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Sample records for acute dengue infections

  1. Acute Renal Failure in Dengue Infection

    PubMed Central

    Subramanyam, Nambakam Tanuja

    2017-01-01

    Introduction Acute Renal Failure (RF) is a rare but well recognized complication of Dengue Infection (DI). There has been paucity of published data regarding renal involvement in DI. Aim The aim of the present study was to elucidate different clinical presentations, disease outcomes of DI. To study the frequency, severity and predictors of RF in DI. Materials and Methods Patients diagnosed either as Dengue Fever (DF) or Dengue Haemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) respectively were enrolled for this study. The diagnostic criteria for DI were febrile illness associated with one of the following: 1) detection of dengue-specific IgM capture antibody or Non-Structural Protein1 (NS1) antigen; or 2) a four-fold or greater increase of dengue-specific IgG capture antibody by ELISA and haemoagglutination inhibition assay. Patients were diagnosed as having Acute RF, if serum creatinine was >1.2 mg/dl or who showed improvement by 50% in serum creatinine from the initial value. It is an observational study of medical charts, data of age, gender, and medical history of any underlying diseases in association with the severity of DI of each patient recorded. All of the laboratory results were collected. Parameters that influenced the clinical presentations and outcomes for development of classical DF or DHF/DSS in patients with or without RF were analysed and compared. Descriptive and inferential statistical analysis was carried. The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, Med Calc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used. Results Most common symptoms were fever followed by headache and pain in abdomen. Among the patients with RF, all patients had recovery. The patients with DHF/DSS were more susceptible to develop renal failure compared to DF group. There were statistically significant higher frequencies of renal failure, haemoconcentration, thrombocytopenia, low serum cholesterol. Patients in the RF group also had significantly

  2. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    PubMed Central

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made. PMID:25709166

  3. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection.

    PubMed

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made.

  4. Acute disseminated encephalomyelitis associated with dengue infection: a case report with literature review.

    PubMed

    Gupta, Meena; Nayak, Rajeev; Khwaja, Geeta A; Chowdhury, Debashish

    2013-12-15

    Dengue is the commonest arboviral illness caused by four antigenically distinct dengue virus serotypes (DEN-1 through DEN-4). The clinical spectrum of the disease ranges from asymptomatic or mild infection to catastrophic dengue shock syndrome (DSS). In last few years, neurological manifestations of dengue infection have been increasingly observed and reported mainly with serotypes DEN-2 and DEN-3. The pathogenesis of neurological manifestations includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. Encephalopathy and encephalitis are the most frequently reported neurological manifestations followed by meningitis, myositis, hypokalemic periodic paralysis, stroke, Guillain-Barré syndrome and transverse myelitis. Acute disseminated encephalomyelitis (ADEM) associated with dengue infection is rarely reported. We herein report a case of ADEM associated with classic dengue fever. Favourable clinical outcome occurred after a five-day course of intravenous methylprednisolone therapy.

  5. Cross reactivity of commercial anti-dengue immunoassays in patients with acute Zika virus infection.

    PubMed

    Felix, Alvina Clara; Souza, Nathalia C Santiago; Figueiredo, Walter M; Costa, Angela A; Inenami, Marta; da Silva, Rosangela M G; Levi, José Eduardo; Pannuti, Claudio Sergio; Romano, Camila Malta

    2017-02-23

    Several countries have local transmission of multiple arboviruses, in particular, dengue and Zika viruses, which have recently spread through many American countries. Cross reactivity among Flaviviruses is high and present a challenge for accurate identification of the infecting agent. Thus, we evaluated the level of cross reactivity of anti-dengue IgM/G Enzyme-Linked Immunosorbent Assays (ELISA) from three manufacturers against 122 serum samples obtained at two time-points from 61 patients with non-dengue confirmed Zika virus infection. All anti-dengue ELISAs cross reacted with serum from patients with acute Zika infection at some level and a worrisome number of seroconversion for dengue IgG and IgM was observed. These findings may impact the interpretation of currently standard criteria for dengue diagnosis in endemic regions.

  6. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

    PubMed

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-05-27

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection.

  7. Dengue NS1 and prM antibodies increase the sensitivity of acute dengue diagnosis test and differentiate from Japanese encephalitis infection.

    PubMed

    Gowri Sankar, S; Balaji, T; Venkatasubramani, K; Thenmozhi, V; Dhananjeyan, K J; Paramasivan, R; Tyagi, B K; John Vennison, S

    2014-05-01

    Accurate and early diagnosis of dengue infection is essential for dengue case management. In outbreak conditions, it is essential to include two different tests to diagnose dengue and the choice depends on the number of days after the onset of illness in which the sample is collected. During the laboratory diagnosis of dengue in late acute and convalescent phase by MAC-ELISA, it is necessary to rule out possible cross reactions of closely related flavivirus, such as Japanese encephalitis virus which is commonly co-circulating. In the present investigation, the usefulness of dengue virus NS1 and prM antibodies in diagnosing and differentiating dengue from Japanese encephalitis infection was assessed using samples collected during out-breaks. It was shown here that, detection of antibodies against dengue NS1 and prM proteins increases the sensitivity of dengue diagnosis until 15days. Moreover, detection of antibodies against both proteins was able to differentiate dengue from Japanese encephalitis infection.

  8. Serologically proven acute rubella infection in patients with clinical diagnosis of dengue.

    PubMed Central

    Bustos, J.; Hamdan, A.; Loroño, M. A.; Montero, M. T.; Gómez, B.

    1990-01-01

    Patients with a clinical diagnosis of dengue but negative by serological testing were studied for rubella infection. Paired sera were obtained from 69 patients during an outbreak in Yucatán, México. The presence of specific anti-viral IgM in the acute sera was considered as diagnostic for rubella infection. The immunoglobulin was determined by measuring the difference in the inhibition of hemagglutination between the non-reduced and the reduced fractionated sera. Immunoglobulins were separated by sucrose density centrifugation. Acute rubella infection was found in 7 (10.1%) of the patients. These results demonstrate active rubella infection in patients clinically diagnosed as dengue. PMID:2323361

  9. Dynamics of cellular immune responses in the acute phase of dengue virus infection.

    PubMed

    Yoshida, Tomoyuki; Omatsu, Tsutomu; Saito, Akatsuki; Katakai, Yuko; Iwasaki, Yuki; Kurosawa, Terue; Hamano, Masataka; Higashino, Atsunori; Nakamura, Shinichiro; Takasaki, Tomohiko; Yasutomi, Yasuhiro; Kurane, Ichiro; Akari, Hirofumi

    2013-06-01

    In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection.

  10. Acute transverse myelitis and subacute thyroiditis associated with dengue viral infection: A case report and literature review

    PubMed Central

    Mo, Zhiming; Dong, Yaxian; Chen, Xiaolian; Yao, Huiyan; Zhang, Bin

    2016-01-01

    Acute transverse myelitis is a rare manifestation of dengue infection. To the best of our knowledge, only 6 cases of acute transverse myelitis as a manifestation of dengue infection have been reported thus far. The present study described a case of acute transverse myelitis complicated with subacute thyroiditis 6 days after the onset of dengue viral infection. In addition, the available literature was searched to identify similar previous cases. Treatment with intravenous pulse methylprednisolone immunoglobulin plasmapheresis and physiotherapy resulted in partial recovery at 3 months post-infection. In conclusion, the involvement of dengue infection should be considered in patients who develop central nervous system manifestations during or after the recovery period of dengue infection. Furthermore, since methylprednisolone and immunoglobulin are effective during the active phase of the infection, prompt diagnosis and initiation of treatment are crucial. PMID:27703498

  11. Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases.

    PubMed

    Viswanathan, S; Botross, N; Rusli, B N; Riad, A

    2016-11-01

    Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients.

  12. Evaluation of a pan-serotype point-of-care rapid diagnostic assay for accurate detection of acute dengue infection.

    PubMed

    Vivek, Rosario; Ahamed, Syed Fazil; Kotabagi, Shalini; Chandele, Anmol; Khanna, Ira; Khanna, Navin; Nayak, Kaustuv; Dias, Mary; Kaja, Murali-Krishna; Shet, Anita

    2017-03-01

    The catastrophic rise in dengue infections in India and globally has created a need for an accurate, validated low-cost rapid diagnostic test (RDT) for dengue. We prospectively evaluated the diagnostic performance of NS1/IgM RDT (dengue day 1) using 211 samples from a pediatric dengue cohort representing all 4 serotypes in southern India. The dengue-positive panel consisted of 179 dengue real-time polymerase chain reaction (RT-PCR) positive samples from symptomatic children. The dengue-negative panel consisted of 32 samples from dengue-negative febrile children and asymptomatic individuals that were negative for dengue RT-PCR/NS1 enzyme-linked immunosorbent assay/IgM/IgG. NS1/IgM RDT sensitivity was 89.4% and specificity was 93.8%. The NS1/IgM RDT showed high sensitivity throughout the acute phase of illness, in primary and secondary infections, in different severity groups, and detected all 4 dengue serotypes, including coinfections. This NS1/IgM RDT is a useful point-of-care assay for rapid and reliable diagnosis of acute dengue and an excellent surveillance tool in our battle against dengue.

  13. Paediatric Dengue Fever diagnosed through parents' epidemiologic report and preventive strategy during the acute phase of infection.

    PubMed

    Poddighe, Dimitri; Bonomelli, Irene; Giardinetti, Silvia; Nedbal, Marco; Bruni, Paola

    2016-01-01

    In Europe, Dengue Fever is one of the most frequent imported diseases and also autochthonous cases occurred in areas where the insect vector is present. Here, we describe a child returning from Philippines and diagnosed with Dengue Fever, through the information provided by parents about an ongoing outbreak in their municipality. An appropriate clinical management in the hospital was established to monitor the occurrence of complications and to cancel the risk of dengue virus transmission in the acute phase of infection.

  14. Evaluation of the SD BIOLINE Dengue Duo rapid test in the course of acute and convalescent dengue infections in a Mexican endemic region.

    PubMed

    Sánchez-Vargas, Luis A; Sánchez-Marce, Elvis E; Vivanco-Cid, Héctor

    2014-04-01

    In this study, we evaluated the performance of a rapid test, the SD BIOLINE Dengue Duo (SD BDD) kit, with a panel of serum samples from 310 Mexican patients with diagnosis of dengue infection previously confirmed by reference enzyme-linked immunosorbent assay tests. Eighty-seven negative samples from other febrile illnesses were included as controls. The SD BDD showed an overall sensitivity of 90.65% and specificity of 89.66%. No statistically significant differences were found in the sensitivity of the SD BDD kit compared between primary or secondary infections (87.05% versus 93.57%, respectively, P = 0.0761) and dengue fever or dengue hemorrhagic fever cases (90.77% versus 89.74%, respectively, P = 0.7716). However, a higher sensitivity in the acute phase of dengue infection was found compared with the convalescent phase (93.03% versus 81.82%, respectively, P = 0.0089). These results indicate that the SD BDD kit is a useful tool to diagnose dengue infections, both in primary or secondary infections and mainly during the acute phase.

  15. False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland.

    PubMed

    Gyurech, Danielle; Schilling, Julian; Schmidt-Chanasit, Jonas; Cassinotti, Pascal; Kaeppeli, Franz; Dobec, Marinko

    2016-01-01

    We report the first case of an acute Zika virus infection imported into Switzerland by a traveller returning from Canoa Quebrada, Ceará state, in the north-eastern part of Brazil. Due to a false positive dengue virus NS1 antigen test, IgG antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. However, because of lack of specific IgM-antibodies, stationary IgG antibody titre and a negative dengue virus PCR test result, a dengue virus infection was excluded and a cross-reaction with other, causative flaviviruses was postulated. Based on recent reports of Zika fever cases in the north-eastern parts of Brazil, an acute Zika virus infection was suspected. Because of a lack of commercially available Zika virus diagnostic tests, the case was confirmed in the WHO reference laboratory. As the clinical presentation of Zika virus infection can be confused with dengue fever and chikungunya fever, and because of possible public health implications, all patients returning from affected areas should be additionally tested for Zika virus. This case illustrates the urgent medical need for a broadly available assay capable of differentiating Zika from Dengue infections.

  16. Dengue viral infections

    PubMed Central

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections. PMID:15466994

  17. Dengue viral infections.

    PubMed

    Malavige, G N; Fernando, S; Fernando, D J; Seneviratne, S L

    2004-10-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing this disease. Early recognition and prompt initiation of appropriate treatment are vital if disease related morbidity and mortality are to be limited. This review outlines aspects of the epidemiology of dengue infections, the dengue virus and its mosquito vector, clinical features and pathogenesis of dengue infections, and the management and control of these infections.

  18. Prevalence and characteristics of dengue and chikungunya infections among acute febrile patients in Nong Khai Province, Thailand.

    PubMed

    Lertanekawattana, Sujet; Anantapreecha, Surapee; Jiraphongsa, Chuleeporn; Duan-ngern, Pawinee; Potjalongsin, Sathit; Wiittayabamrung, Wisanu; Daroon, Pamol; Techolarn, Meta

    2013-09-01

    We conducted a cross sectional study at three hospitals of Nong Khai Province, Thailand to determine the prevalence and characteristics of dengue and chikungunya infection among patients who sought care. The study population was acute febrile patients who visited these hospitals during 1 August -31 October, 2010 who were aged 2-60 years and had clinical symptoms compatible with the case definition. Dengue and chikungunya cases were confirmed by an ELISA IgM titer or RT-PCR. We also reviewed surveillance data of dengue and chikungunya infections from 2003-2009. Of the 200 participants recruited into the study, 103 patients (51.5%) were confirmed to have acute dengue infection; dengue serotype 2 was the most prevalence serotype. The ages of confirmed dengue cases ranged from 2-37 years old. The distribution of cases showed that dengue morbidity tended to be clustered in adjacent areas, particularly in Mueang District. Only a small proportion of the patients uses mosquito repellant and had screens on their windows. One patient (0.5%) had laboratory confirmed chikungunya infection. She was from Rattanawapi District, an area where no chikungunya had been reported before. Since the disease varies by age and geographic location, increased awareness of health care workers and public health officers about the diseases in the area is needed for early detection of cases and to promote early prevention and control measures.

  19. Secretory phospholipase A2 in the pathogenesis of acute dengue infection

    PubMed Central

    Jeewandara, Chandima; Gomes, Laksiri; Udari, Sukhitha; Paranavitane, S.A.; Shyamali, N.L.A.; Ogg, Graham S.

    2016-01-01

    Abstract Introduction Platelet activating factor (PAF) is an important mediator of vascular leak in acute dengue. Phospholipase A2s (PLA2) are inflammatory lipid enzymes that generate and regulate PAF and other mediators associated with mast cells. We sought to investigate if mast cell activation and increases in secretory sPLA2s are associated with an increase in PAF and occurrence of dengue haemorrhagic fever (DHF). Methods The changes in the levels of mast cell tryptase, PAF and the activity of sPLA2 were determined throughout the course of illness in 13 adult patients with DHF, and 30 patients with dengue fever (DF). Results We found that sPLA2 activity was significantly higher in patients with DHF when compared to those with DF, during the first 120 h of clinical illness. sPLA2 activity was significantly associated with PAF levels, which were also significantly higher in patients with DHF. Although levels of mast cell tryptase were higher in patients with DHF, the difference was not significant, and the levels were not above the reference ranges. sPLA2 activity significantly correlated with the degree of viraemia in patients with DHF but not in those with DF. Conclusion sPLA2 appears to play an important role in the pathogenesis of dengue. Since its activity is significantly increased during the early phase of infection in patients with DHF, this suggests that understanding the underlying mechanisms may provide opportunities for early intervention. PMID:28250920

  20. Elevated Levels of Cell-Free Circulating DNA in Patients with Acute Dengue Virus Infection

    PubMed Central

    Ha, Tran Thi Ngoc; Huy, Nguyen Tien; Murao, Lyre Anni; Lan, Nguyen Thi Phuong; Thuy, Tran Thi; Tuan, Ha Manh; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Kikuchi, Mihoko; Yasunami, Michio; Morita, Kouichi; Huong, Vu Thi Que; Hirayama, Kenji

    2011-01-01

    Background Apoptosis is thought to play a role in the pathogenesis of severe dengue and the release of cell-free DNA into the circulatory system in several medical conditions. Therefore, we investigated circulating DNA as a potential biomarker for severe dengue. Methods and Findings A direct fluorometric degradation assay using PicoGreen was performed to quantify cell-free DNA from patient plasma. Circulating DNA levels were significantly higher in patients with dengue virus infection than with other febrile illnesses and healthy controls. Remarkably, the increase of DNA levels correlated with the severity of dengue. Additionally, multivariate logistic regression analysis showed that circulating DNA levels independently correlated with dengue shock syndrome. Conclusions Circulating DNA levels were increased in dengue patients and correlated with dengue severity. Additional studies are required to show the benefits of this biomarker in early dengue diagnosis and for the prognosis of shock complication. PMID:22016795

  1. Combination immunotherapy in the treatment of chronic bilateral panuveitis and uveitic glaucoma during acute dengue fever infection in the Caribbean

    PubMed Central

    Stewart, Kevin P; Tawakol, Jan B; Khan, Tasnim; Capriotti, Joseph A

    2015-01-01

    Background Ocular manifestations of the dengue fever virus include bilateral panuveitis that can occur after the acute systemic infection has resolved. In most reported cases, the inflammation resolves with topical or systemic steroid therapy. We report a case of chronic, refractory bilateral panuveitis and uveitic glaucoma that began during the acute phase of the systemic infection and required treatment with oral steroids, multiple steroid-sparing agents, and surgical therapy for glaucoma. Findings A 22-year-old male with acute systemic dengue fever presented with bilateral pain and decreased vision. Clinical examination revealed bilateral panuveitis with elevated intraocular pressures. Management required oral steroids, mycophenolate mofetil, cyclosporine, and bilateral glaucoma valve implantation. Conclusion This case highlights the fact that dengue-associated panuveitis can begin in the acute stage of systemic infection and persist long after convalescence with progression to chronic bilateral panuveitis and uveitic glaucoma. Dengue-associated chronic panuveitis with uveitic glaucoma may be effectively managed with a combination of steroid-sparing oral immunosuppression and glaucoma surgery. This is, to our knowledge, the first case of bilateral refractory dengue-associated panuveitis from the Caribbean treated with combination steroid-sparing oral immunosuppression and bilateral glaucoma valve implantation. PMID:26229512

  2. Plasmablasts During Acute Dengue Infection Represent a Small Subset of a Broader Virus-specific Memory B Cell Pool.

    PubMed

    Appanna, Ramapraba; Kg, Srinivasan; Xu, Mei Hui; Toh, Ying-Xiu; Velumani, Sumathy; Carbajo, Daniel; Lee, Chia Yin; Zuest, Roland; Balakrishnan, Thavamalar; Xu, Weili; Lee, Bernett; Poidinger, Michael; Zolezzi, Francesca; Leo, Yee Sin; Thein, Tun Linn; Wang, Cheng-I; Fink, Katja

    2016-10-01

    Dengue is endemic in tropical countries worldwide and the four dengue virus serotypes often co-circulate. Infection with one serotype results in high titers of cross-reactive antibodies produced by plasmablasts, protecting temporarily against all serotypes, but impairing protective immunity in subsequent infections. To understand the development of these plasmablasts, we analyzed virus-specific B cell properties in patients during acute disease and at convalescence. Plasmablasts were unrelated to classical memory cells expanding in the blood during early recovery. We propose that only a small subset of memory B cells is activated as plasmablasts during repeat infection and that plasmablast responses are not representative of the memory B cell repertoire after dengue infection.

  3. Dengue and Chikungunya Virus Infections among Young Febrile Adults Evaluated for Acute HIV-1 Infection in Coastal Kenya

    PubMed Central

    Ngoi, Carolyne N.; Price, Matt A.; Fields, Barry; Bonventure, Juma; Ochieng, Caroline; Mwashigadi, Grace; Hassan, Amin S.; Thiong’o, Alexander N.; Micheni, Murugi; Mugo, Peter; Graham, Susan; Sanders, Eduard J.

    2016-01-01

    Background Fever is common among patients seeking care in sub-Saharan Africa (sSA), but causes other than malaria are rarely diagnosed. We assessed dengue and chikungunya virus infections among young febrile adults evaluated for acute HIV infection (AHI) and malaria in coastal Kenya. Methods We tested plasma samples obtained in a cross-sectional study from febrile adult patients aged 18–35 years evaluated for AHI and malaria at urgent care seeking at seven health facilities in coastal Kenya in 2014–2015. Dengue virus (DENV) and chikungunya virus (CHIKV) were amplified using quantitative real-time reverse-transcription polymerase chain reaction. We conducted logistic regression analyses to determine independent predictors of dengue virus infection. Results 489 samples that were negative for both AHI and malaria were tested, of which 43 (8.8%, 95% confidence interval [CI]: 6.4–11.7) were positive for DENV infection. No participant was positive for CHIKV infection. DENV infections were associated with clinic visits in the rainy season (adjusted odds ratio (AOR) = 3.0, 95% CI: 1.3–6.5) and evaluation at a private health facility (AOR 5.2, 95% CI: 2.0–13.1) or research health facility (AOR = 25.6, 95% CI: 8.9–73.2) instead of a public health facility. Conclusion A high prevalence of DENV infections was found in febrile young adult patients evaluated for AHI. Our data suggests that DENV, along with AHI and malaria, should be considered in the differential diagnosis of the adult patient seeking care for fever in coastal Kenya. PMID:27942016

  4. Dengue-associated acute kidney injury

    PubMed Central

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023

  5. Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis.

    PubMed

    Myint, Khin S; Endy, Timothy P; Mongkolsirichaikul, Duangrat; Manomuth, Choompun; Kalayanarooj, Siripen; Vaughn, David W; Nisalak, Ananda; Green, Sharone; Rothman, Alan L; Ennis, Francis A; Libraty, Daniel H

    2006-09-01

    Apoptosis is an important modulator of cellular immune responses during systemic viral infections. Peripheral-blood mononuclear cell (PBMC) apoptosis and plasma soluble levels of CD95, a mediator of apoptosis, were determined in sequential samples from children participating in a prospective study of dengue virus (DV) infections. During the period of defervescence, levels of PBMC apoptosis were higher in children developing dengue hemorrhagic fever (DHF), the most severe form of illness, than in those with dengue fever (DF) and other, nondengue, febrile illnesses. CD8(+) T lymphocytes made up approximately half of the peak circulating apoptotic PBMCs in DHF and DF. Maximum plasma levels of soluble CD95 were also higher in children with DHF than in those with DF. The level of PBMC apoptosis correlated with dengue disease severity. Apoptosis appears to be involved in modulation of the innate and adaptive immune responses to DV infection and is likely involved in the evolution of immune responses in other viral hemorrhagic fevers.

  6. Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever.

    PubMed

    Durbin, Anna P; Vargas, Maria José; Wanionek, Kimberli; Hammond, Samantha N; Gordon, Aubree; Rocha, Crisanta; Balmaseda, Angel; Harris, Eva

    2008-07-05

    In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14(+), CD32(+), CD86(+), CD11c(+)). A subset of samples analyzed for DEN nonstructural protein 3 (NS3) confirmed that approximately half of DEN antigen-positive cells contained replicating virus. A higher percentage of PBMCs from DHF patients expressed prM, CD86, CD32, and CD11c than did those from DF patients. Increased activation of monocytes and greater numbers of DEN-infected cells were associated with more severe dengue, implicating a role for monocyte activation in dengue immunopathogenesis.

  7. Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection

    PubMed Central

    Xu, Meihui; Züst, Roland; Toh, Ying Xiu; Pfaff, Jennifer M.; Kahle, Kristen M.; Davidson, Edgar; Doranz, Benjamin J.; Velumani, Sumathy; Tukijan, Farhana; Wang, Cheng-I

    2016-01-01

    ABSTRACT Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days after natural secondary infection. Among a panel of 18 dengue virus-reactive human monoclonal antibodies, four groups of antibodies were identified based on their binding properties. While antibodies targeting the fusion loop of the glycoprotein of dengue virus dominated the antibody response, two smaller groups of antibodies bound to previously undescribed epitopes in domain II of the E protein. The latter, largely serotype-cross-reactive antibodies, demonstrated increased stability of binding at pH 5. These antibodies possessed weak to moderate neutralization capacity in vitro but were the most efficacious in promoting the survival of infected mice. Our data suggest that the cross-reactive anamnestic antibody response has a protective capacity despite moderate neutralization in vitro and a moderate decrease of viremia in vivo. IMPORTANCE Antibodies can protect from symptomatic dengue virus infection. However, it is not easy to assess which classes of antibodies provide protection because in vitro assays are not always predictive of in vivo protection. During a repeat infection, dengue virus-specific immune memory cells are reactivated and large amounts of antibodies are produced. By studying antibodies cloned from patients with heterologous secondary infection, we tested the protective value of the serotype-cross-reactive “recall” or “anamnestic” response. We found that results from in vitro neutralization assays did not always correlate with the ability of

  8. Cross-reactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans.

    PubMed

    Friberg, Heather; Bashyam, Hema; Toyosaki-Maeda, Tomoko; Potts, James A; Greenough, Thomas; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2011-01-01

    Serotype-cross-reactive memory T cells responding to secondary dengue virus (DENV) infection are thought to contribute to disease. However, epitope-specific T cell responses have not been thoroughly compared between subjects with primary versus secondary DENV infection. We studied CD8(+) T cells specific for the HLA-A*1101-restricted NS3(133) epitope in a cohort of A11(+) DENV-infected patients throughout acute illness and convalescence. We compared the expansion, serotype-cross-reactivity, and activation of these cells in PBMC from patients experiencing primary or secondary infection and mild or severe disease by flow cytometry. Our results show expansion and activation of DENV-specific CD8(+) T cells during acute infection, which are predominantly serotype-cross-reactive regardless of DENV infection history. These data confirm marked T cell activation and serotype-cross-reactivity during the febrile phase of dengue; however, A11-NS3(133)-specific responses did not correlate with prior antigenic exposure or current disease severity.

  9. Analysis of plasma viral RNA levels during acute dengue virus infection using quantitative competitor reverse transcription-polymerase chain reaction.

    PubMed

    Sudiro, T M; Zivny, J; Ishiko, H; Green, S; Vaughn, D W; Kalayanarooj, S; Nisalak, A; Norman, J E; Ennis, F A; Rothman, A L

    2001-01-01

    There is increasing recognition of the potential importance of viral burden in the pathogenesis of dengue hemorrhagic fever (DHF). There is little data available, however, describing the kinetics of viral replication in humans with natural dengue virus (DV) infection. Standard procedures for measuring titers of infectious virus in clinical specimens are either laborious or insensitive. We developed a method for measurement of DV RNA in plasma samples based on reverse transcription-polymerase chain reaction (RT-PCR) using a mutant RNA target as a competitor. This technique was reproducible and accurate for samples containing any of the four DV serotypes, and could be applied to samples containing as few as 250 copies of RNA per reaction. We examined plasma viral RNA levels in 80 children with acute DV infection; sequential plasma samples were tested in 34 of these children. Plasma viral RNA levels ranged as high as 10(9) RNA copies/ml, and correlated with titers of infectious virus measured in mosquitoes (r= 0.69). Plasma viral RNA levels fell rapidly during the last several days of the febrile period. We did not find a significant difference in maximal plasma viral RNA levels between children with DHF and children with dengue fever, but peak viral RNA levels were identified in only 16 subjects. We conclude that this quantitative RT-PCR method will be valuable for further studies of natural DV infections.

  10. Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue haemorrhagic fever.

    PubMed

    Kochel, Tadeusz J; Watts, Douglas M; Halstead, Scott B; Hayes, Curtis G; Espinoza, Angelica; Felices, Vidal; Caceda, Roxana; Bautista, Christian T; Montoya, Ysabel; Douglas, Susan; Russell, Kevin L

    2002-07-27

    In Iquitos, Peru, no cases of dengue haemorrhagic fever have been recorded in individuals infected with dengue-1 virus followed by American genotype dengue-2 (American dengue-2) virus. We assayed serum samples collected in Iquitos that tested positive for antibodies of monotype dengue-1 and monotype dengue-2 using a plaque reduction neutralisation test to determine their ability to neutralise the infectivity of two dengue-1 viruses, two American dengue-2 viruses, and two Asian dengue-2 viruses. Sera positive for the dengue-1 antibody neutralised dengue-1 viruses and American dengue-2 viruses much more effectively than Asian dengue-2 viruses. Neutralisation of American dengue-2 virus by sera positive for dengue-1 antibodies may account for the absence of dengue haemorrhagic fever in individuals infected with dengue-1 in 1990-91 followed by American dengue-2 virus in 1995 in Iquitos, Peru.

  11. Acute dengue in a neonate secondary to perinatal transmission.

    PubMed

    Chin, P S; Khoo, A P C; Asmah Hani, A W; Chem, Y K; Norizah, I; Chua, K B

    2008-08-01

    We report a newborn baby girl with acute dengue due to vertical transmission. A 31 year old factory worker of 38+ week gestation, gravida 5 para 3+1, developed acute dengue fever two days prior to delivery. She delivered a normal term baby girl by spontaneous vaginal delivery and recovered uneventfully without peripartum haemorrhage despite the presence of thrombocytopenia. The baby girl developed low grade fever on day four of post-natal life and except for the transient thrombocytopenia, also recovered uneventfully following three days of mild illness. The clinical diagnosis of acute dengue virus infection was confirmed by laboratory tests.

  12. A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever.

    PubMed

    Ahmad, S; Dhar, M; Mittal, G; Bhat, N K; Shirazi, N; Kalra, V; Sati, H C; Gupta, V

    2016-04-01

    Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono-infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co-infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono-infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross-reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection.

  13. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1989-07-31

    lhuman Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Francis A. Ennis 13a. TYPE OF REPORT 13b. TIME COVERED T14. DATE OF REPORT (Year, Month...Stimulation with live dengue virus of peripheral blood mononuclear cells from a dengue 4-immune donor generated virus-specific serotype cross-reactive CD4- CD8...class I-restricted cytotoxic T lymphocytes (CL) capable of lysing dengue virus-infected autologous fibroblasts and cells pulsed with dengue I

  14. Invariant NKT Cell Response to Dengue Virus Infection in Human

    PubMed Central

    Matangkasombut, Ponpan; Chan-in, Wilawan; Opasawaschai, Anunya; Pongchaikul, Pisut; Tangthawornchaikul, Nattaya; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Duangchinda, Thaneeya; Screaton, Gavin; Mongkolsapaya, Juthathip

    2014-01-01

    Background Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their role in human dengue virus infection is not known. We hypothesized that iNKT cells play a role in human dengue infection. Methods Blood samples from a well-characterized cohort of children with DF, DHF, in comparison to non-dengue febrile illness (OFI) and healthy controls at various time points were studied. iNKT cells activation were analyzed by the expression of CD69 by flow cytometry. Their cytokine production was then analyzed after α-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69 expression on conventional T cells were measured. Results iNKT cells were activated during acute dengue infection. The level of iNKT cell activation associates with the disease severity. Furthermore, these iNKT cells had altered functional response to subsequent ex vivo stimulation with α-GalCer. Moreover, during acute dengue infection, monocytic CD1d expression was also upregulated and conventional T cells also became activated. Conclusion iNKT cells might play an early and critical role in the pathogenesis of severe dengue viral infection in human. Targeting iNKT cells and CD1d serve as a potential therapeutic strategy for severe dengue infection in the future. PMID:24945350

  15. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever.

    PubMed

    Upadhaya, Bala Krishna; Sharma, Alok; Khaira, Ambar; Dinda, Amit K; Agarwal, Sanjay K; Tiwari, Suresh C

    2010-05-01

    Dengue virus infection can clinically manifest as dengue fever, dengue shock syndrome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15-year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.

  16. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1991-06-30

    illness, dengue fever (DF) and dengue hemorrhagic fever (DfIF)/dengue shock syndrome (DSS) (5). Dengue fever is a self- limited febrile disease which is...this syndrome (4). Therefore, dengue virus infections are one of the most important human infectious diseases . Immune responses to dengue viruses have...Number Male Female (Range) Primary Secondary DHF 59 28 31 8.9 + 3.0 7 52 (4-14) DF 41 22 19 9.8 + 2.1 6 35 (5-14) Uncharacterized febrile diseases 26

  17. An unusual case of dengue infection presenting with hypokalemic paralysis with hypomagnesemia.

    PubMed

    Jain, Rajendra Singh; Gupta, Pankaj Kumar; Agrawal, Rakesh; Kumar, Sunil; Khandelwal, Kapil

    2015-08-01

    Neurological manifestations are unusual in dengue fever and can be due to neurotropic effect, systemic complications of dengue infection, or immune mediated. Acute hypokalemic paralysis is a rare systemic complication of dengue infection; however, hypokalemia along with hypomagnesemia has not been reported earlier. We herein report an extremely unusual and probably the first case of dengue infection in a 30-year-old male who presented to us with hypokalemic paralysis along with hypomagnesemia. This case report highlights that hypomagnesemia may be a significant complication in dengue infection. Correction of hypomagnesemia is of paramount importance to avoid refractory hypokalemia leading to severe consequences.

  18. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1988-07-31

    Security Classification) (U) Human Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Francis A. Ennis 13a. TYPE OF’REPORTn 13b. TIME COVERED 14...8217SUBJECT TERMS (Continue on reverse if necessary and identify by Nock rumber) FIELD GROUP SUB-GROUP RA .1, Dengue virus, T lymphopytes. 06 03 InB-GROP1.In...responses to dengue antigens in vitro to elucidate the possible role of T lymphocytes in the pathogeneeis of dengue hemorrhagic fever and dengue

  19. Dengue human infection models to advance dengue vaccine development.

    PubMed

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics.

  20. Predictive value of thrombocytopaenia in the diagnosis of dengue infection in outpatient settings.

    PubMed

    Tong, S F; Aziz, N A; Chin, G L

    2007-12-01

    Thrombocytopaenia is often relied upon as an important criterion for the diagnosis of dengue infection among patients presenting with an acute non-specific febrile illness. This study was aimed to assess usefulness of thrombocytopaenia in the diagnosis of acute dengue virus infection. This was a clinic based prospective cohort study from May to November 2003. Consecutive patients presenting with acute non-specific febrile illness of less than two weeks were selected from two urban primary care centres. We did full blood count examination (FBC) on the day of visit and dengue serology on day five of illness for all patients enrolled. We repeated the FBC examination for patients who had initial normal platelet counts. Thrombocytopaenia was defined as platelet count < 150 X 10(9)/L. Eighty-seven patients enrolled in the study. Complete data was available for 73 patients. The prevalence of acute dengue virus infection was 27.6%. The sensitivity and specificity were 88% and 71% respectively. The likelihood of acute dengue infection in the presence of thrombocytopaenia was 2.52 and likelihood of not having dengue infection in normal platelet count patients was 5.22. Thrombocytopaenia has fair predictive value in diagnosing acute dengue virus infection. It was more useful to exclude than to diagnose dengue infection.

  1. Human Immune Response to Dengue Infections.

    DTIC Science & Technology

    1991-06-30

    DTIC AD-A240 717 AD ____ HUMAN IMMUNE RESPONSE TO DENGUE INFECTIONS ANNUAL REPORT FRANCIS A. ENNIS JUNE 30, 1991 Supported by U.S. ARMY MEDICAL...Immune Response to Dengue Infections DAMDI7-86-C-6208 6. AUTHOR(S) 61102A 1 3M161102BS13 AA Francis A. Ennis WUDA3 12059 7. PERFORMING ORGANIZATION...of NS3, respectively. We also established 16 dengue virus-specific CD8+ CD4_ T cell clones. The clone #/2.8 recognize dengue virus types 2 and 4, and

  2. Development of Dengue Infection Severity Score

    PubMed Central

    Pongpan, Surangrat; Tawichasri, Chamaiporn; Namwongprom, Sirianong

    2013-01-01

    Objectives. To develop a simple scoring system to predict dengue infection severity based on patient characteristics and routine clinical profiles. Methods. Retrospective data of children with dengue infection from 3 general hospitals in Thailand were reviewed. Dengue infection was categorized into 3 severity levels: dengue infection (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Coefficients of significant predictors of disease severity under ordinal regression analysis were transformed into item scores. Total scores were used to classify patients into 3 severity levels. Results. Significant clinical predictors of dengue infection severity were age >6 years, hepatomegaly, hematocrit ≥40%, systolic pressure <90 mmHg, white cell count >5000 /μL, and platelet ≤50000 /μL. The derived total scores, which ranged from 0 to 18, classified patients into 3 severity levels: DF (scores <2.5, n = 451, 58.1%), DHF (scores 2.5–11.5, n = 276, 35.5%), and DSS (scores >11.5, n = 50, 6.4%). The derived score correctly classified patients into their original severity levels in 60.7%. An under-estimation of 25.7% and an over-estimation of 13.5% were clinically acceptable. Conclusions. The derived dengue infection severity score classified patients into DF, DHF, or DSS, correctly into their original severity levels. Validation of the score should be reconfirmed before application of routine practice. PMID:24324896

  3. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1990-07-31

    WUDA312059 11. TITLE (Include Security Classification) (U) Human Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Francis A. Ennis 13a. TYPE OF...COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP RA 1; Vaccines; Dengue ; Cell...mediated; HLA; Interferon 0@ 03 19. ABSTRACT (Continue on reverse if necessary and identify by block number) Thirteen dengue virus-specific, cytotoxic CD4

  4. Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases.

    PubMed

    Sahadeo, Nikita; Mohammed, Hamish; Allicock, Orchid M; Auguste, Albert J; Widen, Steven G; Badal, Kimberly; Pulchan, Krishna; Foster, Jerome E; Weaver, Scott C; Carrington, Christine V F

    2015-11-01

    Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson's χ2 and student's t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson's χ2 and Fisher's exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28-16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever--aOR: 0.56 [0.40-0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71-0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which

  5. Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases

    PubMed Central

    Sahadeo, Nikita; Mohammed, Hamish; Allicock, Orchid M.; Auguste, Albert J.; Widen, Steven G.; Badal, Kimberly; Pulchan, Krishna; Foster, Jerome E.; Weaver, Scott C.; Carrington, Christine V. F.

    2015-01-01

    Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson’s χ2 and student’s t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson’s χ2 and Fisher’s exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28–16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever—aOR: 0.56 [0.40–0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71–0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs

  6. Human Immune Response to Dengue Infections.

    DTIC Science & Technology

    1987-07-30

    W5l "I± H"MN IMMUNE RESPONSE TO DENGUE INFECTIONS(U) i/il MASSACHUSETTS UNIV MEDICAL CENTER NORCESTER MR1 F R ENIS 36 JUL 87 DAMD7-86-C-6200...1 U . AD HUMAN IMMUNE RESPONSE TO DENGUE INFECTIONS ANNUAL REPORT In 00 FRANCIS A. ENNIS JULY 30, 1987 Supported by U.S. ARMY MEDICAL RESEARCH...Human Immune Response to Dengue Infections 12. PERSONAL AUTHOR(S) Ennis, Francis A. 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year

  7. Dengue

    MedlinePlus

    Dengue is an infection caused by a virus. You can get it if an infected mosquito bites you. Dengue does not spread from person to person. It ... the world. Outbreaks occur in the rainy season. Dengue is rare in the United States. Symptoms include ...

  8. Reduced Risk of Disease During Postsecondary Dengue Virus Infections

    PubMed Central

    Olkowski, Sandra; Forshey, Brett M.; Morrison, Amy C.; Rocha, Claudio; Vilcarromero, Stalin; Halsey, Eric S.; Kochel, Tadeusz J.; Scott, Thomas W.; Stoddard, Steven T.

    2013-01-01

    Background. Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1–4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. Methods. DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. Results. Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). Conclusions. Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics. PMID:23776195

  9. Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua

    PubMed Central

    Reller, Megan E.; de Silva, Aravinda M.; Miles, Jeremy J.; Jadi, Ramesh S.; Broadwater, Anne; Walker, Katie; Woods, Christopher; Mayorga, Orlando; Matute, Armando

    2016-01-01

    Background Dengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua’s heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not. Methodology/Principal Findings To prospectively study dengue in semi-urban and rural western Nicaragua, we obtained epidemiologic and clinical data as well as acute and convalescent sera (2 to 4 weeks after onset of illness) from a convenience sample (enrollment Monday to Saturday daytime to early evening) of consecutively enrolled patients (n = 740) aged ≥ 1 years presenting with acute febrile illness. We tested paired sera for dengue IgG and IgM and serotyped dengue virus using reverse transcriptase-PCR. Among 740 febrile patients enrolled, 90% had paired sera. We found 470 (63.5%) were seropositive for dengue at enrollment. The dengue seroprevalance increased with age and reached >90% in people over the age of 20 years. We identified acute dengue (serotypes 1 and 2) in 38 (5.1%) patients. Only 8.1% (3/37) of confirmed cases were suspected clinically. Conclusions/Significance Dengue is an important and largely unrecognized cause of fever in rural western Nicaragua. Since Zika virus is transmitted by the same vector and has been associated with severe congenital infections, the population we studied is at particular risk for being devastated by the Zika epidemic that has now reached Central America. PMID:27792777

  10. Transmission spectroscopy of dengue viral infection Transmission spectroscopy of dengue viral infection

    NASA Astrophysics Data System (ADS)

    Firdous, S.; Ahmed, M.; Rehman, A.; Nawaz, M.; Anwar, S.; Murtaza, S.

    2012-04-01

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 - 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 - 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 - 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients.

  11. Virus-specific T lymphocytes home to the skin during natural dengue infection.

    PubMed

    Rivino, Laura; Kumaran, Emmanuelle A; Thein, Tun-Linn; Too, Chien Tei; Gan, Victor Chih Hao; Hanson, Brendon J; Wilder-Smith, Annelies; Bertoletti, Antonio; Gascoigne, Nicholas R J; Lye, David Chien; Leo, Yee Sin; Akbar, Arne N; Kemeny, David M; MacAry, Paul A

    2015-03-11

    Dengue, which is the most prevalent mosquito-borne viral disease afflicting human populations, causes a spectrum of clinical symptoms that include fever, muscle and joint pain, maculopapular skin rash, and hemorrhagic manifestations. Patients infected with dengue develop a broad antigen-specific T lymphocyte response, but the phenotype and functional properties of these cells are only partially understood. We show that natural infection induces dengue-specific CD8(+) T lymphocytes that are highly activated and proliferating, exhibit antiviral effector functions, and express CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen (CLA). In the same patients, bystander human cytomegalovirus -specific CD8(+) T cells are also activated during acute dengue infection but do not express the same tissue-homing phenotype. We show that CLA expression by circulating dengue-specific CD4(+) and CD8(+) T cells correlates with their in vivo ability to traffic to the skin during dengue infection. The juxtaposition of dengue-specific T cells with virus-permissive cell types at sites of possible dengue exposure represents a previously uncharacterized form of immune surveillance for this virus. These findings suggest that vaccination strategies may need to induce dengue-specific T cells with similar homing properties to provide durable protection against dengue viruses.

  12. Dengue and other flavivirus infections.

    PubMed

    Choumet, V; Desprès, Ph

    2015-08-01

    Flaviviruses are responsible for yellow fever, Zika fever and dengue, all of which are major human diseases found in tropical regions of the globe. They are zoonoses with a transmission cycle that involves primates as reservoirs and mosquitoes of the genus Aedes as vectors. The recent upsurge of urban epidemics of yellow fever, Zika fever and dengue has involved human-to-human transmission with mosquitoes as the vector. This paper is primarily concerned with dengue, which has become the pre-eminent arbovirosis in terms of public health.

  13. Paper-based point-of-care testing for diagnosis of dengue infections.

    PubMed

    Choi, Jane Ru; Hu, Jie; Wang, ShuQi; Yang, Hui; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

    2017-02-01

    Dengue endemic is a serious healthcare concern in tropical and subtropical countries. Although well-established laboratory tests can provide early diagnosis of acute dengue infections, access to these tests is limited in developing countries, presenting an urgent need to develop simple, rapid, and robust diagnostic tools. Point-of-care (POC) devices, particularly paper-based POC devices, are typically rapid, cost-effective and user-friendly, and they can be used as diagnostic tools for the prompt diagnosis of dengue at POC settings. Here, we review the importance of rapid dengue diagnosis, current dengue diagnostic methods, and the development of paper-based POC devices for diagnosis of dengue infections at the POC.

  14. Mouse models of dengue virus infection for vaccine testing.

    PubMed

    Sarathy, Vanessa V; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

    2015-12-10

    Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple

  15. The Cellular Bases of Antibody Responses during Dengue Virus Infection.

    PubMed

    Yam-Puc, Juan Carlos; Cedillo-Barrón, Leticia; Aguilar-Medina, Elsa Maribel; Ramos-Payán, Rosalío; Escobar-Gutiérrez, Alejandro; Flores-Romo, Leopoldo

    2016-01-01

    Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab) responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG) memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell-dependent processes, we know rather little about the (acute, chronic, or memory) B cell responses and the complex cellular mechanisms generating these Abs during DENV infections. This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events such as the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation, and germinal centers (GCs) formation (the source of affinity-matured class-switched memory Abs), till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells, and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated.

  16. The Cellular Bases of Antibody Responses during Dengue Virus Infection

    PubMed Central

    Yam-Puc, Juan Carlos; Cedillo-Barrón, Leticia; Aguilar-Medina, Elsa Maribel; Ramos-Payán, Rosalío; Escobar-Gutiérrez, Alejandro; Flores-Romo, Leopoldo

    2016-01-01

    Dengue virus (DENV) is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab) responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG) memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell-dependent processes, we know rather little about the (acute, chronic, or memory) B cell responses and the complex cellular mechanisms generating these Abs during DENV infections. This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events such as the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation, and germinal centers (GCs) formation (the source of affinity-matured class-switched memory Abs), till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells, and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated. PMID:27375618

  17. Dengue virus antibodies enhance Zika virus infection

    PubMed Central

    Paul, Lauren M; Carlin, Eric R; Jenkins, Meagan M; Tan, Amanda L; Barcellona, Carolyn M; Nicholson, Cindo O; Michael, Scott F; Isern, Sharon

    2016-01-01

    For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies. PMID:28090318

  18. Dengue virus antibodies enhance Zika virus infection.

    PubMed

    Paul, Lauren M; Carlin, Eric R; Jenkins, Meagan M; Tan, Amanda L; Barcellona, Carolyn M; Nicholson, Cindo O; Michael, Scott F; Isern, Sharon

    2016-12-01

    For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.

  19. Hyperferritinaemia in Dengue Virus Infected Patients Is Associated with Immune Activation and Coagulation Disturbances

    PubMed Central

    Pannuti, Cláudio S.; Brouns, Rosalba M.; van den Berg, Riemsdijk W. A.; van den Ham, Henk-Jan; Martina, Byron E. E.; Osterhaus, Albert D. M. E.; Netea, Mihai G.; Meijers, Joost C. M.; van Gorp, Eric C. M.; Kallas, Esper G.

    2014-01-01

    Background During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances. Methodology/Principal Findings Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile. Conclusions/Significance Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully. PMID:25299654

  20. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  1. Validation of dengue infection severity score

    PubMed Central

    Pongpan, Surangrat; Patumanond, Jayanton; Wisitwong, Apichart; Tawichasri, Chamaiporn; Namwongprom, Sirianong

    2014-01-01

    Objective To validate a simple scoring system to classify dengue viral infection severity to patients in different settings. Methods The developed scoring system derived from 777 patients from three tertiary-care hospitals was applied to 400 patients in the validation data obtained from another three tertiary-care hospitals. Percentage of correct classification, underestimation, and overestimation was compared. The score discriminative performance in the two datasets was compared by analysis of areas under the receiver operating characteristic curves. Results Patients in the validation data were different from those in the development data in some aspects. In the validation data, classifying patients into three severity levels (dengue fever, dengue hemorrhagic fever, and dengue shock syndrome) yielded 50.8% correct prediction (versus 60.7% in the development data), with clinically acceptable underestimation (18.6% versus 25.7%) and overestimation (30.8% versus 13.5%). Despite the difference in predictive performances between the validation and the development data, the overall prediction of the scoring system is considered high. Conclusion The developed severity score may be applied to classify patients with dengue viral infection into three severity levels with clinically acceptable under- or overestimation. Its impact when used in routine clinical practice should be a topic for further study. PMID:24623999

  2. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance

    PubMed Central

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  3. Enhanced Surveillance for Fatal Dengue-Like Acute Febrile Illness in Puerto Rico, 2010-2012

    PubMed Central

    Rivera, Aidsa; Torres-Velasquez, Brenda; Hunsperger, Elizabeth A.; Munoz-Jordan, Jorge L.; Sharp, Tyler M.; Rivera, Irma; Sanabria, Dario; Blau, Dianna M.; Galloway, Renee; Torres, Jose; Rodriguez, Rosa; Serrano, Javier; Chávez, Carlos; Dávila, Francisco; Perez-Padilla, Janice; Ellis, Esther M.; Caballero, Gladys; Wright, Laura; Zaki, Sherif R.; Deseda, Carmen; Rodriguez, Edda; Margolis, Harold S.

    2016-01-01

    Background Dengue is a leading cause of morbidity throughout the tropics; however, accurate population-based estimates of mortality rates are not available. Methods/Principal Findings We established the Enhanced Fatal Acute Febrile Illness Surveillance System (EFASS) to estimate dengue mortality rates in Puerto Rico. Healthcare professionals submitted serum and tissue specimens from patients who died from a dengue-like acute febrile illness, and death certificates were reviewed to identify additional cases. Specimens were tested for markers of dengue virus (DENV) infection by molecular, immunologic, and immunohistochemical methods, and were also tested for West Nile virus, Leptospira spp., and other pathogens based on histopathologic findings. Medical records were reviewed and clinical data abstracted. A total of 311 deaths were identified, of which 58 (19%) were DENV laboratory-positive. Dengue mortality rates were 1.05 per 100,000 population in 2010, 0.16 in 2011 and 0.36 in 2012. Dengue mortality was highest among adults 19–64 years and seniors ≥65 years (1.17 and 1.66 deaths per 100,000, respectively). Other pathogens identified included 34 Leptospira spp. cases and one case of Burkholderia pseudomallei and Neisseria meningitidis. Conclusions/Significance EFASS showed that dengue mortality rates among adults were higher than reported for influenza, and identified a leptospirosis outbreak and index cases of melioidosis and meningitis. PMID:27727271

  4. Dengue infection in neotropical forest mammals.

    PubMed

    de Thoisy, Benoît; Lacoste, Vincent; Germain, Adeline; Muñoz-Jordán, Jorge; Colón, Candimar; Mauffrey, Jean-François; Delaval, Marguerite; Catzeflis, François; Kazanji, Mirdad; Matheus, Séverine; Dussart, Philippe; Morvan, Jacques; Setién, Alvaro Aguilar; Deparis, Xavier; Lavergne, Anne

    2009-04-01

    In South America, dengue is the arbovirus-transmitted disease with the highest incidence. Unlike other arboviruses, wild mammals have no confirmed role in the cycle of dengue in the neotropics, although serological studies have suggested a possible secondary amplification cycle involving mammals other than nonhuman primates. In French Guiana, where all four serotypes (DENV-1, DENV-2, DENV-3, DENV-4) are present, the disease is endemic with outbreak events. To determine whether wild mammals can be infected by DENV, rodents, marsupials, and bats were captured over several periods, from 2001 to 2007, at two sites. The first location is a secondary forest surrounded by an urban area where dengue is endemic. The second location is a forest edge site where the disease has not yet emerged. A total of 10,000 trap-nights were performed and 616 mammals were captured. RNAs representing the four DENV serotypes were detected at both sites by reverse-transcriptase polymerase chain reaction in the livers and/or sera of 92 mammals belonging to 14 out of 32 species distributed among all the orders investigated: Rodentia (33 positive/146 tested), Marsupialia (40/318), and Chiroptera (19/152). Sequence analyses of a portion of the capsid and premembrane junction revealed that mammal strains of DENV-1, DENV-2, DENV-3, and DENV-4 had only 92.6%, 89%, 95%, and 95.8% identity, respectively, with strains circulating in the human population during the same periods. Regarding DENV-2, strains related (99% identity) to those responsible for an epidemic event in humans in French Guiana concurrent to the capture sessions were also evidenced, suggesting that wild mammals in edge habitats can be infected by circulating human strains. Our results demonstrate, for the first time, that neotropical wild mammals can be infected with dengue virus. The question of whether mammals maintain DENV in enzootic cycles and can play a role in its reemergence in human populations remains to be answered.

  5. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

    PubMed Central

    Parkash, Om; Hanim Shueb, Rafidah

    2015-01-01

    Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. PMID:26492265

  6. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques.

    PubMed

    Parkash, Om; Shueb, Rafidah Hanim

    2015-10-19

    Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed.

  7. Post dengue neurological complication.

    PubMed

    Hasliza, A H; Tohid, H; Loh, K Y; Santhi, P

    2015-01-01

    Dengue infection is highly endemic in many tropical countries including Malaysia. However, neurological complications arising from dengue infection is not common; Gullain-Barre syndrome (GBS) is one of these infrequent complications. In this paper, we have reported a case in which a 39-year-old woman presented with a neurological complication of dengue infection without typical symptoms and signs of dengue fever. She had a history of acute gastroenteritis (AGE) followed by an upper respiratory tract infection (URTI) weeks prior to her presentation rendering GBS secondary to the post viral URTI and AGE as the most likely diagnosis. Presence of thrombocytopenia was the only clue for dengue in this case.

  8. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

    PubMed Central

    Jamjoom, Ghazi A.; Azhar, Esam I.; Kao, Moujahid A.; Radadi, Raja M.

    2016-01-01

    BACKGROUND Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. METHODS Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA) for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. RESULTS The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939) and 37% (68/184) in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1%) reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others. Availability of

  9. Antiviral activity of lanatoside C against dengue virus infection.

    PubMed

    Cheung, Yan Yi; Chen, Karen Caiyun; Chen, Huixin; Seng, Eng Khuan; Chu, Justin Jang Hann

    2014-11-01

    Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.

  10. Cross-reactive memory CD8(+) T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner.

    PubMed

    Beaumier, Coreen M; Mathew, Anuja; Bashyam, Hema S; Rothman, Alan L

    2008-02-15

    Dengue virus is the causative agent of dengue fever and the more-severe dengue hemorrhagic fever (DHF). Human studies suggest that the increased risk of DHF during secondary infection is due to immunopathology partially mediated by cross-reactive memory T cells from the primary infection. To model T cell responses to sequential infections, we immunized mice with different sequences of dengue virus serotypes and measured the frequency of peptide-specific T cells after infection. The acute response after heterologous secondary infections was enhanced compared with the acute or memory response after primary infection. Also, the hierarchy of epitope-specific responses was influenced by the specific sequence of infection. Adoptive-transfer experiments showed that memory T cells responded preferentially to the secondary infection. These findings demonstrate that cross-reactive T cells from a primary infection alter the immune response during a heterologous secondary infection.

  11. Susceptibility of mouse macrophage J774 to dengue virus infection.

    PubMed

    Moreno-Altamirano, María M B; Sánchez-García, F Javier; Legorreta-Herrera, Martha; Aguilar-Carmona, Israel

    2007-01-01

    The aim of this study was to investigate whether the J774 mouse macrophage cell line could be used as an in vitro model for dengue virus infection (DENV). After 3 days, infection in J774 cells was assessed by detecting dengue virus non-structural protein 1 (NSP-1) production either by dot blot or indirect immunofluorescence assay (IFA) of saponine-permeabilized J774 cells and then confirmed by RT-PCR (171 bp product, corresponding to the DENV-2 core). Based on the presence of NSP-1 in infected but not in non-infected cells by both IFA and dot blot, as well as the amplification of a 171-bp DENV-2-specific RT-PCR product exclusively in the infected cells, the J774 cell line was found to be permissive for dengue virus infection. As far as we know, this is the first report that the J774 mouse macrophage cell line is infected with dengue virus and, thus, that it can be used as an alternative in vitro model for dengue virus infection studies. This finding could help to further elucidate the mechanisms involved in dengue virus infection and pathogenesis.

