Most viruses with non-segmented single stranded RNA genomes complete their life cycle in the cytoplasm of infected cells. However, despite undergoing replication in the cytoplasm, the structural proteins of some of these RNA viruses localize to the nucleus at specific times in the virus life cycle, primarily early in infection. Limited evidence suggests that this enhances successful viral replication by interfering with or inhibiting the host antiviral response. Nucleocapsid proteins of RNA viruses have a well-established, essential cytoplasmic role in virus replication and assembly. Intriguingly, nucleocapsid proteins of some RNA viruses also localize to the nucleus/nucleolus of infected cells. Their nuclear function is less well understood although significant advances have been made in recent years. This review will focus on the nucleocapsid protein of cytoplasmic enveloped RNA viruses, including their localization to the nucleus/nucleolus and function therein. A greater understanding of the nuclear localization of nucleocapsid proteins has the potential to enhance therapeutic strategies as it can be a target for the development of live-attenuated vaccines or antiviral drugs.

BackgroundDengue virus (DENV) infection is a major cause of acute febrile illness in Indonesia. Diagnostic inaccuracy may occur due to its varied and non-specific presentation. Characterization of DENV epidemiology, clinical presentation, and virology will facilitate appropriate clinical management and public health policy.Methodology/Principal findingsA multicenter observational cohort study was conducted in Indonesia to assess causes of acute fever requiring hospitalization. Clinical information and specimens were collected at enrollment, 14–28 days, and 3 months from 1,486 children and adults. Total of 468 (31.9%) cases of DENV infection were confirmed by reference laboratory assays. Of these, 414 (88.5%) were accurately diagnosed and 54 had been misdiagnosed as another infection by sites. One hundred initially suspected dengue cases were finally classified as ‘non-dengue’; other pathogens were identified in 58 of those cases. Mortality of DENV infection was low (0.6%). Prior DENV exposure was found in 92.3% of subjects >12 years. DENV circulated year-round in all cities, with higher incidence from January to March. DENV-3 and DENV-1 were the predominant serotypes. This study identified DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site, leading to failure of serotype determination.Conclusions/SignificanceDENV is a common etiology of acute febrile illness requiring hospitalization in Indonesia. Diagnostic accuracy at clinical sites merits optimization since misdiagnosis of DENV infection and over-estimation of dengue can negatively impact management and outcomes. Mutation at the annealing site of the serotyping primer may confound diagnosis. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing. Policy-makers should prioritize development of laboratory capacity for diagnosis of DENV.

A recent modeling study estimated that there could be as many as 20,000 human melioidosis cases per year in Indonesia, with around 10,000 potential deaths annually. Nonetheless, the true burden of melioidosis in Indonesia is still unknown. The Indonesia Melioidosis Network was formed during the first melioidosis workshop in 2017. Here, we reviewed 101 melioidosis cases (99 human and two animal cases) previously reported and described an additional 45 human melioidosis cases. All 146 culture-confirmed cases were found in Sumatra (n = 15), Java (n = 104), Kalimantan (n = 15), Sulawesi (n = 11) and Nusa Tenggara (n = 1). Misidentification of Burkholderia pseudomallei was not uncommon, and most cases were only recently identified. We also evaluated clinical manifestations and outcome of recent culture-confirmed cases between 2012 and 2017 (n = 42). Overall, 15 (36%) cases were children (age <15 years) and 27 (64%) were adults (age ≥15 years). The overall mortality was 43% (18/42). We conducted a survey and found that 57% (327/548) of healthcare workers had never heard of melioidosis. In conclusion, melioidosis is endemic throughout Indonesia and associated with high mortality. We propose that top priorities are increasing awareness of melioidosis amongst all healthcare workers, increasing the use of bacterial culture, and ensuring accurate identification of B. pseudomalleiand diagnosis of melioidosis.

. Emergence of SARS-CoV-2 in dengue virus (DENV)–endemic areas complicates the diagnosis of both infections. COVID-19 cases may be misdiagnosed as dengue, particularly when relying on DENV IgM, which can remain positive months after infection. To estimate the extent of this problem, we evaluated sera from 42 confirmed COVID-19 patients for evidence of DENV infection. No cases of SARS-CoV-2 and DENV coinfection were identified. However, recent DENV infection, indicated by the presence of DENV IgM and/or high level of IgG antibodies, was found in seven patients. Dengue virus IgM and/or high IgG titer should not exclude COVID-19. SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing is appropriate when dengue nonstructural protein 1 (NS1) or RT-PCR is negative. Given the possibility of coinfection, testing for both DENV and SARS-CoV-2 is merited in the setting of the current pandemic.

