Dengue virus serotype did not contribute to clinical severity or mortality in Taiwan's largest dengue outbreak in 2015.

BACKGROUND: Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan. METHODS: We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality. RESULTS: The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death. CONCLUSIONS: Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death.

Epidemiology and analysis of SARS-CoV-2 Omicron subvariants BA.1 and 2 in Taiwan.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in October 2021, possessed many mutations compared to previous variants. We aimed to identify and analyze SARS-CoV-2 Omicron subvariants among coronavirus disease 2019 (COVID-19) patients between January 2022 and September 2022 in Taiwan. The results revealed that BA.2.3.7, featuring K97E and G1251V in the spike protein compared with BA.2, emerged in March 2022 and persistently dominated between April 2022 and August 2022, resulting in the largest COVID-19 outbreak since 2020. The accumulation of amino acid (AA) variations, mainly AA substitution, in the spike protein was accompanied by increasing severity in Omicron-related COVID-19 between April 2022 and January 2023. Older patients were more likely to have severe COVID-19, and comorbidity was a risk factor for COVID-19-related mortality. The accumulated case fatality rate (CFR) dropped drastically after Omicron variants, mainly BA.2.3.7, entered Taiwan after April 2022, and the CFR was 0.16% in Taiwan, which was lower than that worldwide (0.31%) between April 2021 and January 2023. The relatively low CFR in Omicron-related COVID-19 patients can be attributed to adjustments to public health policies, promotion of vaccination programs, effective antiviral drugs, and the lower severity of the Omicron variant.

COVID-19 outcomes in patients with rheumatoid arthritis with biologic or targeted synthetic DMARDs.

OBJECTIVES: We aimed to investigate the role of rheumatoid arthritis (RA) with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) exposure in COVID-19 outcomes. METHODS: Our study retrieved data from the US Collaborative Network in TriNetX between 1 January 2018 and 31 December 2022. We investigated b/tsDMARD use for RA: interleukin 6 inhibitor (IL-6i), Janus-associated kinase inhibitors (JAKi) or tumour necrosis factor-alpha inhibitors (TNFi, reference group). The outcomes of COVID-19 were the incidence of infection and adverse outcomes (hospitalisation, critical care services, mechanical ventilation and mortality). The HR and 95% CI of the outcomes were calculated between propensity score-matched (PSM) patients with different b/tsDMARDs. RESULTS: After PSM, 2676 JAKi vs 2676 TNFi users and 967 IL-6i vs 967 TNFi users were identified. As for COVID-19 incidence, JAKi users did not reach statistical significance (HR: 1.058, 95% CI: 0.895 to 1.250) than TNFi users. RA with JAKi users had a significant risk for hospitalisation (HR: 1.194, 95% CI: 1.003 to 1.423), mortality (HR: 1.440, 95% CI: 1.049 to 1.976) and composite adverse outcomes (HR: 1.242, 95% CI: 1.051 to 1.468) compared with TNFi users. Mortality risk tended to be significantly higher in the JAKi group without COVID-19 vaccination (HR: 1.511, 95% CI: 1.077 to 2.121). IL-6i users compared with TNFi users did not have the above findings. CONCLUSIONS: RA with JAKi users had a significant risk for hospitalisation, mortality or composite adverse outcomes, especially higher mortality among those without COVID-19 vaccination. COVID-19 vaccination should be encouraged in these target cohorts. When using JAKi for patients with RA, clinicians should be vigilant about these adverse outcomes to prevent their occurrence or detect them early for early intervention.

Corrigendum: Identification and analysis of SARS-CoV-2 alpha variants in the largest Taiwan COVID-19 outbreak in 2021.

[This corrects the article DOI: 10.3389/fmed.2022.869818.].

The identification and phylogenetic analysis of SARS-CoV-2 delta variants in Taiwan.