  12. Interferon-γ-induced protein 10 in Dengue Virus infection.

    PubMed

    Fallahi, P; Elia, G

    2016-01-01

    Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Interferons (IFNs), and IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ-induced protein 10 (IP-10), CXCL9/MIG and CXCL11/I-TAC, and their common receptor chemokine (C-X-C motif) receptor (CXCR)3 are induced by DENV infection; however it has been shown that the latter two could not compensate for the absence of IP-10. This paper reviews studies about DENV and IP-10. Evidences show the importance of IP-10 induction during DENV infection, in macrophages, lymphocytes, hepatic cells, denritic cells, in skin and in the brain. Furthermore it has been shown that chemokines IP-10, I-TAC and their receptor CXCR3 are involved in severity of dengue; in fact, pulmonary effusion or ascites, painful hepatomegaly or aspartate aminotransferase increase, are correlated with IP-10 levels. It has been also demonstrated that IP-10 was more elevated in subjects who subsequently developed dengue hemorrhagic fever or dengue shock syndrome. It has been also shown that IP-10 has a direct action in control of dengue viral replication. Furthermore IP-10 circulating levels may be used to discriminate dengue fever from other febbrile diseases. This is of particular importance in certain situations, for example to discriminate occupationally acquired dengue, in patients with febbrile disorders coming from endemic countries. These studies suggested that these chemokines can be used as potential biomarkers for differential diagnosis and the disease progression, while others can be used to control dengue viral replication, thus representing a viable targets for drug therapy.

  13. Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

    PubMed Central

    Voge, Natalia V.; Perera, Rushika; Mahapatra, Sebabrata; Gresh, Lionel; Balmaseda, Angel; Loroño-Pino, María A.; Hopf-Jannasch, Amber S.; Belisle, John T.; Harris, Eva; Blair, Carol D.; Beaty, Barry J.

    2016-01-01

    Background Epidemic dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis and clinical care of dengue patients throughout the tropical and subtropical world. The ability to predict severe dengue disease outcomes (DHF/DSS) using acute phase clinical specimens would be of enormous value to physicians and health care workers for appropriate triaging of patients for clinical management. Advances in the field of metabolomics and analytic software provide new opportunities to identify host small molecule biomarkers (SMBs) in acute phase clinical specimens that differentiate dengue disease outcomes. Methodology/Principal Findings Exploratory metabolomic studies were conducted to characterize the serum metabolome of patients who experienced different dengue disease outcomes. Serum samples from dengue patients from Nicaragua and Mexico were retrospectively obtained, and hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry (MS) identified small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND) diagnosis groups. In the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes. In the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS). Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. Differential perturbation of the serum metabolome was demonstrated following infection with different DENV serotypes and following primary and secondary DENV infections. Conclusions/Significance These results provide proof-of-concept that a metabolomics approach can be used to identify metabolites or SMBs in serum

  14. Repeated tourniquet testing as a diagnostic tool in dengue infection.

    PubMed

    Norlijah, O; Khamisah, A Nor; Kamarul, A; Paeds, M; Mangalam, S

    2006-03-01

    Prospective evaluation of repeated standard tourniquet testing as a diagnostic indicator of dengue infection was done. Included were patients admitted to a children's hospital in Kuala Lumpur on a clinical suspicion of dengue infection based on the World Health Organization (WHO) criteria. A standard method of tourniquet was performed on 79 patients on a daily basis following admission. subjects and negative in the remaining 14 subjects. Fifty-eight subjects were serologically confirmed cases, 4 indeterminate and the remaining 17 subjects had negative serology. For diagnostic classification, 13 had dengue fever, 49 with dengue haemmorhagic fever (DHF) while 17 had non-dengue infection. The sensitivity and specificity of the tourniquet test was 82.8% and 23.5% respectively. The positive predictive value (PPV) was 78.7% while the negative predictive value (NPV) was 28.6%. In addition, the tourniquet test aided in the diagnosis of one-fifth of patients with DHF, who presented with a positive tourniquet test as the only bleeding manifestation. It seems that in a hospital setting, the tourniquet test adds little to the diagnosis of dengue infection/DHF. A positive tourniquet test, repeatedly performed, was found clinically useful as a preliminary screening test in dengue infection as recommended by WHO. However, it was not very specific and had a high false positive rate.

  15. An unusual cause of acute abdominal pain in dengue fever.

    PubMed

    Waseem, Tariq; Latif, Hina; Shabbir, Bilquis

    2014-07-01

    Dengue fever is an acute febrile viral disease caused by the bite of Aedes aegypti mosquito. It is a major health problem especially in tropical and subtropical areas including South East Asia and Pakistan. In the past few years, dengue fever has been endemic in Northern Punjab. Physicians managing dengue fever come across varied and uncommon complications of dengue fever. We report a case of dengue fever that developed severe right upper quadrant abdominal pain and induration after extreme retching and vomiting for 2 days. A rectus sheath hematoma was confirmed on noncontrast computed tomography (CT). Rectus sheath hematoma as a complication of dengue fever has rarely been reported before and never from this part of the world. Rectus sheath hematoma is an uncommon and often clinically misdiagnosed cause of abdominal pain. It is the result of bleeding into the rectus sheath from damage to the superior or inferior epigastric artery or their branches or from a direct tear of the rectus muscle. It can mimic almost any abdominal condition (See Fig.) (See Table).

  16. A study of acute muscle dysfunction with particular reference to dengue myopathy

    PubMed Central

    Verma, Rajesh; Holla, Vikram V.; Kumar, Vijay; Jain, Amita; Husain, Nuzhat; Malhotra, Kiran Preet; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Sharma, Praveen Kumar; Kumar, Neeraj

    2017-01-01

    Background: Acute myopathy is a common cause of acute motor quadriparesis which has various etiologies with different courses of illness and prognosis depending on the cause. Understanding this diversity helps us in proper approach toward diagnosis, predicting the prognosis, and possible complications and in improving the treatments that are being provided. This study was planned to study the clinical, electrophysiological, and etiological profile of patients presenting with acute myopathy. We also studied how dengue-related acute myopathy differs from other causes and also difference between myopathy due to myositis and hypokalemia in cases of dengue. Materials and Methods: This was a prospective, observational study involving all clinically suspected cases of acute myopathy of not more than 4 weeks duration with raised serum creatine kinase (CK) level. They were subjected to detailed clinical evaluation along with hematological, biochemical, microbiological, and electrophysiological studies and followed-up for outcome at 1 and 3 months. Muscle biopsy and histopathological examination were done in selected patients after taking informed consent. Statistical analysis was performed by appropriate methods using SPSS version 16.0 (Chicago, IL, USA). Results: We evaluated thirty patients of acute myopathy with raised CK level. Seventeen patients had fever, 11 had myalgia, and 5 had skin lesions. All presented with symmetric weakness, 17 (56.7%) patients having predominantly proximal weakness, neck or truncal weakness in 6 (20%), hyporeflexia in 12 (40%), with mean Medical Research Council (MRC) sum score of 46.67 ± 6.0. Eight (mean modified Barthel index [MBI] at presentation - 15 ± 3.7) patients had poor functional status according to MBI and 15 according to modified Rankin scale (MRS) (mean MRS score - 2.5 ± 1.2). Etiology was dengue viral infection in 14 patients; hypokalemia due to various causes other than dengue in 8; pyomyositis in 3; dermatomyositis

  17. Serological characterization of dengue virus infections observed among dengue hemorrhagic fever/dengue shock syndrome cases in upper Myanmar.

    PubMed

    Ngwe Tun, Mya Myat; Thant, Kyaw Zin; Inoue, Shingo; Kurosawa, Yae; Lwin, Yee Yee; Lin, Sanda; Aye, Kay Thi; Thet Khin, Pe; Myint, Tin; Htwe, Khin; Mapua, Cynthia A; Natividad, Filipinas F; Hirayama, Kenji; Morita, Kouichi

    2013-07-01

    In Myanmar, dengue fever (DF)/dengue hemorrhagic fever (DHF) is one of the leading causes of morbidity and mortality among children. From Pyinmana Hospital in 2004 and Mandalay Children Hospital in 2006, 160 patients diagnosed clinically to have DHF/dengue shock syndrome (DSS) were examined for immunoglobulin M (IgM) and IgG levels. A focus reduction neutralization test was also used to determine primary or secondary dengue virus (DENV) infection. By using IgM-capture ELISA, 139 cases were confirmed as DENV infections. Of these IgM-positives, 94 samples were collected 7-24 days from the onset of illness, to which 13 (14%) and 81 (86%) were determined to be primary and secondary DENV infections, respectively. The 13 primary DENV infection cases were spread among the various severity groups (DHF grade I-IV and DSS) and represented age groups ranging from <1 year of age to 9 years of age. The patients in these primary infection cases showed a remarkably high IgM with a low IgG titer response compared with the secondary infection cases. No significant differences were observed in IgG titers with clinical severity. The data obtained in this study suggest that primary DENV infection cases exist certainly among DHF/DSS cases in Myanmar, and that additional mechanism(s) aside from the antibody-dependent enhancement mechanism could have influenced the clinical severity in DHF/DSS cases.

  18. Antibody Avidity Following Secondary Dengue Virus Type 2 Infection Across a Range of Disease Severity

    PubMed Central

    Lau, Louis; Green, Angela M.; Balmaseda, Angel; Harris, Eva

    2015-01-01

    Background The four dengue virus serotypes (DENV1-4) are responsible for the most prevalent mosquito-borne viral illness in humans. DENV causes a spectrum of disease from self-limiting dengue fever (DF) to severe, life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Antibodies from one infection can contribute to either protection or increased disease severity in a subsequent infection with a distinct DENV serotype. The effectiveness of the antibody response is modulated by both the affinity and avidity of the antibody/antigen interaction. Objectives We investigated how antibody avidity developed over time following secondary DENV2 infection across different disease severities. Study design We analyzed sera from 42 secondary DENV2-infected subjects (DF, n=15; DHF, n=16; DSS, n=11) from a pediatric hospital-based dengue study in Nicaragua. IgG avidity against DENV2 virions was measured in samples collected during acute and convalescent phases as well as 3, 6, and 18 months post-illness using a urea enzyme-linked immunosorbent assay. Results The data show a significant increase in avidity from acute to convalescent phase followed by a decrease from convalescent phase to 3 months post-symptom onset, then a plateau. Linear regression analysis comparing antibody avidity between disease severity groups over time indicate that individuals with more severe disease (DHF/DSS) experienced greater decay in antibody avidity over time compared to less severe disease (DF), and ROC curve analysis showed that at 18 months post-illness, lower avidity was associated with previously having experienced more severe disease. Conclusions These data suggest that increased dengue disease severity is associated with lower antibody avidity at later time-points post-illness. PMID:26209381

  19. Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru

    PubMed Central

    Forshey, Brett M.; Reiner, Robert C.; Olkowski, Sandra; Morrison, Amy C.; Espinoza, Angelica; Long, Kanya C.; Vilcarromero, Stalin; Casanova, Wilma; Wearing, Helen J.; Halsey, Eric S.; Kochel, Tadeusz J.; Scott, Thomas W.; Stoddard, Steven T.

    2016-01-01

    Background Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010–2011, 15 years after the first outbreak of DENV-2 in the region. Methodology/Principal Findings We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010–2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%–65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1–17.7). Conclusions/Significance Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics. PMID:26848841

  20. Dengue Fever

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Dengue Fever KidsHealth > For Parents > Dengue Fever Print A ... can help lower the chances of infection. About Dengue Fever Dengue (DEN-gee) fever is caused by ...

  1. Peridomestic Infection as a Determining Factor of Dengue Transmission

    PubMed Central

    Martínez-Vega, Ruth Aralí; Danis-Lozano, Rogelio; Díaz-Quijano, Fredi Alexander; Velasco-Hernández, Jorge; Santos-Luna, René; Román-Pérez, Susana; Kuri-Morales, Pablo; Ramos-Castañeda, José

    2015-01-01

    Background The study of endemic dengue transmission is essential for proposing alternatives to impact its burden. The traditional paradigm establishes that transmission starts around cases, but there are few studies that determine the risk. Methods To assess the association between the peridomestic dengue infection and the exposure to a dengue index case (IC), a cohort was carried out in two Mexican endemic communities. People cohabitating with IC or living within a 50-meter radius (exposed cohort) and subjects of areas with no ICs in a 200-meter radius (unexposed cohort) were included. Results Exposure was associated with DENV infection in cohabitants (PRa 3.55; 95%CI 2.37–5.31) or neighbors (PRa 1.82; 95%CI 1.29–2.58). Age, location, toilets with no direct water discharge, families with children younger than 5 and the House Index, were associated with infection. Families with older than 13 were associated with a decreased frequency. After a month since the IC fever onset, the infection incidence was not influenced by exposure to an IC or vector density; it was influenced by the local seasonal behavior of dengue and the age. Additionally, we found asymptomatic infections accounted for 60% and a greater age was a protective factor for the presence of symptoms (RR 0.98; 95%CI 0.97–0.99). Conclusion The evidence suggests that dengue endemic transmission in these locations is initially peridomestic, around an infected subject who may be asymptomatic due to demographic structure and endemicity, and it is influenced by other characteristics of the individual, the neighborhood and the location. Once the transmission chain has been established, dengue spreads in the community probably by the adults who, despite being the group with lower infection frequency, mostly suffer asymptomatic infections and have higher mobility. This scenario complicates the opportunity and the effectiveness of control programs and highlights the need to apply multiple measures for dengue

  2. Dengue infections in non-immune travellers to Thailand.

    PubMed

    Massad, E; Rocklov, J; Wilder-Smith, A

    2013-02-01

    Dengue is the most frequent arboviral disease and is expanding geographically. Dengue is also increasingly being reported in travellers, in particular in travellers to Thailand. However, data to quantify the risk of travellers acquiring dengue when travelling to Thailand are lacking. Using mathematical modelling, we set out to estimate the risk of non-immune persons acquiring dengue when travelling to Thailand. The model is deterministic with stochastic parameters and assumes a Poisson distribution for the mosquitoes' biting rate and a Gamma distribution for the probability of acquiring dengue from an infected mosquito. From the force of infection we calculated the risk of dengue acquisition for travellers to Thailand arriving in a typical year (averaged over a 17-year period) in the high season of transmission. A traveller arriving in the high season of transmission and remaining for 7 days has a risk of acquiring dengue of 0·2% (95% CI 0·16-0·23), whereas the risk for travel of 15 and 30 days' duration is 0·46% (95% CI 0·41-0·50) and 0·81% (95% CI 0·76-0·87), respectively. Our data highlight that the risk of non-immune travellers acquiring dengue in Thailand is substantial. The incidence of 0·81% after a 1-month stay is similar to that reported in prospective seroconversion studies in Israeli travellers to Thailand, highlighting that our models are consistent with actual data. Risk estimates based on mathematical modelling offer more detailed information depending on various travel scenarios, and will help the travel medicine provider give better evidence-based advice for travellers to dengue-endemic countries.

  3. Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections

    PubMed Central

    Khalid, Bahariah; Ching, Siew-Mooi; Chee, Hui-Yee

    2016-01-01

    Introduction Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus. Methods Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords “(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)”, according to the MESH terms suggested by PUBMED and OVID. Results Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22–53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64–80.89, 4–14 studies, n = 668–3,149, I2 = 14.77–96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47–40.24, 5–8 studies, n = 642–2,530, I2 = 76.93–97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86–54.58, 9 studies, n = 674–2,278, I2 = 55.74–88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4

  4. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015

    PubMed Central

    Signor, Leticia del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E.; Adams, Emily R.

    2016-01-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections. PMID:27767914

  5. Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.

    PubMed

    Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thuy, Tran Thi; Tuan, Nguyen Minh; Hoang, Dang Minh; Dung, Nguyen Thi Phuong; Lien, Le Bich; Quy, Nguyen Thien; Hieu, Nguyen Trong; Hieu, Lu Thi Minh; Hien, Tran Tinh; Hung, Nguyen Thanh; Farrar, Jeremy; Simmons, Cameron P

    2008-08-15

    The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3(133-142)-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.

  6. Influenza and dengue virus co-infection impairs monocyte recruitment to the lung, increases dengue virus titers, and exacerbates pneumonia.

    PubMed

    Schmid, Michael A; González, Karla N; Shah, Sanjana; Peña, José; Mack, Matthias; Talarico, Laura B; Polack, Fernando P; Harris, Eva

    2017-03-01

    Co-infections of influenza virus and bacteria are known to cause severe disease, but little information exists on co-infections with other acute viruses. Seasonal influenza and dengue viruses (DENV) regularly co-circulate in tropical regions. The pandemic spread of influenza virus H1N1 (hereafter H1N1) in 2009 led to additional severe disease cases that were co-infected with DENV. Here, we investigated the impact of co-infection on immune responses and pathogenesis in a new mouse model. Co-infection of otherwise sublethal doses of a Nicaraguan clinical H1N1 isolate and two days later with a virulent DENV2 strain increased systemic DENV titers and caused 90% lethality. Lungs of co-infected mice carried both viruses, developed severe pneumonia, and expressed a unique pattern of host mRNAs, resembling only partial responses against infection with either virus alone. A large number of monocytes were recruited to DENV-infected but not to co-infected lungs, and depletion and adoptive transfer experiments revealed a beneficial role of monocytes. Our study shows that co-infection with influenza and DENV impairs host responses, which fail to control DENV titers and instead, induce severe lung damage. Further, our findings identify key inflammatory pathways and monocyte function as targets for future therapies that may limit immunopathology in co-infected patients.

  7. Occurrence and correlates of symptom persistence following acute dengue fever in Peru.

    PubMed

    Halsey, Eric S; Williams, Maya; Laguna-Torres, V Alberto; Vilcarromero, Stalin; Ocaña, Victor; Kochel, Tadeusz J; Marks, Morgan A

    2014-03-01

    Dengue virus (DENV) infection causes an acute febrile illness generally considered to result in either complete recovery or death. Some reviews describe persistent symptoms after the febrile phase, although empirical data supporting this phenomenon is scarce. We evaluated symptom persistence in acute febrile DENV-infected and DENV-negative (controls) individuals from Peru. Self-reported solicited symptoms were evaluated at an acute and a follow-up visit, occurring 10-60 days after symptom onset. Rate of persistence of at least one symptom was 7.7% and 10.5% for DENV infected and control subjects, respectively (P < 0.01). The DENV-infected individuals had lower rates of persistent respiratory symptoms, gastrointestinal symptoms, headache, and fatigue, but higher rates of persistent rash compared with controls. Older age and female gender were positively associated with symptom persistence. As dengue cases continue to increase annually, even a relatively low frequency of persistent symptoms may represent a considerable worldwide morbidity burden.

  8. Treatment Effectiveness of Amantadine Against Dengue Virus Infection

    PubMed Central

    Lin, Chieh-Cheng; Chen, Wen-Ching

    2016-01-01

    Case series Patient: — Final Diagnosis: Dengue fever infection Symptoms: Bone pain • fever Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Unusual or unexpected effect of treatment Background: About 400 million cases of dengue, a mosquito-borne disease, are reported annually, but no drug is yet available for treatment. In 1988, at Feng Lin Clinic, Taiwan, we encountered about 10,000 cases and tested various drugs before confirming an antiviral effect of amantadine against dengue virus in vitro. After we administered amantadine to patients for 1–2 days, most achieved full remission. None experienced potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. Herein, we present 34 cases from recent clinical experience that show amantadine’s unusual effect against dengue virus infection. Case Report: We divided 34 patients with symptoms of dengue fever, confirmed by a screening test, into 3 groups: 6 Category 1 patients received amantadine at onset, 21 Category 2 patients received amantadine within 2–6 days, and 7 Contrast group patients received no amantadine because they visited other clinics or were admitted to a large hospital. When Category 1 patients were treated with amantadine 100 mg 3 times per day, all symptoms dramatically subsided within 1–2 days. In Category 2 patients, most symptoms diminished within 1–2 days after starting the same regimen. In the Contrast group, all symptoms persisted 7 days after onset. White blood cell and platelet counts in Category 1 and 2 patients recovered to normal range, but remained below low normal in the Contrast group. Conclusions: Amantadine is effective and should be given as soon as possible to stop the disease course if dengue fever is confirmed through screening or clinical signs and symptoms. A well-designed larger sample study is warranted to test this effectiveness. PMID:27920420

  9. A secondary dengue 4 infection in a traveler returning from Haiti confirmed by virus isolation, complete genome sequencing and neutralisation assay: a brief report.

    PubMed

    Menard, Amelie; Ninove, Laetitia; Zandotti, Christine; Leparc-Goffart, Isabelle; Klitting, Raphaelle; Baronti, Cecile; Stein, Andreas; de Lamballerie, Xavier; Charrel, Rémi N

    2015-01-01

    Here we report the clinical and laboratory findings of a dengue 4 virus (DENV) secondary infection in a patient returning from Haiti to France. The diagnostic of acute DEN-4 virus infection was demonstrated by (i) the presence of DEN-4 RNA in two successive serum samples, (ii) the isolation of a DEN-4 virus in Vero cells and subsequent identification of subtype IIb through complete genome sequencing, (iii) the presence of dengue NS1 antigen, (iv) the seroconversion with detection of dengue IgM in the second serum while negative in the first serum. The diagnosis of secondary dengue episode was demonstrated by (i) the presence of dengue IgG in the early serum, and (ii) the demonstration that neutralising antibodies against DEN-3 were present at the acute stage of the disease. Next-generation sequencing has a primary role to play in phylogeographic studies including database sequences, sequences from imported cases, and sequences from autochthonous cases.

  10. C1q binding to Dengue Virus inhibits infection of THP-1 and cellular inflammatory responses

    PubMed Central

    Douradinha, Bruno; McBurney, Sean P.; de Melo, Klecia M. Soares; Smith, Amanda P.; Krishna, Neel K.; Barratt-Boyes, Simon M.; Evans, Jared D.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A

    2014-01-01

    Summary Dengue virus infection elicits a spectrum of clinical presentations ranging from asymptomatic to severe disease. The mechanisms leading to severe dengue are not known, however it has been reported that the complement system is hyper-activated in severe dengue. Screening of complement proteins demonstrated that C1q, a pattern recognition molecule, can bind directly to Dengue Virus Envelope protein and to whole Dengue Virus serotype 2. Incubation of Dengue Virus serotype 2 with C1q prior to infection of THP-1 cells led to decreased virus infectivity and modulation of mRNA expression of immunoregulatory molecules suggesting reduced inflammatory responses. PMID:24246304

  11. Dengue infection in the nervous system: lessons learned for Zika and Chikungunya.

    PubMed

    Puccioni-Sohler, Marzia; Roveroni, Natalia; Rosadas, Carolina; Ferry, Fernando; Peralta, Jose Mauro; Tanuri, Amilcar

    2017-02-01

    Dengue, Zika and Chikungunya are emerging arboviruses and important causes of acute febrile disease in tropical areas. Although dengue does not represent a new condition, a geographic expansion over time has occurred with the appearance of severe neurological complications. Neglect has allowed the propagation of the vector (Aedes spp), which is also responsible for the transmission of other infections such as Zika and Chikungunya throughout the world. The increased number of infected individuals has contributed to the rise of neurological manifestations including encephalitis, myelitis, meningitis, Guillain-Barré syndrome and congenital malformations such as microcephaly. In this narrative review, we characterize the impact of the geographic expansion of the vector on the appearance of neurological complications, and highlight the lack of highly accurate laboratory tests for nervous system infections. This represents a challenge for public health in the world, considering the high number of travelers and people living in endemic areas.

  12. Secondary infection as a risk factor for dengue hemorrhagic fever/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection.

    PubMed

    Guzman, Maria G; Alvarez, Mayling; Halstead, Scott B

    2013-07-01

    Today, dengue viruses are the most prevalent arthropod-borne viruses in the world. Since the 1960s, numerous reports have identified a second heterologous dengue virus (DENV) infection as a principal risk factor for severe dengue disease (dengue hemorrhagic fever/dengue shock syndrome, DHF/DSS). Modifiers of dengue disease response include the specific sequence of two DENV infections, the interval between infections, and contributions from the human host, such as age, ethnicity, chronic illnesses and genetic background. Antibody-dependent enhancement (ADE) of dengue virus infection has been proposed as the early mechanism underlying DHF/DSS. Dengue cross-reactive antibodies raised following a first dengue infection combine with a second infecting virus to form infectious immune complexes that enter Fc-receptor-bearing cells. This results in an increased number of infected cells and increased viral output per cell. At the late illness stage, high levels of cytokines, possibly the result of T cell elimination of infected cells, result in vascular permeability, leading to shock and death. This review is focused on the etiological role of secondary infections (SI) and mechanisms of ADE.

  13. Human and mosquito infections by dengue viruses during and after epidemics in a dengue-endemic region of Colombia.

    PubMed

    Méndez, Fabián; Barreto, Mauricio; Arias, Juan F; Rengifo, Graciela; Muñoz, Jaime; Burbano, María E; Parra, Beatriz

    2006-04-01

    We conducted a study in a dengue-endemic area of Colombia to evaluate the dynamics of transmission of dengue viruses during and after epidemics. Information was simultaneously gathered about occurrence of infection in humans and mosquitoes every three months in four cities with endemic transmission. Viral isolation was confirmed in 6.7% of the persons and most were asymptomatic. Adult mosquito and larvae house indexes were not found associated with increased burden of disease. The only entomologic indicator related to dengue infection in humans was the pooled infection rate of mosquitoes. Aedes aegypti infection rates showed significant differences between the epidemic (10.68, 95% confidence interval [CI] = 7.04-15.62) and after epidemic periods of the study (6.15, 95% CI = 3.46-10.19). In addition, Ae. albopictus were also infected with dengue viruses. Increases in mosquito infection rates were associated with increases in human infection rates in the following trimester.

  14. Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines

    PubMed Central

    Alera, Maria Theresa; Srikiatkhachorn, Anon; Velasco, John Mark; Tac-An, Ilya A.; Lago, Catherine B.; Clapham, Hannah E.; Fernandez, Stefan; Levy, Jens W.; Thaisomboonsuk, Butsaya; Klungthong, Chonticha; Macareo, Louis R.; Nisalak, Ananda; Hermann, Laura; Villa, Daisy; Yoon, In-Kyu

    2016-01-01

    Background The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic. Methodology/Principal Findings A prospective cohort of subjects ≥6 months old in Cebu City, Philippines, underwent active community-based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI) assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naïve individuals was estimated to be high at 11–22%/year. Conclusions/Significance In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases

  15. Enhancing the sensitivity of Dengue virus serotype detection by RT-PCR among infected children in India.

    PubMed

    Ahamed, Syed Fazil; Vivek, Rosario; Kotabagi, Shalini; Nayak, Kaustuv; Chandele, Anmol; Kaja, Murali-Krishna; Shet, Anita

    2017-02-27

    Dengue surveillance relies on reverse transcription-polymerase chain reaction (RT-PCR), for confirmation of dengue virus (DENV) serotypes. We compared efficacies of published and modified primer sets targeting envelope (Env) and capsid-premembrane (C-prM) genes for detection of circulating DENV serotypes in southern India. Acute samples from children with clinically-diagnosed dengue were used for RT-PCR testing. All samples were also subjected to dengue serology (NS1 antigen and anti-dengue-IgM/IgG rapid immunochromatographic assay). Nested RT-PCR was performed on viral RNA using three methods targeting 654bp C-prM, 511bp C-prM and 641bp Env regions, respectively. RT-PCR-positive samples were validated by population sequencing. Among 171 children with suspected dengue, 121 were dengue serology-positive and 50 were dengue serology-negative. Among 121 serology-positives, RT-PCR detected 91 (75.2%) by CprM654, 72 (59.5%) by CprM511, and 74 (61.1%) by Env641. Among 50 serology-negatives, 10 (20.0%) were detected by CprM654, 12 (24.0%) by CprM511, and 11 (22.0%) by Env641. Overall detection rate using three methods sequentially was 82.6% (100/121) among serology-positive and 40.0% (20/50) among serology-negative samples; 6.6% (8/120) had co-infection with multiple DENV serotypes. We conclude that detection of acute dengue was enhanced by a modified RT-PCR method targeting the 654bp C-prM region, and further improved by using all three methods sequentially.

  16. Treatment Effectiveness of Amantadine Against Dengue Virus Infection.

    PubMed

    Lin, Chieh-Cheng; Chen, Wen-Ching

    2016-12-05

    BACKGROUND About 400 million cases of dengue, a mosquito-borne disease, are reported annually, but no drug is yet available for treatment. In 1988, at Feng Lin Clinic, Taiwan, we encountered about 10,000 cases and tested various drugs before confirming an antiviral effect of amantadine against dengue virus in vitro. After we administered amantadine to patients for 1-2 days, most achieved full remission. None experienced potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. Herein, we present 34 cases from recent clinical experience that show amantadine's unusual effect against dengue virus infection. CASE REPORT We divided 34 patients with symptoms of dengue fever, confirmed by a screening test, into 3 groups: 6 Category 1 patients received amantadine at onset, 21 Category 2 patients received amantadine within 2-6 days, and 7 Contrast group patients received no amantadine because they visited other clinics or were admitted to a large hospital. When Category 1 patients were treated with amantadine 100 mg 3 times per day, all symptoms dramatically subsided within 1-2 days. In Category 2 patients, most symptoms diminished within 1-2 days after starting the same regimen. In the Contrast group, all symptoms persisted 7 days after onset. White blood cell and platelet counts in Category 1 and 2 patients recovered to normal range, but remained below low normal in the Contrast group. CONCLUSIONS Amantadine is effective and should be given as soon as possible to stop the disease course if dengue fever is confirmed through screening or clinical signs and symptoms. A well-designed larger sample study is warranted to test this effectiveness.

  17. Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection.

    PubMed

    Liu, Ching-Chuan; Huang, Kao-Jean; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng; Lei, Huan-Yao

    2002-10-01

    The immune status after dengue virus infection was studied in dengue patients from an outbreak of serotype 3 dengue virus infection in the southern part of Taiwan during November and December 1998. Consecutive blood samples from 29 dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic fever/dengue shock syndrome, were collected, and the immunophenotypes of the peripheral blood mononuclear cells were determined by flow cytometry. The early activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the onset of fever, and declined afterward. However, a transient reverse in the CD4/CD8 ratio occurred at days 6-10 after the onset of fever. The CD4/CD8 ratio inversion was manifested in 10 of 29 dengue patients and was encountered more frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever patients. Analysis of the clinical blood cell count of these 10 cases showed that increase of immature neutrophils developed at fever days 5-6, CD4(dim) or CD8(dim) monocytosis at days 6-7, and atypical lymphocytosis at days 8-10 after the onset of fever. Serum IL-6 was found at either day 7 or day 9-11. The PHA-stimulated T-cell response was depressed as well. These changes in immune parameters indicate aberrant immune activation during dengue virus infection and might be involved in the pathogenesis of dengue virus infection.

  18. Persistence of Neutralizing Antibody Against Dengue Virus 2 After 70 Years from Infection in Nagasaki

    PubMed Central

    Ngwe Tun, Mya Myat; Muta, Yoshihito; Inoue, Shingo; Morita, Kouichi

    2016-01-01

    Abstract This study aimed to investigate the duration of humoral immune responses to dengue virus (DENV) infection in Japanese who experienced acute febrile illness with hemorrhagic manifestations 70 years ago, when an epidemic of dengue occurred in Nagasaki, Japan, from 1942 to 1944. A Japanese volunteer requested serological diagnosis of DENV infection in 2014 and donated blood sample to measure the antibody titer against DENV by antiflavi IgG indirect ELISA, focus reduction neutralization test, and plaque reduction neutralization test. The serum sample of the volunteer was positive in flavi IgG ELISA and it indicated primary infection. In the neutralization test, the highest neutralizing titer was ≥218 for DENV-2. We report here the existence of DENV-specific antibodies in the serum of a person after 70 years from infection. Published reports indicated that DENV-1 was responsible for the 1942–1944 outbreak in Nagasaki. However, our data suggested that DENV-2 also played a role in this Nagasaki dengue epidemic. PMID:27493841

  19. HLA Class I Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic Thais

    PubMed Central

    Vejbaesya, Sasijit; Thongpradit, Rungrot; Kalayanarooj, Siripen; Luangtrakool, Komon; Luangtrakool, Panpimon; Gibbons, Robert V.; Srinak, Duangporn; Ngammthaworn, Somporn; Apisawes, Kusuma; Yoon, In-Kyu; Thomas, Stephen J.; Jarman, Richard G.; Srikiakthachorn, Anon; Green, Sharone; Chandanayingyong, Dasnayanee; Park, Sangshin; Friedman, Jennifer; Rothman, Alan L.; Stephens, Henry A.F.

    2015-01-01

    Background. Human leukocyte antigen (HLA) supertypes are groups of functionally related alleles that present structurally similar antigens to the immune system. Objectives. To analyze HLA class I supertype associations with clinical outcome in hospitalized Thai children with acute dengue illness. Methods. Seven hundred sixty-two patients and population-matched controls recruited predominantly in Bangkok were HLA-A and -B typed. HLA supertype frequencies were compared and tested for significant dengue disease associations using logistic regression analyses. Multivariable models were built by conducting forward stepwise selection procedures. Results. In the final logistic regression model, the HLA-B44 supertype was protective against dengue hemorrhagic fever (DHF) in secondary infections (odds ratio [OR] = 0.46, 95% confidence interval [CI], .30–.72), while the HLA-A02 supertype (OR = 1.92, 95% CI, 1.30–2.83) and the HLA-A01/03 supertype (OR = 3.01, 95% CI, 1.01–8.92) were associated with susceptibility to secondary dengue fever. The B07 supertype was associated with susceptibility to secondary DHF in the univariate analysis (OR = 1.60, 95% CI, 1.05–2.46), whereas that was not retained in the final model. Conclusions. As the HLA-B44 supertype is predicted to target conserved epitopes in dengue, our results suggest that B44 supertype-restricted immune responses to highly conserved regions of the dengue proteome may protect against secondary DHF. PMID:25740956

  20. Epidemiological Characteristics and Risk Factors of Dengue Infection in Korean Travelers

    PubMed Central

    2016-01-01

    Dengue viral infection has rapidly spread around the world in recent decades. In Korea, autochthonous cases of dengue fever have not been confirmed yet. However, imported dengue cases have been increased since 2001. The risk of developing severe dengue in Korean has been increased by the accumulation of past-infected persons with residual antibodies to dengue virus and the remarkable growth of traveling to endemic countries in Southeast Asia. Notably, most of imported dengue cases were identified from July to December, suggesting that traveling during rainy season of Southeast Asia is considered a risk factor for dengue infection. Analyzing national surveillance data from 2011 to 2015, males aged 20–29 years are considered as the highest risk group. But considering the age and gender distribution of travelers, age groups 10–49 except 20–29 years old males have similar risks for infection. To minimize a risk of dengue fever and severe dengue, travelers should consider regional and seasonal dengue situation. It is recommended to prevent from mosquito bites or to abstain from repetitive visit to endemic countries. In addition, more active surveillance system and monitoring the prevalence asymptomatic infection and virus serotypes are required to prevent severe dengue and indigenous dengue outbreak. PMID:27822922

  1. Epidemiological Characteristics and Risk Factors of Dengue Infection in Korean Travelers.

    PubMed

    Je, Sungmo; Bae, Wonjun; Kim, Jiyeon; Seok, Seung Hyeok; Hwang, Eung Soo

    2016-12-01

    Dengue viral infection has rapidly spread around the world in recent decades. In Korea, autochthonous cases of dengue fever have not been confirmed yet. However, imported dengue cases have been increased since 2001. The risk of developing severe dengue in Korean has been increased by the accumulation of past-infected persons with residual antibodies to dengue virus and the remarkable growth of traveling to endemic countries in Southeast Asia. Notably, most of imported dengue cases were identified from July to December, suggesting that traveling during rainy season of Southeast Asia is considered a risk factor for dengue infection. Analyzing national surveillance data from 2011 to 2015, males aged 20-29 years are considered as the highest risk group. But considering the age and gender distribution of travelers, age groups 10-49 except 20-29 years old males have similar risks for infection. To minimize a risk of dengue fever and severe dengue, travelers should consider regional and seasonal dengue situation. It is recommended to prevent from mosquito bites or to abstain from repetitive visit to endemic countries. In addition, more active surveillance system and monitoring the prevalence asymptomatic infection and virus serotypes are required to prevent severe dengue and indigenous dengue outbreak.

  2. Characteristics of Mild Dengue Virus Infection in Thai Children

    PubMed Central

    Yoon, In-Kyu; Srikiatkhachorn, Anon; Hermann, Laura; Buddhari, Darunee; Scott, Thomas W.; Jarman, Richard G.; Aldstadt, Jared; Nisalak, Ananda; Thammapalo, Suwich; Bhoomiboonchoo, Piraya; Mammen, Mammen P.; Green, Sharone; Gibbons, Robert V.; Endy, Timothy P.; Rothman, Alan L.

    2013-01-01

    A four-year longitudinal cohort and geographic cluster study in rural Thailand was conducted to characterize the clinical spectrum of dengue virus (DENV) infection. Symptomatic DENV infections in the cohort were detected by active school absence–based surveillance that triggered cluster investigations around ill cohort children. Data from 189 cohort children with symptomatic DENV infection and 126 contact children in the clusters with DENV infection were analyzed. Of infected contacts, only 19% were asymptomatic; 81% were symptomatic, but only 65.9% reported fever. Symptom-based case definitions were unreliable for diagnosis. Symptomatic infections in contacts were milder with lower DENV RNA levels than the cohort. Infections in contacts with fever history were more likely to have detectable DENV RNA than infections without fever history. Mild infections identified by cluster investigations account for a major proportion of all DENV infections. These findings are relevant for disease burden assessments, transmission modeling, and determination of vaccine impact. PMID:24127167

  3. Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase.

    PubMed

    Oliveira, Renato Antônio Dos Santos; Silva, Mayara Marques Carneiro da; Calzavara-Silva, Carlos Eduardo; Silva, Ana Maria; Cordeiro, Marli Tenório; Moura, Patrícia Muniz Mendes Freire de; Baptista, Paulo Neves; Marques, Ernesto Torres de Azevedo; Gil, Laura Helena Vega Gonzales

    2016-05-24

    Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

  4. Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase

    PubMed Central

    Oliveira, Renato Antônio dos Santos; da Silva, Mayara Marques Carneiro; Calzavara-Silva, Carlos Eduardo; Silva, Ana Maria; Cordeiro, Marli Tenório; de Moura, Patrícia Muniz Mendes Freire; Baptista, Paulo Neves; Marques, Ernesto Torres de Azevedo; Gil, Laura Helena Vega Gonzales

    2016-01-01

    Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis. PMID:27223651

  5. Longitudinal Analysis of Natural Killer Cells in Dengue Virus-Infected Patients in Comparison to Chikungunya and Chikungunya/Dengue Virus-Infected Patients

    PubMed Central

    Petitdemange, Caroline; Wauquier, Nadia; Devilliers, Hervé; Yssel, Hans; Mombo, Illich; Caron, Mélanie; Nkoghé, Dieudonné; Debré, Patrice; Leroy, Eric; Vieillard, Vincent

    2016-01-01

    Background Dengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy. Methodology We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients. Principal Findings We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ) by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV. Conclusions/Significance Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections. PMID:26938618

  6. Cloning and application of recombinant dengue virus prM-M protein for serodiagnosis of dengue virus infection.

    PubMed

    Wichit, Sineewanlaya; Yongpradoem, Hatairat; Surasombatpattana, Pornapat; Leaungwuttiwong, Pornsawan; Kalambaheti, Thareerat; Jampangern, Wipawee; Jittmittraphap, Akanitt

    2013-03-01

    We studied the use of the precursor to the M structural protein (prM) found only on the surface of mature dengue virus as a target protein to detect dengue virus infection. Recombinant D2-16681 prM-M protein was constructed and tested for immunogenicity with dengue and Japanese encephalitis patient sera by Western blot analysis and indirect ELISA. The sensitivity and specificity of indirect ELISA were 48.1 and 85.5%, respectively, and Western blot assay were 23.1 and 98.7%, respectively, for detection of dengue virus. Although the sensitivity of the indirect ELISA is low, the indirect ELISA using recombinant D2-16681 prM-M proteins as antigen may be used for early detection of dengue virus infection.

  7. Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus

    PubMed Central

    Priyamvada, Lalita; Quicke, Kendra M.; Hudson, William H.; Onlamoon, Nattawat; Sewatanon, Jaturong; Edupuganti, Srilatha; Pattanapanyasat, Kovit; Chokephaibulkit, Kulkanya; Mulligan, Mark J.; Wilson, Patrick C.; Ahmed, Rafi; Suthar, Mehul S.; Wrammert, Jens

    2016-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus of significant public health concern. ZIKV shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (DENV), resulting in immunological cross-reactivity. Improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as ZIKV is presently circulating in areas that are highly endemic for dengue. To assess the magnitude and functional quality of cross-reactive immune responses between these closely related viruses, we tested acute and convalescent sera from nine Thai patients with PCR-confirmed DENV infection against ZIKV. All of the sera tested were cross-reactive with ZIKV, both in binding and in neutralization. To deconstruct the observed serum cross-reactivity in depth, we also characterized a panel of DENV-specific plasmablast-derived monoclonal antibodies (mAbs) for activity against ZIKV. Nearly half of the 47 DENV-reactive mAbs studied bound to both whole ZIKV virion and ZIKV lysate, of which a subset also neutralized ZIKV. In addition, both sera and mAbs from the dengue-infected patients enhanced ZIKV infection of Fc gamma receptor (FcγR)-bearing cells in vitro. Taken together, these findings suggest that preexisting immunity to DENV may impact protective immune responses against ZIKV. In addition, the extensive cross-reactivity may have implications for ZIKV virulence and disease severity in DENV-experienced populations. PMID:27354515

  8. Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections

    PubMed Central

    SAITO, M; OISHI, K; INOUE, S; DIMAANO, E M; ALERA, M T P; ROBLES, A M P; ESTRELLA, B D; KUMATORI, A; MOJI, K; ALONZO, M T; BUERANO, C C; MATIAS, R R; MORITA, K; NATIVIDAD, F F; NAGATAKE, T

    2004-01-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in inducing thrombocytopenia and its severity of disease in patients with secondary dengue virus infection, the relationship between the PAIgG or PAIgM levels and disease severity as well as thrombocytopenia was examined in 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet count during the acute phase recovered significantly during the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that occurred during the acute phase of these patients decreased significantly during the convalescent phase. An inverse correlation between platelet count and PAIgG or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM activity was found in platelet eluates from 10 patients in an acute phase of secondary infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An increased level of PAIgM was associated independently with the development of DHF, representing a possible predictor of DHF with a high specificity. Our present data suggest that platelet-associated immunoglobulins involving antidengue virus activity play a pivotal role in the induction of thrombocytopenia and the severity of the disease in secondary dengue virus infections. PMID:15498040

  9. The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection

    PubMed Central

    Hu, Hui-Mei; Chen, Hsin-Wei; Hsiao, Yu-Ju; Wu, Szu-Hsien; Chung, Han-Hsuan; Hsieh, Chun-Hsiang; Chong, Pele; Leng, Chih-Hsiang; Pan, Chien-Hsiung

    2016-01-01

    ABSTRACT Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine. PMID:26901482

  10. Discriminating dengue-infected hepatic cells (WRL-68) using dielectrophoresis.

    PubMed

    Yafouz, Bashar; Kadri, Nahrizul Adib; Rothan, Hussin A; Yusof, Rohana; Ibrahim, Fatimah

    2016-02-01

    Dielectrophoresis (DEP), the induced movement of dielectric particles placed in a nonuniform electric field, has been used as a potential technique for manipulation and separation of many biological samples without destructive consequences to the cell. Cells of the same genotype in different physiological and pathological states have unique morphological and structural features, therefore, it is possible to differentiate between them using their DEP responses. This paper reports the experimental discrimination of normal and dengue-infected human hepatic fetal epithelial cells (WRL-68 cells) based on their DEP crossover frequency, at which no resultant movement occurs in the cells in response to the DEP force. A microarray dot electrode was used to conduct the DEP experiments. The DEP forces applied to the cells were quantified by analyzing the light intensity shift within the electrode's dot region based on the Cumulative Modal Intensity Shift image analysis technique. The differences in dielectric properties between infected and uninfected cells were exploited by plotting a unique DEP spectrum for each set of cells. We observed that the crossover frequency decreased from 220 kHz for the normal WRL-68 cells to 140 kHz after infection with the dengue virus in a medium conductivity of 100 μS/cm. We conclude that the change in the DEP crossover frequency between dengue-infected cells and their healthy counterparts should allow direct characterization of these cell types by exploiting their electrophysiological properties.

  11. Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors

    PubMed Central

    Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki

    2016-01-01

    Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection. PMID:26844767

  12. Incidence of dengue virus infection among Japanese travellers, 2006 to 2010

    PubMed Central

    Arima, Yuzo; Shimada, Tomoe; Matsui, Tamano; Tada, Yuki; Okabe, Nobuhiko

    2012-01-01

    Introduction Dengue continues to be a global public health concern. In Japan, although dengue cases are currently seen only among travellers returning from endemic areas, the number of reported cases is rising according to the national case-based surveillance system. We evaluated the characteristics of dengue cases imported into Japan and the relationship between the incidence of infection and season of travel to popular destinations. Methods Dengue cases reported to the national surveillance system were retrospectively examined. The number of reported cases per number of Japanese travellers to a dengue-endemic country was calculated to estimate the country-specific incidence of imported dengue virus infection. The incidence of dengue infection among Japanese travellers was compared between dengue high season and low season in each country using relative risk (RR) and associated 95% confidence intervals (CI). Results Among 540 Japanese residents who were reported as dengue cases from 2006 to 2010, the majority had travelled to Indonesia, India, the Philippines and Thailand. The RR of dengue infection among Japanese travellers during dengue high season versus low season was 4.92 (95% CI: 3.01–8.04) for the Philippines, 2.76 (95% CI: 1.67–4.54) for Thailand and 0.37 (95% CI: 0.15–0.92) for Indonesia. Discussion Overall, higher incidence of imported cases appeared to be related to historic dengue high seasons. Travellers planning to visit dengue-endemic countries should be aware of historic dengue seasonality and the current dengue situation. PMID:23908911

  13. Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection

    PubMed Central

    Costa, Vivian V.; Tan, Hwee Cheng; Horrevorts, Sophie; Ooi, Eng Eong

    2015-01-01

    The mosquito-borne dengue virus (DENV) is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP) to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue. PMID:26565697

  14. Within-host viral dynamics of dengue serotype 1 infection

    PubMed Central

    Clapham, Hannah E.; Tricou, Vianney; Van Vinh Chau, Nguyen; Simmons, Cameron P.; Ferguson, Neil M.

    2014-01-01

    Dengue, the most common mosquito-borne viral infection of humans, is endemic across much of the world, including much of tropical Asia and is increasing in its geographical range. Here, we present a mathematical model of dengue virus dynamics within infected individuals, detailing the interaction between virus and a simple immune response. We fit this model to measurements of plasma viral titre from cases of primary and secondary DENV 1 infection in Vietnam. We show that variation in model parameters governing the immune response is sufficient to create the observed variation in virus dynamics between individuals. Estimating model parameter values, we find parameter differences between primary and secondary cases consistent with the theory of antibody-dependent enhancement (namely enhanced rates of viral entry to target cells in secondary cases). Finally, we use our model to examine the potential impact of an antiviral drug on the within-host dynamics of dengue. We conclude that the impact of antiviral therapy on virus dynamics is likely to be limited if therapy is only started at the onset of symptoms, owing to the typically late stage of viral pathogenesis reached by the time symptoms are manifested and thus treatment is started. PMID:24829280

  15. Intracellular cytokine production by dengue virus-specific T cells correlates with subclinical secondary infection.

    PubMed

    Hatch, Steven; Endy, Tim P; Thomas, Stephen; Mathew, Anuja; Potts, James; Pazoles, Pamela; Libraty, Daniel H; Gibbons, Robert; Rothman, Alan L

    2011-05-01

    The pathophysiology of dengue virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6-11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4(+) and CD8(+) cells in response to stimulation with dengue antigen. We found higher frequencies of dengue virus-specific TNFα, IFNγ-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with those who developed symptomatic secondary dengue virus infection. Although other studies have correlated immune responses during secondary infection with severity of disease, to our knowledge this is the first study to demonstrate a pre-infection dengue-specific immune response that correlates specifically with a subclinical secondary infection.

  16. [Acute gastrointestinal involvement in dengue disease by serotype 4: a case report and literature review].

    PubMed

    Marín, Johan; Vilcarromero, Stalin; Forshey, Brett M; Celis-Salinas, Juan C; Ramal-Asayag, Cesar; Morrison, Amy C; Laguna-Torres, Alberto; Casapía, Martín; Halsey, Eric S

    2013-10-01

    Dengue fever is the world's most important arboviral disease, presenting a wide clinical spectrum. We report for the first time in Peru, a case caused by dengue virus serotype 4 with significant gastrointestinal involvement (acute acalculous cholecystitis and acute hepatitis). In addition we carried out a review of the literature atypical presentation illustrating the importance of the characteristics of abdominal pain (right upper quadrant); presence of Murphy's sign, ultrasound, and liver enzymes levels, for appropriate diagnosis and clinical management.

  17. Dengue

    MedlinePlus

    ... Epidemiology Transmission, information on epidemics and stats... Entomology & Ecology Mosquito that spreads dengue and its ecology... Clinical & Laboratory Guidance Tools for clinicians and laboratorians... ...

  18. Attenuation of Dengue Virus Infection by Adeno-Associated Virus-Mediated siRNA Delivery

    DTIC Science & Technology

    2004-08-09

    Pharmingen) for 7 days prior to infection with DEN. Blocking dengue virus infection in vitro 1 × 105 Vero cells or DCs were seeded into six-well tissue...essential for dengue pathogenesis in the human host. In this study, we also utilized peripheral blood iDCs as a cell model to test our AAV system. Similar to...attenu- ate DEN infection. List of abbreviations AAV, adeno-associated virus; DCs, dendritic cells ; DEN, dengue virus; DHF/DSS, dengue hemorrhagic fever

  19. Early Guillain-Barré Syndrome associated with acute dengue fever.

    PubMed

    Simon, O; Billot, S; Guyon, D; Daures, M; Descloux, E; Gourinat, A C; Molko, N; Dupont-Rouzeyrol, M

    2016-04-01

    Various forms of neurological manifestations are reported in dengue fever. We describe here three cases of concomitant Guillain-Barré syndrome and dengue virus (DENV) infection during the largest DENV-1 outbreak in New Caledonia. Research of viral RNA was positive in both blood and CSF samples. All patients were treated with intravenous polyvalent immunoglobulins and recovered without sequelae within one week.

  20. Prevalence of patients with acute febrile illnesses and positive dengue NS1 tests in a tertiary hospital in Papua New Guinea.

    PubMed

    Asigau, Viola; Lavu, Evelyn K; McBride, William J H; Biloh, Eric; Naroi, Francis; Koana, Egi; Ferguson, John K; Laman, Moses

    2015-01-01

    Because the prevalence of dengue fever in urban settings in Papua New Guinea is unknown, we investigated the presence of dengue using the NS1 antigen test in an outpatient-based prospective observational study at Port Moresby General Hospital. Of 140 patients with acute febrile illnesses, dengue fever was diagnosed in 14.9% (20 of 134; 95% confidence interval [95% CI] = 9.6-22.4). Malaria (2 of 137; 1.5%; 95% CI = 0.3-5.7), chikungunya (3 of 140; 2.1%; 95% CI = 0.6-6.6), and bacterial bloodstream infections (0 of 80; 0%; 95% CI = 0-5.7) were uncommon. Dengue fever should no longer be considered rare in Papua New Guinea.

  1. Callithrix penicillata: a feasible experimental model for dengue virus infection.

    PubMed

    Ferreira, Milene Silveira; de Castro, Paulo Henrique Gomes; Silva, Gilmara Abreu; Casseb, Samir Mansur Moraes; Dias Júnior, Antônio Gregório; Rodrigues, Sueli Guerreiros; Azevedo, Raimunda do Socorro da Silva; Costa e Silva, Matheus Fernandes; Zauli, Danielle Alves Gomes; Araújo, Márcio Sobreira Silva; Béla, Samantha Ribeiro; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Vasconcelos, Pedro Fernando da Costa

    2014-01-01

    Although the murine models have the feasibility to reproduce some signs of dengue Virus (DENV) infection, the use of isogenic hosts with polarized immune response patterns does not reproduce the particularities of human disease. Our goal was to investigate the kinetics of peripheral blood biomarkers in immunocompetent Callithrix penicillata non-human primates subcutaneously infected with DENV-3. The viral load of infected animals was determinated by quantitative real time PCR. Measurements of DENV-3/IgM were performed, and several parameters were assessed by hemogram: red blood cells count, hemoglobin, hematocrit, white blood cells count, neutrophils, monocytes, lymphocytes, and platelets count. The coagulogram was performed by prothrombin time (PT), and activated partial thromboplastin time (APTT) assays. The renal function was monitored by urea and creatinine, and the liver function by the aspartate (AST), and alanine (ALT) aminotransferases. Also, the level of the cytokines IL-6, TNF-α, IL-2, IFN-γ, IL-4 and IL-5 was quantified during the experimental study. Data analysis was performed considering relevant differences when baseline fold changes were found outside from 0.75 to 1.5 range. Our data demonstrated that infected animals presented relevant signs of dengue disease, including peaks of viremia at 5 days-post-infection (dpi), peaks of anti-DENV-3 IgM at 15 dpi and hemaglutination inhibition assay (HIA) from 15 to at 60 dpi. Despite early monocytosis, slight neutrophilia and lymphocytosis, animals developed persistent leucopenia starting at 4 dpi. Anemia episodes were steady at 3-4 dpi. Patent thrombocytopenia was observed from 1 to 15 dpi with sporadic decrease of APTT. A substantial increase of ALT and AST was observed with higher peak at 4 dpi. Moreover, early increases of TNF-alpha and IFN-gamma besides late increase of IFN-gamma were observed. The analysis of biomarkers network pointed out two relevant strong axes during early stages of dengue fever

  2. Hypoxia enhances antibody-dependent dengue virus infection.

    PubMed

    Gan, Esther Shuyi; Cheong, Wei Fun; Chan, Kuan Rong; Ong, Eugenia Ziying; Chai, Xiaoran; Tan, Hwee Cheng; Ghosh, Sujoy; Wenk, Markus R; Ooi, Eng Eong

    2017-03-20

    Dengue virus (DENV) has been found to replicate in lymphoid organs such as the lymph nodes, spleen, and liver in post-mortem analysis. These organs are known to have low oxygen levels (~0.5-4.5% O2) due to the vascular anatomy. However, how physiologically low levels of oxygen affect DENV infection via hypoxia-induced changes in the immune response remains unknown. Here, we show that monocytes adapted to 3% O2 show greater susceptibility to antibody-dependent enhancement of DENV infection. Low oxygen level induces HIF1α-dependent upregulation of fragment crystallizable gamma receptor IIA (FcγRIIA) as well as HIF1α-independent alterations in membrane ether lipid concentrations. The increased FcγRIIA expression operates synergistically with altered membrane composition, possibly through increase membrane fluidity, to increase uptake of DENV immune complexes for enhanced infection. Our findings thus indicate that the increased viral burden associated with secondary DENV infection is antibody-dependent but hypoxia-induced and suggest a role for targeting hypoxia-induced factors for anti-dengue therapy.

  3. Platelet activation determines the severity of thrombocytopenia in dengue infection

    PubMed Central

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  4. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection

    PubMed Central

    Conway, Michael J.; Londono-Renteria, Berlin; Troupin, Andrea; Watson, Alan M.; Klimstra, William B.; Fikrig, Erol; Colpitts, Tonya M.

