Immunogenicity Assessment of the SARS-CoV-2 Protein Subunit Recombinant Vaccine (CoV2-IB 0322) in a Substudy of a Phase 3 Trial in Indonesia.

BACKGROUND: COVID-19 is one of the most devastating pandemics of the 21st century. Vaccination is one of the most effective prevention methods in combating COVID-19, and one type of vaccine being developed was the protein subunit recombinant vaccine. We evaluated the efficacy of the CoV2-IB 0322 vaccine in Depok, Indonesia. METHODS: This study aimed to assess the humoral and cellular immune response of the CoV2-IB 0322 vaccine compared to an active control vaccine (COVOVAX™ Vaccine). A total of 120 subjects were enrolled and randomized into two groups, with 60 subjects in each group. Participants received either two doses of the CoV2-IB 0322 vaccine or two doses of the control vaccine with a 28-day interval between doses. Safety assessments were conducted through onsite monitoring and participant-reported adverse events. Immunogenicity was evaluated by measuring IgG anti-RBD SARS-CoV-2 and IgG-neutralizing antibodies. Cellular immunity was assessed by specific T-cell responses. Whole blood samples were collected at baseline, 14 days, 6 months, and 12 months after the second dose for cellular immunity evaluation. RESULTS: Both vaccines showed high seropositive rates, with neutralizing antibody and IgG titers peaking 14 days after the second dose and declining by 12 months. The seroconversion rate of anti-S IgG was 100% in both groups, but the rate of neutralizing antibody seroconversion was lower in the CoV2-IB 0322 vaccine group at 14 days after the second dose (p = 0.004). The CoV2-IB 0322 vaccine showed higher IgG GMT levels 6 and 12 months after the second dose (p < 0.001 and p = 0.01). T-cell responses, evaluated by IFN-γ, IL-2, and IL-4 production by CD4+ and CD8+ T-cells, showed similar results without significant differences between both groups, except for %IL-2/CD4+ cells 6 months after the second dose (p = 0.038). CONCLUSION: Both vaccines showed comparable B- and T-cell immunological response that diminish over time.

Immunization Simulation Using Actual-Size Infant Manikins for Medical Students in Indonesia: A Quasi-Experimental Study.

INTRODUCTION: Manikins are tools used in simulation training for medical students to develop important skills, one of which is immunization. However, conventional manikins often do not resemble the actual size of an infant's arm or leg. This study aimed to determine the impact of using actual-size manikins on students' knowledge and practical skills, evaluate their confidence in immunization practice, and assess students' responses and feedback regarding the practice using actual-size manikins. METHODS: This was a quasi-experimental study involving medical students at the Faculty of Medicine, Universitas Indonesia, from October 2020 to April 2021. Students in the intervention group used newly developed actual-size infant arm and leg manikins, while the control group used conventional manikins. All students underwent the objective structured clinical examination (OSCE) and the scores were compared between the 2 groups. Within the intervention group, data on pretest and posttest scores, feedback questionnaires, and self-confidence assessments were also obtained and analyzed. RESULTS: A total of 205 students were included. Statistically significant difference was found in the OSCE scores between the intervention and control groups (P < 0.01). Students in the intervention group (n = 108) showed significant improvement in knowledge scores after the workshop (P < 0.01). Most students (81.7%) expressed confidence in administering vaccines to live patients after practicing with manikins. In addition, 98.2% of students (n = 107) acknowledged the benefits of practicing with actual-size manikins in accurately determining the injection sites. CONCLUSIONS: Simulation with the actual-size manikins significantly improved students' knowledge and practical immunization skills, leading to increased confidence and competence in their immunization skills.

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 .

Seroconversion among children with HBsAg-positive mothers in Indonesia and factors affecting the anti-HBs titers.

