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Dengue, caused by infection of any of four dengue virus serotypes (DENV-1 to DENV-4), is a mosquito-borne disease of major public health concern associated with significant morbidity, mortality, and economic cost, particularly in developing countries. Dengue incidence has increased 30-fold in the last 50 years and over 50% of the world’s population, in more than 100 countries, live in areas at risk of DENV infection. We reviews DENV biology, epidemiology, transmission dynamics including circulating serotypes and genotypes, the immune response, the pathogenesis of the disease as well as updated diagnostic methods, treatments, vector control and vaccine developments.

Background. The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods. A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results. A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001–1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025–1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000–1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004–1.074) had an adjusted association with severe plasma leakage. Conclusions. In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.

Objective To provide a national incidence rate and case fatality rate of dengue hemorrhagic fever in Indonesia through an analysis of the National Disease Surveillance database from the Directorate General of Disease Prevention and Control of Ministry of Health. Results Available data has indicated an increasing trend of dengue hemorrhagic fever incidence in Indonesia over the past 50 years. Incidence rates appear to be cyclic, peaking approximately every 6–8 years. In contrast, the case fatality rate has decreased approximately by half each decade, since 1980. Java Island contributed the highest average number of dengue hemorrhagic fever cases each year. In recent years, Bali and Borneo (Kalimantan) have had the highest incidence while Papua Island, the easternmost region of the Indonesian archipelago, has had the lowest incidence.

•Public acceptance toward dengue vaccine and its associated factors were determined.•A community-based, cross-sectional study was conducted among 652 healthy inhabitants in Indonesia.•Approximately 75% of participants expressed that they were likely and very likely to vaccinate their children.•Attitude toward vaccination practice and attitude regarding dengue fever are the independent predictors for vaccine acceptance.•Halal and full protection are the most important dengue vaccine characteristic among inhabitants. The first dengue vaccine (DV) has been licensed in some countries, but an assessment of the public's acceptance of DV is widely lacking. This study aimed to explore and understand DV acceptance and its associated explanatory variables among healthy inhabitants of Aceh, Indonesia. A community-based cross-sectional survey was conducted from November 2014 to March 2015 in nine regencies of Aceh that were selected randomly. A set of validated questionnaires covering a range of explanatory variables and DV acceptance was used to conduct the interviews. A multi-step logistic regression analysis and Spearman's rank correlation were employed to assess the role of explanatory variables in DV acceptance. We included 652 community members in the final analysis and found that 77.3% of them were willing to accept the DV. Gender, monthly income, socioeconomic status (SES), attitude toward dengue fever (DF) and attitude toward vaccination practice were associated with DV acceptance in bivariate analyses (P<0.05). A correlation analysis confirmed that attitude toward vaccination practice and attitude toward DF were strongly correlated with DV acceptance, rs=0.41 and rs=0.39, respectively (P<0.001). The multivariate analysis revealed that a high monthly income, high SES, and a good attitude toward vaccination practice and toward DF were independent predictors of DV acceptance. The acceptance rate of the DV among inhabitants of Aceh, Indonesia was relatively high, and the strongest associated factors of higher support for the DV were a good attitude toward vaccination practices and a good attitude toward DF.

Dengue disease is still a major health problem in Indonesia. Surabaya, the second largest city in the country, is endemic for dengue. We report here on dengue disease in Surabaya, investigating the clinical manifestations, the distribution of dengue virus (DENV) serotypes, and the relationships between clinical manifestations and the genetic characteristics of DENV. A total of 148 patients suspected of having dengue were recruited during February-August 2012. One hundred one (68%) of them were children, and 47 (32%) were adults. Dengue fever (DF) and Dengue hemorrhagic fever (DHF) were equally manifested in all of the patients. We performed DENV serotyping on all of the samples using real-time RT-PCR. Of 148, 79 (53%) samples were detected as DENV positive, with DENV-1 as the predominant serotype (73%), followed by DENV-2 (8%), DENV-4 (8%), and DENV-3 (6%), while 5% were mixed infections. Based on the Envelope gene sequences, we performed phylogenetic analyses of 24 isolates to genotype the DENV circulating in Surabaya in 2012, and the analysis revealed that DENV-1 consisted of Genotypes I and IV, DENV-2 was of the Cosmopolitan genotype, the DENV-3 viruses were of Genotype I, and DENV-4 was detected as Genotype II. We correlated the infecting DENV serotypes with clinical manifestations and laboratory parameters; however, no significant correlations were found. Amino acid analysis of Envelope protein did not find any unique mutations related to disease severity.

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

Background The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient’s isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. Methods We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. Results We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. Conclusion Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.

