ORCID Profile
0000-0003-2378-2386
Current Organisation
University of Oxford
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Publisher: American Society of Tropical Medicine and Hygiene
Date: 15-09-2021
Publisher: Springer Science and Business Media LLC
Date: 19-09-2019
DOI: 10.1007/S13659-019-00218-Z
Abstract: Massive pro-inflammatory cytokines production has been correlated with the pathogenesis of severe dengue disease. The active compound of mangosteen fruit pericarps, α-mangostin, has been commonly used as traditional medicine and dietary supplement. We examined the effect of α-mangostin against dengue virus (DENV) infection in human peripheral blood mononuclear cells (PBMC) by the measurement of virus titer and TNF-α and IFN-γ cytokines concentration post infection. Increasing concentration of α-mangostin inhibited virus replication and reduced inflammatory cytokines expression at 24- and 48-h post infection. Our results support the potential use of α-mangostin as anti-antiviral and anti-inflammatory therapies in the treatment of dengue.
Publisher: Hindawi Limited
Date: 27-03-2021
DOI: 10.1155/2021/6623400
Abstract: Chikungunya (CHIK) is a reemerging arboviral disease caused by chikungunya virus (CHIKV) infection. The disease is clinically hallmarked by prolonged debilitating joint pain. Currently, there is no specific antiviral medication nor commercial vaccine available for treatment of the disease, which makes the discovery or development of specific anti-CHIKV compounds a priority. Ginger (Zingiber officinale Roscoe) is widely known for its various health benefits. The compound [6]-gingerol is the main active ingredient found in ginger. This study sought to determine the potential of [6]-gingerol antiviral activity against CHIKV infection using in vitro human hepatocyte HepG2 cells. The antiviral activity mechanism was investigated using direct virucidal and four indirect (pre-, post-, full-, and prevention) treatment assays. [6]-Gingerol showed weak virucidal activity but significant indirect antiviral activity against CHIKV through post- and full treatment with I C 50 of 0.038 mM and 0.031 mM, respectively, without showing cell cytotoxicity. The results indicated that [6]-gingerol inhibits CHIKV infection through suppression of viral replication. Together, this study confirms the potential use of [6]-gingerol for CHIK antiviral compound.
Publisher: Frontiers Media SA
Date: 2014
Abstract: The dengue disease varies clinically from mild fever to hemorrhagic fever up to potentially fatal shock syndrome. Such differences in manifestation of dengue virus (DENV) infection have been ascribed to intrinsic differences in DENVs. Four DENV serotypes or four dengue viruses (DENV-1 to DENV-4) have been clearly distinguished however, only limited information is available on their biological characteristics in vitro. To shed more light on this subject, replication kinetics of all four DENVs in various cell lines and induction of 26 cytokines/chemokines were investigated. The results showed that, (i) all DENVs replicated relatively similarly in various cell lines, (ii) DENV-1 was most effective in this regard, (iii) A549 cells showed the highest virus replication rate compared to other cells, and (iv) all DENVs induced in A549 cells similar levels of several cytokines/chemokines, namely eotaxin, granulocyte colony stimulating factor (G-CSF), interferon alpha 2 (IFN-α2), interleukins 6, 8 15 (IL-6, IL-8, IL-15), and IP-10. In conclusion, this study revealed a similarity in growth characteristics and cytokine/chemokine induction profile for all four DENV serotypes in vitro.
Publisher: Public Library of Science (PLoS)
Date: 22-05-2017
Publisher: Wiley
Date: 16-05-2019
DOI: 10.1002/RMV.2037
Abstract: Although epidemiological and molecular epidemiological (serotype, genotype, and lineage information) data are available for several major cities in Indonesia, there is yet to be a comprehensive national study of dengue in Indonesia over time. This study was conducted to provide a comprehensive epidemiology of circulating dengue viruses (DENV) in Indonesia between 1973 and 2016. This was conducted through a systematic review of the literature and phylogenetic analysis of available DENV sequences. Available data from National Disease Surveillance System have indicated an increasing trend of dengue incidence in Indonesia over the past 50 years. Incidence rates appear to be cyclic, peaking approximately every 6 to 8 years. In contrast, the case fatality rate has decreased approximately by half with each decade since 1980. Over this 50-year time span, serotype shifts, genotype displacement within DENV-1 and DENV-2, and introduction of DENV-1 and DENV-3 genotype from other countries occurred. These events were associated with increased incidence of dengue cases. Our study also provides a valuable national snapshot of DENV genetic ersity in Indonesia that may contribute to development of more effective dengue vaccine compositions for the region.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2019
Publisher: MDPI AG
Date: 05-06-2022
DOI: 10.3390/TROPICALMED7060091
Abstract: Chikungunya fever is a self-limiting viral illness that is caused by the chikungunya virus (CHIKV). CHIKV is found in multiple provinces of Indonesia, with clustered local outbreaks. This case series investigates a local chikungunya outbreak during the COVID-19 pandemic, involving two virologically confirmed chikungunya cases found in Jambi, Sumatra, Indonesia in 2021 and the contact tracing of 65 people from the same neighborhood (one of which was also virologically confirmed with CHIKV). The two original cases were symptomatic with classic signs of chikungunya fever, while the CHIKV-positive neighbor was asymptomatic. Out of the 65 participants, chikungunya IgM was detected in seven (10.8%) people while chikungunya IgG was detected in six (9.2%) using capture ELISA. Dengue IgG was detected by rapid test in three (4.6%) of the participants, showcasing a history of dengue virus (DENV) infection along with the circulation of CHIKV in the area. A phylogenetic analysis demonstrates a close evolutionary relationship between all three 2021 Jambi CHIKV isolates and the 2015–2016 isolates from Jambi. This case series showcases the endemicity and persistent circulation of CHIKV in Jambi, leaving the area vulnerable to eminent outbreaks of chikungunya fever and doubling the burden of disease during the COVID-19 pandemic. Health staff training for case detection and notification, as well as an integrated vector surveillance should continue to be implemented to provide an early warning indicator of possible chikungunya outbreaks.