In Taiwan, coronavirus disease 2019 (COVID-19) involving the delta variant occurred after that involving the alpha variant in 2021. In this study, we aimed to analyze the Delta variant. A total of 318 patients in Taiwan infected with delta variants were identified. The case fatality rate (CFR) of patients infected with delta variants was 0.94% in Taiwan compared with that of those infected with alpha variants (5.95%). The possible reasons for the low CFR might be hybrid immunity due to infection and rapid promotion of the COVID-19 vaccination program during the alpha variant outbreak. We identified three 21J delta variants. Two long gene deletions were detected in these severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) isolates: ORF7aΔ91 in KMUH-8 and SpikeΔ30 in KMUH-9. Protein structure prediction indicates that ORF7aΔ91 results in malfunction of NS7a as an interferon antagonist and that SpikeΔ30 results in a truncated spike protein (N679-A688del), resulting in a lower infection rate compared with the delta variant without these deletions. The impact of these two deletions on SARS-CoV-2-associated pathogenesis deserves further investigation. Delta variants still exist in many regions in the omicron era, and the backbone of the delta variant genome possibly spread worldwide in the form of delta-omicron hybrids (deltacron; e.g., XBC.1 and XAY.2), which casts a potential threat to public health. Our study further highlighted the importance of more understanding of the delta variants.

Identification and Analysis of SARS-CoV-2 Alpha Variants in the Largest Taiwan COVID-19 Outbreak in 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have originated in Wuhan City, Hubei Province, China, in December 2019. Infection with this highly dangerous human-infecting coronavirus via inhalation of respiratory droplets from SARS-CoV-2 carriers results in coronavirus disease 2019 (COVID-19), which features clinical symptoms such as fever, dry cough, shortness of breath, and life-threatening pneumonia. Several COVID-19 waves arose in Taiwan from January 2020 to March 2021, with the largest outbreak ever having a high case fatality rate (CFR) (5.95%) between May and June 2021. In this study, we identified five 20I (alpha, V1)/B.1.1.7/GR SARS-CoV-2 (KMUH-3 to 7) lineage viruses from COVID-19 patients in this largest COVID-19 outbreak. Sequence placement analysis using the existing SARS-CoV-2 phylogenetic tree revealed that KMUH-3 originated from Japan and that KMUH-4 to KMUH-7 possibly originated via local transmission. Spike mutations M1237I and D614G were identified in KMUH-4 to KMUH-7 as well as in 43 other alpha/B.1.1.7 sequences of 48 alpha/B.1.1.7 sequences deposited in GISAID derived from clinical samples collected in Taiwan between 20 April and July. However, M1237I mutation was not observed in the other 12 alpha/B.1.1.7 sequences collected between 26 December 2020, and 12 April 2021. We conclude that the largest COVID-19 outbreak in Taiwan between May and June 2021 was initially caused by the alpha/B.1.1.7 variant harboring spike D614G + M1237I mutations, which was introduced to Taiwan by China Airlines cargo crew members. To our knowledge, this is the first documented COVID-19 outbreak caused by alpha/B.1.1.7 variant harboring spike M1237I mutation thus far. The largest COVID-19 outbreak in Taiwan resulted in 13,795 cases and 820 deaths, with a high CFR, at 5.95%, accounting for 80.90% of all cases and 96.47% of all deaths during the first 2 years. The high CFR caused by SARS-CoV-2 alpha variants in Taiwan can be attributable to comorbidities and low herd immunity. We also suggest that timely SARS-CoV-2 isolation and/or sequencing are of importance in real-time epidemiological investigations and in epidemic prevention. The impact of D614G + M1237I mutations in the spike gene on the SARS-CoV-2 virus spreading as well as on high CFR remains to be elucidated.

Evaluation of a new NS1 rapid diagnostic test using a single acute-phase serum panel collected during the largest dengue outbreak in Taiwan history in 2015.

Dengue virus (DENV) infection results mostly from the bites of virus-carrying Aedes mosquitoes, which results in dengue fever (DF) with or without warning signs, severe dengue, or asymptomatic infections in humans. For point-of care identification of DENV-infected patients, a rapid diagnostic test (RDT) for DENV nonstructural protein 1 (NS1) has been developed to achieve early diagnosis and timely clinical management. We evaluated the performance of a new commercially available dengue NS1 RDT AsiaGen Dengue NS1 Antigen Rapid Diagnosis Test using real-time qRT-PCR as a reference method and compared the results with SD BIOLINE Dengue NS1 Ag using a single acute-phase serum panel collected during the largest dengue outbreak in the history of Taiwan in 2015. The results suggested that the sensitivity and specificity of AsiaGen Dengue NS1 Antigen RDT (96.9% and 100%) were similar to those of SD BIOLINE Dengue NS1 RDT (100% and 100%) for detection in the acute phase of DENV-2 infection. The results suggested that the sensitivity of both RDTs was similar (95.4% ~ 100%) for the sera collected at less than or equal to three days postsymptom onset (PSO). Our results suggested that the two DENV NS1 RDTs used in this study were promising for the timely diagnosis of DENV infection during dengue outbreaks, at least for DENV-2 in areas where authorized medical laboratories are not available or medical resources are limited. However, the performance of AsiaGen DENV NS1 RDTs in the detection of primary/secondary infections and infection by serotypes of DENV other than DENV-2 requires further investigation.

