Dengue Virus Serotype 4 is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia

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

An update on SARS-CoV-2 clinical trial results—what we can learn for the next pandemic

The coronavirus disease 2019 (COVID-19) pandemic has claimed over 7 million lives worldwide, providing a stark reminder of the importance of pandemic preparedness. Due to the lack of approved antiviral drugs effective against coronaviruses at the start of the pandemic, the world largely relied on repurposed efforts. Here, we summarise results from randomised controlled trials to date, as well as selected in vitro data of directly acting antivirals, host-targeting antivirals, and immunomodulatory drugs. Overall, repurposing efforts evaluating directly acting antivirals targeting other viral families were largely unsuccessful, whereas several immunomodulatory drugs led to clinical improvement in hospitalised patients with severe disease. In addition, accelerated drug discovery efforts during the pandemic progressed to multiple novel directly acting antivirals with clinical efficacy, including small molecule inhibitors and monoclonal antibodies. We argue that large-scale investment is required to prepare for future pandemics; both to develop an arsenal of broad-spectrum antivirals beyond coronaviruses and build worldwide clinical trial networks that can be rapidly utilised

Concurrent infections of dengue virus serotypes in Bali, Indonesia

Objective: To describe cases of dengue virus (DENV) concurrent infections in patients from both local and international traveler visiting Bali, Indonesia. Results: During a hospital-based study, 260 patients (from 161 local and 99 international traveler patients) were recruited. Among them, 190 were positive by DENV RT-PCR in which eight patients (five local and three international travelers) detected as having concurrent infections by two different DENV serotypes. Among the eight patients, the common dengue symptoms diagnosed were fever, headache, and myalgia. Six cases (75%) were diagnosed with dengue fever (DF) while two cases (25%) manifested with bleeding and were diagnosed with dengue hemorrhagic fever (DHF) grade 1. The DENVs concurrent infections involved all four DENV serotypes known to be circulating in Bali. Although cases of DENV concurrent infections have been implicated with severe manifestation, we observed that most of concurrent infections cases in our study were of mild clinical manifestation, that may be related to the changing of DENV serotype predominance which is occurring in Bali, Indonesia

Chikungunya virus infection in Indonesia: a systematic review and evolutionary analysis

Abstract 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.https://deepblue.lib.umich.edu/bitstream/2027.42/148282/1/12879_2019_Article_3857.pd

Distribusi Serotipe Dengue Di Surabaya Tahun 2012

The characteristics of epidemic dengue often presented as periods of hyperendemicity or as the co-circulation of multiple dengue serotypes. Surabaya is an endemic city for Dengue virus (DENV) transmission. Previous study of DENV distribution in 2008-2009 revealed the predominance of DENV-2. DENV serotypes distribution is known to be dynamic and serotype predominance may change through time. This study aims to determine and follow the circulation of DENV serotype in Surabaya in 2012. We recruited 154 denguesuspected patients attending Dr. Soetomo Hospital during February until August 2012. Dengue cases were confirmed by IgG and IgM serology tests and NS1 antigen detection. Serologically-positive samples were further analyzed using two-steps reverse transcriptasepolymerase chain reaction (RT-PCR) and viruses were isolated by propagation in C6/36 mosquito cell line. Seventy one cases (46.1%) were detected as DENV positive infection. Serotyping revealed that 61 samples have monotypic infection with one of all four of DENV serotypes and 10 samples have mix-infections. Overall serotyping result observed the predominance of DENV-1 (60.56%). Our result revealed the circulation of all four serotypes of DENV and the presence of serotype exchange in Surabaya in 2012. Annual change of predominant serotype and the presence of multiple infections may play an important role in the transmission of dengue infection. This information is valuable to dengue surveillance in the region. Therefore, the laboratory diagnosis of DENV serotype should be routinely performed to follow the dynamic of dengue disease Keywords Dengue;serotypes;Surabaya;201

Antiviral activities of curcumin and 6‐gingerol against infection of four dengue virus serotypes in A549 human cell line in vitro

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

Assessment of dengue and COVID-19 antibody rapid diagnostic tests cross-reactivity in Indonesia.

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

Dengue infection in international travellers visiting Bali, Indonesia

Background: Dengue, an acute febrile illness caused by infection with dengue virus (DENV), is endemic in Bali, Indonesia. As one of the world’s most popular tourist destinations, Bali is regularly visited by domestic and international travellers, who are prone to infection by endemic pathogens, including DENV. Currently, limited data are available on the characteristics of dengue in travellers visiting Bali. Information on the epidemiology and virological aspects of dengue in these tourists is important to gain a better understanding of the dengue disease in international travellers. Methods: We performed a prospective cross-sectional dengue study involving foreign travellers visiting Bali, Indonesia in the period of 2015–17. Patients presenting at Kasih Ibu Hospital with fever and clinical symptoms of dengue were asked to participate in the study. Clinical and laboratory assessments were performed and sera were collected for molecular analysis, which included DENV serotyping, genome sequencing and phylogenetic analysis. Results: Among the 201 patients recruited, dengue was confirmed in 133 (66.2%) of them, based on detection of NS1 antigen and/or viral RNA. Of these, 115 (86.5%) manifested dengue fever (DF) and 18 (13.5%) dengue haemorrhagic fever (DHF). The temporal predominance of infecting DENV serotype was DENV-2 (48.7%), followed by DENV-3 (36.1%), DENV-1 (9.2%) and DENV-4 (3.4%). Phylogenetic analysis of DENV based on envelope gene sequences revealed that the source of DENVs was local endemic viruses. Conclusion: Our study confirms that dengue is one of the causes of fever in travellers visiting Bali. Although it is a cause of significant morbidity, the majority of patients only experienced mild DF, with only a small proportion developing DHF. We revealed that DENVs isolated were autochthonous. Accurate diagnosis, preventive measures and continuous disease surveillance will be useful for better management of dengue infection in travellers

Whole genome sequencing of Indonesian dengue virus isolates using next-generation sequencing

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 diversity 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

Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose and have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global ‘Prevent, Detect and Respond’ strategy