Background and aim: Around 2% of newborns are at risk of hepatitis B virus (HBV) infection from their mothers. To prevent this, infants born to HBsAg-positive mothers are given hepatitis B immune globulin (HBIG) and hepatitis B (HB) vaccine as immunoprophylaxis. This study aims to investigate the efficacy of immunoprophylaxis in infants born to HBsAg-positive mothers and the contributing factors. Methods: The study was conducted on a group of 87 children, ranging from nine months to under 36 months, born to HBsAg-positive mothers and received immunoprophylaxis within 24 h after birth followed by a national immunization schedule at the Community Health Center (CHC) in three administrative cities of DKI Jakarta. We measured the levels of HBsAg and anti-HBs, and utilized ordinal logistic regression models to identify factors that influence the anti-HBs titers after vaccination. Results: Out of 87 children, only one child had positive HBsAg results. The data showed that 88.5% of the children had seroprotection with anti-HBs levels ≥10 mIU/mL. Additionally, 48.3% of the children had a high protective response with anti-HBs levels ≥100 mIU/mL, while 11.5% had a non-protective response. Children under one year of age, with a family history of HBV carriers, and who received five doses of the HB vaccine exhibited higher levels of anti-HBs titer category with adjusted OR 3.9 (95%CI: 1.3-11.6), 5.3 (95%CI: 1.1-27.4), and 8.3 (95%CI: 2-34.8), respectively. Conclusion: The administration of HBIG and HB vaccine successfully prevented vertical transmission, resulting in a high seroprotection rate.

The Cohort of Indonesian Preterm Infants for Long-term Outcomes (CIPTO) study: a protocol.

BACKGROUND: Indonesia has high numbers of preterm birth, i.e., around 600,000 preterm births annually. It imposes a significant burden on the Indonesia's healthcare system. Indonesia therefore requires its own evidence-based reference to manage premature neonates and ex-preterm infants who subsequently survived. No long-term study on preterm infants in Indonesia has been conducted, therefore we aim to evaluate growth and development on ex-preterm infants until the pre-pubertal stage. METHODS: We at the Cipto Mangunkusumo General Hospital (CMGH) designed a prospective cohort study of preterm infants, i.e., the Cohort of Indonesian Preterm Infants for Long-term Outcomes (CIPTO) study. At least 500 subjects will be recruited with an estimation of two-year recruitment (i.e., the recruitment phase will be completed before 2024). The CIPTO study will observe long-term outcomes of ex-preterm infants, primarily on growth and developmental milestones until 8 years old. Aims of this study are to determine the ex-preterm outcomes and to generate an evidence-based reference of preterm care for ensuring optimum outcomes. The pre-specified long-term outcomes in this study are survival rates, growth outcomes, neurodevelopmental outcomes, feeding behavior, as well as hearing and vision impairments. Growth and neurodevelopmental outcomes will be assessed at 0, 2, 4, 6, 9, 12, 15, 18 and 24 months of corrected age as well as at 3, 4, 5, 6, 7 and 8 years old. DISCUSSION: The CIPTO study is the first prospective cohort in Indonesia focusing on preterm infants born at the CMGH. With a follow up until 8 years old, this study may provide useful insights to generate an evidence-based, Indonesia's health care reference in managing premature infants and ensuring the optimum outcomes of ex-preterm infants.

Effectiveness of an online mental health strengthening module to build resilience and overcome stress for transitional aged medical students.

