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.

A phase II clinical trial of a Vi-DT typhoid conjugate vaccine in healthy Indonesian adolescents and adults: one-month evaluation of safety and immunogenicity.

BACKGROUND: Typhoid fever is commonly found until today, especially in developing countries. It has fatal complications and measures must be taken to reduce the incidence of typhoid. Vaccinations are a key factor in prevention. This is a phase II randomized observer-blind clinical trial on a novel Vi-DT conjugate vaccine on 200 subjects 12 to 40 years of age. METHODS: Subjects were screened for eligibility after which a blood sample was taken and one dose of vaccine was administered. Investigational vaccine used was Vi-DT and control was Vi-PS. Twenty-eight days after vaccination, subjects visited for providing blood sample to assess immunogenicity and were asked about local and systemic adverse reactions that occurred in the first 28 days. RESULTS: Subjects had minor adverse reactions. Pain was the most common local reaction. Muscle pain was the most common systemic reaction. There were no serious adverse events up to 28 days post vaccination. Seroconversion rates were 100% in the Vi-DT group and 95.96% in the Vi-PS group. Post vaccination GMTs were increased in both groups but it was significantly higher in the Vi-DT group (p < 0.001). CONCLUSIONS: Vi-DT typhoid conjugate vaccine is safe and immunogenic in healthy Indonesian subjects 12 to 40 years. TRIAL REGISTRATION: Approved by ClinicalTrials.gov. CLINICAL TRIAL REGISTRATION NUMBER: NCT03460405. Registered on 09/03/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03460405 .

Safety profile of inactivated COVID-19 in healthy adults aged ≥ 18 years: A passive surveillance in Indonesia.

Coronavirus Disease 2019 (COVID-19) vaccination in Indonesia has shown effectiveness in reducing the morbidity and mortality of Covid-19. The study aims to evaluate the incidence rate and severity of Adverse Events Following Immunization (AEFI) of inactivated SARS-CoV-2 vaccine during the first quarter of 2021 until the second quarter of 2022 in Indonesia. More than two hundred million Sinovac/CoronaVac were given from January 13th, 2021, until June 30th, 2022. Data for this study were collected manually and electronically from the national vaccine safety website managed by the National Committee (NC) of AEFI Indonesia and the Ministry of Health Indonesia. The total number of injections observed in the study was 264,311,992 doses consisting of 142,449,795 (first dose), 121,613,324 (second dose), and 248,873 (booster dose). Of the injections given, 301 subjects with Serious AEFIs (SAE) and 10.261 subjects with non-serious AEFIs (AE) reported, with a majority of SAE and AEs found in the first dose. Most of the SAEs were classified as coincidental events by the NC AEFI (IR 0.8/1 million doses on first dose injection; 0.31 on second dose injection). ISRR (immunization stress-related response) is in the second rank of SAEs reported (0.59 IR/1 million doses on the first dose; 0.14 on the second dose). The incidence rate of SAEs and AEs, both in the variable of age, sex, and symptoms per 1 million dose injections in Indonesia, was very rare according to WHO guidelines. Most SAEs were classified as coincidences or unrelated to the vaccine. The result showed that the Sinovac/CoronaVac in Indonesia is safe.

Comparison of three spot proteinuria measurements for pediatric nephrotic syndrome: based on the International pediatric Nephrology Association 2022 Guidelines.

