Both obesity and DENV infections are growing public health concerns that have far-ranging socioeconomic effects, especially in developing countries. Despite the increasing prevalence of these conditions, there is a scarcity of data investigating the potential relationships between these two entities. Our study aims to examine the influence of obesity on various clinical and laboratory parameters amongst patients with DENV infections. A total of 335 hospitalized patients aged >12 years who were DENV non-structural protein 1 (NS1) antigen-positive were enrolled in this study. Clinical and laboratory variables were compared between patients with and without obesity. Multivariate analysis showed that the following admission clinical findings and laboratory results were independently associated with obesity; chills and rigors (AOR:2.653, 95% CI: 1.286–5.474), higher temperature (AOR:1.485, 95% CI: 1.080–2.042), higher systolic BP (AOR:1.057, 95% CI:1.037–1.078), raised haematocrit (AOR: 1.953, 95% CI: 1.010–3.778), elevated creatinine (AOR:3.504, 95% CI:1.351–9.008) and elevated ALT (AOR: 4.146, 95% CI:1.878–9.154). Obesity was found to be significantly associated with hospitalization >3 days (AOR: 1.990, 95% CI: 1.134–3.494) and the presence of increasing haematocrit with decreasing platelets (AOR: 2.134, 95% CI = 1.235–3.688). Serial assessment of laboratory data revealed that peak haematocrit was significantly higher and nadir platelets levels were significantly lower in obese patients. Both peak and admission levels of leukocyte counts, AST, ALT and creatinine were significantly higher in the obese group. Conversely, both admission and nadir albumin levels were lower for the obese group, although only nadir albumin levels achieved statistical significance. These findings support closer clinical monitoring of obese patients who present with DENV infections, as this patient cohort may possess an increased tendency towards developing more severe clinical manifestations of DENV infections as compared to non-obese patients.

This study investigated the antiviral activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against dengue virus type 2 (DENV-2). The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by sub-fractionation and Amberlite XAD16N column chromatography to obtain betacyanin fractions. The half maximum cytotoxicity concentration for betacyanin fractions from red pitahaya and red spinach on Vero cells were 4.346 and 2.287 mg ml⁻¹, respectively. The half-maximal inhibitory concentration (IC₅₀) of betacyanin fraction from red pitahaya was 125.8 μg ml⁻¹ with selectivity index (SI) of 5.8. For betacyanin fraction from red spinach, the IC₅₀ value was 14.62 µg ml⁻¹ with SI of 28.51. Using the maximum non-toxic betacyanin concentration, direct virucidal effect against DENV-2 was obtained from betacyanin fraction from red pitahaya (IC₅₀ of 126.70 μg ml⁻¹; 95.0 % virus inhibition) and red spinach (IC₅₀ value of 106.80 μg ml⁻¹; 65.9 % of virus inhibition). Betacyanin fractions from red pitahaya and red spinach inhibited DENV-2 in vitro.

Background: Dengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia. Methods: Over six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus. Results: Laboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14–6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77–7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04–1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72–6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33–9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29–0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24–0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients’ serum. Conclusions: Acute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.

Background: Dengue fever is currently endemic in tropical and subtropical countries worldwide and effective drug against DENV infection is still unavailable. Porcupine dates, which are traditionally used to treat dengue fever, might contain potential anti-dengue compounds. Two porcupine dates, black date (BD) and powdery date (PD) from Himalayan porcupine (Hystrix brachyura), were investigated for their antiviral activities against DENV-2 in vitro. Methods: The methanol crude extracts (MBD and MPD) were prepared from the raw material of porcupine dates. The tannin-rich fractions (BDTF and PDTF) were isolated from their methanol crude extracts using column chromatography. The presence of tannins in BDTF and PDTF extracts was determined by fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses. The cytotoxicity and anti-DENV-2 activities including virus yield inhibition, virucidal, virus attachment and pre-treatment assays of the extracts were examined in Vero cells. Results: Our findings revealed that all the extracts of porcupine dates exhibited antiviral activity against DENV-2 in Vero cells. The IC₅₀ of BDTF and PDTF were 25 µg/mL and 11 µg/mL respectively, while their methanol crude extracts demonstrated lower antiviral efficacy (IC₅₀ ≈ 101–107 µg/mL). BDTF and PDTF also exerted a similar higher virucidal effect (IC₅₀ of 11 µg/mL) than methanol crude extracts (IC₅₀ ≈ 52–66 µg/mL). Furthermore, all the extracts inhibited the attachment of DENV-2 by at least 80%. Pre-treatments of cells with BDTF and PDTF markedly prevented DENV-2 infection when compared to methanol crude extracts. Conclusion: This study suggests that porcupine dates possess antiviral properties against DENV-2, which is attributed to its tannin compounds.