Isolation and Identification of a Rare Spike Gene Double-Deletion SARS-CoV-2 Variant From the Patient With High Cycle Threshold Value.

Coronavirus disease 2019 (COVID-19) is an emerging life-threatening pulmonary disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, Hubei Province, China, in December 2019. COVID-19 develops after close contact via inhalation of respiratory droplets containing SARS-CoV-2 during talking, coughing, or sneezing by asymptomatic, presymptomatic, and symptomatic carriers. This virus evolved over time, and numerous genetic variants have been reported to have increased disease severity, mortality, and transmissibility. Variants have also developed resistance to antivirals and vaccination and can escape the immune response of humans. Reverse transcription polymerase chain reaction (RT-PCR) is the method of choice among diagnostic techniques, including nucleic acid amplification tests (NAATs), serological tests, and diagnostic imaging, such as computed tomography (CT). The limitation of RT-PCR is that it cannot distinguish fragmented RNA genomes from live transmissible viruses. Thus, SARS-CoV-2 isolation by using cell culture has been developed and makes important contributions in the field of diagnosis, development of antivirals, vaccines, and SARS-CoV-2 virology research. In this research, two SARS-CoV-2 strains were isolated from four RT-PCR-positive nasopharyngeal swabs using VERO E6 cell culture. One isolate was cultured successfully with a blind passage on day 3 post inoculation from a swab with a Ct > 35, while the cells did not develop cytopathic effects without a blind passage until day 14 post inoculation. Our results indicated that infectious SARS-CoV-2 virus particles existed, even with a Ct > 35. Cultivable viruses could provide additional consideration for releasing the patient from quarantine. The results of the whole genome sequencing and bioinformatic analysis suggested that these two isolates contain a spike 68-76del+spike 675-679del double-deletion variation. The double deletion was confirmed by amplification of the regions spanning the spike gene deletion using Sanger sequencing. Phylogenetic analysis revealed that this double-deletion variant was rare (one per million in public databases, including GenBank and GISAID). The impact of this double deletion in the spike gene on the SARS-CoV-2 virus itself as well as on cultured cells and/or humans remains to be further elucidated.

Evaluation of rapid diagnostic tests to detect dengue virus infections in Taiwan.

Early diagnosis is important for the clinical management of diseases caused by dengue virus (DENV) infections. We investigated the performance of three commercially available DENV nonstructural protein 1 (NS1) rapid diagnostic tests (RDTs) using 173 acute-phase sera collected from dengue fever-suspected patients during the 2012-2013 DENV outbreak in Taiwan. The results of the NS1 RDTs were compared with those of qRT-PCR to calculate the sensitivity and specificity of the NS1 RDTs. The anti-DENV IgM and IgG RDT results were included to increase the probability of detecting acute DENV infection. The anti-DENV IgM/IgG RDT results were also compared with those of IgM/IgG captured ELISA. The sera from DENV qRT-PCR-positive patients were subjected to NS1 RDTs, as well as IgM/IgG captured ELISA. These results suggested that there was no significant difference in the sensitivities of the three commercially available DNEV NS1 RDTs; the SD NS1 RDT results showed the highest agreement with the qRT-PCR reference results, followed in order by the Bio-Rad and CTK NS1 RDT results when the specificity was considered. Inclusion of the IgM or IgG RDT results increased the likelihood of diagnosing either a primary or secondary DENV infection. NS1 RDTs were more sensitive for the detection of primary infections than secondary infections, related to DENV viremia levels determined by qRT-PCR. These results suggested that anti-DENV antibodies reduced the sensitivity of NS1 rapid tests. We also analyzed the sensitivity for the detection of different DENV serotypes, and the results suggested that the NS1 RDTs used in this study were valuable for rapid screening of acute DENV infection with DENV-1, DENV-2 and DENV-3. Our results suggest that the NS1 RDT is a good alternative to qRT-PCR analysis for timely dengue disease management and prevention in dengue-endemic regions where medical resources are lacking or during large dengue outbreaks. However, the relatively low sensitivity for DENV-4 might miss the detection of DENV-4-infected cases.