    2016-01-01

    Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1–4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions. PMID:27632170

  5. Regulation of T lymphocyte apoptotic markers is associated to cell activation during the acute phase of dengue.

    PubMed

    Torrentes-Carvalho, Amanda; Marinho, Cintia Ferreira; de Oliveira-Pinto, Luzia Maria; de Oliveira, Débora Batista; Damasco, Paulo Vieira; Cunha, Rivaldo Venâncio; de Souza, Luiz José; de Azeredo, Elzinandes Leal; Kubelka, Claire Fernandes

    2014-05-01

    Dengue fever, a public health problem in Brazil, may present severe clinical manifestations as result of an increased vascular permeability and coagulation disorders. T cell activation is a critical event for an effective immune response against infection, including the production of cytokines. We aim to reveal mechanisms that modulate the virus-cell interaction, with an emphasis on cell death. Apoptosis is involved in lymphocyte homeostasis, contributes to the clearance of virus-infected cells but also may play a role in the pathogenesis. Phosphatidylserine exposure on CD8T lymphocytes from dengue patients support early apoptotic processes and loss of genomic integrity, observed by DNA fragmentation in T lymphocytes and indicating late apoptosis. These T cells express activation and cytotoxic phenotypes as revealed by CD29 and CD107a upregulation. Higher frequencies of CD95 were detected in T lymphocytes mainly in those with the cytotoxic profile (CD107a+) and lower levels of anti-apoptotic molecule Bcl-2, suggesting that both CD4+ and CD8+ T cell subsets are more susceptible to apoptosis during acute dengue. The analysis of apoptosis-related protein expression profile showed that not only molecules with pro- but also those with anti-apoptotic functions are overexpressed, indicating that survival mechanisms could be possibly protecting cells against apoptosis caused by viral, immune, oxidative and/or genotoxic stresses. These observations led us to propose that in dengue patients there is an association between T cell susceptibility to apoptosis and the activation state. The mechanisms for understanding the immunopathogenesis during dengue infection are discussed.

  6. Dengue co-infection in a blood stream infection caused by Stenotrophomonas maltophilia: A case report.

    PubMed

    Srirangaraj, Sreenivasan; Kali, Arunava; Vijayan, Sivaranjini

    2014-01-01

    Stenotrophomonas maltophilia (S. maltophilia) is an emerging opportunistic bacterial pathogen with resistance to several commonly used antibiotics. Owing to its multidrug resistance (MDR), management of S. maltophilia blood stream infection (BSI) is challenging and requires the selection of appropriate antibiotic therapy. The presence of thrombocytopenia and shock are independent risk factors associated with increased mortality in patients with S. maltophilia BSI. We describe an unusual case of S. maltophilia BSI in a middle-age female complicated by dengue fever. We highlight the importance of early recognition of both dengue and S. maltophilia infection in management of such cases.

  7. Urban epidemic of dengue virus serotype 3 infection, Senegal, 2009.

    PubMed

    Faye, Ousmane; Ba, Yamar; Faye, Oumar; Talla, Cheikh; Diallo, Diawo; Chen, Rubing; Mondo, Mireille; Ba, Rouguiétou; Macondo, Edgard; Siby, Tidiane; Weaver, Scott C; Diallo, Mawlouth; Sall, Amadou Alpha

    2014-03-01

    An urban epidemic of dengue in Senegal during 2009 affected 196 persons and included 5 cases of dengue hemorrhagic fever and 1 fatal case of dengue shock syndrome. Dengue virus serotype 3 was identified from all patients, and Aedes aegypti mosquitoes were identified as the primary vector of the virus.

  8. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus

    PubMed Central

    Dejnirattisai, Wanwisa; Supasa, Piyada; Wongwiwat, Wiyada; Rouvinski, Alexander; Barba-Spaeth, Giovanna; Duangchinda, Thaneeya; Sakuntabhai, Anavaj; Cao-Lormeau, Van-Mai; Malasit, Prida; Rey, Felix A; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2016-01-01

    Zika virus (ZIKV) was discovered in 1947 and was thought to lead to relatively mild disease. The recent explosive outbreak of ZIKV in South America has led to widespread concern with reports of neurological sequelae ranging from Guillain Barré syndrome to microcephaly. ZIKV infection has occurred in areas previously exposed to dengue, a flavivirus closely related to ZIKV. Here we investigate the serological crossreaction between the two viruses. Dengue immune plasma substantially crossreacted with ZIKV and could drive antibody-dependent enhancement of ZIKV infection. Using a panel of human anti-dengue monoclonal antibodies we showed that most antibodies reacting to dengue envelope protein also reacted to ZIKV. Antibodies to linear epitopes including the immunodominant fusion loop epitope while able to bind ZIKV could not neutralize the virus but instead promoted ADE. These data indicate that dengue immunity may drive higher ZIKV replication and have clear implications for disease pathogenesis and future ZIKV and dengue vaccine programs. PMID:27339099

  9. Chikungunya: a reemerging infection spreading during 2010 dengue fever outbreak in National Capital Region of India.

    PubMed

    Ramachandran, V G; Das, Shukla; Roy, Priyamvada; Hada, Vivek; Mogha, Narendra Singh

    2016-06-01

    Chikungunya fever is an important reemerging arbovirus illness, which is transmitted by the same vector as of dengue virus. Many cases of concurrent infections with multiple dengue virus serotypes have been reported in many countries. Also, concurrent infection with Chikungunya virus and dengue virus has been reported in the past in Delhi. Therefore, this study was done to detect Chikungunya IgM antibodies in suspected dengue fever patients. In this study, 1666 serum samples suspected of dengue fever and collected during the outbreak period (August 2010-December 2010) were tested for dengue IgM antibodies, of which 736 tested negative. Of the 736 dengue IgM negative sera, 666 were tested for Chikungunya IgM antibodies. The demographic profile and essential laboratory investigations were recorded. Chikungunya IgM was detected in 9.91 % of the patients. During the post-monsoon period though dengue dominated in numbers, the number of Chikungunya fever cases increased gradually followed by an abrupt decrease with the onset of winter. The Chikungunya IgM positive patients were suffering from fever of more than 5 days duration and had thrombocytopenia. Due to similarity in clinical features and vector transmitting dengue and Chikungunya virus, continuous surveillance of both dengue fever and Chikungunya fever is desirable for better management and epidemiological assessment.

  10. Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Firdous, Shamaraz; Anwar, Shahzad

    2015-08-01

    Raman spectroscopy has been found useful for monitoring the dengue patient diagnostic and recovery after infection. In the present work, spectral changes that occurred in the blood sera of a dengue infected patient and their possible utilization for monitoring of infection and recovery were investigated using 532 nm wavelength of light. Raman spectrum peaks for normal and after recovery of dengue infection are observed at 1527, 1170, 1021 cm-1 attributed to guanine, adenine, TRP (protein) carbohydrates peak for solids, and skeletal C-C stretch of lipids acyl chains. Where in the dengue infected patient Raman peaks are at 1467, 1316, 1083, and 860 attributed to CH2/CH3 deformation of lipids and collagen, guanine (B, Z-marker), lipids and protein bands. Due to antibodies and antigen reactions the portions and lipids concentration totally changes in dengue viral infection compared to normal blood. These chemical changes in blood sera of dengue viral infection in human blood may be used as possible markers to indicate successful remission and suggest that Raman spectroscopy may provide a rapid optical method for continuous monitoring or evaluation of a protein bands and an antibodies population. Accumulate acquisition mode was used to reduce noise and thermal fluctuation and improve signal to noise ratio. This in vitro dengue infection monitoring methodology will lead in vivo noninvasive on-line monitoring and screening of viral infected patients and their recovery.

  11. Hypothesis: Impregnated school uniforms reduce the incidence of dengue infections in school children.

    PubMed

    Wilder-Smith, A; Lover, A; Kittayapong, P; Burnham, G

    2011-06-01

    Dengue infection causes a significant economic, social and medical burden in affected populations in over 100 countries in the tropics and sub-tropics. Current dengue control efforts have generally focused on vector control but have not shown major impact. School-aged children are especially vulnerable to infection, due to sustained human-vector-human transmission in the close proximity environments of schools. Infection in children has a higher rate of complications, including dengue hemorrhagic fever and shock syndromes, than infections in adults. There is an urgent need for integrated and complementary population-based strategies to protect vulnerable children. We hypothesize that insecticide-treated school uniforms will reduce the incidence of dengue in school-aged children. The hypothesis would need to be tested in a community based randomized trial. If proven to be true, insecticide-treated school uniforms would be a cost-effective and scalable community based strategy to reduce the burden of dengue in children.

  12. Early Detection of Dengue Infections using Cluster Sampling Around Index Cases

    DTIC Science & Technology

    2005-01-01

    EARLY DETECTION OF DENGUE INFECTIONS USING CLUSTER SAMPLING AROUND INDEX CASES CHARMAGNE G. BECKETT, HERMAN KOSASIH, INDRA FAISAL, NURHAYATI, RATNA...Abstract. A two-year study using a cluster investigation method was conducted in West Jakarta, Indonesia to demonstrate the detection of dengue cases prior...to onset of clinical illness. The clusters consisted of family members and neighbors of 53 hospitalized dengue index cases. Among 785 adult and child

  13. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints.

    PubMed

    Sessions, October M; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients' sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses.

  14. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints

    PubMed Central

    Sessions, October M.; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M.; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R.; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients’ sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses. PMID:26327586

  15. Detection of Mayaro virus infections during a dengue outbreak in Mato Grosso, Brazil.

    PubMed

    Vieira, Carla Julia da Silva Pessoa; Silva, David José Ferreira da; Barreto, Eriana Serpa; Siqueira, Carlos Eduardo Hassegawa; Colombo, Tatiana Elias; Ozanic, Katia; Schmidt, Diane Johnson; Drumond, Betânia Paiva; Mondini, Adriano; Nogueira, Maurício Lacerda; Bronzoni, Roberta Vieira de Morais

    2015-07-01

    Arboviruses are common agents of human febrile illness worldwide. In dengue-endemic areas illness due to other arboviruses have been misdiagnosed as dengue based only on clinical-epidemiological data. In this study we investigated the presence of Brazilian arboviruses in sera of 200 patients presenting acute febrile illness, during a dengue outbreak in Sinop, MT, Brazil. The results showed that 38 samples were positive to Dengue virus (DENV) type 1, two samples to DENV type 4, and six to Mayaro virus. These results indicate that arboviruses others than DENV are circulating in Sinop and the surrounding region, which are going undiagnosed. In addition, molecular and evolutionary analyses indicate that two MAYV genotypes are co-circulating in Mato Grosso, Brazil. Thus, a strong surveillance program must be implemented to evaluate and monitor the distribution and the true importance of non-dengue arboviruses in the etiology of acute febrile illnesses.

  16. Correlation of measles and dengue infection in Kassala, Eastern Sudan.

    PubMed

    Abdalla, Tajeldin M; Karsany, Mubarak S; Ali, AbdelAziem A

    2015-01-01

    Using the clinical case definition adopted by the World Health Organization, a total of 275 suspected cases of measles were enrolled in this study during January-March 2012 in Kassala Teaching Hospital, Eastern Sudan. Various clinical manifestations (fever, headache, cough, coryza, conjunctivitis, skin rash, vomiting, diarrhoea, convulsion, and hemorrhagic manifestations) were reported among these patients. Blood was withdrawn from the first 64 (23.3%) patients. Two samples were hemolyzed and only 60 samples (21.8%) were investigated for measles and dengue IgM antibodies. Antibodies for measles, dengue, and co-infection were detected in the plasma of 12 (20%), seven (11.7%), and 10 (16.7%) samples, respectively. Although there was no significant difference in age, residence, occupation, and vaccination status among the different groups, a high proportion of male patients (P = 0.011), severe cases (P = 0.004), and death ((P = 0.001) were reported among co-infected cases.

  17. Treatment model of dengue hemorrhagic fever infection in human body

    NASA Astrophysics Data System (ADS)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  18. Meningitis Associated with Simultaneous Infection by Multiple Dengue Virus Serotypes in Children, Brazil

    PubMed Central

    Marinho, Paula Eillanny Silva; Bretas de Oliveira, Danilo; Candiani, Talitah Michel Sanchez; Crispim, Ana Paula Correia; Alvarenga, Pedro Paulo Martins; Castro, Fabrizia Cristina dos Santos; Abrahão, Jonatas Santos; Rios, Maria; Coimbra, Roney Santos

    2017-01-01

    To determine the causes of viral meningitis, we analyzed 22 cerebrospinal fluid samples collected during the 2014–2015 dengue epidemics in Brazil. We identified 3 serotypes of dengue virus (DENV-1, -2, and -3), as well as co-infection with 2 or 3 serotypes. We also detected the Asian II genotype of DENV-2. PMID:27983492

  19. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

    PubMed

    Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Pardo, Lissethe; Rico, Angélica; Campo, Alfonso; Navarro, Edgar; Viasus, Diego

    2016-06-02

    We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease.

  20. Increased phagocytosis of platelets from patients with secondary dengue virus infection by human macrophages.

    PubMed

    Honda, Shoko; Saito, Mariko; Dimaano, Efren M; Morales, Philip A; Alonzo, Maria T G; Suarez, Lady-Anne C; Koike, Natsuki; Inoue, Shingo; Kumatori, Atsushi; Matias, Ronald R; Natividad, Filipinas F; Oishi, Kazunori

    2009-05-01

    The relationship between the percent phagocytosis of platelets by differentiated THP-1 cells was examined using flowcytometry and the peripheral platelet counts as well as platelet-associated IgG (PAIgG) in 36 patients with secondary dengue virus (DV) infections. The percent phagocytosis and the levels of PAIgG were significantly increased in these patients during the acute phase compared with the healthy volunteers. The increased percent phagocytosis and PAIgG found during the acute phase significantly decreased during the convalescent phase. An inverse correlation between platelet count and the percent phagocytosis (P = 0.011) and the levels of PAIgG (P = 0.041) was found among these patients during the acute phase. No correlation was found, however, between the percent phagocytosis and the levels of PAIgG. Our present data suggest that accelerated platelet phagocytosis occurs during the acute phase of secondary DV infections, and it is one of the mechanisms of thrombocytopenia in this disease.

  1. Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

    DTIC Science & Technology

    1993-01-28

    AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN...28, 1993 Final 1 Sep 89 - 31 Dec 92 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Comparative Infectivity Determinations of Dengue DAMD17-89-C-9175 Virus...release; distribution unlimited 13. ABSTRACT (Maximum 200 words) 14. SUBJECT TERMS 1S. NUMBER OF PAGES RA 1; Dengue virus; Vaccines; Infectivity 16

  2. Optical diagnosis of dengue virus infection in human blood serum using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Saleem, M.; Bilal, M.; Anwar, S.; Rehman, A.; Ahmed, M.

    2013-03-01

    We present the optical diagnosis of dengue virus infection in human blood serum using Raman spectroscopy. Raman spectra were acquired from 18 blood serum samples using a laser at 532 nm as the excitation source. A multivariate regression model based on partial least-squares regression is developed that uses Raman spectra to predict dengue infection with leave-one-sample-out cross validation. The prediction of dengue infection by our model yields correlation coefficient r2 values of 0.9998 between the predicted and reference clinical results. The model was tested for six unknown human blood sera and found to be 100% accurate in accordance with the clinical results.

  3. Dengue virus compartmentalization during antibody-enhanced infection

    PubMed Central

    Ong, Eugenia Z.; Zhang, Summer L.; Tan, Hwee Cheng; Gan, Esther S.; Chan, Kuan Rong; Ooi, Eng Eong

    2017-01-01

    Secondary infection with a heterologous dengue virus (DENV) serotype increases the risk of severe dengue, through a process termed antibody-dependent enhancement (ADE). During ADE, DENV is opsonized with non- or sub-neutralizing antibody levels that augment entry into monocytes and dendritic cells through Fc-gamma receptors (FcγRs). We previously reported that co-ligation of leukocyte immunoglobulin-like receptor-B1 (LILRB1) by antibody-opsonized DENV led to recruitment of SH2 domain-containing phosphatase-1 (SHP-1) to dephosphorylate spleen tyrosine kinase (Syk) and reduce interferon stimulated gene induction. Here, we show that LILRB1 also signals through SHP-1 to attenuate the otherwise rapid acidification for lysosomal enzyme activation following FcγR-mediated uptake of DENV. Reduced or slower trafficking of antibody-opsonized DENV to lytic phagolysosomal compartments, demonstrates how co-ligation of LILRB1 also permits DENV to overcome a cell-autonomous immune response, enhancing intracellular survival of DENV. Our findings provide insights on how antiviral drugs that modify phagosome acidification should be used for viruses such as DENV. PMID:28084461

  4. Rainfall, abundance of Aedes aegypti and dengue infection in Selangor, Malaysia.

    PubMed

    Li, C F; Lim, T W; Han, L L; Fang, R

    1985-12-01

    An epidemio-meteorotropic analytical study of Selangor, in the Southwest coast of Peninsular Malaysia, examines the monthly incidence of dengue for the period 1973-1982 to assess possible quantitative association with the monthly rainfall. The relationships between rainfall, abundance of A. aegypti and dengue infection during 1982 in Jinjang, a dengue-prone area in Selangor, were also examined. A quantitative association between rainfall and the number of dengue cases was found during the first wet period. The lag time between the onset of heavy rain and dengue outbreak was about two to three months. A 120% increase in the number of dengue cases was observed when the monthly rainfall was 300 mm or more. Positive associations were seen between the incidence of dengue and the Aedes house index and the Breteau index in Jinjang. The relationships between these three variables and rainfall suggest that the latter might have exerted its effect on dengue infection partly through the creation of more breeding sites for A. aegypti. Assessment of the importance of A. aegypti in the transmission of dengue in this locality was not possible because of the lack of adjustment for A. albopictus, the other known vector of dengue in the state, and for social and other environmental factors influencing infection rates. In spite of this and the interpretational problems common in aggregate studies, the present analyses have provided relatively strong statistical evidence of an association between rainfall and dengue outbreaks in Selangor, thereby indicating that it is a factor worthy of careful surveillance and monitoring.

  5. Clinical Profiles of Dengue Infection during an Outbreak in Northern India

    PubMed Central

    Merugumala, Vamsi; Pathak, Ravi

    2016-01-01

    Introduction. Dengue fever is an arboviral disease, which is transmitted by mosquito vector and presents as varied clinical spectrum of dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS), and expanded dengue syndrome (EDS) with atypical presentations, thus posing a diagnostic dilemma. Unless we are aware of these presentations, diagnosis as well as early initiation of treatment becomes difficult. We studied the various clinical presentations of dengue infection during an outbreak of disease in 2015. Materials and Methods. A total of 115 confirmed cases of dengue infection from Department of Medicine of Deen Dayal Upadhyay Hospital, New Delhi, were enrolled in this observational study. Results. The common signs and symptoms of dengue infection were fever, headache, body ache, backache, retro-orbital pain, bleeding manifestations, and rash in 100%, 87%, 86%, 58%, 41%, 21%, and 21%, respectively. Nonspecific or warning signs and symptoms included vomiting, weakness, abdominal pain, breathlessness, vertigo, sweating, and syncope. Other possible signs and symptoms of coinfections, comorbidities, or complications included diarrhea, sore throat, and neurological manifestations. There were seven patients with coinfections and four with comorbidities. The final diagnosis of these patients was DF (73%), DHF (16.5%), DSS (1.7%), and EDS (4.3%). Among EDS patients, the atypical presentations included encephalopathy, lateral rectus nerve palsy, acalculous cholecystitis, and myocarditis. Four patients required ICU care and there was no death in this study. Conclusion. Knowledge of atypical presentations is a must for early diagnosis and timely intervention to prevent life-threatening complications. PMID:28025597

  6. Findings at brain MRI in children with dengue fever and neurological symptoms.

    PubMed

    Rastogi, Ruchi; Garg, Bhavya

    2016-01-01

    Dengue is a flavivirus of the genus arbovirus with four serotypes, from DEN 1 to DEN 4. There has been an increase in incidence of dengue infection in children in the tropics and subtropics. Dengue has a variable clinical presentation, with many patients being asymptomatic. Its clinical manifestations in children vary from fever and arthralgia to life-threatening dengue hemorrhagic fever and dengue shock syndrome. We describe MRI findings in children with neurological involvement including dengue encephalopathy, acute hypoxic injury and dengue encephalitis. Dengue encephalopathy is usually secondary to multisystem derangement such as shock, hepatitis, coagulopathy and concurrent bacterial infection and is relatively common. Dengue encephalitis from direct neuronal invasion is rare. Nonspecific changes are seen on brain MRI in dengue infection. Clinical and laboratory findings as well as outcome do not necessarily correspond with brain MRI findings.

  7. Characteristics of Mild Dengue Virus Infection in Thai Children

    DTIC Science & Technology

    2013-12-01

    only 65.9% reported fever . Symptom-based case definitions were unreliable for diagnosis. Symptomatic infections in contacts were milder with lower DENV...RNA levels than the cohort. Infections in contacts with fever history were more likely to have detectable DENV RNA than infections without fever ...during June–November each year.19,20 An acute-phase blood sample was drawn from cohort children who were absent from school and reported a fever in

  8. Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. II. Clinical Manifestations

    PubMed Central

    Sirivichayakul, Chukiat; Limkittikul, Kriengsak; Chanthavanich, Pornthep; Jiwariyavej, Vithaya; Chokejindachai, Watcharee; Pengsaa, Krisana; Suvannadabba, Saravudh; Dulyachai, Wut; Letson, G. William; Sabchareon, Arunee

    2012-01-01

    Background Dengue infection is one of the most important mosquito-borne diseases. More data regarding the disease burden and the prevalence of each clinical spectrum among symptomatic infections and the clinical manifestations are needed. This study aims to describe the incidence and clinical manifestations of symptomatic dengue infection in Thai children during 2006 through 2008. Study Design This study is a school-based prospective open cohort study with a 9,448 person-year follow-up in children aged 3–14 years. Active surveillance for febrile illnesses was done in the studied subjects. Subjects who had febrile illness were asked to visit the study hospital for clinical and laboratory evaluation, treatment, and serological tests for dengue infection. The clinical data from medical records, diary cards, and data collection forms were collected and analyzed. Results Dengue infections were the causes of 12.1% of febrile illnesses attending the hospital, including undifferentiated fever (UF) (49.8%), dengue fever (DF) (39.3%) and dengue hemorrhagic fever (DHF) (10.9%). Headache, anorexia, nausea/vomiting and myalgia were common symptoms occurring in more than half of the patients. The more severe dengue spectrum (i.e., DHF) had higher temperature, higher prevalence of nausea/vomiting, abdominal pain, rash, diarrhea, petechiae, hepatomegaly and lower platelet count. DHF cases also had significantly higher prevalence of anorexia, nausea/vomiting and abdominal pain during day 3–6 and diarrhea during day 4–6 of illness. The absence of nausea/vomiting, abdominal pain, diarrhea, petechiae, hepatomegaly and positive tourniquet test may predict non-DHF. Conclusion Among symptomatic dengue infection, UF is most common followed by DF and DHF. Some clinical manifestations may be useful to predict the more severe disease (i.e., DHF). This study presents additional information in the clinical spectra of symptomatic dengue infection. PMID:22389735

  9. Optical diagnosis of dengue virus infected human blood using Mueller matrix polarimetry

    NASA Astrophysics Data System (ADS)

    Anwar, Shahzad; Firdous, Shamaraz

    2016-08-01

    Currently dengue fever diagnosis methods include capture ELISAs, immunofluorescence tests, and hemagglutination assays. In this study optical diagnosis of dengue virus infection in the whole blood is presented utilizing Mueller matrix polarimetry. Mueller matrices of about 50 dengue viral infected and 25 non-dengue healthy blood samples were recorded utilizing light source from 500 to 700 nm with scanning step of 10 nm. Polar decomposition of the Mueller matrices for all the blood samples was performed that yielded polarization properties including depolarization, diattenuation, degree of polarization, retardance and optical activity, out of which, depolarization index clusters up the diseased and healthy in to different separate groups. The average depolarized light in the case of dengue infection in the whole blood at 500 nm is 18%, whereas for the healthy blood samples it is 13.5%. This suggests that depolarization index of polarized light at the wavelengths of 500, 510, 520, 530 and 540 nm, we find that in case of depolarization index values are higher for dengue viral infection as compared to normal samples. This technique can effectively be used for the characterization of the dengue virus infected at an early stage of disease.

  10. Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2–16 Years in Asia and Latin America

    PubMed Central

    Olivera-Botello, Gustavo; Coudeville, Laurent; Fanouillere, Karen; Guy, Bruno; Chambonneau, Laurent; Noriega, Fernando; Jackson, Nicholas

    2016-01-01

    Background. Asymptomatic dengue virus–infected individuals are thought to play a major role in dengue virus transmission. The efficacy of the recently approved quadrivalent CYD-TDV dengue vaccine against asymptomatic dengue virus infection has not been previously assessed. Methods. We pooled data for 3 736 individuals who received either CYD-TDV or placebo at 0, 6, and 12 months in the immunogenicity subsets of 2 phase 3 trials (clinical trials registration NCT01373281 and NCT01374516). We defined a seroconversion algorithm (ie, a ≥4-fold increase in the neutralizing antibody titer and a titer of ≥40 from month 13 to month 25) as a surrogate marker of asymptomatic infection in the vaccine and placebo groups. Results. The algorithm detected seroconversion in 94% of individuals with a diagnosis of virologically confirmed dengue between months 13 and 25, validating its discriminatory power. Among those without virologically confirmed dengue (n = 3 669), 219 of 2 485 in the vaccine group and 157 of 1 184 in the placebo group seroconverted between months 13 and 25, giving a vaccine efficacy of 33.5% (95% confidence interval [CI], 17.9%–46.1%) against asymptomatic infection. Vaccine efficacy was marginally higher in subjects aged 9–16 years (38.6%; 95% CI, 22.1%–51.5%). The annual incidence of asymptomatic dengue virus infection in this age group was 14.8%, which was 4.4 times higher than the incidence for symptomatic dengue (3.4%). Conclusions. The observed vaccine efficacy against asymptomatic dengue virus infections is expected to translate into reduced dengue virus transmission if sufficient individuals are vaccinated in dengue-endemic areas. PMID:27418050

  11. New insights into the immunopathology and control of dengue virus infection.

    PubMed

    Screaton, Gavin; Mongkolsapaya, Juthathip; Yacoub, Sophie; Roberts, Catherine

    2015-12-01

    Dengue virus poses a major threat to global public health: two-thirds of the world's population is now at risk from infection by this mosquito-borne virus. Dengue virus causes a range of diseases with a small proportion of infected patients developing severe plasma leakage that leads to dengue shock syndrome, organ impairment and bleeding. Infection with one of the four viral serotypes results in the development of homotypic immunity to that serotype. However, subsequent infection with a different serotype is associated with an increased risk of developing severe disease, which has led to the suggestion that severe disease is triggered by immunopathology. This Review outlines recent advances in the understanding of immunopathology, vaccine development and human monoclonal antibodies produced against dengue virus.

  12. Molecular profiling of T-helper immune genes during dengue virus infection

    PubMed Central

    Chen, Jincheng; Ng, Mary Mah Lee; Chu, Justin Jang Hann

    2008-01-01

    In this study, we provide a comprehensive molecular profiling of the involvement of T- helper (Th) genes during dengue virus infection of different cell types. The Th gene profiles of three human cell types (monocytes, T-cells and hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection with dengue virus. Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability. Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability. Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome. PMID:19117515

  13. The mannose receptor mediates dengue virus infection of macrophages.

    PubMed

    Miller, Joanna L; de Wet, Barend J M; deWet, Barend J M; Martinez-Pomares, Luisa; Radcliffe, Catherine M; Dwek, Raymond A; Rudd, Pauline M; Gordon, Siamon

    2008-02-08

    Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically to the envelope glycoprotein. Glycan analysis, ELISA, and blot overlay assays demonstrate that MR binds via its carbohydrate recognition domains to mosquito and human cell-produced DV antigen. This binding is abrogated by deglycosylation of the DV envelope glycoprotein. Surface expression of recombinant MR on NIH3T3 cells confers DV binding. Furthermore, DV infection of primary human MØ can be blocked by anti-MR antibodies. MR is a prototypic marker of alternatively activated MØ, and pre-treatment of human monocytes or MØ with type 2 cytokines (IL-4 or IL-13) enhances their susceptibility to productive DV infection. Our findings indicate a new functional role for the MR in DV infection.

  14. Quasispecies of dengue virus.

    PubMed

    Kurosu, Takeshi

    2011-12-01

    Pathogenic viruses have RNA genomes that cause acute and chronic infections. These viruses replicate with high mutation rates and exhibit significant genetic diversity, so-called viral quasispecies. Viral quasispecies play an important role in chronic infectious diseases, but little is known about their involvement in acute infectious diseases such as dengue virus (DENV) infection. DENV, the most important human arbovirus, is a causative agent of dengue fever (DF) and dengue hemorrhagic fever (DHF). Accumulating observations suggest that DENV exists as an extremely diverse virus population, but its biological significance is unclear. In other virus diseases, quasispecies affect the therapeutic strategies using drugs and vaccines. Here, I describe the quasispecies of DENV and discuss the possible role of quasispecies in the pathogenesis of and therapeutic strategy against DENV infection in comparison with other viruses such as Hepatitis C virus, human immunodeficiency virus type 1, and poliovirus.

  15. Characterization of the Myocarditis during the worst outbreak of dengue infection in China.

    PubMed

    Li, Yingying; Hu, Zhongwei; Huang, Yuli; Li, Jianping; Hong, Wenxin; Qin, Zhihui; Tong, Yuwei; Li, Jinglong; Lv, Mingfang; Li, Meiyu; Zheng, Xiaoke; Hu, Jun; Hua, Jinghai; Zhang, Fuchun; Xu, Ding-Li

    2016-07-01

    Myocarditis is a common complication of severe dengue infection. However, data about prevalence and characterization of myocarditis in dengue are still lacking. In 2014, the worst outbreak of dengue in the last two decades in China occurred. In this study, we described the clinical and laboratory diagnostic features of dengue with myocarditis. Totally, 1782 diagnosed dengue patients were admitted from August to October, 2014, all of whom were subjected to electrocardiogram, ultrasound cardiogram, and cardiac enzyme test. About 201 cases of dengue patients were diagnosed with myocarditis and the prevalence of myocarditis in hospitalized dengue was 11.28%. The prevalence of myocarditis in nonsevere dengue with warning signs and severe dengue [NSD(WS+)/SD] and nonsevere dengue without warning signs [NSD(WS-)] was 46.66% and 9.72%, respectively. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac symptoms, supraventricular tachycardia (14.29% vs. 0%, P < 0.001), atrial fibrillation (25.71% vs. 10.24%, P = 0.019) and heart failure compared with NSD (WS-) patients with myocarditis. About 150 cases of dengue patients without myocarditis in the same period of time in department of Cardiology were recruited as control group. The proportion of NSD(WS+)/SD in dengue patients with and without myocarditis was 17.41% and 2.53%, respectively. Dengue patients with myocarditis experienced longer hospital stay than those without myocarditis (7.17 ± 4.64 vs. 5.98 ± 2.69, P = 0.008). There was no difference between patients with and without myocarditis in the proportion of symptoms, auxiliary methods abnormality, arrhythmia, and heart failure on the discharge day. Our study demonstrates the prevalence of myocarditis in worst outbreak of dengue in China was 11.28% and the incidence of myocarditis increased with the severity of dengue. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac complication compared

  16. Establishment of an ’in vitro’ Model of Dengue Infection for the Study of Immunologic Events in this Disease

    DTIC Science & Technology

    1974-09-25

    tbe group B arthropod-born virus family) infection: Dengue fever and dengue hemorrhagic lever (DHF). The association of DHF with a second...vasculitis (18). The failure to detect immune complexes in dengue fever so far reflects the limitations of presently available techniques. A sensitive and...standard curve of *Ab uptake by cell» incubated with various amounts of AHG in serum. This technique was used to study sera from patients with dengue

  17. Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections.

    PubMed

    Toro, Jessica F; Salgado, Doris M; Vega, Rocío; Rodríguez, Jairo A; Rodríguez, Luz-Stella; Angel, Juana; Franco, Manuel A; Greenberg, Harry B; Narváez, Carlos F

    2016-01-01

    The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6-12 months old) and children (1-14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = -0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue.

  18. Total and Envelope Protein-Specific Antibody-Secreting Cell Response in Pediatric Dengue Is Highly Modulated by Age and Subsequent Infections

    PubMed Central

    Toro, Jessica F.; Salgado, Doris M.; Vega, Rocío; Rodríguez, Jairo A.; Rodríguez, Luz-Stella; Angel, Juana; Franco, Manuel A.; Greenberg, Harry B.; Narváez, Carlos F.

    2016-01-01

    The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6–12 months old) and children (1–14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = −0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue. PMID:27560782

  19. Peptide inhibitors of dengue virus and West Nile virus infectivity

    PubMed Central

    Hrobowski, Yancey M; Garry, Robert F; Michael, Scott F

    2005-01-01

    Viral fusion proteins mediate cell entry by undergoing a series of conformational changes that result in virion-target cell membrane fusion. Class I viral fusion proteins, such as those encoded by influenza virus and human immunodeficiency virus (HIV), contain two prominent alpha helices. Peptides that mimic portions of these alpha helices inhibit structural rearrangements of the fusion proteins and prevent viral infection. The envelope glycoprotein (E) of flaviviruses, such as West Nile virus (WNV) and dengue virus (DENV), are class II viral fusion proteins comprised predominantly of beta sheets. We used a physio-chemical algorithm, the Wimley-White interfacial hydrophobicity scale (WWIHS) [1] in combination with known structural data to identify potential peptide inhibitors of WNV and DENV infectivity that target the viral E protein. Viral inhibition assays confirm that several of these peptides specifically interfere with target virus entry with 50% inhibitory concentration (IC50) in the 10 μM range. Inhibitory peptides similar in sequence to domains with a significant WWIHS scores, including domain II (IIb), and the stem domain, were detected. DN59, a peptide corresponding to the stem domain of DENV, inhibited infection by DENV (>99% inhibition of plaque formation at a concentrations of <25 μM) and cross-inhibition of WNV fusion/infectivity (>99% inhibition at <25 μM) was also demonstrated with DN59. However, a potent WNV inhibitory peptide, WN83, which corresponds to WNV E domain IIb, did not inhibit infectivity by DENV. Additional results suggest that these inhibitory peptides are noncytotoxic and act in a sequence specific manner. The inhibitory peptides identified here can serve as lead compounds for the development of peptide drugs for flavivirus infection. PMID:15927084

  20. Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody

    PubMed Central

    Halstead, SB; O’Rourke, EJ

    1977-01-01

    Cultured mononuclear peripheral blood leukocytes (PBL) from nonimmune human beings and monkeys are nonpermissive to dengue 2 virus (D2V) infection at multiplicities of infection of 0.001-0.1, but become permissive when non-neutralizing dengue antibody is added to medium. D2V infection occurred in PBL prepared from anti-coagulated but not from defibrinated plasma. Infection enhancement was produced by multiple lots of heterotypic anti-dengue raised in several mammalian species. Homotypic anti-dengue neutralized D2V at high concentrations but enhanced at low concentrations; enhancement end point in one serum was 1:320,000. The infection-enhancing factor was a noncytophilic antibody of the IgG class. D2V infection occurred in the absence of heat-labile complement components but did not occur when complexes were prepared with anti- dengue F(ab)(2). Treatment of PBL with several proteases increased permissiveness to D2V infection by immune complexes but not by virus alone. Two rhesus monkey serums collected 14 days after D2V infection contained an IgG antibody with high-titered enhancing activity but with no hemagglutination-inhibition or neutralizing activity. Virus-antibody complexes are irreversibly attached to PBL within 15 min and completely internalized in 60 min. There was considerable variation in cellular infection in different experiments, however, maximum virus yields usually exceeded 1,000 plaque-forming units per 1 x 10(6) PBL occurring between 2 and 4 days in culture. In vitro antibody-dependent infection of PBL provides a possible model for study of pathogenetic mechanisms in infants with dengue shock syndrome who passively acquire maternal anti-dengue IgG. PMID:406347

  1. Ear infection - acute

    MedlinePlus

    ... more than 6 children) Changes in altitude or climate Cold climate Exposure to smoke Family history of ear infections ... or fewer children. This can reduce your child's chances of getting a cold or other infection, and ...

  2. Dengue viral infections in Pakistan and other Asian countries: a comprehensive review.

    PubMed

    Zubair, Muhammad; Ashraf, Muhammad; Ahsan, Aitezaz; Nazir, Noor-Ul-Ain; Hanif, Hina; Khan, Haider Ali

    2016-07-01

    Infections due to Dengue virus are widespread throughout the world. Disease starts with mild flu like sickness to a severe intricate condition which results in the death of the patient. Dengue illness has high morbidity and mortality in Pakistan as well as in other Asian countries. The Review article is a discourse analysis that explores the facts about the history, emergence and impact of dengue in Pakistan and other Asian countries. Data was collected from internet sources, mainly using Science Direct and PubMed. The final literature was reviewed and summarised. About 150 articles were identified and 47 articles were shortlisted for final review. Aedesaegypti was found to be a major vector for the transmission and spread of dengue illness. Treatment comprises supportive therapy as no specific treatment was available. During the last couple of years, the incidence of dengue fever was extraordinary in metropolitan cities of Pakistan.

  3. Identification of a Putative Coreceptor on Vero Cells That Participates in Dengue 4 Virus Infection

    PubMed Central

    Martínez-Barragán, José de Jesús; del Angel, Rosa M.

    2001-01-01

    Dengue virus infects target cells by attaching to a cell surface receptor through the envelope (E) glycoprotein, located on the surface of the viral membrane. On Vero and BHK cells, heparan sulfate (HS) moieties of proteoglycans are the receptors for dengue virus; however, additional proteins have also been described as putative dengue virus receptors on C6/36, HL60, and BM cells. HS can also act as a receptor for other types of viruses or as an attachment molecule for viruses that require additional host cell molecules to allow viral penetration. In this study we searched for molecules other than HS that could participate in dengue virus infection of Vero cells. Labeled dengue 4 virus bound with high affinity to two molecules of 74 and 44 kDa. Binding of dengue virus to the 74-kDa molecule was susceptible to protease and sodium periodate treatment and resistant to heparinase treatments. Lectins such as concanavalin A and wheat germ agglutinin prevented dengue virus binding to both the 74- and the 44-kDa protein in overlay assays, while phytohemagglutinin P did not affect binding, suggesting that carbohydrate residues (α-mannose or N-acetylglucosamine) are important in virus binding to host cells. Protease susceptibility, biotin labeling, and immunofluorescence with a polyclonal antibody raised against the 74-kDa protein consistently identified the protein on the surfaces of Vero cells. Moreover, the antibody against the 74-kDa protein was able to inhibit dengue virus infection. These data suggest that HS might serve as a primary receptor, probably concentrating virus particles on the surfaces of Vero cells, and then other molecules, such as the 74-kDa protein, might participate as coreceptors in viral penetration. The 74-kDa protein possibly constitutes part of a putative receptor complex for dengue virus infection of Vero cells. PMID:11483725

  4. Recombinase Polymerase Amplification Assay for Rapid Diagnostics of Dengue Infection

    PubMed Central

    Abd El Wahed, Ahmed; Patel, Pranav; Faye, Oumar; Thaloengsok, Sasikanya; Heidenreich, Doris; Matangkasombut, Ponpan; Manopwisedjaroen, Khajohnpong; Sakuntabhai, Anavaj; Sall, Amadou A.; Hufert, Frank T.; Weidmann, Manfred

    2015-01-01

    Background Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF). Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV). Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA) assays were developed to detect DENV1-4. Methodology/Principal Findings Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand). In Kedougou, the RT-RPA was operated at an ambient temperature of 38°C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively. Conclusions/Significance During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations. PMID:26075598

  5. Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes.

    PubMed

    Kou, Zhihua; Lim, Joanne Y H; Beltramello, Martina; Quinn, Matthew; Chen, Huiyuan; Liu, Shengyong; Liu, Shengyo-ng; Martinez-Sobrido, Luis; Martnez-Sobrido, Luis; Diamond, Michael S; Schlesinger, Jacob J; de Silva, Aravinda; Sallusto, Federica; Jin, Xia

    2011-02-05

    It remains unclear whether antibody-dependent-enhancement (ADE) of dengue infection merely augments viral attachment and entry through Fcγ receptors or immune complex binding to Fcγ receptors triggers an intrinsic signaling cascade that changes the viral permissiveness of the cell. Using human dengue-immune sera and novel human monoclonal antibodies against dengue in combination with virologic and immunologic techniques, we found that ADE infection increased the proportion of infected primary human monocytes modestly from 0.2% ± 0.1% (no Ab) to 1.7% ± 1.6% (with Ab) but the total virus output markedly from 2 ± 2 (× 10(3)) FFU to 120 ± 153 (× 10(3))FFU. However, this increased virus production was not associated with a reduced secretion of type I interferon or an elevated secretion of anti-inflammatory cytokine, IL-10. These results demonstrate that the regulation of virus production in ADE infection of primary human monocytes is more complex than previously appreciated.

  6. Gene expression in human macrophages infected with dengue virus serotype-2.

    PubMed

    Moreno-Altamirano, M M B; Romano, M; Legorreta-Herrera, M; Sánchez-García, F J; Colston, M J

    2004-12-01

    Infection by any of the four serotypes of dengue viruses (DEN-1, -2, -3 and -4) may result in either a relatively benign fever, called dengue fever (DF), a fatal disease, such as dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Several lines of evidence suggest that soluble immune response mediators may be involved in the severity of dengue infections. For instance, elevated seric levels of IL-8 are a common feature in DHF patients. Because other chemokines, cytokines, adhesion molecules, chemokine and cytokine receptors, as well as cytokine-related molecules may also be involved in dengue virus pathogenesis, we aimed at analysing the gene expression of such molecules in the course of an in vitro DEN-2 infection of human peripheral blood monocyte-derived macrophages, a cell type regarded as a primary target for DEN. Nylon membrane gene arrays containing 375 different human cytokine-related genes were used as a first step to search for differentially expressed genes upon infection. Transcripts for IL-8, IL-1beta, osteopontin, GRO-alpha, -beta and -gamma, I-309, and some other molecules showed to be upregulated upon infection, whereas others such as MIC-1, CD27L and CD30L, were downregulated. Four genes were selected for reverse transcriptase-polymerase chain reaction based gene-expression analysis as a way to partially confirm microarray results. This approach pointed out 25 macrophage-expressed cytokine-related genes that could be relevant in DEN-2 pathogenesis.

  7. [Co-infection by Chikungunya virus (CHIK-V) and dengue virus (DEN-V) during a recent outbreak in Cali, Colombia: Report of a fatal case].

    PubMed

    Rosso, Fernando; Pacheco, Robinson; Rodríguez, Sarita; Bautista, Diego

    2016-08-01

    The recent outbreaks of Chikungunya (CHIK-V) virus in endemic areas of dengue (DEN-V) could increase the risk of co-infection. CHIK infection has been considered not severe and with very unusual mortality, however DEN is associated with severe manifestations and increased mortality. Little is known about coinfection. It is possible that co-infection could generate severe cases. We present a case report of co-infection DEN-V -3 and CHIK-V in an elderly patient who developed acute renal failure, dengue shock syndrome (DSS), progresses to multiple organ failure and died. With the recent emergence of CHIK-V in Colombia, the possibility of co-infection with DEN-V should be suspected, especially in severe cases.

  8. High rate of unrecognized dengue virus infection in parts of the rainforest region of Nigeria.

    PubMed

    Onoja, A B; Adeniji, J A; Olaleye, O D

    2016-08-01

    Outbreaks and sporadic dengue virus infections continue to occur in Africa. Several reports of dengue among travellers returning from some African countries to Europe and North America have raised concerns about the epidemiological situation in Africa. We investigated recent dengue infections in febrile patients during the rainy season in various urban centres in the rainforest region of Nigeria, West Africa. This cross-sectional study was conducted for 8 months in 2014 with study participants from Adeoyo Hospital Yemetu - Ibadan, Nigeria. Plasma were collected from 274 febrile patients residing in 11 Local Government Areas of Oyo State. IgM antibodies were determined using semi-quantitative sandwich ELISA. Data was analyzed using Chi - Square and Fisher's exact test with SPSS 16.0. An overall prevalence of 23.4% dengue virus infection was found among study participants. Highest monthly prevalence of 40% was in April and August. The monthly distribution pattern of dengue virus infection indicates efficient virus transmission. Routine diagnosis will enhance dengue virus surveillance and improve patient care in West Africa.

  9. Culture proven Salmonella typhi co-infection in a child with Dengue fever: a case report.

    PubMed

    Srinivasaraghavan, Rangan; Narayanan, Parameswaran; Kanimozhi, Thandapani

    2015-09-27

    Infectious diseases are one of the major causes of morbidity and mortality in developing countries. Sometimes concurrent infections with multiple infectious agents may occur in one patient, which make the diagnosis and management a challenging task. The authors here present a case of co-infection of typhoid fever with dengue fever in a ten-year-old child and discuss the pertinent issues. The authors emphasize that the risk factors predicting the presence of such co-infections, if developed, will be immensely useful in areas where dengue outbreak occurs in the background of high transmission of endemic infections.

  10. Prophylactic Ribavirin Treatment of Dengue Type 1 Infection in Rhesus Monkeys

    DTIC Science & Technology

    1990-01-01

    Fever ,nd Dengue , 15-19 May 1988, Rio de Janeiro. Brazil . Pifat. D.Y., Toribio, F.E., Watson. K.A. and Canonico, P.G. (1990) Effect of human recombinant...FITr’ c COPy 2 Antiviral Research, 13 (1990) 139-150 q Elsevier AVR 00405 Prophylactic ribavirin treatment of dengue type 1 infection in rhesus...with dengue virus. Both placebo- and ribavirin-treated monkeys developed viremia, as measured by direct plaque assay on Aedes albopictus C6/36 cells

  11. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    PubMed

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

  12. Clinical and Laboratory Characteristics of Dengue-Orientia tsutsugamushi co-Infection from a Tertiary Care Center in South India

    PubMed Central

    Basheer, Aneesh; Iqbal, Nayyar; Mookkappan, Sudhagar; Anitha, Patricia; Nair, Shashikala; Kanungo, Reba; Kandasamy, Ravichandran

    2016-01-01

    Background Concurrent infection with multiple pathogens is common in tropics, posing diagnostic and treatment challenges. Although co-infections of dengue, malaria, leptospirosis and typhoid in various combinations have been described, data on dengue and scrub typhus co-infection is distinctly limited. Methodology This study was a retrospective analysis of dengue and scrub typhus co-infection diagnosed between January 2010 and July 2014 at a tertiary care center. Clinical and laboratory features of these cases were compared with age and gender-matched patients with isolated dengue fever and isolated scrub typhus. Positive test for dengue non-structural 1 (NS1) antigen was considered diagnostic of dengue whereas scrub typhus was diagnosed by IgM scrub antibodies demonstrated by ELISA. Results There were 6 cases of dengue-scrub co-infection during the review period which fitted clinical and laboratory profile with a mean age of 42.5 years. Fever, headache, and arthralgia were common. Normal hemoglobin, significant thrombocytopenia, transaminitis, and hypoalbuminemia were identified in these patients. Compared to patients with isolated dengue, those with co-infection had higher pulse rate, lower systolic blood pressure, normal leucocyte counts, higher levels of liver enzymes, greater prolongation of partial thromboplastin time (aPTT) and lower serum albumin. Co-infection was characterized by a lower nadir platelet count compared to scrub typhus, and lesser time to nadir platelet count and longer duration of hospital stay compared to either isolated dengue or scrub typhus. Conclusion Dengue-scrub typhus co-infection may be under-diagnosed in tropics, particularly confounded during dengue epidemics. Normal leukocyte counts, early drop in platelets and hypoalbuminemia in dengue patients could be clues to concurrent scrub typhus infection. Prompt recognition and treatment of scrub typhus in such cases may reduce unnecessary hospital stay and cost. PMID:27413521

  13. Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus.

    PubMed

    Chen, Hsuen-Chin; Lai, Show-Yun; Sung, Jui-Min; Lee, Shu-Hwae; Lin, Yu-Chin; Wang, Wei-Kung; Chen, Yee-Chun; Kao, Chuan-Liang; King, Chwan-Chuen; Wu-Hsieh, Betty A

    2004-07-01

    Activation and expansion of dengue virus-specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus-induced T cell activation. Mice were inoculated with 10(8) PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT-PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O-glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O-glycosylated CD43 and IFN-gamma production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8(+) T cell to CD4(+) T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8(+) T cell to CD4(+) T cell ratio increased to 5.8/1. A strong correlation was found between T cell activation and hepatic cellular infiltration in immunocompetent mice infected with dengue virus. The kinetics of liver enzyme elevation also correlated with that of T cell activation. These data suggest a relationship between T cell infiltration and elevation of liver enzymes.

  14. Acute pancreatitis: Manifestation of acute HIV infection in an adolescent

    PubMed Central

    Bitar, Anas; Altaf, Muhammad; Sferra, Thomas J.

    2012-01-01

    Summary Background: Pancreatitis in the pediatric age group is not as common as in adults. Etiologies are various and differ from those in adults. Although infectious etiology accounts for a significant number of cases of pancreatitis, acute infection with Human Immunodeficiency Virus (HIV) was rarely reported as a possible etiology for acute pancreatitis in adults. Acute pancreatitis has never been reported as a presenting manifestation of acute HIV infection in children. Case Report: We describe a pediatric patient who presented with acute pancreatitis that revealed acute HIV infection. Conclusions: Acute pancreatitis as a primary manifestation of HIV infection is very rare. It may represent an uncommon aspect of primary HIV infection. We suggest that acute HIV infection should be considered in the differential diagnosis of acute pancreatitis at all ages. PMID:23569476

  15. Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort

    PubMed Central

    Katzelnick, Leah C.; Montoya, Magelda; Gresh, Lionel; Balmaseda, Angel; Harris, Eva

    2016-01-01

    The four dengue virus serotypes (DENV1–4) are mosquito-borne flaviviruses that infect ∼390 million people annually; up to 100 million infections are symptomatic, and 500,000 cases progress to severe disease. Exposure to a heterologous DENV serotype, the specific infecting DENV strains, and the interval of time between infections, as well as age, ethnicity, genetic polymorphisms, and comorbidities of the host, are all risk factors for severe dengue. In contrast, neutralizing antibodies (NAbs) are thought to provide long-lived protection against symptomatic infection and severe dengue. The objective of dengue vaccines is to provide balanced protection against all DENV serotypes simultaneously. However, the association between homotypic and heterotypic NAb titers and protection against symptomatic infection remains poorly understood. Here, we demonstrate that the titer of preinfection cross-reactive NAbs correlates with reduced likelihood of symptomatic secondary infection in a longitudinal pediatric dengue cohort in Nicaragua. The protective effect of NAb titers on infection outcome remained significant when controlled for age, number of years between infections, and epidemic force, as well as with relaxed or more stringent criteria for defining inapparent DENV infections. Further, individuals with higher NAb titers immediately after primary infection had delayed symptomatic infections compared with those with lower titers. However, overall NAb titers increased modestly in magnitude and remained serotype cross-reactive in the years between infections, possibly due to reexposure. These findings establish that anti-DENV NAb titers correlate with reduced probability of symptomatic DENV infection and provide insights into longitudinal characteristics of antibody-mediated immunity to DENV in an endemic setting. PMID:26729879

  16. Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580.

    PubMed

    Fu, Yilong; Yip, Andy; Seah, Peck Gee; Blasco, Francesca; Shi, Pei-Yong; Hervé, Maxime

    2014-10-01

    Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients.

  17. Protection from Secondary Dengue Virus Infection in a Mouse Model Reveals the Role of Serotype Cross-reactive B and T cells1,2

    PubMed Central

    Zompi, Simona; Santich, Brian H.; Beatty, P. Robert; Harris, Eva

    2011-01-01

    The four dengue virus (DENV) serotypes cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome. Although severe disease has been associated with heterotypic secondary DENV infection, most secondary DENV infections are asymptomatic or result in classic DF. The role of cross-reactive immunity in mediating cross-protection against secondary heterotypic DENV infection is not well-understood. DENV infection of interferon-α/β and -γ receptor-deficient (AG129) mice reproduces key features of human disease. We previously demonstrated a role in cross-protection for pre-existing cross-reactive antibodies, maintained by long-lived plasma cells (LLPCs). Here we use a sequential infection model, infecting AG129 mice with DENV-1 followed by DENV-2 6–8 weeks later. We find that increased DENV-specific avidity during acute secondary heterotypic infection is mediated by cross-reactive memory B cells, as evidenced by increased numbers of DENV-1-specific cells by ELISPOT and higher avidity against DENV-1 of supernatants from polyclonally-stimulated splenocytes isolated from mice experiencing secondary DENV-2 infection. However, increased DENV-specific avidity is not associated with increased DENV-specific neutralization, which appears to be mediated by naïve B cells. Adoptive transfer of DENV-1-immune B and T cells into naïve mice prior to secondary DENV-2 infection delayed mortality. Mice depleted of T cells developed signs of disease but recovered after secondary DENV infection. Overall, we found that protective cross-reactive antibodies are secreted by both LLPCs and memory B cells and that both cross-reactive B cells and T cells provide protection against a secondary heterotypic DENV infection. Understanding the protective immunity that develops naturally against DENV infection may help design future vaccines. PMID:22131327

  18. Chikungunya Virus Infections among Patients with Dengue-Like Illness at a Tertiary Care Hospital in the Philippines, 2012–2013

    PubMed Central

    Velasco, John Mark; Valderama, Maria Theresa; Lopez, Maria Nila; Chua, Domingo; Latog, Rene; Roque, Vito; Corpuz, June; Klungthong, Chonticha; Rodpradit, Prinyada; Hussem, Kittinun; Poolpanichupatam, Yongyuth; Macareo, Louis; Fernandez, Stefan; Yoon, In-Kyu

    2015-01-01

    Chikungunya virus (CHIKV) often co-circulates with dengue virus (DENV). A cross-sectional surveillance study was conducted at a tertiary hospital in Manila, Philippines, to describe the prevalence and characteristics of DENV and CHIKV infections among patients seeking care for dengue-like illness. Acute blood samples from patients ≥ 6 months of age clinically diagnosed with dengue from November 2012 to December 2013 underwent reverse transcription polymerase chain reaction (RT-PCR) to detect DENV and CHIKV RNA. A total of 118 patients with clinically diagnosed dengue (age range = 1–89 years, mean = 22 years; male-to-female ratio = 1.51) were tested by DENV RT-PCR; 40 (34%) were DENV PCR-positive (age range = 1–45 years, mean = 17 years). All DENV serotypes were detected: 11 (28%) DENV-1, 6 (15%) DENV-2, 6 (15%) DENV-3, and 17 (42%) DENV-4. Of 112 patients clinically diagnosed with dengue and tested by CHIKV RT-PCR, 11 (10%) were CHIKV PCR-positive (age range = 2–47 years, mean = 20.3 years). No coinfections were detected. Presenting signs/symptoms did not differ between DENV- and CHIKV-positive cases. Sequencing of envelope 1 gene from two CHIKV PCR-positive samples showed Asian genotype. This study highlights the potential for misdiagnosis of medically attended CHIKV infections as DENV infection and the difficulty in clinically differentiating dengue and chikungunya based on presenting signs/symptoms alone. This underscores the necessity for diagnostic laboratory tests to distinguish CHIKV infections in the background of actively co-circulating DENV. PMID:26416109

  19. Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development.

    PubMed

    Marques, Rafael E; Guabiraba, Rodrigo; Del Sarto, Juliana L; Rocha, Rebeca F; Queiroz, Ana Luiza; Cisalpino, Daniel; Marques, Pedro E; Pacca, Carolina C; Fagundes, Caio T; Menezes, Gustavo B; Nogueira, Maurício L; Souza, Danielle G; Teixeira, Mauro M

    2015-08-01

    Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5.

  20. Zika, dengue, and chikungunya co-infection in a pregnant woman from Colombia.

    PubMed

    Villamil-Gómez, Wilmer E; Rodríguez-Morales, Alfonso J; Uribe-García, Ana María; González-Arismendy, Edgardo; Castellanos, Jaime E; Calvo, Eliana P; Álvarez-Mon, Melchor; Musso, Didier

    2016-10-01

    The clinical findings of a pregnant woman from Colombia with a triple co-infection caused by dengue, chikungunya, and Zika viruses are described. Weekly obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains under follow-up and management according to the standard guidelines for the management of Zika virus-infected pregnant women.

  1. Laboratory evaluation of the response of Aedes aegypti and Aedes albopictus uninfected and infected with dengue virus to deet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laboratory studies were conducted to compare the response of Aedes aegypti (L.) and Aedes albopictus (Skuse) adults, uninfected and infected with four serotypes of dengue virus, to a repellent containing 5% deet. The results showed that mosquitoes infected with the four serotypes of dengue respond i...