Background: Dengue caused by dengue virus (DENV) serotypes −1 to −4 is the most important mosquito-borne viral disease in the tropical and sub-tropical countries worldwide. Yet many of the pathophysiological mechanisms of host responses during DENV infection remain largely unknown and incompletely understood.Methods: Using a mouse model, the miRNA expressions in liver during DENV-1 infection was investigated using high throughput miRNA sequencing. The differential expressions of miRNAs were then validated by qPCR, followed by target genes prediction. The identified miRNA targets were subjected to gene ontology (GO) annotation and pathway enrichment analysis to elucidate the potential biological pathways and molecular mechanisms associated with DENV-1 infection.Results: A total of 224 and 372 miRNAs out of 433 known mouse miRNAs were detected in the livers of DENV-1-infected and uninfected mice, respectively; of these, 207 miRNAs were present in both libraries. The miR-148a-3p and miR-122-5p were the two most abundant miRNAs in both groups. Thirty-one miRNAs were found to have at least 2-fold change in upregulation or downregulation, in which seven miRNAs were upregulated and 24 miRNAs were downregulated in the DENV-1-infected mouse livers. The miR-1a-3p was found to be the most downregulated miRNA in the DENV-1-infected mouse livers, with a significant fold change of 0.10. To validate the miRNA sequencing result, the expression pattern of 12 miRNAs, which were highly differentially expressed or most abundant, were assessed by qPCR and nine of them correlated positively with the one observed in deep sequencing.In silicofunctional analysis revealed that the adaptive immune responses involving TGF-beta, MAPK, PI3K-Akt, Rap1, Wnt and Ras signalling pathways were modulated collectively by 23 highly differentially expressed miRNAs during DENV-1 infection.Conclusion: This study provides the first insight into the global miRNA expressions of mouse livers in response to DENV-1 infectionin vivoand the possible roles of miRNAs in modulating the adaptive immune responses during DENV-1 infection.

Background: There is an escalation of frequency and magnitude of dengue epidemics in Malaysia, with a concomitant increase in patient hospitalization. Prolonged hospitalization (PH) due to dengue virus (DENV) infections causes considerable socioeconomic burden. Early identification of patients needing PH could optimize resource consumption and reduce health care costs. This study aims to identify clinicopathological factors present on admission that are associated with PH among patients with DENV infections. Methods: This study was conducted in a tertiary referral hospital in Southern Malaysia. Relevant clinical and laboratory data upon admission were retrieved from medical records of 253 consecutive DENV nonstructural protein 1 (NS1) antigen and PCR-positive hospitalized patients. The DENV serotype present in each patient was determined. Patients were stratified based on duration of hospital stay (<4 vs. ≥4 days). Data were analyzed using IBM ^® SPSS ^® 25.0. Multivariate logistic regression was performed to examine the association between PH and admission parameters. Results: Of 253 DENV hospitalized patients, 95 (37.5%) had PH (≥4 days). The mean duration of hospital stay was 3.43 ± 2.085 days (median = 3 days, interquartile range = 7 days). Diabetes mellitus (adjusted odds ratio [AOR] = 6.261, 95% confidence interval [CI] = 2.130–18.406, p = 0.001), DENV-2 serotype (AOR = 2.581, 95% CI = 1.179–5.650, p = 0.018), duration of fever ≤4 days (AOR = 2.423, 95% CI = 0.872–6.734, p = 0.09), and a shorter preadmission fever duration (AOR = 0.679, 95% CI = 0.481–0.957, p = 0.027) were independently associated with PH. However, PH was not found to be associated with symptoms on admission, secondary DENV infections or platelet count, hematocrit, or liver enzyme levels on admission. Conclusions: Early identification of these factors at presentation may alert clinicians to anticipate and recognize challenges in treating such patients, leading to more focused management plans that may shorten the duration of hospitalization.