BACKGROUND: Pediatric nephrotic syndrome (NS) requires routine proteinuria monitoring, which is costly and affects patients' quality of life. The gold-standard 24-h urine protein (UP) measurement is challenging in children, and first-morning urine collection requires specific conditions, making it difficult in outpatient settings. Studies have reported comparability of second or random morning urine sample to the first-morning specimen. This study aimed to compare outcomes of random morning proteinuria measurements to 24-h UP and the roles of the urinary protein creatinine ratio (UPCR) and dipstick tests in pediatric NS, based on International Pediatric Nephrology Association (IPNA) 2022 Guidelines. METHOD: Twenty-four-hour and morning urine samples were collected from 92 pediatric NS patients. These were subjected to automated analyses for 24-h UP, UPCR, and semi-automated dipstick analysis. A blinded doctor performed manual dipstick analysis. RESULTS: UPCR had a stronger correlation with 24-h UP than with automated and manual urine dipstick tests. UPCR had the highest sensitivity and specificity for predicting no remission/relapse and high sensitivity but low specificity for complete remission. The optimal UPCR cutoff for remission was 0.44 mg/mg and for no remission/relapse was 2.08 mg/mg. Automated and manual dipstick tests demonstrated limited sensitivity but high specificity and similar AUC values for remission/relapse. CONCLUSION: UPCR was sensitive and specific for diagnosing no remission/relapse and sensitive but not specific for detecting remission. Manual and automated urine dipstick tests were comparable for remission and no remission/relapse detection. This study supports the IPNA 2022 Guidelines, as 2 mg/mg was the optimal UPCR cutoff for no remission/relapse, while for remission the optimal cutoff was 0.4 mg/mg.

Safety profile of inactivated COVID-19 vaccine in indonesian adults.

Background: Vaccines are urgently needed to handle the morbidity and mortality of the COVID-19 pandemic in Indonesia. The inactivated vaccine is widely used in Indonesia's national immunization program due to its eligibility of stock, easier to transport, and considered to be more established than newer platforms. In this study, we aimed to evaluate the safety profile of the inactivated vaccine and analyze the safety profile between adults and the elderly. Methods: A prospective analytical study was conducted to evaluate the safety profile of inactivated COVID-19 vaccine among healthy adults aged ≥ 18 years from September 2nd to December 28th, 2021, at ten primary health centers from 5 districts in Jakarta, Indonesia. The participants were instructed to record the symptoms after inactivated COVID-19 vaccine injection in the diary card for 28 days. Chi-square tests were carried out to analyze the relationship between the adverse event following immunization (AEFI) in adults and elderly groups. Results: Four of 1113 participants were not included in this study due to the lack of follow-up. Out of 1109 participants, there were 1044 adults (18-59 years) and 65 elderly (>59 years). There were no serious AEFI cases reported. Most AEFI cases were mild to moderate and resolved after several days of injection. Local pain, myalgia and fatigue were the most frequent adverse events reported. We found that there was no correlation between the adults and elderly age group with the incidence of AEFI (p = 0.924) for local reactions (p = 0.181) and most of the systemic reactions (p = 0.629). However, there is an increased risk of fever in the elderly group compared to the adult group (OR 4.046, 95 % CI 1.794-9.124, p = 0.003) following immunization. Conclusions: Our study demonstrated that the inactivated COVID-19 vaccine is safe, considering that all symptoms experienced were mild to moderate and resolved entirely.

Infection prevention and control in Indonesian hospitals: identification of strengths, gaps, and challenges.

BACKGROUND: Infection prevention and control (IPC) in hospitals is key to safe patient care. There is currently no data regarding the implementation of IPC in hospitals in Indonesia. The aim of this study was to assess the existing IPC level in a nationwide survey, using the World Health Organization (WHO) IPC assessment framework tool (IPCAF), and to identify strengths, gaps, and challenges. METHODS: A cross-sectional study was conducted from July to November 2021. Of all general hospitals in Indonesia, 20% (N = 475) were selected using stratified random sampling based on class (A, B, C and D; class D with a maximum of 50 beds and class A with ≥ 250 beds) and region. The IPCAF was translated into Indonesian and tested in four hospitals. Questions were added regarding challenges in the implementation of IPC. Quantitative IPCAF scores are reported as median (minimum-maximum). IPC levels were calculated according to WHO tools. RESULTS: In total, 355 hospitals (74.7%) participated in this study. The overall median IPCAF score was 620.0 (535.0-687.5). The level of IPC was mostly assessed as advanced (56.9% of hospitals), followed by intermediate (35.8%), basic (7.0%) and inadequate (0.3%). In the eastern region of the country, the majority of hospitals scored intermediate level. Of the eight core components, the one with the highest score was IPC guidelines. Almost all hospitals had guidelines on the most important topics, including hand hygiene. Core components with the lowest score were surveillance of healthcare-associated infections (HAIs), education and training, and multimodal strategies. Although > 90% of hospitals indicated that surveillance of HAIs was performed, 57.2% reported no availability of adequate microbiology laboratory capacity to support HAIs surveillance. The most frequently reported challenges in the implementation of IPC were communication with the management of the hospitals, followed by the unavailability of antimicrobial susceptibility testing results and insufficient staffing of full-time IPC nurses. CONCLUSION: The IPC level in the majority of Indonesian hospitals was assessed as advanced, but there was no even distribution over the country. The IPCAF in combination with interviews identified several priority areas for interventions to improve IPC in Indonesian hospitals.

