scholarly journals The role of different serotypes and dengue virus concentration in the prognosis of dengue shock syndrome in children

Author(s):  
Tram Van Ta ◽  
Hai Thanh Tran ◽  
Quyen Nguyen Than Ha ◽  
Xuong Tuyet Nguyen ◽  
Vu Kien Tran ◽  
...  

Dengue haemorrhagic fever (DHF) is a burden of disease in tropical countries, caused by any one of four-dengue virus (DENV) serotypes (DENV-1 to DENV-4). Although there have been many studies on patients with DHF, many things remain unclear, including the role of DENV serotypes and DENV concentration. The objective of this study was to determine the role of different serotypes and DENV concentration in the prognosis of dengue shock syndrome. This was a prospective cohort study, conducted to show information relating to patients’ conditions, such as hematocrit, platelet, leukocytes, and DENV concentration and the differences between DENV serotypes. The study also expressed the relationship between two groups, DHF without shock and DHF with shock, in terms of immune status, different DENV serotypes, and DENV concentration. Two-hundred and thirty-four patients were serologically confirmed as having a DENV infection. On hospital admission day (fever within 72 hours), results showed that almost all patients had a secondary dengue infection (76.5 %). DENV-1 accounted for the highest number of cases (61.11%), and DENV-4 accounted for the lowest (0.43%). No statistically significant difference was found when comparing the two groups (DHF with shock and DHF without shock) or when comparing the groups of different DENV serotypes. The study concluded that different DENV serotypes or DENV concentration in the first day of hospitalization (fever within 72 hours) cannot be used for prognostic of DSS.

Author(s):  
Samir Casseb ◽  
Karla de Melo

Dengue is an acute febrile disease caused by a virus of the genus Flavivirus, family Flaviviridae, endemic in tropical regions of the globe. The agent is a virus with single-stranded RNA, classified into four distinct dengue virus (DENV) serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The host’s innate and adaptive immune responses play an essential role in determining the natural history of viral infections, especially in dengue. In this context, it has observed in recent years that the presence of RNA interference (RNAi) in viral infection processes is increasing, as well as immune defense. The context microRNAs (miRNAs) go for stood out, as their presence during viral infection, both in the replication of the virus and in the defense against these infections, becomes increasingly noticeable, therefore, making it increasingly necessary to better understand the role of these small RNAs within viral infection by DENV and what their consequences are in aggravating the consequences of patients affected by this disease.


2021 ◽  
Vol 6 (3) ◽  
pp. 162
Author(s):  
Kanaporn Poltep ◽  
Juthamas Phadungsombat ◽  
Emi E. Nakayama ◽  
Nathamon Kosoltanapiwat ◽  
Borimas Hanboonkunupakarn ◽  
...  

Dengue is an arboviral disease highly endemic in Bangkok, Thailand. To characterize the current genetic diversity of dengue virus (DENV), we recruited patients with suspected DENV infection at the Hospital for Tropical Diseases, Bangkok, during 2018–2020. We determined complete nucleotide sequences of the DENV envelope region for 111 of 276 participant serum samples. All four DENV serotypes were detected, with the highest proportion being DENV-1. Although all DENV-1 sequences were genotype I, our DENV-1 sequences were divided into four distinct clades with different distributions in Asian countries. Two genotypes of DENV-2 were identified, Asian I and Cosmopolitan, which were further divided into two and three distinct clades, respectively. In DENV-3, in addition to the previously dominant genotype III, a cluster of 6 genotype I viruses only rarely reported in Thailand was also observed. All of the DENV-4 viruses belonged to genotype I, but they were separated into three distinct clades. These results indicated that all four serotypes of DENV with multiple genotypes and/or clades co-circulate in Bangkok. Continuous investigation of DENV is warranted to further determine the relationship between DENV within Thailand and neighboring countries in Southeast Asia and Asia.


Intervirology ◽  
2020 ◽  
Vol 63 (1-6) ◽  
pp. 57-65
Author(s):  
Liming Jiang ◽  
Qiangming Sun

<b><i>Background:</i></b> Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear. <b><i>Methods:</i></b> THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection. <b><i>Results:</i></b> Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upreg­ulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups. <b><i>Conclusion:</i></b> In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.


2019 ◽  
Vol 6 (10) ◽  
pp. 284-287
Author(s):  
Can Özükoç

Objective: Molar incisor hypomineralization (MIH), a quite common condition in pediatric dentistry, whose treatment might seem complicated, manifests itself with severe dental anxiety and fear that can cause behavioral problems. Although dental fear is seen in almost all cases, it is believed that dental fear will increase as the severity of MIH increases. This study evaluates the relationship between MIH severity and dental fear. Material and Methods: Children Fear Survey Schedule-Dental Subscale (CFSS-DS) was used to measure dental fear in 58 (51.79%) children whose teeth suffered from mild, moderate or severe MIH and 54 (48.21%) children with healthy teeth. Scores between 1 (not afraid at all) and 5 (very afraid) were given according to the responses. Each question was evaluated separately in order to obtain the total score. Results: Children with severe MIH who participated in the study were proved to be more afraid of the dentists, drill sounds, injections, placement of instruments in the mouth, choking and going to the hospital; and there was a statistically significant difference (p<0.05). Conclusion: Although it was observed that the severity of MIH and dental fear are correlated and dental fear increases with the increase in the MIH severity, further studies in this subject are necessary.