  2. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  3. Severe acute malnutrition and infection.

    PubMed

    Jones, Kelsey D J; Berkley, James A

    2014-12-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice.

  4. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study.

    PubMed

    Chinnappan, Shobia; Ramachandrappa, Vijayakumar Shettikothanuru; Tamilarasu, Kadhiravan; Krishnan, Uma Maheswari; Pillai, Agiesh Kumar Balakrishna; Rajendiran, Soundravally

    2016-04-01

    Dengue cases were reported to undergo platelet activation and thrombocytopenia by a poorly understood mechanism. Recent studies suggested that Carica papaya leaf extract could recover the platelet count in dengue cases. However, no studies have attempted to unravel the mechanism of the plant extract in platelet recovery. Since there are no available drugs to treat dengue and considering the significance of C. papaya in dengue treatment, the current study aimed to evaluate two research questions: First one is to study if the C. papaya leaf extract exerts its action directly on platelets and second one is to understand if the extract can specifically inhibit the platelet aggregation during dengue viral infection. Sixty subjects with dengue positive and 60 healthy subjects were recruited in the study. Platelet-rich plasma (PRP) and platelet-poor plasma were prepared from both the dengue-infected and healthy control blood samples. Effect of the leaf extract obtained from C. papaya leaves was assessed on plasma obtained as well as platelets collected from both healthy and dengue-infected individuals. Platelet aggregation was significantly reduced when leaf extract preincubated with dengue plasma was added into control PRP, whereas no change in aggregation when leaf extract incubated-control plasma was added into control PRP. Upon direct addition of C. papaya leaf extract, both dengue PRP and control PRP showed a significant reduction in platelet aggregation. Within the dengue group, PRP from severe and nonsevere cases showed a significant decrease in aggregation without any difference between them. From the study, it is evident that C. papaya leaf extract can directly act on platelet. The present study, the first of its kind, found that the leaf extract possesses a dengue-specific neutralizing effect on dengue viral-infected plasma that may exert a protective role on platelets.

  5. A DNA Microarray-Based Assay to Detect Dual Infection with Two Dengue Virus Serotypes

    PubMed Central

    Díaz-Badillo, Alvaro; de Lourdes Muñoz, María; Perez-Ramirez, Gerardo; Altuzar, Victor; Burgueño, Juan; Mendoza-Alvarez, Julio G.; Martínez-Muñoz, Jorge P.; Cisneros, Alejandro; Navarrete-Espinosa, Joel; Sanchez-Sinencio, Feliciano

    2014-01-01

    Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection of unspecific signals. This finding provides evidence that specific probes can effectively identify single and double infections in DENV samples. PMID:24776933

  6. Dengue fever and human T-cell lymphotropic virus type 1 infection.

    PubMed

    Longo, Cecília Lameirinhas; Brasil, Patricia; Espíndola, Otávio de Melo; Leite, Ana Claudia Celestino Bezerra; Nogueira, Rita Maria Ribeiro; Lupi, Otília; Neves, Elizabeth de Souza

    2013-07-01

    Globalization has increased both the number of emergent diseases and the diversity of co-infections, which could in turn mutually influence the pathogenesis of well-known infectious diseases. Here, we report the first series of chronic human T-cell lymphotropic virus type 1 (HTLV-1) patients co-infected with the dengue fever virus. As both of these diseases are immuno-mediated, we anticipated interference in the development of both diseases, with atypical clinical and laboratory parameter results. All the patients had classic dengue fever, and the main outstanding abnormality was leukopenia associated with lymphopenia. Although a mutual influence was expected, dengue fever did not affect the clinical course of HTLV-1 infection, and HTLV-1 proviral loads revealed unpredictable patterns of change.

  7. The effects of mosquito saliva on dengue virus infectivity in humans.

    PubMed

    Wichit, Sineewanlaya; Ferraris, Pauline; Choumet, Valérie; Missé, Dorothée

    2016-12-01

    Arboviruses such as Dengue, Chikungunya, and Zika viruses represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Arthropod vector-derived salivary factors have the capacity to modulate human cells function by enhancing or suppressing viral replication and, therefore, modify the establishment of local and systemic viral infection. Here, we discuss how mosquito saliva may interfere with Dengue virus (DENV) infection in humans. Identification of saliva factors that enhance infectivity will allow the production of vector-based vaccines and therapeutics that would interfere with viral transmission by targeting arthropod saliva components. Understanding the role of salivary proteins in DENV transmission will provide tools to control not only Dengue but also other arboviral diseases transmitted by the same vectors.

  8. A DNA microarray-based assay to detect dual infection with two dengue virus serotypes.

    PubMed

    Díaz-Badillo, Alvaro; Muñoz, María de Lourdes; Perez-Ramirez, Gerardo; Altuzar, Victor; Burgueño, Juan; Mendoza-Alvarez, Julio G; Martínez-Muñoz, Jorge P; Cisneros, Alejandro; Navarrete-Espinosa, Joel; Sanchez-Sinencio, Feliciano

    2014-04-25

    Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection of unspecific signals. This finding provides evidence that specific probes can effectively identify single and double infections in DENV samples.

  9. Monoclonal Antibodies for Dengue Virus prM Glycoprotein Protect Mice against Lethal Dengue Infection

    DTIC Science & Technology

    1989-09-15

    Nile virus and a prelysozomal endosome prM glycoprotein of dengue virus can also be required for viral replication . PrM Mabs 2H2 protective against...tech- bodies can prevent lethal alphavirus encepha- niques to preserve immunogenicity, to deter- litis. Nature 297: 70-72. UI:82173237 mine whether

  10. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java

    PubMed Central

    Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F.; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H.; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G.; Blair, Patrick J.; Burgess, Timothy H.; Williams, Maya; Porter, Kevin R.

    2016-01-01

    Background Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Methodology/Principal Findings Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000–2004 and 2006–2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Conclusions/Significance Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with

  11. Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

    PubMed Central

    2013-01-01

    Background Leukotriene B4, a 5-lipoxygenase product of arachidonic acid with potent chemotactic effects on neutrophils, has not been assessed in dengue patients. In this study, plasma leukotriene B4 and serum high-sensitivity C-reactive protein levels were determined in adult patients during the febrile, convalescent and defervescent stages of dengue serotype-2 (DENV-2) infection, and compared with those of age--matched healthy and non-dengue febrile subjects. In vitro studies were performed to examine the effects of live and heat-inactivated DENV-2 on the activities and expression of 5-lipoxygenase in human neutrophils. Results Plasma leukotriene B4 was elevated during the febrile stages of dengue infection compared to levels during convalescence and in study controls. Plasma leukotriene B4 also correlated with serum high-sensitivity C-reactive protein in dengue patients (febrile, r = 0.91, p < 0.001; defervescence, r = 0.87, p < 0.001; convalescence, r = 0.87, p < 0.001). Exposure of human neutrophils to DENV-2 resulted in a significant rise in leukotriene B4; the extent of increase, however, did not differ between exposure to live and heat-inactivated DENV-2. Pre-incubation of either live or heat-inactivated DENV-2 resulted in reduced leukotriene B4 release by neutrophils, indicating that contact with dengue antigens (and not replication) triggers the neutrophil response. Production of leukotriene B4 was associated with an increase in 5-lipoxygenase expression in human neutrophils; addition of MK886 (a 5-lipoxygenase activating protein inhibitor) attenuated further increase in leukotriene B4 production. Conclusion These findings provide important clinical and mechanistic data on the involvement of 5-lipoxygenase and its metabolites in dengue infection. Further studies are needed to elucidate the therapeutic implications of these findings. PMID:24168271

  12. Performance of Simplexa dengue molecular assay compared to conventional and SYBR green RT-PCR for detection of dengue infection in Indonesia.

    PubMed

    Sasmono, R Tedjo; Aryati, Aryati; Wardhani, Puspa; Yohan, Benediktus; Trimarsanto, Hidayat; Fahri, Sukmal; Setianingsih, Tri Y; Meutiawati, Febrina

    2014-01-01

    Diagnostic tests based on detection of dengue virus (DENV) genome are available with varying sensitivities and specificities. The Simplexa Dengue assay (Focus Diagnostics) is a newly developed real-time RT-PCR method designed to detect and serotype DENV simultaneously. To assess the performance of the Simplexa Dengue assay, we performed comparison with conventional RT-PCR and SYBR Green real-time RT-PCR on patients sera isolated from eight cities across Indonesia, a dengue endemic country. A total of 184 sera that were confirmed using NS1 and/or IgM and IgG ELISA were examined. Using conventional and SYBR Green real-time RT-PCR, we detected DENV in 53 (28.8%) and 81 (44.0%) out of 184 sera, respectively. When the Simplexa Dengue assay was employed, the detection rate was increased to 76.6% (141 out of 184 samples). When tested in 40 sera that were confirmed by virus isolation as the gold standard, the conventional RT-PCR yielded 95% sensitivity while the sensitivity of SYBR Green real-time RT-PCR and Simplexa Dengue assay reached 97.5% and 100%, respectively. The specificities of all methods were 100% when tested in 43 non-dengue illness and 20 healthy human samples. Altogether, our data showed the higher detection rate of Simplexa Dengue compared to conventional and SYBR Green real-time RT-PCR in field/surveillance setting. In conclusion, Simplexa Dengue offers rapid and accurate detection and typing of dengue infection and is suitable for both routine diagnostic and surveillance.

  13. Primary dengue virus infections induce differential cytokine production in Mexican patients

    PubMed Central

    de la Cruz Hernández, Sergio Isaac; Puerta-Guardo, Henry Nelson; Flores Aguilar, Hilario; González Mateos, Silvia; López Martinez, Irma; Ortiz-Navarrete, Vianney; Ludert, Juan E; del Angel, Rosa María

    2016-01-01

    Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis. PMID:27008374

  14. VERTICAL TRANSMISSION OF DENGUE INFECTION: THE FIRST PUTATIVE CASE REPORTED IN CHINA.

    PubMed

    Yin, Xueru; Zhong, Xiaozhu; Pan, Shilei

    2016-12-08

    Dengue is a systemic viral infection that is commonly transmitted between humans via mosquitoes. Other modes of transmission such as the vertical one are rare and have been infrequently reported in the literature. This report investigates one case of vertical transmission of dengue in Guangzhou, China. A G1P1 lady at 39 weeks of gestation was referred to the Huzhong Hospital presenting a fever for two days. She subsequently developed a skin rash on the back and lower limb and at that time she had already experienced five days of fever. She subsequently went into labor and delivered a female neonate weighting 3,500 g at birth. The neonate developed fever on the third day of life which was associated with a systemic erythematous skin rash. There was no report or evidence of mosquito bites after birth. A complete blood count showed leucopenia, thrombocytopenia and anemia and the liver function test showed elevated AST, GGT and bilirubin. Dengue was diagnosed in the mother and the neonate by the ELISA dengue virus NS1 antigen test (Wantai, Beijing, China) and dengue virus fluorogenic quantitative PCR test (Liferiver, Shanghai, China).The case report illustrates the possibility of the vertical transmission of dengue. Clinicians should be alert to this possibility and institute early treatment. Further direct evidence and research are required.

  15. VERTICAL TRANSMISSION OF DENGUE INFECTION: THE FIRST PUTATIVE CASE REPORTED IN CHINA

    PubMed Central

    YIN, Xueru; ZHONG, Xiaozhu; PAN, Shilei

    2016-01-01

    SUMMARY Dengue is a systemic viral infection that is commonly transmitted between humans via mosquitoes. Other modes of transmission such as the vertical one are rare and have been infrequently reported in the literature. This report investigates one case of vertical transmission of dengue in Guangzhou, China. A G1P1 lady at 39 weeks of gestation was referred to the Huzhong Hospital presenting a fever for two days. She subsequently developed a skin rash on the back and lower limb and at that time she had already experienced five days of fever. She subsequently went into labor and delivered a female neonate weighting 3,500 g at birth. The neonate developed fever on the third day of life which was associated with a systemic erythematous skin rash. There was no report or evidence of mosquito bites after birth. A complete blood count showed leucopenia, thrombocytopenia and anemia and the liver function test showed elevated AST, GGT and bilirubin. Dengue was diagnosed in the mother and the neonate by the ELISA dengue virus NS1 antigen test (Wantai, Beijing, China) and dengue virus fluorogenic quantitative PCR test (Liferiver, Shanghai, China).The case report illustrates the possibility of the vertical transmission of dengue. Clinicians should be alert to this possibility and institute early treatment. Further direct evidence and research are required. PMID:27982356

  16. Dengue and dengue haemorrhagic fever: implications of host genetics.

    PubMed

    Chaturvedi, Umeshc; Nagar, Rachna; Shrivastava, Richa

    2006-07-01

    Little is known of the role of human leucocyte antigen (HLA) alleles or non-HLA alleles in determining resistance, susceptibility or the severity of acute viral infections. Dengue fever (DF) and dengue haemorrhagic fever (DHF) are suitable models for immunogenetic studies, yet only superficial efforts have been made to study dengue disease to date. DF and DHF can be caused by both primary and secondary infection by any of the four serotypes of the dengue virus. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virus virulence. Variations in immune response, often associated with polymorphism in the human genome, can now be detected. Data on the influence of human genes in DF and DHF are discussed here in relation to (1) associations between HLA polymorphism and dengue disease susceptibility or resistance, (2) protective alleles influencing progression to severe disease, (3) alleles restricting CD4(+) and CD8(+) T lymphocytes, and (4) non-HLA genetic factors that may contribute to DHF evolution. Recent discoveries regarding genetic associations in other viral infections may provide clues to understanding the development of end-stage complications in dengue disease. The scanty positive data presented here indicate a need for detailed genetic studies in different ethnic groups in different countries during the acute phase of DF and DHF on a larger number of patients.

  17. Toll-like receptor 4 polymorphisms in dengue virus-infected children.

    PubMed

    Djamiatun, Kis; Ferwerda, Bart; Netea, Mihai G; van der Ven, André J A M; Dolmans, Wil M V; Faradz, Sultana M H

    2011-08-01

    Differential viral recognition by cells bearing Toll-like receptor 4 (TLR4) polymorphisms Asp299Gly and Thr399Ile may influence susceptibility and severity of dengue virus infection. In central Java, Indonesia, we investigated 201 children with dengue hemorrhagic fever (DHF) and 179 healthy controls. Patients and controls were mostly ethnic Javanese. A nearly complete cosegregation of the two mutations was observed. The TLR4 299/399 genotype was found in five patients and four controls. Prevalence of the TLR4 299/399 genotype did not differ significantly between controls and DHF patients or between patients with different severities of DHF. Also, vascular leakage in patients with different TLR4 genotypes did not differ. Thus, the 299/399 TLR4 haplotype has only minor influence on susceptibility and severity of complicated dengue virus infection.

  18. Occurrence of concurrent infections with multiple serotypes of dengue viruses during 2013–2015 in northern Kerala, India

    PubMed Central

    Reddy, Manchala Nageswar; Dungdung, Ranjeet; Valliyott, Lathika

    2017-01-01

    Background Dengue is a global human public health threat, causing severe morbidity and mortality. The occurrence of sequential infection by more than one serotype of dengue virus (DENV) is a major contributing factor for the induction of Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), two major medical conditions caused by DENV infection. However, there is no specific drug or vaccine available against dengue infection. There are reports indicating the increased incidence of concurrent infection of dengue in several tropical and subtropical regions. Recently, increasing number of DHF and DSS cases were reported in India indicating potential enhancement of concurrent DENV infections. Therefore, accurate determination of the occurrence of DENV serotype co-infections needs to be conducted in various DENV prone parts of India. In this context, the present study was conducted to analyse the magnitude of concurrent infection in northern Kerala, a southwest state of India, during three consecutive years from 2013 to 2015. Methods A total of 120 serum samples were collected from the suspected dengue patients. The serum samples were diagnosed for the presence of dengue NS1 antigen followed by the isolation of dengue genome from NS1 positive samples. The isolated dengue genome was further subjected to RTPCR based molecular serotyping. The phylogenetic tree was constructed based on the sequence of PCR amplified products. Results Out of the total number of samples collected, 100 samples were positive for dengue specific antigen (NS1) and 26 of them contained the dengue genome. The RTPCR based molecular serotyping of the dengue genome revealed the presence of all four serotypes with different combinations. However, serotypes 1 and 3 were predominant combinations of concurrent infection. Interestingly, there were two samples with all four serotypes concurrently infected in 2013. Discussion All samples containing dengue genome showed the presence of more than one

  19. Acute Respiratory Infections in Children

    PubMed Central

    Laxdal, Oliver E.; Robertson, H. E.; Braaten, Virgil; Walker, W. Alan

    1963-01-01

    During a seven-month period from November 1960 to May 1961, 181 infants and children, hospitalized because of acute respiratory infections, were studied intensively to determine the responsible etiologic agents. Forty-two per cent of the illnesses in this group appeared to be caused by bacterial agents, either primary or secondary to virus. Parainfluenza viruses were identified as causes of laryngotracheobronchitis in nearly 50% of the cases. Adenoviruses were also found to be important pathogens, particularly as causes of pneumonia in infants. The over-all infection rate attributed to adenoviruses was 11.6%. An epidemic due to Influenza B virus affected approximately 40% of children in this city just following the hospital study. This study was conducted as the first step in a long-term project undertaken at the Regina General Hospital to determine the effectiveness of vaccines in the prevention and treatment of respiratory infections in children. PMID:20327546

  20. Magnitude of viremia, antigenemia and infection of circulating monocytes in children with mild and severe dengue.

    PubMed

    Perdomo-Celis, Federico; Salgado, Doris M; Narváez, Carlos F

    2017-03-01

    Dengue is a major public health problem in tropical regions around the world. Viral and immune host factors determine the clinical courses of the infection. We analyzed the dynamics of viremia (by real-time polymerase chain reactions), antigenemia (through detection of the viral non-structural protein [NS]-1 by enzyme-linked immunosorbent assays) and the frequency of virus-infected peripheral blood mononuclear cells (PBMCs) (by multiparametric flow cytometry) in children with primary or secondary dengue virus (DENV) infection in mild to severe cases. Additionally, we evaluated the association of these factors with clinical severity and laboratory parameters. The levels of viremia and antigenemia peaked during the early days of illness and these viral parameters were correlated (rho=0.37, P=0.003). Circulating monocytes were the most naturally infected subset within the PBMCs population, with kinetics similar to those of viremia and antigenemia. The levels of viremia and antigenemia were higher in children with primary infections than in those with secondary infections (P≤0.04). Although there were no associations between the three evaluated factors and clinical severity, the levels of plasma NS1 and the frequency of dengue virus-infected monocytes correlated with prolonged coagulation times. In short, the viremia, antigenemia and infected monocytes were detected early and were not related to clinical severity. The magnitude of antigenemia and infected circulating monocytes was associated with coagulation disorders.

  1. Human Immune Responses to Dengue Virus Infection: Lessons Learned from Prospective Cohort Studies

    PubMed Central

    Endy, Timothy P.

    2014-01-01

    Dengue virus (DENV) continues to spread globally and is a major cause of morbidity and mortality. Currently, there is no antiviral treatment to diminish severe illness or a vaccine to induce protection from infection. An effective dengue vaccine that protects against all four DENV serotypes is a high priority for endemic countries and several candidates are in development by various United States Federal Agencies and private pharmaceutical companies. Challenges faced by dengue vaccine developers include creating tetravalent formulations that provide tetravalent protection, the lack of a correlate of protective immunity, a changing viral landscape as DENV evolves, and a complex viral-host pathogenesis that can result in a spectrum of illness from subclinical infection to severe hemorrhagic fever. There have been a number of long-term prospective studies on DENV transmission and dengue severity that have provided invaluable information on DENV epidemiology and pathogenesis of this disease. In this section, we will review the critical lessons learned from these studies and their application for dengue vaccine development. PMID:24795725

  2. Dengue antibodies in blood donors

    PubMed Central

    Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

    2012-01-01

    Background Dengue is an urban arbovirus whose etiologic agent is a virus of the genus Flavorius with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. The Campo Mourão region in Brazil is endemic for dengue fever. Obtective The aim of this study was to evaluate the presence of IgG and IgM antibodies specific to the four serotypes of dengue in donors of the blood donor service in the city of Campo Mourão. Methods Epidemiological records were evaluated and 4 mL of peripheral blood from 213 blood donors were collected in tubes without anticoagulant. Serum was then obtained and immunochromatographic tests were undertaken (Imuno-Rápido Dengue IgM/IgGTM). Individuals involved in the study answered a social and epidemiological questionnaire on data which included age, gender and diagnosis of dengue. Results Only three (1.4%) of the 213 blood tests were positive for IgG anti-dengue antibodies. No donors with IgM antibody, which identifies acute infection, were identified. Conclusions The results of the current analysis show that the introduction of quantitative or molecular serological methods to determine the presence of anti-dengue antibodies or the detection of the dengue virus in blood donors in endemic regions should be established so that the quality of blood transfusions is guaranteed. PMID:23049418

  3. Transverse Myelitis as an Unusual Complication of Dengue Fever.

    PubMed

    Mota, Mânlio Tasso de Oliveira; Estofolete, Cássia Fernanda; Zini, Nathalia; Terzian, Ana Carolina Bernardes; Gongora, Delzi Vinha Nunes; Maia, Irineu Luiz; Nogueira, Maurício Lacerda

    2017-02-08

    Dengue fever is the most common arbovirus disease, and presents with a large spectrum of clinical manifestations ranging from asymptomatic disease through to the development of dengue hemorrhagic fever. These extreme cases can lead to dengue shock syndrome, and sometimes death. Spinal cord involvement in dengue virus (DENV) infections is rare. Here, we report a case in which the patient developed acute transverse myelitis (TM) without paraparesis following a DENV infection. This case highlights the importance of physicians' awareness of the possible link between DENV and TM in endemic areas.

  4. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection

    PubMed Central

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry AF; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS126–34-specific CD8+ T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS126–34-specific and other DENV epitope-specific CD8+ T cells, as well as total CD8+ T cells, expressed an activated phenotype (CD69+ and/or CD38+) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8+ T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. PMID:23941420

  5. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    PubMed

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation.

  6. Comment on ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’

    NASA Astrophysics Data System (ADS)

    Darvin, Maxim E.; Lademann, Juergen; Brandt, Nikolay N.

    2016-04-01

    The results of the letter ‘Dengue viral infection monitoring from diagnostic to recovery using Raman spectroscopy’ authored by Firdous and Anwar (2015 Laser Phys. Lett. 12 085601) are discussed. We show that the original interpretation of the results is not correct and does not correspond to data in the literature.

  7. Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

    PubMed Central

    Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

    2015-01-01

    Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

  8. High dengue NS1 antigenemia in febrile patients in Ibadan, Nigeria.

    PubMed

    Oyero, Olufunmilayo G; Ayukekbong, James A

    2014-10-13

    We conducted a dengue seroprevalence survey among febrile patients positive or negative for malaria in Ibadan, Nigeria. Dengue IgG and NS1 seroprevalence of 73% and 35%, respectively, was observed, and 43% of those with malaria had acute dengue infection (NS1 determination). On the other hand, all participants with malaria were IgG dengue seropositive consistent with the endemicity of both arthropod-borne infections in the region. These data indicate that dengue is emerging as a major and neglected cause of fever in Nigeria.

  9. The Existence and Stability Analysis of the Equilibria in Dengue Disease Infection Model

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Supriatna, A. K.; Soewono, E.

    2015-06-01

    In this paper we formulate an SIR (Susceptible - Infective - Recovered) model of Dengue fever transmission with constant recruitment. We found a threshold parameter K0, known as the Basic Reproduction Number (BRN). This model has two equilibria, disease-free equilibrium and endemic equilibrium. By constructing suitable Lyapunov function, we show that the disease- free equilibrium is globally asymptotic stable whenever BRN is less than one and when it is greater than one, the endemic equilibrium is globally asymptotic stable. Numerical result shows the dynamic of each compartment together with effect of multiple bio-agent intervention as a control to the dengue transmission.

  10. A Non Mouse-Adapted Dengue Virus Strain as a New Model of Severe Dengue Infection in AG129 Mice

    PubMed Central

    Tan, Grace K.; Ng, Jowin K. W.; Trasti, Scott L.; Schul, Wouter; Yip, George; Alonso, Sylvie

    2010-01-01

    The spread of dengue (DEN) worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable small animal model. Most of the DEN clinical isolates and cell culture-passaged DEN virus strains reported so far require either host adaptation, inoculation with a high dose and/or intravenous administration to elicit a virulent phenotype in mice which results, at best, in a productive infection with no, few, or irrelevant disease manifestations, and with mice dying within few days at the peak of viremia. Here we describe a non-mouse-adapted DEN2 virus strain (D2Y98P) that is highly infectious in AG129 mice (lacking interferon-α/β and -γ receptors) upon intraperitoneal administration. Infection with a high dose of D2Y98P induced cytokine storm, massive organ damage, and severe vascular leakage, leading to haemorrhage and rapid death of the animals at the peak of viremia. In contrast, very interestingly and uniquely, infection with a low dose of D2Y98P led to asymptomatic viral dissemination and replication in relevant organs, followed by non-paralytic death of the animals few days after virus clearance, similar to the disease kinetic in humans. Spleen damage, liver dysfunction and increased vascular permeability, but no haemorrhage, were observed in moribund animals, suggesting intact vascular integrity, a cardinal feature in DEN shock syndrome. Infection with D2Y98P thus offers the opportunity to further decipher some of the aspects of dengue pathogenesis and provides a new platform for drug and vaccine testing. PMID:20436920

  11. A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice.

    PubMed

    Tan, Grace K; Ng, Jowin K W; Trasti, Scott L; Schul, Wouter; Yip, George; Alonso, Sylvie

    2010-04-27

    The spread of dengue (DEN) worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable small animal model. Most of the DEN clinical isolates and cell culture-passaged DEN virus strains reported so far require either host adaptation, inoculation with a high dose and/or intravenous administration to elicit a virulent phenotype in mice which results, at best, in a productive infection with no, few, or irrelevant disease manifestations, and with mice dying within few days at the peak of viremia. Here we describe a non-mouse-adapted DEN2 virus strain (D2Y98P) that is highly infectious in AG129 mice (lacking interferon-alpha/beta and -gamma receptors) upon intraperitoneal administration. Infection with a high dose of D2Y98P induced cytokine storm, massive organ damage, and severe vascular leakage, leading to haemorrhage and rapid death of the animals at the peak of viremia. In contrast, very interestingly and uniquely, infection with a low dose of D2Y98P led to asymptomatic viral dissemination and replication in relevant organs, followed by non-paralytic death of the animals few days after virus clearance, similar to the disease kinetic in humans. Spleen damage, liver dysfunction and increased vascular permeability, but no haemorrhage, were observed in moribund animals, suggesting intact vascular integrity, a cardinal feature in DEN shock syndrome. Infection with D2Y98P thus offers the opportunity to further decipher some of the aspects of dengue pathogenesis and provides a new platform for drug and vaccine testing.

  12. A prospective cohort study to evaluate peridomestic infection as a determinant of dengue transmission: Protocol

    PubMed Central

    2012-01-01

    Background Vector control programs, which have focused mainly on the patient house and peridomestic areas around dengue cases, have not produced the expected impact on transmission. This project will evaluate the assumption that the endemic/epidemic transmission of dengue begins around peridomestic vicinities of the primary cases. Its objective is to assess the relationship between symptomatic dengue case exposure and peridomestic infection incidence. Methods/Design A prospective cohort study will be conducted (in Tepalcingo and Axochiapan, in the state of Morelos, Mexico), using the state surveillance system for the detection of incident cases. Paired blood specimens will be collected from both the individuals who live with the incident cases and a sample of subjects residing within a 25-meter radius of such cases (exposed cohort), in order to measure dengue-specific antibodies. Other subjects will be selected from areas which have not presented any incident cases within 200 meters, during the two months preceding the sampling (non-exposed cohort). Symptomatic/asymptomatic incident infection will be considered as the dependent variable, exposure to confirmed dengue cases, as the principal variable, and the socio-demographic, environmental and socio-cultural conditions of the subjects, as additional explanatory variables. Discussion Results indicating a high infection rate among the exposed subjects would justify the application of peridomestic control measures and call for an evaluation of alternate causes for insufficient program impact. On the other hand, a low incidence of peridomestic-infected subjects would support the hypothesis that infection occurs outside the domicile, and would thus explain why the vector control measures applied in the past have exerted such a limited impact on cases incidence rates. The results of the present study may therefore serve to reassess site selection for interventions of this type. PMID:22471857

  13. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    PubMed

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand.

  14. A Global Airport-Based Risk Model for the Spread of Dengue Infection via the Air Transport Network

    PubMed Central

    Gardner, Lauren; Sarkar, Sahotra

    2013-01-01

    The number of travel-acquired dengue infections has seen a consistent global rise over the past decade. An increased volume of international passenger air traffic originating from regions with endemic dengue has contributed to a rise in the number of dengue cases in both areas of endemicity and elsewhere. This paper reports results from a network-based risk assessment model which uses international passenger travel volumes, travel routes, travel distances, regional populations, and predictive species distribution models (for the two vector species, Aedes aegypti and Aedes albopictus) to quantify the relative risk posed by each airport in importing passengers with travel-acquired dengue infections. Two risk attributes are evaluated: (i) the risk posed by through traffic at each stopover airport and (ii) the risk posed by incoming travelers to each destination airport. The model results prioritize optimal locations (i.e., airports) for targeted dengue surveillance. The model is easily extendible to other vector-borne diseases. PMID:24009672

  15. Response of the mosquito protein interaction network to dengue infection

    PubMed Central

    2010-01-01

    Background Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions. Results We developed the first draft of the mosquito protein interaction network using a computational approach. The weighted network includes 4,214 Aedes aegypti proteins with 10,209 interactions, among which 3,500 proteins are connected into an interconnected scale-free network. We demonstrated the application of this network for the further annotation of mosquito proteins and dissection of pathway crosstalk. Using three datasets based on physical interaction assays, genome-wide RNA interference (RNAi) screens and microarray assays, we identified 714 putative DENV-associated mosquito proteins. An integrated analysis of these proteins in the network highlighted four regions consisting of highly interconnected proteins with closely related functions in each of replication/transcription/translation (RTT), immunity, transport and metabolism. Putative DENV-associated proteins were further selected for validation by RNAi-mediated gene silencing, and dengue viral titer in mosquito midguts was significantly reduced for five out of ten (50.0%) randomly selected genes. Conclusions Our results indicate the presence of common host requirements for DENV in mosquitoes and humans. We discuss the significance of our findings for pharmacological intervention and genetic modification of mosquitoes for blocking dengue transmission. PMID:20553610

  16. Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

    PubMed

    Adikari, T N; Gomes, L; Wickramasinghe, N; Salimi, M; Wijesiriwardana, N; Kamaladasa, A; Shyamali, N L A; Ogg, G S; Malavige, G N

    2016-04-01

    Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.

  17. Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection.

    PubMed

    Elong Ngono, Annie; Chen, Hui-Wen; Tang, William W; Joo, Yunichel; King, Kevin; Weiskopf, Daniela; Sidney, John; Sette, Alessandro; Shresta, Sujan

    2016-11-01

    Infection with one of the four dengue virus serotypes (DENV1-4) presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed "original antigenic sin," secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response. The goal of our study was to compare the roles of serotype-specific and cross-reactive T cells in protection vs. pathogenesis during DENV infection in vivo. Specifically, we utilized IFN-α/βR(-/-) HLA*B0702 transgenic mice in the context of peptide vaccination with relevant human CD8 T cell epitopes. IFN-α/βR(-/-) HLA*B0702 transgenic mice were immunized with DENV serotype 2 (DENV2)-specific epitopes or variants found in any of the other three serotypes (DENV1, DENV3 or DENV4), followed by challenge with DENV. Although cross-reactive T cell responses were lower than responses elicited by serotype-specific T cells, immunization with either serotype-specific or variant peptide epitopes enhanced viral clearance, demonstrating that both serotype-specific and cross-reactive T cells can contribute to protection in vivo against DENV infection.

  18. Determination of Viremia and Concentration of Circulating Nonstructural Protein 1 in Patients Infected with Dengue Virus in Mexico

    PubMed Central

    de la Cruz-Hernández, Sergio I.; Flores-Aguilar, Hilario; González-Mateos, Silvia; López-Martinez, Irma; Alpuche-Aranda, Celia; Ludert, Juan E.; del Angel, Rosa M.

    2013-01-01

    Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity. PMID:23339203

  19. Viremia and Clinical Presentation in Nicaraguan Patients Infected With Zika Virus, Chikungunya Virus, and Dengue Virus

    PubMed Central

    Waggoner, Jesse J.; Gresh, Lionel; Vargas, Maria Jose; Ballesteros, Gabriela; Tellez, Yolanda; Soda, K. James; Sahoo, Malaya K.; Nuñez, Andrea; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A.

    2016-01-01

    Background. Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses. Methods. Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded. Results. A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001). Conclusions. ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance. PMID:27578819

  20. Flow cytometric analysis of dengue virus-infected cells in peripheral blood.

    PubMed

    Baclig, Michael O; Gervacio, Leonora T S; Suarez, Lady-Anne C; Buerano, Corazon C; Matias, Ronald R; Kumatori, Atsushi; Inoue, Shingo; Morita, Kouichi; Natividad, Filipinas F; Hasebe, Futoshi

    2010-11-01

    With the development of permeabilization techniques in flow cytometry and the availability of various monoclonal antibodies (MAbs) that specifically bind with cell surface and intracellular antigens, it is now possible to use flow cytometric assay to identify dengue virus (DEN) infected cells in peripheral blood. Blood samples were analyzed using phycoerythrin (PE) labeled anti-CD3, anti-CD14, anti-CD16, and anti-CD19 antibodies and Alexa Fluor 488 labeled anti-flavivirus monoclonal antibody (MAb) 6B6C-1. The predominant DEN-infected cells were CD19+ in this study. There was dim partial to moderately bright partial expression of CD19 positive cells in the blood samples tested. Virus isolation and serotype-specific RT-PCR revealed the cells were infected with dengue serotype 3 (DEN3). Our results suggest B cells may play an important role in DEN1 and DEN3 replication, and dissemination in vivo.

  1. Inhibitory effects of curcumin on dengue virus type 2-infected cells in vitro.

    PubMed

    Padilla-S, Leonardo; Rodríguez, Andrés; Gonzales, María M; Gallego-G, Juan C; Castaño-O, Jhon C

    2014-03-01

    Curcumin, a traditional Chinese and Indian treatment for many diseases, has recently been found to alter the in vitro infection processes of various viruses, including hepatitis C virus, human immunodeficiency virus, coxsackievirus, and Japanese encephalitis virus. The present study evaluated the cellular effects of curcumin in an in vitro (cellular) infection model of dengue virus. Within a dose range of 10 to 30 μM and a treatment period of 24 hours, the cytotoxicity of curcumin was low, as determined by MTT assays. Cells infected with dengue virus type 2 at a multiplicity of infection of 5 were treated with various concentrations of curcumin or the proteasome inhibitor MG132. Plaque assays, immunofluorescence analysis, western blots, and in-cell western assays were then performed. Treatment with 10, 15, and 20 μM curcumin decreased the number of plaques produced, caused an intracellular accumulation of viral proteins, and increased the level of Lys48 ubiquitin-conjugated proteins. At 20 μM curcumin, changes in cell and nuclear morphology and alterations in the actin cytoskeleton were also observed. Treatment with MG132 also reduced plaque production. These results show that curcumin can interfere with the infection processes of dengue virus and that this interference may not occur through direct effects on viral particle production but may result from curcumin's effects on various cellular systems such as the cytoskeleton, the ubiquitin-proteasome system, or the apoptosis process.

  2. Dengue virus infection induces interferon-lambda1 to facilitate cell migration

    PubMed Central

    Hsu, Yu-Lin; Wang, Mei-Yi; Ho, Ling-Jun; Lai, Jenn-Haung

    2016-01-01

    A marked increase in the rate of dengue virus (DENV) infection has resulted in more than 212 deaths in Taiwan since the beginning of 2015, mostly from fatal outcomes such as dengue hemorrhagic fever and dengue shock syndrome. The pathogenic mechanisms of these fatal manifestations are poorly understood. Cytokines induce an overwhelming immune reaction and thus have crucial roles. Interferon-lambda (IFN-λ), a newly identified IFN subtype, has antiviral effects, but its immunologic effects in DENV infection have not been investigated. In the present study, we show that DENV infection preferentially induced production of IFN-λ1 in human dendritic cells (DCs) and human lung epithelial cells. Virus nonstructural 1 (NS1) glycoprotein was responsible for the effect. DENV-induced production of IFN-λ1 was dependent on signaling pathways involving toll-like receptor (TLR)-3, interferon regulation factor (IRF)-3, and nuclear factor-kappaB (NF-κB). Blocking interaction between IFN-λ1 and its receptor IFN-λR1 through siRNA interference reduced DENV-induced DC migration towards the chemoattractants CCL19 and CCL21, by inhibiting CCR7 expression. Furthermore, IFN-λ1 itself induced CCR7 expression and DC migration. Our study presents the first evidence of the mechanisms and effects of IFN-λ1 induction in DENV-infected DCs and highlights the role of this cytokine in the immunopathogenesis of DENV infection. PMID:27456172

  3. Acute disseminated encephalomyelitis associated with acute Toxoplasma gondii Infection.

    PubMed

    Aksoy, Ayse; Tanir, Gonul; Ozkan, Mehpare; Oguz, Melek; Yıldız, Yasemin Tasci

    2013-03-01

    Acute disseminated encephalomyelitis is an acute demyelinating disorder of the central nervous system, which principally affects the brain and spinal cord. It usually follows a benign infection or vaccination in children. Although a number of infectious agents have been implicated in acute disseminated encephalomyelitis, Toxoplasma gondii infection has not been described previously in children. Acquired T. gondii infection presents with lymphadenopathy and fever and usually spontaneously resolves in immunocompetent patients. We describe a previously healthy 10-year-old boy with acute disseminated encephalomyelitis associated with acute acquired Toxoplasma gondii infection, the symptoms of which initially began with nuchal stiffness, difficulty in walking, and urinary and stool incontinence; he later had development of motor and sensory impairment in both lower extremities and classical magnetic resonance imaging lesions suggestive of the disease. The patient recovered completely after the specific therapy for acquired T. gondii infection and pulse prednisolone. Although acute acquired Toxoplasma gondii infection has not been reported previously in association with acute disseminated encephalomyelitis, clinicians should keep in mind this uncommon cause of a common disease when evaluating a patient with acute disseminated encephalomyelitis.

  4. Climate Change Influences Potential Distribution of Infected Aedes aegypti Co-Occurrence with Dengue Epidemics Risk Areas in Tanzania

    PubMed Central

    Mweya, Clement N.; Kimera, Sharadhuli I.; Stanley, Grades; Misinzo, Gerald; Mboera, Leonard E. G.

    2016-01-01

    Background Dengue is the second most important vector-borne disease of humans globally after malaria. Incidence of dengue infections has dramatically increased recently, potentially due to changing climate. Climate projections models predict increases in average annual temperature, precipitation and extreme events in the future. The objective of this study was to assess the effect of changing climate on distribution of dengue vectors in relation to epidemic risk areas in Tanzania. Methods/Findings We used ecological niche models that incorporated presence-only infected Aedes aegypti data co-occurrence with dengue virus to estimate potential distribution of epidemic risk areas. Model input data on infected Ae. aegypti was collected during the May to June 2014 epidemic in Dar es Salaam. Bioclimatic predictors for current and future projections were also used as model inputs. Model predictions indicated that habitat suitability for infected Ae. aegypti co-occurrence with dengue virus in current scenarios is highly localized in the coastal areas, including Dar es Salaam, Pwani, Morogoro, Tanga and Zanzibar. Models indicate that areas of Kigoma, Ruvuma, Lindi, and those around Lake Victoria are also at risk. Projecting to 2020, we show that risk emerges in Mara, Arusha, Kagera and Manyara regions, but disappears in parts of Morogoro, Ruvuma and near Lake Nyasa. In 2050 climate scenario, the predicted habitat suitability of infected Ae. aegypti co-occurrence with dengue shifted towards the central and north-eastern parts with intensification in areas around all major lakes. Generally, model findings indicated that the coastal regions would remain at high risk for dengue epidemic through 2050. Conclusion/Significance Models incorporating climate change scenarios to predict emerging risk areas for dengue epidemics in Tanzania show that the anticipated risk is immense and results help guiding public health policy decisions on surveillance and control of dengue epidemics. A

  5. Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India.

    PubMed

    Chandele, Anmol; Sewatanon, Jaturong; Gunisetty, Sivaram; Singla, Mohit; Onlamoon, Nattawat; Akondy, Rama S; Kissick, Haydn Thomas; Nayak, Kaustuv; Reddy, Elluri Seetharami; Kalam, Haroon; Kumar, Dhiraj; Verma, Anil; Panda, HareKrushna; Wang, Siyu; Angkasekwinai, Nasikarn; Pattanapanyasat, Kovit; Chokephaibulkit, Kulkanya; Medigeshi, Guruprasad R; Lodha, Rakesh; Kabra, Sushil; Ahmed, Rafi; Murali-Krishna, Kaja

    2016-12-15

    Epidemiological studies suggest that India has the largest number of dengue virus infection cases worldwide. However, there is minimal information about the immunological responses in these patients. CD8 T cells are important in dengue, because they have been implicated in both protection and immunopathology. Here, we provide a detailed analysis of HLA-DR(+) CD38(+) and HLA-DR(-) CD38(+) effector CD8 T cell subsets in dengue patients from India and Thailand. Both CD8 T cell subsets expanded and expressed markers indicative of antigen-driven proliferation, tissue homing, and cytotoxic effector functions, with the HLA-DR(+) CD38(+) subset being the most striking in these effector qualities. The breadth of the dengue-specific CD8 T cell response was diverse, with NS3-specific cells being the most dominant. Interestingly, only a small fraction of these activated effector CD8 T cells produced gamma interferon (IFN-γ) when stimulated with dengue virus peptide pools. Transcriptomics revealed downregulation of key molecules involved in T cell receptor (TCR) signaling. Consistent with this, the majority of these CD8 T cells remained IFN-γ unresponsive even after TCR-dependent polyclonal stimulation (anti-CD3 plus anti-CD28) but produced IFN-γ by TCR-independent polyclonal stimulation (phorbol 12-myristate 13-acetate [PMA] plus ionomycin). Thus, the vast majority of these proliferating, highly differentiated effector CD8 T cells probably acquire TCR refractoriness at the time the patient is experiencing febrile illness that leads to IFN-γ unresponsiveness. Our studies open novel avenues for understanding the mechanisms that fine-tune the balance between CD8 T cell-mediated protective versus pathological effects in dengue.

  6. Dengue-specific CD8+ T cells have both protective and pathogenic roles in dengue virus infection.

    PubMed

    An, Jing; Zhou, De-Shan; Zhang, Jun-Lei; Morida, Hatue; Wang, Jia-Li; Yasui, Kotaro

    2004-09-01

    To analyze roles of memory T cells in the pathogenesis of dengue (DEN) virus infection, a DEN virus-specific CD8+ cell clone (2D42 cell) was employed to investigate its in vivo function after DEN virus infection using an animal model. HepG2 grafted severe combined immunodeficient (HepG2-grafted SCID) mice were divided into three groups--group A: HepG2-grafted SCID mice were inoculated intraperitoneally (ip) with 2D42 cells and then ip-infected with DEN virus type 2 (DEN-2); group B: HepG2-grafted SCID mice were inoculated with naive mouse thymocytes (NMT) and then ip-infected with DEN-2; group C: HepG2-grafted SCID mice were ip-infected with DEN-2 alone. Eighty percentage of group A mice died at average day 12.8 post-infection (p.i.) and 20% of them recovered from the disease after showing clinical signs and survived more than 3 months. They showed severe manifestations including dramatically decreased platelet count, decreased hematocrit, anemia, viremia and high frequency of histopathological changes in several organs. All of group B mice also showed the above severe clinical signs. One hundred percentage mortality rate was noted in these mice and death occurred at average day 10.8 p.i., which was the earliest among three groups. Although the mice from group C showed 100% mortality rate and similar clinical signs, death observed in these mice occurred at average day 17.4 p.i. and the manifestations were slight and developed slowly. Our results suggested both protective and pathogenic roles for DEN-specific CD8+ T cell in DEN virus infection, whereas NMT did not provided any protection.

  7. Symptomatic Dengue Infection during Pregnancy and Infant Outcomes: A Retrospective Cohort Study

    PubMed Central

    Friedman, Eleanor E.; Dallah, Fadi; Harville, Emily W.; Myers, Leann; Buekens, Pierre; Breart, Gerard; Carles, Gabriel

    2014-01-01

    Background Dengue is a mosquito-borne disease that is common in many tropical and subtropical areas. Dengue infections can occur at any age and time in the lifespan, including during pregnancy. Few large scale studies have been conducted to determine the risk of preterm birth (PTB) and low birthweight (LBW) for infants born to women who had symptomatic dengue infection during pregnancy. Methodology/Principal Findings This study is a retrospective cohort study using medical records from 1992–2010 from pregnant women who attended a public regional referral hospital in western French Guiana. Exposed pregnancies were those with laboratory confirmed cases of dengue fever during pregnancy. Each of the 86 exposed infants was matched to the three unexposed births that immediately followed them to form a stratum. Conditional logistic regression was used to analyze these matched strata. Three groups were examined: all infants regardless of gestational age, only infants> = 17 weeks of gestational age and their strata, and only infants> = 22 weeks of age and their strata. Odds ratios were adjusted (aOR) for maternal age, maternal ethnicity, maternal gravidity, interpregnancy interval and maternal anemia. There was an increased risk of PTB among women with symptomatic dengue; (aOR all infants: 3.34 (1.13, 9.89), aOR 17 weeks: 1.89 (0.61, 5.87), aOR 22 weeks: 1.41 (0.39, 5.20)) but this risk was only statistically significant when all infants were examined (p value = 0.03). Adjusted results for LBW were similar, with an increased risk in the exposed group (aOR All infants: 2.23 (1.01, 4.90), aOR 17 weeks: 1.67 (0.71, 3.93), aOR 22 weeks: 1.43 (0.56, 3.70)) which was only statistically significant when all infants were examined (p value = 0.05). Conclusions/Significance Symptomatic dengue infection during pregnancy may increase the risk of PTB and LBW for infants. More research is needed to confirm these results and to examine the role of dengue fever in

  8. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection.

    PubMed

    Alagarasu, K; Walimbe, A M; Jadhav, S M; Deoshatwar, A R

    2016-03-01

    Immunoglobulin A (IgA)-based tests have been evaluated in different studies for their utility in diagnosing dengue infections. In most of the studies, the results were inconclusive because of a small sample size. Hence, a meta-analysis involving nine studies with 2096 samples was performed to assess the diagnostic accuracy of IgA-based tests in diagnosing dengue infections. The analysis was conducted using Meta-Disc software. The results revealed that IgA-based tests had an overall sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios of 73·9%, 95·2%, 66·7, 22·0 and 0·25, respectively. Significant heterogeneity was observed between the studies. The type of test, infection status and day of sample collection influenced the diagnostic accuracy. The IgA-based diagnostic tests showed a greater accuracy when the samples were collected 4 days after onset of symptoms and for secondary infections. The results suggested that IgA-based tests had a moderate level of accuracy and are diagnostic of the disease. However, negative results cannot be used alone for dengue diagnosis. More prospective studies comparing the diagnostic accuracy of combinations of antigen-based tests with either IgA or IgM are needed and might be useful for suggesting the best strategy for dengue diagnosis.

  9. Cytotoxic CD4 T Cells: Differentiation, Function, and Application to Dengue Virus Infection

    PubMed Central

    Tian, Yuan; Sette, Alessandro; Weiskopf, Daniela

    2016-01-01

    Dengue virus (DENV) has spread through most tropical and subtropical areas of the world and represents a serious public health problem. The control of DENV infection has not yet been fully successful due to lack of effective therapeutics or vaccines. Nevertheless, a better understanding of the immune responses against DENV infection may reveal new strategies for eliciting and improving antiviral immunity. T cells provide protective immunity against various viral infections by generating effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring pathogens. Following activation, CD8 T cells can migrate to sites of infection and kill infected cells, whereas CD4 T cells contribute to the elimination of pathogens by trafficking to infected tissues and providing help to innate immune responses, B cells, as well as CD8 T cells. However, it is now evident that CD4 T cells can also perform cytotoxic functions and induce the apoptosis of target cells. Importantly, accumulating studies demonstrate that cytotoxic CD4 T cells develop following DENV infections and may play a crucial role in protecting the host from severe dengue disease. We review our current understanding of the differentiation and function of cytotoxic CD4 T cells, with a focus on DENV infection, and discuss the potential of harnessing these cells for the prevention and treatment of DENV infection and disease. PMID:28003809

  10. Cytotoxic CD4 T Cells: Differentiation, Function, and Application to Dengue Virus Infection.

    PubMed

    Tian, Yuan; Sette, Alessandro; Weiskopf, Daniela

    2016-01-01

    Dengue virus (DENV) has spread through most tropical and subtropical areas of the world and represents a serious public health problem. The control of DENV infection has not yet been fully successful due to lack of effective therapeutics or vaccines. Nevertheless, a better understanding of the immune responses against DENV infection may reveal new strategies for eliciting and improving antiviral immunity. T cells provide protective immunity against various viral infections by generating effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring pathogens. Following activation, CD8 T cells can migrate to sites of infection and kill infected cells, whereas CD4 T cells contribute to the elimination of pathogens by trafficking to infected tissues and providing help to innate immune responses, B cells, as well as CD8 T cells. However, it is now evident that CD4 T cells can also perform cytotoxic functions and induce the apoptosis of target cells. Importantly, accumulating studies demonstrate that cytotoxic CD4 T cells develop following DENV infections and may play a crucial role in protecting the host from severe dengue disease. We review our current understanding of the differentiation and function of cytotoxic CD4 T cells, with a focus on DENV infection, and discuss the potential of harnessing these cells for the prevention and treatment of DENV infection and disease.

  11. Investigation of the First Case of Dengue Virus Infection Acquired in Western Australia in Seven Decades: Evidence of Importation of Infected Mosquitoes?

    PubMed Central

    McCarthy, Suzi; Whittle, Amanda; Lyttle, Heather; Harrington, Sue; Nicholson, Jay

    2015-01-01

    In October 2013, a locally-acquired case of dengue virus (DENV) infection was reported in Western Australia (WA) where local dengue transmission has not occurred for over 70 years. Laboratory testing confirmed recent DENV infection and the case demonstrated a clinically compatible illness. The infection was most likely acquired in the Pilbara region in the northwest of WA. Follow up investigations did not detect any other locally-acquired dengue cases or any known dengue vector species in the local region, despite intensive adult and larval mosquito surveillance, both immediately after the case was notified in October 2013 and after the start of the wet season in January 2014. The mechanism of infection with DENV in this case cannot be confirmed. However, it most likely followed a bite from a single infected mosquito vector that was transiently introduced into the Pilbara region but failed to establish a local breeding population. This case highlights the public health importance of maintaining surveillance efforts to ensure that any incursions of dengue vectors into WA are promptly identified and do not become established, particularly given the large numbers of viraemic dengue fever cases imported into WA by travellers returning from dengue-endemic regions. PMID:26406471

  12. Diagnosis of Chikungunya dominated co-infection with dengue during an outbreak in south India (2010 and 2012).

    PubMed

    Venkatasubramani, K; Paramasivan, R; Thenmozhi, V; Dhananjeyan, K J; Balaji, T; Leo, S Victor Jerald

    2015-07-01

    Following a report of dengue outbreak from January 2010 to 2012 in the Tirunelveli, Theni, Dharmapuri and Thiruvallur districts of Tamil Nadu state, India, an investigation was carried out. The study was to demonstrate the probable presence of Chikungunya viral antibodies in patients clinically suspected of dengue fever. Out of 331 samples analysed, dengue viral antibodies were observed in 14.8% (n = 49) of patients, while 16.6% (n = 55) were positive for Chikungunya viral specific IgM antibodies. In the four districts surveyed, patients found positive for Chikungunya were found to be higher than dengue. The clinician should consider Chikungunya in the differential diagnosis of dengue-like infection appearing in the community.

  13. Imported Dengue Infection in a Spanish Hospital with a High Proportion of Travelers from Africa: A 9-Year Retrospective Study.

    PubMed

    Toro, Carlos; Trevisi, Patricia; López-Quintana, Beatriz; Amor, Aránzazu; Iglesias, Nuria; Subirats, Mercedes; de Guevara, Concepción Ladrón; Lago, Mar; Arsuaga, Marta; de la Calle-Prieto, Fernando; Herrero, Dolores; Rubio, Margarita; Puente, Sabino; Baquero, Margarita

    2017-02-06

    Epidemiological data on dengue in Africa are still scarce. We investigated imported dengue infection among travelers with a high proportion of subjects from Africa over a 9-year period. From January 2005 to December 2013, blood samples from travelers with clinical suspicion of dengue were analyzed. Dengue was diagnosed using serological, antigen detection, and molecular methods. Subjects were classified according to birthplace (Europeans versus non-Europeans) and last country visited. Overall, 10,307 serum samples corresponding to 8,295 patients were studied; 62% were European travelers, most of them from Spain, and 35.9% were non-Europeans, the majority of whom were born in Africa (mainly Equatorial Guinea) and Latin America (mainly Bolivia, Ecuador, and Colombia). A total of 492 cases of dengue were identified, the highest number of cases corresponding to subjects who had traveled from Africa (N = 189), followed by Latin America (N = 174) and Asia (N = 113). The rate of cases for Africa (4.5%) was inferior to Asia (9%) and Latin America (6.1%). Three peaks of dengue were found (2007, 2010, and 2013) which correlated with African cases. A total of 2,157 of past dengue infections were diagnosed. Non-Europeans who had traveled from Africa had the highest rate of past infection (67.8%), compared with non-Europeans traveling from Latin America (38.7%) or Asia (35%). Dengue infection in certain regions of Africa is underreported and the burden of the disease may have a magnitude similar to endemic countries in Latin America. It is necessary to consider dengue in the differential diagnosis of other febrile diseases in Africa.

  14. Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?

    PubMed Central

    Arboleda, John F.; Urcuqui-Inchima, Silvio

    2016-01-01

    Over the last few years, an increasing body of evidence has highlighted the critical participation of vitamin D in the regulation of proinflammatory responses and protection against many infectious pathogens, including viruses. The activity of vitamin D is associated with microRNAs, which are fine tuners of immune activation pathways and provide novel mechanisms to avoid the damage that arises from excessive inflammatory responses. Severe symptoms of an ongoing dengue virus infection and disease are strongly related to highly altered production of proinflammatory mediators, suggesting impairment in homeostatic mechanisms that control the host's immune response. Here, we discuss the possible implications of emerging studies anticipating the biological effects of vitamin D and microRNAs during the inflammatory response, and we attempt to extrapolate these findings to dengue virus infection and to their potential use for disease management strategies. PMID:27293435

  15. Hypokalemic quadriparesis in dengue.

    PubMed

    Mishra, Vikas; Harbada, Rishit; Sharma, Akhilesh; Mishra, Meenakshi

    2015-01-01

    Dengue infection is the leading cause of illness and death in tropical and subtropical regions of the world. The common complications associated with dengue fever are usual hematological abnormalities, shock, and organ failure. The neurological complications of dengue are uncommon. However, evidence of dengue virus neurotropism and complications has been slowly but surely rising as seen from increased literature on this subject over the last decade. We report an uncommon case of hypokalemic quadriparesis with dengue that had a favorable outcome.

