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Rodman Tarigan Girsang, Kusnandi Rusmil, Eddy Fadlyana, Cissy B Kartasasmita, Muhammad Gilang Dwi Putra, Budi Setiabudiawan Department of Child Health, Universitas Padjadjaran/Dr Hasan Sadikin General Hospital, Bandung, IndonesiaCorrespondence: Rodman Tarigan Girsang, Email rodman.tarigan@unpad.ac.idIntroduction: Hepatitis B virus (HBV) infection is a global health problem. Anti-hepatitis B surface antigen (HBsAg) levels increase along with vitamin D levels in adults. However, few studies have examined this relationship in adolescents. Few studies have examined the relationship between vitamin D and HBsAg antibody levels, especially in Indonesia.Methods: This cross-sectional study examined vitamin D and anti-HBsAg levels before and after hepatitis B immunisation. All subjects blood was taken to check for vitamin D level. This study was part of the Safety and Preliminary of Immunogenicity Following Recombinant Hepatitis B (Bio Farma) Vaccine in Adults and Children Phase I trial.Results: This study found that 25-hydroxyvitamin D [25(OH)D] status was primarily deficient based on endocrine criteria. The children’s hepatitis B antibody response was mostly < 10 mIU/mL before and ≥ 10 mIU/mL after vaccination. There was a relationship between sex and 25(OH)D status, with median 25(OH)D levels higher in females (18.2 ng/mL) than in males (9.8 ng/mL). However, the relationship between vitamin 25(OH)D status and anti-HBsAg levels pre- and post-vaccination was not significant.Discussion: However, some research found that vitamin D supplementation after immunisation did not impact vaccine response, several studies have reported that vitamin D can decrease HBV replication through various mechanisms, including reducing viral transcription and interfering with viral protein synthesis.Conclusion: There was no relationship between 25(OH)D status and anti-HBsAg levels. Further research is needed to elucidate the underlying mechanisms and establish optimal treatment strategies.Keywords: hepatitis B, vitamin D, adolescents, Anti-HBsAg

OBJECTIVE: To assess the burden of respiratory syncytial virus (RSV)-associated lower respiratory infections (LRI) in children in four developing countries. METHODS: A WHO protocol for prospective population-based surveillance of acute respiratory infections in children aged less than 5 years was used at sites in Indonesia, Mozambique, Nigeria and South Africa. RSV antigen was identified by enzyme-linked immunosorbent assay performed on nasopharyngeal specimens from children meeting clinical case definitions. FINDINGS: Among children aged < 5 years, the incidence of RSV-associated LRI per 1000 child-years was 34 in Indonesia and 94 in Nigeria. The incidence of RSV-associated severe LRI per 1000 child-years was 5 in Mozambique, 10 in Indonesia, and 9 in South Africa. At all study sites, the majority of RSV cases occurred in infants. CONCLUSION: These studies demonstrate that RSV contributes to a substantial but quite variable burden of LRI in children aged < 5 years in four developing countries. The possible explanations for this variation include social factors, such as family size and patterns of seeking health care; the proportion of children infected by human immunodeficiency syndrome (HIV); and differences in clinical definitions used for obtaining samples. The age distribution of cases indicates the need for an RSV vaccine that can protect children early in life. [ABSTRACT FROM AUTHOR]

Children with stunted growth have an increased risk of wheezing, and studies have shown that low levels of vitamin D and interleukin (IL)-10, along with increased IL-4 levels and CD23+ expression, are present in stunted and asthmatic children. To date, it is not known whether these factors are related to the incidence of asthma in stunted children. This case-control study investigated the association between vitamin D, IL-4, and IL-10 levels and CD23+ expression with bronchial asthma in stunted children. The study included 99 children aged 24-59 months, i.e., 37 stunted-sthmatic children (cases), 38 stunted children without asthma, and 24 non-stunted children with asthma. All children were tested for their 25(OH)D levels using chemiluminescent immunoassay (CLIA), IL-4 and IL-10 levels were measured through enzyme-linked immunosorbent assay (ELISA) testing, and CD23+ expression was measured through flow cytometry bead testing. The data were analyzed using chi-squared, Kruskal-Wallis, and Mann-Whitney tests. The results showed that stunted asthmatic children had a higher incidence of atopic family members than those without asthma. Additionally, stunted asthmatic children had a higher prevalence of vitamin D deficiency (48.6%) than the control group (44.7% and 20.8%). Furthermore, stunted asthmatic children had significantly lower levels of 25(OH)D [20.55 (16.18-25.55), p = 0.042] and higher levels of IL-4 [1.41 (0.95-2.40), p = 0.038], although there were no significant differences in IL-10 levels and CD23+ expression. The study concluded that low vitamin D and high IL-4 levels are associated with bronchial asthma in stunted children, while IL-10 and CD23+ do not show a significant association.