Expert review of global real-world data on COVID-19 vaccine booster effectiveness and safety during the omicron-dominant phase of the pandemic.

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies. AREAS COVERED: Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines. EXPERT OPINION: Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

Educational videos to address vaccine hesitancy in childhood immunization.

BACKGROUND: As one of the essential programs that have been developed for decades, childhood immunizations are mandatory to protect children from vaccine-preventable diseases. Despite its availability and accessibility, immunization coverage has not reached the intended goals. Vaccine hesitancy and COVID-19 pandemic may threaten immunization coverage in children. This study aimed to evaluate the tailored educational videos to reduce vaccine hesitancy and analyze the changes in childhood routine immunization status. METHODS: This was an interventional quasi-experimental study in three subdistricts of North Jakarta, Indonesia. Participants were allocated into educational videos exposures (intervention group, n = 116) or to the digital version of the maternal and child health handbook (control group, n = 104). We administered a pre- and post-intervention vaccine hesitancy survey using the Parent Attitudes about Childhood Vaccines (PACV) questionnaire with cut-off scores of 50. RESULTS: A total of 220 parents were recruited in this study from June 18, 2021, to December 10, 2021. The pre-intervention PACV survey showed that 19 (8.6%) parents were vaccine-hesitant from both groups: 12 (10.3%) and 7 (6.7%) of parents among intervention and control groups. After the interventions, there were 8 (6.9%) and 8 (7.7%) vaccine-hesitant parents in the intervention and control groups, respectively. We found a significant difference in the post-intervention PACV median score between the intervention and control groups (17 vs 23; p = 0.035). Around 25% of parents have not completed their children's immunization status: 22.4% and 28.8% in the intervention and control groups, respectively. There was a significant difference between the proportion of PACV hesitancy on the immunization status within intervention and control groups (p = 0.001). CONCLUSION: There was a reduction in vaccine hesitancy after interventions. Educational videos intervention distributed through WhatsApp group was associated with lower vaccine hesitancy and can be used as health education tools among Indonesian parents in the community.

Diphtheria outbreak in Jakarta and Tangerang, Indonesia: Epidemiological and clinical predictor factors for death.

BACKGROUND: In 2017, a diphtheria outbreak occurred in several provinces in Indonesia. The aim of this study was to identify predictors of mortality outcome of pediatric patients with clinical diphtheria. METHODS: A retrospective cohort study was conducted using patient medical records at five referral hospitals in the Province of Jakarta and one in Tangerang District, Banten Province during January 2017 to 31 August 2018. All children in the age group of 1-18 years old discharged with diagnosis of clinical diphtheria formed the study group. All anonymized patient data were evaluated for demographic issues, clinical features, immunization status, complication, laboratory profiles and outcome. RESULTS: A total of 283 patients with clinical diphtheria were included in the study group with case fatality rate of 3.5%. All mortal patients had the complication of myocarditis. Regression analyses revealed factors for predicting mortality. Incomplete primary diphtheria toxoid immunization, stridor, bull neck, leukocytosis ≥15 x109 cells/L and thrombocytopenia ≤150 x109 cells/L in each combination for 2 predictors modeling were correlated with death. CONCLUSIONS: We report key predictors of mortality in pediatric patients with clinical diphtheria. The presence of these features when admitted to the hospital must be taken into account, because they can lead to fatal outcome.