Introduction: Transitional-aged youths (17-to-24-years-old) are prone to mental-health problems. Students in higher education, especially medical students, are more exposed to stressors and thus need training to increase resilience. However, there have been limited mental-health strengthening modules specifically developed for medical students of transitional age, and none in Indonesia. This study intends to test the effectiveness of an online mental-health strengthening module in altering resilience. Methods: A pragmatic randomized trial with repeated measurements was employed to evaluate biopsychosocial outcomes of resilience. The intervention module was delivered in 4 weeks to 105 eligible students. Participants were divided into intervention group (n = 52) and control group (n = 53). Outcomes were measured in the 4th, 8th, and 12th weeks. Primary outcome was resilience level as measured by Connor-Davidson Resilience Scale (CD-RISC). Perceived Stress Scale (PSS), Depression Anxiety Stress Scale (DASS) were utilized to measure stress, depression and anxiety. Knowledge and attitude toward mental-health were also measured through validated questionnaires. Stress levels of participants were measured biologically by measuring salivary cortisol and alpha-amylase levels at the baseline and 12th-week. Results: Compared to the control group, there were no significant difference in resilience score of the intervention group compared to control group [F(1, 103) = 2.243, P = .137]; however, there was a significant main effect of time [F(3, 309) = 18.191, P < .001] and interaction effect between intervention and time in resilience score [F(3, 309) = 5.056, P = .002]. Additionally, compared to the control group, there were significant increases in knowledge [F(1, 103) = 66.805, P < .001], attitudes and behavior towards mental-health [F(1, 103) = 5.191, P = .025], and a significant decrease in stress perception score [F(1, 103) = 27.567, P < .001]. The mean salivary delta cortisol during pre-test and post-test at week 12 in the intervention group showed significant difference (P < .001). However, there was no significant difference in the mean delta salivary alpha-amylase between pre-test and post-test at week 12, both in the intervention and control groups. Conclusion: The mental-health strengthening module was accepted and applicable to first-year medical students and was found to be effective in increasing resilience from various biopsychosocial aspects. It is also advisable to have similar modules throughout the medical school to maintain sustainability.

When did the substantial loss of child linear growth occur?

BACKGROUND: Epidemiological studies show that the height-for-age Z-scores (HAZ) falter dramatically shortly after birth until the end of the first two years. Understanding these changes in linear growth in the first two years can help us understand the critical period of child linear growth and propose interventions. OBJECTIVES: This study objectives were to describe the pattern of linear growth faltering and analyze the changes in length-for-age Z-scores (LAZs) throughout the first two years based on birthweight and length status. METHODS: This study analyzed 408 children, participants in Longitudinal Study on Child Growth and Development in Bogor, Indonesia. The linear growth pattern was described based on birthweight and length status. Birthweight and length status was categorized into normal and Small for Gestational Age (SGA). Changes in LAZs (Δ LAZs) in 0-6 months, 6-12 months, and 12-23 months were calculated. General Linear Model Univariate analysis was conducted to analyze the difference of Δ LAZ between SGA and normal children. RESULTS: Though full-term SGA children have significantly higher linear growth velocity during the first 6 months of the infancy period, full-term SGA children could not catch up with the attained growth/height of normal children throughout the first two years. Thus, full-term SGA children ended up with a higher prevalence of stunted. Both in SGA and normal children, the substantial loss of LAZ occurred between 0-6 months. CONCLUSION: The finding in this study showed that the first 1000 days of life is still the best period in stunting prevention; however, the stunting prevention program should start earlier, focusing on the first 500 days of life, and potentially the prenatal period.

Development of clinical-based scoring system to diagnose tuberculous meningitis in children.

OBJECTIVE: Diagnosing tuberculous meningitis (TBM) in children is challenging due to the low sensitivity with time delay of bacterial culture techniques and the lack of brain imaging facilities in many low- and middle-income settings. This study aims to establish and test a scoring system consisting of clinical manifestations on history and examination for diagnosing TBM in children. DESIGN: A retrospective study was conducted using a diagnostic multivariable prediction model. PARTICIPANTS: 167 children diagnosed with meningitis (tuberculous, bacterial, viral and others) aged 3 months to 18 years who were hospitalised from July 2011 until November 2021 in a national tertiary hospital in Indonesia. RESULTS: Eight out of the 10 statistically significant clinical characteristics were used to develop a predictive model. These resulted in good discrimination and calibration variables, which divided into systemic features with a cut-off score of ≥3 (sensitivity 78.8%; specificity 86.6%; the area under the curve (AUC) value 0.89 (95% CI 0.85 to 0.95; p<0.001)) and neurological features with a cut-off score of ≥2 (sensitivity 61.2%; specificity 75.2%; the AUC value 0.73 (95% CI 0.66 to 0.81; p<0.001)). Combined together, this scoring system predicted the diagnosis of TBM with a sensitivity, specificity and positive predictive value of 47.1%, 95.1% and 90.9%, respectively. CONCLUSION: The clinical scoring system consisting of systemic and neurological features can be used to predict the diagnosis of TBM in children with limited resource setting. The scoring system should be assessed in a prospective cohort.