Publisher: Universitas Gadjah Mada
Date: 30-03-2021
Abstract: Dengue virus (DENV) is the most geographically widespread arbovirus causing dengue disease epidemics in tropical and subtropical regions. Nature provides abundant plants as a source for lead molecules against various diseases including DENV infection. We investigated the antiviral effect of curcumin and 6‐gingerol, the major active constituent of turmeric (Curcuma longa Linn.) and ginger (Zingiber officinale Roscoe), respectively, against all four serotypes of DENV infecting human lung epithelial carcinoma (A549) cell line in vitro. Both compounds generated cell cytotoxicity to A549 cells at CC50 values of 108 µM for curcumin and 210 µM for 6‐gingerol. The compound curcumin showed antiviral properties as described by IC50 of 20.60, 13.95, 25.54, and 12.35 µM, while 6‐gingerol of 14.70, 14.17, 78.76, and 112.84 µM for DENV‐1, ‐2, ‐3, and ‐4, respectively. Different levels of antiviral properties were observed between DENV serotypes. Our findings suggest that the antiviral assay of compounds against DENV should be performed to all four serotypes and not limited to a particular serotype. In conclusion, curcumin and 6‐gingerol exhibit antiviral properties against DENV infection and could provide a new therapeutic approach for dengue disease treatment strategies.
Publisher: Public Library of Science (PLoS)
Date: 21-12-2020
DOI: 10.1371/JOURNAL.PNTD.0008934
Abstract: Chikungunya virus (CHIKV) is an important emerging and re-emerging public health problem worldwide. In Indonesia, where the virus is endemic, epidemiological information from outside of the main islands of Java and Bali is limited. Four hundred and seventy nine acutely febrile patients presenting between September 2017–2019 were recruited from three city hospitals situated in Ambon, Maluku Banjarmasin, Kalimantan and Batam, Batam Island as part of a multi-site observational study. CHIKV RNA was detected in a single serum s le while a separate s le was IgM positive. IgG seroprevalence was also low across all three sites, ranging from 1.4–3.2%. The single RT-PCR positive s le from this study and 24 archived s les collected during other recent outbreaks throughout Indonesia were subjected to complete coding region sequencing to assess the genetic ersity of Indonesian strains. Phylogenetic analysis revealed all to be of a single clade, which was distinct from CHIKV strains recently reported from neighbouring regions including the Philippines and the Pacific Islands. Chikungunya virus strains from recent outbreaks across Indonesia all belong to a single clade. However, low-level seroprevalence and molecular detection of CHIKV across the three study sites appears to contrast with the generally high seroprevalences that have been reported for non-outbreak settings in Java and Bali, and may account for the relative lack of CHIKV epidemiological data from other regions of Indonesia.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2019
Publisher: American Society of Tropical Medicine and Hygiene
Date: 08-11-2017
Publisher: Informa UK Limited
Date: 02-04-2016
Publisher: Springer Science and Business Media LLC
Date: 11-03-2021
DOI: 10.1186/S12985-021-01522-2
Abstract: 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. 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 s les (2) testing 95 RT-PCR-confirmed COVID-19 s les on dengue RDT and (3) testing s les positive for COVID-19 IgG and/or IgM on dengue RDT. 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 s les, 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 s les, 6.3% of COVID-19 IgG-positive s les also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive s les also tested positive for dengue IgG. 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.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Oxford University Press (OUP)
Date: 2018
DOI: 10.1093/JTM/TAY061
Publisher: Springer Science and Business Media LLC
Date: 13-02-2020
DOI: 10.1186/S12985-020-1294-6