One of the newest strategies developed by the Global Influenza Strategy has been to broaden the composition of the current influenza vaccine formulations from trivalent products to quadrivalent products. This study aimed to assess the immunogenicity and safety of Quadrivalent Influenza HA vaccine (QIV) compared with Trivalent Influenza HA vaccine (TIV) and to evaluate three consecutive batches of QIV equivalence in Indonesian children and adults. This was an experimental, randomized, double blind, four arm parallel group bridging study involving unprimed healthy children and adults aged 9-40 years. A total of 540 subjects were enrolled in this study and randomized into four arm groups. Each subject received one dose of TIV or QIV with three different batch codes. Serology tests were performed at baseline and 28 days after vaccination. Hemagglutination inhibition (HI) antibody titers were analyzed for Geometric Mean Titer (GMT), seroprotection, and seroconversion rates. Solicited, unsolicited, and serious adverse events were observed up to 28 days after vaccination. A total of 537 subjects completed the study per protocol and were analyzed for immunogenicity criteria. All randomized subjects were analyzed for safety criteria. The percentage of the subjects with anti-HI titer ≥1:40 28 days after QIV vaccination was 99.5% for A/H1N1; 99.5% for A/H3N2; 93.1% for B/Texas, and 99.0% for B/Phuket. The seroprotection, GMT, and seroconversion rates of QIV were not significantly different from those of TIV for the common vaccine strains (p > 0.01) and were significantly different from those of TIV for the added B/Phuket strains (p < 0.01). Most solicited injection-site and systemic reactions with either vaccine were mild to moderate and resolved within a few days. Antibody response to QIV were equivalence among vaccine batches and comparable between age groups for each of the 4 strains. QIV was immunogenic and well-tolerated and had immunogenicity and safety profiles compared with TIV for all common strains. The immunogenicity of the three batches of QIV was equivalent for the four strains. Trial registration. Clinical Trial registration: NCT03336593., Competing Interests: Novilia Sjafri Bachtiar and Rini Mulia Sari are employees of PT Bio Farma at the time of the conduct of this study and manuscript preparation. PT Bio Farma Indonesia was involved in the study design, data collection, data analysis and preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Fadlyana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Inactivated COVID-19 vaccines effectively prevent death, but their effectiveness for preventing infection or severe illness is known to decrease within 3-6 months following the second priming dose. Here we aimed to evaluate the immunogenicity and safety of three potential booster vaccines administered as a full-dose homologous booster or full-dose or half-dose heterologous boosters among individuals primed with CoronaVac., Methods: We did an observer and participant masked, randomised controlled trial study of healthy Indonesian adults from five recruitment sites in Bandung and Jakarta, Indonesia, aged 18 years and older who had previously received two doses of CoronaVac within 3 to less than 6 months or 6 to 9 months before the booster dose. Participants were randomly assigned (1:1:1:1:1) by means of stratified randomisation with random block size to a homologous booster with full-dose CoronaVac or heterologous boosters with ChAdOx1-S or BNT162b2 in full dose or half dose. The primary outcome was to evaluate the seropositive, seroconversion rate, and the geometric mean titres of IgG anti-spike-receptor binding domain and neutralising antibodies, 28 days after booster dose vaccination in the per-protocol population. Safety was assessed as a secondary outcome in all vaccinated booster participants by the incidence rate and intensity of adverse events within 24 h, 7 days, and 28 days after the booster dose. This study is registered with ina-registry.org, INA-GO0HLGB, and is complete., Findings: Between Nov 26 and Dec 16, 2021, 1015 people were screened, and 960 healthy adults were enrolled; 190-193 were included in each group. 28 days after receiving the booster, combining the 3 to less than 6 months and 6 to 9 months groups, the proportions of seroconversion rates in each vaccine group were ChAdOx1-S 75 (82%) of 92 to 87 (88%) of 99 for full dose and half dose, BNT162b2 92 (92%) of 100 to 90 (98%) of 92 for full dose and half dose, and CoronaVac in 38 (41%) of 92 to 65 (66%) of 98. All booster groups achieved 100% seropositivity 28 days after the booster dose. Participants in the 6 to 9 months priming group achieved higher titres compared with participants in the 3 to less than 6 months priming group. The geometric mean titres in participants in the 6 to 9 months priming group in each vaccine group were ChAdOx1-S 11258·69 (9562·43-13 255·85) and 7853·04 (6698·92-9206·00) for full dose and half dose, BNT162b2 19999·84 (17 720·58-22 572·25) and 17 017·62 (14 694·40-19 708·16) for full dose and half dose and CoronaVac 1440·55 (1172·81-1769·42) achieved higher