Prevalence, Risk Factors, and Pediatrician Awareness of Infant Dyschezia in Indonesia.

Purpose: This study aimed to evaluate the prevalence and risk factors of infant dyschezia as well as pediatrician awareness regarding this disease in Indonesia. Methods: This is a two-part cross-sectional study, which was divided into study A and B. Study A: Parents whose infants were under 9 months old and attended well-baby clinics were recruited at two randomly selected primary health centers. Parents also provided information on the infant's previous medical history, and socio-demographic and family details. The Rome IV criteria was translated and validated to be used for diagnosis of infant dyschezia. Study B: Randomly selected pediatricians were surveyed by using a questionnaire to evaluate their knowledge regarding infant dyschezia. Results: The prevalence of infant dyschezia based on the result of this study was 11.8%. Three risk factors had a significant relationship with infant dyschezia i.e., the number of children in the family (odds ratio [OR], 5.619; 95% confidence interval [CI], 2.194-14.390; p<0.001), complementary food diet (OR, 4.238; 95% CI, 1.902-9.443; p<0.001), and social-emotional disturbance (OR, 5.670; 95% CI, 2.550-12.609; p<0.001). The percentage of pediatricians correctly diagnosed infant dyschezia was 71.5%. Most pediatricians agreed that they did not perform any diagnostic testing (79.7%) and only provided education in cases of infant dyschezia (58.5%). Conclusion: The prevalence of infant dyschezia identified in our study was higher than that in other neighboring Asian countries, with the highest prevalence observed in infants 7-9 months old. Being an only child, receiving complementary food diet, and sociao-emotional disturbances were significant risk factors of infant dyschezia.

Corrigendum on: Pediatric COVID-19: Report from Indonesian pediatric society data registry.

[This corrects the article DOI: 10.3389/fped.2021.716898.].

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.

Parents' Perspectives Toward School Reopening During COVID-19 Pandemic in Indonesia-A National Survey.

Background: All sectors are affected due to COVID-19 pandemic occurring worldwide, including the education industry. School closure had been taking place for more than a year in Indonesia. Despite the controversies, Indonesian government had decided to begin school reopening. Objectives: This study aims to assess parental readiness for school reopening, and factors affecting parental attitude toward school reopening. Methods: A cross-sectional study using online questionnaire distributed via official Indonesian Pediatric Society (IPS) official social media account collected between March and April 2021. The questionnaire contained the general characteristics of study participants, parents' knowledge, and perspectives on COVID-19, and health protocols for school reopening. Results: A total of 17,562 responses were collected, of which 55.7% parents were ready to send their children to school should school reopens. Factors significantly contribute to parental decision to keep their child at home were: presence of vulnerable population at home [OR = 1.18 (1.10-1.27), p < 0.001], children with comorbidities [OR = 2.56 (2.29-2.87), p < 0.001], perception of COVID-19 as a dangerous disease [OR = 28.87 (14.29-58.33), p < 0.001], experience with COVID-19 positive cases in the community [OR = 1.75 (1.61-1.90), p < 0.001], COVID-19 related death in the community [OR = 2.05 (1.90-2.21), P < 0.001], approval for adult COVID-19 vaccination [OR = 1.69 (1.53-1.87), p < 0.001], and ownership of private transportation [OR = 1.46 (1.30-1.66), p <0.001]. Conclusion: We identified several factors affecting parental perception on school reopening during COVID-19 pandemic that should be addressed. This study can be used for policy-maker to make further recommendations and health educations prior to school reopening in Indonesia.

Effect of tactile-kinesthetic stimulation on growth, neurobehavior and development among preterm neonates.

