Background The ZF2001 vaccine, which contains a dimeric form of the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 and aluminum hydroxide as an adjuvant, was shown to be safe, with an acceptable side-effect profile, and immunogenic in adults in phase 1 and 2 clinical trials. Methods We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to investigate the efficacy and confirm the safety of ZF2001. The trial was performed at 31 clinical centers across Uzbekistan, Indonesia, Pakistan, and Ecuador; an additional center in China was included in the safety analysis only. Adult participants (≥18 years of age) were randomly assigned in a 1:1 ratio to receive a total of three 25-μg doses (30 days apart) of ZF2001 or placebo. The primary end point was the occurrence of symptomatic coronavirus disease 2019 (Covid-19), as confirmed on polymerase-chain-reaction assay, at least 7 days after receipt of the third dose. A key secondary efficacy end point was the occurrence of severe-to-critical Covid-19 (including Covid-19–related death) at least 7 days after receipt of the third dose. Results Between December 12, 2020, and December 15, 2021, a total of 28,873 participants received at least one dose of ZF2001 or placebo and were included in the safety analysis; 25,193 participants who had completed the three-dose regimen, for whom there were approximately 6 months of follow-up data, were included in the updated primary efficacy analysis that was conducted at the second data cutoff date of December 15, 2021. In the updated analysis, primary end-point cases were reported in 158 of 12,625 participants in the ZF2001 group and in 580 of 12,568 participants in the placebo group, for a vaccine efficacy of 75.7% (95% confidence interval [CI], 71.0 to 79.8). Severe-to-critical Covid-19 occurred in 6 participants in the ZF2001 group and in 43 in the placebo group, for a vaccine efficacy of 87.6% (95% CI, 70.6 to 95.7); Covid-19–related death occurred in 2 and 12 participants, respectively, for a vaccine efficacy of 86.5% (95% CI, 38.9 to 98.5). The incidence of adverse events and serious adverse events was balanced in the two groups, and there were no vaccine-related deaths. Most adverse reactions (98.5%) were of grade 1 or 2. Conclusions In a large cohort of adults, the ZF2001 vaccine was shown to be safe and effective against symptomatic and severe-to-critical Covid-19 for at least 6 months after full vaccination. (Funded by the National Science and Technology Major Project and others; ClinicalTrials.gov number, NCT04646590 .)

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

We assessed Zika virus seroprevalence among healthy 1–4-year-old children using a serum sample collection assembled in 2014 representing 30 urban sites across Indonesia. Of 662 samples, 9.1% were Zika virus seropositive, suggesting widespread recent Zika virus transmission and immunity. Larger studies are needed to better determine endemicity in Indonesia.

BackgroundWHO recommended incorporation of Haemophilus influenzae type b (Hib) vaccination into immunization program. Indonesia would adopt Hib as a National Immunization Program in 2013. We aimed at analyzing immunogenicity, safety, and consistency of a new combined DTP-HB-Hib (diphtheria-tetanus-pertussis-Hepatitis B-Haemophilus influenza B) vaccine.MethodsA prospective, randomized, double blind, multicenter, phase III study of Bio Farma DTP-HB-Hib vaccine conducted in Jakarta and Bandung, August 2012 - January 2013.Subjects were divided into three groups with different batch number. Healthy infants 6–11 weeks of age at enrollment were immunized with 3 doses of DTP-HB-Hib vaccine with interval of 4 weeks, after birth dose of hepatitis B vaccine. Blood samples obtained prior to vaccination and 28 days after the third dose. Safety measures recorded until 28 days after each dose.ResultsOf 600 subjects, 575 (96 %) completed study protocol. After 3 doses, 100.0 and 96.0 % had anti-PRP concentration ≥0.15 and ≥1.0 μg/ml. Anti-diphtheria and anti-tetanus concentration ≥0.01 IU/ml detected in 99.7 and 100.0 %; while concentration ≥0.1 IU/ml achieved in 84.0 and 97.4 %. Protective anti-HBs found in 99.3 %. The pertussis vaccine response rate was 84.9 %.None Serious Adverse events (SAEs) considered related to study vaccine or procedure.ConclusionsThe 3-dose of DTP-HB-Hib was immunogenic, well tolerated and suitable for replacement of licensed-equivalent vaccines based on immunologic and safety profiles.Trial registrationNCT01986335 – October 30th 2013.

Demam tifoid pada anak besar (lebih dari usia sepuluh tahun) pada umumnya mempunyai gambaran klinisdemam tifoid menyerupai dewasa. Demikian juga derajat berat penyakit akan lebih parah dibandingkanpasien anak yang lebih muda. Oleh karena itu, pengamatan keadaan klinis pasien selama mendapatpengobatan harus dievaluasi dengan cermat terutama mengenai parameter keberhasilan pengobatan sepertikeadaan umum, suhu, gejala intestinal, komplikasi baik intra maupun ekstra intestinal, hitung leukosit, fungsihati, dan asupan cairan serta nutrisi. Pemeriksaan biakan darah terhadap Salmonella typhi merupakan bakuemas untuk diagnosis demam tifoid. Walaupun pada saat ini telah terdapat berbagai uji diagnostik cepat(rapid diagnostic test) yang dapat dipergunakan untuk pasien rawat jalan, untuk pasien rawat inap harusdilakukan pemeriksaan biakan Salmonella typhi. Selain untuk menegakkan diagnosis, adanya biakan positifsangat berguna untuk menilai apakah pengobatan empiris yang diberikan saat pertama kali pasien datang kerumah sakit sudah tepat. Perlu diperhatikan bahwa uji resistensi bakteri harus disertakan pada hasil biakan.Hasil uji resistensi diperlukan dalam menilai antibiotik pilihan alternatif apabila pengobatan empiris tidakseperti yang kita harapkan. Kloramfenikol sampai saat ini masih merupakan pengobatan lini pertama untukdemam tifoid pada anak yang dirawat di Departemen Ilmu Kesehatan RS Cipto Mangunkusumo Jakarta.Namun saat ini banyak dilaporkan adanya keadaan multidrug resistance Salmonella typhi (MDSRT), sepertidilaporkan di Pakistan, Mesir, dan Thailand. Maka untuk kasus MDRST diberikan pilihan pengobatanlini kedua yaitu seftriakson atau kuinolon. Namun karena penggunaan kuinolon masih kontroversi untukanak mengingat dapat menyebabkan artropati, maka seftriakson menjadi pilihan kedua untuk demam tifoidpada anak.

Background Approximately 70% of the global burden of dengue disease occurs on the Asian continent, where many large urban centres provide optimal environments for sustained endemic transmission and periodic epidemic cycles. Jakarta, the capital of Indonesia, is a densely populated megacity with hyperendemic dengue transmission. Characterization of the spatiotemporal distribution of dengue transmission intensity is of key importance for optimal implementation of novel control and prevention programmes, including vaccination. In this paper we use mathematical models to provide the first detailed description of spatial and temporal variability in dengue transmission intensity in Jakarta. Methodology/Principal findings We applied catalytic models in a Bayesian framework to age-stratified dengue case notification data to estimate dengue force of infection and reporting probabilities in 42 subdistricts of Jakarta. The model was fitted to yearly and average annual data covering a 10-year period between 2008 and 2017. We estimated a long-term average annual transmission intensity of 0.130 (95%CrI: 0.129-0.131) per year in Jakarta province, ranging from 0.090 (95%CrI: 0.077-0.103) to 0.164 (95%CrI: 0.153-0.174) across subdistricts. Annual average transmission intensity in Jakarta province during the 10-year period ranged from 0.012

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

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