titres compared with participants in the 3 to less than 6 months priming group which in each vaccine group were ChAdOx1-S 7730·39 (6401·87-9334·60) and 6684·34 (5678·94-7867·73) for full dose and half dose, BNT162b2 16594·08 (13 993·08-19 678·55) and 12 121·67 (9925·21-14 804·19) for full dose and half dose, and CoronaVac 1210·23 (976·49-1499·92). The median percentage inhibition for the surrogate virus neutralisation test against the delta B.1.617.2 and wild-type (WT) variant before the booster and 28 days after the booster dose was very high in all groups (p<0·001), all with greater than 90% inhibition against both delta and WT strains. No serious adverse events were associated with the vaccines. Within the heterologous booster groups, the adverse event rates in the half-dose groups were lower compared with the full-dose groups., Interpretation: Geometric mean titre values between participants in the 6 to 9 months priming group and the 3 to less than 6 months priming group before the booster dose and between half-dose and full-dose groups 28 days before the booster were not significantly different for half-dose ChAdOx1-S, full-dose BNT162b2, and CoronaVac and were significantly different for full-dose ChAdOx1-S and half-dose BNT162b2. Among individuals primed with CoronaVac, boosting with BNT162b2 (full dose or half dose) or ChAdOx1-S (full dose or half dose) produces substantially better immune responses than in those boosted with CoronaVac. Full-dose and half-dose boosting with either BNT162b2 or ChAdOx1-S produced similar responses. Heterologous booster with half-dose might be considered in adults primed with two doses of CoronaVac vaccine., Funding: Ministry of Health, Indonesia., Translation: For the Indonesian translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests PM is employed by the National Institute of Health Research and Development. CBK, SRH, and JS are members of the Indonesian Technical Advisory Group on Immunization. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors., Methods: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors., Results: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32)., Conclusion: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Satisfying the needs of the national immunization program requires maintaining diphtheria-tetanus-pertussis (DTP)-hepatitis B (HB)- Haemophilus influenza B (Hib) production. Therefore, new hepatitis B sources are needed. This study aimed to evaluate the immunogenicity of the DTP-HB-Hib vaccine (Bio Farma) that used a different source of hepatitis B. A prospective randomized, double-blind, bridging study was conducted. Subjects were divided into two groups with different batch numbers. Healthy infants 6-11 weeks of age at enrollment were immunized with three doses of the DTP-HB-Hib vaccine after a birth dose of hepatitis B vaccine. Blood samples were obtained prior to vaccination and 28 days after the third dose. Adverse events were recorded until 28 days after each dose. Of the 220 subjects, 205 (93.2%) completed the study protocol. The proportion of infants with anti-diphtheria and anti-tetanus titers ≥ 0.01 IU/mL was 100%, with anti-HBsAg titers ≥ 10 mIU/mL was 100%, and with Polyribosylribitol Phosphate-Tetanus Conjugate (PRP-TT) titers > 0.15 µg/mL was 96.1%. The pertussis response rate was 84.9%. No serious adverse events related to the study vaccine occurred. The three-dose DTP-HB-Hib vaccine (Bio Farma) is immunogenic, well tolerated, and suitable to replace licensed-equivalent vaccines.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines., Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set., Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males., Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: YBN is staff member of the World Health Organization., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Introduction: Diarrhea is a global leading cause of morbidity and mortality among children under five, with rotaviruses being the most common cause. This study aimed to determine the genotypes of rotavirus in children under 5 years with diarrhea in Bandung, Indonesia., Methods: This cross-sectional study was conducted from 2014 to 2018 on 450 children under five with acute diarrhea in primary health centers in Bandung, Indonesia. Fecal samples were examined for rotavirus antigen using an enzyme-linked immunosorbent assay method, and genotype was determined through sequencing using polymerase chain reaction. Results were statistically analyzed using Pearson Chi-square in Epi Info version 3.5.4, with P < 0.05 considered statistically significant., Results: Rotavirus was identified in 8.9% of the subjects, slightly higher in boys ( n = 24, 9.8%) than girls ( n = 16, 7.8%). We found that the most rotavirus positive in age group is >12-24 months and >24-59 months, while the highest percentage is at the age of ≤6 months (11.8%). Moderate malnutrition was observed in more subjects (12.8%). Vomiting was more frequent in patients positive (55%, P = 0.013) and fever was seen in 32.5% ( P = 0.645). No signs of dehydration were seen in most subjects (75%), P = 0.227. Rotavirus genotypes identified were G1P[8] (18, 45%), G3P[8] (14, 35%), G3P[6] (4, 10%), G3P[9] (2, 5%), G2P[4] (1, 2.5%), and nontypeable (NT) (1, 2.5%)., Conclusions: The dominant rotavirus genotype is G1P[8], followed by G3P[8], G3P[6], G3P[9], G2P[4], and NT. The most common rotavirus positive in age group is >12-24 months and >24-59 months, while the highest percentage is at the age of ≤6 months., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Global Infectious Diseases.)

Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1-Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.

Introduction: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings., Methods: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool., Results: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84)., Conclusions: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Various studies in adults have shown a strong association between vitamin D and tuberculosis (TB), both in terms of vitamin D status and the benefits of vitamin D in managing TB. Studies on vitamin D and its relationship with childhood TB still lack in Indonesia as a country with the second-highest TB incidence globally. This study evaluated the effect of vitamin D supplementation on resolution of cough and fever in Indonesian children with pulmonary TB., Methods: We conducted a randomized controlled trial of vitamin D supplementation in children with pulmonary TB and vitamin D insufficiency. Patients were randomly allocated with 1:1 ratio to receive either 1000 IU vitamin D or placebo daily after starting standard TB treatment. The primary outcome in this study was the resolution of fever and cough symptoms reviewed weekly after starting the treatment until the symptoms are resolved. The secondary outcome in this study was 25-hydroxyvitamin D serum level and nutritional status which was reviewed at the end of the trial. Intention to treat analyses were applied. Differences in clinical outcomes between two groups were calculated using Mann-Whitney U test or χ 2 test, where appropriate., Findings: A total of 84 patients met the inclusion criteria, aged 6 to 18 years old, newly diagnosed with pulmonary TB and vitamin D insufficiency. Eighty patients (95,2%) completed the six months follow-up. Faster resolution of fever, cough, improved malnutrition status, and higher vitamin D level were found in the intervention group compared to the placebo group (all P  < 0.001)., Conclusions: Vitamin D is beneficial in improving fever and cough resolution, and improving nutritional status in children with pulmonary TB and vitamin D insufficiency. Determination of adequate supplementation levels of more than 1000 IU requires further research to achieve normal vitamin D levels during the duration of treatment for pulmonary TB in children., Trial Registration: ClinicalTrials.gov (NCT05073965)., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest Form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: The WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine., Methods: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose., Results: Most of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%., Conclusions: From the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores., Methods: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules., Results: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73)., Conclusions: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting., Competing Interests: Competing interests: The authors have completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no conflicts of interest. YBN is staff member of the World Health Organization., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Although risk factors for hospitalization from a respiratory syncytial virus (RSV) are well known, RSV lower respiratory tract infections (LRIs) in the community are much less studied or understood, especially in developing countries. In a prospective, cohort study we studied factors predisposing Indonesian infants and children under 5 years of age to developing RSV LRIs. Subjects were enrolled in two cohorts: a birth cohort and a cross-sectional cohort of children <48 months of age. Subjects were visited weekly at home to identify any LRI, using the World Health Organization's criteria. RSV etiology was determined through analysis of nasal washings by enzyme immunoassay and polymerase chain reaction. Risk factors for the development of the first documented RSV LRI were identified by multivariate analysis using logistic regression and Cox proportional hazard modeling. Of the 2014 children studied, 999 were enrolled within 30 days of birth. There were 149 first episodes of an RSV. Risk factors for an RSV LRI were poverty ( p < 0.01), use of kerosene as a cooking fuel ( p < 0.05), and household ownership of rabbits and chickens ( p < 0.01). Our findings suggested that in a middle-income country such as Indonesia, with a substantial burden of RSV morbidity and mortality, lower socioeconomic status, environmental air quality, and animal exposure are predisposing factors for developing an RSV LRI.