BACKGROUND: Preterm neonates are at risk of delayed growth and development. Hence, early tactile-kinesthetic stimulation (TKS) is required to improve their growth and development. OBJECTIVE: To evaluate the effect of TKS on growth, neurobehavior and development among preterm neonates. METHOD: An interventional study was conducted from August 2015 to July 2017 in the neonatal unit of Dr. Cipto Mangunkusumo Hospital. Preterm neonates were recruited via random sampling and divided into two groups (the intervention group and control group). TKS was performed for 15 min, three times a day, for 10 days. The anthropometric measurements, neurobehavior (Dubowitz score) and development (Capute Scale score) of neonates in both groups were assessed. RESULTS: There were 126 preterm neonates (n = 63 in each group). During the 10-day TKS period, the intervention group had a significant increment in weight and length compared to the control group (p < 0.05) at 11-14 days, at term and 3 months. Moreover, increased tone, reflexes, and improvement in behavior based on the Dubowitz score were observed during monitoring. However, the result did not differ significantly (p > 0.05). There was no significant difference in terms of cognitive and language development in both groups (Developmental Quotient of Clinical Linguistic Adaptive Milestone Scale, Developmental Quotient of Clinical Adaptive Test and Full Scale Developmental Quotient scores, p > 0.05). CONCLUSION: TKS was significantly effective in promoting growth, particularly weight and length, among preterm neonates. However, it did not significantly influence neurobehavior and development at 3 months of chronological age.

Pediatric COVID-19: Report From Indonesian Pediatric Society Data Registry.

Background: Indonesia has a high number of COVID-19 cases and mortalities relative to not only among the Asia Pacific region but the world. Children were thought to be less affected by the virus compared to adults. Most of the public data reported combined data between adults and children. The Indonesian Pediatric Society (IPS) was involved in the COVID-19 response, especially in the area of child health. One of IPS's activities is collecting data registries from each of their chapters to provide a better understanding of COVID-19 in children. Objective: The objective of this study was to share the data of suspected and confirmed COVID-19 cases in children from IPS's COVID-19 data registry. Method: This is a retrospective study from the IPS's COVID-19 registry data. We collected the data of COVID-19 in children during March to December 2020 from each of the IPS chapters. We analyzed the prevalence, case fatality rate (CFR), age groups, diagnosis, and comorbidities of the children diagnosed with COVID-19. Result: As of December 21, 2020, there were 35,506 suspected cases of children with COVID-19. In total, there were 522 deaths, with a case fatality ratio (CFR) of 1.4. There were 37,706 confirmed cases with 175 fatalities (CFR 0.46). The highest mortality in confirmed COVID-19 cases was from children ages 10-18 years (42 out of 159 cases: 26%). The most common comorbidity and diagnosis found were malignancy (17.3%) and respiratory failure (54.5%). Conclusion: The CFR of confirmed COVID-19 cases in children in Indonesia is high and should be a major public concern.

Mental Health Problems and Needs among Transitional-Age Youth in Indonesia.

"Transitional-age youth" describes those whose ages range from 16-24 years old. In this phase, the youth face new challenges and new experiences which may increase the risk for having mental health problems, yet not very many seek help from mental health professionals. In Indonesia, no data are available about mental health problems and the needs of transitional-age youth. This study explores common mental health problems experienced during this stage and assesses how they cope with problems and their expectations from health services. This was a cross-sectional study involving 393 Indonesians aged 16-24 years in May 2020. More than 90% of students had financial and academic difficulties and felt lonely. The most prevalent mental health problem among students was anxiety (95.4%). Most of the students, ranging from 90% to 96.4%, had positive coping strategies. However, around 50% of respondents reported self-harming and having suicidal thoughts. The results of subcategories analysis between ages and faculties were similar. Their most important expectations from mental health services included confidentiality (99.2%) and being welcoming and friendly (99.2%). In conclusion, this study highlighted the most common problems transitional-age youth experience in Indonesia. While some of them already knew how to deal with their problems, not all the participants had good coping mechanisms. Their healthcare expectations were also explored, thereby providing a useful background to revise and amend the current conditions.

Translation, Validity, and Reliability of Mental Health Literacy and Help-Seeking Behavior Questionnaires in Indonesia.

