Scrub typhus in Indonesia: A cross-sectional analysis of archived fever studies samples.

BACKGROUND: Scrub typhus is an understudied vector-borne bacterial infection. METHODS: We tested archived fever samples for scrub typhus seropositivity to begin charting its geographic distribution in Indonesia. We analysed 1033 serum samples from three sites. IgM and IgG enzyme-linked immunosorbent assay (ELISA) against Orientia tsutsugamushi was performed using Karp, Kato, Gilliam, TA 716 antigens. To determine the cutoff in the absence of a presumed unexposed population and gold standard tests, we identified the visual inflection point, performed change point analysis, and used finite mixture models. RESULTS: The optical density cutoff values used for IgM and IgG were 0.49 and 0.13, respectively. Across all sites, IgM seropositivity was 4.6% (95% CI: 3.4 to 6.0%) while IgG seropositivity was 4.4% (95% CI: 3.3 to 5.8%). The overall seropositivity across sites was 8.8% (95% CI: 8.1 to 11.7%). The overall seropositivity for Jambi, Denpasar, Tabanan were 9.7% (95% CI: 7.0 to 13.3%), 8.0% (95% CI: 5.7 to 11.0%), 9.0% (95% CI: 6.1 to 13.0%), respectively. CONCLUSIONS: We conclude that O. tsutsugamushi exposure in humans occurred at all sites analysed and could be the cause of illness in some cases. Though it was not the main cause of acute fever in these locations, it is still important to consider scrub typhus in cases not responding to beta-lactam antibiotics. Future seroprevalence surveys and testing for scrub typhus in acute febrile illness studies will be essential to understand its distribution and burden in Indonesia.

Neurological Disease Associated with Chikungunya in Indonesia.

Chikungunya virus (CHIKV) is recognized but rarely considered as a cause of central nervous system infection in endemic areas. A total of 244 patients with acute meningoencephalitis in Indonesia were retrospectively tested to identify whether any CHIKV infection was associated with neurological manifestations, especially in provinces known for CHIKV endemicity. Cerebrospinal fluid (CSF) and blood specimens were tested using CHIKV-specific real-time reverse transcription polymerase chain reaction and IgM ELISA, alongside a panel of neurotropic viruses. We report four cases of suspected or confirmed CHIKV-associated neurological disease, including CHIKV RNA detection in CSF of one patient and in acute serum of another, and CHIKV IgM in CSF of three patients and in serum of a fourth. In conclusion, CHIKV should be considered as a cause of neurologic disease in endemic areas and especially during outbreaks, in addition to the more common arboviral diseases such as dengue and Japanese encephalitis viruses.

Continuous Circulation of Chikungunya Virus during COVID-19 Pandemic in Jambi, Sumatra, Indonesia.

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.

Combining rapid diagnostic tests to estimate primary and post-primary dengue immune status at the point of care.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSION: 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.

Co-Circulation of Chikungunya and Multiple DENV Serotypes and Genotypes, Western Indonesia 2015-2016.

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.

Stigma Associated with COVID-19 Among Health Care Workers in Indonesia.

OBJECTIVE: The aim of this study was to assess the stigma associated with coronavirus disease - 2019 (COVID-19) among health care workers (HCWs) in Indonesia during the early phase of the pandemic. METHODS: A cross-sectional study was conducted in 12 hospitals across the country in March, 2020. A logistic regression was employed to assess the association between stigma and explanatory variables. RESULTS: In total, 288 HCWs were surveyed, of which 93.4% had never experienced any outbreaks. Approximately 21.9% of the respondents had stigma associated with COVID-19. HCWs who were doctors, had not participated in trainings related to COVID-19, worked in the capital of the province, worked at private hospitals, or worked at a hospital with COVID-19 triage protocols were likely to have no stigma associated with COVID-19. CONCLUSIONS: The stigma associated with COVID-19 is relatively high among HCWs in the early phase of the COVID-19 pandemic in Indonesia. Adequate dissemination of knowledge and adequate protection are necessary to reduce stigma among HCWs.

Molecular epidemiology of dengue in a setting of low reported endemicity: Kupang, East Nusa Tenggara province, Indonesia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 <10 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. CONCLUSIONS: 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.

Comparative cytokine profiling identifies common and unique serum cytokine responses in acute chikungunya and dengue virus infection.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

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.