In Indonesia, pneumococcal disease represents a considerable public health concern; however, published data on the epidemiology, nasopharyngeal carriage, serotype prevalence, and antibiotic resistance of Streptococcus pneumoniae in this region are limited. Therefore, this article reviews the available data from a variety of sources and also summarizes pneumococcal conjugate vaccine implementation and recommendations in Indonesia and subsequent impact on pneumococcal disease. Regional pneumococcal vaccination recommendations in Asia were also reviewed. Studies showed that pneumococcal nasopharyngeal carriage prevalence in Indonesia was approximately 43% to 55% in healthy children aged less than 5 years, which varied by age group, region, and year. Serotype analysis of pneumococcal nasopharyngeal carriage isolates in Indonesia revealed that 38% to 60% of isolates would be covered by the 13-valent pneumococcal conjugate vaccine (PCV13). The antimicrobial resistance of pneumococcal disease has increased over time; between 1997 and 2012, resistance to penicillin and sulfamethoxazole increased from 0% to 28% and 9% to 62%, respectively. Inclusion of pneumococcal conjugate vaccines into immunization programs is being implemented gradually. In 2017, Indonesia implemented a regional PCV13 immunization program in Lombok with a 2 + 1 vaccination schedule that was expanded in 2018-2019 to West Nusa Tenggara and Bangka Belitung Provinces; this expansion is predicted to substantially reduce the burden of pneumococcal disease in Indonesia. Overall, the limited data available regarding pneumococcal disease in Indonesia highlight the unmet need for comprehensive disease surveillance studies in this region that can help direct vaccination strategies.

Introduction: Healthcare providers in resource-limited settings rely on the presence of tachypnoea and chest indrawing to establish a diagnosis of pneumonia in children. We aimed to determine the test characteristics of commonly assessed signs and symptoms for the radiographic diagnosis of pneumonia in children 0-59 months of age., Methods: We conducted an analysis using patient-level pooled data from 41 shared datasets of paediatric pneumonia. We included hospital-based studies in which >80% of children had chest radiography performed. Primary endpoint pneumonia (presence of dense opacity occupying a portion or entire lobe of the lung or presence of pleural effusion on chest radiograph) was used as the reference criterion radiographic standard. We assessed the sensitivity, specificity, and likelihood ratios for clinical findings, and combinations of findings, for the diagnosis of primary endpoint pneumonia among children 0-59 months of age., Results: Ten studies met inclusion criteria comprising 15 029 children; 24.9% (n=3743) had radiographic pneumonia. The presence of age-based tachypnoea demonstrated a sensitivity of 0.92 and a specificity of 0.22 while lower chest indrawing revealed a sensitivity of 0.74 and specificity of 0.15 for the diagnosis of radiographic pneumonia. The sensitivity and specificity for oxygen saturation <90% was 0.40 and 0.67, respectively, and was 0.17 and 0.88 for oxygen saturation <85%. Specificity was improved when individual clinical factors such as tachypnoea, fever and hypoxaemia were combined, however, the sensitivity was lower., Conclusions: No single sign or symptom was strongly associated with radiographic primary end point pneumonia in children. Performance characteristics were improved by combining individual signs and symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, we aimed to evaluate the immunological protectivity of infants following four doses of bivalent oral polio vaccine (bOPV; Bio Farma), which were given simultaneously with DTwP-Hb-Hib (Pentabio®), along with one dose of inactivated poliovirus vaccine (IPV) at the fourth visit. A total of 143 newborn infants who fulfilled the inclusion criteria were enrolled and completed the study. Subjects received the first dose of bOPV at birth. On days 60, 90 and 120, bOPV was given simultaneously with Pentabio®. On day 120, one dose of IPV was also administered. Serum samples for serology analysis were collected before the first dose of bOPV (at day 0), before the second dose of bOPV (at day 60) and 30 days after the last dose of bOPV. In addition, the intensity, duration and relationship of each adverse event to the trial vaccines were assessed. Seroprotection rates after the fourth dose of bOPV were 100%, 91.6% and 99.3% for poliovirus P1, P2 and P3, respectively. Seroconversion rates after the fourth dose of bOPV were 100.0%, 93.3% and 100% for poliovirus P1, P2 and P3, respectively. There were no severe adverse events, and systemic reactions were generally mild during the 1-28 day post-vaccination period. Collectively, our findings indicate that bOPV given simultaneously with