Background and Aim: Mental health is an integral part of adolescent wellbeing. However, only few adolescents understand the importance of mental health and are aware of the right time to seek help. Lack of knowledge and stigma may impede help-seeking behavior. To assess these aspects, three questionnaires have been developed in the English language. This study aims to assess the validity and reliability of an Indonesian version of the Mental Health Literacy and Help-Seeking Behavior set of questionnaires among adolescents in Indonesia. Methods: This is a cross-sectional study that used The Mental Health Literacy and Help-Seeking Behavior set of questionnaires developed by Kutcher and Wei. The set consists of three questionnaires: the Mental Health Knowledge, Attitude Toward Mental Health, and Help-Seeking Behavior questionnaire. The study was conducted between October 2020 and January 2021 with 68 first-year medical students at the University of Indonesia, who represented adolescents in a transitional phase. The questionnaires were translated into the Indonesian language by a bilingual psychiatrist and reviewed by 10 expert psychiatrists to determine content validity [Item-Level Content Validity Index (I-CVI) and Scale-Level Content Validity Index (S-CVI)]. Cronbach's alpha values were used to assess internal consistency (reliability). Results: The content validity test produced positive results with an I-CVI scores of 0.7-1.0 and S-CVI scores of 0.87, 0.90, and 0.99 for the knowledge, attitude, and help-seeking behavior questionnaires, respectively. For the reliability test, Cronbach's alpha values were 0.780 for the attitude questionnaire and 0.852 for the help-seeking behavior questionnaire, while the value for the knowledge questionnaire was 0.521. Conclusion: The ability to properly measure mental health through the availability of accessible, valid, and understandable tools plays an important role in addressing mental health issues among adolescents. In the current study, the Indonesian translations of all three questionnaires examining knowledge, attitude, and help-seeking behavior were considered to be valid and reliable.

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 .

Effect of Supplementation of Zinc, Glutamine, Fiber, and Prebiotics in Presumed Healthy Indonesian Children Aged 1-3 Years.

PURPOSE: Impaired intestinal mucosal integrity may affect the gastrointestinal function, especially in relation to nutrition, absorption, and barrier function. The purpose of this study was to measure the prevalence of impaired intestinal mucosal integrity in presumed healthy children aged 1-3 years and assess the effects of zinc, glutamine, fiber, and prebiotic supplementation in them. METHODS: A cross-sectional study was conducted in 200 children aged 1-3 years in Pasar Minggu, South Jakarta, Indonesia. A randomized double-blind parallel group method clinical trial was then performed to assess the effects of zinc, glutamine, fiber, and prebiotic supplementation. RESULTS: Elevated calprotectin was found in 91/200 subjects (45.5%) at the onset of the study. After 10 months, 144 subjects completed the study: 72 subjects received the trial formula, whereas the other 72 received the standard formula. A transitory decrease in fecal calprotectin (FC) was observed after 6 months in the subgroup with normal FC levels, who were fed the test formula (p=0.012). CONCLUSION: The prevalence of impaired intestinal mucosal integrity in this group of Indonesian children aged 1-3 years was high. Supplementation with zinc, glutamine, fiber, and prebiotics during 6 months reduced FC only in those who had low levels at baseline but not in those with impaired integrity.

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.

Global immunization systems strengthening through pediatric societies: the promise of private-public partnerships in Indonesia.

Vaccines are one of the most successful health interventions in history. Yet, vaccine-preventable diseases still claim the lives of 2.5 million individuals globally every year. Approximately 60% of the 19.4 million infants that did not have access to routine immunization services in 2018 live in 10 countries, one of which is Indonesia. In order to reach global targets, it is critical for countries such as Indonesia to prioritize, tailor, and operationalize vaccination strategies to address immunization gaps. Pediatricians and national pediatric societies (NPS) are trusted stakeholders in their countries and are uniquely qualified to promote vaccination programs. The American Academy of Pediatrics (AAP) partnered with the Indonesian Pediatric Society (IPS), with support from the US Centers for Disease Control and Prevention (CDC), to initiate a multiyear project to build the capacity of IPS, individual members, and other child health clinicians to strategically advocate for improved immunization services across both public and private sectors.