Distinct Dengue Disease Epidemiology, Clinical, and Diagnosis Features in Western, Central, and Eastern Regions of Indonesia, 2017-2019.

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 diverse 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 samples was performed using pan-flavivirus and -alphavirus RT-PCRs; however, only one chikungunya infection was detected in Ambon. A diverse 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.

Diagnostic accuracy of 5 different brands of dengue virus non-structural protein 1 (NS1) antigen rapid diagnostic tests (RDT) in Indonesia.

Indonesia is hyper-endemic for dengue. Dengue virus non-structural protein 1 (NS1) antigen detection is now increasingly used by clinicians in Indonesia to confirm dengue infection, but many available brands have not had any evaluation on their performance. We evaluated the diagnostic accuracy of 5 different brands of NS1 rapid tests against reference standards consisting of 100 virologically confirmed dengue samples covering all 4 serotypes and 49 non-dengue samples. These rapid tests had sensitivity ranging from 73% to 80%, and specificity of 100%. The tests had better sensitivity for detection during the first 4 days of fever, for DENV-3 serotype, and in primary infections. The evaluated tests can be easily used with adequate sensitivity, very good specificity, and no significant difference in performance between brands. However, certain characteristics such as age, fever day onset, serotype, and immunologic status may affect the accuracy of these tests and need to be taken into consideration.

Parents' hesitancy towards vaccination in Indonesia: A cross-sectional study in Indonesia.

BACKGROUND: Hesitancy towards vaccination has been studied as a barrier to vaccination among children, as well as participation in vaccine trials. This study aimed to investigate hesitancy towards vaccination among parents in Indonesia, as a part of the Indonesia Zika Vaccine Study. METHODS: A cross-sectional study was conducted in eleven regencies and municipalities in Aceh and West Sumatra province, Indonesia. Parents were recruited from families at outpatient clinics of community health centers or hospitals. The survey included various questions about sociodemographic factors and the Parent Attitudes about Childhood Vaccination (PACV) scale. Linear regression was employed to assess the association between explanatory variables and vaccine hesitancy. RESULTS: A total of 956 parents were interviewed and 26.4% of participants had heard about Zika. Overall, 152 parents (15.9%) were vaccine hesitant, and this proportion was the highest in the safety and efficacy subdomain (61.6%). In the unadjusted analysis, having a diploma certificate, working in the health sector, and having heard about Zika were significantly associated with non-hesitancy towards children vaccination. Having heard about Zika was the only factor that was significantly associated with hesitancy towards vaccination in multivariate model (aOR: 0.43, 95% CI: 0.26-0.71). Mothers, younger parents (aged 20-29 years old), and those with only a primary school education were more concerned about vaccine safety and efficacy compared to fathers, older groups, and individuals with more education, respectively. CONCLUSIONS: Hesitancy towards pediatric vaccination is observed in 15% of respondents and most of the hesitancy was expressed in terms of vaccine safety and efficacy. Therefore, continuous dissemination of vaccine information needs to be carried out to earn parents' trust and increase vaccination coverage in Indonesia.

Clinical features and virological confirmation of perinatal dengue infection in Jambi, Indonesia: A case report.

The hyper-endemicity of dengue in Indonesia poses a significant threat of dengue virus (DENV) vertical transmission during pregnancy. A 29-year-old female at 38 weeks of pregnancy presented to hospital with acute fever and later confirmed with DENV infection. Due to signs of fetal distress, the neonate was delivered by emergency caesarean section. The mother developed a dengue critical phase post-caesarean with excessive bleeding and required blood transfusion. During the 6th day of life, the neonate was diagnosed and later confirmed with dengue. Next-generation sequencing of DENV RNA isolated directly from sera of both mother and neonate revealed identical DENV-2 whole-genome sequences. Plaque reduction neutralization test (PRNT) detected anti-dengue antibodies in both mother and neonate. Altogether, our data confirmed the occurrence of vertical transmission. Dengue vertical transmission during pregnancy may lead to severe manifestation, hence early diagnosis, close monitoring, and prompt intervention are critical.

Multiple introductions of dengue virus strains contribute to dengue outbreaks in East Kalimantan, Indonesia, in 2015-2016.