Abstract: Dengue virus (DENV) infects hundreds of thousands of people annually in Indonesia. However, DENV sequence data from the country are limited, as s les from outbreaks must be shipped across long-distances to suitably equipped laboratories to be sequenced. This approach is time-consuming, expensive, and frequently results in failure due to low viral load or degradation of the RNA genome. We evaluated a method designed to address this challenge, using the ‘Primal Scheme’ multiplex PCR tiling approach to rapidly generate short, overlapping licons covering the complete DENV coding-region, and sequencing the licons on the portable Nanopore MinION device. The resulting sequence data was assessed in terms of genome coverage, consensus sequence accuracy and by phylogenetic analysis. The multiplex approach proved capable of producing near complete coding-region coverage from all s les tested ( $$ \\overline{x} $$ x ¯ = 99.96%, n = 18), 61% of which could not be fully lified using the current, long- licon PCR, approach. Nanopore-generated consensus sequences were found to be between 99.17–99.92% identical to those produced by high-coverage Illumina sequencing. Consensus accuracy could be improved by masking regions below 20X coverage depth (99.69–99.92%). However, coding-region coverage was reduced at this depth ( $$ \\overline{x} $$ x ¯ = 93.48%). Nanopore and Illumina consensus sequences generated from the same s les formed monophyletic clades on phylogenetic analysis, and Indonesian consensus sequences accurately clustered by geographical origin. The multiplex, short- licon approach proved superior for lifying DENV genomes from clinical s les, particularly when the virus was present at low concentrations. The accuracy of Nanopore-generated consensus sequences from these licons was sufficient for identifying the geographic origin of the s les, demonstrating that the approach can be a useful tool for identifying and monitoring DENV clades circulating in low-resource settings across Indonesia. However, the inaccuracies in Nanopore-generated consensus sequences mean that the approach may not be appropriate for higher resolution transmission studies, particularly when more accurate sequencing technologies are available.
Publisher: Elsevier BV
Date: 10-2017
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.MEEGID.2022.105308
Abstract: Dengue has been endemic in Yogyakarta, Indonesia for decades. Here, we report the dengue epidemiology, entomology, and virology in Yogyakarta in 2016-2017, prior to the commencement of the Applying Wolbachia to Eliminate Dengue (AWED) randomized trial. Dengue epidemiological data were compiled and blood s les from dengue-suspected patients were tested for dengue virus (DENV). Ae. aegypti mosquito s les were caught from the field using BG-Sentinel traps and tested for the presence of DENV infection. Sequencing of the DENV E gene was used to determine the phylogeny and genotypes of circulating DENV. Within the last decade, the 2016-2017 dengue incidence was considered very high. Among the 649 plasma s les collected between March 2016-February 2017 and 36,910 mosquito s les collected between December 2016-May 2017, a total of 197 and 38 s les were DENV-positive by qRT-PCR, respectively. All four DENV serotypes were detected, with DENV-3 (n = 88 44.67%) and DENV-1 (n = 87 44.16%) as the predominant serotype, followed by DENV-4 (n = 12 6.09%) and DENV-2 (n = 10 5.08%). The Yogyakarta DENV-1 isolates were classified into Genotype I and IV, while DENV-2, DENV-3, and DENV-4 isolates were classified into the Cosmopolitan genotype, Genotype I, and Genotype II, respectively. Yogyakarta DENV isolates were closely related to Indonesian strains from neighboring Javanese cities, consistent with the endemic circulation of DENV on this highly populous island. Our study provides comprehensive baseline information on the DENV population genetic characteristics in Yogyakarta, which are useful as baseline data for the AWED trial and the future DENV surveillance in the city in the presence of a Wolbachia-infected Ae. aegypti population.