A fully automated sample-to-answer PCR system for easy and sensitive detection of dengue virus in human serum and mosquitos.

BACKGROUND: The insulated isothermal PCR (iiPCR) technology enables consistent PCR amplification and detection in a simple heating device. A pan-dengue virus (DENV) RT-iiPCR, targeting the 5' untranslated region, was validated previously on the semi-automated POCKIT combo system (involving separate devices for nucleic acid extraction and PCR amplification/detection) to offer performance comparable to a laboratory real-time PCR. Working on the same technologies, a compact automated sample-in-answer-out system (POCKIT Central Nucleic Acid Analyser) has been available commercially for iiPCR, minimizing human error risks and allowing easy molecular bio-detection near points of need. Here, we evaluated the analytical and clinical performance of the pan-DENV RT-iiPCR on the fully automated system by comparison to those on the semi-automated system. METHODOLOGY/PRINCIPAL FINDINGS: Testing sera containing serial diluted DENV-1, -2, -3, or -4 cell culture stock, the pan-DENV RT-iiPCR system had similar 100% detection endpoints on the two systems; i.e. at 1, 10, 1 and 10 PFU/ml, respectively, on the fully automated system, and at 10, 1, 10 and 10 PFU/ml, respectively, on the semi-automated system. Furthermore, both fully automated and semi-automated PCR system can detect all four DENV serotypes in mosquitos. Clinical performance of the reagent on the two systems was evaluated by testing 60 human serum samples. Both systems detected the same 40 samples (ten DENV-1, -2, -3, and -4 positive each) and did not detect the other 20; 100% agreement (κ = 1) was found between the two systems. CONCLUSIONS/SIGNIFICANCE: With performance comparable to a previously validated system, the fully-automated PCR system allows applications of the pan-DENV reagent as a useful tool near points of need to facilitate easy, fast and effective detection of dengue virus and help mitigate versatile public health challenges in the control and management of dengue disease.

An RT-PCR panel for rapid serotyping of dengue virus serotypes 1 to 4 in human serum and mosquito on a field-deployable PCR system.

BACKGROUND: Dengue fever, a mosquito-borne disease, is caused by dengue virus (DENV) which includes four major serotypes (DENV-1, -2, -3, and -4). Some serotypes cause more severe diseases than the other; severe dengue is associated with secondary infections by a different serotype. Timely serotyping can provide early warning of dengue epidemics to improve management of patients and outbreaks. A mobile insulated isothermal PCR (iiPCR) system is available to allow molecular detection of pathogens near points of need. METHODOLOGY/PRINCIPLE FINDINGS: In this study, side-by-side comparison with the CDC DENV-1-4 Real Time RT-PCR (qRT-PCR) was performed to evaluate the performance of four singleplex DENV-1-4 serotyping reverse transcription-iiPCR (RT-iiPCR) reagents for DENV subtyping on the mobile PCR system. The four RT-iiPCRs did not react with Zika virus and chikungunya virus; tests with serial dilutions of the four DENV serotypes made in human serum showed they had detection endpoints comparable to those of the reference method, indicating great analytical sensitivity and specificity. Clinical performance of the RT-iiPCR reagents was evaluated by testing 40 serum samples each (around 20 target serotype-positive and 20 DENV-negative); all four reagents had high agreement (97.5-100%) with the reference qRT-PCR. Moreover, testing of mosquitoes separately infected experimentally with each serotype showed that the four reagents detected specifically their target DENV serotypes in mosquito. CONCLUSIONS/SIGNIFICANCE: With analytical and clinical performance comparable to the reference qRT-PCR assay, the four index RT-iiPCR reagents on the field-deployable PCR system can serve as a useful tool for DENV detection near points of needs.

Low frequency of asymptomatic dengue virus-infected donors in blood donor centers during the largest dengue outbreak in Taiwan.

