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Is Total Serum Nitrite and Nitrate (NOx) Level in Dengue Patients a Potential Prognostic Marker of Dengue Hemorrhagic Fever?

ABSTRACT: Potential use of total nitrite plus nitrate (NOx) and nitrite (NO₂^-) separately as surrogate markers for serum nitric oxide in severe dengue and their longitudinal changes along with the progression of infection was studied. Deproteinized sera from confirmed dengue fever (DF, n = 145) and dengue hemorrhagic fever (DHF, n = 74) patients on admission-A, critical-C, discharge-D, and convalescence-CON stages and from age-gender matched healthy individuals (HC, n = 77) were taken to assess NO₂^- and NOx levels using Griess and modified Griess assays. Serum NOx in DHFA was significantly lower compared to DFA (p < 0.001). HC had the lowest NOx and NO₂^- compared to all patient categories (p < 0.001) except NO₂^- in DF-CON and DHF-CON and NOx in DHF-CON. Serum NOx and NO₂^- in DHF patients admitted on fever day 3 (DHFA-3) was significantly lower compared to DFA-3 (p < 0.05). Cut-off values of 4.46??M for NOx (91.3% sensitivity and 80.1% specificity) and 1.25??M for NO₂^- (75.0% sensitivity and 73.3% specificity) were obtained for day 3 of fever. Serum NOx may be used as potential prognostic marker of DHF in patients presenting with DF in the early stage (on day 3 of fever) of the disease.

SUBMITTER: Mapalagamage M

PROVIDER: S-EPMC6057279 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Is Total Serum Nitrite and Nitrate (NOx) Level in Dengue Patients a Potential Prognostic Marker of Dengue Hemorrhagic Fever?

Mapalagamage Maheshi M Handunnetti Shiroma S Premawansa Gayani G Thillainathan Sharmila S Fernando Tharanga T Kanapathippillai Karunayokiny K Wickremasinghe Rajitha R De Silva Aruna Dharshan AD Premawansa Sunil S

Disease markers 20180705

Potential use of total nitrite plus nitrate (NOx) and nitrite (NO2-) separately as surrogate markers for serum nitric oxide in severe dengue and their longitudinal changes along with the progression of infection was studied. Deproteinized sera from confirmed dengue fever (DF, n = 145) and dengue hemorrhagic fever (DHF, n = 74) patients on admission-A, critical-C, discharge-D, and convalescence-CON stages and from age-gender matched healthy individuals (HC, ...[more]

PMID: 30069272

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Project description:BACKGROUND: Dengue virus (DENV) infection is the most common arthropod-borne viral disease in man and there are approximately 100 million infections annually. Despite the global burden of DENV infections many important questions regarding DENV pathogenesis remain unaddressed due to the lack of appropriate animal models of infection and disease. A major problem is the fact that no non-human species naturally develop disease similar to human dengue fever (DF) or dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Apart from other risk factors for severe dengue such as host genetics and secondary infection with a heterologous DENV, virus virulence is a risk factor that is not well characterized. RESULTS: Three clinical DENV-1 isolates from Cambodian patients experiencing the various forms of dengue disease (DF, DHF, and DSS) were inoculated in BALB/c mice at three different concentrations. The DENV-1 isolates had different organ and cell tropism and replication kinetics. The DENV-1 isolate from a DSS patient infected the largest number of mice and was primarily neurotropic. In contrast, the DENV-1 isolates from milder clinical dengue cases infected predominantly lungs and liver, and to a lesser extent brain. In addition, infection with the DENV isolate derived from a DSS patient persisted for more than two weeks in a majority of mice compared to the other DENV-1 isolates that peaked during the first week. CONCLUSIONS: These results confirm the in vitro findings of the same DENV-1 isolates, that showed that the isolate derived from a DSS patient can be distinguished based on phenotypic characteristics that differ from the isolates derived from a DF and DHF case 1. We observed in this study that the DSS virus isolate persist longer in vivo with extensive neuroinvasion in contrast to the other DENV-1 isolates originating in milder human cases. Genomic characterization of the three clinical isolates identified six amino acid substitutions unique for the DSS isolates that were located both in structural genes (M and E) and in non-structural genes (NS1, NS3, and NS5). The characterization of these clinically distinct DENV-1 isolates highlight that DENVs within the same genotype may have different in vivo phenotypes. HIGHLIGHTS: • Clinical DENV-1 isolates have different organ tropism in BALB/c mice.• The isolate from a DSS patient is primarily neurotropic compared to the other isolates.• The DENV-1 isolates have different in vivo replication kinetics.• The isolate from a DSS patient persists longer compared to the other isolates.• These phenotypic differences confirm our earlier in vitro findings with the same DENV-1 isolates. Thus, DENVs within the same serotype and genotype may differ enough to affect clinical conditions in vivo.

Dataset Information

Is Total Serum Nitrite and Nitrate (NOx) Level in Dengue Patients a Potential Prognostic Marker of Dengue Hemorrhagic Fever?

Publications

Is Total Serum Nitrite and Nitrate (NOx) Level in Dengue Patients a Potential Prognostic Marker of Dengue Hemorrhagic Fever?

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