Pentabio® and one dose of IPV at the 4th visit was immunogenic and well tolerated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Influenza B (Yamagata/Victoria lineage) can cause severe forms of respiratory infection among the pediatric population as well as influenza A strains (H3N2/H1N1). Vaccination against all four strains is required to prevent infection and severe outcome. This study is the first study to assess the immunogenicity of Quadrivalent Influenza HA vaccine (QIV) and ascertain safety among children in Indonesia., Methods: This is an open labeled, single arm, bridging clinical study involving unprimed healthy children 6-35 months of age (Group I) and 3-8 years of age (Group II). Subjects on both groups receiving two doses of QIV with a 28 days interval. Serology tests were performed on baseline and 28 days post-vaccination. Hemagglutination inhibition antibody titers were analyzed for Geometric Mean Titer (GMT), seroprotection, and seroconversion rates. Solicited reactions, unsolicited adverse events, and serious adverse events were observed up to 28 days post-vaccination., Results: Out of 270 subjects enrolled, 269 subjects completed the study. Immunogenicity analysis were evaluated on 254 subjects. Seroprotection rates were ≥85% for all vaccine strains in both groups. Seroconversion of more than 4 folds for all strains occurred in both groups post-vaccination. In Group I, the increase of GMT for A/H1N1, A/H3N2, B/Texas, and B/Phuket was 12.5, 14.5, 8.2, and 6.4 folds, respectively. In Group II the increase of GMT for A/H1N1, A/H3N2, B/Texas, and B/Phuket was 14, 17, 10, and 8 folds, respectively. The majority of local adverse events (AEs) after the first and second immunizations were immediate injection-site pain (10.4% and 12.6%). The majority of systemic AEs after the first and second immunizations were delayed unsolicited AEs (14.8% and 14.9%). No vaccine-related serious adverse events or deaths were reported., Conclusion: The investigational QIV was immunogenic with an acceptable safety profile in children 6 months to 8 years of age., Clinical Trial Registration: NCT03336593., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Meita Dhamayanti, Kusnandi Rusmil, Eddy Fadlyana, Rodman Tarigan, Dwi Prasetyo, Nelly Amalia, Viramitha, K Rusmil, Hadyana Sukandar, Cissy B Kartasasmita, received grant support through their institutions. Rini Mulia Sari and Novilia Sjafri Bachtiar are employees of PT Bio Farma at the time of this study and manuscript preparation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: There are scant recent studies from low middle-income countries that investigate the impact of otitis media (OM) on hearing loss (HL) in school children., Methods: This was a prospective epidemiological survey conducted by otorhinolaryngologists and audiologists in a sample of 7005 public school children (6-15 years) from 6 urban and rural sub-districts, in Indonesia. Children with otoscopic abnormalities or who failed a hearing-screening test conducted at school, underwent diagnostic audiometry and tympanometry., Results: OM was detected in 172 children (2.5%), acute otitis media - AOM (17%), otitis media with effusion - OME (15%), and chronic suppurative otitis media - CSOM (67%). The overall rate of HL in the school children was 181/10,000, which was almost three-fold higher in rural (273/10,000) than urban areas 92.6/10,000. OME accounted for much of the mild HL, while CSOM accounted for most of the moderate HL. There was a significantly higher rate of OM related HL in rural areas (116.2/10,000), than in urban areas (47.4/10,000), p = 0.002. OM related disabling HL was found at a rate of 44.2/10,000, mostly due to CSOM (37.1/10,000)., Conclusion: Otitis media contributed to 57% of all HL in school children, and posed a significant burden on Indonesian school children. Most of the disabling HL was due to CSOM. Efforts to find these children and offer ear and hearing care are important., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The new combination of DTwP-HB-Hib vaccines has been developed in Indonesia following World Health Organization (WHO) recommendation and integrated into national immunization program. The aims of the study were to measure 1) antibody persistence 12-18 months after a primary series, 2) immune response and safety after a booster dose of DTwP-HB-Hib., Methods: This was a multi-center, open-labeled, prospective, interventional study. Subjects who had received complete primary dose of DTwP-HB-Hib vaccine from the previous phase III trial were recruited in this trial. Subjects were given one dose of DTwP-HB-Hib (Pentabio®) booster at age 18-24 months old. Diphtheria, tetanus, pertussis, hepatitis B, Hemophilus influenza type B antibodies were measured before and after booster to determine antibody persistence and immune response. Vaccine adverse