  16. Germinal Center Reaction Following Cutaneous Dengue Virus Infection in Immune-Competent Mice

    PubMed Central

    Yam-Puc, Juan Carlos; García-Cordero, Julio; Calderón-Amador, Juana; Donis-Maturano, Luis; Cedillo-Barrón, Leticia; Flores-Romo, Leopoldo

    2015-01-01

    Dengue virus (DENV) has four serotypes, which can cause from asymptomatic disease to severe dengue. Heterologous secondary infections have been associated to a greater risk of potentially fatal dengue due to non-neutralizing memory antibodies (Abs), which facilitate the infection, such as anti-precursor membrane (prM) Abs, among other mechanisms. Usually, class-switched memory Abs are generated mainly through germinal centers (GCs). However, the cellular events underlying these Ab responses to DENV, especially during repeated/secondary infections, have been poorly studied. We wanted to know whether there is involvement of GC reactions during cutaneous DENV infection and whether there is any sort of preferential Ab responses to defined viral proteins. Intradermal DENV inoculation at a relatively low dose efficiently infects immune-competent BALB/c mice, inducing higher quantities of DENV-specific GC B cells and larger GCs than the control conditions. Interestingly, GCs exhibited as much prM as envelope (E) and non-structural 3 viral proteins in situ. Intriguingly, despite the much larger abundance of E protein than of prM protein in the virions, infected animals showed similar amounts of circulating Abs and Ag-specific GC B cells both for prM and for E proteins, even significantly higher for prM. To the best of our knowledge, there are no reports of the GC responses during DENV infection. This relatively stronger anti-prM response could be triggered by DENV to preferentially promote Abs against certain viral proteins, which might favor infections by facilitating DENV invasion of host cells. It is thus conceivably that DENV might have evolved to induce this kind of Ab responses. PMID:25964784

  17. Dengue Epidemiology

    MedlinePlus

    ... Address What's this? Submit What's this? Submit Button ... fever (DF) is caused by any of four closely related viruses, or serotypes: dengue 1-4. Infection with one serotype does not protect against the ...

  18. Miscarriage following dengue virus 3 infection in the first six weeks of pregnancy of a dengue virus-naive traveller returning from Bali to Italy, April 2016

    PubMed Central

    Zavattoni, Maurizio; Rovida, Francesca; Campanini, Giulia; Percivalle, Elena; Sarasini, Antonella; Cristini, Graziella; Tomasoni, Lina Rachele; Castelli, Francesco; Baldanti, Fausto

    2016-01-01

    We report miscarriage following dengue virus (DENV)-3 infection in a pregnant woman returning from Bali to Italy in April 2016. On her arrival, the woman had fever, rash, asthenia and headache. DENV RNA was detected in plasma and urine samples collected the following day. Six days after symptom onset, she had a miscarriage. DENV RNA was detected in fetal material, but in utero fetal infection cannot be demonstrated due to possible contamination by maternal blood. PMID:27526349

  19. Miscarriage following dengue virus 3 infection in the first six weeks of pregnancy of a dengue virus-naive traveller returning from Bali to Italy, April 2016.

    PubMed

    Zavattoni, Maurizio; Rovida, Francesca; Campanini, Giulia; Percivalle, Elena; Sarasini, Antonella; Cristini, Graziella; Tomasoni, Lina Rachele; Castelli, Francesco; Baldanti, Fausto

    2016-08-04

    We report miscarriage following dengue virus (DENV)-3 infection in a pregnant woman returning from Bali to Italy in April 2016. On her arrival, the woman had fever, rash, asthenia and headache. DENV RNA was detected in plasma and urine samples collected the following day. Six days after symptom onset, she had a miscarriage. DENV RNA was detected in fetal material, but in utero fetal infection cannot be demonstrated due to possible contamination by maternal blood.

  20. Ongoing dengue epidemic - Angola, June 2013.

    PubMed

    2013-06-21

    On April 1, 2013, the Public Health Directorate of Angola announced that six cases of dengue had been reported to the Ministry of Health of Angola (MHA). As of May 31, a total of 517 suspected dengue cases had been reported and tested for dengue with a rapid diagnostic test (RDT). A total of 313 (60.5%) specimens tested positive for dengue, including one from a patient who died. All suspected cases were reported from Luanda Province, except for two from Malanje Province. Confirmatory diagnostic testing of 49 specimens (43 RDT-positive and six RDT-negative) at the CDC Dengue Branch confirmed dengue virus (DENV) infection in 100% of the RDT-positive specimens and 50% of the RDT-negative specimens. Only DENV-1 was detected by molecular diagnostic testing. Phylogenetic analysis indicated this virus has been circulating in the region since at least 1968, strongly suggesting that dengue is endemic in Angola. Health-care professionals throughout Angola should be aware of the ongoing epidemic, the recommended practices for clinical management of dengue patients, and the need to report cases to MHA. Persons in Angola should seek medical care for acute febrile illness to reduce the risk for developing complications. Laboratory-confirmed dengue also has been reported from seven countries on four continents among persons who had recently traveled to Luanda, including 79 persons from Portugal. Angola is the third of four African countries to report a dengue outbreak in 2013. Persons returning from Africa with acute febrile illness should seek medical care, including testing for DENV infection, and suspected cases should be reported to public health authorities.

  1. Dendritic Cells in Dengue Virus Infection: Targets of Virus Replication and Mediators of Immunity

    PubMed Central

    Schmid, Michael A.; Diamond, Michael S.; Harris, Eva

    2014-01-01

    Dendritic cells (DCs) are sentinels of the immune system and detect pathogens at sites of entry, such as the skin. In addition to the ability of DCs to control infections directly via their innate immune functions, DCs help to prime adaptive B- and T-cell responses by processing and presenting antigen in lymphoid tissues. Infected Aedes aegypti or Aedes albopictus mosquitoes transmit the four dengue virus (DENV) serotypes to humans while probing for small blood vessels in the skin. DENV causes the most prevalent arthropod-borne viral disease in humans, yet no vaccine or specific therapeutic is currently licensed. Although primary DENV infection confers life-long protective immunity against re-infection with the same DENV serotype, secondary infection with a different DENV serotype can lead to increased disease severity via cross-reactive T-cells or enhancing antibodies. This review summarizes recent findings in humans and animal models about DENV infection of DCs, monocytes, and macrophages. We discuss the dual role of DCs as both targets of DENV replication and mediators of innate and adaptive immunity, and summarize immune evasion strategies whereby DENV impairs the function of infected DCs. We suggest that DCs play a key role in priming DENV-specific neutralizing or potentially harmful memory B- and T-cell responses, and that future DC-directed therapies may help induce protective memory responses and reduce dengue pathogenesis. PMID:25566258

  2. Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever

    PubMed Central

    Chanthick, Chanettee; Kanlaya, Rattiyaporn; Kiatbumrung, Rattanaporn; Pattanakitsakul, Sa-nga; Thongboonkerd, Visith

    2016-01-01

    Vascular leakage is a life-threatening complication of dengue virus (DENV) infection. Previously, association between “paracellular” endothelial hyperpermeability and plasma leakage had been extensively investigated. However, whether “transcellular” endothelial leakage is involved in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) remained unknown. We thus investigated effects of DENV (serotype 2) infection on transcellular transport of albumin, the main oncotic plasma protein, through human endothelial cell monolayer by Western blotting, immunofluorescence staining, fluorescence imaging, and fluorometry. The data showed that Alexa488-conjugated bovine serum albumin (Alexa488-BSA) was detectable inside DENV2-infected cells and its level was progressively increased during 48-h post-infection. While paracellular transport could be excluded using FITC-conjugated dextran, Alexa488-BSA was progressively increased and decreased in lower and upper chambers of Transwell, respectively. Pretreatment with nystatin, an inhibitor of caveolae-dependent endocytic pathway, significantly decreased albumin internalization into the DENV2-infected cells, whereas inhibitors of other endocytic pathways showed no significant effects. Co-localization of the internalized Alexa488-BSA and caveolin-1 was also observed. Our findings indicate that DENV infection enhances caveolae-mediated albumin transcytosis through human endothelial cells that may ultimately induce plasma leakage from intravascular compartment. Further elucidation of this model in vivo may lead to effective prevention and better therapeutic outcome of DHF/DSS. PMID:27546060

  3. Stress and acute respiratory infection

    SciTech Connect

    Graham, N.M.; Douglas, R.M.; Ryan, P.

    1986-09-01

    To examine the relationship between stress and upper respiratory tract infection, 235 adults aged 14-57 years, from 94 families affiliated with three suburban family physicians in Adelaide, South Australia, participated in a six-month prospective study. High and low stress groups were identified by median splits of data collected from the Life Events Inventory, the Daily Hassles Scale, and the General Health Questionnaire, which were administered both before and during the six months of respiratory diary data collection. Using intra-study stress data, the high stress group experienced significantly more episodes (mean of 2.71 vs. 1.56, p less than 0.0005) and symptom days (mean of 29.43 vs. 15.42, p = 0.005) of respiratory illness. The two groups were almost identical with respect to age, sex, occupational status, smoking, passive smoking, exposure to air pollution, family size, and proneness to acute respiratory infection in childhood. In a multivariate model with total respiratory episodes as the dependent variable, 21% of the variance was explained, and two stress variables accounted for 9% of the explained variance. Significant, but less strong relationships were also identified between intra-study stress variables and clinically definite episodes and symptom days in both clinically definite and total respiratory episodes. Pre-study measures of stress emphasized chronic stresses and were less strongly related to measures of respiratory illness than those collected during the study. However, significantly more episodes (mean of 2.50 vs. 1.75, p less than 0.02) and symptom days (mean of 28.00 vs. 17.06, p less than 0.03) were experienced in the high stress group. In the multivariate analyses, pre-study stress remained significantly associated with total respiratory episodes nd symptom days in total and ''definite'' respiratory episodes.

  4. Retrospective analysis of prognostic factors in dengue infected patients with intracranial bleed

    PubMed Central

    Gautam, Sachidanand; Meena, Rajesh K.; Meena, Shyam C.; Gautam, Bhawana

    2016-01-01

    Background: Dengue is one of the most common mosquito-transmitted arboviral disease of tropical and a few subtropical areas in the world. It is estimated that approximately 100 million cases occur per year and approximately 2.5 billion people are at risk of developing dengue infection. Hemorrhagic complications causing encephalopathy are quite rare but fatal consequences of this deadly disease. This study was conducted to discuss the prognostic factors in the management of intracranial hemorrhage in dengue infected patients. Methods: This retrospective study was conducted in the neurosurgery department of our tertiary healthcare centre. Duration of the study was 1 year, and 18 patients who presented with intracranial bleed and required neurosurgical care were included in this study. All patients had deranged coagulation profile and were thrombocytopenic. All the patients were given platelet concentrates for correction of thrombocytopenia. Eight of these patients had deterioration in their neurological status, and 6 of them underwent surgery. Results: Out of 18 patients, 12 (66.66%) were managed conservatively, including one case of cervical extradural hemorrhage. Five patients who were conservatively managed died because they had deep-seated bleed and rapid deterioration. The remaining 7 patients who were managed conservatively improved well with few residual deficits. Six (33.33%) patients who underwent surgery had excellent outcome with one case of mortality. Conclusion: Very high index of suspicion is required in dengue infected patients for neurological complications, especially during the convalescence period. Special attention should be given to those patients who have altered sensorium, and should not be misinterpreted as fever delirium or toxic encephalopathy. It requires immediate attention and further neurological investigation (including thorough clinical examination). Timely diagnosis using a computed tomography scan and early neurosurgical intervention

  5. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    PubMed

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

  6. Discovery and Validation of Prognostic Biomarker Models to Guide Triage among Adult Dengue Patients at Early Infection

    PubMed Central

    Tolfvenstam, Thomas; Thein, Tun-Linn; Naim, Ahmad Nazri Mohamed; Ling, Ling; Chow, Angelia; Chen, Mark I-Cheng; Ooi, Eng Eong; Leo, Yee Sin; Hibberd, Martin L.

    2016-01-01

    Background Dengue results in a significant public health burden in endemic regions. The World Health Organization (WHO) recommended the use of warning signs (WS) to stratify patients at risk of severe dengue disease in 2009. However, WS is limited in stratifying adult dengue patients at early infection (Day 1–3 post fever), who require close monitoring in hospitals to prevent severe dengue. The aim of this study is to identify and validate prognostic models, built with differentially expressed biomarkers, that enable the early identification of those with early dengue infection that require close clinical monitoring. Methods RNA microarray and protein assays were performed to identify differentially expressed biomarkers of severity among 92 adult dengue patients recruited at early infection from years 2005–2008. This comprised 47 cases who developed WS after first presentation and required hospitalization (WS+Hosp), as well as 45 controls who did not develop WS after first presentation and did not require hospitalization (Non-WS+Non-Hosp). Independent validation was conducted with 80 adult dengue patients recruited from years 2009–2012. Prognostic models were developed based on forward stepwise and backward elimination estimation, using multiple logistic regressions. Prognostic power was estimated by the area under the receiver operating characteristic curve (AUC). Results The WS+Hosp group had significantly higher viral load (P<0.001), lower platelet (P<0.001) and lymphocytes counts (P = 0.004) at early infection compared to the Non-WS+Non-Hosp group. From the RNA microarray and protein assays, the top single RNA and protein prognostic models at early infection were CCL8 RNA (AUC:0.73) and IP-10 protein (AUC:0.74), respectively. The model with CCL8, VPS13C RNA, uPAR protein, and with CCL8, VPS13C RNA and platelets were the best biomarker models for stratifying adult dengue patients at early infection, with sensitivity and specificity up to 83% and 84

  7. Mapping the Human Memory B Cell and Serum Neutralizing Antibody Responses to Dengue Virus Serotype 4 Infection and Vaccination.

    PubMed

    Nivarthi, Usha K; Kose, Nurgun; Sapparapu, Gopal; Widman, Douglas; Gallichotte, Emily; Pfaff, Jennifer M; Doranz, Benjamin J; Weiskopf, Daniela; Sette, Alessandro; Durbin, Anna P; Whitehead, Steve S; Baric, Ralph; Crowe, James E; de Silva, Aravinda M

    2017-03-01

    The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses responsible for dengue fever and dengue hemorrhagic fever. People exposed to DENV develop antibodies (Abs) that strongly neutralize the serotype responsible for infection. Historically, infection with DENV serotype 4 (DENV4) has been less common and less studied than infections with the other three serotypes. However, DENV4 has been responsible for recent large and sustained epidemics in Asia and Latin America. The neutralizing antibody responses and the epitopes targeted against DENV4 have not been characterized in human infection. In this study, we mapped and characterized epitopes on DENV4 recognized by neutralizing antibodies in people previously exposed to DENV4 infections or to a live attenuated DENV4 vaccine. To study the fine specificity of DENV4 neutralizing human antibodies, B cells from two people exposed to DENV4 were immortalized and screened to identify DENV-specific clones. Two human monoclonal antibodies (MAbs) that neutralized DENV4 were isolated, and their epitopes were finely mapped using recombinant viruses and alanine scan mutation array techniques. Both antibodies bound to quaternary structure epitopes near the hinge region between envelope protein domain I (EDI) and EDII. In parallel, to characterize the serum neutralizing antibody responses, convalescence-phase serum samples from people previously exposed to primary DENV4 natural infections or a monovalent DENV4 vaccine were analyzed. Natural infection and vaccination also induced serum-neutralizing antibodies that targeted similar epitope domains at the EDI/II hinge region. These studies defined a target of neutralizing antigenic site on DENV4 targeted by human antibodies following natural infection or vaccination.IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever and dengue hemorrhagic fever. People exposed to primary DENV infections develop long-term neutralizing antibody responses

  8. Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

    PubMed Central

    Halsey, Eric S.; Marks, Morgan A.; Gotuzzo, Eduardo; Fiestas, Victor; Suarez, Luis; Vargas, Jorge; Aguayo, Nicolas; Madrid, Cesar; Vimos, Carlos; Kochel, Tadeusz J.; Laguna-Torres, V. Alberto

    2012-01-01

    Background Disease caused by the dengue virus (DENV) is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype. Methodology and Principal Findings Between the years 2005–2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%), DENV-2 (4.3%), DENV-3 (41.5%), or DENV-4 (14.4%). When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations. Conclusions/Significance Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype. PMID:22563516

  9. Lactate based optical screening of dengue virus infection in human sera using Raman spectroscopy

    PubMed Central

    Bilal, Muhammad; Ullah, Rahat; Khan, Saranjam; Ali, Hina; Saleem, Muhammad; Ahmed, Mushtaq

    2017-01-01

    This study presents the screening of dengue virus (DENV) infection in human blood sera based on lactate concentration using Raman spectroscopy. A total of 70 samples, 50 from confirmed DENV infected patients and 20 from healthy volunteers have been used in this study. Raman spectra of all these samples have been acquired in the spectral range from 600 cm−1 to 1800 cm−1 using a 532 nm laser as an excitation source. Spectra of all these samples have been analyzed for assessing the biochemical changes resulting from infection. In DENV infected samples three prominent Raman peaks have been found at 750, 830 and 1450 cm−1. These peaks are most probably attributed to an elevated level of lactate due to an impaired function of different body organs in dengue infected patients. This has been proven by an addition of lactic acid solution to the healthy serum in a controlled manner. By the addition of lactic acid solution, the intense Raman bands at 1003, 1156 and 1516 cm−1 found in the spectrum of healthy serum got suppressed when the new peaks appeared around 750, 830, 925, 950, 1123, 1333, 1450, 1580 and 1730 cm−1. The current study predicts that lactate may possibly be a potential biomarker for the diagnosis of DENV infection. PMID:28271015

  10. Seroepidemiology of dengue virus infection in the adult population in tropical Singapore.

    PubMed

    Ang, L W; Cutter, J; James, L; Goh, K T

    2015-06-01

    To assess the impact of past dengue epidemics in Singapore, we undertook a national seroepidemiological study to determine the prevalence of past dengue virus (DENV) infection in the adult population in 2010 and make comparisons with the seroprevalence in 2004. The study involved residual sera from 3293 adults aged 18-79 years who participated in a national health survey in 2010. The overall prevalence of anti-DENV IgG antibodies was 56·8% (95% confidence interval 55·1-58·5) in 2010. The seroprevalence increased significantly with age. Males had significantly higher seroprevalence than females (61·5% vs. 53·2%). Among the three major ethnic groups, Malays had the lowest seroprevalence (50·2%) compared to Chinese (57·0%) and Indians (62·0%). The age-standardized seroprevalence in adults was significantly lower in 2010 (54·4%) compared to 2004 (63·1%). Older age, male gender, Indian ethnicity, permanent residency and being home-bound were independent risk factors significantly associated with seropositivity. About 43% of the Singapore adult resident population remain susceptible to DENV infection as a result of the successful implementation of a comprehensive nationwide Aedes surveillance and control programme since the 1970s. Vector suppression and concerted efforts of all stakeholders in the community remain the key strategy in the prevention and control of dengue.

  11. Prospective Cohort Study with Active Surveillance for Fever in Four Dengue Endemic Countries in Latin America

    PubMed Central

    Dayan, Gustavo; Arredondo, Jose L.; Carrasquilla, Gabriel; Deseda, Carmen C.; Dietze, Reynaldo; Luz, Kleber; Costa, Maria Selma N.; Cunha, Rivaldo V.; Rey, Luis C.; Morales, Javier; Reynales, Humberto; Miranda, Maria; Zambrano, Betzana; Rivas, Enrique; Garbes, Pedro; Noriega, Fernando

    2015-01-01

    To prepare for a Phase III dengue vaccine efficacy trial, 20 investigational sites were selected for this observational study to identify dengue infections in a closed cohort (N = 3,000 children 9–16 years of age). Of 255 acute febrile episodes experienced by 235 children, 50 (21.3%) were considered serologically probable dengue, and 18 (7.7%) were considered virologically confirmed (i.e., dengue NS1 antigen positive) dengue cases. Considering the disease-free and at-risk period from study start to onset of symptoms, the overall incidence density of acute febrile episodes was 17.7 per 100 person-years of follow-up, ranging from 15.3 in Colombia to 22.0 in Puerto Rico. This study showed that all sites were capable of capturing and following up acute febrile episodes within a specific timeframe among the established cohort and to detect dengue cases. PMID:26013373

  12. Prospective cohort study with active surveillance for fever in four dengue endemic countries in Latin America.

    PubMed

    Dayan, Gustavo; Arredondo, Jose L; Carrasquilla, Gabriel; Deseda, Carmen C; Dietze, Reynaldo; Luz, Kleber; Costa, Maria Selma N; Cunha, Rivaldo V; Rey, Luis C; Morales, Javier; Reynales, Humberto; Miranda, Maria; Zambrano, Betzana; Rivas, Enrique; Garbes, Pedro; Noriega, Fernando

    2015-07-01

    To prepare for a Phase III dengue vaccine efficacy trial, 20 investigational sites were selected for this observational study to identify dengue infections in a closed cohort (N = 3,000 children 9-16 years of age). Of 255 acute febrile episodes experienced by 235 children, 50 (21.3%) were considered serologically probable dengue, and 18 (7.7%) were considered virologically confirmed (i.e., dengue NS1 antigen positive) dengue cases. Considering the disease-free and at-risk period from study start to onset of symptoms, the overall incidence density of acute febrile episodes was 17.7 per 100 person-years of follow-up, ranging from 15.3 in Colombia to 22.0 in Puerto Rico. This study showed that all sites were capable of capturing and following up acute febrile episodes within a specific timeframe among the established cohort and to detect dengue cases.

  13. Analysis of Murine CD8+ T-Cell Clones Specific for the Dengue Virus NS3 Protein: Flavivirus Cross-Reactivity and Influence of Infecting Serotype

    PubMed Central

    Spaulding, Anne C.; Kurane, Ichiro; Ennis, Francis A.; Rothman, Alan L.

    1999-01-01

    Serotype-cross-reactive dengue virus-specific cytotoxic T lymphocytes (CTL) induced during a primary dengue virus infection are thought to play a role in the immunopathogenesis of dengue hemorrhagic fever (DHF) during a secondary dengue virus infection. Although there is no animal model of DHF, we previously reported that murine dengue virus-specific CTL responses are qualitatively similar to human dengue virus-specific CTL responses. We used BALB/c mice to study the specificity of the CTL response to an immunodominant epitope on the dengue virus NS3 protein. We mapped the minimal H-2Kd-restricted CTL epitope to residues 298 to 306 of the dengue type 2 virus NS3 protein. In short-term T-cell lines and clones, the predominant CD8+ CTL to this epitope in mice immunized with dengue type 2 virus or vaccinia virus expressing the dengue type 4 virus NS3 protein were cross-reactive with dengue type 2 or type 4 virus, while broadly serotype-cross-reactive CTL were a minority population. In dengue type 3 virus-immunized mice, the predominant CTL response to this epitope was broadly serotype cross-reactive. All of the dengue virus-specific CTL clones studied also recognized the homologous NS3 sequences of one or more closely related flaviviruses, such as Kunjin virus. The critical contact residues for the CTL clones with different specificities were mapped with peptides having single amino acid substitutions. These data demonstrate that primary dengue virus infection induces a complex population of flavivirus-cross-reactive NS3-specific CTL clones in mice and suggest that CTL responses are influenced by the viral serotype. These findings suggest an additional mechanism by which the order of sequential flavivirus infections may influence disease manifestations. PMID:9847344

  14. Current Therapy in Acute Mouth Infections

    ERIC Educational Resources Information Center

    Goldfarb, George; Burnstein, Irwin L.

    1970-01-01

    Until a dental department is added to a college health service, a physician or nurse can give treatment for acute oral infections. Treatment excludes the use of caustic, escharotic chemicals in favor of more benign agents. (Author)

  15. Sero-prevalence of dengue infections in the Kassala state in the eastern part of the Sudan in 2011.

    PubMed

    Himatt, Sayed; Osman, Kamal E; Okoued, Somia I; Seidahmed, Osama E; Beatty, Mark E; Soghaier, Mohammed A; Elmusharaf, Khalifa

    2015-01-01

    Dengue fever is a vector-borne disease that is transmitted to humans by infected Aedes aegypti mosquitoes. The eastern part of the Sudan is one of the regions that is affected by dengue virus circulation. In this study, we estimated the prevalence of dengue infections in the Kassala state in the eastern part of the Sudan. The study objective was to estimate the sero-prevalence of dengue IgG/IgM antibodies in the Kassala locality in 2011. This was a cross sectional community-based study that utilized a multi-stage cluster sampling technique regarding the probability sampling the study participants. Capture ELISA serological techniques were used for both IgM and IgG, with the specific cut-offs for each set by the manufacturer. The prevalence of dengue infection was found to be 9.4% (95% CI: 7.1-12.3). In conclusion, there is evidence that the dengue virus is being transmitted in Kassala. Disease surveillance, including the clinical, serological and entomological components, should be strengthened, and additional epidemiological studies are needed to better understand of the disease burden and effects in the area.

  16. Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients from India

    PubMed Central

    Chandele, Anmol; Sewatanon, Jaturong; Gunisetty, Sivaram; Singla, Mohit; Onlamoon, Nattawat; Akondy, Rama S.; Kissick, Haydn Thomas; Nayak, Kaustuv; Reddy, Elluri Seetharami; Kalam, Haroon; Kumar, Dhiraj; Verma, Anil; Panda, HareKrushna; Wang, Siyu; Angkasekwinai, Nasikarn; Pattanapanyasat, Kovit; Chokephaibulkit, Kulkanya; Lodha, Rakesh; Kabra, Sushil; Ahmed, Rafi

    2016-01-01

    ABSTRACT Epidemiological studies suggest that India has the largest number of dengue virus infection cases worldwide. However, there is minimal information about the immunological responses in these patients. CD8 T cells are important in dengue, because they have been implicated in both protection and immunopathology. Here, we provide a detailed analysis of HLA-DR+ CD38+ and HLA-DR− CD38+ effector CD8 T cell subsets in dengue patients from India and Thailand. Both CD8 T cell subsets expanded and expressed markers indicative of antigen-driven proliferation, tissue homing, and cytotoxic effector functions, with the HLA-DR+ CD38+ subset being the most striking in these effector qualities. The breadth of the dengue-specific CD8 T cell response was diverse, with NS3-specific cells being the most dominant. Interestingly, only a small fraction of these activated effector CD8 T cells produced gamma interferon (IFN-γ) when stimulated with dengue virus peptide pools. Transcriptomics revealed downregulation of key molecules involved in T cell receptor (TCR) signaling. Consistent with this, the majority of these CD8 T cells remained IFN-γ unresponsive even after TCR-dependent polyclonal stimulation (anti-CD3 plus anti-CD28) but produced IFN-γ by TCR-independent polyclonal stimulation (phorbol 12-myristate 13-acetate [PMA] plus ionomycin). Thus, the vast majority of these proliferating, highly differentiated effector CD8 T cells probably acquire TCR refractoriness at the time the patient is experiencing febrile illness that leads to IFN-γ unresponsiveness. Our studies open novel avenues for understanding the mechanisms that fine-tune the balance between CD8 T cell-mediated protective versus pathological effects in dengue. IMPORTANCE Dengue is becoming a global public health concern. Although CD8 T cells have been implicated both in protection and in the cytokine-mediated immunopathology of dengue, how the balance is maintained between these opposing functions remains

  17. Dengue virus serotype 2 infection alters midgut and carcass gene expression in the Asian tiger mosquito, Aedes albopictus

    PubMed Central

    Hanley, Kathryn A.; Sundararajan, Anitha; Devitt, Nicholas P.; Schilkey, Faye D.; Hansen, Immo A.

    2017-01-01

    Background The Asian tiger mosquito, Aedes albopictus is currently an important vector for dengue, chikungunya and Zika virus, and its role in transmission of arthropod-borne viruses (arboviruses) may increase in the future due to its ability to colonize temperate regions. In contrast to Aedes aegypti, the dominant vector of dengue, chikungunya and Zika virus, genetic responses of Ae. albopictus upon infection with an arbovirus are not well characterized. Here we present a study of the changes in transcript expression in Ae. albopictus exposed to dengue virus serotype 2 via feeding on an artificial bloodmeal. Methodology/Principal findings We isolated midguts and midgut-free carcasses of Ae. albopictus fed on bloodmeals containing dengue virus as well as controls fed on virus-free control meals at day 1 and day 5 post-feeding. We confirmed infection of midguts from mosquitoes sampled on day 5 post-feeding via RT-PCR. RNAseq analysis revealed dynamic modulation of the expression of several putative immunity and dengue virus-responsive genes, some of whose expression was verified by qRT-PCR. For example, a serine protease gene was up-regulated in the midgut at 1 day post infection, which may potentially enhance mosquito susceptibility to dengue infection, while 14 leucine-rich repeat genes, previously shown to be involved in mosquito antiviral defenses, were down-regulated in the carcass at 5 days post infection. The number of significantly modulated genes decreased over time in midguts and increased in carcasses. Conclusion/Significance Dengue virus exposure results in the modulation of genes in a time- and site-specific manner. Previous literature on the interaction between mosquitoes and mosquito-borne pathogens suggests that most of the changes that occurred in Ae. albopictus exposed to DENV would favor virus infection. Many genes identified in this study warrant further characterization to understand their role in viral manipulation of and antiviral response of

  18. A two-dimensional simulation of plasma leakage due to dengue infection

    NASA Astrophysics Data System (ADS)

    Nuraini, N.; Windarto, Jayanti, Swarna; Soewono, Edy

    2014-03-01

    Dengue Hemorrhagic Fever (DHF) is a disease caused by Dengue virus infection. One major characteristic in a patient with DHF is the occurrence of plasma leakage. Plasma leakage is a consequence of the immune system mechanism which activates cytokine. As a result, permeability of vascular will increase. Another characteristic in a DHF patient is hypoalbuminea (decreasing of albumin concentration). Plasma leakage can be modelled by constructing mathematical model of albumin concentration in plasma blood due to increasing of cytokine. In this paper, decreasing of albumin concentration in blood plasma is modelled using diffusion equation. In addition, two-dimensional numerical simulations of albumin concentration are also presented. From the simulation, it is found that the greater leakage rate or the wider leakage area, the greater decreasing albumin concentration will be. Furthermore, when time t increases, the albumin concentration decreases to zero.

  19. Limiting influenza virus, HIV and dengue virus infection by targeting viral proteostasis

    PubMed Central

    Heaton, Nicholas S.; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J.; Aguirre, Sebastian; Shah, Priya S.; Zhao, Nan; Manganaro, Lara; Hultquist, Judd; Noel, Justine; Sachs, David; Hamilton, Jennifer; Leon, Paul E.; Chawdury, Amit; Tripathy, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V.; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan; Mulder, Lubbertus C.F.; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-01

    Viruses are obligate parasites as they require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy to suppress viral replication and a potential pan antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling, genetic, and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses, and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication we have identified targetable host factors for broad-spectrum antiviral therapies. PMID:26789921

  20. Transstadial Effects of Bti on Traits of Aedes aegypti and Infection with Dengue Virus

    PubMed Central

    Alto, Barry W.; Lord, Cynthia C.

    2016-01-01

    Most mosquito control efforts are primarily focused on reducing the adult population size mediated by reductions in the larval population, which should lower risk of disease transmission. Although the aim of larviciding is to reduce larval abundance and thus recruitment of adults, nonlethal effects on adults are possible, including transstadial effects on phenotypes of adults such as survival and pathogen infection and transmission. In addition, the mortality induced by control efforts may act in conjunction with other sources of mosquito mortality in nature. The consequences of these effects and interactions may alter the potential of the population to transmit pathogens. We tested experimentally the combined effects of a larvicide (Bacillus thuringiensis ssp. israelensis, Bti) and competition during the larval stages on subsequent Aedes aegypti (Linnaeus) traits, population performance, and susceptibility to dengue-1 virus infection. Ae. aegypti that survived exposure to Bti experienced accelerated development, were larger, and produced more eggs with increasing amounts of Bti, consistent with competitive release among surviving mosquitoes. Changing larval density had no significant interactive effect with Bti treatment on development and growth to adulthood. Larval density, but not Bti or treatment interaction, had a strong effect on survival of adult Ae. aegypti females. There were sharper declines in cumulative daily survival of adults from crowded than uncrowded larval conditions, suggesting that high competition conditions of larvae may be an impediment to transmission of dengue viruses. Rates of infection and dengue-1 virus disseminated infections were found to be 87±13% and 88±12%, respectively. There were no significant treatment effects on infection measurements. Our findings suggest that larvicide campaigns using Bti may reduce the number of emerged adults, but survivors will have a fitness advantage (growth, development, enhanced production of eggs

  1. Larval Temperature–Food Effects on Adult Mosquito Infection and Vertical Transmission of Dengue-1 Virus

    PubMed Central

    Buckner, Eva A.; Alto, Barry W.; Lounibos, L. Philip

    2016-01-01

    Temperature–food interactions in the larval environment can affect life history and population growth of container mosquitoes Aedes aegypti (L.) and Aedes albopictus Skuse, the primary vectors of chikungunya and dengue viruses. We used Ae. aegypti, Ae. albopictus, and dengue-1 virus (DENV-1) from Florida to investigate whether larval rearing temperature can alter the effects of larval food levels on Ae. aegypti and Ae. albopictus life history and DENV-1 infection and vertical transmission. Although we found no effect of larval treatments on survivorship to adulthood, DENV-1 titer, or DENV-1 vertical transmission, rates of vertical transmission up to 16–24% were observed in Ae. albopictus and Ae. aegypti, which may contribute to maintenance of this virus in nature. Larval treatments had no effect on number of progeny and DENV-1 infection in Ae. aegypti, but the interaction between temperature and food affected number of progeny and DENV-1 infection of the female Ae. albopictus parent. The cooler temperature (24°C) yielded the most progeny and this effect was accentuated by high food relative to the other conditions. Low and high food led to the highest (∼90%) and lowest (∼65%) parental infection at the cooler temperature, respectively, whereas intermediate infection rates (∼75–80%) were observed for all food conditions at the elevated temperature. These results suggest that temperature and food availability have minimal influence on rate of vertical transmission and a stronger influence on adults of Ae. albopictus than of Ae. aegypti, which could have consequences for dengue virus epidemiology. PMID:26489999

  2. Dengue and hepatitis E virus infection in pregnant women in Eastern Sudan, a challenge for diagnosis in an endemic area.

    PubMed

    Elduma, Adel Hussein; Osman, Waleed Mohammed

    2014-01-01

    Dengue fever and hepatitis E virus infection are both a public health problem in developing countries due to poor sanitation. Infection with viral hepatitis and dengue fever can present with similar clinical such and fever, headache and abortion. This study was conducted in Port-Sudan city in the eastern part of the country. ELISA and Real Time PCR tests were used to detect the infection. A total number of 39 pregnant women with a mean age 26 ±7.8 were included in the study. All of them had fever, 32 (92.3%) admitted with headache, 11 (28.2%) of them had vomiting, and abortion was reported in two cases (5.1%). The study showed that 4 (10.3%) of pregnant women were positive for the Hepatitis E virus, 5 (12.8%) positive for Dengue virus IgG, and only one sample (2.6%) was positive for IgM capture ELISA and real time PCR. Death due to hepatitis E infection was reported in one case with 7(th) month of pregnancy. Most of hepatitis cases were reported in the central sector of the Portsudan city. The diagnosis of hepatitis E virus and dengue virus in an endemic area is a great challenge for health care staff working in these areas. Both Dengue virus and Hepatitis E virus infection should be considered in pregnant women especially in similar settings.

  3. Natural transovarial dengue virus infection rate in both sexes of dark and pale forms of Aedes aegypti from an urban area of Bangkok, Thailand.

    PubMed

    Thongrungkiat, Supatra; Wasinpiyamongkol, Ladawan; Maneekan, Pannamas; Prummongkol, Samrerng; Samung, Yudthana

    2012-09-01

    Transovarial dengue virus infection status of two forms of adult Aedes aegypti (dark or Ae. aegypti type form and pale or form queenslandensis), reared from field-collected larval and pupal stages, was determined by one-step RT-PCR and dengue viral serotype by nested-PCR. Natural transovarial transmission (TOT) of dengue virus was detected in the two Ae. aegypti forms, and in both adult males and females. Male Ae. aegypti had a higher rate of TOT dengue virus infection than female. The overall minimum infection rate among the male and female populations was 19.5 and 12.3 per 1,000 mosquitoes, respectively. All four dengue serotypes were detected in mosquito samples, with DEN-4 being the predominant serotype. Thus, both male and female Ae. aegypti have influences on the epidemiology of dengue virus transmission.

  4. Transmission of dengue virus without a mosquito vector: nosocomial mucocutaneous transmission and other routes of transmission.

    PubMed

    Chen, Lin H; Wilson, Mary E

    2004-09-15

    We report a case of dengue fever in a Boston-area health care worker with no recent history of travel but with mucocutaneous exposure to infected blood from a febrile traveler who had recently returned from Peru. Serologic tests confirmed acute dengue virus infection in both the traveler and the health care worker. We believe that this is the first documented case of dengue virus transmission via the mucocutaneous route. We present case reports and review other ways that dengue virus has been transmitted without a mosquito vector.

  5. Dengue fever as an acute febrile disease after overseas travel: a report of two cases.

    PubMed

    Tarumoto, Norihito; Abe, Yoshinobu; Yamaguchi, Toshiyuki; Takasaki, Tomohiko; Kurane, Ichiro; Maesaki, Shigefumi

    2011-01-01

    Dengue fever (DF) is a relatively common infection in travelers, with about 100 cases being reported annually in Japan, and this number is increasing. We herein describe two patients who developed a fever after returning to Japan from Southeast Asia and who were serologically diagnosed with DF. Patient 1 was a 19-year-old man who spent 6 days in Thailand and developed diarrhea and a fever after returning to Japan. Virological studies showed dengue virus (DV) serotype 3 by reverse transcriptase PCR (RT-PCR), and anti-DV IgM and IgG antibodies were both positive by enzyme-linked immunosorbent assay (ELISA). Patient 2 was a 43-year-old man who spent time in various Asian countries and developed a fever and arthralgia after returning to Japan. Virological studies showed DV serotype 2 by RT-PCR, and anti-DV IgM and IgG antibodies were both positive by ELISA. DF and other febrile diseases, including Chikungunya fever, should be strongly suspected in patients who develop fever after returning to Japan from other Asian countries, irrespective of whether patients remember being bitten by mosquitoes.

  6. Time-varying, serotype-specific force of infection of dengue virus.

    PubMed

    Reiner, Robert C; Stoddard, Steven T; Forshey, Brett M; King, Aaron A; Ellis, Alicia M; Lloyd, Alun L; Long, Kanya C; Rocha, Claudio; Vilcarromero, Stalin; Astete, Helvio; Bazan, Isabel; Lenhart, Audrey; Vazquez-Prokopec, Gonzalo M; Paz-Soldan, Valerie A; McCall, Philip J; Kitron, Uriel; Elder, John P; Halsey, Eric S; Morrison, Amy C; Kochel, Tadeusz J; Scott, Thomas W

    2014-07-01

    Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission parameters such as the force of infection (FoI), which is the per-capita risk of a susceptible person being infected. The FoI captures the fundamental dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne, multiserotype pathogen that currently infects ∼390 million people a year. Existing estimates of the DENV FoI are inaccurate because they rely on the unrealistic assumption that risk is constant over time. Dengue models are thus unreliable for designing vaccine deployment strategies. Here, we present to our knowledge the first time-varying (daily), serotype-specific estimates of DENV FoIs using a spline-based fitting procedure designed to examine a 12-y, longitudinal DENV serological dataset from Iquitos, Peru (11,703 individuals, 38,416 samples, and 22,301 serotype-specific DENV infections from 1999 to 2010). The yearly DENV FoI varied markedly across time and serotypes (0-0.33), as did daily basic reproductive numbers (0.49-4.72). During specific time periods, the FoI fluctuations correlated across serotypes, indicating that different DENV serotypes shared common transmission drivers. The marked variation in transmission intensity that we detected indicates that intervention targets based on one-time estimates of the FoI could underestimate the level of effort needed to prevent disease. Our description of dengue virus transmission dynamics is unprecedented in detail, providing a basis for understanding the persistence of this rapidly emerging pathogen and improving disease prevention programs.

  7. Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity.

    PubMed

    Weiskopf, Daniela; Bangs, Derek J; Sidney, John; Kolla, Ravi V; De Silva, Aruna D; de Silva, Aravinda M; Crotty, Shane; Peters, Bjoern; Sette, Alessandro

    2015-08-04

    Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8(+) T-cell responses have been extensively studied, the breadth and specificity of CD4(+) T-cell responses remains to be defined. Here we define HLA-restricted CD4(+) T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+) Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4(+) T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development.

  8. Fatal case of co-infection with dengue virus and Neisseria meningitidis during a dengue epidemic in the state of Rio de Janeiro, Brazil

    PubMed Central

    Guerra Nunes, Priscila Conrado; de Andrade, Claudia Ferreira; Gonçalves, Bianca de Santis; de Araújo, Eliane Saraiva; Bezerra, Itacirema de Oliveira; da Silva, Ivan Rocha Ferreira; Nogueira, Rita Maria; de Filippis, Ana Maria Bispo

    2016-01-01

    Introduction: Dengue and meningococcal disease are caused by two different agents: a flavivirus and a Gram-negative bacterium, respectively. The first symptoms of both diseases can be indistinct and a rapid and accurate diagnosis is crucial, considering that both diseases are associated with high morbidity and mortality, representing a major public-health problem in Brazil. Case presentation: We report a fatal case of co-infection of dengue virus (DENV) and Neisseria meningitidis in a 54-year-old patient. The serum tested positive for DENV NS1 antigen, and N. meningitidis serogroup C was detected by nspA-PCR. Following the initial positive result for DENV infection, rRT-PCRwas performed and DENV-4 was confirmed. Conclusion: Our report highlights the importance of accurate differential diagnosis during periods of high circulation of DENV, in order to provide adequate management and an improved outcome. PMID:28348777

  9. DENGUE VACCINES.

    PubMed

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  10. High rates of co-infection of Dengue and Chikungunya virus in Odisha and Maharashtra, India during 2013.

    PubMed

    Saswat, Tanuja; Kumar, Abhishek; Kumar, Sameer; Mamidi, Prabhudutta; Muduli, Sagarika; Debata, Nagen Kumar; Pal, Niladri Shekhar; Pratheek, B M; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-10-01

    Dengue viral (DENV) infection is endemic in different parts of India and because of similar primary signs and symptoms, Chikungunya virus (CHIKV) is mostly undiagnosed. Hence, we investigated 204 suspected Dengue cases in a hospital based cross-sectional study in Odisha, India in 2013. It was observed that 50 samples were positive for DENV only, 28 were positive for CHIKV only and interestingly, 28 patients were co-infected with both DENV and CHIKV. Additionally, a total of 18 confirmed Dengue samples from Maharashtra, India were screened for CHIKV and out of those, 15 were co-infected. All CHIKV strains were of East Central South African (ECSA) type and serotype 2 (genotype IV) was predominant in the DENV samples. Additionally, Dengue serotype 1 and 3 were also detected during this time. Further, sequence analysis of E1 gene of CHIKV strains revealed that two substitution mutations (M269V and D284E) were observed in almost 50% strains and they were from co-infected patients. Similarly, sequence analysis of C-prM gene showed the presence of five substitution mutations, (G70S, L72F, N90S, S93N and I150L) in all serotype 1 and two consistent mutations (A101V and V112A) in serotype 2 Dengue samples. Together, it appears that a significantly high number of dengue patients (43, 44.8%) were co-infected with DENV and CHIKV during this study. This emphasizes the need of a routine diagnosis of CHIKV along with DENV for febrile patients. This will be useful in early and proper recognition of infecting pathogen to study the correlation of clinical symptoms with single or co-infection which will ultimately help to implement proper patient care in future.

  11. EFFICIENCY OF DENGUE SEROTYPE 2 VIRUS STRAINS TO INFECT AND DISSEMINATE IN AEDES AEGYPTI

    PubMed Central

    ARMSTRONG, PHILIP M.; RICO-HESSE, REBECA

    2011-01-01

    Dengue serotype 2 (DEN-2) viruses with the potential to cause dengue hemorrhagic fever have been shown to belong to the Southeast (SE) Asian genotype. These viruses appear to be rapidly displacing the American genotype of DEN-2 in the Western Hemisphere. To determine whether distinct genotypes of DEN-2 virus are better adapted to mosquito transmission, we classified 15 viral strains of DEN-2 phylogenetically and compared their ability to infect and disseminate in different populations of Aedes aegypti mosquitoes. Envelope gene nucleotide sequence analysis confirmed that six strains belonged to the American genotype and nine strains were of the SE Asian genotype. The overall rate of disseminated infection in mosquitoes from Texas was 27% for the SE Asian genotype versus 9% for the American genotype. This pattern of infection was similar in another population of mosquitoes sampled from southern Mexico (30% versus 13%). Together, these findings suggest that Ae. aegypti tends to be more susceptible to infection by DEN-2 viruses of the SE Asian genotype than to those of the American genotype, and this may have epidemiologic implications. PMID:12812340

  12. Flavone enhances dengue virus type-2 (NGC strain) infectivity and replication in vero cells.

    PubMed

    Zandi, Keivan; Lani, Rafidah; Wong, Pooi-Fong; Teoh, Boon-Teong; Sam, Sing-Sin; Johari, Jefree; Mustafa, Mohd Rais; AbuBakar, Sazaly

    2012-02-28

    This study investigates the effects of 2-phenyl-1-benzopyran-4-one (flavone) on DENV-2 infectivity in Vero cells. Virus adsorption and attachment and intracellular virus replication were investigated using a foci forming unit assay (FFUA) and quantitative RT-PCR, respectively. Addition of flavone (100 μg/mL) significantly increased the number of DENV-2 foci by 35.66% ± 1.52 and 49.66% ± 2.51 when added during and after virus adsorption to the Vero cells, respectively. The average foci size after 4 days of infection increased by 33% ± 2.11 and 89% ± 2.13. The DENV-2 specific RNA copy number in the flavone-treated infected cells increased by 6.41- and 23.1-fold when compared to the mock-treated infected cells. Flavone (100 μg/mL) did not promote or inhibit Vero cell proliferation. The CC₅₀ value of flavone against Vero cells was 446 µg/mL. These results suggest that flavone might enhance dengue virus replication by acting antagonistically towards flavonoids known to inhibit dengue virus replication.

  13. Development of a FACS-based assay for evaluating antiviral potency of compound in dengue infected peripheral blood mononuclear cells.

    PubMed

    Fu, Yilong; Chen, Yen-Liang; Herve, Maxime; Gu, Feng; Shi, Pei-Yong; Blasco, Francesca

    2014-02-01

    Dengue fever is the most important arthropod-transmitted viral disease affecting humans. It is a blood-borne disease characterized by persistent fever and joint pain. In the blood, primary peripheral blood mononuclear cells (PBMCs), in particular monocytes, are the main target of the dengue virus (DENV). These cells are poorly permissive for in vitro dengue virus infection and their infectivity varies from donor to donor. To overcome this barrier, an anti-dengue antibody was used to improve the infectivity of DENV-2 clinical isolates to PBMCs, the monocytic leukemia cell line, THP-1 and the granulocyte cell line, KU812. A higher throughput 96-well-format assay based on a fluorescent-activated cell sorter could potentially be developed to evaluate the antiviral potency of compounds in DENV-infected PBMCs in vitro. The results correlate well with data obtained by a standard plaque assay. Altogether, an assay has been developed that enables evaluation of the antiviral activity of test compounds in a physiologically-relevant cell system (PBMCs). These screening processes are urgently needed for dengue drug discovery.

  14. Association DENV1 and DENV2 infection with high serum levels of soluble thrombomodulin and VEGF in patients with dengue fever and dengue hemorrhagic fever.

    PubMed

    Del Moral-Hernández, Oscar; Martínez-Hernández, Norma E; Mosso-Pani, Manuel A; Hernández-Sotelo, Daniel; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Antonio-Vejar, Verónica; Leyva-Vázquez, Marco Antonio

    2014-01-01

    INFECTION BY DENGUE VIRUS (DENV) CAN BE ASYMPTOMATIC OR MANIFEST IN TWO CLINICALLY DIFFERENTIATED FORMS: dengue fever (DF) and denguehemorrhagic fever (DHF). The principal pathophysiological characteristic of DHF is the increase in vascular permeability and the loss of plasma caused by the malfunction of the vascular endothelium that induces the release of chemical mediators. However, so far there is nothing that allows for the identification the patients that are at risk of developing the more severe form of the illness. The objective of this study was to investigate the relationship between the serum levels of soluble thrombomodulin (sTM) and VEGF with the severity of dengue and the viral serotype. 231 serum samples were analyzed, 70 DF, 80 DHF and 81 control group, all were residents of Guerrero state in Mexico. The infection by dengue virus as well and the levels of sTM and VEGF were determined using the ELISA sandwich, while the serotype was determined by real time RT-PCR. Our results show that the concentrations of sTM correlate with the degree of severity of the disease given that they are significantly higher (p<0.001) in the DHF group (median = 10.2 ng/mL) than in the DF group (median = 7.2 ng/mL), and these in turn higher than those of the control group (median = 3.3 ng/mL). The concentration of sTM was significantly higher (p=0.0002) in the patients infected with DENV2. For the VEGF, the highest levels were found in DF (median = 291.3 pg/mL) and did not correlate with the severity of the disease. In conclusion, our results indicate that sTM is a good marker for the severity of the infection by DENV, better than VEGF, and with higher sensibility and specificity.

  15. Association DENV1 and DENV2 infection with high serum levels of soluble thrombomodulin and VEGF in patients with dengue fever and dengue hemorrhagic fever

    PubMed Central

    del Moral-Hernández, Oscar; Martínez-Hernández, Norma E; Mosso-Pani, Manuel A; Hernández-Sotelo, Daniel; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Antonio-Vejar, Verónica; Leyva-Vázquez, Marco Antonio

    2014-01-01

    Infection by dengue virus (DENV) can be asymptomatic or manifest in two clinically differentiated forms: dengue fever (DF) and denguehemorrhagic fever (DHF). The principal pathophysiological characteristic of DHF is the increase in vascular permeability and the loss of plasma caused by the malfunction of the vascular endothelium that induces the release of chemical mediators. However, so far there is nothing that allows for the identification the patients that are at risk of developing the more severe form of the illness. The objective of this study was to investigate the relationship between the serum levels of soluble thrombomodulin (sTM) and VEGF with the severity of dengue and the viral serotype. 231 serum samples were analyzed, 70 DF, 80 DHF and 81 control group, all were residents of Guerrero state in Mexico. The infection by dengue virus as well and the levels of sTM and VEGF were determined using the ELISA sandwich, while the serotype was determined by real time RT-PCR. Our results show that the concentrations of sTM correlate with the degree of severity of the disease given that they are significantly higher (p<0.001) in the DHF group (median = 10.2 ng/mL) than in the DF group (median = 7.2 ng/mL), and these in turn higher than those of the control group (median = 3.3 ng/mL). The concentration of sTM was significantly higher (p=0.0002) in the patients infected with DENV2. For the VEGF, the highest levels were found in DF (median = 291.3 pg/mL) and did not correlate with the severity of the disease. In conclusion, our results indicate that sTM is a good marker for the severity of the infection by DENV, better than VEGF, and with higher sensibility and specificity. PMID:24600491

  16. Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.

    PubMed

    Clapham, Hannah E; Quyen, Than Ha; Kien, Duong Thi Hue; Dorigatti, Ilaria; Simmons, Cameron P; Ferguson, Neil M

    2016-05-01

    Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.

  17. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein.

    PubMed

    Londono-Renteria, Berlin; Troupin, Andrea; Conway, Michael J; Vesely, Diana; Ledizet, Michael; Roundy, Christopher M; Cloherty, Erin; Jameson, Samuel; Vanlandingham, Dana; Higgs, Stephen; Fikrig, Erol; Colpitts, Tonya M

    2015-10-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were ≥5-fold differentially upregulated during flavivirus infection of the mosquito. Here, we examined the impact of silencing 100 of the most highly upregulated gene targets on DENV infection in its mosquito vector. We identified 20 genes that reduced DENV infection by at least 60% when silenced. We focused on one gene, a putative cysteine rich venom protein (SeqID AAEL000379; CRVP379), whose silencing significantly reduced DENV infection in Aedes aegypti cells. Here, we examine the requirement for CRVP379 during DENV infection of the mosquito and investigate the mechanisms surrounding this phenomenon. We also show that blocking CRVP379 protein with either RNAi or specific antisera inhibits DENV infection in Aedes aegypti. This work identifies a novel mosquito gene target for controlling DENV infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

  18. Analysis of the miRNA profile in C6/36 cells persistently infected with dengue virus type 2.

    PubMed

    Avila-Bonilla, Rodolfo Gamaliel; Yocupicio-Monroy, Martha; Marchat, Laurence A; De Nova-Ocampo, Mónica A; Del Ángel, Rosa María; Salas-Benito, Juan Santiago

    2017-03-15

    Dengue virus (DENV) is the most important arbovirus in the world; DENV is transmitted by the Aedes genus of mosquitoes and can establish a life-long persistent infection in mosquitoes. However, the exact mechanism by which persistent infection is established remains unknown. In this study the differential expression of miRNAs was analysed by deep sequencing and RT-qPCR using a previously established C6/36-HT cell line persistently infected with DENV 2 (C6-L) as a model. miR-927, miR-87, miR-210, miR-2a-3p, miR-190 and miR-970 were up-regulated, whereas miR-252, miR-263a-3p, miR-92b, miR-10-5p miR-9a-5p, miR-9a-1, miR-124, miR-286a and miR-286b were down-regulated in C6-L cells compared with C6/36 cells acutely infected with the same virus or mock-infected cells. Deep sequencing results were validated by RT-qPCR for the highly differentially expressed miR-927 and miR-9a-5p, which were up- and down-regulated, respectively, compared with both acutely and mock-infected C6/36 cells. The putative targets of these miRNAs include components of the ubiquitin conjugation pathway, vesicle-mediated transport, autophagy, and the JAK-STAT cascade as well as proteins with endopeptidase activity. Other putative targets include members of the Toll signalling pathway and proteins with kinase, ATPase, protease, scavenger receptor or Lectin C-type activity or that participate in fatty acid biosynthesis or oxidative stress. Our results suggest that several specific miRNAs help regulate the cellular functions that maintain equilibrium between viral replication and the antiviral response during persistent infection of mosquito cells. This study is the first report of a global miRNA profile in a mosquito cell line persistently infected with DENV.

  19. Changing pattern of dengue virus serotypes circulating during 2008-2012 and reappearance of dengue serotype 3 may cause outbreak in Kolkata, India.

    PubMed

    Saha, Kallol; Ghosh, Monika; Firdaus, Rushna; Biswas, Aritra; Seth, Bikash; Bhattacharya, Debojyoti; Mukherjee, Kheya; Sadhukhan, Provash Chandra

    2016-10-01

    Dengue virus infection is a major cause of morbidity within the endemic tropical and subtropical regions of the world. Dengue virus has four distinct serotypes with specific clinical manifestations. In this study, we observed the changing pattern of dengue serotypes, age-wise dengue infection and useful sero-detection methods needed in a dengue endemic region. We identified dengue serotypes during a period of 5 years among patients with dengue symptoms visiting one of the largest tertiary care infectious disease hospitals of eastern India in Kolkata. A total of 433 dengue RNA positive samples were isolated from 712 acute dengue suspected cases. Age wise distribution highlighted the susceptible age group being >21 years (24.02%) followed by 11-15 years (21.71%) and 5-10 years (21.02%) of the total infected population. Higher numbers of infected cases were found within females as they are involved in more indoor works. The period of study experienced two dengue outbreaks one in 2008 and another in 2012. For early dengue detection, NS1 was found to be more confirmatory than IgM ELISA regarding sensitivity and specificity. DENV-1, 2, and 4 serotypes were the common circulating strains from 2008 until 2010, after which DENV-3 serotype infections rise and led to a massive dengue outbreak in Kolkata with increased numbers of DHF and DSS cases in 2012. The finding within our study emphasizes the public health importance of such prospective surveillance programs with respect to the changing dengue viral etiology and serotypes. J. Med. Virol. 88:1697-1702, 2016. © 2016 Wiley Periodicals, Inc.

  20. Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti.

    PubMed

    Ferguson, Neil M; Kien, Duong Thi Hue; Clapham, Hannah; Aguas, Ricardo; Trung, Vu Tuan; Chau, Tran Nguyen Bich; Popovici, Jean; Ryan, Peter A; O'Neill, Scott L; McGraw, Elizabeth A; Long, Vo Thi; Dui, Le Thi; Nguyen, Hoa L; Chau, Nguyen Van Vinh; Wills, Bridget; Simmons, Cameron P

    2015-03-18

    Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75%. Our results suggest that establishment of wMelPop-infected A. aegypti at a high frequency in a dengue-endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel-infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.

  1. Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection.