2021 ◽  
Vol 118 (14) ◽  
pp. e2013941118
Author(s):  
Laura W. Alexander ◽  
Rotem Ben-Shachar ◽  
Leah C. Katzelnick ◽  
Guillermina Kuan ◽  
Angel Balmaseda ◽  
...  

Dengue is the most prevalent arboviral disease worldwide, and the four dengue virus (DENV) serotypes circulate endemically in many tropical and subtropical regions. Numerous studies have shown that the majority of DENV infections are inapparent, and that the ratio of inapparent to symptomatic infections (I/S) fluctuates substantially year-to-year. For example, in the ongoing Pediatric Dengue Cohort Study (PDCS) in Nicaragua, which was established in 2004, the I/S ratio has varied from 16.5:1 in 2006–2007 to 1.2:1 in 2009–2010. However, the mechanisms explaining these large fluctuations are not well understood. We hypothesized that in dengue-endemic areas, frequent boosting (i.e., exposures to DENV that do not lead to extensive viremia and result in a less than fourfold rise in antibody titers) of the immune response can be protective against symptomatic disease, and this can explain fluctuating I/S ratios. We formulate mechanistic epidemiologic models to examine the epidemiologic effects of protective homologous and heterologous boosting of the antibody response in preventing subsequent symptomatic DENV infection. We show that models that include frequent boosts that protect against symptomatic disease can recover the fluctuations in the I/S ratio that we observe, whereas a classic model without boosting cannot. Furthermore, we show that a boosting model can recover the inverse relationship between the number of symptomatic cases and the I/S ratio observed in the PDCS. These results highlight the importance of robust dengue control efforts, as intermediate dengue control may have the potential to decrease the protective effects of boosting.


2021 ◽  
Vol 102 (10) ◽  
Author(s):  
Wisam-Hamzah Al Shujairi ◽  
Luke P. Kris ◽  
Kylie van der Hoek ◽  
Evangeline Cowell ◽  
Gustavo Bracho-Granado ◽  
...  

Viperin has antiviral function against many viruses, including dengue virus (DENV), when studied in cells in culture. Here, the antiviral actions of viperin were defined both in vitro and in a mouse in vivo model of DENV infection. Murine embryonic fibroblasts (MEFs) derived from mice lacking viperin (vip−/−) showed enhanced DENV infection, accompanied by increased IFN-β and induction of ISGs; IFIT1 and CXCL-10 but not IRF7, when compared to wild-type (WT) MEFs. In contrast, subcutaneous challenge of immunocompetent WT and vip−/− mice with DENV did not result in enhanced infection. Intracranial infection with DENV resulted in body weight loss and neurological disease with a moderate increase in mortality in vip−/− compared with WT mice, although this was not accompanied by altered brain morphology, immune cell infiltration or DENV RNA level in the brain. Similarly, DENV induction of IFN-β, IFIT1, CXCL-10, IRF7 and TNF-α was not significantly different in WT and vip−/− mouse brain, although there was a modest but significant increase in DENV induction of IL-6 and IfI27la in the absence of viperin. NanoString nCounter analysis confirmed no significant difference in induction of a panel of inflammatory genes in WT compared to vip−/− DENV-infected mouse brains. Further, polyI:C stimulation of bone marrow-derived macrophages (BMDMs) induced TNF-α, IFN-β, IL-6 and Nos-2, but responses were not different in BMDMs generated from WT or vip−/− mice. Thus, while there is significant evidence of anti-DENV actions of viperin in some cell types in vitro, for DENV infection in vivo a lack of viperin does not affect systemic or brain susceptibility to DENV or induction of innate and inflammatory responses.


mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Vivian Vasconcelos Costa ◽  
Weijian Ye ◽  
Qingfeng Chen ◽  
Mauro Martins Teixeira ◽  
Peter Preiser ◽  
...  

ABSTRACT Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo, identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection.


2019 ◽  
Vol 20 (10) ◽  
pp. 2382 ◽  
Author(s):  
Juliano G. Haddad ◽  
Andrea Cristine Koishi ◽  
Arnaud Gaudry ◽  
Claudia Nunes Duarte dos Santos ◽  
Wildriss Viranaicken ◽  
...  