events were assessed immediately and monitored until 28 days after the booster recorded with parent's diary cards., Results: There were 396 subjects who completed the study. Increased proportion of seroprotected subjects from pre-booster to post-booster were noted in all vaccine antigens: 74.5 to 99.7% for diphtheria; 100 to 100% for tetanus; 40.4 to 95.5% for pertussis; 90.2 to 99.5% for hepatitis B; and 97.7 to 100% for Hib. Common systemic adverse events (AEs) were irritability (23.7-25%) and fever (39.9-45.2%). Local AEs such as redness, swelling, and induration were significantly less common in the thigh group (7.7, 11.3, and 7.1%) than in the deltoid group (28.9, 30.7, and 25%) (P < 0.001). Most AEs were mild and resolved spontaneously within three-day follow-up period., Conclusions: Booster of DTwP-HB-Hib vaccine at age 18-24 months is required to achieve and maintain optimal protective antibody. The vaccine is safe and immunogenic to be used for booster vaccination., Trial Registration: NCT02095314 (retrospectively registered, March 24, 2014).

Background: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java., Methods: analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB  to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group., Results: heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels.

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015., Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity., Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population., Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group., Funding: The Bill & Melinda Gates Foundation., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Although the epidemiology of otitis media is well-known in industrialized countries, the extent of otitis media in developing Asian countries, especially in south East Asia is not well studied., Methods: To define the burden of otitis media and its sequelae in children 6-15 years of age, we enrolled elementary and junior high school children in 6 areas in rural and urban Indonesia. Randomly selected schools and classrooms were selected. All children were administered a questionnaire and had ear examinations, pneumatic otoscopy and screening audiometry. Children with any abnormality on examination or with a relevant history underwent diagnostic audiometry and tympanometry, if indicated., Results: Of the 7005 children studied, 116 had chronic suppurative otitis media (CSOM), 30 had acute otitis media and 26 had otitis media with effusion. 2.7% of rural children had CSOM compared with 0.7% of urban children (P < 0.0001). The rates per 1000 of CSOM in rural Bali and Bandung were significantly higher (75 and 25, respectively) than in the rest of Indonesia (P < 0.05). In rural Bali, the rate per 1000 children of inactive CSOM was 63 in 6- to 9-year-old children, compared with 37 in children aged 13-15 years. Concomitantly, the rates of tympanosclerosis were 7 and 26/1000, respectively, in these age groups., Conclusions: In Indonesia, the prevalence of CSOM is relatively high with most disease occurring in rural areas. The high rates in rural Bali with early progression to tympanosclerosis suggest a significant burden of potentially vaccine preventable illness.

Background: Although the epidemiology of respiratory syncytial virus (RSV) lower respiratory tract infections (LRI) is well known in industrialized countries, the burden in developing Asian countries is not well studied., Methods: To define the burden of RSV disease in children <5 years of age in rural and urban Indonesia, infants and children were enrolled from peri-urban and rural subdistricts, in the following 2 cohorts: (a) a cross-sectional cohort of approximately 100 children from each of 2 subdistricts in the following 5 age groups: 3 to 5, 6 to 8, 9 to 11, 12 to 23, and 24 to 48 months; (b) a birth cohort of all newborns in both subdistricts during the 28 months of the study. All subjects were visited weekly at home. Children with World Health Organization-defined LRI or wheezing had a nasal wash for detection of RSV using an enzyme immunoassay and polymerase chain reaction., Results: Of the 2014 children studied, 1074 were in the cross-sectional and 940 in the newborn cohorts. Of the 802 episodes of LRI, 163 were caused by RSV. The RSV LRI incidence per 1000 child-years (C-Y) was higher in rural areas (57.25 vs. 38.54), P < 0.05. No RSV LRI occurred in the first 2 months of life and the peak incidence was in the 6- to 8-month-old infants (103/1000 C-Y). The rates were lowest in those <6 months, 16.5 per 1000 C-Y, compared with 83.1 per 1000 C-Y in those 6 to 11 months of age (P < 0.001), 66.99 in those 12 to 23 months of age, and 28.1 in 2- to 5-year-olds., Conclusions: In Indonesia, the incidence of RSV LRI in the first 6 months of life is relatively low with most disease occurring in older children.

