Consensus Guidelines for Influenza Vaccination in Patients with Diabetes.

Influenza is a prevalent health issue encountered in daily practice. Patients with diabetes mellitus face a higher risk of infections, including influenza, owing to the compromised immune system associated with diabetes. This susceptibility arises from the potential of diabetes mellitus to weaken the immune system. Moreover, elevated blood glucose levels can create a conducive environment for the growth of bacteria and viruses. This consensus is formulated by a multidisciplinary team to serve as practical guidance for the administration of influenza vaccinations to patients with diabetes mellitus in daily practice.

Stunting as a Risk Factor for Asthma: The Role of Vitamin D, Leptin, IL-4, and CD23.

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.

DTwP-HB-Hib: antibody persistence after a primary series, immune response and safety after a booster dose in children 18-24 months old.

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).

Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population.

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-1ß, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-ß. 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.

Understanding COVID-19 Vaccine Acceptance among Healthcare Workers in Indonesia: Lessons from Multi-Site Survey.

The COVID-19 pandemic presented an unprecedented challenge to public health as well as an extraordinary burden on health systems worldwide. COVID-19 vaccines were attributed as a key tool to control the pandemic, with healthcare workers (HCWs) as a priority group to receive the vaccine. Healthcare workers are considered one of the most trusted sources of information on vaccines and vaccination. This study was conducted to evaluate the acceptability of the COVID-19 vaccine among HCWs in four different provinces of Indonesia. An anonymous cross-sectional study was conducted online among HCWs between December 2020 and February 2021. Out of 2732 participants, 80.39% stated that they would accept the COVID-19 vaccine, while 19.61% were hesitant to receive the vaccine. Concerns about the safety profile of COVID-19 vaccines and potential side-effects after vaccination were the main reasons among the participants to refuse the vaccine. Male gender, single status, higher education level, and higher risk perception increased the acceptability of the COVID-19 vaccine. Other motivators of COVID-19 vaccine acceptance include a high level of trust in the government and increased confidence in vaccine safety and efficacy studies. Dissemination of information in a timely manner as well as training programs for HCWs are crucial to increasing confidence in the COVID-19 vaccination program.

COVID-19 Vaccine Perspective Among University Lecturers and Students: A Qualitative Study of Pre Implementation of Vaccination.

Background: The determinants of vaccine preferences and hesitancy varied by time and place. Objective: The aim of this study was to assess the perspective of a COVID-19 vaccine among university-based groups. Methodology: This qualitative research involved lecturers and students, and a selection of online focused group discussion was conducted based on the following criteria, including representatives of the health and non-health faculties, with at least 8 attendees in lecturer groups, and 8 participants in student groups. Results: This study is described in 8 themes covering various issues about COVID-19 vaccine, such as views on COVID-19 vaccine, fake news, vaccine implementation by government. Conclusion: The assessment of vaccine perspective shows that although awaited by some people, it also creates contradictions. This is due to the massive amount of information available regarding the vaccine descriptions. The role of the government as the main policy maker is to provide the right information and to make the right decisions about vaccines and vaccination implementation.

Correlation Between Vitamin D Status and HBsAg Antibody Levels in Indonesian Adolescents Immunised Against Hepatitis B.

Introduction: 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.

The Association between Vitamin D, Interleukin-4, and Interleukin-10 Levels and CD23+ Expression with Bronchial Asthma in Stunted Children.

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.

Immunogenicity and safety of Quadrivalent Influenza HA vaccine compared with Trivalent Influenza HA vaccine and evaluation of Quadrivalent Influenza HA vaccine batch-to-batch consistency in Indonesian children and adults.

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.

Comparison of Immunogenicity and Safety of Diphtheria-Tetanus-Pertussis-Hepatitis B-Haemophilus influenza B (Bio Farma) with Pentabio® Vaccine Primed with Recombinant Hepatitis B at Birth (Using Different Source of Hepatitis B) in Indonesian Infants.

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.

COVID-19 Vaccine Acceptance among University Students and Lecturers in Different Provinces of Indonesia: A Cross-Sectional Study.

The coronavirus disease 2019 (COVID-19) pandemic imposed a pressing global threat. Vaccines against COVID-19 are a key tool to control the ongoing pandemic. The success of COVID-19 vaccination programs will largely depend on public willingness to receive the vaccine. This study aimed to evaluate the acceptability of COVID-19 vaccines among university students and lecturers in four different provinces of Indonesia. An anonymous, cross-sectional study was conducted online among university students and lecturers in Indonesia between 23 December 2020 and 15 February 2021. Of 3433 respondents, 50.3% stated that they would accept COVID-19 vaccination, while 10.7% expressed unwillingness and 39% were not sure about receiving the vaccine. Concern regarding the side effects after COVID-19 vaccination was the main reason among the participants for not willing to receive the vaccine. Being male, associated with the health sector, having a higher monthly expenditure and having health insurance could increase the acceptability of the COVID-19 vaccine. Low trust in the government and low confidence towards vaccine safety and efficacy could hinder participants' decision to be vaccinated. Simple, clear and fact-based information from trusted sources on a regular basis will be important for building confidence towards the COVID-19 vaccination program in Indonesia.