Background Despite the high number of chikungunya cases in Indonesia in recent years, comprehensive epidemiological data are lacking. The systematic review was undertaken to provide data on incidence, the seroprevalence of anti-Chikungunya virus (CHIKV) IgM and IgG antibodies, mortality, the genotypes of circulating CHIKV and travel-related cases of chikungunya in the country. In addition, a phylogenetic and evolutionary analysis of Indonesian CHIKV was conducted. Methods A systematic review was conducted to identify eligible studies from EMBASE, MEDLINE, PubMed and Web of Science as of October 16th 2017. Studies describing the incidence, seroprevalence of IgM and IgG, mortality, genotypes and travel-associated chikungunya were systematically reviewed. The maximum likelihood phylogenetic and evolutionary rate was estimated using Randomized Axelerated Maximum Likelihood (RAxML), and the Bayesian Markov chain Monte Carlo (MCMC) method identified the Time to Most Recent Common Ancestors (TMRCA) of Indonesian CHIKV. The systematic review was registered in the PROSPERO database (CRD42017078205). Results Chikungunya incidence ranged between 0.16-36.2 cases per 100,000 person-year. Overall, the median seroprevalence of anti-CHIKV IgM antibodies in both outbreak and non-outbreak scenarios was 13.3% (17.7 and 7.3% for outbreak and non-outbreak events, respectively). The median seroprevalence of IgG antibodies in both outbreak and non-outbreak settings was 18.5% (range 0.0–73.1%). There were 130 Indonesian CHIKV sequences available, of which 120 (92.3%) were of the Asian genotype and 10 (7.7%) belonged to the East/Central/South African (ECSA) genotype. The ECSA genotype was first isolated in Indonesia in 2008 and was continually sampled until 2011. All ECSA viruses sampled in Indonesia appear to be closely related to viruses that caused massive outbreaks in Southeast Asia countries during the same period. Massive nationwide chikungunya outbreaks in Indonesia were reported during 2009–2010 with a total of 137,655 cases. Our spatio-temporal, phylogenetic and evolutionary data suggest that these outbreaks were likely associated with the introduction of the ECSA genotype of CHIKV to Indonesia. Conclusions Although no deaths have been recorded, the seroprevalence of anti-CHIKV IgM and IgG in the Indonesian population have been relatively high in recent years following re-emergence in early 2001. There is sufficient evidence to suggest that the introduction of ECSA into Indonesia was likely associated with massive chikungunya outbreaks during 2009–2010.

Dengue, an acute febrile disease caused by dengue virus (DENV) infection, is endemic to Indonesia. During early 2020, an outbreak of severe dengue occurred in Maumere, East Nusa Tenggara province, a region with low dengue endemicity with limited data on the characteristics of the circulating DENV. By 18 March 2020, 1396 cases were reported with 14 fatalities. Investigation was conducted to understand the cause and characteristics of the outbreak. Sera were collected from 133 patients with dengue-like symptoms through random sampling at TC Hillers Hospital, Maumere during outbreak between February and June 2020. Dengue was confirmed using NS1 and/or RT-PCR detection. Serological status was determined using IgG/IgM ELISA and plaque reduction neutralization test (PRNT). DENV serotyping and genome sequencing were performed to identify the DENV serotype and genotype. We recruited suspected dengue patients attending the hospital during the outbreak. Dengue was confirmed in 72.2% (96/133), while 18.8% (25/133) were diagnosed as probable dengue. Children under 18 years old accounted for 85.1% (103/121) of dengue cases. Severe dengue accounted for 94.2% (81/86) of cases. Secondary infections made up 92.6% (112/121) of cases. Serotyping detected 87.3% (62/71) as DENV-3, 7.0% (5/71) as DENV-4, 2.8% (2/71) as DENV-1, and 2.8% (2/71) as DENV-2. Phylogenetic analysis revealed close evolutionary relationship of Maumere DENV to viruses from other Indonesian regions, especially Bali and Kupang. PRNT on DENV-3 secondary infections patients detected the presence of DENV-2 and DENV-4 neutralizing antibodies. The severe dengue outbreak in Maumere is caused by DENV-3 introduced from nearby islands. The high proportion of secondary infections likely contributes to the severity of the disease. The high percentage of anti-dengue neutralizing antibodies for multiple serotypes and the high proportion of anti-dengue IgG in young children suggests a history of dengue transmission with a high infection rate in the area.

Dengue disease is currently a major health problem in Indonesia and affects all provinces in the country, including Semarang Municipality, Central Java province. While dengue is endemic in this region, only limited data on the disease epidemiology is available. To understand the dynamics of dengue in Semarang, we conducted clinical, virological, and demographical surveillance of dengue in Semarang and its surrounding regions in 2012. Dengue cases were detected in both urban and rural areas located in various geographical features, including the coastal and highland areas. During an eight months' study, a total of 120 febrile patients were recruited, of which 66 were serologically confirmed for dengue infection using IgG/IgM ELISA and/or NS1 tests. The cases occurred both in dry and wet seasons. Majority of patients were under 10 years old. Most patients were diagnosed as dengue hemorrhagic fever, followed by dengue shock syndrome and dengue fever. Serotyping was performed in 31 patients, and we observed the co-circulation of all four dengue virus (DENV) serotypes. When the serotypes were correlated with the severity of the disease, no direct correlation was observed. Phylogenetic analysis of DENV based on Envelope gene sequence revealed the circulation of DENV-2 Cosmopolitan genotype and DENV-3 Genotype I. A striking finding was observed for DENV-1, in which we found the co-circulation of Genotype I with an old Genotype II. The Genotype II was represented by a virus strain that has a very slow mutation rate and is very closely related to the DENV strain from Thailand, isolated in 1964 and never reported in other countries in the last three decades. Moreover, this virus was discovered in a cool highland area with an elevation of 1,001 meters above the sea level. The discovery of this old DENV strain may suggest the silent circulation of old virus strains in Indonesia.