Publisher: Public Library of Science (PLoS)
Date: 28-06-2018
Publisher: Public Library of Science (PLoS)
Date: 12-05-2022
DOI: 10.1371/JOURNAL.PONE.0268241
Abstract: We determined the prevalence and epidemiological characteristics of COVID-19 in Jakarta and neighboring areas, Indonesia from March 2020 to February 2021, based on nasopharyngeal/oropharyngeal (NP/OP) swab specimens that were tested at the Eijkman Institute for Molecular Biology, Jakarta. NP/OP swab specimens were collected from COVID-19 suspects or in iduals in contact tracing programs from primary healthcare centers (PHC) and hospitals. The specimens were screened for the SARS-CoV-2 by qRT-PCR. Demography data and clinical symptoms were collected using national standardized laboratory form. Of 64,364 specimens, 10,130 (15.7%) were confirmed positive for SARS-CoV-2, with the peak prevalence of infection in March 2020 (26.3%) follow by in January 2021 (23.9%) and February 2021 (21.8%). We found that the positivity rate of the specimens from Jakarta, West Java, and Banten was 16.3%, 13.3%, and 16.8%, respectively. Positivity rate was higher in specimens from hospitals (16.9%) than PHC (9.4%). Of the positive specimens, 29.6% were from in iduals aged years old, followed by in iduals aged 41–60 years old (24.2%). Among symptomatic cases of SARS-CoV-2, the most common symptoms were cough, fever, and a combination of both cough & fever. In conclusion, this study illustrates the prevalence and epidemiological characteristics from one COVID-19 diagnostic center in Jakarta and neighbouring areas in Indonesia.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JIPH.2017.09.019
Abstract: Dengue is hyper-endemic in Indonesia. Purwokerto city in Central Java province is routinely ravaged by the disease. Despite the endemicity of dengue in this city, there is still no data on the virological aspects of dengue in the city. We conducted a molecular surveillance study of the circulating dengue viruses (DENV) in Purwokerto city to gain information on the virus origin, serotype and genotype distribution, and phylogenetic characteristics of DENV. A cross-sectional dengue molecular surveillance study was conducted in Purwokerto. Sera were collected from dengue-suspected patients attending three hospitals in the city. Diagnosis was performed using dengue NS1 antigen and IgG/IgM antibodies detection. DENV serotyping was performed using Simplexa Dengue real-time RT-PCR. Sequencing was conducted to obtain full-length DENV Envelope (E) gene sequences, which were then used in phylogenetic and genotypic analyses. Patients' clinical and demographic data were collected and analyzed. A total of 105 dengue-suspected patients' sera were collected, in which 80 (76.2%) were positive for IgM and/or IgG, and 57 (54.2%) were confirmed as dengue by NS1 antigen and/or DENV RNA detection using RT-PCR. Serotyping was successful for 47 isolates. All four serotypes circulated in the area with DENV-3 as the predominant serotype. Phylogenetic analyses grouped the isolates into Genotype I for DENV-1, Cosmopolitan genotype for DENV-2, and Genotype I and II for DENV-3 and -4, respectively. The analyses also revealed the close relatedness of Purwokerto isolates to other DENV strains from Indonesia and neighboring countries. We reveal the molecular and virological characteristics of DENV in Purwokerto, Banyumas regency, Central Java. The genotype and phylogenetic analyses indicate the endemicity of the circulating DENV in the city. Our serotype and genotype data provide references for future dengue molecular epidemiology studies and disease management in the region.
Publisher: Universitas Gadjah Mada
Date: 24-12-2018
Abstract: Indonesia is a tropical country and hyperendemic for dengue. The disease prevalently affected Indonesian and it caused high morbidity and substantial economic burden. This vector-borne viral disease is caused by infection of dengue viruses (DENVs), which are the member of Flaviviridae family. While most of dengue studies in Indonesia focused on the epidemiology, the clinical aspects, the vectors, and to certain extent the virology, there were still gaps in the DENVs genomic aspects. Considering their high mutation rate, the DENVs were known for their high genetic ersity and it might affect the characteristics of the viruses. Comprehensive DENV genomic data were thus important for many aspects of disease management, including virus surveillance, pathogenesis, diagnostics, antiviral drug design, and vaccine development. We established in this study a method for DENV whole genome sequencing using the advanced Next-Generation Sequencing (NGS) and Nextera XT DNA library preparation kit, coupled with simplified bioinformatic analysis methods. The Indonesian DENVs from four serotypes were isolated from patients’ sera, while library was prepared from enriched templates and sequenced using Illumina NGS. Our study highlighted the potential of a robust NGS method in producing whole genome sequence of DENVs, which would be important for future dengue studies.
Publisher: Frontiers Media SA
Date: 20-11-2020
Abstract: The people of Indonesia have been afflicted by dengue, a mosquito-borne viral disease, for over 5 decades. The country is the world's largest archipelago with erse geographic, climatic, and demographic conditions that may impact the dynamics of disease transmissions. A dengue epidemiology study was launched by us to compare and understand the dynamics of dengue and other arboviral diseases in three cities representing western, central, and eastern Indonesia, namely, Batam, Banjarmasin, and Ambon, respectively. A total of 732 febrile patients were recruited with dengue-like illness during September 2017–2019 and an analysis of their demographic, clinical, and virological features was performed. The seasonal patterns of dengue-like illness were found to be different in the three regions. Among all patients, 271 (37.0%) were virologically confirmed dengue, while 152 (20.8%) patients were diagnosed with probable dengue, giving a total number of 423 (57.8%) dengue patients. Patients' age and clinical manifestations also differed between cities. Mostly, mild dengue fever was observed in Batam, while more severe cases were prominent in Ambon. While all dengue virus (DENV) serotypes were detected, distinct serotypes dominated in different locations: DENV-1 in Batam and Ambon, and DENV-3 in Banjarmasin. We also assessed the diagnostic features in the study sites, which revealed different patterns of diagnostic agreements, particularly in Ambon. To detect the possibility of infection with other arboviruses, further testing on 461 DENV RT-PCR-negative s les was performed using pan-flavivirus and -alphavirus RT-PCRs however, only one chikungunya infection was detected in Ambon. A erse dengue epidemiology in western, central, and eastern Indonesia was observed, which is likely to be influenced by local geographic, climatic, and demographic conditions, as well as differences in the quality of healthcare providers and facilities. Our study adds a new understanding on dengue epidemiology in Indonesia.