    PubMed

    Fang, Chih-Yeu; Chen, Siang-Jyun; Wu, Huey-Nan; Ping, Yueh-Hsin; Lin, Ching-Yen; Shiuan, David; Chen, Chi-Long; Lee, Ying-Ray; Huang, Kao-Jean

    2015-09-10

    Dengue is the most widespread arbovirus infection and poses a serious health and economic issue in tropical and subtropical countries. Currently no licensed vaccine or compounds can be used to prevent or manage the severity of dengue virus (DENV) infection. Honokiol, a lignan biphenol derived from the Magnolia tree, is commonly used in Eastern medicine. Here we report that honokiol has profound antiviral activity against serotype 2 DENV (DENV-2). In addition to inhibiting the intracellular DENV-2 replicon, honokiol was shown to suppress the replication of DENV-2 in baby hamster kidney (BHK) and human hepatocarcinoma Huh7 cells. At the maximum non-toxic dose of honokiol treatment, the production of infectious DENV particles was reduced >90% in BHK and Huh7 cells. The underlying mechanisms revealed that the expression of DENV-2 nonstructural protein NS1/NS3 and its replicating intermediate, double-strand RNA, was dramatically reduced by honokiol treatment. Honokiol has no effect on the expression of DENV putative receptors, but may interfere with the endocytosis of DENV-2 by abrogating the co-localization of DENV envelope glycoprotein and the early endosomes. These results indicate that honokiol inhibits the replication, viral gene expression, and endocytotic process of DENV-2, making it a promising agent for chemotherapy of DENV infection.

  2. Atomic-level functional model of dengue virus Envelope protein infectivity

    PubMed Central

    Christian, Elizabeth A.; Kahle, Kristen M.; Mattia, Kimberly; Puffer, Bridget A.; Pfaff, Jennifer M.; Miller, Adam; Paes, Cheryl; Davidson, Edgar; Doranz, Benjamin J.

    2013-01-01

    A number of structures have been solved for the Envelope (E) protein from dengue virus and closely related flaviviruses, providing detailed pictures of the conformational states of the protein at different stages of infectivity. However, the key functional residues responsible for mediating the dynamic changes between these structures remain largely unknown. Using a comprehensive library of functional point mutations covering all 390 residues of the dengue virus E protein ectodomain, we identified residues that are critical for virus infectivity, but that do not affect E protein expression, folding, virion assembly, or budding. The locations and atomic interactions of these critical residues within different structures representing distinct fusogenic conformations help to explain how E protein (i) regulates fusion-loop exposure by shielding, tethering, and triggering its release; (ii) enables hinge movements between E domain interfaces during triggered structural transformations; and (iii) drives membrane fusion through late-stage zipper contacts with stem. These results provide structural targets for drug and vaccine development and integrate the findings from structural studies and isolated mutagenesis efforts into a cohesive model that explains how specific residues in this class II viral fusion protein enable virus infectivity. PMID:24158478

  3. Beyond attachment: Roles of DC-SIGN in dengue virus infection.

    PubMed

    Liu, Ping; Ridilla, Marc; Patel, Pratik; Betts, Laurie; Gallichotte, Emily; Shahidi, Lidea; Thompson, Nancy L; Jacobson, Ken

    2017-04-01

    Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization. To examine this question, we used 4 cell types: human immature dendritic cells and NIH3T3 cells expressing either wild-type DC-SIGN or 2 internalization-deficient DC-SIGN mutants, in which either the 3 cytoplasmic internalization motifs are silenced by alanine substitutions or the cytoplasmic region is truncated. Using confocal and super-resolution imaging and high content single particle tracking, we investigated DENV binding, DC-SIGN surface transport, endocytosis, as well as cell infectivity. DC-SIGN was found colocalized with DENV inside cells suggesting hand-off at the plasma membrane to another receptor did not occur. Moreover, all 3 DC-SIGN molecules on NIH3T3 cells supported cell infection. These results imply the involvement of a co-receptor because cells expressing the internalization-deficient mutants could still be infected.

  4. Differential Induction of Cytokines by Human Neonatal, Adult, and Elderly Monocyte/Macrophages Infected with Dengue Virus

    PubMed Central

    Valero, Nereida; Levy, Alegria; Añez, Germán; Marcucci, Rafael; Alvarez-Mon, Melchor

    2014-01-01

    Abstract Immunosuppressive status against infections in monocytes from neonates and elderly subjects has been reported. The interaction between dengue virus and monocytes/macrophages plays an important role during dengue disease. The aim of this study was to determine the cytokine response of monocytes from individuals with different ages after infection with dengue virus. Monocyte/macrophage cultures from neonatal, adult, and elderly subjects (n=10 each group) were incubated with all four dengue virus types (DENV-1 to -4). After 1 and 3 days of culture, cytokine concentrations (TNF-α, IL-6, and IL-1β) were determined in culture supernatants by enzyme-linked immunosorbant assay. Increased production of all studied cytokines was induced by the different viral types in monocyte/macrophage cultures regardless of their source. However, lower cytokine concentrations were found in neonatal and elderly monocytes. The relative monocyte/macrophage immunosuppressive status observed in neonates and the elderly could be relevant during dengue infection in those age groups and important in innate and adaptive immunity responses against this virus. PMID:24801946

  5. Force of infection of dengue serotypes in a population-based study in the northeast of Brazil.

    PubMed

    Castanha, P M S; Cordeiro, M T; Martelli, C M T; Souza, W V; Marques, E T A; Braga, C

    2013-05-01

    This study investigated anti-dengue serotype-specific neutralizing antibodies in a random sample of dengue IgG-positive individuals identified in a survey performed in a hyperendemic setting in northeastern Brazil in 2005. Of 323 individuals, 174 (53.8%) had antibodies to dengue virus serotype 1 (DENV-1), 104 (32.2%) to DENV-2 and 301 (93.2%) to DENV-3. Monotypic infections by DENV-3 were the most frequent infection (35.6%). Of 109 individuals aged <15 years, 61.5% presented multitypic infections. The force of infection estimated by a catalytic model was 0.9%, 0.4% and 2.5% person-years for DENV-1, DENV-2 and DENV-3, respectively. By the age of 5 years, about 70%, 30% and 40% of participants were immune to DENV-3, DENV-2 and DENV-1, respectively. The data suggest that infection with DENV-1, -2 and -3 is intense at early ages, demonstrating the need for research efforts to investigate dengue infection in representative population samples of Brazilian children during early infancy.

  6. The Phosphatidylserine and Phosphatidylethanolamine Receptor CD300a Binds Dengue Virus and Enhances Infection

    PubMed Central

    Carnec, Xavier; Meertens, Laurent; Dejarnac, Ophélie; Perera-Lecoin, Manuel; Hafirassou, Mohamed Lamine; Kitaura, Jiro; Ramdasi, Rasika; Schwartz, Olivier

    2015-01-01

    ABSTRACT Dengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM and TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles and enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus and Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) and to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth and PtdSer present on virions and enhance infection. IMPORTANCE Dengue disease, caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease of humans and is a major global health concern. The molecular bases of DENV-host cell interactions during virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. We recently discovered that the TIM and TAM proteins, two receptor families involved in the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, interact with DENV particles-associated PtdSer through a mechanism that mimics the recognition of apoptotic cells and mediate DENV infection. In this study, we show that CD300a, a novel identified phospholipid receptor, mediates DENV infection. CD300a

  7. Antibodies against the Envelope Glycoprotein Promote Infectivity of Immature Dengue Virus Serotype 2

    PubMed Central

    da Silva Voorham, Júlia M.; Rodenhuis-Zybert, Izabela A.; Ayala Nuñez, Nilda Vanesa; Colpitts, Tonya M.; van der Ende-Metselaar, Heidi; Fikrig, Erol; Diamond, Michael S.; Wilschut, Jan; Smit, Jolanda M.

    2012-01-01

    Cross-reactive dengue virus (DENV) antibodies directed against the envelope (E) and precursor membrane (prM) proteins are believed to contribute to the development of severe dengue disease by facilitating antibody-dependent enhancement of infection. We and others recently demonstrated that anti-prM antibodies render essentially non-infectious immature DENV infectious in Fcγ-receptor-expressing cells. Immature DENV particles are abundantly present in standard (st) virus preparations due to inefficient processing of prM to M during virus maturation. Structural analysis has revealed that the E protein is exposed in immature particles and this prompted us to investigate whether antibodies to E render immature particles infectious. To this end, we analyzed the enhancing properties of 27 anti-E antibodies directed against distinct structural domains. Of these, 23 bound to immature particles, and 15 enhanced infectivity of immature DENV in a furin-dependent manner. The significance of these findings was subsequently tested in vivo using the well-established West Nile virus (WNV) mouse model. Remarkably, mice injected with immature WNV opsonized with anti-E mAbs or immune serum produced a lethal infection in a dose-dependent manner, whereas in the absence of antibody immature WNV virions caused no morbidity or mortality. Furthermore, enhancement infection studies with standard (st) DENV preparations opsonized with anti-E mAbs in the presence or absence of furin inhibitor revealed that prM-containing particles present within st virus preparations contribute to antibody-dependent enhancement of infection. Taken together, our results support the notion that antibodies against the structural proteins prM and E both can promote pathogenesis by enhancing infectivity of prM-containing immature and partially mature flavivirus particles. PMID:22431958

  8. Acute transverse myelitis complicating breakthrough varicella infection.

    PubMed

    Aslan, Asli; Kurugol, Zafer; Gokben, Sarenur

    2014-11-01

    We report a 10-year-old girl who presented with acute transverse myelitis after breakthrough varicella infection. The diagnosis was based on the development of motor weakness, paraparesis and bladder dysfunction, spinal magnetic resonance imaging findings and detection of anti-varicella zoster virus IgG antibody in the cerebrospinal fluid. This case report highlights that breakthrough varicella can result in serious complications such as acute transverse myelitis.

  9. The dengue viruses.

    PubMed Central

    Henchal, E A; Putnak, J R

    1990-01-01

    Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made. Images PMID:2224837

  10. Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.

    PubMed

    Colpitts, Tonya M; Cox, Jonathan; Vanlandingham, Dana L; Feitosa, Fabiana M; Cheng, Gong; Kurscheid, Sebastian; Wang, Penghua; Krishnan, Manoj N; Higgs, Stephen; Fikrig, Erol

    2011-09-01

    West Nile (WNV), dengue (DENV) and yellow fever (YFV) viruses are (re)emerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥ 5-fold differentially up-regulated (DUR) and 202 genes that were ≥ 10-fold differentially down-regulated (DDR) during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

  11. Zika virus infection-the next wave after dengue?

    PubMed

    Wong, Samson Sai-Yin; Poon, Rosana Wing-Shan; Wong, Sally Cheuk-Ying

    2016-04-01

    Zika virus was initially discovered in east Africa about 70 years ago and remained a neglected arboviral disease in Africa and Southeast Asia. The virus first came into the limelight in 2007 when it caused an outbreak in Micronesia. In the ensuing decade, it spread widely in other Pacific islands, after which its incursion into Brazil in 2015 led to a widespread epidemic in Latin America. In most infected patients the disease is relatively benign. Serious complications include Guillain-Barré syndrome and congenital infection which may lead to microcephaly and maculopathy. Aedes mosquitoes are the main vectors, in particular, Ae. aegypti. Ae. albopictus is another potential vector. Since the competent mosquito vectors are highly prevalent in most tropical and subtropical countries, introduction of the virus to these areas could readily result in endemic transmission of the disease. The priorities of control include reinforcing education of travellers to and residents of endemic areas, preventing further local transmission by vectors, and an integrated vector management programme. The container habitats of Ae. aegypti and Ae. albopictus means engagement of the community and citizens is of utmost importance to the success of vector control.

  12. Dengue and Severe Dengue

    MedlinePlus

    ... can significantly reduce mortality rates from severe dengue. Global Strategy for dengue prevention and control, 2012–2020, Chapter ... vaccine: WHO position paper – July 2016 pdf, 437kb Global Strategy for dengue prevention and control, 2012–2020 Global ...

  13. Protect Yourself and Your Baby from Dengue

    MedlinePlus

    Protect Yourself and Your Baby from Dengue Avoid mosquito bites during pregnancy to prevent dengue in your ... To prevent dengue virus infection during pregnancy » Use mosquito repellents with up to 50% DEET, picaridin, IR3535 ...

  14. Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection

    PubMed Central

    Taguwa, Shuhei; Maringer, Kevin; Li, Xiaokai; Bernal-Rubio, Dabeiba; Rauch, Jennifer N.; Gestwicki, Jason E.; Andino, Raul; Fernandez-Sesma, Ana; Frydman, Judith

    2015-01-01

    Summary Viral protein homeostasis depends entirely on the machinery of the infected cell. Accordingly, viruses can illuminate the interplay between cellular proteostasis components and their distinct substrates. Here we define how the Hsp70 chaperone network mediates the dengue virus life cycle. Cytosolic Hsp70 isoforms are required at distinct steps of the viral cycle, including entry, RNA replication and virion biogenesis. Hsp70 function at each step is specified by nine distinct DNAJ cofactors. Of these, DnaJB11 relocalizes to virus-induced replication complexes to promote RNA synthesis, while DnaJB6 associates with capsid protein and facilitates virion biogenesis. Importantly, an allosteric Hsp70 inhibitor, JG40, potently blocks infection of different dengue serotypes in human primary blood cells without eliciting viral resistance or exerting toxicity to the host cells. JG40 also blocks replication of other medically-important flaviviruses including yellow fever, West Nile and Japanese encephalitis viruses. Thus, targeting host Hsp70 subnetworks provides a path for broad-spectrum antivirals. PMID:26582131

  15. Evaluation of a dengue IgG indirect enzyme-linked immunosorbent assay and a Japanese encephalitis IgG indirect enzyme-linked immunosorbent assay for diagnosis of secondary dengue virus infection.

    PubMed

    Inoue, Shingo; Alonzo, Maria T G; Kurosawa, Yae; Mapua, Cynthia A; Reyes, Joyce D; Dimaano, Efren M; Alera, Maria Theresa P; Saito, Mariko; Oishi, Kazunori; Hasebe, Futoshi; Matias, Ronald R; Natividad, Filipinas F; Morita, Kouichi

    2010-03-01

    To establish a new method for the diagnosis of dengue secondary infection, 187 serum samples from the patients with dengue secondary infection, 40 serum samples from the patients with dengue primary infection, and 44 serum samples from the healthy volunteers were tested using the dengue IgG indirect enzyme-linked immunosorbent assay (DEN IgG ELISA). The results of the test were compared with those from the dengue hemagglutination inhibition (DEN HI) test, which has been recommended as the gold standard by the World Health Organization (WHO, 1997). Japanese encephalitis IgG indirect ELISA (JE IgG ELISA) was also performed to measure anti-flavivirus IgG, which cross-reacts with the Japanese encephalitis virus, to test the possibility of an alternative to DEN IgG ELISA. The results of DEN IgG and JE IgG ELISAs were highly correlated with those of the DEN HI test. In the DEN IgG ELISA, a titer of 1:29,000 was the cut-off value for the diagnosis of dengue secondary infection (91.5% accuracy [95% confidence interval, CI], 90.9% sensitivity [95%CI], and 92.9% specificity [95%CI]). A titer of 1:52,000 was the cut-off value for dengue secondary infection using JE IgG ELISA (95.6% accuracy [95%CI], 98.9% sensitivity [95%CI], and 88.1% specificity [95%CI]). In conclusion, this study confirmed that the results of both DEN IgG and JE IgG ELISAs were highly correlated with the results of DEN HI test. Thus, these ELISAs are simple, rapid, sensitive, and quantitative tests that can be used in the determination of dengue secondary infection.

  16. Paradoxical role of antibodies in dengue virus infections: considerations for prophylactic vaccine development.

    PubMed

    Acosta, Eliana G; Bartenschlager, Ralf

    2016-01-01

    Highly effective prophylactic vaccines for flaviviruses including yellow fever virus, tick-borne encephalitis virus and Japanese encephalitis virus are currently in use. However, the development of a dengue virus (DENV) vaccine has been hampered by the requirement of simultaneous protection against four distinct serotypes and the threat that DENV-specific antibodies might either mediate neutralization or, on the contrary, exacerbate disease through the phenomenon of antibody-dependent enhancement (ADE) of infection. Therefore, understanding the cellular, biochemical and molecular basis of antibody-mediated neutralization and ADE are fundamental for the development of a safe DENV vaccine. Here we summarize current structural and mechanistic knowledge underlying these phenomena. We also review recent results demonstrating that the humoral immune response triggered during natural DENV infection is able to generate neutralizing antibodies binding complex quaternary epitopes only present on the surface of intact virions.

  17. First Complete Genome Sequence of a Chikungunya Virus Strain Isolated from a Patient Diagnosed with Dengue Virus Infection in Malaysia

    PubMed Central

    Gan, Han Ming; Rohani, Ahmad

    2016-01-01

    Here, we report the complete genome sequence of a chikungunya virus coinfection strain isolated from a dengue virus serotype 2-infected patient in Malaysia. This coinfection strain was determined to be of the Asian genotype and contains a novel insertion in the nsP3 gene. PMID:27563048

  18. Infection Rates by Dengue Virus in Mosquitoes and the Influence of Temperature May Be Related to Different Endemicity Patterns in Three Colombian Cities

    PubMed Central

    Peña-García, Víctor Hugo; Triana-Chávez, Omar; Mejía-Jaramillo, Ana María; Díaz, Francisco J.; Gómez-Palacio, Andrés; Arboleda-Sánchez, Sair

    2016-01-01

    Colombia is an endemic country for dengue fever where the four serotypes of virus dengue (DENV1–4) circulate simultaneously, and all types are responsible for dengue cases in the country. The control strategies are guided by entomological surveillance. However, heterogeneity in aedic indices is not well correlated with the incidence of the disease in cities such as Riohacha, Bello and Villavicencio. As an alternative, molecular detection of dengue virus in mosquitoes has been proposed as a useful tool for epidemiological surveillance and identification of serotypes circulating in field. We conducted a spatiotemporal fieldwork in these cities to capture adult mosquitoes to assess vector infection and explain the differences between Breteau indices and disease incidence. DENV infection in females and DENV serotype identification were evaluated and infection rates (IR) were estimated. The relationship between density, dengue cases and vector index was also estimated with logistic regression modeling and Pearson’s correlation coefficient. The lack of association between aedic indices and dengue incidence is in agreement with the weak associations between the density of the mosquitoes and their infection with DENV in the three cities. However, association was evident between the IR and dengue cases in Villavicencio. Furthermore, we found important negative associations between temperature and lag time from two to six weeks in Riohacha. We conclude that density of mosquitoes is not a good predictor of dengue cases. Instead, IR and temperature might explain better such heterogeneity. PMID:27455289

  19. Rhombencephalitis associated with Dengue fever.

    PubMed

    Verma, Rajesh; Bharti, Kavita; Mehta, Mannan; Bansod, Amrit

    2016-05-01

    Dengue infection is gradually disseminating throughout the world in alarming proportions. It is a arbovirus infection,transmitted by aedes mosquitoes. It is a multi-systemic disorder associated with varied neurological complications. There is increased trend of development of neurological complications in dengue fever. The neurological complications arising due to dengue infection can be categorized into central and neuromuscular complications. The central nervous system disorders reported with dengue fever are encephalopathy,encephalitis and myelitis.Here we report a case of rhombencephalitis associated with dengue fever. The literature does not mention rhombencephalitis occurring with dengue illness.

  20. Association of FCGR2A p.R131H and CCL2 c.-2518 A>G gene variants with thrombocytopenia in patients with dengue virus infection.

    PubMed

    Alagarasu, Kalichamy; Bachal, Rupali V; Damle, Indraneel; Shah, Paresh S; Cecilia, Dayaraj

    2015-11-01

    FCGR2A and CCL2 gene variants are important in dengue pathogenesis and were investigated in 122 dengue patients (DENs) [89 dengue fever (DF) and 33 dengue hemorrhagic fever (DHF)] and 107 healthy controls (HCs) to find out their association with severity of dengue. Genotype frequencies of FCGR2A p.R131H and CCL2 c.-2518 A > G polymorphisms were not different between DF, DHF and HC. Significantly higher frequency of R/R genotype of FCGR2A p.R131H was observed in DEN cases with thrombocytopenia (TP) while the G/G genotype of CCL2 c.-2518 A > G was observed only in DEN cases with TP (p < 0.005). These results suggest that FCGR2A and CCL2 gene variants were associated with the risk of TP in dengue infections.

  1. Acute renal failure in Plasmodium malariae infection.

    PubMed

    Neri, S; Pulvirenti, D; Patamia, I; Zoccolo, A; Castellino, P

    2008-04-01

    We report an unusual case of transfusion-transmitted malaria which remained undiagnosed for several months in an Italian woman splenectomised and polytransfused for thalassaemia major. The infecting species was Plasmodium malariae, and the patient developed acute renal failure, severe thrombocytopenia, and hepatic failure. Treatment with chlorochine was followed by a slow, but complete recovery of renal function.

  2. Infection with dengue-2 virus alters proteins in naturally expectorated saliva of Aedes aegypti mosquitoes

    PubMed Central

    2014-01-01

    Background Dengue virus (DENV) is responsible for up to approximately 300 million infections and an increasing number of deaths related to severe manifestations each year in affected countries throughout the tropics. It is critical to understand the drivers of this emergence, including the role of vector-virus interactions. When a DENV-infected Aedes aegypti mosquito bites a vertebrate, the virus is deposited along with a complex mixture of salivary proteins. However, the influence of a DENV infection upon the expectorated salivary proteome of its vector has yet to be determined. Methods Therefore, we conducted a proteomic analysis using 2-D gel electrophoresis coupled with mass spectrometry based protein identification comparing the naturally expectorated saliva of Aedes aegypti infected with DENV-2 relative to that of uninfected Aedes aegypti. Results Several proteins were found to be differentially expressed in the saliva of DENV-2 infected mosquitoes, in particular proteins with anti-hemostatic and pain inhibitory functions were significantly reduced. Hypothetical consequences of these particular protein reductions include increased biting rates and transmission success, and lead to alteration of transmission potential as calculated in our vectorial capacity model. Conclusions We present our characterizations of these changes with regards to viral transmission and mosquito blood-feeding success. Further, we conclude that our proteomic analysis of Aedes aegypti saliva altered by DENV infection provides a unique opportunity to identify pro-viral impacts key to virus transmission. PMID:24886023

  3. Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections

    PubMed Central

    Niloofa, Roshan; Rodrigo, Chaturaka; Karunanayake, Lilani; de Silva, H. Janaka; Wickremesinghe, A. R.; Premawansa, Sunil; Rajapakse, Senaka; Handunnetti, Shiroma M.

    2016-01-01

    Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to

  4. Rare occurrence of natural transovarial transmission of dengue virus and elimination of infected foci as a possible intervention method.

    PubMed

    Angel, Annette; Angel, Bennet; Joshi, Vinod

    2016-03-01

    Transovarial transmission of dengue virus has been studied in 33 districts of Rajasthan, India. Small proportion (1.09%) of breeding containers positive for the virus and their elimination has been demonstrated as a possible intervention method of disease control. Dengue virus was isolated from individual mosquitoes employing Indirect Fluorescence Antibody Test and Reverse Transcriptase Polymerase Chain Reaction. Out of 1,30,525 containers examined only 1432(1.09%) showed transovarially transmitted virus activity. Elimination of larvae from all the 1432 virus positive containers resulted in substantial control over prospective transmission of dengue. The study highlights rarity of transovarial transmission under natural conditions and sensitizes whether elimination of vertically infected foci could be used as a new intervention method.

  5. Expression of dengue virus NS3 protein in Drosophila alters its susceptibility to infection

    PubMed Central

    Querenet, Matthieu; Danjoy, Marie-Laure; Mollereau, Bertrand; Davoust, Nathalie

    2015-01-01

    We developed a Drosophila model in which the dengue virus NS3 protein is expressed in a tissue specific and inducible manner. Dengue virus NS3 is a multifunctional protein playing a major role during viral replication. Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery. We characterized the NS3 transgenic flies showing that NS3 expression did not affect fly development. To further study the links between NS3 and the innate immune response, we challenge the flies with gram-positive and gram-negative bacteria. Interestingly, the Drosophila transgenic flies expressing NS3 were more susceptible to bacterial infections than control flies. However ubiquitous or immune-specific NS3 expression affected neither the life span nor the response to a non-infectious stress of the flies. In conclusion, we generated a new in vivo system to study the functional impact of DENV NS3 protein on the innate immune response. PMID:26267447

  6. Noninvasive bioluminescence imaging of dengue virus infection in the brain of A129 mice.

    PubMed

    Li, Xiao-Feng; Deng, Yong-Qiang; Zhao, Hui; Ye, Qing; Wang, Hong-Jiang; Li, Shi-Hua; Zhu, Shun-Ya; Shi, Pei-Yong; Qin, E-De; Zhang, Bo; Qin, Cheng-Feng

    2013-05-01

    Dengue virus (DENV) infection is one of the most important public health threats globally; however, no vaccines or effective antivirals are currently available. The bioluminescence imaging technique has emerged as a powerful tool for studies on viral pathogenesis in vitro and in vivo. In this study, using a recombinant DENV that stably expressed Renilla luciferase (Rluc-DENV), we used bioluminescence for imaging of DENV infection in the brain of A129 mice that lacked type I interferon receptors. Upon intracranial inoculation with Rluc-DENV, A129 mice developed typical neurological symptoms and rapidly succumbed to viral infection. Real-time bioluminescence intensity analysis revealed the replication kinetics of Rluc-DENV in the brain of A129 mice. Linear regression analyses showed a good correlation between photon flux and viral titers (R(2) = 0.9923). Finally, the bioluminescence model was validated using a known mouse monoclonal antibody, 2A10G6, and the therapeutic effects of this neutralizing antibody were readily monitored by live imaging in the same animal. The noninvasive bioluminescence imaging of DENV infection as described here shows distinct advantages over traditional animal models and provides a powerful tool for potential antiviral or vaccine assays against DENV infection in vivo.

  7. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    PubMed Central

    Krishnan, Manoj N.; Garcia-Blanco, Mariano A.

    2014-01-01

    West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. PMID:24517970

  8. Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.

    PubMed

    Heaton, Nicholas S; Moshkina, Natasha; Fenouil, Romain; Gardner, Thomas J; Aguirre, Sebastian; Shah, Priya S; Zhao, Nan; Manganaro, Lara; Hultquist, Judd F; Noel, Justine; Sachs, David; Sachs, David H; Hamilton, Jennifer; Leon, Paul E; Chawdury, Amit; Tripathi, Shashank; Melegari, Camilla; Campisi, Laura; Hai, Rong; Metreveli, Giorgi; Gamarnik, Andrea V; García-Sastre, Adolfo; Greenbaum, Benjamin; Simon, Viviana; Fernandez-Sesma, Ana; Krogan, Nevan J; Mulder, Lubbertus C F; van Bakel, Harm; Tortorella, Domenico; Taunton, Jack; Palese, Peter; Marazzi, Ivan

    2016-01-19

    Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.

  9. Involvement of voltage-dependent anion channel (VDAC) in dengue infection

    PubMed Central

    Jitobaom, Kunlakanya; Tongluan, Natthida; Smith, Duncan R.

    2016-01-01

    During infection, dengue virus (DENV) proteins interact with host cellular constituents promoting the remodeling of the cell to facilitate virus production. While a number of interacting proteins have been identified for DENV non-structural proteins, far fewer interacting partners have been identified for the DENV structural proteins. One protein that has been identified as a DENV E protein interacting protein is the cellular chaperone GRP78. GRP78 has been shown to have a number of cellular interacting partners including the voltage-dependent anion channel (VDAC). In this study we confirmed the interactions between GRP78 and DENV E protein and between GRP78 and VDAC. VDAC was shown to be re-localized during DENV infection, with no change in levels of protein expression. VDAC is predominantly located on the outer membrane of mitochondria and our result is consistent with movement of the mitochondria towards the ER during DENV infection. Down regulation of VDAC through siRNA significantly reduced DENV protein expression, as well as the percentage infection and output virus titer. Our results suggest that VDAC plays an important role in DENV infection. PMID:27779201

  10. Characteristics of a dengue outbreak in a remote pacific island chain--Republic of The Marshall Islands, 2011-2012.

    PubMed

    Sharp, Tyler M; Mackay, Andrew J; Santiago, Gilberto A; Hunsperger, Elizabeth; Nilles, Eric J; Perez-Padilla, Janice; Tikomaidraubuta, Kinisalote S; Colon, Candimar; Amador, Manuel; Chen, Tai-Ho; Lalita, Paul; Muñoz-Jordán, Jorge L; Barrera, Roberto; Langidrik, Justina; Tomashek, Kay M

    2014-01-01

    Dengue is a potentially fatal acute febrile illness caused by four mosquito-transmitted dengue viruses (DENV-1-4). Although dengue outbreaks regularly occur in many regions of the Pacific, little is known about dengue in the Republic of the Marshall Islands (RMI). To better understand dengue in RMI, we investigated an explosive outbreak that began in October 2011. Suspected cases were reported to the Ministry of Health, serum specimens were tested with a dengue rapid diagnostic test (RDT), and confirmatory testing was performed using RT-PCR and IgM ELISA. Laboratory-positive cases were defined by detection of DENV nonstructural protein 1 by RDT, DENV nucleic acid by RT-PCR, or anti-DENV IgM antibody by RDT or ELISA. Secondary infection was defined by detection of anti-DENV IgG antibody by ELISA in a laboratory-positive acute specimen. During the four months of the outbreak, 1,603 suspected dengue cases (3% of the RMI population) were reported. Of 867 (54%) laboratory-positive cases, 209 (24%) had dengue with warning signs, six (0.7%) had severe dengue, and none died. Dengue incidence was highest in residents of Majuro and individuals aged 10-29 years, and ∼95% of dengue cases were experiencing secondary infection. Only DENV-4 was detected by RT-PCR, which phylogenetic analysis demonstrated was most closely related to a virus previously identified in Southeast Asia. Cases of vertical DENV transmission, and DENV/Salmonella Typhi and DENV/Mycobacterium leprae co-infection were identified. Entomological surveys implicated water storage containers and discarded tires as the most important development sites for Aedes aegypti and Ae. albopictus, respectively. Although this is the first documented dengue outbreak in RMI, the age groups of cases and high prevalence of secondary infection demonstrate prior DENV circulation. Dengue surveillance should continue to be strengthened in RMI and throughout the Pacific to identify and rapidly respond to future outbreaks.

  11. Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

    PubMed Central

    Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

    2016-01-01

    Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management. PMID:27845374

  12. Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

    NASA Astrophysics Data System (ADS)

    Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

    2016-11-01

    Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

  13. A Lethal Murine Infection Model for Dengue Virus 3 in AG129 Mice Deficient in Type I and II Interferon Receptors Leads to Systemic Disease

    PubMed Central

    Sarathy, Vanessa V.; White, Mellodee; Li, Li; Gorder, Summer R.; Pyles, Richard B.; Campbell, Gerald A.; Milligan, Gregg N.

    2014-01-01

    ABSTRACT The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs. IMPORTANCE Dengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness

  14. Intrahepatic infiltrating NK and CD8 T cells cause liver cell death in different phases of dengue virus infection.

    PubMed

    Sung, Jui-Min; Lee, Chien-Kuo; Wu-Hsieh, Betty A

    2012-01-01

    Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of liver injury has not been clearly demonstrated. In this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. Immunocompetent C57BL/6 mice were infected intravenously with dengue virus strain 16681. Infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. In the mean time, NK cell and T cell infiltrations peaked at days 1 and 5, respectively. Neutralizing CXCL10 or depletion of Asialo GM1(+) cells reduced cleaved caspase 3 and TUNEL(+) cells in the liver at day 1 after infection. CD8(+) T cells infiltrated into the liver at later time point and at which time intrahepatic leukocytes (IHL) exhibited cytotoxicity against DENV-infected targets. Cleaved caspase 3 and TUNEL(+) cells were diminished in mice with TCRβ deficiency and in those depleted of CD8(+) T cells, respectively, at day 5 after infection. Moreover, intrahepatic CD8(+) T cells were like their splenic counterparts recognized DENV NS4B(99-107) peptide. Together, these results show that infiltrating NK and CD8(+) T cells cause liver cell death. While NK cells were responsible for cell death at early time point of infection, CD8(+) T cells were for later. CD8(+) T cells that recognize NS4B(99-107) constitute at least one of the major intrahepatic cytotoxic CD8(+) T cell populations.

  15. Acute neck infections in children.

    PubMed

    Cengiz, A Bülent; Kara, Ateş; Kanra, Güler; Seçmeer, Gülten; Ceyhan, Mehmet; Ozen, Metehan

    2004-01-01

    A retrospective review was conducted on 132 patients aged between two and 15 years with cervical lymphadenitis and/or with abscess formation to determine the epidemiologic and clinical presentation of these infections. The most common locations were the upper anterior cervical space (43.2%) and the submandibular space (27.3%). The duration of symptoms ranged from 12 hours to 20 days. Results of the pus cultures were available in 31 patients (23.5%). Of these, 16 cultures (51.6%) were positive. The isolated organisms were Staphylococcus aureus (50%), Staphylococcus epidermidis (31.3%), group A beta-hemolytic streptococcus (12.5%), Streptococcus pneumoniae (6.3%) and Escherichia coli (6.3%). One of the specimens yielded mixed organisms (Staphylococcus epidermidis and Streptococcus pneumoniae). Penicillin resistance was documented in six (37.5%) of the 16 gram-positive bacteria isolated from the pus culture. Both throat and blood cultures were available in all 132 patients. Seven throat cultures (5.3%) were positive for group A beta hemolytic streptococci, whereas five blood cultures (3.8%) were reported to have bacterial growth. Sixty-seven patients (50.8%) were treated with ampicillin-sulbactam, 53 patients (40.1%) with ampicillin-sulbactam and ornidazole and 12 patients (9.1%) with ceftriaxone parenterally. The mean duration of hospital stay related to the infection was 7.30 +/- 3.89 days (range, 2-28 days). The mean period for downsizing of the cervical mass by half was 4.05 +/- 2.05 days, and the recovery period (total antibiotic usage period) was 13.72 +/- 5.33 days. All of the patients had an uneventful recovery without complications. Results of both throat and blood cultures were not predictive for etiologic agents in our study group. Since ultrasonographic evaluation of each patient has limited additional benefits in clinical management, it must be reserved for selected cases to document abscess formation.

  16. Cell type specificity and host genetic polymorphisms influence antibody-dependent enhancement of dengue virus infection.

    PubMed

    Boonnak, Kobporn; Dambach, Kaitlyn M; Donofrio, Gina C; Tassaneetrithep, Boonrat; Marovich, Mary A

    2011-02-01

    Antibody-dependent enhancement (ADE) is implicated in severe, usually secondary, dengue virus (DV) infections. Preexisting heterotypic antibodies, via their Fc-gamma receptor (FcγR) interactions, may increase disease severity through enhanced target cell infection. Greater numbers of infected target cells may contribute to higher viremia and excess cytokine levels often observed in severe disease. Monocytes, macrophages, and immature and mature dendritic cells (DC) are considered major cellular targets of DV. Apheresis of multiple donors allowed isolation of autologous primary myeloid target cell types for head-to-head comparison of infection rates, viral output, and cytokine production under direct infection (without antibody) or ADE conditions (with antibody). All studied cell types except immature DC supported ADE. All cells undergoing ADE secreted proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]) at enhancement titers, but distinct cell-type-specific patterns were observed for other relevant proteins (alpha/beta interferon [IFN-α/β] and IL-10). Macrophages produced type I interferons (IFN-α/β) that were modulated by ADE. Mature DC mainly secreted IFN-β. Interestingly, only monocytes secreted IL-10, and only upon antibody-enhanced infection. While ADE infection rates were remarkably consistent in monocytes (10 to 15%) across donors, IL-10 protein levels varied according to previously described regulatory single nucleotide polymorphisms (SNPs) in the IL-10 promoter region. The homozygous GCC haplotype was associated with high-level IL-10 secretion, while the ACC and ATA haplotypes produced intermediate and low levels of IL-10, respectively. Our data suggest that ADE effects are cell type specific, are influenced by host genetics, and, depending on relative infection rates, may further contribute to the complexity of DV pathogenesis.

  17. Suppressing dengue-2 infection by chemical inhibition of Aedes aegypti host factors.

    PubMed

    Kang, Seokyoung; Shields, Alicia R; Jupatanakul, Natapong; Dimopoulos, George

    2014-08-01

    Dengue virus host factors (DENV HFs) that are essential for the completion of the infection cycle in the mosquito vector and vertebrate host represent potent targets for transmission blocking. Here we investigated whether known mammalian DENV HF inhibitors could influence virus infection in the arthropod vector A. aegypti. We evaluated the potency of bafilomycin (BAF; inhibitor of vacuolar H+-ATPase (vATPase)), mycophenolic acid (MPA; inhibitor of inosine-5'-monophosphate dehydrogenase (IMPDH)), castanospermine (CAS; inhibitor of glucosidase), and deoxynojirimycin (DNJ; inhibitor of glucosidase) in blocking DENV infection of the mosquito midgut, using various treatment methods that included direct injection, ingestion by sugar feeding or blood feeding, and silencing of target genes by RNA interference (RNAi). Injection of BAF (5 µM) and MPA (25 µM) prior to feeding on virus-infected blood inhibited DENV titers in the midgut at 7 days post-infection by 56% and 60%, and in the salivary gland at 14 days post-infection by 90% and 83%, respectively, while treatment of mosquitoes with CAS or DNJ did not affect susceptibility to the virus. Ingestion of BAF and MPA through a sugar meal or together with an infectious blood meal also resulted in various degrees of virus inhibition. RNAi-mediated silencing of several vATPase subunit genes and the IMPDH gene resulted in a reduced DENV infection, thereby indicating that BAF- and MPA-mediated virus inhibition in adult mosquitoes most likely occurred through the inhibition of these DENV HFs. The route and timing of BAF and MPA administration was essential, and treatment after exposure to the virus diminished the antiviral effect of these compounds. Here we provide proof-of-principle that chemical inhibition or RNAi-mediated depletion of the DENV HFs vATPase and IMPDH can be used to suppress DENV infection of adult A. aegypti mosquitoes, which may translate to a reduction in DENV transmission.

  18. Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM.

    PubMed

    Luo, Yayan; Guo, Xiaolan; Yan, Huijun; Fang, Danyun; Zeng, Gucheng; Zhou, Junmei; Jiang, Lifang

    2015-07-01

    Dengue vaccine development is considered a global public health priority, but the antibody-dependent enhancement (ADE) issues have critically restricted vaccine development. Recent findings have demonstrated that pre-membrane (prM) protein was involved in dengue virus (DENV) infection enhancement. Although the importance of prM antibodies have been well characterized, only a few epitopes in DENV prM protein have ever been identified. In this study, we screened five potential linear epitopes located at positions pr1 (1-16aa), pr3 (13-28aa), pr4 (19-34aa), pr9 (49-64aa), and pr10 (55-70aa) in pr protein using peptide scanning and comprehensive bioinformatics analysis. Then, we found that only pr4 (19-34aa) could elicit high-titer antibodies in Balb/c mice, and this epitope could react with sera from DENV2-infected patients, suggesting that specific antibodies against epitope peptide pr4 were elicited in both DENV-infected mice and human. In addition, our data demonstrated that anti-pr4 sera showed limited neutralizing activity but significant ADE activity toward standard DENV serotypes and imDENV. Hence, it seems responsible to hypothesize that anti-pr4 serum was infection-enhancing antibody and pr4 was infection-enhancing epitope. In conclusion, we characterized a novel infection-enhancing epitope on dengue pr protein, a finding that may provide new insight into the pathogenesis of DENV infection and contribute to dengue vaccine design.

  19. Dengue shock syndrome

    PubMed Central

    Sudulagunta, Sreenivasa Rao; Sodalagunta, Mahesh Babu; Sepehrar, Mona; Bangalore Raja, Shiva Kumar; Nataraju, Aravinda Settikere; Kumbhat, Mounica; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

    2016-01-01

    Dengue fever is a mosquito-borne arthropod-borne viral (arboviral) tropical disease in humans affecting 50–528 million people worldwide. The acute abdominal complications of dengue fever are acute appendicitis, acute pancreatitis, acute acalculous cholecystitis and non-specific peritonitis. Acute pancreatitis with new onset diabetes in dengue shock syndrome (DSS) is very rarely reported. We describe a case of 30-year-old man admitted in intensive care unit and was diagnosed with DSS with RT-PCR, NS1 antigen and dengue IgM antibody being positive. Abdominal ultrasound and computerized tomography confirmed acute pancreatitis. Patient required insulin after recovery. Diabetes mellitus caused by DSS is under-reported and lack of awareness may increase mortality and morbidity. PMID:28031845

  20. A Critical Protection Level Derived from Dengue Infection Mathematical Model Considering Asymptomatic and Symptomatic Classes

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Supriatna, A. K.; Soewono, E.

    2013-04-01

    In this paper we formulate a model of dengue fever transmission by considering the presence of asymptomatic and symptomatic compartments. The model takes the form as a system of differential equations representing a host-vector SIR (Susceptible - Infective -Recovered) disease transmission. It is assumed that both host and vector populations are constant. It is also assumed that reinfection of recovered hosts by the disease is possible due to a wanning immunity in human body. We analyze the model to determine the qualitative behavior of the model solution and use the concept of effective basic reproduction number (fraktur Rp) as a control criteria of the disease transmission. The effect of mosquito biting protection (e.g. by using insect repellent) is also considered. We compute the long-term ratio of the asymptomatic and symptomatic classes and show a condition for which the iceberg phenomenon could appear.

  1. Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test

    PubMed Central

    Lukman, Nurhayati; Susanto, Nugroho Harry; Parwati, Ida; Fitri, Silvita; Alisjahbana, Bachti; Widjaja, Susana; Williams, Maya

    2016-01-01

    Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73). PMID:27446953

  2. Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro

    PubMed Central

    Paul, Amber M.; Shi, Yongliang; Acharya, Dhiraj; Douglas, Jessica R.; Cooley, Amanda; Anderson, John F.; Huang, Faqing

    2014-01-01

    Dengue virus (DENV) infection in humans can cause flu-like illness, life-threatening haemorrhagic fever or even death. There is no specific anti-DENV therapeutic or approved vaccine currently available, partially due to the possibility of antibody-dependent enhancement reaction. Small interfering RNAs (siRNAs) that target specific viral genes are considered a promising therapeutic alternative against DENV infection. However, in vivo, siRNAs are vulnerable to degradation by serum nucleases and rapid renal excretion due to their small size and anionic character. To enhance siRNA delivery and stability, we complexed anti-DENV siRNAs with biocompatible gold nanoparticles (AuNPs) and tested them in vitro. We found that cationic AuNP–siRNA complexes could enter Vero cells and significantly reduce DENV serotype 2 (DENV-2) replication and infectious virion release under both pre- and post-infection conditions. In addition, RNase-treated AuNP–siRNA complexes could still inhibit DENV-2 replication, suggesting that AuNPs maintained siRNA stability. Collectively, these results demonstrated that AuNPs were able to efficiently deliver siRNAs and control infection in vitro, indicating a novel anti-DENV strategy. PMID:24828333

  3. Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia.

    PubMed

    Hoh, B P; Umi-Shakina, H; Zuraihan, Z; Zaiharina, M Z; Rafidah-Hanim, S; Mahiran, M; Khairudin, N Y Nik; Benedict, L H Sim; Masliza, Z; Christopher, K C Lee; Sazaly, A B

    2015-06-01

    Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and "AGTTTAC" of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.

  4. Dengue fever

    MedlinePlus

    ... to occur and you have symptoms of the disease. Prevention Clothing, mosquito repellent, and netting can help reduce the risk of mosquito bites that can spread dengue fever and other infections. Limit outdoor activity during mosquito season, especially when they are most active, at ... Mosquito, adult feeding on the ...

  5. High-Content Assay to Identify Inhibitors of Dengue Virus Infection

    PubMed Central

    Shum, David; Smith, Jessica L.; Hirsch, Alec J.; Bhinder, Bhavneet; Radu, Constantin; Stein, David A.; Nelson, Jay A.; Früh, Klaus

    2010-01-01

    Abstract Dengue virus (DENV) infections are vectored by mosquitoes and constitute one of the most prevalent infectious diseases in many parts of the world, affecting millions of people annually. Current treatments for DENV infections are nonspecific and largely ineffective. In this study, we describe the adaptation of a high-content cell-based assay for screening against DENV-infected cells to identify inhibitors and modulators of DENV infection. Using this high-content approach, we monitored the inhibition of test compounds on DENV protein production by means of immunofluorescence staining of DENV glycoprotein envelope, simultaneously evaluating cytotoxicity in HEK293 cells. The adapted 384-well microtiter-based assay was validated using a small panel of compounds previously reported as having inhibitory activity against DENV infections of cell cultures, including compounds with antiviral activity (ribavirin), inhibitors of cellular signaling pathways (U0126), and polysaccharides that are presumed to interfere with virus attachment (carrageenan). A screen was performed against a collection of 5,632 well-characterized bioactives, including U.S. Food and Drug Administration–approved drugs. Assay control statistics show an average Z' of 0.63, indicative of a robust assay in this cell-based format. Using a threshold of >80% DENV inhibition with <20% cellular cytotoxicity, 79 compounds were initially scored as positive hits. A follow-up screen confirmed 73 compounds with IC50 potencies ranging from 60 nM to 9 μM and yielding a hit rate of 1.3%. Over half of the confirmed hits are known to target transporters, receptors, and protein kinases, providing potential opportunity for drug repurposing to treat DENV infections. In summary, this assay offers the opportunity to screen libraries of chemical compounds, in an effort to identify and develop novel drug candidates against DENV infections. PMID:20973722

  6. Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism.

    PubMed

    Thullier, P; Demangel, C; Bedouelle, H; Mégret, F; Jouan, A; Deubel, V; Mazié, J C; Lafaye, P

    2001-08-01

    Dengue virus infections are a growing public health concern and strategies to control the spread of the virus are urgently needed. The murine monoclonal antibody 4E11 might be of interest, since it neutralizes dengue viruses of all serotypes by binding to the 296-400 segment of the major dengue virus envelope glycoprotein (DE). When phage-displayed peptide libraries were screened by affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared three of nine residues with DE(306-314) and showed significant reactivity to 4E11 in ELISA. C1-induced antibodies cross-reacted with DE(296-400) in mice, suggesting that it was a structural equivalent of the native epitope of 4E11 on DE. Accordingly, 4E11 bound to the DE(306-314) synthetic peptide and this reaction was inhibited by DE(296-400). Moreover, DE(306-314) could block dengue virus infection of target cells in an in vitro assay. A three-dimensional model of DE revealed that the three amino acids shared by DE(296-400) and C1 were exposed to the solvent and suggested that most of the amino acids comprising the 4E11 epitope were located in the DE(306-314) region. Since 4E11 blocked the binding of DE(296-400) to heparin, which is a highly sulfated heparan sulfate (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE(306-314) with target cell-displayed HSHS. Our data suggest that the DE(306-314) segment is critical for the infectivity of all dengue virus serotypes and that molecules that block the binding of DE(306-314) to HSHS may be antiviral reagents of therapeutic interest.

  7. Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration.

    PubMed

    Bustos-Arriaga, José; Mita-Mendoza, Neida K; Lopez-Gonzalez, Moises; García-Cordero, Julio; Juárez-Delgado, Francisco J; Gromowski, Gregory D; Méndez-Cruz, René A; Fairhurst, Rick M; Whitehead, Stephen S; Cedillo-Barrón, Leticia

    2016-04-01

    When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood vessels, may get exposed to or infected with DENV. In these microenvironments of the skin, the presence of DENV initiates a complex interplay among the DENV-infected and non-infected neighboring cells at the initial bite site. Previous studies suggested that DENV-infected human dermal fibroblasts (HDFs) participate in the immune response against DENV by secreting soluble mediators of innate immunity. In the present study, we investigated whether DENV-infected HDFs activate human dermal microvascular endothelial cells (HDMECs) in co-cultures. Our results suggest that co-cultures of DENV-infected HDFs and HDMECs elicit soluble mediators that are sufficient to reduce viral replication, activate HDMECs, and induce leukocyte migration through HDMEC monolayers. These effects were partly dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease.

  8. Differential Expression of Toll-like Receptors in Dendritic Cells of Patients with Dengue during Early and Late Acute Phases of the Disease

    PubMed Central

    Torres, Silvia; Hernández, Juan Carlos; Giraldo, Diana; Arboleda, Margarita; Rojas, Mauricio; Smit, Jolanda M.; Urcuqui-Inchima, Silvio

    2013-01-01

    Background Dengue hemorrhagic fever (DHF) is observed in individuals that have pre-existing heterotypic dengue antibodies and is associated with increased viral load and high levels of pro-inflammatory cytokines early in infection. Interestingly, a recent study showed that dengue virus infection in the presence of antibodies resulted in poor stimulation of Toll-like receptors (TLRs), thereby facilitating virus particle production, and also suggesting that TLRs may contribute to disease pathogenesis. Methodology/Principal Findings We evaluated the expression levels of TLR2, 3, 4 and 9 and the co-stimulatory molecules CD80 and CD86 by flow cytometry. This was evaluated in monocytes, in myeloid and plasmacytoid dendritic cells (mDCs and pDCs) from 30 dengue patients with different clinical outcomes and in 20 healthy controls. Increased expression of TLR3 and TLR9 in DCs of patients with dengue fever (DF) early in infection was detected. In DCs from patients with severe manifestations, poor stimulation of TLR3 and TLR9 was observed. In addition, we found a lower expression of TLR2 in patients with DF compared to DHF. Expression levels of TLR4 were not affected. Furthermore, the expression of CD80 and CD86 was altered in mDCs and CD86 in pDCs of severe dengue cases. We show that interferon alpha production decreased in the presence of dengue virus after stimulation of PBMCs with the TLR9 agonist (CpG A). This suggests that the virus can affect the interferon response through this signaling pathway. Conclusions/Significance These results show that during dengue disease progression, the expression profile of TLRs changes depending on the severity of the disease. Changes in TLRs expression could play a central role in DC activation, thereby influencing the innate immune response. PMID:23469297

  9. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775–875 cm‑1, lectins at 1003, 1238, 1340, 1449 and 1672 cm‑1, DNA in the region 1040–1140 cm‑1 and alpha and beta structures of proteins in the region 933–967 cm‑1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  10. Antibody-Dependent Enhancement of Dengue Virus Infection in Primary Human Macrophages; Balancing Higher Fusion against Antiviral Responses

    PubMed Central

    Flipse, Jacky; Diosa-Toro, Mayra A.; Hoornweg, Tabitha E.; van de Pol, Denise P. I.; Urcuqui-Inchima, Silvio; Smit, Jolanda M.

    2016-01-01

    The dogma is that the human immune system protects us against pathogens. Yet, several viruses, like dengue virus, antagonize the hosts’ antibodies to enhance their viral load and disease severity; a phenomenon called antibody-dependent enhancement of infection. This study offers novel insights in the molecular mechanism of antibody-mediated enhancement (ADE) of dengue virus infection in primary human macrophages. No differences were observed in the number of bound and internalized DENV particles following infection in the absence and presence of enhancing concentrations of antibodies. Yet, we did find an increase in membrane fusion activity during ADE of DENV infection. The higher fusion activity is coupled to a low antiviral response early in infection and subsequently a higher infection efficiency. Apparently, subtle enhancements early in the viral life cycle cascades into strong effects on infection, virus production and immune response. Importantly, and in contrast to other studies, the antibody-opsonized virus particles do not trigger immune suppression and remain sensitive to interferon. Additionally, this study gives insight in how human macrophages interact and respond to viral infections and the tight regulation thereof under various conditions of infection. PMID:27380892

  11. Dengue virus infection induces expansion of a CD14(+)CD16(+) monocyte population that stimulates plasmablast differentiation.

    PubMed

    Kwissa, Marcin; Nakaya, Helder I; Onlamoon, Nattawat; Wrammert, Jens; Villinger, Francois; Perng, Guey Chuen; Yoksan, Sutee; Pattanapanyasat, Kovit; Chokephaibulkit, Kulkanya; Ahmed, Rafi; Pulendran, Bali

    2014-07-09

    Dengue virus (DENV) infection induces the expansion of plasmablasts, which produce antibodies that can neutralize DENV but also enhance disease upon secondary infection with another DENV serotype. To understand how these immune responses are generated, we used a systems biological approach to analyze immune responses to dengue in humans. Transcriptomic analysis of whole blood revealed that genes encoding proinflammatory mediators and type I interferon-related proteins were associated with high DENV levels during initial symptomatic disease. Additionally, CD14(+)CD16(+) monocytes increased in the blood. Similarly, in a nonhuman primate model, DENV infection boosted CD14(+)CD16(+) monocyte numbers in the blood and lymph nodes. Upon DENV infection in vitro, monocytes upregulated CD16 and mediated differentiation of resting B cells to plasmablasts as well as immunoglobulin G (IgG) and IgM secretion. These findings provide a detailed picture of innate responses to dengue and highlight a role for CD14(+)CD16(+) monocytes in promoting plasmablast differentiation and anti-DENV antibody responses.

  12. Symptoms and Immune Markers in Plasmodium/Dengue Virus Co-infection Compared with Mono-infection with Either in Peru

    PubMed Central

    Halsey, Eric S.; Baldeviano, G. Christian; Edgel, Kimberly A.; Vilcarromero, Stalin; Sihuincha, Moises; Lescano, Andres G.

    2016-01-01

    Background Malaria and dengue are two of the most common vector-borne diseases in the world, but co-infection is rarely described, and immunologic comparisons of co-infection with mono-infection are lacking. Methodology and Principal Findings We collected symptom histories and blood specimens from subjects in a febrile illness surveillance study conducted in Iquitos and Puerto Maldonado, Peru, between 2002–2011. Nineteen symptoms and 18 immune markers at presentation were compared among those with co-infection with Plasmodium/dengue virus (DENV), Plasmodium mono-infection, and DENV mono-infection. Seventeen subjects were identified as having Plasmodium/DENV co-infection and were retrospectively matched with 51 DENV mono-infected and 44 Plasmodium mono-infected subjects. Those with Plasmodium mono-infection had higher levels of IL-4, IL-6, IL-10, IL-12, IL-13, IL-17A, IFN-γ, and MIP1-α/CCL3 compared with DENV mono-infection or co-infection; those with Plasmodium mono-infection had more cough than those with DENV mono-infection. Subjects with DENV mono-infection had higher levels of TGF-β1 and more myalgia than those with Plasmodium mono-infection. No symptom was more common and no immune marker level was higher in the co-infected group, which had similar findings to the DENV mono-infected subjects. Conclusions/Significance Compared with mono-infection with either pathogen, Plasmodium/DENV co-infection was not associated with worse disease and resembled DENV mono-infection in both symptom frequency and immune marker level. PMID:27128316

  13. Potential biomarkers for the clinical prognosis of severe dengue.

    PubMed

    Silva, Mayara Marques Carneiro da; Gil, Laura Helena Vega Gonzales; Marques, Ernesto Torres de Azevedo; Calzavara-Silva, Carlos Eduardo

    2013-09-01

    Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  14. An epidemiological cluster pattern of dengue outbreak amongst close contacts in Selangor, Peninsular Malaysia.

    PubMed

    Ang, K T; Ruhaini, I; Chua, K B

    2006-08-01

    Dengue fever is major public health problem especially among the highly urbanized states of Malaysia, such as, Selangor and Kuala Lumpur Federal Territory. We report an epidemiological cluster pattern of dengue outbreak in the district of Gombak, Selangor that may mimic other acute febrile illnesses in which the transmission mode is via close contact. This dengue outbreak consisted of two waves; an initial cluster of three cases (including the first deceased, JI) which occurred between 20th and 21st of July, followed by a later larger cluster of 11 cases that occurred between 1st and 8th of August 2005. This epidemiological clustering pattern of acute dengue virus infection among close contacts suggests an intense rate of dengue virus transmission within the vicinity of the first deceased's house.

  15. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection

    PubMed Central

    Pinto, Amelia K.; Brien, James D.; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V.; Barrett, Alan D.; Shresta, Sujan

    2015-01-01

    ABSTRACT With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre+ Ifnarflox/flox [denoted as Ifnarf/f herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre+ Ifnarf/f mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre+ Ifnarf/f mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. PMID:26374123

  16. Dengue hemorrhagic fever

    MedlinePlus

    ... a severe, potentially deadly infection spread by some mosquitos. Causes Four different dengue viruses are known to ... occurs when a person is bitten by a mosquito that is infected with the virus. The mosquito ...