BACKGROUND: Dengue fever is a febrile disease caused by dengue virus (DENV), which affects people throughout the tropical and subtropical regions of the world, including Indonesia. East Kalimantan (Borneo) province suffered a dramatic increase in dengue cases in 2015 and 2016, making it the province with the second highest incidence of dengue in Indonesia. Despite this, dengue in East Kalimantan is understudied; leaving transmission dynamics of the disease in the area are mostly unknown. In this study, we investigate the factors contributing to the outbreaks in East Kalimantan. METHODS: Prospective clinical and molecular virology study was conducted in two main cities in the province, namely Samarinda and Balikpapan, in 2015-2016. Patients' clinical, hematological, and demographic data were recorded. Dengue detection and confirmation was performed using NS1-antigen and IgG/IgM antibody detection. RT-PCR was conducted to determine the serotypes of the virus. Phylogenetic analysis was performed based on envelope gene sequences. RESULTS: Three hundred patients with suspected dengue were recruited. Among these, 132 (44%) were diagnosed with dengue by NS1 antigen and/or nucleic acid detection. The majority of the infections (60%) were primary, with dengue hemorrhagic fever (DHF) the predominant manifestation (71.9%). Serotyping detected all four DENV serotypes in 112 (37.3%) cases, with the majority of patients (58.9%) infected by DENV-3. Phylogenetic analysis based on envelope gene sequences revealed the genotypes of the viruses as DENV-1 Genotype I, DENV-2 Cosmopolitan, and DENV-3 Genotype I. Most virus strains were closely-related to strains from cities in Indonesia. CONCLUSIONS: Our observations indicate that multiple introductions of endemic DENV from surrounding cities in Indonesia, coupled with relatively low herd immunity, were likely responsible for the outbreak of the dominant viruses. The study provides information on the clinical spectrum of the disease, together with serology, viral genetics, and demographic data, which will be useful for better understanding of dengue disease in Borneo.

Attitudes towards Zika virus infection among medical doctors in Aceh province, Indonesia.

Zika virus (ZIKV) infection, a public health emergency of international concern, has recently been confirmed in Indonesia. However, to date, there has been no study to assess how prepared healthcare workers in Indonesia are to confront this emerging infectious disease. The aim of this study was to assess the attitudes of medical doctors in Indonesia towards ZIKV infection and its associated explanatory variables. A cross-sectional self-administered online survey was conducted from 3 May to 3 June 2016 in Aceh province, Indonesia. A pre-tested questionnaire was used to collect data on doctors' attitudes towards ZIKV infection and a range of explanatory variables (basic demographic data, professional characteristics, workplace characteristics and facilities, and medical experience related to ZIKV infection). Associations between attitude and explanatory variables were assessed using multiple-step logistic regression. We received 631 responses, 424 (67.19%) of which were included in the final analysis. Approximately 64% (271) of doctors had a poor attitude towards ZIKV infection. Experience considering ZIKV infection as a differential diagnosis and attendance at a national conference was associated with a good attitude, with odds ratios (OR) of 3.93 (95% confidence interval [CI]: 1.15-13.49) and 1.69 (95% CI: 1.03-2.76), respectively. Unexpectedly, doctors who had attended an international conference and those working at places that had molecular diagnostic (polymerase chain reaction based testing) facilities had lower odds of having a good attitude (OR: 0.35 [95% CI: 0.15-0.84] and 0.42 [95% CI: 0.19-0.95], respectively). In conclusion, the attitude towards ZIKV infection is relatively poor among doctors in Aceh. Therefore, strategies for enhancing their capacity to respond to ZIKV infection are needed. The survey concept and tools were well accepted by the participants of this study, suggesting that this rapid assessment could be rolled out across the Indonesian archipelago and elsewhere to identify and regionally differentiate unmet needs of disease and outbreak preparedness.

Chikungunya Detection during Dengue Outbreak in Sumatra, Indonesia: Clinical Manifestations and Virological Profile.