A novel Vi-diphtheria toxoid typhoid conjugate vaccine is safe and can induce immunogenicity in healthy Indonesian children 2-11 years: a phase II preliminary report.

BACKGROUND: Typhoid fever caused by Salmonella enteric serovar Typhi (S. Typhi) is a common cause of morbidity in the world. In 2017, 14.3 million cases of Typhoid and paratyphoid fever occurred globally. School age children between 3 to 19 years old are the most affected. Poor sanitation and multi drug resistance have increased the need for vaccines to reduce the global burden of disease. Based on previous trials, typhoid conjugate vaccines have longer- lasting protection, higher efficacy, require fewer doses and are suitable from infancy that allows them to be incorporated into the routine immunization program. Our previous phase I trial proved that a novel Vi-DT typhoid conjugate vaccine is safe and immunogenic in subjects 2-5 and 18-40 years. Our phase II trial consisted of subjects 6 months to 40 years. Our previously published paper on subjects 6 to < 24 months proved that this vaccine is safe and immunogenic for this age group. Therefore, with this paper we aimed to evaluate the safety and immunogenicity in children 2-11 years. METHODS: A randomized, observer-blind, superiority design of Vi-DT Typhoid conjugate vaccine compared to Vi-polysaccharide vaccine (Vi-PS) phase II study was conducted from October 2018 to December 2018 where 200 subjects aged 2-11 years were recruited. A blood sample prior to vaccination was taken, followed by administration of a single dose of either test vaccine (Vi-DT) or control vaccine (Vi-PS) and then a second blood sample was collected 28 days post vaccination. Adverse reactions were assessed and antibody increment was evaluated at 28 days post vaccination through collected serum sample. RESULTS: Pain was the most common local reaction. Fever and muscle pain were the most common systemic reactions. Both Vi-DT and Vi-PS groups had roughly the same number of adverse reactions. At 28 days post vaccination, 100% of subjects in the Vi-DT group and 93% of subjects in the Vi-PS group produced antibody increment ≥4 times. The Vi-DT group produced a higher GMT as compared to Vi-PS. CONCLUSION: Vi-DT vaccine is safe and immunogenic in children 2-11 years old. TRIAL REGISTRATION: Trial registration number: NCT03460405 .

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.

Spatiotemporal variability in dengue transmission intensity in Jakarta, Indonesia.

BACKGROUND: Approximately 70% of the global burden of dengue disease occurs on the Asian continent, where many large urban centres provide optimal environments for sustained endemic transmission and periodic epidemic cycles. Jakarta, the capital of Indonesia, is a densely populated megacity with hyperendemic dengue transmission. Characterization of the spatiotemporal distribution of dengue transmission intensity is of key importance for optimal implementation of novel control and prevention programmes, including vaccination. In this paper we use mathematical models to provide the first detailed description of spatial and temporal variability in dengue transmission intensity in Jakarta. METHODOLOGY/PRINCIPAL FINDINGS: We applied catalytic models in a Bayesian framework to age-stratified dengue case notification data to estimate dengue force of infection and reporting probabilities in 42 subdistricts of Jakarta. The model was fitted to yearly and average annual data covering a 10-year period between 2008 and 2017. We estimated a long-term average annual transmission intensity of 0.130 (95%CrI: 0.129-0.131) per year in Jakarta province, ranging from 0.090 (95%CrI: 0.077-0.103) to 0.164 (95%CrI: 0.153-0.174) across subdistricts. Annual average transmission intensity in Jakarta province during the 10-year period ranged from 0.012 (95%CrI: 0.011-0.013) in 2017 to 0.124 (95%CrI: 0.121-0.128) in 2016. CONCLUSIONS/SIGNIFICANCE: While the absolute number of dengue case notifications cannot be relied upon as a measure of endemicity, the age-distribution of reported dengue cases provides valuable insights into the underlying nature of transmission. Our estimates from yearly and average annual case notification data represent the first detailed estimates of dengue transmission intensity in Jakarta's subdistricts. These will be important to consider when assessing the population-level impact and cost-effectiveness of potential control and prevention programmes in Jakarta province, such as the controlled release of Wolbachia-carrying mosquitoes and vaccination.