  17. Paper-based point-of-care testing for cost-effective diagnosis of acute flavivirus infections.

    PubMed

    Bedin, Frederic; Boulet, Laurent; Voilin, Elodie; Theillet, Gerald; Rubens, Agnes; Rozand, Christine

    2017-03-11

    Flavivirus infections are a serious healthcare concern in tropical and subtropical countries. Although well-established laboratory tests can provide early diagnosis of acute dengue or Zika infections, access to these tests is limited in developing countries, presenting an urgent need to develop simple, rapid, and robust diagnostic tools. Microfluidic Paper-based Analytical Devices (μPAD), are typically rapid, cost-effective, user-friendly, and they can be used as diagnostic tools for the diagnosis of these infections at Point of Care settings. Early and prompt diagnosis is crucial to improve patient management and reduce the risk of complications. In the present study, we developed and evaluated a wax-printed paper-based device for the detection of the dengue and Zika non-structural NS1 viral protein in blood and plasma. Experiments have been carried out to increase specificity, while maintaining the required sensitivity. As a consequence, the quality of the raw materials and the washing steps were proved to be crucial. The μPAD was able to detect specifically in 6-8 min 10 ng/mL of protein in various sample types. A prototype for the differential detection of dengue and/or Zika NS1 protein was developed. The reading of the results was simplified by using a dedicated application on a smartphone.

  18. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

    PubMed Central

    Viktorovskaya, Olga V.; Greco, Todd M.; Cristea, Ileana M.; Thompson, Sunnie R.

    2016-01-01

    Background There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication. Methodology/Principal Findings Seventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated. Conclusions/Significance The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with

  19. Differential targeting of viral components by CD4+ versus CD8+ T lymphocytes in dengue virus infection.

    PubMed

    Rivino, Laura; Kumaran, Emmanuelle A P; Jovanovic, Vojislav; Nadua, Karen; Teo, En Wei; Pang, Shyue Wei; Teo, Guo Hui; Gan, Victor Chih Hao; Lye, David C; Leo, Yee Sin; Hanson, Brendon J; Smith, Kenneth G C; Bertoletti, Antonio; Kemeny, David M; MacAry, Paul A

    2013-03-01

    Dengue virus (DENV) is the principal arthropod-borne viral pathogen afflicting human populations. While repertoires of antibodies to DENV have been linked to protection or enhanced infection, the role of T lymphocytes in these processes remains poorly defined. This study provides a comprehensive overview of CD4(+) and CD8(+) T cell epitope reactivities against the DENV 2 proteome in adult patients experiencing secondary DENV infection. Dengue virus-specific T cell responses directed against an overlapping 15mer peptide library spanning the DENV 2 proteome were analyzed ex vivo by enzyme-linked immunosorbent spot assay, and recognition of individual peptides was further characterized in specific T cell lines. Thirty novel T cell epitopes were identified, 9 of which are CD4(+) and 21 are CD8(+) T cell epitopes. We observe that whereas CD8(+) T cell epitopes preferentially target nonstructural proteins (NS3 and NS5), CD4(+) epitopes are skewed toward recognition of viral components that are also targeted by B lymphocytes (envelope, capsid, and NS1). Consistently, a large proportion of dengue virus-specific CD4(+) T cells have phenotypic characteristics of circulating follicular helper T cells (CXCR5 expression and production of interleukin-21 or gamma interferon), suggesting that they are interacting with B cells in vivo. This study shows that during a dengue virus infection, the protein targets of human CD4(+) and CD8(+) T cells are largely distinct, thus highlighting key differences in the immunodominance of DENV proteins for these two cell types. This has important implications for our understanding of how the two arms of the human adaptive immune system are differentially targeted and employed as part of our response to DENV infection.

  20. Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection

    PubMed Central

    Chen, Jincheng; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

    2015-01-01

    Dengue virus (DV) infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR) 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC. IL-6 and TNF-α production by PBMC were reduced when TLR2 and TLR6 were blocked using TLR2 and TLR6 neutralizing antibodies during DV infection. These results suggested that signaling pathways of TLR2 and TLR6 were activated during DV infection and its activation contributed to IL-6 and TNF-α production. DV NS1 protein was found to significantly increase the production of IL-6 and TNF-α when added to PBMC. The amount of IL-6 and TNF-α stimulated by DV NS1 protein was reduced when TLR2 and TLR6 were blocked, suggesting that DV NS1 protein is the viral protein responsible for the activation of TLR2 and TLR6 during DV infection. Secreted alkaline phosphatase (SEAP) reporter assay was used to further confirm activation of TLR2 and TLR6 by DV NS1 protein. In addition, DV-infected and DV NS1 protein-treated TLR6-/- mice have higher survivability compared to DV-infected and DV NS1 protein-treated wild-type mice. Hence, activation of TLR6 via DV NS1 protein could potentially play an important role in the immunopathogenesis of DV infection. PMID:26226614

  1. [Risk factors associated to the epidemic outbreak of dengue virus infection.

    PubMed

    García-Gutiérrez, María Del Rocío; Romero-Zepeda, Hilda; Salvador Romero-Márquez, Rubén

    2013-01-01

    Objective: to identify the risk factors associated to the epidemic of dengue virus infections occurred at Queretaro, Mexico. Methods: a case-control study was carried out on 49 cases and 49 controls. The data included: age, sex, residency, schooling, occupation, clinical data, sources infected with Aedes aegypti, travelling, source of waters, and protection to water recipients. The protection to door and windows was investigated. χ(2) test and odds ratio were estimated. Results: the age group of 20-39 years was the most affected and women predominated. The Satellite area contributed with 38 cases (77.1 %). The absence of mosquito nettings on windows had an OR = 1.8, and ignorance of preventive activities had an OR = 2.8, while the use of insecticides (OR = 0.30) and mosquito repellents (OR = 0.54) were protective factors. Conclusions: the epidemic outbreak in Queretaro confirmed that Aedes aegypti has adapted to greater heights. This fact should alert to the sanitary authorities to face the possibility of an epidemic outbreak with great affectation among population.

  2. [Evaluation of the infectivity of dengue 1 strains in the HepG2 and Vero cell lines].

    PubMed

    Aguilar Barroso, Alicia; Amin Blanco, Nevis; Morier Díaz, Luis; Pérez Hernández, Ela María

    2005-01-01

    Viral infectivity of Hawaii, 3 Peri and Riberao Pretto dengue 1 strains was evaluated in Vero and HepG2 cell lines by indirect immunofluorescence techniques. Dengue virus cellular tropism in vitro is diverse. They may replicate themselves in a great variety of cellular cultures, whose sensibility to viral infection is variable. The greatest percentage of infected cells in the HepG2 cell line was obtained with the highest multiplicities of infection (0.04 for Hawaii and Riberao Pretto strains and 0.01 for 3 Perú). The highest percentage of infected HepG2 and Vero cells for the studied strains and the greatest titer in the viral overnadant was obtained on the 5th day. Vero cell line was more sensitive to viral infection, since for the same multiplicity values it was detected a higher number of fluorescent cells and a better viral titre in the line of this overnadant than in the HepG2. The best result was obtained with the Hawaii strain that allowed to confirm faster the infection of the studied cellular lines.

  3. Acute disseminated encephalomyelitis (ADEM) after pertussis infection.

    PubMed

    Budan, B; Ekici, B; Tatli, B; Somer, A

    2011-01-01

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder of the central nervous system which is usually precipitated by a viral infection or vaccination. A 3-month-old boy is reported who developed ADEM a week after full recovery from pertussis. MRI detected a high-intensity lesion extending from the pons to the mesencephalon, compatible with ADEM. Following the administration of intravenous immunoglobulins, the patient's clinical symptoms improved. This case report demonstrates that pertussis is capable of inducing an immune-mediated demyelinating disorder of the central nervous system.

  4. Accuracy of AccessBio Immunoglobulin M and Total Antibody Rapid Immunochromatographic Assays for the Diagnosis of Acute Scrub Typhus Infection

    DTIC Science & Technology

    2010-02-01

    Median no. of Median (range) reciprocal Infection group or specimens days of fever Verification scrub typhus lgM titer on Geographical source...five for the murine typhus group, seven for the leptospirosis group, nine for the malaria group, four for the dengue fever group, and five for the...diagnoses of a variety of acute tropical fevers prevalent in Southeast Asia suggest that the AccessBio scrub typhus IgM ICT is suitably accurate for

  5. Clinico-radiological profile and outcome of dengue patients with central nervous system manifestations: A case series in an Eastern India tertiary care hospital

    PubMed Central

    Pal, Souren; Sen, Kaushik; Biswas, Nirendra Mohan; Ghosal, Anirban; Rousan Jaman, S. K.; Yashavantha Kumar, K. Y.

    2016-01-01

    Background and Objective: Dengue, an acute viral disease, transmitted by Aedes mosquitoes, has a variable clinical spectrum ranging from asymptomatic infection to life-threatening dengue hemorrhagic fever and dengue shock syndrome. However, neurological complications, in general, are unusual but have been observed more frequently in the recent past, and some studies highlighted varied neurological complications during the course of illness. Although dengue is classically considered a nonneurotropic virus, there is increasing evidence for dengue viral neurotropism. In this study, we have evaluated clinico-radiological profile and outcome of nine serologically confirmed dengue patients having varied manifestations of central nervous system (CNS) involvement. Materials and Methods: All the consecutive patients presented with neurological complications with positive serology for dengue infection (IgM positivity) in Department of Medicine, in a tertiary care hospital in Eastern India from August 2013 to October 2014 were included in the study. These patients were subjected to a detailed clinical evaluation, laboratory assessment including complete hemogram, coagulation profile, liver function test, serum electrolytes, and routine CSF (Cerebrospinal Fluid) study with the exclusion of other common neuroinvasive pathogens. Results: Out of 9 patients with neurological complications associated with confirmed dengue infection, 2 (22%) patients had dengue encephalopathy, 5 (56%) patients have dengue encephalitis, 1 (11%) patient had dengue meningitis, and 1 (11%) patient had postdengue immune-mediated CNS involvement. Conclusion: This case series reaffirms the occurrence of varied CNS manifestations in dengue virus infection and underlines the importance of inclusion of dengue in the differential diagnosis of acute encephalitis syndrome. PMID:26933357

  6. Acute encephalitis as initial presentation of primary HIV infection.

    PubMed

    Nzwalo, Hipólito; Añón, Rosário Pazos; Àguas, Maria João

    2012-07-03

    Acute encephalitis is a life-threatening condition. A wide variety of infectious agents are implicated and in many patients no cause is found. HIV acute seroconversion illness can rarely present as acute encephalitis. Although most experts agree in starting antiretroviral treatment in severe acute HIV infection, the evidence of the benefits are still lacking. The authors report a case of severe acute encephalitis as a primary presentation of HIV infection in which introduction of highly active antiretroviral treatment resulted in clinical recovery. This case highlights the need to consider HIV infection in the differential diagnosis of treatable viral encephalitis.

  7. Clinically Profiling Pediatric Patients with Dengue

    PubMed Central

    Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingham, Mahalaskhmy; Sampath, Srinivasan

    2016-01-01

    Objective: To study the clinical profile and outcome of dengue fever in children at a tertiary care hospital in Puducherry. Materials and Methods: All children (0-12 years of age) diagnosed and confirmed as dengue fever from August 2012 to January 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization guidelines for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies, and the data were analyzed using SPSS 16.0 statistical software. After collecting the data, all the variables were summarized by descriptive statistics. Results: Among the 261 confirmed cases of dengue fever non-severe and severe dengue infection was seen in 60.9% and 39.1%, respectively. The mean age (standard deviation) of the presentation was 6.9 + 3.3 years and male: female ratio was 1.2:1. The most common clinical manifestations were fever (94.6%), conjunctival congestion (89.6%), myalgia (81.9%), coryza (79.7%), headache (75.1%), palmar erythema (62.8%), and retro-orbital pain (51.3%). The common early warning signs at the time of admission were persistent vomiting (75.1%), liver enlargement (59.8%), cold and clammy extremities (45.2%), pain abdomen (31.0%), hypotension (29.5%), restlessness (26.4%), giddiness (23.0%), bleeding (19.9%), and oliguria (18.4%). The common manifestation of severe dengue infection was shock (39.1%), bleeding (19.9%), and multi-organ dysfunction (2.3%). The most common complications were liver dysfunction, acute respiratory distress syndrome, encephalopathy, pleural effusion, ascites, myocarditis, myositis, acute kidney injury, and disseminated intravascular coagulopathy. Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.3%) and out of them four presented with impaired consciousness (66.6%). The common causes for poor outcome were multiorgan failure, encephalopathy, and fluid refractory shock

  8. Prevalence of dengue viral and malaria parasitic co-infections in an epidemic district, Angul of Odisha, India: An eco-epidemiological and cross-sectional study for the prospective aspects of public health.

    PubMed

    Rao, M Rajesh Kumar; Padhy, Rabindra N; Das, Manoj K

    2016-01-01

    The co-existence of dengue and malaria infection in an individual and the primary and secondary dengue infection during co-infection were assessed. Over 1 year, 1980 blood samples were collected from suspected cases of dengue fever and analyzed by rapid diagnostic test (RDT), enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods to detect dengue infection. RDT and microscopic methods were used to detect malaria. Of the 1980 samples, only 22 (3.0%) cases were identified as dengue-malaria co-infection cases, out of which 13 were male and 9 were female. The highest number of confirmed cases were found during the hot and humid months of September and October (7 cases, 31.8%) and within the over 15 years age group. Of the cases of co-infection, dengue primary infection (21 cases, 95.5%) was significantly more common than dengue secondary infection (1 case, 4.5%) among all of the age groups. There were 12 cases of Plasmodium falciparum and 10 cases of Plasmodium vivax infection among malarial cases. A high prevalence of concurrence of dengue and malaria infection was recorded in this ecosystem. In light of the severity of co-infection and overlapping symptoms, a multidimensional diagnostic approach is suggested.

  9. Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection.

    PubMed

    Callaway, Justin B; Smith, Scott A; McKinnon, Karen P; de Silva, Aravinda M; Crowe, James E; Ting, Jenny P-Y

    2015-07-10

    Approximately 500,000 people are hospitalized with severe dengue illness annually. Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is believed to contribute to the pathogenic cytokine storm described in severe dengue patients, but the precise signaling pathways contributing to elevated cytokine production are not elucidated. IL-1β is a potent inflammatory cytokine that is frequently elevated during severe dengue, and the unique dual regulation of IL-1β provides an informative model to study ADE-induced cytokines. This work utilizes patient-derived anti-DENV mAbs and primary human monocytes to study ADE-induced IL-1β and other cytokines. ADE of DENV serotype 2 (DENV-2) elevates mature IL-1β secretion by monocytes independent of DENV replication by 4 h postinoculation (hpi). Prior to this, DENV immune complexes activate spleen tyrosine kinase (Syk) within 1 hpi. Syk induces elevated IL1B, TNF, and IL6 mRNA by 2 hpi. Syk mediates elevated IL-1β secretion by activating ERK1/2, and both Syk and ERK1/2 inhibitors ablated ADE-induced IL-1β secretion. Maturation of pro-IL-1β during ADE requires caspase-1 and NLRP3, but caspase-1 is suboptimally increased by ADE and can be significantly enhanced by a typical inflammasome agonist, ATP. Importantly, this inflammatory Syk-ERK signaling axis requires DENV immune complexes, because DENV-2 in the presence of serotype-matched anti-DENV-2 mAb, but not anti-DENV-1 mAb, activates Syk, ERK, and IL-1β secretion. This study provides evidence that DENV-2 immune complexes activate Syk to mediate elevated expression of inflammatory cytokines. Syk and ERK may serve as new therapeutic targets for interfering with ADE-induced cytokine expression during severe dengue.

  10. Towards a Casa Segura: A Consumer Product Study of the Effect of Insecticide-Treated Curtains on Aedes aegypti and Dengue Virus Infections in the Home

    PubMed Central

    Loroño-Pino, María Alba; García-Rejón, Julián E.; Machain-Williams, Carlos; Gomez-Carro, Salvador; Nuñez-Ayala, Guadalupe; del Rosario Nájera-Vázquez, Maria; Losoya, Arturo; Aguilar, Lyla; Saavedra-Rodriguez, Karla; Lozano-Fuentes, Saul; Beaty, Meaghan K.; Black, William C.; Keefe, Thomas J.; Eisen, Lars; Beaty, Barry J.

    2013-01-01

    The home, or domicile, is the principal environment for transmission of dengue virus (DENV) between humans and mosquito vectors. Community-wide distribution of insecticide-treated curtains (ITCs), mimicking vector control program-driven interventions, has shown promise to reduce DENV infections. We conducted a Casa Segura consumer product intervention study in Mérida, Mexico to determine the potential to reduce intradomicillary DENV transmission through ITC use in individual homes. Dengue virus infections in mosquitoes and in humans were reduced in homes with ITCs in one of two study subareas. Overall, ITCs reduced intradomicillary DENV transmission; ITC homes were significantly less likely to experience multiple DENV infections in humans than NTC homes. Dengue virus–infected Aedes aegypti females were reduced within the ITC homes where curtain use was highest. Some homes yielded up to nine infected Ae. aegypti females. This study provides insights regarding best practices for Casa Segura interventions to protect homes from intradomicillary DENV transmission. PMID:23732254

  11. Unusual Presentation of Dengue Fever Leading to Unnecessary Appendectomy.

    PubMed

    Kumar, Lovekesh; Singh, Mahendra; Saxena, Ashish; Kolhe, Yuvraj; Karande, Snehal K; Singh, Narendra; Venkatesh, P; Meena, Rambabu

    2015-01-01

    Dengue fever is the most important arbovirus illness with an estimated incidence of 50-100 million cases per year. The common symptoms of dengue include fever, rash, malaise, nausea, vomiting, and musculoskeletal pain. Dengue fever may present as acute abdomen leading to diagnostic dilemma. The acute surgical complications of dengue fever include acute pancreatitis, acute acalculous cholecystitis, nonspecific peritonitis, and acute appendicitis. We report a case of dengue fever that mimicked acute appendicitis leading to unnecessary appendectomy. A careful history examination for dengue-related signs, and serial hemogram over the first 3-4 days of disease may prevent unnecessary appendectomy.

  12. Unusual Presentation of Dengue Fever Leading to Unnecessary Appendectomy

    PubMed Central

    Kumar, Lovekesh; Singh, Mahendra; Saxena, Ashish; Kolhe, Yuvraj; Karande, Snehal K.; Singh, Narendra; Venkatesh, P.; Meena, Rambabu

    2015-01-01

    Dengue fever is the most important arbovirus illness with an estimated incidence of 50–100 million cases per year. The common symptoms of dengue include fever, rash, malaise, nausea, vomiting, and musculoskeletal pain. Dengue fever may present as acute abdomen leading to diagnostic dilemma. The acute surgical complications of dengue fever include acute pancreatitis, acute acalculous cholecystitis, nonspecific peritonitis, and acute appendicitis. We report a case of dengue fever that mimicked acute appendicitis leading to unnecessary appendectomy. A careful history examination for dengue-related signs, and serial hemogram over the first 3-4 days of disease may prevent unnecessary appendectomy. PMID:26167314

  13. Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus.

    PubMed

    Hsieh, Ming-Fang; Lai, Szu-Liang; Chen, Jia-Perng; Sung, Jui-Ming; Lin, Yi-Ling; Wu-Hsieh, Betty A; Gerard, Craig; Luster, Andrew; Liao, Fang

    2006-08-01

    We examined the extent to which CXCR3 mediates resistance to dengue infection. Following intracerebral infection with dengue virus, CXCR3-deficient (CXCR3(-/-)) mice showed significantly higher mortality rates than wild-type (WT) mice; moreover, surviving CXCR3(-/-) mice, but not WT mice, often developed severe hind-limb paralysis. The brains of CXCR3(-/-) mice showed higher viral loads than those of WT mice, and quantitative analysis using real-time PCR, flow cytometry, and immunohistochemistry revealed fewer T cells, CD8(+) T cells in particular, in the brains of CXCR3(-/-) mice. This suggests that recruitment of effector T cells to sites of dengue infection was diminished in CXCR3(-/-) mice, which impaired elimination of the virus from the brain and thus increased the likelihood of paralysis and/or death. These results indicate that CXCR3 plays a protective rather than an immunopathological role in dengue virus infection. In studies to identify critical CXCR3 ligands, CXCL10/IFN-inducible protein 10-deficient (CXCL10/IP-10(-/-)) mice infected with dengue virus showed a higher mortality rate than that of the CXCR3(-/-) mice. Although CXCL10/IP-10, CXCL9/monokine induced by IFN-gamma, and CXCL11/IFN-inducible T cell alpha chemoattractant share a single receptor and all three of these chemokines are induced by dengue virus infection, the latter two could not compensate for the absence of CXCL10/IP-10 in this in vivo model. Our results suggest that both CXCR3 and CXCL10/IP-10 contribute to resistance against primary dengue virus infection and that chemokines that are indistinguishable in in vitro assays differ in their activities in vivo.

  14. Role of Microparticles in Dengue Virus Infection and Its Impact on Medical Intervention Strategies

    PubMed Central

    Bargeron Clark, Kristina; Hsiao, Hui-Mien; Noisakran, Sansanee; Tsai, Jih-Jin; Perng, Guey Chuen

    2012-01-01

    Dengue virus (DV) is one of the most important vector-borne diseases in the world. It causes a disease that manifests as a spectrum of clinical symptoms, including dengue hemorrhagic fever. DV is proficient at diverting the immune system to facilitate transmission through its vector host, Aedes spp. mosquito. Similar to other vector-borne parasites, dengue may also require a second structural form, a virus of alternative morphology (VAM), to complete its life cycle. DV can replicate to high copy numbers in patient plasma, but no classical viral particles can be detected by ultra-structural microscopy analysis. A VAM appearing as a microparticle has been recapitulated with in vitro cell lines Meg01 and K562, close relatives to the cells harboring dengue virus in vivo. VAMs are likely to contribute to the high viremia levels observed in dengue patients. This review discusses the possible existence of a VAM in the DV life cycle. PMID:22461739

  15. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  16. Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis

    PubMed Central

    Biswas, Hope H.; Ortega, Oscar; Gordon, Aubree; Standish, Katherine; Balmaseda, Angel; Kuan, Guillermina; Harris, Eva

    2012-01-01

    Background Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. Methods Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. Results One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. Conclusions Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management. PMID:22413033

  17. Comparison of Stable and Transient Wolbachia Infection Models in Aedes aegypti to Block Dengue and West Nile Viruses.

    PubMed

    Joubert, Dirk Albert; O'Neill, Scott L

    2017-01-01

    Pathogen replication and transmission in Wolbachia infected insects are currently studied using three Wolbachia infection systems: naturally infected Wolbachia hosts, hosts transinfected with Wolbachia (stably maintained and inherited infections) and hosts transiently infected with Wolbachia. All three systems have been used to test the effect of Wolbachia on mosquito transmitted pathogens such as dengue virus (DENV), West Nile virus (WNV) and Plasmodium. From these studies it is becoming increasingly clear that the interaction between a particular pathogen and Wolbachia is heavily influenced by the host-Wolbachia interaction and the model of infection. In particular, there is some evidence that under very specific conditions, Wolbachia can enhance pathogen infection in some hosts. In this study, we compared the effect of Wolbachia in two infection models (stable transinfected and transiently infected) on the replication, infection- and transmission rates of two flaviviruses, DENV and WNV (Kunjin strain). Our results indicate that Wolbachia had similar blocking effects in both stable and transient models of infection, however, the magnitude of the blocking effect was significantly lower in mosquitoes transiently infected with Wolbachia. More importantly, no evidence was found for any enhancement of either DENV or WNV (Kunjin strain) infection in Ae. aegypti infected with Wolbachia, supporting a role for Wolbachia as an effective and safe means for restricting transmission of these viruses.

  18. Comparison of Stable and Transient Wolbachia Infection Models in Aedes aegypti to Block Dengue and West Nile Viruses

    PubMed Central

    Joubert, Dirk Albert; O’Neill, Scott L.

    2017-01-01

    Pathogen replication and transmission in Wolbachia infected insects are currently studied using three Wolbachia infection systems: naturally infected Wolbachia hosts, hosts transinfected with Wolbachia (stably maintained and inherited infections) and hosts transiently infected with Wolbachia. All three systems have been used to test the effect of Wolbachia on mosquito transmitted pathogens such as dengue virus (DENV), West Nile virus (WNV) and Plasmodium. From these studies it is becoming increasingly clear that the interaction between a particular pathogen and Wolbachia is heavily influenced by the host-Wolbachia interaction and the model of infection. In particular, there is some evidence that under very specific conditions, Wolbachia can enhance pathogen infection in some hosts. In this study, we compared the effect of Wolbachia in two infection models (stable transinfected and transiently infected) on the replication, infection- and transmission rates of two flaviviruses, DENV and WNV (Kunjin strain). Our results indicate that Wolbachia had similar blocking effects in both stable and transient models of infection, however, the magnitude of the blocking effect was significantly lower in mosquitoes transiently infected with Wolbachia. More importantly, no evidence was found for any enhancement of either DENV or WNV (Kunjin strain) infection in Ae. aegypti infected with Wolbachia, supporting a role for Wolbachia as an effective and safe means for restricting transmission of these viruses. PMID:28052065

  19. Proteomic analysis of the secretome of HepG2 cells indicates differential proteolytic processing after infection with dengue virus.

    PubMed

    Caruso, Marjolly B; Trugilho, Monique R O; Higa, Luiza M; Teixeira-Ferreira, André S; Perales, Jonas; Da Poian, Andrea T; Zingali, Russolina B

    2017-01-16

    Secretome analysis can be described as a subset of proteomics studies consisting in the analysis of the molecules secreted by cells or tissues. Dengue virus (DENV) infection can lead to a broad spectrum of clinical manifestations, with the severe forms of the disease characterized by hemostasis abnormalities and liver injury. The hepatocytes are a relevant site of viral replication and a major source of plasma proteins. Until now, we had limited information on the small molecules secreted by hepatic cells after infection by DENV. In the present study, we analysed a fraction of the secretome of mock- and DENV-infected hepatic cells (HepG2 cells) containing molecules with <10kDa, using different proteomic approaches. We identified 175 proteins, with 57 detected only in the samples from mock-infected cells, 59 only in samples from DENV-infected cells, and 59 in both conditions. Most of the peptides identified were derived from proteins larger than 10kDa, suggesting a proteolytic processing of the secreted molecules. Using in silico analysis, we predicted consistent differences between the proteolytic processing occurring in mock and DENV-infected samples, raising, for the first time, the hypothesis that differential proteolysis of secreted molecules would be involved in the pathogenesis of dengue.

  20. Infective substructures of measles virus from acutely and persistently infected cells.

    PubMed Central

    Rozenblatt, S; Koch, T; Pinhasi, O; Bratosin, S

    1979-01-01

    Ribonucleoprotein from cells acutely or persistently infected with measles virus were shown to be infectious by the calcium phosphate technique. Very little or no infectivity was obtained when calcium phosphate precipitation was omitted. Electron microscopy showed that the majority of ribonucleoprotein structures isolated from acutely infected cells were folded, whereas those from persistently infected cells were linear in appearance. Images PMID:120450

  1. Invasive Fungal Infections in Acute Leukemia

    PubMed Central

    Bhatt, Vijaya R.; Viola, George M.; Ferrajoli, Alessandra

    2011-01-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed. PMID:23556092

  2. Invasive fungal infections in acute leukemia.

    PubMed

    Bhatt, Vijaya R; Viola, George M; Ferrajoli, Alessandra

    2011-08-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.

  3. Observations on Hospitalized Dengue Patients

    DTIC Science & Technology

    1987-01-01

    DENGUE PATIENTS IN MANILA Carman. R. Min oto* be" S. Siqpo Ommon D. Leus** Curds G. Ibyes* INTRODUCION to the Hospital of Infant Jesus between October...31, 1983 and March 31, 1984: Criteria for the diagnosis of dengue Dengue hemorrhagic fever (DHF) has been recognized infection were based on the...titer of later sample < 1:640. DHF epidemic.4𔃿 Since that time, there have only been a few- was differentiated from dengue fever (DF), and DHF was

  4. Detection of dengue virus in platelets isolated from dengue patients.

    PubMed

    Noisakran, Sansanee; Gibbons, Robert V; Songprakhon, Pucharee; Jairungsri, Aroonroong; Ajariyakhajorn, Chuanpis; Nisalak, Ananda; Jarman, Richard G; Malasit, Prida; Chokephaibulkit, Kulkanya; Perng, Guey Chuen

    2009-03-01

    Though thrombocytopenia or dysfunction of platelets is common in dengue virus infection, the role of platelets has not been established. We enrolled 33 hospitalized children with serologically confirmed dengue virus infection. Blood specimens were collected during hospitalization. Platelets and plasma were isolated from the whole blood. Detection of dengue virus in plasma and platelets was carried out by RT-PCR with primers that can differentiate different dengue serotypes simultaneously, and by electron transmission microscopy (EM). Dengue viral RNA was detected in the platelets and plasma by conventional RT-PCR. A significantly higher percentage of dengue viral RNA was detected in platelets than in plasma (p = 0.03). Platelets isolated 5 days after onset of fever were most likely positive for viral RNA. Concurrent infection or co-circulation with multiple dengue serotypes was observed in 12% of patients. Infrequently, negative-stranded dengue viral RNA was detected in platelets and in plasma. Importantly, EM confirmed the presence of dengue viral-like particles inside platelets prepared from dengue patients. Our findings suggest the presence of dengue virus in platelets may be associated with the dysfunction of platelets observed in dengue patients.

  5. Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?

    PubMed

    Valdés, Iris; Gil, Lázaro; Lazo, Laura; Marcos, Ernesto; Martín, Jorge; Suzarte, Edith; Castro, Jorge; Romero, Yaremis; Guillén, Gerardo; Hermida, Lisset

    2016-02-01

    There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.

  6. Human CD4(+) T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity.

    PubMed

    Angelo, Michael A; Grifoni, Alba; O'Rourke, Patrick H; Sidney, John; Paul, Sinu; Peters, Bjoern; de Silva, Aruna D; Phillips, Elizabeth; Mallal, Simon; Diehl, Sean A; Kirkpatrick, Beth D; Whitehead, Stephen S; Durbin, Anna P; Sette, Alessandro; Weiskopf, Daniela

    2017-03-01

    Dengue virus (DENV) is responsible for growing numbers of infections worldwide and has proven to be a significant challenge for vaccine development. We previously demonstrated that CD8(+) T cell responses elicited by a dengue live attenuated virus (DLAV) vaccine resemble those observed after natural infection. In this study, we screened peripheral blood mononuclear cells (PBMCs) from donors vaccinated with a tetravalent DLAV vaccine (TV005) with pools of dengue virus-derived predicted major histocompatibility complex (MHC) class II binding peptides. The definition of CD4(+) T cell responses after live vaccination is important because CD4(+) T cells are known contributors to host immunity, including cytokine production, help for CD8(+) T and B cells, and direct cytotoxicity against infected cells. While responses to all antigens were observed, DENV-specific CD4(+) T cells were focused predominantly on the capsid and nonstructural NS3 and NS5 antigens. Importantly, CD4(+) T cell responses in vaccinees were similar in magnitude and breadth to those after natural infection, recognized the same antigen hierarchy, and had similar profiles of HLA restriction. We conclude that TV005 vaccination has the capacity to elicit CD4(+) cell responses closely mirroring those observed in a population associated with natural immunity.IMPORTANCE The development of effective vaccination strategies against dengue virus infection is of high global public health interest. Here we study the CD4 T cell responses elicited by a tetravalent live attenuated dengue vaccine and show that they resemble responses seen in humans naturally exposed to dengue virus. This is an important issue, since it is likely that optimal immunity induced by a vaccine requires induction of CD4(+) responses against the same antigens as those recognized as dominant in natural infection. Detailed knowledge of the T cell response may further contribute to the identification of robust correlates of protection against

  7. Dengue in India

    PubMed Central

    Gupta, Nivedita; Srivastava, Sakshi; Jain, Amita; Chaturvedi, Umesh C.

    2012-01-01

    Dengue virus belongs to family Flaviviridae, having four serotypes that spread by the bite of infected Aedes mosquitoes. It causes a wide spectrum of illness from mild asymptomatic illness to severe fatal dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. Dengue disease presents highly complex pathophysiological, economic and ecologic problems. In India, the first epidemic of clinical dengue-like illness was recorded in Madras (now Chennai) in 1780 and the first virologically proved epidemic of dengue fever (DF) occurred in Calcutta (now Kolkata) and Eastern Coast of India in 1963-1964. During the last 50 years a large number of physicians have treated and described dengue disease in India, but the scientific studies addressing various problems of dengue disease have been carried out at limited number of centres. Achievements of Indian scientists are considerable; however, a lot remain to be achieved for creating an impact. This paper briefly reviews the extent of work done by various groups of scientists in this country. PMID:23041731

  8. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

    PubMed

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-11-24

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared.

  9. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses

    PubMed Central

    Richard, Audrey Stéphanie; Zhang, Adam; Park, Sun-Jin; Farzan, Michael; Zong, Min; Choe, Hyeryun

    2015-01-01

    Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared. PMID:26575624

  10. Comparative Susceptibility of Aedes albopictus and Aedes aegypti to Dengue Virus Infection After Feeding on Blood of Viremic Humans: Implications for Public Health.

    PubMed

    Whitehorn, James; Kien, Duong Thi Hue; Nguyen, Nguyet Minh; Nguyen, Hoa L; Kyrylos, Peter P; Carrington, Lauren B; Tran, Chau Nguyen Bich; Quyen, Nguyen Thanh Ha; Thi, Long Vo; Le Thi, Dui; Truong, Nguyen Thanh; Luong, Tai Thi Hue; Nguyen, Chau Van Vinh; Wills, Bridget; Wolbers, Marcel; Simmons, Cameron P

    2015-10-15

    Aedes albopictus is secondary to Aedes aegypti as a vector of dengue viruses (DENVs) in settings of endemicity, but it plays an important role in areas of dengue emergence. This study compared the susceptibility of these 2 species to DENV infection by performing 232 direct blood-feeding experiments on 118 viremic patients with dengue in Vietnam. Field-derived A. albopictus acquired DENV infections as readily as A. aegypti after blood feeding. Once infected, A. albopictus permitted higher concentrations of DENV RNA to accumulate in abdominal tissues, compared with A. aegypti. However, the odds of A. albopictus having infectious saliva were lower than the odds observed for A. aegypti (odds ratio, 0.70; 95% confidence interval, .52-.93). These results quantitate the susceptibility of A. albopictus to DENV infection and will assist parameterization of models for predicting disease risk in settings where A. albopictus is present.

  11. Dengue Serotype Cross-Reactive, Anti-E Protein Antibodies Confound Specific Immune Memory for 1 Year after Infection

    PubMed Central

    Toh, Ying Xiu; Gan, Victor; Balakrishnan, Thavamalar; Zuest, Roland; Poidinger, Michael; Wilson, Solomonraj; Appanna, Ramapraba; Thein, Tun Linn; Ong, Adrian Kheng-Yeow; Ng, Lee Ching; Leo, Yee Sin; Fink, Katja

    2014-01-01

    Dengue virus has four serotypes and is endemic globally in tropical countries. Neither a specific treatment nor an approved vaccine is available, and correlates of protection are not established. The standard neutralization assay cannot differentiate between serotype-specific and serotype cross-reactive antibodies in patients early after infection, leading to an overestimation of the long-term serotype-specific protection of an antibody response. It is known that the cross-reactive response in patients is temporary but few studies have assessed kinetics and potential changes in serum antibody specificity over time. To better define the specificity of polyclonal antibodies during disease and after recovery, longitudinal samples from patients with primary or secondary DENV-2 infection were collected over a period of 1 year. We found that serotype cross-reactive antibodies peaked 3 weeks after infection and subsided within 1 year. Since secondary patients rapidly produced antibodies specific for the virus envelope (E) protein, an E-specific ELISA was superior compared to a virus particle-specific ELISA to identify patients with secondary infections. Dengue infection triggered a massive activation and mobilization of both naïve and memory B cells possibly from lymphoid organs into the blood, providing an explanation for the surge of circulating plasmablasts and the increase in cross-reactive E protein-specific antibodies. PMID:25177321

  12. In Vitro Infection with Dengue Virus Induces Changes in the Structure and Function of the Mouse Brain Endothelium

    PubMed Central

    Castellanos, Jaime E.

    2016-01-01

    Background The neurological manifestations of dengue disease are occurring with greater frequency, and currently, no information is available regarding the reasons for this phenomenon. Some viruses infect and/or alter the function of endothelial organs, which results in changes in cellular function, including permeability of the blood-brain barrier (BBB), which allows the entry of infected cells or free viral particles into the nervous system. Methods In the present study, we standardized two in vitro models, a polarized monolayer of mouse brain endothelial cells (MBECs) and an organized co-culture containing MBECs and astrocytes. Using these cell models, we assessed whether DENV-4 or the neuro-adapted dengue virus (D4MB-6) variant infects cells or induces changes in the structure or function of the endothelial barrier. Results The results showed that MBECs, but not astrocytes, were susceptible to infection with both viruses, although the percentage of infected cells was higher when the neuro-adapted virus variant was used. In both culture systems, DENV infection changed the localization of the tight junction proteins Zonula occludens (ZO-1) and Claudin-1 (Cln1), and this process was associated with a decrease in transendothelial resistance, an increase in macromolecule permeability and an increase in the paracellular passing of free virus particles. MBEC infection led to transcriptional up-regulation of adhesion molecules (VCAM-1 and PECAM) and immune mediators (MCP-1 and TNF- α) that are associated with immune cell transmigration, mainly in D4MB-6-infected cells. Conclusion These results indicate that DENV infection in MBECs altered the structure and function of the BBB and activated the endothelium, affecting its transcellular and paracellular permeability and favoring the passage of viruses and the transmigration of immune cells. This phenomenon can be harnessed for neurotropic and neurovirulent strains to infect and induce alterations in the CNS. PMID

  13. Diagnosis of Dengue Virus Infection by Detection of Specific Immunoglobulin M (IgM) and IgA Antibodies in Serum and Saliva

    PubMed Central

    Balmaseda, Angel; Guzmán, María G.; Hammond, Samantha; Robleto, Guillermo; Flores, Carolina; Téllez, Yolanda; Videa, Elsa; Saborio, Saira; Pérez, Leonel; Sandoval, Erick; Rodriguez, Yoryelin; Harris, Eva

    2003-01-01

    To evaluate alternative approaches to the serological diagnosis of dengue virus (DEN) infection, the detection of DEN-specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva specimens was assessed in 147 patients with symptoms of DEN infection seen at the Ministry of Health in Nicaragua. Seventy-two serum samples were determined to be positive for anti-DEN antibodies by IgM capture enzyme-linked immunosorbent assay, the routine diagnostic procedure. Serum and saliva specimens were obtained from 50 healthy adults as additional controls. IgM was detected in the saliva of 65 of the 72 serum IgM-positive cases, 6 of the 75 serum IgM-negative cases, and none of the control group, resulting in a sensitivity of 90.3% and a specificity of 92.0% and demonstrating that salivary IgM is a useful diagnostic marker for DEN infection. Detection of IgA in serum may be another feasible alternative for the diagnosis of DEN infection, with serum IgA found in 68 (94.4%) of the IgM-positive cases. In contrast, detection of IgA in saliva was not found to be a useful tool for DEN diagnosis in the present study. Further studies of the kinetics of antibody detection in another set of 151 paired acute- and convalescent-phase serum samples showed that DEN-specific IgA antibodies were detected in more acute-phase samples than were IgM antibodies. Thus, we conclude that DEN-specific IgA in serum is a potential diagnostic target. Furthermore, given that saliva is a readily obtainable, noninvasive specimen, detection of DEN-specific salivary IgM should be considered a useful, cheaper diagnostic modality with similar sensitivity and specificity to IgM detection in serum. PMID:12626461

  14. Epidemiological and ecological characteristics of past dengue virus infection in Santa Clara, Peru.

    PubMed

    Reiskind, M H; Baisley, K J; Calampa, C; Sharp, T W; Watts, D M; Wilson, M L

    2001-03-01

    To determine risk factors associated with dengue (DEN) virus infection among residents of Santa Clara, Peru, a rural Amazonian village near Iquitos, a cross-sectional serological, epidemiological and environmental survey was conducted. Demographic, social and behavioural information was obtained by standardized questionnaire from 1225 Santa Clara residents (61.3%) aged 5 years or older. Additional data were obtained on the environmental variables and immature mosquito species and abundance surrounding each household (n = 248). Sera that had been collected previously by the Peruvian Ministry of Health from residents were tested by an enzyme-linked immunosorbent assay (ELISA) for DEN virus IgG antibody. Antibody identity was verified as DEN by plaque reduction neutralization test. Data on individuals were analysed by univariate and multivariable methods, and independent sample t-tests. Spatial clustering was evaluated by comparing distances among DEN positive households. Overall, antibody prevalence was 29.4 % and more than doubled from the youngest to the oldest age groups, but did not differ by sex. Curiously, length of residence in Santa Clara was negatively associated with DEN virus antibodies. More frequent travel to Iquitos was positively associated with seroprevalence. Residents who obtained water from a river source rather than a local well also had significantly higher antibody prevalence. None of the environmental variables measured at each household corresponded to the patterns of antibody distribution. Of the larval mosquitoes found around residences, all were determined to be species other than Aedes. No evidence of spatial autocorrelation among antibody-positive households was detected. These results strongly suggested that recent DEN virus transmission did not occur in the village and that most infections of residents of this rural village were acquired while visiting the city of Iquitos.

  15. Raman spectroscopy based discrimination of NS1 positive and negative dengue virus infected serum

    NASA Astrophysics Data System (ADS)

    Bilal, M.; Saleem, M.; Bilal, Maria; Khurram, M.; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, M.

    2016-09-01

    This study is intended to develop a multivariate statistical model for the prediction of nonstructural protein 1 (NS1) in dengue virus (DENV) infected blood serum in humans. The model has been developed on the basis of partial least squares regression using the Raman spectra of NS1 positive and NS1 negative samples. Human blood sera of 218 subjects is included in this study, of which 95 were NS1 positive and 123 were NS1 negative, which was confirmed with the enzyme linked immunosorbent assay method. For model development, 80 NS1 positive and 98 NS1 negative samples were used, while 40 DENV suspected samples were used for double blind testing of the model. This selection of samples was performed by the code in an automatic manner to avoid biasing. A laser at 785 nm was used as the excitation source to acquire Raman spectra of samples with an integration time of 15 s. The multivariate model yields coefficients of regression at corresponding Raman shifts. These coefficients represent changes in the molecular structures associated with NS1 positive and negative samples. The analysis of the regression coefficients which differentiate NS1 positive and NS1 negative groups shows an increasing trend for phosphatidylinositol, ceramide, and amide-III, and a decreasing trend for thiocyanate in the DENV infected serum. The R-squared value of the model was found to be 0.91, which is clinically acceptable. The blind testing of 40 suspected samples yields an accuracy, sensitivity, and specificity of about 100% each.

  16. Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007

    PubMed Central

    Ochieng, Caroline; Ahenda, Petronella; Vittor, Amy Y.; Nyoka, Raymond; Gikunju, Stella; Wachira, Cyrus; Waiboci, Lilian; Umuro, Mamo; Kim, Andrea A.; Nderitu, Leonard; Juma, Bonventure; Montgomery, Joel M.; Breiman, Robert F.; Fields, Barry

    2015-01-01

    Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007) to test for the presence of IgG antibodies to dengue virus (DENV), chikungunya virus (CHIKV) and Rift Valley fever virus (RVFV).The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2%) were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive), followed by RVFV and CHIKV (4.5% and 0.97%, respectively). For DENV and RVFV, the participant’s province of residence was significantly associated (P≤.01) with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01). These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV. PMID:26177451

  17. Expanded dengue syndrome: subacute thyroiditis and intracerebral hemorrhage

    PubMed Central

    2012-01-01

    Background Although most symptomatic dengue infections follow an uncomplicated course, complications and unusual manifestations are increasingly being reported due to rising disease burden. Expanded dengue syndrome is a new entity added into World Health Organization (WHO) classification system to incorporate this wide spectrum of unusual manifestations. We report a case of expanded dengue syndrome with subacute thyroiditis and intracerebral hemorrhage. This is the first case report of thyroiditis in dengue infection. Case presentation A 20 years old man presented with fever, myalgias, arthralgias, retro-orbital pain, vomiting and gum bleeding during a large dengue outbreak in Lahore, Pakistan. On 7th day of illness patient became afebrile, but he developed severe headaches, unconsciousness followed by altered behavior. On 9th day of illness patient developed painful neck swelling accompanied by fever, tremors, palpitations, hoarseness of voice and odynophagia. Examination revealed acutely swollen, tender thyroid gland along with features of hyperthyroidism. Laboratory evaluation revealed stable hematocrit, thrombocytopenia and leukopenia. Patient had seroconverted for anti-dengue IgM antibodies on the 10th day of illness. A non-contrast Computed Tomogram (CT) of the brain showed right frontal lobe hematoma. Thyroid profile showed increased free T3 and T4 and low TSH. Technetium thyroid scan showed reduced tracer uptake. He was diagnosed as having subacute thyroiditis and treated with oral prednisolone and propranolol. Follow up CT brain showed resolving hematoma. Patient’s recovery was uneventful. Conclusion Subacute thyroiditis may develop during the course of dengue fever and should be included as a manifestation of expanded dengue syndrome. It should be suspected in patients with dengue fever who develop painful thyroid swelling and clinical features of hyperthyroidism. PMID:23033818

  18. Evaluation of chimeric DNA vaccines consisting of premembrane and envelope genes of Japanese encephalitis and dengue viruses as a strategy for reducing induction of dengue virus infection-enhancing antibody response.

    PubMed

    Sjatha, Fithriyah; Kuwahara, Miwa; Sudiro, T Mirawati; Kameoka, Masanori; Konishi, Eiji

    2014-02-01

    Neutralizing antibodies induced by dengue virus (DENV) infection show viral infection-enhancing activities at sub-neutralizing doses. On the other hand, preimmunity against Japanese encephalitis virus (JEV), a congener of DENV, does not increase the severity of DENV infection. Several studies have demonstrated that neutralizing epitopes in the genus Flavivirus are mainly located in domain III (DIII) of the envelope (E) protein. In this study, chimeric premembrane and envelope (prM-E) gene-based expression plasmids of JEV and DENV1 with DIII substitution of each virus were constructed for use as DNA vaccines and their immunogenicity evaluated. Sera from C3H/He and ICR mice immunized with a chimeric gene containing DENV1 DIII on a JEV prM-E gene backbone showed high neutralizing antibody titers with less DENV infection-enhancing activity. Our results confirm the applicability of this approach as a new dengue vaccine development strategy.

  19. Dengue virus vaccine development.

    PubMed

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.

  20. Climate variation drives dengue dynamics

    PubMed Central

    Xu, Lei; Stige, Leif C.; Chan, Kung-Sik; Zhou, Jie; Yang, Jun; Sang, Shaowei; Wang, Ming; Yang, Zhicong; Yan, Ziqiang; Jiang, Tong; Lu, Liang; Yue, Yujuan; Liu, Xiaobo; Lin, Hualiang; Xu, Jianguo; Liu, Qiyong; Stenseth, Nils Chr.

    2017-01-01

    Dengue, a viral infection transmitted between people by mosquitoes, is one of the most rapidly spreading diseases in the world. Here, we report the analyses covering 11 y (2005–2015) from the city of Guangzhou in southern China. Using the first 8 y of data to develop an ecologically based model for the dengue system, we reliably predict the following 3 y of dengue dynamics—years with exceptionally extensive dengue outbreaks. We demonstrate that climate conditions, through the effects of rainfall and temperature on mosquito abundance and dengue transmission rate, play key roles in explaining the temporal dynamics of dengue incidence in the human population. Our study thus contributes to a better understanding of dengue dynamics and provides a predictive tool for preventive dengue reduction strategies. PMID:27940911

  1. Economic Burden of Dengue Virus Infection at the Household Level Among Residents of Puerto Maldonado, Peru.

    PubMed

    Salmon-Mulanovich, Gabriela; Blazes, David L; Lescano, Andres G; Bausch, Daniel G; Montgomery, Joel M; Pan, William K

    2015-10-01

    Dengue virus (DENV) was reintroduced to Peru in the 1990s and has been reported in Puerto Maldonado (population ~65,000) in the Peruvian southern Amazon basin since 2000. This region also has the highest human migration rate in the country, mainly from areas not endemic for DENV. The objective of this study was to assess the proportion of household income that is diverted to costs incurred because of dengue illness and to compare these expenses between recent migrants (RMs) and long-term residents (LTRs). We administered a standardized questionnaire to persons diagnosed with dengue illness at Hospital Santa Rosa in Puerto Maldonado from December 2012 to March 2013. We compared direct and indirect medical costs between RMs and LTRs. A total of 80 participants completed the survey, of whom 28 (35%) were RMs and 52 (65%) were LTRs. Each dengue illness episode cost the household an average of US$105 (standard deviation [SD] = 107), representing 24% of their monthly income. Indirect costs were the greatest expense (US$56, SD = 87), especially lost wages. The proportion of household income diverted to dengue illness did not differ significantly between RM and LTR households. The study highlights the significant financial burden incurred by households when a family member suffers dengue illness.

  2. Economic Burden of Dengue Virus Infection at the Household Level among Residents of Puerto Maldonado, Peru

    PubMed Central

    Salmon-Mulanovich, Gabriela; Blazes, David L.; Lescano, Andres G.; Bausch, Daniel G.; Montgomery, Joel M.; Pan, William K.

    2015-01-01

    Dengue virus (DENV) was reintroduced to Peru in the 1990s and has been reported in Puerto Maldonado (population ~65,000) in the Peruvian southern Amazon basin since 2000. This region also has the highest human migration rate in the country, mainly from areas not endemic for DENV. The objective of this study was to assess the proportion of household income that is diverted to costs incurred because of dengue illness and to compare these expenses between recent migrants (RMs) and long-term residents (LTRs). We administered a standardized questionnaire to persons diagnosed with dengue illness at Hospital Santa Rosa in Puerto Maldonado from December 2012 to March 2013. We compared direct and indirect medical costs between RMs and LTRs. A total of 80 participants completed the survey, of whom 28 (35%) were RMs and 52 (65%) were LTRs. Each dengue illness episode cost the household an average of US$105 (standard deviation [SD] = 107), representing 24% of their monthly income. Indirect costs were the greatest expense (US$56, SD = 87), especially lost wages. The proportion of household income diverted to dengue illness did not differ significantly between RM and LTR households. The study highlights the significant financial burden incurred by households when a family member suffers dengue illness. PMID:26217040

  3. Lack of Clinical Manifestations in Asymptomatic Dengue Infection Is Attributed to Broad Down-Regulation and Selective Up-Regulation of Host Defence Response Genes

    PubMed Central

    Yeo, Adeline S. L.; Azhar, Nur Atiqah; Yeow, Wanyi; Talbot, C. Conover; Khan, Mohammad Asif; Shankar, Esaki M.; Rathakrishnan, Anusyah; Azizan, Azliyati; Wang, Seok Mui; Lee, Siew Kim; Fong, Mun Yik; Manikam, Rishya; Sekaran, Shamala Devi

    2014-01-01

    Objectives Dengue represents one of the most serious life-threatening vector-borne infectious diseases that afflicts approximately 50 million people across the globe annually. Whilst symptomatic infections are frequently reported, asymptomatic dengue remains largely unnoticed. Therefore, we sought to investigate the immune correlates conferring protection to individuals that remain clinically asymptomatic. Methods We determined the levels of neutralizing antibodies (nAbs) and gene expression profiles of host immune factors in individuals with asymptomatic infections, and whose cognate household members showed symptoms consistent to clinical dengue infection. Results We observed broad down-regulation of host defense response (innate, adaptive and matrix metalloprotease) genes in asymptomatic individuals as against symptomatic patients, with selective up-regulation of distinct genes that have been associated with protection. Selected down-regulated genes include: TNF α (TNF), IL8, C1S, factor B (CFB), IL2, IL3, IL4, IL5, IL8, IL9, IL10 and IL13, CD80, CD28, and IL18, MMP8, MMP10, MMP12, MMP15, MMP16, and MMP24. Selected up-regulated genes include: RANTES (CCL5), MIP-1α (CCL3L1/CCL3L3), MIP-1β (CCL4L1), TGFβ (TGFB), and TIMP1. Conclusion Our findings highlight the potential association of certain host genes conferring protection against clinical dengue. These data are valuable to better explore the mysteries behind the hitherto poorly understood immunopathogenesis of subclinical dengue infection. PMID:24727912

  4. Transcriptome analysis of Aedes aegypti in response to mono-infections and co-infections of dengue virus-2 and chikungunya virus.

    PubMed

    Shrinet, Jatin; Srivastava, Pratibha; Sunil, Sujatha

    2017-02-01

    Chikungunya virus (CHIKV) and Dengue virus (DENV) spread via the bite of infected Aedes mosquitoes. Both these viruses exist as co-infections in the host as well as the vector and are known to exploit their cellular machinery for their replication. While there are studies reporting the changes in Aedes transcriptome when infected with DENV and CHIKV individually, the effect both these viruses have on the mosquitoes when present as co-infections is not clearly understood. In the present study, we infected Aedes aegypti mosquitoes with DENV and CHIKV individually and as co-infection through nanoinjections. We performed high throughput RNA sequencing of the infected Aedes aegypti to understand the changes in the Aedes transcriptome during the early stages of infection, i.e., 24 h post infection and compared the transcriptome profiles during DENV and CHIKV mono-infections with that of co-infections. We identified 190 significantly regulated genes identified in CHIKV infected library, 37 genes from DENV library and 100 genes from co-infected library and they were classified into different pathways. Our study reveal that distinct pathways and transcripts are being regulated during the three types of infection states in Aedes aegypti mosquitoes.

  5. Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical.

    PubMed

    Shresta, Sujan; Kyle, Jennifer L; Snider, Heidi M; Basavapatna, Manasa; Beatty, P Robert; Harris, Eva

    2004-03-01

    Dengue virus (DEN) causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease are neither well understood nor easy to examine in humans. In this study, we used wild-type and congenic mice lacking various components of the immune system to study the immune mechanisms in the response to DEN infection. Our results demonstrate that alpha/beta interferon (IFN-alpha/beta) and IFN-gamma receptors have critical, nonoverlapping functions in resolving primary DEN infection. Furthermore, we show that IFN-alpha/beta receptor-mediated action limits initial DEN replication in extraneural sites and controls subsequent viral spread into the central nervous system (CNS). In contrast, IFN-gamma receptor-mediated responses seem to act at later stages of DEN disease by restricting viral replication in the periphery and eliminating virus from the CNS. Mice deficient in B, CD4(+) T, or CD8(+) T cells had no increased susceptibility to DEN; however, RAG mice (deficient in both B and T cells) were partially susceptible to DEN infection. In summary, (i) IFN-alpha/beta is critical for early immune responses to DEN infection, (ii) IFN-gamma-mediated immune responses are crucial for both early and late clearance of DEN infection in mice, and (iii) the IFN system plays a more important role than T- and B-cell-dependent immunity in resistance to primary DEN infection in mice.

  6. Dot enzyme immunoassay: an alternative diagnostic aid for dengue fever and dengue haemorrhagic fever.

    PubMed Central

    Cardosa, M. J.; Tio, P. H.