In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

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.

Comparative study of patients in correct usage of and preference for the Swinghaler and Turbuhaler multidose inhalers.

OBJECTIVE: Current dry powder inhalers (DPIs), introduced to overcome problems associated with pressurized metered dose inhalers (pMDIs), possess not only difficulties originating from their designs but also other barriers that prevent their correct usage. The authors of this study investigated the ease and correctness of use of Swinghaler, a new device in the form of multidose DPI, as well as the preference of the study participants for either a Swinghaler or a Turbuhaler. METHODS: A total of 260 patients from Korea, China, Indonesia, the Philippines, Taiwan, and Thailand were prospectively recruited. Patients who had stable asthma, were more than 12 years old, had no experience with DPIs, and provided informed consents were included, whereas those with limited physical or intellectual ability and prior experience with any DPIs were excluded. RESULTS: There were no group or time effects between the patients who were assigned to use a Swinghaler or a Turbuhaler first. Forty-one (16.1%) participants correctly performed the inhalation maneuver with a Swinghaler, whereas 28 (10.9%) did so with a Turbuhaler; the difference was not statistically significant. The overall assessment on the precise use of the devices indicated that there were no differences between Swinghaler and Turbuhaler usage. Comparing the preference scales between the two devices, the participants gave higher scores to the Swinghaler for all assessment items and were more satisfied with the Swinghaler compared with the Turbuhaler (78.5% vs. 55.0%, p < .001). CONCLUSIONS: The participants showed no difference in their ability to correctly use a Swinghaler when compared with a Turbuhaler and preferred the Swinghaler. These results suggest that the Swinghaler may be an effective and valuable tool for the management of airway diseases.

Effects of Vitamin D supplementation on resolution of fever and cough in children with pulmonary tuberculosis: A randomized double-blind controlled trial in Indonesia.

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 χ2 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).

Genotype Profiles of Rotavirus Strains in Children under 5-year-old Outpatients with Diarrhea in Bandung, West Java, Indonesia.

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.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

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.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

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.

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis.

BACKGROUND: The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. METHODS: We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. FINDINGS: In 2005, an estimated 33.8 (95% CI 19.3-46.2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3.4 (2.8-4.3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000-199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. INTERPRETATION: Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. FUNDING: WHO; Bill & Melinda Gates Foundation.

Knowledge, Attitude and Acceptability of the Human Papilloma Virus Vaccine and Vaccination Among University Students in Indonesia.

Introduction: Cervical cancer, a major consequence of persistent HPV infection, is the third most common cancer in women worldwide and has claimed around 311,000 women lives in 2018. The majority of these deaths took place in low- and middle-income countries (LMICs). In LMICs, where cervical cancer screening coverage is low, the HPV vaccine is a promising tool for preventing HPV infections and, thus, averting cervical cancer cases. In Indonesia, cervical cancer is the second most common cancer and HPV vaccination demonstration programs are underway in several provinces, but the HPV vaccine has not yet been introduced nationally. Since students are an important source of information for the community, and medical and nursing students are the future healthcare professionals, this study explored the knowledge, attitude, and acceptability of the HPV vaccine among University students in Indonesia. Methodology: A self-administered online questionnaire was used to assess the knowledge, attitude, and willingness of University students toward HPV vaccination. Result: A total of 433 students from Medical, Nursing, Social Sciences, and other faculties participated in the survey. It was identified that over 90% of the students were aware of cervical cancer and HPV, but only 68% knew about the HPV vaccine before participating in the study. Despite an average knowledge on the HPV vaccine, the students showed a strong willingness to receive the vaccine (95.8% acceptance rate). They believed that the HPV vaccine is safe and effective and that it will protect against HPV infection. The high cost and the lack of adequate information flow on HPV-related topics have been identified as potential barriers to the adoption of the HPV vaccine in Indonesia. Conclusion: Despite a high willingness for HPV vaccine uptake among students, there is a need to provide education on HPV vaccine-related topics to Indonesian students through awareness and training programs and improving the academic curriculum on vaccination for the long-term sustainability of the HPV vaccination program.

Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infections: Evidence from an Indonesian Cohort.

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.