspected GERD in adolescents was 32.9% or 10.9%, depending on the cutoff score used. There was a statistically significant difference in PGSQ-A scores between the subjects suspected or not of GERD, indicating an impaired QoL.

Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia.

OBJECTIVES: Little is known about the birth prevalence and characteristics of congenital cytomegalovirus (CMV) infection in developing countries. To determine the prevalence and characteristics of congenital CMV infection in Indonesia, we conducted a prospective study in an urban birth cohort of neonates at a national referral hospital in 2016-2017, Jakarta, Indonesia. METHODS: Consecutively born neonates were screened for the presence of CMV by using pan-herpesvirus nested-PCR and Sanger sequencing in saliva and/or urine specimens. Both the neonatal clinical findings as well as maternal characteristics were also evaluated. RESULTS: From a total of 411 newborns screened, congenital CMV infection was confirmed in 5.8% of the neonates. These CMV-positive newborns were more likely to have ventriculomegaly and thrombocytopenia compared to CMV-negative neonates. Notably, 67% CMV-positive neonates in our study had clinical findings that required medical intervention, from which only nine presented with symptoms suggestive of congenital CMV infection. Furthermore, congenital CMV infected babies were almost four times more likely to be born to mothers that had placenta previa and placental abruption. CONCLUSIONS: Our work highlights the high prevalence of congenital CMV infection in neonates born in one of the biggest referral hospitals in metropolitan Jakarta, Indonesia.

Serological Evidence of Japanese Encephalitis Virus Circulation in Asian Children From Dengue-Endemic Countries.

Background: Japanese encephalitis virus (JEV) is a zoonotic, mosquito-borne flavivirus, distributed across Asia. Infections are mostly mild or asymptomatic, but symptoms include neurological disorders, sequelae, and fatalities. Data to inform control strategies are limited due to incomplete case reporting. Methods: We used JEV serological data from a multicountry Asian dengue vaccine study in children aged 2-14 years to describe JEV endemicity, measuring antibodies by plaque reduction neutralization test (PRNT50). Results: A total 1479 unvaccinated subjects were included. A minimal estimate of pediatric JEV seroprevalence in dengue-naive individuals was 8.1% in Indonesia, 5.8% in Malaysia, 10.8% in the Philippines, and 30.7% in Vietnam, translating to annual infection risks varying from 0.8% (in Malaysia) to 5.2% (in Vietnam). JEV seroprevalence and annual infection estimates were much higher in children with history of dengue infection, indicating cross-neutralization within the JEV PRNT50 assay. Conclusions: These data confirm JEV transmission across predominantly urban areas and support a greater emphasis on JEV case finding, diagnosis, and prevention.