Publisher: Bentham Science Publishers Ltd.
Date: 06-02-2020
DOI: 10.2174/2211738507666191210163408
Abstract: Curcumin has been used as a traditional medicine showing antiinflammatory, antimicrobial, and antiviral properties. Despite the promising potentials, curcumin-based drug development is hindered due to its poor solubility and cell uptake. This study aims to produce curcumin nanoemulsion (nanocurcumin) and evaluate its physical characteristics and in vitro cell cytotoxicity and antiviral activity against dengue virus (DENV). Nanocurcumin was generated by self-nanoemulsion technique. Cytotoxicity was determined using MTT assay in A549 cell line. Anti-DENV properties were determined by calculation of inhibitory concentration 50 (IC50) and plaque assay. The resulting nanoemulsion showed uniform droplet size distribution with the average droplet size of 40.85 ± 0.919 nm. Nanocurcumin exhibited higher cell cytotoxicity compared to curcumin solution and may be explained by better cell uptake. Nanocurcumin treatment suppressed DENV growth, although no significant difference observed compared to the curcumin solution counterpart. Greater virus reduction was observed for DENV-1 and DENV-2. The synthesis of nanocurcumin improved curcumin physicochemical properties with potential as antiviral against DENV.
Publisher: Springer Science and Business Media LLC
Date: 02-07-2021
DOI: 10.1186/S12879-021-06339-6
Abstract: Infection by chikungunya (CHIKV) and dengue virus (DENV) can cause a wide spectrum of clinical features, many of which are undifferentiated. Cytokines, which broadly also include chemokines and growth factors, have been shown to play a role in protective immunity as well as DENV and CHIKV pathogenesis. However, differences in cytokine response to both viruses remain poorly understood, especially in patients from countries where both viruses are endemic. Our study is therefore aimed to provide a comparative profiling of cytokine response induced by acute DENV and CHIKV infections in patients with similar disease stages and in experimental in vitro infections. By using multiplex immunoassay, we compared host cytokine profiles between acute CHIKV and DENV infections by analysing serum cytokine levels of IL-1α, IL-4, IL-5, IL-8, IL-13, RANTES, MCP-3, eotaxin, PDGF-AB/BB, and FGF-2 from the sera of acute chikungunya and dengue fever patients. We further investigated the cytokine profile responses using experimental in vitro CHIKV and DENV infections of peripheral blood mononuclear cells (PBMCs). We found that both CHIKV and DENV-infected patients had an upregulated level of IL-8 and IL-4, with the highest IL-4 level observed in DENV-2 infected patients. Higher IL-8 level was also correlated with lower platelet count in dengue patients. IL-13 and MCP-3 downregulation was observed only in chikungunya patients, while conversely PDGF-AB/BB and FGF-2 downregulation was unique in dengue patients. Age-associated differential expression of IL-13, MCP-3, and IL-5 was also observed, while distinct kinetics of IL-4, IL-8, and FGF-2 expression between CHIKV and DENV-infected patients were identified. Furthermore, the unique pattern of IL-8, IL-13 and MCP-3, but not IL-4 expression was also recapitulated using experimental in vitro infection in PBMCs. Taken together, our study identified common cytokine response profile characterized by upregulation of IL-8 and IL-4 between CHIKV and DENV infection. Downregulation of IL-13 and MCP-3 was identified as a unique cytokine response profile of acute CHIKV infection, while distinct downregulation of PDGF-AB/BB and FGF-2 characterized the response from acute DENV infection. Our study provides an important overview of the host cytokine responses between CHIKV and DENV infection, which is important to further understand the mechanism and pathology of these diseases.
Publisher: Bentham Science Publishers Ltd.
