Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study

Pang, Junxiong; Hsu, Jung Pu; Yeo, Tsin Wen; Leo, Yee Sin; Lye, David C.

doi:10.1038/srep39872

Cited by 65 publications

(59 citation statements)

References 63 publications

(86 reference statements)

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“…Under this perspective, it could be suggested that the use of therapeutically doses of MET in healthy patient could increase AMPK activity, inhibiting the HMGCR function generating a beneficial effects during DENV infection. This suggesting can not be extrapolated to type 2 diabetes patients treated with MET because present evidence indicates that diabetes per se , adversely influence the clinical presentation of any infection because patients have dysfunction in several organs and systems [91] and impairment in host defenses mechanisms [92]. Specifically, type 2 diabetes patients have endothelial dysfunction, which can condition more severe forms of dengue infection[93].…”

Section: Discussionmentioning

confidence: 99%

DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target

Soto-Acosta¹,

et al. 2017

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Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK. AMPK activation by metformin declined the HMGCR activity suggesting that AMPK inactivation mediates the enhanced activity of HMGCR. A reduction on AMPK phosphorylation activity was observed in DENV infected cells at 12 and 24 hpi. HMGCR and cholesterol co-localized with viral proteins NS3, NS4A and E, suggesting a role for HMGCR and AMPK activity in the formation of DENV replicative complexes. Furthermore, metformin and lovastatin (HMGCR inhibitor) altered this co-localization as well as replicative complexes formation supporting that active HMGCR is required for replicative complexes formation. In agreement, metformin prompted a significant dose-dependent antiviral effect in DENV infected cells, while compound C (AMPK inhibitor) augmented the viral genome copies and the percentage of infected cells. The PP2A activity, the main modulating phosphatase of HMGCR, was not affected by DENV infection. These data demonstrate that the elevated activity of HMGCR observed in DENV infected cells is mediated through AMPK inhibition and not by increase in PP2A activity. Interestingly, the inhibition of this phosphatase showed an antiviral effect in an HMGCR-independent manner. These results suggest that DENV infection increases HMGCR activity through AMPK inactivation leading to higher cholesterol levels in endoplasmic reticulum necessary for replicative complexes formation. This work provides new information about the mechanisms involved in host lipid metabolism during DENV replicative cycle and identifies new potential antiviral targets for DENV replication.

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Section: Discussionmentioning

confidence: 99%

DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target

Soto-Acosta¹,

et al. 2017

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“…This was similar to the finding in the study by Pang et al which reported that the median length of hospitalization was five days (IQR: 4-7 days) longer in patients with comorbidities than dengue patients without comorbidities. 12 To our knowledge this is the first study to find evidence of increased levels of hyperglycaemia in patients with comorbidities compared to those without any comorbidities. In the study done by Aggarwal et al, diabetes (OR: 2.12; 95% CI:1.34-4.65) (<0.0001) was associated with severe Dengue.…”

Section: Discussionmentioning

confidence: 82%

Effect of co morbidities on the clinical outcome of Dengue fever

2019

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Background: Dengue is the most rapidly spreading mosquito-borne viral disease in the world. A number of Dengue Haemorrhagic Fever (DHF) risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF/ Dengue shock syndrome (DSS).Methods: A hospital based prospective case control study was done by taking 40 cases each of dengue fever with diabetes mellitus, hypertension, diabetes and hypertension and 30 cases of dengue with asthma/COPD and these patients were compared with controls of 100 patients with dengue fever but no comorbidities. All patients had Dengue serology NS1 or IgM positive.Results: Patients admitted with dengue fever with comorbidities had increased duration of hospitalization with P value of 0.012. The clinical outcome of the 250 patients. In the subgroup of dengue fever patients with DM and Dengue fever with DM and HTN, they were noted to have a 2.69 and 3.06 times increased risk effect of DHF.Conclusions: Dengue fever with DM or DM with HTN have a higher risk of developing DHF when compared with patients with dengue fever with no comorbidities. This finding helps us in triaging patients with comorbidities who develop dengue fever for specialized care and closer clinical monitoring.

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“…Many travelers are older adults, and older travelers may have more comorbidities [79,80]. Diabetes has been identified as a risk factor for dengue, and so have other comorbidities such as hypertension, cardiovascular disease, and asthma [81,82]. Travelers with sickle cell disease are thought to be at increased risk of severe dengue [83].…”

Section: Host Factors Relevant For Travelersmentioning

confidence: 99%

Risk of Dengue in Travelers: Implications for Dengue Vaccination

Wilder‐Smith

2018

Curr Infect Dis Rep

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Purpose of Review Dengue is found in tropics and subtropics that are considered to be popular travel destinations. We set out to review the burden of dengue on international travelers. Recent Findings GeoSentinel, a global network of travel medicine providers, has seen an increasing trend of dengue in returning travelers over the past decades. In Southeast Asia, annual proportionate morbidity increased from 50 dengue cases per 1000 illreturned travelers in non-epidemic years to an average of 159 cases per 1000 travelers during epidemic years. Dengue is the leading cause of fever in returning travelers, having overtaken malaria for travelers to Southeast Asia. Most dengue seroconversion studies in travelers report an attack rate of around 5% depending on duration of travel and destination. Summary Dengue vaccination would be justified for travelers. The first licensed dengue vaccine CYD-TDV is only recommended in seropositive individuals. This review considers preventive measures including how best to use the first licensed dengue vaccine CYD-TDV.

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Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study

Cited by 65 publications

References 63 publications

DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target

DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target

Effect of co morbidities on the clinical outcome of Dengue fever

Risk of Dengue in Travelers: Implications for Dengue Vaccination

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