    1991-01-01

    A dot enzyme immunoassay (DEIA) for the detection of antibodies to dengue virus was tested for use as a tool in the presumptive diagnosis of dengue fever and dengue haemorrhagic fever. Paired sera from the following groups of patients were tested using the DEIA and the haemagglutination inhibition (HI) test: those with primary dengue fever; those experiencing a second dengue infection; and febrile patients who did not have dengue. The data obtained show that the DEIA can be effectively used at a serum dilution of 1:1000 to confirm presumptive recent dengue in patients with a second dengue infection. However, demonstration of seroconversion proved necessary for patients with primary dengue. At a serum dilution of 1:1000 the DEIA has a specificity of 97.3%. The role of this simple and rapid test in improving the effectivity of programmes for the control of dengue virus infection is discussed. PMID:1786623

  7. Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue

    PubMed Central

    Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

    2017-01-01

    Background: Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. Materials and Methods: We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Results: Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (<4000, 4001–7000 and >7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (<2 and ≥2 mg/dL), serum glutamic oxaloacetic transaminase (>200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79–0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. Conclusion: In areas of high burden of ST and dengue, model 2 (the “clinical score to differentiate scrub typhus and dengue fever”) is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation. PMID:28250620

  8. Understanding dengue pathogenesis: implications for vaccine design.

    PubMed Central

    Stephenson, John R.

    2005-01-01

    In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease. PMID:15868023

  9. Geo-database use to promote dengue infection prevention and control.

    PubMed

    Wongbutdee, Jaruwan; Chaikoolvatana, Anun; Saengnill, Wacharapong; Krasuaythong, Nantaya; Phuphak, Surajit

    2010-07-01

    Dengue infection (DI) is a major health problem in Thailand and is especially prevalent in Ubon Ratchathani Province. The objectives of the project were: (1) to develop a geo-database system for DI prevention and control, (2) to perform an Aedes aegypti larval vector survey for DI prevention and control in Ubon Ratchathani Province, (3) to study the behavior and perceptions regarding DI prevention among the target population in Ubon Ratchathani Province. Ten villages with high incidences of DI over a 3 year period from 2005 to 2007 were selected. The survey was divided into 2 periods, pre-outbreak period (February-April 2008) and outbreak period (June-August 2008). The data were collected in April and June 2008. The households in each village were purposively sampled. Water containers inside and outside of the houses were surveyed using the World Health Organization's house index (HI), container index (CI), and Breteau index (BI). The location of each household was recorded using the global positioning system (GPS). Data regarding people's perceptions and behaviors concerning DI prevention were collected during interviews of 383 families in Mach 2008. A database for DI was developed using ArcView version 9.2. The results showed during the pre-outbreak period, Non Jig, Non Sawang, and Huai Teeneu villages had the highest risk level (BI > or =50). During the outbreak period, Non Jig and Huai Teeneu village had the highest risk level (BI > or =50). Results regarding DI perceptions showed the target population had high levels of DI perceptions. DI preventive behavior was found in 50.9%.

  10. Dengue virus-infected human dendritic cells reveal hierarchies of naturally expressed novel NS3 CD8 T cell epitopes.

    PubMed

    Piazza, P; Campbell, D; Marques, E; Hildebrand, W H; Buchli, R; Mailliard, R; Rinaldo, C R

    2014-09-01

    Detailed knowledge of dengue virus (DENV) cell-mediated immunity is limited. In this study we characterize CD8(+) T lymphocytes recognizing three novel and two known non-structural protein 3 peptide epitopes in DENV-infected dendritic cells. Three epitopes displayed high conservation (75-100%), compared to the others (0-50%). A hierarchy ranking based on magnitude and polyfunctionality of the antigen-specific response showed that dominant epitopes were both highly conserved and cross-reactive against multiple DENV serotypes. These results are relevant to DENV pathogenesis and vaccine design.

  11. Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association

    PubMed Central

    Theochari, Evangelia; Vincent-Smith, Lisa; Ellis, Cathy

    2015-01-01

    Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis. PMID:25739795

  12. A rare cause of acute abdomen in adults: Parasitic infection-related acute appendicitis.

    PubMed

    Küpeli, Aydın Hakan; Özdemir, Murat; Topuz, Sezgin; Sözütek, Alper; Paksoy, Tuğba

    2015-01-01

    Ascaris lumbricoides is a common parasitic disease all over the world, especially in less developed countries. Acute appendicitis related to parasitic infection is a rare condition. Parasitic infections should be kept in mind in patients who are admitted to the emergency department with acute abdomen, especially in endemic areas.

  13. Factors influencing preventive behaviors for dengue infection among housewives in Colombo, Sri Lanka.

    PubMed

    Chanyasanha, Charnchudhi; Guruge, Geethika Rathnawardana; Sujirarat, Dusit

    2015-01-01

    Dengue is an infectious disease prevalent in Sri Lanka. Some factors may influence preventive behaviors. This cross-sectional study aimed to determine the knowledge, attitude, and preventive behaviors associated with dengue and analyzed the factors influencing preventive behaviors among housewives in Colombo, Sri Lanka. The analytical study was designed, and data were collected using a structured questionnaire. The χ(2) test and binary logistic regression were used to analyze data. The mean age of housewives was 39.41 years, 91% were married, 52% were Buddhist, and 46.5% had a family monthly income of 15 000 to 25 000 rupees. The knowledge of dengue preventive behaviors was 69.2%. The majority (91.5%) had a positive attitude toward dengue prevention. Only 39.3% used a mosquito net, and 89.3% had water storage container covers. Overall, 58.5% were knowledgeable about preventive measures. Age, religion, family income, education, knowledge, and attitude were associated with preventive behaviors. These findings are useful for dengue control in Colombo.

  14. Dengue among American missionaries returning from Jamaica, 2012.

    PubMed

    Moncayo, Abelardo C; Baumblatt, Jane; Thomas, Dana; Harvey, Kira A; Atrubin, David; Stanek, Danielle; Sotir, Mark; Hunsperger, Elizabeth; Muñoz-Jordan, Jorge L; Jentes, Emily S; Sharp, Tyler M; Arguello, D Fermin

    2015-01-01

    Dengue is an acute febrile illness caused by any of four mosquito-transmitted dengue virus (DENV) types. Dengue is endemic in Jamaica, where an epidemic occurred in 2012. An investigation was conducted by multiple agencies for 66 missionaries traveling from nine US states to Jamaica after 1 missionary from the group was confirmed to have dengue. Travelers were offered diagnostic testing, and a survey was administered to assess knowledge, behaviors, and illness. Of 42 survey respondents, 9 (21%) respondents reported an acute febrile illness during or after travel to Jamaica. Of 15 travelers that provided serum specimens, 4 (27%) travelers had detectable anti-DENV immunoglobulin M antibody, and 1 traveler also had DENV-1 detected by reverse transcriptase polymerase chain reaction. Recent or past infection with a DENV was evident in 93% (13 of 14) missionaries with available sera. No behavioral or demographic factors were significantly associated with DENV infection. This investigation shows that even trips of short duration to endemic areas present a risk of acquiring dengue.

  15. Dengue encephalitis

    PubMed Central

    Borawake, Kapil; Prayag, Parikshit; Wagh, Atul; Dole, Swati

    2011-01-01

    We report a case of dengue fever with features of encephalitis. The diagnosis of dengue was confirmed by the serum antibodies to dengue and the presence of a dengue antigen in the cerebrospinal fluid. This patient had characteristic magnetic resonance imaging brain findings, mainly involving the bilateral thalami, with hemorrhage. Dengue is not primarily a neurotropic virus and encephalopathy is a common finding in Dengue. Hence various other etiological possibilities were considered before concluding this as a case of Dengue encephalitis. This case explains the importance of considering the diagnosis of dengue encephalitis in appropriate situations. PMID:22013316

  16. Analysis of dengue infection based on Raman spectroscopy and support vector machine (SVM)

    PubMed Central

    Khan, Saranjam; Ullah, Rahat; Khan, Asifullah; Wahab, Noorul; Bilal, Muhammad; Ahmed, Mushtaq

    2016-01-01

    The current study presents the use of Raman spectroscopy combined with support vector machine (SVM) for the classification of dengue suspected human blood sera. Raman spectra for 84 clinically dengue suspected patients acquired from Holy Family Hospital, Rawalpindi, Pakistan, have been used in this study.The spectral differences between dengue positive and normal sera have been exploited by using effective machine learning techniques. In this regard, SVM models built on the basis of three different kernel functions including Gaussian radial basis function (RBF), polynomial function and linear functionhave been employed to classify the human blood sera based on features obtained from Raman Spectra.The classification model have been evaluated with the 10-fold cross validation method. In the present study, the best performance has been achieved for the polynomial kernel of order 1. A diagnostic accuracy of about 85% with the precision of 90%, sensitivity of 73% and specificity of 93% has been achieved under these conditions. PMID:27375941

  17. 2nd International External Quality Control Assessment for the Molecular Diagnosis of Dengue Infections

    PubMed Central

    Domingo, Cristina; Niedrig, Matthias; Teichmann, Anette; Kaiser, Marco; Rumer, Leonid; Jarman, Richard G.; Donoso-Mantke, Oliver

    2010-01-01

    Background Currently dengue viruses (DENV) pose an increasing threat to over 2.5 billion people in over 100 tropical and sub-tropical countries worldwide. International air travel is facilitating rapid global movement of DENV, increasing the risk of severe dengue epidemics by introducing different serotypes. Accurate diagnosis is critical for early initiation of preventive measures. Different reverse transcriptase PCR (RT-PCR) methods are available, which should be evaluated and standardized. Epidemiological and laboratory-based surveillance is required to monitor and guide dengue prevention and control programmes, i.e., by mosquito control or possible vaccination (as soon as an effective and safe vaccine becomes available). Objective The purpose of the external quality assurance (EQA) study described is to assess the efficiency and accuracy of dengue molecular diagnosis methods applied by expert laboratories. Study Design A panel of 12 human plasma samples was distributed and tested for DENV-specific RNA. The panel comprised 9 samples spiked with different DENV serotypes (DENV-1 to DENV-4), including 10-fold dilution series of DENV-1 and DENV-3. Two specificity controls consisted of a sample with a pool of 4 other flaviviruses and a sample with chikungunya virus. A negative control sample was also included. Results Thirty-seven laboratories (from Europe, Middle East Asia, Asia, the Americas/Caribbean, and Africa) participated in this EQA study, and reports including 46 sets of results were returned. Performance among laboratories varied according to methodologies used. Only 5 (10.9%) data sets met all criteria with optimal performance, and 4 (8.7%) with acceptable performance, while 37 (80.4%) reported results showed the need for improvement regarding accomplishment of dengue molecular diagnosis. Failures were mainly due to lack of sensitivity and the presence of false positives. Conclusions The EQA provides information on each laboratory's efficacy of RT

  18. [PROGNOSTICATION OF LIMITED ACCUMULATIONS LIQUID INFECTION BY SEVERE ACUTE PANCREATITIS].

    PubMed

    Sheiko, V D; Oganezyan, A G

    2015-07-01

    The results of examination and treatment of 53 patients on limited accumulations of liquid (LAL) for severe acute pancreatitis (SAP) were analysed. In 62.5% of patients on acute aseptic LAL celebrated parapancreatyc liquid accumulation were determinened. Most (94.6%) patients infected by LAL revealed heterogeneity of their structure according ultrasonography, in 81.1%--secvestral mass in their cavity. Systemic inflammatory response syndrome (SIRS) observed both aseptic and infected LAL. Prognostically important criteria LAL infection in patients on SAP is the heterogeneity of echostructure in absence of a downward trend. Diagnostic puncture under ultrasound control and microbiological studies are safe methods of diagnosis by infected LAL in SAP.

  19. Progress towards a dengue vaccine.

    PubMed

    Webster, Daniel P; Farrar, Jeremy; Rowland-Jones, Sarah

    2009-11-01

    The spread of dengue virus throughout the tropics represents a major, rapidly growing public health problem with an estimated 2.5 billion people at risk of dengue fever and the life-threatening disease, severe dengue. A safe and effective vaccine for dengue is urgently needed. The pathogenesis of severe dengue results from a complex interaction between the virus, the host, and, at least in part, immune-mediated mechanisms. Vaccine development has been slowed by fears that immunisation might predispose individuals to the severe form of dengue infection. A pipeline of candidate vaccines now exists, including live attenuated, inactivated, chimeric, DNA, and viral-vector vaccines, some of which are at the stage of clinical testing. In this Review, we present what is understood about dengue pathogenesis and its implications for vaccine design, the progress that is being made in the development of a vaccine, and the future challenges.

  20. Acute cerebellar ataxia with human parvovirus B19 infection

    PubMed Central

    Shimizu, Y.; Ueno, T.; Komatsu, H.; Takada, H.; Nunoue, T.

    1999-01-01

    A 2 year old boy developed acute cerebellar ataxia in association with erythema infectiosum. During the disease, genomic DNA and antibodies against human parvovirus B19 were detected in serum but not in cerebrospinal fluid. Parvovirus B19 associated acute cerebellar ataxia might occur due to transient vascular reaction in the cerebellum during infection.

 PMID:10325764

  1. Universal Single-Probe RT-PCR Assay for Diagnosis of Dengue Virus Infections

    PubMed Central

    Alm, Erik; Lesko, Birgitta; Lindegren, Gunnel; Ahlm, Clas; Söderholm, Sandra; Falk, Kerstin I.; Lagerqvist, Nina

    2014-01-01

    Background Dengue is a mosquito-borne viral disease that has become more prevalent in the last few decades. Most patients are viremic when they present with symptoms, and early diagnosis of dengue is important in preventing severe clinical complications associated with this disease and also represents a key factor in differential diagnosis. Here, we designed and validated a hydrolysis-probe-based one-step real-time RT-PCR assay that targets the genomes of dengue virus serotypes 1–4. Methodology/Principal Findings The primers and probe used in our RT-PCR assay were designed to target the 3′ untranslated region of all complete genome sequences of dengue virus available in GenBank (n = 3,305). Performance of the assay was evaluated using in vitro transcribed RNA, laboratory-adapted virus strains, external control panels, and clinical specimens. The linear dynamic range was found to be 104–1011 GCE/mL, and the detection limit was between 6.0×102 and 1.1×103 GCE/mL depending on target sequence. The assay did not cross-react with human RNA, nor did it produce false-positive results for other human pathogenic flaviviruses or clinically important etiological agents of febrile illnesses. We used clinical serum samples obtained from returning travelers with dengue-compatible symptomatology (n = 163) to evaluate the diagnostic relevance of our assay, and laboratory diagnosis performed by the RT-PCR assay had 100% positive agreement with diagnosis performed by NS1 antigen detection. In a retrospective evaluation including 60 archived serum samples collected from confirmed dengue cases 1–9 days after disease onset, the RT-PCR assay detected viral RNA up to 9 days after appearance of symptoms. Conclusions/Significance The validation of the RT-PCR assay presented here indicates that this technique can be a reliable diagnostic tool, and hence we suggest that it be introduced as the method of choice during the first 5 days of dengue symptoms. PMID:25522325

  2. Potential for Extrinsic Incubation Temperature to Alter Interplay Between Transmission Potential and Mortality of Dengue-Infected Aedes aegypti

    PubMed Central

    Christofferson, Rebecca C.; Mores, Christopher N.

    2016-01-01

    The extrinsic incubation period is a critical component in the assessment of arboviral transmission potential. It defines the time it takes for a mosquito to become infectious following exposure to an arbovirus. Since this is a temporal process, the lifespan of a mosquito is intimately tied to the extrinsic incubation period and thus transmission potential of these viruses. Temperature is a known effector of both vector competence (the ability of a vector to transmit a pathogen) and mosquito mortality, but the interaction among temperature, vector competence, and mosquito mortality is not well characterized. Herein, we investigate this interaction for dengue virus, serotype 2, and its primary vector Aedes aegypti where we found that at 30 °C, infection and/or dissemination shortened the average lifespan of the mosquito and that when considering only mosquitoes with a disseminated infection, those incubated at 26 °C lived significantly longer. PMID:27478382

  3. Acute pancreatitis, ascites, and acute renal failure in Plasmodium vivax malaria infection, a rare complication

    PubMed Central

    Lakhotia, Manoj; Pahadiya, Hans Raj; Kumar, Harish; Singh, Jagdish; Sangappa, Jainapur Ravi; Choudhary, Prakash Kumar

    2015-01-01

    A 22-year-old male presented with 6 days history of intermittent fever with chills, 2 days history of upper abdomen pain, distension of abdomen, and decreased urine output. He was diagnosed to have Plasmodium vivax malaria, acute pancreatitis, ascites, and acute renal failure. These constellations of complications in P. vivax infection have never been reported in the past. The patient responded to intravenous chloroquine and supportive treatment. For renal failure, he required hemodialysis. Acute pancreatitis, ascites, and acute renal failure form an unusual combination in P. vivax infection. PMID:26629455

  4. Lower activation-induced T-cell apoptosis is related to the pathological immune response in secondary infection with hetero-serotype dengue virus.

    PubMed

    Yang, Wang; Yan, Huacheng; Ma, Yuling; Yu, Tiantian; Guo, Hongxia; Kuang, Yuchan; Ren, Ruiwen; Li, Jintao

    2016-03-01

    The available evidence suggests that dengue virus-specific T lymphocytes and cytokine storm play a pivotal role in the immunopathogenesis of plasma leakage. Investigations are underway to identify the immune profiles associated with increased or decreased risk for severe disease. In this study, CD14+ cells from the peripheral blood mononuclear cells (PBMCs) of patients who recovered from DENV-1 infection were infected with DENV-1 or DENV-2 and co-cultured with memory T cells. We found that secondary infection with DENV-2 suppresses the cell reproductive capacity but forms more cell clones and more functional cells to produce more proinflammatory factors (IFN-γ, TNF-α, IL-6, IL-8, IL-12 and IL-17) and less regulatory cytokines (IL-10, TGF-β) which results in higher viral replication compared to secondary infection with DENV-1. Memory dengue virus-specific T cells which are induced in a primary dengue virus infection are reactivated by the heterologous serotype of dengue virus and antigen-presenting cells (APCs) during a secondary infection. Dramatically, less apoptosis and more continuous activation of T cells in secondary infection with hetero-serotype DENV were observed. This discovery which has not been reported previously may be the reasonable and vital interpretation for the cytokine storm and severe symptoms observed in secondary infection with DENV. In summary, secondary infection with hetero-serotype DENV elicits the relatively pathological immune response while secondary infection with homologous-serotype DENV induces the relatively protective immune response by activation-induced cell death (AICD) of T cells.

  5. Dengue: etiology of acute febrile illness in Abidjan, Côte d'Ivoire, in 2011–2012

    PubMed Central

    L'Azou, Maïna; Succo, Tiphanie; Kamagaté, Mamadou; Ouattara, Abdoulaye; Gilbernair, Elia; Adjogoua, Edgar; Luxemburger, Christine

    2015-01-01

    Background The burden of dengue in Africa is not well understood. A prospective study was conducted in Abidjan, Côte d'Ivoire from December 2011 to December 2012 to estimate the proportion of dengue and malaria cases among febrile patients during a period when dengue was not known to be circulating in the region, and to describe the clinical and virological characteristics of laboratory-diagnosed dengue cases. Methods Blood samples were taken from febrile patients (body temperature ≥38°C) at two study sites. Patients with fever lasting more than 7 days, with fever of known origin and with jaundice were excluded. Thick blood film tests, ELISA for anti-dengue IgM and reverse transcription-PCR (RT-PCR) were performed. Results A total of 812 patients were enrolled (51.7% male [48.3% female]; 46.4% aged <10 years) of whom 796 (98.0%) provided IgM ELISA and RT-PCR data, and 807 (99.4%) had thick blood film results. Three (0.4%) patients had laboratory-diagnosed dengue (one with DENV-3 serotype), none of whom were diagnosed clinically, and 234 (28.8%) had confirmed malaria. Conclusions This study suggests that dengue virus circulates in Abidjan outside an epidemic and that there should be an increase in awareness of dengue as a possible diagnosis in cases of undifferentiated fever. These results stress the importance of implementing laboratory capacity to assess dengue burden in Africa. PMID:26385938

  6. Identification of Aedes aegypti Long Intergenic Non-coding RNAs and Their Association with Wolbachia and Dengue Virus Infection

    PubMed Central

    Etebari, Kayvan; Asad, Sultan; Zhang, Guangmei; Asgari, Sassan

    2016-01-01

    Long intergenic non-coding RNAs (lincRNAs) are appearing as an important class of regulatory RNAs with a variety of biological functions. The aim of this study was to identify the lincRNA profile in the dengue vector Aedes aegypti and evaluate their potential role in host-pathogen interaction. The majority of previous RNA-Seq transcriptome studies in Ae. aegypti have focused on the expression pattern of annotated protein coding genes under different biological conditions. Here, we used 35 publically available RNA-Seq datasets with relatively high depth to screen the Ae. aegypti genome for lincRNA discovery. This led to the identification of 3,482 putative lincRNAs. These lincRNA genes displayed a slightly lower GC content and shorter transcript lengths compared to protein-encoding genes. Ae. aegypti lincRNAs also demonstrate low evolutionary sequence conservation even among closely related species such as Culex quinquefasciatus and Anopheles gambiae. We examined their expression in dengue virus serotype 2 (DENV-2) and Wolbachia infected and non-infected adult mosquitoes and Aa20 cells. The results revealed that DENV-2 infection increased the abundance of a number of host lincRNAs, from which some suppress viral replication in mosquito cells. RNAi-mediated silencing of lincRNA_1317 led to enhancement in viral replication, which possibly indicates its potential involvement in the host anti-viral defense. A number of lincRNAs were also differentially expressed in Wolbachia-infected mosquitoes. The results will facilitate future studies to unravel the function of lncRNAs in insects and may prove to be beneficial in developing new ways to control vectors or inhibit replication of viruses in them. PMID:27760142

  7. Mosquitoes, models, and dengue.

    PubMed

    Lifson, A R

    1996-05-04

    In the last 10 years dengue has spread markedly through Latin America and the Caribbean (Dominican Republic, Jamaica, Barbados, Mexico, Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Ecuador, Colombia, Venezuela, and Brazil). The mosquito Aedes aegypti has taken advantage of increased urbanization and crowding to transmit the dengue virus. The mosquito infests tires, cans, and water jars near dwellings. The female mosquito practices multiple, interrupted feeding. Thus, mosquito infesting and feeding practices facilitate dengue transmission in crowded conditions. Factors contributing to the spread of dengue include numbers of infected and susceptible human hosts, strain of dengue virus, size of mosquito population, feeding habits, time from infection to ability to transmit virus for both vector and host, likelihood of virus transmission from human to mosquito to human, and temperature (which affects vector distribution, size, feeding habits, and extrinsic incubation period). Public health models may use simulation models to help them plan or evaluate the potential impact of different intervention strategies and/or of environmental changes (e.g., global warming). Other factors contributing to the dengue epidemic are international travel, urbanization, population growth, crowding, poverty, a weakened public health infrastructure, and limited support for sustained disease control programs. Molecular epidemiology by nucleic acid sequence analysis is another sophisticated technique used to study infectious diseases. It showed that dengue type 3 isolated from Panama and Nicaragua in 1994 was identical to that responsible for the major dengue hemorrhagic fever epidemics in Sri Lanka and India in the 1980s. Public health officials must remember three priorities relevant to dengue and other emerging infections: the need to strengthen surveillance efforts, dedicated and sustained involvement in prevention and control needs at the local level, and a strong

  8. NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease.

    PubMed

    Azeredo, E L; De Oliveira-Pinto, L M; Zagne, S M; Cerqueira, D I S; Nogueira, R M R; Kubelka, C F

    2006-02-01

    During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.

  9. Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

    PubMed Central

    Ellis, Esther M.; Pérez-Padilla, Janice; González, Liza; Poole-Smith, B. Katherine; Lebo, Emmaculate; Baker, Charlotte; Delorey, Mark J.; Torres-Velasquez, Brenda; Ochoa, Eduardo; Rivera-Garcia, Brenda; Díaz-Pinto, Hector; Clavell, Luis; Puig-Ramos, Anabel; Janka, Gritta E.; Tomashek, Kay M.

    2016-01-01

    Background Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. Methodology/Principal Findings After a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02). Conclusions/Significance During this cluster of dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than

  10. A Native Wolbachia Endosymbiont Does Not Limit Dengue Virus Infection in the Mosquito Aedes notoscriptus (Diptera: Culicidae).

    PubMed

    Skelton, Ellie; Rancès, Edwige; Frentiu, Francesca D; Kusmintarsih, Endang Srimurni; Iturbe-Ormaetxe, Iñaki; Caragata, Eric P; Woolfit, Megan; O'Neill, Scott L

    2016-03-01

    The endosymbiotic bacterium Wolbachia pipientis infects many species of insects and has been transinfected into the mosquito Aedes aegypti (L.), the primary vector of dengue virus (DENV). Recently, it has been shown that Wolbachia blocks the replication and transmission of RNA viruses, such as DENV, in a number of mosquito species including Ae. aegypti and Aedes albopictus (Skuse), which is naturally infected with Wolbachia and considered a secondary vector for DENV. The mosquito species Aedes notoscriptus (Skuse) is highly prevalent in Australia, including in areas where DENV outbreaks have been recorded. The mosquito has been implicated in the transmission of Ross River and Barmah Forest viruses, but not DENV. We investigated whether Wolbachia naturally infects this mosquito species and whether it has an impact on the ability of Ae. notoscriptus to transmit DENV. We show, for the first time, that Ae. notoscriptus is naturally infected with a strain of Wolbachia that belongs to supergroup B and is localized only in the ovaries. However, Wolbachia infection in Ae. notoscriptus did not induce resistance to DENV and had no effect on overall DENV infection rate or titer. The presence of a native Wolbachia in Ae. notoscriptus cannot explain why this mosquito is an ineffective vector of DENV.

  11. Impact of dengue virus (serotype DENV-2) infection on liver of BALB/c mice: A histopathological analysis.

    PubMed

    Sakinah, S; Priya, Sivan Padma; Kumari, Sharmilah; Amira, Fatin; K, Poorani; Alsaeedy, Hiba; Ling, Mok Pooi; Chee, Hui-Yee; Higuchi, Akon; Alarfaj, Abdullah A; Munusamy, Murugan A; Murugan, Kadarkarai; Taib, Che Norma Mat; Arulselvan, Palanisamy; Rajan, Mariappan; Neela, Vasantha Kumari; Hamat, Rukman Awang; Benelli, Giovanni; Kumar, S Suresh

    2017-02-01

    In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.

  12. Suppressed expression of miR-378 targeting gzmb in NK cells is required to control dengue virus infection.

    PubMed

    Liu, Shuyan; Chen, Lingming; Zeng, Ying; Si, Lulu; Guo, Xiaolan; Zhou, Junmei; Fang, Danyun; Zeng, Gucheng; Jiang, Lifang

    2016-09-01

    Dengue virus (DENV) remains a major public health threat because no vaccine or drugs are available for the prevention and treatment of DENV infection, and the immunopathogenesis mechanisms of DENV infection are not fully understood. Cytotoxic molecules, such as granzyme B (GrzB), may be necessary to control viral infections. However, the exact role of GrzB during DENV infection and the mechanisms regulating GrzB expression during DENV infection are not clear. This study found that miR-27a*, miR-30e, and miR-378 were down-regulated in DENV-infected patients, and DENV infection in humans induced a significant up-regulation of GrzB in natural killer (NK) cells and CD8(+) T cells. Further investigation indicated that NK cells, but not CD8(+) T cells, were the major sources of GrzB, and miR-378, but not miR-27a* or miR-30e, suppressed GrzB expression in NK cells. Notably, we found that overexpression of miR-378 using a miR-378 agomir in DENV-infected mice inhibited GrzB expression and promoted DENV replication. These results suggest the critical importance of miR-378 in the regulation of GrzB expression and a protective role for GrzB in controlling DENV replication in vivo. Therefore, this study provides a new insight into the immunopathogenesis mechanism of DENV infection and a biological basis for the development of new therapeutic strategies to control DENV infection.

  13. Evaluation of a commercial real-time PCR kit for detection of dengue virus in samples collected during an outbreak in Goiania, Central Brazil, in 2005.

    PubMed

    Levi, José Eduardo; Tateno, Adriana Fumie; Machado, Adriana Freire; Ramalho, Débora Camillo; de Souza, Vanda Akico Ueda Fick; Guilarde, Adriana Oliveira; de Rezende Feres, Valéria Christina; Martelli, Celina Maria Turchi; Turchi, Marília Dalva; Siqueira, João Bosco; Pannuti, Cláudio Sérgio

    2007-06-01

    In the past 2 decades, dengue has reemerged in Brazil as a significant public health problem. Clinicians demand a diagnostic test with high sensitivity that is applicable during the early symptomatic phase. We aimed to test two distinct molecular methods on samples from suspected dengue cases during an outbreak in Central Brazil. Acute-phase serum specimens from 254 patients suspected of having dengue were collected during 2005 in the city of Goiânia, Central Brazil. Samples were blindly evaluated by real-time and multiplex PCR in addition to routine immunoglobulin M serology and virus culture. Overall, acute dengue was confirmed by serology, multiplex PCR, or virus isolation for 80% of patients (203/254). Another four patients presented real-time PCR-positive results as the unique marker of dengue. Higher real-time PCR positivity levels and viral loads were observed in the early symptomatic phase of disease (< or =5 days) than after this period. Multiplex and real-time PCR assays presented a high kappa agreement (0.85). According to multiplex PCR, 60 samples harbored dengue virus type 3 (DEN-3), 4 samples harbored DEN-2, and 1 sample displayed a pattern compatible with a double infection with DEN-2 and -3. The dengue virus real-time kit was found to be practical and adjustable for high throughput, to display the best performance in the early symptomatic phase of dengue cases, and to be valuable for confirming dengue diagnosis in a timely manner.

  14. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2017-02-13

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. Micronutrients and dengue.

    PubMed

    Ahmed, Sundus; Finkelstein, Julia L; Stewart, Anna M; Kenneth, John; Polhemus, Mark E; Endy, Timothy P; Cardenas, Washington; Mehta, Saurabh

    2014-11-01

    Dengue virus infection is the most widespread mosquito-borne viral infection in humans and has emerged as a serious global health challenge. In the absence of effective treatment and vaccine, host factors including nutritional status, which may alter disease progression, need investigation. The interplay between nutrition and other infections is well-established, and modulation of nutritional status often presents a simple low-cost method of interrupting transmission, reducing susceptibility, and/or ameliorating disease severity. This review examines the evidence on the role of micronutrients in dengue virus infection. We found critical issues and often inconsistent results across studies; this finding along with the lack of sufficient literature in this field have limited our ability to make any recommendations. However, vitamins D and E have shown promise in small supplementation trials. In summary, the role of micronutrients in dengue virus infection is an exciting research area and needs to be examined in well-designed studies with larger samples.

  16. A Shorter Time Interval Between First and Second Dengue Infections Is Associated With Protection From Clinical Illness in a School-based Cohort in Thailand

    PubMed Central

    Anderson, Kathryn B.; Gibbons, Robert V.; Cummings, Derek A.T.; Nisalak, Ananda; Green, Sharone; Libraty, Daniel H.; Jarman, Richard G.; Srikiatkhachorn, Anon; Mammen, Mammen P.; Darunee, Buddhari; Yoon, In-Kyu; Endy, Timothy P.

    2014-01-01

    Background. Despite the strong association between secondary dengue virus (DENV) infections and dengue hemorrhagic fever (DHF), the majority of secondary infections are subclinical or mild. The determinants of clinical severity remain unclear, though studies indicate a titer-dependent and time-dependent role of cross-protective anti-DENV antibodies. Methods. Data from 2 sequential prospective cohort studies were analyzed for subclinical and symptomatic DENV infections in schoolchildren in Kamphaeng Phet, Thailand (1998–2002 and 2004–2007). Children experiencing ≥1 DENV infection were selected as the population for analysis (contributing 2169 person-years of follow-up). Results. In total, 1696 children had ≥1 DENV infection detected during their enrollment; 268 experienced 2 or more infections. A shorter time interval between infections was associated with subclinical infection in children seronegative for DENV at enrollment, for whom a second-detected DENV infection is more likely to reflect a true second infection (average of 2.6 years between infections for DHF, 1.9 for DF, and 1.6 for subclinical infections). Conclusions. These findings support a pathogenesis model where cross-reactive antibodies wane from higher-titer, protective levels to lower-titer, detrimental levels. This is one of the first studies of human subjects to suggest a window of cross-protection following DENV infection since Sabin's challenge studies in the 1940s. PMID:23964110

  17. Influenza virus infections in the tropics during the first year of life.

    PubMed

    Libraty, Daniel H; Zhang, Lei; Caponpon, Mercydina; Capeding, Rosario Z

    2015-08-01

    Pediatric influenza virus infections in the tropics, particularly during infancy, are not well described. We identified influenza virus infections among infants with non-dengue acute undifferentiated febrile illnesses in San Pablo, Laguna, Philippines, as part of an ongoing clinical study of dengue virus infections during infancy. We found that 31% of infants with non-dengue acute undifferentiated febrile illnesses in San Pablo, Laguna, Philippines, had influenza virus infections. The majority were influenza A virus infections and outpatient cases. The infant ages were 11.1 [9.8-13.0] months (median [95% confidence interval]), and the cases clustered between June and December. Influenza episodes are a common cause of non-dengue acute undifferentiated febrile illnesses in the tropics during the first year of life.

  18. Repertoire of virus-derived small RNAs produced by mosquito and mammalian cells in response to dengue virus infection.

    PubMed

    Schirtzinger, Erin E; Andrade, Christy C; Devitt, Nicholas; Ramaraj, Thiruvarangan; Jacobi, Jennifer L; Schilkey, Faye; Hanley, Kathryn A

    2015-02-01

    RNA interference (RNAi) is the major defense of many arthropods against arthropod-borne RNA viruses (arboviruses), but the role of RNAi in vertebrate immunity to arboviruses is not clear. RNA viruses can trigger RNAi in vertebrate cells, but the vertebrate interferon response may obscure this interaction. We quantified virus-derived small RNAs (vRNAs) generated by mosquito (U4.4) cells and interferon-deficient (Vero) and interferon-competent (HuH-7) mammalian cells infected with a single isolate of mosquito-borne dengue virus. Mosquito cells produced significantly more vRNAs than mammalian cells, and mosquito cell vRNAs were derived from both the positive- and negative-sense dengue genomes whereas mammalian cell vRNAs were derived primarily from positive-sense genome. Mosquito cell vRNAs were predominantly 21 nucleotides in length whereas mammalian cell vRNAs were between 12 and 36 nucleotides with a modest peak at 24 nucleotides. Hot-spots, regions of the virus genome that generated a disproportionate number of vRNAs, overlapped among the cell lines.

  19. Differences in Perceived Severity of Zika Virus Infection and Dengue Fever and its Influence on Mosquito Control Practices in Malaysia.

    PubMed

    Wong, Li Ping; Alias, Haridah; Aghamohammadi, Nasrin; Sam, I-Ching; AbuBakar, Sazaly

    2017-02-25

    The aims of this study were to explore the differences in (1) the perception of severity towards ZIKV infection and dengue fever, and (2) mosquito control practices before and after the ZIKV outbreak were declared a Public Health Emergency of International Concern (PHEIC). Data were collected between February 2015 and May 2016 using a computer-assisted telephone interviewing system. The median scale score for perceived severity of ZIKV was 3 (interquartile range [IQR] 1-5) versus 4 (IQR 3-5) for dengue (P < 0.001). The scores for mosquito control practices before and after ZIKV was declared a PHEIC were similar, at 4 (IQR 3-5). Multivariate analysis revealed that participants with a higher score for perception of severity of ZIKV were more likely to report greater mosquito control practices after the declaration of the PHEIC (OR 1.822 [95% CI 1.107-2.998]). The emerging ZIKV pandemic requires concerted efforts to enhance mosquito control practices among the Malaysian public. Efforts to improve public mosquito control practices should focus on enhancing the perception of the severity of ZIKV.

  20. Detection of Hepatitis C Virus Coinfection in Patients with Dengue Diagnosis

    PubMed Central

    Machain-Williams, Carlos; Talavera-Aguilar, Lourdes; Cetina-Trejo, Rosa Carmina; Carrillo-Navarrete, Jaquelin; Rivero-Cárdenas, Nubia; Salazar, Ma. Isabel; Farfán-Ale, José Arturo; Castro-Mussot, María Eugenia

    2014-01-01

    Coinfection produced by dengue virus (DENV) and hepatitis C virus (HCV) is a serious problem of public health in Mexico, as they both circulate in tropical zones and may lead to masking or complicating symptoms. In this research, we detected active coinfected patients by HCV residing in the endemic city of Mérida, Yucatán, Mexico, with positive diagnosis to dengue during the acute phase. We performed a retrospective analysis of 240 serum samples from dengue patients. The IgM-ELISA serological test was used for dengue diagnosis, as well as viral isolation to confirm infection. DENV and HCV were detected by RT-PCR. Thus, 31 (12.9%) samples showed DENV-HCV coinfection, but interestingly the highest frequency of coinfection cases was found in male patients presenting hemorrhagic dengue in 19/31 (61.29%), with a predominance of 12 : 7 in males. Firstly, coinfection of DENV-HCV in Mérida, Mexico, was detected in young dengue patients, between 11 and 20 years old (38.7%), followed by those between 21 and 30 years old (32%); only 16.13% were between 0 and 10 years of age. Diagnosis of HCV infection in patients with dengue is highly recommended in order to establish potential risk in clinical manifestations as well as dictate patients' special care. PMID:24949433

  1. Detection of hepatitis C virus coinfection in patients with dengue diagnosis.

    PubMed

    Machain-Williams, Carlos; Talavera-Aguilar, Lourdes; Cetina-Trejo, Rosa Carmina; Carrillo-Navarrete, Jaquelin; Rivero-Cárdenas, Nubia; Salazar, Ma Isabel; Farfán-Ale, José Arturo; Puerto, Fernando I; Castro-Mussot, María Eugenia

    2014-01-01

    Coinfection produced by dengue virus (DENV) and hepatitis C virus (HCV) is a serious problem of public health in Mexico, as they both circulate in tropical zones and may lead to masking or complicating symptoms. In this research, we detected active coinfected patients by HCV residing in the endemic city of Mérida, Yucatán, Mexico, with positive diagnosis to dengue during the acute phase. We performed a retrospective analysis of 240 serum samples from dengue patients. The IgM-ELISA serological test was used for dengue diagnosis, as well as viral isolation to confirm infection. DENV and HCV were detected by RT-PCR. Thus, 31 (12.9%) samples showed DENV-HCV coinfection, but interestingly the highest frequency of coinfection cases was found in male patients presenting hemorrhagic dengue in 19/31 (61.29%), with a predominance of 12 : 7 in males. Firstly, coinfection of DENV-HCV in Mérida, Mexico, was detected in young dengue patients, between 11 and 20 years old (38.7%), followed by those between 21 and 30 years old (32%); only 16.13% were between 0 and 10 years of age. Diagnosis of HCV infection in patients with dengue is highly recommended in order to establish potential risk in clinical manifestations as well as dictate patients' special care.

  2. Chromobacterium Csp_P Reduces Malaria and Dengue Infection in Vector Mosquitoes and Has Entomopathogenic and In Vitro Anti-pathogen Activities

    PubMed Central

    Bahia, Ana C.; Saraiva, Raul G.; Dong, Yuemei; Kang, Seokyoung; Tripathi, Abhai; Mlambo, Godfree; Dimopoulos, George

    2014-01-01

    Plasmodium and dengue virus, the causative agents of the two most devastating vector-borne diseases, malaria and dengue, are transmitted by the two most important mosquito vectors, Anopheles gambiae and Aedes aegypti, respectively. Insect-bacteria associations have been shown to influence vector competence for human pathogens through multi-faceted actions that include the elicitation of the insect immune system, pathogen sequestration by microbes, and bacteria-produced anti-pathogenic factors. These influences make the mosquito microbiota highly interesting from a disease control perspective. Here we present a bacterium of the genus Chromobacterium (Csp_P), which was isolated from the midgut of field-caught Aedes aegypti. Csp_P can effectively colonize the mosquito midgut when introduced through an artificial nectar meal, and it also inhibits the growth of other members of the midgut microbiota. Csp_P colonization of the midgut tissue activates mosquito immune responses, and Csp_P exposure dramatically reduces the survival of both the larval and adult stages. Ingestion of Csp_P by the mosquito significantly reduces its susceptibility to Plasmodium falciparum and dengue virus infection, thereby compromising the mosquito's vector competence. This bacterium also exerts in vitro anti-Plasmodium and anti-dengue activities, which appear to be mediated through Csp_P -produced stable bioactive factors with transmission-blocking and therapeutic potential. The anti-pathogen and entomopathogenic properties of Csp_P render it a potential candidate for the development of malaria and dengue control strategies. PMID:25340821

  3. The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand

    PubMed Central

    2012-01-01

    Background There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. Methods A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7–18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Discussion Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. Trial registration clinicaltrial.gov. Registration number: NCT01563640 PMID:23153360

  4. An alphavirus vector-based tetravalent dengue vaccine induces a rapid and protective immune response in macaques that differs qualitatively from immunity induced by live virus infection.

    PubMed

    White, Laura J; Sariol, Carlos A; Mattocks, Melissa D; Wahala M P B, Wahala; Yingsiwaphat, Vorraphun; Collier, Martha L; Whitley, Jill; Mikkelsen, Rochelle; Rodriguez, Idia V; Martinez, Melween I; de Silva, Aravinda; Johnston, Robert E

    2013-03-01

    Despite many years of research, a dengue vaccine is not available, and the more advanced live attenuated vaccine candidate in clinical trials requires multiple immunizations with long interdose periods and provides low protective efficacy. Here, we report important contributions to the development of a second-generation dengue vaccine. First, we demonstrate that a nonpropagating vaccine vector based on Venezuelan equine encephalitis virus replicon particles (VRP) expressing two configurations of dengue virus E antigen (subviral particles [prME] and soluble E dimers [E85]) successfully immunized and protected macaques against dengue virus, while antivector antibodies did not interfere with a booster immunization. Second, compared to prME-VRP, E85-VRP induced neutralizing antibodies faster, to higher titers, and with improved protective efficacy. Third, this study is the first to map antigenic domains and specificities targeted by vaccination versus natural infection, revealing that, unlike prME-VRP and live virus, E85-VRP induced only serotype-specific antibodies, which predominantly targeted EDIII, suggesting a protective mechanism different from that induced by live virus and possibly live attenuated vaccines. Fourth, a tetravalent E85-VRP dengue vaccine induced a simultaneous and protective response to all 4 serotypes after 2 doses given 6 weeks apart. Balanced responses and protection in macaques provided further support for exploring the immunogenicity and safety of this vaccine candidate in humans.

  5. Uncaria tomentosa alkaloidal fraction reduces paracellular permeability, IL-8 and NS1 production on human microvascular endothelial cells infected with dengue virus.

    PubMed

    Lima-Junior, Raimundo Sousa; Mello, Cintia da Silva; Siani, Antonio Carlos; Valente, Ligia M Marino; Kubelka, Claire Fernandes

    2013-11-01

    Dengue is the major Arbovirus in the world, annually causing morbidity and death. Severe dengue is associated with changes in the endothelial barrier function due to the production of inflammatory mediators by immune cells and by the endothelium. Dengue virus (DENV) replicates efficiently in human endothelial cells in vitro and elicits immune responses resulting in endothelial permeability. Uncaria tomentosa (Willd.) DC.(Rubiaceae), known as cat's claw, has been used in folk medicine for the treatment of a wide-array of symptoms, and several scientific studies reported its antiviral, immunomodulatory, anti-inflammatory and antioxidant properties. Here we infected a human lineage of dermal microvascular endothelial cells (HMEC-1) with DENV-2 and treated it with an alkaloidal fraction from U. tomentosa bark (AFUT). We showed antiviral and immunomodulatory activities of U. tomentosa by determining the NS1 antigen and IL-8 in supernatant of DENV-2 infected HMEC-1. Furthermore, by measurement of transendothelial electrical resistance (TEER) we demonstrated, for the first time, that a plant derivative contributed to the reduction of paracellular permeability in DENV-2 infected HMEC-1. We also showed that IL-8 contributed significantly to the induction of permeability. Although further investigations should be conducted before a new drug can be suggested, our in vitro data support evidence that AFUT could be potentially useful in developing a treatment for severe dengue.

  6. Acute Human Inkoo and Chatanga Virus Infections, Finland.

    PubMed

    Putkuri, Niina; Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-05-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001-2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children.

  7. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  8. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  9. Memory CD8+ T cells from naturally-acquired primary dengue virus infection are highly cross-reactive

    PubMed Central

    Friberg, Heather; Burns, Lynne; Woda, Marcia; Kalayanarooj, Siripen; Endy, Timothy P.; Stephens, Henry A.F.; Green, Sharone; Rothman, Alan L.; Mathew, Anuja

    2010-01-01

    Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to play an immunopathological role in secondary heterologous DENV infection. To define the T cell response to heterologous serotypes, we isolated HLA-A*1101-restricted epitope-specific CD8+ T cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity towards peptide variants representing the four DENV serotypes in tetramer binding and functional assays. Many clones responded similarly to homologous and heterologous serotypes with striking cross-reactivity between the DENV-1 and DENV-3 epitope variants. In vitro-stimulated T cell lines consistently revealed a hierarchical induction of MIP-1β > degranulation > TNFα > IFNγ, which depended on the concentration of agonistic peptide. Phosphoflow assays demonstrated peptide dose-dependent phosphorylation of ERK1/2, which correlated with cytolysis, degranulation, and induction of TNFα and IFNγ but not MIP-1β production. This is the first study to demonstrate significant DENV serotype-cross-reactivity of CD8+ T cells after naturally-acquired primary infection. We also demonstrate qualitatively different T cell receptor signaling after stimulation with homologous and heterologous peptides. Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes. PMID:20421879

  10. Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive.

    PubMed

    Friberg, Heather; Burns, Lynne; Woda, Marcia; Kalayanarooj, Siripen; Endy, Timothy P; Stephens, Henry A F; Green, Sharone; Rothman, Alan L; Mathew, Anuja

    2011-01-01

    Cross-reactive memory T cells induced by primary infection with one of the four serotypes of dengue virus (DENV) are hypothesized to have an immunopathological function in secondary heterologous DENV infection. To define the T-cell response to heterologous serotypes, we isolated HLA-A(*)1101-restricted epitope-specific CD8(+) T-cell lines from primary DENV-immune donors. Cell lines exhibited marked cross-reactivity toward peptide variants representing the four DENV serotypes in tetramer binding and functional assays. Many clones responded similarly to homologous and heterologous serotypes with striking cross-reactivity between the DENV-1 and DENV-3 epitope variants. In vitro-stimulated T-cell lines consistently revealed a hierarchical induction of MIP-1β>degranulation>tumor necrosis factor α (TNFα)>interferon-γ (IFNγ), which depended on the concentration of agonistic peptide. Phosphoflow assays showed peptide dose-dependent phosphorylation of ERK1/2, which correlated with cytolysis, degranulation, and induction of TNFα and IFNγ, but not MIP-1β production. This is the first study to show significant DENV serotype-cross-reactivity of CD8(+) T cells after naturally acquired primary infection. We also show qualitatively different T-cell receptor signaling after stimulation with homologous and heterologous peptides. Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes.

  11. Time-Varying, Serotype-Specific Force of Infection of Dengue Virus

    DTIC Science & Technology

    2014-05-20

    Branch, Division of Parasitic Diseases and Malaria , Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333; jDepartment...August 15, 2013) Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission...dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne

  12. CD8 epitope escape and reversion in acute HCV infection.

    PubMed

    Timm, Joerg; Lauer, Georg M; Kavanagh, Daniel G; Sheridan, Isabelle; Kim, Arthur Y; Lucas, Michaela; Pillay, Thillagavathie; Ouchi, Kei; Reyor, Laura L; Schulze zur Wiesch, Julian; Gandhi, Rajesh T; Chung, Raymond T; Bhardwaj, Nina; Klenerman, Paul; Walker, Bruce D; Allen, Todd M

    2004-12-20

    In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.

  13. Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells.

    PubMed

    Olagnier, David; Peri, Suraj; Steel, Courtney; van Montfoort, Nadine; Chiang, Cindy; Beljanski, Vladimir; Slifker, Michael; He, Zhong; Nichols, Carmen N; Lin, Rongtuan; Balachandran, Siddharth; Hiscott, John

    2014-12-01

    Dengue virus (DENV) is a re-emerging arthropod borne flavivirus that infects more than 300 million people worldwide, leading to 50,000 deaths annually. Because dendritic cells (DC) in the skin and blood are the first target cells for DENV, we sought to investigate the early molecular events involved in the host response to the virus in primary human monocyte-derived dendritic cells (Mo-DC). Using a genome-wide transcriptome analysis of DENV2-infected human Mo-DC, three major responses were identified within hours of infection - the activation of IRF3/7/STAT1 and NF-κB-driven antiviral and inflammatory networks, as well as the stimulation of an oxidative stress response that included the stimulation of an Nrf2-dependent antioxidant gene transcriptional program. DENV2 infection resulted in the intracellular accumulation of reactive oxygen species (ROS) that was dependent on NADPH-oxidase (NOX). A decrease in ROS levels through chemical or genetic inhibition of the NOX-complex dampened the innate immune responses to DENV infection and facilitated DENV replication; ROS were also essential in driving mitochondrial apoptosis in infected Mo-DC. In addition to stimulating innate immune responses to DENV, increased ROS led to the activation of bystander Mo-DC which up-regulated maturation/activation markers and were less susceptible to viral replication. We have identified a critical role for the transcription factor Nrf2 in limiting both antiviral and cell death responses to the virus by feedback modulation of oxidative stress. Silencing of Nrf2 by RNA interference increased DENV-associated immune and apoptotic responses. Taken together, these data demonstrate that the level of oxidative stress is critical to the control of both antiviral and apoptotic programs in DENV-infected human Mo-DC and highlight the importance of redox homeostasis in the outcome of DENV infection.

  14. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease.

    PubMed

    Azeredo, Elzinandes L; Zagne, Sonia M O; Alvarenga, Allan R; Nogueira, Rita M R; Kubelka, Claire F; de Oliveira-Pinto, Luzia M

    2006-06-01

    The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4 and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8) express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

  15. Convergence analysis of particle swarm optimization (PSO) method on the with-in host dengue infection treatment model

    NASA Astrophysics Data System (ADS)

    Handayani, D.; Nuraini, N.; Tse, O.; Saragih, R.; Naiborhu, J.

    2016-04-01

    PSO is a computational optimization method motivated by the social behavior of organisms like bird flocking, fish schooling and human social relations. PSO is one of the most important swarm intelligence algorithms. In this study, we analyze the convergence of PSO when it is applied to with-in host dengue infection treatment model simulation in our early research. We used PSO method to construct the initial adjoin equation and to solve a control problem. Its properties of control input on the continuity of objective function and ability of adapting to the dynamic environment made us have to analyze the convergence of PSO. With the convergence analysis of PSO we will have some parameters that ensure the convergence result of numerical simulations on this model using PSO.

  16. Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion

    SciTech Connect

    Butrapet, Siritorn; Childers, Thomas; Moss, Kelley J.; Erb, Steven M.; Luy, Betty E.; Calvert, Amanda E.; Blair, Carol D.; Roehrig, John T.; Huang, Claire Y.-H.

    2011-04-25

    Fifteen mutant dengue viruses were engineered and used to identify AAs in the molecular hinge of the envelope protein that are critical to viral infection. Substitutions at Q52, A54, or E133 reduced infectivity in mammalian cells and altered the pH threshold of fusion. Mutations at F193, G266, I270, or G281 affected viral replication in mammalian and mosquito cells, but only I270W had reduced fusion activity. T280Y affected the pH threshold for fusion and reduced replication in C6/36 cells. Three different mutations at L135 were lethal in mammalian cells. Among them, L135G abrogated fusion and reduced replication in C6/36 cells, but only slightly reduced the mosquito infection rate. Conversely, L135W replicated well in C6/36 cells, but had the lowest mosquito infection rate. Possible interactions between hinge residues 52 and 277, or among 53, 135, 170, 186, 265, and 276 required for hinge function were discovered by sequence analysis to identify compensatory mutations.

  17. Dengue Antibody and Zika: Friend or Foe?

    PubMed

    Durbin, Anna P

    2016-10-01

    Zika virus is a mosquito-borne Flavivirus related to dengue that is rapidly spreading through the Americas. This outbreak is occurring in dengue-endemic areas where the population has acquired antibodies to dengue. Recent studies reveal that preexisting dengue antibodies may have opposite effects on Zika infection, transmission, and clinical outcome. Discerning these effects is critical to a better understanding of Zika pathogenesis and the prevention of future outbreaks.

  18. Global Cross-Talk of Genes of the Mosquito Aedes aegypti in Response to Dengue Virus Infection

    PubMed Central

    Behura, Susanta K.; Gomez-Machorro, Consuelo; Harker, Brent W.; deBruyn, Becky; Lovin, Diane D.; Hemme, Ryan R.; Mori, Akio; Romero-Severson, Jeanne; Severson, David W.

    2011-01-01

    Background The mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in humans, and DENV is the most important arbovirus across most of the subtropics and tropics worldwide. The early time periods after infection with DENV define critical cellular processes that determine ultimate success or failure of the virus to establish infection in the mosquito. Methods and Results To identify genes involved in these processes, we performed genome-wide transcriptome profiling between susceptible and refractory A. aegypti strains at two critical early periods after challenging them with DENV. Genes that responded coordinately to DENV infection in the susceptible strain were largely clustered in one specific expression module, whereas in the refractory strain they were distributed in four distinct modules. The susceptible response module in the global transcriptional network showed significant biased representation with genes related to energy metabolism and DNA replication, whereas the refractory response modules showed biased representation across different metabolism pathway genes including cytochrome P450 and DDT [1,1,1-Trichloro-2,2-bis(4-chlorophenyl) ethane] degradation genes, and genes associated with cell growth and death. A common core set of coordinately expressed genes was observed in both the susceptible and refractory mosquitoes and included genes related to the Wnt (Wnt: wingless [wg] and integration 1 [int1] pathway), MAPK (Mitogen-activated protein kinase), mTOR (mammalian target of rapamycin) and JAK-STAT (Janus Kinase - Signal Transducer and Activator of Transcription) pathways. Conclusions Our data revealed extensive transcriptional networks of mosquito genes that are expressed in modular manners in response to DENV infection, and indicated that successfully defending against viral infection requires more elaborate gene networks than hosting the virus. These likely play important roles in the global-cross talk among the mosquito host

  19. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed.

  20. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  1. Dengue in a changing climate.

    PubMed

    Ebi, Kristie L; Nealon, Joshua

    2016-11-01

    Dengue is the world's most important arboviral disease in terms of number of people affected. Over the past 50 years, incidence increased 30-fold: there were approximately 390 million infections in 2010. Globalization, trade, travel, demographic trends, and warming temperatures are associated with the recent spread of the primary vectors Aedes aegypti and Aedes albopictus and of dengue. Overall, models project that new geographic areas along the fringe of current geographic ranges for Aedes will become environmentally suitable for the mosquito's lifecycle, and for dengue transmission. Many endemic countries where dengue is likely to spread further have underdeveloped health systems, increasing the substantial challenges of disease prevention and control. Control focuses on management of Aedes, although these efforts have typically had limited effectiveness in preventing outbreaks. New prevention and control efforts are needed to counter the potential consequences of climate change on the geographic range and incidence of dengue, including novel methods of vector control and dengue vaccines.

  2. Epidemic dengue 2 in the city of Djibouti 1991-1992.

    PubMed

    Rodier, G R; Gubler, D J; Cope, S E; Cropp, C B; Soliman, A K; Polycarpe, D; Abdourhaman, M A; Parra, J P; Maslin, J; Arthur, R R

    1996-01-01

    From October 1991 to February 1992, an outbreak of acute fever (in which thick blood films were negative for malaria) spread rapidly in the city of Djibouti, Djibouti Republic, affecting all age groups and both nationals and foreigners. The estimated number of cases was 12,000. The clinical features were consistent with a non-haemorrhagic dengue-like illness. Serum samples from 91 patients were analysed serologically for flavivirus infection (dengue 1-4, West Nile, yellow fever, Zika, Banzi, and Uganda-S), and virus isolation was attempted. Twelve strains of dengue 2 virus were isolated. Dengue infection was confirmed by a 4-fold or greater rise in immunoglobulin (Ig) G antibody in paired serum specimens, the presence of IgM antibody, or isolation of the virus. Overall, 46 of the suspected cases (51%) were confirmed virologically or had serological evidence of a recent flavivirus infection. Statistical analysis showed that the presence of a rash was the best predictor of flavivirus seropositivity. In November 1992, Aedes aegypti was widespread and abundant in several districts of Djibouti city. A serological study of serum samples collect