Date: 06-2021
DOI: 10.2174/2211738509666210204121258
Abstract: Curcumin is a well-documented bioactive compound present in Curcuma sp., a tropical, medicinal plant. This substance exhibits broad-spectrum biological activities, including antivirus. Despite the lack of pharmaceutical properties of curcumin limits its clinical use. This study aims to produce curcumin nanoemulsion with different surface charge (curcumin (+) nanoemulsion and curcumin (-) nanoemulsion) and to evaluate its physical characteristics, in vitro cell cytotoxicity, and antiviral activity against dengue virus (DENV) 1 and 2. Two forms of nanoemulsion were prepared, which were differed from their surface charge through spontaneous procedure resulting in similar characteristics except for the zeta potential value. Cytotoxicity was determined using the RT-PCR method in the A549 cell line, and anti- DENV properties were determined by calculation of inhibitory concentration 50 (IC 50 ) value. The positive charge of curcumin-loaded nanoemulsion showed a better effect in reducing the viral replication represented by a lower IC 50 value. In addition, DENV-1 was more sensitive and responsive to curcumin as compared to DENV-2. Positive surface charge of curcumin-loaded nanoemulsion improves the antiviral effect of the curcumin, suggesting a promising approach for alternative treatment for dengue virus infection.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 09-2018
Publisher: Faculty of Medicine, Universitas Indonesia
Date: 30-06-2020
Abstract: BACKGROUND Infections of Zika (ZIKV), dengue (DENV), and chikungunya viruses (CHIKV) are presented with similar clinical symptoms these often lead to misdiagnosis. Viremia levels and host immune responses may contribute to disease severity. This study was aimed to characterize the ability of ZIKV, CHIKV, and DENV to infect human peripheral blood mononuclear cells (PBMCs) and assess the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, and interferon gamma-induced protein (IP)- 10 genes in response to the viral infections. METHODS PBMCs were isolated from healthy donors using gradient centrifugation. Cells were infected with Indonesian isolates of ZIKV, CHIKV, and DENV for 48 hours. Plaque assays were performed to measure viable virus titers, while viral genomic RNA and the gene expression of TNF-α, IL-10, and IP-10 were determined using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS The susceptibility of PBMCs to ZIKV, CHIKV, and DENV infection was observed, and the viable virus titer and viral genome quantity were found to be significantly higher in ZIKV and CHIKV. All viruses induced the expression of immune-related proteins. The TNF-α gene was upregulated by all viruses to relatively similar levels. IL-10 expression was highest in response to ZIKV, followed by CHIKV. In contrast, IP-10 expression was highly upregulated in DENV-infected cells and only moderately expressed in ZIKV- and CHIKV-infected cells. CONCLUSIONS ZIKV, CHIKV, and DENV clinical isolates infected PBMCs with different levels of virus infectivity. The gene expression of IL-10 was highly upregulated in ZIKV infection and IP-10 in DENV infection.
Publisher: MDPI AG
Date: 20-08-2020
DOI: 10.3390/V12090913
Abstract: Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1 -2 or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia. Dengue is endemic in the region and outbreaks occur annually. We investigated the clinical characteristics and etiology of dengue-like febrile illness in this regency to understand the disease dynamics. A total of 191 patients with clinical symptoms similar to dengue were recruited during an 11-month study in 2019–2020. Children accounted for the majority of cases and dengue burden was estimated in 41.4% of the cases based on NS1 antigen, viral RNA, and IgG/IgM antibody detection with the majority (73.4%) being primary infections. Secondary infection was significantly associated with a higher risk of severe dengue manifestation. All four DENV serotypes were detected in Jember. Strikingly, we observed the predominance of DENV-4, followed by DENV-3, DENV-1, and DENV-2. Genotype determination using Envelope gene sequence revealed the classification into Genotype I, Cosmopolitan Genotype, Genotype I, and Genotype II for DENV-1, -2, -3, and -4, respectively. The predominance of DENV-4 in Jember may be associated with a new wave of DENV infections and spread in a non-immune population lacking a herd-immunity to this particular serotype.