One-month follow up of a randomized clinical trial-phase II study in 6 to <24 months old Indonesian subjects: Safety and immunogenicity of Vi-DT Typhoid Conjugate Vaccine.

INTRODUCTION: World Health Organization estimates the annual global incidence of typhoid fever at 11-21 million cases and approximately 128 000 to 161 000 deaths. The currently used Vi-polysaccharides (Vi-PS) vaccines have been proven to be safe and efficacious in children 2 years and above. However, poor immunogenicity of Vi-PS was observed in children below 2 years of age. This Phase II study is the continuation of the previously published Phase I study that aims to evaluate the safety and immunogenicity of a novel Vi-DT Typhoid Conjugate Vaccine (Bio Farma) in subjects 6 to <24 months. METHODS: An interventional, blinded, comparative, randomized phase II study was conducted from July 2018 until January 2019. There were 200 healthy subjects divided into two groups: trial and control groups. Inactivated poliovirus vaccine was given to control group. Immediate and delayed local and systemic reactions up to 28 days post vaccination were recorded. Antibody titers were measured prior to vaccination (V1) and 28 days post vaccination (V2). RESULT: The study showed that the seroconversion of Vi-DT vaccine 98.99%. One dose of Vi-DT vaccine induced higher geometric mean titers (GMT) in all subjects compared to that of baseline. Pain was the most common immediate and delayed local reaction. Immediate and delayed systemic reactions that mostly occurred was fever. There were no serious adverse events reported within 28 days post vaccination. CONCLUSION: The novel typhoid Vi-DT conjugate vaccine is safe and immunogenic in children 6 to <24 months. TRIAL REGISTRATION NUMBER: NCT03460405.

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.

Diphtheria Epidemiology in Indonesia during 2010-2017.

BACKGROUND: in recent years, diphtheria has reemerged in several countries including Venezuela, Yemen, Bangladesh, and Haiti. Similarly, Indonesia also showed an increased number of diphtheria cases in 2010-2017 despite the Diphteria, Tetanus, Pertussis (DTP) immunization program applied in Indonesia for children. This study aimed to evaluate the epidemiology of diphtheria cases which occurred in Indonesia during 2010-2017. METHODS: this was a retrospective study of diphtheria cases in Indonesia. The following source of data about diphtheria disease burden and vaccine coverage was obtained from Ministry of Health Republic of Indonesia, Indonesian Pediatric Society and World Health Organization South East Asia Regional Office. RESULTS: the number of diphtheria cases in Indonesia were distributed across 30 provinces with a total of 811 cases in 2011; 1,192 cases in 2012; 296 cases in 2014; and 939 cases in 2017. Based on age group, the highest number of case fatality rate were in age group of 5-9 years old. Diphtheria immunization coverage in Indonesia among children was fluctuated, reported as 67.7 % in 2007, 61.9 % in 2010, 75.6% in 2013 and 61.3% in 2018. In addition to that, the organization of internal medicine has recommend booster of DPT immunization every 10 years for those children that had received complete DPT vaccination during childhood, however this was not applied. As the countermeasure towards this trend, the Ministry of Health implemented three rounds of Outbreak Response Immunization (ORI) targeted for the age group of 0-1-6 months old and 1-18 years old in 2017 and tailor approached for adults that had exposed to cases. Banten, DKI Jakarta and West Java were the first three provinces to implement this program considering their condensed population and high risk of disease transmission. CONCLUSION: in Indonesia, there was dramatic increase of diphtheria case in 2010-2017, where immunization in children should be reinforced by increasing coverage more than 95% and adult boosted vaccination approaches should be initiated to prevent the spread of these fatal diphtheria diseases in Indonesia.