Zika virus (ZIKV) and Dengue virus (DENV) are mosquito-borne viruses of the Flavivirus genus that could cause congenital microcephaly and hemorrhage, respectively, in humans, and thus present a risk to global public health. A preventive vaccine against ZIKV remains unavailable, and no specific antiviral drugs against ZIKV and DENV are licensed. Medicinal plants may be a source of natural antiviral drugs which mostly target viral entry. In this study, we evaluate the antiviral activity of Doratoxylum apetalum, an indigenous medicinal plant from the Mascarene Islands, against ZIKV and DENV infection. Our data indicated that D. apetalum exhibited potent antiviral activity against a contemporary epidemic strain of ZIKV and clinical isolates of four DENV serotypes at non-cytotoxic concentrations in human cells. Time-of-drug-addition assays revealed that D. apetalum extract acts on ZIKV entry by preventing the internalisation of virus particles into the host cells. Our data suggest that D. apetalum-mediated ZIKV inhibition relates to virus particle inactivation. We suggest that D. apetalum could be a promising natural source for the development of potential antivirals against medically important flaviviruses.


2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Mohamed Alblooshi ◽  
Mohammad Shamsuzzaman ◽  
Salah Haridy

PurposeThis study explores the role of leadership in organisational innovation by reviewing several publications that discuss the relationship between various leadership styles and innovation.Design/methodology/approachThe study followed a descriptive research methodology by reviewing 64 journal articles on the relationship between various leadership styles and innovation. The articles were analysed descriptively and then reviewed based on the leadership style it discusses to derive meaningful findings on the relationship between leadership and innovation.FindingsVarious leadership styles had a positive impact on organisational innovation either directly or indirectly, by influencing the organisational climate, employees' and leaders' behaviours or other organisational variables such as learning and knowledge sharing. Some leadership styles had both direct and indirect impacts on organisational innovation.Research limitations/implicationsThis study collected journal articles published in almost all major electronic databases such as Emerald, ScienceDirect, Taylor & Francis and Scopus. However, the review is limited to journal articles in which the title, abstract or author-specified keywords contain the search terms “leadership” and “innovation,” and published between 2000 and 2019. Therefore, this review may miss some relevant research insights mentioned in the literature that discussed innovation or leadership separately not combined.Originality/valueThis study contributes to the existing body of research on leadership and innovation by extensively discussing the role of various leadership styles in determining organisational innovation. The analysis reveals that prior studies had many limitations and focused on specific leadership styles only. The study goes a step further by explaining how the leadership and innovation aspects are related, and classifying various leadership styles according to their impact on organisational innovation being direct, indirect or both.


2015 ◽  
Vol 89 (12) ◽  
pp. 6494-6505 ◽  
Author(s):  
Raphaël M. Zellweger ◽  
William W. Tang ◽  
William E. Eddy ◽  
Kevin King ◽  
Marisa C. Sanchez ◽  
...  

ABSTRACTDengue virus (DENV) is a major public health threat worldwide. Infection with one of the four serotypes of DENV results in a transient period of protection against reinfection with all serotypes (cross-protection), followed by lifelong immunity to the infecting serotype. While a protective role for neutralizing antibody responses is well established, the contribution of T cells to reinfection is less clear, especially during heterotypic reinfection. This study investigates the role of T cells during homotypic and heterotypic DENV reinfection. Mice were sequentially infected with homotypic or heterotypic DENV serotypes, and T cell subsets were depleted before the second infection to assess the role of DENV-primed T cells during reinfection. Mice primed nonlethally with DENV were protected against reinfection with either a homotypic or heterotypic serotype 2 weeks later. Homotypic priming induced a robust neutralizing antibody response, whereas heterotypic priming elicited binding, but nonneutralizing antibodies. CD8+T cells were required for protection against heterotypic, but not homotypic, reinfection. These results suggest that T cells can contribute crucially to protection against heterotypic reinfection in situations where humoral responses alone may not be protective. Our findings have important implications for vaccine design, as they suggest that inducing both humoral and cellular responses during vaccination may maximize protective efficacy across all DENV serotypes.IMPORTANCEDengue virus is present in more than 120 countries in tropical and subtropical regions. Infection with dengue virus can be asymptomatic, but it can also progress into the potentially lethal severe dengue disease. There are four closely related dengue virus serotypes. Infection with one serotype results in a transient period of resistance against all serotypes (cross-protection), followed by lifelong resistance to the infecting serotype, but not the other ones. The duration and mechanisms of the transient cross-protection period remain elusive. This study investigates the contribution of cellular immunity to cross-protection using mouse models of DENV infection. Our results demonstrate that cellular immunity is crucial to mediate cross-protection against reinfection with a different serotype, but not for protection against reinfection with the same serotype. A better understanding of the mediators responsible for the cross-protection period is important for vaccine design, as an ideal vaccine against dengue virus should efficiently protect against all serotypes.


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