Publisher: Cold Spring Harbor Laboratory
Date: 19-12-2018
DOI: 10.1101/499111
Abstract: Dengue virus (DENV) sequencing is a vital tool for surveillance and epidemiology studies. However, the current methods employed for sequencing DENV are expensive, laborious and technically demanding, often due to intra- and inter-serotype variability. Therefore, on-site DENV sequencing is not feasible in many of the areas where DENV is endemic. Surveillance in these areas can only be performed by shipping s les to well-equipped central laboratories for sequencing. However, long periods of inadequate storage and unreliable shipping conditions mean that such s les can arrive degraded, rendering sequence recovery difficult. We therefore aimed to develop an approach that is simple, portable and effective, to be used for on-site DENV sequencing in limited resource settings. To achieve this, we first used the ‘Primal Scheme’ primer design tool to develop a simple and robust protocol for generating multiple short licons, covering the complete coding-region of DENV isolates. We then paired this method with the Nanopore MinION, a portable and affordable sequencing device, well-suited to minimal resource settings. The multiplex PCR method produced full-coding-region coverage of all DENV s les tested with no optimisation required, and Nanopore sequencing of the short licons generated consensus sequences with high accuracy (99.52 - 99.92 %). Phylogenetic analysis of the consensus sequences generated using the new method showed that they formed monophyletic clusters with those produced by the current, long- licon, Illumina method, thus demonstrating that the two approaches are comparable. The multiplex method’s simplicity and portability compared to the current DENV sequencing approach make it well-suited for use in resource-limited, DENV-endemic regions. Deployment of the method in these regions would increase the capacity for DENV surveillance and has the potential to provide vital resolution for future DENV epidemiology studies.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2019
Publisher: Springer Science and Business Media LLC
Date: 20-10-2022
Publisher: IOP Publishing
Date: 03-2018
Publisher: American Society of Tropical Medicine and Hygiene
Date: 02-06-2021
Abstract: The presence of Zika virus (ZIKV) in Indonesia has been recognized since the 1970s, but its transmission dynamics there have been poorly understood. To understand more fully the geographic distribution and burden of ZIKV infection, we performed retrospective serological tests on specimens collected from asymptomatic children age 5 to 9 years old living at 30 sites in 14 provinces. Of 870 serum s les tested, 9.2% were found to be positive for anti-ZIKV antibodies, as confirmed by plaque reduction neutralization assays. This was the same overall prevalence reported previously for 1- to 4-year-old children collected at the same sites at the same time. Together with geographic differences in seroprevalence between the age groups, these data suggest that, although ZIKV might be endemic in Indonesia, its occurrence has been focal and episodic.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 05-2016
Publisher: MDPI AG
Date: 06-01-2022
DOI: 10.3390/V14010099
Abstract: Dengue is a mosquito-borne disease of public health concern affecting tropical and subtropical countries, including Indonesia. Although studies on dengue epidemiology have been undertaken in Indonesia, data are lacking in many areas of the country. The aim of this study was to determine dengue virus (DENV) and chikungunya virus (CHIKV) molecular epidemiology in western regions of the Indonesian archipelago. A one-year prospective study was conducted in Aceh and Jambi in 2015 and 2016, respectively, where patients with dengue-like illness were enrolled. Of 205 patients recruited, 29 and 27 were confirmed with dengue in Aceh and Jambi, respectively, and three from Jambi were confirmed with chikungunya. DENV-1 was the predominant serotype identified in Aceh while DENV-2 was predominant in Jambi. All DENV-1 and DENV-2 from both regions were classified as Genotype I and Cosmopolitan genotype, respectively, and all DENV-3 viruses from Jambi were Genotype I. Some viruses, in particular DENV-1, displayed a distinct lineage distribution, where two DENV-1 lineages from Aceh were more closely related to viruses from China instead of Jambi highlighting the role of travel and flight patterns on DENV transmission in the region. DENV-2 from both Aceh and Jambi and DENV-3 from Jambi were all closely related to Indonesian local strains. All three CHIKV belonged to Asian genotype and clustered closely with Indonesian CHIKV strains including those previously circulating in Jambi in 2015, confirming continuous and sustainable transmission of CHIKV in the region. The study results emphasize the importance of continuous epidemiological surveillance of arboviruses in Indonesia and simultaneous testing for CHIKV among dengue-suspected patients.
Publisher: Medknow
Date: 02-2016
DOI: 10.1016/J.APJTM.2016.01.013
Abstract: To describe the clinical manifestation of patient with severe dengue, to identify the serotypes and genotypes of dengue viruses (DENV) which concurrently infecting the patient, and to explore the possible relationship of severe dengue with the concurrent infection of DENV. Dengue diagnosis was performed using NS1 antigen detection and IgG/IgM ELISA. Standard clinical and laboratory examinations were performed to obtain the clinical and hematological data. DENV concurrent infections were detected and confirmed using RT-PCR and DENV Envelope gene sequencing. Phylogenetic analyses were performed to determine the genotypes of the viruses. The patient was classified as having severe dengue characterized by severe plasma leakage, hemorrhage, and organ damage involving lung, liver, and kidney. Concurrent infection of DENV serotype 2 and 3 was observed. The infecting DENV-2 virus was grouped into Cosmopolitan genotype while DENV-3 virus was classified into Genotype I. Both viruses were closely related to isolates that were endemic in Jakarta. Viremia measurement was conducted and revealed a significantly higher virus titer of DENV-3 compared to DENV-2. The occurrence of multi-serotype DENV infections was presented in a patient with severe clinical manifestation in Indonesia. The hyperendemicity of dengue in Indonesia may contribute to the DENV concurrent infections cases and may underlie the severity of the disease.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.MEEGID.2021.105036