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BackgroundSeoul virus (SEOV) is a member of hantavirus family, which is transmitted to humans by Rattus rattus and Rattus norvegicus. Diagnosing SEOV infection is difficult because the clinical presentations are often undifferentiated with other viral or bacterial infections and assays to test antibodies seroconversion and RNA detection are not available in resource-limited setting like Indonesia.Case presentationWe report two confirmed cases of SEOV infection from Indonesia. Here, we illustrate the clinical presentations, hematology and biochemistry profiles, and outcomes of the two cases. Phylogenetic analysis revealed that SEOV sequences have highest homology to isolates obtained from rodents in Indonesia.ConclusionsThis report highlights the importance of considering SEOV infection in febrile patients with lymphopenia, thrombocytopenia, and elevation of liver enzyme despite the absence of hemorrhagic manifestations and renal syndromes. The public health importance of rodent-borne diseases such as SEOV infection urges an integrated epidemiological surveillance both in humans and rodents in Indonesia.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3482-1) contains supplementary material, which is available to authorized users.

BackgroundDiscrimination of bacterial and viral etiologies of childhood community-acquired pneumonia (CAP) is often challenging. Unnecessary antibiotic administration exposes patients to undue risks and may engender antimicrobial resistance. This study aimed to develop a prediction model using epidemiological, clinical and laboratory data to differentiate between bacterial and viral CAP.MethodsData from 155 children with confirmed bacterial or mixed bacterial and viral infection (N = 124) and viral infection (N = 31) were derived from a comprehensive assessment of causative pathogens [Partnerships for Enhanced Engagement in Research-Pneumonia in Pediatrics (PEER-PePPeS)] conducted in Indonesia. Epidemiologic, clinical and biomarker profiles (hematology and inflammatory markers) were compared between groups. The area under the receiver operating characteristic curve (AUROC) for varying biomarker levels was used to characterize performance and determine cut-off values for discrimination of bacterial and mixed CAP versus viral CAP. Diagnostic predictors of bacterial and mixed CAP were assessed by multivariate logistic regression.ResultsDiarrhea was more frequently reported in bacterial and mixed CAP, while viral infections more frequently occurred during Indonesia’s rainy season. White blood cell counts (WBC), absolute neutrophil counts (ANC), neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), and procalcitonin (PCT) were significantly higher in bacterial and mixed cases. After adjusting for covariates, the following were the most important predictors of bacterial or mixed CAP: rainy season (aOR 0.26; 95% CI 0.08–0.90; p = 0.033), CRP ≥5.70 mg/L (aOR 4.71; 95% CI 1.18–18.74; p = 0.028), and presence of fever (aOR 5.26; 95% CI 1.07–25.91; p = 0.041). The model assessed had a low R-squared (Nagelkerke R2 = 0.490) but good calibration (p = 0.610 for Hosmer Lemeshow test). The combination of CRP and fever had moderate predictive value with sensitivity and specificity of 62.28 and 65.52%, respectively.ConclusionCombining clinical and laboratory profiles is potentially valuable for discriminating bacterial and mixed from viral pediatric CAP and may guide antibiotic use. Further studies with a larger sample size should be performed to validate this model.

HIV prevalence in Indonesia is increasing, and only 64% of infected individuals know their status. In a prospective cohort of 1,453 hospitalized patients with unexplained fever, 46 (3.2%) had HIV, including 15 (1.1%) patients without a prior HIV diagnosis. Among 31 subjects previously known to have HIV, 21 (68%) had been receiving combination antiretroviral therapy (cART) at the time of enrollment. Of 39 HIV cases with HIV RNA levels ≥ 100 copies/mL, sequencing for genotype analysis and resistance testing was successful in 30 (77%) subjects. The most common HIV subtypes were AE (90%) and B (10%). Five (16.7%) subjects had resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors, and all of them were on cART. No evidence of transmitted drug resistance was found in newly diagnosed individuals. Hospital-based screening may be an efficient method to expand HIV testing and identify a significant number of new cases. Access to care, close monitoring, expansion of anti-retroviral options, and ensuring availability of CD4 determinations, viral load testing, and genotyping are crucial to control of the epidemic in Indonesia.