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.

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.

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 .

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.

Urinary iron excretion for evaluating iron chelation efficacy in children with thalassemia major.

BACKGROUND: In patients with thalassemia major, examination routinely used for the evaluation of iron load in Indonesia is serum ferritin, but it is strongly influenced by other factors such as infections, inflammation and vitamin C levels. Evaluation of urinary iron excretion is an important and easy method to indicate iron chelation efficacy. OBJECTIVE: To determine the efficacy of iron chelation therapy by urinary iron examination and to evaluate its correlation with the time of transfusion, serum ferritin level, transferrin saturation and T2* MRI. METHODS: Prospective cohort study was conducted in children with thalassemia major aged 7-<18 years old who received DFP therapy. Twenty-four-hour urine collections were examined through inductively coupled plasma - mass spectrometry (ICP-MS). Patient's serum ferritin, transferrin saturation, peripheral blood, differential count and T2* MRI was documented during the study. Data analysis is based on urine iron level, body iron balance and the correlation between urine iron level, serum ferritin, transferrin saturation and T2* MRI and dosage of DFP. RESULTS: Thirty (55%) subjects showed a higher urine iron level on the day prior to transfusion (mean: 12,828 SD ±12,801 µg/24 h) in comparison to post transfusion (mean: 10,985 SD ±10,023 µg/24 h). All subjects had positive iron balance (mean 524 SD ±230 mg). There were positive correlation between urine iron level and transferrin saturation (r = 0.559, p = 0.01) and serum ferritin (r = 0.291, p = 0.03), no correlation found with T2* MRI results. CONCLUSIONS: There is a relationship to urinary iron excretion in response to chelation therapy and the degree of iron load.

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.].

Immunogenicity and safety of a Trivalent Influenza HA vaccine in Indonesian infants and children.

INTRODUCTION: High rate of influenza infection in children made influenza vaccination strongly recommended for all person aged >6 months in Indonesia. Bio Farma Trivalent Influenza HA (Flubio®) vaccine has been used in adolescents and adults, resulted in increased seroconversion, seroprotection rates and geometric mean titer (GMT). However, no data is available regarding its efficacy and safety in children. This study aimed to assess the immunogenicity and safety of Flubio® vaccine in infants and children. MATERIALS AND METHODS: This was a phase II, open-labeled, clinical trial conducted on healthy children aged 6 month-11 years, vaccinated with 1 or 2 doses of Influenza HA vaccine, with a 28-day interval. Flubio® vaccine composed of A/California/7/2009 (H1N1) pandemic 09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 strain. This study was held at East Jakarta, Indonesia from May until July 2014. A Total of 405 subjects were included and divided into three groups: A(6-35 months), B(3-8 years), and C(9-11 years). Antibody titer was measured at visit V1 (Day 0), V2 (28 days/+7days after the first dose) and V3 (28 days/+7days after second dose). The seroprotection and seroconversion rates were assessed. Safety was assessed up to 28 days following each dose. RESULTS: A total of 404 subjects completed the study. After vaccination, all subjects achieved seroprotection and increased seroconversion rates, with post-vaccination antibody titer of ≥1:40 HI for all strains. The GMT also increased significantly. Within 30 min after vaccination, 14.6% and 2% had local and systemic reactions; meanwhile, between 30 min to 72 h after vaccination, 35.1% and 13.6% subjects had local and systemic reactions, respectively. Most reactions were mild. No serious adverse event (SAE) was reported related to vaccine. CONCLUSION: Flubio® (Influenza HA Trivalent) vaccine is immunogenic and safe for children aged 6 months-11 years. TRIAL REGISTRATION: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02093260.

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

BACKGROUND: Indonesia reports the second highest dengue disease burden in the world; these data are from passive surveillance reports and are likely to be significant underestimates. Age-stratified seroprevalence data are relatively unbiased indicators of past exposure and allow understanding of transmission dynamics. METHODOLOGY/PRINCIPAL FINDINGS: To better understand dengue infection history and associated risk factors in Indonesia, a representative population-based cross-sectional dengue seroprevalence study was conducted in 1-18-year-old urban children. From October to November 2014, 3,210 children were enrolled from 30 geographically dispersed clusters. Serum samples were tested for anti-dengue IgG antibodies by indirect ELISA. A questionnaire investigated associations between dengue serologic status and household socio-demographic and behavioural factors. Overall, 3,194 samples were tested, giving an adjusted national seroprevalence in this urban population of 69.4% [95% CI: 64.4-74.3] (33.8% [95% CI: 26.4-41.2] in the 1-4-year-olds, 65.4% [95% CI: 69.1-71.7] in the 5-9-year-olds, 83.1% [95% CI: 77.1-89.0] in the 10-14-year-olds, and 89.0% [95% CI: 83.9-94.1] in the 15-18-year-olds). The median age of seroconversion estimated through a linear model was 4.8 years. Using a catalytic model and considering a constant force of infection we estimated 13.1% of children experience a primary infection per year. Through a hierarchical logistic multivariate model, the subject's age group (1-4 vs 5-9 OR = 4.25; 1-4 vs. 10-14 OR = 12.60; and 1-4 vs 15-18 OR = 21.87; p<0.0001) and the number of cases diagnosed in the household since the subject was born (p = 0.0004) remained associated with dengue serological status. CONCLUSIONS/SIGNIFICANCE: This is the first dengue seroprevalence study in Indonesia that is targeting a representative sample of the urban paediatric population. This study revealed that more than 80% of children aged 10 years or over have experienced dengue infection at least once. Prospective incidence studies would likely reveal dengue burdens far in excess of reported incidence rates.