Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis

Imad, Hisham Ahmed; Phumratanaprapin, Weerapong; Phonrat, Benjaluck; Chotivanich, Kesinee; Charunwatthana, Prakaykaew; Muangnoicharoen, Sant; Khusmith, Srisin; Tantawichien, Terapong; Phadungsombat, Juthamas; Nakayama, Emi E.; Konishi, Eiji; Shioda, Tatsuo

doi:10.4269/ajtmh.19-0487

Cited by 56 publications

(53 citation statements)

References 34 publications

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“…Higher levels of inflammatory cytokines including IFN-γ in acute phase than in defervescence phase were reported ( 36 , 50 ). Because our study focuses on T cells and the subsets, inflammatory cytokines (e.g., IL-1β, TNF-α) were not well-covered in analysis.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

et al. 2020

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Background: The protective or pathogenic role of T lymphocytes during the acute phase of dengue virus (DENV) infection has not been fully understood despite its importance in immunity and vaccine development. Objectives: This study aimed to clarify the kinetics of T lymphocyte subsets during the clinical course of acute dengue patients. Study design: In this hospital-based cohort study, 59 eligible Vietnamese dengue patients were recruited and admitted. They were investigated and monitored for T cell subsets and a panel of clinical and laboratory parameters every day until discharged and at post-discharge from the hospital. Results: We described for the first time the kinetics of T cell response during the clinical course of DENV infection. Severe cases showed significantly lower levels of effector CD8 + T cells compared to mild cases at day −1 (p = 0.017) and day 0 (p = 0.033) of defervescence. After defervescence, these cell counts in severe cases increased rapidly to equalize with the levels of mild cases. Our results also showed a decline in total CD4 + T, Th1, Th1/17 cells during febrile phase of dengue patients compared to normal controls or convalescent phase. On the other hand, Th2 cells increased during DENV infection until convalescent phase. Cytokines such as interferon-γ, IL-12p70, IL-5, IL-23, IL-17A showed tendency to decrease on day 0 and 1 compared with convalescence and only IL-5 showed significance indicating the production during acute phase was not systemic.

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Section: Discussionmentioning

confidence: 99%

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

et al. 2020

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“…Several arboviral infections are endemic to Thailand (1)(2)(3). Amongst these, chikungunya virus has the potential for re-emerging and is notorious for its morbidity (4).…”

Section: Introductionmentioning

confidence: 99%

Chikungunya Manifestations and Viremia in Patients Who Presented to the Fever Clinic at Bangkok Hospital for Tropical Diseases During the 2019 Outbreak in Thailand

Imad¹,

Phadungsombat²,

Nakayama³

et al. 2020

Preprint

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Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients

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“…On the other hand, patients #14 and #46 did not show a remarkable shift during the observation period. As patient #14 was classified as primary infection by IgG/IgM immunochromatography tests in the previous study (21), no functional antibody activity was observed. Although patient #46 showed strong neutralization with a wide range of serum dilutions (1:10~1:2560), this patient was diagnosed with DHF with severe clinical symptoms.…”

Section: Balance Between the Neutralizing And Enhancing Activities Agmentioning

confidence: 86%

“…Six hospitalized adult patients, who were enrolled in the previous study (21), were recruited into the present study, and an autologous DENV clinical strain was successfully isolated from each of them. The demographic information (infecting serotype, diagnosis [DF or DHF], ID number, days after fever onset and sample collection period [h] after the hospitalization) is shown in Fig.…”

Section: Balance Between the Neutralizing And Enhancing Activities Agmentioning

confidence: 99%

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Antibody-dependent enhancement representingin vitroinfective progeny virus titer correlates with the viremia level in dengue patients

Yamanaka

Imad

Phumratanaprapin

et al. 2020

Preprint

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Dengue virus (DENV) distributes throughout tropical and subtropical countries and causes dengue fever (DF) and dengue hemorrhagic fever in humans. Some DF patients suddenly develop severe symptoms after the defervescent period. Although the pathogenic mechanism of the severe symptoms has not been fully elucidated, the viremia level in the early phase has been shown to correlate with the disease severity. One of the hypotheses is that a phenomenon called antibody-dependent enhancement (ADE) of infection leads to a high level of viremia. To examine the plausibility of this hypothesis, we examined the relationship between in vitro ADE activity and in vivo viral load quantity in six patients with dengue diseases. An autologous DENV strain was isolated from each of the six patients. Blood samples were then collected at multiple time points between the acute and defervescent phases, and the balance between neutralizing and enhancing activities against the autologous and prototype viruses was examined. As the antibody levels against DENV were rapidly increased, ADE activity was decreased over time or partially maintained against some viruses at low serum dilution. In addition, positive correlations were observed between ADE activity representing in vitro progeny virus production and viremia levels in patient plasma samples. Therefore, the measurement of ADE activity in dengue-seropositive samples may help to predict the impact of viral load in the subsequent DENV infection.IMPORTANCEIt has not been fully elucidated how the phenomenon of antibody-dependent enhancement (ADE) affects the pathogenesis of severe dengue diseases, although high viremia levels have been epidemiologically demonstrated to be associated with the disease severity. Here, we show that ADE in the acute-phase patient sera exhibited significantly different activities against autologous and lab strains than ADE in the defervescent-phase sera. Further, the enhancement of progeny virus production activity, which is one of the factors to evaluate ADE in vitro, was significantly correlated with the levels of viral load in the patient blood circulation. This suggests that measurement of the in vitro enhancing progeny virus titers might be used to predict the impact of in vivo DENV viremia level. Our present findings could contribute to a method to forecast disease severity for seropositive populations who would be at risk of developing severe disease in the event of heterotypic DENV infection.

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Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis

Cited by 56 publications

References 34 publications

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

Chikungunya Manifestations and Viremia in Patients Who Presented to the Fever Clinic at Bangkok Hospital for Tropical Diseases During the 2019 Outbreak in Thailand

Antibody-dependent enhancement representingin vitroinfective progeny virus titer correlates with the viremia level in dengue patients

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