To determine the prevalence of asymptomatic dengue virus-infected blood donors during the largest dengue outbreak in Taiwan history occurred in 2015, we examined the evidence of dengue virus (DENV) infection by the detection of DENV RNA genome using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), DENV NS1 antigen using rapid diagnosis test (RDT) and anti-dengue antibody using IgM/IgG capture enzyme-linked immunosorbent assay (capture ELISA) and RDT in eight thousand serum samples from blood donations to the blood centers of the Taiwan Blood Services Foundation (TBSF) in Kaohsiung City and Tainan City during the largest dengue outbreak in Taiwan history occurred in 2015. Only one serum sample was positive for DENV RNA detection by using dengue-specific real-time RT-PCR, the virus was DENV-2 determined by serotype-specific real-time RT-PCR and sequencing, and the DENVs in the serum were confirmed as being infectious by a plaque assay. The recipient of this blood did not develop any dengue fever symptom on follow-up. None of the samples was NS1 RDT-reactive. Seventeen IgM-positive samples were identified. There was a low prevalence of asymptomatic confirmed or probable DENV-infected blood donors in our study (0.013% and 0.21%, respectively), and no symptomatic transfusion-transmitted dengue (TT dengue) was developed during the largest dengue outbreak in Taiwan history in highly endemic areas and periods.

Seroprevalence of dengue virus in two districts of Kaohsiung City after the largest dengue outbreak in Taiwan since World War II.

Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. In this study, we investigated the seroprevalence of DENV infection in two districts of Kaohsiung City, a metropolis in southern Taiwan, where major dengue outbreaks have occurred in the past three decades. We enrolled 1,088 participants from the Sanmin and Nanzih districts after the dengue outbreak of 2015, the largest in Taiwan since World War II, and found an overall DENV seroprevalence of 12.4% (95% confidence interval: 10.5-13.4%) based on the InBios DENV IgG ELISA kit. The ratios of clinically inapparent to symptomatic infections were 2.86 and 4.76 in Sanmin and Nanzih districts, respectively. Consistent with higher case numbers during recent outbreaks, the DENV seroprevalence was higher in Sanmin district (16.4%) than in Nanzih district (6.9%), suggesting district differences in seroprevalence and highlighting the importance of screening the DENV immune status of each individual before using the currently available DENV vaccine, Dengvaxia. In the two districts, the seroprevalence rates increased from 2.1% (in the 30-39-year age group) to 17.1% (60-69) and 50% (70-79). The pattern of a sharp and significant increase in seroprevalence in the 70-79-year age group correlated with a dramatic increase in the proportion of clinically severe DENV infections among total dengue cases in that age group. This differed from observations in the Americas and Southeast Asia and suggested that a large proportion of monotypically immune individuals together with other risk factors may contribute to clinically severe dengue among the elderly in Taiwan.

Comparison of two rapid diagnostic tests during a large dengue virus serotype 3 outbreak in the Solomon Islands in 2013.

Dengue virus (DENV) infection causes various clinical presentations, including asymptomatic infection, dengue with or without warning signs and severe dengue. An early and accurate diagnosis of DENV infection during the first few days of illness supports clinical management and significantly reduces dengue-associated mortality and morbidity. However, it is very difficult to confirm DENV infection in endemic regions without qualified dengue diagnostic laboratories. In this study, we evaluated the performance of two commercially available rapid diagnostic tests (RDTs) using serum samples collected in the Solomon Islands during the 2013 DENV-3 outbreak. The sensitivity and specificity of the tests were calculated by comparing the results of DENV nonstructural protein 1 (NS1), IgM and IgG RDTs with those obtained by qRT-PCR. We also compared the results of the DENV IgM/IgG RDT with those obtained using an IgM/IgG capture enzyme-linked immune-sorbent assay (ELISA). The sensitivities of the SD and CTK NS1 RDTs were similar (90.9% and 92.6%), and the specificity of the SD NS1 RDT was significantly higher than that of the CTK NS1 RDT (100% versus 78.8%). The inclusion of IgM and IgG in the RDT did not significantly increase the sensitivity for DENV diagnosis. Compared with the SD IgM RDT, IgM capture ELISA had the same specificity but higher sensitivity. User-friendly RDTs remain the first choice and the most convenient tool in dengue endemic regions, where laboratory facilities and the corresponding infrastructure are lacking. Our study provided important and practical information for comparing the performance and validity of the different RDTs for rapid dengue detection.

Validation of the Pockit Dengue Virus Reagent Set for Rapid Detection of Dengue Virus in Human Serum on a Field-Deployable PCR System.