DNA microarrays used as 'genomic sensors' have great potential in clinical diagnostics. Biases inherent in random PCR-amplification, cross-hybridization effects, and inadequate microarray analysis, however, limit detection sensitivity and specificity. Here, we have studied the relationships between viral amplification efficiency, hybridization signal, and target-probe annealing specificity using a customized microarray platform. Novel features of this platform include the development of a robust algorithm that accurately predicts PCR bias during DNA amplification and can be used to improve PCR primer design, as well as a powerful statistical concept for inferring pathogen identity from probe recognition signatures. Compared to real-time PCR, the microarray platform identified pathogens with 94% accuracy (76% sensitivity and 100% specificity) in a panel of 36 patient specimens. Our findings show that microarrays can be used for the robust and accurate diagnosis of pathogens, and further substantiate the use of microarray technology in clinical diagnostics.

Study Objective: To evaluate the relationship between vitamin A supplementation, plasma retinol level (PRL) and incidence, severity and duration of acute respiratory infect ions (ARI) in children 1-5 years old., Design and Setting: A one year prospective randomized intervention study from June 1989 to May 1990 in Cikutra, a suburb of Bandung, Indonesia., Subjects and Measurements: Out of almost 2000 children aged 12-54 months, 269 were selected by stratified randomization. Vitamin A (200,000 IU orally) was administered at 6-monthly intervals in a double blind, placebo controlled programme. Every 2 weeks, primary health care workers collected data on respiratory symptoms in the children, and every month a pediatrician examined the children. Venous blood samples were obtained at the start and at 3 and 6 months for plasma retinol levels (PRL)., Results: The mean PRL at the start of the study was 20 +/- 8 micrograms/dl; 8% of the children showed a deficient level of less than 10 micrograms/dl. The incidence or ARI was 6.7 +/- 3.5 episodes per child per year with a mean duration of 5.3 +/- 3.1 days per episode. In vitamin A supplemented children the duration of ARI was slightly shorter (5.2 +/- 3.1 versus 5.6 +/- 3.1 days, P < 0.01) but no effect on the incidence or severity of ARI was detected. Low, and especially deficient, PRL had improved after 3 months and even after 6 months, but this was unrelated to vitamin A supplementation. There was also no relationship between PRL and incidence, severity or duration of ARI., Conclusions: Only a slight relationship is found between vitamin A supplementation and ARI duration in under-fives.

By questionnaire we studied the occurrence of acute respiratory infections (ARI) in 1961 children between 0 and 5 years old from a total of 3225 families in Cikutra, Bandung. In 38.7% of them 200.000 IU vitamin A supplement had been given at least once during the preceding year. Mild or moderate ARI occurred in 54.7% of the children during the previous month and in 87.9% during the previous year; severe ARI occurred in 5.5% during the previous month and in 16.8% during the previous year. Surprisingly slightly more ARI occurred in children with vitamin A supplementation. However, vitamin A had been distributed more to low income than high income families, and in the latter group significantly less children suffered from ARI (p less than 0.05; 44% versus 54 a 56%).

Although the hazards of smoking is well known, the number of smokers among high school students is still high. There are many factors influencing these students to start smoking. This study was conducted to discover the size of the population of smokers among high school students is still high. There are many factors influencing these students to start smoking. This study was conducted to discover the size of the population of smokers among high school students, their smoking behaviour, and what factors might be associated as risk factors. Questionnaires were filled by 1627 respondents between 12 and 22 years of age of which 955 (58.7%) are boys and 672 (41.3%) are girls. Among all male respondents there were found 622 (86.2%) experimental smokers; among all the girls there were only 99 (13.7%) experimental smokers. From the total number of experimental smokers, 377 (95.2%) boys and 19 (4.8%) girls eventually became smokers. One hundred and seventeen (16.2%) students tried smoking before 13 years old, 65 of these students became smokers. This study found that socio-economic status, parents, friends, and siblings who smoked, and social environment, have significant influence on high school students' smoking habits. To prevent and lower the number of smokers among students in high schools, health and smoking education must be started in the schools as early as possible.