Abstract: Dengue is endemic to Indonesia, a country that has largely varied geographical and demographic conditions across different regions. In 2019, dengue epidemic occurred in North Kalimantan province and recorded as the highest incidence rate in Indonesia. This study aims to investigate the molecular epidemiology of dengue during outbreak in the province and compare the epidemiological characteristics between two cities/towns in North Kalimantan, namely Malinau, an inland town surrounded by a dense rainforest, and Tarakan, an island city. A cross sectional study was conducted between September 2018 and July 2019. Dengue-like illness patients were recruited in hospitals and tested for dengue NS1 and IgG/IgM. Serological prevalence was measured using IgG ELISA, dengue virus (DENV) serotyping was conducted using RT-PCR and Envelope gene sequencing was performed to infer the virus origins and phylogeny. Clinical, demographical, and diagnostics data were also recorded and analyzed. We recruited 523 patients, 261 from Malinau and 262 from Tarakan. Among them, 349 patients were confirmed dengue. Cases in Malinau had a higher proportion of confirmed dengue (82.0%) compared to those in Tarakan (51.5%). Cases in Malinau were more likely to be dengue hemorrhagic fever with more severe hematological features compared to those in Tarakan. All four DENV serotypes were detected in both cities, the most prevalent serotype being DENV-2. The genetic characteristics of the viruses in the two towns was similar except for DENV-3. No sylvatic DENV was detected as well as alphaviruses and non-dengue flaviviruses during the outbreak. The molecular epidemiology of dengue in North Kalimantan revealed the similar virological characteristics but different clinical and demographic aspects in Malinau and Tarakan. The distinct dengue dynamics between different regions of Indonesia is prominent and this knowledge will be important for understanding future patterns of DENV transmission in the region.
Publisher: Oxford University Press (OUP)
Date: 16-09-2021
Abstract: Most regions in Indonesia experience annual dengue epidemics. However, the province of East Nusa Tenggara has consistently reported low incidence. We conducted a dengue molecular epidemiology study in Kupang, the capital of the province. Dengue patients were recruited from May 2016 to September 2017. Dengue virus (DENV) screening was performed using NS1 and immunoglobulin G (IgG)/IgM detection. Serotype was determined using reverse transcription polymerase chain reaction and the envelope genes were sequenced to infer the genetic identity and phylogeny. From 119 patients, dengue was confirmed in 62 (52%). Compared with official data, underreporting of dengue incidence was observed. The majority (36%) of patients were children & y of age. Most patients (80%) experienced mild fever. All serotypes were detected, with DENV-3 as the predominant (57%). Kupang DENV-1 isolate was classified as genotype IV, an old and endemic strain, DENV-2 as cosmopolitan, DENV-3 as genotype I and DENV-4 as genotype II. Most isolates showed relatively low evolutionary rates and are closely related with strains from Bali and Timor Leste. The low dengue incidence was most likely caused by sustained local circulation of endemic viruses. This study provides information on the epidemiology of dengue in a low-endemicity setting that should help future mitigation and disease management.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Public Library of Science (PLoS)
Date: 04-05-2022
DOI: 10.1371/JOURNAL.PNTD.0010365
Abstract: Characterising dengue virus (DENV) infection history at the point of care is challenging as it relies on intensive laboratory techniques. We investigated how combining different rapid diagnostic tests (RDTs) can be used to accurately determine the primary and post-primary DENV immune status of reporting patients during diagnosis. Serum from cross-sectional surveys of acute suspected dengue patients in Indonesia (N:200) and Vietnam (N: 1,217) were assayed using dengue laboratory assays and RDTs. Using logistic regression modelling, we determined the probability of being DENV NS1, IgM and IgG RDT positive according to corresponding laboratory viremia, IgM and IgG ELISA metrics. Laboratory test thresholds for RDT positivity/negativity were calculated using Youden’s J index and were utilized to estimate the RDT outcomes in patients from the Philippines, where only data for viremia, IgM and IgG were available (N:28,326). Lastly, the probabilities of being primary or post-primary according to every outcome using all RDTs, by day of fever, were calculated. Combining NS1, IgM and IgG RDTs captured 94.6% (52/55) and 95.4% (104/109) of laboratory-confirmed primary and post-primary DENV cases, respectively, during the first 5 days of fever. Laboratory test predicted, and actual, RDT outcomes had high agreement (79.5% (159/200)). Among patients from the Philippines, different combinations of estimated RDT outcomes were indicative of post-primary and primary immune status. Overall, IgG RDT positive results were confirmatory of post-primary infections. In contrast, IgG RDT negative results were suggestive of both primary and post-primary infections on days 1–2 of fever, yet were confirmatory of primary infections on days 3–5 of fever. We demonstrate how the primary and post-primary DENV immune status of reporting patients can be estimated at the point of care by combining NS1, IgM and IgG RDTs and considering the days since symptoms onset. This framework has the potential to strengthen surveillance operations and dengue prognosis, particularly in low resource settings.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Benediktus Yohan Arman.