Dengue virus (DENV) infection, a mosquito-borne disease, is a major public health problem in tropical countries. Point-of-care DENV detection with good sensitivity and specificity enables timely early diagnosis of DENV infection, facilitating effective disease management and control, particularly in regions of low resources. The Pockit dengue virus reagent set (GeneReach Biotech), a reverse transcription insulated isothermal PCR (RT-iiPCR), is available to detect all four serotypes of DENV on the field-deployable Pockit system, which is ready for on-site applications. In this study, analytical and clinical performances of the assay were evaluated. The index assay did not react with 14 non-DENV human viruses, indicating good specificity. Compared to the U.S. CDC DENV-1-4 real-time quantitative RT-PCR (qRT-PCR) assay, testing with serial dilutions of virus-spiked human sera demonstrated that the index assay had detection endpoints that were separately comparable with the 4 serotypes. Excellent reproducibility was observed among repeat tests done by six operators at three sites. In clinical performance, 195 clinical sera collected around Kaohsiung city in 2012 and 21 DENV-4-spiked sera were tested with the RT-iiPCR and qRT-PCR assays in parallel. The 121 (11 DENV-1, 78 DENV-2, 11 DENV-3, and 21 DENV-4) qRT-PCR-positive and 95 qRT-PCR-negative samples were all positive and negative by the RT-iiPCR reagent results, respectively, demonstrating high (100%) interrater agreement (95% confidence interval [CI95%], ∼98.81% to 100%; κ = 1). With analytical and clinical performance equivalent to those of the reference qRT-PCR assay, the index PCR assay on the field-deployable system can serve as a highly sensitive and specific on-site tool for DENV detection.

Transient Monocytosis Subjugates Low Platelet Count in Adult Dengue Patients.

BACKGROUND: Dengue is one of the most important vector-borne human viral diseases globally. The kinetic changes of hematological parameters of dengue in adult Taiwanese patients have seldomly been systematically investigated and characterized. METHODOLOGY/PRINCIPAL FINDINGS: Serial laboratory data of 1,015 adult patients who were diagnosed with dengue virus serotype 2 (DENV2) and 3 (DENV3) infections in southern Taiwan were retrospectively examined. Prominent parameters were verified with specimens from a 2015 dengue outbreak. Higher absolute monocyte counts on day 5 in severe patients than mild fever subjects after the onset of fever was seen. The absolute number of monocytes was significantly greater in those with DENV2 than DENV3 infections in spite of subtle differences in laboratory tests. Platelet counts were lowest and activated partial thromboplastin time was highest on day 5 in patients with severe conditions. In addition, sudden downward platelet counts corresponding to a transient surge of monocytes on day 4 onward was observed. Fluorescence-activated cell sorting analysis of peripheral blood mononuclear cells obtained from acute dengue patients and experimental investigations revealed that phagocytic effects of innate immune cells contribute to thrombocytopenia in dengue patients. CONCLUSION: Innate phagocytic cells play an essential role in low platelet counts in adult patients with dengue virus infections.

Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome.

Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis.

Mortality from septic shock in a dengue infected patient: a case report.

Dengue infection can be associated with secondary infections which may be challenging to recognize due to the overlap with the symptoms of dengue infection. We report here the case of a 48 year old Chinese female with dengue fever with a fatal secondary bacterial infection due to Enterococcus faecium.

Spatiotemporal dynamics and epistatic interaction sites in dengue virus type 1: a comprehensive sequence-based analysis.

The continuing threat of dengue fever necessitates a comprehensive characterisation of its epidemiological trends. Phylogenetic and recombination events were reconstructed based on 100 worldwide dengue virus (DENV) type 1 genome sequences with an outgroup (prototypes of DENV2-4). The phylodynamic characteristics and site-specific variation were then analysed using data without the outgroup. Five genotypes (GI-GV) and a ladder-like structure with short terminal branch topology were observed in this study. Apparently, the transmission of DENV1 was geographically random before gradual localising with human activity as GI-GIII in South Asia, GIV in the South Pacific, and GV in the Americas. Genotypes IV and V have recently shown higher population densities compared to older genotypes. All codon regions and all tree branches were skewed toward a negative selection, which indicated that their variation was restricted by protein function. Notably, multi-epistatic interaction sites were found in both PrM 221 and NS3 1730. Recombination events accumulated in regions E, NS3-NS4A, and particularly in region NS5. The estimated coevolution pattern also highlights the need for further study of the biological role of protein PrM 221 and NS3 1730. The recent transmission of emergent GV sublineages into Central America and Europe mandates closely monitoring of genotype interaction and succession.