Chikungunya fever (CHIK) is an acute viral infection caused by infection with chikungunya virus (CHIKV). The disease affects people in areas where certain Aedes species mosquito vectors are present, especially in tropical and subtropical countries. Indonesia has witnessed CHIK disease since the early 1970s with sporadic outbreaks occurring throughout the year. The CHIK clinical manifestation, characterized by fever, headache, and joint pain, is similar to that of dengue (DEN) disease. During a molecular study of a DEN outbreak in Jambi, Sumatra, in early 2015, DENV-negative samples were evaluated for evidence of CHIKV infection. Among 103 DENV-negative samples, eight samples were confirmed (7.8%) as positive for CHIKV by both molecular detection and virus isolation. The mean age of the CHIK patients was 21.3 ± 9.1 (range 11-35 years). The clinical manifestations of the CHIK patients were mild and mimicked DEN, with fever and headache as the main symptoms. Only three out of eight patients presented with classical joint pain. Sequencing of the envelope glycoprotein E1 gene and phylogenetic analysis identified all CHIKV isolates as belonging to the Asian genotype. Overall, our study confirms sustained endemic CHIKV transmission and the presence of multiple arboviruses circulating during a DEN outbreak in Indonesia. The co-circulation of arboviruses poses a public health threat and is likely to cause misdiagnosis and underreporting of CHIK in DEN-endemic areas such as Indonesia.

Genomic characterization of Zika virus isolated from Indonesia.

Zika virus (ZIKV) JMB-185 strain was isolated from a febrile patient in Jambi, Indonesia in 2014. To understand its genetic characteristics, we performed whole genome sequencing using the Ion Torrent PGM platform on the supernatant of the first passage. The phylogenetic analysis showed that the isolate was not closely related to the Brazilian ZIKV associated with microcephaly or isolates from the recent Singapore Zika outbreak. Molecular evolution analysis indicated that JMB-185 strain may have been circulating in the Southeast Asia region, including Indonesia since 2000. We observed high nucleotide sequence identity between Indonesia, Thailand, Singapore, and American strains although unique amino acid substitutions were also observed. This report provides information on the genomic characteristics of Indonesian ZIKV which may be used for further studies.

Healthcare workers' knowledge towards Zika virus infection in Indonesia: A survey in Aceh.

OBJECTIVE: To assess the knowledge on Zika virus infection among healthcare providers (doctors) in Aceh province, Indonesia. METHODS: A self-administered internet based survey was conducted from 3 May to 3 June 2016 among the members of doctor organizations in Aceh province. A set of validated, pre-tested questionnaire was used to measure knowledge regarding Zika infection and to collect a range of explanatory variables. A two-steps logistic regression analysis was employed to assess the association of participants' demographic, workplace characteristics and other explanatory variables with the knowledge. RESULTS: A total of 442 participants included in the final analysis and 35.9% of them (159) had a good knowledge on Zika infection. Multivariate model revealed that type of occupation, type of workplace, availability of access to medical journals and experience made Zika disease as differential diagnose were associated with knowledge on Zika infection. In addition, three significant source of information regarding Zika were online media (60%), medical article or medical news (16.2%) and television (13.2%). CONCLUSION: The knowledge of the doctors in Aceh regarding Zika infection is relatively low. Doctors who have a good knowledge on Zika infection are more confident to established Zika disease as differential diagnosis in their clinical setting. Therefore, such program to increase healthcare providers' knowledge regarding Zika infection is needed to screen potential carriers of Zika infection.

The molecular and clinical features of dengue during outbreak in Jambi, Indonesia in 2015.

Dengue is hyperendemic in Indonesia. In 2015, reported cases of dengue fever doubled those of 2014 in the Jambi municipality of Sumatra. We examined viral aetiology and its relationship with disease outcome in Jambi. Dengue-suspected patients' sera were collected and NS1 detection and IgM/IgG serology were performed. Dengue virus (DENV) serotyping was performed using real-time RT-PCR. Envelope genes were sequenced to determine the genotypes of DENV. Clinical, haematologic, and demographic data were recorded. Of 210 dengue-suspected patients, 107 were confirmed. The disease manifested as Dengue Fever (62%), Dengue Haemorrhagic Fever (36%), and Dengue Shock Syndrome (2%). The serotypes of 94 DENV were determined. All DENV serotypes were detected with DENV-1 as the predominant serotype (66%). Genotypically, the DENV-1 viruses belong to Genotype I, DENV-2 was of Cosmopolitan genotype, DENV-3 as Genotype I, and DENV-4 belonged to Genotype II. Comparison with historical data revealed serotype predominance switched from DENV-3 to DENV-1, and the replacement of Genotype IV of DENV-1 with Genotype I. In summary, DENV-1 predominated during the 2015 dengue outbreak in Jambi. The full spectrum of dengue disease occurred and was characterized by a switch in predominant serotypes.