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.

Post Marketing Surveillance Study of 2nd Dose Quadrivalent Human Papilloma Virus Vaccine in Elementary School Children in Jakarta, Indonesia: Safety Result and Implementation of School-Based HPV Immunization Program

Objective: Quadrivalent human papillomavirus (QHPV) vaccine has been advised for routine vaccination of pre-adolescent girls globally, and a two-dose QHPV vaccination schedule has been introduced in Indonesia to vaccinate 5th and 6th grade elementary school female students. This post-marketing surveillance study evaluated the possible adverse events following immunization with the two-dose QHPV vaccine in Indonesia. Methods: Girls studying in grade 6 of five designated elementary schools in Jakarta, receiving their 2nd dose of QHPV vaccine and provided informed consent (represented by their parents), were included in the study. Students who had received other immunizations either simultaneously or <1 month ago were excluded. Local and systemic reactions noted at 30 min, and 72 h to 28th day, after the immunization were recorded using a Children Symptom Dairy Card/Kartu Harian Anak Sekolah (KHAS/ Student Daily Card). Results: A total of 500 students from 20 schools were included. No serious adverse events were reported during the study period. Fever (systemic reaction) of mild intensity was noted in 1.6 % (n=8) of participants, which subsided after day 6. Local reactions such as pain, redness and swelling were noted in 59.6% (n=295), 23.6% (n=118), and 17.2% (n=86) of participants, respectively. These resolved without any intervention in majority of the cases after day 5. Conclusion: These results along with the safety data from the pre-licensure clinical trials confirm the favorable safety profile of QHPV vaccine in pre-adolescent girls. The school-based two-dose QHPV immunization program in Indonesia is a safe and effective strategy for optimizing HPV vaccine coverage among pre-adolescent girls.

Six-month follow up of a randomized clinical trial-phase I study in Indonesian adults and children: Safety and immunogenicity of Salmonella typhi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine.

INTRODUCTION: There is a high global incidence of typhoid fever, with an annual mortality rate of 200,000 deaths. Typhoid fever also affects younger children, particularly in resource-limited settings in endemic countries. Typhoid vaccination is an important prevention tool against typhoid fever. However, the available polysaccharide typhoid vaccines are not recommended for children under 2 years of age. A new typhoid conjugate Vi-diphtheria toxoid (Vi-DT) vaccine has been developed for infant immunization. We aimed to define the safety and immunogenicity of the Vi-DT vaccine among adults and children in Indonesia. METHODS: An observational, blinded, comparative, randomized, phase I safety study in two age de-escalating cohorts was conducted in East Jakarta, Indonesia, from April 2017 to February 2018. We enrolled 100 healthy subjects in 2 age groups: adults and children (18-40 and 2-5 years old). These groups were randomized into study groups (Vi-DT vaccine), and comparator groups (Vi-polysaccharide (Vi-PS) vaccine and another additional vaccine) which was administered in 4 weeks apart. Subjects were followed up to six months. RESULT: One hundred healthy adults and children subjects completed the study. The Vi-DT and Vi-PS vaccines showed no difference in terms of intensity of any immediate local and systemic events within 30 minutes post-vaccination. Overall, pain was the most common local reaction, and muscle pain was the most common systemic reaction in the first 72 hours. No serious adverse events were deemed related to vaccine administration. The first and second doses of the Vi-DT vaccine induced seroconversion and higher geometric mean titers (GMT) in all subjects compared to that of baseline. However, in terms of GMT, the second dose of Vi-DT did not induce a booster response. CONCLUSION: The Vi-DT vaccine is safe and immunogenic in adults and children older than two years. A single dose of the vaccine is able to produce seroconversion and high GMT in all individuals.

Correction: Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children.

[This corrects the article DOI: 10.1371/journal.pntd.0005621.].